Epidemiology and Mechanism of Bacterial Resistance to Antibiotics

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

Deadline for manuscript submissions: 31 March 2025 | Viewed by 11590

Special Issue Editors


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Guest Editor
1. Department of Microbiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
2. Parasitic Disease Department, Colentina Clinical Hospital, 020125 Bucharest, Romania
Interests: infectious diseases; microbiology; antimicrobial resistance; virulence
Special Issues, Collections and Topics in MDPI journals

E-Mail
Guest Editor
1. Department of Microbiology II, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
2. Cantacuzino National Military Medical Institute for Research and Development, 050096 Bucharest, Romania
Interests: infectious diseases; microbiology; chronic infections; bacteriophage; microcalorimetry; tuberculosis; blood-borne pathogens
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antibiotics still play an important role in global public health, especially in the case of infectious disease emergencies. However, the overuse of antibiotics and the decline in infection prevention and measures have accelerated the emergence and dissemination of multi- (MDR), extended- (XDR) and even pan-drug (PDR)-resistant clones. In addition, bacteria acquire drug resistance genes from other resistant bacteria in the environment through horizontal gene transfer mediated by mobile genetic elements such as plasmids, leading to the changes in the environmental resistome with the occurrence of complex resistance and even MDR phenotypes in the extraclinical sectors. In recent decades, the researchers focused not only on the clinical but also on the environmental drug-resistant strains. By utilizing phenotypic and genomic techniques, it is essential to understand the epidemiology of multi-drug-resistant bacteria isolated from human and environmental microbiomes as well as for the development of new and faster diagnostic tools.

In this Special Issue, we welcome papers of phenotypic and molecular epidemiology, diagnostic methods and antibiotic sensitivity with innovative phenotypic and molecular approaches. Submissions addressing the horizontal transfer of antibiotic resistance genes are also welcome.

Prof. Dr. Gabriela Loredana Popa
Prof. Dr. Mircea Ioan Popa
Guest Editors

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Keywords

  • multi-drug resistant (MDR)
  • classic and molecular epidemiology
  • plasmids
  • resistance gene

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Published Papers (6 papers)

