title: Effect of clarithromycin in experimental empyema by multidrug-resistant Pseudomonas aeruginosa.
abstract: Evidence from a recent randomized study of our group suggests that intravenous clarithromycin resulted in earlier resolution of ventilator-associated pneumonia. The need to understand the mechanism of action of clarithromycin guided to the study of a model of experimental empyema by multidrug-resistant Pseudomonas aeruginosa in 40 rabbits. Animals were randomized into controls (group A); treatment with clarithromycin (group B); treatment with piperacillin/tazobactam (group C); and treatment with both agents (group D). Pleural fluid was collected at regular time intervals for quantitative culture, estimation of cell apoptosis and of concentrations of tumour necrosis factor-alpha (TNFα). After 7 days, animals were euthanized for estimation of tissue growth. Bacterial growth in the pleural fluid of group D was significantly decreased compared with the other groups on day 5. Lung growth of group D was lower than group A. That was also the case of cytokine stimulation by pleural fluid samples on U937 monocytes. It is concluded that administration of clarithromycin enhanced the antimicrobial efficacy of piperacillin/tazobactam and decreased bacterial growth in the pleural fluid and in tissues. It also attenuated the pro-inflammatory phenomena induced by the β-lactam.
authors: 4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece.
authors: Eirini-Charikleia
authors: EC
authors: Tsovolou
authors: Ira-Maria
authors: IM
authors: Tzepi
authors: Aikaterini
authors: A
authors: Spyridaki
authors: Thomas
authors: T
authors: Tsaganos
authors: Vassiliki
authors: V
authors: Karagianni
authors: Evangelos
authors: E
authors: Menenakos
authors: Paraskevi
authors: P
authors: Liakou
authors: Lambros
authors: L
authors: Sabracos
authors: George
authors: G
authors: Zografos
authors: Evangelos J
authors: EJ
authors: Giamarellos-Bourboulis
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D017291:Clarithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D016724:Empyema, Pleural / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010878:Piperacillin / Q000008:administration & dosage; D000077725:Piperacillin, Tazobactam Drug Combination; D010996:Pleural Effusion / Q000276:immunology / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D020298:U937 Cells
chemical_list: D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D017291:Clarithromycin; D010878:Piperacillin
keywords: Pseudomonas aeruginosa; clarithromycin; cytokines; β-lactams