Molecular Characterization of Gram-Negative Bacteria: Antimicrobial Resistance, Virulence and Epidemiology

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: closed (15 April 2024) | Viewed by 30024

Special Issue Editor


E-Mail Website
Guest Editor
Microbiology Department, Papanikolaou General Hospital, Thessaloniki, Greece
Interests: antimicrobial resistance; molecular epidemiology; Gram-negative bacteria; infection control

Special Issue Information

Dear Colleagues,

Multidrug-resistant (MDR), extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Gram-negative bacteria constitute a huge public health problem. Among them, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii are the main bacteria contributing to increased rates of antimicrobial resistance. Infections caused by these bacteria can have a negative impact on the financial costs and the outcome of patients’ hospitalization. The increased consumption of antimicrobials and the poor implementation of infection control measures in the hospital setting are the two main causative factors for their emergence. The deep knowledge of the virulent factors that these bacteria produce could provide useful information regarding their spread.

The main problem concerning infections caused by these bacteria is that treatment options are extremely limited, as there has been a poor launch of novel antimicrobials over the last few years. The molecular epidemiology of infections caused by Gram-negative bacteria is significant as it can determine which of these few new antimicrobial agents could be effective for their treatment. This Special Issue seeks manuscript submissions that expand our knowledge of antimicrobial resistance in Gram-negative bacteria. Submissions on the mechanisms of antimicrobial resistance, the presence and function of virulent factors, as well as the molecular epidemiology of Gram-negative bacterial infections are especially encouraged.

Dr. Theodoros Karampatakis
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 2900 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

  • Gram-negative bacteria
  • virulent factors
  • antimicrobial resistanc
  • molecular epidemiology
  • Klebsiella pneumoniae
  • Pseudomonas aeruginosa
  • Acinetobacter baumannii

Published Papers (12 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 2509 KiB  
Article
Assessment of Colistin Heteroresistance among Multidrug-Resistant Klebsiella pneumoniae Isolated from Intensive Care Patients in Europe
by Anouk J. M. M. Braspenning, Sahaya Glingston Rajakani, Adwoa Sey, Mariem El Bounja, Christine Lammens, Youri Glupczynski and Surbhi Malhotra-Kumar
Antibiotics 2024, 13(3), 281; https://doi.org/10.3390/antibiotics13030281 - 20 Mar 2024
Viewed by 877
Abstract
Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug-resistant (MDR) K. pneumoniae are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) K. pneumoniae [...] Read more.
Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug-resistant (MDR) K. pneumoniae are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) K. pneumoniae (n = 676) isolated from patients hospitalized in 13 intensive care units (ICUs) in six European countries in a clinical trial assessing the impact of decolonization strategies. All isolates were whole-genome-sequenced and studied for in vitro colistin susceptibility. The majority were colistin-susceptible (CS) (n = 597, MIC ≤ 2 µg/mL), and 79 were fully colistin-resistant (CR) (MIC > 2 µg/mL). A total of 288 CS isolates were randomly selected for population analysis profiling (PAP) to assess CHR prevalence. CHR was detected in 108/288 CS K. pneumoniae. No significant association was found between the occurrence of CHR and country, MIC-value, K-antigen type, and O-antigen type. Overall, 92% (617/671) of the K. pneumoniae were MDR with high prevalence among CS (91%, 539/592) and CR (98.7%, 78/79) isolates. In contrast, the proportion of carbapenemase-producing K. pneumoniae (CP-Kpn) was higher among CR (72.2%, 57/79) than CS isolates (29.3%, 174/594). The proportions of MDR and CP-Kpn were similar among CHR (MDR: 85%, 91/107; CP-Kpn: 29.9%, 32/107) and selected CS isolates (MDR: 84.7%, 244/288; CP-Kpn: 28.1%, 80/285). WGS analysis of PAP isolates showed diverse insertion elements in mgrB or even among technical replicates underscoring the stochasticity of the CHR phenotype. CHR isolates showed high sequence type (ST) diversity (Simpson’s diversity index, SDI: 0.97, in 52 of the 85 STs tested). CR (SDI: 0.85) isolates were highly associated with specific STs (ST101, ST147, ST258/ST512, p ≤ 0.003). The widespread nature of CHR among MDR K. pneumoniae in our study urge the development of rapid HR detection methods to inform on the need for combination regimens. Full article
Show Figures

