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102 PharmacyTimes.org December 2015 nary exacerbation, patients often com- plain of increased cough and sputum production, shortness of breath, exercise intolerance, myalgias, weight loss, and an overall lack of energy. 29 Since it is very difficult or impossible to eradicate the organism and chronic infection often leads to resistant organisms, antibiotic therapy must be aggressive and tailored to a patient's needs. Studies had shown that chronic colonization of mucoid strains of P. aeruginosa and MRSA leads to more rapid loss of lung function. Therefore, most CF centers use a com- bination of antipseudomonal antibiotics and/or antibiotics to treat MRSA. Aminoglycosides, along with other antipseudomonal agents, are used with most patients. 29 Since a majority of patients with CF have increased clear- ance and volume of distribution with these agents, therapy needs to be tailored to the pharmacokinetic requirement of the patient. High-dose, once-daily tobra- mycin is often used at a dose of 10 to 12 mg/kg/day; higher doses are required in some cases. 29 Antipseudomonal penicillins and cephalosporins have an increased clearance, and higher doses are required in this patient population. Given the rapid clearance of these drugs and the increasing minimum inhibitory concentrations, a prolonged infusion or continuous infusion of these agents may be warranted. A list of commonly used doses is found in Table 1. 30,31 Since these patients have recurrent pulmonary exacerbations, it is imperative to follow renal markers of clearance (ie, creatinine clearance at least twice a week in these patients to minimize the risk of acute kidney injury). Vancomycin, linezolid, and ceftaro- line have been used to treat MRSA that is not sensitive to trimethoprim/sulfa- methoxazole. 32 Given that many patients may be coinfected with MRSA and P. aeruginosa, extremely close monitor- ing of renal function is essential to prevent acute kidney injury, especially in patients with prolonged courses of therapy or who have received many courses of these agents over the years. Treatment usually consists of a 10- to 14-day course; however, depending on patient response, an additional week or two of therapy may be required. 28,29 This therapy may be completed as an outpa- tient, but given the level of therapy and resources, a prolonged hospitalization may be needed. Chronic Antibiotic Therapy Because chronic colonization of certain organisms, such as mucoid P. aeruginosa and MRSA in the lung, leads to increased loss of lung function and increased mor- bidity, chronic inhaled antibiotics are often used. 33 Aminoglycosides, particu- larly tobramycin, have been used for nearly 30 years as aerosol preparations as chronic suppressive therapy. In 1999, tobramycin solution for inhalation at a prescribed dose of 300 mg twice daily was approved for an alternating 28-day cycle on drug and with an equal period of time off inhaled tobramycin. 34 This approach was taken to maximize deliv- ery of a high concentration of tobramy- cin to the airway while minimizing the risk of systemic toxicity and resistance. It is often referred to as "on-1-month- off-1-month therapy." Due to the rise of more resistant organ- isms, many clinicians are using alternat- ing therapies of inhaled antibiotics in a rotational style (ie, tobramycin 300 mg twice daily for 1 month followed by aztreonam lysine 75 mg 3 times a day for 1 month). This approach is commonly taken in patients with frequent exacer- bations or deteriorating lung function. To date, no clinical trials have evalu- ated the approach of rotating an inhaled antibiotic every other month, but it has been helpful in some patients to avoid hospitalization for an acute pulmonary exacerbation. Some CF caregivers even use systemic antibiotics on the off month to try to suppress antimicrobial growth. In addition, even though it is con- sidered to be off-label, colistimethate inhalation has been used for more than CONTINUING EDUCATION TABLE 1: ANTIBIOTIC THERAPY FOR ACUTE PULMONARY EXACERBATION 30,31 Antibiotic a Dosing Regimen b For Pseudomonas aeruginosa Amikacin 7.5-10 mg/kg/dose IV q8hr c or 30 mg/kg/day Aztreonam 50-70 mg/kg/dose IV q8hr (up to 8 g/day) Cefepime 50-70 mg/kg/dose IV q8hr (up to 2.5 g/dose) Ceftazidime 50-70 mg/kg/dose IV q8hr (up to 8 g/day) Ciprofloxacin (IV) 10 mg/kg/dose IV q8hr (up to 400 mg/dose) Ciprofloxacin (oral) 40-50 mg/kg/day PO q8-12hr (up to 750 mg/dose) Colistin 3-6 mg/kg/day IV q8-12hr Levofloxacin Children: 7-10 mg/kg/dose IV or PO q24hr Adults: 500-750 mg/day IV or PO q24hr Meropenem 40 mg/kg/dose IV q8h (up to 2 g/dose) Piperacillin/Tazobactam 300-500 mg/kg/day IV q4-6hr (up to 24 g of piperacillin/day) Ticarcillin/Clavulanate 300-500 mg/kg/day IV q4-6hr (up to 24 g ticaracillin/day) Tobramycin 10-12 mg/kg/dose IV q24hr c or 6-7 mg/kg q12hr For Staphylococcus aureus, methicillin resistant Ceftaroline 600 mg IV q8-12hr Linezolid Children: 10 mg/kg/dose IV or PO q8hr Adults: 600 mg IV or PO q12hr Minocycline > 8 years 50-100 mg PO q12hr Tigecycline Children: N/A Adults: 100 mg loading dose, then 50 mg IV q12hr Trimethoprim- Sulfamethoxazole 6-10 mg/kg/dose PO q12hr (up to 960 mg of trimethoprim/day) Vancomycin 15-20 mg/kg/dose IV q6-8hr a Combination therapy is recommended b Doses assume normal renal and hepatic function. Dose adjustments may be necessary for renal and hepatic impairment c Use of historical therapeutic milligram-per-kilogram dosage if available Adapted from Phan H, Kuhn R. Cystic fibrosis. In: Benavides S, Nahata MC. Pediatric Pharmacotherapy. Lenexa, KS: American College of Clinical Pharmacy; 2013:223.