Combination Therapy with Levofloxacin and Metronidazole
The combination of levofloxacin (Levaquin) and metronidazole is specifically recommended by IDSA/SIS guidelines for treating complicated intra-abdominal infections, providing comprehensive coverage against both aerobic gram-negative bacteria and anaerobic organisms that commonly cause these polymicrobial infections. 1
Primary Indication: Complicated Intra-Abdominal Infections
The most legitimate and evidence-based reason to prescribe both agents together is for complicated intra-abdominal infections (cIAIs), which include:
- Perforated appendicitis with peritonitis or abscess formation 1
- Complicated diverticulitis with perforation or abscess 1
- Secondary peritonitis from bowel perforation 1
- Intra-abdominal abscesses requiring source control 1
- Post-operative intra-abdominal infections 1
Severity-Based Recommendations
For mild-to-moderate severity community-acquired cIAIs: Levofloxacin plus metronidazole is a first-line recommended regimen by IDSA/SIS guidelines 1
For high-severity infections (APACHE II ≥15): This combination remains appropriate as one of several broad-spectrum options 1
Microbiological Rationale
The combination provides complementary antimicrobial coverage:
- Levofloxacin covers: Aerobic and facultative gram-negative bacilli (E. coli, Klebsiella, Proteus), some gram-positive cocci, and atypical organisms 1
- Metronidazole covers: Obligate anaerobes including Bacteroides fragilis, Bacteroides thetaiotaomicron, and Peptostreptococcus species 2, 3
Pharmacodynamic studies demonstrate that levofloxacin 750mg daily plus metronidazole 1,500mg daily achieves rapid bactericidal activity against mixed E. coli and B. fragilis infections, with faster killing rates than moxifloxacin monotherapy. 2
Additional Legitimate Indications
Pelvic inflammatory disease (PID): Levofloxacin plus metronidazole provides coverage for sexually transmitted pathogens (Chlamydia, Neisseria gonorrhoeae), anaerobes, and vaginal flora, with clinical cure rates of 97% at end of treatment 4
Diabetic foot infections with anaerobic involvement: When deep tissue or bone infection includes anaerobic organisms alongside aerobic gram-negatives 5
Critical Resistance Considerations
Do NOT use this combination if local fluoroquinolone resistance rates among E. coli exceed 20% - alternative regimens should be selected in such settings 1
Verify local antibiogram data before empiric use, as quinolone-resistant E. coli have become common in many communities, and guidelines specify that quinolones should only be used when hospital surveys indicate ≥90% E. coli susceptibility 1
Dosing Regimens
Standard dosing for intra-abdominal infections:
- Levofloxacin 750mg IV/PO once daily 1, 2
- Metronidazole 500mg IV/PO every 8 hours OR 1,500mg IV once daily 1, 3
Once-daily metronidazole (1,500mg q24h) is as efficacious as divided dosing and offers pharmacokinetic advantages with similar AUIC/AUBC values when combined with levofloxacin 750mg. 5, 3
Duration and Transition
Treatment duration should not exceed 7 days for most patients with adequate source control 1
Oral step-down therapy: Both agents can be transitioned to oral formulations once clinical improvement occurs (resolution of fever, decreasing leukocytosis, tolerating oral intake), allowing outpatient completion 1
Common Pitfalls to Avoid
- Using this combination without confirming local fluoroquinolone susceptibility patterns - resistance may render the regimen ineffective 1
- Continuing therapy beyond resolution of clinical signs - prolonged courses increase C. difficile risk and promote resistance 1
- Failing to obtain source control - antibiotics alone are insufficient for abscesses or ongoing contamination 1
- Using for simple appendicitis or cholecystitis without perforation - these require only prophylactic narrow-spectrum coverage for <24 hours 1