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Research

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21 pages, 4269 KiB  
Article
Machine Learning in FTIR Spectrum for the Identification of Antibiotic Resistance: A Demonstration with Different Species of Microorganisms
by Claudia Patricia Barrera Patiño, Jennifer Machado Soares, Kate Cristina Blanco and Vanderlei Salvador Bagnato
Antibiotics 2024, 13(9), 821; https://doi.org/10.3390/antibiotics13090821 - 30 Aug 2024
Viewed by 1064
Abstract
Recent studies introduced the importance of using machine learning algorithms in research focused on the identification of antibiotic resistance. In this study, we highlight the importance of building solid machine learning foundations to differentiate antimicrobial resistance among microorganisms. Using advanced machine learning algorithms, [...] Read more.
Recent studies introduced the importance of using machine learning algorithms in research focused on the identification of antibiotic resistance. In this study, we highlight the importance of building solid machine learning foundations to differentiate antimicrobial resistance among microorganisms. Using advanced machine learning algorithms, we established a methodology capable of analyzing the FTIR structural profile of the samples of Streptococcus pyogenes and Streptococcus mutans (Gram-positive), as well as Escherichia coli and Klebsiella pneumoniae (Gram-negative), demonstrating cross-sectional applicability in this focus on different microorganisms. The analysis focuses on specific biomolecules—Carbohydrates, Fatty Acids, and Proteins—in FTIR spectra, providing a multidimensional database that transcends microbial variability. The results highlight the ability of the method to consistently identify resistance patterns, regardless of the Gram classification of the bacteria and the species involved, reinforcing the premise that the structural characteristics identified are universal among the microorganisms tested. By validating this approach in four distinct species, our study proves the versatility and precision of the methodology used, in addition to bringing support to the development of an innovative protocol for the rapid and safe identification of antimicrobial resistance. This advance is crucial for optimizing treatment strategies and avoiding the spread of resistance. This emphasizes the relevance of specialized machine learning bases in effectively differentiating between resistance profiles in Gram-negative and Gram-positive bacteria to be implemented in the identification of antibiotic resistance. The obtained result has a high potential to be applied to clinical procedures. Full article
(This article belongs to the Special Issue Epidemiology and Mechanism of Bacterial Resistance to Antibiotics)
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11 pages, 779 KiB  
Article
Clinical Outcomes of Patients with AmpC-Beta-Lactamase-Producing Enterobacterales Bacteremia Treated with Carbapenems versus Non-Carbapenem Regimens: A Single-Center Study
by Orjowan Shalabi, Livnat Kashat, Omer Murik, Shoshana Zevin, Marc V. Assous and Eli Ben-Chetrit
Antibiotics 2024, 13(8), 709; https://doi.org/10.3390/antibiotics13080709 - 29 Jul 2024
Viewed by 1025
Abstract
Introduction: Bloodstream infections caused by AmpC-producing Enterobacterales pose treatment challenges due to the risk of AmpC overproduction and treatment failure. Current guidelines recommend carbapenems or cefepime as optimal therapy. We aimed to evaluate empiric and definitive non-carbapenem regimens for these infections. Methods: In [...] Read more.
Introduction: Bloodstream infections caused by AmpC-producing Enterobacterales pose treatment challenges due to the risk of AmpC overproduction and treatment failure. Current guidelines recommend carbapenems or cefepime as optimal therapy. We aimed to evaluate empiric and definitive non-carbapenem regimens for these infections. Methods: In a retrospective study from June 2014 to March 2023, adult bacteremic patients with Enterobacter cloacae complex strains and Morganella morganii were evaluated. Demographic, clinical and lab data and outcomes were assessed. Results: The cohort comprised 120 bacteremic patients, 17 receiving empiric carbapenem and 103 non-carbapenem regimens. Both groups had similar Charlson and Norton scores and previous antimicrobial exposure. The most common sources of bacteremia were urinary, abdominal and central-line-associated sources. Empiric non-carbapenem regimens (primarily piperacillin–tazobactam and cephalosporins) were not associated with recurrent bacteremia or 30-day mortality. Definitive regimens included mainly carbapenems (n = 41) and ciprofloxacin (n = 46). Beta-lactams were administered to 25 patients. Recurrent bacteremia and 30-day mortality rates were similar among treatment groups. Ciprofloxacin showed comparable outcomes to carbapenems, however, severity of illness among these patients was lower. Conclusions: Empiric and definitive non-carbapenem regimens for bacteremia with AmpC-producing organisms were not associated with treatment failure or increased 30-day mortality. Ciprofloxacin appears promising for selected, stable patients, potentially enabling early discharge. Full article
