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Background: Among enterobacteria E. coli and Klebsiella spp. are of great concern in health care settings, as these bacteria sometimes may contaminate the milk due to unhygienic practices and poor udder condition which have been associated with various illnesses. Therefore, this study aimed to detect the carbapenem resistant E. coli and Klebsiella spp. of bovine milk origin with regard to the risk of human transfer via the food chain in community. Methods: Total 240 samples were collected from Ayodhya and Sultanpur districts of Eastern Plain Zone of Uttar Pradesh (India). Confirmation of E. coli and Klebsiella spp. isolates was done by using species specific uidA and 16S rRNA gene, respectively. Then, carbapenemase positive E. coli and Klebsiella spp. were confirmend by DDST, MBL E-strip test and PCR analysis by targeting (bla-NDM, bla-OXA-48 and bla-KPC). Antibiogram of all carbapenemase positive isolates was performed against 20 antibiotics of 12 different classes. XResult: In the present study, total 74(30.83%) isolates were identified including 55(22.92%) E. coli and 19(7.92%) Klebsiella spp. by PCR, out of which 12(16.21%) isolates were confirmed as carbapenemase producers comprising 7(12.72%) E. coli and 5(26.31%) Klebsiella spp by DDST and E-strip. All carbapenemase positive E. coli were found 100% sensitive to polymyxin-B and chloramphenicol, while all Klebsiella spp. were 100% sensitive to amikacin and polymyxin-B. Resistance against imipenem, meropenem, cefotaxime, cefpodoxime, ceftazidime, ceftriazone, aztreonam and ampicillin ranged between 80.0%-100%. All carbapenemase positive isolates were found multidrug resistant. Carbapenemase genes bla-NDM and bla-KPC were detected in E. coli while bla-OXA-48 and bla-KPC were detected in Klebsiella spp. [ABSTRACT FROM AUTHOR]

Periodontal disease is caused by different gram-negative anaerobic bacteria; however, Escherichia coli has also been isolated from periodontitis and its role in periodontitis is less known. This study aimed to determine the variability in virulence genotype, antibiotic resistance phenotype, biofilm formation, phylogroups, and serotypes in different emerging periodontal strains of Escherichia coli, isolated from patients with periodontal disease and healthy controls. E. coli, virulence genes, and phylogroups, were identified by PCR, antibiotic susceptibility by the Kirby-Bauer method, biofilm formation was quantified using polystyrene microtiter plates, and serotypes were determined by serotyping. Although E. coli was not detected in the controls (n = 70), it was isolated in 14.7% (100/678) of the patients. Most of the strains (n = 81/100) were multidrug-resistance. The most frequent adhesion genes among the strains were fimH and iha, toxin genes were usp and hlyA, iron-acquisition genes were fyuA and irp2, and protectin genes were ompT, and KpsMT. Phylogroup B2 and serotype O25:H4 were the most predominant among the strains. These findings suggest that E. coli may be involved in periodontal disease due to its high virulence, multidrug-resistance, and a wide distribution of phylogroups and serotypes. [ABSTRACT FROM AUTHOR]

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Abstract Background Little is known about the role of COVID-19 pandemic period on the epidemiology of fracture-related infection (FRI). The present study summarizes the changes in the prevalence, microbiology, and risk factors of FRI during this period. Methods A prospective single-center cohort study assessed in the setting of COVID-19 pandemic (2020–2021), clinical, microbiological aspects, and independent risk factors (RF) of FRI. RFs were estimated by bivariate and multivariable analyses using prevalence ratio (PR) with significance at P

In the last few decades, foodborne disease has become one of the world's health problems with various pathogenic bacteria that accompanies the contamination of food products of animal origin. One of the foodborne diseases that is always reported every year is related to Salmonella contamination in poultry products which can cause Salmonellosis in humans. Salmonella contamination become important not because of its virulence ability to invade humans, but also because of its increased resistance to various clinical antimicrobial classes, with various cellular genetic elements that can be spread in humans along the food chain. The purpose of this review is to provide an overview of the role of poultry product in the spread of multidrug resistance Salmonella which may have implications for public health.

Key points Growing multidrug-resistance and emerging pathogens need new antimicrobial drugs Different species of Phoma produce antimicrobial metabolites Phoma spp. are potential synthesizers of silver nanoparticles demonstrating antimicrobial activity.

Antibiotic resistance is one of the most serious global health crisis and threats in human life today. Multidrug-resistant is a condition obtained when bacteria are resistant to at least one of the agents of 3 or more antimicrobial categories. Cases of multi-resistant gram-negative bacilli infection continue to increase so that the use of standard antibiotics is non-susceptible leading to increased morbidity and mortality. Therefore, this study aims to find out which antibiotics are still sensitive as empirical therapy. This retrospective descriptive research uses secondary data in the form of the status of patients infected with A. baumannii, P. aeruginosa, E. coli and K. pneumoniae at the Central Laboratory Installation of Mohammad Hoesin Hospital Palembang during the period January 2020 – June 2020. The samples in this study were all medical records of inpatients who met the inclusion criteria. Data is processed and analyzed univariately using Microsoft Excel 2020 and IBM SPSS Statistics Version 26 to determine the frequency distribution of each variable studied. Prevalence of MDR gram-negative bacilli at Mohammad Hoesin Hospital Palembang was MDR A. baumannii (66.5%), MDR P. aeruginosa (34.6%), ESBL-E. coli (61.3%), CRE-E. coli (2.7%), ESBL-K. pneumoniae (51.7%) and CRE-K. pneumoniae (20.1%). Based on the inpatient room, prevalence of MDR gram-negative bacilli is found in intensive care compared to non-intensive care rooms. Based on specimen type, MDR gram-negative bacilli isolates are often found in all types of specimens namely sputum, blood, pus, swab, others. Based on sensitivity patterns, Enterobacteriaceae producing ESBL isolates are sensitive to carbapenem, amikacin, tigecyclin and nitrofurantoin, while in CRE isolates are sensitive to tigecycline. MDR A. baumannii is sensitive to tigecycline and amikacin, but MDR P. aeruginosa is only sensitive to amikacin. The prevalence of MDR gram-negative bacilli is the highest in the intensive inpatient rooms and varies in specimen type. Antibiotics that are sensitive to the entire MDR gram negative bacilli is tigecycline, except MDR P. aeruginosa is sensitive to amikacin.

Danni Bao,1,2 Linyao Huang,3 Jianxin Yan,3 Yexuzi Li,4 Zhi Ruan,2 Tian Jiang2,3 1Department of Clinical Laboratory, Sanmen People’s Hospital, Taizhou, Zhejiang, 317100, People’s Republic of China; 2Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China; 3Department of Clinical Laboratory, The Affiliated Wenling Hospital, Wenzhou Medical University, Wenling, 317500, People’s Republic of China; 4Department of Critical Care Medicine, The Affiliated Wenling Hospital, Wenzhou Medical University, Wenling, 317500, People’s Republic of ChinaCorrespondence: Tian Jiang; Zhi Ruan, Email jiangtianhw@zju.edu.cn; r_z@zju.edu.cnAbstract: The emergence of multidrug-resistant Pseudomonas spp. in the clinical settings has heightened public awareness. Here, we described the genomic characteristics of a P. putida isolate co-carrying five β-lactam resistance genes recovered from a urinary tract infection in China. Whole-genome sequencing was performed using Illumina NovaSeq 6000 and Oxford Nanopore MinION platforms. The genome sequence was annotated and further subjected to identify the sequence type (ST), antibiotic resistance and virulence genes. Phylogenetic analysis of 193 P. putida strains stored in NCBI public database based on core genome single nucleotide polymorphism (cgSNP) strategy were also performed and visualized. Our study indicated that P. putida PP_2463 was resistant to a wide range of antimicrobial agents tested, including aminoglycosides, carbapenems and fluoroquinolones. The complete genome sequence of P. putida PP_2463 is made up of one chromosome and two plasmids, which could be assigned to a new sequence type (ST) 148. The co-occurrence of β-lactam resistance genes blaIPM-15, blaPME-1, blaCARB-2, and blaNDM-1 were first identified in P. putida, and a novel β-lactamase gene located in the chromosome were among the antimicrobial resistance genes discovered. The closest relative of P. putida PP_2463 was identified in 2012 from a urine sample in China, with a difference of 143 SNPs. Along with the presence of multiple β-lactamase genes and mobile genetic elements, the multidrug-resistant phenotype suggests a significant potential as an antibiotic resistance reservoir for Pseudomonas spp.Keywords: Pseudomonas putida, whole genome sequencing, multidrug-resistance, blaPME-1, blaNDM-5, blaIPM-15, blaCARB-2, urinary tract infection

