Does previous treatment failure with fosfomycin (phosphonic acid antibiotic) affect the prognosis of a patient with a bacterial infection, such as one caused by Enterococcus faecalis?

Impact of Previous Fosfomycin Treatment Failure on Prognosis

Previous treatment failure with fosfomycin does not significantly impact the prognosis of subsequent infections, provided that susceptibility testing is performed before initiating another course of fosfomycin therapy. 1

Understanding Fosfomycin and Treatment Failure

Fosfomycin is a phosphonic acid antibiotic with activity against various gram-positive and gram-negative bacteria, including Enterococcus faecalis. When considering its use after a previous treatment failure, several key factors must be evaluated:

• Susceptibility testing is mandatory before initiating (or re-initiating) fosfomycin therapy, as resistance patterns can develop and vary significantly (39-99% susceptibility rates have been reported for certain organisms) 1
• FosA-like genes may cause fosfomycin resistance, particularly in carbapenem-resistant Klebsiella pneumoniae (CRKP) 1
• For urinary tract infections specifically, fosfomycin is FDA-approved only for uncomplicated UTIs in women due to susceptible strains of E. coli and E. faecalis 2
• If persistence or reappearance of bacteriuria occurs after fosfomycin treatment, alternative therapeutic agents should be selected 2

Clinical Considerations After Treatment Failure

Susceptibility Testing

• Antimicrobial susceptibility testing must be performed before re-treatment with fosfomycin to confirm the organism remains susceptible 1
• For combination therapy, synergy testing may be beneficial to confirm potential enhanced activity 1

Patient-Specific Factors

• Patients with hypernatremia, cardiac insufficiency, or renal insufficiency should avoid fosfomycin use, regardless of previous treatment history 1
• Chronic kidney disease has been associated with persistent infection despite fosfomycin therapy (OR = 3.56,95% CI = 1.02-12.40, P = 0.04) 3

Therapeutic Drug Monitoring

• For serious infections, therapeutic drug monitoring (TDM) should be considered, especially when treating carbapenem-resistant gram-negative bacilli (CRGNB) infections 1
• TDM is particularly important for narrow therapeutic index drugs and in cases of organ dysfunction 1

Evidence for Retreatment After Failure

Studies examining fosfomycin's effectiveness after previous treatment failure are limited, but available evidence suggests:

• In vitro studies show fosfomycin maintains activity against many multidrug-resistant organisms, including vancomycin-resistant enterococci (VRE) 4, 5
• A retrospective analysis of 60 patients receiving fosfomycin for MDR UTIs showed a 55% success rate, with no association between treatment failure and the infecting organism, fosfomycin MIC, or number of doses received 3
• For biofilm-associated infections (such as implant-associated infections), fosfomycin has shown activity against adherent E. faecalis, suggesting potential efficacy even in difficult-to-treat scenarios 6

Combination Therapy After Failure

For serious infections where previous fosfomycin monotherapy failed:

• Fosfomycin-containing combination therapies may be effective for carbapenem-resistant Enterobacteriaceae (CRE) infections when the isolate remains susceptible 1
• Combinations with tigecycline, polymyxin, or carbapenems have shown efficacy in treating various CRE infections 1
• In vitro studies demonstrate synergistic or additive effects when fosfomycin is combined with linezolid, tigecycline, or gentamicin against VRE 1
• For biofilm infections, combinations with rifampin and/or daptomycin may enhance fosfomycin's activity 6

Practical Approach After Treatment Failure

1. Confirm true infection versus colonization 1
2. Perform susceptibility testing to confirm the organism remains fosfomycin-susceptible 1
3. Consider synergy testing if combination therapy is planned 1
4. Evaluate patient factors that might contribute to treatment failure (renal function, site of infection) 1, 3
5. Consider therapeutic drug monitoring for serious infections 1
6. For UTIs specifically, if persistence or reappearance of bacteriuria occurs after fosfomycin treatment, select alternative agents 2

Common Pitfalls to Avoid

• Failing to perform susceptibility testing before re-treatment 1
• Ignoring patient factors that might contribute to treatment failure 1, 3
• Using fosfomycin for indications beyond its approved use without careful consideration 2
• Not considering combination therapy for serious infections after monotherapy failure 1
• Overlooking the potential for development of resistance during therapy 1