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Special Issue "Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria"

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A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: 31 December 2023 | Viewed by 13427

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Special Issue Editor

Dr. Valerie Carabetta

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Guest Editor

Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA
Interests: antibiotic resistance; multidrug resistance; lysine acetylation; KAT; KDAC; histone-like proteins; post-translational modifications; mass spectrometry; proteomics; antimicrobial peptides; biofilm

Special Issue Information

Dear Colleagues,

Infections and mortality caused by Gram-negative bacteria (GNB) are increasing all over the world. Moreover, these types of infections are becoming increasingly more difficult to treat, given the concurrent increase in the prevalence of antibiotic-resistant bacteria. Further compounding this problem is that GNB have a tendency to become resistant to multiple drug classes and are referred to as multidrug-resistant (MDR) GNB, which often leaves physicians with few or no treatment options. GNB possess a plethora of resistance strategies, either intrinsic or acquired, to avoid antibiotic-mediated cell death. Resistance genes and determinants rapidly spread among bacterial populations, which contributes to the rapid emergence MDR strains. Intrinsically, the main weapon of GNB is their cell wall, specifically the outer membrane, which serves as an excellent permeability barrier to drugs and environmental insults. Bacteria can also acquire or evolve resistance to common skin antiseptics and disinfectants, which could contribute to hospital outbreaks of MDR bacteria. Novel strategies to treat and limit the spread of drug-resistant GNB are imperative, and will serve as the primary focus of this Special Issue. This research topic focuses on studies (including original research, methods, perspectives, reviews, and commentaries) that explore and discuss:

New insights into the mechanisms of antibiotic or antiseptic resistance
Determination of novel combinations of drugs to eliminate MDR bacteria
Discovery of novel drug targets for antibiotic development
Evaluation of disinfection practices
Evaluation of the effectiveness of new antibiotics on MDR bacteria
Emergence of new resistance determinants in hospital populations

Dr. Valerie Carabetta
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Antibiotic resistance
Antiseptic resistance
Multidrug resistant
MDR
Efflux pumps
Mechanisms of resistance
Beta-lactamase
Outer membrane

Published Papers (7 papers)

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Research

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Open AccessArticle

Synergistic Activity of Cefiderocol in Combination with Piperacillin-Tazobactam, Fosfomycin, Ampicillin-Sulbactam, Imipenem-Relebactam and Ceftazidime-Avibactam against Carbapenem-Resistant Gram-Negative Bacteria

and

Antibiotics 2023, 12(5), 858; https://doi.org/10.3390/antibiotics12050858 - 05 May 2023

Viewed by 413

Abstract

Limited treatment options are among the main reasons why antimicrobial resistance has become a leading major public health problem. In particular, carbapenem-resistant Enterobacteriales (CRE), Pseudomonas aeruginosa and Acinetobacter baumannii have been included by the World Health Organization (WHO) among the pathogens for which new therapeutic agents are needed. The combination of antibiotics represents an effective strategy to treat multidrug-resistant (MDR) pathogen infections. In this context, the aim of this study is to evaluate the in vitro activity of cefiderocol (CFD) in combination with different antimicrobial molecules against a collection of well-characterized clinical strains, exhibiting different patterns of antimicrobial susceptibility. Clinical strains were genomically characterized using Illumina iSeq100 platform. Synergy analyses were performed by combining CFD with piperacillin-tazobactam (PIP-TAZ), fosfomycin (FOS), ampicillin-sulbactam (AMP-SULB), ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MER-VAB) and imipenem-relebactam (IMI-REL). Our results demonstrated the synergistic effect of CFD in combination with FOS and CAZ-AVI against CRE and carbapenem-resistant Acinetobacter baumannii (CR-Ab) clinical strains owing CFD-resistant profile, while the CFD and AMP-SULB combination was effective against CR-Pa strain displaying AMP-SULB-resistant profile. Moreover, the combination of CAZ-AVI/SULB showed synergistic activity in CAZ-AVI-resistant CRE strain. In conclusion, although further analyses are needed to confirm these results, our work showed the efficacy of CFD when used for synergistic formulations. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria)

Open AccessArticle

Evaluating the Efficacy of Eravacycline and Omadacycline against Extensively Drug-Resistant Acinetobacter baumannii Patient Isolates

