Temocillin against Enterobacteriaceae isolates from community-acquired urinary tract infections: low rate of resistance and good accuracy of routine susceptibility testing methods

Alexandre, Kévin; Réveillon-Istin, Mathilde; Fabré, R.; Delbos, V.; Etienne, Manuel; Pestel-Caron, Martine; Dahyot, Sandrine; Caron, François

doi:10.1093/jac/dky101

Cited by 18 publications

(15 citation statements)

References 31 publications

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“…Temocillin has been used for several years in some European countries, and is approved for the treatment of septicaemia, and urinary tract and lower respiratory tract infections [13][14][15][16]. However, it is still not available in Poland.…”

Section: Discussionmentioning

confidence: 99%

Activity of temocillin against ESBL-, AmpC-, and/or KPC-producing Enterobacterales isolated in Poland

Kuch

Zieniuk

Żabicka

et al. 2020

Eur J Clin Microbiol Infect Dis

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We evaluated the in vitro effectiveness of temocillin and several commonly used antimicrobials against Enterobacterales bacteria in isolates from Polish patients. We tested 400 isolates: 260 extended-spectrum β-lactamase (ESBL)-and/or ampC β-lactamase (AmpC)-producing isolates; 40 Klebsiella pneumoniae carbapenemase (KPC)-producing isolates; and 100 ESBL-, AmpC-, and KPC-negative isolates. The minimal inhibitory concentrations (MICs) of temocillin and 16 other antimicrobials were determined by reference microdilution. We also determined the activities of fosfomycin and ceftazidime/avibactam in KPC-producing isolates. The antibiotic sensitivities were interpreted according to EUCAST, BSAC, and CLSI criteria. Overall, 91% of the isolates were susceptible to temocillin using the urinary tract infection breakpoint (≤ 32 mg/L), and 61.8% were susceptible using the systemic infection breakpoint (≤ 8 mg/L). Meropenem and imipenem were the most active drugs (MIC 50 values of 0.06 and 0.5 mg/L, respectively). Colistin and ertapenem (both MIC 50 = 0.12 mg/L) were less active than meropenem or imipenem, but some strains were 77% susceptible to each of them. Among the KPC-producing isolates, 42.5% had MIC values of ≤ 32 mg/L (urinary tract infection breakpoint), but 100% were resistant to temocillin (systemic infection breakpoint). Ceftazidime/avibactam was active against 100% of the KPC-producing isolates, and fosfomycin was active against 40%. The empirical susceptibility rate observed among the urinary isolates suggests that temocillin may be considered as an alternative to carbapenems in the absence of KPC-producing bacteria. With regard to isolates from other sources, temocillin might be useful as a documented therapy agent or an empirical treatment in hospitals with a low prevalence of ESBL/AmpC-producing strains.

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Section: Discussionmentioning

confidence: 99%

Activity of temocillin against ESBL-, AmpC-, and/or KPC-producing Enterobacterales isolated in Poland

Kuch

Zieniuk

Żabicka

et al. 2020

Eur J Clin Microbiol Infect Dis

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“…These rates increased to 98.7% and 98.9% according to the urinary tract infection breakpoint (i.e., 32 mg/L) of the British Society for Antimicrobial Chemotherapy [73]. Similarly, susceptibility rate was 94.6% according to the 8 mg/L clinical breakpoint against ESBL-producing isolates from community-acquired UTI [74]. The largest experience on the efficacy of temocillin refers to a retrospective study in 92 patients in whom the drug was given for UTIs, bacteremia and hospital-acquired pneumonia (HAP) caused by Enterobacterales-producing ESBL and/or derepressed AmpC b-lactamases.…”

