Ceftaroline (active form of the prodrug ceftaroline fosamil) is a novel cephalosporin with activity against pathogens commonly associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and Gram-negative pathogens. This randomized, double-blind, Phase III study evaluated the efficacy and safety of ceftaroline fosamil in treating patients with CAP. The primary objective was to determine non-inferiority [lower limit of 95% confidence interval (CI) ≥ -10%] of clinical cure rates achieved with ceftaroline fosamil compared with those achieved with ceftriaxone in the clinically evaluable (CE) and modified intent-to-treat efficacy (MITTE) populations.Patients hospitalized in a non-intensive care unit setting with CAP of Pneumonia Outcomes Research Team (PORT) risk class III or IV requiring intravenous (iv) therapy were randomized (1:1) to receive 600 mg of ceftaroline fosamil iv every 12 h or 1 g of ceftriaxone iv every 24 h. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 2 registration number NCT00509106 (http://clinicaltrials.gov/ct2/show/NCT00509106).The study enrolled 627 patients, 315 of whom received ceftaroline fosamil and 307 of whom received ceftriaxone. Patients in both treatment groups had comparable baseline characteristics. Clinical cure rates were as follows: CE population, 82.1% (193/235) for ceftaroline fosamil and 77.2% (166/215) for ceftriaxone [difference (95% CI), 4.9% (-2.5, 12.5)]; and MITTE population, 81.3% (235/289) for ceftaroline fosamil and 75.5% (206/273) for ceftriaxone [difference (95% CI), 5.9% (-1.0, 12.7)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE (mMITTE) population were 83.3% (35/42) and 70.0% (28/40) for ceftaroline fosamil and ceftriaxone, respectively. Ceftaroline fosamil and ceftriaxone were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations due to an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, hypokalaemia, insomnia and phlebitis, and the most common AEs for ceftriaxone-treated patients were diarrhoea, insomnia, phlebitis and hypertension.Ceftaroline fosamil achieved high clinical cure and microbiological response rates in patients hospitalized with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile that is similar to that of ceftriaxone and other cephalosporins. Ceftaroline fosamil is a promising agent for the treatment of CAP.
The study aimed to investigate behaviour, knowledge and practices towards antibiotic (AB) use among patients who purchased ABs with a prescription across Russia.
To assess the in vitro activity of ceftobiprole and comparators against a recent collection of Gram-positive and Gram-negative pathogens, in order to detect potential changes in susceptibility patterns, and to evaluate the Etest assay for ceftobiprole susceptibility testing. Contemporary Gram-positive and Gram-negative isolates (excluding extended-spectrum β-lactamase-producing isolates) from across Europe and the Middle East were collected, and their susceptibility to ceftobiprole, vancomycin, teicoplanin, linezolid, ceftazidime and cefepime was assessed using the Etest method. Quality testing [using Etest and broth microdilution (BMD)] was conducted at a central reference laboratory. Some 5041 Gram-positive and 4026 Gram-negative isolates were included. Against Gram-positive isolates overall, ceftobiprole had the lowest MIC50 (0.5 mg/L), compared with 1 mg/L for its comparators (vancomycin, teicoplanin and linezolid). Against methicillin-resistant Staphylococcus aureus, all four agents had a similar MIC90 (2 mg/L), but ceftobiprole had a 4-fold better MIC90 (0.5 mg/L) against methicillin-susceptible strains. Only 38 Gram-positive isolates were confirmed as ceftobiprole resistant. Among Gram-negative strains, 86.9%, 91.7% and 95.2% were susceptible to ceftobiprole, ceftazidime and cefepime, respectively. Pseudomonas aeruginosa was less susceptible to all three antimicrobials than any other Gram-negative pathogen. There was generally good agreement between local Etest results and those obtained at the reference laboratory (for ceftobiprole: 86.8% with Gram-negatives; and 94.7% with Gram-positives), as well as between results obtained by BMD and Etest methods (for ceftobiprole: 98.2% with Gram-negatives; and 98.4% with Gram-positives). Ceftobiprole exhibits in vitro activity against a wide range of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains. No changes in its known susceptibility profile were identified.
