Should Aerosolized Antibiotics be Used to Treat Gram-Negative, Multidrug-Resistant, Ventilator-Associated Pneumonia?
By Richard H. Kallet, MS, RRT, FAARC, FCCM, Director of Quality Assurance, Respiratory Care Services, San Francisco General Hospital
Mr. Kallet reports no financial relationships relevant to this field of study.
Synopsis: This prospective, single-center, comparative observational study found aerosolized colistin to be effective in treating ventilator-associated pneumonia caused by multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii.
Source: Lu Q, et al. Efficacy of high-dose nebulized coilstin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acincetobacter baumannii. Anesthesiology 2012;117:1335-1347.
Lu et al prospectively studied 165 patients with culture-confirmed (bronchoalveolar lavage samples), ventilator-associated pneumonia (VAP) caused by either Pseudomonas aeruginosa or Acinetobacter baumannii. Antibiotic therapy was based on antibiotic sensitivity. A cohort of 122 patients had strains that were susceptible to beta-lactam antibiotics; these patients were treated with a 14-day course of systemic beta-lactam antibiotics, supplemented with a 3-day course of either an aminoglycoside or a quinolone. The remaining 43 patients had multidrug-resistant (MDR) strains and were treated for up to 14 days (or until extubation) with high-dose (400 mg) aerosolized colistin every 8 hours. A state-of-the-art vibrating-mesh nebulizer (AeronebTM), in conjunction with a comprehensive ventilator and sedation protocol, was used to maximize lower respiratory tract antibiotic deposition. Twenty-eight patients (65%) in the MDR cohort received antibiotic monotherapy, whereas the managing physicians chose to supplement therapy with a 3-day systemic course with an aminoglycoside in the remaining 15 patients.
The average duration of aerosolized antibiotic therapy in the MDR cohort was 12 days with a reported cure rate of 67%, compared to 66% in the beta-lactam susceptible cohort who received systemic antibiotic therapy. Also, there was no difference in the cure rate between those who received aerosolized antibiotic monotherapy (68%) and those who also received supplemental systemic antibiotic therapy (67%). In the MDR cohort, there was a nonsignificant trend toward a higher incidence of both persistent VAP at day 14 (31% vs 19%, P = 0.12) and recurrent VAP after day 14 (26% vs 10%; P = 0.16), as compared to the beta-lactam susceptible cohort. Only two patients (4.7%) receiving aerosolized colistin showed evidence of acquired antibiotic resistance. All-cause ICU mortality also was not different between cohorts.
Commentary
VAP is the leading cause of death among critically ill patients with hospital-acquired infection and accounts for more than 50% of antibiotic use in some ICUs. Pulmonary infections caused by Pseudomonas aeruginosa are particularly problematic as they are characterized by both recurrent infection and a high tendency toward antibiotic resistance despite appropriate antibiotic management.1 The difficulty in achieving a pulmonary drug concentration capable of eradicating bacterial reservoirs residing within thick secretions and biofilm limits the effectiveness of systemic antibiotic therapy. Moreover, systemic antibiotic therapy requires drug dosages that increase the likelihood of systemic toxicity, as well as eliminate the normal flora of the gastrointestinal tract that paradoxically promotes the selection of MDR organisms.
For several decades, aerosolized antibiotics have been used successfully to treat both cystic fibrosis and Pneumocystis jiroveci pneumonia. The recent advent of high-efficiency, vibrating-mesh nebulizer technology represents an important advance in aerosolized antibiotic therapy. The current study by Lu and colleagues adds to a growing body of literature suggesting that the administration of aerosolized antibiotics may be a more effective strategy to treat VAP, particularly in cases caused by MDR microorganisms. Particular attention should be focused on ventilator settings, circuit conditions, and patient-ventilator synchrony, as described by Lu and colleagues. This underscores what is needed to maximize lower respiratory tract drug deposition and largely determines whether aerosolized antibiotic therapy can be effective in treating VAP.
Unfortunately, most available studies on this topic have been either relatively small randomized, controlled trials or uncontrolled studies, some with methodological concerns. Therefore, lacking a sufficiently large Phase III randomized, controlled trial, aerosolized antibiotics cannot be advocated for general use in the treatment of VAP. However, it is reasonable to consider using aerosolized antibiotics in highly selected individual cases of VAP caused by MDR microorganisms that are unresponsive to traditional intravenous antibiotic therapy, or when avoiding renal toxicity is of paramount importance.
Reference
- Rello J, et al. Recurrent Pseudomonas aeruginosa pneumonia in ventilated patients: Relapse or reinfection? Am J Respir Crit Care Med 1998;157: 912-916.
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