(This article belongs to the Special Issue Epidemiology and Mechanism of Bacterial Resistance to Antibiotics)
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13 pages, 1531 KiB  
Article
Comparative Genomics of an Emerging Multidrug-Resistant blaNDM-Carrying ST182 Lineage in Enterobacter cloacae Complex
by Angeliki Mavroidi, Elisavet Froukala and Athanasios Tsakris
Antibiotics 2024, 13(6), 535; https://doi.org/10.3390/antibiotics13060535 - 8 Jun 2024
Viewed by 2429
Abstract
Background: Enterobacter cloacae, E. hormaechei and related subspecies remain the most clinically relevant among the Enterobacter cloacae complex (ECC). Carbapenemase-producing ECC strains are increasingly identified in hospital-acquired infections and usually belong to four main multilocus sequence types (MLST STs) named ST114, ST93, [...] Read more.
Background: Enterobacter cloacae, E. hormaechei and related subspecies remain the most clinically relevant among the Enterobacter cloacae complex (ECC). Carbapenemase-producing ECC strains are increasingly identified in hospital-acquired infections and usually belong to four main multilocus sequence types (MLST STs) named ST114, ST93, ST90 and ST78. Instead, ST182 has been sporadically reported among E. hormaechei strains, and recently, outbreaks of blaNDM-producing ST182 clonal strains have emerged. Herein, we aimed to investigate the presence of ST182 and explore its evolution and modes of blaNDM acquisition. Methods: A phylogenetic analysis of 646 MLST STs identified among 4685 E. hormaechei whole-genome sequencing (WGS) assemblies deposited in public repositories was performed, as well as an in silico comparative and phylogenomic analyses for 55 WGS assemblies of ST182. blaNDM-harboring contigs were also compared to published plasmid sequences. Results: ST182 E. hormaechei strains were recovered from patients on five continents during 2011–2021. They were divided into three major genomic clusters, comprising a separate clonal complex with six other STs. In 30 out of 55 ST182 WGS assemblies, blaNDM-harboring structures were identified that were similar to the plasmids predominant in Gram-negative bacteria, harboring resistance genes to multiple antibiotic classes and virulence genes. No associations between the genomic clusters and the country/continent of isolation or the presence and the plasmid types of the blaNDM-harboring contigs were observed. Conclusions: Our findings show that ST182 E. hormaechei strains have been identified in the past decade worldwide; 54.5% of them carried diverse blaNDM genetic structures, suggesting recent acquisition of the blaNDM alleles. Thus, blaNDM-harboring ST182 is an emerging multidrug-resistant and virulent lineage in ECC strains that requires close monitoring. Full article
(This article belongs to the Special Issue Epidemiology and Mechanism of Bacterial Resistance to Antibiotics)
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14 pages, 920 KiB  
Article
Synergistic Activity of Temocillin and Fosfomycin Combination against KPC-Producing Klebsiella pneumoniae Clinical Isolates
by Venera Costantino, Luigi Principe, Jai Mehat, Marina Busetti, Alessandra Piccirilli, Mariagrazia Perilli, Roberto Luzzati, Verena Zerbato, Antonietta Meliadò, Roberto La Ragione and Stefano Di Bella
Antibiotics 2024, 13(6), 526; https://doi.org/10.3390/antibiotics13060526 - 4 Jun 2024
Viewed by 1120
Abstract
Infections caused by KPC-producing K. pneumoniae continue to pose a significant clinical challenge due to their emerging resistance to new antimicrobials. We investigated the association between two drugs whose roles have been repurposed against multidrug-resistant bacteria: fosfomycin and temocillin. Temocillin exhibits unusual stability [...] Read more.
Infections caused by KPC-producing K. pneumoniae continue to pose a significant clinical challenge due to their emerging resistance to new antimicrobials. We investigated the association between two drugs whose roles have been repurposed against multidrug-resistant bacteria: fosfomycin and temocillin. Temocillin exhibits unusual stability against KPC enzymes, while fosfomycin acts as a potent “synergizer”. We conducted in vitro antimicrobial activity studies on 100 clinical isolates of KPC-producing K. pneumoniae using a combination of fosfomycin and temocillin. The results demonstrated synergistic activity in 91% of the isolates. Subsequently, we assessed the effect on Galleria mellonella larvae using five genetically different KPC-Kp isolates. The addition of fosfomycin to temocillin increased larvae survival from 73 to 97% (+Δ 32%; isolate 1), from 93 to 100% (+Δ 7%; isolate 2), from 63 to 86% (+Δ 36%; isolate 3), from 63 to 90% (+Δ 42%; isolate 4), and from 93 to 97% (+Δ 4%; isolate 10). Among the temocillin-resistant KPC-producing K. pneumoniae isolates (24 isolates), the addition of fosfomycin reduced temocillin MIC values below the resistance breakpoint in all isolates except one. Temocillin combined with fosfomycin emerges as a promising combination against KPC-producing K. pneumoniae, warranting further clinical evaluation. Full article
(This article belongs to the Special Issue Epidemiology and Mechanism of Bacterial Resistance to Antibiotics)
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Review

