Pharmacodynamics of doxycycline for chemoprophylaxis of Lyme disease: preliminary findings and possible implications for other antimicrobials

Lee, Joo Yun; Wormser, Gary P.

doi:10.1016/j.ijantimicag.2007.11.011

Cited by 16 publications

(7 citation statements)

References 30 publications

(48 reference statements)

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“…While it has been suggested that the lower efficacy of doxycycline in the murine studies was related to differences between mice and humans with regard to the duration of time that doxycycline levels exceeded the minimal inhibitory concentration for B. burgdorferi following a single oral dose of doxycycline (T > minimal inhibitory concentration) [71] , subsequent pharmacodynamic modeling found that other pharmacodynamic parameters correlated better with efficacy [72] . However, these findings were based on flawed assumptions.…”

Section: The Complete Discussion Of the Individual Clinical Questionsmentioning

confidence: 99%

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease

Cameron

Johnson²,

Maloney

2014

Expert Review of Anti-infective Therapy

166

206

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Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions – the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1–13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols.

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Section: The Complete Discussion Of the Individual Clinical Questionsmentioning

confidence: 99%

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease

Cameron

Johnson²,

Maloney

2014

Expert Review of Anti-infective Therapy

166

206

View full text Add to dashboard Cite

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“…30 Although doxycycline efficacy was not assessed in the present study, it can be estimated on the basis of the AUC:MIC ratio. As tetracyclines have both time-dependent and concentration-dependent pharmacodynamics, multiple studies 31,32 have determined that the AUC:MIC ratio is the best predictor of efficacy for tetracyclines. The calculated AUC:MIC ratio was > 100 for bacteria for which the MIC of doxycycline was ≤ 0.25 µg/ mL for the 20 mg/kg dose on both days 1 and 4 and for the 10 mg/kg dose on day 1.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

Freeman¹,

Thomasy²,

Stanley³

et al. 2013

javma

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Objective-To assess tear and plasma concentrations of doxycycline following oral administration to northern elephant seals (Mirounga angustirostris). Design-Pharmacokinetic study. Animals-18 juvenile northern elephant seals without signs of ocular disease. Procedures-Study seals were receiving no medications other than a multivitamin and were free from signs of ocular disease as assessed by an ophthalmic examination. Doxycycline (10 or 20 mg/kg [4.5 or 9.1 mg/lb]) was administered orally every 24 hours for 4 days. Tear and plasma samples were collected at fixed time points, and doxycycline concentration was assessed by means of liquid chromatography-tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis. Results-Following administration of doxycycline (10 mg/kg/d, PO), maximum plasma doxycycline concentration was 2.2 µg/mL at 6.1 hours on day 1 and was 1.5 µg/mL at 4.0 hours on day 4. Administration of doxycycline (20 mg/kg/d, PO) produced a maximum plasma doxycycline concentration of 2.4 µg/mL at 2.3 hours on day 1 and 1.9 µg/mL at 5.8 hours on day 4. Doxycycline elimination half-life on day 4 in animals receiving doxycycline at a dosage of 10 or 20 mg/kg/d was 6.7 or 5.6 hours, respectively. Mean plasma-to-tear doxycycline concentration ratios over all days were not significantly different between the low-dose (9.85) and high-dose (9.83) groups. For both groups, doxycycline was detectable in tears for at least 6 days following cessation of dosing. Conclusions and Clinical Relevance-Oral administration of doxycycline at the doses tested in the present study resulted in concentrations in the plasma and tears of northern elephant seals likely to be clinically effective for treatment of selected cases of systemic infectious disease, bacterial ulcerative keratitis, and ocular surface inflammation. This route of administration should be considered for treatment of corneal disease in northern elephant seals and possibly other related pinniped species. (J Am Vet

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“…For clarithromycin, an oral dose of 250 mg/kg BID was used, as this dosage was expected to result in free peak plasma concentrations of approximately 1 μg/mL 49 50 . For doxycycline, oral administration of 150 mg/kg BID was used, with an expected peak of 0.3 μg/mL for free concentrations 51 52 .…”

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo Evaluation of Synergism between Anti-Tubercular Spectinamides and Non-Classical Tuberculosis Antibiotics

Bruhn

Scherman

Liu

et al. 2015

Sci Rep

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Spectinamides are new semi-synthetic spectinomycin derivatives with potent anti-tubercular activity. The reported synergism of the precursor spectinomycin with other antibiotics prompted us to examine whether spectinamides sensitize M. tuberculosis to other antibiotics not traditionally used in the treatment of tuberculosis to potentially expand therapeutic options for MDR/XDR Tuberculosis. Whole cell synergy checkerboard screens were performed using the laboratory strain M. tuberculosis H37Rv, lead spectinamide 1599, and a broad panel of 27 antibiotics. In vitro, 1599 synergized with 11 drugs from 6 antibiotic classes. The observed synergy was tested against clinical isolates confirming synergy with Clarithromycin, Doxycycline and Clindamycin, combinations of which were taken forward for in vivo efficacy determination. Co-administration of 1599 and clarithromycin provided additional bacterial killing in a mouse model of acute tuberculosis infection, but not in a chronic infection model. Further studies indicated that mismatched drug exposure profiles likely permitted induction of phenotypic clarithromycin resistance and subsequent loss of synergism. These studies highlight the importance of validating in vitro synergism and the challenge of matching drug exposures to obtain a synergistic outcome in vivo. Results from this study indicate that a 1599 clarithromycin combination is potentially viable, providing the drug exposures can be carefully monitored.

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Pharmacodynamics of doxycycline for chemoprophylaxis of Lyme disease: preliminary findings and possible implications for other antimicrobials

Cited by 16 publications

References 30 publications

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease

Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

In vitro and in vivo Evaluation of Synergism between Anti-Tubercular Spectinamides and Non-Classical Tuberculosis Antibiotics

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