This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log in
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct 18;65(11):e0067321.
doi: 10.1128/AAC.00673-21. Epub 2021 Aug 9.

Evaluation of the Efficacy of Doxycycline, Ciprofloxacin, Levofloxacin, and Co-trimoxazole Using In Vitro and In Vivo Models of Q Fever

Affiliations

Evaluation of the Efficacy of Doxycycline, Ciprofloxacin, Levofloxacin, and Co-trimoxazole Using In Vitro and In Vivo Models of Q Fever

K A Clay et al. Antimicrob Agents Chemother. .

Abstract

Q fever, caused by the intracellular pathogen Coxiella burnetii, is traditionally treated using tetracycline antibiotics, such as doxycycline. Doxycycline is often poorly tolerated, and antibiotic-resistant strains have been isolated. In this study, we have evaluated a panel of antibiotics (doxycycline, ciprofloxacin, levofloxacin, and co-trimoxazole) against C. burnetii using in vitro methods (determination of MIC using liquid and solid media; efficacy assessment in a THP cell infection model) and in vivo methods (wax moth larvae and mouse models of infection). In addition, the schedule for antibiotic treatment has been evaluated, with therapy initiated at 24 h pre- or postchallenge. Both doxycycline and levofloxacin limited overt clinical signs during treatment in the AJ mouse model of aerosol infection, but further studies are required to investigate the possibility of disease relapse or incomplete bacterial clearance after the antibiotics are stopped. Levofloxacin was well tolerated and therefore warrants further investigation as an alternative to the current recommended treatment with doxycycline.

Keywords: Coxiella; Q fever; antibiotic; treatment.

PubMed Disclaimer

Figures

FIG 1
FIG 1
Survival of G. mellonella following challenge with 1 ×ばつ 106 GE of C. burnetii NMII and treated with 50 mg/kg of either PBS (solid black line), levofloxacin (blue line), or doxycycline (green line) 24 h prechallenge (A) or postchallenge (B) and co-trimoxazole (purple line) or ciprofloxacin (orange line) 24 h prechallenge (C) or postchallenge (D). Significance by log-rank (Mantel-Cox) test is shown; *, P < 0.05; ***, P < 0.001.
FIG 2
FIG 2
The efficiency of drug eradication from mouse serum over time following a single dose of doxycycline (50 mg/kg), levofloxacin (100 mg/kg), ciprofloxacin (50 mg), and co-trimoxazole (48 mg/kg; consists of 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim). The MIC determined from growth in ACCM-2 broth and the significant inhibitory concentration determined in the cell based THP-1 assay are marked.
FIG 3
FIG 3
Mean percentage change in body weight of mice as a measurement of efficacy of 105 mg/kg oral doxycycline (A), 40 mg/kg intraperitoneal levofloxacin (B), 22 mg/kg intraperitoneal ciprofloxacin (C), and 48 mg/kg oral co-trimoxazole (D); all given twice daily and commenced at 24 h prechallenge (gray diamonds) or 24 h postchallenge (colored diamonds) with C. burnetii. Mice were challenged inhalationally with 1 ×ばつ 107 GE/ml of C. burnetii. Significant differences from PBS-treated control mice (black diamonds) are marked. *, P < 0.05; **, P < 0.01; ***, P < 0.001; significance determined by ANOVA. Arrows denote mice culled on welfare grounds.
FIG 4
FIG 4
Physiological features of disease in mice 14 days postchallenge treated twice daily with 105 mg/kg doxycycline, 40 mg/kg levofloxacin, 22 mg/kg ciprofloxacin, or 48 mg/kg co-trimoxazole, commenced 24 h pre- or 24 h postchallenge for 7 days postchallenge and PBS-treated control. Mice were challenged by inhalation with 1 ×ばつ 107 GE/ml of C. burnetii. (A) Weight of lungs (colored bars) and spleens (striped bars) as a percentage of body weight as mean and SE and the corresponding bacterial colonization of lung (black outlined diamonds) and spleen (gray outlined circles) as determined by qPCR (mean and SE). Significant differences from the PBS-treated control group are indicated as follows: *, P < 0.05; **, P < 0.01; ***, P < 0.001. (B) Occurrence of the histological features associated with Q fever at day 14 pc (regardless of severity). Features are focal granulomatous splenitis (FGS), acute focal bronchiolitis (AFB), acute focal alveolitis (AFA), granulomatous alveolitis (GA), perivascular lymphoid cuffs (PVLC), and vasculitis (V).

References

    1. van der Hoek W, Hogema BM, Dijkstra F, Rietveld A, Wijkmans CJ, Schneeberger PM, Zaaijer HL. 2012. Relation between Q fever notifications and Coxiella burnetii infections during the 2009 outbreak in The Netherlands. Euro Surveill 17:20058. - PubMed
    1. Limonard GJ, Nabuurs-Franssen MH, Weers-Pothoff G, Wijkmans C, Besselink R, Horrevorts AM, Schneeberger PM, Groot CA. 2010. One-year follow-up of patients of the ongoing Dutch Q fever outbreak: clinical, serological and echocardiographic findings. Infection 38:471–477. 10.1007/s15010-010-0052-x. - DOI - PMC - PubMed
    1. Kampschreur LM, Delsing CE, Groenwold RH, Wegdam-Blans MC, Bleeker-Rovers CP, de Jager-Leclercq MG, Hoepelman AI, van Kasteren ME, Buijs J, Renders NH, Nabuurs-Franssen MH, Oosterheert JJ, Wever PC. 2014. Chronic Q fever in the Netherlands 5 years after the start of the Q fever epidemic: results from the Dutch chronic Q fever database. J Clin Microbiol 52:1637–1643. 10.1128/JCM.03221-13. - DOI - PMC - PubMed
    1. Parker NR, Barralet JH, Bell AM. 2006. Q fever. Lancet 367:679–688. 10.1016/S0140-6736(06)68266-4. - DOI - PubMed
    1. Pebody RG, Wall PG, Ryan MJ, Fairley C. 1996. Epidemiological features of Coxiella burnetii infection in England and Wales: 1984 to 1994. Commun Dis Rep CDR Rev 6:R128–32. - PubMed

LinkOut - more resources

Full text links
Atypon full text link Atypon Free PMC article
Cite

AltStyle によって変換されたページ (->オリジナル) /