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A time-kill evaluation of clarithromycin and azithromycin against two extracellular pathogens and the development of resistance.

Publication ,  Journal Article
Burgess, DS; Hastings, RW; Horan, JL
Published in: Ann Pharmacother
December 1999

OBJECTIVE: To determine the activity of clarithromycin, its metabolite (14-hydroxyclarithromycin), and azithromycin against Haemophilus influenzae and Staphylococcus aureus using time-kill methodology and to evaluate the susceptibility of the organisms following exposure to various concentrations of the azalide macrolides. DATA SOURCES AND METHODS: Clinical isolates of H. influenzae and S. aureus were obtained from the Clinical Microbiology Laboratory at University Hospital, San Antonio, Texas. Susceptibility testing was performed according to National Committee for Clinical Laboratory Standards guidelines. 14-Hydroxyclarithromycin was added to clarithromycin solutions used for H. influenzae. Time-kill studies were performed using antimicrobial concentrations of 0.25-8x minimum inhibitory concentration (MIC) and an initial inoculum of approximately 10(5) CFU/mL. Samples were plated onto solid agar at 0, 4, 8, 12, and 24 hours. At 0, 12, and 24 hours, samples were then plated onto solid agar incorporated with antibiotic. After incubating plates at 35 degrees C for 24 hours, colony counts were determined. RESULTS: The MICs of clarithromycin and clarithromycin plus 14-hydroxyclarithromycin for H. influenzae were 4 and 2 microg/mL, respectively. For S. aureus, the MIC of clarithromycin was 0.25 microg/mL, and the MIC of azithromycin for both organisms was 1 microg/mL. H. influenzae developed resistance to both macrolides within 12 hours when exposed to sub-MICs of clarithromycin plus 14-hydroxyclarithromycin. However, when exposed to concentrations less than or equal to the MIC of azithromycin, resistance was not conferred to clarithromycin. S. aureus, on the other hand, became resistant to azithromycin and less susceptible to clarithromycin following exposure to sub-MICs of either macrolide. CONCLUSIONS: Clarithromycin and azithromycin elicited a concentration-independent bacteriostatic effect against H. influenzae and S. aureus at concentrations at least two times the MIC. In addition, concentrations maintained above the MIC prevented changes in the susceptibility of H. influenzae and S. aureus to both macrolides.

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Published In

Ann Pharmacother

DOI

ISSN

1060-0280

Publication Date

December 1999

Volume

33

Issue

12

Start / End Page

1262 / 1265

Location

United States

Related Subject Headings

  • Time Factors
  • Staphylococcus aureus
  • Pharmacology & Pharmacy
  • Microbial Sensitivity Tests
  • Haemophilus influenzae
  • Colony-Forming Units Assay
  • Clarithromycin
  • Azithromycin
  • Anti-Bacterial Agents
  • 3214 Pharmacology and pharmaceutical sciences
 

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Burgess, D. S., Hastings, R. W., & Horan, J. L. (1999). A time-kill evaluation of clarithromycin and azithromycin against two extracellular pathogens and the development of resistance. Ann Pharmacother, 33(12), 1262–1265. https://doi.org/10.1345/aph.19074
Burgess, D. S., R. W. Hastings, and J. L. Horan. “A time-kill evaluation of clarithromycin and azithromycin against two extracellular pathogens and the development of resistance.Ann Pharmacother 33, no. 12 (December 1999): 1262–65. https://doi.org/10.1345/aph.19074.
Burgess, D. S., et al. “A time-kill evaluation of clarithromycin and azithromycin against two extracellular pathogens and the development of resistance.Ann Pharmacother, vol. 33, no. 12, Dec. 1999, pp. 1262–65. Pubmed, doi:10.1345/aph.19074.
Journal cover image

Published In

Ann Pharmacother

DOI

ISSN

1060-0280

Publication Date

December 1999

Volume

33

Issue

12

Start / End Page

1262 / 1265

Location

United States

Related Subject Headings

  • Time Factors
  • Staphylococcus aureus
  • Pharmacology & Pharmacy
  • Microbial Sensitivity Tests
  • Haemophilus influenzae
  • Colony-Forming Units Assay
  • Clarithromycin
  • Azithromycin
  • Anti-Bacterial Agents
  • 3214 Pharmacology and pharmaceutical sciences