A retrospective observational study on the efficacy of colistin by inhalation as compared to parenteral administration for the treatment of nosocomial pneumonia associated with multidrug-resistant Pseudomonas aeruginosa

Abstract

BackgroundColistin is used as last treatment option for pneumonia associated with multidrug-resistant (MDR) Pseudomonas spp.. Literature about the best administration mode (inhalation versus parenteral treatment) is lacking.MethodsA retrospective study of 20 intensive care patients with a pneumonia associated with MDR P. aeruginosa receiving colistin sulphomethate sodium (Colistineb®) between 2007 and 2009 was performed. A strain was considered multidrug-resistant if it was resistant to at least 6 of the following antibiotics: piperacillin-tazobactam, ceftazidime, cefepime, meropenem, aztreonam, ciprofloxacin, and amikacin. The administration mode, predicted mortality based on the SAPS3 score, SOFA score at onset of the colistin treatment, clinical and microbiological response, and mortality during the episode of the infection were analysed. The non parametric Kruskal-Wallis and Fisher's Exact test were used for statistical analysis of respectively the predicted mortality/SOFA score and mortality rate.ResultsSix patients received colistin by inhalation only, 5 were treated only parenterally, and 9 by a combination of both administration modes. All patients received concomitant beta-lactam therapy. The mean predicted mortalities were respectively 72%, 68%, and 69% (p = 0.91). SOFA scores at the onset of the treatment were also comparable (p = 0.87). Clinical response was favorable in all patients receiving colistin by inhalation (6/6) and in 40% (2/5) of the patients receiving colistin parenterally (p = 0.06). In the patients with colistin administered both via inhalation and parenterally, clinical response was favorable in 78% of the patients (7/9) (p = 0.27 as compared to the treatment group receiving colistin only parenterally). When all patients with inhalation therapy were compared to the group without inhalation therapy, a favorable clinical response was present in respectively 87% and 40% (p = 0.06). In none of the patients, the Pseudomonas spp. was eradicated from the follow-up cultures.All patients in the parenterally treated group died. None of the patients receiving colistin by inhalation, and 3 of 9 patients of the combination group eventually died (p = 0.002 and p = 0.03 respectively as compared to the group receiving colistin only parenterally).ConclusionsAerosolized colistin could be beneficial as adjunctive treatment for the management of pneumonia due to MDR P. aeruginosa.

Potential Toxicity of Polymyxins in Human Lung Epithelial Cells

“…Pulmonary delivery of polymyxins has offered a great promise for the treatment of lung infections (13,14) caused by MDR Gram-negative pathogens, as intravenous administration leads to poor drug disposition at the infection site (7) and nephrotoxicity can occur in up to 60% of patients (9)(10)(11). However, the mechanism of polymyxin-associated pulmonary toxicity has not been examined.…”

“…efficacy superior to that of intravenous administration in the treatment of patients with ventilator-associated pneumonia (13) and other nosocomial pneumonia (14). Despite the aforementioned advantages, current inhaled polymyxin therapy is empirical and has never been optimized by using pharmacokinetics/pharmacodynamics (PK/PD).…”

Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii

“…Although there have been reports of the efficacy of nebulized colistin as monotherapy for nosocomial pneumonia caused by gram-negative bacteria, the main drawbacks of the previous studies were small number of patients, lack of a control group, and different causative microorganisms (12,13,22,23). One recent study reinforced the efficacy and safety of aerosolized colistin in the treatment of gram-negative VAP (24).…”

Inhaled Antibiotics for Gram-Negative Respiratory Infections

“…Only 3 of the other 15 patients died during the study. Nephrotoxicity was difficult to establish in this study, as many patients had baseline renal dysfunction, although patients on only inhaled colistin experienced less toxicity than did those in the other two groups (300). Although this study included a very small number of patients, in general, the patients receiving inhaled colistin either alone or with i.v.…”