Ceftolozane/Tazobactam for Treating Children With Exacerbations of Cystic Fibrosis Due to Pseudomonas aeruginosa: A Review of Available Data

Abstract

Ceftolozane-tazobactam is a novel fifth-generation cephalosporin/β-lactamase inhibitor combination recently approved for treatment of both complicated intra-abdominal and urinary tract infections in adults. Considering its potent bactericidal activity against Pseudomonas aeruginosa, it might represent an important option also for treating children with exacerbations of cystic fibrosis due to Pseudomonas aeruginosa when other alternative treatments have been exhausted. We hereby review available data on the use of ceftolozane-tazobactam in children, focusing on cystic fibrosis.

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis

“…Currently, real-world data is scarce and does not show superiority of an agent compared to another and therefore the choice of antimicrobial therapy should be based on the susceptibility profile which can vary according to the local epidemiology with regional variability [ 81 ]. Since the introduction of C/T, case reports and case series of MDR P. aeruginosa infections treated with C/T have demonstrated the clinical efficacy of this formulation, including its use to treat infections in critically ill patients, and those with cystic fibrosis [ 82 , 83 ]. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recent guidelines for the treatment of infections caused by MDR Gram-negative bacilli suggest treatment with C/T as the single first choice for severe pseudomonal infections like severe sepsis [ 35 ].…”

Trends of Antimicrobial Resistance and Combination Susceptibility Testing of Multidrug-Resistant Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients: a 10-Year Update

“…The use of antimicrobials has been demonstrated to greatly improve the life expectancy of CF patients (15). However, a major drawback of this management approach is the development of antimicrobial resistance due to exposure to several multiple antimicrobial cocktails (1)(2)(3)(4)16). To manage infective pulmonary exacerbations, CF patients are treated with antimicrobial combinations of which one/both are generally effective as single agents and there is a lack of evidence guiding the clinician to decide the best antimicrobial combination that would give a positive treatment outcome (5).…”

“…In cystic fibrosis (CF) patients, Pseudomonas aeruginosa is the most commonly isolated pathogen and more than 70% of CF patients are colonized with this bacterium by the age of 25 (1,2). P. aeruginosa is the primary cause of acute respiratory exacerbations in CF patients with persistent infections leading to a progressive decline in pulmonary function (3). It has been established that the presence of P. aeruginosa in respiratory cultures is a major predictor of mortality and morbidity (2).…”

“…It has been established that the presence of P. aeruginosa in respiratory cultures is a major predictor of mortality and morbidity (2). Therefore, in clinical practice to improve life expectancy and the quality of life especially for patients awaiting lung transplantation aggressive antimicrobial treatment is employed (1)(2)(3). But the cumulative lifetime treatment of CF patients with antibiotics leads to the development of multidrug-resistant (MDR) P. aeruginosa (4).…”

Modern Approaches in Management of Children with Cystic fibrosis

“…Антибактериальная терапия при выявлении в мокроте / бронхиальном секрете Pseudomonas aeruginosa Рекомендуется одновременное назначение 2-3 противомикробных препаратов из разных групп, что предотвращает развитие устойчивости P. aeruginosa и способствует достижению максимального клинического эффекта (эрадикации P. aeruginosa) (табл. 9) [2,6,20,[134][135][136]150, 151] (УУР -C, УДД -5).…”