Chronic ESBL-Klebsiella pneumoniae prostatitis treated with once-daily tigecycline monotherapy in home hospitalization

Dear Editor,

We present the case of a 79-year-old male with a history of low-risk myelodysplastic syndrome diagnosed in 2013, currently without specific treatment. He required a resection of the terminal ileum due to hemorrhagic ileitis in 2014. Afterwards, he presented several episodes of urinary tract infections (UTI). The first consisted of an acute prostatitis in 2015 caused by an extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae. Thereafter, he suffered from prostatic and seminal vesicle abscesses requiring bilateral orchiectomy in 2016. Abscesses were drained, and the patient received empirically linezolid and meropenem. Treatment was switched to ertapenem according to culture results, for a total of 21 days. No new episodes of prostatic or seminal vehicle abscesses have been observed. In 2017, he was admitted twice for sepsis secondary to prostatitis due to the ESBL-K. pneumoniae. In November 2020, he was diagnosed with voiding syndrome, being prescribed two months of fosfomycin-trometamol 3 g every 48 h with good tolerance. Minimum inhibitory concentration (MIC) was < 16 mg/L at the beginning of the treatment, with development of resistance after the antibiotic course (MIC > 256 mg/L). In December 2020, he was admitted because of persistence of lower UTI symptoms with the presence of ESBL-K. pneumoniae, being treated with ertapenem 1 g/24 h for one week.

In February 2021, he was readmitted with astheny, general malaise, dysuria and vesical tenesmus, low-grade fever (37.5 °C) and perianal discomfort, being diagnosed of recurrent prostatitis. A new course-treatment of ertapenem (1 g/24 h) was started (glomerular filtration rate 31 mL/min/1.73 m²). After 3 days, urine culture showed ESBL-K. pneumoniae susceptible to carbapenems, without other potential alternatives. Clinical follow-up was satisfactory, with resolution of voiding symptoms and improvement of analytical parameters including glomerular filtration rate. However, on the 13th day of treatment, the patient presented neutropenia (initial neutrophils 5.8 × 10³ u/mcl, nadir 0.43 × 10³ u/mcl), and diarrhea, which caused hypernatremia, hypokalemia, hypomagnesemia, and hypocalcemia. Intravenous fluids and electrolyte replacement were required. Clostridioides difficile associated diarrhea was ruled out, so side effects were attributed to ertapenem. Treatment was firstly switched to tigecycline 100 mg followed by 50 mg/12 h. After the change, a significant improvement was noticed. Diarrhea went away, ion values were corrected, and neutropenia improved (although one dose of filgrastim was administered). After 48 h with tigecycline, the patient was discharged to home hospitalization with tigecycline 100 mg/24 h for 14 days to complete 4 weeks of antibiotic treatment. The patient did not present any recurrence nine months after this episode, with negative control urine cultures. Unfortunately, semen culture was not requested at any time.

We present the first case of chronic prostatitis due to ESBL-K. pneumoniae treated with once-daily tigecycline. This approach resolved the adverse events caused by ertapenem and allowed the patient to be early discharged.

Carbapenems are associated with diarrhea, neutropenia or astheny.¹ In our case, ertapenem caused numerous adverse events, with a probable causal relationship according to the Naranjo Scale. Due to the absence of therapeutic alternatives, need for prolonged antibiotic duration, penetration issues, risk of adverse effects and possibility of discharge, tigecycline was chosen as a potential alternative.²

Tigecycline is a third generation tetracycline whose use in UTI is controversial due to its limited urinary excretion (5–35%).^3,4 However, it may be an alternative in the treatment of prostatitis.²

In terms of pharmacokinetics, tigecycline presents an excellent tissue penetration, showing a high volume of distribution (7–9 L/kg).^5–7 Prostate penetration depends on the lipophilicity and degree of ionization of the drug. Tetracyclines, due to their high lipophilicity, penetrate up to 90–100% in the prostatic tissue, although specific data for tigecycline are lacking.^5–7 Other interesting characteristics include its long elimination half-life (42 h), allowing the once-daily administration.^7,8 This dosing has shown optimal therapeutic levels (maximum concentration 1.5 mg/L), considering that, for Enterobacterales, its pharmacokinetic/pharmacodynamic index is the area under the curve/MIC ≥ 15–20. These concentrations guarantee sufficient levels based on the established cut-off of 0.5 mg/L.^5–8 However, this approach is experimental with very limited clinical evidence.^7,8

Tigecycline has demonstrated clinical and microbiological cure in complicated UTIs (77.4–78.6% and 85.7%, respectively).^3,9 Concerning prostatitis, some cases have demonstrated its clinical effectiveness without safety issues.^3,6,9,10

In our case, the use of tigecycline for the treatment of ESBL-K. pneumoniae prostatitis optimized tolerability, avoiding ertapenem-associated adverse effects while maintaining clinical effectiveness. Once-daily administration regimen allowed early hospital discharge to home hospitalization, reducing the risk of nosocomial complications, and improving patient's quality of life.

Conflict of interest

There is no conflict of interest or source of funding for the present study.