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Antibiotics
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Antibiotics Resistance in Gram-Negative Bacteria
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Antibiotics Resistance in Gram-Negative Bacteria

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

Deadline for manuscript submissions: closed (8 August 2022) | Viewed by 38065

Special Issue Editor

Prof. Dr. Simone Simionatto

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Guest Editor
Laboratório de Pesquisa em Ciências da Saúde, Universidade Federal da Grande Dourados-UFGD, Dourados, Mato Grosso do Sul, Brazil
Interests: antibiotic resistance; molecular epidemiology of Gram-negative bacteria; antimicrobial effects of natural products on bacteria; antisense therapy; drug repositioning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antimicrobial resistance has been recognized as one of the most serious global threats to human health. The ability of Gram-negative bacteria to acquire resistance to antimicrobials via horizontal gene transfer and mutation is a real threat to and burden on the health and economy. Even though they are most commonly detected in hospital settings, multidrug-resistant Gram-Negative bacteria have also been described in other ecological niches. The epidemiology of Gram-negative bacteria is complex, and the importance of an integrated surveillance system based on the One Health approach has been widely recognized. The use of antimicrobials in medicine, agriculture, and livestock has favored the selection of these pathogens. Additionally, increases in hospitalization and the indiscriminate use of antimicrobials during the COVID-19 pandemic may have contributed to increased rates of multidrug-resistant Gram-negative bacteria. Thus, the effects of antimicrobial resistance in public health and in the economy in the short and medium term are enormous. Efforts must focus on implementing new policies and control programs on how to use and dispense antibiotics. Furthermore, understanding resistance mechanisms and epidemiology is critical for the development of the novel antibacterial products needed to meet future demands. This Special Issue invites manuscript submissions that further our understanding of antimicrobial resistance in Gram-negative bacteria. Submissions on the search for new drugs developed through structural modification agents, production of synthetic derivatives, or repositioning are especially encouraged.

Prof. Dr. Simone Simionatto
Guest Editor

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Keywords

  • antimicrobial resistance
  • epidemiology
  • genomics
  • one-Health
  • enterobacteriaceae
  • multidrug resistance

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Published Papers (7 papers)

