Cellulitis, Osteomyelitis and Sepsis
- Abidia A, Laden G, Kuhan G, Johnson BF, Wilkinson AR,
Renwick PM, Masson EA, McCollum PT: The role of
hyperbaric oxygen therapy in ischaemic diabetic lower extremity
ulcers: a double-blind randomised-controlled trial. Eur J
Vasc Endovasc Surg. 25:513-8, 2003. OBJECTIVE: ischaemic
lower-extremity ulcers in the diabetic population are a source of
major concern because of the associated high risk of
limb-threatening complications. The aim of this study was to
evaluate the role of hyperbaric oxygen in the management of these
ulcers. METHOD: eighteen diabetic patients with ischaemic,
non-healing lower-extremity ulcers were recruited in a double-blind
study. Patients were randomly assigned either to receive 100%
oxygen (treatment group) or air (control group), at 2.4 atmospheres
of absolute pressure for 90 min daily (total of 30 treatments).
RESULTS: healing with complete epithelialisation was achieved in
five out of eight ulcers in the treatment group compared to one out
of eight ulcers in the control group. The median decrease of the
wound areas in the treatment group was 100% and in the control
group was 52% (p=0.027). Cost-effectiveness analysis has shown that
despite the extra cost involved in using hyperbaric oxygen, there
was a potential saving in the total cost of treatment for each
patient during the study. CONCLUSION: hyperbaric oxygen enhanced
the healing of ischaemic, non-healing diabetic leg ulcers and may
be used as a valuable adjunct to conventional therapy when
reconstructive surgery is not possible. Comments: The patients
were judged to have ischemic disease if their ankle-brachial index
was under 0.8 or great toe-brachial index under 0.7 (if calf
vessels incompressible). The study was small involving 18 patients,
nine in the treated and 9 in the control groups. Both control and
the treatment group received hyperbaric treatments, the difference
being that the treatment group was given 100% oxygen in the
chamber. The ulcers were generally Wagner grade II and, while
larger and deeper in the treatment group, they had been there
longer in the control group (9 months, 3-60) than in the treatment
group (6 months, 3-60 months). While the patients undoubtedly had
arteriosclerosis, the importance of the arteriosclerosis and the
propriety of adding "ischaemia" to the title might be questioned as
the transcutaneous partial pressures of oxygen (TcPO2) were normal
in both groups (treatment 46+/-15 and control 43+/-19).
- Ahmed S, Meghji S, Williams RJ et al: Staphylococcus aureus fibronectin binding proteins are essential for internalization by osteoblasts but do not account for differences in intracellular levels of bacteria. Infect Immun 69:2872-7, 2001. Staphylococcus aureus is a major pathogen of bone that has been shown to be internalized by osteoblasts via a receptor-mediated pathway. Here we report that there are strain-dependent differences in the uptake of S. aureus by osteoblasts. An S. aureus septic arthritis isolate, LS-1, was internalized some 10-fold more than the laboratory strain 8325-4. Disruption of the genes for the fibronectin binding proteins in these two strains of S. aureus blocked their ability to be internalized by osteoblasts, thereby demonstrating the essentiality of these genes in this process. However, there were no differences in the capacity of these two strains to bind to fibronectin or osteoblasts. Analysis of the kinetics of internalization of the two strains by osteoblasts revealed that strain 8325-4 was internalized only over a short period of time (2 h) and to low numbers, while LS-1 was taken up by osteoblasts in large numbers for over 3 h. These differences in the kinetics of uptake explain the fact that the two strains of S. aureus are internalized by osteoblasts to different extents and suggest that in addition to the fibronectin binding proteins there are other, as yet undetermined virulence factors that play a role in the internalization process. Comments: This article is one of several included here pointing out that bacteria may hide within the cell where the concentration of antibiotics may not approach that in the extracellular fluid. As a result, cure with the administration of systemic antibiotics may be difficult. The injection of local antibiotics in and around the bone obviously increases the gradient of the concentration of antibiotics across the cell wall.
- Apelqvist J et al: Wound classification is more
important than site of ulceration in the outcome of diabetic foot
ulcers. Diabetic Medicine 6:526-520, 1989. 314 consecutive
patients classified according to Wagner as having superficial
(through the full thickness of the dermis, N=150), deep (N=50),
osteomyelitis &/or abscess (N=46), minor gangrene (N=39), or
major gangrene (N=29). Healing for at least 6 months: 88% and 78%
for superficial and deep, 57% for abscess and osteomyelitis, 2 of
68 with gangrene... lowest healing rate (5%) in patients with
multiple ulcers who had the worst blood flow.
- Arbeit RD, Maki D et al: The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis 38: 1673-81, 2004. Daptomycin is the first available agent from a new class of antibiotics, the cyclic lipopeptides, that has activity against a broad range of gram-positive pathogens, including organisms that are resistant to methicillin, vancomycin, and other currently available agents. Daptomycin (4 mg/kg intravenously [iv] every 24 h for 7-14 days) was compared with conventional antibiotics (penicillinase-resistant penicillins [4-12 g iv per day] or vancomycin [1 g iv every 12 h]) in 2 randomized, international trials involving 1092 patients with complicated skin and skin-structure infections. Among 902 clinically evaluable patients, clinical success rates were 83.4% and 84.2% for the daptomycin- and comparator-treated groups, respectively (95% confidence interval, -4.0 to 5.6). Among patients successfully treated with iv daptomycin, 63% required only 4-7 days of therapy, compared with 33% of comparator-treated patients (P<.0001). The frequency and distribution of adverse events were similar among both treatment groups. Overall, the safety and efficacy of daptomycin were comparable with conventional therapy. Comments: Daptomycin is a welcome new antibiotic with a distinct mechanism of action: disrupting multiple aspects of bacterial cell membrane function. Presumably binding to the membrane, it causes rapid depolarisation, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which in turn results in bacterial cell death. The bactericidal activity of daptomycin is concentration-dependent. There is in vitro evidence of synergy with ß-lactam antibiotics. It is inactivated by pulmonary surfactants and, hence, is not indicated for the treatment of pneumonia. In skin and soft tissue infections, 4 mg/kg daptomycin is given intravenously once daily.
- Bamberger DM, Daus GP and Gerding DN:
Osteomyelitis in the feet of diabetic patients; Long-term results,
prognostic factors and the role of antimicrobial and surgical
therapy. Am J Med 83:653-660, 1987. Of 51 patients, 15
patients had a BK amputation and 9 a toe amputation. The absence of
necrosis and/or gangrene, the presence of swelling and the use of
antimicrobial therapy active against the isolated pathogens for at
least 4 weeks intravenously or combined orally-intravenously for
ten weeks predicted a good outcome.
- Calhoun JH, Cantrell J, et al: Treatment of
diabetic foot infections: Wagner classification, therapy, and
outcome. Foot & Ankle 9:101-108, 1988. 850 foot
infections in 355 patients. Patients treated with the Wagner
algorithms did better than those not so treated. Healing in various
grades protocol (nonprotocol): 0-89% (1/1 failed); 1- 86% (53%) ;
2- 73% (12%); 3 - 79% (12%); 4 - 88% (20%); 5 - 97% (?). Overall:
355 patients, 710 legs, 805 operations, 32 vascular procedures, 9
AK amputations, 121 BK amputations, 8 Syme amputations, 24 ankle
disarticulations, 21 metatarsal amputations, 72 ray resections, 158
toe amputations, 47 incision and drainage, 42 skin grafts and 273
debridements.
- Croll SD, Nicholas GG, Osborne MA, Wasser TE, Jones S:
Role of magnetic resonance imaging in the diagnosis of
osteomyelitis in diabetic foot infections. J Vasc Surg
24(2):266-70, 1996. PURPOSE: The role of magnetic resonance imaging
(MRI) in the diagnosis of osteomyelitis in foot infections in
diabetics was investigated. The accuracy, sensitivity, and
specificity of MRI, plain radiography, and nuclear scanning were
determined for diagnosing osteomyelitis, and a cost comparison was
made. METHODS: Twenty-seven patients with diabetic foot infections
were studied prospectively. All patients underwent MRI and plain
radiography. Twenty-two patients had technetium bone scans, and 19
patients had Indium scans. Nineteen patients had all four tests
performed. Patients with obvious gangrene or a fetid foot were
excluded. RESULTS: The diagnosis of osteomyelitis was established
by pathologic specimen (n = 18), bone culture (n = 3), or
successful response to medical management (n = 6). Osteomyelitis
was confirmed in nine of the pathologic specimens. The diagnostic
sensitivity, specificity, and accuracy for MRI was 88%, 100%, and
95%, respectively, for plain radiography it was 22%, 94%, and 70%,
respectively, for technetium bone scanning it was 50%, 50%, and
50%, respectively, and for Indium leukocyte scanning it was 33%,
69%, and 58%, respectively. The data were analyzed statistically
with the two-tailed Fisher's exact test. MRI was the only test that
was statistically significant (p < 0.01). CONCLUSIONS: MRI
appeared to be the single best test for the diagnosis of
osteomyelitis associated with diabetic foot infections. It had a
better diagnostic accuracy than conventional modalities and
appeared to be more cost-effective than the frequently used Indium
scan.
- Delcourt A, Huglo D et al: Comparison between
Leukoscan (Sulesomab) and Gallium-67 for the diagnosis of
osteomyelitis in the diabetic foot. Diabetes
Metab.31:125-33, 2005. OBJECTIVES: The diagnosis of osteomyelitis
in patients with diabetic foot is difficult both clinically and
radiologically. An early diagnosis is crucial to optimize
therapeutic strategy. Among the diagnostic methods currently used,
scintigraphy with ex-vivo labelled white blood cells is the gold
standard, but cannot be performed in all centers; therefore
67Gallium citrate (67Ga) imaging in combination with a bone
scintigraphy is still widely used. METHOD: The results of imaging
24 diabetic patients with 31 suspected osteomyelitic lesions using
the antigranulocyte Fab' fragment (Sulesomab or LeukoScan or
immunoscintigraphy) were prospectively compared with results from
the bone scan coupled with 67Ga. The diagnosis of osteomyelitis was
confirmed by either biopsy or follow-up, radiological imaging and
clinical outcome. RESULTS AND CONCLUSION: Sulesomab correctly
identified 12 of 18 osteomyelitic lesions while 67Ga was able to
detect only 8 of 18. Therefore the sensitivity is 67% for Sulesomab
and 44% for 67Ga. Among the 13 non-osteomyelitic lesions imaging
with Sulesomab was able to rule out infection in 11 cases and 67Ga
in 10 cases. The specificity is therefore 85% for Sulesomab and 77%
for 67Ga. Image interpretation for Sulesomab in this group of
patients is occasionally suboptimal when imaging is performed at 3
hours post injection. High vascular background in the early images
may obscure infection especially in small bones. Practically,
scintigraphy with Sulesomab is fast and simple due to ease of
labeling, no ex-vivo handling of blood, low radiation and provides
rapid diagnosis. The diagnosis of osteomyelitis obtained by the
antibody fragment scintigraphy influences the management (guided
biopsy) and therapy. In several patients, imaging with Sulesomab
was able to rule out osteomyelitis, helping to avoid useless
antibiotic therapy and its associated side effects.
- Dillon RS: Saving on soaks. Letter to the
editor in New Eng Journal of Medicine 311:540, 1984. Volume of
expensive soak solutions markedly reduced by placing foot in a
plastic bag and putting bagged foot then in basin of water. Soak
solution then poured into bag giving a thin layer of soak solution
around foot. Allows local use of expensive antibiotics.
- Dillon RS: Successful treatment of osteomyelitis
and soft tissue infections in ischemic diabetic legs by local
antibiotic injections and the end-diastolic pneumatic compression
boot. Ann Surg 204(6):643-9, 1986. Abstract: Thirty-four
legs at risk of amputation due to peripheral arterial insufficiency
associated with ischemic necrosis, soft tissue infections,
osteomyelitis, and variable degrees of peripheral neuropathy were
reported in 28 diabetic patients. Amputation had been considered in
27 legs for which standard therapies had failed for the current
illness and in two legs in which standard therapy had failed for
previous illnesses. Local therapy was the initial form of therapy
for five legs in which standard therapy appeared likely to fail.
Infection was controlled in all patients with the use of local
antibiotics and compression boot therapy. Early leg amputation was
avoided in all but one patient. Late leg amputation occurred in two
patients who were lost to follow-up care. Osteomyelitis, ischemic
necrosis, and advanced soft tissue infection were shown not to be
clear-cut indications for amputation in the ischemic diabetic foot. Comments: It should be appreciated that significant ischemia was present in every patient. All had abnormal Doppler waveforms. Twenty legs had ABI's less than 0.5 in one tibial artery, 11 had ABI's below 0.5 in both tibial arteries, 12 had ABI's over 0.5 but faint to absent Doppler sounds and 6 had pseudohypertension. Review the entire article.
- Dillon RS: Management of soft-tissue infections in
elderly persons with diabetes. Geriatric Medicine Today
6:21-35, 1987. Rationale of boot therapy and local antibiotic usage
presented. Immune problems in elderly diabetic also discussed.
- Dorigo B, Cameli AM, Trapani M, Raspanti D, Torri M and
Mosconi G: Efficacy of femoral intra-arterial
administration of Teicoplanin in gram-positive diabetic foot
infections. Angiology 46:1115-1122, 1995. Twenty-five
hospitalized diabetic patients with foot ulcers alone or together
with metatarsophalangeal osteomyelitis reported. Forty-four percent
of the patients had abnormal arterial Doppler studies. With the use
of a severity grading system like that of Wagner, the patients
included 12 "class 2", 10 "class 3" and 3 "class 4" patients.
Staphylococcus aureus was present alone in 16 patients and
associated with Pseudomonas aeruginosa in 2 patients, with Candida
albicans in two and with coagulase-negative staphylococcus in one.
In 4 patients other gram-positive cocci were isolated. All of the
isolated strains were resistant to the antibiotics tested.
