Official statements of the expert meeting on pneumococcal vaccination in adults in Russia

The purpose of the meeting is to obtain an opinion on approaches and recommendations for vaccine prevention of pneumococcal infections in adults.

Ventilatorassociated lower respiratory tract infections: etiology and diagnosis

Objective. To review a literature published over the past 5 years and our own data on the etiology of lower respiratory tract infections (LRTI), antimicrobial resistance and its relationships between sepsis and choice of appropriate antibiotic therapy. Materials and Methods. National Nosocomial Infections Surveillance (NNIS) criteria were used to diagnose LRTI. A review of the articles regarding LRTI from the Russian and international English language journals published over 6 years was performed. Identification of microorganisms was performed by culture over the period of 2003–2013; since 2014, MALDI-TOF MS method was used for this purpose. Results. Despite the ongoing policy to limit the use of antimicrobial therapy in the ICUs, there is an increase in carbapenemase-producing isolates in the ICUs from 2.2% (2018) to 11.7% (2020, 9 months). Along with the trend to increase in carbapenemase-producing pathogens causing LRTI, their variability is also increasing. In particular, it applies to strains producing carbapenemases OXA-48 or combination of OXA-48 with KPC; with the trend to combined production of carbapenemase beginning at 2019. Conclusions. Carbapenemase producers are becoming more widespread in the ICU settings, including the lower respiratory tract in mechanically ventilated patients. Practitioners didn’t get used to associate VAP with the Sepsis-3 criteria. The changes in etiology include the increased rate of carbapenem-resistant Enterobacterales and non-fermenting Gram-negative bacteria, primarily Acinetobacter spp., in Russia. It’s due to improved quality of respiratory support and increased consumption of carbapenems, tigecycline and polymyxins. Significant increase of OXA-48-producing pathogens is likely to be associated with a poor compliance with temporary guidelines on COVID-19 with regard to antibiotic therapy.

New regimens and new medications in the treatment of tuberculosis: keeping step?

Rapid tests detecting Mycobacterium tuberculosis and drug resistance which are universally implemented in medical practice has dramatically improved the diagnosis of rifampicin-resistant tuberculosis and shortened turnaround time thus enabling early etiotropic therapy. However, permanently increasing drug resistance of M. tuberculosis makes treatment less effective. Furthermore, long treatment courses are required due to low sterilizing activity of treatment regimens used for drug-resistant tuberculosis which leads to greater toxic effects, reduces patients’ adherence to treatment and consumes resources of medical care systems. Current phthisiology needs new effective medications and short treatment regimens, otherwise elimination of tuberculosis by 2050 is impossible. This review summarizes the information about treatment of drugresistant TB, including repurposed drugs, new medications and treatment regimens.

In vitro activity of biapenem and other carbapenems against Russian clinical isolates of Pseudomonas aeruginosa, Acinetobacter spp., and Enterobacterales