The inappropriate use of antibiotics in the poultry industry for prophylaxis and growth promotion has contributed to the development and spread of antibiotic resistance in zoonotic pathogens. This study aimed to understand the prevalence of pathogenic Escherichia coli (E. coli) in chicken faeces and their antibiotic susceptibility profiles. Forty-five E. coli isolated from the chicken faeces were further tested for virulence genes associated with diarrheagenic E. coli and extended-spectrum β-lactamase (ESBL) genes blaCTX, blaTEM, blaSHV and Metallo-beta-lactamase gene blaNDM. Results showed that eaeA and astA genes were detected in 60% of the isolates, followed by bfpA in 57.8 %, lt in 26.7% and st gene in 2.2% of the isolates. Further, 15.5% of the isolates produced ESBL phenotypically whereas genotypically, one isolate was positive for blaCTX, one for blaTEM, and one for the blaSHV gene. Twelve isolates (26.7%) harboured gene blaNDM. High levels of resistance were observed against cefepime (93.3%), ertapenem (78.9%), meropenem (73.6%), tetracycline (88.9%), and cotrimoxazole (75.6%). The study highlights the importance of poultry as a source of human pathogenic multidrug-resistant (MDR) E. coli and their environmental dissemination. [ J Adv Biotechnol Exp Ther 2022; 5(1.000): 148-162]

Danni Bao, Xiaohong Xu, Yizhang Wang, Fengjiao Zhu Department of Clinical Laboratory, Sanmen People’s Hospital, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Fengjiao Zhu, Department of Clinical Laboratory, Sanmen People’s Hospital, Taizhou, Zhejiang, People’s Republic of China, Email sm.zfj@foxmail.comBackground: Carbapenem-resistant Enterobacterales (CRE) are a significant threat to worldwide public health, resulting in increased morbidity, death, hospitalization time and healthcare expenses. Here, the genomic and phylogenetic characteristics of a multidrug-resistant Escherichia coli isolate carrying both the new mcr-1.33 variant and blaNDM-5 gene obtained from a urinary tract infection in China are investigated.Methods: Antimicrobial susceptibility of E. coli 779 was evaluated by using the broth microdilution method. Short-read Illumina NovaSeq 6000 and long-read Oxford Nanopore MinION platforms were applied to sequence the bacterial whole genomic DNA and then de novo assembled. The genome sequence was annotated using the NCBI Prokaryotic Genome Annotation Pipeline and further subjected to identify the sequence type (ST), capsular type, and antibiotic resistance genes. BacWGSTdb 2.0 was used to perform the core genome multilocus sequence typing (cgMLST) analysis with other closely related E. coli isolates deposited in the public database.Results: E. coli 779 was resistant to aztreonam, levofloxacin, fosfomycin, cefoxitin, cefepime, cefotaxime, imipenem, meropenem, polymyxin, and tigecycline. The complete genome sequence of E. coli 779 is made up of nine contigs totaling 5,667,876 bp, including one chromosome and eight plasmids. The isolate was assigned to ST101, serotype O-:H31, and phylogroup B1. The colistin resistance gene mcr-1.33 (located in a 242,460 bp IncHI2/IncHI2A plasmid) and the β-lactam resistance gene blaNDM-5 (located in a 46,161 bp IncX3 plasmid) were among the 27 antimicrobial resistance genes discovered. The closest relative of E. coli 779, another ST101 strain (E. coli 443) obtained from a sewage sample in Shandong, China in 2015, differs by only 24 cgMLST alleles.Conclusion: We discovered the first multidrug-resistant ST101 E. coli strain with plasmid-mediated mcr-1.33 variant and blaNDM-5 gene in China. These findings would help us to better understanding the genomic traits, antimicrobial resistance mechanisms and epidemiological aspects of this bacterial pathogen.Keywords: whole genome sequencing, Escherichia coli, multidrug-resistance, mcr-1.33, blaNDM-5, urinary tract infection

The emergence of multidrug-resistant Acinetobacter baumannii (MDR-AB), which most commonly manifests as pneumonia, has posed significant clinical challenges and called for novel treatment strategies. Phage depolymerases, which degrade bacterial surface carbohydrates, have emerged as potential antimicrobial agents. However, their preclinical application is limited to systemic infections due to their dependency on serum-mediated bacterial killing. To extend the treatment paradigm of depolymerase to low-serum lung infections, we explored the feasibility of applying phage depolymerase to potentiate antibiotic efficacy in controlling MDR-AB pneumonia. Using a model depolymerase, Dpo71, we observed that it could effectively potentiate antibiotic efficacy against MDR-AB2 bacteria in low-serum conditions mimicking lung milieu but showed no adjuvant effect in serum-free conditions. Unprecedentedly, we reported this low-serum-dependent mechanism that polysaccharide-degrading enzyme Dpo71 exposed bacteria to serum-induced membrane permeabilization and oxidative phosphorylation pathway inhibition, leading to a weakened ATP-dependent efflux pump and strengthened ROS-induced membrane permeabilization. These joint effects facilitated antibiotic (ceftazidime, CFZ) binding, ultimately exerting bactericidal effects. Resultantly, the bacterial load in the lungs of the Dpo71-CFZ combination group was significantly reduced compared with the Dpo71-alone and CFZ-alone groups. Overall, this study unravels the low-serum-dependent mechanisms by which depolymerase potentiated antibiotic efficacy, highlighting its potential as a novel strategy to enhance antibiotic activity against severe pneumonia. [ABSTRACT FROM AUTHOR]

The Beijing genotype is the most distributed M. tuberculosis family in Kazakhstan. In this study, we identified dominant Beijing clusters in Kazakhstan and assessed their drug susceptibility profiles and association with the most widely spread mutation Ser531Leu of the rpoB gene and the mutation Ser315Thr of the katG gene associated with resistance to rifampicin and isoniazid, respectively. M. tuberculosis isolates (n = 540) from new TB cases were included in the study. MIRU-VNTR genotyping was performed for 540 clinical isolates to determine M. tuberculosis families using 24 loci. RD analysis was additionally performed for the Beijing isolates. The identification of mutations in the drug-resistance genes of M. tuberculosis was performed with allele-specific real-time PCR and Sanger sequencing. The Beijing genotype was identified in 60% (324/540) of the clinical isolates. Central Asian/Russian cluster 94-32 was the most distributed cluster among the Beijing isolates (50.3%; 163/324). Three other dominant Beijing clusters were identified as 94-33 (3.4%; 11/324), 100-32 (3.1%; 10/324) and 99-32 (3.1%; 10/324). The Beijing genotype was associated with drug-resistant TB (p < 0.0001), including multidrug-resistant TB (p < 0.0001), in our study. An association of the mutation Ser531Leu of the rpoB gene with the Beijing genotype was found (p < 0.0001; OR = 16.0000; 95%CI: 4.9161–52.0740). Among the Beijing isolates, cluster 94-32 showed an association with MDR-TB (p = 0.021). This is why the evaluation of the Beijing genotype and its clusters is needed to control MDR-TB in Kazakhstan.

