Impact of borderline minimum inhibitory concentration on the outcome of invasive infections caused by Enterobacteriaceae treated with β-lactams: a systematic review and meta-analysis.

Minimum inhibitory concentrations (MICs) have been used to denote susceptibility in vitro and to guide clinical practice. Our objective was to investigate whether the clinical outcomes of patients with invasive infections caused by Enterobacteriaceae treated with β-lactams were worse among those with a borderline susceptible MIC according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints than those with a lower MIC. Studies reporting MICs of β-lactams used for infection and clinical outcome were identified through a systematic literature search. Isolates were classified as "highly susceptible" (HS, those with MIC ≤1 dilution below the susceptibility breakpoint for the antibiotic used) and "borderline susceptible" (BS, isolates with MIC at the susceptibility breakpoint) using EUCAST criteria. Clinical outcomes were clinical cure and 30-day mortality. A meta-analysis was performed. Twenty-four studies were included. Taking all antimicrobials into consideration, the meta-analysis revealed no significant difference in mortality between HS and BS [odds ratio (OR) = 0.58; 95 % confidence interval (CI): 0.28-1.21; p = 0.148). However, HS was associated with higher cure rates than BS (OR = 3.73; 95 % CI: 1.76-7.92; p < 0.001). For specific antibiotics, no differences were found except for piperacillin-tazobactam, where higher clinical cure and lower mortality rates were seen with HS compared with BS isolates (OR = 3.17; 95 % CI: 1.09-9.20; p = 0.034 and OR = 0.12; 95 % CI: 0.02-0.92; p = 0.042; respectively). Our data suggest that HS isolates are associated with higher clinical cure rates than BS isolates according to EUCAST susceptibility breakpoints; this effect was evident only for piperacillin-tazobactam, probably because of limited numbers.