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27 pages, 796 KiB  
Review
The Importance of Carbapenemase-Producing Enterobacterales in African Countries: Evolution and Current Burden
by Edgar-Costin Chelaru, Andrei-Alexandru Muntean, Mihai-Octav Hogea, Mădălina-Maria Muntean, Mircea-Ioan Popa and Gabriela-Loredana Popa
Antibiotics 2024, 13(4), 295; https://doi.org/10.3390/antibiotics13040295 - 24 Mar 2024
Cited by 2 | Viewed by 2157
Abstract
Antimicrobial resistance (AMR) is a worldwide healthcare problem. Multidrug-resistant organisms (MDROs) can spread quickly owing to their resistance mechanisms. Although colonized individuals are crucial for MDRO dissemination, colonizing microbes can lead to symptomatic infections in carriers. Carbapenemase-producing Enterobacterales (CPE) are among the most [...] Read more.
Antimicrobial resistance (AMR) is a worldwide healthcare problem. Multidrug-resistant organisms (MDROs) can spread quickly owing to their resistance mechanisms. Although colonized individuals are crucial for MDRO dissemination, colonizing microbes can lead to symptomatic infections in carriers. Carbapenemase-producing Enterobacterales (CPE) are among the most important MDROs involved in colonizations and infections with severe outcomes. This review aimed to track down the first reports of CPE in Africa, describe their dissemination throughout African countries and summarize the current status of CRE and CPE data, highlighting current knowledge and limitations of reported data. Two database queries were undertaken using Medical Subject Headings (MeSH), employing relevant keywords to identify articles that had as their topics beta-lactamases, carbapenemases and carbapenem resistance pertaining to Africa or African regions and countries. The first information on CPE could be traced back to the mid-2000s, but data for many African countries were established after 2015–2018. Information is presented chronologically for each country. Although no clear conclusions could be drawn for some countries, it was observed that CPE infections and colonizations are present in most African countries and that carbapenem-resistance levels are rising. The most common CPE involved are Klebsiella pneumoniae and Escherichia coli, and the most prevalent carbapenemases are NDM-type and OXA-48-type enzymes. Prophylactic measures, such as screening, are required to combat this phenomenon. Full article
(This article belongs to the Special Issue Epidemiology and Mechanism of Bacterial Resistance to Antibiotics)
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27 pages, 1503 KiB  
Review
Pan-Genome Plasticity and Virulence Factors: A Natural Treasure Trove for Acinetobacter baumannii
by Theodoros Karampatakis, Katerina Tsergouli and Payam Behzadi
Antibiotics 2024, 13(3), 257; https://doi.org/10.3390/antibiotics13030257 - 14 Mar 2024
Cited by 7 | Viewed by 2960
Abstract
Acinetobacter baumannii is a Gram-negative pathogen responsible for a variety of community- and hospital-acquired infections. It is recognized as a life-threatening pathogen among hospitalized individuals and, in particular, immunocompromised patients in many countries. A. baumannii, as a member of the ESKAPE group, encompasses [...] Read more.
Acinetobacter baumannii is a Gram-negative pathogen responsible for a variety of community- and hospital-acquired infections. It is recognized as a life-threatening pathogen among hospitalized individuals and, in particular, immunocompromised patients in many countries. A. baumannii, as a member of the ESKAPE group, encompasses high genomic plasticity and simultaneously is predisposed to receive and exchange the mobile genetic elements (MGEs) through horizontal genetic transfer (HGT). Indeed, A. baumannii is a treasure trove that contains a high number of virulence factors. In accordance with these unique pathogenic characteristics of A. baumannii, the authors aim to discuss the natural treasure trove of pan-genome and virulence factors pertaining to this bacterial monster and try to highlight the reasons why this bacterium is a great concern in the global public health system. Full article
(This article belongs to the Special Issue Epidemiology and Mechanism of Bacterial Resistance to Antibiotics)
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