A comparative study of the in vitro activity of meropenem and representatives of the major classes of broad-spectrum antibiotics.
OBJECTIVE: To compare the in vitro activity of meropenem with that of other agents with a broad-spectrum of antibacterial activity, and which may therefore be candidates for empirical use. The agents tested were imipenem, third-generation and newer cephalosporins, penicillins combined with a beta-lactamase inhibitor, ciprofloxacin and amino-glycosides. METHODS: Using agar dilution methods, all agents were tested against 900 clinical isolates (many of which were multiresistant), including Gram-positive aerobes, nutritionally fastidious aerobes, Enterobacteriaceae, non-fermenters and anaerobes, collected from 17 UK hospitals during 1994. In addition, some agents were tested against strains expressing defined beta-lactamases, including extended-spectrum beta-lactamases. RESULTS: The potency and spectrum of the carbapenems, unequalled against aerobes and anaerobes, were undoubtedly influenced by their stability to serine beta-lactamases. Meropenem and imipenem exhibited essentially the same spectrum of activity but imipenem was often less potent, notably against Gram-negative aerobes, including Pseudomonas aeruginosa and Burkholderia cepacia. Conversely, the activity of the third-generation (MIC90s 0.016--64 mg/L) and, to some extent, the newer cephalosporins (MIC90s 0.06--8 mg/L) and the augmented penicillins (MIC90s 1 to >128 mg/L) was unreliable against many genera of Enterobacteriaceae because of chromosomally mediated enzymes or the, now commonplace, plasmid-mediated beta-lactamases. Ciprofloxacin had modest activity (MIC90s 1--64 mg/L) against Gram-positive aerobes, was potent against nutritionally fastidious species, had again variable activity against the Enterobacteriaceae (MIC90s 0.008--4 mg/L) and was inactive against many strains of Pseudomonas, Burkholderia and Acinetobacter, resulting in MIC90s of 4 to >128 mg/L. The aminoglycosides were impressive only against the Enterobacteriaceae, with amikacin alone active (MIC90s 2--8 mg/L) against the 11 species tested. CONCLUSIONS: This study demonstrates that it is difficult on grounds of spectrum to differentiate third-generation cephalosporins, and that neither cefepime nor cefpirome materially enhance utility. The study suggests also that, judged on activity in vitro, meropenem or imipenem are the only monotherapy options for empirical antibacterial therapy of polymicrobic infections or when local epidemiology indicates the predominance of multiresistant Enterobacteriaceae. Instability to current and emerging beta-lactamases is progressively compromising the use of all other beta-lactam compounds.
Greenhalgh
J. Moira
JM
Anti-infectives Development and Technical Support Group, Target Discovery and Infection Department, Zeneca Pharmaceuticals, Alderley Park, Macclesfield, UK.
Edwards
Jeffrey R.
JR