Community-acquired pneumonia: Empiric outpatient antibiotic selection in adults

ATS/IDSA: American Thoracic Society/Infectious Diseases Society of America; COPD: chronic obstructive pulmonary disease; CAP: community-acquired pneumonia; IgE: immunoglobulin E.

* Major comorbidities include but are not limited to chronic heart, renal, or liver disease, diabetes mellitus, asplenia, and immunosuppression.

¶ Patients with mild non-IgE-mediated reactions (eg, maculopapular rash) to penicillin or known cephalosporin tolerance can generally use later-generation cephalosporins safely. Patients with IgE-mediated reactions (hives, angioedema, anaphylaxis) or severe delayed reactions should generally use other agents. Refer to the UpToDate text on penicillin hypersensitivity reactions for detail.

Δ Reasons to avoid macrolides include baseline prolonged QTc interval or risk for QTc prolongation (eg, hypokalemia, hypomagnesemia, clinically significant bradycardia, or use of other QT-prolonging agents).

◊ Our approach differs from the ATS/IDSA, which recommend monotherapy with amoxicillin, doxycycline, or a macrolide (in areas where macrolide resistance is low) as options for patients without comorbidities or risk factors for drug-resistant S. pneumoniae. By contrast, we prefer to treat all patients with a regimen that treats most strains of drug-resistant S. pneumoniae and atypical pathogens for all patients because the potential to reduce morbidity is high and the downside of a short course of therapy for most patients is low. Refer to the UpToDate text for detail.

§ For macrolides, resistance rates among S. pneumoniae are often >30% in the United States and typically >25% for most parts of the world, apart from some regions in Northern Europe. For doxycycline, resistance rates are less well established but are approximately 10 to 20% in the United States and likely rising.

¥ Lefamulin is a newer agent that is active against most CAP pathogens including S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, and atypical pathogens. Although lefamulin lacks activity against Enterobacteriaceae (eg, Klebsiella spp and E. coli) and thus is not appropriate for patients with structural lung disease, its more targeted spectrum makes it less disruptive to the microbiome. Clinical experience with lefamulin is limited, and it is not recommended in moderate to severe hepatic dysfunction, pregnancy, breastfeeding, known long QT syndrome, or with concomitant QT-prolonging agents. There are drug interactions with CYP3A4 and P-gp inducers and substrates; in addition, lefamulin tablets are contraindicated with QT-prolonging CYP3A4 substrates. Refer to the Lexicomp drug monograph and UpToDate text for detail.

‡ Omadacycline is another newer agent that is active against most CAP pathogens, including Enterobacteriaceae. It is a potential alternative for patients who cannot tolerate beta-lactams (or other agents) and want to avoid fluoroquinolones.