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

Antimicrobial resistance of clinical isolates of Klebsiella pneumoniae and Escherichia coli in Russian hospitals: results of a multicenter epidemiological study

Objective. To study the prevalence and mechanisms of antibiotic resistance, including carbapenemase production, in clinical isolates of Klebsiella pneumoniae and Escherichia coli isolated in different regions of Russia as part of the sentinel multicenter surveillance study in 2020–2021, and to explore the population structure of K. pneumoniae and the impact of “high-risk clones” on antibiotic resistance. Materials and Methods. Consecutive, non-duplicate isolates of K. pneumoniae (n = 2503) and E. coli (n = 2055) isolated from various specimens (blood, cerebrospinal fluid, respiratory samples, urine, wound secretions, etc.) of hospitalized patients with clinical signs of infection in 55 hospitals of 29 cities of Russia were studied. Species identification of isolates was performed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibilities were determined by serial broth microdilution or, in the case of fosfomycin, by agar dilution method, and results were interpreted according to EUCAST v13 MIC breakpoints. Carbapenemase production was determined phenotypically by carbapenem inactivation method (CIM), the presence of genes of the most common serine carbapenemases (KPC, OXA-48) and metallo-β-lactamases (VIM, IMP, NDM) was determined by real-time PCR. K. pneumoniae clinical isolates were genotyped and assigned to the known clonal complexes (CC) and sequence types (ST) using SNP typing and multilocus sequencing typing (MLST) methods. K- and O-serotypes, acquired resistance and virulence genes, and plasmids carrying these genes were characterized using whole-genome sequencing of selected isolates (n = 215). Results. The resistance rates of nosocomial/community-acquired isolates of K. pneumoniae were as follows: amoxicillin-clavulanate – 88.63/57.99%, piperacillin-tazobactam – 82.92/45.49%, cefotaxime – 87.74/56.97%, ceftazidime – 84.76/53.07%, cefepime – 81.43/49.18%, aztreonam – 1.63/53.28%, ceftazidime-avibactam – 30, 88/9.22%, ceftolozan-tazobactam – 70.06/31.35%, ertapenem – 72.10/28.69%, meropenem – 49.60/15.16%, imipenem – 44.54/13.73%, gentamicin – 60.82/30.33%, amikacin – 42.06/17.21%, ciprofloxacin – 85.10/49.39%; trimethoprimsulfamethoxazole – 74.38/48.16%, colistin – 5.96/2.25%. The resistance of nosocomial/outpatient isolates of E. coli were: ampicillin – 84.93/67.67%, amoxicillin-clavulanate – 57.37/39.73%, piperacillin-tazobactam – 19.48/8.70%, cefotaxime – 63.83/34.19%, ceftazidime – 45.32/20.34%, cefepime – 35.95/16.61%, aztreonam – 51.78/26.11%, ceftazidime-avibactam – 5.71/0.80%, ceftolozane-tazobactam – 11, 95/2.22%, ertapenem – 8.18/1.42%, meropenem – 5.17/0.53%, imipenem – 4.95/0.36%, gentamicin – 24.54/13.68%, amikacin – 5.49/1.42%, ciprofloxacin – 54, 14/32.50%, trimethoprim-sulfamethoxazole – 52.21/38.54%, fosfomycin – 2.48/1.43%, colistin – 1.60/1.07%, tigecycline – 6.35/3.11%. The frequency of carbapenemase production among K. pneumoniae nosocomial isolates was 65.32% (OXA-48 – 40.75%, NDM – 30.28%, KPC – 8.74%, OXA-48 + NDM – 10.62%, OXA-48 + KPC – 2.98%, NDM + KPC – 0.45%, OXA-48 + NDM + KPC – 0.20%). More than 70% of nosocomial isolates of K. pneumoniae belonged to only 7 major genetic lineages known as “high-risk international clones”: CC395 – 37.40%, CC23 – 9.59%, CC307 – 8.64%, CC147 – 7.61%, CC15 – 2.95%, CC258 – 2.92%, and CC11 – 2.41%. The population of community-acquired K. pneumoniae was characterized by significantly greater genetic diversity (Simpson diversity index: D = 0.919; 95% CI: 0.904 to 0.933) compared with the population of nosocomial strains (Simpson diversity index: D = 0.815; 95% CI: 0.802 to 0.827). Strains of the “hypervirulent” genetic lineage of K. pneumoniae CC23 were more common in community-acquired infections. Conclusions. The extremely high frequency of resistance to cephalosporins in K. pneumoniae (> 80%) and E. coli (> 60%), as well as the high frequency of combined resistance to aminoglycosides and fluoroquinolones precludes their empirical use for the treatment of serious nosocomial infections caused by these pathogens. K. pneumoniae shows a rapid increase in resistance to carbapenems, mainly due to the spread of carbapenemases of three major groups: OXA-48, NDM and KPC. The overall increase in the frequency of carbapenemase production is accompanied by the growing diversity of carbapenemases, the increasing prevalence of strains producing NDM and KPC enzymes and those co-producing multiple carbapenemases simultaneously. In community-acquired infections, the high prevalence of resistance to cephalosporins in E. coli (> 30%) and K. pneumoniae (> 50%) remains the most important problem

