Evaluation of the safety and effectiveness of colistin under actual use conditions in patients with various infections —Final report of a drug use investigation—

<p>To investigate the safety and effectiveness of colistin (Aldreb^®, hereinafter referred to as “this drug”) under actual use conditions in Japan, a drug use investigation was conducted using the all-case investigation method. The subjects were patients who were diagnosed with infection and received this drug for the first time, and the observation period was from the day that administration of this drug was started to the day that it was discontinued or completed. Regarding safety, the development of adverse reactions was evaluated. Regarding effectiveness, global assessment was performed by physicians in charge of the investigation, and the susceptibility of causative bacteria to colistin were evaluated. Between May 25, 2015 and September 20, 2022, 815 patients were enrolled. Case report forms were collected from 282 patients who were enrolled by October 31, 2017. There were 280 patients in the safety analysis set and 169 patients in the effectiveness analysis set. In terms of preventing nephrotoxicity and the emergence of resistant bacteria, the package insert mentions dosage adjustment based on creatinine clearance and the testing of the colistin susceptibility of causative bacteria. However, among 262 patients in the safety analysis set whose creatinine clearance was measured before the administration of this drug was started, no dosage adjustment based on creatinine clearance (as described in the package insert of this drug) was performed in 34.4% of the patients (90/262 patients), and among 261 patients in whom this drug was used for appropriate bacterial species, no colistin susceptibility testing was performed in 26.4% (69/261 patients).The total number of days (mean ± standard deviation) on which this drug was administered to patients in the safety analysis set was 13.9±18.08 days, and adverse reactions were observed in 32.5% (91/280 patients).The proportion of patients who developed adverse reactions related to safety specifications, i.e., “renal impairment,” “neurotoxicity,” and “pseudomembranous colitis,” was 27.1% (76/280 patients), 2.9% (8/280 patients), and 0.4% (1/280 patients), respectively. In the effectiveness analysis set of 169 patients, the drug was effective in 75.1% (127/169 patients) according to global assessment by the physicians in charge. The results of this investigation found no new problem with the safety and effectiveness of this drug under the actual use conditions. We thought that in terms of preventing nephrotoxicity and the emergence of resistant bacteria, it is important to properly use this drug as indicated in the package insert of this drug and “Practical guide for appropriate use of colistin: update.”</p>