What is the recommended treatment for an Enterobacter cloacae complex infection with a urine culture showing >100,000 CFU/ML non-lactose fermenting Gram-negative rods?

Treatment of Enterobacter cloacae Complex Urinary Tract Infection

For this Enterobacter cloacae complex urinary tract infection with excellent susceptibility to multiple agents, ciprofloxacin or levofloxacin are the preferred first-line treatments, given their high urinary concentrations, oral bioavailability, and proven efficacy for complicated UTIs caused by Enterobacter species. 1

Primary Treatment Recommendations

Fluoroquinolones (First-Line)

• Ciprofloxacin 500 mg PO twice daily or levofloxacin 750 mg PO once daily for 7-14 days are optimal choices given the isolate's susceptibility (ciprofloxacin MIC ≤0.06, levofloxacin MIC ≤0.12) 1
• Levofloxacin is FDA-approved specifically for complicated UTIs caused by Enterobacter cloacae, including cases with concurrent bacteremia 1
• These agents achieve excellent urinary concentrations and allow for oral outpatient therapy if the patient is clinically stable 1

Alternative Oral Options

• Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg PO twice daily is an excellent alternative given the isolate's susceptibility (MIC ≤20) 2
• TMP-SMX is FDA-approved for UTIs caused by Enterobacter species and provides effective urinary concentrations 2
• This option is particularly valuable from an antimicrobial stewardship perspective, reserving broader-spectrum agents 3

Carbapenem-Sparing Approach

When to Use Carbapenems

• Reserve ertapenem or meropenem for severe sepsis, septic shock, or failure of first-line therapy 3
• While the isolate is susceptible to both ertapenem (MIC ≤0.12) and meropenem (MIC ≤0.25), carbapenem use should be minimized due to stewardship considerations 3
• The ESCMID guidelines emphasize using older, narrower-spectrum antibiotics for non-severe infections when active in vitro 3

Cefepime Considerations

• Cefepime 1-2 g IV every 8-12 hours is appropriate for hospitalized patients requiring IV therapy, given the excellent susceptibility (MIC ≤0.12) 4
• Clinical data demonstrate cefepime achieves 88.9% favorable outcomes in Enterobacter cloacae bloodstream infections when isolates are susceptible 4
• Cefepime maintains activity even against derepressed AmpC-producing strains with MIC₉₀ of 3 μg/mL 4

Critical Pitfalls to Avoid

AmpC β-Lactamase Concerns

• Avoid amoxicillin-clavulanate, first- and second-generation cephalosporins, and cefoxitin - the isolate shows expected resistance (amoxicillin-clavulanate MIC ≥32) due to chromosomal AmpC β-lactamase 5
• Approximately 60% of E. cloacae possess inducible AmpC enzymes, and 32% have derepressed (constitutively expressed) AmpC 4
• Third-generation cephalosporins like ceftriaxone can select for derepressed AmpC mutants during therapy, leading to treatment failure 4

Nitrofurantoin Limitation

• Do not use nitrofurantoin despite intermediate susceptibility (MIC 64) - it is inadequate for infections beyond uncomplicated cystitis and should not be used for complicated UTIs or any systemic infection 3

Aminoglycoside Role

Single-Dose for Uncomplicated Cystitis

• Tobramycin or gentamicin as a single dose may be considered for uncomplicated cystitis only, given excellent susceptibility (tobramycin MIC ≤1) 3
• Aminoglycosides achieve urinary concentrations 25-100 fold higher than serum levels and maintain therapeutic levels for days after a single dose 3
• Meta-analysis data show 87-100% microbiologic cure rates for lower UTIs with single-dose aminoglycosides 3

Combination Therapy Indications

• Reserve aminoglycoside combination therapy for severe infections, sepsis, or carbapenem-resistant scenarios 3
• For complicated UTIs without septic shock, aminoglycosides can be used for short durations when active in vitro 3
• Monitor closely for nephrotoxicity and ototoxicity; perform therapeutic drug monitoring when available, especially with prolonged use 3

Treatment Duration and Monitoring

Duration Guidelines

• 7-10 days for uncomplicated pyelonephritis or complicated UTI 1
• 10-14 days for complicated UTI with systemic symptoms or bacteremia 1
• Shorter courses (5-7 days) may be adequate for fluoroquinolones in less severe cases 1

Clinical Monitoring

• Assess clinical response within 48-72 hours of initiating therapy 3
• Consider repeat cultures if fever persists beyond 72 hours or symptoms worsen 3
• Monitor renal function if using aminoglycosides or in patients with baseline renal impairment 3, 6

Stewardship Considerations

The excellent multi-drug susceptibility pattern of this isolate allows for targeted, narrow-spectrum therapy rather than empiric broad-spectrum coverage 3. This approach:

• Preserves newer β-lactam/β-lactamase inhibitor combinations (ceftazidime-avibactam, meropenem-vaborbactam) for truly resistant organisms 3
• Reduces selective pressure for carbapenem resistance 3
• Minimizes collateral damage to normal flora 3