Colistin in Ventilator-Associated Pneumonia

It is interesting to observe how advances in research, as well as unmet medical needs, change attitudes and decisions in clinical practice. The expansion of use of intravenous colistin for the treatment of patients with multidrug-resistant (MDR) gram-negative bacterial infections is certainly such an example. Even a few years ago there were many opponents to the use of colistin. The medication was not considered adequately effective. More so, most considered its use to be probably dangerous because of safety issues. Others questioned the scientific validity of the various studies that emerged on the clinical effectiveness and safety of colistin. However, the necessity to treat infections due to MDR gram-negative bacteria led to the revival of colistin in clinical practice at the dawn of the 21st century [1]. In this issue of Clinical Infectious Diseases, Florescu et al [2] specifically evaluate the published clinical evidence on the use of colistin for ventilator-associated pneumonia (VAP). They conclude that the effectiveness and safety of colistin are not statistically different from those of frontline antibiotics for the treatment of VAP. Indeed, their meta–regression analysis shows no significant change in clinical response after controlling for concomitant antibiotic treatment. Their analysis reinforces that colistin is indeed an effective and acceptably safe choice in the treatment of VAP in the era of ‘‘bad bugs—no drugs.’’ The conclusion of this study is significant as it conveys the current standing of the therapeutic role of colistin in VAP. It is of particular importance because there have been concerns in the past regarding the pharmacokinetics and pharmacodynamics of colistin, especially whether the drug could achieve appropriate levels in the lung. This hesitation by physicians to use colistin in its intravenous and nebulized forms is interesting because colistin has been used uninterruptedly during the last decades in patients with cystic fibrosis for severe Pseudomonas aeruginosa respiratory tract infections. Gradually, the use of colistin has entered successfully clinical practice mainly in the intensive care unit (ICU) setting in most parts of the world, including now the United States [3]. More so, various patient populations have received colistin (intravenously and/or nebulized) including neonates, children [4], and patients with cancer [3]. To address the effectiveness of colistin in the treatment of VAP is far from an easy task. It is important that one be aware of the differences in the groups compared. It is almost predictable that colistin is administered in patients in whom there is no other therapeutic choice. In contrast, in the comparator group, there are always more classes of antibiotics that could be used. This difference may be an important confounding factor when comparing outcomes. Also, the attributable mortality associated with MDR bacteria, including Acinetobacter baumannii, cannot be questioned nowadays, because inappropriate empirical antibiotic treatment is associated with increased mortality [5]. Hence, physicians use colistin mostly when there is resistance to all other available antibiotics (including carbapenems) or when clinical failure ensues after using other antibiotics or even empirically in the ICU setting when MDR, extensively drug-resistant (XDR), or pandrug-resistant (PDR) [6] gram-negative bacteria constitute a significant proportion of isolated bacteria. Obviously, one would not consider treating carbapenem-resistant bacteria with carbapenem monotherapy nor carbapenem-susceptible bacteria with colistin monotherapy as this would be not considered medically acceptable. However, one must take this very point into consideration, namely, that colistin was used in the published studies in a potentially different patient population against that of other comparators. Although the APACHE score may help us in the Received 31 October 2011; accepted 7 November 2011. Correspondence: Matthew E. Falagas, MD, MSc, DSc, Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos St, 151 23 Marousi, Athens, Greece (m.falagas@aibs.gr). Clinical Infectious Diseases 2012;54(5):681–3 The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/cir931