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Research

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16 pages, 905 KiB  
Article
Predictive Score for Carbapenem-Resistant Gram-Negative Bacilli Sepsis: Single-Center Prospective Cohort Study
by Marisa Zenaide Ribeiro Gomes, Douglas Quintanilha Braga, Debora Otero Britto Passos Pinheiro, Renata Cristina Amorim Silveira Verduc, Letícia Vellozo dos Reis, Elisangela Martins de Lima, Newton Dias Lourenço, Patrícia Aquen Cid, Debora Souza Beck, Luiz Henrique Zanata Pinheiro, João Pedro Silva Tonhá, Luiza Silva de Sousa, Mayra Lopes Secundo Dias, Amanda Aparecida da Silva Machado, Murillo Marçal Castro, Vitoria Pinson Ruggi Dutra, Luciana Sênos de Mello, Maxuel Cassiano da Silva, Thaisa Medeiros Tozo, Yann Rodrigues Mathuiy, Lucas Lameirão Pinto de Abreu Rosas, Paulo Cesar Mendes Barros, Jeane Oliveira da Silva, Priscila Pinho da Silva, Carolina Souza Bandeira, Scyla Maria de Sant′Anna Reis Di Chiara Salgado, Marcio Zenaide de Oliveira Alves, Roberto Queiroz Santos, José Aurélio Marques, Caio Augusto Santos Rodrigues and Saint Clair dos Santos Gomes Junioradd Show full author list remove Hide full author list
Antibiotics 2023, 12(1), 21; https://doi.org/10.3390/antibiotics12010021 - 23 Dec 2022
Cited by 1 | Viewed by 2120
Abstract
A clinical–epidemiological score to predict CR-GNB sepsis to guide empirical antimicrobial therapy (EAT), using local data, persists as an unmet need. On the basis of a case–case–control design in a prospective cohort study, the predictive factors for CR-GNB sepsis were previously determined as [...] Read more.
A clinical–epidemiological score to predict CR-GNB sepsis to guide empirical antimicrobial therapy (EAT), using local data, persists as an unmet need. On the basis of a case–case–control design in a prospective cohort study, the predictive factors for CR-GNB sepsis were previously determined as prior infection, use of mechanical ventilation and carbapenem, and length of hospital stay. In this study, each factor was scored according to the logistic regression coefficients, and the ROC curve analysis determined its accuracy in predicting CR-GNB sepsis in the entire cohort. Among the total of 629 admissions followed by 7797 patient-days, 329 single or recurrent episodes of SIRS/sepsis were enrolled, from August 2015 to March 2017. At least one species of CR-GNB was identified as the etiology in 108 (33%) episodes, and 221 were classified as the control group. The cutoff point of ≥3 (maximum of 4) had the best sensitivity/specificity, while ≤1 showed excellent sensitivity to exclude CR-GNB sepsis. The area under the curve was 0.80 (95% CI: 0.76–0.85) and the number needed to treat was 2.0. The score may improve CR-GNB coverage and spare polymyxins with 22% (95% CI: 17–28%) adequacy rate change. The score has a good ability to predict CR-GNB sepsis and to guide EAT in the future. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria)
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20 pages, 2487 KiB  
Article
Characterisation of Non-Carbapenemase-Producing Carbapenem-Resistant Klebsiella pneumoniae Based on Their Clinical and Molecular Profile in Malaysia
by Yee Qing Lee, Sasheela Sri La Sri Ponnampalavanar, Chun Wie Chong, Rina Karunakaran, Kumutha Malar Vellasamy, Kartini Abdul Jabar, Zhi Xian Kong, Min Yi Lau and Cindy Shuan Ju Teh
Antibiotics 2022, 11(11), 1670; https://doi.org/10.3390/antibiotics11111670 - 21 Nov 2022
Cited by 5 | Viewed by 2372
Abstract
Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia [...] Read more.
Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia from January 2013 to October 2019. During the study period, 54 NC-CRKP-infected/colonised patients’ isolates were obtained. Clinical parameters were assessed in 52 patients. The all-cause in-hospital mortality rate among NC-CRKP patients was 46.2% (24/52). Twenty-three (44.2%) patients were infected, while others were colonised. Based on the Charlson Comorbidity Index (CCI) score, 92.3% (48/52) of the infected/colonised patients had a score of ≥ 1. Resistance genes found among the 54 NC-CRKP isolates were blaTEM, blaSHV, blaCTX-M, blaOXA, and blaDHA. Porin loss was detected in 25/54 (46.3%) strains. None of the isolated strains conferred carbapenem resistance through the efflux pumps system. In conclusion, only 25/54 (46.3%) NC-CRKP conferred carbapenem resistance through a combination of porin loss and the acquisition of non-carbapenemase resistance mechanisms. The carbapenem resistance mechanisms for the remaining strains (53.7%) should be further investigated as rapid identification and distinction of the NC-CRKP mechanisms enable optimal treatment and infection control efforts. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria)
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13 pages, 1070 KiB  
Article
Prevalence and Molecular Mechanisms of Carbapenem Resistance among Gram-Negative Bacilli in Three Hospitals of Northern Lebanon
by Mariam Rima, Saoussen Oueslati, Laura Dabos, Dina Daaboul, Hassan Mallat, Elie Bou Raad, Marcel Achkar, Osman Mawlawi, Sandrine Bernabeu, Rémy A. Bonnin, Delphine Girlich, Marwan Osman, Monzer Hamze and Thierry Naas
Antibiotics 2022, 11(10), 1295; https://doi.org/10.3390/antibiotics11101295 - 22 Sep 2022
Cited by 11 | Viewed by 2459
Abstract
Carbapenem resistance (CR) is an emerging health issue. Epidemiological surveys on carbapenem-resistant Gram-negative bacilli (CR-GNB) in Lebanon remain scarce. In this study, we determined the prevalence of CR-GNB isolated between 2015 to 2019 in three hospitals in northern Lebanon: 311 CR-Enterobacterales (out [...] Read more.
