What is the best treatment for a patient with a Staphylococcus epidermidis urinary tract infection (UTI) who has failed treatment with cefixime (third-generation cephalosporin)?

Treatment of Staphylococcus epidermidis UTI After Cefixime Failure

For S. epidermidis urinary tract infection that has failed cefixime therapy, vancomycin is the definitive treatment choice, particularly given the high likelihood of methicillin resistance in this clinical scenario. 1

Understanding the Clinical Context

S. epidermidis UTIs typically occur in healthcare-associated settings and are frequently resistant to multiple antibiotics, including cephalosporins. 1 The failure of cefixime (a third-generation cephalosporin) strongly suggests either:

• Methicillin-resistant S. epidermidis (MRSE), which exhibits cross-resistance to all cephalosporins despite appearing susceptible on standard testing 1
• Inadequate urinary concentrations of cefixime for this pathogen, as cefixime has poor activity against staphylococci 2

Primary Treatment Recommendation

Vancomycin is the drug of choice for this clinical scenario because:

• Virtually all S. epidermidis isolates remain susceptible to vancomycin 1
• It is specifically recommended for methicillin-resistant staphylococcal infections 1
• Cross-resistance between methicillin and cephalosporins occurs in vitro, making all cephalosporins unreliable 1

Dosing approach:

• Standard vancomycin dosing with monitoring of trough levels
• Treatment duration of 7-14 days depending on clinical severity and whether this is complicated UTI 3, 4

Alternative First-Line Options for Uncomplicated Cases

If the infection is uncomplicated cystitis without systemic symptoms, consider:

• Nitrofurantoin 100mg twice daily for 5 days - excellent activity against gram-positive cocci including enterococci, with maintained susceptibility 5, 4
• Fosfomycin 3g single dose - demonstrates excellent activity against gram-positive uropathogens 5, 4
• Trimethoprim-sulfamethoxazole - effective for staphylococcal UTIs if local resistance <20% 5, 6

Combination Therapy for Serious Infections

For severe or persistent S. epidermidis infections:

Vancomycin PLUS rifampin or gentamicin (or both) is recommended for serious infections caused by methicillin-resistant strains. 1 This combination approach:

• Enhances bacterial killing
• Prevents resistance emergence
• Is particularly important for device-associated infections

Critical Pitfalls to Avoid

• Do not use cephalosporins (including cefotaxime, ceftriaxone, or cefepime) for suspected methicillin-resistant S. epidermidis, as cross-resistance occurs despite in vitro susceptibility testing suggesting otherwise 1
• Avoid fluoroquinolones as first-line due to increasing resistance rates 3, 5
• Do not assume susceptibility - obtain urine culture and susceptibility testing before finalizing therapy 5, 4
• Ensure adequate treatment duration - inadequate courses lead to treatment failure; use 7 days minimum for women, 14 days for men when prostatitis cannot be excluded 4

Device-Associated Considerations

If this UTI is catheter-associated:

• Remove or replace the indwelling catheter or device whenever possible, as antimicrobial therapy alone is often insufficient 1
• Empiric anti-staphylococcal coverage is recommended for catheter-associated UTIs, especially with prolonged catheterization 4

De-escalation Strategy

Once culture and susceptibility results are available:

• If the isolate is methicillin-susceptible, narrow to penicillinase-resistant penicillins (nafcillin, oxacillin) or first-generation cephalosporins (cephalexin) 1
• Continue vancomycin if methicillin-resistant 1
• Ensure patient has been afebrile for at least 48 hours before considering treatment completion 4