Ninety-four patients infected with carbapenem-resistant Acinetobacter baumannii were randomized to receive colistin alone or colistin plus fosfomycin for 7 to 14 days. The patients who received combination therapy had a significantly more favorable microbiological response and a trend toward more favorable clinical outcomes and lower mortality than those who received colistin alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01297894.)

The global antimicrobial resistance surveillance system (GLASS) was launched by the World Health Organization (WHO) in 2015. GLASS is a surveillance system for clinical specimens that are sent to microbiology laboratory for clinical purposes. The unique feature of GLASS is that clinical data is combined with microbiological data, and deduplication of the microbiological results is performed. The objective of the study was to determine feasibility and benefit of GLASS for surveillance of blood culture specimens. GLASS was implemented at Siriraj Hospital in Bangkok, Thailand using a locally developed web application program (app) to transfer blood culture specimen data, and to enter clinical data of patients with positive blood culture by infection control nurses and physicians via the app installed in their smart phones. The rate of positive blood culture specimens with true infection was 15.2%. Escherichia coli was the most common cause of bacteremia. Secondary bacteremia, primary bacteremia, and central line-associated blood stream infection was observed in 61.8%, 30.6%, and 12.6% of cases, respectively. Sepsis was observed in 56.9% of patients. E.coli was significantly more common in community-acquired bacteremia, whereas Klebsiella pneumoniae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Acinetobacter baumannii were significantly more common in hospital-acquired bacteremia. Hospital-acquired isolates of E.coli, K.pneumoniae, A.baumannii, P.aeruginosa, S.aureus and Enterococcus faecium were more resistant to antibiotics than community-acquired isolates. In-hospital mortality was significantly higher in patients with antibiotic-resistant bacteremia than in patients with antibiotic non-resistant bacteremia (40.5% vs. 28.5%, p<0.001). The patients with antibiotic-resistant bacteremia consumed more resources than those with antibiotic non-resistant bacteremia. Blood culture results combined with patient clinical data were shown to have more benefit for surveillance of antimicrobial resistance, and to be more applicable for developing local antibiotic treatment guidelines for patients suspected of having bacteremia. However, GLASS consumed more time and more resources than the conventional laboratory-based surveillance system.

Nephrotoxicity is a dose-limiting factor of colistin, a last-line therapy for multidrug-resistant Gram-negative bacterial infections. An earlier animal study revealed a protective effect of ascorbic acid against colistin-induced nephrotoxicity. The present randomized controlled study was conducted in 28 patients and aimed to investigate the potential nephroprotective effect of intravenous ascorbic acid (2 g every 12 h) against colistin-associated nephrotoxicity in patients requiring intravenous colistin. Thirteen patients received colistin plus ascorbic acid, whereas 15 received colistin alone. Nephrotoxicity was defined by the RIFLE classification system. Additionally, urinary neutrophil gelatinase-associated lipocalin (NGAL) andN-acetyl-beta-d-glucosaminidase (NAG) were measured as markers of renal damage, and plasma colistin concentrations were quantified. The baseline characteristics, clinical features, and concomitant treatments of the patients in the two groups were comparable. The incidences of nephrotoxicity were 53.8% (7/13) and 60.0% (9/15) in the colistin-ascorbic acid group and the colistin group, respectively (P= 0.956; relative risk [RR], 0.9; 95% confidence interval, 0.47 to 1.72). In both groups, the urinary excretion rates of NGAL and NAG on day 3 or 5 of colistin treatment and at the end of colistin treatment were significantly higher than those at the respective baselines (P< 0.05). However, the urinary excretion rates of these biomarkers at the various times during colistin treatment did not differ significantly between the groups (P> 0.05). The plasma colistin concentrations in the two groups were not significantly different (P> 0.28). The clinical and microbiological outcomes and mortality of the patients in the two groups were not significantly different. This preliminary study suggests that ascorbic acid does not offer a nephroprotective effect for patients receiving intravenous colistin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01501968.)

Colistin, administered intravenously as its inactive prodrug colistin methanesulfonate (CMS), is increasingly used as last-line therapy to combat multidrug-resistant Gram-negative bacteria. CMS dosing needs to be adjusted for renal function. The impact of continuous ambulatory peritoneal dialysis (CAPD) on the pharmacokinetics of both CMS and colistin has not been studied. No CMS dosing recommendations are available for patients receiving CAPD. Eight CAPD patients received a single intravenous CMS dose (150 mg colistin base activity [CBA]) over 30 min. Serial blood and dialysate samples, and cumulative urine where applicable, were collected over 25 h. CMS and colistin concentrations were determined by high-performance liquid chromatography. Population pharmacokinetic modeling and Monte Carlo simulations were conducted. The total body clearance of CMS (excluding CAPD clearance) was 1.77 liters/h (44%) [population mean (between-subject variability)], while CAPD clearance was 0.088 liter/h (64%). The population mean terminal half-life of CMS was 8.4 h. For colistin, the total clearance/fraction of CMS metabolized to colistin (fm) (excluding CAPD clearance) was 2.74 liters/h (50%), the CAPD clearance was 0.101 liter/h (34%), and the mean terminal half-life was 13.2 h. Monte Carlo simulations suggested a loading dose of 300 mg CBA on day 1 and a maintenance dose of either 150 mg or 200 mg CBA daily to achieve a target average steady-state plasma colistin concentration of 2.5 mg/liter. Clearance by CAPD was low for both CMS and formed colistin. Therefore, CMS doses should not be increased during CAPD. Modeling and simulation enabled us to propose the first evidence-based CMS dosage regimen for CAPD patients.