Updates in the Management of Cephalosporin-Resistant Gram-Negative Bacteria

Abstract

Resistance to cephalosporins is now common among Gram-negative bacterial infections, including those caused by the Enterobacteriaceae and Pseudomonas aeruginosa, posing a major threat to public health. As resistance to the traditional drugs of choice for these infections, carbapenems, has also become increasingly common, interest in cefepime and piperacillin-tazobactam as carbapenem-sparing alternatives has increased. Additionally, the availability of the novel β-lactam-β-lactamase inhibitor combinations ceftolozane-tazobactam and ceftazidime-avibactam has added to the antimicrobial armamentarium available to treat these multidrug-resistant infections. Here, we review the recent literature on the use of carbapenem-sparing alternatives and highlight the potential utility of novel antimicrobials.

An antibiotic stewardship exercise in the ICU: building a treatment algorithm for the management of ventilator-associated pneumonia based on local epidemiology and the 2016 Infectious Diseases Society of America/American Thoracic Society guidelines

“… 36 FEP and the β-lactam-β-lactamase inhibitors (BLBLIs) have been the most widely studied carbapenem-sparing options based on their favorable in vitro susceptibility profile to ESBL-producing organisms. 37 …”

“…Different factors may explain such divergent conclusions, including the geographic variations in the distribution of ESBL phenotypes where the enzyme background plays a significant role and the likely source of infection reflecting the inoculum effect. 37 The results of a randomized controlled study (MERINO trial) comparing TZP to meropenem for the definitive treatment of bacteremia caused by ceftriaxone non-susceptible Escherichia coli and Klebsiella spp. are definitely awaited to resolve this important issue (MERINO, ClinicalTrials.gov : NCT02176122).…”

Spectrum of Uropathogens and Antimicrobial Susceptibility in Clinically Diagnosed Cases of Urinary Tract Infection in the Bamenda Regional Hospital, Cameroon

“…Furthermore, all E. coli isolates were resistant to ceftriaxone, amoxicillin and clindamycin while all Enterobacter species were resistant to doxycycline, amoxicillin and clindamycin (figure 1). Resistance of gram negative bacteria to cephalosporins and other cell wall antimicrobials are common [24,25,26]. Ciprofloxacin is a common drug in the treatment of UTI in our setup.…”

Carbapenem versus Cefepime or Piperacillin-Tazobactam for Empiric Treatment of Bacteremia Due to Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Patients with Hematologic Malignancy

“…These findings have important implications for the management of the increasingly common problem of ESBL-producing E. coli bacteremia in these vulnerable patients (14). Previous studies conducted in general patient populations have identified an increased risk of treatment failure with cefepime as empiric therapy for ESBL-producing E. coli bacteremia, while retrospective studies evaluating piperacillin-tazobactam as empiric therapy for these infections have shown conflicting results (6,9,11,15,16). A recent international, multicenter study conducted by Gudiol et al comparing BLBLI combination therapy to carbapenems for the treatment of ESBL-producing Enterobacteriaceae bacteremia in neutropenic patients with hematologic malignancy identified a…”

“…Although cefepime and piperacillin-tazobactam are frequently active in vitro against ESBL-producing E. coli, clinical data regarding their use in patients with bacteremia caused by ESBL-producing Enterobacteriaceae are conflicting (6). Retrospective studies comparing cefepime to carbapenems as empiric treatment for ESBL-producing E. coli bacteremia have identified increased mortality in patients treated with cefepime; therefore, cefepime is not generally recommended in this situation (9). A large, singlecenter study identified increased mortality in patients treated empirically with piperacillin-tazobactam compared to that for patients treated empirically with meropenem for bacteremia caused by ESBL-producing Enterobacteriaceae, although a multicenter study conducted primarily in Europe did not identify significantly increased mortality in patients treated empirically with ␤-lactam-␤-lactamase inhibitor (BLBLI) combinations, including piperacillin-tazobactam (10,11).…”