Figure 1

18 pages, 11791 KiB  
Article
Virulence of Pseudomonas aeruginosa in Cystic Fibrosis: Relationships between Normoxia and Anoxia Lifestyle
by Rosanna Papa, Esther Imperlini, Marika Trecca, Irene Paris, Gianluca Vrenna, Marco Artini and Laura Selan
Antibiotics 2024, 13(1), 1; https://doi.org/10.3390/antibiotics13010001 - 19 Dec 2023
Viewed by 1243
Abstract
The airways of cystic fibrosis (CF) patients are colonized by many pathogens and the most common is Pseudomonas aeruginosa, an environmental pathogen that is able to infect immunocompromised patients thanks to its ability to develop resistance to conventional antibiotics. Over 12% of [...] Read more.
The airways of cystic fibrosis (CF) patients are colonized by many pathogens and the most common is Pseudomonas aeruginosa, an environmental pathogen that is able to infect immunocompromised patients thanks to its ability to develop resistance to conventional antibiotics. Over 12% of all patients colonized by P. aeruginosa harbour multi-drug resistant species. During airway infection in CF, P. aeruginosa adopts various mechanisms to survive in a hostile ecological niche characterized by low oxygen concentration, nutrient limitation and high osmotic pressure. To this end, P. aeruginosa uses a variety of virulence factors including pigment production, biofilm formation, motility and the secretion of toxins and proteases. This study represents the first report that systematically analyzes the differences in virulence features, in normoxia and anoxia, of clinical P. aeruginosa isolated from CF patients, characterized by multi- or pan-drug antibiotic resistance compared to antibiotic sensitive strains. The virulence features, such as biofilm formation, protease secretion and motility, are highly diversified in anaerobiosis, which reflects the condition of chronic CF infection. These findings may contribute to the understanding of the real-world lifestyle of pathogens isolated during disease progression in each particular patient and to assist in the design of therapeutic protocols for personalized medicine. Full article
Show Figures

Figure 1

12 pages, 2153 KiB  
Article
Probable Three-Species In Vivo Transfer of blaNDM-1 in a Single Patient in Greece: Occurrence of NDM-1-Producing Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii
by Georgios Meletis, Andigoni Malousi, Areti Tychala, Angeliki Kassomenaki, Nikoletta Vlachodimou, Paraskevi Mantzana, Simeon Metallidis, Lemonia Skoura and Efthymia Protonotariou
Antibiotics 2023, 12(7), 1206; https://doi.org/10.3390/antibiotics12071206 - 20 Jul 2023
Viewed by 1383
Abstract
NDM carbapenemase-encoding genes disseminate commonly among Enterobacterales through transferable plasmids carrying additional resistance determinants. Apart from the intra-species dissemination, the inter-species exchange of plasmids seems to play an additional important role in the spread of blaNDM. We here present the genetics [...] Read more.
NDM carbapenemase-encoding genes disseminate commonly among Enterobacterales through transferable plasmids carrying additional resistance determinants. Apart from the intra-species dissemination, the inter-species exchange of plasmids seems to play an additional important role in the spread of blaNDM. We here present the genetics related to the isolation of three species (Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii) harboring the blaNDM-1 gene from a single patient in Greece. Bacterial identification and antimicrobial susceptibility testing were performed using the Vitek2. Whole genome sequencing and bioinformatic tools were used to identify resistance genes and plasmids. BlaNDM-1 harboring plasmids were found in all three isolates. Moreover, the plasmid constructs of the respective incomplete or circular contigs showed that the blaNDM-1 and its neighboring genes form a cluster that was found in all isolates. Our microbiological findings, together with the patient’s history, suggest the in vivo transfer of the blaNDM-1-containing cluster through three different species in a single patient. Full article
Show Figures

