Efficacy of prophylaxis with beta-lactams and beta-lactam-beta-lactamase inhibitor combinations against wound infection by methicillin-resistant and borderline-susceptible Staphylococcus aureus in a guinea pig model

Abstract

Although some j-lactams and K1-lactam-13-lactamase inhibitor combinations exhibit activity against methicillin-resistant Staphylococcus aureus, there remains the concern that therapeutic failures may result from the selection of resistant subpopulations. The prophylactic use of these antibiotics in clean surgery, however, may prove adequate since wound infections arise from the inoculation of small numbers of bacteria. In (4,28,41).The detection of resistance in MRSA and ,B-lactamaseproducing S. aureus, including BSSA, is inoculum size dependent (6,8,15,22,35,36). Although small numbers of bacteria may appear to be susceptible to ,B-lactam antibiotics in vitro, the testing of large inocula facilitates the recognition of resistance. The clinical implications of this observation are that the use of any ,-lactam cannot be recommended as therapy against infection by MRSA, and vancomycin is the preferred treatment (1,15,39). Similarly, although 1-lactamase-susceptible antibiotics such as penicillin G exhibit marked in vitro activity against small numbers of P-lactamase-producing S. aureus (36), penicillin G is ineffective in * Corresponding author. treating infections caused by these strains (3, 6). The penicillinase-resistant antistaphylococcal penicillins are the therapy of choice for serious infections caused by such strains (39).Since wound infections that complicate clean surgical procedures are believed to originate with the inoculation of small numbers of bacteria into the surgical field (12,16,17), the prophylactic use of ,-lactams, including relatively ,-lactamase-labile antibiotics, may prove to be effective in preventing these infections. In this clinical setting, heterogeneity in the phenotypic expression of 1-lactam resistance among MRSA may permit in vivo antibiotic efficacy. Similarly, the amount of preformed and induced P-lactamase accompanying 3-lactamase-producing S. aureus within the wound site may be insufficient to protect the strain against antibiotics in the serum and tissues. To test this hypothesis, we determined the prophylactic efficacies of ampicillin and cefazolin, alone and in combination with ,-lactamase inhibitors, against two MRSA strains and one BSSA strain using a low-inoculum guinea pig model of wound infection. MATERIALS AND METHODS

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

“…ID50s were calculated from the logistic regression curves of these prophylactic regimen-strain combinations ( Fig. 2 and (22,25,26). In contrast, S. haemolyticus 9011 had an ID50 that was 2-to 3-log1o-fold higher (P < 0.0001 for each comparison), demonstrating that it is less virulent in this model.…”

“…On the other hand, the rapid emergence of quinolone-resistant strains associated with quinolone use in some institutions raises concerns about the role of these agents in staphylococcal infection (8,36 In vivo procedures. Details of this small-inoculum prophylaxis model have been described previously (22,25,26). All in vivo experiments were approved by the institutional committee for animal care at the Nashville Veterans Administration Medical Center.…”

Comparative efficacies of imipenem, oxacillin and vancomycin for therapy of chronic foreign body infection due to methicillin-susceptible and -resistant Staphylococcus aureus

“…High levels of /Mactamase have recently been documented in so-called borderlinesusceptible strains of 5. aureus (Kernodle & Kaiser, 1993), which are devoid of intrinsic methicillin-resistance. High production of /Mactamase by MSSA strain 120 was recently observed (Berger-Bachi, B., personal communication), after completion of this study.…”

Impact of Methicillin-Resistant Staphylococcus aureus Prevalence among S. aureus Isolates on Surgical Site Infection Risk after Coronary Artery Bypass Surgery

“…33,34 Furthermore, several investigations confirm that β-lactams are ineffective in the treatment of MRSA infections. 35,36 The net result is that a relatively low MRSA prevalence quickly tips the balance in favor of glycopeptides as the agent more likely to minimize SSIs.Several important aspects of our results should be emphasized. First, although the 3% threshold was consistent for both the SSI incidence and cost-minimization models, the superiority of glycopeptides for reducing the incidence of SSIs in the face of low MRSA prevalence was modest (Table 3).…”