MILAN, ITALY—Chlamydia pneumoniae, the most common nonviral intracellular respiratory pathogen, is thought to contribute to chronic bronchitis. A recent study associated C pneumoniae infection with higher functional impairment and elevated rates of acute exacerbations in patients with chronic bronchitis.[1] Further, it found even extended antibiotic treatment only partially effective in clearing the pathogen.

“C pneumoniae appears to be involved in about 4% of acute exacerbations, but we also know that C pneumoniae can sustain chronic infection,” explained Francesco Blasi, MD, Professor in the Institute of Respiratory Diseases at the University of Milan. In addition to investigating chronic infection’s etiological role, he and colleagues sought to eradicate the microbe using the macrolide azithromycin, “which, in vitro, has excellent activity against C pneumoniae,” he noted.

The researchers first examined the relationship between pulmonary function and C pneumoniae infection in 42 chronic bronchitis patients who had not experienced acute exacerbations within the preceding four weeks. During a 12-month period, sputum samples collected every four weeks were tested for C pneumoniae colonization using culture and polymerase chain reaction (PCR).

LOWER FEV1, MORE COINFECTIONS

Forced expiratory volume in one second (FEV1) measured above 50% of expected in only one quarter and was below 35% in half of the 16 PCR-positive patients. By contrast, FEV1 was greater than 50% in 16 of 26 PCR-negative patients (62%) and was lower than 35% in only two (8%). Sputum samples testing positive for chlamydia by PCR also contained a significantly higher number of other pathogens than did the samples that tested negative for C pneumoniae.

CHRONIC INFECTION RAISES EXACERBATION INCIDENCE

The researchers then examined the relationship of C pneumoniae infection to exacerbation rates in an additional 141 patients with mild to moderate chronic bronchitis. Serum samples from 80 (57%) patients tested positive for C pneumoniae by PCR. Said Dr. Blasi, “When we followed the patients for two years, we found that patients who had demonstrated C pneumoniae in the blood … had a higher number of exacerbations when compared to PCR-negative” patients: On average, the two groups had 2.03 and 1.43 exacerbations, respectively.

Thirty-four of the 61 PCR-positive patients who suffered an acute exacerbation agreed to receive a six-week course of azithromycin. Clearance was achieved in only 20 (59%) of these patients by the end of treatment; approximately two months later, only 10 (29%) of the patients remained clear as shown by PCR. However, serologic evaluation indicated reinfection or reactivation of C pneumoniae infection in only two of the 34 patients.

Dr. Blasi concluded, “Six weeks of treatment are not enough … to eradicate the bacteria.” Still, antibiotics “can probably reduce the burden of infection,” he suggested; thus, treatment could reduce inflammation.

WHY IS CHLAMYDIA HARD TO KILL?

First, the microbe’s intracellular location requires a penetrant antibiotic, limiting choices. Second, C pneumoniae’s slow 72-hour replication cycle renders it resistant to antibiotics. Third, treatment may prompt the microbe to adopt an alternative phenotype with even slower replication and protein synthesis, “so the antibiotics are not active—it’s quite difficult to eradicate,” Dr. Blasi explained.

—Mimi Zucker, PhD