Three Days of Antibiotics Prevails for Community-Acquired Pneumonia

AMSTERDAM, The Netherlands, June 9 ? Longer is not necessarily better when it comes to antibiotic therapy for hospitalized patients with uncomplicated community-acquired pneumonia, according to Dutch researchers.

A three-day course of antibiotics was just as effective as the conventional treatment lasting seven to 10 days, with a 10-day clinical success rate of 93% for both groups, they reported in the June 10 issue of BMJ.

Intravenous amoxicillin is the preferred empirical treatment in The Netherlands for mild-to-moderate severe community-acquired pneumonia. After three days of parenteral therapy, patients are typically treated for an additional five days with oral amoxicillin. Yet recommended protocols in North America differ significantly from this approach.

The seven-to-10 days recommendation for antibiotic treatment in uncomplicated pneumonia is not based on scientific evidence, wrote Jan Prins, M.D., Ph.D., of the Academic Medical Center here and colleagues.

If a shorter duration of therapy is equally effective, it could be of "major importance in decreasing antibiotic consumption and therefore resistance rates for several antimicrobials," Dr. Prins said. Two studies in children have shown that three days of therapy is as effective as five days of treatment, he noted.

In the current study, the investigators evaluated 119 patients with mild to moderate-severe pneumonia (severity score ? 110), all were admitted to one of nine hospitals in The Netherlands.

All patients had substantially improved after being treated for three days with intravenous amoxicillin, the researchers emphasized. Sixty-three were then randomly assigned to 750 mg of oral amoxicillin (eight days' total treatment) and 56 to placebo (three days' treatment), three times daily for five days.

Sputum studies showed that pneumonia was caused by a single pathogen in 92% of the three-day group and in 75% in the eight-day group. Baseline characteristics were comparable, with the exception of symptom severity, which was worse in the three-day treatment group, the researchers said.

In the three-day and eight-day treatment groups, the clinical cure rate at day 10 (two days after oral treatment ended) was 93% for both groups and at day 28, it was 90% (three-day treatment) compared with 88% for the eight-day patients (difference 2%, ? 9% to 15%) the researchers reported.

Both groups had a similar resolution of symptoms. At day 10, radiological success rates were 86% for the three-day patients compared with 83% for the eight-day group (difference 3.0%, CI, -10%-16%). At day 28, the rates were 86% versus 79% (difference 6%, CI -7%-20%).

In the intention-to-treat analysis, 50 of 56 patients (89%) in the three-day group and 56 of 63 (89%) in the eight-day group were considered cured.

The length of hospital stay was similar in both groups. The bootstrap estimated mean length of hospital stay was 7.9 days (6.5 to 9.3 days) in the three-day group and 8.9 days (6.8 to 11 days) in the eight-day group.

Six patients (11%) in the three-day group and 13 patients in the active-treatment group reported adverse events (P=0.1). These results do not apply to patients with severe community acquired pneumonia, patients with severe immunodeficiency, or those with a significant amount of pleural fluid, the researchers said.

They also noted that the sample size in this study was moderate, leaving open the possibility of chance findings. Yet of all hospitalized patients with community-acquired pneumonia, 60% to 80% have a pneumonia severity score below 100, as do most patients not admitted to a hospital, including those seen by general practitioners, they said.

Community-acquired pneumonia is a major indication for antibiotic prescriptions in hospitals, Dr. Prins said. "Shorter treatment can help contain the growing resistance rates among respiratory pathogens," he wrote.

Dr. Prins noted that GlaxoSmithKline provided the amoxicillin and placebo capsules for this study.

In a commentary, microbiologist John Paul of Royal Sussex Hospital in Brighton, England, said that the Dutch study suggested that current guidelines recommending seven to 10 days should be revised. In fact, he said, "the lack of evidence to support short-course therapy for many common infections is surprising, and it has become accepted practice to continue treatment for days after symptoms have improved."

Not only did the study yield strong evidence in favor of short-course therapy, Dr. Paul said, but it also showed how centers might cooperate to tackle longstanding areas of uncertainty in clinical microbiology and infectious disease.

When managing treatment, many variables have to be juggled, including choice of antibiotic, the infecting agent, and the patient's immune status. Despite such difficulties, he said, the Dutch researchers have shown that "it is possible to make medicine into more of a science."