Carbapenem resistance (CR) is an emerging health issue. Epidemiological surveys on carbapenem-resistant Gram-negative bacilli (CR-GNB) in Lebanon remain scarce. In this study, we determined the prevalence of CR-GNB isolated between 2015 to 2019 in three hospitals in northern Lebanon: 311 CR-Enterobacterales (out of 11210; 2.8%), 155 CR-Pseudomonas (out of 1034; 15%) and 106 CR- Acinetobacter (out of 184; 57.6%) were identified. CR mechanisms were determined for 146 randomly chosen isolates: the Carba NP test revealed an enzymatic resistance to carbapenems in 109 isolates (out of 146, 74.7%). Produced carbapenemases were evaluated by the NG-Test Carba5, NG-Test OXA-23 immunochromatographic assays and PCR. Carbapenemase-producing (CP) Enterobacterales expressed blaOXA-48-like, blaNDM-like and blaVIM-like genes and CP-Pseudomonas expressed blaIMP-like and blaVIM-like genes, whereas CP-Acinetobacter expressed blaOXA-23-like genes. The NG-Test Carba5 results were confirmed by PCR sequencing and revealed several variants, such as NDM-19, VIM-62 and OXA-162, never described so far in Lebanon. Isolates with discordant results were sequenced by WGS and highlighted novel variants of the natural oxacillinases of Pseudomonas aeruginosa: blaOXA-50-like genes. Their role in carbapenem resistance should be further studied. Overall, our findings highlight an alarming situation and encourage health care centers to establish performant registration systems that could help in limiting resistance spread. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria)
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9 pages, 1040 KiB  
Article
Genetic Diversity of Virulent Polymyxin-Resistant Klebsiella aerogenes Isolated from Intensive Care Units
by Kesia Esther da Silva, Gleyce Hellen de Almeida de Souza, Quézia Moura, Luana Rossato, Letícia Cristina Limiere, Nathalie Gaebler Vasconcelos and Simone Simionatto
Antibiotics 2022, 11(8), 1127; https://doi.org/10.3390/antibiotics11081127 - 19 Aug 2022
Cited by 5 | Viewed by 2422
Abstract
This study evaluated the scope and genetic basis of polymyxin-resistant Klebsiella aerogenes in Brazil. Eight polymyxin-resistant and carbapenemase-producing K. aerogenes strains were isolated from patients admitted to the ICU of a tertiary hospital. Bacterial species were identified by automated systems and antimicrobial susceptibility [...] Read more.
This study evaluated the scope and genetic basis of polymyxin-resistant Klebsiella aerogenes in Brazil. Eight polymyxin-resistant and carbapenemase-producing K. aerogenes strains were isolated from patients admitted to the ICU of a tertiary hospital. Bacterial species were identified by automated systems and antimicrobial susceptibility profile was confirmed using broth microdilution. The strains displayed a multidrug resistant profile and were subjected to whole-genome sequencing. Bioinformatic analysis revealed a variety of antimicrobial resistance genes, including the blaKPC-2. No plasmid-mediated colistin resistance gene was identified. Nonetheless, nonsynonymous mutations in mgrB, pmrA, pmrB, and eptA were detected, justifying the colistin resistance phenotype. Virulence genes encoding yersiniabactin, colibactin, and aerobactin were also found, associated with ICEKp4 and ICEKp10, and might be related to the high mortality observed among the patients. In fact, this is the first time ICEKp is identified in K. aerogenes in Brazil. Phylogenetic analysis grouped the strains into two clonal groups, belonging to ST93 and ST16. In summary, the co-existence of antimicrobial resistance and virulence factors is deeply worrying, as it could lead to the emergence of untreatable invasive infections. All these factors reinforce the need for surveillance programs to monitor the evolution and dissemination of multidrug resistant and virulent strains among critically ill patients. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria)
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12 pages, 1399 KiB  
Article
Nosocomial Outbreak of Extensively Drug-Resistant (Polymyxin B and Carbapenem) Klebsiella pneumoniae in a Collapsed University Hospital Due to COVID-19 Pandemic
by Gilberto G. Gaspar, Gustavo Tamasco, Nathália Abichabki, Ana Flavia T. Scaranello, Maria Auxiliadora-Martins, Renata Pocente, Leonardo N. Andrade, María-Eugenia Guazzaroni, Rafael Silva-Rocha and Valdes R. Bollela
Antibiotics 2022, 11(6), 814; https://doi.org/10.3390/antibiotics11060814 - 17 Jun 2022
Cited by 11 | Viewed by 3034
Abstract
We correlated clinical, epidemiological, microbiological, and genomic data of an outbreak with polymyxin B (PB)- and carbapenem-resistant Klebsiella pneumoniae during the COVID-19 pandemic. Twenty-six PB- and carbapenem-resistant K. pneumoniae were isolated from patients in the COVID-19 ICU (Intensive Care Unit), non-COVID-19 ICU (Intensive [...] Read more.
We correlated clinical, epidemiological, microbiological, and genomic data of an outbreak with polymyxin B (PB)- and carbapenem-resistant Klebsiella pneumoniae during the COVID-19 pandemic. Twenty-six PB- and carbapenem-resistant K. pneumoniae were isolated from patients in the COVID-19 ICU (Intensive Care Unit), non-COVID-19 ICU (Intensive Care Unit), clinical, or surgical ward. Bacterial identification, drug susceptibility tests, and DNA sequencing were performed, followed by in silico resistance genes identification. All isolates showed extensively drug-resistant (XDR) phenotypes. Four different sequence types (ST) were detected: ST16, ST11, ST258, and ST437. Nineteen isolates were responsible for an outbreak in the ICU in September 2020. They belong to ST258 and harbored the 42Kb IncX3plasmid (pKP98M3N42) with the same genomic pattern of two K. pneumoniae identified in 2018. Twenty-four isolates carried bla-KPC-2 gene. No plasmid-mediated colistin (mcr) resistance genes were found. Eight isolates presented mgrB gene mutation. The clonal isolates responsible for the outbreak came from patients submitted to pronation, with high mortality rates in one month. XDR-K. pneumoniae detected during the outbreak presented chromosomal resistance to PB and plasmid-acquired carbapenem resistance due to KPC production in most isolates and 42Kb IncX3(pKP98M3N42) plasmid carrying blaKPC-2 was associated with ST258 isolates. The outbreak followed the collapse of the local healthcare system with high mortality rates. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria)
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Review

