Fosfomycin for Chronic Bacterial Prostatitis

Prostatitis is the inflammation and infection of the

prostate. The bacterial pathogens involved are similar to those involved in

other urologic infections. Although Escherichia coli is

the most common causative pathogen, other etiologies include Pseudomonas aeruginosa, Klebsiella spp.,

Enterococcus spp., Enterobacter spp., Proteus spp., and Serratia spp. In sexually active

men, Neisseria gonorrhoeae and Chlamydia trachomatis should also

be consid­ered.1 Treatment of prostatitis can be difficult, as many

antimicrobials cannot penetrate into the prostate. Current oral treatment

options include fluoroquinolones, tetracyclines, and sulfame­thoxazole/trimethoprim.

However, adverse reac­tions and increasing resistance against these

antimicrobials warrant alternative options for oral therapy.

Fosfomycin is an attractive potential option because it does not cross-react

with other antimicrobials, making it a good choice in patients with extensive

drug allergies. It retains activity against many of the impli­cated organisms,

including multidrug-resistant strains such as extended-spectrum beta-lact­amase

(ESBL)-producing Enterobacteriales and

vancomycin-resistant enterococci. It is also available in an oral dosage form.

However, aside from a few case reports, there are limited data regarding the

dosing, duration, and efficacy of fosfomycin for the treatment of prostatitis.2,3

Karaiskos and colleagues conducted a prospective observation study that set out

to identify the effectiveness and safety of oral fosfomycin in the treatment of

chronic pros­tatitis.⁴ Patients were enrolled if they had more than 3 months of

symptoms consis­tent with prostatitis, positive urine/prostatic secretion

cultures, a negative polymerase chain reaction for sexually transmitted

infections, imaging suggesting prostatic inflammation and did not have other

orally available antimicrobial options (eg, were resistant, had allergies or

adverse reactions). Patients provided consent to participate. Fosfomycin was

dosed at 3 g orally daily for 1 week, then 3 g orally every 48 hours for the

remainder of therapy. Patients were treated for either 6 weeks or 12 weeks, if

they had evidence of prostatic calcifica­tions. Minimum inhibitory concentrations

(MICs) were evaluated via Etest (bioMérieux). Primary outcomes included cure at

end of therapy, defined as resolution or improve­ment of all signs of

infection, and relapse rates, defined as isolation of the same caus­ative

pathogen during treatment or follow-up, at 3 and 6 months of follow-up.

Forty-four male patients were enrolled, ranging in age from 28 to 82 years

(median 54). Most patients had experienced 2 episodes of chronic bacterial

prostatitis. E coli was the most common

causative pathogen (66%), followed by Klebsiella (14%),

and Enterococcus faecalis (14%). Most

isolates were multi­drug-resistant (59%), with 23% displaying evidence of ESBL.

The median fosfomycin MIC was 1.5 mcg/ mL (range, 0.125-32 mcg/ mL) for

gram-negatives and 8 mcg/mL (range 4-24 mcg/ mL) for E faecalis.

Cure was achieved in 82% (36/44 patients) of participants at end of therapy,

with a similar breakdown between the 6- and 12-week groups (Table).

Cure at the 3- and 6-month follow-ups were 80% and 73%, respectively. Fosfomycin

resistance emerged in 5 patients, 2 were in the 6-week group and 3 in the

12-week group. Overall, fosfo­mycin was well tolerated. Eight patients (18%)

reported diarrhea, which resolved in 4 patients by extending the dosing

interval from every 48 hours to every 72 hours. One patient discontinued

treatment due to diarrhea. No patients tested positive for Clostridioides difficile.

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