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

Abstract

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.

Comparative Activity of Ciprofloxacin, Levofloxacin and Moxifloxacin against Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia Assessed by Minimum Inhibitory Concentrations and Time-Kill Studies

“…A “susceptible” MIC value close to clinical breakpoint could indicate that the antibiotic could be less effective than what can be expected from a strain with a much lower MIC far from the clinical breakpoint. Our data go in the same meaning as Torres et al who have recently shown that “highly susceptible” isolates are associated with higher clinical cure rates than “borderline isolates”[ 22 ].This consideration should be taken into account when choosing between different antibiotic that are all “susceptible”.…”

Is It Time to Rethink the Notion of Carbapenem-Sparing Therapy Against Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae Bloodstream Infections? A Critical Review

“…Examining the effect of PTZ MIC on outcomes with non-ESBL infections has not shown a difference. 29,30 Different infection sites and organisms in this study diminish the external validity of the effect of MIC on mortality and cure.…”

Breakpoint to MIC quotient: A parameter to rapidly evaluate the in vitro bactericidal activity of β-lactams on Enterobacteriaceae

“…Since isolates with MICs near the breakpoint have lower clinical response to the antibiotic [6][7][8] , the choice between two antibiotics with the same MIC for the same pathogenic isolate but with two different clinical breakpoints would likely benefit from consideration of this 'distance' to the breakpoint. This is especially true for immunocompromised patients, who need antibiotics with high bactericidal activity because of their impaired immune system [10] .…”

“…Pseudomonas aeruginosa isolates showing borderline MICs (near the breakpoint) may be at higher risk of clinical failure, even mortality, than those with infections having lower MICs [6,7] . Similarly, Falagas et al found that more treatment failures occurred in patients infected with Salmonella enterica strains with high fluoroquinolone MICs (near the breakpoint) than those with Salmonella strains with low MICs, and mortality rate for patients infected by Gram-negative non-fermentative bacilli with high MICs was also higher than for those with low MICs [8] .…”