Case 198: Necrotizing Cellulitis, Osteomyelitis, Peripheral Neuropathy... Will Never Heal They All Said

He presented in the Circulator Boot Clinic on Tuesday, March 3rd, 1998 with a oral temperature of 100.2 degrees F (37.9 degrees C). He had previously been seen in our diabetic office in 1979 when he was found to have diabetic retinopathy and peripheral neuropathy. He was introduced to home blood glucose testing and a multidose insulin program. In 1983, his insurance program led him to a family practice where he continued our insulin program with little change. He returned now concerned he needed the help of specialist. He had left work the previous Friday having worn new shoes all day. His foot was swollen. He thought he had flu because of nausea and vomiting. He stayed in bed from Friday until Tuesday when he presented with the foot shown below. After a culture was taken, his foot was infiltrated with gentamicin and vancomycin and he was given a Mini-Boot treatment. Immediate hospitalization was advised. His HMO physician, a new doctor to our hospital, preferred he report first to his office. On seeing the patient the doctor admitted him to the hospital and asked for consultants from infection disease and general surgery. Intravenous Unisyn and oral Levaquin were ordered along with vascular studies, foot x-rays and a bone scan. The latter two studies were negative. The vascular laboratory technician was unable to find any palpable pulses in the legs, but found pseudohypertension (ABI 1.72) at the ankles. The pulse volume in the left foot was significantly reduced.


[early necrotizing cellulitis]
March 3rd, 1998: The tissue between the first two toes was meaty and seemingly necrotic. The dorsum of the foot was crimson.

[early necrotizing cellulitis]
March 5th: Two days of intravenous antibiotics had made little difference.

[early osteomyelitis]
March 5th: The tissue between the first two toes was breaking down. A culture stick could be introduced between the 1st and 2nd metatarsal heads, but his x-rays did not show osteomyelitis.


On the evening of the 4th, a boot consultation was requested at the insistence of the patient and family. His insulin and diet were adjusted. Boot therapy was begun again the morning of the 5th. The foot was little changed. While the margins of the red area had capillary refill, the skin over the 3rd, 4th and 5th metatarsals did not. The significance of this was noted on the chart. The skin did not blanch with elevation or direct pressure meaning that the blood, lending the color to the tissues, was trapped locally (extravasated or isolated by thrombi). It was pointed out that his intravenous antibiotics were unlikely to reach such areas and that the tissue was likely eventually to breakdown. Booting at least twice daily to restablish capillary blood flow and local antibiotic injections once daily were recommended. On 5th, the HMO also encouraged the family doctor to discharge the patient for home intravenous therapy and outpatient booting. On the 6th, the boot consultant noted that capillary refill was improved but that the foot remained in guarded state. Continued hospitalization and booting three to four times a day was recommended until his diabetes was stable and full capillary refill had been restored. His family physician discharged him nonetheless.



Plantar Aspect of left foot: The infection between the first two toes was coming under control but the lateral foot was breaking down.

[mummification after necrotizing cellulitis]
He received five boot treatments a week throught April and May. In June, his treatments were reduced to three a week. He was ambulatory and back to work. The lateral distal foot went on to mummify while Doppler flow became detectable in the rest of the distal foot. Both the 4th and 5th toes were threatened.


The patient was sent home to receive intravenous antibiotics and he was approved to receive boot treatments in the office once daily. He had periodic cultures and received antibiotics as shown in the table below. His family physician was advised of his progress periodically. On June 8th he was advised that although the black eschar had developed on the lateral side of his foot, the necrotic area between he first and second toes was improving and his Doppler tests were likewise improving. By May 22nd, for example, biphasic Doppler sounds were found in his posterior tibial, monophasic sounds in his anterior tibial and loud monophasic sounds in his first dorsal metatarsal artery... all significant improvements. It was pointed out at that time that a transmetatarsal amputation would not heal as his lateral flap would not heal. He was advised that with continued therapy the black eschar would slough off leaving a scarred but intact foot. In view of the fact that the patient was now ambulatory and pain-free, continued therapy was recommended. Alternative therapy appeared to be a BK-amputation. The family doctor sought the opinion of a vascular surgeon at a nearby hospital who suggested he be studied again for possible bypass surgery, that he see an orthopedic surgeon to consider a Syme amputation or that he settle for a beneath-the-knee amputation, which he thought he would eventually require anyhow. The family doctor encouraged the patient to follow this advice and, when he would not he suggested he might not approve more boot therapy, the patient sought out another physician who would approve his treatment.



The space between the 1st and 2nd toes still had not healed.


The black eschar has been periodically debrided back to allow drainage and access to our antibiotic solutions, to promote granulations and to allow room for the skin margins to grow in. The 5th toe had mummified and was clipped off.



