Antianaerobic Activity of Sulopenem Compared to Six Other Agents

Ednie, Lois M.; Appelbaum, Peter C.

doi:10.1128/aac.01557-08

Cited by 12 publications

(5 citation statements)

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“…Limited reports on sulopenem activity are available for recent, clinically relevant anaerobic species. Data from previous studies by both Gootz et al 13 and Ednie and Applebaum 35 gave comparable results to our study. Overall, the activity of sulopenem (MIC 50/90 , 0.12/1 mg/L), clindamycin (MIC 50/90 , 0.5/>4 mg/L), piperacillin/tazobactam (MIC 50/90 , 0.25/16 mg/L) and metronidazole (MIC 50/90 , 1/>16 mg/L) against anaerobic isolates agreed with published data.…”

Section: Discussionsupporting

confidence: 92%

“…Overall, the activity of sulopenem (MIC 50/90 , 0.12/1 mg/L), clindamycin (MIC 50/90 , 0.5/>4 mg/L), piperacillin/tazobactam (MIC 50/90 , 0.25/16 mg/L) and metronidazole (MIC 50/90 , 1/>16 mg/L) against anaerobic isolates agreed with published data. 35 Against all anaerobic isolates, sulopenem (98.9% inhibited at ≤4 mg/L) and meropenem [98.4% S (CLSI)] were the most active agents assessed. The potent in vitro activity of sulopenem suggests the potential of this agent to treat mixed anaerobic infections; however, additional data from complicated IAI clinical trials are needed.…”

Section: Discussionmentioning

confidence: 99%

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In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program

Maher

Huband

Blankers

et al. 2023

Journal of Antimicrobial Chemotherapy

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Objectives Physicians must leverage several factors when making antibiotic therapy decisions, including route of administration and duration of therapy. Oral administration provides several potential advantages including increased accessibility, prevention of hospitalizations and earlier discharges. Sulopenem—a broad-spectrum, synthetic penem β-lactam agent—uniquely possesses both oral and IV formulations along with noted stability among antimicrobial-resistant subsets. This study evaluated the in vitro activity of sulopenem and comparator agents against contemporary Enterobacterales and anaerobic clinical isolates predominantly from patients with bloodstream, intra-abdominal and urinary tract infections. Methods A contemporary collection of 1647 Enterobacterales and 559 anaerobic isolates was assembled from medical centres in Europe and the USA. Isolates were susceptibility tested using the CLSI reference methods: broth microdilution for Enterobacterales and agar dilution for anaerobes. Results Sulopenem demonstrated potent in vitro antimicrobial activity (MIC50/90, 0.03/0.25 mg/L) against Enterobacterales isolates regardless of infection type, inhibiting 99.2% of isolates at ≤1 mg/L. This activity was conserved against resistant phenotypes including ESBL-phenotype Escherichia coli (MIC50/90, 0.03/0.06 mg/L) and ESBL-phenotype Klebsiella pneumoniae (MIC50/90, 0.06/1 mg/L). Sulopenem maintained activity against ciprofloxacin-, nitrofurantoin- and trimethoprim/sulfamethoxazole-non-susceptible subsets (MIC50/90, 0.03–0.06/0.12–0.5 mg/L). Against anaerobic isolates, sulopenem (98.9% inhibited at ≤4 mg/L) and meropenem [98.4% susceptible (CLSI)] were the most active compounds tested. Conclusions The potent in vitro activity of sulopenem against this large collection of recent Enterobacterales and anaerobic clinical isolates from multiple infection types supports its further clinical evaluation in the treatment of intra-abdominal and urinary tract infections.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program

Maher

Huband

Blankers

et al. 2023

Journal of Antimicrobial Chemotherapy

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“…Although several reports have focused on the antianaerobic activities of newly developed antibiotics in vitro (Ednie & Appelbaum, 2009;Tanaka et al, 2009;Tran et al, 2011), there are few suitable animal models for testing the action of antimicrobial agents against anaerobic infections that are accompanied by abscesses.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, anaerobic infections often occur with abscesses, which impair the activity of antimicrobial agents and require surgical debridement as standard treatment (Giamarellou, 2000; Brook, 2012). Although several reports have focused on the anti-anaerobic activities of newly developed antibiotics in vitro (Ednie & Appelbaum, 2009; Tanaka et al ., 2009; Tran et al ., 2011), there are few suitable animal models for testing the action of antimicrobial agents against anaerobic infections that are accompanied by abscesses.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a new murine model of liver abscess induced by Fusobacterium necrophorum injected into the caudal vein

Nagaoka

Yanagihara

Harada

et al. 2013

Journal of Medical Microbiology

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Anaerobic bacterial infection is often accompanied by abscess formation; however, few in vivo studies have been published with descriptive data specifically evaluating antimicrobial activity in the presence of abscesses. The aim of this study was to establish a murine model of anaerobic infection with abscess formation and to verify the utility of this model for evaluating the in vivo efficacy of an antimicrobial agent. A clinical isolate of Fusobacterium necrophorum was inoculated into the caudal vein of immunocompetent BALB/c mice at 10 8 c.f.u. per mouse. Changes in body weight, bacterial load and histopathology of key organs were evaluated. After inoculation, bacterial counts in the liver increased from 10 4 to 10 8 c.f.u. after 1-3 days, and liver abscess formation was observed on the day following infection. Abscess formation and bacterial growth were not observed in other organs. In this model, 3 days of treatment with 5 mg metronidazole kg "1 eradicated F. necrophorum in the liver; however, a reduction in bacterial load was not observed with 0.05 mg metronidazole kg "1. In this study, we established a novel murine model of F. necrophorum liver abscess via haematogenous infection that may be useful for investigating in vivo antimicrobial activity against anaerobic abscesses and understanding the pathogenesis of F. necrophorum infection.

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“…limited. Sulopenem has been reported to inhibit the growth of most isolates of aerobic and anaerobic Gram-positive and Gram-negative bacteria, including methicillinsusceptible Staphylococcus aureus, Streptococcus pneumoniae (penicillin-susceptible and -resistant isolates), group A and B ␤-hemolytic streptococci, Listeria monocytogenes, Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis but excluding P. aeruginosa and Stenotrophomonas maltophilia, at a concentration of Յ1 g/ml (10,13,(23)(24)(25)(26)(27).…”

mentioning

confidence: 99%

In Vitro Activity of Sulopenem, an Oral Penem, against Urinary Isolates of Escherichia coli

Karlowsky

Adam

Baxter

et al. 2019

Antimicrob Agents Chemother

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The in vitro activity of sulopenem was assessed against a collection from 2014 to 2016 of 539 urinary isolates of Escherichia coli from Canadian patients by using CLSI-defined broth microdilution methodology. A concentration of sulopenem 0.03 µg/ml inhibited both 50% (MIC50) and 90% (MIC90) of isolates tested; sulopenem MICs ranged from 0.015 to 0.25 µg/ml. The in vitro activity of sulopenem was unaffected by nonsusceptibility to trimethoprim-sulfamethoxazole and/or ciprofloxacin, multidrug-resistant phenotypes, extended-spectrum β-lactamases, or AmpC β-lactamases.

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Antianaerobic Activity of Sulopenem Compared to Six Other Agents

Cited by 12 publications

References 12 publications

In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program

In vitro activity of sulopenem and comparator agents against Enterobacterales and anaerobic clinical isolates collected during the SENTRY Antimicrobial Surveillance Program

Establishment of a new murine model of liver abscess induced by Fusobacterium necrophorum injected into the caudal vein

In Vitro Activity of Sulopenem, an Oral Penem, against Urinary Isolates of Escherichia coli

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