A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial.

BACKGROUND: Clinical failures in ventilator-associated pneumonia (VAP) caused by gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. METHODS: We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via the investigational eFlow Inline System (PARI GmbH). The primary efficacy end point was change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of AFIS/placebo, using the subset of patients with microbiologically proven baseline infections with gram-negative bacteria. RESULTS: There were 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group. Comparison of CPIS change from baseline between treatment groups was not different (P = .70). The secondary hierarchical end point of no mortality and clinical cure at day 14 or earlier was also not significant (P = .68) nor was the hierarchical end point of no mortality and ventilator-free days (P = .06). The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo group (P = .32). The AFIS group had significantly fewer positive tracheal cultures on days 3 and 7 than placebo. CONCLUSIONS: In this trial of adjunctive aerosol therapy compared with standard of care IV antibiotics in patients with gram-negative VAP, the AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov.

Solitary adenoma in the proventriculus of a budgerigar (Melopsittacus undulatus) diagnosed by immunochemistry - short communication.

The authors describe a solitary adenoma in a 5.5-year-old female Budgerigar (Melopsittacus undulatus). The tumour was partially blocking the lumen of the proventriculus and filled it almost completely. Decreased passage of food towards the gizzard and the intestines developed in the bird as result of the obstruction, which periodically hindered the passage, leading to slow emaciation. An epithelial tumour composed of irregular glandular acini was diagnosed by histological examination. Immunohistochemical reaction with pancytokeratin showed a positive cytoplasmic reaction both in the neoplastic and the normal glandular structures.