Objective. To evaluate in vitro activity of biapenem and other clinically available carbapenems against Russian clinical isolates of Enterobacterales, Pseudomonas aeruginosa и Acinetobacter spp., including isolates with acquired fermentative mechanisms of resistance to β-lactams. Materials and Methods. A total of 3139 Enterobacterales isolates, 793 P. aeruginosa isolates and 634 Acinetobacter spp. isolates from hospitalized patients in 63 hospitals from 35 Russian cities were included in the study during 2018-2019. Minimal inhibitory concentrations (MIC) for biapenem and other antimicrobials were determined in accordance with ISO 20776-1:2006. Carbapenemases genes were detected by commercially available real-time PCR kits AmpliSens® MDR KPC/OXA-48-FL and AmpliSens® MDR MBL-FL (Central Research Institute of Epidemiology, Russia). Data analysis and reporting was performed using AMRcloud online platform (www.amrcloud.net). Results. For all tested Escherichia coli isolates MIC50/90 were 0.06/0.125 mg/l for biapenem, 0.125⁄0.25 mg/l for imipenem, and 0.06/0.06 mg/l for meropenem. When MIC50/90 for ertapenem (0.015/0.125 mg/l for all isolates tested) were comparable to those of biapenem, a greater number of nosocomial E. coli isolates had MIC >4 mg/l for ertapenem (3.6%) than for biapenem (2.6%). MIC50/90 of Klebsiella pneumoniae for biapenem were 0.5⁄16 mg/l, for both imipenem and meropenem – 0.5⁄32 mg/l, for ertapenem – 2⁄32 mg/l. Resistance to oxyimino-β-lactams had no significant influence on activity of biapenem against Enterobacterales isolates. For 321 carbapenemase-producing K. pneumoniae isolates (ОХА-48 – 63.9%, NDM – 27.7%) biapenem has shown no advantages over imipenem and meropenem. МПК50/90 for nosocomial and community-acquired P. aeruginosa isolates were 8⁄64 mg/l and 0,5⁄16 mg/l for biapenem, 8⁄128 mg/l and 1⁄16 mg/l – for imipenem, 16⁄64 mg/l and 0,5⁄32 mg/l – for meropenem. All carbapenems, including biapenem, had very low in vitro activity against carbapenemaseproducing P. aeruginosa isolates. МПК50/90 of Acinetobacter spp. were 64⁄128 mg/l for biapenem, 64⁄128 mg/l – for imipenem, and 128⁄128 mg/l – for meropenem. Conclusions. According to the MIC distributions and MICs50/90 values independently of the presence of fermentative mechanisms of resistance to β-lactams, in vitro activity of biapenem against Russian clinical isolates of Enterobacterales, P. aeruginosa and Acinetobacter spp. was comparable to those of imipenem and meropenem.

Almost two years with COVID-19: some aspects of antibiotic use

The objective of this review was to summarize impact of the widespread administration of antibiotics in treatment algorithms for patients with COVID-19 on treatment outcomes. The experience of antimicrobial use agents during COVID-19 pandemic did not show any life-saving effect. It justifies a need to limit their administration to COVID-19 patients.

Official statements of the board of experts on the use of topical thiamphenicol in patients with communityacquired respiratory infections

Currently, there is a steady growth antimicrobial resistance (AMP) worldwide. This is especially true now when antibiotic use has become uncontrolled due to its use in COVID-19 treatment regimens. Antibiotics do not have antiviral effect, their appointment is justified only with complicated forms of COVID-19. Moreover, such a massive use antibiotics creates the prerequisites for the formation antibiotic resistance, including among the causative agents of community-acquired infections. Due to the relentless the growth of antibiotic resistance of community-acquired pathogens of respiratory diseases, it becomes necessary to revise approaches to antibacterial therapy (ABT) and assessing the potential use of thiamphenicol for the treatment of community-acquired infections caused by respiratory pathogens.

Cefazolin inoculum effect among methicillinsusceptible Staphylococcus aureus isolated from patients with skin infections

Objective. To evaluate frequency and intensity of cefazolin inoculum effect among methicillin-susceptible staphylococci isolated from patients with skin infections. Materials and Methods. A total of 80 methicillin susceptible isolates of Staphylococcus aureus were identified by cefoxitin disk-diffusion test and negative results of real-time PCR for mecA gene. Inoculum effect was measured by broth microdilution test with two inocula with concentrations of 5 × 105 CFU/mL and 5 × 107 CFU/mL. The disk-diffusion test with cefoxitin was also performed. Penicillin susceptibility was determined by disk-diffusion method. Beta-lactamase blaZ gene was identified by real-time PCR. Results. The frequency of cefazolin inoculum effect in tested isolates was 30% which is consistent with data from different countries. The MIC values for concentrated inoculum reached CLSI breakpoint for cefazolin resistance in 2.5% of isolates. The isolates with inoculum effect and those without it had the similar MIC values for cefazolin in broth microdilution test for standard inocula and similar diameters of inhibition zone in disk-diffusion test with cefazolin. Penicillin resistance was more frequent in inoculum effect-positive isolates. Beta-lactamase activity is considered as a main cause of cefazolin inoculum effect in staphylococci. The beta-lactamase blaZ gene was identified in the majority of isolates with cefazolin inoculum effect, but it was also prevalent among inoculum effect-negative isolates. Conclusions. Up to 30% of MSSA isolates from skin lesions in dermatological patients from SaintPetersburg are positive for cefazolin inoculum effect. Those isolates are usually characterized by penicillin resistance. Most of the cefazolin inoculum effect-positive isolates also carry beta-lactamase blaZ gene.

