Antimicrobial susceptibility testing (AST) and associated clinical outcomes in individuals with cystic fibrosis: A systematic review

Abstract

Background: Antimicrobial susceptibility testing (AST) is a cornerstone of infection management. Cystic fibrosis (CF) treatment guidelines recommend AST to select antimicrobial treatments for CF airway infection but its utility in this setting has never been objectively demonstrated. Methods: We conducted a systematic review of primary published articles designed to address two PICO (patient, intervention, comparator, outcome) questions: 1) "For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection predictable from AST results available at treatment initiation?" and 2) "For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection affected by the method used to guide antimicrobial selection?" Relationships between AST results and clinical response (changes in pulmonary function, weight, signs and symptoms of respiratory tract infection, and time to next event) were assessed for each article and results were compared across articles when possible. Results: Twenty-five articles describing the results of 20 separate studies, most of which described Pseudomonas aeruginosa treatment, were identified. Thirteen studies described pulmonary exacerbation (PEx) treatment and seven described 'maintenance' of chronic bacterial airways infection. In only three of 16 studies addressing PICO question #1 was there a suggestion that baseline bacterial isolate antimicrobial susceptibility was associated with clinical response to treatment. None of the four studies addressing PICO question #2 suggested that antimicrobial selection methods influenced clinical outcomes. Conclusions: There is little evidence that AST predicts the clinical outcome of CF antimicrobial treatment, suggesting a need for careful consideration of current AST use by the CF community.

Susceptibility of Pseudomonas aeruginosa Recovered from Cystic Fibrosis Patients to Murepavadin and 13 Comparator Antibiotics

“…For example, studies in which sputa from CF patients were analyzed by deep sequencing of 16S rRNA genes have failed to establish differences between the microbiota of CF patients during chronic infection, during acute exacerbations, and after systemic antibiotic treatment (15). The correlation between susceptibility test results and outcome of antibiotic treatment is also not clearly established for pulmonary infection in CF (16). Nevertheless, the use of antipseudomonal antibiotics for early eradication of P. aeruginosa, for treatment of exacerbations, and for chronic suppressive inhalation therapy have significantly contributed to improving the quality of life and life expectancy of CF patients (17).…”

Acute Pulmonary Exacerbations in Cystic Fibrosis

“…Recently, Somayaji et al with the Antimicrobial Resistance in Cystic Fibrosis International Working Group published a systematic review of antimicrobial susceptibility testing (AST) in CF. 104 The review addressed two key questions: (1) "For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection predictable from antimi-crobial susceptibility testing results available at treatment initiation?" and (2) "For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection affected by the method used to guide antimicrobial selection?"…”

Adult Care in Cystic Fibrosis

“…A further problem with many of these bacteria and fungi is that they frequently demonstrate resistance to antibiotics due to a combination of intrinsic resistance and the effect of frequent antibiotic treatment. [55][56][57][58][59] Chronic infection with bacteria, fungi, and viruses are also associated with recurrent pulmonary exacerbations, which cause a more rapid decline in lung function, impaired quality of life, and reduced survival. [60][61][62][63] Prevention of these events is a key priority in CF care, and this can be achieved by the optimization of mucoactive, antimicrobial, and CFTR modulator therapies, all of which have been shown to reduce the frequency of these events.…”