Intravenous fosfomycin-containing regimens are associated with reduced acute kidney injury in carbapenem-resistant Gram-negative infections: a retrospective cohort study

BackgroundCR-GN (Carbapenem-resistant Gram-negative) infections pose a significant global public health threat due to their high mortality rates. Furthermore, many treatments carry substantial renal toxicity. This study aims to compare renal injury associated with the most commonly used therapeutic regimens in clinical practice.MethodsA retrospective study was designed selecting patients with invasive CR-GN infections, successfully treated (evideced by microbiological clearance or clinical resolution) in Intensive Care Unit (ICU) and Medicine Department at “Cristo Re” General Hospital in Rome. Renal injury was defined as either a doubling of serum creatinine or a 50% reduction in glomerular filtration rate (GFR) at the end of treatment. Patients on dialysis, those treated for less than 5 days, and those with a baseline GFR of less than 30 mL/min were excluded. Chi-square tests were employed to compare frequencies, and multivariable logistic regression was performed to identify predictors of kidney injury.ResultsWe collected data from 59 patients (28 with Acinetobacter baumannii, 7 KPC-producing Klebsiella pneumoniae, 24 Pseudomonas aeruginosa) with a median age of 74 years (IQR 64.8–80), 33 of whom (55.9%) were treated with IV fosfomycin (in combination 28 patients with colistin, 2 pts with colistin and tigecycline and 3 with Ceftazidime/avibactam (CAZ/AVI), 26 patients with other regimens (21 of which including colistin). The median treatment duration was 10 days (IQR 7–14). At the end of treatment, 11 patients (18.6%) developed acute kidney injury, with a statistically significant difference favoring fosfomycin containing regimens (9.1% vs. 30.8% P = 0.037). Among colistin-containing regimens, the renal injury rate was significantly lower when fosfomycin was included (10.7% vs. 33.3%, P = 0.05). Logistic regression analysis identified the use of fosfomycin as an independent predictor of kidney injury prevention (OR = 0.074; IC 0.008–0.678 p = 0.021).ConclusionThis study confirms that regimens used for treating carbapenem-resistant Gram-negative bacterial infections cause a high rate of acute kidney injury, largely due to the frequent use of known nephrotoxic drugs, like colistin. However, our data suggest that combining these drugs with intravenous fosfomycin may offer renal protective benefits.