Comparative prophylactic efficacies of ciprofloxacin, ofloxacin, cefazolin, and vancomycin in experimental model of staphylococcal wound infection

Abstract

Recent shifts in the species and antibiotic resistance patterns of bacteria causing nosocomial infections present new challenges for providing effective prophylaxis in surgery. Traditional regimens lack activity against methicillin-resistant staphylococci and many gram-negative species causing nosocomial infections. The new fluoroquinolones exhibit in vitro activity against many emerging surgical wound pathogens. To determine the potential of this class of antimicrobial agents for use in surgery, we compared the prophylactic efficacies of ciprofloxacin and ofloxacin with those of cefazolin and vancomycin in a guinea pig model of abscess formation. Four Staphylococcus aureus strains, one Staphylococcus epidermidis strain, and one Staphylococcus haemolyticus strain were evaluated. Vancomycin was the most effective prophylactic agent, exhibiting in vivo activity against all strains which was superior or equivalent to those of all other agents tested. Cefazolin was the least effective agent and surpassed the two quinolones in prophylactic efficacy against only one organism, a quinolone-and methicillin-resistant strain of S. aureus. The two quinolones provided excellent protection against infection with all but the quinolone-resistant isolate. The in vivo emergence of quinolone resistance among quinolonesusceptible isolates was not detected. The methicillin-resistant, quinolone-susceptible S. epidermidis and S. haemolyticus isolates were extremely susceptible to prophylaxis, exhibiting 50% infective doses above 4 x 106 CFU for seven of the eight antibiotic-strain combinations. We conclude that ciprofloxacin and ofloxacin may be effective antistaphylococcal agents in surgery. The role of these agents remains to be defined, and the definition should include consideration of an adverse effect upon antibiotic resistance patterns of organisms causing nosocomial infections.The magnitude of the problem of surgical wound infections in the United States, as many as 920,000 infections annually (45), underscores the need for improved perioperative prophylaxis. While most surgeons use cephalosporins, the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci as surgical wound pathogens in many institutions (34, 38) has prompted a search for alternative prophylactic regimens. Although vancomycin use in neurologic, cardiothoracic, and vascular surgery (5,16,18,19,29,41,44)

Constant rate infusion of vancomycin in premature neonates: a new dosage schedule

“…Optimal vancomycin time‐kill kinetics are observed with 3 to 4 times the minimum inhibitory concentration (MIC) [5, 6] and seem to remain unchanged with higher concentrations of the antibiotic [4]. The vancomycin MIC was shown to be within the range of 0.25 and 4 mg l −1 for most strains of staphylococci [6, 13–16]. We therefore assumed that the optimal steady state concentration was 12 mg l −1 , i.e.…”

“…The optimal steady state concentration was defined as 12 mg l −1 , i.e. three times the value of the minimum inhibitory concentration (MIC) [6, 13–16]. Results obtained in group 1 led us to design a second dosage schedule of vancomycin administered by constant rate infusion, that was tested in another group of 29 neonates again admitted to our unit for suspected penicillin‐resistant staphylococcal infections (group 2).…”

Continuous-infusion vancomycin therapy for preterm neonates with suspected or documented Gram-positive infections: a new dosage schedule

“…The required therapeutic range for vancomycin was 10–25 mg/l. The lower limit was based on data that vancomycin time-kill kinetics are optimal when serum vancomycin is three or four times the Staphylococcus MIC which is 1–4 mg/l 7 26 – 28. The upper limit was set based on previous reports,19 even though no renal side effects have been described under 40 mg/l or ototoxicity under 80 mg/l 29 30.…”

Prophylactic Anti-Infective Activity of Poly-[1-6]-β-d-Glucopyranosyl-[1-3]-β-d-Glucopyranose Glucan in a Guinea Pig Model of Staphylococcal Wound Infection

“…In vivo procedures. Details of this small-inoculum prophylaxis model have been described previously (13)(14)(15)(16). All in vivo experiments were approved by the Institutional Committee for Animal Care at the Nashville Veterans Affairs Medical Center.…”