Doxycycline

Doxycycline belongs to a class of antibiotics known as tetracyclines and it is used in the treatment of various bacterial infections, the most common of which pneumonia, chronic bronchitis, acne, malaria and lyme disease. It can also be beneficial in several sexually transmitted diseases and stomach or bone infections. Recent studies have shown that doxycycline is beneficial in cases where someone has been exposed to any form of anthrax. The way it works is by stopping the production of proteins which are essential to the growth and reproductive functions of bacteria, so that bacteria populations stop reproducing and die. Doxycycline is relatively safe, although dangerous drug interactions may occur; side effects are not very common and include photosensitivity and digestive problems.
The most common names of the drug are Doryx, Doxy and Vibramycin.

Nat Med. 2005 May 1;
Doxycycline attenuates and delays toxicity of the oculopharyngeal muscular dystrophy mutation in transgenic mice.
Davies JE, Wang L, Garcia-Oroz L, Cook LJ, Vacher C, O'donovan DG, Rubinsztein DC.
Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK.

The muscular dystrophies are a heterogeneous group of disorders for which there are currently no cures. Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late-onset, progressive disease that generally presents in the fifth or sixth decade with dysphagia, ptosis and proximal limb weakness. OPMD is caused by the abnormal expansion of a (GCG)(n) trinucleotide repeat in the coding region of the poly-(A) binding protein nuclear 1 (PABPN1) gene. In unaffected individuals, (GCG)(6) codes for the first six alanines in a homopolymeric stretch of ten alanines. In most individuals with OPMD this (GCG)(6) repeat is expanded to (GCG)(8-13), leading to a stretch of 12-17 alanines in mutant PABPN1. PABPN1 with an expanded polyalanine tract forms aggregates consisting of tubular filaments within the nuclei of skeletal muscle fibers. We have developed a transgenic mouse model of OPMD that manifests progressive muscle weakness accompanied by intranuclear aggregates and TUNEL-stained nuclei in skeletal muscle fibers. The onset and severity of these abnormalities were substantially delayed and attenuated by doxycycline treatment, which may exert its therapeutic effect by reducing aggregates and by distinct antiapoptotic properties. Doxycycline may represent a safe and feasible therapeutic for this disease.

Skinmed. 2005 May-Jun;4(3):138-46.
Combination therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter, investigator-blind, randomized, controlled study.
Thiboutot DM, Shalita AR, Yamauchi PS, Dawson C, Arsonnaud S, Kang S; on behalf of the Differin Study Group.
The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA dthiboutot@psu.edu.

Background. Combination therapy with a topical retinoid and an antibiotic is recognized as a rational and effective approach for the treatment of acne vulgaris. Adapalene, a naphthoic acid derivative with anti-inflammatory and receptor-selective retinoid properties, is safe and well tolerated. While the combination of adapalene with oral or topical antibiotics has been shown to deliver a superior and faster response than an antibiotic alone, the clinical benefits of a combination of adapalene and doxycycline, the most frequently prescribed oral antibiotic for acne in the United States, have yet to be evaluated. Objective and Methods. In a 12-week study, the efficacy and safety of the combination of adapalene gel 0.1% with doxycycline was compared with doxycycline alone for the treatment of severe acne. Subjects were randomized to receive doxycycline once daily in the morning and either adapalene or vehicle once daily in the evening. Results. At Week 12, the combination adapalene-doxycycline was significantly superior to doxycycline alone for change from baseline in total (p<0.001), inflammatory (p=0.02), and noninflammatory (p<0.001) lesions. Significant differences in total lesions were observed as early as Week 4 (p=0.04). Both treatments were well tolerated, and no serious adverse events were reported. Conclusions. The study demonstrates that the combination of adapalene and an oral antibiotic provides a superior and faster benefit than antibiotic therapy alone and should be considered at the initiation of treatment.

J Periodontol. 2004 Dec;75(12):1600-4. Related Articles, Links
Microbiological changes with the use of locally delivered doxycycline in the periodontal treatment of smokers.
Machion L, Andia DC, Saito D, Klein MI, Goncalves RB, Casati MZ, Nociti FH Jr, Sallum EA.
Department of Periodontics and Prosthodontics, School of Dentistry at Piracicaba (UNICAMP), Sao Paulo, Brazil.

BACKGROUND: The aim of this study was to evaluate the effect of the association of locally delivered doxycycline 10% and scaling and root planing in the subgingival plaque of smokers. METHODS: Sixteen smokers with chronic periodontitis and a minimum of four pockets (> or = 5 mm) on anterior teeth that bled on probing were selected. Patients were randomly assigned to one of the following groups: scaling and root planing (SRP) or scaling and root planing followed by local application of doxycycline (SRP-D). Subgingival plaque samples were collected from initially moderate (5 to 6 mm) and deep (> or = 7 mm) pockets at baseline and 3 months. Polymerase chain reaction (PCR) analysis was used to detect the frequency of Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Tannerella forsythensis (Tf). RESULTS: No statistically significant difference was found in the reduction of Aa in either the SRP-D or SRP group (P > 0.05). The reduction in Tf, Pg, and Tf + Pg was statistically significant for SRP-D only (P = 0.016, 0.027, and 0.027, respectively). The proportion of sites free of Tf at 3 months was 53% for SRP-D and 9% for SRP (P = 0.02). For Pg, this proportion was 82% and 40%, respectively (P = 0.05). CONCLUSION: The use of locally delivered doxycycline may promote the elimination of T. forsythensis and P. gingivalis in a greater proportion of sites compared to conventional scaling and root planing in smokers.

