BACKGROUND: Nosocomial pneumonia due to antimicrobial-resistant pathogens is associated with high mortality. We assessed the efficacy and safety of the combination antibacterial drug ceftolozane-tazobactam versus meropenem for treatment of Gram-negative nosocomial pneumonia. METHODS: We conducted a randomised, controlled, double-blind, non-inferiority trial at 263 hospitals in 34 countries. Eligible patients were aged 18 years or older, were undergoing mechanical ventilation, and had nosocomial pneumonia (either ventilator-associated pneumonia or ventilated hospital-acquired pneumonia). Patients were randomly assigned (1:1) with block randomisation (block size four), stratified by type of nosocomial pneumonia and age (<65 years vs ≥65 years), to receive either 3 g ceftolozane-tazobactam or 1 g meropenem intravenously every 8 h for 8-14 days. The primary endpoint was 28-day all-cause mortality (at a 10% non-inferiority margin). The key secondary endpoint was clinical response at the test-of-cure visit (7-14 days after the end of therapy; 12·5% non-inferiority margin). Both endpoints were assessed in the intention-to-treat population. Investigators, study staff, patients, and patients' representatives were masked to treatment assignment. Safety was assessed in all randomly assigned patients who received study treatment. This trial was registered with ClinicalTrials.gov, NCT02070757. FINDINGS: Between Jan 16, 2015, and April 27, 2018, 726 patients were enrolled and randomly assigned, 362 to the ceftolozane-tazobactam group and 364 to the meropenem group. Overall, 519 (71%) patients had ventilator-associated pneumonia, 239 (33%) had Acute Physiology and Chronic Health Evaluation II scores of at least 20, and 668 (92%) were in the intensive care unit. At 28 days, 87 (24·0%) patients in the ceftolozane-tazobactam group and 92 (25·3%) in the meropenem group had died (weighted treatment difference 1·1% [95% CI -5·1 to 7·4]). At the test-of-cure visit 197 (54%) patients in the ceftolozane-tazobactam group and 194 (53%) in the meropenem group were clinically cured (weighted treatment difference 1·1% [95% CI -6·2 to 8·3]). Ceftolozane-tazobactam was thus non-inferior to meropenem in terms of both 28-day all-cause mortality and clinical cure at test of cure. Treatment-related adverse events occurred in 38 (11%) of 361 patients in the ceftolozane-tazobactam group and 27 (8%) of 359 in the meropenem group. Eight (2%) patients in the ceftolozane-tazobactam group and two (1%) in the meropenem group had serious treatment-related adverse events. There were no treatment-related deaths. INTERPRETATION: High-dose ceftolozane-tazobactam is an efficacious and well tolerated treatment for Gram-negative nosocomial pneumonia in mechanically ventilated patients, a high-risk, critically ill population. FUNDING: Merck & Co.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• bakteriální pneumonie farmakoterapie   mikrobiologie   MeSH
• cefalosporiny farmakologie   terapeutické užití   MeSH
• infekce spojené se zdravotní péčí farmakoterapie   mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• meropenem farmakologie   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tazobaktam farmakologie   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

V analýze je prezentován soubor 94 pacientů operovaných na Klinice otorinolaryngologie a chirurgie hlavy a krku FN u sv. Anny v Brně v letech 1998 – 2005 pro bilaterální nosní polypózu refrakterní na konzervativní terapii. V rámci zachování homogenity souboru byli hodnoceni pacienti operovaní a sledovaní jedním operatérem. Rozsah NP byl hodnocen dle předoperačního radiologického stagingu dle Lund-Mackaye, přičemž medián CT skóre činil 16 bodů, Q0,25, Q0,75 (13, 18). U 42 (45 %) pacientů hodnota radiologického CT stagingu byla vyšší než 16 bodů, což odpovídá tzv. difuzní NP. Operační výkon byl proveden dle konceptu funkční endonazální chirurgie a rozsah operace hodnocen dle operačního skóre. Průměrná doba sledování byla 73 (45-125) měsíců. Hodnoceným kritériem úspěšnosti léčby bylo stanovení četnosti recidiv. Ve sledovaném období bylo diagnostikováno 24 (25,5 %) recidiv. Hodnota mediánu časového intervalu do rozvoje recidivy činila 39,5 měsíce. Dle přítomnosti systémových rizikových faktorů byli pacienti rozděleni do 4 skupin. U první skupiny tvořené 29 pacienty bez prokázaných rizikových faktorů (bez alergie, astma bronchiale i ASA senzitivity) nebyla v průběhu sledování diagnostikována recidiva NP. Druhou skupinu tvořili pacienti s prokázanou alergií (bez astma bronchiale a ASA senzitivity), n=15, počet recidiv 3, 20 %. Třetí skupinu představovali pacienti s astma bronchiale (s nebo bez alergie, bez ASA senzitivity), n=30, počet recidiv 8, 27 %. Čtvrtá skupina byla reprezentována pacienty s ASA intolerancí (n=20), počet recidiv 13,65 %. Dle Kaplan-Maierovy analýzy pravděpodobnost recidivy v 5 letech po operaci u pacientů bez rizikových faktorů činila 0 %, u alergiků 13 %, u astmatiků 17 % a u pacientů s ASA senzitivitou 50 %.

