What is the appropriate treatment for a patient allergic to quinolones (fluoroquinolones) with pneumonia caused by Methicillin-resistant Staphylococcus aureus (MRSA), a Gram-positive bacterium, and a Gram-negative bacterium, and being augmented with Augmentin (amoxicillin-clavulanate)?

From the Guidelines

For a patient with pneumonia caused by MRSA and gram-negative organisms who has a quinolone allergy, I recommend a combination of vancomycin plus a carbapenem, such as meropenem, as the most effective treatment option. This recommendation is based on the guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia 1.

Key Considerations

• Vancomycin should be dosed at 15-20 mg/kg IV every 8-12 hours (adjusted based on renal function) to target trough levels of 15-20 μg/mL for MRSA coverage.
• Meropenem should be given at 1 gram IV every 8 hours for gram-negative coverage, including P. aeruginosa and ESBL Enterobacteriaceae.
• This regimen should be continued for 7-14 days depending on clinical response, with consideration for de-escalation once culture results are available.
• Alternative options for MRSA include linezolid (600 mg IV/PO twice daily), which may be preferred in patients with renal insufficiency or those receiving other nephrotoxic agents 1.
• For gram-negative coverage alternatives, consider ceftazidime (2 grams IV every 8 hours) if not cross-reactive with the patient's quinolone allergy, or other carbapenems such as imipenem 1.

Rationale

• The combination of vancomycin and a carbapenem provides broad coverage against both MRSA and gram-negative organisms, including P. aeruginosa and ESBL Enterobacteriaceae.
• This approach is supported by the guidelines, which recommend combination therapy for P. aeruginosa pneumonia to avoid the development of resistance and ensure effective treatment 1.
• Monitoring of renal function, complete blood counts, and clinical response is crucial throughout treatment to adjust the regimen as needed and minimize potential adverse effects.

From the FDA Drug Label

1. 2 Nosocomial Pneumonia Piperacillin and Tazobactam for Injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of nosocomial pneumonia (moderate to severe) caused by beta-lactamase producing isolates of Staphylococcus aureus and by piperacillin and tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa

• Piperacillin-tazobactam is indicated for the treatment of nosocomial pneumonia caused by Gram-positive (Staphylococcus aureus) and Gram-negative (Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa) bacteria.
• However, there is no direct information about the use of piperacillin-tazobactam in patients with a quinolone allergy or for the treatment of pneumonia caused by MRSA. 2

From the Research

Treatment Options for MRSA and Pseudomonas aeruginosa Infections

• The treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia involves several antibiotics with varying properties and activities 3.
• For Pseudomonas aeruginosa infections, combination therapy with a beta-lactam and an aminoglycoside or a fluoroquinolone is commonly used 4.
• Ceftazidime, carbapenems, and piperacillin-tazobactam are effective as single definitive therapy for Pseudomonas aeruginosa bloodstream infections, with no significant difference in mortality or clinical outcomes 5.

Effectiveness of Linezolid Against MRSA Bacteremia

• Linezolid has been shown to be effective against MRSA bacteremia, with comparable outcomes to vancomycin, teicoplanin, or daptomycin 6.
• The use of linezolid as a first-line drug against MRSA bacteremia is supported by its superior tissue penetration and utility as a salvage therapy for persistent MRSA bacteremia.

Synergy Between Vancomycin and Piperacillin-Tazobactam

• The combination of vancomycin and piperacillin-tazobactam has been shown to be effective against MRSA and vancomycin-intermediate Staphylococcus aureus (VISA) in an in vitro pharmacokinetic/pharmacodynamic model 7.
• This combination therapy demonstrated enhanced antimicrobial activity against MRSA and VISA compared to vancomycin alone, supporting its use in clinical practice.

Quinolone Use in Treating Pseudomonas aeruginosa Infections

• Quinolones, such as ciprofloxacin and levofloxacin, have been used in combination with beta-lactams to treat Pseudomonas aeruginosa infections, with comparable synergy to beta-lactam and aminoglycoside combinations 4.