Teicoplanin, 200 mg, was administered once a day by femoral
intra-arterial injection for an average period of 14.72±7.16
days (range 10 to 36 days). Six patients were treated with
additional antibiotic intramuscularly or intravenously because of a
mixed infection. Gram-positive infection was eliminated in all
patients. Healing occurred in 72% and improvement in 28% of the
patients. The authors chose Teicoplanin as opposed to Vancomycin
because of the potential for ototoxicity and renal toxicity of the
latter. They chose the intra-arterial route in an attempt to
improve tissue antibiotic concentrations and shorten the duration
of treatment.Comments: This article is included because of its
novel approach in the administration of the antibiotic. One might
ask if they had an indwelling arterial line or used a daily
arterial stick. In recent years the Vancomycin preparation
available in the United States has been relatively free from renal
and ear toxicity raising the possibility that impurities in
previous preparations were related to the toxicity problem. We have
approached these same patients with local injections of
antibiotics. No question about it: if you put the antibiotic there,
you know it is there.
- Duckworth C, Fisher JF, Carter SA Newman CL, Cogburn C,
Nesbit RR and Wray CH: Tissue penetration of clindamycin
in diabetic foot infections. J Antimicrobial Chem
31:581-584, 1993. Among 4 diabetics having debridements or
amputations for foot infections, in 9 of 11 tissue samples the
clindamycion levels exceeded the MICs reported for many commonly
involved pathogens.
- Ellington JK, Harris M, Webb L et al: Intracellular Staphylococcus aureus. A mechanism for the indolence of osteomyelitis. J Bone Joint Surg Br 85:918-21, 2003. Staphylococcus aureus is the bacterial pathogen which is responsible for approximately 80% of all cases of human osteomyelitis. It can invade and remain within osteoblasts. The fate of intracellular Staph. aureus after the death of the osteoblast has not been documented. We exposed human osteoblasts to Staph. aureus. After infection, the osteoblasts were either lysed with Triton X-100 or trypsinised. The bacteria released from both the trypsinised and lysed osteoblasts were cultured and counted. Colonies of the recovered bacteria were then introduced to additional cultures of human osteoblasts. The number of intracellular Staph. aureus recovered from the two techniques was equivalent. Staph. aureus recovered from time zero and 24 hours after infection, followed by lysis/trypsinisation, were capable of invading a second culture of human osteoblasts. Our findings indicate that dead or dying osteoblasts are capable of releasing viable Staph. aureus and that Staph. aureus released from dying or dead osteoblasts is capable of reinfecting human osteoblasts in culture.
- El-Maghraby TA, Moustafa HM, Pauwels EK: Nuclear
medicine methods for evaluation of skeletal infection among other
diagnostic modalities. Q J Nucl Med Mol Imaging 50:167-92,
2006. Skeletal infection continues to be a common and difficult
condition in clinical practice and early accurate diagnosis is very
challenging. Clinical and laboratory features of skeletal
infections are not always present, may be confusing, and are
nonspecific for bone infection in its early stages, therefore,
several imaging modalities are used for early detection of
osteomyelitis. Plain films should always be the first step in the
imaging assessment of osteomyelitis, however, the sensitivity for
X-ray radiography has been reported to range from 43% to 75%, and
the specificity from 75% to 83%. Over years, scintigraphic
procedures have become an essential part of the diagnostic
procedure for osteomyelitis. The standard approach for bone
scintigraphy with tech (99m)Tc labeled methylene diphosphonate to
assess for osteomyelitis is to perform a three-phase procedure. The
positive uptake on all three phases is highly sensitive for
osteomyelitis (sensitivity 73% to 100%). (67)Ga citrate gained more
attention for the more specific diagnosis of osteomyelitis due to
its known capacity to localize in cases of active infection and
pus. The reported specificity for (67)Ga scintigraphy in
osteomyelitis is around 67-70% and the specificity is much higher
(92%) when (67)Ga single photon emission tomography was obtained.
Labeled white blood cell (WBC) imaging has become the procedure of
choice to diagnose most cases of skeletal infections except for
those of the spine. Labeling of leucocytes can be done either by
(111)In or (99m)Tc labeled hexamethylpropylene amineoxime. The
sensitivity and specificity for labeled WBCs are in the high range
of 80% to 90%. [(18)F]fluorodeoxyglucose positron emission
tomography (PET) has been found to accumulate non-specifically at
sites of infection and inflammation. Investigational studies showed
that PET is particularly valuable in the evaluation of chronic
osteomyelitis and infected prostheses. Other imaging modalities
include sonography, computed tomography (CT) and magnetic resonance
imaging (MRI). The sensitivity and specificity of CT for the
diagnosis of osteomyelitis has not been established clearly and are
in the range of 65% to 75%. The sensitivity of MRI for
osteomyelitis has been generally reported as being between 82% and
100%, and specificity between 75% and 96%. Cases of osteomyelitis
commonly referred to diagnostic imaging departments include chronic
osteomyelitis, diabetic foot infections, vertebral osteomyelitis,
joint prostheses and patients with suspected reinfection. These
specific entities need special attention and careful selection of
the correct tracer or combination of imaging modalities that is
best suited for the proper therapeutic management protocols.
- Faglia E, Favales F, Aldeghi A, Calia P, Quarantiello A,
Oriani G, Michael M, Campagnoli P and Marabito A:
Adjunctive systemic hyperbaric oxygen therapy in treatment of
severe prevalently ischemic diabetic foot ulcers, A randomized
study. Diabetes Care 19: 1338-1343, 1996. Authors' results:
Of the treated group (mean session = 38.8±8), three subjects
(8.6%) underwent major amputation: two below the knee and one above
the knee. In the nontreated group, 11 subjects (11%) underwent
major amputations: 7 below the knee and 4 above the knee. The
difference is statistically significant (P= 0.016). The relative
risk for the treated group was 0.26 (95% CI 0.08-0.84). The
transcutaneous oxygen tension measured on the dorsum of the foot
significantly increased in subjects treated with hyperbaric oxygen
therapy: 14.0±11.8 mmHg in treated group, 5.0±5.4mmHg
in nontreated group (P=0.0002). Multivariate analysis of major
amputation on all the considered variables confirmed the protective
role of s-HBOT (odds ratio 0.084, P=0.033, 95% CI 0.008-0.821) and
indicated as negative prognostic determinants low ankle-brachial
index values (odds ration 1.1715, P=0.013, 95% CI 1.121-2.626) and
high Wagner grade (odds ratio 11.199, P=0.022, 95% CI
1.406-89.146). Comments: On the surface, this is a persuasive
paper. The patients are well randomized and an important end-point
is compared, major amputations. Closer examination of their case
material would be helpful, however. Neither their treated or
control group had major amputations (MA) in the Wagner I class of
patients. Their treated group had one MA in the Wagner III class
and the untreated group none. The rest of the amputations in both
groups were in the Wagner IV class (gangrene of toe or forefoot).
What does one do with a gangrenous toe? In the treated group, 16
toes were amputated among 22 class IV patients and in the control
group 8 toes were amputated among 20 class IV patients. If the
amputations of the toes are added to the major amputations, there
is no difference between the groups. If both groups had equal
numbers of gangrenous toes, the control group fared better (unless
their surgeon removed a foot for a gangrenous toe). More likely,
the control group had fewer gangrenous toes and a larger number of
patients with gangrene of the forefoot and the latter may be more
likely to come to a MA. The statistics in this paper dazzle those
of us who find CHI squares challenging. One is reminded of the UGDP
Phenformin Study in which phenformin appeared to promote death.
However, if one notes who dies (the older patients) and then
compares the control and the phenformin groups, one finds the
phenformin group had more very old and very young people than the
control group.. while both groups had the same average age. In this
study, we have already seen that one of the major factors the
authors report has poor prognostic significance (Wagner IV) class,
may be misleading. We are told that both groups had the same degree
of ischemia as determined by similar ABI's. However, 30.3% of the
control group presented with claudication compared to 11.4% of the
treated group. If the reader suspects I am skeptical of the value
of hyperbaric treatments for all patients, he is right. The
University of Pennsylvania has had a large hyperbaric chamber for
over 50 years. It has been available for the treatment of diabetic
feet but has not found great use. For more on hyperbaric
treatments, see the articles of Gabb and Robin and of Kindwall
below. Gawlik et al describe the reaction of the German
reimbursement committees to the data available in 2001.
- Fejfarova V, Jirkovska A, Skibova J, Petkov V:
Pathogen resistance and other risk factors in the frequency of
lower limb amputations in patients with the diabetic foot
syndrome. Vnitr Lek 48(4):302-6, 2002. Patients with
diabetes mellitus undergo more amputations due to peripheral
vascular disease, neuropathy and especially to infection requiring
long-lasting antibiotic therapy than non diabetic patients. The aim
of our study was to assess the association between the presence of
resistant pathogens presented in diabetic ulcers and the frequency
of lower limb amputations. METHODS: 191 diabetic patients
consecutively treated for the diabetic foot in our foot clinic were
included into two years retrospective study. Peripheral ischemia,
the presence of osteomyelitis and the incidence of all Gram
positive and negative resistant pathogens (defined as resistance to
all oral antibiotics) especially of resistant Staphylococcus
species presenting in diabetic foot ulcers were determined.
RESULTS: 50/191 (26%) patients underwent amputation, of whom 44/50
(88%) had minor and 6/50 (12%) had major amputations. 53/181 (29%)
patients with diabetic foot ulcers had resistant pathogens in their
defects. Amputated patients had significantly more resistant
microorganisms than patients without amputations--24/42 (57%) vs.
29/139 (21%); p < 0.001. Resistant Staphylococcus species were
found in 21% (38/181) of all patients. Patients with amputations
had significantly more resistant Staphylococcus species in
comparison with patients without amputations--18/42 (43%) vs.
20/139 (14%); p < 0.001. Significantly higher incidence of
peripheral vascular disease--79% (38/48) vs. 60% (81/136); p <
0.05 and osteomyelitis--69% (33/48) vs. 13% (18/140); p <
0.001--were found in patients with amputations in comparison with
patients without amputations. CONCLUSION: The presence of pathogens
resistant to all oral antibiotics and especially of resistant
Staphylococcus species was significantly higher in diabetic
patients with lower limb amputations in comparison with patients
without amputations.
- Fife CE, Buyukcakir C, Otto GH, Sheffield PJ, Warriner RA,
Love TL, Mader J: The predictive value of transcutaneous
oxygen tension measurement in diabetic lower extremity ulcers
treated with hyperbaric oxygen therapy: a retrospective analysis of
1,144 patients. Wound Repair Regen. 10:198-207, 2002. The
objective of this retrospective analysis was to determine the
reliability of transcutaneous oxygen tension measurement (TcPO2) in
predicting outcomes of diabetics who underwent hyperbaric oxygen
therapy for lower extremity wounds. Six hyperbaric facilities
provided TcPO2 data under several possible conditions: breathing
air, breathing oxygen at sea level, and breathing oxygen in the
chamber. Overall, 75.6% of the patients improved after hyperbaric
oxygen therapy. Baseline sea-level air TcPO2 identified the degree
of tissue hypoxia but had little statistical relationship with
outcome prediction because some patients healed after hyperbaric
oxygen therapy despite very low prehyperbaric TcPO2 values.
Breathing oxygen at sea level was unreliable for predicting
failure, but 68% reliable for predicting success after hyperbaric
oxygen therapy. TcPO2 measured in chamber provides the best single
discriminator between success and failure of hyperbaric oxygen
therapy using a cutoff score of 200 mmHg. The reliability of
in-chamber TcPO2 as an isolated measure was 74% with a positive
predictive value of 58%. Better results can be obtained by
combining information about sea-level air and in-chamber oxygen. A
sea-level air TcPO2 < 15 mmHg combined with an in-chamber TcPO2
< 400 mmHg predicts failure of hyperbaric oxygen therapy with a
reliability of 75.8% and a positive predictive value of
73.3%.Comments: See comments under Kalani below.
- Fischer BH: Treatment of ulcers on legs with
hyperbaric oxygen. J Dermatologic Surg 1:55-58, 1975. (From
New York Univ Med Ctr) 30 patients with lesions present 15 days to
six years. Most patients had failed other forms of Rx. 28 patients
healed and other 2 improved. Pressure chamber had pure O2 under
pressure of 22mm Hg (1.03 atmospheres)... avoided higher pressures
lest capillary flow impeded. O2 flow at 4L/min with continuous
humidification. Each O2 Rx lasted 2-3 hours and performed twice
daily. Saline dressings applied during off O2 hours. After 2nd or
3rd day of O2 Rx, demarcation line seen between necrotic and viable
tissue allowing debridements as necessary. Pure O2 under ambient
pressure said to have little effect on skin lesions. Pressurized O2
failed to heal lesions associated with severe ischemia. Mechanism
of benefit for pressurized O2: reduction of edema, rise in tissue
PO2, O2-stimulation of granulation tissue, suppression of bacterial
proliferation by rise in redox potentia. Comments: This is an
old method that has fallen by the wayside. When an O2 catheter is
placed on the leg within the Circulator Boot bags, O2 is
essentially given at 55mm Hg in the long boot and 75mm Hg in the
Miniboot without impeding blood flow. The possible benefits of
topical O2 therapy can be added to Circulator Boot Rx. Fischer's
technique is really topical O2 application under slight pressure.
See Kindwall below for true hyperbaric Rx. For more on topical
oxygen therapy as used with the Circulator Boot, see our
introduction (Topical
O2 vs CB therapy).
- Gabb G and Robin ED: Hyperbaric oxygen, a therapy
in search of diseases. Chest 92: 1074-1082, 1987. Summary:
The application of HBO to the therapy of various human diseases
developed over a 300 year period. Like most of medicine, the basis
of these applications was and continues to be pragmatic in nature,
and involves uncritical and untested judgments. The possibility of
risks has been understated and possible benefits overstated.