Figure 1

6 pages, 232 KiB  
Communication
Efficacy of Novel Combinations of Antibiotics against Multidrug-Resistant—New Delhi Metallo-Beta-Lactamase-Producing Strains of Enterobacterales
by Shamsi Khalid, Antonella Migliaccio, Raffaele Zarrilli and Asad U. Khan
Antibiotics 2023, 12(7), 1134; https://doi.org/10.3390/antibiotics12071134 - 30 Jun 2023
Viewed by 1272
Abstract
The emergence of multidrug-resistance (MDR)—New Delhi metallo-beta-lactamase (NDM)-producing microorganisms—has become a serious concern for treating such infections. Therefore, we investigated the effective antimicrobial combinations against multidrug-resistant New Delhi metallo-beta-lactamase-producing strains of Enterobacterales. The tests were carried out using the 2D(two-dimensional) checkerboard method. [...] Read more.
The emergence of multidrug-resistance (MDR)—New Delhi metallo-beta-lactamase (NDM)-producing microorganisms—has become a serious concern for treating such infections. Therefore, we investigated the effective antimicrobial combinations against multidrug-resistant New Delhi metallo-beta-lactamase-producing strains of Enterobacterales. The tests were carried out using the 2D(two-dimensional) checkerboard method. Of 7 antimicrobials, i.e., doripenem (DRP), streptomycin (STR), cefoxitin (FOX), imipenem (IPM), cefotaxime (CTX), meropenem (MER), and gentamicin (GEN), 19 different combinations were used, and out of them, three combinations showed synergistic effects against 31 highly drug-resistant strains carrying blaNDM and other associated resistance markers. Changes in the minimum inhibitory concentration (MIC) values were interpreted using the test fractional inhibitory concentration index (FIC Index). The FIC Index values of these combinations were found in the range of 0.1562 to 0.5, which shows synergy, whereas no synergism was observed in the remaining antimicrobial combinations. We conclude that these antibiotic combinations can be analyzed in in vivo and pharmacological studies to establish an effective therapeutic approach. Full article
17 pages, 3382 KiB  
Article
Genetic Characterization of Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates in a Tertiary Hospital in Greece, 2018–2022
by Charalampos Zarras, Theodoros Karampatakis, Styliani Pappa, Elias Iosifidis, Eleni Vagdatli, Emmanuel Roilides and Anna Papa
Antibiotics 2023, 12(6), 976; https://doi.org/10.3390/antibiotics12060976 - 28 May 2023
Cited by 1 | Viewed by 1412
Abstract
Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious public health issue. The study aimed to identify the antimicrobial resistance and accessory genes, the clonal relatedness, and the evolutionary dynamics of selected CRKP isolates recovered in an adult and pediatric intensive care unit of [...] Read more.
Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious public health issue. The study aimed to identify the antimicrobial resistance and accessory genes, the clonal relatedness, and the evolutionary dynamics of selected CRKP isolates recovered in an adult and pediatric intensive care unit of a tertiary hospital in Greece. Methods: Twenty-four CRKP isolates recovered during 2018–2022 were included in the study. Next-generation sequencing was performed using the Ion Torrent PGM Platform. The identification of the plasmid content, MLST, and antimicrobial resistance genes, as well as the comparison of multiple genome alignments and the identification of core genome single-nucleotide polymorphism sites, were performed using various bioinformatics software. Results: The isolates belonged to eight sequence types: 11, 15, 30, 35, 39, 307, 323, and 512. A variety of carbapenemases (KPC, VIM, NDM, and OXA-48) and resistance genes were detected. CRKP strains shared visually common genomic regions with the reference strain (NTUH-K2044). ST15, ST323, ST39, and ST11 CRKP isolates presented on average 17, 6, 16, and 866 recombined SNPs, respectively. All isolates belonging to ST15, ST323, and ST39 were classified into distinct phylogenetic branches, while ST11 isolates were assigned to a two-subclade branch. For large CRKP sets, the phylogeny seems to change approximately every seven SNPs. Conclusions: The current study provides insight into the genetic characterization of CRKP isolates in the ICUs of a tertiary hospital. Our results indicate clonal dispersion of ST15, ST323, and ST39 and highly diverged ST11 isolates. Full article
Show Figures