Etiology of severe community-acquired pneumonia in adults: Results of the first Russian multicenter study [Этиология тяжелой внебольничной пневмонии у взрослых: результаты первого российского многоцентрового исследования]

Aim: to study the etiology of severe community-acquired pneumonia (SCAP) in adults in Russian Federation. SCAP is distinguished by high mortality and socio-economic burden. Both etiology and antimicrobial resistance are essential for appropriate antibiotic choice. Materials and methods. A prospective cohort study recruited adults with confirmed diagnosis of SCAP admitted to multi-word hospitals of six Russian cities in 2014-2018. Etiology was confirmed by routine culture of blood, respiratory (sputum, endotracheal aspirate or bronchoalveolar lavage) and when appropriate, autopsy samples, urinary antigen tests (L. pneumophila serogroup 1, S. pneumoniae); real-time PCR for identification of “atypical” bacterial pathogens (M. pneumoniae, C. pneumoniae, L. pneumophila) and respiratory viruses (influenza viruses A and B, parainfluenza, human metapneumovirus, etc.) was applied. Results. Altogether 109 patients (60.6% male; mean age 50.8±18.0 years old) with SCAP were enrolled. Etiological agent was identified in 65.1% of patients, S. pneumoniae, rhinovirus, S. aureus and K. pneumoniae were the most commonly isolated pathogens (found in 43.7, 15.5, 14.1 and 11.3% of patients with positive results of microbiological investigations, respectively). Bacteriemia was seen in 14.6% of patients and most commonly associated with S. pneumoniae. Co-infection with 2 or more causative agents was revealed in 36.6% of cases. Combination of bacterial pathogens (mainly S. pneumoniae with S. aureus or/and Enterobacterales) prevailed - 57.7% of cases; associations of bacteria and viruses were identified in 38.5% of patients, different viruses - in one case. Conclusion. S. pneumoniae was the most common pathogen in adults with SCAP. A high rate of respiratory viruses (mainly rhinovirus and influenza viruses) identification both as mixt infection with bacteria and mono-infection should be taken into account. © 2020 Consilium Medikum. All rights reserved

Этиология тяжелой внебольничной пневмонии у взрослых: результаты первого российского многоцентрового исследования