Individual physicians offering HBO and organized groups, such as
the Undersea Medical Society, advocating its use may be highly
motivated, well meaning, and sincerely convinced that HBO is an
important therapeutic approach. It may be that buried among the
host of indications, will be some disorders for which HBO is
uniquely and highly effective. If so, the present nonsystem for
evaluating responses to HBO will require modification, so that
these potentially valuable additions to therapeutics are not lost.
Because of its almost global application to a wide variety of
diseases, HBO therapy lends itself easily to medical adventurism
(therapy in search of a disease) and economic exploitation. If
there is some patient benefit to come from the experience of the
last 300 years, changes in approach, initiated by baromedical
devotees or by medicine generally, or resulting from pressures
outside of medicine, will be required. Comments: This is a
hard-nosed review of hyperbaric medicine listing its multiple
unproven indications for treatment, a surprising number of risks,
and a charge that the growth of the treatment has been more due to
its coverage by third party payers than any clinical efficacy.
- Gadepalli R, Dhawan B et al: A
clinico-microbiological study of diabetic foot ulcers in an Indian
Tertiary Care Hospital. Diabetes Care. 29:1727-32, 2006.
OBJECTIVE: To determine the microbiological profile and antibiotic
susceptibility patterns of organisms isolated from diabetic foot
ulcers. Also, to assess potential risk factors for infection of
ulcers with multidrug-resistant organisms (MDROs) and the outcome
of these infections. RESEARCH DESIGN AND METHODS: Pus samples for
bacterial culture were collected from 80 patients admitted with
diabetic foot infections. All patients had ulcers with Wagner's
grade 3-5. Fifty patients (62.5%) had coexisting osteomyelitis.
Gram-negative bacilli were tested for extended spectrum
beta-lactamase (ESBL) production by double disc diffusion method.
Staphylococcal isolates were tested for susceptibility to oxacillin
by screen agar method, disc diffusion, and mec A-based PCR.
Potential risk factors for MDRO-positive samples were explored.
RESULTS: Gram-negative aerobes were most frequently isolated
(51.4%), followed by gram-positive aerobes and anaerobes (33.3 and
15.3%, respectively). Seventy-two percent of patients were positive
for MDROs. ESBL production and methicillin resistance was noted in
44.7 and 56.0% of bacterial isolates, respectively. MDRO-positive
status was associated with presence of neuropathy (P = 0.03),
osteomyelitis (P = 0.01), and ulcer size >4 cm(2) (P < 0.001)
but not with patient characteristics, ulcer type and duration, or
duration of hospital stay. MDRO-infected patients had poor glycemic
control (P = 0.01) and had to be surgically treated more often (P
< 0.01). CONCLUSIONS: Infection with MDROs is common in diabetic
foot ulcers and is associated with inadequate glycemic control and
increased requirement for surgical treatment. There is a need for
continuous surveillance of resistant bacteria to provide the basis
for empirical therapy and reduce the risk of complications.
- Gawlik C, Schmacke N, Gibis B, Sander G, Rheinberger P:
[Reimbursement and importance of hyperbaric oxygenation for
diabetic foot ulcers in German publically funded ambulatory health
care] [Article in German]. Z Arztl Fortbild Qualitatssich.
95:715-8, 2001. The Standing Committee of Statutory Health
Insurance Physicians and Sickness Funds is the legal body that
makes decisions on reimbursement for health care services in the
German ambulatory health care sector. In 1994, the Committee
declined the reimbursement of hyperbaric oxygen therapy (HBO). In
1999, a new deliberation of the efficacy, appropriateness and
cost-effectiveness of HBO was initiated as the proponents of this
technology claimed that the efficacy of HBO had since been proven
in clinical trials. The deliberation was announced and published in
the journal of the German Medical Association (Deutsches
Arzteblatt) and the federal register (Bundesanzeiger). All
institutions, groups, and interested individuals were given the
opportunity to provide a written statement. The statements and, in
particular, the scientific literature cited in those statements,
were critically appraised by the Committee. In addition, the
Committee conducted a thorough review of the literature, guidelines
and status of the therapy in other health care systems. More than
40 potential indications for the use of HBO were reviewed by the
committee. One indication was for diabetic foot ulcers. Most
clinical trials related to this field represented only
retrospective case series, which, in view of the established
therapies, cannot be used as a sound basis for the acceptance of
HBO as a new technology for the therapy of diabetic foot ulcers.
Some studies were planned as randomized controlled trials but had
serious methodological flaws in conduct and analysis. The main
problems were the low numbers of patients included and serious
inbalances of important and well known prognostic factors between
the treatment groups. Systematic reviews that were published in the
international literature after the decision of the Committee drew
similar conclusions in view of the methodological flaws in the
clinical trial data. In summary, the Committee decided once again
to decline coverage of HBO in German ambulatory health care.
- Garrett S, Johnson L, Drisko CH et al.: Two
multi-center studies evaluating locally delivered doxycycline
hyclate, placebo control, oral hygiene, and scaling and root
planing in the treatment of periodontitis. J Periodontol.
70:490-503, 1999. BACKGROUND: The clinical efficacy and safety of
doxycycline hyclate (8.5% w/w) delivered subgingivally in a
biodegradable polymer (DH) was compared to placebo control (VC),
oral hygiene (OH), and scaling and root planing (SRP) in 2
multi-center studies. METHODS: Each study entered 411 patients who
demonstrated moderate to severe periodontitis. Patients had 2 or
more quadrants each with a minimum of 4 qualifying pockets > or
=5 mm that bled on probing. At least 2 of the pockets were > or
=7 mm. Treatment with DH, VC, OH, or SRP was provided at baseline
and again at month 4. Clinical parameters were recorded monthly.
RESULTS: DH and SRP resulted in nearly identical clinical changes
over time in both studies. Mean 9 month clinical attachment level
gain (ALG) was 0.8 mm for the DH group and 0.7 mm for the SRP group
in Study 1, and 0.8 mm (DH) and 0.9 mm (SRP) in Study 2. Mean
probing depth (PD) reduction was 1.1 mm for the DH group and 0.9 mm
for the SRP group in Study 1 and 1.3 mm for both groups in Study 2.
Frequency distributions showed an ALG > or =2 mm in 29% of DH
sites versus 27% of SRP sites in Study 1 and 31% of DH sites versus
34% of SRP sites in Study 2. PD reductions > or =2 mm were seen
in 32% of DH sites versus 31% of SRP sites in Study 1 and 41% of DH
sites versus 43% of SRP sites in Study 2. Comparisons between DH,
VC, and OH treatment groups showed DH treatment to be statistically
superior to VC and OH. Safety data demonstrated a benign safety
profile with use of the DH product. CONCLUSIONS: Results of this
trial demonstrate that treatment of periodontitis with
subgingivally delivered doxycycline in a biodegradable polymer is
equally effective as scaling and root planing and superior in
effect to placebo control and oral hygiene in reducing the clinical
signs of adult periodontitis over a 9-month period. This represents
positive changes resulting from the use of subgingivally applied
doxycycline as scaling and root planing was not limited regarding
time of the procedure or use of local anesthesia. Comments: 25
authors listed in the original article before their "et al."
- Gilbert DN, Dworkin RJ, Raber SR, and Leggett
JE.:Outpatient parenteral antimicrobial-drug
therapy. N Engl J Med 337: 829-838, 1997. The authors report
enthusiastically on the use of outpatient intravenous antibiotic
infusions. They tell of a series of 538 patients with clinical
improvement in 99% and cure in 92%... and need for hospitalization
in but 8%. Significant cost savings are described. Potential
complications are many: sterile phlebitis in 2-10%, large vein
thrombosis soon after or many months after catheter placement,
pulmonary emboli, superior vena cava syndrome, air embolism
(potentially fatal), catheter fragment embolization, catheter tip
migration to the right atrium or the jugular vein, catheter erosion
through a vein or the right atrium (producing pericardial
tamponade), intracatheter clots, fluid leaks through small holes in
the catheter causing fluid extravasation or contiguous mass
formation, rare idiosyncratic hypersensitivity reactions to the
catheter substance, and exit-site infections, tunnel infections and
catheter-related bloodstream infections. A rare form of infective
endocarditis may occur when a malpositioned catheter traumatizes
the tricuspid valve resulting in platelet-fibrin thrombi that
become infected. The authors point out that infusions should not be
prescribed if there is an equally effective and safe oral
antibiotic regimen. Cost savings were illustrated using the DRG
model in which a hospital received a given lump payment regardless
how long the patient is in the hospital; the hospital profits by
sending the patient home even if it provides the antibiotics for
nothing. See article by Maki et al below. The real costs of the
procedure include the costs of the antibiotics, the infusion
equipment, the visiting nurse and any complications. The visiting
nurse commonly is reimbursed more than the physician who provides
both antibiotic local injections and boot therapy in his office!
The HMO that does not embrace the latter is really losing an
opportunity to safe money.
- Grady JF, Winters CL: The Boyd amputation as a
treatment for osteomyelitis of the foot. J Am Podiatr Med
Assoc 90(5):234-9,2000. The Boyd amputation is a surgical technique
used to treat osteomyelitis of the foot. This amputation is a
technically more difficult procedure to perform than the Syme
amputation, but it offers certain advantages. The Boyd amputation
provides a more solid stump because it preserves the function of
the plantar heel pad. Also, because a portion of the calcaneus is
left and fused to the tibia, the weightbearing surface is more
solid than in the case of a Syme amputation. The authors recommend
a Boyd amputation as an alternative to a Syme or a below-the-knee
amputation to treat patients with osteomyelitis of the forefoot and
midfoot.
- Grayson ML, Gibbons GW, Balogh K, Levin E, Karchmer AW:
Probing to bone in infected pedal ulcers. A clinical sign of
underlying osteomyelitis in diabetic patients. JAMA
273:721-3, 1995. OBJECTIVE--To assess a bedside technique for
diagnosing osteomyelitis. DESIGN--We prospectively assessed
infected pedal ulcers for detectable bone by probing with a
sterile, blunt, stainless steel probe. We then examined the
relationship between detection of bone and the presence or absence
of osteomyelitis that was defined histopathologically and/or
clinically. SETTING--A tertiary care center. PATIENTS--Seventy-five
hospitalized diabetic patients with a total of 76 infected foot
ulcers were studied. RESULTS--Osteomyelitis was diagnosed in 50
instances (66%) and was excluded in 26 instances. Bone was detected
by probing in 33 of 50 ulcers with contiguous osteomyelitis; in
contrast, bone was probed in only four of 26 ulcers without
contiguous osteomyelitis (P < .001). Bone detected on probing
was visible in only three instances. Palpating bone on probing the
pedal ulcer had a sensitivity of 66% for osteomyelitis, a
specificity of 85%, a positive predictive value of 89%, and a
negative predictive value of 56%. CONCLUSIONS--Palpation of bone in
the depths of infected pedal ulcers in patients with diabetes is
strongly correlated with the presence of underlying osteomyelitis.
If bone is palpated on probing, specialized roentgenographic and
radionuclide tests to diagnose osteomyelitis are unnecessary.
Probing for bone should be included in the initial assessment of
all diabetic patients with infected pedal ulcers.
- Hamill RJ, Vann JM, Proctor RA: Phagocytosis of Staphylococcus aureus by cultured bovine aortic endothelial cells: model for postadherence events in endovascular infections. Infect Immun 54:833-6, 1986. We examined the interaction of Staphylococcus aureus with cultured bovine aortic endothelial cells as a model for the initial events in the pathogenesis of endovascular infections. Confluent monolayers of cultured endothelial cells were incubated with S. aureus. Cell-associated bacteria were measured by washing away nonadherent organisms, disrupting the monolayers, and performing quantitative cultures. Phagocytosis was differentiated from adherence by treating the cells with lysostaphin; approximately 60% of cell-associated bacteria was found to be intracellular. Phagocytosis could be blocked by using cytochalasin B, which interferes with microfilament function. Addition of fibronectin resulted in a 63% increase in adherence of S. aureus to the endothelial cells but did not increase ingestion. Transmission electron microscopy demonstrated a sequence of events similar to that which occurs during ingestion by professional phagocytes, including: adherence of bacteria to the endothelial cell; formation and elongation of surface extensions of the endothelial cell to surround the adherent bacteria; and complete enclosure within apparent phagosomes. Phagocytosis of bacteria by endothelial cells, followed by intracellular persistence, may be an important postadherence event in the pathogenesis and pathophysiology of endovascular infections.
- Harding,Edwards R: Bacteria and wound healing. Curr Opin Infect Dis 17:91-6.2004. PURPOSE OF REVIEW: Wound healing is a complex process with many potential factors that can delay healing. There is increasing interest in the effects of bacteria on the processes of wound healing. All chronic wounds are colonized by bacteria, with low levels of bacteria being beneficial to the wound healing process. Wound infection is detrimental to wound healing, but the diagnosis and management of wound infection is controversial, and varies between clinicians. RECENT FINDINGS: There is increasing recognition of the concept of critical colonization or local infection, when wound healing may be delayed in the absence of the typical clinical features of infection. The progression from wound colonization to infection depends not only on the bacterial count or the species present, but also on the host immune response, the number of different species present, the virulence of the organisms and synergistic interactions between the different species. There is increasing evidence that bacteria within chronic wounds live within biofilm communities, in which the bacteria are protected from host defences and develop resistance to antibiotic treatment. SUMMARY: An appreciation of the factors affecting the progression from colonization to infection can help clinicians with the interpretation of clinical findings and microbiological investigations in patients with chronic wounds. An understanding of the physiology and interactions within multi-species biofilms may aid the development of more effective methods of treating infected and poorly healing wounds. The emergence of consensus guidelines has helped to optimize clinical management.
