Antiretroviral (ARV) drugs have played a vital role in controlling the HIV-1 epidemic; however, some challenges remain. ARV drugs vary in their ability to control HIV infection, displaying differences in treatment-limiting factors and genetic barriers to resistance. The current report assesses the prevalence of HIV-1 drug resistance mutations (DRMs) among patients who failed first-line antiretroviral therapy (ART) and evaluates the genetic barrier of different regimens. The study cohort (n=271) included HIV-infected individuals who visited the Novosibirsk, Russia, HIV/AIDS clinic in 2018-2022. All patients received first-line ART prior to virological failure. Sociodemographic and HIV-related data were collected from medical records and self-reported questionnaires. HIV-1 pol gene sequences were generated, and the presence of HIV-1 DRM was assessed. The genetic barrier to resistance was assessed by combining treatment regimen and adherence data. Nonoptimal ART adherence was identified in 48.3% of patients and correlated with male sex, PWID, unemployment, and rural area residence. Most of the patients with high-level adherence were identified among those who were on TDF+3TC+DTG. HIV-1 DRMs were identified in 54.6% of the patients. The analysis of HIV-1 DRM, ART regimen, and adherence data classified TDF+3TC+DTG and TDF+3TC+LPV/r as treatment regimens with a high genetic barrier, whereas EFV-containing ART was classified as a regimen with a low genetic barrier. The current study delivers results on the efficacy of HIV-1 ART and treatment adherence in real-world practice settings. This report suggests that ART regimens with a high genetic barrier to resistance combined with improved treatment adherence may reduce the transmission of HIV-1 resistant variants.

Antibiotic resistance (AR) is a global health issue with multidimensional repercussions. There is a paucity of data regarding the molecular epidemiology of multidrug-resistant Enterobacterales (MDR-E) and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) in Africa, especially among people living with HIV (PLHIV). This study aimed at determining the prevalence, risk factors, phenotypic and genotypic profiles of MDR-E and ESBL-PE isolated from PLHIV in Yaoundé, Cameroon. In total, samples were collected from 185 PLHIV during a three-month period (April-June 2021) at the Yaoundé Central Hospital. Stool samples and rectal swabs were collected and cultured on MacConkey agar. The API 20E kit was used for the phenotypic identification of the isolates, whereas antibiotic susceptibility testing was performed using the Kirby-Bauer disk diffusion method. The ß-lactamase genes and genotypic relatedness were studied by PCR and ERIC-PCR, respectively. The prevalence of MDR-E among PLHIV was 81%, of which 39% were ESBL-PE. A high level of resistance to fosfomycin (89%), chloramphenicol (63%), and gentamicin (56%) was observed. Escherichia coli was the predominant MDR non-ESBL-PE (80.8%) and MDR ESBL-PE (73.77%). The principal ß-lactamases genes in MDR non-ESBL and MDR ESBL-PE were blaTEM (62.90%) and blaCTX-M (40.86%), respectively. Genetic fingerprinting revealed high genetic relatedness among E. coli isolates. This study shows a high prevalence of MDR-E and ESBL-PE in the gut of PLHIV in Yaoundé, withblaTEM andblaCTX-M being the most prevalent. It demonstrates the need to strengthen real-time surveillance of these resistant bacteria in order to improve management of infection among PLHIV.

Non-tuberculous mycobacteria are opportunistic pathogens that cause disease mainly in immunocompromised hosts. The present study assessed the prevalence of antibiotic resistance among such mycobacteria from domestic and wild animals in Croatia sampled during several years within a national surveillance program. A total of 44 isolates belonging to nine slow-growing species were genotyped and analyzed for susceptibility to 13 antimicrobials often used to treat non-tuberculous mycobacterial infections in humans. Most prevalent resistance was to moxifloxacin (77.3%), doxycycline (76.9%), and rifampicin (76.9%), followed by ciprofloxacin (65.4%), trimethoprim-sulfamethoxazole (65.4%), and linezolid (61.4%). Few isolates were resistant to rifabutin (7.7%) or amikacin (6.8%). None of the isolates was resistant to clarithromycin. Nearly all isolates (86.4%) were resistant to multiple antibiotics. Our findings suggest substantial risk that human populations may experience zoonotic infections with non-tuberculous mycobacteria that will be difficult to treat using the current generation of antibiotics. Future work should clarify how resistance emerges in wild populations of non-tuberculous mycobacteria.

