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To investigate the evolutionary trends in non-susceptibility of carbapenems against the isolates of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae from patients hospitalized in intensive care units (ICUs) of major teaching hospitals throughout Taiwan during 2005-2009, we applied the breakpoints of MICs recommended by Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing in 2013. Escalations in imipenem MIC levels for overall E. coli and E. cloacae isolates and extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates were noted during this period. The overall MIC levels against imipenem and meropenem for subgroups of ESBL producers of 3 Enterobacteriaceae species were significantly higher than those of respective overall groups in 2007 and 2009. Compared with meropenem, we found that significant evidence of imipenem MIC creep and evidence of extraordinarily high rates of non-susceptibility to ertapenem among isolates of 3 species in 2009 existed. The prominent rises in rates of ertapenem non-susceptibility for ESBL-producing E. coli and K. pneumoniae during 2005-2009 and rate of ESBL positivity for E. cloacae between 4 years were notably found. Based on our findings, ertapenem should be used cautiously in management of the ICU infections caused by these potentially ESBL-producing Enterobacteriaceae isolates in Taiwan., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We report the case of a patient with vertebral osteomyelitis and concurrent urinary tract infection (UTI) in which extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (EC(1)) isolated from urine culture was ciprofloxacin-resistant and ertapenem/imipenem-susceptible. The empirically used oral form of ciprofloxacin was switched to parenteral ertapenem based on the antimicrobial susceptibility. However, vertebral osteomyelitis deteriorated, and despite the disappearance of pyuria and a negative urine culture, ESBL-producing E. coli was isolated from a biopsy of the bony material from the fifth lumbar vertebra (EC(2)) and blood culture (EC(3)) at 10 and 12 days after starting ertapenem, respectively. Ertapenem was switched to imipenem, and defervescence occurred 2 days later; a subsequent blood culture was negative. Genotyping indicated that EC(1), EC(2), and EC(3) were of the same clone, with the ESBL being CTX-M-14. The tested antibiotics had identical minimum inhibitory concentrations against each of these isolates. From the pharmacokinetics/pharmacodynamics points of view, it is reasonable to attribute the ertapenem treatment failure in vertebral osteomyelitis due to ESBL-producing E. coli in this case to the suboptimal ertapenem concentration in the inflammatory bone tissue of the host., (Copyright © 2009. Published by Elsevier Ltd.)

Objective We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. Methods This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. Results CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15–29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45–141.82, P = 0.023). Discussion CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality. [ABSTRACT FROM AUTHOR]

This study compared treatment outcomes of adult patients with bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae (ESBL-EK) receiving flomoxef versus those receiving a carbapenem as definitive therapy. In propensity score matching (PSM) analysis, case patients receiving flomoxef shown to be active in vitro against ESBL-EK were matched with controls who received a carbapenem. The primary endpoint was 30-day crude mortality. The flomoxef group had statistically significantly higher sepsis-related mortality (27.3% vs. 10.5%) and 30-day mortality (28.8% vs. 12.8%) than the carbapenem group. Of the bacteraemic episodes caused by isolates with a MIC flomoxef of ≤1 mg/L, sepsis-related mortality rates were similar between the two treatment groups (8.7% vs. 6.4%; P = 0.73). The sepsis-related mortality rate of the flomoxef group increased to 29.6% and 50.0% of episodes caused by isolates with a MIC flomoxef of 2–4 mg/L and 8 mg/L, respectively, which was significantly higher than the carbapenem group (12.3%). In the PSM analysis of 86 case–control pairs infected with strains with a MIC flomoxef of 2–8 mg/L, case patients had a significantly higher 30-day mortality rate (38.4% vs. 18.6%). Multivariate regression analysis revealed that flomoxef therapy for isolates with a MIC flomoxef of 2–8 mg/L, concurrent pneumonia or urosepsis, and a Pitt bacteraemia score ≥4 were independently associated with 30-day mortality. Definitive flomoxef therapy appears to be inferior to carbapenems in treating ESBL-EK bacteraemia, particularly for isolates with a MIC flomoxef of 2–8 mg/L, even though the currently suggested MIC breakpoint of flomoxef is ≤8 mg/L. [ABSTRACT FROM AUTHOR]