Approaches to Navigating Multi-Drug Resistance in Gram-Negative Pathogens

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

Deadline for manuscript submissions: 31 July 2024 | Viewed by 10421

Special Issue Editors


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Guest Editor
1. Department of Pharmacy Practice, School of Pharmacy, Loma Linda University, Loma Linda, CA, USA
2. Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, USA
Interests: antibiotic treatment; antibiotic resistance

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Guest Editor
Division of Host-Microbe Systems and Therapeutics, University of California-San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA
Interests: microbial pathogenesis; antibiotic resistance; novel anti-infective therapeutics; antibacterial; Acinetobacter baumannii
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Special Issue Information

Dear Colleagues,

Gram-negative bacteria, including fermenting (Enterobacterales) and non-fermenting organisms (A. baumannii, P. aeruginosa, S. maltophilia, and B. cepacia) are a public health threat. Gram-negative organisms are often characterized by multiple mechanisms of resistance, resulting in the reduced effectiveness of multiple agents in the current antimicrobial armamentarium, or in multidrug resistance (MDR). While innovative strategies, including antimicrobial combination therapy, have been employed in the treatment of various MDR infections, the preferred treatments have yet to be elucidated. This Special Issue welcomes various submission types, such as perspectives, reviews, case reports, brief reports, and original research papers, that discuss treatment for MDR Gram-negative infections. Potential topics for this Special Issue include, but are not limited to, the following:

  • Mechanisms of resistance in hard-to-treat Gram-negative organisms;
  • Epidemiology of MDR or carbapenem-resistant Gram-negative organisms;
  • Combination therapies used in the treatment of MDR Gram-negative organisms;
  • Novel antibiotic pharmacokinetic and pharmacodynamic principles utilized to overcome MDR Gram-negative organisms;
  • Infection prevention methods that are utilized to reduce the spread of MDR Gram-negative organisms in nosocomial settings.

Dr. Jacinda C. Abdul-Mutakabbir
Prof. Dr. Victor Nizet
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • multidrug-resistant pathogens
  • pharmacokinetics
  • pharmacodynamics
  • antibacterial
  • Acinetobacter baumannii
  • difficult to treat pathogens
  • carbapenem-resistant Acinetobacter baumannii

Published Papers (4 papers)

