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 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

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

Objective. To determine in vitro activity of oral III generation cephalosporin cefpodoxime against clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes isolated from patients with community-acquired respiratory tract infections in different regions of the Russian Federation. Materials and Methods. The study included isolates of bacterial pathogens of community-acquired respiratory tract infections isolated from outpatients and hospitalized patients in different regions of the Russian Federation. A total of 558 isolates were included in the study, including 184 isolates of H. influenzae, 186 isolates of S. pneumoniae and 188 isolates of S. pyogenes. Species identification was performed using the MALDI-TOF mass spectrometry (Bruker Daltonics, Germany), for S. pneumoniae identification was also performed taking into account the morphology of colonies on blood agar, the presence of α-hemolysis, negative catalase reaction, sensitivity to optochin and positive results of latex-agglutination using DrySpot kit (OXOID, UK). Antimicrobial susceptibility to cefpodoxime and comparative antimicrobials was determined using broth microdilution method; interpretation of susceptibility testing results was performed in accordance with the recommendations of EUCAST, v.13.0. Data analysis and visualization were performed using the online platform AMRcloud. Results. Despite the generally low incidence of antibiotic resistance in the tested H. influenzae isolates, cefpodoxime, to which all tested isolates were susceptible, was superior to all other oral antibiotics in terms of in vitro activity: aminophenocillins (R – 8.7%), amoxicillin/clavulanate (R – 1.1%), co-trimoxazole (R – 31.5%), levofloxacin (R – 3.8%), moxifloxacin (R – 3.8%), tetracycline (R – 11%), cefixime (R – 2.2%), ceftibuten (R – 3.3%). Among the studied S. pneumoniae isolates, 81.7% were susceptible to cefpodoxime. All isolates resistant to penicillin, amoxicillin and ceftriaxone were also resistant to cefpodoxime. Cefpodoxime was inferior to levofloxacin (R – 0%), moxifloxacin (R – 0%), linezolid (R – 0%), vancomycin (R – 0%), ertapenem (R – 8.6%), ceftaroline (R – 2.3%), and chloramphenicol (R – 3.2%) in terms of in vitro activity against S. pneumoniae. However, all these drugs are either not available in oral form or have a less favorable safety profile compared to cefpodoxime. When compared with other III generation oral cephalosporins cefixime and ceftibuten, the activity of cefpodoxime against S. pneumoniae was significantly higher based on MIC50/90 values (cefixime – 0.125/8 mg/l, ceftibuten – 2/≥ 128 mg/l, cefpodoxime – 0.06/4 mg/l) and MICs range (cefixime – 0.06/≥ 128 mg/l, ceftibuten – 0.06/≥ 128 mg/l, cefpodoxime – 0.03/32 mg/l). No strains resistant to β-lactam antibiotics were detected among the tested S. pyogenes isolates. Based on the MIC50/90 values and the range of MIC values, the in vitro activity of cefpodoxime was higher than that of ceftibuten and comparable to that of cefixime. Conclusions. According to the results of our study, as well as in view of its pharmacokinetic profile, high safety and compliance, cefpodoxime can be considered as one of the options for oral therapy of community-acquired bacterial upper and lower respiratory tract infections

AMRexpert – online platform for interpretation, verification and validation of antimicrobial susceptibility testing

Objective. To review the key principles and functionality of AMRexpert online platform. Materials and Methods. The information part of the platform is comprised of rules based on the EUCAST recommendations and various standards for interpreting the results of antimicrobial susceptibility testing (EUCAST, CLSI versions 2020-2022). The technical part of the platform was developed using C# programming language, Angular and Bootstrap frameworks. AST results of Serratia marcescens, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Enterococcus faecium specific isolates were analyzed for practical testing of the platform using EUCAST v.12.0, 2022 interpretation criteria. Results. The developed platform for the evaluation of microbiological reports includes a wide list of expert rules, various standards for the interpretation of the AST results. Consistent data input, the ability to switch forms between several microorganisms, and the presentation of evaluation results in the form of blocks allows all necessary information to be structured. Practical use of the platform is available for various infectious pathogens. Fast and efficient interaction between users is provided by different options for sharing and saving the results. Conclusions. The web-based application evaluates microbiological reports in a comprehensive approach, with the ability to apply the results later to prescribe antimicrobial therapy. The platform for the interpretation, verification and validation of the AST results – AMRexpert can be accessed at https://amrexpert.ru

COVID-19 risk factors for mortality in hospitalized patients: results of a retrospective study

Objective. To identify risk factors for fatal outcome and COVID-19-associated liver damage in hospitalized adult patients with coronavirus infection. Materials and Methods. In a retrospective cohort study, 389 cases of patients with coronavirus infection complicated by bilateral viral pneumonia were studied. Demographic characteristics, clinical features of the course of the disease, anamnestic data, results of laboratory and instrumental methods of examination were analyzed and correlated with mortality. At the time of admission, the following were taken into account: fever, severity of the patient's condition according to COVID-19 classification of severity, body mass index (BMI), oxygen saturation (SpO2), percentage of lung tissue damage according to computed tomography (CT). Laboratory indices of biochemical blood analysis were assessed in dynamics: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, total protein, albumin, C-reactive protein (CRP). Data analysis was performed using the R programming language (ver. 4.1.1.). Results. The following risk factors, assessed at the time of hospitalization, increased the likelihood of death: severe and extremely severe condition of the patient (RR = 4.77; 95% CI: 3.33–6.83); SpO2 less than 93% (RR = 3.76; 95% CI: 2.57–5.49); diabetes mellitus (RR = 2.94; 95% CI: 2.01–4.30); lung tissue damage CT-3 and CT-4 (RR = 2.66; 95% CI: 1.79–3.75); concomitant chronic pyelonephritis and chronic kidney disease (CKD) (RR = 2.59; 95% CI: 1.79–3.74); age 65 years and older (RR = 2.50; 95% CI: 1.70–3.67); ischemic heart disease (IHD) (RR = 2.39; 95% CI: 1.42–4.01); an increase in the level of CRP more than 15 mg/l (RR = 2.22; 95% CI: 1.16–4.24); BMI 35 kg/m2 or more (RR = 1.89; 95% CI: 1.28–2.77); AST level more than 2 upper limit of normal (ULN) (RR = 1.75; 95% CI: 1.20–2.55). Risk factors for an increase in AST more than 2 ULN were: SpO2 less than 93% (RR = 1.53; 95% CI: 1.15– 2.03), severe and extremely severe course of coronavirus infection (RR = 1.83; 95% CI: 1.38–2.43), concomitant chronic liver disease (RR = 1.45, 95% CI: 1.08–1.95). Conclusions. Risk factors for fatal COVID-19 in hospitalized patients are: severe and extremely severe initial condition of the patient, oxygen saturation less than 93%, lung tissue damage more than 50%, age older than 65 years, presence of concomitant diabetes mellitus, chronic pyelonephritis and CHD, CHD, obesity, increased CRP level more than 15 mg/l, and AST more than 70 units/l. Elevation of AST over 2 IU/L can be considered as one of the prognostic laboratory markers of adverse prognosis COVID-19