Background Imipenem combined with the β-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). Methods This was a randomized, controlled, double-blind phase 3 trial. Adults with HABP/VABP were randomized 1:1 to imipenem/cilastatin/relebactam 500 mg/500 mg/250 mg or piperacillin/tazobactam 4 g/500 mg, intravenously every 6 hours for 7–14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (patients who received study therapy, excluding those with only gram-positive cocci at baseline). The key secondary endpoint was clinical response 7–14 days after completing therapy in the MITT population. Results Of 537 randomized patients (from 113 hospitals in 27 countries), the MITT population comprised 264 imipenem/cilastatin/relebactam and 267 piperacillin/tazobactam patients; 48.6% had ventilated HABP/VABP, 47.5% APACHE II score ≥15, 24.7% moderate/severe renal impairment, 42.9% were ≥65 years old, and 66.1% were in the intensive care unit. The most common baseline pathogens were Klebsiella pneumoniae (25.6%) and Pseudomonas aeruginosa (18.9%). Imipenem/cilastatin/relebactam was noninferior (P < .001) to piperacillin/tazobactam for both endpoints: day 28 all-cause mortality was 15.9% with imipenem/cilastatin/relebactam and 21.3% with piperacillin/tazobactam (difference, −5.3% [95% confidence interval {CI}, −11.9% to 1.2%]), and favorable clinical response at early follow-up was 61.0% and 55.8%, respectively (difference, 5.0% [95% CI, −3.2% to 13.2%]). Serious adverse events (AEs) occurred in 26.7% of imipenem/cilastatin/relebactam and 32.0% of piperacillin/tazobactam patients; AEs leading to treatment discontinuation in 5.6% and 8.2%, respectively; and drug-related AEs (none fatal) in 11.7% and 9.7%, respectively. Conclusions Imipenem/cilastatin/relebactam is an appropriate treatment option for gram-negative HABP/VABP, including in critically ill, high-risk patients. Clinical Trials Registration NCT02493764.
Background SAB is common, serious, and potentially lethal. Antibiotic options are limited, especially for MRSA. Ceftobiprole is an advanced-generation cephalosporin with bactericidal activity against Gram-positive (including MRSA) and Gram-negative pathogens, with efficacy and safety demonstrated in previous Phase 3 studies in acute bacterial skin infections and pneumonia. The present study evaluated ceftobiprole in patients with complicated SAB. Methods ERADICATE was a randomized (1:1), double-blind, multicenter, Phase 3, non-inferiority trial comparing ceftobiprole (BPR) vs daptomycin (DAP) ± optional aztreonam, for up to 42 days of treatment, in patients with complicated SAB (NCT03138733). The primary efficacy endpoint was overall clinical success 70 days post-randomization, adjudicated by a blinded independent Data Review Committee. Success required survival, no new SAB complications, symptom improvement, SAB clearance, and no receipt of other potentially effective antibiotics. The non-inferiority margin for the difference in success rates was -15% (BPR-DAP, 95% CI, 2-sided, lower bound). Safety was assessed through adverse events (AE) and laboratory data. Results Of 390 patients randomized, 387 (189 BPR, 198 DAP) were in the modified intent-to-treat (mITT) population who received study medication and had a positive baseline blood culture for S. aureus (94 MRSA). Median treatment duration was 21 days for both groups. Key baseline characteristics were balanced (Fig. 1). In the BPR group 69.8% experienced success, compared to 68.7% for DAP (adjusted difference 2.0%, 95% CI -7.1% to 11.1%, Fig. 2). There were no significant differences in mortality, microbiological eradication, or in key subgroup analyses (Fig. 3). The proportion of patients experiencing ≥1 AE was 63% for BPR and 59% for DAP. Treatment-related severe or serious AEs were infrequent. Gastrointestinal AEs, mostly mild nausea, were more frequent with BPR, consistent with data from previous Phase 3 studies. Conclusion Ceftobiprole is non-inferior to daptomycin for overall success in patients with complicated SAB. All-cause mortality, microbiological eradication rates and new SAB complications were similar between treatment groups. Both treatments were well tolerated. Disclosures Thomas L. Holland, MD, Aridis: Advisor/Consultant|Basilea Pharmaceutica: Advisor/Consultant|Karius: Advisor/Consultant|Lysovant: Advisor/Consultant Sara E. Cosgrove, MD, Basilea: Advisor/Consultant|Debiopharma: Advisor/Consultant Sarah B. Doernberg, MD, MAS, Basilea: Advisor/Consultant|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Johnson and Johnson: Advisor/Consultant|NIH: Grant/Research Support|Regeneron: Grant/Research Support Maziar Assadi Gehr, MD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Marc Engelhardt, MD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Kamal Hamed, MD, Basilea Pharmaceutica: previous full time employee of Basilea Pharmaceutica International Ltd|Lysovant: full time employee of Lysovant Daniel Ionescu, MD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Mark Jones, PhD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Mikael Sauley, MSc, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Jennifer Smart, PhD, Basilea Pharmaceutica: full time employee of Basilea Pharmaceutica International Ltd Harald Seifert, MD, Basilea Pharmaceutica: Advisor/Consultant|Debiopharm: Advisor/Consultant|Eumedica: Advisor/Consultant|Gilead: Advisor/Consultant|MSD: Advisor/Consultant|Shionogi: Advisor/Consultant Timothy C. Jenkins, MD, Basilea: Clinical outcomes adjudication committee Vance G. Fowler, Jr, MD, MHS, Armata Valanbio Akagera Aridis Roche: Advisor/Consultant|BASILEA: Grant/Research Support|Basilea Novartis Debiopharm Genentech: Advisor/Consultant|MedImmune Bayer Janssen Contrafect Regeneron Destiny Amphliphi Integrated Bioth: Advisor/Consultant|NIH MedImmune Allergan Theravance Novartis Merck Contrafect Karius Genentech Regeneron Janssen: Grant/Research Support.
A clinical and psychopathological examination of 120 COPD patients undergoing in-patient treatment was conducted on the basis of the Ivano-Frankivsk Regional Clinical Hospital. The aim of the work was to detect the prevalence and adequacy of diagnosis of systemic effects and concomitant diseases in patients with COPD. The article deals with the issue of depression in patients with chronic obstructive pulmonary disease (COPD). The results of clinical and psychopathological examination of 120 patients with stage II-IV COPD with the help of Hamilton's depression scale and Spilberger-Hanin anxiety scale are presented. Based on the analysis of the results of the study, anxiety and depression disorders were observed in patients with COPD: in patients with COPD II-III stage - severe mild depression was diagnosed, and in patients with COPD IV stage - moderate severity. In addition, the study suggests the need for appropriate medical or psychotherapeutic treatment.
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