Shining a light on MBL-producing bacteria: how they impact your patients and your hospitals

Footnotes

^*A retrospective observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteraemia. There were 83 unique episodes of monomicrobial CRE bacteraemia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE.³

^†At least 1 antibiotic demonstrating in vitro activity to the isolate recovered within 24 hours of the time the first positive blood culture was obtained; meropenem minimum inhibitory concentrations (MICs) up to 8 µg/mL considered active in vitro as modelling of extended infusion-strategies suggest that reasonable target attainment can be anticipated with MICs up to 8–16 µg/mL.³

^‡Active empiric antibiotic therapy was defined as at least 1 antibiotic with in vitro activity, based on antimicrobial susceptibility testing (AST), against the isolate within 24 hours of the time the first positive blood culture was obtained.³

^§At least 1 antibiotic demonstrating in vitro activity to the isolate any time after antibiotic susceptibility results were available, up to 7 days after the first positive blood culture was obtained; meropenem minimum inhibitory concentrations up to 8 µg/mL were considered active in vitro (excluding 5 patients in the CP-CRE group and 4 patients in the non-CP-CRE group who died in the first 72 hours, before an antibiotic susceptibility test would have returned).³

^ǁActive directed antibiotic therapy was defined as at least 1 antibiotic with in vitro activity against the isolate any time after AST results were available, up to 7 days after the first positive blood culture was obtained.³

^¶The primary outcome was 14-day mortality, with Day 1 as the day the first positive blood culture was collected. Fourteen-day mortality was selected as the primary endpoint, as it was thought to be most reflective of death attributable to CRE bacteraemia. Secondary outcomes included 30-day mortality and 30-day recurrence of CRE bacteremia.³

^#Adjusting for receipt of active empiric therapy and Pitt bacteraemia score ≥4.3

^**A matched case-control study was conducted during a nosocomial outbreak of NDM-1-producers in an adult intensive care unit (ICU) in South Africa. All patients from whom NDM1-producers were identified were considered (n=105). Cases included patients admitted during the study period in whom NDM-1-producing Gram-negative bacteria were isolated from clinical specimens collected ≥48 hours after admission, and where surveillance definitions for healthcare-associated infections were met. Controls were matched for age, sex, date of hospital admission and intensive-care admission. 38 cases and 68 controls were included. Klebsiella pneumoniae was the most common NDM-1-producer (28/38, 74%).¹⁰

^††Adjusting for comorbid disease.¹⁰

^‡‡A prospective observational study was conducted in three tertiary-care hospitals located in the Athens metropolitan area; in hospital A, a 500-bed hospital, between February 2004 and March 2006 and in hospitals B and C, 1000- and 400-bed hospitals, respectively, between February 2005 and March 2006. A total of 162 patients were included in the analysis and of the 162 isolates, 67 (41.4%) produced MBL type VIM-1. The endpoint was all-cause mortality at Day 14 after the onset of bacteraemia. Patients discharged from the hospital before Day 14 were considered survivors.⁶

^§§Appropriate empirical antibiotic therapy for an episode of bacteraemia was defined as treatment with at least one antibiotic that had in vitro activity against the infecting organism, initiated within 48 h of the initial positive blood culture, and given in adequate dosage.⁶

^ǁǁA multicentre prospective cohort study at 11 tertiary care facilities in Japan. Patients with isolation of CRE from 1 October 2016 to 31 March 2018 were included in the study. CRE were defined as Enterobacteriaceae with either meropenem MIC ≥2 mg/L or imipenem MIC ≥2 mg/L and cefmetazole MIC ≥64 mg/L. During the study period, 90 isolates (27 carbapenemase-producing Enterobacteriaceae (CPE) and 63 non-CPE) were collected from 88 patients (25 with CPE and 63 with non-CPE) in 9 of 11 hospitals. All CPE were positive for IMP-type carbapenemase, including 11 (40.7%) IMP-11, 6 (22.2%) IMP-42, 4 (14.8%) IMP-6 and 3 (11.1%) each of IMP-10 and IMP-1.¹¹

^¶¶Effective empirical therapy was defined as antibiotics given prior to obtaining susceptibility results regarding which CPE/non-CPE were susceptible based on CLSI criteria including carbapenems.¹¹

^##Covariates included to generate the propensity score were the following: age-adjusted Charlson combined condition score, leukaemia or lymphoma, dependent functional status, use of nasogastric tube, exposure to a carbapenem within 1 month, polymicrobial isolation and history of admission in the past 3 months. Propensity score adjustments were performed using the stabilized inverse probability weighting. Maximum/median (IQR) standardized bias: (i) unadjusted [0.83/0.21 (0.11–0.37)]; (ii) propensity score-adjusted [0.19/0.08 (0.03–0.11)].¹¹

^***Length of stay after isolation of CPE/non-CPE. Excluding cases who died in hospital.¹¹

Abbreviations

AOR, adjusted odds ratio; CI, confidence interval; CLSI, Clinical & Laboratory Standards Institute; CRE, carbapenem resistant Enterobacterales; CP-CRE, carbapenemase-producing-CRE; CPE, carbapenemase-producing Enterobacteriaceae; ESBLs, extended-spectrum β-lactamases; ICU, intensive care unit; IMP, imipenemase metallo-β-lactamase; KPC, Klebsiella pneumoniae carbapenemase; MBL, metallo-β-lactamase; MIC, minimal inhibitory concentration; NDM, New Delhi metallo-β-lactamase; OR, odds ratio; OXA, oxacillinase; SBL, serine-β-lactamases; SME, Serratia marcescens enzymes; VIM, Verona Integron-encoded metallo-β-lactamase.

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