Figure 1

14 pages, 5409 KiB  
Article
F18:A-:B1 Plasmids Carrying blaCTX-M-55 Are Prevalent among Escherichia coli Isolated from Duck–Fish Polyculture Farms
by Li-Juan Zhang, Jin-Tao Yang, Hai-Xin Chen, Wen-Zi Liu, Yi-Li Ding, Rui-Ai Chen, Rong-Min Zhang and Hong-Xia Jiang
Antibiotics 2023, 12(6), 961; https://doi.org/10.3390/antibiotics12060961 - 25 May 2023
Cited by 1 | Viewed by 1251
Abstract
We determined the prevalence and molecular characteristics of blaCTX-M-55-positive Escherichia coli (E. coli) isolated from duck–fish polyculture farms in Guangzhou, China. A total of 914 E. coli strains were isolated from 2008 duck and environmental samples (water, soil and [...] Read more.
We determined the prevalence and molecular characteristics of blaCTX-M-55-positive Escherichia coli (E. coli) isolated from duck–fish polyculture farms in Guangzhou, China. A total of 914 E. coli strains were isolated from 2008 duck and environmental samples (water, soil and plants) collected from four duck fish polyculture farms between 2017 and 2019. Among them, 196 strains were CTX-M-1G-positive strains by PCR, and 177 (90%) blaCTX-M-1G-producing strains were blaCTX-M-55-positive. MIC results showed that the 177 blaCTX-M-55-positive strains were highly resistant to ciprofloxacin, ceftiofur and florfenicol, with antibiotic resistance rates above 95%. Among the 177 strains, 37 strains carrying the F18:A-:B1 plasmid and 10 strains carrying the F33:A-:B- plasmid were selected for further study. Pulse field gel electrophoresis (PFGE) combined with S1-PFGE, Southern hybridization and whole-genome sequencing (WGS) analysis showed that both horizontal transfer and clonal spread contributed to dissemination of the blaCTX-M-55 gene among the E. coli. blaCTX-M-55 was located on different F18:A-:B1 plasmids with sizes between ~76 and ~173 kb. In addition, the presence of blaCTX-M-55 with other resistance genes (e.g., tetA, floR, fosA3, blaTEM, aadA5 CmlA and InuF) on the same F18:A-:B1 plasmid may result in co-selection of resistance determinants and accelerate the dissemination of blaCTX-M-55 in E. coli. In summary, the F18:A-:B1 plasmid may play an important role in the transmission of blaCTX-M-55 in E. coli, and the continuous monitoring of the prevalence and transmission mechanism of blaCTX-M-55 in duck–fish polyculture farms remains important. Full article
Show Figures

