Background:Despite the increasing use of colistin in clinical practice, the optimal dosing, and administration route have not been established. This study aimed to evaluate the clinical outcome and safety of intravenous (IV) colistin with a loading dose (LD) and adjunctive aerosolized (AS) colistin administration in critically ill patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) caused by carbapenem-resistant gram-negative bacteria (CRGNB).Methods:We retrospectively reviewed 191 critically ill patients who received colistin for the treatment of HAP or VAP caused by CRGNB. Patients were divided into three groups: non-LD IV (patients received only IV colistin without LD), LD IV (patients received only IV colistin with LD), and AS–LD (patients received IV colistin with LD and adjunctive AS colistin).Results:There was no difference in clinical response between the three groups. However, the rate of microbiological eradication was significantly higher in the AS–LD group (60%) than in the non-LD IV (31%), and LD IV (33%) groups (p = 0.010). Patients treated with adjunctive AS colistin in combination with LD IV had significantly lower 30-day mortality rates than patients treated with IV colistin alone (p = 0.027). After adjusting for potential confounding factors, adjunctive AS colistin was still significantly associated with lower mortality (adjusted OR 0.338, CI 95% 0.132–0.864, p = 0.024). However, nephrotoxicity did not change according to the use of LD regimen and AS colistin administration (p = 0.100).Conclusions:Adjunctive AS colistin in combination with IV colistin with LD was related to an improved 30-day mortality and microbiological outcome without an increase in nephrotoxicity in critically ill patients with HAP and VAP caused by CRGNB. The reviews of this paper are available via the supplemental material section.

ObjectiveTo be utilized for the development of pharmacists’ intervention service by determining factors which affect pharmacists’ prescription interventions.SettingPatients who were admitted to intensive care units (ICUs) in internal medicine departments in Korea.MethodsData including age, gender, clinical departments, length of hospital stay, status of organ dysfunction, intervention status, frequently intervened drugs, and health care providers’ questions were prospectively collected in ICUs in the department of internal medicine in a tertiary teaching hospital from January to December, 2012.Main outcome measurePrimary outcome was factors which affect pharmacists’ prescription interventions. Secondary outcomes included frequencies of the intervention, intervention acceptance rates, intervention issues, and frequently intervened drugs.ResultsA total of 1,213 prescription interventions were made for 445 patients (33.1%) of the 1,344 patients that were analyzed. Length of hospital stay was significantly longer for the group that needed pharmacists’ interventions (p < 0.001). Pharmacists’ intervention requirements were significantly higher in patients with kidney dysfunction (p < 0.001). The percentage of intervention accepted was 96.8%, and interventions that were common were as follows (in order): clinical pharmacokinetic service, dosage or dosing interval changes, dosing time changes or dose changes, and total parenteral nutrition consultation. The five medications with the highest intervened frequency were (in order) vancomycin, famotidine, ranitidine, meropenem, and theophylline.ConclusionThe need for pharmacists’ prescription interventions was highest among patients with longer length of stay and patients with kidney dysfunction. Based on these findings, prescription intervention activities could be initiated with severely ill patients. The results could be utilized in countries which are planning to develop pharmacists’ intervention service.

Purpose Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated. Materials and Methods A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery. Results A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group ( p =0.024). In multivariable analyses, peak FiO 2 within 3 days and tocilizumab combination were consistently significant for 30-day recovery (all p <0.05). The DexaToci group showed a significantly steeper decrease in FiO 2 (-4.2±2.6) than the Dexa group (-2.7±2.6; p =0.021) by hospital day 15. The duration of oxygen requirement was significantly shorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p =0.006). Infectious complications and cellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescence stage were not different between the two groups. Conclusion A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.