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In vitro effectiveness of azithromycin against doxycycline-resistant and -susceptible strains of Rickettsia tsutsugamushi, etiologic agent of scrub typhus.
Antimicrob Agents Chemother. 1995 Nov; 39(11):2406-10.AA

Abstract

In an effort to find a potential alternative treatment for scrub typhus, we evaluated the effectiveness of the standard drug doxycycline and the new macrolide azithromycin against a doxycycline-susceptible strain (Karp) and a doxycycline-resistant strain (AFSC-4) of Rickettsia tsutsugamushi. The antibiotics were tested in an in vitro assay system in which infected mouse fibroblast cells (L929) were incubated for 3 days in various concentrations of the drugs. Rickettsial growth was evaluated by direct visual counts of rickettsiae in Giemsastained cells or by flow cytometry. Initial tests were conducted at the concentration of each antibiotic considered to be the upper breakpoint for susceptibility (16 micrograms/ml for doxycycline and 8 micrograms/ml for azithromycin). Growth of both Karp and AFSC-4 was strongly inhibited with both antibiotics, as measured by visual counts, although the percentage of cells infected with AFSC-4 in the presence of doxycycline was three times greater than the percentage of cells infected with Karp but was only 60% as great as the percentage of cells infected with Karp in the presence of azithromycin. Flow cytometry confirmed that rickettsial growth occurred in the absence of antibiotics, but it failed to detect it in the presence of high concentrations of either drug. Visual counts of rickettsial growth at lower concentrations of the antibiotics (0.25 to 0.0078 microgram/ml) showed that the Karp strain was 16 times more susceptible that the AFSC-4 strain to doxycycline. Azithromycin was much more effective than doxycycline against AFSC-4, inhibiting rickettsial growth at 0.0156 microgram/ml to levels below that achieved by 0.25 microgram of doxycycline per ml. Azithromycin was also more effective than doxycycline against the Karp strain, causing greater reductions in the number of rickettsiae per cell at lower concentrations. If in vivo testing confirms the in vitro effectiveness of azithromycin, it may prove to be the drug of choice for the treatment of scrub typhus in children and pregnant women, who should not take doxycycline, and in patients with refractory disease from locations where doxycycline-resistant strains of R. tsutsugamushi have been found. When tested in an in vitro assay system, azithromycin was more effective than doxycycline against doxycycline-susceptible and -resistant strains of R. tsutsugamushi.

Authors+Show Affiliations

Department of Rickettsial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

8585717

Citation

Strickman, D, et al. "In Vitro Effectiveness of Azithromycin Against Doxycycline-resistant and -susceptible Strains of Rickettsia Tsutsugamushi, Etiologic Agent of Scrub Typhus." Antimicrobial Agents and Chemotherapy, vol. 39, no. 11, 1995, pp. 2406-10.
Strickman D, Sheer T, Salata K, et al. In vitro effectiveness of azithromycin against doxycycline-resistant and -susceptible strains of Rickettsia tsutsugamushi, etiologic agent of scrub typhus. Antimicrob Agents Chemother. 1995;39(11):2406-10.
Strickman, D., Sheer, T., Salata, K., Hershey, J., Dasch, G., Kelly, D., & Kuschner, R. (1995). In vitro effectiveness of azithromycin against doxycycline-resistant and -susceptible strains of Rickettsia tsutsugamushi, etiologic agent of scrub typhus. Antimicrobial Agents and Chemotherapy, 39(11), 2406-10.
Strickman D, et al. In Vitro Effectiveness of Azithromycin Against Doxycycline-resistant and -susceptible Strains of Rickettsia Tsutsugamushi, Etiologic Agent of Scrub Typhus. Antimicrob Agents Chemother. 1995;39(11):2406-10. PubMed PMID: 8585717.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro effectiveness of azithromycin against doxycycline-resistant and -susceptible strains of Rickettsia tsutsugamushi, etiologic agent of scrub typhus. AU - Strickman,D, AU - Sheer,T, AU - Salata,K, AU - Hershey,J, AU - Dasch,G, AU - Kelly,D, AU - Kuschner,R, PY - 1995/11/1/pubmed PY - 1995/11/1/medline PY - 1995/11/1/entrez SP - 2406 EP - 10 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 39 IS - 11 N2 - In an effort to find a potential alternative treatment for scrub typhus, we evaluated the effectiveness of the standard drug doxycycline and the new macrolide azithromycin against a doxycycline-susceptible strain (Karp) and a doxycycline-resistant strain (AFSC-4) of Rickettsia tsutsugamushi. The antibiotics were tested in an in vitro assay system in which infected mouse fibroblast cells (L929) were incubated for 3 days in various concentrations of the drugs. Rickettsial growth was evaluated by direct visual counts of rickettsiae in Giemsastained cells or by flow cytometry. Initial tests were conducted at the concentration of each antibiotic considered to be the upper breakpoint for susceptibility (16 micrograms/ml for doxycycline and 8 micrograms/ml for azithromycin). Growth of both Karp and AFSC-4 was strongly inhibited with both antibiotics, as measured by visual counts, although the percentage of cells infected with AFSC-4 in the presence of doxycycline was three times greater than the percentage of cells infected with Karp but was only 60% as great as the percentage of cells infected with Karp in the presence of azithromycin. Flow cytometry confirmed that rickettsial growth occurred in the absence of antibiotics, but it failed to detect it in the presence of high concentrations of either drug. Visual counts of rickettsial growth at lower concentrations of the antibiotics (0.25 to 0.0078 microgram/ml) showed that the Karp strain was 16 times more susceptible that the AFSC-4 strain to doxycycline. Azithromycin was much more effective than doxycycline against AFSC-4, inhibiting rickettsial growth at 0.0156 microgram/ml to levels below that achieved by 0.25 microgram of doxycycline per ml. Azithromycin was also more effective than doxycycline against the Karp strain, causing greater reductions in the number of rickettsiae per cell at lower concentrations. If in vivo testing confirms the in vitro effectiveness of azithromycin, it may prove to be the drug of choice for the treatment of scrub typhus in children and pregnant women, who should not take doxycycline, and in patients with refractory disease from locations where doxycycline-resistant strains of R. tsutsugamushi have been found. When tested in an in vitro assay system, azithromycin was more effective than doxycycline against doxycycline-susceptible and -resistant strains of R. tsutsugamushi. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/8585717/In_vitro_effectiveness_of_azithromycin_against_doxycycline_resistant_and__susceptible_strains_of_Rickettsia_tsutsugamushi_etiologic_agent_of_scrub_typhus_ L2 - https://journals.asm.org/doi/10.1128/AAC.39.11.2406?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -