What is the appropriate management of an adult with a urinary tract infection caused by a non‑lactose‑fermenting, non‑haemolytic uropathogenic Escherichia coli that is multidrug‑resistant?

Management of MDR Non-Lactose-Fermenting UPEC

For multidrug-resistant uropathogenic E. coli causing urinary tract infection, nitrofurantoin is the most appropriate empiric oral therapy, with fosfomycin or pivmecillinam as alternatives, while parenteral carbapenems or newer beta-lactamase inhibitor combinations should be reserved for severe infections or treatment failures.

Initial Antibiotic Selection

The phenotypic characteristics (non-lactose-fermenting, non-haemolytic) suggest an atypical UPEC strain, but the critical factor driving management is the multidrug resistance pattern rather than these laboratory characteristics.

First-Line Oral Options for Uncomplicated UTI

• Nitrofurantoin remains the most reliable oral agent with resistance rates below 20% even among ESBL-producing and MDR UPEC strains 1
• A 5-day course is recommended for acute uncomplicated cystitis 2
• Fosfomycin tromethamine as a single 3-g dose represents an alternative first-line option with preserved activity against MDR strains 2
• Pivmecillinam (5-day course) is another oral option effective against ESBL-producing E. coli 2

Agents to Avoid in MDR UPEC

• Trimethoprim-sulfamethoxazole shows high resistance rates (58-73% in hospital settings, 29% in community settings) and should not be used empirically 3
• Fluoroquinolones (ciprofloxacin, norfloxacin) demonstrate resistance rates of 31% or higher in MDR strains 3
• First-generation cephalosporins like cephalexin show 58% resistance rates 3
• Ampicillin and amoxicillin demonstrate 65-73% resistance and are ineffective 3

Management Algorithm Based on Infection Severity

For Uncomplicated Cystitis (Lower UTI)

• Start with nitrofurantoin 100 mg twice daily for 5 days 2, 1
• If nitrofurantoin is contraindicated (renal impairment with CrCl <30 mL/min), use fosfomycin 3-g single dose 2
• Obtain urine culture with susceptibility testing to guide therapy adjustment 1

For Complicated UTI or Pyelonephritis

When systemic symptoms, fever, flank pain, or comorbidities are present:

• Parenteral carbapenems (meropenem, imipenem-cilastatin, or ertapenem) are the most reliable options for ESBL-producing MDR UPEC 2
• Newer beta-lactamase inhibitor combinations provide targeted alternatives:
  • Meropenem-vaborbactam 2
  • Imipenem-cilastatin-relebactam 2
  • Ceftazidime-avibactam 2
  • Piperacillin-tazobactam (only for ESBL-E. coli, not for AmpC producers or Klebsiella) 2

For Treatment Failures

• Aminoglycosides including plazomicin remain options for parenteral therapy 2
• Cefiderocol, a siderophore cephalosporin, demonstrates activity against MDR organisms 2
• Parenteral fosfomycin can be considered 2

Critical Considerations

Antibiotic Stewardship

• The alarming prevalence of virulent MDR ESBL-producing UPEC (96.3% of ESBL-producers being MDR) necessitates judicious antibiotic use 1
• Reserve newer agents (ceftazidime-avibactam, meropenem-vaborbactam) for documented resistant infections to prevent further resistance development 2

Virulence Factor Correlation

• MDR UPEC strains paradoxically show lower prevalence of certain virulence genes (hemagglutinin, hemolysin, invasin) compared to non-MDR strains, though adhesins remain highly prevalent 1
• This suggests that while MDR strains may have reduced virulence in some aspects, their antibiotic resistance poses the primary clinical threat 1

Common Pitfalls to Avoid

• Do not use empiric fluoroquinolones or TMP-SMX in patients with recent antibiotic exposure or known local resistance rates exceeding 20% 2, 3
• Avoid oral cephalosporins as empiric therapy for suspected ESBL-producers 2
• Do not delay culture-directed therapy adjustment once susceptibilities are available 1

Duration and Monitoring

• For uncomplicated cystitis: 5 days for nitrofurantoin or pivmecillinam, single dose for fosfomycin 2
• For complicated infections: 7-14 days depending on clinical response and infection severity
• Obtain repeat cultures if symptoms persist beyond 48-72 hours of appropriate therapy 1