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23 pages, 1323 KiB  
Review
The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies
by Fusheng Zhang and Wei Cheng
Antibiotics 2022, 11(9), 1215; https://doi.org/10.3390/antibiotics11091215 - 8 Sep 2022
Cited by 49 | Viewed by 20061
Abstract
Bacterial drug resistance is rapidly developing as one of the greatest threats to human health. Bacteria will adopt corresponding strategies to crack the inhibitory effect of antibiotics according to the antibacterial mechanism of antibiotics, involving the mutation of drug target, secreting hydrolase, and [...] Read more.
Bacterial drug resistance is rapidly developing as one of the greatest threats to human health. Bacteria will adopt corresponding strategies to crack the inhibitory effect of antibiotics according to the antibacterial mechanism of antibiotics, involving the mutation of drug target, secreting hydrolase, and discharging antibiotics out of cells through an efflux pump, etc. In recent years, bacteria are found to constantly evolve new resistance mechanisms to antibiotics, including target protective protein, changes in cell morphology, and so on, endowing them with multiple defense systems against antibiotics, leading to the emergence of multi-drug resistant (MDR) bacteria and the unavailability of drugs in clinics. Correspondingly, researchers attempt to uncover the mystery of bacterial resistance to develop more convenient and effective antibacterial strategies. Although traditional antibiotics still play a significant role in the treatment of diseases caused by sensitive pathogenic bacteria, they gradually lose efficacy in the MDR bacteria. Therefore, highly effective antibacterial compounds, such as phage therapy and CRISPER-Cas precision therapy, are gaining an increasing amount of attention, and are considered to be the treatments with the moist potential with regard to resistance against MDR in the future. In this review, nine identified drug resistance mechanisms are summarized, which enhance the retention rate of bacteria under the action of antibiotics and promote the distribution of drug-resistant bacteria (DRB) in the population. Afterwards, three kinds of potential antibacterial methods are introduced, in which new antibacterial compounds exhibit broad application prospects with different action mechanisms, the phage therapy has been successfully applied to infectious diseases caused by super bacteria, and the CRISPER-Cas precision therapy as a new technology can edit drug-resistant genes in pathogenic bacteria at the gene level, with high accuracy and flexibility. These antibacterial methods will provide more options for clinical treatment, and will greatly alleviate the current drug-resistant crisis. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria)
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Other