- Isenberg JS, Costigan WM and Thordarson
DB:Subtotal calcanectomy of osteomyelitis of the os
calcis: A reasonable alternative to free tissue transfer.Ann
Plast Surg 35:660-663, 1995.From authors' summary: Subtotal
calcanectomy, traditionally a technique of the orthopedic surgeon,
can in selected cases eradicate infection and achieve wound closure
and limb preservation. A review was undertaken of one hospital's
experience with this procedure over a 4-year period. Five patients
with osteomyelitis of the os calcis were identified who were
successfully managed with subtotal calcanectomy. Comments: Many
patients are referred with decubitus heel ulcers that have become
infected and involve the os calcis superficially. We have treated
these with local antibiotic injections followed by Mini-Boot
therapy with the foot immersed in Sea Soaks containing antibiotics.
As shown in case history 97, occasionally infection involves much
of the os calcis. In such cases, we scrape away the soft and
necrotic elements at each boot session and continue with our local
treatments. We have been gratified to find that over time the
cavities may fill in and the ulcers close.
- Kalani M, Jorneskog G, Naderi N, Lind F, Brismar K:
Hyperbaric oxygen (HBO) therapy in treatment of diabetic foot
ulcers. Long-term follow-up. J Diabetes Complications.
16:153-8, 2002. BACKGROUND: The cause of diabetic foot ulcers is
multifactorial, e.g., neuropathy and angiopathy, leading to
functional disturbances in the macrocirculation and skin
microcirculation. Adequate tissue oxygen tension is an essential
factor in infection control and wound healing. Hyperbaric oxygen
(HBO) therapy, daily sessions of oxygen breathing at 2.5-bar
increased pressure in a hyperbaric chamber, has beneficial actions
on wound healing including antimicrobial action, prevention of
edema and stimulation of fibroblasts. The aim of the present study
was to investigate the long-term effect of HBO in treatment of
diabetic foot ulcers. METHODS: Thirty-eight diabetic patients (30
males) with chronic foot ulcers were investigated in a prospective
study. The mean age was 60+/-13 years and the mean diabetes
duration 27+/-14 years. All patients were evaluated with
measurements of transcutaneous oxygen tension (tcPO(2)), peripheral
blood pressure, and HbA(1c). All patients had a basal tcPO(2) value
lower than 40 mmHg, which increased to >/=100 mmHg, or at least
three times the basic value, during inhalation of pure oxygen.
Seventeen patients underwent 40-60 sessions of HBO therapy, while
21 patients were treated conventionally. The follow-up time was 3
years. RESULTS: 76% of the patients treated with HBO (Group A) had
healed with intact skin at a follow-up time of 3 years. The
corresponding value for patients treated conventionally (Group B)
was 48%. Seven patients (33%) in Group B compared to two patients
(12%) in Group A went to amputation. Peripheral blood pressure,
HbA(1c), diabetes duration, and basal values of tcPO(2) were
similar in both groups. CONCLUSIONS: Adjunctive HBO therapy can be
valuable for treating selected cases of hypoxic diabetic foot
ulcers. It seems to accelerate the rate of healing, reduce the need
for amputation, and increase the number of wounds that are
completely healed on long-term follow-up. Additional studies are
needed to further define the role of HBO, as part of a
multidisciplinary program, to preserve a functional extremity, and
reduce the short- and long-term costs of amputation and disability.
Comments: TcPO2 values of 40, of course are normal, while values
under 20 are not compatible with healing (see our vascular testing
library). The rise in TcPO2 with breathing pure oxygen meant that
the foot blood flow was adequate to bring some of the
hyperoxygenated blood to the foot electrodes. The treated patients
reported to the clinic 40-60 times for hyperbaric treatments when
their lesions were likely inspected and local treatments
administered. We are not told what attention the "conventional"
patients received. Reports on Circulator Boot patients must also be
viewed with similar reservations. Those patients failing daily care
in the hospital or nursing home by a wound care nurse prior to
Circulator Boot therapy received, indeed, aggressive "conventional
care". Those who were sent home to receive a visiting nurse a few
times a week received less than maximal "conventional care".
- Kaplan B and Gibson LB: Topical metronidazole for
arterial insufficiency ulcers.JAOA 95:201-203, 1995. Topical
metronidazole was approved by the FDA in 1988 for treatment of acne
rosacea. It has also been tried to treat infected foot ulcers
associated with diabetes, varicose veins, irradiation damage,
dental conditions and decubitus ulcers. Here the authors report
some benefit in a patient with an ischemic ulcer. Metronidazole is
generally active against most obligately anaerobic bacteria and
many protozoa. It is inactive against most aerobic or facultatively
anaerobic bacteria, fungi or viruses.
- Kessler L, Bilbault P, Ortega F, Grasso C, Passemard R,
Stephan D, Pinget M, Schneider F: Hyperbaric oxygenation
accelerates the healing rate of nonischemic chronic diabetic foot
ulcers: a prospective randomized study. Diabetes Care
26:2378-82, 2003.OBJECTIVE: To study the effect of systemic
hyperbaric oxygenation (HBO) therapy on the healing course of
nonischemic chronic diabetic foot ulcers. RESEARCH DESIGN AND
METHODS: From 1999 to 2000, 28 patients (average age 60.2 +/- 9.7
years, diabetes duration 18.2 +/- 6.6 years), of whom 87% had type
2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers
without clinical symptoms of arteriopathy, were studied. They were
randomized to undergo HBO because their ulcers did not improve over
3 months of full standard treatment. All the patients demonstrated
signs of neuropathy. HBO was applied twice a day, 5 days a week for
2 weeks; each session lasted 90 min at 2.5 ATA (absolute
temperature air). The main parameter studied was the size of the
foot ulcer measured on tracing graphs with a computer. It was
evaluated before HBO and at day 15 and 30 after the baseline.
RESULTS: HBO was well tolerated in all but one patient
(barotraumatic otitis). The transcutaneous oxygen pressure
(TcPO(2)) measured on the dorsum of the feet of the patients was
45.6 +/- 18.1 mmHg (room air). During HBO, the TcPO(2) measured
around the ulcer increased significantly from 21.9 +/- 12.1 to
454.2 +/- 128.1 mmHg (P < 0.001). At day 15 (i.e., after
completion of HBO), the size of ulcers decreased significantly in
the HBO group (41.8 +/- 25.5 vs. 21.7 +/- 16.9% in the control
group [P = 0.037]). Such a difference could no longer be observed
at day 30 (48.1 +/- 30.3 vs. 41.7 +/- 27.3%). Four weeks later,
complete healing was observed in two patients having undergone HBO
and none in the control group. CONCLUSIONS: In addition to standard
multidisciplinary management, HBO doubles the mean healing rate of
nonischemic chronic foot ulcers in selected diabetic patients. The
time dependence of the effect of HBO warrants further
investigations.Comments: Small studies are always hard to
randomize without some imbalances occurring between the treated and
control groups. While no specific risk factor separated the groups,
the control group here was on average 7.5 years older, had had
their diabetes 4 years longer, had renal impairment in 10.4 % more
patients, had coronary disease in 16.2% more patients and required
antibiotic therapy in 12% more patients. Neither group by design
had vascular disease and had similar normal TcPO2 levels on average
on the dorsum of the feet; the standard deviation of the TcPO2 was
18.1 in the treated group and 24.2 in the control group likely
signifying the control group had one or two patients with TcPO2
values well below those in the treated group. The treated group
closed their ulcers faster during their two week hospitalization
but the benefit was lost during their outpatient followup. One
wonders how the study would have turned out if the patients had
been able to remain in the hospital (the HBO continuing in the
treated group) until all were cured.
- Kessler L, Piemont Y et al:: Comparison of
microbiological results of needle puncture vs. superficial swab in
infected diabetic foot ulcer with osteomyelitis. Diabet Med.
23: 99-102, 2006. AIM: To study prospectively two methods for the
bacteriological diagnosis of osteomyelitis related to diabetic foot
ulcer: needle puncture performed across normal skin surrounding the
foot ulcer and superficial swabbing of the ulcer. PATIENTS AND
METHODS: Diabetic patients with a foot ulcer complicated by bone or
joint infection, as detected by X-ray imaging, were included in the
study. Ulcer swabbing and needle puncture were performed in each
patient. To reach the tissue nearest the bone surface, needle
puncture was guided by X-ray imaging and the drop of fluid obtained
by aspiration was used for both aerobic and anaerobic bacterial
culture. RESULTS: Twenty-one diabetic patients were included. The
mean number of microorganisms isolated by needle puncture was
significantly lower compared with that obtained by superficial
swabbing: 1.09 vs. 2.04 (P < 0.02). Three bacterial species were
isolated by needle puncture only in one patient while three or more
bacterial isolates were obtained by superficial swabbing in six
patients. No bacterial isolate was detected in five patients by
needle puncture and in two patients by superficial swabbing.
Staphylococcus aureus accounted for 70% of cases (seven patients)
when a single bacterial species was obtained by needle puncture.
After needle puncture, no wound complication or infection was
observed. CONCLUSION: Culture of samples obtained by needle
puncture revealed one or two bacterial isolates in two-thirds of
diabetic patients with osteomyelitis following foot ulcer. Given
the lack of complications, this invasive diagnostic technique
should be considered for deep direct sampling in diabetic patients
with osteomyelitis related to foot ulcer when surgical debridement
is contraindicated or delayed. Needle aspiration can be done on
presentation with minimal equipment and fanfare. It has few if any
harmful sequelae. Unlike bone biopsies, it does not extend the
lesion. When a significant sample size has entered the syringe, the
needle can be left in place and separated from the syringe.
Antibiotics may then be injected through the syringe and therapy
commenced.
- Kindwall, EP: Uses of hyperbaric oxygen therapy in
the 1990's. Cleveland Clinic J Med 59: 517-528, 1992.
Summary: Hyperbaric oxygen (HO) can produce a variety of effects in
addition to reducing air and gas embolism.. It increases the
killing ability of leukocytes and is lethal to certain anaerobic
bacteria. It inhibits toxin formation by certain anerobes,
increases the flexibility of red cells, reduces tissue edema,
preserves intracellular ATP, maintains tissue oxygentation in the
absence of hemoglobin. In addition, it stimulates fibroblast
growth, increases collagen formation, promotes rapid growth of
capillaries, and terminates lipid peroxidation. These actions of HO
are useful in treating anaerobic infections that result in gas
gangrene, as well as severe aerobic infections such as necrotizing
fasciitis, malignant external otitis, and chronic refractory
osteomyelitis. HO can help preserve ischemic tissues and
facilitates the rapid spread and arborization of new capillaries.
It promotes healing in certain problem wounds. Adjunctive HO
treatment is a new approach to the management of radionecrosis. HO
treatment reduces morbidity and mortality resulting from carbon
monoxide poisoning. Protocols for HO therapy are at present mostly
empirical; much additional research is needed to better define
therapeutic indications. Constant O2 Rx at 2 ATA produces pulmonary
O2 toxicity in about 6 hours. O2 at 3 ATA will produce a grand mal
seizure in 3 hours... Generally 2 chamber types: large walk-in
chamber filled with compressed air and in which patient breathes O2
by mask and 2nd, a monoplace chamber which is filled with 100% O2.
In the case of ischemic diabetic ulcers Kindwall concludes, "IF THE
ANKLE-TO BRACHIAL BLOOD PRESSURE RATIO (ISCHEMIC INDEX) IS LESS
THAN 0.45, OR IF THE DOPPLER ANKLE PRESSURE IS LESS THAN 75MM HG,
THERE IS LITTLE CHANCE OF HEALING EVEN WITH HBO. " See Knighton in
Vascular Test Ref.
- Kumar V: Radiolabeled white blood cells and direct
targeting of micro-organisms for infection imaging. Q J Nucl
Med Mol Imaging.49:325-38, 2005. Infection imaging is complicated
due to multitude of factors interfering with the design of
radiopharmaceuticals. More than 3 decades ago, labeled leukocytes
have been introduced for infection imaging and new
radiopharmaceuticals have been emerging on regular basis. However,
labeled leukocytes by in vivo and in vitro methods are very
effective for diagnosing various lesions such as osteomyelitis,
cellulitis, diabetic foot, Crohn's disease, inflammatory bowel
disease and in distinguishing prosthetic infection from loosening
of prosthesis. But in vitro labeling method using (111)In-oxine,
(99m)Tc-HMPAO or (99m)Tc-stannous colloid have the inherent
limitation of personnel safety risks of infection and cross
contamination. To overcome these problems, attempts have been made
to directly target leukocytes by in vivo labeling techniques. There
are several receptors present on the leukocytes and the
granulocytes, which can be targeted with suitable ligands. These
will include anti-NCA90-Fab, murine MoAb IgG(1) that is
cross-reactive to antigen 95 on neutrophils, anti-CD15 antigen and
DPC-11870 that targets the leukotriene B4 receptors of
granulocytes. In a new approach, (99m)Tc-labeled ciprofloxacin has
been developed to directly target ''live bacteria'' to detect
infection by in vivo method. This approach showed considerable
promise in the preliminary studies but clinical trials showed
limitations. Analogs of a natural mammalian antimicrobial agents,
such as Ubiquicidin were successful in animal studies and have now
entered clinical trials. (99m)Tc-labeled fluconazole (a fungal
antibiotic) and labeled Chitinase ((123)I-ChiB_E144Q), have been
developed to detect fungal infection. The ability to distinguish
between fungal and bacterial infection is considered important, as
patients undergoing chemotherapy are prone to fungal infection.
Undoubtedly, the new trends and new radiopharmaceuticals developed
for infection and inflammation imaging have contributed towards a
better understanding of the underlying processes.Comments: The
possibility of fungal infection should be considered when what
appears to be appropriate antibiotic therapy is failing. Here a
scanning technique is in the offing to help determine the presence
of fungus. Of course, needle aspiration and repeat culture would be
cheaper.
