Purpose: Extensively drug-resistant Acinetobacter baumannii (XDRAB) is an important cause of nosocomial pneumonia with limited therapeutic options. Colistin-based regimen is the recommended treatment. Which drugs should be combined with colistin remains uncertain. The aim of this study was to investigate the clinical outcomes of patients with XDRAB pneumonia who were treated with colistin, combined with either 6-g sulbactam or carbapenems, in the setting of high MIC to sulbactam. Patients and methods: In this prospective cohort study, hospitalized patients diagnosed with XDRAB pneumonia in Phramongkutklao Hospital were enrolled. The primary outcome was 28-day mortality. Secondary outcomes were 7- and 14-day mortality, length of stay, ventilator days and factors associated with mortality. Results: From 1 July 2016 to 30 September 2017, 182 patients were included; 92 received colistin plus sulbactam and 90 received colistin plus carbapenems. Most of the patients were males diagnosed with ventilator-associated pneumonia in medical intensive care unit. Overall mortality rates at 7, 14, 28 days were 24.2%, 37.4%, and 53.3%, respectively. Mortality rates did not differ between sulbactam group and carbapenem groups at 7 days (19.6% vs 28.9%, p-value 0.424, adjusted HR 1.277; 95% CI = 0.702–2.322), 14 days (34.8% vs 40%, p = 0.658, adjusted HR 1.109; 95% CI = 0.703–1.749) and 28 days (51.1% vs 55.6%, p = 0.857, adjusted HR 1.038; 95% CI = 0.690–1.562). Length of stay, ICU days and ventilator days did not differ. Complications of treatment including acute kidney injury were not statistically different. Conclusion: In XDRAB pneumonia with high MIC to sulbactam, differences in mortality rates were not statistically significant between colistin plus 6-g sulbactam and colistin plus carbapenems.

Extensively drug-resistant A. baumannii (XDRAB) pneumonia has a high mortality rate in hospitalized patients. One of the recommended treatments is colistin combined with sulbactam; however, the optimal dosage of sulbactam is unclear. In an open-label, superiority, randomized controlled trial, patients diagnosed with XDRAB pneumonia were randomly assigned (1:1) to receive colistin in combination with sulbactam at either 9 g/day or 12 g/day. The primary outcome was the 28-day mortality rate in the intention-to-treat population. A total of 88 patients received colistin in combination with sulbactam at a dosage of either 12 g/day (n = 45) or 9 g/day (n = 43). Trends toward a lower mortality rate were observed in the 12 g/day group at 7 days (11.1% vs. 23.3%), 14 days (33.3% vs. 41.9%), and 28 days (46.7% vs. 58.1%). The microbiological cure rate at day 7 was significantly higher in the 12 g/day group (90.5% vs. 58.1%; p = 0.02). Factors associated with mortality at 28 days were asthma, cirrhosis, APACHEII score ≥ 28, and a dosage of sulbactam of 9 g/day for mortality at any timepoint. Treatment with colistin combined with sulbactam at 12 g/day was not superior to the combination treatment with sulbactam at 9 g/day. However, due to being an interim analysis, this trial was underpowered to detect mortality differences.

The current treatment recommendation involves administering a high dose of sulbactam alongside at least one additional agent. However, there remains a lack of data regarding the optimal dosage of sulbactam. We investigated whether administering sulbactam at a dosage of 12 g/day decreases the mortality rate among patients with CRAB pneumonia compared to 9 g/day. The study was an open-label, superiority, randomized controlled trial conducted at Phramongkutklao Hospital between September 2019 and September 2023 in patients diagnosed with CRAB. Participants were randomly assigned to receive a combination of colistin with either 9 or 12 g/day of sulbactam. The primary endpoint was the all-cause mortality rate at 28 days post-randomization. Among the 138 participants, there was a trend toward a lower mortality rate in the 12 g/day group (59.4% vs. 47.8%; p = 0.158). After adjusting for factors associated with mortality, a lower mortality was observed in the 12 g/day group (adjusted HR 0.54 [95% CI 0.33-0.87]; p = 0.0110). The microbiological cure rate at day 7 was higher in the 12 g/day group (73.2% vs. 89.4%; p = 0.02). Colistin in combination with sulbactam at a dosage of 12 g/day may improve mortality compared to 9 g/day.

Cheh-Oh N, et al. Infect Chemother. 2025 Feb;57:e9. https://doi.org/10.3947/ic.2024.0125

To determine whether oral fosfomycin trometamol is noninferior to carbapenem continuation as step-down therapy for cUTIs caused by third-generation cephalosporin-resistant Enterobacterales. In this open-label, randomized, noninferiority trial, adults with 3GCRE cUTIs who received 3 days of intravenous carbapenem were assigned to oral fosfomycin trometamol or continued carbapenem to complete 7 days. The primary outcome was day-7 clinical cure; secondary outcomes included day-28 clinical and microbiological cure, readmission, and length of stay. A total of 124 participants were enrolled (62 per group). The mean age was 73 years, 62.1% were female, and Escherichia coli accounted for 91% of isolates. Clinical cure at day 7 occurred in 98.4% in both groups (risk difference 0.0; 95% CI -0.04 to 0.04). Clinical cure at day 28 was also similar (91.9% in each group). Microbiological cure at day 7 was 100% with fosfomycin and 98.1% with carbapenem, and at day 28 was 90.3% and 85.5%, respectively. Hospital stay was shorter with fosfomycin (7.9 vs 12.0 days). Oral fosfomycin trometamol as step-down therapy was comparable to continued carbapenem therapy for cUTIs caused by 3GCRE and significantly reduced hospital stay, supporting role of carbapenem-sparing option.

Pulmonary infections among patients with acquired immunodeficiency syndrome (AIDS) may be caused by more than 1 organism. Pulmonary nocardiosis co-infection with cryptococcosis among patients with AIDS was extremely rare and has never been reported. Here, we report a case of pulmonary co-infection with nocardiosis and cryptococcosis in a 54-year-old HIV-positive man presenting productive cough and constitutional symptoms. Bronchoalveolar lavage and lung biopsy culture were positive for Nocardia species and Cryptococcus neoformans. The patient was treated with cotrimoxazole plus ceftriaxone for Nocardia species and fluconazole for C. neoformans. Etiology of pulmonary infections among patients with AIDS may be caused by multiple organisms. Among patients with AIDS having chest radiographic abnormality, an aggressive diagnostic approach should be warranted to accurately diagnose and appropriately manage.