Microbial drug resistance最新文献

Intestinal colonization with carbapenem-resistant Enterobacterales (CRE) has been shown as a significant risk factor for subsequent CRE infections, especially in intensive care units (ICUs). The aim of this study was to determine the prevalence of intestinal CRE colonization among ICU patients in a Chinese tertiary hospital. Fecal sample screenings for CRE were performed on ICU patients weekly. Antibiotic-susceptibility profile of CRE strains was determined using the Vitek-2 analysis system and broth microdilution method. The carbapenemases of all isolates were determined by phenotypes and genotypes. Clonal relatedness was analyzed by pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing was used to identify the multilocus sequence type (ST), plasmid replicons, and insertion sequences (ISs) of isolates. The overall colonization rate of CRE was 40.4% (82/203). A total of 84 CRE strains were detected, mostly with Klebsiella pneumoniae (92.9%). Antibiotic susceptibility testing profile revealed that 84 CRE strains were resistant to most antibiotics except for tigecycline and colistin. The carbapenemase-encoding genes including bla_KPC-2, bla_NDM-1, and bla_IMP-4 were detected, and bla_KPC-2 was the predominant genotype (90.8%). A total of 9 STs were identified among 84 CRE strains, and ST11 was the most common type (83.3%). A variety of mobile genetic elements, including plasmids and ISs, were detected via online tool prediction. PFGE analysis of the 78 K. pneumoniae strains showed 8 different pulsotypes, and pulsotype A was highly prevalent. This study found that the prevalence of CRE colonization was alarmingly high in the ICU, and that effective infection control measures are urgently needed to prevent the dissemination of CRE.

The study aimed to determine the prevalence of extended-spectrum β-lactamase resistance and CTX-M-group 1 gene in Escherichia coli from the water and sediment of three urbanized mangrove ecosystems of Kerala. A total of 119 E. coli isolates were screened for antibiotic susceptibility to 16 antibiotics. According to the phylogenetic analysis of E. coli isolates, nonpathogenic group A and pathogenic group D (29.4% and 23.5%) were the predominant phylotypes found in water samples. The most frequent phylotypes found in sediment samples were nonpathogenic groups A and B1 (27.9% and 26.4%). The highest incidence of antibiotic resistance in E. coli was against cefotaxime and colistin (100%). A significant difference in the prevalence of CTX-M-group 1 gene was observed among E. coli isolates in water samples (p < 0.05). The results indicate a high prevalence of β-lactamase harboring E. coli in the mangrove ecosystems that can hamper mangrove-dependent aquaculture practices and human health.

Purpose: Chryseobacterium indologenes is a clinically relevant microorganism that has been on the rise, with multidrug-resistant (MDR) strains being reported. C. indologenes carrying tet(X2) has been demonstrated to be resistant to the antibiotic tigecycline, yet, sensitive to all other members of the tetracycline family. This inconsistency in resistance prompts an inquiry into the contribution of tet(X2) to tigecycline resistance in C. indologenes. Materials and Methods: In this study, we report on a comprehensive analysis of the genomic mechanisms underlying tigecycline resistance in a MDR C. indologenes strain (CI3125) that was resistant to tigecycline but sensitive to tetracycline, doxycycline, and minocycline. We used whole-genome sequencing, quantitative reverse transcription PCR, Western blot, antibiotic-degrading tests, and efflux pump inhibiting tests to reveal the mechanism of tigecycline resistance in C. indologenes and elucidate the inconsistency in the antibiotic resistance mechanism for the tetracycline family. Results: Our findings demonstrate that CI3125 carries 60 antibiotic resistance genes distributed on 6 different genetic islands (GIs), with the potential for horizontal transfer. Notably, the tet(X2) gene is located on GI06 of CI3125. Genetic environment analysis of tet(X2) showed that all tet(X2) genes in Flavobacterium and Bacteroides share a conservative and functional ribosome-binding site upstream. Contrary to expectation, our RT-qPCR showed that tet(X2) was not transcribed in CI3125, and Western blot suggested the absence of tet(X2) protein in CI3125. Rather, we demonstrate that minimum inhibitory concentration values for tigecycline decreased two- to eight-folds in the presence of five different efflux pump inhibitors [1-(1-naphthyl- methyl)-piperazine, phenyl-arginine-β-naphthylamide, verapamil, reserpine, and carbonyl cyanide 3-chlorophenylhydrazone]. This finding provides evidence for the involvement of efflux pumps in tigecycline resistance, which is likely to be a universal mechanism among C. indologenes. Our study proposes that the inconsistency in resistance to the tetracycline family in CI3125 may be ascribed to the silence of tet(X2) and the functions of efflux pumps for tigecycline. Conclusions: Overall, our results highlight the importance of genomic approaches in understanding the underlying mechanisms of antibiotic resistance in clinically relevant microorganisms. While tet(X2) in CI3125 is silent, our findings suggest that it may be horizontally spread through GIs. Hence, our findings have significant implications for the management of C. indologenes infections in clinical settings.

