Antibiotics Resistance and Molecular Epidemiology of Carbapenem-Resistance Bacteria

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 7365

Special Issue Editors

Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Interests: enzymes; PCR; microbiology; cloning; biochemistry; electrophoresis; SDS-PAGE; protein expression; next generation sequencing; antibiotic resistance
Special Issues, Collections and Topics in MDPI journals
Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Interests: molecular and epidemiological characterization of mechanisms of resistance to antibiotics in Gram-negatove pathogens; mobile genetic elements; beta-lactamases; beta-lactamase inhibitors; mechanisms of serine- and metallo-beta-lactamases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The evolution and spread of antibiotic-resistant pathogens has emerged as one of the most important public health problems worldwide over the preceding decades. In the scenario unfolding, the spread of carbapenem-resistant and multi-drug-resistant infections is limiting therapeutic options and increasing hospital stay, healthcare costs, morbidity, and mortality. Among Gram-negative bacteria, Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii are the main emergent pathogens. In these species, resistance may affect all major classes of antimicrobial agents. This even includes carbapenems, our “last line” of defence against difficult infections. Many of these organisms harbor antibiotic-resistant genes (ARGs), eventually being inserted into genetic mobile platforms (plasmids, transposons, integrons) able to move between different DNA molecules and transfer the genetic determinants in different bacteria species. Carbapenem-resistant Gram-negative bacteria are listed by the World Health Organization as pathogens with critical priority for the development of new drugs. Currently, several new drugs and combinations, as well as old, revived drugs, have been used for the treatment of infections due to the emergence of carbapenem-resistant pathogens. The surveillance of antimicrobial resistance is critical to providing early warning of emerging problems, monitoring changing patterns of resistance, and targeting and evaluating prevention and control measures. Epidemiological data are of primary importance to eventually identify new emerging resistance determinants in order to adapt the antibiotic usage at the local level with the aim of limiting therapeutic failures.

In this Special Issue, original research articles and reviews are welcome. Research areas may include, but are not limited to, the following:

  • Molecular epidemiology of multi-drug-resistant Gram-negative bacteria
  • Diagnostics of mobile genetic elements with innovative molecular approaches
  • Role of beta-lactamases in carbapenem resistance

I look forward to receiving your contributions.

Dr. Alessandra Piccirilli
Prof. Dr. Mariagrazia Perilli
Guest Editors

Manuscript Submission Information

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Keywords

  • Carbapenems
  • carbapenemases
  • gram-negative
  • multi-drug resistant (MDR)
  • enterobacterales
  • Acinetobacter baumannii
  • Pseudomonas aeruginosa
  • Antimicrobial resistance
  • mobile genetic elements

Published Papers (7 papers)

