What is the appropriate treatment for a patient allergic to Quinolone (Fluoroquinolone) and Augmentin (Amoxicillin-Clavulanate) with pneumonia caused by Methicillin-resistant Staphylococcus aureus (MRSA), a Gram-positive bacterium, and a Gram-negative bacterium?

From the Guidelines

For a patient with pneumonia caused by MRSA and gram-negative organisms who has allergies to quinolones and Augmentin, I recommend using vancomycin plus aztreonam as the initial treatment regimen. According to the 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society 1, vancomycin should be dosed at 15-20 mg/kg IV every 8-12 hours (with appropriate monitoring of trough levels aiming for 15-20 mcg/mL for serious infections) to target the MRSA component. Aztreonam should be given at 2 grams IV every 8 hours to cover gram-negative pathogens. This combination provides comprehensive coverage while avoiding the allergenic medications. Some key points to consider in the management of such patients include:

• The importance of appropriate dosing and monitoring of vancomycin to ensure efficacy and minimize toxicity, as outlined in the guidelines 1.
• The need to adjust doses in patients with renal impairment.
• The typical treatment duration ranges from 7-14 days depending on clinical response, with reassessment after obtaining culture results to potentially narrow therapy.
• If the patient shows signs of clinical improvement and cultures reveal specific sensitivities, therapy can be tailored accordingly. This combination is recommended because vancomycin remains the standard treatment for MRSA infections, while aztreonam specifically targets gram-negative organisms without cross-reactivity to beta-lactam allergies. Alternative options for MRSA coverage could include linezolid (600 mg IV/PO twice daily) or daptomycin (6 mg/kg IV daily), though these would still need to be paired with gram-negative coverage, as suggested by the guidelines 1.

From the FDA Drug Label

The micro-ITT population consisted of 77 patients with at least one Gram-negative uropathogen at baseline (greater or equal to 105 CFU/mL). A total of 870 hospitalized adults with HABP/VABP were randomized and received trial medications in a multinational, multi-center, double-blind trial comparing AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0. 5 grams) intravenously every 8 hours to meropenem 1 gram intravenously every 8 hours for 7 to 14 days of therapy. Patients with infections only due to Gram-positive organisms were excluded from the trial, when this could be determined before enrollment Following randomization, patients in both treatment groups could receive empiric open-label linezolid or vancomycin to cover for Gram-positive pathogens while awaiting culture results.

The patient alleges to quinolone and augmentin with pneumonia MRSA Gram-positive and Gram-negative.

• The drug label does not provide information on the use of ceftazidime-avibactam for MRSA or Gram-positive coverage.
• The study excluded patients with infections only due to Gram-positive organisms.
• The use of ceftazidime-avibactam is indicated for Gram-negative infections.
• Augmentin is not mentioned in the drug label.
• Quinolone is not mentioned in the drug label as a treatment option for the patient's condition. The FDA drug label does not answer the question.

From the Research

Patient Allegations and Antibiotic Resistance

• The patient alleges to be allergic to quinolone and Augmentin, which are commonly used antibiotics to treat various infections, including pneumonia caused by MRSA (methicillin-resistant Staphylococcus aureus), Gram-positive, and Gram-negative bacteria 2, 3, 4.
• Quinolones are broad-spectrum antibiotics that are active against both Gram-positive and Gram-negative bacteria, including mycobacteria and anaerobes, by inhibiting bacterial nucleic acid synthesis through disrupting the enzymes topoisomerase IV and DNA gyrase 5.
• However, bacteria have acquired resistance to quinolones due to overuse, with mechanisms contributing to quinolone resistance mediated by chromosomal mutations and/or plasmid gene uptake that alter the topoisomerase targets, modify the quinolone, and/or reduce drug accumulation 5.

Treatment Options for MRSA Pneumonia

• The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines suggest that linezolid (LZD) is preferred over vancomycin (VCM) for treating MRSA pneumonia 6.
• A meta-analysis of vancomycin versus linezolid in pneumonia with proven MRSA found that clinical cure and microbiological eradication rates were significantly increased in patients treated with LZD, but mortality was comparable between patients treated with VCM and LZD 6.

Allergic Reactions to Quinolones

• Allergic reactions to quinolones can be immediate or delayed, with anaphylaxis and maculopapular exanthema being the most frequent clinical entities 4.
• A precise diagnosis of quinolone allergy is particularly difficult, and drug provocation testing is considered the gold standard to establish diagnosis, which is not a risk-free procedure 4.
• Cross-reactivity between quinolones is difficult to predict, and hypersensitivity to quinolones has also been associated with beta-lactam and neuromuscular blocking agent allergies 4.