Meropenem: Clinical response in relation to in vitro susceptibility

Abstract

Objective. To collate the clinical response and pathogen eradication rates for meropenem monotherapy with in vitro susceptibility of the causative pathogens. Methods. Data were compiled from 17 randomized clinical studies that compared meropenem monotherapy with standard treatment options, often combinations. A total of 4906 pathogens from lower respiratory tract, intra-abdominal, obstetric/gynecological, skin/soft tissue, meningitis, or pediatric infections were assessed. Of these, 3713 pathogens (1963 meropenem, 1750 comparators) were evaluable. Results. The overall rates of satisfactory clinical response (cure or improvement) and pathogen eradication (eradication or presumed eradication) at the end of therapy were similar with meropenem (93% for both responses) and the comparators (92%), as were the rates in each infection type. For each pathogen, the clinical response and eradication rates with meropenem were similar across the minimum inhibitory concentration (MIC) range of ≤ 0.25 to 4 mg/L. Overall, a satisfactory clinical response occurred in 93% (1580 of 1708) of infections caused by nonfastidious pathogens with MICs ≤ 4 mg/L and in 84% (16 of 19) of those with an MIC of 8 mg/L. Pathogen eradication rates were similar (93 and 79%, respectively). A similar profile was observed for fastidious pathogens. The high rates of satisfactory clinical response and pathogen eradication produced by meropenem in each type of infection were generally independent of the causative pathogen, whether Gram-positive or -negative aerobe or anaerobe or when occurring as mono- or polymicrobial infections. Conclusions. The attractive in vitro profile of meropenem translates into good clinical efficacy. The National Committee for Clinical Laboratory Standards has now defined meropenem MIC breakpoints for nonfastidious aerobes or anaerobes as ≤ 4 (susceptible), 8 (intermediate) and ≥ 16 mg/L (resistant), respectively. The susceptibility breakpoint for Streptococcus spp. (excluding Streptococcus pneumoniae) is ≤ 0.5 mg/L and, since meropenem is indicated for the treatment of meningitis, the susceptibility breakpoint for S. pneumoniae and Haemophilus influenzae is ≤ 0.25 and ≤ 0.5 mg/L, respectively. Meropenem monotherapy is therefore a valid option for the initial empirical treatment of a range of serious infections caused by single or multiple bacterial pathogens.