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

Pseudomonas aeruginosa PAO1 became considerably more sensitive to the actio n of ampicillin when grown in the presence of certain phospholipids. Only p hospholipids capable of forming lipid bilayers or micelles proved to be cap able of enhancing ampicillin activity. Of the phospholipids tested, 1-palmi toyl-2-hydroxy-sn-glycero-3-phosphate, also called monopalmitoylphosphatidi c acid (MPPA), was the best enhancer. in the absence of MPPA, the MIC and M BC 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. MP PA 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 t he growth of four mucoid multiply antibiotic-resistant strains of P. aerugi nosa recently isolated from the sputum of cystic fibrosis patients, and enh anced their sensitivity to piperacillin. It also increased the sensitivity of two ceftazidime-resistant P. aeruginosa cystic fibrosis strains to cefta zidime.