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Successful Use of Azithromycin as Adjunctive Therapy for Pseudomonas aeruginosa Sepsis in a Murine Model.

DOWDY L, CASTRO JG, AGER A, MARTINEZ O; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 54 (abstract no. 788).

Univ. of Miami, Miami, FL.

BACKGROUND: By conventional criteria macrolides have no therapeutic activity against Pseudomonas aeruginosa. However, it has been shown in vitro that macrolides suppress production of some toxins in P. aeruginosa. The objective of this study was to evaluate the effect of azithromycin adjunctive therapy on survival in mice with P. aeruginosa sepsis. Materials andMETHODS: Pathogen-free male Balb-C mice were housed in sterile cages with filter hoods and given sterile diet and water. Each of four groups of 25 mice received ampicillin (200 mg/kg /d) by intraperitoneal (IP) injection on days 1 to 5 to disturb the intestinal flora, and cyclophosphamide IP (250 mg/kg/d) on days 6 and 9. P. aeruginosa strain ATCC 27854 (in sterile water at a concentration of 10[7 ] cfu/ml) was fed to groups B, C, and D for 24 hours in their drinking water, on days 2 and 5. Group A was not infected. On day 8, antibiotics were started as follows: Group A: piperacillin (PIP) 200 mg/kg twice a day, IP; tobramycin (TBR) 5 mg/kg/d once a day, IP; and azithromycin (ZTH) 20 mg/kg/d once a day, orally. Group C: PIP and TBR. Group D: PIP, TBR and ZTH. Group B was not given antibiotics. Antibiotics were continued for 10 days. Spleen homogenates from two mice per group were cultured. Crude mortality at day 14 was compared using the chi square test.RESULTS: The overall mortality rate in the study was 35% (35/100). Mortality in group A was 12% (3/25), in group B, 96% (24/ 25), in group C, 92% (23/25), and group D was 60% (15/25). There was a statistically significant difference in the mortality rate between groups C and D (P < 0.05), and between groups D and A (P < 0.10). The cultures from the spleen from the mice in groups B, C, and D yielded pure growth of P. aeruginosa, those cultures from the mice in group A were negative.CONCLUSION: The use of azithromycin as adjunctive therapy in the treatment of endogenous P. aeruginosa sepsis in mice significantly reduced the mortality compared to standard therapy.

Publication Types:
  • Meeting Abstracts
Keywords:
  • Animals
  • Anti-Bacterial Agents
  • Azithromycin
  • Bacteremia
  • In Vitro
  • Intestines
  • Male
  • Mice
  • Models, Biological
  • Muridae
  • Piperacillin
  • Pseudomonas Infections
  • Pseudomonas aeruginosa
  • Sepsis
  • Tobramycin
  • therapy
Other ID:
  • GWAIDS0007323
UI: 102244819

From Meeting Abstracts




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