Comparison of culture and isolation methods for Clostridioides difficile and other anaerobes from stool samples in a routine microbiological laboratory practice

Objective. To improve stool sample culture and isolation of anaerobic flora, including Clostridioides difficile in the routine microbiological laboratory practice at the children’s oncology hospital. Materials and Methods. A total of 517 stool samples collected from patients in children’s oncology hospital from 2013 to 2015 were studied. All samples were analyzed by ELISA for C. difficile toxins and by culture according to dedicated 5 schemes for isolation of anaerobic bacteria, including C. difficile. Statistical significance of differences in isolation rates between the studied groups (culture schemes) was assessed by Pearson test. Results. Culture in liver broth and covering with technical agar followed by culture on anaerobic agar yielded 100% isolation rate of toxigenic C. difficile strains. This culture scheme is also suitable for isolating concomitant anaerobic flora: non-toxigenic C. difficile strains, Clostridium perfringens, other Clostridia spp. and Bacteroides spp. Conclusions. Use of the liquid accumulation medium and covering with technical agar make it possible to isolate anaerobic flora from stool samples and increase an isolation rate of toxigenic C. difficile strains to 100% of ELISA-positive samples.

Regional spread of Candida auris

The geographical routes and time schedule of spread of C. auris – the fungus first identified in 2009 are discussed. Data on the increasing frequency of C. auris infections and rapid dissemination of the fungus from the regions of origin – southern Asia, eastern Asia, southern Africa and southern America – towards different regions of all continents except Antarctica, especially after 2016, are presented. Three different clades are encountered in Great Britain, all four clades – in the USA. South Asian clade is currently present in Russia: the introduction was associated with labor migration from Middle Asia. The necessity of C. auris surveillance, essential for the establishment of sources and routes of transmission and dissemination of different clades is emphasized. A window of possibilities is still present to prevent further spread of the fungus with the ability to cause outbreaks of hospital infections including intensive care departments. Rapid implementation of preventive measures during the pandemic of COVID-19 are needed taking into account introduction of fungus in new countries and clinics, as well as increased frequency of C. auris infections in some hospitals for patients infected with SARS-CoV-2 virus.

In vitro activity of thiamphenicol against Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes clinical isolates

Objective. To determine in vitro activity of thiamphenicol and other clinically available antimicrobials against clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. Materials and Methods. We included in the study 875 clinical isolates from 20 Russian cities during 2018–2019. Among tested strains, 126 were H. influenzae, 389 – S. pneumoniae, 360 – S. pyogenes. Antimicrobial susceptibility testing was performed using broth microdilution method according to ISO 20776-1:2006. AST results were interpreted according to EUCAST v.11.0 clinical breakpoints. Results. The minimum inhibitory concentrations (MICs) of thiamphenicol did not exceed 2 mg/L for 94.4% of H. influenzae strains (MIC50 and MIC90 were 0.5 and 1 mg/L, respectively). Thiamphenicol was active against 76.9% of ampicillin-resistant H. influenzae strains (MIC of thiamphenicol < 2 mg/L). The MIC of thiamphenicol was in the range of 0.06–2 mg/L for 96.7% of S. pneumoniae strains (MIC50 and MIC90 were 0.5 and 2 mg/L, respectively). The MIC of thiamphenicol for 90.6% of S. pneumoniae strains with reduced susceptibility to penicillin (MIC of penicillin > 0.06 mg/L) did not exceed 2 mg/L. A total of 88.1% of S. pneumoniae strains resistant to erythromycin were highly susceptible to thiamphenicol (MIC < 2 mg/L). The MIC of thiamphenicol did not exceed 8 mg/L for 96.1% of S. pyogenes strains (MIC50 and MIC90 were 2 and 4 mg/L, respectively). Conclusions. Thiamphenicol was characterized by relatively high in vitro activity, comparable to that of chloramphenicol, against tested strains of H. influenzae, S. pneumoniae and S. pyogenes, including S. pneumoniae isolates with reduced susceptibility to penicillin.