Figure 1

16 pages, 5319 KiB  
Article
Cloning and Molecular Characterization of the phlD Gene Involved in the Biosynthesis of “Phloroglucinol”, a Compound with Antibiotic Properties from Plant Growth Promoting Bacteria Pseudomonas spp.
by Payal Gupta, Prasanta K. Dash, Tenkabailu Dharmanna Sanjay, Sharat Kumar Pradhan, Rohini Sreevathsa and Rhitu Rai
Antibiotics 2023, 12(2), 260; https://doi.org/10.3390/antibiotics12020260 - 28 Jan 2023
Cited by 3 | Viewed by 1734
Abstract
phlD is a novel kind of polyketide synthase involved in the biosynthesis of non-volatile metabolite phloroglucinol by iteratively condensing and cyclizing three molecules of malonyl-CoA as substrate. Phloroglucinol or 2,4-diacetylphloroglucinol (DAPG) is an ecologically important rhizospheric antibiotic produced by pseudomonads; it exhibits [...] Read more.
phlD is a novel kind of polyketide synthase involved in the biosynthesis of non-volatile metabolite phloroglucinol by iteratively condensing and cyclizing three molecules of malonyl-CoA as substrate. Phloroglucinol or 2,4-diacetylphloroglucinol (DAPG) is an ecologically important rhizospheric antibiotic produced by pseudomonads; it exhibits broad spectrum anti-bacterial and anti-fungal properties, leading to disease suppression in the rhizosphere. Additionally, DAPG triggers systemic resistance in plants, stimulates root exudation, as well as induces phyto-enhancing activities in other rhizobacteria. Here, we report the cloning and analysis of the phlD gene from soil-borne gram-negative bacteria—Pseudomonas. The full-length phlD gene (from 1078 nucleotides) was successfully cloned and the structural details of the PHLD protein were analyzed in-depth via a three-dimensional topology and a refined three-dimensional model for the PHLD protein was predicted. Additionally, the stereochemical properties of the PHLD protein were analyzed by the Ramachandran plot, based on which, 94.3% of residues fell in the favored region and 5.7% in the allowed region. The generated model was validated by secondary structure prediction using PDBsum. The present study aimed to clone and characterize the DAPG-producing phlD gene to be deployed in the development of broad-spectrum biopesticides for the biocontrol of rhizospheric pathogens. Full article
Show Figures

Figure 1

13 pages, 809 KiB  
Article
Klebsiella pneumonia in Sudan: Multidrug Resistance, Polyclonal Dissemination, and Virulence
by Einas A. Osman, Maho Yokoyama, Hisham N. Altayb, Daire Cantillon, Julia Wille, Harald Seifert, Paul G. Higgins and Leena Al-Hassan
Antibiotics 2023, 12(2), 233; https://doi.org/10.3390/antibiotics12020233 - 21 Jan 2023
Cited by 4 | Viewed by 1877
Abstract
The emergence and global expansion of hyper-virulent and multidrug resistant (MDR) Klebsiella pneumoniae is an increasing healthcare threat worldwide. The epidemiology of MDR K. pneumoniae is under-characterized in many parts of the world, particularly Africa. In this study, K. pneumoniae isolates from hospitals [...] Read more.
The emergence and global expansion of hyper-virulent and multidrug resistant (MDR) Klebsiella pneumoniae is an increasing healthcare threat worldwide. The epidemiology of MDR K. pneumoniae is under-characterized in many parts of the world, particularly Africa. In this study, K. pneumoniae isolates from hospitals in Khartoum, Sudan, have been whole-genome sequenced to investigate their molecular epidemiology, virulence, and resistome profiles. Eighty-six K. pneumoniae were recovered from patients in five hospitals in Khartoum between 2016 and 2020. Antimicrobial susceptibility was performed by disk-diffusion and broth microdilution. All isolates underwent whole genome sequencing using Illumina MiSeq; cgMLST was determined using Ridom SeqSphere+, and 7-loci MLST virulence genes and resistomes were identified. MDR was observed at 80%, with 35 isolates (41%) confirmed carbapenem-resistant. Thirty-seven sequence types were identified, and 14 transmission clusters (TC). Five of these TCs involved more than one hospital. Ybt9 was the most common virulence gene detected, in addition to some isolates harbouring iuc and rmp1. There is a diverse population of K. pneumoniae in Khartoum hospitals, harbouring multiple resistance genes, including genes coding for ESBLs, carbapenemases, and aminoglycoside-modifying enzymes, across multiple ST’s. The majority of isolates were singletons and transmissions were rare. Full article
Show Figures

