Aerosol Polymyxin and Pneumonia in Seriously Ill Patients

Abstract

Pneumonia caused by Pseudomonas aeruginosa occurs frequently in critically ill patients and is associated with a mortality rate of 70 per cent. An aerosol of polymyxin B was administered (2.5 mg per kilogram per day) to the upper airways of 292 patients in a respiratory-surgical intensive-care unit during a seven-month period, in an attempt to prevent Ps. aeruginosa pneumonia. Although only one of the patients studied acquired pneumonia due to Ps. aeruginosa, 10 others acquired pneumonia caused by a polymysinx-resistant organism. Seven pneumonias were caused by organisms not frequently pathogenic to man (flavobacteria, serratia and Streptococcus faecalis). The mortality rate for acquired pneumonia in this study, 64 per cent, is greater than that in previous studies in which either no polymyxin or cyclic polymyxin therapy was used. Continuous use of polymyxin B aerosol appears to be a dangerous form of therapy.

Intratracheal Administration of Antimicrobial Agents in Mechanically Ventilated Adults: An International Survey on Delivery Practices and Safety

“…[4][5][6] Forty years ago, studies were published suggesting that aerosolized polymyxins administered to critically ill subjects could decrease the rate of nosocomial bronchopneumonia. 7,8 The technique, however, was abandoned due to the development of antibiotic resistance and questionable efficacy and/or frequent adverse events.…”

Pharmaceutical strategies to prevent ventilator-associated pneumonia

“…Unfortunately, the short duration of SDD regimens means that there is insufficient data regarding their long-term microbiological effects, unlike early studies using long-term tracheal instillation of antibiotics, which reported the emergence of MDR bacteria (Feeley et al 1975). To demonstrate a significant reduction in mortality, a larger number of patients would have to be investigated than has been the case to date.…”

“…Although overt infection with MDR bacteria has not been reported, this does not mean that the use of SDD, if applied on a larger scale, would not lead eventually to the emergence of resistance. Unfortunately, in light of the short duration of SDD regimens, there is insufficient information about the long-term microbiological effect, whereas early studies using long-term tracheal instillation of antibiotics have reported the emergence of MDR bacteria (Feeley et al 1975). To demonstrate a significant reduction in mortality, larger number of patients would have to be investigated than has been the case to date.…”

“…Klick et al (1975), using aerosolised polymixin directly into the oropharynx, decreased upper-airway Gram-negative colonisation in ICU patients. When used continually, rather than intermittently, oropharyngeal antibiotics were associated with an increased incidence of pneumonia with resistant bacteria and this regimen was abandoned (Feeley et al 1975). Palmer et al (1998) demonstrated that nebulised antibiotics can be effectively delivered to patients receiving mechanical ventilation, with measurable changes in clinical and airway inflammatory indicators (decreased levels of inflammatory cells and mediators), significant reduction in sputum volume, and eradication of P. aeruginosa and other Gram-negative pathogens in most cases.…”

Actualización Consenso Neumonía asociada a ventilación mecánica: Segunda parte. Prevención

“…La mayoría de sus aplicaciones han sido relacionadas a terapia, habiendo mucha menor información respecto a profi laxis 80 . Los trabajos iniciales para esta intervención (utilizando polimixina B en faringe y tubo endotraqueal) mostraron en una serie controlada, en que no todos los pacientes se encontraban en ventilación mecánica, una disminución de la colonización por P. aeruginosa 81 , por lo que posteriormente el mismo grupo realizó un estudio no controlado que mostró baja incidencia de neumonía por este microorganismo, pero aumento de la neumonía por bacilos gramnegativos resistentes a polimixina B, con una alta mortalidad asociada 82 . Otro estudio similar, en 744 pacientes utilizando polimixina B en aerosol en pacientes no necesariamente en ventilación mecánica, pero usando ciclos de dos meses para enrolar pacientes que se asignaban a control o placebo, demostró disminución de la colonización por P. aeruginosa, pero sin cambios en la mortalidad 83 ; asimismo, hubo una tendencia a la disminución en la neumonía nosocomial por este agente.…”