Treatment approaches for carbapenem-resistant Enterobacteriaceae (CRE) urinary tract infections (UTIs) are typically limited to salvage agents with considerable toxicity or novel β-lactam/β-lactamse inhibitor combinations that are best used judiciously. Doxycycline (DOX) and fosfomycin (FOS) are orally available alternatives that demonstrate in vitro susceptibility against CRE; however, clinical data demonstrating their efficacy is limited.
We performed a retrospective review of patients (pts) with CRE UTIs who received ≥1 dose of FOS or ≥5 days of oral DOX. UTI was defined as a positive urine culture growing ≥1000 CFU/ml of CRE among pts with dysuria, increased urinary frequency, suprapubic or flank pain or tenderness, fevers, or altered mental status without an alternative etiology. Cure was defined as resolution of symptoms within 7 days without reoccurrence within 30 days. Microbiological failure was defined as a positive urine culture within 14 days.
22 pts were included, 14 and 8 were treated with FOS and DOX, respectively. Median age was 59 (range: 24-86), 32% were male, 27% were transplant recipients, and the median Charlson score was 4 (0-9). 86% of cases were healthcare associated and 73% met CDC criteria for UTI. UTIs were complicated by pyelonephritis in 3 patients, but none had concomitant bacteremia. There were no differences in baseline characteristics, underlying diseases, or severity of illness among pts treated with FOS or DOX. 14% of FOS-treated pts received >1 dose. The median duration of DOX treatment was 10 days (6 – 21). Cure occurred in 100% and 75% of pts treated with FOS and DOX, respectively (p= 0.36; figure 1). Pts treated with DOX had numerically higher rates of microbiological failure (38% vs 21%; p=0.62) and statistically higher rates of clinical relapse (38% vs 0%; p=0.04). Only one adverse event was recorded in a pt receiving FOS.
In our experience, FOS and DOX were effective in treating CRE UTIs; however, higher rates of microbiologic failures and clinical relapse occurred among pts receiving DOX. FOS should be considered the preferred option for CRE UTI among pts who are candidates for treatment with oral antibiotics. Comparisons between FOS and intravenous antibiotics for CRE UTI are warranted.
R. K. Shields, None