Nosocomial outbreaks of multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) are often reported worldwide, mostly associated with a small number of multilocus-sequence types of E. hormaechei and E. cloacae strains. In Europe, the largest clonal outbreak of blaNDM-1-producing ECC has been recently reported, involving an ST182 E. hormaechei strain in a Greek teaching hospital. In the current study, we aimed to further investigate the genetic make-up of two representative outbreak isolates. Comparative genomics of whole genome sequences (WGS) was performed, including whole genome-based taxonomic analysis and in silico prediction of virulence determinants of the bacterial cell surface, plasmids, antibiotic resistance genes and virulence factors present on genomic islands. The enterobacterial common antigen and the colanic antigen of the cell surface were identified in both isolates, being similar to the gene clusters of the E. hormaechei ATCC 49162 and E. cloacae ATCC 13047 type strains, whereas the two strains possessed different gene clusters encoding lipopolysaccharide O-antigens. Other virulence factors of the bacterial cell surface, such as flagella, fimbriae and pili, were also predicted to be encoded by gene clusters similar to those found in Enterobacter spp. and other Enterobacterales. Secretion systems and toxin–antitoxin systems, which also contribute to pathogenicity, were identified. Both isolates harboured resistance genes to multiple antimicrobial classes, including β-lactams, aminoglycosides, quinolones, chloramphenicol, trimethoprim, sulfonamides and fosfomycin; they carried blaTEM-1, blaOXA-1, blaNDM-1, and one of them also carried blaCTXM-14, blaCTXM-15 and blaLAP-2 plasmidic alleles. Our comprehensive analysis of the WGS assemblies revealed that blaNDM-1-producing outbreak isolates possess components of the bacterial cell surface as well as genomic islands, harbouring resistance genes to several antimicrobial classes and various virulence factors. Differences in the plasmids carrying β-lactamase genes between the two strains have also shown diverse modes of acquisition and an ongoing evolution of these mobile elements.

Abstract Background A substantial body of evidence has recently emphasized the risks associated with antibiotic resistance (ABR) in conflicts in the Middle East. War-related, and more specifically weapon-related wounds can be an important breeding ground for multidrug resistant (MDR) organisms. However, the majority of available evidence comes from the military literature focused on risks and patterns of ABR in infections from combat-related injuries among military personnel. The overall aim of this study is to contribute to the scarce existing evidence on the burden of ABR among patients, including civilians with war-related wounds in the Middle East, in order to help inform the revision of empirical antibiotic prophylaxis and treatment protocols adopted in these settings. The primary objectives of this study are to: 1) describe the microbiology and the corresponding resistance profiles of the clinically relevant bacteria most commonly isolated from skin, soft tissue and bone biopsies in patients admitted to the WTTC; and 2) describe the association of the identified bacteria and corresponding resistance profiles with sociodemographic and specimen characteristics. Methods We retrospectively evaluated the antibiograms of all consecutive, non-duplicate isolates from samples taken from patients admitted to the ICRC WTTC between 2016 and 2019, limited to skin and soft tissue samples and bone biopsies. We collected data on socio-demographic characteristics from patient files and data on specimens from the WHONET database. We ran univariate and multivariable logistic regression models to test the association between bacterial and resistance profiles with sociodemographic and specimen characteristics. Results Patients who were admitted with war-related trauma to the ICRC reconstructive surgical project in Tripoli, Lebanon, from 2016 to 2019, presented with high proportion of MDR in the samples taken from skin and soft tissues and bones, particularly Enterobacterales (44.6%), MRSA (44.6%) and P. aeruginosa (7.6%). The multivariable analysis shows that the odds of MDR isolates were higher in Iraqi patients (compared to Syrian patients) and in Enterobacterales isolates (compared to S. aureus isolates). Conclusions Our findings stress the importance of regularly screening patients who present with complex war-related injuries for colonization with MDR bacteria, and of ensuring an antibiotic-sensitivity testing-guided antimicrobial therapeutic approach.

The use of tigecycline is becoming increasingly important because of the high levels of antibiotic resistance in Acinetobacter baumannii (A. baumannii) isolates. In this prospective study, multidrug-resistant A. baumannii isolates were obtained from various tissue and fluid samples of patients admitted to or treated at various departments and tested in Laboratory of Microbiology, Duzce University Medical Faculty between January 2013 and December 2015. Tigecycline resistance in multidrug-resistant A. baumannii isolates were analyzed using the disc diffusion test (DDT), agar gradient test (AGT), and gold standard test [broth microdilution test (BMT)]. A. baumannii isolates resistant to multiple drugs were included in the study (N=94). Using the BMT method, 89 (95%), 4 (4%) and 1 (1%) A. baumannii isolates were determined as tigecycline susceptible, intermediate and resistant isolates, respectively. Using the Food and Drug Administration criteria, the rates of major error (ME), minor error (mE) and categorical agreement (CA) for DDT were 26%, 67% and 9%, respectively. In contrast, for AGT, the rates of ME, mE and CA were 0%, 4%, 95%, respectively. Tigecycline resistance as assessed by BMT showed no increase between 2013 and 2015. Accordingly, isolates found to be resistant or intermediate by DDT should be confirmed by BMT. Due to the ease of application, AGT is a safe method of detecting susceptibility.

ABSTRACT The presence or absence of BlsA, a protein with a blue light-sensing flavin domain in the genomes of Acinetobacter species has aroused curiosity about its roles in the regulation of bacterial lifestyle under light. Genomic and transcriptomic analyses revealed the loss of BlsA in several multidrug-resistant (MDR) A. baumannii strains as well as the light-mediated induction of blsA, along with a possible BlsA-interacting partner BipA. Their direct in vivo interactions were verified using a bacterial two-hybrid system. The results demonstrated that the C-terminal region of BipA could bind to the C-terminal residues of BlsA under blue light at 23°C but not at 37°C. Genetic manipulations of blsA and bipA revealed that the coexistence of BlsA and BipA was required to induce the light-dependent expression of ompA in A. baumannii ATCC 17978 at 23°C. The same phenomenon occurred in the BlsA-deficient MDR strain in our functional complementation assay; however, the underlying molecular mechanism remains poorly understood. BlsA-modulated amounts of OmpA, the most abundant porin, in the outer membrane affected the membrane integrity and permeability of small molecules. Dark conditions or the deletion of ompA made the membrane more permeable to lipophilic ethidium bromide (EtBr) but not to meropenem. Interestingly, light illumination and low temperature conditions made the cells more sensitive to meropenem; however, this bactericidal effect was not noted in the blsA mutant or in the BlsA-deficient MDR strains. Light-mediated cell death and the reduction of biofilm formation at 23°C were abolished in the blsA mutant strain, suggesting multifaceted roles of BlsA in A. baumannii strains. IMPORTANCE Little is known about the functional roles of BlsA and its interacting partners in Acinetobacter species. Intriguingly, no BlsA homolog was found in several clinical isolates, suggesting that BlsA was not required inside the host because of the lack of blue light and the warm temperature conditions. As many chromophore-harboring proteins interact with various partners to control light-dependent cellular behaviors, the maintenance of blsA in the genomes of many Acinetobacter species during their evolution may be beneficial when fluctuations occur in two important environmental factors: light and temperature. Our study is the first to report the novel protein partner of BlsA, namely, BipA, and its contribution to multiple phenotypic changes, including meropenem resistance and biofilm formation. Rapid physiological acclimation to changing light or temperature conditions may be possible in the presence of the light-sensing BlsA protein, which may have more interacting partners than expected.

Abstract Systematic administration of antibiotics to treat infections often leads to the rapid evolution and spread of multidrug‐resistant bacteria. Here, an in situ‐formed biotherapeutic gel that controls multidrug‐resistant bacterial infections and accelerates wound healing is reported. This biotherapeutic gel is constructed by incorporating stable microbial communities (kombucha) capable of producing antimicrobial substances and organic acids into thermosensitive Pluronic F127 (polyethylene‐polypropylene glycol) solutions. Furthermore, it is found that the stable microbial communities‐based biotherapeutic gel possesses a broad antimicrobial spectrum and strong antibacterial effects in diverse pathogenic bacteria‐derived xenograft infection models, as well as in patient‐derived multidrug‐resistant bacterial xenograft infection models. The biotherapeutic gel system considerably outperforms the commercial broad‐spectrum antibacterial gel (0.1% polyaminopropyl biguanide) in pathogen removal and infected wound healing. Collectively, this biotherapeutic strategy of exploiting stable symbiotic consortiums to repel pathogens provides a paradigm for developing efficient antibacterial biomaterials and overcomes the failure of antibiotics to treat multidrug‐resistant bacterial infections.

The article discusses the challenges of antibiotic resistance (AR) and the impact of the COVID-19 pandemic on AR rates. It highlights the increase in antibiotic use and the emergence of multidrug-resistant infections during the pandemic in both high-income and low- and middle-income countries. The study presents specific data from various countries, demonstrating the rise in broad-spectrum antibiotics and antibiotic resistance genes, emphasizing the need for effective solutions to combat AR.

