Microbial drug resistance最新文献

Purpose: The Gram-negative bacterium Aeromonas caviae is an important opportunistic facultative anaerobic pathogen. In the present study, we aimed to elucidate the whole-genome sequence of the multidrug-resistant (MDR) A. caviae strain AC1520, detailing its acquired antibiotic resistance genes (ARGs) and their genetic elements. Patients and Methods: The A. caviae strain AC1520 was isolated from a urine sample taken from a patient with urinary tract infection. Whole-genome sequencing was performed following strain identification and antimicrobial susceptibility testing. Overall, we identified ARGs, integrons, insertion sequences (IS), and transposons acquired by strain AC1520, systematically analyzing the genetic elements associated with these ARGs. Results: The A. caviae strain AC1520 contained a circular chromosome and a plasmid. Multilocus sequence typing revealed that this strain belonged to ST-1056. All ARGs within this strain were distributed on the circular chromosome. We identified two MDR regions: (1) IS common region 1 (ISCR1) and class 1 integron (IntI1) elements associated with aadA16, aac(6')-Ib-cr, catB3, qacE (two copies), sul1 (two copies), and bla_PER-3; one gene cluster structure (IS6100-mphR(A)-mph(A)-mrx(A)-IS26); (2) Two IntI1 elements, linked to ant(2'')-Ia, bla_OXA-10, aadA2b, aph(3'')-Ib, aph(6)-Id, ARR-2, aac(6')-Ib3, dfrA1, qacE, and sul1. Notably, these two MDR regions were not only present in A. caviae but also in other bacteria, such as Aeromonas hydrophila, Aeromonas media, and Edwardsiella tarda. Conclusion: The A. caviae strain AC1520 with two separate MDR regions and 20 ARGs, conferring resistance to aminoglycoside, fluoroquinolone, phenicol, sulfonamide, beta-lactam, macrolide, rifampicin, and trimethoprim, was identified in a hospital in China. Mobile genetic elements including TnAs1, ISCR1, ISAs25, IS6100, IS26, TnAs3, ISAs1, and Tn3, were found within the MDR region, which could play important roles in the global dissemination of these resistance genes.

Objectives: Cefepime (FEP), a fourth-generation cephalosporin combined with tazobactam (TAZ), a β-lactamase inhibitor, is being developed by Wockhardt as a pharmacodynamically optimized fixed dose combination (FEP-2 g + TAZ-2 g) for the treatment of multidrug-resistant Gram-negative infections. To undertake an exposure-response analysis for establishing pharmacokinetic (PK)/pharmacodynamic (PD) targets, it is crucial to characterize the PK profile of compounds in surrogate compartments, such as plasma and lung, in clinically relevant animal infection models used to evaluate in vivo efficacy. In the current study, PKs of FEP and TAZ were assessed in plasma and in epithelial lining fluid (ELF) of neutropenic noninfected, lung-infected, and thigh-infected mice. Methods: Neutropenic mice were infected by intranasal or intramuscular administration of 10⁶-10⁷ colony-forming units per milliliter of Escherichia coli to develop infection in lung or thigh. Post 2 hours of infection, single doses of WCK 4282 at 25 + 25, 50 + 50, and 100 + 100 mg/kg were subcutaneously administered. Plasma and bronchoalveolar lavage fluid were collected up to 8 hours post-administration of doses. Results: The PK of FEP and TAZ in plasma/ELF in healthy and infected mice did not differ significantly. The plasma PK profiles of FEP and TAZ were linear and dose proportional with modest ELF penetrations in the neutropenic infected mice. The ELF exposures of FEP and TAZ were slightly lower in thigh-infected mice and higher in lung-infected mice when compared with healthy mice. Irrespective of health condition, the mean ELF/plasma area under the curve penetration ratio for FEP and TAZ was similar and comparable (0.42-0.43). Conclusion: The estimates of FEP and TAZ PK parameters estimated in the current study would help in PK-PD studies for the selection of doses for upcoming in vivo efficacy studies.

Antimicrobial resistance (AMR) is one of the most important concerns in the world, occurring for both Gram-positive and Gram-negative bacteria. Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative bacterium belonging to the family of Enterobacteriaceae and also plays an important role in development of nosocomial infections. Three forms have emerged as a result of AMR including multi-drug resistant (MDR), extensively drug-resistant, and pan-drug-resistant. Nowadays, physicians cannot save most of the patients that suffer from MDR K. pneumoniae infections by typical antibiotics, so they should try other useful alternative treatments. Our aim in this review study was to search about the latest useful alternative methods against MDR K. pneumoniae infections. We collected some articles from PubMed, MEDLINE, and Google Scholar by the keywords of multi-drug-resistant K. pneumoniae, AMR, and alternative treatments, where finally 183 articles were selected. Also, inclusion criteria and exclusion criteria were identified separately. It was understood that there are novel therapeutic options against MDR K. pneumoniae infections, which include odilorhabdins, drug delivery systems, antibody drug conjugation treatments, nano-antibiotics, bacteriocins, probiotics, fecal transplant therapy, predatory bacteria, combined antibiotics, double-carbapenem therapy, synthetic lipopeptides, and phage therapy.

