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Journal of Antimicrobial Chemotherapy (2000) 46, 377-384
© 2000 The British Society for Antimicrobial Chemotherapy

Specific phospholipids enhance the activity of ß-lactam antibiotics against Pseudomonas aeruginosa

Karen A. Krogfelta,*, Maryjane Utleyb, Howard C. Krivanc, David C. Lauxb and Paul S. Cohenb

a Department of Gastrointestinal Infections, Statens Serum Institut, 2300 Copenhagen S, Denmark; b Department of Biochemistry, Microbiology and Molecular Genetics, University of Rhode Island, Kingston, RI 02881; c Legere Pharmaceuticals Inc., Carson City, NV 89706, USA

Pseudomonas aeruginosa PAO1 became considerably more sensitive to the action of ampicillin when grown in the presence of certain phospholipids. Only phospholipids capable of forming lipid bilayers or micelles proved to be capable of enhancing ampicillin activity. Of the phospholipids tested, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphate, also called monopalmitoylphosphatidic acid (MPPA), was the best enhancer. In the absence of MPPA, the MIC and MBC of ampicillin for P. aeruginosa PAO1 were 1 and 2 g/L, respectively. In the presence of MPPA, the MIC and MBC were 20 and 40 mg/L, respectively. MPPA was shown to enhance ampicillin activity by binding both Ca2+ and Mg2+, suggesting that the mechanism of enhancement is similar to that previously reported for Ca2+ and Mg2+ chelators. Surprisingly, MPPA by itself slowed the growth of four mucoid multiply antibiotic-resistant strains of P. aeruginosa recently isolated from the sputum of cystic fibrosis patients, and enhanced their sensitivity to piperacillin. It also increased the sensitivity of two ceftazidime-resistant P. aeruginosa cystic fibrosis strains to ceftazidime.

* Corresponding author. Tel: +45-3268-3745; Fax: +45-3268-8238; E-mail: kak{at}ssi.dk


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