Cefepime/sulbactam is a combined antibiotic consisting of the 4 th generation cephalosporin cefepime and the beta-lactamase inhibitor sulbactam in 1:1 ratio. Cefepime/sulbactam antibiotic was developed in Russia in 2006, it had passed preclinical and clinical studies, was approved for medical use, and has been produced in Russia since 2019. Cefepime has a wide spectrum of antimicrobial activity against gram-positive and gram-negative microorganisms, sulbactam adds two clinically important pathogens to the antimicrobial spectrum of cefepime — Acinetobacter baumannii and Bacteroides fragilis. In addition, sulbactam protects cefepime from hydrolysis by class A broad- and extended-spectrum beta-lactamases, and cefepime itself is stable against class C chromosomal beta-lactamases and partially stable to OXA-type class D carbapenemases. In vitro studies have shown that most clinical strains of ESBL-producing Klebsiella pneumoniae, Escherichia coli, Proteus spp. are sensitive to cefepime/sulbactam, as well as some strains of K.pneumoniae and A.baumannii that are resistant to carbapenems as a result of the production of class D carbapenemases. The efficacy and safety of cefepime/sulbactam have been determined in three clinical studies. Clinical and bacteriological efficacy of the drug was 97.9% and 97.6% in patients with acute community-acquired pyelonephritis. In the MAXI-19 multicenter study, the clinical efficacy of cefepime/sulbactam in patients with intra-abdominal infections, nosocomial pneumonia, and ventilator-associated pneumonia was 78.4, 90.3, and 80.7%, respectively. A comparative study examined the efficacy of cefepime/sulbactam and carbapenems in severe nosocomial infections (84% of patients had sepsis or septic shock). Clinical efficacy of cefepime/sulbactam and carbapenems was high and did not significantly differ (71% vs. 62%), as well as the bacteriological efficacy — 87% vs. 73%, while typical hospital pathogens characterized by MDR or XDR were identified in the majority of patients (most often — K.pneumoniae, A.baumannii, E.coli). During treatment with carbapenems, carbapenem-resistant bacteria were detected significantly more often (74.5%, most often A.baumannii — 44.7%, K.pneumoniae — 38.3%), compared to cefepime/sulbactam (20.0%, P.aeruginosa and K.pneumoniae, both at 15.5%), P=0.0001. The risk of superinfection was also significantly higher with carbapenems than with cefepime/sulbactam (53.3% vs. 22.2%, P=0.001). For severe infections, cefepime/sulbactam was administered at a dose of 4 g (2 g + 2 g) every 12 hours or 2 g (1 g + 1 g) every 8 hours. Currently, cefepime/sulbactam should be considered as a reliable option for the treatment of severe infections in the hospital as a carbapenem-replacement strategy to reduce the risks of selection of carbapenem-resistant gram-negative bacteria.

The aim of the study was to evaluate the effectiveness of cefepime/sulbactam in patients with intra-abdominal infection, nosocomial pneumonia (NP) or ventilator-associated pneumonia (VAP) in actual clinical practice. Material and methods. The study was conducted in 14 Russian Clinics from October 2019 to March 2020. Study design: an open-label, prospective, non-comparative, multicenter, observational study. The study included patients who met the inclusion/exclusion criteria and signed a written informed consent. The studied antibiotic: cefepime/sulbactam (Maxictam®-AF). The primary parameter for effectiveness evaluation was the clinical effect after the conclusion of cefepime/sulbactam therapy — recovery/improvement or no effect. Results. The study included 140 patients (average age — 60.8 years) who received at least one dose of cefepime/sulbactam; 37 of them had intraabdominal infection, 72 — NP, and 31 — VAP. Most of the included patients were in the ICU department (82.1%) and their condition was severe: the average APACHE II score was 15.5 points, SOFA — 5.4 points, the Mannheim peritonitis index value in patients with intra-abdominal infection was from 14 to 35 points, with an average of 24.3 points. The majority of patients treated with cefepime/sulbactam (68.6%) had one or more risk factors for multi-resistant pathogens upon hospital or ICU admission. Cefepime/sulbactam was prescribed as the 1st or 2nd line of empirical therapy at a daily dose of 4 g (in 68.3%), 6 g (2.9%) or 8 g (28.8%); most patients were prescribed cefepime/sulbactam in monotherapy (72.3%). The average duration of therapy with cefepime/sulbactam was 9.6±3.5 days. The final assessment of treatment effectiveness was carried out in 132 patients: recovery or improvement was noted in 80.6% of patients with intra-abdominal infection, the effectiveness in NP and VAP was slightly higher — 95.6 and 89.3%. The effect was absent in 5.3% of patients, relapse or superinfection was noted in 3.0 and 1.5%. The majority of patients (81.3%) treated with cefepime/sulbactam were discharged from the hospital. No serious side effects were observed. In patients with a positive effect, age and values of APACHE II were significantly lower (59.58 years and 14.79 points) compared to those with no effect (67.95 years and 18.39 points). A multivariate analysis found that the probability of recovery of patients treated with cefepime/sulbactam did not depend on the diagnosis of infection, ICU admission, the presence of sepsis or septic shock. Conclusion. The multicenter study has established a high clinical efficacy of cefepime/sulbactam in real clinical practice in the treatment of patients with severe intraabdominal infection, nosocomial pneumonia or ventilator-associated pneumonia.

В 2021 г. в России был зарегистрирован новый антибиотик из группы карбапенемов биапенем, ранее применявшийся только в Японии и Юго-Восточной Азии. В статье подробно анализируются антимикробные, фармакокинетические и клинические характеристики биапенема, приводятся фармакодинамические обоснования дозирования антибиотика. Подчёркнуты наиболее важные свойства и преимущества биапенема, связанные с антимикробными свойствами (более высокая активность и эрадикационный потенциал в отношении Pseudomonas aeruginosa), наиболее высокая среди карбапенемов стабильность к карбапенемазам классов D (OXA-48-тип) и В (NDM-тип), что определяет новую опцию лечения инфекций, вызванных карбапенеморезистентными Enterobacterales (биапенем в комбинации с полимиксином/колистином и/или тигециклином). Из особенностей фармакокинетики следует выделить низкую связь с альбумином плазмы (3,7%), хорошую тканевую пенетрацию, а также стабильную фармакокинетику биапенема у больных, находящихся в критическом состоянии, септическом шоке и требующим проведения заместительной почечной терапии. Фармакодинамическое моделирование установило наиболее оптимальное дозирование биапенема при сепсисе и септическом шоке: 300 мг (в виде 3-часовой инфузии) каждые 6 ч или 600 мг каждые 12 ч. У пациентов, получающих продлённую заместительную почечную терапию, предпочтителен режим дозирования 300 мг 4 раза в день. Эффективность биапенема документирована в многочисленных исследованиях, в которых показана также хорошая переносимость и безопасность антибиотика: частота побочных эффектов составила в среднем 2% и была ниже, чем у других карбапенемов. Биапенем может эффективно и безопасно назначаться наиболее проблемным пациентам пожилого возраста, имеющим серьёзную коморбидность и нарушение функции почек и печени.