Figure 1

17 pages, 3966 KiB  
Article
Molecular Characteristics and Quantitative Proteomic Analysis of Klebsiella pneumoniae Strains with Carbapenem and Colistin Resistance
by Ling Hao, Xiao Yang, Huiling Chen, Zexun Mo, Yujun Li, Shuquan Wei and Ziwen Zhao
Antibiotics 2022, 11(10), 1341; https://doi.org/10.3390/antibiotics11101341 - 30 Sep 2022
Cited by 2 | Viewed by 1683
Abstract
Carbapenem-resistant Klebsiella pneumoniae (CRKP) are usually multidrug resistant (MDR) and cause serious therapeutic problems. Colistin is a critical last-resort therapeutic option for MDR bacterial infections. However, increasing colistin use has led to the emergence of extensively drug-resistant (XDR) strains, raising a significant challenge [...] Read more.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) are usually multidrug resistant (MDR) and cause serious therapeutic problems. Colistin is a critical last-resort therapeutic option for MDR bacterial infections. However, increasing colistin use has led to the emergence of extensively drug-resistant (XDR) strains, raising a significant challenge for healthcare. In order to gain insight into the antibiotic resistance mechanisms of CRKP and identify potential drug targets, we compared the molecular characteristics and the proteomes among drug-sensitive (DS), MDR, and XDR K. pneumoniae strains. All drug-resistant isolates belonged to ST11, harboring blaKPC and hypervirulent genes. None of the plasmid-encoded mcr genes were detected in the colistin-resistant XDR strains. Through a tandem mass tag (TMT)-labeled proteomic technique, a total of 3531 proteins were identified in the current study. Compared to the DS strains, there were 247 differentially expressed proteins (DEPs) in the MDR strains and 346 DEPs in the XDR strains, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that a majority of the DEPs were involved in various metabolic pathways, which were beneficial to the evolution of drug resistance in K. pneumoniae. In addition, a total of 67 DEPs were identified between the MDR and XDR strains. KEGG enrichment and protein–protein interaction network analysis showed their participation in cationic antimicrobial peptide resistance and two-component systems. In conclusion, our results highlight the emergence of colistin-resistant and hypervirulent CRKP, which is a noticeable superbug. The DEPs identified in our study are of great significance for the exploration of effective control strategies against infections of CRKP. Full article
Show Figures

Figure 1

Review

Jump to: Research

19 pages, 1476 KiB  
Review
Cefiderocol and Sulbactam-Durlobactam against Carbapenem-Resistant Acinetobacter baumannii
by Arta Karruli, Antonella Migliaccio, Spyros Pournaras, Emanuele Durante-Mangoni and Raffaele Zarrilli
Antibiotics 2023, 12(12), 1729; https://doi.org/10.3390/antibiotics12121729 - 14 Dec 2023
Viewed by 1738
Abstract
Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain a clinical challenge due to limited treatment options. Recently, cefiderocol, a novel siderophore cephalosporin, and sulbactam-durlobactam, a bactericidal β-lactam–β-lactamase inhibitor combination, have been approved by the Food and Drug Administration for the treatment of A. [...] Read more.
Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain a clinical challenge due to limited treatment options. Recently, cefiderocol, a novel siderophore cephalosporin, and sulbactam-durlobactam, a bactericidal β-lactam–β-lactamase inhibitor combination, have been approved by the Food and Drug Administration for the treatment of A. baumannii infections. In this review, we discuss the mechanisms of action of and resistance to cefiderocol and sulbactam-durlobactam, the antimicrobial susceptibility of A. baumannii isolates to these drugs, as well as the clinical effectiveness of cefiderocol and sulbactam/durlobactam-based regimens against CRAB. Overall, cefiderocol and sulbactam-durlobactam show an excellent antimicrobial activity against CRAB. The review of clinical studies evaluating the efficacy of cefiderocol therapy against CRAB indicates it is non-inferior to colistin/other treatments for CRAB infections, with a better safety profile. Combination treatment is not associated with improved outcomes compared to monotherapy. Higher mortality rates are often associated with prior patient comorbidities and the severity of the underlying infection. Regarding sulbactam-durlobactam, current data from the pivotal clinical trial and case reports suggest this antibiotic combination could be a valuable option in critically ill patients affected by CRAB infections, in particular where no other antibiotic appears to be effective. Full article
Show Figures

