Microbial drug resistance最新文献

Streptococcus anginosus is an important cause of pyogenic infections, bacteremia, and chronic maxillary sinusitis. Mobile genetic elements (MGEs) play a key role in lateral gene transfer, resulting in broad transfer of antibiotic resistance genes (ARGs). However, studies on ARG-associated MGEs in S. anginosus are still rare. To fill this gap, we used sequencing data from 11 clinical S. anginosus to characterize their mobilome diversity through comparative analysis. We found 47 well-characterized MGEs, including 23 putative integrative and conjugative elements (ICEs), 16 prophages/integrative mobilizable elements, and 8 composites. They were inserted into 16 positions, 4 of which were hot spots. A comprehensive analysis revealed that ARG-associated ICEs belong to four groups as follows: single serine integrases (ICESan49.2), tyrosine integrases (ICESan26.2), triple serine integrase ICEs (ICESan195.1), and a putative transposon integrase (ICESan49.1), all of which were similar to ICEs/transposons widely distributed among other streptococci. The eight composites were composed of multiple ICEs or transposons through successive accretion events (tandem or/and internal integration). In conclusion, we found that S. anginosus accumulates a variety of ARG-associated ICE/composites that may enable S. anginosus to serve as an ARG-associated MGE repository for other streptococci. The analysis of composites here provides a paradigm to further study mobilome evolution.

As an opportunistic pathogen, Pseudomonas aeruginosa is often associated with severe respiratory infections. A study conducted in an ICU of a tertiary hospital in Vietnam, where infection management is relatively good, yielded only 18 clinical isolates of P. aeruginosa over 6 months. Though the number is small, treating P. aeruginosa infections is highly complicated. Out of 18 patients, 15 showed no improvement after treatment, leading to worsening conditions or death, possibly due to various factors. High rates of mechanical ventilation (83.3%) may be a contributing factor, suggesting a certain correlation between ventilation and treatment failure. The antibiotic resistance rate in these isolates is relatively high, with a multidrug-resistant rate of 44.4%, resulting in treatment failures when empirical antibiotics are used without susceptibility testing. All isolates have the ability to form biofilms. Moreover, bacteria in stationary phase or within biofilms exhibited poor responses to meropenem and amikacin (about 10% of bacteria survive after antibiotic exposure). Conversely, ciprofloxacin shows much better efficacy, indicating that fluoroquinolones should be used in combination therapy for P. aeruginosa infection to eliminate persistent cells and biofilm-embedded microorganisms, thus enhancing treatment effectiveness.

Even if in the past years new effective, safe, and orally administrable drugs are available to create shorter regimens, drug-resistant (DR) tuberculosis (TB) treatment remains a critical issue and a major challenge faced by clinicians worldwide. We present the first case of transborder pulmonary pre-extensively drug-resistant (pre-XDR)-TB treated in Italy with the bedaquiline-pretomanid-linezolid regimen. Diagnosis and treatment were started in Ukraine, and, after a month of treatment, due to the Russo-Ukrainian war, the patient moved to Italy, where the diagnosis was confirmed both by genotypic and phenotypic drug susceptibility tests, and treatment continued. In this short report, we highlight challenges and future opportunities to improve the clinical management of patient with DR-TB.

Carbapenenemase producers, particularly the metallo-β-lactamase (MBL) types in Pseudomonas aeruginosa, have emerged as an urgent threat in health care settings. MBLs require zinc at their catalytic site and can be inhibited by dimercaptosuccinic acid (DMSA), a metal chelator known for the treatment of lead and mercury intoxication. Isogenic strains of wild-type and OprD-deleted P. aeruginosa PA14, were constructed, producing the MBLs VIM-2, NDM-1, SPM-1, IMP-1, and AIM-1, or the non-MBL carbapenemases, GES-5 and KPC-2. In addition, 59 previously characterized clinical isolates of P. aeruginosa producing different ß-lactamases (including carbapenemases), and with known outer-membrane porin OprD status, were utilized. Minimal inhibitory concentrations values of imipenem and meropenem, and DMSA combinations were determined, and time-kill assays were performed with PA14 expressing VIM-2. Results indicated a significant additive effect of DMSA (most effective at 3 mM) and carbapenems in recombinant and clinical strains of P. aeruginosa expressing MBLs, in particular against VIM producers, which are the most prevalent carbapenemases in P. aeruginosa. This effect was best evidenced with meropenem and in strains without OprD modification. DMSA shows promising efficacy, particularly in combination therapy with meropenem, for treating infections caused by MBL-producing P. aeruginosa.

Intermittent negative blood cultures, known as the skip phenomenon (SP), frequently occur in patients with Staphylococcus aureus bacteremia (SAB), yet the clinical implications of SP in persistent SAB are not well understood. In this retrospective cohort study conducted at four university hospitals, SP was observed in 25 (11.3%) of 221 patients with persistent SAB. Infections involving methicillin-resistant S. aureus (MRSA) were more prevalent in patients with SP, who also experienced longer durations of bacteremia and delayed active antibiotic therapy compared with those without SP. The 30-day in-hospital mortality was lower in patients with SP than in those without SP (12.0% vs. 30.6%, respectively, p = 0.052). The median time from the initiation of active antibiotic therapy to the occurrence of SP was 6 days, and from SP to the last positive blood culture was 7 days. The duration of bacteremia and MRSA were independent predictors of SP. These findings suggest that SP can cause the duration of bacteremia to be underestimated by more than 1 week, indicating that confirmation of serial negative blood cultures might be necessary to reliably rule out SP in patients with prolonged MRSA bacteremia.

