Enhanced bacterial killing with a combination of sulbactam/minocycline against dual carbapenemase-producing Acinetobacter baumannii

Chandran, Suriya; Manokaran, Yuvasri; Vijayakumar, Saranya; Shankar, Baby Abirami; Bakthavatchalam, Yamuna Devi; Dwarakanathan, Hariharan Triplicane; Yesudason, Binesh Lal; Veeraraghavan, Balaji

doi:10.1007/s10096-023-04583-z

Cited by 5 publications

(1 citation statement)

References 24 publications

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“… 6 A recent study by Chandran et al showed that minocycline and sulbactam were an effective combination in vitro against those isolates which produced the OXA-23 and NDM enzymes. 12 Hence, more data is needed on the efficacy of sulbactam in our settings. Also, more data is needed on the local enzyme patterns, especially as newer therapeutic options emerge.…”

Section: Discussionmentioning

confidence: 99%

Enzyme Patterns and Factors Associated with Mortality among Patients with Carbapenem Resistant Acinetobacter Baumannii (CRAB) Bacteremia: Real World Evidence from a Tertiary Center in India

Prayag,

Panchakshari,

Patwardhan

et al. 2023

Indian Journal of Critical Care Medicine

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A bstract Introduction In the Indian setting, antimicrobial resistance in A. baumannii is a considerable problem, especially in intensive care units (ICUs). Due to the limited data, clinicians are left with very few choices except polymyxins for treating serious infections caused by A. baumannii . There is sparse data regarding the local mechanisms of resistance. Given the current therapeutic challenges, it is critical to know the local enzymatic patterns and antibiograms. Materials and methods A retrospective analysis of 50 episodes of bacteremia caused by CRAB. We analyzed the enzyme patterns and the susceptibility rates to various antibiotics. Results The resistance rates for amikacin, tigecycline, minocycline, and fluoroquinolones were 88, 82, 50, and 88% respectively. OXA-23 was the most commonly isolated enzyme (86% of the isolates produced OXA-23) followed by OXA-51 and NDM. The overall mortality was high (58%). On univariate analysis, pneumonia, and higher Pitt's bacteremia score were significantly associated with mortality ( p = 0.04 and p = 0.001 respectively). Of the total patients who received combination therapy, a majority (58%) received polymyxin plus meropenem. Combination therapy using polymyxins as a backbone was not associated with reduced mortality ( p = 0.1). Conclusion A. baumannii is associated with significant morbidity and mortality, as shown in our study. The rates of resistance for aminoglycosides were very high, and minocycline showed better susceptibility rates in comparison with tigecycline. In our study, OXA-23 and NDM remained the most important enzymes. The routine use of the combination of polymyxin and meropenem may not offer a significant advantage over monotherapy. How to cite this article Prayag PS, Patwardhan SA, Joshi RS, Panchakshari SP, Rane T, Prayag AP. Enzyme Patterns and Factors Associated with Mortality among Patients with Carbapenem Resistant Acinetobacter Baumannii (CRAB) Bacteremia: Real World Evidence from a Tertiary Center in India. Indian J Crit Care Med 2023;27(9):663–668.

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Section: Discussionmentioning

confidence: 99%

Enzyme Patterns and Factors Associated with Mortality among Patients with Carbapenem Resistant Acinetobacter Baumannii (CRAB) Bacteremia: Real World Evidence from a Tertiary Center in India

Prayag,

Panchakshari,

Patwardhan

et al. 2023

Indian Journal of Critical Care Medicine

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A systematic review and individual bacterial species level meta-analysis of in vitro studies on the efficacy of ceftazidime/avibactam combined with other antimicrobials against carbapenem-resistant Gram-negative bacteria