Escherichia coli sequence type (ST) 127 is a pandemic lineage that belongs to the extraintestial pathogenic (ExPEC) family, mainly associated with urinary tract infections and bloodstream infections. Here, we report the complete genome of an E. coli ST 127 isolate which was identified in the saliva of a patient with treatment-resistant schizophrenia (TRS) exhibiting no signs of infection. The objective of this work is to determine the mobile genetic elements (MGEs), antibiotic resistance genes (ARGs), and virulence factors (VFs) that contribute to the pathogenicity of such ST127 isolates. Whole-genome sequencing (WGS) of isolate GABEEC10 was performed using DNABseq and Nanopore MinION platforms. Hybrid assembly of GABEEC10 was conducted with Unicycler v. 0.5.0. and annotated using PROKKA v1.14.5. Comparative genomics and phylogenomics were conducted using average nucleotide identity (ANI) and approximately-maximum-likelihood phylogenetic inference. ARGs, VFs, and serotyping were identified with Abricate v1.0.0 using CARD, vfdb, and EcOH databases, respectively. Escherichia coli salivary isolate GABEEC10 was identified to belong to phylogroup B2 and have a serotype of O6 H31 with a total genome length of 4,940,530 bp and a mean guanine-cytosine (GC) content of 50.40 %. GABEEC10 was identified to have a highly virulent genotype with the presence of 84 VFs in addition to 44 ARGs, including an acquired blaTEM-30. The strain was identified to additionally carry four mobilisable plasmids. We report the complete genome of E. coli GABAEEC10 that can be used for gaining insights into the pathogenicity, drug resistance mechanisms, and dissemination patterns of the emerging pandemic lineage ST 127.

This is the first nationally representative study to estimate the prevalence of viral load (VL) suppression and acquired HIV drug resistance (ADR) among people living with HIV (PLHIV) in Nepal. A cross-sectional study recruited 1418 PLHIV from 20 ART centres in Nepal, using a two-stage cluster design. Participants were eligible if they were HIV-positive individuals on ART for 9-15 months or at least 48 months. Plasma specimens were collected and tested for the quantification of HIV-1 RNA. Specimens with a VL ≥1000 copies/mL were further processed for sequencing of PR and RT genes of HIV-1. The sequences were then analysed to detect mutations causing HIV drug resistance. The prevalence of ADR was 3.7% (95% confidence interval [CI]: 1.8-7.6) and 3.0% (95% CI: 1.8-5.2) among PLHIV who received ART for 9-15 months and 48 months or more, respectively. The prevalence of VL suppression was 95.3% (95% CI: 91.7-97.4) among those on ART for 9-15 months, and 96.5% (95% CI: 94.7-97.7) among those on ART for at least 48 months. The prevalence of any detectable acquired resistance to antiretroviral drugs was 80.7% (95% CI: 58.6-92.5) among those on ART for 9-15 months with VL ≥1000 copies/mL and 81.6% (95% CI: 55.4-94.0) among those on ART for at least 48 months with VL ≥1000 copies/mL. This study suggests that improved accessibility to VL monitoring and timely assessment of drug resistance in routine HIV programs are crucial in Nepal to ensure access to HIV treatment for all in need.