Acinetobacter baumannii forms robust biofilms, which aid protection against antimicrobials and account for adaptation in hospital settings. Biofilm formation by A. baumannii has worsens the scenario of drug resistance. Therefore, new strategies are required to tackle biofilm-forming multidrug-resistant A. baumannii. The present study investigated compounds with antimicrobials and antibiofilm properties against A. baumannii. Different antimicrobials were selected from available reports. Initially, comparative antimicrobial activity against A. baumannii isolates was assessed. Most potent antimicrobial compounds were further analyzed for time-kill kinetics, biofilm inhibition, and exopolysaccharide (EPS) reduction in their presence and absence. The antibiofilm potentials were also confirmed with SEM analysis. The relative gene expression of the csuE gene and molecular docking was carried out to investigate the molecular mechanism of mature biofilm disruption. The results demonstrated eugenol and geraniol as the most potent inhibitors with MICs of 6.08 mM and 3.24 mM, respectively, with the potential to significantly inhibit growth and EPS production. Complete inhibition of A. baumannii mature biofilms was observed with a maximum of 60.89 mM and 129.6 mM concentrations of eugenol and geraniol, respectively. The SEM analysis and lower expression of the csuE gene showed the effectiveness of potent antibiofilm agents. In-silico docking showed efficient binding of eugenol and geraniol with the csuE protein of archaic pilus. The findings of molecular docking concordant the assumption that these molecules may prevent the assembly of mature pilus, which results in abolished biofilms. In conclusion, the antibiofilm virtues of eugenol and geraniol were elucidated to be used in the future to control the persistence of biofilm-forming drug-resistant A. baumannii. [Display omitted] • Acinetobacter baumannii biofilms aid protection against available antimicrobials, resulting in increment of antimicrobial resistance and therefore it is of higher priority to develop alternative antimicrobials. • The present study is reporting the usage of eugenol and geraniol as efficient inhibitors of the growth and biofilm formation in A. baumannii. • Findings may assist the development of novel drugs to tackle infections of biofilm-forming MDR A. baumannii. [ABSTRACT FROM AUTHOR]

Patients with malignancy are highly prone to infections by extended spectrum beta-lactamases producing Enterobacteriaceae (ESBL-PE). Knowledge on local resistance profile and resistance genes is essential to decide empirical drug. Hence, the study aims to find the resistance profile and the resistance genes of ESBL-PE from cancer patients. 172 oxyimino-cephalosporins resistant enterobacterial isolates from clinical specimens of cancer patients were obtained. Study isolates were speciated by conventional biochemical methods. Resistance to antibiotics was detected by disc diffusion method. Phenotypic detection of eSBls was performed as stated in CLSI guidelines. Genotypic characterization of resistance determinants of ESBL-PE was done by PCR. Among 172 enterobacterial isolates, 151 (87.7%) were ESBL producers. E. coli (67.5%) was the major species producing ESBL enzymes followed by K. pneumoniae (27.8%). Antibiotic susceptibility pattern showed lowest resistance to imipenem 11.2%, and netilmicin 13.9%. 72% of ESBL-PE was found to be Multidrug-resistant. Among ESBL genes, blaCTX M gp-1 (83.4%) was dominant followed by blaTEM (32.4%) and blaSHV (27.8%). 36% of the isolates were found to be positive for more than one eSBl gene. High level of plasmid encoding quinolone resistance genes (64.2%) was identified in ESBL-PE. low levels of plasmid mediated AmpC gene (15.8%) and 16S rRNA genes (9.2%) were found in ESBL-PE. the predominant ESBL encoding gene belongs to blaCTX M group 1. High proportion of ESBL-PE was found to co-harbor PMQR genes. ESBL-PE had highest sensitivity for imipenem and netilmicin. [ABSTRACT FROM AUTHOR]

Prior to the Severe Acute Respiratory Syndrome Coronavirus Disease 2 (SARS-CoV-2) pandemic, the rise in antimicrobial resistance was a major source of concern in public health. However, due to the novelty of SARS-CoV-2 infection during the pandemic, antibiotics were administered prior to laboratory testing for secondary gram-negative bacteria (SGNB) in order to avoid or reduce the occurrence of SGNB infection. the purpose of this study was to investigate the etiology, prevalence, and antimicrobial susceptibility pattern of gram-negative bacteria (GNB) isolated from SARS-CoV-2 positive patients. Respiratory and blood samples were collected from confirmed SARS-CoV-2 positive patients. they were subsequently cultured and bacterial isolates identified according to standard microbiological protocols. Antimicrobial susceptibility testing (ASt) was performed and interpreted according to Clinical & laboratory Standards institute (ClSi) 2021 guidelines. A total of sixty-four non-repetitive GNB were isolated from respiratory samples and twenty-two GNB from blood samples. K. pneumoniae was the major cause of SGNB, followed by Acinetobacter species. K. pneumoniae had over 60% resistance to β-lactam combination agents, cephalosporin, and the carbapenem group of antibiotics. in the current study, we observed that K. pneumoniae was the major cause of SGNB and had high resistance to the antimicrobial agents. Hence, it is important that the epidemiology and susceptibility patterns of circulating organisms causing SGNB infection are always monitored to inform clinical treatment and decrease the occurrence of antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Salmonella is a Gram-negative enteric bacterium responsible for the foodborne and waterborne disease salmonellosis, which is the second most reported bacterial zoonosis in humans. Many animals are potential sources of salmonellosis, including dogs, cats, and other pets. We report the case of an outbreak of salmonellosis in a family in central Italy, affecting two children and involving their three dogs as carriers. One of the children needed medical care and hospitalisation. Isolation and analysis of stool samples from the sibling and the animals present in the house were carried out. Serotyping allowed the identification of S. enterica subsp. enterica serovar Typhimurium in its monophasic variant for all the isolates. The results of whole-genome sequencing confirmed that the strains were tightly related. The minimum inhibitory concentration (MIC) test documented the resistance to ampicillin, sulfamethoxazole, and tetracycline. The origin of the zoonotic outbreak could not be assessed; however, the case study showed a clear passage of the pathogen between the human and non-human members of the family. The possibility of a transmission from a dog to a human suggests the need for further studies on the potential ways of transmission of salmonellosis through standard and alternative feed. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to global public health due to its capacity of tolerate conventional antibiotics. Medicinal plants are traditionally used to treat infectious diseases caused by bacterial pathogens. In the present study, 16 medicinal plants were screened for antibacterial activities to preselect more effective species. Ethanol extracts of selected medicinal plants (Caesalpinia sappan L., Glycyrrhiza uralensis Fisch., Sanguisorba officinalis L., and Uncaria gambir Roxb) were partitioned successively with different solvents (n-hexane, chloroform, ethyl acetate, 1-butanol, and water). Disc diffusion assay and broth microdilution were performed to evaluate the antibacterial activities of plant extracts and fractions against Staphylococcus aureus strains. Furthermore, the cytotoxicity of the extracts and fractions was determined against the human hepatoma (HepG2) and human lung carcinoma (A549) cell lines using a trypan blue exclusion method. A few extracts and fractions showed significant inhibitory effects on the bacterial growth of all tested strains, including multidrug-resistance (MDR) clinical isolates. The ethyl acetate fraction of C. sappan had the most potent effects with minimum inhibitory/bactericidal concentrations (MIC/MBC) of 31.2/62.5 μg/mL and showed low cytotoxicity with over 90% cell viability in both cells. Our results suggest that medicinal plants have considerable potential as alternatives to conventional antibiotics. [ABSTRACT FROM AUTHOR]

Disinfectants and biosecurity are critically important to control microbial diseases. Resistance to disinfectants compromises sectors such as agriculture and healthcare systems. Currently, efflux pumps are the most common mechanism of antimicrobial resistance. This study aimed to identify the efflux transporters responsible for disinfectant resistance in a multidrug-resistant isolate Serratia sp. HRI compared to a susceptible Serratia sp. type strain. An efflux system profile was generated using the Transporter Automatic Annotation Pipeline (TransAAP) for both isolates. Thereafter, the efflux pump inhibitors, reserpine (RSP) and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) were used to reveal the role of efflux pumps in susceptibility to three disinfectants (Didecyldimethylammonium chloride, HyperCide®, and benzalkonium chloride). Interestingly, the resistant isolate had fewer efflux systems in total compared to the type strain and fewer efflux systems classified as resistance efflux pumps. After the addition of RSP, a significant reduction in resistance capabilities against all three antimicrobials was observed for both isolates. However, CCCP supplementation produced mixed results with some outcomes suggesting the involvement of the Eagle effect. This study provides evidence that efflux pumps are responsible for the disinfectant resistance phenotype of the Serratia species due to the increased susceptibility when efflux pump inhibitors are added. [ABSTRACT FROM AUTHOR]

