Community-acquired pneumonia (CAP) ranks among the most infectious diseases and is responsible for significant morbidity and mortality around the world. It’s an infection of the lungs acquired from normal social contact and can often be treated with the right combination of medicines.

But there have been several debates of late regarding which are the right combination of antibiotics to treat CAP, specifically among international medical societies. A new randomized clinical trial for CAP put to rest these debates by concluding that monotherapy with beta-lactam alone was not worse than a combination therapy with a macrolide in patients hospitalized with moderately severe pneumonia. The study was conducted by researchers Dr. Nicolas Garin, Hôpital Riviera-Chablais, Switzerland, and colleagues.

CAP can affect people of all ages, but children below the age of 5 and the elderly are most susceptible. It is estimated that globally more than one million children die of CAP each year. In America, the situation is not any better off. About one million people are hospitalized with pneumonia, and about 50,000 people die from the disease each year. But most hospitalizations and deaths in America are seen in adults rather than children.

But this is a disease that can be treated with the right medicines. Beta-lactam is a broad class of antibiotics that include derivatives of penicillin, cephalosporins, monobactums, and carbapenems are given as first-line therapy. But the use of these antibiotics differs, as countries have their own set of guidelines on how to treat CAP. The North American guidelines recommend treatment of atypical pathogens with respiratory antibiotics or with a combination of a macrolide and a beta-lactam for all hospitalized patients. While European guidelines recommend combination therapy only for more severely ill patients.

This new trial was conducted to ascertain if monotherapy with beta-lactam alone was noninferior (not worse than) to a combination therapy with a macrolide for patients in the hospital with moderately severe pneumonia. 

The randomized trial included 580 patients (291 received monotherapy and 289 had combination therapy). The median age of patients was 76 years. After seven days of treatment, researchers found that 120 of 291 patients (41.2 percent) who received monotherapy vs. 97 of 289 (33.6 percent) who had combination therapy had not reached clinical stability.

Patients who were infected with atypical pathogens, such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila, or with more severe pneumonia were less likely to reach clinical stability with monotherapy. Patients not infected with atypical pathogens or with less severity of illness had equivalent outcomes in the two treatment groups. There were more 30-day readmissions in the monotherapy treatment group (7.9 percent vs. 3.1 percent).

Mortality, admission to the intensive care unit, complications, length of stay, and pneumonia recurrence did not differ between the two groups within 90 days.

"We were unable to demonstrate noninferiority of initial empirical treatment with a beta-lactam agent alone in hospitalized patients with moderately severe community-acquired pneumonia. There was a nonsignificant trend toward superiority of combination therapy, which could represent a chance finding or true superiority that was not significant because of insufficient power,” Garin said in a statement.

Commenting on the significance of this trial, authors Dr. Jonathan S. Lee and Dr. Michael J. Fine, of the University of Pittsburgh School of Medicine wrote that while the trial gave evidence on the line of treatment to be used for atypical and typical pneumonia, future trials need to be conducted to maximize accurate detection and treatment of CAP caused by atypical 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,” they concluded.

Source: Garin N, Genne D, Carballo S, et al. β-Lactam Monotherapy vs β-Lactam–Macrolide Combination Treatment in Moderately Severe Community-Acquired PneumoniaA Randomized Noninferiority Trial. JAMA Internal Medicine. 2014.