Although many drug-resistant nontyphoidal Salmonella (NTS) infections are reported globally, their treatment is challenging owing to the ineffectiveness of the currently available antimicrobial drugs against resistant bacteria. It is therefore essential to discover novel antimicrobial drugs for the management of these infections. In this study, we report high inhibitory activities of the novel fluoroquinolones (FQs; WQ-3810 and WQ-3334) with substitutions at positions R-1 by 6-amino-3,5-difluoropyridine-2-yl and R-8 by methyl group or bromine, respectively, against wild-type and mutant DNA gyrases of Salmonella Typhimurium. The inhibitory activities of these FQs were assessed against seven amino acid substitutions in DNA gyrases conferring FQ resistance to S. Typhimurium, including high-level resistant mutants, Ser83Ile and Ser83Phe-Asp87Asn by in vitro DNA supercoiling assay. Drug concentrations of WQ compounds with 6-amino-3,5-difluoropyridine-2-yl that suppressed DNA supercoiling by 50% (IC₅₀) were found to be ∼150-fold lower than ciprofloxacin against DNA gyrase with double amino acid substitutions. Our findings highlight the importance of the chemical structure of an FQ drug on its antimicrobial activity. Particularly, the presence of 6-amino-3,5-difluoropyridine-2-yl at R-1 and either methyl group or bromine at R-8 of WQ-3810 and WQ-3334, respectively, was associated with improved antimicrobial activity. Therefore, WQ-3810 and WQ-3334 are promising candidates for use in the treatment of patients infected by FQ-resistant Salmonella spp.

The indoor environment of hospitals should be considered as an important reservoir of azole resistant Aspergillus species. In this study, we evaluated azole-containing agar plates (ACAPs) and antifungal susceptibility testing (AFST) for the detection of azole-resistant Aspergillus species in hospital environmental samples. Between September 2021 and January 2022, environmental samples (108 instruments and 12 air) were collected from different wards of 4 educational hospitals in Mazandaran province, Iran. All samples were cultured using ACAPs. Recovered Aspergillus isolates were molecularly identified at species level using partial DNA sequencing of beta-tubulin gene. AFST of Aspergillus species was performed using the Clinical and Laboratory Standards Institute M38-A3 guideline. Screening for cyp51A mutations was also done. Overall, 18 (15.0%) isolates of Aspergillus species were recovered from ACAPs, of which Aspergillus tubingensis (50%) and Aspergillus fumigatus (38.9%) were the commonest species. No isolate of Aspergillus species grew on posaconazole (PCZ)-containing agar plates. Among the 18 Aspergillus isolated species from ACAPs, 83.3% were related to samples from instruments. Of the nine isolates of A. tubingensis, 22.2% and 44.4% isolates showed minimum inhibitory concentration (MIC) = 2 μg/mL against voriconazole (VCZ) and itraconazole, respectively; and 44.4% isolates showed MIC = 1 μg/mL against PCZ. Of the seven isolates of A. fumigatus, one (14.3%) was resistant to VCZ. This isolate showed F46Y, G54E, G138C, M172V, M220I, D255E, T289F, G432C, and G448S mutation in cyp51A. Our finding showed the emergence of high MICs in cryptic and non-fumigatus species of Aspergillus such as A. tubingensis and VCZ resistance in A. fumigatus in indoor environment of hospitals.

The current study aimed to determine the occurrence and antimicrobial resistance of oral Aerococcus viridans in stray dogs and cats in Algeria. Oral swabs from 200 stray animals (100 dogs and 100 cats) were collected and cultured on Columbia agar medium supplemented with 5% defibrinated sheep blood. Isolates were identified using analytical profile index Rapid 20 Strep commercial kits, and antibiotic susceptibility was determined using the disk diffusion method. Of the 200 animals sampled, 34 carried A. viridans in their oral cavities, with 26 isolates (76.47%) resistant to at least 2 drugs. Multidrug resistance profiles (to more than three different antimicrobials) were observed only in cats (26.08% of isolates). More isolates were resistant to erythromycin and tetracycline (71% and 65%, respectively) than to other antimicrobials. This is the first research study in Algeria detecting antimicrobial resistance in oral A. viridans isolated from dogs and cats and highlights potential public health concerns. Clinical trials registration number: 01/2018.

Fosfomycin can be used alone or in combination to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. However, fosfomycin resistance has been observed in MRSA. In S. aureus, fosfomycin resistance is mediated by the fosfomycin-modifying enzyme FosB, or mutations in the target enzyme MurA. Mutations in the chromosomal glpT and uhpT genes, which encode fosfomycin transporters, also result in fosfomycin resistance. The three-component regulatory system HptRSA mediates the expression of uhpT and glpT in S. aureus. This study aimed to investigate the role of hptRSA mutation in fosfomycin resistance in MRSA clinical isolates. We found that hptRSA mutations were common in MRSA strains isolated from our hospital. Most mutations were amino acid substitutions and widely distributed in fosfomycin-sensitive and fosfomycin-resistant strains. However, HptA-truncated mutations were only found in fosB-negative fosfomycin-resistant strains with wild-type uhpT and glpT genes. Quantitative real-time PCR results showed that the transcription level of uhpT decreased by 13.7-25.6-fold in the HptA-truncated strains. Concordantly, the fosfomycin minimum inhibitory concentration (MIC) of HptA-truncated strains was 64-128 μg/mL, while SA240 was 2 μg/mL. The low transcription level of uhpT and high increase in MIC suggest that hptA mutation may lead to fosfomycin resistance in MRSA. We complemented hptA in one of the HptA-truncated clinical strains (SA179), showing reversal of fosfomycin resistance (from 128 to 32 μg/mL). Then we knocked out hptA in S. aureus Newman; fosfomycin MIC increased from 4 to 64 μg/mL, suggesting that HptA mutation may play an important role in fosfomycin resistance.