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Research

11 pages, 1201 KiB  
Article
Interhospital Spread of blaVIM-1- and blaCTX-M-15-Producing K. pneumoniae ST15 on an IncR Plasmid in Southern Spain
Antibiotics 2023, 12(12), 1727; https://doi.org/10.3390/antibiotics12121727 - 13 Dec 2023
Viewed by 766
Abstract
In 2014–2015, the main CTX-M-15- and OXA-48-producing clone in our region was ST15. Recently, K. pneumoniae ST15 isolates co-producing VIM-1 and CTX-M-15 were detected in several hospitals. The aim was to study the emergence and acquisition of this carbapenemase. Between 2017 and 2019, [...] Read more.
In 2014–2015, the main CTX-M-15- and OXA-48-producing clone in our region was ST15. Recently, K. pneumoniae ST15 isolates co-producing VIM-1 and CTX-M-15 were detected in several hospitals. The aim was to study the emergence and acquisition of this carbapenemase. Between 2017 and 2019, four hospitals submitted twenty-nine VIM-1- and CTX-M-15-producing K. pneumoniae ST15 isolates to our laboratory. Seven representatives of each XbaI PFGE pulsotype were sequenced using short- and long-read technologies. RAST, CGE databases, and Pathogenwatch were used for resistance determinants and capsule-type analysis. Plasmid comparison was performed with Easyfig2.1. Phylogenetic analysis included other contemporary ST15 isolates from Spain. The 29 isolates were clustered into seven different pulsotypes. The selected genomes, from three hospitals in two different provinces, were clustered together (fewer than 35 alleles) and differed by more than 100 alleles from other ST15 isolates obtained in the region. These seven isolates harbored one IncR plasmid (200–220 kb) with a common backbone and four regions flanked by IS26: one contained blaVIM-1, another contained blaCTX-M-15, the third contained blaOXA-1, and the fourth harbored heavy-metal-tolerance genes. The two initial plasmids, from two different centers, were identical, and rearrangement of four regions was observed in the five subsequent plasmids. Our findings showed the first intercenter dissemination of IncR plasmids carrying blaVIM-1, blaCTX-M-15, and metal-tolerance genes mediated by a new lineage of K. pneumoniae ST15. Two different capture events of the blaVIM-1 gene or different IS26-mediated plasmid rearrangements from a common ancestor may explain plasmid variations. Full article
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13 pages, 962 KiB  
Article
Identification of IncA Plasmid, Harboring blaVIM-1 Gene, in S. enterica Goldcoast ST358 and C. freundii ST62 Isolated in a Hospitalized Patient
Antibiotics 2023, 12(12), 1659; https://doi.org/10.3390/antibiotics12121659 - 25 Nov 2023
Viewed by 761
Abstract
In the present study, we analyzed the genome of two S. enterica strains TS1 and TS2 from stool and blood cultures, respectively, and one strain of C. freundii TS3, isolated from a single hospitalized patient with acute myeloid leukemia. The S. enterica Goldcoast [...] Read more.
In the present study, we analyzed the genome of two S. enterica strains TS1 and TS2 from stool and blood cultures, respectively, and one strain of C. freundii TS3, isolated from a single hospitalized patient with acute myeloid leukemia. The S. enterica Goldcoast ST358 (O:8 (C2-C3) serogroup), sequenced by the MiSeq Illumina system, showed the presence of β-lactamase genes (blaVIM-1, blaSHV-12 and blaOXA-10), aadA1, ant(2″)-Ia, aac(6′)-Iaa, aac(6′)-Ib3, aac(6′)-Ib-cr, qnrVC6, parC(T57S), and several incompatibility plasmids. A wide variety of insertion sequences (ISs) and transposon elements were identified. In C. freundii TS3, these were the blaVIM-1, blaCMY-150, and blaSHV-12, aadA1, aac(6′)-Ib3, aac(6′)-Ib-cr, mph(A), sul1, dfrA14, ARR-2, qnrVC6, and qnrB38. IncA plasmid isolated from E.coli/K12 transconjugant and C. freundii exhibited a sequence identity >99.9%. The transfer of IncA plasmid was evaluated by conjugation experiments. Full article
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12 pages, 591 KiB  
Article
Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study
Antibiotics 2023, 12(11), 1619; https://doi.org/10.3390/antibiotics12111619 - 11 Nov 2023
Viewed by 963
Abstract
Background: Pseudomonas aeruginosa shows resistance to several antibiotics and often develops such resistance during patient treatment. Objective: Develop an in vitro model, using clinical isolates of P. aeruginosa, to compare the ability of the imipenem and imipenem/relebactam to generate resistant mutants to [...] Read more.
Background: Pseudomonas aeruginosa shows resistance to several antibiotics and often develops such resistance during patient treatment. Objective: Develop an in vitro model, using clinical isolates of P. aeruginosa, to compare the ability of the imipenem and imipenem/relebactam to generate resistant mutants to imipenem and to other antibiotics. Perform a genotypic analysis to detect how the selective pressure changes their genomes. Methods: The antibiotics resistance was studied by microdilution assays and e-test, and the genotypic study was performed by NGS. Results: The isolates acquired resistance to imipenem in an average of 6 days, and to imipenem/relebactam in 12 days (p value = 0.004). After 30 days of exposure, 75% of the isolates reached a MIC > 64 mg/L for imipenem and 37.5% for imipenem/relebactam (p value = 0.077). The 37.5% and the 12.5% imipenem/relebactam mutants developed resistance to piperacillin/tazobactam and ceftazidime, respectively, while the 87.5% and 37.5% of the imipenem mutants showed resistance to these drugs (p value = 0.003, p value = 0.015). The main biological processes altered by the SNPs were the glycosylation pathway, transcriptional regulation, histidine kinase response, porins, and efflux pumps. Discussion: The addition of relebactam delays the generation of resistance to imipenem and limits the cross-resistance to other beta-lactams. The clinical relevance of this phenomenon, which has the limitation that it has been performed in vitro, should be evaluated by stewardship programs in clinical practice, as it could be useful in controlling multi-drug resistance in P. aeruginosa. Full article