This study aims to delineate the epidemiological trends of carbapenem-resistant Klebsiella pneumoniae (CRKP) in pediatric patients before, during, and after coronavirus disease 2019 (COVID-19) pandemic and to assess the risk factors of CRKP hospital-acquired infections (CRKP-HAIs) across these three periods. We retrospectively collected the clinical data of pediatric patients diagnosed with K. pneumoniae infection at the Children's Hospital of Nanjing Medical University from January 2018 to March 2024. Carbapenemase-related genes were detected by PCR, and statistical analysis was conducted using SPSS 25.0. The current study found that modifications in the COVID-19 pandemic prevention and control measures and antibiotic therapies impact the epidemiological trends and antimicrobial resistance of CRKP. Binary logistic regression analyses revealed various independent risk factors for CRKP-HAIs before, during, and after the COVID-19 pandemic. Healthcare institutions must intensify surveillance for HAIs, continuously monitor and avoid risk factors for CRKP-HAIs, and formulate targeted preventive and control measures to effectively reduce the incidence and spread of these infections. Further, consistent surveillance of CRKP strains coproducing carbapenemase genes is crucial for mitigating the potential health risks in pediatric patients.

This study aimed to characterize the first vancomycin-resistant Enterococcus faecalis (VREfs) isolate from patient with neutropenic in Tunisia by whole-genome sequencing (WGS). This strain was detected from routine rectal swab from an 8-year-old child with bone marrow aplasia, residing in a rural area, on September 20, 2021. The strain was isolated after 12 days of hospitalization at the National Bone Marrow Transplant Center. Minimum Inhibitory Concentrations of vancomycin and teicoplanin were >256 and 16 mg/L, respectively. WGS revealed that the strain belonged to the ST249 clone, exclusively reported in avian (poultry and ducks) vancomycin-susceptible E. faecalis isolates in six studies from four countries, primarily Denmark. The vanA gene was carried by the Tn1546 transposon mobilized by a pTW9-like plasmid. The ardA gene, a CRISPR-Cas system neutralization factor, was detected in this strain. In summary, this is the first report of avian-associated E. faecalis ST249 in clinical samples. Initially vancomycin susceptible, the strain acquired a pTW9-like plasmid carrying the classical vanA-Tn1546 transposon. This acquisition was facilitated by the sex pheromone-response mechanisms and the ardA gene and CRISPR-Cas system neutralization.

Salmonella infections have become increasingly resistant to antibiotics, including fluoroquinolones, third-generation cephalosporins (C3G), and even carbapenems. This report describes the emergence of a strain of Salmonella enterica serovar Heidelberg that produces the carbapenemase OXA 48. The strain was isolated from a stool sample taken from a newborn. Antimicrobial susceptibility testing was carried out following the recommendations of the Clinical and Laboratory Standard Institute. Whole genome sequencing was performed on MiSeq Illumina™. The strain was resistant to ertapenem (minimal inhibitory concentration [MIC] = 12 µg/mL), intermediate to imipenem (MIC = 1.5 µg/mL), resistant to nalidixic acid, and intermediate to fluoroquinolones but was susceptible to C3G, cotrimoxazole, chloramphenicol, and colistin (MIC = 0.064 µg/mL). The strain was identified as ST-15. The strain of Salmonella Heidelberg ST-15 was found to have antimicrobial resistance genes, specifically blaOXA-48, aac(6')-Iaa and fosA7, which mediate resistance to carbapenems, aminoglycosides and fosfomycin, respectively. Additionally, mutations were detected in the gyrA, parC. Three plasmid replicon type IncL, IncX1, and Col156 have been identified. The strain has the potential to cause an epidemic. The genomic analysis of the strain allowed us to understand the mechanisms of resistance. Preventing the spread of Salmonella carbapenemase-producing strains is crucial, particularly in hospital settings. Epidemiological measures are necessary to achieve this goal.

Aztreonam/avibactam (ATM/AVI) has been recently approved drug for clinical use in the European Union. The aim of this study was to develop and evaluate a novel selective medium for the isolation of ATM/AVI-resistant strains (Super ATM/AVI selective medium) to help to control their spread. Minimum inhibitory concentrations of ATM/AVI were determined using the broth microdilution method for 77 Gram-negative isolates, including 62 Enterobacterales and 15 Pseudomonas aeruginosa. The Super ATM/AVI selective medium was elaborated using optimal final concentrations of ATM at 5 mg/L and AVI at 4 mg/L, being supplemented with amphotericin B and vancomycin to prevent growth of yeasts and Gram-positive bacteria and with ZnSO₄ to optimize the expression of metallo-β-lactamase producers. Super ATM/AVI showed high sensitivity (94.6%) and specificity (100%) at a detection limit of 10³ CFU/mL.