Results from a Prospective
            <i>In Vitro</i>
            Study on the Mecillinam (Amdinocillin) Susceptibility of
            <i>Enterobacterales</i>

Fuchs, Frieder; Hamprecht, Axel

doi:10.1128/aac.02402-18

Cited by 18 publications

(13 citation statements)

References 15 publications

(12 reference statements)

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“…It is safe to use. It has been used in Scandinavian counties for a long time and the mecillinam resistance is low . This study shows low‐level resistance as 95% isolates were sensitive to mecillinam.…”

Section: Discussionmentioning

confidence: 82%

“…It has been widely used in the Scandinavian countries to treat UTIs because of ESBL‐producing Enterobacteriaceae and also recommended as an empirical treatment for uncomplicated UTIs in international guidelines . Two studies from Scandinavia and Germany reported that mecillinam resistance is still low despite its widespread use over several decades . One study from the UK reported that pivmecillinam is low risk for Clostridium difficile infection .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Emerging clinical role of pivmecillinam in the treatment of urinary tract infections caused by Extended Spectrum βeta‐lactamase (ESBL) producing Enterobacteriaceae

Raja

2019

Int J Clin Pract

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Background: Extended Spectrum βeta-lactamase (ESBL)-producing Enterobacteriaceae causing urinary tract infections (UTIs) appear resistant to many common oral agents. There is a growing need to discover new antibiotics to combat with emerging antibiotic resistance problem. Until the discovery of new antimicrobials, we can bring back forgotten antibiotics to our clinical formulary. Pivmecillinam (prodrug of mecillinam), an oral antimicrobial agent is effective against ESBL producing organisms. We analysed the sensitivity rates of ESBL-producing Enterobacteriaceae from urine samples to mecillinam and to document if pivmecillinam is a suitable alternative option in the treatment of UTI. Materials/methods: This retrospective study was conducted from September 2015to September 2017. Data were collected from the pathology information system.Antimicrobial sensitivity testing on ESBL-producing Enterobacteriaceae isolates was carried out by disc diffusion method in accordance with The European Committee on Antimicrobial Susceptibility Testing. Results:A total of 986 ESBL-producing Enterobacteriaceae were tested for mecillinam during the study period. Of 986 organisms, Escherichia coli was the most common organism (889); followed by Klebsiella species (71) and others Enterobacteriaceae (26). Mecillinam sensitivity was found in 96% Escherichia coli (855/889 isolates), 83%Klebsiella species (59/71 isolates) and 88% other Enterobacteriaceae (23/26 isolates).Overall 95% (935/986 isolates) of ESBL-producing urinary isolates were sensitive to mecillinam.Conclusions: Pivmecillinam appears to be suitable option to treat ESBL-producing Enterobacteriaceae causing uncomplicated UTI. Our results showed low resistance rate to mecillinam. We recommend the use of pivmecillinam in uncomplicated UTIs because of ESBL-producing Enterobacteriaceae. More studies on in vitro activity of mecillinam against ESBL producing organism and its use and clinical outcome should be tried in future.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Emerging clinical role of pivmecillinam in the treatment of urinary tract infections caused by Extended Spectrum βeta‐lactamase (ESBL) producing Enterobacteriaceae

Raja

2019

Int J Clin Pract

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“…In contrast to IMI-producers, mecillinam susceptibility in OXA-48-like-producers has been previously described (Marrs et al, 2014;Mutters et al, 2015;Fuchs and Hamprecht, 2019a). For further analysis, we included E. coli (N = 18) and K. pneumoniae (N = 18) isolates with OXA-48 and different OXA-48-like carbapenemases in the challenge collection.…”

Section: Discussionmentioning

confidence: 99%

“…Most of the data on mecillinam susceptibility in multidrug-resistant Enterobacterales focus on E. coli and frequent resistance mechanisms, e.g., Extended-spectrum beta-lactamases (ESBL), AmpC, and some of the more common types of carbapenemases such as OXA-48 or NDM-1 ( Perry et al, 2011 ; Marrs et al, 2014 ; Mutters et al, 2015 ; Samuelsen et al, 2017 ; Fuchs and Hamprecht, 2019a ; Zykov et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of Clinical Enterobacterales Isolates With Common and Rare Carbapenemases to Mecillinam

