Antimicrobial Chemotherapy in Cystic Fibrosis Patients

Abstract

Høiby, N., Friis, B., Jensen, K., Koch, C, Møller, N.E., Støvring, S. and Szaff, M. (Statens Seruminstitut, Departments of Clinical Microbiology at Rigshospitalet and Hvidovre Hospital, and Paediatric Department TG, Rigshospitalet, Copenhagen, Denmark). Antimicrobial chemotherapy in cystic fibrosis patients. Acta Paediatr Scand 1982; suppl 301: 75‐100. — Every effort should be undertaken to combat recurrent and chronic bacterial respiratory tract infections in patients with cystic fibrosis because infections are the main pathogenetic factors of lung damage in these patients. The principles and antibiotics used to treat bacterial infections in the Danish Cystic Fibrosis centre are outlined. The chemotherapy is based on microbiological diagnosis of secretions from the lower respiratory tract. S. aureus infections are efficiently treated with oral fusidic acid in combination with isoxazolyl penicillins or rifampicin in case of penicillin allergy or methicillin‐resistant S. aureus. H. influenzae infections are treated efficiently with oral pivampicillin or amoxicillin or with erythromycin sometimes in combination with rifampicin in case of penicillin allergy or ampicillin‐resistant H. influenzae. As a result of the efficient chemotherapy S. aureus and H. influenzae infections are now minor problems generally not related to prognosis of cystic fibrosis patients. Chronic P. aeruginosa infections are treated regularly four times per year with intravenous anti‐pseudomonas β‐lactam antibiotics in combination with tobramycin. P. aeruginosa is rarely permanently eradicated by this treatment, but significantly improved survival of the patients is obtained. The problems of resistant bacterial strains, allergy, and other side effects caused by the antibiotics are discussed.

Dynamic interactions of biofilms of mucoid Pseudomonas aeruginosa with tobramycin and piperacillin

“…Despite the use of aggressive antibiotic therapy in the treatment of Pseudomonas infections in CF patients (15), eradication of the organism from the lungs of CF patients is difficult to achieve at present (15,21,25,30). It has been suggested that this is because of the biofilm mode of growth of the organism in the lungs of CF patients (8,19,24).…”

High-level beta-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment

“…,B-Lactam antibiotics in combination with tobramycin are the drugs of choice for the treatment of these patients, but the development of resistance is a common problem (7,9,16). Even when an apparently susceptible P. aeruginosa isolate is cultured from the patients prior to and during the treatment, the P-lactam antibiotics often seem to be ineffective.…”

“…A total of 43 patients with CF who produced large amounts of purulent (dark green) sputum (3 to 5 ml per sample) entered the study. The patients had suffered from chronic bronchopulmonary P. aeruginosa infection for more than 3 years and had a mean number of precipitating antibodies to P. aeruginosa of 31 (range, 18 to 50 normal values; 0 to 1 precipitins) (7). The patients had previously received between 12 and 30 courses of antibiotics.…”

“…pulmonary testing, and bacteriological investigation. The principles of the antibiotic treatment policy have previously been published in detail (7). In summary, they are the requirement of bacteriological diagnosis based on sputum samples before chemotherapy is initiated.…”

“…Another possibility is that the P-lactam antibiotic is inactivated in the lungs by 3-lactamases. Chromosomal ,-lactamases of the Richmond and Sykes (11) class I are inducible in most strains of P. aeruginosa (7), and the inducibilities of these enzymes are associated with several resistance problems. In a previous study (5), we have shown a rapid emergence of resistance in P. aeruginosa in patients with CF because of in vivo selection of '-lactamase-producing strains that exhibit stable partial derepression of the class I enzyme, supporting the importance of ,-lactamase production as a major resistance mechanism in patients with CF.…”