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

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

Cefpodoxime proxetil – new opportunities in antibacterial therapy of respiratory infections

The purpose of the expert council was to determine the place of cefpodoxime in the ABT algorithms for upper and lower respiratory tract infections and to form a consensus position on its use in clinical practice. Based on the available data, the possibility of including cefpodoxime in national guidelines for the treatment of rhinosinusitis, acute tonsillopharyngitis, community-acquired pneumonia (CAP), as well as infectious exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) is being considered

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

Методические рекомендации Российской некоммерческой общественной организации "Ассоциация анестезиологов-реаниматологов", Межрегиональной общественной организации "Альянс клинических химиотерапевтов и микробиологов", Межрегиональной ассоциации по клинической микробиологии и антимикробной химиотерапии (МАКМАХ), общественной организации "Российский Сепсис Форум" "Диагностика и антимикробная терапия инфекций, вызванных полирезистентными микроорганизмами"

Introduction. Strains of microorganisms resistant to antimicrobial agents are commonly found in medical units throughout most regions of the world, including Russia. This leads to lower antimicrobial therapy efficacy when treating nosocomial infections. In this regard, the timely implementation of adequate antibiotic therapy is of great importance. The objective of the guidelines: To provide summarized information on contemporary approaches to microbiological diagnostics and the assessment of results, as well as the principles of rational use of antimicrobial and antifungal agents, including treatment of infections caused by multiple drug-resistant strains of microorganisms. Subjects and methods. These guidelines are based on published data obtained in the course of randomized trials, as well as information presented in the provisions of international guidelines supported by high-level evidence. The guidelines were prepared by a working group of Russian experts with extensive experience in research and practical work in this area. On October 11, 2019, the final version of the guidelines was reviewed and approved at a joint meeting of the working group and representatives of the public organizations which initiated the development of these guidelines (Association of Anesthesiologists-Intensivists, the Interregional Non-Governmental Organization Alliance of Clinical Chemotherapists and Microbiologists, the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC), NGO Russian Sepsis Forum). Conclusion. The guidelines reflect an interdisciplinary consensus of approaches to the diagnostics and antibiotic therapy of infections caused by multiresistant microorganisms. The provisions set forth should be used to decide on the strategy of empirical and etiotropic therapy of the most severe infections.Введение. В большинстве регионов мира, в том числе и в России, получают широкое распространение штаммы микроорганизмов, характеризующиеся устойчивостью к большинству используемых в медицинских организациях антимикробных препаратов, что закономерно ведет к снижению эффективности антимикробной терапии при лечении нозокомиальных инфекций. В этой связи своевременное назначение адекватной антибактериальной терапии приобретает очень большое значение. Цель рекомендаций: представить в обобщенном виде информацию о современных подходах к микробиологической диагностике и оценке ее результатов, а также о принципах рационального использования антимикробных и противогрибковых препаратов, в том числе при инфекциях, вызванных полирезистентными штаммами микроорганизмов. Материал и методы. В основу положены данные из публикаций, полученные в ходе рандомизированных исследований, а также изложенные в международных клинических рекомендациях в виде положений, имеющих высокую степень доказательности. Рекомендации подготовлены рабочей группой российских экспертов, обладающих большим опытом исследовательской и практической работы в рассматриваемой области. Окончательный вариант рекомендаций был рассмотрен и утвержден 11.10.2019 г. на совместном заседании рабочей группы и представителей общественных организаций - инициаторов разработки Методических рекомендаций (Российская некоммерческая общественная организация «Ассоциация анестезиологов-реаниматологов», Межрегиональная общественная организация «Альянс клинических химиотерапевтов и микробиологов», Межрегиональная ассоциация по клинической микробиологии и антимикробной химиотерапии (МАКМАХ), общественная организация «Российский Сепсис Форум»). Заключение. Рекомендации отражают междисциплинарное консенсусное мнение о подходах к диагностике и антибактериальной терапии инфекций, вызванных полирезистентными микрорганизмами. Изложенные в них положения целесообразно использовать при определении тактики эмпирической и этиотропной терапии наиболее тяжелых инфекций