In high-burden tuberculosis (TB) settings such as Iran, non-tuberculous mycobacteria (NTM) are increasingly identified among presumptive TB cases. However, their epidemiology and drug resistance patterns remain inadequately described. This study investigated the prevalence, species distribution, and antimicrobial susceptibility of NTM isolates from 3,000 clinical specimens collected from patients with presumptive TB at the Pasteur Institute of Iran between March 2022 and March 2023. Identification was performed through culture and sequencing of the 16S rDNA, rpoB, and hsp65 genes. Drug susceptibility testing (DST) was conducted using the broth microdilution method in accordance with Clinical and Laboratory Standards Institute guidelines. Among 145 acid-fast bacilli-positive cultures, 45 (31%) were identified as NTM. The predominant species were Mycobacterium fortuitum (51.1%) and M. simiae (40.0%), followed by less common isolates of M. abscessus, M. kansasii, and M. flavescens. The majority of NTM isolates (86.7%) originated from respiratory specimens. Phenotypic analyses revealed high resistance rates to first-line anti-TB drugs such as isoniazid and rifampicin, while susceptibility varied across fluoroquinolones, aminoglycosides, and sulfonamides. These findings underscore the importance of species-level identification and DST-guided therapy to improve the clinical management of NTM infections in TB-endemic regions.

Background: Antimicrobial resistance is a critical global threat in resource-limited settings with underdeveloped laboratory capacity and stewardship programs. Intensive care unit (ICU) patients are at high risk for complicated urinary tract infections (cUTIs) caused by multidrug-resistant (MDR) uropathogens. Local resistance data are essential to guide empirical therapy and design effective stewardship interventions. Methods: We conducted a retrospective, cross-sectional study (March 2020-December 2022) of 127 adult ICU patients with cUTIs at a tertiary hospital in Tehran, Iran. Urine isolates were identified by standard phenotypic methods, and antimicrobial susceptibility testing (AST) was performed via disk diffusion following Clinical and Laboratory Standards Institute guidelines. Resistance phenotypes-extended-spectrum beta-lactamase (ESBL) production, carbapenem-resistant Enterobacteriaceae, vancomycin-resistant enterococci (VRE), difficult-to-treat Pseudomonas, and pan-drug-resistant (PDR) Acinetobacter baumannii-were defined using current breakpoints. Results: Escherichia coli (52.2%) and Klebsiella pneumoniae (26.9%) predominated. Among Enterobacterales, 60.4% produced ESBL and 30.2% were carbapenem resistant. VRE comprised all enterococcal isolates; PDR A. baumannii occurred in one case. No significant associations were found between resistance profiles and sepsis, septic shock, or mortality. Multivariable analysis identified heart failure (odds ratio [OR] 2.45; 95% confidence interval [CI] 1.15-5.21; p = 0.017) and longer ICU stay (OR 1.03 per day; 95% CI 1.01-1.05; p = 0.012) as independent predictors of MDR infection. Conclusions: We report an alarming burden of MDR uropathogens in Tehran ICUs, underscoring the need for tailored empirical-therapy guidelines, enhanced antimicrobial stewardship programs, and multicenter surveillance to curb resistance and improve patient outcomes.

Purpose: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an opportunistic infectious agent that can cause bacterial colonization and nosocomial infection. This study aims to explore independent risk factors associated with progression from respiratory colonization to infection among CRAB-colonized patients in the general wards. Methods: We performed a retrospective study among 202 CRAB-colonized patients in the general wards of our hospital between January 2021 and December 2023. We employed both univariate and multivariable logistic regression models to explore factors associated with the progression from colonization to infection. Results: Among 202 CRAB-colonized patients, 66 experienced progression to subsequent infection and 36 died within 28 days. CRAB-colonized patients with subsequent infection had a significantly higher mortality rate (27.27% vs. 13.24%) than patients without infection (p = 0.014). After performing multivariate logistic regression analysis, CRAB-colonized patients with lower albumin (ALB) levels (OR = 0.94, p = 0.029), as well as those receiving antibiotics (OR = 2.49, p = 0.020) or glucocorticoids (OR = 2.49, p = 0.005), were at higher risk of subsequent infection. Furthermore, among patients with CRAB infection developed after colonization, the use of antifungal drugs (OR = 18.06, p = 0.002) and central venous catheter (OR = 10.73, p = 0.002) was the factors that associated with 28-day mortality. Conclusion: Our study analyzed CRAB colonization and infection in general medicine wards. Lower ALB levels and antibiotic/glucocorticoid use were risk factors for infection in colonized patients. Among those developing CR-CRAB infection, antifungal use and central venous catheters were associated with 28-day mortality. These findings can inform preventive and therapeutic guidelines for CRAB infections.