A high level of resistance to carbapenems in Acinetobacter baumannii strains severely limits therapeutic possibilities. Colistin is the last resort drug against such strains, although the cases of resistance to this drug have become more frequent. This article presents the epidemiological features and genetic diversity of colistin nonsusceptible A. baumannii strains collected as part of a national multicenter epidemiological study of the antibiotic resistance of pathogens of nosocomial infections (MARATHON), which was conducted in 2013-2014 in Russia. A total of 527 A. baumannii isolates were collected, 10 (1.9%) of which were nonsusceptible to colistin. The majority of nonsusceptible A. baumannii isolates to colistin showed resistance to carbapenems and had the genes of the acquired OXA-40-like carbapenemases (n = 6). In one case, a combination of OXA-23-like + OXA-40-like (n = 1) genes was identified. One strain had the multidrug-resistant (MDR) phenotype, 6 isolates had extensively drug-resistant (XDR) phenotype, and 3 isolates had pandrug-resistant (PDR) phenotype. Among the colistin nonsusceptible A. baumannii isolates, 6 individual genotypes were identified, most of which belonged to successful international clones (CC92OXF/CC2PAS, n = 4; CC944OXF/ST78PAS, n = 4; CC109OXF/CC1PAS, n = 1).
The purpose of this study was to compare antimicrobial resistance of clinical strains of S. pneumoniae isolated in different Russian regions. Identification of strains was done on the basis of colony morphology, Gram stain, optochin susceptibility and bile solubility tests. Susceptibility to penicillin G (PEN), amoxicillin (AMO), amoxicillin/clavulanate (AMC), cefotaxime (CTX), cefepime (CFP), erythromycin (ERY), azithromycin (AZI), clarithromycin (CLA), midecamycin (MID), clindamycin (CLI), levofloxacin (LEV), tetracycline (TET), co-trimoxazole (SXT), chloramphenicol (CHL) and vancomycin (VAN) was determined by broth microdilution. Breakpoints were those of NCCLS (2002) except for MID (†1; 2-4; >4 mg/L) for susceptible, intermediate resistant and resistant isolates, respectively. A total of 210 and 581 pneumococci, respectively were isolated in 15 Russian centers in 10 cities in 1999-2000 and 25 centers in 21 cities in 2001-2002. The susceptibility testing results are presented in the Table.
Сeftaroline fosamil is a fifth-generation cephalosporin and a unique β-lactam and the only currently registered in the Russian Federation cephalosporin with activity against MRSA. Сeftaroline is approved for use in pediatric practice for the treatment of children with community-acquired pneumonia and complicated skin and soft tissue infections, including cases of patients with concomitant bacteremia. The place of ceftaroline in the treatment of severe and life-threatening infections in children is primarily due to its high activity against the key causative agents of community-acquired pneumonia and skin and soft tissue infections (first of all, S. pneumoniae and S. aureus, including MRSA), bactericidal mechanism of action, creation of effective concentrations and penetration into the infection’s site, low potential for resistance development, proven significant development of clinical effect, high clinical efficacy in these infections and favorable tolerability and safety profile. The review presents the results of the program of clinical evaluation of ceftaroline in children, analyzes current data on etiology and antimicrobial resistance of the key pathogens of community-acquired pneumonia and skin and soft tissue infections in the Russian Federation, defines the place of ceftaroline in clinical recommendations in children, and characterizes the patient’s profile to whom the prescription of ceftaroline in hospital is indicated.
The problem of infectious endocarditis currently deserves special attention. According to the data, intrahospital mortality caused by this pathology reaches 20%, which is largely due to the development of potential complications, the most common among which are the development and progression of heart failure, as well as thromboembolic manifestations with the damage to target organs of various localization. The article presents the results of a multicenter study establishing the features of antimicrobial therapy in patients with infectious endocarditis under the conditions of the dominance of gram-positive microorganisms in the etiological structure in the Russian Federation. 440 cases of definite and probable infectious endocarditis in the period from September 2006 to December 2020 were analyzed.
