What is the combination of quinolones and tetracyclines used in?

Combination of Quinolones and Tetracyclines in Clinical Practice

The combination of quinolones and tetracyclines is primarily used in the treatment of complicated intra-abdominal infections, ciprofloxacin-resistant Bacillus anthracis infections, and certain multidrug-resistant bacterial infections. 1

Intra-abdominal Infections

• Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) in combination with metronidazole are recommended for community-acquired complicated intra-abdominal infections of mild-to-moderate severity 1
• For high-severity community-acquired intra-abdominal infections, ciprofloxacin or gatifloxacin in combination with metronidazole is recommended 1
• The combination provides coverage against facultative and aerobic gram-negative organisms as well as anaerobic microorganisms commonly found in gastrointestinal perforations beyond the proximal ileum 1
• Caution is warranted as increasing resistance of Bacteroides fragilis group isolates to quinolones has been reported, necessitating the combination with metronidazole 1

Bacillus anthracis Infections (Anthrax)

• For treatment of ciprofloxacin-resistant B. anthracis, combinations of doxycycline (tetracycline) with either a β-lactam or rifampin have shown efficacy 1
• This combination approach is particularly important for engineered or multidrug-resistant strains of B. anthracis 1
• Newer tetracyclines (minocycline, omadacycline, eravacycline) may be better alternatives against fluoroquinolone-resistant strains as they are less affected by efflux pump overexpression 1
• The combination addresses the concern that fluoroquinolone use might increase bacterial efflux of other antibiotics including tetracyclines 1

Hospital-Acquired and Ventilator-Associated Pneumonia

• Combination therapy with agents from different antibiotic classes, including quinolones and tetracyclines, may be used to provide broad-spectrum empiric coverage for suspected multidrug-resistant pathogens 1
• This approach ensures at least one drug is active against the often multidrug-resistant etiologic agent(s) 1
• For gram-negative infections, combinations typically involve two drugs from the β-lactam, quinolone, or aminoglycoside classes, but tetracyclines may be included for specific pathogens 1
• Quinolones penetrate into the lung better than aminoglycosides and have less potential for nephrotoxicity 1

Multidrug-Resistant Organisms

• For infections caused by extensively drug-resistant or pandrug-resistant bacteria, combinations of quinolones and tetracyclines may be part of salvage therapy regimens 1
• Tigecycline (a tetracycline derivative) in combination with other agents may be used for carbapenemase-producing and carbapenem-resistant Enterobacteriaceae 1
• The combination approach may help prevent the emergence of resistance during therapy, although this benefit has not been consistently demonstrated 1

Clinical Considerations and Pitfalls

• Monotherapy should be used when possible as combination therapy is often expensive and exposes patients to unnecessary antibiotics, potentially increasing the risk of multidrug-resistant pathogens 1
• Resistance can develop in 30-50% of patients receiving monotherapy for Pseudomonas aeruginosa infections, and combination therapy may reduce this risk 1
• When using combination therapy, agents from different antibiotic classes should be selected to avoid antagonism of therapeutic mechanisms 1
• For infectious colitis when doxycycline cannot be used, ciprofloxacin plus metronidazole is the preferred empiric regimen 2

Evidence Quality and Limitations

• Most studies on combination therapy have used an aminoglycoside with a β-lactam, with limited prospective studies comparing quinolone-based combination therapy with monotherapy 1
• A meta-analysis of β-lactam monotherapy compared with β-lactam-aminoglycoside combination regimens showed clinical failure was more common with combination therapy and there was no advantage in the therapy of P. aeruginosa infections 1
• The emergence of resistance to both quinolones and tetracyclines is a growing concern, particularly in staphylococci, P. aeruginosa, and various Enterobacteriaceae 3
• Combination therapy may reduce the emergence of resistant mutants, but this hypothesis requires assessment in larger studies 3