In vitro activity of N-formimidoyl thienamycin and other beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus

Abstract

Of 43 isolates of methicillin-resistant Staphylococcus aureus, 90% were inhibited by 8 ,ug or less of N-formimidoyl thienamycin per ml by the agar-dilution technique. Cefamandole, cefotaxime, cefoperazone, moxalactam, and cefsulodin showed relatively poor activity. Vancomycin was the most active compound by weight, inhibiting 93% of strains at 1 ,ug/ml. Third-generation cephalosporins, including cefoperazone, cefotaxime, and cefsulodin, are generally less active than cephalothin against staphylococci and other gram-positive organisms (12). Moxalactam, a 1-oxa cephalosporin, resembles these compounds in its spectrum of activity (12). Recently a unique P-lactam, Nformimidoyl thienamycin (MK0787) has been shown to be very active against facultative gram-positive cocci. The minimum inhibitory concentration of N-formimidoyl thienamycin against over 350 methicillin-susceptible S. aureus isolates was less than 1.0 pLg/ml, with at least 90%o of the strains in five studies inhibited by 0.125 ,ug/ml (6, 9, 10, 15, 16). The purpose of this study was to compare and contrast the in vitro activity of the compounds against MRSA strains isolated from patients at a university medical center.A total of 43 clinical isolates of MRSA submitted to the University of Virginia clinical microbiology laboratory was used in the study. These isolates of S. aureus were selected based upon their resistance to nafcillin, using disk diffusion by the method of Bauer et al. (2) and by minimum inhibitory concentration susceptibility procedures. The 43 isolates were cultured from 27 wounds, 3 lower respiratory secretions, 2 blood cultures, and 11 miscellaneous sites, including urine, peritoneal fluid, stool, and catheter tips.

Subinhibitory concentrations of imipenem induce increased resistance to methicillin and imipenem in vitro in methicillin-resistant Staphylococcus aureus

“…Imipenem is a ,B-lactam antibiotic with a unique structure and a broad activity (8,12); there have been reports of in vitro activity against methicillin-resistant (MR) Staphylococcus aureus (16). However, studies in our and other institu-tions have shown differences in the in vitro susceptibility of methicillin-susceptible versus MR S. aureus strains to imipenem (17).…”

Comparative imipenem treatment of Staphylococcus aureus endocarditis in the rat

“…aureus and Staph. 79 0305-7453/83/12D079 + 09 S02.00/0 © 1983 The British Society for Antimicrobial Chemotherapy epidermidis, including some methicillin-resistant strains (Cherubin et al, 1981;Livingston et al, 1981;Thompson et al, 1982) justified in-vivo studies of this drug in infections caused by these organisms. We selected a model of left-sided Staph.…”

“…Its spectrum of action is unusually broad, with important in-vitro activity against the majority of bacteria often creating therapeutic problems, such as (Cherubin et al 1981;Kesado, Hashizume & Ashai, 1980;Kesado et al, 1982;Livingston, Elliott & Cobbs, 1981;Michael, Alford & McGee, 1981;Thompson, Fischer & Wenzel, 1982;Verbist & Verhaegen, 1981). Only a small incidence of crossresistance to penicillins and cephalosporins has been demonstrated with imipenem.…”

Methicillin-Susceptible “Methicillin-ResistantStaphylococcus aureus:” A Sheep in Wolves' Clothing

“…19 However, concerns about the expense and possible toxicity of vancomycin as well as the specter of emergence of resistance to this agent have led to the evaluation of a plethora of newer antimicrobics for their activity against MRSA. 20,21 Although recent data demonstrate an ever-increasing prevalence of MRSA isolations, 12 reported rates may in fact underestimate the true extent of the problem. It has been suggested that small community hospitals which lack ongoing infection control programs may frequently underreport the actual numbers of MRSA isolations/ infections.…”