DI MODUGNO E, ANDREETTA V, ZANONCELLI A, PICCOLI L, CRISTOFORI P, FAUSTINELLI I, GOZZI A; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. B-985.

GlaxoSmithKline, Verona, Italy

BACKGROUND: Azithromycin (AZI) is a macrolide antibiotic with a peculiar pharmacokinetic profile, showing a marked tropism toward infected tissues and low serum concentrations. This aspect has raised some concern about the efficacy of AZI for the treatment of pneumococcal pneumonia, which frequently evolves into septicemia. The efficacy of AZI at a dosage resembling the serum AUC achieved in humans was investigated in murine pneumonia caused by two S. pneumoniae (SP) isolates with different invasive properties. METHODS:Pneumonia in ICR mice was induced by intranasal instillation of 10[7] CFU of either Sp Bg1 (type 3) or Sp 30 (type 19). MIC of AZI for the two strains was 0.06 and 0.015 mg/ml, respectively. AZI was given orally at 20 mg/kg once a day starting 6 h after infection (a.i.) and maintained for up to 3 days. Survival rate, bacterial growth in blood and lungs, cytokine release, and histopathology of lungs were performed at various times a.i. RESULTS: Both strains induced a 100% lethal infection, although differences in the progression of the pathology were seen. As expected, Sp Bg1 induced an acute inflammatory reaction in lungs with prominent vascular involvement and rapid onset of bacteremia, whereas Sp 30 caused a non-septicaemic pneumonia. AZI treatment ensured survival of mice, and led to complete lung eradication of both pathogens after 78 h of therapy. In Bg1-infected mice, blood sterility was achieved after 48 h of therapy. AZI was also effective in progressively reducing the deleterious release of IL-6, TNF-a and IFN-g in lungs and serum of infected mice. CONCLUSION: Despite an unfavorable serum PK profile, the therapeutic efficacy of AZI against S. pneumoniae isolates appeared unaffected by the different pathological evolution between localized and bacteremic murine pneumococcal pneumonia.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Anti-Bacterial Agents
• Azithromycin
• Cytokines
• Humans
• Inflammation
• Interleukin-6
• Lung
• Mice
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Inbred ICR
• Microbial Sensitivity Tests
• Pneumonia, Pneumococcal
• etiology
• microbiology

Other ID:

• GWAIDS0030833

UI: 102270470

From Meeting Abstracts