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11 pages, 2087 KiB  
Article
Exploring Roles of the Polysaccharide Capsule in Pathogenesis of Hypervirulent Acinetobacter baumannii Clinical Isolate Lac-4
by Elisabet Bjånes, Truman Koh, Tariq Qayum, Raymond Zurich, Sinead McCabe, Kegan Hampel, Lisa Cartwright and Victor Nizet
Antibiotics 2024, 13(1), 10; https://doi.org/10.3390/antibiotics13010010 (registering DOI) - 20 Dec 2023
Viewed by 1205
Abstract
The frequently multidrug-resistant bacterial pathogen Acinetobacter baumannii is a leading cause of nosocomial infections, including ventilator-associated pneumonia, such that the World Health Organization and US Centers for Disease Control and Prevention have declared it a top priority candidate for novel drug development. Nearly [...] Read more.
The frequently multidrug-resistant bacterial pathogen Acinetobacter baumannii is a leading cause of nosocomial infections, including ventilator-associated pneumonia, such that the World Health Organization and US Centers for Disease Control and Prevention have declared it a top priority candidate for novel drug development. Nearly all clinical A. baumannii strains express a thick surface polysaccharide capsule that protects against desiccation, host defenses, and disinfectants. In this study, we investigated the contribution of the polysaccharide capsule to virulence caused by the A. baumannii clinical isolate Ab Lac-4, which is rare in its ability to cause pneumonia and disseminated sepsis in healthy mice. We assessed the role of the capsule in wildtype Lac-4 (WT) by generating a premature stop codon in wza, which codes for the polysaccharide export protein. The wza# mutant was hypersensitive to killing by complement, whole blood, and healthy human neutrophils compared to WT and a revertant mutant (wza-Rev). Furthermore, the wza# mutant was highly attenuated in murine sepsis and unable to disseminate from the lungs during pneumonia. This study reinforces the capsule as a key contributor to Ab Lac-4 hypervirulence. Full article
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10 pages, 247 KiB  
Article
Colistin Monotherapy versus Colistin plus Sitafloxacin for Therapy of Carbapenem-Resistant Acinetobacter baumannii Infections: A Preliminary Study
by Rujipas Sirijatuphat, Supawas Thawornkaew, Darat Ruangkriengsin and Visanu Thamlikitkul
Antibiotics 2022, 11(12), 1707; https://doi.org/10.3390/antibiotics11121707 - 26 Nov 2022
Cited by 4 | Viewed by 1678
Abstract
The in vitro study of sitafloxacin against carbapenem-resistant (CR) Acinetobacter baumannii demonstrated activity against most strains of CR A. baumannii, and the combination of colistin and sitafloxacin showed an in vitro synergistic effect against CR A. baumannii. This study aimed to [...] Read more.
The in vitro study of sitafloxacin against carbapenem-resistant (CR) Acinetobacter baumannii demonstrated activity against most strains of CR A. baumannii, and the combination of colistin and sitafloxacin showed an in vitro synergistic effect against CR A. baumannii. This study aimed to compare efficacy and safety between colistin plus sitafloxacin with colistin alone for therapy for CR A. baumannii infection. This randomized controlled trial enrolled 56 patients with CR A. baumannii infection (28/group) during 2018–2021, and the treatment duration was 7–14 days. The study outcomes were 28-day mortality, clinical and microbiological responses, and adverse events. There was no significant difference in 28-day mortality between groups (32.1% combination vs. 32.1% monotherapy, p = 1.000). Favorable clinical response at the end of treatment was comparable between groups (81.5% combination vs. 77.8% monotherapy, p = 0.788). Microbiological response at the end of treatment was also comparable between groups (73.1% combination vs. 74.1% monotherapy, p = 0.934). Acute kidney injury was found in 53.8% of the combination group, and in 45.8% of the monotherapy group (p = 0.571). In conclusion, there was no significant difference in 28-day mortality between the colistin monotherapy and the colistin plus sitafloxacin groups. There was also no significant difference in adverse events between groups. Full article
13 pages, 1715 KiB  
Article
A Randomized Controlled Trial of Colistin Combined with Sulbactam: 9 g per Day versus 12 g per Day in the Treatment of Extensively Drug-Resistant Acinetobacter baumannii Pneumonia: An Interim Analysis
by Chutchawan Ungthammakhun, Vasin Vasikasin and Dhitiwat Changpradub
Antibiotics 2022, 11(8), 1112; https://doi.org/10.3390/antibiotics11081112 - 17 Aug 2022
Cited by 4 | Viewed by 3345
Abstract
Extensively drug-resistant A. baumannii (XDRAB) pneumonia has a high mortality rate in hospitalized patients. One of the recommended treatments is colistin combined with sulbactam; however, the optimal dosage of sulbactam is unclear. In an open-label, superiority, randomized controlled trial, patients diagnosed with XDRAB [...] Read more.
Extensively drug-resistant A. baumannii (XDRAB) pneumonia has a high mortality rate in hospitalized patients. One of the recommended treatments is colistin combined with sulbactam; however, the optimal dosage of sulbactam is unclear. In an open-label, superiority, randomized controlled trial, patients diagnosed with XDRAB pneumonia were randomly assigned (1:1) to receive colistin in combination with sulbactam at either 9 g/day or 12 g/day. The primary outcome was the 28-day mortality rate in the intention-to-treat population. A total of 88 patients received colistin in combination with sulbactam at a dosage of either 12 g/day (n = 45) or 9 g/day (n = 43). Trends toward a lower mortality rate were observed in the 12 g/day group at 7 days (11.1% vs. 23.3%), 14 days (33.3% vs. 41.9%), and 28 days (46.7% vs. 58.1%). The microbiological cure rate at day 7 was significantly higher in the 12 g/day group (90.5% vs. 58.1%; p = 0.02). Factors associated with mortality at 28 days were asthma, cirrhosis, APACHEII score ≥ 28, and a dosage of sulbactam of 9 g/day for mortality at any timepoint. Treatment with colistin combined with sulbactam at 12 g/day was not superior to the combination treatment with sulbactam at 9 g/day. However, due to being an interim analysis, this trial was underpowered to detect mortality differences. Full article
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12 pages, 590 KiB  
Systematic Review
Efficacy of Cefoperazone Sulbactam in Patients with Acinetobacter Infections: A Systematic Review of the Literature
by Gowthami Sai Kogilathota Jagirdhar, Kaanthi Rama, Shiva Teja Reddy, Harsha Pattnaik, Rakhtan K. Qasba, Praveen Reddy Elmati, Rahul Kashyap, Marco Schito and Nitin Gupta
Antibiotics 2023, 12(3), 582; https://doi.org/10.3390/antibiotics12030582 - 15 Mar 2023
Cited by 3 | Viewed by 3281
Abstract
Introduction: Acinetobacter baumannii (AB) is a multidrug-resistant pathogen commonly associated with nosocomial infections. The resistance profile and ability to produce biofilm make it a complicated organism to treat effectively. Cefoperazone sulbactam (CS) is commonly used to treat AB, but the associated data are [...] Read more.
Introduction: Acinetobacter baumannii (AB) is a multidrug-resistant pathogen commonly associated with nosocomial infections. The resistance profile and ability to produce biofilm make it a complicated organism to treat effectively. Cefoperazone sulbactam (CS) is commonly used to treat AB, but the associated data are scarce. Methods: We conducted a systematic review of articles downloaded from Cochrane, Embase, PubMed, Scopus, and Web of Science (through June 2022) to study the efficacy of CS in treating AB infections. Our review evaluated patients treated with CS alone and CS in combination with other antibiotics separately. The following outcomes were studied: clinical cure, microbiological cure, and mortality from any cause. Results: We included 16 studies where CS was used for the treatment of AB infections. This included 11 studies where CS was used alone and 10 studies where CS was used in combination. The outcomes were similar in both groups. We found that the pooled clinical cure, microbiological cure, and mortality with CS alone for AB were 70%, 44%, and 20%, respectively. The pooled clinical cure, microbiological cure, and mortality when CS was used in combination with other antibiotics were 72%, 43%, and 21%, respectively. Conclusions: CS alone or in combination needs to be further explored for the treatment of AB infections. There is a need for randomized controlled trials with comparator drugs to evaluate the drug’s effectiveness. Full article
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