Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.
Because of the frequency of penicillin allergies in children receiving β-lactam antibacterial agents, the macrolides are frequently chosen as alternatives in patients with group A β-haemolytic streptococcal (GABHS) infections. Spiramycin, amacrolide widely used in paediatrics, achieving remarkably high tonsillar tissue concentrations, was evaluated in this study in comparison with penicillin V (Phenoxymethylpenicillin). 298 children aged 1.5 to 14 years with acute tonsillitis and a positive rapid antigen test for GABHS were randomised to receive either a 5-day course of spiramycin 100 000 IU/kg twice daily or a 7-day course of penicillin V 25 000 IU/kg 3 times daily. Clinical and bacteriological assessments were recorded at inclusion (day 1), at the end of the treatment visit (days 8 to 12), and at the follow-up visit (days 25 to 35). GABHS isolated during the study were analysed by total DNA restriction fragment length polymorphism analysis. Of the 237 children with a positive GABHS culture at day 1,210 (88.6%) were evaluable for complete clinical and bacteriological efficacy at the end of treatment. Clinical efficacy was evident in 96.1% (98 of 102) for spiramycin and in 98.1% (106 of 108) for penicillin V. Bacteriological eradication was achieved in 79.4% (81 of 102) for spiramycin and in 89.8% (97 of 108) for penicillin V. Three failures occurred in the spiramycin group. In intent-to-treat analysis, the success rate (clinical cure and bacteriological eradication) for spiramycin was 77.9% (116 of 149) and that for penicillin V was 83.9% (125 of 149). At the follow-up visit, 182 children were evaluable for efficacy. Clinical cure with or without asymptomatic carriage of GABHS was observed in 97.7% (86 of 88) for spiramycin and in 89.4% (89 of 94) for penicillin V. Three relapses and 1 reinfection occurred in the penicillin V group. Adverse events, mainly gastrointestinal, occurred in 10.7% of spiramycin patients versus 12.8% of penicillin V patients. These results show that a 5-day treatment regimen with spiramycin twice daily is effective and well tolerated in GABHS tonsillitis, and is an alternative to penicillin V when necessary in children.
Background The severe forms of influenza infection requiring intensive care unit (ICU) admission remain a medical challenge due to its high mortality. New H1N1 strains were hypothesized to increase mortality. The studies below represent a large series focusing on ICU‐admitted influenza patients over the last decade with an emphasis on factors related to death. Methods A retrospective study of patients admitted in ICU for influenza infection over the 2010–2019 period in Réunion Island (a French overseas territory) was conducted. Demographic data, underlying conditions, and therapeutic management were recorded. A univariate analysis was performed to assess factors related to ICU mortality. Results Three hundred and fifty adult patients were analyzed. Overall mortality was 25.1%. Factors related to higher mortality were found to be patient age >65, cancer history, need for intubation, early intubation within 48 h after admission, invasive mechanical ventilation (MV), acute respiratory distress syndrome (ARDS), vaso‐support drugs, extracorporal oxygenation by membrane (ECMO), dialysis, bacterial coinfection, leucopenia, anemia, and thrombopenia. History of asthma and oseltamivir therapy were correlated with a lower mortality. H1N1 did not impact mortality. Conclusion Patient's underlying conditions influence hospital admission and secondary ICU admission but were not found to impact ICU mortality except in patients age >65, history of cancer, and bacterial coinfections. Pulmonary involvement was often present, required MV, and often evolved toward ARDS. ICU mortality was strongly related to ARDS severity. We recommend rapid ICU admission of patients with influenza‐related pneumonia, management of bacterial coinfection, and early administration of oseltamivir.
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