The Treatment of Respiratory Pseudomonas Infection in Cystic Fibrosis

Abstract

Pseudomonas aeruginosa is a non-capsulate and non-sporing Gram-negative bacillus that most commonly affects the lower respiratory system in humans. Burkholderia (previously Pseudomonas) cepacia has emerged as an important respiratory pathogen in patients with cystic fibrosis (CF). The ability of P. aeruginosa to persist and multiply in moist environments and equipment, such as humidifiers in hospital wards, bathrooms, sinks and kitchens, maybe of importance in cross-infection. P. aeruginosa infections of the lower respiratory tract can range in severity from colonisation (without an immunological response) to a severe necrotising bronchopneumonia. Infection is seen in patients with CF and other chronic lung diseases such as non-CF bronchiectasis. In patients with CF, once P. aeruginosa is established in the airways it is almost impossible to eradicate, but prior to this, aggressive treatment can delay the development of chronic infection. 30 to 40% of the present paediatric population with CF will have chronic pseudomonal infection. B. cepacia has a particular predisposition to infect patients with CF and may be distinguished from P. aeruginosa by accelerated lung disease in about one-third of patients. Overwhelming septicaemia and necrotising pneumonia are well described (cepacia syndrome); events that are rare with P. aeruginosa. With the propensity for social cross-infection, segregation policies have been accepted as means of controlling outbreaks. A number of antipseudomonal agents are available. The most commonly used are the extended-spectrum penicillins, aminoglycosides, cephalosporins, fluoro-quinolones, polymixins and the monobactams. An aminoglycoside with a β-lactam penicillin is usually considered to be the first line treatment. No trial has shown any significant clinical advantage of any particular combination regimen over another. The emergence of resistance continues to be a concern. Pipericillin, piperacillin/tazobactam and meropenem have good but equivalent antibacterial activity against P. aeruginosa. However, B. cepacia is characterised by in vitro resistance to colistin (colomycin), aminoglycosides and ciprofloxacin but better susceptibility to ceftazidime. Nebulised delivery of antipseudomonal antibiotics is thought to prevent recurrent exacerbations, reduce antibiotic usage and maintain lung function, particularly in patients with CF. Colistin, tobramycin and gentamicin are currently the most commonly prescribed nebulised antibiotics. Much effort is directed at treating chronic P. aeruginosa infection but as chronic infection is seldom if ever eradicated when first established, prevention is preferable. Early intensive treatment for P. aeruginosa infection is advocated in order to maintain pulmonary function and postpone the onset of chronic P. aeruginosa infection.