Is the combination of rifampin (Rifampicin) and nitrofurantoin synergistic and beneficial for treating chronic bacterial prostatitis caused by Enterococcus faecalis?

Rifampin and Nitrofurantoin Combination for Chronic Bacterial Prostatitis

The combination of rifampin and nitrofurantoin has been shown to be synergistic and beneficial for treating chronic bacterial prostatitis caused by vancomycin-resistant Enterococcus faecalis, with documented success in achieving long-lasting cure after a 6-week treatment course. 1

Rationale for Combination Therapy

• Enterococcus faecalis is one of the most common pathogens associated with chronic bacterial prostatitis, requiring targeted antimicrobial therapy 2
• Chronic bacterial prostatitis is challenging to treat due to the relative impermeability of the prostate to many antimicrobial agents, necessitating lipid-soluble antibiotics for effective penetration 3
• Rifampin has been successfully used in combination therapy for difficult-to-treat enterococcal infections, including those resistant to conventional therapies 4
• Nitrofurantoin has good in vitro activity against enterococci, including vancomycin-resistant strains, and is FDA-approved for lower urinary tract infections 4

Evidence Supporting This Combination

• A documented case of chronic prostatitis due to vancomycin-resistant E. faecium (resistant to vancomycin, ampicillin, ciprofloxacin, and doxycycline) in a liver transplant recipient was successfully treated with a combination of rifampin and nitrofurantoin for 6 weeks, resulting in long-lasting cure 1
• This combination is particularly valuable when conventional treatment options are limited due to resistance patterns 1, 5
• Other antimicrobial agents that show in vitro activity against vancomycin-resistant enterococci, such as quinupristin/dalfopristin and chloramphenicol, may not achieve sufficient prostatic tissue levels for effective treatment 1

Treatment Recommendations

• For chronic bacterial prostatitis caused by resistant E. faecalis:
  • Rifampin (dosage as per clinical situation) combined with nitrofurantoin 100 mg PO every 6 hours 4, 1
  • Treatment duration of 6 weeks is recommended based on successful clinical outcomes 1
• This combination is particularly valuable when the pathogen shows resistance to conventional therapies like fluoroquinolones, which are typically first-line agents for prostatitis 2

Important Clinical Considerations

• Chronic bacterial prostatitis typically requires extended antimicrobial therapy (4-16 weeks) to achieve cure due to the difficulty in achieving therapeutic levels in prostatic tissue 6
• Monitor for potential side effects of nitrofurantoin, including pulmonary reactions, hepatic toxicity, and gastrointestinal disturbances 7
• Rifampin has numerous drug interactions due to its potent induction of cytochrome P450 enzymes, requiring careful medication review before initiating therapy 5
• Complete the full prescribed course of antibiotics to ensure complete eradication of infection and prevent relapse 7

Limitations and Alternatives

• The evidence for this specific combination is limited, with most data coming from case reports rather than randomized controlled trials 1
• For E. faecalis strains susceptible to other antibiotics, fluoroquinolones may be preferred due to their generally good prostatic penetration and lower resistance rates (9.7% for ciprofloxacin, 4.8% for levofloxacin) 2
• Daptomycin in high doses (8-12 mg/kg/day) or in combination with β-lactams may be considered for systemic enterococcal infections, though prostatic penetration may be limited 4