Viewing the Community-acquired Pneumonia Guidelines through an Antibiotic Stewardship Lens.

To the Editor:

We read with interest the article titled “Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America” (1). We congratulate the authors on their comprehensive review of the evidence. Although we understand that they are limited in their ability to establish recommendations based on the Grading of Recommendations Assessment, Development, and Evaluation system process, we believe it would be helpful for the practicing clinician to understand how to interpret the guidelines through an antibiotic stewardship (AS) lens. Below, we discuss three AS-guided recommendations that should be considered when interpreting the community-acquired pneumonia (CAP) guidelines.

Fluoroquinolone Use

Fluoroquinolones (FQs) are recommended as a first-line option along with β-lactam plus macrolide combination therapy for ambulatory patients with CAP and comorbidities and for inpatients. The increased compliance issues regarding the use of two medications may drive clinicians to prescribe FQs, especially in the outpatient setting. The authors mention that adverse reactions to FQs are rare; however, FQ use is among the strongest risk factors for Clostridioides difficile infections (2), and the list of U.S. Food and Drug Administration black-box warnings associated with FQ use continues to grow.

Inpatient Empiric Antimicrobial Therapy for Nonsevere CAP and No Risk Factors for Methicillin-Resistant Staphylococcus aureus or Pseudomonas aeruginosa

The guidelines recommend combination therapy with a β-lactam and a macrolide for all patients who receive a non-FQ regimen. Although one randomized trial failed to demonstrate noninferiority of β-lactam monotherapy versus β-lactam plus macrolide combination therapy in attainment of clinical stability on hospital Day 7, a clinical benefit of combination therapy was seen in patients with confirmed atypical pathogens or patients with Pneumonia Severity Index category IV pneumonia (3). Another cluster randomized trial that was not discussed in the guidelines demonstrated noninferiority of β-lactam monotherapy versus β-lactam plus macrolide combination therapy in 90-day mortality, favoring β-lactam monotherapy in non-ICU patients (4). A subsequently published meta-analysis that included observational data and results from the above-mentioned randomized trials found a mortality benefit from combination therapy only for severe CAP. Because atypical pathogens account for <5% of CAP in U.S. population studies (5) and combination therapy may only benefit patients with severe CAP, routine atypical coverage may not be necessary in outpatients or inpatients with nonsevere CAP; therefore, β-lactam monotherapy is recommended in CAP guidelines in other countries (6, 7).

Antibiotic Recommendations and Influenza

The guidelines recommend antibiotics for both inpatients and outpatients with clinical and radiographic evidence of CAP who test positive for influenza, with a consideration to stop antibiotics within 72 hours if no bacterial pathogen is found and the patient achieves early clinical stability. This recommendation is likely to lead to increases in unnecessary antibiotic prescriptions for patients with influenza. In the outpatient setting, sputum cultures and chest X-rays are not routinely obtained; hence, providers may not know when to stop antibiotics. Additionally, the rate of bacterial complications of influenza is low (∼<2.5%) (8, 9). Antibiotics may not be necessary for most outpatients with influenza or those who are hospitalized but are not severely ill.

Guidelines regarding the use of antibiotics must balance treatment recommendations with AS considerations and specifically note when regimens are supported by clinical trials but may be suboptimal because of side effects or costs. Many providers regard the guidelines as strict recommendations rather than as a starting point for clinical decision-making. Thus, discussions about areas in which the available evidence is inconclusive should include the viewpoint of antibiotic stewards at the patient and population levels. We strongly encourage active engagement from AS on future guidelines to facilitate discussions about judicious prescribing of antibiotics and to inform practical interpretation and implementation of those guidelines.