Carbapenemases in Gram-Negative Bacteria: A Global Health Threat and Therapeutic Challenge

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 3762

Special Issue Editors


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Guest Editor
Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
Interests: b-lactamases; carbapenemase

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Guest Editor
Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals and Geneva University, Geneva, Switzerland
Interests: infectious diseases; bacteriology; AMR; gram-negative; klebsiella pneumoniae

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Guest Editor
1. Medical and Molecular Microbiology, University of Fribourg, Fribourg, Switzerland
2. Food Hygiene and Control, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt
Interests: antibiotic resistance; one health; rapid diagnostics; susceptibility testing; gram negatives; genomics
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Special Issue Information

Dear Colleagues,

The World Health Organization (WHO) has identified antimicrobial resistance (AMR) as a major global public health threat, ranking it among the top ten challenges humanity will face in the next decade. Of particular concern is the rapid rise of AMR coupled with a decline in the development of new antimicrobial drugs. Recently, the WHO published a list of pathogenic bacteria urgently requiring new antimicrobials, with carbapenem-resistant Gram-negative bacterial pathogens, including Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae, placed in the “critical” priority category 1. Among the mechanisms causing carbapenem-resistance, carbapenemase-production stands out as a critical factor, as it confers bacteria with resistance towards classical beta-lactam antibiotics and often occurs in combination with mechanisms causing resistance towards other antibiotic classes. This Special Issue seeks manuscript submissions reporting on the epidemiology of carbapenemase-production in Enterobacterales, P. aeruginosa and A. baumannii, their susceptibility towards novel antimicrobial options as well as towards old antibiotics, alone or in combination with conventional antibacterial compounds. Also being considered for publication are manuscripts reporting on the performance of novel phenotypic and immunological as well molecular detection and characterization methods of carbapenemases, providing crucial insights for the scientific community and healthcare practitioners in the relentless battle against antimicrobial resistance.

Dr. Stefano Mancini
Dr. Diego O. Andrey
Dr. Mustafa Sadek
Guest Editors

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Keywords

  • carbapenemase-producing Enterobacteriaceae (CPE)
  • carbapenemase-producing Pseudomonas aeruginosa (CPPA)
  • carbapenemase-producing Acinetobacter baumannii (CPAB)
  • antimicrobial susceptibility of CPE, CPPA or/and CPAB
  • carbapenemase detection

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Published Papers (2 papers)

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12 pages, 1643 KiB  
Article
Synergistic Combination of Aztreonam and Ceftazidime–Avibactam—A Promising Defense Strategy against OXA-48 + NDM Klebsiella pneumoniae in Romania
by Ioana Miriana Cismaru, Maria Cristina Văcăroiu, Elif Soium, Tiberiu Holban, Adelina Maria Radu, Violeta Melinte and Valeriu Gheorghiță
Antibiotics 2024, 13(6), 550; https://doi.org/10.3390/antibiotics13060550 - 12 Jun 2024
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Abstract
With the increasing burden of carbapenem-resistant Klebsiella pneumoniae (CR-Kp), including high rates of healthcare-associated infections, treatment failure, and mortality, a good therapeutic strategy for attacking this multi-resistant pathogen is one of the main goals in current medical practice and necessitates the use of [...] Read more.
With the increasing burden of carbapenem-resistant Klebsiella pneumoniae (CR-Kp), including high rates of healthcare-associated infections, treatment failure, and mortality, a good therapeutic strategy for attacking this multi-resistant pathogen is one of the main goals in current medical practice and necessitates the use of novel antibiotics or new drug combinations. Objectives: We reviewed the clinical and microbiological outcomes of seven patients treated at the “Agrippa Ionescu” Clinical Emergency Hospital between October 2023 and January 2024, aiming to demonstrate the synergistic activity of the ceftazidime–avibactam (C/A) plus aztreonam (ATM) combination against the co-producers of blaNDM + blaOXA-48-like CR-Kp. Material and Methods: Seven CR-Kp with blaNDM and blaOXA-48 as resistance mechanisms were tested. Seven patients treated with C/A + ATM were included. The synergistic activity of C/A + ATM was proven through double-disk diffusion in all seven isolates. Resistance mechanisms like KPC, VIM, OXA-48, NDM, IMP, and CTX-M were assessed through immunochromatography. Results: With a mean of nine days of treatment with the synergistic combination C/A + ATM, all patients achieved clinical recovery, and five achieved microbiological recovery. Conclusions: With the emerging co-occurrence of blaOXA-48 and blaNDM among Kp in Romania, the combination of C/A and ATM could be a promising therapeutic option. Full article
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7 pages, 647 KiB  
Brief Report
Comparative In Vitro Activity of Ceftazidime-Avibactam, Imipenem-Relebactam, and Meropenem-Vaborbactam against Carbapenem-Resistant Clinical Isolates of Klebsiella pneumoniae and Pseudomonas aeruginosa
by Anthony Sophonsri, Michelle Kalu and Annie Wong-Beringer
Antibiotics 2024, 13(5), 416; https://doi.org/10.3390/antibiotics13050416 - 1 May 2024
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Abstract
Co-infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) is associated with poor outcomes and historically relied on combination therapy with toxic agents for management. However, several novel β-lactam/β-lactamase inhibitor combination agents have been developed, offering potential monotherapy options. Here, we compare [...] Read more.
Co-infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) is associated with poor outcomes and historically relied on combination therapy with toxic agents for management. However, several novel β-lactam/β-lactamase inhibitor combination agents have been developed, offering potential monotherapy options. Here, we compare the in vitro activity of ceftazidime-avibactam (CZA), imipenem-relebactam (IRL), and meropenem-vaborbactam (MVB) against both CRKP and CRPA clinical isolates. Minimum inhibitory concentrations (MICs) for each agent were determined using broth microdilution. Carbapenemase gene detection was performed for representative isolates of varying carbapenem resistance phenotypes. IRL demonstrated excellent activity against CRKP and CRPA with susceptibility rates at 95.8% and 91.7%, respectively. While CZA and MVB showed comparable susceptibility to IRL against CRKP (93.8%), susceptibility of CRPA to CZA was modest at 79.2%, whereas most CRPA strains were resistant to MVB. Of the 35 CRKP isolates tested, 91.4% (32/35) carried a blaKPC gene. Only 1 of 37 (2.7%) CRPA isolates tested carried a blaVIM gene, which conferred phenotypic resistance to all three agents. None of the CRKP strains were cross-resistant to all three agents. Source of infection and co-infection did not significantly influence antimicrobial activity for IRL and CZA; none of the CRPA isolates from co-infected patients were susceptible to MVB. Our results suggest that novel β-lactam agents with antipseudomonal activity and stability against carbapenemases, such as IRL and CZA, offer potential monotherapy options for the treatment of co-infection involving both CRKP and CRPA, but not MVB. Full article
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