Mycobacterium abscessus and β-Lactams: Emerging Insights and Potential Opportunities

Story-Roller, Elizabeth; Maggioncalda, Emily C.; Cohen, Keira A.; Lamichhane, Gyanu

doi:10.3389/fmicb.2018.02273

Cited by 39 publications

(32 citation statements)

References 100 publications

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“…Recent studies suggest that combining different classes of ␤-lactams against MABC members (30,33) and other bacteria (34,35) may be synergistic due to targeting a wider spectrum of enzymes that appear to be uniquely relevant to synthesis of peptidoglycan in MABC organisms (36,37). For example, Kumar et al recently demonstrated synergy between doripenem and cefdinir against MABC strains (30).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical Isolates

Kaushik

Ammerman

Liu

et al. 2019

Antimicrob Agents Chemother

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Pulmonary disease due to infection withMycobacterium abscessuscomplex (MABC) is notoriously difficult to treat, in large part due to the intrinsic resistance of MABC strains to most antibiotics, including β-lactams. MABC organisms express a broad-spectrum β-lactamase that is resistant to traditional β-lactam-based β-lactamase inhibitors but inhibited by a newer non-β-lactam-based β-lactamase inhibitor, avibactam. Consequently, the susceptibility of MABC members to some β-lactams is increased in the presence of avibactam. Therefore, we hypothesized that two new non-β-lactam-based β-lactamase inhibitors, relebactam and vaborbactam, would also increase the susceptibility of MABC organisms to β-lactams. The objective of the present study was to evaluate thein vitroactivity of various marketed β-lactams alone and in combination with either relebactam or vaborbactam against multidrug-resistant MABC clinical isolates. Our data demonstrate that both β-lactamase inhibitors significantly improved the anti-MABC activity of many carbapenems (including imipenem and meropenem) and cephalosporins (including cefepime, ceftaroline, and cefuroxime). As a meropenem-vaborbactam combination is now marketed and an imipenem-relebactam combination is currently in phase III trials, these fixed combinations may become the β-lactams of choice for the treatment of MABC infections. Furthermore, given the evolving interest in dual β-lactam regimens, our results identify select cephalosporins, such as cefuroxime, with superior activity in the presence of a β-lactamase inhibitor that are deserving of further evaluation in combination with these carbapenem–β-lactamase inhibitor products.

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Section: Discussionmentioning

confidence: 99%

In Vitro Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical Isolates

Kaushik

Ammerman

Liu

et al. 2019

Antimicrob Agents Chemother

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“…13,15 Recent evidence suggests that dual βlactam therapy may be more effective than using a single β-lactam. 16 In this study, MABC isolates were assessed for susceptibility to various antimicrobials, and the relationship between the erm(41) gene and inducible CLA resistance in each subspecies of MABC was explored. The results provide guidance for the empirical therapy of RGM infections.…”

Section: Introductionmentioning

confidence: 99%

<p>Antimicrobial Susceptibility of <em>Mycobacterium abscessus</em> Complex Clinical Isolates from a Chinese Tertiary Hospital</p>

Guo

Cao

et al. 2020

IDR

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Introduction: Mycobacterium abscessus complex (MABC) is a group of important infectious agents that are highly associated with drug resistance, and antibiotic treatment is usually ineffective. This study investigated the characteristics of antimicrobial susceptibility of MABC isolates and the synergy between certain β-lactam combinations against MABC infection. Methods: We collected 129 MABC isolates from patients with lower respiratory tract infections and categorized them into three subspecies. The minimum inhibitory concentrations (MICs) of 15 antimicrobials for the MABC isolates were determined using commercial Sensititre RAPMYCOI MIC plates and the broth microdilution method, as recommended in the CLSI (M24-A2). In addition, the MICs of imipenem, alone and with ceftazidime and/or avibactam, were assessed in vitro for all isolates. The erm(41) and rrl genes were also sequenced. Results: The MABC isolates exhibited >80% resistance to 11 of the 15 antimicrobials. Regarding the remaining four antimicrobials, the isolates were least resistant to tigecycline (12.4%) and amikacin (3.9%), and only partially resistant to two cefoxitin (39.5%) and imipenem (40.3%). Compared with M. massiliense isolates, M. abscessus and M. bolletii isolates were more resistant to amikacin and imipenem, whereas M. abscessus was significantly less resistant to tigecycline relative to M. massiliense and M. bolletii isolates. The clarithromycin inducible resistance rate was 68.4% and 74.3% among M. bolletii and M. abscessus isolates. Furthermore, 88.7% of the M. abscessus isolates carried a T at position 28 of erm(41), which is associated with inducible clarithromycin resistance. In addition, compared to imipenem with avibactam only, the MIC 50 and MIC 90 values of imipenem after adding ceftazidime plus avibactam were decreased fourfold. Conclusion: The antimicrobial resistance rates and the characteristics of the erm(41) gene associated with inducible clarithromycin resistance were different among the three MABC subspecies. There was also synergy between imipenem and 100μg/mL ceftazidime against MABC isolates.

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“…The recent recognition of macrolide resistance has further narrowed treatment options (2). Combination drug regimens, which may include a β-lactam, aminoglycoside, macrolide, linezolid, or tigecycline, are routinely prescribed, but fewer than one-half of patients with pulmonary disease achieve sputum culture conversion (6, 7). Regrettably, treatment failures and recurrences are frequently reported (7–9).…”

Section: Introductionmentioning

confidence: 99%

Dual β-Lactam Combinations Highly Active against Mycobacterium abscessus Complex In Vitro

Pandey

Chen

Manca

et al. 2019

mBio

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The emergence of chronic MABC infections among immunocompromised populations and their inherent and acquired resistance to effective antibiotic therapy have created clinical challenges in advancing patients for transplant surgery and treating those with disease. There is an urgent need for new treatment regimens, and the repurposing of existing antibiotics provides a rapid strategy to advance a laboratory finding to patient care. Our recent discoveries that dual β-lactams, specifically the combination of ceftazidime with ceftaroline or ceftazidime with imipenem, have significant in vitro MIC values and kill curve activities and are effective against infected THP-1 human macrophages provide optimism for a dual β-lactam treatment strategy against MABC infections. The unexpected synergistic activities reported in this study create a new path of discovery to repurpose the large family of β-lactam drugs.

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Mycobacterium abscessus and β-Lactams: Emerging Insights and Potential Opportunities

Cited by 39 publications

References 100 publications

In Vitro Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical Isolates

In Vitro Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical Isolates

<p>Antimicrobial Susceptibility of <em>Mycobacterium abscessus</em> Complex Clinical Isolates from a Chinese Tertiary Hospital</p>

Dual β-Lactam Combinations Highly Active against Mycobacterium abscessus Complex In Vitro

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