Last update:
   09-Jul-2004
 

Arch Hellen Med, 19(5), September-October 2002, 553-560

ORIGINAL PAPER

Enhancement by arachidonic acid of the activity of antibiotics
on experimental by multidrug-resistant Pseudomonas aeruginosa sepsis

S. SKIATHITIS,1 Ε.J. GIAMARELLOS-BOURBOULIS,2 Th. ADAMIS,1
M. MOUKTAROUDI,2 V. KOUSOULAS,3 L. SAMPRAKOS,1
A. DIONYSSIOU-ASTERIOU,3 P.E. KARAYANNACOS,1 H. GIAMARELLOU2
1Department of Experimental Surgery and Surgical Research
24th Department of Internal Medicine
3Department of Biological Chemistry, University of Athens, Medical School, Greece.

OBJECTIVE Treatment of experimental multidrug-resistant Pseudomonas aeruginosa sepsis with intravenous co-administration of arachidonic acid (AA), ceftazidime and amikacin.

METHOD The study was conducted using 21 rabbits, of which 5 were used for the determination of the dose of AA, 5 became septic and were left untreated as controls, 5 became septic and were treated with ceftazidime and amikacin, 5 became septic and were treated with ceftazidime, amikacin and AA, and one became septic and was treated with ceftazidime, amikacin and the diluent of AA. Sepsis was induced by intravenous (IV) administration of one multidrugresistant P. aeruginosa isolate and treatment was given thirty minutes after bacterial challenge. Ceftazidime was administered by bolus IV at 50 mg/kg, amikacin by bolus IV at 15 mg/kg and AA at 25 mg/kg within 10 minutes. Hemodynamic monitoring was performed and blood was sampled at regular time intervals for quantitative culture and determination of the concentrations of malonodialdehyde (MDA), endotoxins (LPS) and antimicrobials. Three hours after treatment the animals were sacrificed and tissue samples were collected for culture.

RESULTS Both the controls and the animals treated with ceftazidime and amikacin showed hemodynamic instability characterized by wide fluctuations of blood pressure and bradycardia. Administration of AA resulted in fall of blood pressure followed by stabilization and adequate pulse rate. Reduction of viable cell counts was detected in the blood 3,0 hours after AA administration, and in the mesenterial lymph nodes and the lung. MDA concentrations were raised after the administration of AA whereas concentrations of LPS were similar in all study groups. No correlation was found between MDA and drug levels.

CONCLUSIONS AA administered with ceftazidime and amikacin holds new promise for the treatment of multidrug-resistant P. aeruginosa sepsis. Its therapeutic activity might be attributed to its peroxidation properties.

Key words: Amikacin, Arachidonic acid, Ceftazidime, Pseudomonas, Sepsis.

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