Susceptibility to penicillin derivatives among third-generation cephalosporin-resistant Enterobacteriaceae recovered on hospital admission

Mischnik, Alexander; Baumert, Philipp; Hamprecht, Axel; Rohde, Anna M.; Peter, Silke; Feihl, Susanne; Knobloch, J; Gölz, Hanna; Kola, Axel; Obermann, Birgit; Querbach, Christiane; Willmann, Matthias; Gebhardt, Friedemann; Tacconelli, Evelina; Gastmeier, Petra; Seifert, Harald; Kern, Winfried V.

doi:10.1016/j.diagmicrobio.2016.09.012

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…When MICs were calculated only for isolates from urine, the MIC 50 and MIC 90 values were similar (data not shown), suggesting a possible role for temocillin in the treatment of urinary tract infections in Poland, regardless of the clinical breakpoint used. As expected, based on the literature non-ESBL/AmpC/KPC-producing isolates were very susceptible (100% and 99%), regardless of the clinical breakpoint used [15][16][17][18].…”

Section: Discussionsupporting

confidence: 78%

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: Discussionsupporting

confidence: 78%

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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“…Our data further demonstrate that mecillinam and temocillin are often hydrolysed to a lesser extent than other β-lactams. 36 In MDR Enterobacterales mecillinam may be particularly promising for ESBL-, AmpC- or OXA-48-like-producing E. coli and Enterobacter spp., while temocillin is particularly active in ESBL-expressing isolates.…”

Section: Discussionmentioning

confidence: 99%

In vitro activity of mecillinam, temocillin and nitroxoline against MDR Enterobacterales

Plambeck

Fuchs

Sattler

et al. 2022

JAC-Antimicrobial Resistance

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Background With increasing resistance to common antibiotics the treatment of urinary tract infections has become challenging and alternative therapeutic options are needed. In the present study, we evaluate the activity of three older and less frequently used antibiotics against MDR Enterobacterales. Methods Susceptibility of mecillinam, temocillin and nitroxoline was assessed in Enterobacterales isolated from urinary specimens with elevated MICs of third-generation cephalosporins. Susceptibility was determined by the recommended reference MIC methods and additionally by disc diffusion. All isolates were characterized for common β-lactamases by phenotypic and molecular assays. Results In total 394 Enterobacterales were included. The most common resistance mechanisms were ESBLs (n = 273), AmpC (n = 132), carbapenemases [n = 12, including OXA-48-like (n = 8), VIM (n = 2), KPC (n = 1) and NDM (n = 1)] or others (n = 2). Resistance was observed in 59% of isolates to ceftazidime, in 41% to piperacillin/tazobactam and in 54% to ciprofloxacin. In comparison, resistance was less frequent against mecillinam (15%), temocillin (13%) or nitroxoline (2%). Mecillinam showed higher activity in Enterobacter spp., Escherichia coli and in OXA-48-like-producing isolates compared with temocillin, which was more active in Proteus mirabilis and in ESBL-producing isolates. Activity of nitroxoline was high against all isolates, including carbapenemase-producing isolates. Correlation between disc diffusion and MIC methods was good for mecillinam and moderate for temocillin and nitroxoline. Conclusions Mecillinam, temocillin and nitroxoline show good to excellent in vitro activity in MDR Enterobacterales. The activity of mecillinam and temocillin was higher in certain species and restricted depending on β-lactamase production while nitroxoline showed universally high activity irrespective of species or β-lactamase present.

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“…Temocillin, because of its in vitro activity, is a potential alternative to carbapenems for the treatment of infections caused by 3GCR-E and might help to reduce the consumption of these drugs. [13][14][15] As comparative clinical data for temocillin is scarce, ASTARTÉ is expected to provide evidence for the use of this drug in the setting of BSI due to 3GCR-E, which represents a substantial proportion of all BSI caused by Enterobacterales.…”

Section: Discussionmentioning

confidence: 99%

Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant Enterobacterales (ASTARTÉ): protocol for a randomised, pragmatic trial

et al. 2021

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IntroductionAlternatives to carbapenems are needed in the treatment of third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Temocillin is a suitable candidate, but comparative randomised studies are lacking. The objective is to investigate if temocillin is non-inferior to carbapenems in the targeted treatment of bacteraemia due to 3GCR-E.Methods and analysisMulticentre, open-label, randomised, controlled, pragmatic phase 3 trial. Patients with bacteraemia due to 3GCR-E will be randomised to receive intravenously temocillin (2 g three times a day) or carbapenem (meropenem 1 g three times a day or ertapenem 1 g once daily). The primary endpoint will be clinical success 7–10 days after end of treatment with no recurrence or death at day 28. Adverse events will be collected; serum levels of temocillin will be investigated in a subset of patients. For a 10% non-inferiority margin, 334 patients will be included (167 in each study arm). For the primary analysis, the absolute difference with one-sided 95% CI in the proportion of patients reaching the primary endpoint will be compared in the modified intention-to-treat population.Ethics and disseminationThe study started after approval of the Spanish Regulatory Agency and the reference institutional review board. Data will be published in peer-reviewed journals.Trial registration numberNCT04478721.

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Susceptibility to penicillin derivatives among third-generation cephalosporin-resistant Enterobacteriaceae recovered on hospital admission

Cited by 7 publications

References 21 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

In vitro activity of mecillinam, temocillin and nitroxoline against MDR Enterobacterales

Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant Enterobacterales (ASTARTÉ): protocol for a randomised, pragmatic trial

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