Please cite this article in press as: Cunha BA, et al. Persistent extended-spectrum -lactamase-positive Escherichia coli chronic prostatitis successfully treated with a combination of fosfomycin and doxycycline. Int J Antimicrob Agents (2015), http://dx.doi.org/10.1016/j.ijantimicag.2014.12.019 ARTICLE IN PRESS G Model ANTAGE-4498; No. of Pages 3 International Journal of Antimicrobial Agents xxx (2015) xxx–xxx Contents lists available at ScienceDirect International Journal of Antimicrobial Agents j o ur nal ho me pag e: http://www.elsevier.com/locate/ijantimicag Short communication Persistent extended-spectrum -lactamase-positive Escherichia coli chronic prostatitis successfully treated with a combination of fosfomycin and doxycycline Burke A. Cunha a,b,∗ , Arthur Gran a,b , Muhammad Raza a,b a Infectious Disease Division, Winthrop-University Hospital, Mineola, NY, USA b State University of New York, School of Medicine, Stony Brook, NY, USA a r t i c l e i n f o Article history: Received 2 December 2014 Accepted 3 December 2014 Keywords: MDROs Urinary tract infections Antibiotic tissue penetration Oral antibiotic therapy a b s t r a c t For chronic bacterial prostatitis, there are few oral antibiotics available that are active against com- mon uropathogens and are able to penetrate the non-inflamed prostate at therapeutic concentrations. Oral options to treat chronic prostatitis due to Gram-negative bacillary multidrug-resistant organisms are even more limited. We report a case of persistent extended-spectrum -lactamase (ESBL)-positive Escherichia coli chronic prostatitis refractory to antibiotic therapy. Prolonged courses of fosfomycin failed to eradicate the infection. Re-treatment with high-dose fosfomycin again failed to clear the infection. After repeated courses of fosfomycin, the ESBL-positive E. coli remained susceptible to fosfomycin. Transrec- tal ultrasound revealed prostatic calcifications that were thought to be the reason for antibiotic failure. Following transurethral resection of the prostate (TURP) to remove the prostatic calcifications, the pro- static calcifications remained and the infection persisted. Although the patient’s ESBL-positive E. coli was resistant to doxycycline, he was treated with a combination of fosfomycin plus doxycycline. Treatment with fosfomycin and doxycycline rapidly cured his chronic prostatitis. © 2015 Published by Elsevier B.V. 1. Introduction Successful antimicrobial therapy of bacterial prostatitis depends on several factors. In acute bacterial prostatitis, the prostate is inflamed and antibiotics penetrate well into the prostate parenchyma. As the infection resolves, prostatic tissue concen- trations rapidly decrease and therapy of chronic prostatitis is problematic since the inflammatory component of acute prostatitis is not present. In chronic prostatitis, penetration of antimicrobials into the non-inflamed prostate is dependent on lipid solubility, protein binding, ionisation potential (pKa) and prostate pH. The activity of most antimicrobials is pH-dependent, which may be important in treating chronic prostatitis since in chronic prostati- tis the prostate pH is 8.5 versus a pH of 7.5 in normal prostate. For these reasons, relatively few antimicrobials are able to penetrate into the non-inflamed prostate in chronic prostatitis at therapeuti- cally effective concentrations [1,2]. Because the suggested duration ∗ Corresponding author. Present address: Winthrop-University Hospital, 222 Sta- tion Plaza North, Suite no. 432, Mineola, NY 11501, USA. Tel.: +1 516 663 2505; fax: +1 516 663 2753. E-mail address: bacunha@winthrop.org (B.A. Cunha). of therapy for chronic prostatitis is prolonged, oral antibiotic ther- apy is preferred to parenteral therapy [3,4]. Oral antimicrobials effective against the uropathogens causing prostatitis that also penetrate well into the uninflamed prostate (chronic prostati- tis) are trimethoprim/sulfamethoxazole, amoxicillin, doxycycline, quinolones and fosfomycin [1,3,5,6]. 2. Case A 53-year-old man was referred for treatment of persistent chronic prostatitis. He had mild benign prostatic hypertrophy (BPH) and was allergic to penicillin. Over the past 6 months, urinalyses revealed high-grade pyuria, few red blood cells and abundant mucous threads. Urine cultures repeatedly grew extended-spectrum -lactamase (ESBL)-positive Escherichia coli resistant to doxycycline [minimum inhibitory concentration (MIC) > 16 g/mL] and quinolones (MIC > 8 g/mL) but susceptible to ampicillin/sulbactam, carbapenems, aminoglycosides and nitro- furantoin. The patient’s urologist treated him for 1 month with oral (p.o.) nitrofurantoin 100 mg every 12 h (q12 h), but after discon- tinuing nitrofurantoin therapy his symptoms (dysuria, frequency and foul smelling urine) returned and urine cultures remained positive for ESBL-positive E. coli. During this time the patient had http://dx.doi.org/10.1016/j.ijantimicag.2014.12.019 0924-8579/© 2015 Published by Elsevier B.V.