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Combo therapy didn’t top beta-lactams alone in most community-acquired pneumonia

Key clinical point: Beta-lactam monotherapy was noninferior to combined beta-lactam/macrolide therapy for adults with community-acquired pneumonia, except in cases of atypical pathogen infections or more severe pneumonia.

Major finding: Patients with atypical infections were less likely to reach clinical stability when they received only a beta-lactam compared with dual treatment (hazard ratio, 0.33; 95% CI, 0.13 to 0.85).

Data source: Randomized trial of 580 adults with moderately severe community-acquired pneumonia.

Disclosures: The study was supported by the Swiss National Science Foundation, the Clinical Trial Unit, and Geneva University Hospitals. The authors reported no conflicts of interest.

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Continue dual therapy for now

Evidence from this trial pushes the pendulum further in favor of antibiotic therapy covering atypical and typical bacterial pathogens for patients hospitalized for CAP. Lessons learned from its design and results should inform future trials required to definitively settle this debate.

Although most patients in the current study had a low-risk severity profile (PSI categories I-III), future trials should focus on hospitalized ward patients with more severe disease (PSI categories III-V) to detect clinically meaningful differences in such outcomes. To assess the role of other commonly recommended agents with atypical coverage, future trials should directly compare fluoroquinolone only, beta-lactam and macrolide, and beta-lactam–only therapies.

Finally, to maximize the detection of atypical pathogens and ensure their timely treatment in all study arms, future trials should use the most comprehensive point-of-care diagnostic testing for pneumonia pathogens. Although trials with these features would bring us substantially closer to ending the debate, until that time, dual therapy should remain the recommended treatment for patients hospitalized for CAP.

Dr. Jonathan S. Lee and Dr. Michael J. Fine are at the University of Pittsburgh, and Dr. Fine is also at the Center for Health Equity Research and Promotion in Pittsburgh. Dr. Lee has received royalties from UpToDate and has owned mutual funds that invest in health care companies. These remarks were taken from their editorial accompanying Dr. Garin’s report (JAMA Intern. Med. 2014 Oct. 6 [doi: 10.1001/jamainternmed.2014.3996]).


 

FROM JAMA INTERNAL MEDICINE

References

A beta-lactam alone was not inferior to combined macrolide plus beta-lactam treatment for moderately severe community-acquired pneumonia, investigators reported. The results were published Oct. 6 in JAMA Internal Medicine.

Combination therapy was superior in subgroups of patients who had more severe pneumonia or infections of atypical pathogens, said Dr. Nicolas Garin of Hospital Riviera-Chablais, Switzerland.

Guidelines differ on whether to use a beta-lactam alone or together with a macrolide when empirically treating moderately severe community-acquired pneumonia, noted Dr. Garin and his associates. They carried out a multicenter, open-label noninferiority trial of 580 patients who received either intravenous cefuroxime or amoxicillin and clavulanic acid alone, or a beta-lactam plus a macrolide in the form of intravenous or oral clarithromycin. Patients in the monotherapy group switched to dual treatment if their urine tested positive for the Legionella pneumophila antigen, said the investigators.

Median age of the patients was 76 years.

Beta-lactam therapy was alone was not found to be inferior to combination beta-lactam/macrolide therapy in treating pneumonia. © CDC / Dr. Jim Feeley
Beta-lactam therapy was alone was not found to be inferior to combination beta-lactam/macrolide therapy in treating pneumonia.

After 7 days of treatment, 41.2% of patients in the monotherapy group had not reached clinical stability, compared with 33.6% of patients in the combination arm (P = .07), the researchers said. Kaplan-Meier curves showed that the difference between the two groups peaked on day 7 and persisted until day 30, but never reached statistical significance, they added.

At the same time, patients with atypical infections were less likely to stabilize with monotherapy compared with dual treatment (hazard ratio, 0.33; 95% CI, 0.13 to 0.85), the researchers said. The superiority of dual therapy in these patients “may be explained by failure to provide timely coverage of the Legionella infection,” the investigators said. Patients randomized to monotherapy whose urine tested positive went an average of almost 2 days before starting macrolides, they noted. “This long interval reflects real-life practice, with delays in collecting a urine sample for testing, receiving the results, and prescribing the appropriate antibiotic,” they said.

Patients with Pneumonia Severity Index) category IV pneumonia also were less likely to reach clinical stability on monotherapy (HR, 0.81; 95% CI, 0.59-1.10), the researchers noted. “Future work might test a strategy of tailoring the initial therapy on the severity of the pneumonia, with combination therapy reserved for patients with PSI category IV or higher pneumonia,” they wrote.

In addition, 7.9% of patients in the monotherapy group were readmitted within 30 days, compared with 3.1% of the dual therapy group (P = .01), the researchers reported (JAMA Intern. Med. 2014 Oct. 6 [doi: 10.1001/jamainternmed.2014.4887]).

Clinical stability was defined as a heart rate less than 100/min, systolic blood pressure of more than 90 mm Hg, tympanic temperature less than 38.0° C, respiratory rate less than 24/min, and oxygen saturation by pulse oximetry of more than 90% on room air, the authors wrote.

The study was supported by the Swiss National Science Foundation, the Clinical Trial Unit, and Geneva University Hospitals. The authors reported no conflicts of interest.