Increased resistance with uropathogens is primarily the result of prescribing “high resistance potential” antibiotics, e.g., ciprofloxacin (not levofloxacin), TMP-SMX, or ampicillin (not amoxicillin) instead preferentially use “low resistance potential” antibiotics, e.g., nitrofurantoin, doxycycline, fosfomycin. During the past decade there has been a gradual increase in resistant (ESBL+) uropathogens, e.g., E. coli and K. pneumoniae. Antibiotic selection to treat these infections depends on the site of infection, i.e., kidney, prostate, bladder, urine, or urinary catheter (Foley) urine. For hospitalized patients with urosepsis due to ESBL+ uropathogens from the kidney or prostate, initial therapy is usually with a parenteral carbapenem, e.g., meropenem. The use of nitrofurantoin doxycycline, or fosfomycin are ideal oral agents to treat acute uncomplicated cystitis ( AUC) and catheter associated bacteriuria (CAB) due to ESBL+ uropathogens.
In the outpatient setting, oral (PO) antibiotic therapy is preferred to IV therapy (lower cost, and fewer side effects, i.e., phlebitis, fungemia). IV therapy is often used to treat pyelonephritis or prostatitis due to ESBL+ uropathogens because of a lack of understanding of pharmacokinetic (PK) principles in treating UTIs. Oral quinolones, e.g., levofloxacin provides the same blood/tissue levels as the same dose when administered IV.
In the case described, the uropathogen is a strain of E. coli (ESBL+) and the infection was chronic prostatitis. While most antibiotics penetrate and inflamed prostate (acute prostatitis), very few have the PK properties needed to penetrate, in therapeutic concentrations, the subacute, chronically inflamed prostate. For this reason, the mainstay for antibiotic therapy of prostatitis has been oral doxycycline or levofloxacin or moxifloxin. Oral fosfomycin is a highly effective antibiotic therapy of E. coli and K. pneumoniae ( ESBL+) uropathogens in AUC. However, there is little data in treating prostatitis with fosfomycin in humans. Recently, it has been shown that fosfomycin penetrates well into the non-inflamed prostate. For this reason, we used prolonged, high dose fosfomycin to treat our patient with recurrent prostatitis and prostatic calcifications. However, we were unable to cure his chronic prostatitis until doxycycline was added to the regimen. (Table 1) The rationale of this remains unclear. Perhaps, like a ß-lactam given to increase the intracellular penetration of daptomycin into S. aureus, doxycycline may potentiate the entry or activity of fosfomycin.
Burke A. Cunha, MD, MACP
Chief, Infectious Disease Division
Mineola, NY 11501, and
Professor of Medicine
State University of New York
School of Medicine
Stony Brook, New York
Cunha BA, Comer JB. Pharmacokinetic considerations in the treatment of urinary tract infections. Conn Med 1979; 43:347-53.
Cunha BA, Gran A, Raza M. Persistent extended-spectrum ß-lactamase-positive Escherichia coli chronic prostatitis successfully treated with a combination of fosfomycin and doxycycline. Int J of Antimic Agent 2015;45:427-429.
Cunha BA. Antibiotic Essentials (13th ed), New Delhi, JP Medical Publishers, 2015. pp. 110-1, 595-7, 617-8.
Cunha BA. Antibiotic tissue penetration. Bull NY Acad Med 1983;59:443-9.
Cunha BA. Multidrug-resistant Gram-negative bacilli causing urinary tract infections: clinical coniderations. J Chemother 2011;23:171-4.
Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE. Fosfomycin for the treatment of multidrug-resistant, including extended spectrum beta-lactamase producing Enterobacteriaceae infections: a systematic review. Lancet Infect Dis 2010;10:43-50.
Fournier D, Chirouze C, Leroy J, et al. Alternatives to carbapenems in ESBL-producing Escherichia coli infections. Med Mal Infect 2013;43:62-6.
Gardiner BJ, Mahony AA, Ellis AG, Lawrentschuk N, Bolton DM, Zeglinski PT, et al. Is fosfomycin a potential treatment alternative for multidrug-resistant Gram-negative prostatitis? Clin Infect Dis 2014;58:e101-5.
Lipsy BA, Byren I, Hoey CT. Treatment of bacterial prostatitis. Clin Infect Dis 2010;50:1641-2.
Mehta S, Singh C, Plata KB, et al. ß-lactams increase the antibacterial activity of daptomycin against clinical methicillin-resistant S. aureus strains and prevent selection of daptomycin-resistant derivatives. Antimicrob Agents Chemo 2012;56:6192-6200.
Ristuccia AM, Cunha BA. Current concepts in antimicrobial therapy of prostatitis. Urology 1982; 20:338-45.