- Ledermann HP, Morrison WB: Differential diagnosis
of pedal osteomyelitis and diabetic neuroarthropathy: MR
Imaging. Semin Musculoskelet Radiol. 9:272-83, 2005. Almost
all diabetic foot infections originate from a foot ulcer. Decreased
pain perception and structural deformities such as previous partial
foot amputation, Charcot joints, and toe deformity in combination
with chronic ischemia lead to a propensity for skin breakdown and
subsequent infection. Magnetic resonance (MR) imaging is
increasingly performed to evaluate for potential bone infection,
but diagnosis of osteomyelitis can be complicated because signal
changes from acute Charcot arthropathy, fractures, and
postoperative residues may be mistaken for infection. Signal
alterations of bone infection may be atypical in sclerosing
osteomyelitis and gangrene. Differentiation between osteomyelitis
and acute or subacute neuroarthropathy requires careful analysis of
the location of bone signal alterations, their distribution, and
pattern because qualitative changes are often identical. Presence
of secondary signs such as adjacent ulcer, cellulitis, and sinus
tract is indicative of osteomyelitis. Differentiation of
noninfected neuroarthropathy from infected neuroarthropathy based
on MR examinations is difficult. Presence of a sinus tract,
disappearance of subchondral cysts, diffuse bone marrow
abnormality, and bone erosions are in favor of infection.
Comments: Obviously the MRI is an expensive test that does not
easily determine the presence of osteomyelitis. Clinical signs
(reddening, drainage, an ulcer, probing to bone) and simple tests
(sedimentation rate, x-ray of the foot, and needle aspiration of
the suspected area on the x-ray) will properly direct the clinician
in almost all instances.
- Lew DP and Waldvogel FA: Current Concepts:
Osteomyelitis. N Engl J Med 336:999-1007, 1997. Perhaps 5%
of this review addresses the ischemic or diabetic foot. In the
discussion on pathogenesis, one learns that Staphylococcus aureus
may have receptors ("adhesins") for components of bone matrix and
cartilage. The fibronectin-binding adhesin may allow the S aureus
to bind to surgically implanted devices. Again, the S. aureus can
be internalized by cultured osteoblasts and survive intracellularly
possibly explaining the persistence of some infections. Phenotypic
resistance to antibiotics associated with adherence to the bone may
provide another explanation. In discussing clinical features, the
authors point out that clinical signs persisting for more than ten
days correlate roughly with the development of necrotic bone and
chronic osteomyelitis. They note that surgical sampling or needle
biopsy provides indispensable information. While various new
imaging methods are available, they note that conventional
radiography is still necessary at both presentation and follow-up.
In the case of the diabetic foot, they quote the Joslin group in
claiming that if one can gently advance a sterile surgical probe to
reach bone, the diagnosis of osteomyelitis is clearly established.
For successful treatment, they suggest that parenteral antibiotics
must be administered at least four and usually six weeks to achieve
acceptable cure rates. They dismiss the local use of antibiotics,
noting that the diffusion of antibiotic given in this way is
limited in time and area and that such methods have not undergone
controlled study. For the patient with ischemia and/or diabetes,
they note that the treatment depends on the oxygen tension of the
tissue at the infected site, the potential for revascularization,
the extent of local infection and the preference of the patient.
Comments: Those of us interested in the diabetic foot are likely
to be disappointed in this article. Certainly the large number of
diabetic infections deserve more attention. The importance of
glycemic control is worth mentioning. It is to be appreciated that
a bone biopsy does provide immediate reliable culture
information... but at a cost of introducing further trauma to both
skin and bone. It is likely rare that serial cultures of draining
fistula do not include the important pathogenic bacteria. Local
oxygen tension may fall to very low values due to oxygen
consumption by cells and bacteria in cellulitic tissue and may not
reflect poor arterial flow; such measurements are best combined
with Doppler laser or PPG studies for an accurate interpretation of
the data. Finally, being advocates of the local injections of
antibiotics disseminated with the use of Circulator Boot therapy,
we claim a reduced cost, increased safety and increased
effectiveness versus their recommended therapy. In patients with
very low transcutaneous oxygen levels and obvious pulsatile PPG
blood flow, we consider the local administration of antibiotics a
necessity and expect to almost immediately improve the oxygenation
of the tissue. We invite the authors to visit this website and to
review Dr. Dillon's publications referenced elsewhere in this
library.
- Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS,
Karchmer AW, LeFrock JL, Lew DP, Mader JT, Norden C :
Diagnosis and treatment of diabetic foot infections. Plast
Reconstr Surg.117(7 Suppl):212S-238S, 2006. EXECUTIVE SUMMARY: 1.
Foot infections in patients with diabetes cause substantial
morbidity and frequent visits to health care professionals and may
lead to amputation of a lower extremity. 2. Diabetic foot
infections require attention to local (foot) and systemic
(metabolic) issues and coordinated management, preferably by a
multidisciplinary foot-care team (A-II). The team managing these
infections should include, or have ready access to, an infectious
diseases specialist or a medical microbiologist (B-II). 3. The
major predisposing factor to these infections is foot ulceration,
which is usually related to peripheral neuropathy. Peripheral
vascular disease and various immunological disturbances play a
secondary role. 4. Aerobic Gram-positive cocci (especially
Staphylococcus aureus) are the predominant pathogens in diabetic
foot infections. Patients who have chronic wounds or who have
recently received antibiotic therapy may also be infected with
Gram-negative rods, and those with foot ischemia or gangrene may
have obligate anaerobic pathogens. 5. Wound infections must be
diagnosed clinically on the basis of local (and occasionally
systemic) signs and symptoms of inflammation. Laboratory (including
microbiological) investigations are of limited use for diagnosing
infection, except in cases of osteomyelitis (B-II). 6. Send
appropriately obtained specimens for culture before starting
empirical antibiotic therapy in all cases of infection, except
perhaps those that are mild and previously untreated (B-III).
Tissue specimens obtained by biopsy, ulcer curettage, or aspiration
are preferable to wound swab specimens (A-I). 7. Imaging studies
may help diagnose or better define deep, soft-tissue purulent
collections and are usually needed to detect pathological findings
in bone. Plain radiography may be adequate in many cases, but MRI
(in preference to isotope scanning) is more sensitive and specific,
especially for detection of soft-tissue lesions (A-I). 8.
Infections should be categorized by their severity on the basis of
readily assessable clinical and laboratory features (B-II). Most
important among these are the specific tissues involved, the
adequacy of arterial perfusion, and the presence of systemic
toxicity or metabolic instability. Categorization helps determine
the degree of risk to the patient and the limb and, thus, the
urgency and venue of management. 9. Available evidence does not
support treating clinically uninfected ulcers with antibiotic
therapy (D-III). Antibiotic therapy is necessary for virtually all
infected wounds, but it is often insufficient without appropriate
wound care. 10. Select an empirical antibiotic regimen on the basis
of the severity of the infection and the likely etiologic agent(s)
(B-II). Therapy aimed solely at aerobic Gram-positive cocci may be
sufficient for mild-to-moderate infections in patients who have not
recently received antibiotic therapy (A-II). Broad-spectrum
empirical therapy is not routinely required but is indicated for
severe infections, pending culture results and antibiotic
susceptibility data (B-III). Take into consideration any recent
antibiotic therapy and local antibiotic susceptibility data,
especially the prevalence of methicillin-resistant S. aureus (MRSA)
or other resistant organisms. Definitive therapy should be based on
both the culture results and susceptibility data and the clinical
response to the empirical regimen (C-III). 11. There is only
limited evidence with which to make informed choices among the
various topical, oral, and parenteral antibiotic agents. Virtually
all severe and some moderate infections require parenteral therapy,
at least initially (C-III). Highly bioavailable oral antibiotics
can be used in most mild and in many moderate infections, including
some cases of osteomyelitis (A-II). Topical therapy may be used for
some mild superficial infections (B-I). 12. Continue antibiotic
therapy until there is evidence that the infection has resolved but
not necessarily until a wound has healed. Suggestions for the
duration of antibiotic therapy are as follows: for mild infections,
12 weeks usually suffices, but some require an additional 12 weeks;
for moderate and severe infections, usually 24 weeks is sufficient,
depending on the structures involved, the adequacy of debridement,
the type of soft-tissue wound cover, and wound vascularity (A-II);
and for osteomyelitis, generally at least 46 weeks is required, but
a shorter duration is sufficient if the entire infected bone is
removed, and probably a longer duration is needed if infected bone
remains (B-II). 13. If an infection in a clinically stable patient
fails to respond to 1 antibiotic courses, consider discontinuing
all antimicrobials and, after a few days, obtaining optimal culture
specimens (C-III). 14. Seek surgical consultation and, when needed,
intervention for infections accompanied by a deep abscess,
extensive bone or joint involvement, crepitus, substantial necrosis
or gangrene, or necrotizing fasciitis (A-II). Evaluating the limb's
arterial supply and revascularizing when indicated are particularly
important. Surgeons with experience and interest in the field
should be recruited by the foot-care team, if possible. 15.
Providing optimal wound care, in addition to appropriate antibiotic
treatment of the infection, is crucial for healing (A-I). This
includes proper wound cleansing, debridement of any callus and
necrotic tissue, and, especially, off-loading of pressure. There is
insufficient evidence to recommend use of a specific wound dressing
or any type of wound healing agents or products for infected foot
wounds. 16. Patients with infected wounds require early and careful
follow-up observation to ensure that the selected medical and
surgical treatment regimens have been appropriate and effective
(B-III). 17. Studies have not adequately defined the role of most
adjunctive therapies for diabetic foot infections, but systematic
reviews suggest that granulocyte colony-stimulating factors and
systemic hyperbaric oxygen therapy may help prevent amputations
(B-I). These treatments may be useful for severe infections or for
those that have not adequately responded to therapy, despite
correcting for all amenable local and systemic adverse factors. 18.
Spread of infection to bone (osteitis or osteomyelitis) may be
difficult to distinguish from noninfectious osteoarthropathy.
Clinical examination and imaging tests may suffice, but bone biopsy
is valuable for establishing the diagnosis of osteomyelitis, for
defining the pathogenic organism(s), and for determining the
antibiotic susceptibilities of such organisms (B-II). 19. Although
this field has matured, further research is much needed. The
committee especially recommends that adequately powered prospective
studies be undertaken to elucidate and validate systems for
classifying infection, diagnosing osteomyelitis, defining optimal
antibiotic regimens in various situations, and clarifying the role
of surgery in treating osteomyelitis (A-III).
- Littenberg B, Mushlin AI and the Diagnostic Technology
Assessment Consortium. Technetium bone scanning in the
diagnosis of osteomyelitis. A meta-analysis of test
performance. J Gen Inter Med 7:158-163, 1992. A relatively
poor test. In many clinical situations, the specificity of the bone
scan will not be high enough to confirm the diagnosis of
osteomyelitis.
- Lowy FD: Staphylococcus Aureus Infections.
New Engl J Med 339:520-532, 1998. "In an elegant series of clinical
observations and laboratory studies in 1880 and 1882, Ogston
described staphylococcal disease and its role in sepsis and abscess
formation. More than 100 years later, Staphylococcus aureus
remains a versatile and dangerous pathogen in humans. The
frequencies of both community-acquired and hospital acquired
staphylococcal infections have increased steadily with little
change in overall mortality. Treatment of these infections has
become more difficult because of the emergence of drug-resistant
strains."....Of the 11 types of microcapsular polysaccharide
serotypes, "types 5 and 8 account for 75% of human
infections"..."Staphylococci produce numerous toxins that are
grouped on the basis of their mechanism of action": cytoxins,
pyrogenic toxin, enterotoxins (toxic shock syndrome and food
poisoning) and exfoliative toxins... "Humans are a natural
reservoir of S.aureus. Thirty to 50 percent of healthy
adults of healthy adults are colonized, with 10 to 20 percent
persistently colonized. Both methicillin-sensitive and
methicillin-resistant isolates are persistent colonizers. Patients
colonized with S. aureus are at increased risk for
subsequent infection". Comments: We have provided but a few
excerpts from this paper. It is a good overall recent review of the
Staphylococcus and is recommended to the interested reader. A
resistant Staphylococcus on the rampage is a frightening thing to
behold.
- Maki DG, Stolz SM, Wheeler S, and Mermel
LA:Prevention of central venous catheter-related
bloodstream infection by use of an antiseptic-impregnated catheter.
A Randomized, controlled trial. Ann Intern Med 127:257-266,
1997. Authors' conclusions: The chlorhexidine-silver sulfadiazine
catheter is well tolerated, reduces the incidence of
catheter-related infection, extends the time that noncuffed central
venous catheters can be safely left in place for the short term,
and should allow cost savings. Comments: The indwelling
intravenous catheter has become more important today as HMO's force
patients to be discharged from the hospital to receive long-term
antibiotics at home. In an editorial accompanying this article,
Pearson and Abrutyn point out that central venous catheters account
for an estimated 90% of all nosocomial bloodstream infections with
multiple lumen catheters especially having a high risk. In a
companion article, Raaad et al report similar success in reducing
infection with their antibiotic-coated (rifampin and minocycline)
catheter. Finally, Marr et all recount their experience with
catheter-related bacteremia in patients undergoing hemodialysis;
40% of 102 patients developed 62 episodes of bacteremia over 16081
catheter days resulting in infective endocarditis in 4 patients and
death in 2 patients. We have no such problems with our local
antibiotic approach.
- Mempel M, Schnopp C, Hojka M et al: Invasion of human keratinocytes by Staphylococcus aureus and intracellular bacterial persistence represent haemolysin-independent virulence mechanisms that are followed by features of necrotic and apoptotic keratinocyte cell death. Br J Dermatol 146:943-51, 2002. BACKGROUND: Colonization of human skin by Staphylococcus aureus is a characteristic feature of several inflammatory skin diseases, which is often followed by tissue invasion and severe cell damage. A crucial role has been attributed to staphylococcal haemolysins in the cytotoxicity to epidermal structures. OBJECTIVES: To investigate haemolysin-independent virulence to human keratinocytes. METHODS: The stable alpha-haemolysin, beta-haemolysin double-negative S. aureus mutant DU 5720 was compared with the fully virulent parent strain 8325-4 and with its isogenic fibronectin-binding protein A/B-negative variant DU 5883 in an invasion model. RESULTS: This assay showed dose-dependent internalization of all the strains investigated by human HaCaT keratinocytes, with reduced internalization of DU 5883. Transmission electron microscopy revealed adhesion of staphylococci to cellular pilus-like extrusions, followed by the embedding of the bacteria in cellular grooves. Following attachment to the keratinocytes the staphylococci were engulfed into vesicles within the cytoplasm where some bacteria persisted for 24-48 h. Addition of cytochalasin D strongly reduced the bacterial uptake, suggesting an active keratinocyte process. Bacterial invasion was followed by severe keratinocyte cell damage showing the morphological changes of cytotoxic and, to a lesser extent, apoptotic cell death as determined by the trypan blue exclusion test and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling assay. The highest levels of lethal cytotoxicity were observed in haemolysin-producing strains, whereas the induction of apoptosis seemed to depend on internalization. CONCLUSIONS: Staphylococcal invasion of human keratinocytes represents a potent staphylococcal virulence factor, which, independently of alpha- and beta-haemolysins, leads to necrotic and apoptotic cell damage.