This study reports the discovery of a Klebsiella pneumoniae (KPN) strain carrying the bla_NDM-1, bla_OXA-1, and mcr-9 genes in China for the first time. This strain was isolated from the blood of a 2-year-old pediatric patient with acute lymphoblastic leukemia and sepsis. The strain exhibited high resistance to various antibiotics, including β-lactams, carbapenems, and ceftazidime-avibactam. Through whole-genome sequencing and comparative genomic analysis, we found that these resistance genes coexisted on the transferable IncHI2/IncHI2A-type plasmid pK708696_1, which showed high similarity to plasmid pK710429_2 from strain KPN710429 previously identified in our hospital, indicating their potential for rapid spread through horizontal gene transfer. We also performed conjugation experiments to verify the transferability of the plasmid. The results show that the resistance of this strain to traditional antibiotics significantly limited clinical treatment options, thereby posing a serious threat, especially for pediatric leukemia patients with compromised immune systems. This study provides important scientific evidence and new therapeutic approaches for combating carbapenem-resistant Klebsiella pneumoniae infections and highlights the urgency of developing new antibiotics and alternative therapies.

Background: Antimicrobial resistance (AMR) is a growing global threat that complicates the treatment of infectious diseases, including plague. Yersinia pestis, the causative agent of plague, remains a serious public health concern in natural foci, such as those in Kazakhstan, where approximately 40% of the territory is plague-endemic. Despite the last reported human case in 2003, data on antibiotic resistance among Y. pestis isolates from these foci, especially historical ones, remain limited. Materials and Methods: A total of 75 Y. pestis strains were examined, including 61 isolates obtained from patients and deceased individuals during epidemic outbreaks (1926-2003) and 14 isolates from carriers and vectors in natural plague foci. Taxonomic identification was conducted using the Vitek 2 Compact 30 system. Antibiotic susceptibility was assessed by Kirby-Bauer disk diffusion and E-test methods. Extended-spectrum β-lactam (ESBL) activity was evaluated phenotypically, and resistance genes to glycopeptides and β-lactams were screened by real-time polymerase chain reaction (RT-PCR) using the BacResista GLA Detection Kit. Results: All isolates showed complete susceptibility (100%) to β-lactams, tetracyclines, aminoglycosides, amphenicols, glycopeptides, lincosamides, and quinolones. The overall susceptibility rate across antibiotic classes was 97.5%. Macrolides exhibited low activity (0.0-58.0%), consistent with known limitations against Gram-negative bacteria. No ESBL production was detected phenotypically, and RT-PCR screening found no resistance genes (vanA/B, mecA, tem, ctx-M-1, shv, oxa, imp, kpc, ndm, etc.). Conclusions: These findings confirm a lack of resistance to key antibiotic classes in historical Y. pestis isolates from Kazakhstan. Despite the absence of recent human cases, ongoing epizootics among wild animals highlight a persistent risk of transmission. This study, conducted for the first time in Kazakhstan, has important implications for public health preparedness and clinical management during plague outbreaks.

A notable increase in the incidence of vancomycin-resistant Enterococcus faecium (VREfm) was observed at a hospital in Guangzhou, China, during 2022-2023. We conducted a retrospective cross-sectional study from January 1, 2022, to August 31, 2023, to investigate the clinical and genomic characteristics of VREfm. Clinical data were extracted from electronic medical records, and infection control measures were reviewed from the relevant department. VREfm confirmation was performed using antimicrobial susceptibility testing. Genomic characteristics were analyzed via the whole-genome sequencing. The prevalence of VREfm among E. faecium isolates rose significantly from 13.3% (10/75) in 2022 to 26.4% (40/151) by August 2023 (p < 0.001). Concurrently, usage of third-generation cephalosporins increased by 8.4% (22.47 to 24.36 defined daily doses per 100 patient days), carbapenems by 34% (51.47-68.97), and vancomycin by 18% (21.15-24.97) (all p ≤ 0.001). Molecular analysis revealed ST80/CC17 (78%, 39/50) as the dominant clone, carrying vanA and virulence genes (scm, acm, and fss3), suggesting clonal expansion of a lineage rarely reported in Guangzhou. Our study documented an outbreak of ST80/CC17 vanA-positive VREfm, characterized by virulence genes (scm, acm, and fss3) and clonal dominance (78%, 39/50). The temporal association between reduced sodium hypochlorite disinfection (2.7-fold decline, p = 0.002), increased antibiotic selective pressure, and pathogen transmission highlights multifactorial drivers of this epidemic. These findings underscore the complex multifactorial nature of pathogen transmission, including the role of antibiotic use, infection control measures, and environmental factors in the spread of multidrug-resistant clones. Strengthened infection control strategies-integrating targeted disinfection, antibiotic stewardship, and genomic surveillance-are imperative to curb the spread of such multidrug-resistant clones.