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14 pages, 3292 KiB  
Article
Prevalence of Carbapenem Resistance Genes among Acinetobacter baumannii Isolated from a Teaching Hospital in Taiwan
Antibiotics 2023, 12(9), 1357; https://doi.org/10.3390/antibiotics12091357 - 23 Aug 2023
Viewed by 1032
Abstract
The problem of antibiotic-resistant strains has become a global public issue; antibiotic resistance not only limits the choice of treatments but also increases morbidity, mortality and treatment costs. The multi-drug resistant Acinetobacter baumannii is occurring simultaneously in hospitals and has become a major [...] Read more.
The problem of antibiotic-resistant strains has become a global public issue; antibiotic resistance not only limits the choice of treatments but also increases morbidity, mortality and treatment costs. The multi-drug resistant Acinetobacter baumannii is occurring simultaneously in hospitals and has become a major public health issue worldwide. Although many medical units have begun to control the use of antibiotics and paid attention to the issue of drug resistance, understanding the transmission pathways of clinical drug-resistant bacteria and drug-resistant mechanisms can be effective in real-time control and prevent the outbreak of antibiotic-resistant pathogens. In this study, a total of 154 isolates of Acinetobacter baumannii obtained from Chia-Yi Christian Hospital in Taiwan were collected for specific resistance genotyping analysis. Ten genes related to drug resistance, including blaOXA-51-like, blaOXA-23-like, blaOXA-58-like, blaOXA-24-like, blaOXA-143-like, tnpA, ISAba1, blaPER-1, blaNDM and blaADC, and the repetitive element (ERIC2) were selected for genotyping analysis. The results revealed that 135 A. baumannii isolates (87.6%) carried the blaOXA-51-like gene, 4.5% of the isolates harbored the blaOXA-23-like gene, and 3.2% of the isolates carried the blaOXA-58-like gene. However, neither the blaOXA-24-like nor blaOXA-143-like genes were detected in the isolates. Analysis of ESBL-producing strains revealed that blaNDM was not found in the test strains, but 38.3% of the test isolates carried blaPER-1. In addition, blaADC, tnpA and ISAba1genes were found in 64.9%, 74% and 93% of the isolates, respectively. Among the carbapenem-resistant strains of A. baumannii, 68% of the isolates presenting a higher antibiotic resistance carried both tnpA and ISAba1 genes. Analysis of the relationship between their phenotypes (antibiotic resistant and biofilm formation) and genotypes (antibiotic-resistant genes and biofilm-related genes) studied indicated that the bap, ompA, ISAba1and blaOXA-51 genes influenced biofilm formation and antibiotic resistance patterns based on the statistical results of a hierarchical clustering dendrogram. The analysis of the antibiotic-resistant mechanism provides valuable information for the screening, identification, diagnosis, treatment and control of clinical antibiotic-resistant pathogens, and is an important reference pointer to prevent strains from producing resistance. Full article
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12 pages, 316 KiB  
Article
Carbapenem-Resistant Gram-Negative Bacilli Characterization in a Tertiary Care Center from El Bajio, Mexico
Antibiotics 2023, 12(8), 1295; https://doi.org/10.3390/antibiotics12081295 - 08 Aug 2023
Viewed by 1273
Abstract
Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a major public health concern. We aimed to evaluate the prevalence of CR-GNB and the frequency of carbapenemase-encoding genes in a tertiary referral center from El Bajio, Mexico. A cross-sectional study was conducted between January and October 2022; [...] Read more.
Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a major public health concern. We aimed to evaluate the prevalence of CR-GNB and the frequency of carbapenemase-encoding genes in a tertiary referral center from El Bajio, Mexico. A cross-sectional study was conducted between January and October 2022; Gram-negative bacilli (GNB) were screened for in vitro resistance to at least one carbapenem. CR-GNB were further analyzed for carbapenemase-production through phenotypical methods and by real-time PCR for the following genes: blaKPC, blaGES, blaNDM, blaVIM, blaIMP, and blaOXA-48. In total, 37 out of 508 GNB were carbapenem-resistant (7.3%, 95% CI 5.2–9.9). Non-fermenters had higher rates of carbapenem resistance than Enterobacterales (32.5% vs. 2.6%; OR 18.3, 95% CI 8.5–39, p < 0.0001), and Enterobacter cloacae showed higher carbapenem resistance than other Enterobacterales (27% vs. 1.4%; OR 25.9, 95% CI 6.9–95, p < 0.0001). Only 15 (40.5%) CR-GNB had a carbapenemase-encoding gene; Enterobacterales were more likely to have a carbapenemase-encoding gene than non-fermenters (63.6% vs. 30.8%, p = 0.08); blaNDM-1 and blaNDM-5 were the main genes found in Enterobacterales; and blaIMP-75 was the most common for Pseudomonas aeruginosa. The mcr-2 gene was harbored in one polymyxin-resistant E. cloacae. In our setting, NDM was the most common carbapenemase; however, less than half of the CR-GNB showed a carbapenemase-encoding gene. Full article