- Nelson CL, McLaren SG, Skinner RA, Smeltzer MS, Thomas JR,
Olsen KM: The treatment of experimental osteomyelitis by
surgical debridement and the implantation of calcium sulfate
tobramycin pellets. J Orthop Res. 20:643-7, 2002. Calcium
sulfate was used as a biodegradable delivery system for the
administration of antibiotics in musculoskeletal infection. New
Zealand white rabbits were infected with Staplylococcus aureus,
debrided, and randomized to one of four treatment groups: calcium
sulfate pellets with 10% tobramycin sulfate, placebo calcium
sulfate pellets and IM tobramycin, placebo calcium sulfate pellets,
or debridement. Serum and wound exudate tobramycin concentrations
and serum calcium levels were measured. Radiographs, cultures, and
histology were analyzed for efficacy and treatment. Rabbits treated
with 10% tobramycin sulfate pellets showed a significantly higher
eradication of infection (11/13) than rabbits treated with
debridement only (5/12), placebo pellets and IM tobramycin (5/14).
or placebo pellets (3/13). In the group receiving 10% tobramycin
sulfate pellets, serum tobramycin concentrations peaked 3 h
post-operatively at 5.87 microg/ml and were non-detectable after
day 1. In the group receiving placebo pellets and IM tobramycin,
serum concentrations peaked at 7.82 microg/ml 1 h post-operatively,
fell to 6.12 microg/ml on day 2, and averaged 4.18 microg/ ml for
the remainder of the treatment period. The wound exudate tobramycin
concentrations in the animals treated with tobramycin sulfate
pellets peaked at 11.9 mg/ml on day 1 and dropped to 2.5 microg/ml
on day 7. There was no significant difference in the serum calcium
levels in any of the treatment groups. Calcium sulfate containing
tobramycin sulfate has potential utility as a biodegradable local
antibiotic delivery system in the treatment of musculoskeletal
infections.
- Newman Lg, Waller J, Palestro J, Schwartz M, Klein MJ et
al: Unsuspected osteomyelitis in diabetic foot ulcers.
Diagnosis and monitoring by leukocyte scanning with Indium in 111
oxyquinoline. JAMA 266:1246-1251. 1991. As determined by
bone biopsy and culture, osteomyelitis was found to underlie 28
(68%) of 41 ulcers. 9/28 were clinically diagnosed. 19/28 no
evidence of inflammation. All patients with exposed bone had
osteomyelitis. In diagnosing the osteomyelitis, the leukocyte scan
had an 89% sensitivity. The image intensity decreased by 16-34 days
of antibiotic therapy and normalized by 36-54 days.
- Newman LG, Waller J, Palestro CJ, Hermann G, Klein MJ et
al: Leukocyte scanning with 111 In is superior to
magnetic resonance imaging in diagnosis of clinically unsuspected
osteomyelitis in diabetic foot ulcers. Diabetes Care 15:
1527-1530, 1992. Sixteen foot ulcers in 12 diabetic patients
studied with scans both with 111In leukocytes and MRI... then bone
biopsy and culture. Biopsy-proven osteomyelitis in 7 (44%),
clinically suspected in none, seen on leukocyte scan 100% and on
MRI in 29% (specificities 67% & 78% respectively). The + and -
predictive values (70% & 100%) respectively) for the leukocyte
scan were greater than for the MRI (50 & 58%).
- Niinikoski J: Hyperbaric oxygen therapy of
diabetic foot ulcers, transcutaneous oxymetry in clinical decision
making. Wound Repair Regen. 11:458-61, 2003. The foot ulcer
is one of most common and devastating complications of diabetes and
is associated with considerable morbidity and mortality. The major
causes of these ulcers are ischemia/hypoxia, neuropathy, and
infection, and they often coexist. Despite conventional therapy
including revascularization procedures when appropriate, three
situations lead frequently to amputation: persistent critical limb
ischemia, soft tissue infection, and impaired wound healing from
osteomyelitis. In these conditions, hyperbaric oxygen therapy may
be used as an adjunctive treatment and is associated with a better
outcome. Randomized, prospective, controlled trails have shown the
benefit of hyperbaric oxygen therapy in diabetic ulcers of the
lower extremity. Transcutaneous oxygen measurement performed under
hyperbaric oxygen therapy has a prognostic significance when used
to select patients who are the most likely to benefit from therapy.
Hyperbaric oxygen should be added to conventional treatment if the
transcutaneous oxygen tension close to the trophic lesion in 2.5
ATA hyperbaric oxygen is over 200 mmHg. Peri-wound transcutaneous
oxygen tensions over 400 mmHg in 2.5 ATA hyperbaric oxygen or over
50 mmHg in normobaric pure oxygen predict healing success with
adjuncted hyperbaric oxygen therapy with high accuracy.
Comments: Increasing the delivery of oxygen to the tissues is, of
course, the goal of therapy. To do this, one must either increase
arterial flow or the amount of oxygen in a given amount of blood.
As tissue hypoxia is a most potent vasodilator, it's relief with
hyperbaric oxygen would tend to decrease blood flow. The oxygen
content of blood (CaO2)is given by the formula: CaO2 = Hb (gm/dl) x
1.34 ml O2/gm Hb x SaO2 + PaO2 x (.003 ml O2/mm Hg/dl) where Hb is
the hemoglobin, SaO2 the hemoglobin O2 saturation, and PaO2 the
arterial partial pressure of oxygen. While the partial pressure of
oxygen in the air is 20% of 760 mmHg or 152 mmHg, the partial
pressures of nitrogen, carbon dioxide and water reduce it to about
100 mmHg in the alveoli. For a patient with normal lungs, a
hemoglobin of 14 grams, an oxygen saturation of 95%, an alveolar
PO2 of 100 and a PaO2 of 95, CaO2 would equal 18.1 ml O2 with 98.3%
of the oxygen carried on the hemoglobin. Giving the patient 100%
oxygen by mask rids the lungs of the nitrogen but not the water
vapor and carbon dioxide; the alveolar PO2 might approximate 508
mmHg. the hemoglobin O2 saturation rise to 100% and the dissolved
O2 content rises to about 1.5 ml, altogether raising the CaO2 to
20.4 (an increase of 12.7%). In an environment of 100% oxygen and
2.5 atmospheres, the oxygen tension becomes 1890 mmHg which
administered too long can produce significant oxygen toxicity. If
all 1890 mmHg (no alveolar block and no CO2 or water vapor)reached
the blood, the dissolved O2 rises to 5.7 ml and the hemoglobin
saturation rises to 100%. The hemoglobin carries now 18.7 ml and
the CaO2 is 24.4 ml O2. The oxygen content of the blood, hence, is
increased by about one third. In our vascular testing library, one
learns that normal transcutaneous PO2 in room air is over 40 mmHg
and that healing can be expected if it is over 30 mmHg. One might
calculate if one had a transcutaneous PO2 of 22.5 mmHg and lived in
a hyperbaric chamber on 100% oxygen at 2.5 atmospheres, the
treatment would raise the tissue PO2 to 30 mm Hg (blood flow
remaining equal). Likewise, one might calculate that if one had a
baseline transcutaneous oxygen of 44.5 mmHg, it would rise to 50
mmHG with the application of the pure oxygen mask. These various
calculations are somewhat favorable to hyperbaric oxygen therapy,
however, as the administration of oxygen either by mask or in the
hyperbaric chamber may significantly reduce oxygen-stimulated
respiratory drive resulting in carbon dioxide retention and
reductions in alveolar oxygen and arterial oxygen
tensions....Points to consider: (a) the hemoglobin concentration is
much more important than the alveolar PO2; a small improvement in
blood flow (perhaps from 5% of normal to 10% of normal) is much
more effective in raising tissue oxygen levels than a large rise in
alveolar PO2; and (b) in any case for the oxygen tension to rise
with either an oxygen mask at one atmosphere or 2.5 atmospheres,
there must be some blood flow to the periwound area. What would be
impressive is not claimed here: wound healing in patients with
baseline oxygen tensions under 20 mmHg.
- Niezgoda, J: PW116 - Circulator Boot Therapy to Heal Diabetic Foot Ulcers with Osteomyelitis. Poster Session at Third Congress of the World Union of Wound Healing Societies, June 2008, Toronto, Canada. Goals and Objectives: 1. Discuss impact of osteomyelitis and digit amputation in the diabetic population. 2. Define diastolic pneumatic compression and identify potential patients.
Purpose: Current standard of care for osteomyelitis associated with diabetic foot ulcers (DFU) is surgical resection of the infected bone and systemic antibiotics. Despite aggressive therapy amputation is common leaving the patient at risk for additional amputations and an associated five-year mortal;ity rate of 39-68%. Preventing amputation therefore critical to maintaining quality of life. Circulator boot therapy (CBT) utilizes end diastolic pneumatic compression to improve arterial circulation in the leg, thereby promoting wound healing. CBT has been used in the management of DFU complicated by osteomyelitis by combining compression with local injection of antibiotics into the affected area. We have validated the effectiveness of this technique to treat patients with DFU and underlying osteomyelitis. Methods: The study group consisted of patients with DFU and radiographically diagnosed osteomyelitis who failed to heal despite antibiotics, aggressive offloading and appropriate local wound care. Surgical debridement was refused by all study patients. Patients received three, forty-five minute CBT sessions per week plus weekly local injections of antibiotic solution into the wound as determined by culture results. Aggressive offloading and appropriate local wound care efforts were continued. Results: We present a series of healed patients who completed a 4-6 week course of CBT plus local injection of an antibiotic. Discussion/Conclusion: Osteomyelitis complicating a DFU is often associated with amputation. CBT combined with local antibiotic injection has been shown to be effective in the management of selected patients in this group and should be considered prior to amputation.
- O'Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard
SO, Maki DG, Masur H, McCormick RD, Mermel LA, Pearson ML, Raad II,
Randolph A, Weinstein RA; Healthcare Infection Control Practices
Advisory Committee.: Guidelines for the prevention of
intravascular catheter-related infections. Infect Control
Hosp Epidemiol. 23:759-69, 2002. BACKGROUND: Although many
catheter-related bloodstream infections (CRBSIs) are preventable,
measures to reduce these infections are not uniformly implemented.
OBJECTIVE: To update an existing evidenced-based guideline that
promotes strategies to prevent CRBSIs. DATA SOURCES: The MEDLINE
database, conference proceedings, and bibliographies of review
articles and book chapters were searched for relevant articles.
STUDIES INCLUDED: Laboratory-based studies, controlled clinical
trials, prospective interventional trials, and epidemiologic
investigations. OUTCOME MEASURES: Reduction in CRBSI, catheter
colonization, or catheter-related infection. SYNTHESIS: The
recommended preventive strategies with the strongest supportive
evidence are education and training of healthcare providers who
insert and maintain catheters; maximal sterile barrier precautions
during central venous catheter insertion; use of a 2% chlorhexidine
preparation for skin antisepsis; no routine replacement of central
venous catheters for prevention of infection; and use of
antiseptic/antibiotic-impregnated short-term central venous
catheters if the rate of infection is high despite adherence to
other strategies (ie, education and training, maximal sterile
barrier precautions, and 2% chlorhexidine for skin antisepsis).
CONCLUSION: Successful implementation of these evidence-based
interventions can reduce the risk for serious catheter-related
infection.Comments: The cost-savings of outpatient parenteral
antimicrobial-drug therapy have been emphasized by many authors who
would avoid hospitalization. Catheters are commonly used for
long-term antibiotic administration in the hospital also, however.
Whereever used, they may be associated with complications that
necessitate hospitalization. Potential complications include
sterile phlebitis in 2-10%, large vein thrombosis soon after or
many months after catheter placement, pulmonary emboli, superior
vena cava syndrome, air embolism (potentially fatal), catheter
fragment embolization, catheter tip migration to the right atrium
or the jugular vein, catheter erosion through a vein or the right
atrium (producing pericardial tamponade), intracatheter clots,
fluid leaks through small holes in the catheter causing fluid
extravasation or contiguous mass formation, rare idiosyncratic
hypersensitivity reactions to the catheter substance, and exit-site
infections, tunnel infections and catheter-related bloodstream
infections. Finally, a rare form of infective endocarditis may
occur when a malpositioned catheter traumatizes the tricuspid valve
resulting in platelet-fibrin thrombi that become infected. Gilbert
et al (Outpatient parenteral antimicrobial-drug therapy. N Engl J
Med 337: 829-838, 1997) point out that infusions should not be
prescribed if there is an equally effective and safe oral
antibiotic regimen. Central venous catheters may account for an
estimated 90% of all nosocomial bloodstream infections with
multiple lumen catheters especially having a high risk. The risk of
such infections can be reduced at added expense with the use of
antiseptic- or antibiotic-coated catheters. In this article,
O'Grady et al provide us with common sense on how to decrease the
risk of infection.
