Phenotypic and genotypic analysis of antimicrobial resistance in Nocardia species.

BACKGROUND: Antimicrobial resistance is common in Nocardia species but data regarding the molecular mechanisms beyond their resistance traits are limited. Our study aimed to determine the species distribution, the antimicrobial susceptibility profiles, and investigate the associations between the resistance traits and their genotypic determinants. METHODS: The study included 138 clinical strains of Nocardia from nine Israeli microbiology laboratories. MIC values of 12 antimicrobial agents were determined using broth microdilution. WGS was performed on 129 isolates of the eight predominant species. Bioinformatic analysis included phylogeny and determination of antimicrobial resistance genes and mutations. RESULTS: Among the isolates, Nocardia cyriacigeorgica was the most common species (36%), followed by Nocardia farcinica (16%), Nocardia wallacei (13%), Nocardia abscessus (9%) and Nocardia brasiliensis (8%). Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%). Resistance to other antibiotics was species-specific, often associated with the presence of resistance genes or mutations: (1) aph(2″) in N. farcinica and N. wallacei (resistance to tobramycin); (ii) blaAST-1 in N. cyriacigeorgica and Nocardia neocaledoniensis (resistance to amoxicillin/clavulanate); (iii) blaFAR-1 in N. farcinica (resistance to ceftriaxone); (iv) Ser83Ala substitution in the gyrA gene in four species (resistance to ciprofloxacin); and (v) the 16S rRNA m1A1408 methyltransferase in N. wallacei isolates (correlating with amikacin resistance). CONCLUSIONS: Our study provides a comprehensive understanding of Nocardia species diversity, antibiotic resistance patterns, and the molecular basis of antimicrobial resistance. Resistance appears to follow species-related patterns, suggesting a lesser role for de novo evolution or transmission of antimicrobial resistance.

Evolution of spike mutations following antibody treatment in two immunocompromised patients with persistent COVID-19 infection.

Immunocompromised patients have an increased risk of persistent COVID-19 disease. We report here the clinical course of two patients with hematologic malignancies hospitalized due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In both patients, viral evolution including new spike gene mutations that occurred following treatment with anti-SARS-CoV-2 antibodies preparations, including convalescent plasma and bamlanivimab. These cases demonstrate the possibility of antibody-resistant SARS-CoV-2 infections evolution in immunocompromised patients.

An outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infections among hospital personnel with high mRNA vaccine uptake.

Real-world studies have demonstrated impressive effectiveness of the BNT162b2 COVID-19 vaccine in preventing symptomatic and asymptomatic SARS-CoV-2 infection. We describe an outbreak of SARS-CoV-2 infections in a hospital with high vaccine uptake. We found a low secondary attack rate (7%), suggesting low infectivity of vaccinated persons with vaccine breakthrough SARS-CoV-2 infections.

Nosocomial transmission of MPOX virus to health care workers -an emerging occupational hazard: A case report and review of the literature.

We present an unusual case of monkeypox (MPOX) virus transmission to a dermatology resident during examination of affected patients. Viral DNA sequencing led to the identification of the most likely contact. This case, along with a review of all published cases so far, emphasizes the possible hazard of MPOX transmission to health care personnel, even when wearing personal protective equipment. It also emphasizes the need for maintaining high index of suspicion when examining patients with new dermatological lesions and strict compliance with the revised Centers for Disease Control and Prevention recommendations for specimen collection from such patients.

The Dissemination of a Single Staphylococcusaureus Strain, Spa-t2873, as the Predominant Cause of Bovine Mastitis in Israeli Dairy Farms.

Staphylococcus aureus is one of the most important pathogens causing intramammary infection (IMI) in dairy herds. The goals of this study were (1) to describe the prevalence of S. aureus in Israeli dairy farms; (2) to characterize the spa-based clonal structure of mastitis-related S. aureus isolates; (3) to analyze the transmission network of a large outbreak within a single farm and (4) to characterize the virulence factors of the outbreak strain. The prevalence and the molecular survey were performed on all Israeli IMI-related isolates, 9.2019-8.2020. Molecular methods included spa-typing for the survey and whole-genome sequencing (WGS) for the investigation of the farm 'A' outbreak. During the one-year survey, S. aureus was identified in 152 dairy farms, with a total of 440 positive samples. The spa t2873 was found in 284 isolates (64.5%) across 112 farms (73.6%). Other common types included t529 (n = 46), t9303 (n = 34) and the methicillin-resistant S. aureus t011 (n = 11). The highest number of cases (n = 25) was detected in Farm 'A', all of which were found to be spa t2873. Phylogenetic analysis confirmed that most transmission events occurred within the same milking group, and inter-group transmission was due to the transfer of cows between groups or due to consecutive milking order. The spa t2873 strain contained putative virulence genes, including various intracellular and collagen adhesion proteins. Our study revealed the dissemination of the t2873 strain to the majority of Israeli dairy farms. The possibility of inter-farm transmission should be monitored and prevented.

Drivers of adaptive evolution during chronic SARS-CoV-2 infections.

In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient's body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.