Section: Temocillinmentioning

confidence: 97%

Carbapenem-Sparing Strategies for ESBL Producers: When and How

2020

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Extended spectrum β-lactamase (ESBL)-producing bacteria are prevalent worldwide and correlated with hospital infections, but they have been evolving as an increasing cause of community acquired infections. The spread of ESBL constitutes a major threat for public health, and infections with ESBL-producing organisms have been associated with poor outcomes. Established therapeutic options for severe infections caused by ESBL-producing organisms are considered the carbapenems. However, under the pressure of carbapenem overuse and the emergence of resistance, carbapenem-sparing strategies have been implemented. The administration of carbapenem-sparing antibiotics for the treatment of ESBL infections has yielded conflicting results. Herein, the current available knowledge regarding carbapenem-sparing strategies for ESBL producers is reviewed, and the optimal conditions for the “when and how” of carbapenem-sparing agents is discussed. An important point of the review focuses on piperacillin–tazobactam as the agent arousing the most debate. The most available data regarding non-carbapenem β-lactams (i.e., ceftolozane–tazobactam, ceftazidime–avibactam, temocillin, cephamycins and cefepime) are also thoroughly presented as well as non β-lactams (i.e., aminoglycosides, quinolones, tigecycline, eravacycline and fosfomycin).

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“…According to recent reports, temocillin MIC 90 values for relevant ESBL and AmpC producers range between 8 and 16 mg/L, but the epidemiological cut-off (ECOFF) for key species has not been defined yet. 20,21,25 As a result of these shortcomings, currently no EUCAST susceptibility breakpoints exist for temocillin. The definition of solid breakpoints and accordingly the issuing of widely accepted dosing recommendations will strongly depend on a more precise elucidation of the mentioned PK/PD aspects.…”

Section: Discussionmentioning

confidence: 99%

“…19 Previously described MIC 90 values for relevant ESBL and AmpC producers (8 and 16 mg/L, respectively) were used. 20,21 Statistical analysis was performed using version 20 of a commercially available computer program (SPSS, IBM, Armonk, NY). The Shapiro-Wilk test was used to test for normal distribution.…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

Single-dose pharmacokinetics of temocillin in plasma and soft tissues of healthy volunteers after intravenous and subcutaneous administration: a randomized crossover microdialysis trial

Matzneller

Pokem

Capron

et al. 2020

Journal of Antimicrobial Chemotherapy

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Background The antibiotic temocillin has recently been rediscovered as a promising therapeutic option against MDR Gram-negative bacteria. However, some aspects of the pharmacokinetic (PK) profile of the drug are still to be elucidated: subcutaneous administration of temocillin might be of interest as an alternative to the intravenous route in selected patients. Similarly, information on the penetration of temocillin into human soft tissues is lacking. Objectives To investigate the feasibility and plasma PK of subcutaneous dosing as well as soft tissue PK of temocillin after intravenous administration to healthy volunteers. Methods Eight healthy volunteers received 2 g of temocillin both as intravenous and subcutaneous infusion in a randomized two-period crossover study. Concentration–time profiles of total temocillin in plasma (after both routes) and of unbound temocillin in plasma, muscle and subcutis (only after intravenous dosing) were determined up to 12 h post-dose. Results Subcutaneous dosing caused some infusion site discomfort but resulted in sustained drug concentrations over time with only slightly decreased overall exposure compared with intravenous dosing. Plasma protein binding of temocillin showed concentration-dependent behaviour and was higher than previously reported. Still, unbound drug concentrations in muscle and subcutis determined by microdialysis markedly exceeded those in plasma, suggesting good tissue penetration of temocillin. Conclusions The subcutaneous administration of temocillin is a valid and feasible alternative to intravenous dosing. With the description of plasma protein binding and soft tissue PK of temocillin in healthy volunteers, this study provides important information that adds to the ongoing characterization of the PK profile of temocillin and might serve as input for PK/PD considerations.

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Temocillin against Enterobacteriaceae isolates from community-acquired urinary tract infections: low rate of resistance and good accuracy of routine susceptibility testing methods

Abstract: Temocillin showed a high level of activity against Enterobacteriaceae from community-acquired UTI and good to excellent reliability of routine methods for susceptibility testing in such a setting.

Cited by 18 publications

References 31 publications

Activity of temocillin against ESBL-, AmpC-, and/or KPC-producing Enterobacterales isolated in Poland

Activity of temocillin against ESBL-, AmpC-, and/or KPC-producing Enterobacterales isolated in Poland

Carbapenem-Sparing Strategies for ESBL Producers: When and How

Single-dose pharmacokinetics of temocillin in plasma and soft tissues of healthy volunteers after intravenous and subcutaneous administration: a randomized crossover microdialysis trial

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