et al. 2021

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Purpose: To investigate the susceptibility of carbapenemase-producing Enterobacterales (CPE) to mecillinam based on the recently updated European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for uncomplicated Urinary Tract Infection (uUTI).Methods: The challenge collection consisted of 105 molecularly characterized Enterobacterales [Klebsiella spp. (N = 49), Escherichia coli (N = 30), Enterobacter cloacae (n = 13), Citrobacter freundii (N = 9), Proteus mirabilis (N = 3), and Raoultella ornithinolytica (N = 1)]. Isolates produced OXA-48 (N = 18), OXA-48-like (N = 18), VIM (N = 22), NDM (N = 22), KPC (N = 12), IMI (N = 9), IMP (N = 6), GES (N = 1), OXA-58 (N = 2) or combinations thereof (N = 5). MICs of carbapenems were determined by agar gradient diffusion (AGD). MICs of mecillinam were assessed by agar dilution (reference method) and compared to disk diffusion (DD) and AGD.Results: Overall 23/105 CPE (21.9%) were susceptible to mecillinam. Susceptibility was observed in E. coli (N = 12), E. cloacae (N = 7), and Klebsiella pneumoniae (N = 4) producing IMI, OXA-48, OXA-48-like, and NDM-1 carbapenemases. MIC50 for mecillinam in all isolates was 128 mg/L while MIC50 for meropenem was 8 mg/L. Lower MICs for mecillinam were found in IMI (MIC50 8 mg/L) and OXA-48-like (MIC50 16 mg/L) producers. The comparison of the different susceptibility methods showed very major errors of 12.2% with AGD and 8.5% with disk diffusion when compared to the reference method.Conclusion: Mecillinam susceptibility was restricted to isolates producing IMI-, OXA-48-like, and NDM-1 carbapenemases and was documented despite high carbapenem MICs in some isolates. Mecillinam could be a promising oral antimicrobial in uUTI caused by E. coli and E. cloacae isolates carrying IMI- and OXA-48-like carbapenemases; however, susceptibility testing by AGD and disk diffusion remains problematic.

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“…Mecillinam belongs to the group of broad-spectrum penicillins and historically it has not been widely used in veterinary medicine, possibly due to its poor oral absorption; however, some authors believe that mecillinam has potential in veterinary medicine if administered parenterally [ 31 ]. No data are available on the ESBL-producing E. coli resistance to mecillinam in pigs, but several authors have reported the high susceptibility of ESBL-producing E. coli (96.9.2%) and MRD E. coli (96.5%) to mecillinam in humans [ 32 ]; therefore, since 2019, mecillinam has been included in category A, which is not authorized for use in veterinary medicine [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

The Prevalence and Characterization of Fecal Extended-Spectrum-Beta-Lactamase-Producing Escherichia coli Isolated from Pigs on Farms of Different Sizes in Latvia

2021

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The aim of this study was to determine the prevalence of fecal ESBL-producing Escherichia coli (E. coli) in pigs on large and small farms in Latvia, to characterize beta-lactamase genes and establish an antimicrobial resistance profile. Fecal samples (n = 615) were collected from 4-week, 5-week, 6-week, 8-week, 12-week and 20-week-old piglets, pigs and sows on four large farms (L1, L2, L3, L4) and three small farms (S1, S2, S3) in Latvia. ChromArt ESBL agar and combination disc tests were used for the screening and confirmation of ESBL-producing E. coli. The antimicrobial resistance was determined by the disc diffusion method and ESBL genes were determined by polymerase chain reaction (PCR). Subsequently, ESBL-producing E. coli was confirmed on three large farms, L1 (64.3%), L2 (29.9%), L3 (10.7%) and one small farm, S1 (47.5%); n = 144 (23.4%). The prevalence of ESBL-producing E. coli differed considerably between the large and small farm groups (26.9% vs. 12.7%). Of ESBL E. coli isolates, 96% were multidrug-resistant (MDR), demonstrating there were more extensive MDR phenotypes on large farms. The distribution of ESBL genes was blaTEM (94%), blaCTX-M (94%) and blaSHV (48%). On the small farm, blaSHV dominated, thus demonstrating a positive association with resistance to amoxicillin-clavulanic acid, ceftazidime and cefixime, while on the large farms, blaCTX-M with a positive association to cephalexin and several non-beta lactam antibiotics dominated. The results indicated the prevalence of a broad variety of ESBL-producing E. coli among the small and large farms, putting the larger farms at a higher risk. Individual monitoring of ESBL and their antimicrobial resistance could be an important step in revealing hazardous MDR ESBL-producing E. coli strains and reviewing the management of antibiotic use.

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Results from a Prospective In Vitro Study on the Mecillinam (Amdinocillin) Susceptibility of Enterobacterales

Cited by 18 publications

References 15 publications

Emerging clinical role of pivmecillinam in the treatment of urinary tract infections caused by Extended Spectrum βeta‐lactamase (ESBL) producing Enterobacteriaceae

Emerging clinical role of pivmecillinam in the treatment of urinary tract infections caused by Extended Spectrum βeta‐lactamase (ESBL) producing Enterobacteriaceae

Susceptibility of Clinical Enterobacterales Isolates With Common and Rare Carbapenemases to Mecillinam

The Prevalence and Characterization of Fecal Extended-Spectrum-Beta-Lactamase-Producing Escherichia coli Isolated from Pigs on Farms of Different Sizes in Latvia

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