Fosfomycin is a first-line treatment for uncomplicated urinary tract infections (UTIs) in several European countries, and it is increasingly becoming the treatment of choice globally. Resistance to fosfomycin in Escherichia coli can be exerted through several mechanisms, including the acquisition of fosfomycin-modifying enzymes, of which the FosA-type enzymes are the most common. This study analysed, both phenotypically and genotypically, an international collection of E. coli strains harbouring acquired fosA genes. Thirty-one fosA-positive E. coli isolates were obtained from both clinical and environmental sources, from seven countries (Portugal (n=12), Switzerland (n=9), China (n=3), France (n=2), Nepal (n=2), South Africa (n=2), Kuwait (n=1)). MICs were determined according to EUCAST guidelines. Whole genome sequencing (WGS) was performed on 23 isolates, and complete fosA plasmid sequences were determined for 12. Conjugation assays were performed on seven isolates. All isolates exhibited high-level resistance to fosfomycin (64 to >256 mg/L). WGS of 23 isolates identified 17 sequence types (STs), and 16 harboured fosA3, four fosA4, two fosA8, and one fosA10. ESBLs, pAmpC, or carbapenemase genes were present in 15, four, and three isolates, respectively. The fosA plasmids of 12 isolates were determined and were diverse in size (∼67 kb to ∼235 kb), resistance gene carriage, and replicon types. Six fosA plasmids additionally carried ESBL or carbapenemase genes. Conjugation assays, performed on seven isolates harbouring diverse plasmids, identified that all were capable of being transmitted. This study highlights the necessity of the surveillance and close monitoring of fosfomycin resistance in E. coli, essential to maintain the optimal use of this treatment option.

Hypervirulent Klebsiella pneumoniae (hvKp) and Klebsiella variicola (hvKv) cause hospital/community-acquired infections, often associated with antimicrobial resistance (AMR). This study aimed to investigate the molecular epidemiology of hvKp and hvKv in northern Japan. A total of 500 K. pneumoniae and 421 K. variicola clinical isolates collected from August to December 2021 were studied. Prevalence of virulence factor-encoding genes, wzi sequence and associated K/KL type, sequence type (ST), and beta-lactamases and their types were characterized. Any virulence gene (rmpA, rmpA2, peg-344, iucA, iutA, and iroB) and/or magA was detected in 25% (n=125) of K. pneumoniae and 1% (n=5) of K. variicola. Among these hvKp/hvKv, 22 wzi types (18 and 4 types, respectively) and 24 STs (20 and 4 STs, respectively) were identified. Sequence types of hvKp were classified into some clonal groups (CGs), among which CG35, including six STs, was the most common (n=59; 47%), followed by CG23, and CG65. ST268 (CG35) associated with wzi95-K20 or wzi720 was the dominant lineage (n=43, 34%), while K1:ST23/ST249 and K2:ST65/ST86 accounted for 26% and 13% of hvKp, respectively. Extended-spectrum beta-lactamase (ESBL) genes (blaCTX-M-2, blaCTX-M-3, blaCTX-M-15, and blaCTX-M-27) were detected in only ST23 and CG35 (ST268 and ST412) hvKp. No isolate was resistant to carbapenems, without detection of the ESBL gene in K. variicola. Phylogenetically, wzi was differentiated into two main clusters of K. pneumoniae and K. variicola. A major clonal group CG347 was identified in K. variicola. Clonal structures were revealed for hvKp and hvKv clinical isolates with their AMR status in northern Japan.

