Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study

Abstract

Background Temocillin is a β-lactam that is not hydrolysed by ESBLs Objectives To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Methods Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Results Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ± 15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were Escherichia coli (49.6%), Klebsiella pneumoniae (44.2%) and Enterobacter cloacae (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5–358.2) and neurological disease (aOR 5.3, 95% CI 1.5–18.6). Conclusions The main use of temocillin was UTI due to ESBL-producing E. coli and K. pneumoniae, with a favourable clinical outcome. The main risk factor for failure was neurological disease.

Impact of revised breakpoints on the categorization of susceptibility of Enterobacterales to temocillin

“…12 The drug can be used for the documented treatment of complicated urinary tract infections (UTIs), pulmonary infections, bacteraemia and cutaneous infections, but it is mainly used for the treatment of UTIs. 13 , 14 In Belgium temocillin is also recommended for the empirical treatment of complicated UTIs. 15 Empirical treatment for UTIs is recommended according to the antibiotic resistance risk level adapted for the clinical criteria.…”

“… 4 There are no differences in the clinical outcome of patients treated with temocillin for infections due to E. coli , K. pneumoniae and P. mirabilis , compared with those involving E. cloacae complex or other cephalosporinase-producing strains. 13 , 18 , 19 Nevertheless, a few isolates of cephalosporinase-producing species were included in these studies. It would seem advisable to conduct further studies on infections other than those of the urinary tract, distinguishing the species of Enterobacterales and adapting the dosage.…”

Comparative Analysis between Salmonella enterica Isolated from Imported and Chinese Native Chicken Breeds

“…Recent studies have shown that Salmonella strains isolated from several countries (China, Thailand, the Republic of Bulgari, and Denmark) carry extended-spectrum β-lactamases (ESBLs), which have attracted much attention around the world [ 26 , 27 , 28 , 29 ]. ESBL strains complicate antibiotic therapy [ 30 ] as ESBL-encoding plasmids can carry additional β-lactamase genes and other antibiotic resistance genes, which may limit treatment options for ESBL-producing pathogens [ 31 ]. Both the US Centers for Disease Control and Prevention (CDC) [ 32 ] and the WHO [ 33 ] list Gram-negative bacteria that produce beta-lactamases as one of the world’s most pressing threats.…”