Newer antibacterial agents and their potential role in cystic fibrosis pulmonary exacerbation management--authors' response

Sir, In response to the comments of Cooreman and Jeurissen1 on our recent article2 we would like to make several clarifications. Although Pseudomonas aeruginosa remains the most commonly isolated pathogen in cystic fibrosis (CF), this pattern is changing. The practice of early eradication of P. aeruginosa with aerosolized antibiotics has become the standard of care.3 In clinics in which this practice has been aggressively adopted, P. aeruginosa prevalence rates have dwindled to <5% in those CF patients <18 years of age.4 Accordingly, CF physicians are increasingly treating pulmonary exacerbations (PEx) caused by pathogens other than P. aeruginosa such as Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Staphylococcus aureus and so on. It is PEx with these pathogens, and not P. aeruginosa, for which we have advocated the use of tigecycline, as clearly indicated in our review. The FDA has recently released a drug safety communication cautioning practitioners on the use of tigecycline in severe infections based on the pooled analysis of 13 trials involving >7000 patients where all-cause mortality was observed to be increased by 0.6% [95% confidence interval (CI) 0.1–1.2] relative to comparator antibiotics.5 However, the FDA did not warn that tigecycline should not be used in pulmonary infections as asserted by Cooreman and Jeurissen.1 Furthermore, community-acquired pneumonia remains an approved indication for the use of tigecycline. Most of the increased mortality in tigecycline-treated patients was attributable to hospital-acquired pneumonia, in particular, ventilator-associated pneumonia (VAP). This observation may not be relevant to CF PEx, a disease for which no antibiotic has an FDA-approved indication. PEx in CF are overwhelmingly caused by chronically colonizing pathogens and not through the new acquisition of pathogens,6,7 and as such the empirical provision of PEx antibacterials based on prior sputum results is commonplace and supported. The bacteriostatic nature of tigecycline, postulated to be a potential detractor in the management of respiratory infections, is not relevant in CF PEx as eradication of chronically infecting pathogens is generally not possible.3 The use of tigecycline in CF has been reported only rarely, but clinical outcomes have been favourable.8 CF-specific pharmacokinetic data for tigecycline (as well as for many antibiotics) continue to be lacking and the lower AUC data observed in patients in tigecycline trials with VAP and associated lower clinical cure rates9 emphasize the importance of understanding the pharmacokinetics of antimicrobials in disease-specific settings. With the increasing burden of multidrug-resistant pathogens in CF and their associated increased risk of mortality,10 new therapeutic options are desperately required. J. S. E. has consulted for Bayer and Gilead. M. D. P. has none to declare.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.