Aim: to study the etiology of severe community - acquired pneumonia (SCAP) in adults in Russian Federation. SCAP is distinguished by high mortality and socio - economic burden. Both etiology and antimicrobial resistance are essential for appropriate antibiotic choice. Materials and methods. A prospective cohort study recruited adults with confirmed diagnosis of SCAP admitted to multi - word hospitals of six Russian cities in 2014-2018. Etiology was confirmed by routine culture of blood, respiratory (sputum, endotracheal aspirate or bronchoalveolar lavage) and when appropriate, autopsy samples, urinary antigen tests (L. pneumophila serogroup 1, S. pneumoniae); real - time PCR for identification of “atypical” bacterial pathogens (M. pneumoniae, C. pneumoniae, L. pneumophila) and respiratory viruses (influenza viruses A and B, parainfluenza, human metapneumovirus, etc.) was applied. Results. Altogether 109 patients (60.6% male; mean age 50.8±18.0 years old) with SCAP were enrolled. Etiological agent was identified in 65.1% of patients, S. pneumoniae, rhinovirus, S. aureus and K. pneumoniae were the most commonly isolated pathogens (found in 43.7, 15.5, 14.1 and 11.3% of patients with positive results of microbiological investigations, respectively). Bacteriemia was seen in 14.6% of patients and most commonly associated with S. pneumoniae. Co - infection with 2 or more causative agents was revealed in 36.6% of cases. Combination of bacterial pathogens (mainly S. pneumoniae with S. aureus or/and Enterobacterales) prevailed - 57.7% of cases; associations of bacteria and viruses were identified in 38.5% of patients, different viruses - in one case. Conclusion. S. pneumoniae was the most common pathogen in adults with SCAP. A high rate of respiratory viruses (mainly rhinovirus and influenza viruses) identification both as mixt infection with bacteria and mono - infection should be taken into account.Цель - изучить структуру возбудителей тяжелой внебольничной пневмонии (ТВП) у взрослых больных в Российской Федерации (РФ). ТВП относится к заболеваниям с высокой летальностью и отличается значимым социально - экономическим бременем для общества. Адекватная эмпирическая антибактериальная терапия должна основываться на знании спектра ключевых возбудителей и их чувствительности к антимикробным препаратам. Материалы и методы. В проспективное исследование, выполнявшееся в многопрофильных стационарах 6 городов РФ в 2014-2018 гг., включались взрослые пациенты с подтвержденным диагнозом ТВП. Для верификации этиологии культуральным методом исследовались кровь, респираторные образцы (мокрота, эндотрахеальный аспират, бронхоальвеолярный лаваж), аутопсийные образцы у умерших пациентов; использовались экспресс - тесты для выявления антигенурии (L. pneumophila cерогруппа 1 и S. pneumoniae). «Aтипичные» бактериальные патогены (M. pneumoniae, C. pneumoniae, L. pneumophila) и респираторные вирусы (вирусы гриппа А и В, парагриппа, риновирус, метапневмовирус человека и др.) выявлялись методом полимеразной цепной реакции в режиме реального времени с помощью коммерческих тестов. Результаты. Всего в исследование включено 109 пациентов (мужчин - 60,6%, средний возраст 50,8±18,0 лет) с ТВП. Этиологически значимые возбудители ТВП обнаружены в 65,1% случаев; наиболее часто выявлялись S. pneumoniae, риновирусы, S. aureus и K. pneumoniae (43,7, 15,5, 14,1 и 11,3% пациентов c положительными результатами микробиологического исследования соответственно). Бактериемия выявлена в 14,6% случаев, S. pneumoniae являлся наиболее часто идентифицируемым патогеном. Два и более возбудителя ТВП выявлены в 36,6% случаев. Среди комбинаций превалировало сочетание бактериальных возбудителей (чаще всего S. pneumoniae с S. aureus или/и Enterobacterales) - 57,7%; ассоциации бактериальных возбудителей и вирусов выявлены у 38,5% пациентов, в 1 случае выявлена ко - инфекция двумя респираторными вирусами. Заключение. В структуре этиологии ТВП у госпитализированных взрослых больных преобладал S. pneumoniae. Следует отметить высокую частоту выявления респираторных вирусов (преимущественно риновирус и вирусы гриппа) как в ассоциации с бактериальными возбудителями, так и в монокультуре