Hospital-acquired pneumonia and ventilator-associated pneumonia are severe nosocomial infections leading to high morbidity and mortality. Broad-spectrum antibiotics with coverage against all likely pathogens are recommended by the international guidelines. Inappropriate empirical treatment is one of the most important prognostic factors. Knowledge of local epidemiology and continuous microbiological surveillance is crucial for improving clinical approaches to empirical antimicrobial treatment. The development of protocols and policies for training healthcare professionals on preventive strategies, such as the "Pneumonia Zero" project, and improved implementation of antimicrobial stewardship practices, will aid early de-escalation of antibiotics and prevent resistance. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most frequent malignancies and, despite screening programs, it is often diagnosed at late stages. Although current first- and second-line therapies stratify for KRAS/NRAS/BRAF mutations, microsatellite instability, tumour location and co-morbidities, the therapeutic mainstay for the first- and second-line treatment of the majority of patients consists of 5-fluorouracil (5-FU)-based chemo-immunotherapy. The present study evaluated the responses of patients with stage IV CRC, treated at the University Hospital Krems between January 1, 2015 and December 31, 2021, who received at least two therapy lines (n=49), with the aim of investigating whether the response to first-line therapy could predict the response to second-line therapy. All patients with first-line complete response (CR) had at least stable disease in response to second-line treatment [overall response rate (ORR)=66.6%]. On the other hand, all patients with progressive disease (PD) in response to first-line treatment (n=7) did not respond to second-line therapy (ORR=0%). These findings also translated to overall survival (OS): Patients with first-line CR had a median OS time of 80 months, whereas patients with PD had a median OS time of 12 months (P<0.001). Furthermore, different parameters were analysed for their impact on OS; the results revealed that BRAF alterations were associated with poor prognosis. Other factors (sex, tumor sidedness, KRAS and MSS/MSI status) had in this cohort no significant effect on OS. In conclusion, the present study demonstrated that, with current treatment strategies applying 5-FU-based chemo-immunotherapy as first- and second-line treatment for patients with metastatic CRC, response to first-line therapy may be a strong predictor for the response to second-line therapy and OS. By exchanging the chemotherapeutic combination partner from oxaliplatin to irinotecan or vice versa, plus the additive anti-epidermal growth factor receptor/anti-vascular endothelial growth factor antibody, the negative factor of non-response to first-line therapy could not be overcome by second-line treatment in this study population. These findings must be confirmed in larger studies, but indicate the need for novel treatment options, especially for patients not responding to first-line 5-FU-based chemo-immunotherapy., Competing Interests: JS declares honorarium payments from Abbvie, Amgen, Gilead, Janssen, Kite, Merck, Merck Sharp & Dohme, Miltenyi, Novartis, Pfizer, Roche and Servier as an invited speaker or expert consulting, which are not relevant for this study. MP declares financial support from Roche for research projects, also not relevant for this study. The other authors declare that they have no competing interests., (Copyright: © 2024 Peyerl et al.)

Convergence of virulence and antibiotic-resistance has been reported in Klebsiella pneumoniae, but not in Klebsiella variicola. We, hereby, report the detection and genomic characterization of hypervirulent and hypermucoviscous K. pneumoniae and K.variicola recovered in Chile from health-care associated infections, which displayed resistance to broad-spectrum cephalosporins. One hundred forty-six K. pneumoniae complex isolates were screened by hypermucoviscosity by the “string test.” Two hypermucoid isolates, one hypermucoviscous K. pneumoniae (hmKp) and one K. variicola (hmKv), were further investigated by whole-genome sequencing. In vivo virulence was analyzed by the Galleria mellonella killing assay. In silico analysis of hmKp UCO-494 and hmKv UCO-495 revealed the presence of multiple antibiotic-resistance genes, such as blaCTX-M-1, blaDHA-1 and blaLEN-25 among others clinically relevant resistance determinants, including mutations in a two-component regulatory system related to colistin resistance. These genetic features confer a multidrug-resistant (MDR) phenotype in both strains. Moreover, virulome in silico analysis confirmed the presence of the aerobactin gene iutA, in addition to yersiniabactin and/or colicin V encoding genes, which are normally associated to high virulence in humans. Furthermore, both isolates were able to kill G. mellonella and displayed higher virulence in comparison with the control strain. In summary, the convergence of virulence and the MDR-phenotype in K. pneumoniae complex members is reported for the first time in Chile, denoting a clinical problem that deserves special attention and continuous surveillance in South America.

Background: Diabetic foot ulcer is a common cause of mortality among patients admitted to Mulago hospital. Peripheral neuropathy and peripheral arterial disease are the major risk factors for diabetic foot ulceration and the severity of these two conditions may determine treatment options and ulcer outcomes. General objective: The study assessed the clinical presentation of foot ulcers in diabetic patients and identified the common bacterial isolates from diabetic foot ulcers and their susceptibility patterns. Methods: This was a prospective study involving 60 consecutive patients with diabetic foot ulcers admitted to the endocrinology unit at Mulago hospital between July and December 2010. Patients were recruited after the provision of written informed consent. Deep tissue swabs from the ulcers were then taken at debridement for both aerobic and anaerobic cultures and susceptibility tests using standard microbiological methods. Results: Of the 60 patients, 57% had neuroischemic foot ulcers, 18% had neuropathic ulcers, 18% had ischemic ulcers and 7% had unclassified ulcers. 98.3% of the samples grew 93 aerobic bacteria and no anaerobe was isolated. Polymicrobial infection occurred in 41% of samples of which 10% had mixed growth. 80.6% of the isolates were Gram-negative aerobes, mainly E.coli Klebsiella, Pseudomonas, and Proteus while eighteen (19.4%) were Gram-positive, mainly Staphylococcus aureus and Enterococcus faecalis. The prevalence of MuMultidrug-resistant organisms (MDRO) was 84% and Methicillin-resistant staphylococcus aureus (MRSA) was 60% while Extended-spectrum beta-lactamases (ESBL) was 43.5%. Conclusion: Diabetic foot ulcers were mostly neuroischemic with moderate neuropathy severity. Infection was mostly due to aerobic Gram-negative organisms with a high prevalence of MDRO, ESBL, and MRSA. Most isolates were susceptible to vancomycin, imipenem, and ciprofloxacin. Recommendation: Deep tissue culture and sensitivity tests should be done to make appropriate antibiotic choices for diabetic patients with foot ulcers.

The Enterobacterales order is a massive group of Gram-negative bacteria comprised of pathogenic and nonpathogenic members, including beneficial commensal gut microbiota. The pathogenic members produce several pathogenic or virulence factors that enhance their pathogenic properties and increase the severity of the infection. The members of Enterobacterales can also develop resistance against the common antimicrobial agents, a phenomenon called antimicrobial resistance (AMR). Many pathogenic Enterobacterales members are known to possess antimicrobial resistance. This review discusses the virulence factors, pathogenicity, and infections caused by multidrug-resistant Enterobacterales, especially E. coli and some other bacterial species sharing similarities with the Enterobacterales members. We also discuss both conventional and modern approaches used to combat the infections caused by them. Understanding the virulence factors produced by the pathogenic bacteria will help develop novel strategies and methods to treat infections caused by them.

