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Background/purpose: A substantial number of carbapenem-resistant Gram-negative bacilli (CR GNB) have been identified among the etiologic multidrug-resistant GNB in healthcare-associated infections. For achieving a better therapeutic outcome by minimizing inappropriate empirical antibiotic treatment before blood culture and susceptibility testing results are available, it is very important to identify patients who are at risk for the development of CR GNB bacteremia., Methods: Retrospective analysis of propensity-score matched (PSM) adult patients with CR GNB bacteremia (PSM-group 1 [n = 95]) and those with non-CR GNB bacteremia (PSM-group 2 [n = 190])., Results: PSM-group 1 was found to a significantly longer length of hospital stay (27 vs. 18 days; p < 0.001) after emerging GNB bacteremia and a higher 30-day all-cause mortality rate (27.4% vs. 5.8%; p < 0.001), when compared with PSM-2 group. Independent risk factors for the acquisition of CR GNB bacteremia were previous exposure to an antipseudomonal penicillin (odds ratio [OR] = 3.58; 95% confidence interval [CI] = 1.30-9.90), an antipseudomonal cephalosporin (OR = 3.49; 95% CI = 1.09-11.24), and a carbapenem (OR = 3.60; 95% CI = 1.37-9.47), and longer length of hospital stay before the development of GNB bacteremia (OR = 1.03; 95% CI = 1.01-1.05)., Conclusion: Risk factors for acquisition of CR GNB bacteremia identified in this study each may serve as a reminder alerting clinicians to hospitalized patients at risk for CR GNB bacteremia requiring appropriate antibiotic coverage, and in these circumstances, combined antibiotics may be used until antimicrobial de-escalation/adjustment is clearly indicated by the subsequently identified pathogenic GNB and its susceptibility profile., (Copyright © 2017. Published by Elsevier B.V.)

Background: Data on susceptibility to ceftobiprole and colistin, and the complete evolutionary trends of minimum inhibitory concentrations (MICs) of important carbapenem agents among important pathogens collected in intensive care units (ICUs) in Taiwan are lacking., Methods: We surveyed the MIC distribution patterns of ceftobiprole and colistin and susceptibility profiles of some important pathogens collected from patients hospitalized in intensive care units (ICUs) of major teaching hospitals throughout Taiwan in 2007. We also investigated the rates of nonsusceptibility to powerful carbapenems (imipenem, meropenem) among four important species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Proteus mirabilis) collected during the same period. MIC breakpoints recommended by the Clinical and Laboratory Standards Institute in 2014 were applied., Results: Colistin showed excellent in vitro activity (susceptibility rate, 96%) against Acinetobacter baumannii isolates but moderate (73-77% susceptibility rate) activity against isolates of Pseudomonas aeruginosa and E. cloacae. The ceftobiprole MIC 90 value was 4 μg/mL for methicillin-resistant Staphylococcus aureus and 16 μg/mL for P. aeruginosa. The phenotype of methicillin resistance did not markedly increase the MIC value of ceftobiprole among S. aureus isolates. Interestingly, the proportion of isolates that displayed nonsusceptibility to imipenem was significantly higher among P. mirabilis isolates than among isolates of the other three Enterobacteriaceae species, regardless of the production of extended-spectrum β-lactamase., Conclusion: Continuous monitoring of susceptibility profiles of ICU pathogens to important antibiotics is warranted to provide appropriate antimicrobial regimens against infections in the ICU., (Copyright © 2015. Published by Elsevier B.V.)

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 MICflomoxef 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 MICflomoxef 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 MICflomoxef 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 MICflomoxef 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 MICflomoxef of 2-8 mg/L, even though the currently suggested MIC breakpoint of flomoxef is ≤8 mg/L., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

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.)

