We describe the case of a 51 years-old Portuguese man whose previous medical history was relevant only for a stable pulmonary nodule under regular follow-up and frequent work-related trips to Angola.
In December 2014 he had a first case of acute urinary tract infection, with dysuria, fever, a white blood cell (WBC) count of 25.880/muL, a C-reactive protein of 250.9 mg/L and a prostate-specific antigen (PSA) value of 8.15 ng/mL. He was medicated with 2 weeks of ciprofloxacin 500 mg once daily and improved clinically. A urine sample was collected prior to antibiotherapy and sent for culture, which revealed growth of ESBL-producing E coli, resistant to the ongoing therapy with ciprofloxacin and susceptible only to nitrofurantoin, carbapenems and fosfomycin.
Subsequently, between January 2015 and November 2015, the patient had 5 more episodes of urinary symptoms and fever. ESBL-producing E Coli with a similar pattern of susceptibility as the one described above was isolated in urine samples in each episode. The first two episodes were managed with oral antibiotics (cefixime 400 mg for one week and prulifloxacine 600 mg for 3 weeks). In the following 3 episodes, the patient was admitted as an inpatient and managed with prolonged periods of intravenous ertapenem (1 g daily for 25, 69 and 85 days).
Ultrasound performed in January 2015 revealed a heterogeneous prostate of 40cc with central hypoechogenic calcified regions. Pelvic magnetic resonance imaging (MRI) performed in August 2015 showed no relevant structural changes in the remaining urinary system except for two simple cysts on the right kidney. Recurrence of infection was interpreted as being caused by persistence of the infectious foci in prostatic calcifications and the patient was referred for transurethral resection of the prostate (TUR-P) in November/2015. During the following 10 months, the patient was free of recurrence of urinary symptoms.
However, since September 2016, the patient developed three further urinary tract infection episodes. He was hospitalized in September due to epididymitis, which was managed with 2 weeks of oral ciprofloxacin 500 mg/day. Afterwards, in December, he was medicated with cefixime (400 mg/day) for 2 weeks as an outpatient due to a new episode of epidydimitis. In March 2017, 2 weeks of trimethoprim/sulfamethoxazole were performed due to cystitis. In these episodes, all of the urine samples yielded polymicrobial growth except for one which was positive only for a multisusceptible strain of Streptococcus agalactiae.
During the aforementioned period, two urine samples were also sent for culture in the mycobacteriology lab and yielded no mycobacteria growth. Mycobacterium tuberculosis nucleic acid amplification testing (NAAT) was performed in both samples and was negative. Neisseria gonorrhea, Chlamydia trachomatis, Mycoplasma genitalium and Trichomonas vaginalis NAAT in urine samples was also negative.
The patient presented to our hospital's Infectious Diseases department in March 2017. He had finished his last trimethoprim/sulfamethoxazole course 3 days before his appointment. He was heavily distressed with the impact on daily activities caused by the recurring infections. He was asymptomatic and clinically well. Due to the recurrence of urinary tract infections after prostate resection, and due to the absence of other structural abnormalities in MRI, we concluded that a more effective long-term antimicrobial therapy strategy was necessary for erradication.
After confirmation that the urine was sterile, we started the patient on 3 g oral fosfomycin daily, for a planned duration of 15 days, and a subsequent 3 g every 48 h regimen for 3 months. The patient developed diarrhea, with 2-3 daily liquid dejections. Therefore, on day 10 of treatment, dosing was switched to 3 g every 48 h, with resolution of the diarrhea.
After three months with this dosage, fosfomycin was switched to a once-weekly regimen which was maintained 9 months further, for a total treatment duration of one year. After 9 months of follow-up without fosfomycin or other antibiotics, there was no recurrence of urinary tract infection.