Caseous lymphadenitis (CLA) is a bacterial infection caused by Corynebacterium pseudotuberculosis (C. pseudotuberculosis) that affects sheep and goats, leading to abscess formation in their lymph nodes. The present study aimed to isolate and identify C. pseudotuberculosis from CLA in smallholder sheep and goats, and determine the resistance patterns, virulence, and resistance genes of the isolates. Additionally, genotypic and phylogenetic analysis of the isolates was conducted using ERIC-PCR and DNA sequencing techniques. A cross-sectional study examined 220 animals (130 sheep and 90 goats) from 39 smallholder flocks for clinical signs of CLA. Fifty-four (24.54%) animals showed CLA-compatible lesions, confirmed by C. pseudotuberculosis isolation and PCR identification. Sheep had a lower infection rate of CLA (18.46%) compared with goats (33.3%). Antimicrobial susceptibility testing of 54 C. pseudotuberculosis isolates to 24 antimicrobial drugs revealed that they were 100% resistant to bacitracin and florfenicol, while none of the isolates were resistant to norfloxacin. A high resistance rate was observed for penicillin and erythromycin (92.6% each). Interestingly, 16.7% of C. pseudotuberculosis isolates recovered from sheep showed vancomycin resistance. Molecular characterization of C. pseudotuberculosis isolates revealed that PLD, PIP, and FagA virulence genes were present in all examined isolates. However, the FagB, FagC, and FagD genes were detected in 24 (100%), 20 (83%), and 18 (75%) of the sheep isolates, and 26 (87%), 26 (87%), and 18 (60%) of the goat isolates, respectively. The β-lactam resistance gene was present in all isolates. Furthermore, 83% of the sheep isolates carried the aminoglycoside (aph(3″)-lb), chloramphenicol (cat1), and bacitracin (bcrA) resistance genes. Among the isolates recovered from goats, 73% were found to contain macrolides (ermX), sulfonamide (sul1), and bacitracin (bcrA) resistance genes. It is worrisome that the glycopeptide (vanA) resistance gene was detected in 8% of the sheep isolates as a first report. ERIC-PCR genotyping of 10 multi-drug-resistant C. pseudotuberculosis isolates showed a high similarity index of 83.6% between isolates from sheep and goats. Nucleotide sequence analysis of partial 16S rRNA sequences of C. pseudotuberculosis revealed 98.83% similarity with biovar Ovis of globally available reference sequences on the Genbank database. Overall, our findings might indicate that C. pseudotuberculosis infection in smallholders in Egypt might be underestimated despite the significant financial impact on animal husbandry and potential health hazards it poses. Moreover, this study highlights the importance of implementing a sustainable control strategy and increasing knowledge and awareness among smallholder breeders to mitigate the economic impact of CLA.

Simple Summary: Acinetobacter baumannii (A. baumannii) is one of the ESKAPE organisms and has the competency to build biofilms. These biofilms account for the most nosocomial infections all over the world. This review reflects on the various physicochemical and environmental factors such as adhesion, pili expression, growth surfaces, drug-resistant genes, and virulence factors that profoundly affect its resistant forte. Emerging drug-resistant issues and limitations to newer drugs are other factors affecting the hospital environment. Here, we discuss newer and alternative methods that can significantly enhance the susceptibility to Acinetobacter spp. Many new antibiotics are under trials, such as GSK-3342830, The Cefiderocol (S-649266), Fimsbactin, and similar. On the other hand, we can also see the impact of traditional medicine and the secondary metabolites of these natural products' application in searching for new treatments. The field of nanoparticles has demonstrated effective antimicrobial actions and has exhibited encouraging results in the field of nanomedicine. The use of various phages such as vWUPSU and phage ISTD as an alternative treatment for its specificity and effectiveness is being investigated. Cathelicidins obtained synthetically or from natural sources can effectively produce antimicrobial activity in the micromolar range. Radioimmunotherapy and photodynamic therapy have boundless prospects if explored as a therapeutic antimicrobial strategy. Acinetobacter species is one of the most prevailing nosocomial pathogens with a potent ability to develop antimicrobial resistance. It commonly causes infections where there is a prolonged utilization of medical devices such as CSF shunts, catheters, endotracheal tubes, and similar. There are several strains of Acinetobacter (A) species (spp), among which the majority are pathogenic to humans, but A. baumannii are entirely resistant to several clinically available antibiotics. The crucial mechanism that renders them a multidrug-resistant strain is their potent ability to synthesize biofilms. Biofilms provide ample opportunity for the microorganisms to withstand the harsh environment and further cause chronic infections. Several studies have enumerated multiple physiological and virulence factors responsible for the production and maintenance of biofilms. To further enhance our understanding of this pathogen, in this review, we discuss its taxonomy, pathogenesis, current treatment options, global resistance rates, mechanisms of its resistance against various groups of antimicrobials, and future therapeutics. [ABSTRACT FROM AUTHOR]

The article discusses a case of an older female patient with very late-onset multi-drug resistant schizophrenia-like psychosis (VLOSLP). Topics mentioned include the effectiveness and safety of electroconvulsive therapy for long-term prognosis of late paraphrenia and VLOSLP , the use of low-dose risperidone, the symptoms experienced by the patients, and the patient's global clinical dementia rating, mini-mental state examination, and frontal assessment battery scores.

Foodborne diseases and infection caused by associated pathogens is a public health concern. Majority of the investigations focus on common foodborne pathogens like Vibrio parahaemolyticus, Escherichia coli, Listeria monocytogenes, Shigella, Salmonella and Staphylococcus aureus. Limited knowledge has been accounted on Klebsiella pneumoniae. Presence of multidrug-resistant K. pneumoniae in the food supply is disturbing. Hence, this study assessed the presence of K. pneumoniae isolates from food samples (fresh vegetables and chicken), ascertained the presence of drug-resistant phenotypes, extended spectrum beta lactamase production, antibiotic resistance determinants, genes associated with virulence and their ability to form biofilm. Resistance towards ceftazidime and tetracycline was noted among all the isolates in the study, while they exhibited sensitivity to chloramphenicol and cotrimoxazole. All the isolates were potent ES BL producers carrying at least one ES BL encoding genes. Plasmid mediated quinolone resistance gene was detected in one isolate each from onion and chicken respectively. The isolates marked the absence of tetracycline and chloramphenicol resistance genes. Multiple virulence genes (ureA, khe, fimH, mrkD, wabG, uge and elt) were possessed by each of the isolates. K. pneumoniae from chicken and cucumber were moderate biofilm formers and those from tomato exhibited weak biofilm formation. Increased expression of the mrkA gene and reduction in the expression of the biofilm forming gene fimH gene was observed among the biofilm formers. One of the moderate and non-biofilm formers exhibited increased mrkD gene expression. The results from our study stipulate, that raw vegetables and meat serve as dormant source of drug-resistant and virulent K. pneumoniae. [ABSTRACT FROM AUTHOR]

Introduction The study objective was to compare the prevalence of antimicrobial resistance (AMR) in clinical Escherichia coli and Pseudomonas aeruginosa isolates obtained from a secondary-care hospital prior to and during the COVID-19 pandemic in Kuwait. Methods A retrospective descriptive study was conducted based on AMR profiles of clinical Escherichia coli and Pseudomonas aeruginosa isolates. The AMR data represented isolates from five specimen types (body fluids; blood; respiratory; wound, bone, or other tissues; and urine) of patients admitted to four wards (surgical, medical, pediatric, and maternal-postnatal). Tested isolates between January 2019 and February 2020 represented the pre-COVID-19 pandemic period in Kuwait, whereas those from February 2020 until April 2021 represented the 'during COVID-19' period. Results A total of 1,303 isolates (57.2% E. coli and 42.8% P. aeruginosa) were analyzed. For ceftazidime, ertapenem and meropenem, the prevalence of AMR in E. coli was significantly (p<0.05) lower in pre-COVID-19 wards compared to that during COVID-19, whereas for other antibiotics (i.e., cefepime, gentamicin, and trimethoprim/sulfamethoxazole), the prevalence of AMR in pre-COVID-19 was significantly higher than that during COVID-19. The prevalence of AMR to gentamicin in P. aeruginosa isolates from non-COVID-19 wards (52.8%) was significantly higher (p<0.001) than that from COVID-19 wards (35.0%) and from the pre-COVID-19 period (32.9%). The multidrug-resistance (MDR) prevalence was 37.4% for E. coli and 32.1% for P. aeruginosa isolates. The odds of MDR in E. coli isolates from the COVID-19 medical wards were significantly lower (OR=0.27, [95%CI: 0.09-0.80], p=0.018) compared to the pre-COVID-19 wards. The odds of MDR E. coli and P. aeruginosa isolates by COVID-19 status stratified by specimen type were not different (p>0.05). Conclusions No major differences in AMR in E. coli and P. aeruginosa prevalence by specimen type and wards prior to and during the COVID-19 pandemic was observed at this hospital. The high reported MDR prevalence calls for better infection control and prevention. [ABSTRACT FROM AUTHOR]