Med J Aust. 2005 Feb 21;182(4):168-171. Related Articles, Links
Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in East Timor.
Kitchener SJ, Nasveld PE, Gregory RM, Edstein MD.
Centre for Military and Veterans' Health, Mayne Medical School, Herston Road, Herston, QLD 4006, Australia. s.kitchener@uq.edu.au.

OBJECTIVES: To describe the tolerability of mefloquine in Australian soldiers for malaria prophylaxis, including a comparison with doxycycline. DESIGN: Open-label, prospective study and cross-sectional questionnaire and interview. SETTING AND PARTICIPANTS: Two contingents of Australian soldiers, each deployed to East Timor for peacekeeping duties over a 6-month period (April 2001-October 2001 and October 2001-May 2002). OUTCOME MEASURES: Withdrawals during the study; adverse events relating to mefloquine prophylaxis; willingness to use mefloquine again on deployment. RESULTS: Of 1157 soldiers starting on mefloquine, 75 (6.5%) withdrew because of adverse responses to the drug. There were three serious adverse events of a neuropsychiatric nature, possibly relating to mefloquine. Fifty-seven per cent of soldiers using mefloquine prophylaxis reported at least one adverse event, compared with 56% using doxycycline. The most commonly reported adverse effects of both drugs were sleep disturbance, headache, tiredness and nausea. Of the 968 soldiers still taking mefloquine at the end of their deployments, 94% indicated they would use mefloquine again. Of 388 soldiers taking doxycycline prophylaxis who were deployed with the first mefloquine study contingent, 89% indicated they would use doxycycline again. CONCLUSIONS: Mefloquine was generally well tolerated by Australian soldiers and should continue to be used for those intolerant of doxycycline.

Cornea. 2004 Jan;23(1):106-9.
Oral tetracyclines for ocular rosacea: an evidence-based review of the literature.
Stone DU, Chodosh J.
Molecular Pathogenesis of Eyer Infection Research Center, Dean A. McGee Eye Institute, Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton I. Young Boulevard, Oklahoma City, OK 73104, USA.
PURPOSE: To review the basis for the use of oral tetracyclines in ocular rosacea. METHODS: Review of the published literature. RESULTS: Two prospective, masked, and placebo-controlled studies of oxytetracycline for ocular rosacea demonstrated a modest treatment benefit. Studies performed with tetracycline and doxycycline for ocular rosacea were not placebo controlled, and the optimal drug, dose, and schedule of administration were not evaluated. CONCLUSIONS: Available evidence supports a moderate treatment benefit in ocular rosacea for oxytetracycline, a tetracycline derivative not currently available in the United States. The efficacies of doxycycline and tetracycline, including treatment effect, optimal dose, duration of therapy, and side effects when used for ocular rosacea have not been established.

Antimicrob Agents Chemother. 2004 Jan;48(1):168-71.
San Gabriel P, Zhou J, Tabibi S, Chen Y, Trauzzi M, Saiman L.
Department of Pediatrics, Columbia University, New York, New York 10032, USA.
Stenotrophomonas maltophilia is a newly emerging pathogen being detected with increasing frequency in patients with cystic fibrosis (CF). The impact of this multidrug-resistant organism on lung function is uncertain. The optimal treatment for S. maltophilia in CF patients is unknown. We studied the in vitro activity of ten antimicrobial agents, and conducted synergy studies by using checkerboard dilutions of eight pairs of antimicrobial agents against strains isolated from 673 CF patients from 1996 to 2001. This represents approximately 7 to 23% of the CF patients in the United States who harbor S. maltophilia annually. Doxycycline was the most active agent and inhibited 80% of 673 initial patient isolates, while trimethoprim-sulfamethoxazole inhibited only 16%. High concentrations of colistin proved more active than high concentrations of tobramycin and gentamicin. Serial isolates (n = 151) from individual patients over time (median, 290 days) showed minimal changes in resistance. Synergistic or additive activity was demonstrated by trimethoprim-sulfamethoxazole paired with ticarcillin-clavulanate (65% of strains), ciprofloxacin paired with ticarcillin-clavulanate (64% of strains), ciprofloxacin paired with piperacillin-tazobactam (59% of strains), trimethoprim-sulfamethoxazole paired with piperacillin-tazobactam (55% of strains), and doxycycline paired with ticarcillin-clavulanate (49% of strains). In all, 522 (78%) isolates were multidrug resistant (i.e., resistant to all agents in two or more antimicrobial classes) but 473 (91%) of these were inhibited by at least one antimicrobial combination (median, four; range, one to eight). To determine appropriate treatment for patients with CF, it is important to monitor the prevalence, antimicrobial susceptibility, and clinical impact of S. maltophilia in this patient population.

