Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-pseudomonal cephalosporins (i.e., ceftazidime and cefepime) and penicillins (i.e., piperacillin-tazobactam and ticarcillin-clavulanate) in the treatment of APE and to identify areas where further study is warranted. The ceftazidime and cefepime dosing ranges from the literature are 200-400 mg/kg/day divided every 6-8 hr, maximum 8-12 g/day, and 150-200 mg/kg/day divided every 6-8 hr, up to 6-8 g/day, respectively. The literature supported dosing ranges for piperacillin and ticarcillin are 350-600 mg/kg/day divided every 4 hr, maximum 18-24 g/day of piperacillin component, and 400-750 mg/kg/day divided every 6 hr, up to 24-30 g/day of ticarcillin component, respectively. As a large portion of CF patients will not regain their lung function following an APE, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat an APE in efforts to improve outcomes for CF patients infected with Pseudomonas aeruginosa. Future studies are needed to determine the clinical efficacy of higher than FDA-approved doses of ceftazidime, cefepime, and ticarcillin-clavulanate in APE. The usefulness of high dose piperacillin (>600 mg/kg/day) may be limited due to treatment-related adverse effects. Further understanding of these adverse effects in CF patients is needed.

Intravenous (IV) anti-pseudomonal aminoglycosides (i.e., amikacin and tobramycin) have been shown to be tolerable and effective in the treatment of acute pulmonary exacerbations (APEs) in both pediatric and adult patients with cystic fibrosis. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic, tolerability, and efficacy studies utilizing IV amikacin, gentamicin, and tobramycin in the treatment of APE and to highlight areas where further investigation is needed. The Cystic Fibrosis Foundation Pulmonary Guidelines recommend that once-daily administration of aminoglycosides is preferred over three times per day in the treatment of an APE. The literature supports dosing ranges for amikacin and tobramycin of 30-35 and 7-15 mg/kg/day, respectively, given once daily, with subsequent doses determined by therapeutic drug concentration monitoring. The literature does not support the routine use of gentamicin in the treatment of APE due to a lack of studies showing efficacy and evidence indicating an increased risk of nephrotoxicity. Further studies are needed to determine the optimal dosing strategy of amikacin in the treatment of an APE, and to further identify risk factors and determinants that influence the development of P. aeruginosa resistance with once-daily administration of tobramycin.

The epidemiologic characteristics of invasive GAS disease in Utah has changed substantially over the past decade, including a significant increase in the overall incidence of invasive disease-driven primarily by increasing disease in younger persons-that coincided temporally with a decrease in the incidence of acute rheumatic fever.

Acute pulmonary exacerbations (APE) in cystic fibrosis (CF) are associated with loss of lung function that may require aggressive management with intravenous antibiotics. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing aztreonam and anti-pseudomonal carbapenems (i.e., doripenem, imipenem-cilastatin, and meropenem) in the treatment of an APE, and to identify areas where further study is warranted. The current dosing recommendations in the United States and Europe for aztreonam are lower than the literature supported dosing range of 200-300 mg/kg/day divided every 6 hr, maximum 8-12 g/day. In vitro, PK/PD, and tolerability studies show the potential of doripenem 90 mg/kg/day divided every 8 hr, infused over 4 hr, maximum 6 g/day in the treatment of APE. Imipenem-cilastatin 100 mg/kg/day divided every 6 hr, maximum 4 g/day and meropenem 120 mg/kg/day divided every 8 hr, maximum 6 g/day have been shown to be tolerable and effective in the treatment of APE. With availability issues of new anti-pseudomonal agents and a large percentage of CF patients will not regain their lung function following an APE, we suggest the need to determine optimization of aztreonam and meropenem dosing in CF, as well as to determine the clinical efficacy of doripenem in the treatment of APE. The usefulness of imipenem-cilastatin may be limited due to the rapid development of resistance.

Influenza diagnoses made in association with RIDT resulted in fewer tests and antibiotic prescriptions and more frequent use of antivirals. This finding suggests that test results influence physician behavior.