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Antibiotics 2022, 11(10), 1298; https://doi.org/10.3390/antibiotics11101298 - 23 Sep 2022

Viewed by 2041

Abstract

For decades, the spread of multidrug-resistant (MDR) Acinetobacter baumannii has been rampant in critically ill, hospitalized patients. Traditional antibiotic therapies against this pathogen have been failing, leading to rising concerns over management options for patients. Two new antibiotics, eravacycline and omadacycline, were introduced to the market and have shown promising results in the treatment of Gram-negative infections. Since these drugs are newly available, there is limited in vitro data about their effectiveness against MDR A. baumannii or even susceptible strains. Here, we examined the effectiveness of 22 standard-of-care antibiotics, eravacycline, and omadacycline against susceptible and extensively drug-resistant (XDR) A. baumannii patient isolates from Cooper University Hospital. Furthermore, we examined selected combinations of eravacycline or omadacycline with other antibiotics against an XDR strain. We demonstrated that this collection of strains is largely resistant to monotherapies of carbapenems, fluoroquinolones, folate pathway antagonists, cephalosporins, and most tetracyclines. While clinical breakpoint data are not available for eravacycline or omadacycline, based on minimum inhibitory concentrations, eravacycline was highly effective against these strains. The aminoglycoside amikacin alone and in combination with eravacycline or omadacycline yielded the most promising results. Our comprehensive characterization offers direction in the treatment of this deadly infection in hospitalized patients. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria)

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Open AccessArticle

Guanidinylated Polymyxins as Outer Membrane Permeabilizers Capable of Potentiating Rifampicin, Erythromycin, Ceftazidime and Aztreonam against Gram-Negative Bacteria

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Antibiotics 2022, 11(10), 1277; https://doi.org/10.3390/antibiotics11101277 - 20 Sep 2022

Cited by 2 | Viewed by 1125

Abstract

Polymyxins are considered a last-line treatment against infections caused by multidrug-resistant (MDR) Gram-negative bacteria. In addition to their use as a potent antibiotic, polymyxins have also been utilized as outer membrane (OM) permeabilizers, capable of augmenting the activity of a partner antibiotic. Several polymyxin derivatives have been developed accordingly, with the objective of mitigating associated nephrotoxicity. The conversion of polymyxins to guanidinylated derivatives, whereby the L-γ-diaminobutyric acid (Dab) amines are substituted with guanidines, are described herein. The resulting guanidinylated colistin and polymyxin B (PMB) exhibited reduced antibacterial activity but preserved OM permeabilizing properties that allowed potentiation of several antibiotic classes. Rifampicin, erythromycin, ceftazidime and aztreonam were particularly potentiated against clinically relevant MDR Gram-negative bacteria. The potentiating effects of guanidinylated polymyxins with ceftazidime or aztreonam were further enhanced by adding the β-lactamase inhibitor avibactam. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria)

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Open AccessEditor’s ChoiceArticle

In Vitro and In Vivo Antimicrobial Activity of the Novel Peptide OMN6 against Multidrug-Resistant Acinetobacter baumannii

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Antibiotics 2022, 11(9), 1201; https://doi.org/10.3390/antibiotics11091201 - 05 Sep 2022

Viewed by 1482

Abstract

The rapid worldwide spread of antimicrobial resistance highlights the significant need for the development of innovative treatments to fight multidrug-resistant bacteria. This study describes the potent antimicrobial activity of the novel peptide OMN6 against a wide array of drug-resistant Acinetobacter baumannii clinical isolates. OMN6 prevented the growth of all tested isolates, regardless of any pre-existing resistance mechanisms. Moreover, in vitro serial-passaging studies demonstrated that no resistance developed against OMN6. Importantly, OMN6 was highly efficacious in treating animal models of lung and blood infections caused by multidrug-resistant A. baumannii. Taken together, these results point to OMN6 as a novel antimicrobial agent with the potential to treat life-threatening infections caused by multidrug-resistant A. baumannii avoiding resistance. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria)

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Open AccessArticle

Evaluating the Effectiveness of Hospital Antiseptics on Multidrug-Resistant Acinetobacter baumannii: Understanding the Relationship between Microbicide and Antibiotic Resistance