- Pathare NA, Sathe SR: Antibiotic combinations in
polymicrobic diabetic foot infections. Indian J Med Sci
55(12):655-62, 2001. OBJECTIVE: The aim of this study was to
evaluate synergistic potential of antibiotic combinations against
pathogenic microorganisms isolated from patients with diabetic foot
wounds. RESEARCH DESIGN AND METHODS: 272 diabetic foot patients
were studied prospectively over a two-year period. Tissue curettage
samples from ulcer base were processed microbiologically to isolate
aerobic as well as anaerobic pathogens. [775 isolates] Antibiotic
susceptibility testing [MIC/MBC], from amongst these organisms
revealed 75 multiresistant organisms, of which only 69 strains
could be further studied to assess synergistic effect of various
antibiotic combinations by the microtitre checkerboard assay
technique. RESULTS: The checkerboard synergy studies showed that
overall, synergy could be demonstrated in 21.74% to 59.57%. Amongst
the 14 combinations tested, it was found that four combinations
could be of worthwhile clinical significance, namely
Amikacin/Piperacillin [AK + PP] [77.50%];
Ampicillin-Sulbactum/Piperacillin [AS + PP] [76.92%]; Ampicillin
Sulbactum/Cefoperazone [AS + CP] [74.47%], and
Ofloxacillin/Cefotaxime [OF + CT] [71.43%]. CONCLUSIONS:
Amikacin/Piperacillin is a combination that has been proven to be
of synergistic potential. This study not only confirms this
observation but also showed that Ampitum-Sulbactum in combination
with either Piperacillin or Cefoperazone was equally efficacious.
Furthermore, it was also observed that Ofloxacillin/Cefotaxime
combination could be almost equally useful. The study thus
emphasizes that antibiotic combinations which are synergistic can
be of great clinical significance in the management of patients
with diabetic foot infections.
- Perry CR, Hulsey RE, Mann FA, Miller GA, Pearson RL:
Treatment of acutely infected arthroplasties with incision,
drainage, and local antibiotics delivered via an implantable
pump. Clin Orthop. 281:216-23, 1992. Twelve patients with
acutely (symptomatic less than ten weeks) infected arthroplasties
were treated with minimal debridement and intraarticular
antibiotic, amikacin, delivered via an implantable pump. The
infection was suppressed in ten cases. Intraarticular levels of
amikacin were obtained in eight cases. These levels ranged from
greater than 150 micrograms/ml to 1688 micrograms/ml. The systemic
level of amikacin remained below 10 micrograms/ml in all but one
case. Duration of hospitalization averaged 19 days. There were no
significant toxic side effects to amikacin.Comments: This was
the last of several publications from this group dating back to
1986 involving an antibiotic pumping device for the treatment of
osteomyelitis. Daily injections of antibiotics obviate the need for
a pump and its complications. Booting helps disseminate the
antibiotic around the joint space without greatly increasing
systemic antibiotic levels (no renal or ear toxicity).
- Raymakers JT, Houben AJ, van der Heyden JJ, Tordoir JH,
Kitslaar PJ, Schaper NC: The effect of diabetes and
severe ischaemia on the penetration of ceftazidime into tissues of
the limb. Diabet Med. 18:229-34, 2001. AIMS: To determine
the effect of diabetes and of different degrees of ischaemia on the
penetration of ceftazidime into different tissues. METHODS: Sixteen
patients (10 with diabetes mellitus) undergoing lower extremity
amputation for severe ischaemia (in 12 in combination with
infection), received 2000 mg ceftazidime intravenously as a bolus
30 min prior to the operation. Skin perfusion was determined by
transcutaneous oxygen pressure measurements (TcPO2) on the dorsal
side of the midfoot. After amputation bone, skin and muscle samples
were obtained from the forefoot, midfoot and proximal tibia. Tissue
and plasma concentrations were determined by HPLC. The tissue
concentrations were corrected for blood contamination. RESULTS: No
differences were observed in skin, muscle or bone ceftazidime
levels between diabetic and non-diabetic patients. Multiple
regression analysis suggested that tissue perfusion was a major
determinant of skin and bone ceftazidime concentrations, predicting
40-47% of the ceftazidime concentrations at several biopsy sites.
CONCLUSIONS: The present study suggests that tissue perfusion is
the major determinant of the penetration of a third generation
cephalosporin into the tissues of the ischaemic (diabetic) foot.
Diabetes alone however, has no major effects upon this penetration.
- Sapico FL, Witte JL, Canawati HN, Montgomerie JZ and Bessman
AN: The infected foot of the diabetic patient:
Quantitative microbiology and analysis of clinical features.
Rev Infectious Dis 6 (Suppl 1) : S171-S176, 1984. Study of 32
amputated diabetic limbs: 6 only aerobes, 1 only anerobes, and 25 a
mixtureof aerobes and anaerobes... a mean of 4.81 species isolated.
Cultures obtained by curettage of base of ulcers correlated better
with deep tissue cultures than did needle aspiration or swabs of
the ulcer. Anaerobes associated with higher frequency of fever and
foul smelling lesions. Prior antibiotic therapy did not appear to
influence the nature of the microorganisms isolated.
- Scher KS and Steele FJ: The septic foot in
patients with diabetes. Surgery 104:661-666, 1988. 65 lower
extremity amputations in diabetics over 3 years (98 in nondiabetics
not included). Chronic planter ulcer most frequent cause of
infection. Other causes included ischemic gangrene, trauma, and
web-space fissures. Advanced ischemia infrequent (32.3%) and
defined as arm-ankle indices 0.5). 23.5% died and 35.3% stumps
failed when closed amputation was done in 35 patients vs no deaths
and 12.9% stump failures when open amputations done. Recommends
guillotine transmalleolar amputation with later BK for highest
success.
- Seabrook GR, Edminston CE, Schmitt DD, Krepel C, Bandyk DF
and Towne JB: Comparison of serum and tissue antibiotic
levels in diabetes-related foot infections. Surgery
110:671-677, 1991. 26 patients given one dose of
gentamycin/clindamicin, ticarcillin/clavulanate, or
ampicillin/sulbactam one hour before surgical debridement when
serum and tissue levels measured. Adequate antibiotic levels were
reached in the serum in 16 and in the tissues in 6 patients.
Initial intravenous antibiotic administration provides inadequate
tissue concentrations for treating foot infections in diabetics.
- Senneville E, Melliez H, Beltrand E, Legout L, Valette M,
Cazaubiel M, Cordonnier M, Caillaux M, Yazdanpanah Y, Mouton Y:
Culture of percutaneous bone biopsy specimens for diagnosis
of diabetic foot osteomyelitis: concordance with ulcer swab
cultures. Clin Infect Dis 42:57-62, 2006. BACKGROUND: We
assessed the diagnostic value of swab cultures by comparing them
with corresponding cultures of percutaneous bone biopsy specimens
for patients with diabetic foot osteomyelitis. METHODS: The medical
charts of patients with foot osteomyelitis who underwent a surgical
percutaneous bone biopsy between January 1996 and June 2004 in a
single diabetic foot clinic were reviewed. Seventy-six patients
with 81 episodes of foot osteomyelitis who had positive results of
culture of bone biopsy specimens and who had received no antibiotic
therapy for at least 4 weeks before biopsy constituted the study
population. RESULTS: Pathogens isolated from bone samples were
predominantly staphylococci (52%) and gram-negative bacilli
(18.4%). The distributions of microorganisms in bone and swab
cultures were similar, except for coagulase-negative staphylococci,
which were more prevalent in bone samples (P < .001). The
results for cultures of concomitant foot ulcer swabs were available
for 69 of 76 patients. The results of bone and swab cultures were
identical for 12 (17.4%) of 69 patients, and bone bacteria were
isolated from the corresponding swab culture in 21 (30.4%) of 69
patients. The concordance between the results of cultures of swab
and of bone biopsy specimens was 42.8% for Staphylococcus aureus,
28.5% for gram-negative bacilli, and 25.8% for streptococci. The
overall concordance for all isolates was 22.5%. No adverse
events--such as worsening peripheral vascular disease, fracture, or
biopsy-induced bone infection--were observed, but 1 patient
experienced an episode of acute Charcot osteoarthropathy 4 weeks
after bone biopsy was performed. CONCLUSIONS: These results suggest
that superficial swab cultures do not reliably identify bone
bacteria. Percutaneous bone biopsy seems to be safe for patients
with diabetic foot osteomyelitis.Comments: Hopefully an article
with ten authors offers valid information. Kessler et al above
arrived at the same conclusions.
- Shompole S, Henon KT, Liou LE et al: Biphasic intracellular expression of Staphylococcus aureus virulence factors and evidence for Agr-mediated diffusion sensing. Mol Microbiol 49:919-27, 2003. Staphylococcus aureus invades a variety of mammalian cells and escapes from the endosome to multiply in the cytoplasm. We had previously hypothesized that the molecular events leading to escape of S. aureus from the endosome involved the Agr virulence factor regulatory system. In this report we demonstrate that temporal changes in intracellular activation of the Agr regulon correlates with expression of membrane active toxins. Also, the initial expression of Agr by even small numbers of staphylococci resulted in the permeabilization of the endosomal membrane and the eventual escape of bacteria into the cytoplasm by 3 h post invasion. After Agr downregulation, a second peak of expression coincided with increased permeability of the host cell membrane. In contrast to the parental strain, an Agr-mutant was unable to escape into the cytoplasm and was observed in intact endosomes as late as 5 h post invasion. These data provide evidence that staphylococcal virulence factor production during invasion of host cells is mediated by an Agr-dependent process that is most accurately described in the context of diffusion sensing.
- Smith AJ, Daniels T and Bohnen JMA: Soft tissue
infections and the diabetic foot. Am J Surg 172 (suppl
6A):7S-12S, 1966. Abstract: Soft tissue infections are classified
as local or spreading. Spreading soft tissue infections are
potentially life-threatening conditions, requiring prompt diagnosis
and treatment. The information presented is based on a literature
review and the author's clinical experience. Diagnosis of soft
tissue infection is aimed at determining the level of infection
(skin, fascia, muscle) and whether necrosis is present. The
bacteriology of these infections is varied and of secondary
importance. Treatment of skin infections that have no dead tissue
is with antibiotics alone. Infections at the fascial or muscle
level and those with necrosis at any level require surgical
debridement and adjuvant antibiotics. The feet of diabetic patients
are prone to plantar forefoot ulcers associated with tissue
destruction and infection. The vast majority are caused by
mechanical factors. If localized immune defenses are adequate,
bacterial colonization occurs without infection. Most diabetic foot
ulcers will respond to relief of pressure, which may require total
contact casting. Antibiotics and debridement are required in
infected or deep ulcers, or when the ulcer does not respond to
total contact casting. Comments: Smith et al provide us with the
current surgical gospel. Perusal of our case histories will show
that we break virtually all of his rules quite effectively. The
Joslin group has reported that they consider cellulitis over a few
centimeters as an ominous sign. Such cellulitis may spread in spite
of antibiotics and surgical debridement may merely create an open
wound in inflamed tissue. A tender enlarging red area with a low
transcutaneous PO2 and a high PCO2 and detectable PPG pulse waves
commonly portends significant cellulitis. We infiltrate the area
with gentamicin or other antibiotic and disseminate it locally with
the boot virtually sterilizing the area immediately. When abscesses
form, we aspirate them dry and may irrigate them with Sea Soaks and
appropriate antibiotics. Then again, we infiltrate the local area
with antibiotics and pump on the foot... no wide debridement or
large surgical wound. Contact casting makes wound observation
difficult and our local measures impossible. Rather, we use a
walking air cast with padding to relieve pressure points.... Again,
we do most all cases as outpatients hospitalizing only those with
other illnesses that require the hospital.
- Smith DG, Stuck RM, Ketner L, Sage RM and Pinzur MS:
Partial calcanectomy for the treatment of large ulcerations
of the heel and calcaneal osteomyelitis. J Bone and Joint
Surg 74A: 571-576, 1992. 12 patients with arm/ankle index >0.45,
TcPO2>28 mm Hg, serum albumen >3.0, lymphocyte count >1500
and availaable soft tissue adequate to cover the hind foot. Wound
healed in 10 of the 12 and 9 maintained their preoperative level of
mobility.
- Spanu T, Santangelo R, Andreotti F et al: Antibiotic therapy for severe bacterial infections: correlation between the inhibitory quotient and outcome. Int J Antimicrob Agents 23:120-8, 2004. In severe bacterial infections, treatment failure can occur even when the infecting organism has displayed in vitro susceptibility to the antibiotics used. Several pharmacokinetic-pharmacodynamic parameters show better correlation with therapeutic outcome than susceptibility results. This study was devised to assess the relation between the inhibitory quotient (IQ), i.e., the ratio of achievable antibiotic concentration at the infection site to the minimum inhibitory concentration for the infecting organism, and both clinical and bacteriological outcomes in 290 severe bacterial infections. Multivariate analysis showed that the IQ was a strong predictor of therapeutic outcome ( P< 0.001-0.002): values <4 predicted failure, and those >or=6 cure. This simple parameter could be routinely used to guide effective antibiotic therapy. Comments: Obviously the local injection of antibiotics will produce an IQ well over 6 in the area of th4e injection.
- Spittell JA et al: Concentration of orally
administered erythromycin and tetracycline in ischemic
tissue. Proc Staff Meet May Clin. 36:11, 1961. High dose
antibiotics do reach ischemic tissue.
- Tascini C, Gemignani G et al: Clinical and
Microbiological Efficacy of Colistin Therapy in Combination With
Rifampin and Imipenem in Multidrug-Resistant Pseudomonas aeruginosa
Diabetic Foot Infection With Osteomyelitis. Int J Low Extrem
Wounds. 5(3):213-6, 2006. The evaluation of the safety and
effectiveness of colistin in association with rifampin and imipenem
in 1 diabetic patient with severe diabetic foot infection (DFI) due
to multidrug-resistant (MDR) Pseudomonas aeruginosa, complicated by
osteomyelitis, is presented in this "Case Report". The patient
received colistin after other ineffective antimicrobial treatment
when an MDR P aeruginosa strain was isolated by cultural
examination, together with a multidisciplinary care approach
including surgical debridement and adequate offloading. The
efficacy of combination colistin plus rifampin plus imipenem was
observed with a checkerboard method and bactericidal activity of
the serum. The patient received colistin combination therapy for 6
weeks with cure of the infection and without renal toxicity. These
data suggest that colistin, in combination with rifampin and
imipenem, is safe and effective, in promoting healing in DFI due to
MDR P aeruginosa and suggest the need for controlled clinical
studies. Resistant Pseudomonas can be a problem. Our case #155
lost his leg because none of us could rid him of his
Pseudomonas.