On January 7th, he again saw the vascular surgeon who now found the large vessels in the foot to be improved and advised that surgery would not help the small vessels. The space between the first two toes still had some fibrous necrotic tissue but was no longer clinically infected.


Granulations and new skin were moving in. He was receiving three Mini-Boot treatments a week with his foot immersed in appropriate antibiotics in Sea Soaks. He was asked to soak his foot at home twice daily with his foot immersed in Sea Soaks and again appropriate antibiotics.



The necrotic dark areas were injected with appropriate antibiotics at the time of his boot treatments.


The foot had cleaned up now leaving healthy granulations. The HMO did not give permission for grafting, but some ApliGraft material was left over from another patient and was applied on October 7th.


Vancomycin diluted to 100mg/ml and given by local injections in 0.25ml (25mg) amounts had been used successfully from March through May 1998. With the emergence of a new Staphylococcal methicillin-resistant infection in May, 1999, the local injections were again resumed. However, the patient experienced a hypotensive episode presumably due to histamine release and the local injection route was discontinued. Vancomycin continued to be used successfully in his soaks during his boot treatments, which had been reduced to three times a week for insurance purposes. In early September, he developed fever and malaise and lost both weight and control of his diabetes. A culture of his ulcer revealed Staphylococcus aureus sensitive only to Vancomycin along with two strains of Pseudomonas aeruginosa. He was hospitalized for intravenous Vancomycin which was administered after a desensitization procedure. He was provided with both Tagamet and Benadryl in anticipation of the medication. Still he experienced numbness in his hands and face and became diaphoretic when very dilute Vancomycin was first given. Eventually, he was able to tolerate 2000mg per 24 hours and eradicated his infection. He was discharged on September 22nd to continue the infusions at home. His other medications at this time included Flagyl, Pepcid, Levaquin, Benadryl and locally on his ulcer, Diabegel after his morning boot treatment and Regranex after his evening soak.



Review of his March 3rd, 1998 films showed no obvious osteomyelitis. Calcifications seen in the pedal vessels.


Likewise, review of the March 24th, 1998 x-rays were unremarkable.


[serial x-rays of osteomyelitis]
Now on September 9th, 1999, the radiologist noted the absent 5th toe, destuction of the end of the 5th metatarsal, resorption of the end of the 4th metatarsal, destructive changes in the 4th proximal phalanx, and lack of cortical definition at the base of the proximal phalanx of the 2nd toe and the head of the 2nd metatarsal.


In May 2000, he returned with a small abscess draining from the plantar aspect of his ulcer. Pseudomonas was recovered and quickly cured with local injections of antibiotics (see chart below). His x-rays showed osteopenia, but there was recalcification in many of the areas showing previous demineralization and loss of cortical outline.



The space between the first two toes was close to healed. It was a spot his surgeons had said would never close. His toenails were growing.


Healing occurred from the top and proximal skin edges. His ambulation tended to separate the skin edges deeper tissues on the plantar surface and slowed healing.



The black eschar on the top of the 4th toe had long separated and skin closed. Suspected osteomyelitis at the base of the fourth toe had been treated with local antibiotic injections.


His boot treatments had been reduced to 3 to 4 per month after April. He continued his home soaks and dressing changes. He has been going to work everyday for the last year except during his hospital stays.


His treatments were reduced to once weekly both because of his work demands and the personal costs of the treatment.



November 27th, 2000: His foot went on to heal.

 


December 11th, 2000: He was working full time. He felt comfortable coming in monthly for a booster treatment and a checkup.


A pink spot marks the areas between the first and second toes where little callus was removed. His toes were intact and the osteomyelitis long gone.


In the table below, bacteria sensitive to antibiotics are shown by listing the antibiotics in bold and those intermediate to antibiotics are given in non-bold type. Heavy growth of the bacteria is signified by giving the antibiotics in regular type while a light growth is signified by giving the antibiotics in italics.

Date

Pseudomonas aeruginosa

Coag(-) staphylococci

Methicillin-Resistant Staphylococci

Stenotrophomonas maltophilia

Yeast

03/03/98

-

-

Augmentin, Cephalothin, Cipro, Clindamycin, Erythromycin, Gentamicin, Oxacillin, Tetracycline, TMS, Vancomycin (This was the only Staphylococcus with multiple sensitivities. A Streptococcus viridans with multiple sensitivities was also found here.)