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Antibiotics 2022, 11(5), 614; https://doi.org/10.3390/antibiotics11050614 - 03 May 2022

Cited by 5 | Viewed by 1806

Abstract

Acinetobacter baumannii hospital infections are difficult to treat due to the rapid emergence of multidrug-resistant (MDR) strains. In addition, A. baumannii can survive in numerous adverse environments, including in the presence of common hospital antiseptics. We hypothesized that in addition to accumulating drug resistance determinants, MDR A. baumannii strains also accumulate mutations that allow for greater microbicide tolerance when compared to pan-susceptible (PS) strains. To test this hypothesis, we compared the survival of five MDR and five PS patient isolates when exposed to bleach, ethanol, quaternary ammonium compounds, chlorhexidine gluconate, and povidone. We evaluated bacteria in a free-living planktonic state and under biofilm conditions. Each disinfectant eliminated 99.9% of planktonic bacteria, but this was not the case for bacterial biofilms. Next, we characterized strains for the presence of the known microbicide-resistance genes cepA, qacEΔ1, qacE, and qacA. MDR strains did not survive more than PS strains in the presence of microbicides, but microbicide-resistant strains had higher survival rates under some conditions. Interestingly, the PS strains were more likely to possess microbicide-resistance genes. Microbicide resistance remains an important topic in healthcare and may be independent of antimicrobial resistance. Hospitals should consider stricter isolation precautions that take pan-susceptible strains into account. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria)

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Review

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Open AccessReview

Extracellular Vesicles of Pseudomonas: Friends and Foes

Tania Henriquez

and

Chiara Falciani

Antibiotics 2023, 12(4), 703; https://doi.org/10.3390/antibiotics12040703 - 04 Apr 2023

Viewed by 647

Abstract

Extracellular vesicles (Evs) are small spherical vesicles capable of transporting molecules (such as proteins, nucleic acids and lipids) from one cell to another. They have been implicated in processes such as cell-to-cell communication, pathogenicity, biofilm formation and metabolism. In parallel, Evs have been proposed as interesting biotechnological tools. In recent years, antibiotic resistance has become a major problem for human health worldwide. A pathogen singled out as among the most lethal antibiotic-resistant organisms is Pseudomonas aeruginosa, an important Gram-negative bacterium that has been extensively studied for the production and characterization of Evs. Here, we describe the advances made in the last decade regarding understanding of the role of Evs in the pathogenicity of Pseudomonas. We also examine the potential of Evs for the development of new treatment strategies. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria)

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Open AccessReview

Antimicrobial Peptides: From Design to Clinical Application

Chunye Zhang

and

Ming Yang

Antibiotics 2022, 11(3), 349; https://doi.org/10.3390/antibiotics11030349 - 06 Mar 2022

Cited by 27 | Viewed by 4940

Abstract

Infection of multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, brings public health issues and causes economic burden. Pathogenic bacteria develop several methods to resist antibiotic killing or inhibition, such as mutation of antibiotic function sites, activation of drug efflux pumps, and enzyme-mediated drug degradation. Antibiotic resistance components can be transferred between bacteria by mobile genetic elements including plasmids, transposons, and integrons, as well as bacteriophages. The development of antibiotic resistance limits the treatment options for bacterial infection, especially for MDR bacteria. Therefore, novel or alternative antibacterial agents are urgently needed. Antimicrobial peptides (AMPs) display multiple killing mechanisms against bacterial infections, including directly bactericidal activity and immunomodulatory function, as potential alternatives to antibiotics. In this review, the development of antibiotic resistance, the killing mechanisms of AMPs, and especially, the design, optimization, and delivery of AMPs are reviewed. Strategies such as structural change, amino acid substitution, conjugation with cell-penetration peptide, terminal acetylation and amidation, and encapsulation with nanoparticles will improve the antimicrobial efficacy, reduce toxicity, and accomplish local delivery of AMPs. In addition, clinical trials in AMP studies or applications of AMPs within the last five years were summarized. Overall, AMPs display diverse mechanisms of action against infection of pathogenic bacteria, and future research studies and clinical investigations will accelerate AMP application. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria)

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