Anticancer Drugs. 2003 Nov;14(10):773-8.
Saikali Z, Singh G.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Doxycycline and other tetracyclines in the treatment of bone metastasis.
The tetracycline family includes tetracycline, doxycycline and minocycline, all of which have been used as antibiotics effectively for decades. New uses emerged for these compounds after their effect on mitochondrial function was discovered. Cytostatic and cytotoxic activity of these compounds was shown against cell lines of various tumor origins. In addition, tetracyclines and chemically modified tetracyclines inhibit the activity of several matrix metalloproteinases (MMPs). Given the importance of these enzymes in tumor cell invasion and metastatic ability, the potential use of tetracyclines in cancer therapy needed to be investigated. Col-3, a chemically modified tetracycline, is now the subject of clinical trials in cancer patients. However, the potential of tetracyclines in cancer therapy takes on an added dimension in the bone. MMPs have been shown to be important mediators of metastasis formation in the bone, contributing largely to the morbidity of breast cancer and prostate cancer patients. The natural osteotropism of tetracyclines would allow them to be highly effective in the inhibition of MMPs produced by osteoclasts or tumor cells in the bone. This hypothesis has now been confirmed by experimental evidence showing that doxycycline reduces tumor burden in a mouse model of breast cancer-derived osteolytic bone metastasis. This effect is likely due to a combination of multiple roles of doxycycline, including MMP inhibition and a negative effect on osteoclast differentiation and survival. These encouraging results have now paved the way for an ongoing trial of doxycycline in early combination therapy for breast cancer and prostate cancer patients.

Antimicrob Agents Chemother. 2003 Nov;47(11):3630-3.
Krakauer T, Buckley M.
Department of Immunology and Molecular Biology, United States Army Medical Research Institute of Infectious Diseases, Maryland, USA.
Doxycycline is anti-inflammatory and inhibits staphylococcal exotoxin-induced cytokines and chemokines.
Proinflammatory cytokines mediate the toxic effect of superantigenic staphylococcal exotoxins (SE). Doxycycline inhibited SE-stimulated T-cell proliferation and production of cytokines and chemokines by human peripheral blood mononuclear cells. These results suggest that the antibiotic doxycycline has anti-inflammatory effects and is therapeutically useful for mitigating the pathogenic effects of SE.

Pol J Pharmacol. 2003 May-Jun;55(3):433-41.
Folwarczna J, Pytlik M, Janiec W.
Department of Pharmacology, Medical University of Silesia, Jagiellonska 4, PL 41-200 Sosnowiec, Poland.
Effects of doxycycline on development of changes in histomorphometric parameters of bones induced by bilateral ovariectomy in rats.
Tetracyclines are considered potential medication for the treatment of osteoporosis. The aim of the present study was to investigate the effects of doxycycline on development of unfavorable changes in bone histomorphometric parameters induced by bilateral ovariectomy in rats. Doxycycline at a dose of 20 mg/kg po daily was administered for 28 days to bilaterally ovariectomized and sham-operated 3-month-old Wistar rats. Bone histomorphometric parameters of the tibia (transverse growth, width of periosteal and endosteal osteoid, area of the transverse cross-section of the diaphysis and area of the transverse cross-section of the marrow cavity) and the femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were examined. Bilateral ovariectomy caused symptoms of osteopenia in the rat bones. Doxycycline counteracted the unfavorable changes in bone structure caused by estrogen deficiency. However, in the sham-operated rats doxycycline itself induced deleterious effects in the trabecular bone.

J Chemother. 2003 Aug;15(4):369-73.
Maraki S, Margioris AN, Orfanoudaki E, Tselentis Y, Koumantakis E, Kontoyiannis DP, Rovithi M, Samonis G.
School of Medicine, The University of Crete, P.O. Box 1393, Heraklion 711 10, Crete, Greece.
Effects of doxycycline, metronidazole and their combination on Candida species colonization of the human oropharynx, intestinal lumen and vagina.
The present study reports about the effect of doxycycline and/or metronidazole on colonization by Candida organisms of the human gastrointestinal (GI), oropharyngeal tract and vagina. Treatment with doxycycline or metronidazole for 10 days increased, but not significantly, the GI, oropharyngeal or vaginal colonization by Candida species. The combination of doxycycline and metronidazole, used for the same period, caused a significant increase of 2.5 log10 CFU/g of stools (mean) colonization by Candida. Likewise, 2 out of 9 patients treated with the combination had substantially increased colonization of their vagina by Candida species. This effect, however, could not be expressed statistically due to the semiquantitative nature of the vaginal cultures. In contrast, the combination did not increase oropharyngeal colonization. In conclusion, doxycycline and metronidazole as monotherapies, did not increase significantly Candida colonization in the cavities examined. The combination of doxycycline and metronidazole had a substantial effect, increasing the GI and vaginal colonization by Candida organisms.