Aeromonas has recently been recognized as an emerging human pathogen. Aeromonas- associated diarrhea is a phenomenon occurring worldwide. This study was designed to determine the prevalence, genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas strains isolated from food products in Shanghai. Aeromonas isolates (n = 79) collected from food samples were analyzed using concatenated gyrB-cpn60 sequencing. The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing. Pathogenicity was assessed using β-hemolytic, extracellular protease, virulence gene detection, C. elegans liquid toxicity (LT), and cytotoxicity assays. Eight different species were identified among the 79 isolates. The most prevalent Aeromonas species were A. veronii [62 (78.5%)], A. caviae [6 (7.6%)], A. dhakensis [3 (3.8%)], and A. salmonicida [3 (3.8%)]. The Aeromonas isolates were divided into 73 sequence types (STs), of which 65 were novel. The isolates were hemolytic (45.6%) and protease-positive (81.0%). The most prevalent virulence genes were act (73.4%), fla (69.6%), aexT (36.7%), and ascV (30.4%). The results of C. elegans LT and cytotoxicity assays revealed that A. dhakensis and A. hydrophila were more virulent than A. veronii, A. caviae, and A. bivalvium. Antibiotic resistance genes [tetE, blaTEM, tetA, qnrS, aac(6)-Ib, mcr-1, and mcr- 3] were detected in the isolates. The multidrug-resistance rate of the Aeromonas isolates was 11.4%, and 93.7% of the Aeromonas isolates were resistant to cefazolin. The taxonomy, antibiotic resistance, and pathogenicity of different Aeromonas species varied. The Aeromonas isolates A. dhakensis and A. hydrophila were highly pathogenic, indicating that food-derived Aeromonas isolates are potential risks for public health and food safety. The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) Pseudomonas aeruginosa poses a great challenge to clinical treatment. In this study, we characterized a ST768 MDR P. aeruginosa strain, Pa150, that was isolated from a diabetic foot patient. The minimum inhibitory concentration (MIC) assay showed that Pa150 was resistant to almost all kinds of antibiotics, especially aminoglycosides. Whole genome sequencing revealed multiple antibiotic resistant genes on the chromosome and a 437-Kb plasmid (named pTJPa150) that harbors conjugation-related genes. A conjugation assay verified its self-transmissibility. On the pTJPa150 plasmid, we identified a 16S rRNA methylase gene, rmtB, that is flanked by mobile genetic elements (MGEs). The transfer of the pTJPa150 plasmid or the cloning of the rmtB gene into the reference strain, PAO1, significantly increased the bacterial resistance to aminoglycoside antibiotics. To the best of our knowledge, this is the first report of an rmtB-carrying conjugative plasmid isolated from P. aeruginosa, revealing a novel possible transmission mechanism of the rmtB gene. [ABSTRACT FROM AUTHOR]

The rapid emergence of multidrug-resistant (MDR) bacteria indisputably constitutes a major global health problem. Pathogenic Escherichia coli are listed among the most critical group of bacteria that require fast development of new antibiotics and innovative treatment strategies. Among harmful extraintestinal Enterobacteriaceae strains, uropathogenic E. coli (UPEC) pose a significant health threat. UPEC are considered the major causative factor of urinary tract infection (UTI), the second-most commonly diagnosed infectious disease in humans worldwide. UTI treatment places a substantial financial burden on healthcare systems. Most importantly, the misuse of antibiotics during treatment has caused selection of strains with the ability to acquire MDR via miscellaneous mechanisms resulting in gaining resistance against many commonly prescribed antibiotics like ampicillin, gentamicin, cotrimoxazole and quinolones. Mobile genetic elements (MGEs) such as transposons, integrons and conjugative plasmids are the major drivers in spreading resistance genes in UPEC. The co-occurrence of various bacterial evasion strategies involving MGEs and the SOS stress response system requires further research and can potentially lead to the discovery of new, much-awaited therapeutic targets. Here, we analyzed and summarized recent discoveries regarding the role, mechanisms, and perspectives of MDR in the pathogenicity of UPEC. [ABSTRACT FROM AUTHOR]

The spread of carbapenemase-producing (CP) Enterobacterales is currently a worldwide concern, especially in the elderly. Twelve CP-E. coli isolated from rectal swabs of colonized inpatients aged ≥65 years from four hospitals in two Italian cities (Milan and Rome) were analyzed by whole genome sequencing (WGS) to obtain multi-locus sequence typing (MLST), identification of carbapenemase-encoding genes, resistome, plasmid content, and virulence genes. MLST analysis showed the presence of 10 unrelated lineages: ST410 (three isolates from three different hospitals in two cities) and ST12, ST38, ST69, ST95, ST131, ST189, ST648, ST1288, and ST1598 (one isolate each). Most isolates (9/12, 75%) contained a serine-β-lactamase gene (5 blaKPC-3, 2 blaKPC-2, and 2 blaOXA-181), while three isolates harbored a metallo-β-lactamase gene (two blaNDM-5 and one blaVIM-1). In most CP-E. coli, the presence of more than one plasmid was observed, with the predominance of IncF. Several virulence genes were detected. All isolates contained genes enhancing the bacterial fitness, such as gad and terC, and all isolates but one, fimH, encoding type 1 fimbriae. In conclusion, CP-E. coli clones colonizing elderly patients showed heterogeneous genetic backgrounds. We recommend strict surveillance to monitor and prevent the spread of successful, high-risk clones in healthcare settings. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine carbapenems, colistin resistance genes, and antimicrobial susceptibility profiles of Pseudomonas aeruginosa and Acinetobacter baumannii isolates. Materials and Methods: In this cross-sectional study, specimens of patients with bloodstream, urinary tract, and surgical site nosocomial infections were enrolled. P. aeruginosa and A. baumannii isolates were identified using conventional methods. Antimicrobial susceptibility testing (AST) on isolates was performed using the disk diffusion method and minimum inhibitory concentration (MIC) for colistin as recommended by the Clinical and Laboratory Standards Institute (CLSI). The combination meropenem disk method was used to detect metallo-β-lactamases (MBLs). The blaNDM, blaVIM, blaIMP, and mcr-1 genes were identified using the polymerase chain reaction (PCR) method and Sequencing. Results: Forty strains of P. aeruginosa and forty strains of A. baumannii were isolated from hospitalized patients. The overall prevalence of multidrug-resistance (MDR) was 50% and 95% in P. aeruginosa and A. baumannii isolates, respectively. Almost all the MDR isolates were resistant to cefepime and piperacillin. Colistin had significant inhibitory activity against the isolates. MBL was detected in 25.0% and 15.0% of clinical isolates of P. aeruginosa and A. baumannii, respectively. We detected no blaNDM, blaVIM, blaIMP, and mcr-1 genes in our A. baumannii isolates. Moreover, only three P. aeruginosa isolates were positive for blaIMP gene. Conclusion: The alarming proportion of MDR P. aeruginosa and A. baumannii isolates was reported in the current study. Effective infection prevention practices are required and AST should guide patients' treatment. [ABSTRACT FROM AUTHOR]

Background and Aim: Fowl cholera (FC) caused by Pasteurella multocida is a highly contagious bacterial disease of global importance for poultry production. The severity and incidence of FC caused by P. multocida may vary considerably depending on several factors associated with the host (including species and age of infected birds), the environment, and the bacterial strain. This study aimed to investigate the genetic diversity of multidrug-resistant P. multocida strains isolated from FC outbreaks in laying hens from commercial farms of Bangladesh. Materials and Methods: We collected 57 samples of suspected FC, including 36 live and 21 dead laying hens. P. multocida isolates were characterized by biochemical and molecular-biological methods. Results: Twenty-two strains of P. multocida were isolated from these samples through phenotypic and genotypic characterization. The strains were grouped into two distinct random amplification of polymorphic DNA (RAPD) biotypes harboring a range of pathogenic genes; exbB, ompH, ptfA, nanB, sodC, and hgbA. In this study, 90.90% and 81.82% P. multocida strains were multidrug-resistant and biofilm formers, respectively. Whole-genome sequencing of the two representative RAPD phylotypes confirmed as P. multocida type B: L2:ST122, harboring a number of virulence factors-associated genes (VFGs), and antimicrobial resistance (AMR) genes (ARGs). In addition, pan-genome analysis revealed 90 unique genes in the genomes of P. multocida predicted to be associated with versatile metabolic functions, pathogenicity, virulence, and AMR. Conclusion: This is first-ever report on the association of P. multocida genotype B: L2:ST122 and related VFGs and ARGs in the pathogenesis of FC in laying hens. This study also provides a genetic context for future researches on the evolutionary diversity of P. multocida strains and their host adaptation.