Figure 1

23 pages, 2443 KiB  
Review
Carbapenem-Resistant Klebsiella pneumoniae: Virulence Factors, Molecular Epidemiology and Latest Updates in Treatment Options
by Theodoros Karampatakis, Katerina Tsergouli and Payam Behzadi
Antibiotics 2023, 12(2), 234; https://doi.org/10.3390/antibiotics12020234 - 21 Jan 2023
Cited by 51 | Viewed by 10366
Abstract
Klebsiella pneumoniae is a Gram-negative opportunistic pathogen responsible for a variety of community and hospital infections. Infections caused by carbapenem-resistant K. pneumoniae (CRKP) constitute a major threat for public health and are strongly associated with high rates of mortality, especially in immunocompromised and [...] Read more.
Klebsiella pneumoniae is a Gram-negative opportunistic pathogen responsible for a variety of community and hospital infections. Infections caused by carbapenem-resistant K. pneumoniae (CRKP) constitute a major threat for public health and are strongly associated with high rates of mortality, especially in immunocompromised and critically ill patients. Adhesive fimbriae, capsule, lipopolysaccharide (LPS), and siderophores or iron carriers constitute the main virulence factors which contribute to the pathogenicity of K. pneumoniae. Colistin and tigecycline constitute some of the last resorts for the treatment of CRKP infections. Carbapenemase production, especially K. pneumoniae carbapenemase (KPC) and metallo-β-lactamase (MBL), constitutes the basic molecular mechanism of CRKP emergence. Knowledge of the mechanism of CRKP appearance is crucial, as it can determine the selection of the most suitable antimicrobial agent among those most recently launched. Plazomicin, eravacycline, cefiderocol, temocillin, ceftolozane–tazobactam, imipenem–cilastatin/relebactam, meropenem–vaborbactam, ceftazidime–avibactam and aztreonam–avibactam constitute potent alternatives for treating CRKP infections. The aim of the current review is to highlight the virulence factors and molecular pathogenesis of CRKP and provide recent updates on the molecular epidemiology and antimicrobial treatment options. Full article
Show Figures

Figure 1

21 pages, 3356 KiB  
Review
Uncovering the Secretion Systems of Acinetobacter baumannii: Structures and Functions in Pathogenicity and Antibiotic Resistance
by Pu Li, Sirui Zhang, Jingdan Wang, Mona Mohamed Al-Shamiri, Bei Han, Yanjiong Chen, Shaoshan Han and Lei Han
Antibiotics 2023, 12(2), 195; https://doi.org/10.3390/antibiotics12020195 - 17 Jan 2023
Cited by 8 | Viewed by 3777
Abstract
Infections led by Acinetobacter baumannii strains are of great concern in healthcare environments due to the strong ability of the bacteria to spread through different apparatuses and develop drug resistance. Severe diseases can be caused by A. baumannii in critically ill patients, but [...] Read more.
Infections led by Acinetobacter baumannii strains are of great concern in healthcare environments due to the strong ability of the bacteria to spread through different apparatuses and develop drug resistance. Severe diseases can be caused by A. baumannii in critically ill patients, but its biological process and mechanism are not well understood. Secretion systems have recently been demonstrated to be involved in the pathogenic process, and five types of secretion systems out of the currently known six from Gram-negative bacteria have been found in A. baumannii. They can promote the fitness and pathogenesis of the bacteria by releasing a variety of effectors. Additionally, antibiotic resistance is found to be related to some types of secretion systems. In this review, we describe the genetic and structural compositions of the five secretion systems that exist in Acinetobacter. In addition, the function and molecular mechanism of each secretion system are summarized to explain how they enable these critical pathogens to overcome eukaryotic hosts and prokaryotic competitors to cause diseases. Full article
Show Figures

Figure 1

Back to TopTop