To investigate the in vitro susceptibilities to various carbapenems amongst clinical Gram-negative bacteria isolated from patients in intensive care units of ten major teaching hospitals in Taiwan in 2009, a survey was conducted to determine the minimum inhibitory concentrations (MICs) of ertapenem, imipenem, meropenem and doripenem against isolates of Enterobacteriaceae (n = 594), Pseudomonas aeruginosa (n = 185), Acinetobacter baumannii (n = 192) and Burkholderia cepacia (n = 23) using the agar dilution method. Susceptibilities were determined according to 2009, 2011 and 2012 MIC breakpoints recommended by the CLSI as well as 2012 MIC breakpoints recommended by EUCAST. Based on CLSI 2012 criteria, the ertapenem susceptible rate was 93%, 81%, 68% and 92% for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens, respectively. All Proteus mirabilis and Morganella morganii isolates were susceptible to ertapenem; however, 64% of P. mirabilis and all M. morganii isolates were non-susceptible to imipenem. Meropenem and doripenem had better activities than imipenem against ertapenem-non-susceptible Enterobacteriaceae isolates. E. coli, K. pneumoniae and E. cloacae with ertapenem MICs≥4 mg/L were synchronously not susceptible to imipenem, meropenem and doripenem. Imipenem susceptibility was 65% and 29% for P. aeruginosa and A. baumannii, respectively. Additionally, P. aeruginosa and A. baumannii isolates with imipenem MICs≥8 mg/L were also not susceptible to meropenem and doripenem. These data provide a better understanding of choosing appropriate carbapenem agents to treat infections caused by ertapenem-non-susceptible Enterobacteriaceae as well as P. aeruginosa and A. baumannii isolates with imipenem MICs≥4 mg/L., (Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Background: Risk factors and outcome in patients who acquire nosocomial infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) are rarely investigated., Methods: A multicenter retrospective study was conducted to analyze the clinical and microbiological data of patients with nosocomial infections due to A. baumannii in 10 hospitals around Taiwan from May 2004 to December 2006. Comparisons were made between patients with infections due to CRAB and patients with infections due to carbapenem-susceptible A. baumannii (CSAB)., Results: One hundred and twenty-one patients carrying CRAB (infections, n=91) and 127 patients carrying CSAB (infections, n=97) were recruited for analysis. Compared with patients with CSAB infections, patients with CRAB infections had a longer duration of hospital stay before A. baumannii was isolated (median 48 vs. 21 days, p<0.001) and were more likely to have had exposure to a carbapenem (adjusted odds ratio (AOR) 2.57, 95% confidence interval (95% CI) 1.43-5.35; p=0.02) and an intensive care unit (ICU) stay (AOR 3.42, 95% CI 1.76-5.26; p=0.008). Risk factors associated with CRAB bacteremia included duration of hospital stay before onset of bacteremia (AOR 1.009 per 1-day longer, 95% CI 1.03-1.24; p=0.049), prior colonization with A. baumannii (AOR 3.27, 95% CI 1.99-5.93; p=0.002), and hospitalization in the ICU (AOR 6.12, 95% CI 1.58-13.68; p=0.009). Patients with CRAB bacteremia had a higher mortality rate than patients with CSAB bacteremia (46.0% vs. 28.3%, p=0.04). Multivariate analysis showed that carbapenem resistance (AOR 5.31, 95% CI 1.88-13.25; p=0.002), central venous catheterization (AOR 3.27, 95% CI 1.55-10.56; p=0.009), and ICU stay (AOR 2.56, 95% CI 1.15-8.85; p=0.04) were independent variables associated with mortality in patients with A. baumannii bacteremia., Conclusions: Patients with CRAB infections have a higher mortality rate than those with CSAB infections. Longer hospital stay, colonization with A. baumannii, and admission to the ICU were associated with the development of CRAB bacteremia., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To better understand the clinical outcomes of patients with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteraemia treated with either flomoxef or a carbapenem, and to evaluate the in vitro activities of these antibiotics against ESBL-KP., Methods: Retrospective analyses to identify risk factors for mortality in patients with flomoxef-susceptible ESBL-KP, especially addressing the therapeutic roles of flomoxef and carbapenem. In vitro activities of flomoxef and carbapenem against flomoxef-susceptible ESBL-KP isolates were evaluated by susceptibility testing and time-kill study., Results: Twenty-seven patients (flomoxef group, n=7; carbapenem group, n=20) were included. Clinical severity reflected by high Pitt bacteraemia score (>or=6) was an independent risk factor for mortality (OR 13.43; 95% CI, 1.08-166.73; P=0.043), while use of flomoxef or a carbapenem was not. The MICs of flomoxef and carbapenem indicated that the tested ESBL-KP were susceptible to these antibiotics regardless of the inoculum size of 10(5) or 10(7) cfu/mL. Time-kill study showed that these antibiotics (flomoxef 8 mg/L and meropenem 4 mg/L) each acted actively against and inhibited the regrowth of the tested ESBL-KP for at least 24 h., Conclusions: Flomoxef might be as clinically effective as a carbapenem in treating flomoxef-susceptible ESBL-KP bacteraemia.

Summary: 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 (EC1) 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 (EC2) and blood culture (EC3) 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 EC1, EC2, and EC3 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. [ABSTRACT FROM AUTHOR]