Abstract Objective Klebsiella pneumoniae is one of most opportunistic pathogens that can be related to nosocomial infections. Increased acquisitions of multidrug resistance in this bacterium as well as the transfer of genes to other strains have caused concern. Integrons play key role in the acquisition and the spread of resistance genes. The aim of this study was evaluated the frequency of resistance genes sulI, sulII, tetA, tetB, class I (intI gene), class II integrons (intII gene) and the association between multidrug resistance and the presence of integrons in K. pneumoniae. Results Antibiotics susceptibility test was performed on 126 of K. pneumoniae isolates. Also, DNA extraction was done and genes were detected using PCR method. In this study, 67 isolates (53%), carrying both the sulI and sulII genes. Forty-five percent tetracycline-resistant isolates were tetA or tetB positive. The prevalence of intI gene was 96%, while only sixteen isolate harboring intII gene (12.5%). Our results showed the high prevalence of integrons in MDR K. pneumoniae, indicating the important role of these genes in the transmission of antibiotic resistance.

Hui Zhang,1,&ast; Peiyao Jia,1,2,&ast; Ying Zhu,1,2,&ast; Ge Zhang,1 Jingjia Zhang,1 Wei Kang,1 Simeng Duan,1 Weijuan Zhang,3 Qiwen Yang,1 Yingchun Xu1 1Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People’s Republic of China; 3MRL Global Medical Affairs, MSD China, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiwen Yang; Yingchun XuDepartment of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86-18600100521; Tel/Fax +86-010-69159766Email yangqiwen81@vip.163.com; xycpumch@139.comPurpose: In recent years, less options are available for treating carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa. The present study investigates the susceptibility rates to imipenem/relebactam for the treatment of intra-abdominal infections (IAIs), respiratory tract infections (RTIs) and urinary tract infections (UTIs) caused by A. baumannii and P. aeruginosa in China.Patients and Methods: A total of 1886 P. aeruginosa and 1889 A. baumannii isolates were collected in 21 centers (7 regions) as a part of the global SMART surveillance program between 2015 and 2018. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) recommendations using the broth microdilution methodology at Peking Union Medical College Hospital.Results: For P. aeruginosa, overall susceptibility rates to imipenem/relebactam were 84.2% at a CLSI breakpoint of ≤ 2 mg/L compared to 55.7% for imipenem. Susceptibility rates of imipenem-non-susceptible P. aeruginosa to imipenem/relebactam were 64.4% and for multidrug-resistance (MDR) P. aeruginosa susceptibility rates were increased from 25.2% for imipenem to 65.8% for imipenem/relebactam. The susceptibilities of imipenem-non-susceptible and MDR P. aeruginosa strains were similarly restored by imipenem/relebactam in non-ICU and ICU wards. The rate of imipenem-non-susceptibilities A. baumannii isolates was 79.0%, whereas the MDR rate was 81.9%. Relebactam did not change the susceptibilities of imipenem-non susceptible or MDR A. baumannii isolates.Conclusion: Imipenem/relebactam provides a therapy option to treat infections caused by MDR or imipenem-non-susceptible P. aeruginosa but not A. baumannii infections in China.Keywords: carbapenem-resistance, extended-spectrum β-lactamase, multidrug-resistance, β-lactamase inhibitor, carbapenemase

Colorectal cancer (CRC) is one of the most frequent malignancies and, despite screening programs, it is often diagnosed at late stages. Although current first- and second-line therapies stratify for KRAS/NRAS/BRAF mutations, microsatellite instability, tumour location and co-morbidities, the therapeutic mainstay for the first- and second-line treatment of the majority of patients consists of 5-fluorouracil (5-FU)-based chemo-immunotherapy. The present study evaluated the responses of patients with stage IV CRC, treated at the University Hospital Krems between January 1, 2015 and December 31, 2021, who received at least two therapy lines (n=49), with the aim of investigating whether the response to first-line therapy could predict the response to second-line therapy. All patients with first-line complete response (CR) had at least stable disease in response to second-line treatment [overall response rate (ORR)=66.6%]. On the other hand, all patients with progressive disease (PD) in response to first-line treatment (n=7) did not respond to second-line therapy (ORR=0%). These findings also translated to overall survival (OS): Patients with first-line CR had a median OS time of 80 months, whereas patients with PD had a median OS time of 12 months (P<0.001). Furthermore, different parameters were analysed for their impact on OS; the results revealed that BRAF alterations were associated with poor prognosis. Other factors (sex, tumor sidedness, KRAS and MSS/MSI status) had in this cohort no significant effect on OS. In conclusion, the present study demonstrated that, with current treatment strategies applying 5-FU-based chemo-immunotherapy as first- and second-line treatment for patients with metastatic CRC, response to first-line therapy may be a strong predictor for the response to second-line therapy and OS. By exchanging the chemotherapeutic combination partner from oxaliplatin to irinotecan or vice versa, plus the additive anti-epidermal growth factor receptor/anti-vascular endothelial growth factor antibody, the negative factor of non-response to first-line therapy could not be overcome by second-line treatment in this study population. These findings must be confirmed in larger studies, but indicate the need for novel treatment options, especially for patients not responding to first-line 5-FU-based chemo-immunotherapy. [ABSTRACT FROM AUTHOR]

Candida aurisis an emerging multidrug-resistant pathogen that can be difficult to identify using traditional biochemical methods. C. auris is capable of causing invasive fungal infections, particularly among hospitalized patients with significant medical comorbidities. Echinocandins are the empiric drugs of choice for C. auris, although not all isolates are susceptible and resistance may develop on therapy. Nosocomial C. auris outbreaks have been reported in a number of countries and aggressive infection control measures are paramount to stopping transmission.

The high burden of Salmonella infections has been aggravated by the emergence and spread of multidrug-resistant strains affecting almost all antibiotic classes recommended for treatment. Several tetrahydroisoquinolines, both natural and synthetic, are important pharmaceuticals for a wide range of pathologies. Medicinal chemistry exploration of the tetrahydroisoquinoline scaffold has yielded analogues with considerable antimicrobial activity against bacteria, viruses, and fungi, amongst other pharmacological properties. We report here on a series of seventeen tetrahydroisoquinoline analogues of Dioncophyllines that were synthesized and screened against multidrug-resistant strains of Salmonella using standard methods. The cytotoxicity of selected compounds was assessed. Two compounds, 3b and 3n, were found to have activity, presenting zones of inhibition ≥ 20 mm and the best minimum inhibitory concentration (MIC) of 16 µg/mL), comparable to current anti-Salmonella drugs. Furthermore, most MBC:MIC ratios were

The rise in multidrug-resistant pathogens and biofilms has become a significant issue to address. In the rise of the hour, various innovating technologies are being used to combat these deadly pathogens. One of the emerging technologies is cold atmospheric plasma (CAP) which could bring a revolution to this aspect. The antimicrobial property of CAP makes it a powerful tool in the inactivation of multidrug-resistant pathogens and biofilms. This review paper emphasizes how the antimicrobial efficacy of CAP is affected by the types of the devices, operating gas composition and flow rate, variation of source frequency, voltage and power, exposure distance, treatment time, initial concentration of microorganism suspension, and growth media and nature of target microorganisms. Further, the role of various CAP agents i.e., reactive species, charged particles, UV radiation, and electric field in the inactivation mechanism has been reviewed. A brief idea of some of CAP technology's prospects and its effectiveness has been discussed at the end. Overall, the content of this review provides a global thought on the influence of CAP parameters on drug-resistant pathogens and biofilms, which will aid researchers in this field.