We present a study group of 94 patients operated on for bilateral nasal polyposis refractory to medical treatment in the Department of Otorhinolaryngology and Head and Neck Surgery of St. Anne's University Hospital Brno between 1998 and 2005. In order to ensure homogeneity of the group, patients operated on and followed-up by one surgeon were evaluated. The extent of NP was assessed using the preoperative radiological staging according to Lund-Mackay; the median CT score was 16 points, Q0.25, Q0.75 (13.18). In 42 patients (45%) the value of radiological CT staging was higher than 16 points, which corresponds to the category of the diffuse NP. The surgery was performed in accordance with the principles of the functional endonasal surgery concept and the extent of the surgery was classified according to a surgical score. The average follow-up period was 73 (45-125) months. Determination of recurrence rate was an important criterion to evaluate the success of treatment. In the follow-up period, 24 (25.5%) recurrences were diagnosed. The median value of the recurrence-free interval was 39. months. For evaluation of the prognostic significance of systemic risk factors, the patients were divided into 4 subgroups. In the first subgroup which consisted of 29 patients without proved allergy, bronchial asthma or ASA sensitivity, no recurrence of NP was diagnosed during the follow-up period. The second subgroup consisted of patients with proved allergy without bronchial asthma and ASA sensitivity (n=15), recurrence rate was 20% (3). In the third subgroup there were patients with bronchial asthma without ASA sensitivity (n=30), recurrence rate was 27% (8). In the fourth group there were patients with ASA intolerance (n=20), recurrence rate was 65% (13). According to Kaplan-Meier analysis, the probability of recurrence 5 years after surgery in patients without risk factors was 0%, in allergy patients about 13%, in asthmatics about 17% and in patients with ASA sensitivity about 50%.

• Klíčová slova
• četnost recidiv,
• MeSH
• alergie MeSH
• Aspirin MeSH
• bronchiální astma MeSH
• dospělí MeSH
• interpretace statistických dat MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nosní polypy chirurgie   MeSH
• pacienti klasifikace   MeSH
• recidiva MeSH
• rizikové faktory MeSH
• senioři MeSH
• statistika jako téma MeSH
• výběr pacientů MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

BACKGROUND: A monoclonal antibody such as mepolizumab typically first appears as a parenteral lyophilized formulation (LYO), then as various parenteral solution forms, and finally as a self-administered form at homecare. While more studies compare mepolizumab safety and efficacy across dosage forms, no data exists on the impact of switching to more successive dosage forms in real-world settings. This study aims to assess clinical outcomes in patients from five national Czech asthma centers who were switched from the LYO to the liquid formulation and then to home self-administration. METHODS: Mepolizumab was administered in three phases: LYO for 6-9 months, followed by prefilled syringes (PFS) or autoinjectors (AI) in hospitals for 6-9 months, and finally, liquid forms at homecare for another 6-9 months. Data collected included age, BMI, nasal polyposis (NP), gastroesophageal reflux (GERD), and other comorbidities. The results were statistically evaluated using exacerbation rate (ER), asthma control test, forced expiratory volume, blood eosinophil count, and required systemic oral corticosteroid (OCS) daily dose. RESULTS: Three months after initiation of administration, all methods showed improvement compared to the values at the beginning of treatment, with ER decreasing from a median of 4 to 0. Similarly, the median OCS decreased from 5 mg to 0 mg across all methods throughout the treatment. A more significant OCS dose reduction was observed in patients with NP (87.5% vs. 50%) and GERD (70% vs. 50%), who typically require higher OCS doses to achieve asthma control. AI/PFS outperformed LYO in ER (97.5-100% vs. 50-100% after 6-9 months of treatment) and OCS reduction (50-100% vs. 31.2-100% after 6-9 months of treatment), which was influenced rather by the later usage of AI/PFS and thus longer overall treatment times than the administrating method. CONCLUSION: Mepolizumab improved real-life clinical outcomes in patients with severe asthma, regardless of the dosage forms or homecare settings.

• Publikační typ
• časopisecké články MeSH

• MeSH
• klinické lékařství MeSH
• rehabilitace MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• rehabilitační a fyzikální medicína
• NLK Publikační typ
• kolektivní monografie