-

-

11/09/98

-

Vancomycin, Tetracycline, Gentamicin

-

TMS po, Cipro

Fungizonein soaks, Fluconazole po

12/09/98

-

-

-

TMS po, Cipro

Fungizonein soaks

01/13/99

-

-

-

TMS po

-

05/12/99

-

-

Vancomycin L. Inj

TMS po, Ticarcillin/ca

-

06/09/99

-

-

Vancomycin in soaks

Resistant to all

-

06/25/99

Tobramycin, Ticarcillin, Mezlocillin, Gentamicin, Imipenem, Ceftazidime

-

Vancomycin in soaks

Resistant to all

-

08/04/99

Tobramycin, Imipenem, Cipro po, Ceftazidime, Gentamicinby injections and in soaks

Vancomycin, TMS, Tetracycline, Gentamicin, Cipro

Vancomycin in soaks

-

-

09/03/99

Tobramycin, Ticarcillin, Mezlocillin, Imipenem, Cipro, Ceftazidime in soaks, Gentamicin

-

Vancomycin in soaks

-

-

09/08/99

-

-

Vancomycin

-

-

10/27/99

-

-

-

Ticarcillin/ca

-

12/10/99

Tobramycin, Imipenem, Ceftazidime

-

Vancomycin in soaks, TMS oral

TMS, Ticarcillin, ceftazidime

-

03/01/00

Tobramycin by injection, Imipenem, Ceftazidime

Vancomycin, Erythromycin

Vancomycin in soaks, Erythromycin

-

-

05/22/00

Tobramycin, Imipenem, Ceftazidimeby injection and in soaks

-

Vancomycin, Gentamicin by injection and in soaks, TMS

-

-

06/27/00

Tobramycin in soaks, Imipenem

Vancomycin in soaks, Gentamicin

Vancomycin, Levofloxacin

-

-

Comments: There is much to comment on on this case. First, in the weeks prior to the onset of the infection in this man, the blood flow in his left foot was likely like that in his right: some impairment but enough flow to maintain his foot intact. Next, the importance and the severity of the initial infection of this patient was not appreciated by the family physician who was advised in our initial hospital note that in Joslin's Diabetes text the authors noted that one third of their patients with their class III infection (those with an area of cellulitis over 2.5 cm) came to leg amputations and most had debridements and lengthy hospitalizations. Further, the importance of the physical signs were ignored: the failure to blanch on direct pressure. He had routine pulse volume measurements in the hospital vascular laboratory, which the vascular surgeon read as showing mild tibioperoneal disease with elevated ABI's likely due to stiff vessels. The tests were reassuring to the family physician and the infectious disease consultant. The routine testing did not include Doppler testing in the foot itself (no flow) or PPG tracings (no flow) eventually done in our office. Capitated tests are more economical for the HMO but frequently are not helpful in evaluating a specific patient. Further, since PPG's, toe pressures, and transcutaneous gases are not routinely ordered or interpreted by many physicians they may not appreciate their significance. Again, the initial x-rays were falsely reassuring. As seen in previous patients, the changes seen pointing to osteomyelitis may occur weeks after the cellulitis appears to have abated. Bone resorption requires restoration of blood flow and may be part of the healing process. On the boot service, our first goals in these patients is to stop the infection and prevent tissue breakdown. The choice of intravenous antibiotics by the infectious disease specialist has rarely been crucial. Patients with no blanching on direct pressure are not likely to have intravenous antibiotics reach the infection. The bacteria are likely to continue to produce the various enzymes that digest the tissue and destroy it. Further, as these enzymes move through the lymph channels into the adjacent tissue they have the potential to damage and occlude the nearby small vessels and extend the damage. The abscess shown in Case #1 is the result of such a process. It should be noted that we successfully treated case #1 using oral erythromycin to block sepsis while we treated the infection with local injections ensuring good tissue levels of antibiotics. Such injections were helpful in this patient in treating his tissue infection and his various sites of osteomyelitis. We know of no other way than what was recommended for this man to arrest this process and preserve his foot. He did not get the multiple treatments a day recommended early in his care. His foot broke down producing lesions that then led his observing physicians to believe he needed a leg amputation and, indeed, at least one felt it was malpractice not to proceed in such a direction. None of the physicians with such opinions have studied the material in this website. Again, the risks involved in belonging to an HMO are to be noted. We were not reimbursed for the vascular tests that we did. Many physicians do not have the equipment to do needed tests and certainly would not do them if not reimbursed. The reduction in treatments allowed by the HMO slowed the healing process. The longer the wound is exposed, the more likely it is to develop a new infection. The HMO stopped paying for his boot treatments leading him to reduce their number. He went on to heal his foot. The physicians he consulted through his HMO said it could not be done... and given their treatment programs, it would not have been done had he heeded their advice. The statisticians among our readers might note that the course of this patient, like many in this series, was added in segments. We have not only added patients whose outcomes were known to be favorable. As in this case, we have shown the course of our treatment expecting a favorable outcome.


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