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BackgroundUnderstanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection.MethodsWe performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index.ResultsDuring follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG.ConclusionWe discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.

Species of the family Enterobacteriaceae represent the most prevalent group of nosocomial pathogens. In this paper, we report the data on antimicrobial susceptibility of 1670 isolates of Enterobacteriaceae collected in 35 hospitals of 22 cities of Russia in 2013-2014 as part of the national multicenter surveillance study on antimicrobial resistance of nosocomial pathogens, «MARATHON». Enterobacteriaceae isolates jointly comprised 43.1% of all bacterial nosocomial isolates. The most abundant species were Klebsiella pneumoniae (20.7%), Escherichia coli (11.2%) and Enterobacter cloacae (2.6%). Most of the isolates were insusceptible to oxyimino-β-lactams: cefotaxime (75.6%), ceftazidime (71.9%), cefepime (72.0%) and aztreonam (72.5%). The non-susceptibility rates to carbapenems were: 6.9% to meropenem, 7.8% to doripenem, 8.5% to imipenem and 18.0% to ertapenem. The majority of carbapenem resistant isolates were K. pneumoniae. 7.8% of all isolates were found to produce carbapenemases of OXA-48 (6.3%) and NDM-1-group (1.6%). Only 1.9% и 2.6% were insusceptible to aztreonam/avibactam and ceftazidime/avibactam correspondingly. Among non-β-lactam agents, the lowest resistance rates were observed with amikacin (16.6%), colistin (18.8%), tigecycline (23.5%) and fosfomycin (28.2%). Notably, 1.1% of the isolates were categorised as extensively drug-resistant (XDR).

Acinetobacter baumannii and related species of the A. baumannii complex are the common and one of the most difficult-to-treat nosocomial pathogens. In this paper, we report the data on antimicrobial susceptibility of 568 isolates of Acinetobacter spp., including 542 A. baumannii, collected in 31 hospitals of 21 cities of Russia in 2013-2014 as part of the national multicenter surveillance study on antimicrobial resistance of nosocomial pathogens, «MARATHON». Acinetobacter spp. and, specifically, A. baumannii isolates comprised, respectively, 14.4% and 13.7% of all bacterial nosocomial isolates. In A. baumannii, the non-susceptibility rates to carbapenems were: 74.7% to meropenem, 79.9% to doripenem, and 70.9% to imipenem; the genes for acquired molecular class D carbapenemases were detected in 63.5% of isolates. Those included the genes for OXA-24/40-like (39.7%), OXA-23-like (23.8%) и OXA-58-like (0.6%) enzymes (three isolates carried simultaneously the genes for OXA-23- and OXA-24/40-like β-lactamases). Most of the isolates were insusceptible to ciprofloxacin (98.0%), to aminoglycosides: gentamicin (71.2%), amikacin (88.0%) and netilmicin (61.0%), and to trimethoprim/sulfamethoxazole (68.5%). Colistin had the highest in vitro activity with resistance rate being as low as 1.9%. A total of 47.1% and 82.1% isolates had the MICs of tigecycline and sulbactam exceeding the epidemiological cut-off values of 1 mg/l and 4 mg/l, respectively. Notably, 98.0% of the A. baumannii isolates were categorised as multidrug resistant (MDR) and 64.4% - as extensively drug-resistant (XDR).

Pseudomonas aeruginosa is the most abundant bacterial species causing nosocomial infections in Russia. In this paper, we report the data on antimicrobial susceptibility of 743 isolates of P. aeruginosa collected in 63 hospitals of 22 cities of Russia in 2013-2014 as part of the national multicenter surveillance study on antimicrobial resistance of nosocomial pathogens, «MARATHON». P. aeruginosa isolates comprised 19.6% of all bacterial nosocomial isolates. Among them, the non-susceptibility rates to main antipseudomonal β-lactams were: 51.9% to cefepime, 55.9% to ceftazidime, 57.9% to piperacillin-tazobactam, 65.7% to imipenem, and 59.7% to meropenem. Production metallo-β-lactamases was detected in 21.3% of the isolates: VIM-type – 20.7, IMP-type – 0.5%. Most of the isolates were insusceptible to fluoroquinolones: ciprofloxacin (61.1%) and levofloxacin (62.8%), and to aminoglycosides: gentamicin (57.7%), amikacin (50.5%), and tobramycin (46.4%). Polymyxins had the highest in vitro activity with non-susceptibility rates being as low as 2.6% to colistin and strains not sensitivity to polymyxin B were not detected. Twenty nine percent of the isolates had the MIC of fosfomycin exceeding the epidemiological cut-off value of 128 mg/l. Notably, 51.4% of the isolates were categorised as extensively drug-resistant (XDR) and pan-resistance (PDR) strain was detected in 1 case.

The study included 418 of the 841 clinical isolates of S. aureus, which were regarded as nosocomial. These 418 clinical nosocomial S. aureus strains were isolated in 2013-2014 from patients hospitalized in 25 hospitals in 19 Russian cities. Methicillin-resistance rate was 24.9% (n=104). Antimicrobials with the highest activity with no resistance detected were vancomycin, linezolid, cefilavancin, telavancin, daptomycine, tigecycline and fusidic acid. Other highly in-vitro active antimicrobials were trimethoprim-sulfamethoxazole, mupirocin and ceftaroline (0.5%, 2.2% and 4.3% non-susceptible isolates respectively). MRSA isolates were substantially less susceptible compare with MSSA to gentamicin (1.3% vs. 83.7%), clindamycin (1.6% vs. 40.4%), rifampicin (2.2% vs. 27.9%), tetracycline (12.1% vs. 35.6%), chloramphenicol (9.9% vs. 71.2%), ceftaroline (0% vs. 17.3%), ciprofloxacin (6.1% vs. 89.4%), and erythromycin (18.5% vs. 58.7%).