The aim of this study was to characterize the blaKPC-33 in a ST15-K19 ceftazidime-avibactam (CAZ-AVI)-resistant Klebsiella pneumoniae strain after the antibiotic CAZ-AVI was approved for use in Wuxi No. 2 People's Hospital, China. Antimicrobial susceptibility testing was performed by the microdilution broth method. Whole genome sequencing (WGS) was performed using PacBio II and MiSeq sequencers. High-quality reads were assembled using the SOAPdenovo and GapCloser v1.12, and genome annotation was performed using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). Genomic characteristics were analysed by using bioinformatics methods. K. pneumoniae strain KPHRJ showed resistance to CAZ-AVI. WGS analysis showed that strain KPHRJ had one 5 536 506 bp chromosome (57.25% G+C content) and one plasmid (133 451 bp, G+C 54.29%). KPHRJ was classified as ST15 and K19 serotype. Resistome analysis showed that KPHRJ carries seven antimicrobial resistance genes (ARGs). WGS analysis and conjugation experiments demonstrated that the blaKPC-33 gene was carried by plasmid pKPHRJ, flanked by two copies of IS26 mobile elements (IS26-ISKpn27-blaKPC-33-ISKpn6-korC-TnAs1-tetR-tetA-Tn3-IS26). Besides these acquired resistance genes, mutations in porin protein-coding genes, such as OmpK36 and OmpK37, which may reduce susceptibility to the CAZ-AVI, were also identified from the genome. Here, we present the WGS of a CAZ-AVI resistant K. pneumoniae isolate, strain KPHRJ, with capsular serotype K19 and belonging to ST15. CAZ-AVI resistance is likely conferred by a KPC-2 variant, blaKPC-33 and mutations in porin-coding genes. We speculate that the approval of the CAZ-AVI in hospital could contribute to the emergence of these genomic features by providing a selective pressure leading to the emergence of CAZ-AVI resistant bacteria.

Acinetobacter bereziniae has been found to cause health care-associated infections, especially in immunocompromised patients. The emergence of two carbapenemase-producing A. bereziniae strains complicates clinical management. Here, we present the genome sequence of a clinical A. bereziniae strain from China co-carrying blaOXA-301 and blaNDM-1. The genomic DNA of BZAB1 was subjected to whole-genome sequencing using the Illumina NovaSeq 6000 system and assembled using SPAdes 3.13.0. Using the resfinder database of ABRicate V1.01, antimicrobial resistance genes were identified. The Snippy application was used to carry out the phylogenetic analysis. The genome sequence of A. bereziniae BZAB1 consists of 122 contigs consisting of 4 596 983 bp. A total of nine antimicrobial resistance genes were predicted in BZAB1, including two carbapenemase genes: blaOXA-301 and blaNDM-1. Sixty-nine A. bereziniae strains can be retrieved from the National Centre for Biotechnology Information database, 29 of which possess the blaOXA-301 gene and five of which contain the blaNDM-1 gene. Only three strains carry both blaNDM-1 and blaOXA-301. It is worth noting that all three strains carrying both blaNDM-1 and blaOXA-301 are from China, two of which are clonally related to BZAB1. We report the genome sequence of a multidrug-resistant A. bereziniae strain co-carrying blaOXA-301 and blaNDM-1. A. bereziniae strains carrying various beta-lactam resistance genes have been identified sporadically over the world. Our findings could help us aid in understanding the genomic insights of this pathogen. Their future prevalence must be given more consideration.

Postoperative central nervous system infections (PCNSIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) frequently result in unfavourable outcomes. However, CRE PCNSIs have not been well describedfrom aclinical and microbiological perspective. A total of 254 PCNSIs cases were included (January 2017 through June 2020), and clinical features were compared based on pathogenic classification. Cox regression analysis was performed to assess risk factors for mortality. Antibiotic susceptibility testing and whole genome sequencing were conducted on CRE isolates preserved. MLST, cgMLST, resistance genes and virulence genes were further analysed. Among 254 PCNSI cases, 15.4% were caused by Enterobacteriaceae including 28 cases by CRE. The 28-day mortality rates for CRE, CSE and non-Enterobacteriaceae PCNSIs were 50.0%, 27.3%, and 7.4%, respectively. 42.9% (12/28) of the CRE PCNSIs patients achieved clinical cure, with 25.0% achieved microbiological clearance. ST11-KL64 carrying blaKPC-2 was dominant in CRE (17/23, 73.9%), and the 28-day mortality rate of its infection was 58.5%. Most CRKP carried rampA/rampA2 genes (17/23, 73.9%). ST11-KL64 CRKP carrying blaKPC-2 dominated among CRE PCNSIs. Targeted anti-infective combination therapy based on ceftazidime/avibactam or amikacin, combined with intrathecal administration of amikacin, was found to be effective. These findings render a new insight into the clinical and microbiological landscape of CRE PCNSIs.