Sequential fosfomycin therapy beneficial in bacterial prostatitis caused by multidrug-resistant E coli

Sequential treatment with the oral antibiotic fosfomycin appears to be safe and effective in the management of patients with acute bacterial prostatitis secondary to multidrug-resistant Escherichia coli, according to the phase IV FOS-PROST study.

Interim analysis showed that the primary endpoints of microbiological cure (ie, negative urine culture) and clinical cure (ie, resolution of the fever and all urinary symptoms that were present at baseline) occurred less frequently among patients who received fosfomycin (case) but with no significant difference than among those who received cotrimoxazole or ciprofloxacin (control) as sequential therapy, reported lead investigator Dr Laura Marina Gisbert Pérez of MútuaTerrassa University Hospital in Terrassa, Barcelona, Spain.

At the end of treatment (21 days ±3 days), the microbiological cure rate was 66.7 percent in the case group versus 80.0 percent in the control group (p=0.44), while the clinical cure rate was 91.7 percent versus 94.3 percent (p=1), respectively. [ESCMID Global 2024, abstract O1176]

Microbiological and clinical cure rates remained similar between the case and control groups at 2 weeks after the end of treatment (57 days ±3 days): 70 percent versus 92.9 percent (p=0.1) and 100 percent versus 97.1 percent (p=1), respectively.

“All microbiological failures were defined as asymptomatic bacteriuria that did not require antibiotic treatment,” Gisbert Pérez said.

Fosfomycin was safe, with the most common side effect being diarrhoea (33.3 percent), which was mostly mild, she added.

None of the patients in the case group required interruption of fosfomycin treatment, and no deaths occurred during the follow-up.

Challenging to treat

“Acute bacterial prostatitis is a challenging condition,” in terms of both diagnosis and treatment, Gisbert Pérez noted. Patients with this condition require extended treatment, between 14 and 21 days, “although it’s possible to do an early oral sequential oral treatment when clinical stability is reached.”

However, the rising antimicrobial resistance in E coli hampers the oral approach because of the limited treatment options, she said.

What makes oral fosfomycin viable, according to Gisbert Pérez, is that the drug offers adequate in vitro activity, tissue penetration, and tolerability.

Overall, the findings from the FOS-PROST study suggest that oral fosfomycin may help reduce parenteral treatment duration in multidrug resistant E coli-related acute bacterial prostatitis when no other oral treatment is available, she concluded.

FOS-PROST included 47 adult patients (29 percent had bacteraemia) with acute bacterial prostatitis who underwent a 1-to-5–day course of parenteral targeted or empirical treatment (median duration 3 days). Acute bacterial prostatitis was defined as the presence of febrile syndrome, prostate-specific antigen of >4 ng/ml, one microbiologic criterion (positivity for either urine or blood E coli culture), and two clinical criteria (urinary tract symptom, perineal pain, or prostate disease).

Of the patients, 12 had multidrug-resistant E coli (ie, nonsusceptibility to one or more agents in three or more antimicrobial categories) and were subsequently treated with 3-g oral fosfomycin every 24 hours and were included in the case group. The control group comprised the remaining 35 patients with nonmultidrug-resistant E coli who subsequently received standard dose cotrimoxazole or ciprofloxacin. Sequential treatment was administered through day 21.

The case and control groups were comparable in terms of age (mean 72.5 vs 66.1 years), Charlson comorbidity index (0.5 vs 0), and Pitt score (0 for both). Most patients had community-acquired infection (83.3 percent vs 97.1 percent), but fewer patients in the case group received active empiric treatment (25.0 percent vs 100 percent).