RISK FACTORS FOR MORTALITY AND TREATMENT OUTCOMES OF PATIENTS WITH CEFTRIAXONE RESISTANT E. COLI BACTEREMIA RECEIVING CARBAPENEM VERSUS BETA LACTAM/BETA LACTAMASE INHIBITOR THERAPY

Background: Extended spectrum β-lactamases (ESBL) producing Enterobacteriaceae predominantly E. coli and K. pneumonia bacteremia have limited treatment options and high mortality. Objective: To determine the risk factors for in-hospital mortality particularly treatment with Carbapenem versus Beta lactam/beta lactamase combination (BL/BLI) in patients with Ceftriaxone resistant E. coli bacteremia. Methods: A retrospective descriptive study was conducted at the Aga Khan University, Karachi, Pakistan. Adult patients with monomicrobial Ceftriaxone resistant E. coli bacteremia were enrolled. Factors associated with mortality in patients were determined using logistic regression analysis. Results: Mortality rate was 37% in those empirically treated with carbapenem compared to 20% treated with BL/BLI combination therapy (p-value: 0.012) and was 21% in those treated with a carbapenem compared to 13% in patients definitively treated with BL/BLI combination therapy (p-value: 0.152). In multivariable logistic regression analysis, only Pitt bacteremia score of ≥ four was significantly associated with mortality (OR: 7.7 CI: 2.6-22.8) while a urinary source of bacteremia was protective (OR: 0.26 CI: 0.11-0.58). Conclusions: In-hospital mortality in patients with Ceftriaxone resistant E. coli bacteremia did not differ in patients treated with either a carbapenem or BL/BLI combination. However, Pitt bacteremia score of ≥ 4 was strongly associated with mortality.

[1]  M. Sfeir Post-MERINO trial: Any role for piperacillin-tazobactam in treating bloodstream infections caused by extended-spectrum beta-lactamase producing Enterobacteriaceae? , 2019, International journal of antimicrobial agents.

[2]  P. Christos,et al.  Beta-lactam/beta-lactamase inhibitors versus carbapenem for bloodstream infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae: systematic review and meta-analysis. , 2018, International journal of antimicrobial agents.

[3]  S. Beatson,et al.  Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial , 2018, JAMA.

[4]  Subia Jamil,et al.  Phenotypic expression and prevalence of multi drug resistant extended spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae in Karachi, Pakistan. , 2018, Pakistan journal of pharmaceutical sciences.

[5]  A. Farcomeni,et al.  Predictors of outcome in patients with severe sepsis or septic shock due to extended-spectrum β-lactamase-producing Enterobacteriaceae. , 2018, International journal of antimicrobial agents.

[6]  Mitchell M. Levy,et al.  The Surviving Sepsis Campaign Bundle: 2018 update , 2018, Intensive Care Medicine.

[7]  Rehan Ahmad Khan,et al.  Prevalence of extended-spectrum-β-lactamase-producing Enterobacteriaceae: first systematic meta-analysis report from Pakistan , 2018, Antimicrobial Resistance & Infection Control.

[8]  H. Albrecht,et al.  Association between inappropriate empirical antimicrobial therapy and hospital length of stay in Gram-negative bloodstream infections: stratification by prognosis. , 2015, The Journal of antimicrobial chemotherapy.

[9]  K. Kaye,et al.  Risk factors for bloodstream infection caused by extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae: A focus on antimicrobials including cefepime. , 2015, American journal of infection control.

[10]  Yonghong Xiao,et al.  Nationwide high prevalence of CTX-M and an increase of CTX-M-55 in Escherichia coli isolated from patients with community-onset infections in Chinese county hospitals , 2014, BMC Infectious Diseases.

[11]  C. di Ilio,et al.  Escherichia coli in Europe: An Overview , 2013, International journal of environmental research and public health.

[12]  L. Baddour,et al.  Predictive scoring model of mortality in Gram-negative bloodstream infection. , 2013, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[13]  M. Scheetz,et al.  Correlations of Antibiotic Use and Carbapenem Resistance in Enterobacteriaceae , 2013, Antimicrobial Agents and Chemotherapy.

[14]  M. Falagas,et al.  Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis. , 2012, The Journal of antimicrobial chemotherapy.

[15]  J. Rodríguez-Baño,et al.  β-Lactam/β-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum β-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  M. Falagas,et al.  Extended-spectrum b-lactamase-producing organisms , 2022 .

[17]  K. Laupland,et al.  Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern , 2008 .

[18]  R. Hasan,et al.  Frequency and sensitivity pattern of Extended Spectrum beta Lactamase producing isolates in a tertiary care hospital laboratory of Pakistan. , 2005, JPMA. The Journal of the Pakistan Medical Association.

[19]  Sung-Han Kim,et al.  Bloodstream Infections Due to Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae: Risk Factors for Mortality and Treatment Outcome, with Special Emphasis on Antimicrobial Therapy , 2004, Antimicrobial Agents and Chemotherapy.

[20]  J. Campos,et al.  Extended-spectrum [beta]-lactamase producing Escherichia coli: changing epidemiology and clinical impact. , 2010, Current opinion in infectious diseases.