Perspectives in Circulation Today

Should Systemic Antibiotics be Avoided if Locally-Injected Antibiotics are a Possibility?

MERSA and Other Resistant Organisms

Resistance is relative. The administration of systemic antibiotics has indeed systemic coverage. Intravenous, oral or intramuscular antibiotics administered to treat a toe infection, for example, alters the bacterial populations throughout the body. Generally, systemic antibiotics are administered in sufficient quantities and for a sufficient duration to produce serum and tissue levels capable of killing the presumed target bacteria. In the laboratory, studies with antibiotic disks or serum titers are employed to determine what level of various antibiotics might be successfully employed. If the concentration of antibiotic needed exceeds the level commonly achieved with tolerated doses of antibiotics the bacterium in question is declared to be resistant. There is not an absolute sharp breakpoint for resistance. Rather there is a gradient and there exists for most antibiotics a concentration of antibiotic above that reported as constituting resistance which can effectively kill the bacteria were it possible to achieve that concentration in the tissues. The administration of an insufficient dosage of antibiotic or administration by a route that does not achieve a cidal concentration of antibiotic where the bacteria are florishing may allow the selection of resistant bacteria. The application of an antibiotic cream to an infected ulcer, for example, may sterilize the surface of the ulcer and have no effect on the underlying cellulitis which may continually feed organisms to the ulcer eventually selecting out resistant strains.

Innocent victims of your antibiotic therapy The effect of systemic antibiotics on the intestinal flora or intestinal microbiota is commonly overlooked. While the average human body might consist of about ten trillion cells, the number of bacteria in the gut may number 100 trillion where they have metabolic activity making them a virtual organ. While 300-1000 different bacterial species may live in the gut, probably 99% may come from 30-40 species and make up about 60% of the dry mass of stool. The introduction of antibiotics to the gut shocks the gut flora necessitating the rapid evolution of tolerance to the changed environment. Sterilization of the gut in ruminants would result in their starvation. Commonly, 99% of the bacteria in the healthy human gut are anaerobes while in the cecum high concentrations of aerobes may be found. The antibiotic sensitivities of these organisms change rapidly and necessarily after the introduction of antibiotics; change or die. The patient commonly smears these changed bacterial around the anus and may contaminate the tub bath or shower. The effect of contaminated bath water on open wounds can be rapidly disastrous. One patient of Dr. Dillon left the hospital with a clean sterilized ulcer closing over the interphalangeal joint of his big toe, took a tub bath at home, and returned the next day with a black distal phlalanx of the toe; the tub water had entered the joint space and the few millimeters of skin around the toe were infected and quickly devitalized. The patient in intensive care who commonly has a diminished oral intake and a minimal fecal stream/output may be expected to have more difficulty with the adverse GI effects of antibiotics than the relatively healthy outpatient . The surgical patient given prophylactic antibiotics, for example, does have significant changes. Thus, Takesue Y, Yokoyama T et al (2002) found the number of Bifidobacterium, Lactobacillus, Eubacterium, and Veillonella spp. decreased by an average of 100-fold accompanied by an overgrowth of Enterococcus spp. and Pseudomonas aeruginosa in such patients. However, they thought that preservation of Bacteroides fragilis group may have had a role in lessening overgrowth of antibiotic-resistant species. Besides promoting the overgrowth of such species as C difficile, antibiotics commonly cause diarrhea by reducing the ability of the gut to ferment carbohydrate and metabolize bile acids.

Methicillin-resistant Staphylococci aureus (MRSA) has achieved notoriety and deservedly so. Perhaps half of staph isolates are now methicillin-resistant and are the primary cause of serious nosocomial infections significantly increasing hospital costs let alone mortality. As patients with nasal colonization have an increased incidence of complications due to their MRSA (such as post-operative infections), many hospitals are culturing the noses of patients on admission to identify and isolate those especially at risk (those with surgical wounds, pressure ulcers and intravenous catheterization). Laboratory techniques to identify MRSA have become progressively faster. The culture and tube dilution techniques of the past have been replaced with a series of more rapid molecular diagnostic procedures: Southern blots (weeks), PCR’s (1-2 days to hours) to newer technologies such as “Gene Expert” with results under an hour. The rapidity of the identification of MRSA not only allows for quicker diagnosis but quicker institution of appropriate therapy. The latter most commonly has been the use of vancomycin and as vancomycin resistant organisms have become more frequent, the use of new antibiotics (linezolid and daptomycin). Appropriate levels of vancomycin do kill MRSA but not as fast as do appropriate levels of the beta-lactam antibiotics. And, in spite of MIC levels suggesting vancomycin will likely be successful in ridding a patient of MRSA, vancomycin may fail with MIC’s as low as 1.5mg/L leading some to recommend lowering the the vancomycin susceptibility breakpoint for MRSA bloodstream infection from MIC values of 2.0 mg/L or lower to 1.0 mg/L or lower. For a successful outcome, the issue remains: get a potentially effective antibiotic to the site of infection in appropriate levels without damaging other tissues such as the kidneys, the ears, gut etc.

Need for doctors to learn techniques of local antibiotics administation In a previous Newsletter, http://www.circulatorboot.com/Newsletter/vol3numb1.html, a patient was presented who, failing standard antibiotic administration procedures, was referred for boot therapy in hopes of avoiding leg amputation. Initially, she responded nicely to the injection of local antibiotics and the boot. However, she relapsed when her local therapy was discontinued when the boot doctor went on vacation. The refusal of her attending physicians to continue the therapy in the absence of the boot doctor was the problem and continues to be an occasional problem. Their explanations have included: (1) local therapy is not standard care; (2) their other time commitments do not allow them to be at the bedside at the time the boot therapy is scheduled; (3) rounding for the infectious disease specialist commonly requires but the time needed to write progress notes and orders; they do not have the time to devote to local antibiotic injections. Fortunately, the patient refused leg amputation to await the return of the boot doctor and her leg was saved with the reinstitution of the local antibiotics and boot therapy.

Table 1
Advantages of the Circulator Boot and Local Antibiotic Techniques