- Taylor LM Jr, Porter JM: The clinical course of
diabetics who require emergent foot surgery because of infection or
ischemia. J Vasc Surg 6:454-459, 1987. All acute diabetic
foot problems were treated on vascular surgery service where
aggressive local surgery emphasized. 114 diabetics, 138 limbs, and
212 urgent operations... followed 1 month to 11 years... 36 major
amputations in 33 patients over 0-86 months from presentation.
- Thordarson DB, Perry JR and Patzakis J: Tetanus
complicating a polymicrobial diabetic foot infection: Case
presentation and review of current treatment. Foot and Ankle
International 16: 97-99, 1995. The authors point out the rarity of
tetanus in the United States, approximately 100 cases per year
primarily among persons who have not been immunized or had not
received the recommended booster immunization. They describe a
patient with a clinical course like tetanus from whom they never
isolated the tetanus organism. They had difficulty controlling the
lesion which presented as a plantar wound approximately 5 mm in
diameter without drainage. Subsequently, the web space was
debrided, a second debridement was done, an open 2nd ray amputation
was performed and later a beneath-the-knee amputation was
performed. Their patient had many complications including
contractions they attributed to tetanus. They point out that left
untreated 80% of these patients would die, while with appropriate
therapy (aggresssive debridement of toxin-containing tissue,
tetanus toxoid, tetanus immune globulin, appropriate antibiotics
that also include penicillin, and support of vital functions as
needed in an intensive care unit) 10 to 20% may die, with the
higher rates occurring in the elderly. We all have seen very
sick patients with sepsis from foot lesions and did not consider
the possibility of tetanus. This article reminds us that the
possibility should be considered because the patient may die
without proper therapy.
- Van GH, Siney H, Danan J-P, Sachon C, Grimaldi A:
Treatment of osteomyelitis in the diabetic foot. Diabetes
Care 19: 1257-1260, 1996. Healing and duration of treatment were
compared in two groups of diabetics with similar characteristics
other than calendar time of treatment. The first 32 were treated
with the antibiotics available from 1986 to 1993, offloading and
wound care. The second group of 32 patients were treated with the
antibiotics available from September 1993 to march 1995,
offloading, wound care and conservative orthopedic surgery
performed by the same surgeon ( limited resection of the infected
part of the phalanx or metatarsal bone under the wound with no
other resection, with removal of the ulcer site). The antibiotics
were given by the oral route when there was no cellulitis of
general signs of infection and otherwise by the parenteral route.
Healing occurred in 57% of the first group and 78% of the second
(P<0.008) and the duration of healing was reduced from
462±98 days in the first group to 181±30 days
(P<0.008) in the second group. Comments: The authors do not
tell us what differences in antibiotic regimes were used over the
nine year course of the study. Nor do they tell us which patients
were hospitalized. Presumably those receiving intravenous
antibiotics were hospitalized at least initially and presumably
those receiving surgery were hospitalized again at least initially.
Hospitalization affords opportunity for better wound care, improved
glycemic control and bed rest... all significant factors likely to
benefit the surgical group. Treatment was prolonged in both groups,
six to fifteen months. With the use of locally injected antibiotics
and boot therapy, we like to feel we can beat these statistics
anytime.
- Vann JM, Proctor RA: Ingestion of Staphylococcus aureus by bovine endothelial cells results in time- and inoculum-dependent damage to endothelial cell monolayers. Infect Immun 55:2155-63, 1987. Cultured endothelial cells phagocytize Staphylococcus aureus, but the resultant effects are unknown. Monolayers of cultured bovine endothelial cells with or without [3H]adenine label were exposed to 100, 10, or 1 S. aureus organism per endothelial cell for 3.5 h. Lysostaphin was then applied to all cultures to destroy extracellular but not phagocytized S. aureus. In cultures treated for only 20 min with lysostaphin, S. aureus multiplied exponentially after a 9- to 12-h lag period. In cultures treated continuously with lysostaphin, numbers of S. aureus remained constant or decreased. These results indicate that S. aureus became extracellular and multiplied but did not multiply intracellularly. In parallel experiments, the release of 3H-adenine from prelabeled endothelial cell monolayers was assayed to indicate cytotoxicity. Results indicated that the loss of 3H-adenine from endothelial cell monolayers depended on the following: (i) the size of the S. aureus inoculum, (ii) the strain of S. aureus, and (iii) the length of time after exposure to S. aureus. S. aureus endocarditis and persistent septicemia could arise, at least in part, from ingestion of S. aureus by host endothelium. The intracellular location would afford S. aureus protection from host defenses and antibiotics. Eventual damage to endothelial cells could expose collagen, thus resulting in platelet adherence and vegetation formation. Intracellular S. aureus would be continuously released into the circulation, possibly accounting for the persistent bacteremia that is found in S. aureus endovascular infections.
- Venkatesan P, Macfarlane RM, Fletcher EM, Finch RG Jeffcoate
WJ: Conservative management of osteomyelitis in the feet
of diabetic patients. Diabetic Medicine 14: 487-490, 1997.
Abstract: Experience of conservative management of osteomyelitis in
a specialized, multidisciplinary, diabetic foot clinic was
reviewed. The records of all patients attending the clinic over a
10-year period were examined retrospectively, and 22 patients with
overt osteomyelitis were identified. Median age was 66 (31-87)
years. In 12 cases the bone infection was a complication of a
pre-existing ulcer.; the most prevalent organism cultured from
swabs was Staphylococcus aureus. The main site of infection
was the first toe. The total duration of antibiotic treatment was
12 weeks (median, range 5-72), and clindamycin was the most
commonly used oral agent. Four patients did not respond to initial
conservative therapy and proceeded to amputation, while one patient
responded clinically but had a recurrence of osteomyelitis at the
same site 6 years later. In the remaining 17 patients resolution of
osteomyelitis was achieved with conservative management over a
median period of follow-up of 27 (range 5-73) months. The success
of conservative therapy with prolonged courses of oral antibiotics
challenges conventional advice that excision of infected bone is
essential in the management of osteomyelitis affecting the foot in
diabetes. Comments: A small series and reasonably good
results.
- von Eiff C, Becker K, Metze D et al: Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with darier's disease. Clin Infect Dis 32:1643-7, 2001. Intracellular persistence assays were performed with small-colony variants (SCVs) derived from a patient with Darier's disease from whom different phenotypes and genotypes of Staphylococcus aureus were isolated over a 28-month period; the assays revealed that >100-fold more SCV cells persisted intracellularly relative to the normal phenotype. The presence of intracellular S. aureus SCVs may protect against host defenses and antibiotic therapy and thus may have contributed to this patient's very prolonged skin infection.
- Walenkamp GH, Kleijn LL, de Leeuw M: Osteomyelitis
treated with gentamicin-PMMA beads: 100 patients followed for 1-12
years. Acta Orthop Scand. 69:518-22, 1998. We treated 100
patients having osteomyelitis with debridement and gentamicin-PMMA
beads and followed them for 5 (1-12) years. 66 of the infections
were chronic, in 18 cases combined with arthritis and in 3 cases
with pseudarthrosis. They underwent 117 "treatment periods",
consisting of one or more operations (total 152), in most cases
with an interval of 2 weeks. No systemic antibiotics were necessary
besides the local antibiotic treatment in 52 of the treatment
periods. Healing was achieved in 92 patients, in 78 after a single
treatment period which included 1-5 operations, in 14 after two or
three treatment periods. Healing was more difficult to achieve when
the infection was chronic, especially with a duration of more than
6 years or when caused by elective surgery. Local antibiotic
treatment with gentamicin PMMA beads has the advantage that the
wound can be closed primarily and that a higher local antibiotic
concentration in the tissues can be achieved, often making systemic
antibiotic treatment unnecessary.
- Weaver LK, Churchill S: Pulmonary edema associated
with hyperbaric oxygen therapy. Chest 120:1407-9, 2001. We
report three cases of pulmonary edema associated with hyperbaric
oxygen therapy, including one fatality. All three patients had
cardiac disease and reduced left ventricular (LV) ejection
fractions (EFs). Two patients had diabetes, and one patient had
severe aortic stenosis. Hyperbaric oxygen therapy may contribute to
pulmonary edema by increasing LV afterload, increasing LV filling
pressures, increasing oxidative myocardial stress, decreasing LV
compliance by oxygen radical-mediated reduction in nitric oxide,
altering cardiac output between the right and left hearts, inducing
bradycardia with concomitant LV dysfunction, increasing pulmonary
capillary permeability, or by causing pulmonary oxygen toxicity. We
advise caution in the use of hyperbaric oxygen therapy in patients
with heart failure or in patients with reduced cardiac EFs.
Comments: Heart disease, of course, is common in diabetics with
peripheral vascular disease. Indeed, heart disease is one reason
physicians may refer their patient for treatments other than
surgical revascularization. Hopefully the problems described here
are not to be commonly expected in such patients.
- Weinstein D, Wang A, Chambers R, Stewart CA and Motz HA:
Evaluation of magnetic resonance imaging in the diagnosis of
osteomyelitis in diabetic foot infections. Foot & Ankle
14:18-22, 1993. Forty-seven patients with possible osteomelitis,
nonhealing foot ulcer or soft tissue infection. MRI significantly
more sensitive than plain x-rays and technesium and gallium scans.
At early follow-up, complete resection of abnormal bone on MRI
correlated with clinical healing.
- Weigelt J, Itani K, Stevens D et al: Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother 49: 2260-6, 2005. Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P=0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P<0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.
- Wheat LJ, Allen SD, Henry M, Kernek CB, Siders JA, Kuebler
T, Fineberg N and Norton J: Diabetic foot infections,
Bacteriologic analysis. Arch Intern Med 146:1935-1940, 1986.
"Unreliable" cultures were in contact with the ulcer or other
openly draining lesion..."Reliable" cultures obtained by aspiration
of bullae or abscesses or by surgical biopsy of bone or soft tissue
had minimal contact with ulcers or draining lesion. Reliable
aerobes: Staphylococcal species, Enterococcus species,
Cornybacterium species and various Enterobacteriaceae. Reliable
anaerobes: Peptostreptococcus magnus and prevotii and Bacteroides
species. Reliable and unreliable cultures agreed in 27% of 26
patients while antibiotics selected to cover the unreliable results
would have covered the reliable cultures in 93% of cases. Empirical
coverage possibilities: (1) Clindamycin, ampicillin and gentamicin;
(2) cefoxitin, pipercillin and gentamicin; (3) clindamycin,
pipercillin, and gentamicin; (4) moxalactam and ampicillin; (5) 3rd
generation cephalosporin, clindamycin and ampicillin; and (6)
Imipenem...all potentially effective in 90% of patients.
Aminoglycosides alone poor coverage for gram negative bacteria
because of low concentrations in infected tissues. "Osteomyelitis"
soft tissue infection accompanied by x-ray changes of erosion or
demineralization.
- Wilson CL, Cameron J, Powell SM, Cherry G and Ryan TJ:
High incidence of contact dermatitis in leg-ulcer patients
-implications for management. Clin and Exper Dermatol
16:250-253, 1991. Summary: A retrospective review of patch test
results from all new patients with venous leg ulcers was performed
for the preceding 11 months. Eighty-one patients referred from
general practitioners and district nurses with venous stasis ulcers
were included. Positive patch tests were found in 54 patients
(67%), including a high incidence to lanolin and topical
antibiotics. Multiple allergies were found in 48 patients (58%). In
addition, a new problem of allergy to cetearyl alcohol, a
constituent of commonly used creams and paste bandages, was
identified in 13 patients. There is a continuing high incidence of
contact sensitivity in patients with venous stasis ulcers which has
important implications for the management of these patients.
Comments: The authors comment that there is no absolute proof that
contact dermatitis reduces healing of ulcers but believe in their
experience that it is an adverse factor. One can imagine redness,
swelling and oozing mistaken for evidence of cellulitis and leading
to inappropriate treatments. The authors recommend soft parrafin as
a simple, cheap and effect emollient.
- Zuluaga AF, Galvis W Saldarriaga JG, Agudelo M , Salazar
BE : Etiologic diagnosis of chronic osteomyelitis: a
prospective study. Arch Intern Med 166:95-100, 2006.
BACKGROUND: Although bone specimens were established 25 years ago
as the gold standard for etiologic diagnosis of chronic
osteomyelitis, recent studies suggest that nonbone specimens are as
accurate as bone to identify the causative agent. We examined
concordance rates between cultures from nonbone and bone specimens
in 100 patients. METHODS: Prospective study conducted at Hospital
Universitario San Vicente de Paul, a 750-bed university-based
hospital located in Medellin, Colombia. We included patients with
chronic osteomyelitis who had been free of antibiotic therapy for
at least 48 hours, excluding those with diabetic foot and decubitus
ulcers. At least 1 nonbone and 1 bone specimen were taken from each
individual and subjected to complete microbiologic analysis.
RESULTS: Bone cultures allowed agent identification in 94% of
cases, including anaerobic bacteria in 14%. Cultures of nonbone and
bone specimens gave identical results in 30% of patients, with
slightly better concordance in chronic osteomyelitis caused by
Staphylococcus aureus (42%) than by all other bacterial species
(22%). However, statistical concordance determined by the Cohen
kappa statistic was less than 0 (-0.0092+/-0.0324), indicating that
the observed concordance was no better than that expected by chance
alone (P>.99). CONCLUSIONS: Appropriate diagnos