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21 pages, 3894 KiB  
Systematic Review
Prevalence of Multidrug-Resistant Diarrheagenic Escherichia coli in Asia: A Systematic Review and Meta-Analysis
by Mohd Zulkifli Salleh, Nik Mohd Noor Nik Zuraina, Khalid Hajissa, Mohamad Ikram Ilias and Zakuan Zainy Deris
Antibiotics 2022, 11(10), 1333; https://doi.org/10.3390/antibiotics11101333 - 29 Sep 2022
Cited by 16 | Viewed by 4003
Abstract
Diarrhea is one of the leading causes of morbidity and mortality in developing countries. Diarrheagenic Escherichia coli (DEC) is an important bacterial agent for diarrhea in infants, children, and international travelers, and accounts for more than 30% of diarrheal cases in children less [...] Read more.
Diarrhea is one of the leading causes of morbidity and mortality in developing countries. Diarrheagenic Escherichia coli (DEC) is an important bacterial agent for diarrhea in infants, children, and international travelers, and accounts for more than 30% of diarrheal cases in children less than 5 years old. However, the choices of antimicrobial agents are now being limited by the ineffectiveness of many first-line drugs, in relation to the emergence of antimicrobial-resistant E. coli strains. The aim of this systematic review and meta-analysis was to provide an updated prevalence of antimicrobial-resistant DEC in Asia. A comprehensive systematic search was conducted on three electronic databases (PubMed, ScienceDirect, and Scopus), where 40 eligible studies published between 2010 and 2022 were identified. Using meta-analysis of proportions and a random-effects model, the pooled prevalence of DEC in Asian diarrheal patients was 22.8% (95% CI: 16.5–29.2). The overall prevalence of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing DEC strains was estimated to be 66.3% (95% CI: 58.9–73.7) and 48.6% (95% CI: 35.1–62.1), respectively. Considering antimicrobial drugs for DEC, the resistance prevalence was highest for the penicillin class of antibiotics, where 80.9% of the DEC isolates were resistant to amoxicillin and 73.5% were resistant to ampicillin. In contrast, resistance to carbapenems such as imipenem (0.1%), ertapenem (2.6%), and meropenem (7.9%) was the lowest. The relatively high prevalence estimation signifies that the multidrug-resistant DEC is a public health threat. Effective antibiotic treatment strategies, which may lead to better outcomes for the control of E. coli infections in Asia, are necessary. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria)
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