Gentamicin- and Methicillin-Resistant <i>Staphylococcus aureus: </i>in vitro Susceptibility to Antimicrobial Drugs

Abstract

Thirteen nosocomially significant, gentamicin- and methicillin-resistant (GRMR) Staphylococcus aureus isolates, all of phage group III/M (lysotype 42E/47/53/54/75/77/83A/84/85/94/96), were uniformly resistant against augmentin, erythromycin, fosfomycin, gentamicin, methicillin, oxacillin, penicillin G, tetracycline, and tobramycin, but differed in susceptibility to cefamandole, ciprofloxacin, clindamycin, imipenem, josamycin, the synthetic chinolone Ro 23–6240, and ofloxacin. All isolates were susceptible to chloramphenicol, coumermycin, fusidic acid, novobiocin, rifampin, teicoplanin, trimethoprim-sulfamethoxazole (cotrimoxazole), and vancomycin. One isolate was of intermediate susceptibility to netilmicin. On a weight-for-weight basis, the 7 most active drugs were rifampin, coumermycin, cotrimoxazole, novobiocin, teicoplanin, fusidic acid, and vancomycin (in decreasing order) in terms of minimal inhibitory concentrations. With regard to minimal bactericidal concentrations, coumermycin, rifampin, vancomycin, teicoplanin, cotrimoxazole, ofloxacin, and ciprofloxacin (in decreasing order) were the 7 most potent antimicrobial drugs. Freshly defibrinated human blood [65% (v/v)] combined with chloramphenicol and rifampin, respectively, resulted in a weak additive effect (time kill curves). Indifferent effects were observed following combination of blood with ciprofloxacin, cotrimoxazole, coumermycin, fusidic acid, imipenem, netilmicin, novobiocin, ofloxacin, compound Ro 23–6240, teicoplanin, and vancomycin. Rifampin combined with novobiocin, teicoplanin, and vancomycin, respectively, in the presence of 65% (v/v) human blood, resulted in an additive effect. Combinations of rifampin with 9 other antimicrobial drugs in blood yielded essentially indifferent effects.

Gentamicin- and Methicillin-Resistant <i>Staphylococcus aureus</i>: Phenotypic and Genotypic Characterization of Three Putative Nosocomial Outbreak Strains

“…As before [5,6,30], none of the donors of defibrinated blood was capa ble of eliminating any of the MRSA isolates in vitro; CFU counts were transiently reduced by at most 2 logio units, and invariably there occurred rebound growth of the staphylococci 2-4 h following exposure. With few excep tions, the antimicrobial drugs tested in these assays were more active in MHB than in the presence of human blood.…”

“…Reference substances of 31 antimicrobial drags (table 2), with precise statements regarding activity, solvent and expiration date, were gifts of the respective manufacturers. Stock solutions of the antibiotics (or combinations thereof) were pre pared as described previously [6,29] to contain 2,560 pg/ml [exception: co-trimoxazole = 320 pg tri methoprim (TMP) plus 6.080 pg sulfamethoxazole/ ml] and stored at -65 °C.…”

“…Agar disk diffusion tests using Mueller-Hinton agar were carried out in accordance with the method of Bauer et al [36]; the results were interpreted according to specifications of the National Committee for Clinical Laboratory Stan dards [37] where applicable. A microtitcr broth dilu tion method, carried out according to the recommen dations of the National Committee for Clinical Labo ratory Standards [38] served to determine the minimal inhibitory (MIC) and minimal bactericidal (MBC) concentrations of all 31 drags in MHB [6,39]. The concentration ranges tested were 0.125-128 pg/ml (cotrimoxazole = 0.015/0.3-16/304 pg/ml; rifampin = 0.0017-2 pg/ml).…”

“…Eighteen experiments (final assay volume = 2 ml) were performed according to our pre viously published method [5,6], Briefly, one half (= 9) of the polystyrene assay tubes (Sarstedt, Nümbrecht, Germany) received 65% v/v of fresh defibrinated hu man blood (donors B. G, L and T), the other 9 assay tubes received MHB. Tcicoplanin and vancomycin were employed at final concentrations of 1 or 2 pg/ml (= 1-2 x MIC); nitrofurantoin and piperacillin plus tazobactam were used at 8 pg/ml (= 1-2 x MIC) and 16/2 pg/ml (= 1/8-1/4 x MIC), respectively.…”

“…Since the early 1980s, gentamicin-and methicillin-resistant Staphylococcus aureus (MRSA) strains have caused multiple epi demics of nosocomial infections in Australia and North America [1][2][3] and in Europe, although marked regional differences were noted [4], In 1982/1983 we encountered the first nosocomially significant MRSA strain [5] which continued to cause problems in 1986 [6] and persisted into 1993; this strain was designed operationally as strain I, be cause in the summer or 1992 there emerged a second MRSA strain, labelled strain II, which, in contrast to strain I, was inhibited by doxycycline and failed to hydrolyze nitrocefin. Thus, these two strains were easily recognized based on these two phenotypic markers.…”