Levofloxacin versus azithromycin on the oropharyngeal carriage and selection of antibacterial- resistant streptococci in the microflora of healthy adults

ABSTRACT

Objective: To determine the proportion of subjects with oropharyngeal streptococci resistant to either levofloxacin or azithromycin prior to and during antibacterial exposure, and to follow temporal changes in the proportion of resistant and susceptible isolates through 6 weeks post-exposure. This randomized, open-label, single-center study is registered with ClinicalTrials.gov (identifier: NCT00821 782).

Research design and methods: A total of 143 healthy volunteers (levofloxacin, n = 71; azithromycin, n = 72) without antibacterial exposure in the previous 90 days received either levofloxacin 750 mg once daily for 5 days or azithromycin 500 mg once daily on day 1 and 250 mg once daily on days 2 through 5. Oropharyngeal cultures were obtained pre-exposure, at day 5, and at 2, 4, and 6 weeks post-dosing. Bacterial strains were identified and the minimum inhibitory concentrations for levofloxacin and azithromycin were determined.

Results: At study entry 117 streptococci were isolated from 72 subjects randomized to azithromycin and 53 (45.3%) were azithromycin-resistant. None of the 121 streptococci isolated from 71 subjects randomized to.levofloxacin were colonized by a levofloxacin-resistant microorganism prior to dosing. At the end of dosing, the number of subjects with resistant streptococci (S. mitis, S. salivarius, S. sanguis, or alpha streptococcus species [spp.]) increased in azithromycin-exposed subjects and resistant isolates remained through 6 weeks post-dosing. In contrast, a small number of levofloxacin-resistant streptococci were observed at the end of dosing but decreased by week 2 post-dosing and continued to decrease through the 6-week evaluation period (p < 0.001 azithromycin vs. levofloxacin for S. mitis, S. salivarius, S. sanguis and alpha streptococcus spp. at week 6). Limitations of this study included the fact that, since previous antibiotic use was self-reported, genetic typing was not done. The results of this study may not be completely generalizable, because subjects in this study received study drug under directly-observed conditions, thus ensuring compliance.

Conclusions: Both antibacterial agents were well tolerated. Levofloxacin 750 mg administered for 5 days was associated with less microbial resistance than that observed with azithromycin in healthy subjects.

Trial registration: ClinicalTrials.gov identifier: NCT00821782.

Key words: :

• Azithromycin
• Levofloxacin
• Oral microflora
• Resistance
• Streptococci

Transparency

Declaration of funding

Ortho-McNeil Janssen Scientific Affairs, LLC provided the financial support for this study.

Declaration of financial/other relationships

J.P., M.A. and A.C.F. have disclosed that they are employees of Ortho-McNeil Janssen Scientific Affairs. C.E.N. has disclosed that he has no relevant financial relationships.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she is an investigator and has initiated a research grant from Cubist. Peer Reviewer 2 has disclosed that he/she has no relevant financial relationships.

Acknowledgments

The authors thank James B. Kahn for his guidance in developing the study concept and J.P. Guggenbichler for his study in children that provided guidance in the development of the current study. Ira Mills, PhD and Craig Ornstein, PhD of Advogent provided editorial assistance in the preparation of this manuscript, with financial support from Ortho-McNeil Janssen.