Meropenem: clinical response in relation to in vitro susceptibility

Objective To collate the clinical response and pathogen eradication rates f or meropenem monotherapy with in vitro susceptibility of the causative path ogens. Methods Data were compiled from 17 randomized clinical studies that compare d 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 infecti ons were assessed. Of these, 3713 pathogens (1963 meropenem, 1750 comparato rs) were evaluable. Results The overall rates of satisfactory clinical response (cure or improv ement) and pathogen eradication (eradication or presumed eradication) at th e end of therapy were similar with meropenem (93% for both responses) and t he comparators (92%), as were the rates in each infection type. For each pa thogen, the clinical response and eradication rates with meropenem were sim ilar across the minimum inhibitory concentration (MIC) range of less than o r equal to 0.25 to 4 mg/L. Overall, a satisfactory clinical response occurr ed in 93% (1580 of 1708) of infections caused by nonfastidious pathogens wi th MICs less than or equal to 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%, respec tively). A similar profile was observed For fastidious pathogens. The high rates of satisfactory clinical response and pathogen eradication produced b y meropenem in each type of infection were generally independent of the cau sative pathogen, whether Gram-positive or -negative aerobe or anaerobe or w hen occurring as mono- or polymicrobial infections. Conclusions The attractive in vitro profile of meropenem translates into go od clinical efficacy. The National Committee for Clinical Laboratory Standa rds has now defined meropenem MIC breakpoints for nonfastidious aerobes or anaerobes as less than or equal to 4 (susceptible), 8 (intermediate) and mu ch less than 16 mg/L (resistant), respectively. The susceptibility breakpoi nt for Streptococcus spp. (excluding Streptococcus pneumoniae) is less than or equal to 0.5 mg/L and, since meropenem is indicated for the treatment o f meningitis, the susceptibility breakpoint for S. pneumoniae and Haemophil us influenzae is less than or equal to 0.25 and less than or equal to 0.5 m g/L, respectively. Meropenem monotherapy is therefore a valid option for th e initial empirical treatment of a range of serious infections caused by si ngle or multiple bacterial pathogens.