<i>In Vitro</i>
            Activities of β-Lactam–β-Lactamase Inhibitor Antimicrobial Agents against Cystic Fibrosis Respiratory Pathogens

Caverly, Lindsay J.; Spilker, Theodore; Kalikin, Linda M.; Stillwell, Terri; Young, Carol; Huang, David B.; LiPuma, John J.

doi:10.1128/aac.01595-19

Cited by 22 publications

(27 citation statements)

References 13 publications

(12 reference statements)

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“…Notably, although AVI did not restore the activity of CAZ against the two MDR S. maltophilia isolates, it did restore the activity of ATM against the two MDR S. maltophilia strains with significant MIC reductions of 32- and 8-fold respectively. The poor activity of CAZ-AVI against MDR S. maltophilia isolates was in accordance with a previous study by Lindsay J. Caverly et al [ 17 ], who demonstrated that the activity of CAZ-AVI was poor against most MDR/XDR S. maltophilia strains. Recently, the efficacy of CAZ-AVI (2.5 g i.v.…”

Section: Discussionsupporting

confidence: 91%

Avibactam potentiated the activity of both ceftazidime and aztreonam against S. maltophilia clinical isolates in vitro

Lin

Zhang²,

Chen

et al. 2021

BMC Microbiol

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Background Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM), and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011–2018. Methods We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011–2018, a collection of 76 isolates were selected for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of CAZ, CAZ-AVI, ATM and ATM-AVI were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more active in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” or “Intermediate” with CAZ or ATM alone to “Susceptible” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 4-fold lower than the MIC of CAZ or ATM alone. Results For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03–64, 1–1024, 0.016–64, and 0.06–64 μg/mL, respectively. In combined therapy, AVI was active at restoring the activity of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs. 56.58%, P < 0.001), and MIC50 (2 μg/mL vs. 8 μg/mL, P < 0.05) when compared to CAZ. According to our definition, CAZ-AVI was more active in vitro than CAZ alone for 81.58% (62/76) of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79% vs.10.53%, P < 0.001) and MIC50 (2 μg/mL vs. 64 μg/mL, P < 0.001) when compared to ATM. According to our definition, ATM-AVI was also more active in vitro than ATM alone for 94.74% (72/76) of the isolates. Conclusions AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

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Section: Discussionsupporting

confidence: 91%

Avibactam potentiated the activity of both ceftazidime and aztreonam against S. maltophilia clinical isolates in vitro

Lin

Zhang²,

Chen

et al. 2021

BMC Microbiol

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“…However, acquired resistance to these are increasingly being reported (64). The proportion of ceftazidime-susceptible isolates was 71% in a U.S. collection (susceptibility breakpoint, Յ8 g/ml; CLSI other non-Enterobacterales; MIC 50/90 , 8/32 g/ml) (65). In another collection from Europe, trimethoprimsulfamethoxazole MIC 50/90 was 0.5/8 g/ml (susceptibility breakpoint Յ 2 g/ml, CLSI other non-Enterobacterales), and it was one of the two most active agents against 59 Achromobacter isolates, the other being imipenem (MIC 50/90 , 2/8 g/ml) (66).…”

Section: Antibiotic Susceptibilitymentioning

confidence: 99%

Achromobacter Infections and Treatment Options

Isler

Kidd

Stewart

et al. 2020

Antimicrob Agents Chemother

107

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Achromobacter is a genus of non-fermenting Gram negative bacteria under order Burkholderiales. Although primarily isolated from respiratory tract of people with cystic fibrosis, Achromobacter spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse outcomes, and optimal treatment. Achromobacter spp. are intrinsically resistant to several antibiotics (e.g. most cephalosporins, aztreonam and aminoglycosides), and are increasingly acquiring resistance to carbapenems. Carbapenem resistance is mainly caused by multidrug efflux pumps and metallo-β-lactamases, which are not expected to be overcome by new β-lactamase inhibitors. Among the other new antibiotics, cefiderocol and eravacycline were used as salvage therapy for a limited number of patients with Achromobacter infections. In this article, we aim to give an overview of the antimicrobial resistance in Achromobacter species, highlighting the possible place of new antibiotics in their treatment.

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“…In vitro data indicate similar resistance profiles to ceftazidime and ceftazidime-avibactam (MIC 50/90 of 32/> 32 and 16/> 32 mg/L, respectively), meropenem and meropenem-vaborbactam (MIC 50/90 of> 32/ > 32 and > 32/> 32 mg/L, respectively), and imipenem and imipenem-relebactam (MIC 50/90 of > 64/> 64 and > 64/> 64 mg/L, respectively). 12,13 Ceftolozane-tazobactam offers no additional benefit to ceftazidime-resistant isolates.…”

Section: Mechanisms Of Resistancementioning

confidence: 99%

An Overview of the Treatment of Less Common Non–Lactose‐Fermenting Gram‐Negative Bacteria

et al. 2020

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Stenotrophomonas maltophilia, Burkholderia cepacia complex, Elizabethkingia spp., Chryseobacterium spp., Achromobacter spp., and Alcaligenes spp. are less‐common non–lactose‐fermenting bacteria that have emerged as important opportunistic pathogens. Patients at the highest risk for these infections include the immunocompromised, those with cystic fibrosis, and the critically ill. These opportunistic pathogens are frequently drug resistant through the expression of β‐lactamases, multidrug efflux pumps, aminoglycoside‐modifying enzymes, and target site alterations discussed in detail throughout this review. As a result, treatment is extremely challenging. For each pathogen, this review will examine the epidemiology, mechanisms of resistance, and in vitro and in vivo data including that for novel β‐lactam/β‐lactamase inhibitors and cefiderocol. Treatment recommendations are provided based on the available literature.

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In Vitro Activities of β-Lactam–β-Lactamase Inhibitor Antimicrobial Agents against Cystic Fibrosis Respiratory Pathogens

Cited by 22 publications

References 13 publications

Avibactam potentiated the activity of both ceftazidime and aztreonam against S. maltophilia clinical isolates in vitro

Avibactam potentiated the activity of both ceftazidime and aztreonam against S. maltophilia clinical isolates in vitro

Achromobacter Infections and Treatment Options

An Overview of the Treatment of Less Common Non–Lactose‐Fermenting Gram‐Negative Bacteria

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