Efficacy of cefoxitin for the treatment of urinary tract infection due to extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates

Abstract

Introduction:Cefoxitin has a good in vitro activity and stability in resistance to hydrolysis by extended-spectrum beta-lactamases and is a good candidate for the treatment of urinary tract infection. However, data are scarce regarding its use in clinical practice.Methods:We conducted a retrospective study from September 2014 to November 2017, in a tertiary care hospital in Garches (France). We gathered all prescriptions of cefoxitin for urinary tract infection due to extended-spectrum beta-lactamase isolates. We compared the clinical outcomes between Escherichia coli and Klebsiella pneumoniae extended-spectrum-beta-lactamase-producing isolates after a 90-day follow-up. When available, we assessed whether cefoxitin-based regimen was associated with an emergence of resistance.Results:The treatment of 31 patients with a mean age of 60 ± 18 years was analyzed. We observed a clinical cure of 96.7% (n = 30/31) at day 30 and of 81.2% (n = 13/16) and 85.7% (12/14) at day 90 for extended-spectrum beta-lactamase Escherichia coli and Klebsiella pneumoniae isolates, respectively (p = 0.72). No adverse events were reported. One patient who relapsed carried a Klebsiella pneumoniae isolate that became intermediate to cefoxitin in the follow-up.Conclusion:In a period of major threat with a continuous increase of extended-spectrum beta-lactamase obliging to a policy of carbapenem-sparing regimens, it seems detrimental to deprive physicians of using cefoxitin for extended-spectrum beta-lactamase Enterobacteriaceae for the treatment of urinary tract infection while our data show its efficacy.

Phenotypic and genotypic characteristics of carbapenemase- and extended spectrum β-lactamase-producing Klebsiella pneumoniae ozaenae clinical isolates within a hospital in Panama City

“…Multidrug-resistant bacteria remain difficult to treat. 30 Further characterization using a pan-genomic approach would contribute to a more complete depiction of the genes conferring the phenotypic resistance pattern. 31 We also recommend strengthening microbiological surveillance to assure a complete description of these bacterial communities within hospitals.…”

Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center study

“…The presence of the molecule was based on the mass of its parent ion with an accuracy of 5 ppm and on its retention time. The quantification was based on the principle of internal calibration using cefazolin- [13]C2 [15]N as internal standard. This method was validated over a range of 0.5 to 100 mg/L.…”

“…On the first TDM occasion, sampling was performed at a median time of 19 [13][14][15][16][17][18][19][20][21][22][23][24] hours after cefoxitin bolus. The median total cefoxitin serum concentration was 37 mg/L, 7 patients (18%) had a cefoxitin serum concentration over 100 mg/L and 9 patients (22%) did not reach the target serum concentration.…”

“…Cefoxitin has long been known as effective against some multiresistant bacteria [10], making it an appealing carbapenem-sparing candidate drug for ESBL-PE infections [11,12]. Its clinical use is deemed relevant in many infectious situations [13], such as urinary tract infections in non-ICU patients [14][15][16][17]. Studies assessing the efficacy of cefoxitin for other indications are scarce [18].…”

High-throughput, multiplex microfluidic test strip for the determination of antibiotic susceptibility in uropathogenic E. coli with smartphone detection

“…During pregnancy, the need for safe and effective drugs is increased, while nitrofurantoin remains first choice, amoxicillin is only recommended if the susceptibility is known due to resistance rates above 50% in some demographics (Watts et al, 2020). Cefoxitin, while not currently used for clinical prescription, has been cited as an effective in vitro against UTI pathogens including extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) (Mambie et al, 2016, Senard et al, 2018, Guet-Revillet et al, 2014). Since antibiotic loading of the strips is by freeze-drying, it is expected that the test can be adapted to most antibiotics for different applications.…”