Diabetic Foot Infections: Bacteriology and activity of 10 oral antimicrobial agents against bacteria isolated from consecutive cases

N A L A R T I C L E Diabetic Foot Infections Bacteriology and activity of 10 oral antimicrobial agents against bacteria isolated from consecutive cases has yet to be established, most authors agree to the need to use an agent against aerobic and anaerobic organisms (6-11). The fluoroquinolones are a new class of agents that are exceptionally active against gram-negative aerobic bacteria but have had relatively poor activity OBJECTIVE — To study the relative frequency of bacterial isolates cultured from communi- against anaerobic bacteria (13). Several ty-acquired foot infections and assess their comparative in vitro susceptibility to sparfloxacin, fluoroquinolones currently under devellevofloxacin, and eight other commonly used oral antimicrobial agents. opment have been noted to have anaerobic activity (13-17). Consequently, we RESEARCH DESIGN A N D METHODS— This is a prospective study in which the studied the activity of sparfloxacin and infected wounds of 25 consecutive diabetic patients seen by one of the authors were cultured as they entered the hospital. Isolates were stored and tested for susceptibility to 10 oral antimicro- levofloxacin against aerobic and anaerobic bacteria isolated from 25 consecutive bial agents using the agar dilution method. cases of diabetic foot infection and comRESULTS •—• Staphylococcus aureus was the most common isolate (76% of patients), including pared their activity with eight other commethicillin-resistant 5. aureus (MRSA) in 5 of 25 (20%) patient wounds. Streptococci, entero- monly used oral agents. cocci, lintcwbactaiaceae, and anaerobes were also present in ^40% of patient wounds. Sparfloxacin and levofloxacin were the most active agents tested with activity against >88% of isolates. Isolates resistant to sparfloxacin and levofloxacin included MRSA, enterococci, and RESEARCH DESIGN A N D some anaerobes. When analyzed by prior exposure to antibiotics, patients who had previously METHODS— Aerobic and anaerobic received oral antibiotics were more likely to have MRSA, enterococci, and Pseudomonas aerugi- bacteria isolated from patients admitted nosa isolated and less likely to have Entcrobacteriaceae and anaerobes isolated from their wounds. to the St. John's Hospital and Health Center of Santa Monica with diabetic foot inCONCLUSIONS — MRSA and enterococci are now a common cause of diabetic foot infec- fections and consecutively seen by one of tions, and the increased prevalence may be due to antimicrobial use. These wounds may require the authors (E.J.C.G.) were studied. All use of combined antimicrobial therapy for initial outpatient management. The new fluoroquinopatients had signs of mild to moderate lones, sparfloxacin and levofloxacin, were the most active oral agents tested. localized infection (cellulitis, exudate, etc.). Wounds were cultured after curettage by either deep surface swab culture n 1984, it was estimated that there this accounts for ~30,000 lower extrem- or deep tissue aspiration of pus. Isolates were > 3 million diabetic people in the ity amputations annually in the U.S. (5). were identified according to standard criU.S. and that 14.5% of U.S. nursing Therefore, the bacterial etiology of these teria (18,19) and stored at -70°C until home residents had diabetes (1). Foot wound infections has been the focus of testing. Isolates were taken from frozen wounds account for 20% of all hospital- several studies (6-12). cultures and transferred twice to assure izations of diabetic patients (2), and treatWhile many diabetic foot infec- purity. Bacteria were tested by standard ment may cost more than $200 million tions ultimately result in hospitalization procedures by the appropriate methods annually. Diabetic subjects have a relative and intravenous antimicrobial therapy, for the particular organism as previously risk up to 15-40 times greater than non- initial management is usually in an outpa- described (18,19). Brucella blood agar diabetic subjects to require an amputa- tient setting. Empirical antimicrobial supplemented with hemin, vitamin K 1( tion (3,4), usually due to vascular, neuro- therapy is often initiated with oral agents and 5% laked sheep blood was the mepathic, and infectious complications. and based on susceptibility data extrapo- dium used for anaerobic isolates. Diabetic subjects have a lifetime risk of lated from studies performed on general Agar plates were inoculated with a 5-15% (4) to require an amputation, and clinical isolates. While optimal therapy Steers replicator (Craft Machine, Chester, PA). The inoculum used for aerobic bacteria was 104 colony forming units (CFU) per spot, and the inoculum for anaerobic From the R.M. Aldcn Research Laboratory (E.J.C.G., D.M.C., C.A.N.), Santa Monica Hospital Medical bacteria was 105 CFU per spot. AntimiCenter, Santa Monica; and the UCLA School of Medicine (E.J.C.G.), Los Angeles, California. Address correspondence and reprint requests to EllieJ.C. Goldstein, MD, 2021 Santa Monica Blvd., Suite crobial solutions (doubling serial dilu(i40E, Santa Monica, CA 90404. E-mail: . tions) were added to molten agar to Received for publication 22 May 1995 and accepted in revised form 14 December 1995. achieve final concentrations of 0.015-32 li.J.C.G. is on an advisory panel for SmithKline Beecham and holds shares in Johnson and Johnson. /ag/ml for the clindamycin and fluoroCVV, colony forming units; MIC, minimum inhibitor)1 concentration; MRSA, methicillin-resistant Staphquinolones tested. The other agents were vloiowus iiuivus. Eiin: J.C. GOLDSTEIN, MD DIANI: M. CITRON, BS CATHERINE A. NESBIT, MS I 638 DlABETHS CARH, VOllMK 19, Nl'MBl R 6, Jl'Nl 1996 Goldstein and Associates tested at concentrations ranging from 0.03 to 128 jag/ml. Control plates without antimicrobial agents were inoculated before and after each set of drug-containing plates. Care was taken to avoid drug carryover for the fluoroquinolones tested. Plates with aerobic isolates were incubated at 35°C in an aerobic environment for 24 h and then examined. Anaerobic bacteria were incubated for 48 h in anaerobic jars and then examined. Control strains of Staphylococcus aureus ATCC 20213, Fschaichia coli ATCC 25922, Entciococcus faccalis ATCC 29212, Bactenricks fragilis ATCC 25285, and Bacteroides thetaiotaomicron ATCC 29741 were tested simultaneously with the appropriate plates and environments. Susceptibility powders were supplied as follows: sparfloxacin, RhonePoulenc Rorer, Collegeville, MD; cipro(loxacin, Miles, New Haven, CT; levofloxacin and ofloxacin, R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ; loracarbef and cephalexin, Eli Lilly, Indianapolis IN; cefprozil, BristolMyers Squibb, Evansville, IN; cefuroxime, Glaxo, Research Triangle Park, NC; elindamycin, Upjohn, Kalamazoo, Ml; doxycycline, Lederle, Pearl River, NY; and amoxicillin/clavulanic acid, SmithKline Beecham, Philadelphia, PA. RESULTS— There were 25 consecutive patients with diabetic foot infections seen and enr (...truncated)