IntroductionAminoglycosides aerosolization might achieve better diffusion into the alveolar compartment than intravenous use. The objective of this multicenter study was to evaluate aerosol-delivered amikacin penetration into the alveolar epithelial lining fluid (ELF) using a new vibrating mesh nebulizer (Pulmonary Drug Delivery System (PDDS), Nektar Therapeutics), which delivers high doses to the lungs.MethodsNebulized amikacin (400 mg bid) was delivered to the lungs of 28 mechanically ventilated patients with Gram-negative VAP for 7-14 days, adjunctive to intravenous therapy. On treatment day 3, 30 minutes after completing aerosol delivery, all the patients underwent bronchoalveolar lavage in the infection-involved area and the ELF amikacin concentration was determined. The same day, urine and serum amikacin concentrations were determined at different time points.ResultsMedian (range) ELF amikacin and maximum serum amikacin concentrations were 976.1 (135.7-16127.6) and 0.9 (0.62-1.73) μg/mL, respectively. The median total amount of amikacin excreted in urine during the first and second 12-hour collection on day 3 were 19 (12.21-28) and 21.2 (14.1-29.98) μg, respectively. During the study period, daily through amikacin measurements were below the level of nephrotoxicity. Sixty-four unexpected adverse events were reported, among which 2 were deemed possibly due to nebulized amikacin: one episode of worsening renal failure, and one episode of bronchospasm.ConclusionsPDDS delivery of aerosolized amikacin achieved very high aminoglycoside concentrations in ELF from radiography-controlled infection-involved zones, while maintaining safe serum amikacin concentrations. The ELF concentrations always exceeded the amikacin minimum inhibitory concentrations for Gram-negative microorganisms usually responsible for these pneumonias. The clinical impact of amikacin delivery with this system remains to be determined.Trial RegistrationClinicalTrials.gov Identifier: NCT01021436.

CVVHDF appears to provide adequate clearance of systemically absorbed amikacin in mechanically ventilated patients with ARF, suggesting that dose adjustments for BAY41-6551 are probably not necessary for this patient population. Nonetheless, the standard precautionary measures for critically ill patients receiving i.v. amikacin should be followed for patients with ARF who are treated with BAY41-6551.

ABSTRACr Nedocromil sodium (FPL 59002) is a pyranoquinoline dicarboxylic acid that has been developed for the management of bronchial asthma. We report the results of a double blind group comparative trial in which the disodium salt of nedocromil delivered by pressurised aerosol and a placebo were compared in the management of patients with a diagnosis of bronchial asthma who entered the double blind period on a minimum dose of beclomethasone dipropionate. In almost all the assessments of clinical activity nedocromil sodium was shown to be more effective than placebo. These include improvements in diary card symptom scores, reduction in concomitant use of a bronchodilator aerosol, and patients' and investigators' assessments of efficacy. Unwanted effects were few and mild. No patients were withdrawn from the trial.Nedocromil (FPL 59002) is a pyranoquinoline dicarboxylic acid (chemical name 9-ethyl-6, 9-dihydro-4,6-dioxo-10-propyl-4H-pyrano (3,2-g) quinoline-2,8-dicarboxylic acid) and its disodium salt (FPL 59002KP) was identified from a range of pharmacological and immunological tests as a compound worthy of clinical evaluation in asthmatic patients. In antigen challenge studies nedocromil sodium was shown to protect against the immediate reaction, and the results suggested that the compound may be useful in the treatment of bronchial asthma.We Nine patients were found to have minimal symptoms even when beclomethasone dipropionate was discontinued altogether. These patients were then managed with a 12 agonist only and did not take further part in the study. One group received nedocromil sodium at a dose of 4 mg (two inhalations of 2 mg from a pressurised aerosol) four times daily.The other group received two inhalations four times daily from an identical placebo pressurised aerosol containing the same propellants and surfactant but without the active drug. Both treatments were continued for 28 days. Before starting on the trial aerosols each patient completed a diary card for two weeks to establish baseline values. They rated symptoms of night time and daytime asthma, morning chest tightness, and cough on a 0-4 scale related to each symptom-for example, night asthma would be rated from 0 (undisturbed sleep) to 4 (being awake all night). Patients were supplied with a mini Wright peak flow meter and they recorded the best of three readings morning and evening on the diary card. They also recorded all medication taken, including the test medication.At each clinic visit the severity of the patient's 809 on 12 May 2018 by guest. Protected by copyright.

Single doses of BAY41-6551 were well tolerated in subjects with CKD. HD effectively removed amikacin from serum in subjects with ESRD, and the timing relative to BAY41-6551 administration was an important determinant of systemic amikacin exposure. Nevertheless, standard precautionary measures for intravenous amikacin should apply for patients receiving BAY41-6551, and dose adjustments and/or dialysis should be considered for subjects with severe renal impairment.

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