Antimicrobial Use Guidelines (AMUG) version 21 - UW Health

Indications1. Serious infections with aerobic Gram-negative bacilli in patients allergic to beta-lactams. Has activity againstPseudomonas aeruginosa, but does not provide synergy in combination with other beta-lactams.2. Aminoglycoside alternative in patients at increased risk for oto- or nephrotoxicity (not for double coverage with otherbeta-lactams).CommentsDose adjustment required for renal impairment. See renal dosing guideline on uconnect.Aztreonam has no anaerobic or Gram-positive coverage. Many nosocomial Gram-negative organisms that are resistant tocephalosporins are also resistant to aztreonam, and the drug should not be used alone for nosocomial Gram-negativeinfection until it is known that the organisms are susceptible. Safety and effectiveness of aztreonam have not beenestablished in infants and children. Since aztreonam and ceftazidime have the same side chain, animal models suggestthat aztreonam may be cross-allergenic with ceftazidime but not other beta-lactams, which have different side chains.An aztreonam product specifically created for nebulization (Cayston ® ) was approved in 2010. The dose is 75 mg Q8Husing an Altera ® Nebulizer System. Cayston® is approved for the improvement of respiratory symptoms in cystic fibrosispatients with Pseudomonas aeruginosa. Safety and efficacy are not established in patients under 7, in patients with FEV 175% predicted or in patients colonized with Burkholderia. The product has a Black Box Warning indicating thatsevere allergic reactions have occurred in patients without a history of exposure to aztreonam, and warns against using inpatients with a history of beta-lactam allergy, bronchospasm, decline in FEV z after a 28-day cycle and about the risk of thedevelopment of drug-resistant bacteria.CASPOFUNGIN – non-formulary at UWHCInfectious Disease approval is required for all use of caspofungin (See Appendix I)Anidulafungin, caspofungin and micafungin are therapeutically interchangeable at UWHC. Micafungin is the currentformulary choice.Usual DoseAdult: 70 mg IV on day 1, then 50 mg Q24H IV (UWHC cost/day $338.72).Pediatric: 70 mg/m 2 on day 1, then 50 mg/m 2Indications1. Invasive aspergillosis in patients intolerant or unresponsive to treatment with other therapies including: amphotericin B,lipid formulations of amphotericin B, and/or itraconazole. Occasionally used in combination with voriconazole.2. Systemic candidemia in patients at risk for infection by yeasts that may be resistant to azole antifungal agents.See Guidelines for Use of Antifungal Agents (Appendix E) or on uconnect.CommentsReduce maintenance dose to 35 mg/day in patients with moderate hepatic impairment (Child-Pugh score 7-9); clinicalexperience in patients with severe hepatic impairment (Child-Pugh score>9) is limited; further dose adjustments orwithholding caspofungin may be warranted. For established filamentous fungal infections, the usual dose is 70mg IV daily.The most common side effects are infusion-related reactions, nausea, fever and frequent headaches. Transient elevationsof liver function tests up to four times the upper limit of normal have been reported. Cyclosporine exacerbates this effectand concomitant administration should be weighed carefully. Caspofungin is not compatible with dextrose-containingsolutions.Drug InteractionsThe clearance of caspofungin is increased by carbamazepine, dexamethasone, efavirenz, nelfinavir, nevirapine,phenytoin and rifampin, resulting in decreased serum levels of caspofungin. Cyclosporine increases the AUC ofcaspofungin. Caspofungin causes a decrease in the AUC of tacrolimus; dose adjustments of tacrolimus may benecessary in order to maintain therapeutic levels.