Assefa,

Roberts,

Aslan

et al. 2024

Journal of Antimicrobial Chemotherapy

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Background Carbapenem-resistant Gram-negative bacteria (CR-GNB) develop resistance to many antimicrobials. To effectively manage infections caused by these organisms, novel agents and/or combinations of antimicrobials are required. Objectives Evaluated the in vitro efficacy of ceftazidime/avibactam in combination with other antimicrobials against CR-GNB. Methods PubMed, Web of Science, Embase and Scopus were searched. Study outcomes were quantified by counting the number of isolates exhibiting synergy, defined as a fractional inhibitory concentration index ≤ 0.5 for checkerboard and Etest, and a >2 log cfu/mL reduction for time-kill studies. The proportion of synergy was calculated as the ratio of isolates exhibiting synergy to the total number of isolates tested. These proportions were analysed using a random-effects model, following the Freeman–Tukey double-arcsine transformation. Results Forty-five in vitro studies were included. A total of 734 isolates were tested, and 69.3% of them were resistant to ceftazidime/avibactam. The combination of ceftazidime/avibactam with aztreonam showed a high synergy rate against carbapenem-resistant Klebsiella pneumoniae (effect size, ES = 0.91–0.98) and Escherichia coli (ES = 0.75–1.00). Ceftazidime/avibactam also demonstrated a high synergy rate (ES = 1) in time-kill studies when combined with azithromycin, fosfomycin and gentamicin against K. pneumoniae. Compared to ceftazidime/avibactam alone, a higher bactericidal rate was reported when ceftazidime/avibactam was combined with other antimicrobials against carbapenem-resistant K. pneumoniae (57% versus 31%) and E. coli (93% versus 0%). Conclusions Ceftazidime/avibactam frequently demonstrates synergistic bactericidal activity when combined with various antimicrobials against CR-GNB in in vitro tests. Further pre-clinical and clinical studies are warranted to validate the utility of ceftazidime/avibactam-based combination regimens for CR-GNB infections.

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Nosocomial transmission of tet(x3), blaNDM-1 and blaOXA-97-carrying Acinetobacter baumannii conferring resistance to eravacycline and omadacycline, the Netherlands, March to August 2021

Talsma,

Monteiro,

Flores-Vallejo

et al. 2024

Eurosurveillance

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Carbapenem-resistant Acinetobacter baumannii (CRAb) is an important pathogen causing serious nosocomial infections. We describe an outbreak of CRAb in an intensive care unit in the Netherlands in 2021. During an outbreak of non-resistant A. baumannii, while infection control measures were in place, CRAb isolates carrying highly similar bla NDM-1 - and tet(x3)-encoding plasmids were isolated from three patients over a period of several months. The chromosomal and plasmid sequences of the CRAb and non-carbapenemase-carrying A. baumannii isolates cultured from patient materials were analysed using hybrid assemblies of short-read and long-read sequences. The CRAb isolates revealed that the CRAb outbreak consisted of two different strains, carrying similar plasmids. The plasmids contained multiple antibiotic resistance genes including the tetracycline resistance gene tet(x3), and the bla NDM-1 and bla OXA-97 carbapenemase genes. We determined minimal inhibitory concentrations (MICs) for 13 antibiotics, including the newly registered tetracycline antibiotics eravacycline and omadacycline. The CRAb isolates showed high MICs for tetracycline antibiotics including eravacycline and omadacycline, except for minocycline which had a low MIC. In this study we show the value of sequencing multidrug-resistant A. baumannii for outbreak tracking and guiding outbreak mitigation measures.

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Enhanced bacterial killing with a combination of sulbactam/minocycline against dual carbapenemase-producing Acinetobacter baumannii

Cited by 5 publications

References 24 publications

Enzyme Patterns and Factors Associated with Mortality among Patients with Carbapenem Resistant Acinetobacter Baumannii (CRAB) Bacteremia: Real World Evidence from a Tertiary Center in India

Enzyme Patterns and Factors Associated with Mortality among Patients with Carbapenem Resistant Acinetobacter Baumannii (CRAB) Bacteremia: Real World Evidence from a Tertiary Center in India

A systematic review and individual bacterial species level meta-analysis of in vitro studies on the efficacy of ceftazidime/avibactam combined with other antimicrobials against carbapenem-resistant Gram-negative bacteria

Nosocomial transmission of tet(x3), blaNDM-1 and blaOXA-97-carrying Acinetobacter baumannii conferring resistance to eravacycline and omadacycline, the Netherlands, March to August 2021

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