High rate of coadministration of di- or tri-valent cation-containing compounds with oral fluoroquinolones: Risk factors and potential implications

BACKGROUND: The characteristics of fluoroquinolone use that increase the risk of selecting for fluoroquinolone resistance remain unclear. Exposure to subtherapeutic levels of fluoroquinolone promotes bacterial development of fluoroquinolone resistance. Oral fluoroquinolone absorption is significantly impaired by coadministration with many common di- or tri-valent cation-containing compounds (DTCCs), and this interaction has been associated with therapeutic failure. However, the prevalence of, and risk factors for, in-hospital coadministration of oral fluoroquinolones with DTCCs is unknown. DESIGN: Case-control study. SETTING: A 625-bed, tertiary-care medical center. PATIENTS: All inpatients who were dispensed oral levofloxacin from July. l; 1999, to June 30, 2001, were included. Coadministration was defined by documented administration of any DTCC within 2 hours of levofloxacin. Complete coadministration was defined as coadministration complicating every dose of a course of levofloxacin. RESULTS: A subset of 3.227 (41.0%) of 7,871 doses of levofloxacin that occurred during the same calendar day as any DTCC was selected for further review. Overall, 1.90-4 (77.1%) of 2,470 doses of oral levofloxacin reviewed were complicated by coadministration with at least one DTCC. On multivariable analysis, an increased number of prescribed medications was significantly associated with complete coadministration (per increase of one medication: OR, 1.05; CI95. 1.01-1.10; P = .036), whereas patient location in an ICU was protective (OR, 0.51; CI95, 0.30-0.87; P = .013). If our prevalence results are extrapolated to all patients receiving oral levofloxacin at our hospital, approximately one in three doses was complicated by coadministration. CONCLUSION: Coadministration of fluoroquinolones with DTCCs is extremely common and significantly associated with polypharmacy.