Discrepancy between effects of carbapenems and flomoxef in treating nosocomial hemodialysis access-related bacteremia secondary to extended spectrum beta-lactamase producing klebsiella pneumoniaein patients on maintenance hemodialysis

Abstract

BackgroundHemodialysis (HD) patients are susceptible to extended spectrum beta-lactamase (ESBL)-producing bacterial infections. Because the optimal treatment and clinical significance of ESBL-producing Klebsiella pneumoniae (ESBL-Kp) HD access-related bacteremia remain unclear, we conducted this retrospective study to determine the clinical outcomes of patients treated with either flomoxef or a carbapenem.MethodsThe eligibility criterion was fistula or graft- or catheter- related ESBL-Kp bacteremia in patients on maintenance HD. The clinical characteristics and antibiotic management were analyzed. Outcome was determined by mortality resulting from bacteremia during the 14‐day period after the first positive blood culture for flomoxef-susceptible ESBL-Kp.ResultsThe 57 patients studied were predominantly elderly, malnourished, with a history of severe illnesses and broad-spectrum antibiotic use before the onset of bacteremia, and with severe septicemia as determined by the Pitt bacteremia score (PBS). The study population comprised 7 fistula, 8 graft, and 42 HD catheter-related bacteremia (CRB) cases, and the mortality rate was high (36/57, 63.2%) in these 57 patients. Of 42 patients with CRB, those in the deceased group (27/42, 64.3%) had significantly lower levels of serum albumin, longer prior hospital stay and duration of catheter-dependent HD, and higher PBS than patients in the survived group. Failure to receive effective antibiotics (flomoxef or a carbapenem) within 5 days after onset of bacteremia and treatment with flomoxef both significantly contributed to higher mortality. Multivariate analyses revealed that flomoxef use, PBS, and catheter-dependent HD >30 days were independently associated with increased mortality (OR, 3.52; 95% CI, 1.19–58.17, OR, 2.92; 95% CI, 1.36–6.26 and OR, 5.73; 95% CI, 1.21–63.2, respectively).ConclusionsConsidering the high mortality rate, ESBL-Kp should be recognized as a possible pathogen in patients on maintenance HD at high risk of acquiring HD access infections associated with ESBL-producing bacteria. Carbapenems rather than flomoxef should be the therapy of choice in these critically vulnerable patients.

Multicenter Retrospective Study of Cefmetazole and Flomoxef for Treatment of Extended-Spectrum-β-Lactamase-Producing Escherichia coli Bacteremia

“…The MIC of flomoxef was Յ1 g/ml. (21,22). Flomoxef treatment was associated with higher mortality than that of the controls.…”

“…To date, 5 reports have evaluated the efficacy of cephamycins for the treatment of infections ESBL-producing members of the Enterobacteriaceae (8,(19)(20)(21)(22). All of these single-center retrospective studies included a small number of patients and a control group comprised of patients receiving carbapenem.…”

The Use of Noncarbapenem β-Lactams for the Treatment of Extended-Spectrum β-Lactamase Infections

“…Existing observational studies comparing cephamycins and carbapenems are plagued by the inherent limitations of observational studies-most notably confounding by indication-as well as small sample sizes (Table 2) [15][16][17][18][19][20]. Only 1 of these studies showed improved outcomes among ESBL-infected patients treated with carbapenems compared with cephamycins, while the others could not detect differences [18] (Table 3). Optimal dosing regimens and achievable target attainment for various cephamycin minimum inhibitory concentrations (MICs) need to be explored [21].…”

Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology

“…Two small observational studies evaluated flomoxef in comparison with carbapenems with contradictory results. 118,94 Also, a retrospective cohort study showed similar efficacy of cefmetazole and carbapenems in patients with pyelonephritis due to ESBL-producers (cure rate, 9/10 vs 12/12, respectively). 119 Regarding BLBLI, a post hoc analysis of prospective cohorts of patients with bloodstream infections due to ESBL-producing E. coli showed similar results for empirical or definitive therapy with in vitro active BLBLIs and carbapenems after controlling for confounders 120 ; the sources of BSI in this study were mostly urinary and biliary tracts, and high doses were used (amoxicillin/clavulanic acid: 2/0.2 g/8 h; piperacillin/tazobactam, 4/0.5 g/6 h).…”