L-679. Dichotomy Between In Vitro and In Vivo: Does Azithromycin Extended Release (AZM-ER) Show Clinical Efficacy in Macrolide Resistant Pneumococcal Pneumonia?
Session: Poster Session: The World of Community-Acquired Pneumonia
Saturday, October 25, 2008: 12:00 AM
Room: Hall C
Background: In the treatment of pneumococcal pneumonia, it has been reported that macrolides can demonstrate clinical effects even if isolates are resistant to macrolides. This discrepancy is referred to as thein vivo-in vitro paradox”, and controversies are arising. We conducted a phase 3 trial of AZM-ER in Japanese adults to evaluate clinical efficacy in CAP caused by S. pneumoniae, which provides an insight into this paradox. Methods: This was a multicenter, open label study. AZM-ER (2 g single-dose) was administered to 153 adults with mild to moderate CAP. Clinical and bacteriological parameters were assessed at baseline, 7 days and 15 days after dosing. Causative organisms were isolated from clinical specimens for susceptibility test and genotyping of mef (A) and erm (B) by PCR (for isolates with MIC > 0.5 μg/mL). Results: Of 153 enrolled CAP patients, causative organisms were isolated from 82 patients (53.6%). S. pneumoniae was isolated from 21 patients; 7 of these isolates were susceptible to AZM (MIC < 0.25 μg/mL) whereas 14 isolates (66.7%) were resistant. Of 14 resistant strains, only 2 strains showed relatively low MIC (4 μg/mL) and had only mef (A) gene. The other 12 strains were highly resistant (MICs > 64 μg/mL), and 11 of 12 had only the erm (B) gene. A single isolate was positive for both the mef (A) and erm (B) genes. Despite dominance of macrolide-resistant strains, clinical efficacy was observed in 20 of 21 patients (95.2 %) and bacterial eradication was achieved in 18 of 21 (85.7 %) patients. Conclusion: AZM-ER demonstrated excellent clinical and bacteriological effect on pneumococcal pneumonia in spite of high MIC and resistance gene development. The current study has revealed the unique property of AZM-ER against S. pneumoniae; clinical and bacteriological effects in vivo can be anticipated in most patients despite low susceptibility to AZM suggested by in vitro testing.
Akira Watanabe1, Masahito Nagashima2, Nobuki Aoki1, Shigeru Kohno, MD, PhD3, Yoshihito Niki1 and  S. Kohno,
Pfizer Role(s): Research Relationship, Received: Research Grant.
Bayer Role(s): Research Relationship, Received: Research Grant.
Janzen Role(s): Research Relationship, Received: Research Grant.
Dainipponsumitomo Role(s): Research Relationship, Received: Research Grant.
Shionogi Role(s): Research Relationship, Received: Research Grant.
Merck Role(s): Research Relationship, Received: Research Grant., (1)AZM-ER Phase III Study Group, (2)Pfizer Japan Inc., (3)Nagasaki University School of Medicine, 1-7-1 Sakamoto, Japan