11 pages, 981 KiB  
Article
Whole-Genome Sequencing and Molecular Analysis of Ceftazidime–Avibactam-Resistant KPC-Producing Klebsiella pneumoniae from Intestinal Colonization in Elderly Patients
Antibiotics 2023, 12(8), 1282; https://doi.org/10.3390/antibiotics12081282 - 03 Aug 2023
Viewed by 870
Abstract
Ceftazidime–avibactam (CAZ-AVI) is an active antibiotic combination of a β-lactam–β-lactamase inhibitor against carbapenemase-producing Enterobacterales. Reports of resistance to CAZ-AVI other than metallo-β-lactamases have increased in recent years. The aim of this study was to analyze KPC-Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI [...] Read more.
Ceftazidime–avibactam (CAZ-AVI) is an active antibiotic combination of a β-lactam–β-lactamase inhibitor against carbapenemase-producing Enterobacterales. Reports of resistance to CAZ-AVI other than metallo-β-lactamases have increased in recent years. The aim of this study was to analyze KPC-Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI from the intestinal carriage of hospitalized elderly patients in Italy, in February 2018–January 2020. Characterization of CAZ-AVI-resistant KP isolates, including MLST, resistome, virulome and plasmid content, was performed by WGS analysis. Out of six CAZ-AVI-resistant KP isolates, three belonged to ST101 and three to ST512; two isolates produced KPC-3 (both ST512), four had mutated KPC-3 (KPC-31, in ST101 and ST512, and KPC-46, both ST101). All CAZ-AVI-resistant KP isolates were multidrug-resistant and carried several resistance genes. The yersiniabactin ybt9 gene cluster was present in all ST101 isolates, while, in ST512 isolates, no virulence genes were detected. Several plasmids were detected: IncF was present in all isolates, as well as IncR and Col440 in ST101 and IncX3 in ST512 isolates. In conclusion, it is important to monitor the circulation of K. pneumoniae resistant to CAZ-AVI to prevent the spread of clones causing difficult-to-treat infections. The presence of mutated KPC-3 in high-risk K. pneumoniae clones resistant to CAZ-AVI in hospitalized patients deserves attention. Full article
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9 pages, 1171 KiB  
Communication
Emergence of Carbapenem-Resistant Gram-Negative Isolates in Hospital Settings in Djibouti
Antibiotics 2023, 12(7), 1132; https://doi.org/10.3390/antibiotics12071132 - 30 Jun 2023
Cited by 1 | Viewed by 1173
Abstract
Introduction: The antimicrobial resistance (AMR) of bacteria is increasing rapidly against all classes of antibiotics, with the increasing detection of carbapenem-resistant isolates. However, while growing prevalence has been reported around the world, data on the prevalence of carbapenem resistance in developing countries [...] Read more.
Introduction: The antimicrobial resistance (AMR) of bacteria is increasing rapidly against all classes of antibiotics, with the increasing detection of carbapenem-resistant isolates. However, while growing prevalence has been reported around the world, data on the prevalence of carbapenem resistance in developing countries are fairly limited. In this study, we investigated and determined the resistance rate to carbapenems among multidrug-resistant Gram-negative bacteria (MDR-GNB) isolated in Djibouti and characterized their resistance mechanisms. Results: Of the 256 isolates, 235 (91.8%) were identified as Gram-negative bacteria (GNB). Of these GNBs, 225 (95.7%) isolates exhibited a multidrug resistance phenotype, and 20 (8.5%) isolates were resistant to carbapenems, including 13 Escherichia coli, 4 Acinetobacter baumannii, 2 Klebsiella pneumoniae and 1 Proteus mirabilis. The most predominant GNB in this hospital setting were E. coli and K. pneumoniae species. Carbapenemase genes such as blaOXA-48 and blaNDM-5 were identified, respectively, in six and four E. coli isolates, whereas the carbapenemase blaNDM-1 was identified in three E. coli, two K. pneumoniae, one P. mirabilis and one A. baumannii. Moreover, three A. baumannii isolates co-hosted blaOXA-23 and blaNDM-1. Materials and Methods: A total of 256 clinical strains collected between 2019 and 2020 were identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Antibiotic susceptibility testing was performed using disk diffusion and E-test methods. Real-time polymerase chain reaction (RT-PCR), standard PCR and sequencing were used to investigate genes encoding for extended-spectrum-β-lactamases, carbapenemases and colistin resistance genes. Conclusions: We report, for the first time, the presence of MDR-GNB clinical isolates and the emergence of carbapenem-resistant isolates in Djibouti. In addition to performing antimicrobial susceptibility testing, we recommend phenotypic and molecular screening to track the spread of carbapenemase genes among clinical GNB isolates. Full article
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