minocycline and Central-Nervous-System-Diseases

The goal of this review was to summarize the available literature covering the safety profiles of oral doxycycline and minocycline.. Scientific literature published between 1966 and August 2003 was searched using the MEDLINE, EMBASE, and Biosis databases (search terms: minocycline or doxycycline, each paired with adverse reaction, adverse event, and side effect, and doxycycline or minocycline with the limits English language, human, and clinical trials). Safety information was collected from case reports and clinical trials. Adverse event (AE) rates in the United States were calculated by comparing data from the MedWatch AE reporting program used by the US Food and Drug Administration (FDA) with the number of new prescriptions dispensed for each drug from January 1998 to August 2003.. Between 1966 and 2003, a total of 130 and 333 AEs were published in case reports of doxycycline and minocycline, respectively. In 24 doxycycline clinical trials (n = 3833) and 11 minocycline trials (n = 788), the ranges in incidence of AEs were 0% to 61% and 11.7% to 83.3%, respectively. Gastrointestinal AEs were most common with doxycycline; central nervous system and gastrointestinal AEs were most common with minocycline. From January 1998 to August 2003, the FDA MedWatch data contained 628 events for doxycycline and 1099 events for minocycline reported in the United States. Approximately 47,630,000 doxycycline and 15,234,000 minocycline new prescriptions were dispensed in the United States during that period, yielding event rates of 13 per million for doxycycline and 72 per million for minocycline, based on FDA data.. Between 1998 and 2003, doxycycline was prescribed 3 times as often as minocycline. The incidence of AEs with either drug is very low, but doxycycline had fewer reported AEs. Although more head-to-head clinical trials are needed for a direct comparison of AE frequency, these preliminary data from separate reports suggest the possibility that AEs may be less likely with doxycycline than minocycline.

Topics: Acne Vulgaris; Adverse Drug Reaction Reporting Systems; Anti-Bacterial Agents; Central Nervous System Diseases; Clinical Trials as Topic; Doxycycline; Drug Prescriptions; Gastrointestinal Diseases; Humans; Incidence; MEDLINE; Minocycline; Skin Diseases; United States; United States Food and Drug Administration

Topics: Animals; Central Nervous System Diseases; Cephalexin; Disease Models, Animal; Humans; Hyperalgesia; Microglia; Minocycline; Muscle Spasticity; Neuralgia; Sarcoidosis

Meningeal worms (Parelaphostrongylus tenuis) are a common malady of alpacas, often refractory to conventional treatments. Ivermectin is a very effective anthelmintic used against a variety of parasites but this drug is not consistently effective against alpaca meningeal worms once the parasite has gained access to the CNS, even if used in a protracted treatment protocol. Ivermectin is not effective against clinical cases of P. tenuis, raising the possibility that the drug is not sustained at therapeutic concentrations in the central nervous system (CNS). A specific protein (designated as p-glycoprotein (PGP)) effluxes ivermectin from the brain at the blood-brain barrier, thus hampering the maintenance of therapeutic concentrations of the drug in the CNS. Minocycline is a synthetic tetracycline antibiotic with an excellent safety profile in all animals tested to date. Minocycline has three unique characteristics that could be useful for treating meningeal worms in conjunction with ivermectin. First, minocycline is an inhibitor of PGP at the blood-brain barrier and this inhibition could maintain effective concentrations of ivermectin in the brain and meninges. Second, minocycline protects neurons in vivo through a number of different mechanisms and this neuroprotection could alleviate the potential untoward neurologic effects of meningeal worms. Third, minocycline is a highly lipid-soluble drug, thus facilitating efficient brain penetration. We thus hypothesized that minocycline will maintain ivermectin, or a related avermectin approved in ruminants (abamectin, doramectin, or eprinomectin), in the alpaca CNS. To test this hypothesis, we cloned the gene encoding the alpaca PGP, expressed the alpaca PGP in a heterologous expression system involving MDCK cells, and measured the ability of minocycline to inhibit the efflux of avermectins from the MDCK cells; doxycycline was used as a putative negative control (based on studies in other species). Our in vitro studies surprisingly revealed that doxycycline was effective at inhibiting the efflux of ivermectin and doramectin (minocycline had no effect). These two avermectins, in combination with doxycycline, should be considered when treating meningeal worms in alpacas.

Topics: Amino Acid Sequence; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Camelids, New World; Cell Line; Central Nervous System Diseases; Dogs; Doxycycline; Drug Interactions; Gene Expression Regulation; Ivermectin; Minocycline; Molecular Sequence Data

Topics: Anti-Bacterial Agents; Ceftriaxone; Central Nervous System Diseases; Chloroquine; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Male; Meropenem; Microbial Sensitivity Tests; Minocycline; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Whipple Disease

Nocardia concava was identified as a new species in 2005; however, the clinical manifestations of Nocardia concava infection have yet to be clarified. We herein present the case of an immunosuppressed patient who developed disseminated nocardiosis caused by N. concava with multiple abscesses in the lungs, cutis, subcutaneous tissue, skeletal muscles and kidneys accompanied by central nervous system involvement, including meningitis and ventriculitis. The patient was cured with appropriate treatment including linezolid after testing for susceptibility. Linezolid should be considered as an alternative agent for treating disseminated nocardiosis because of its effective distribution to multiple sites.

Topics: Acetamides; Acute Disease; Aged; Anti-Bacterial Agents; Central Nervous System Diseases; Humans; Immunocompromised Host; Linezolid; Male; Microbial Sensitivity Tests; Minocycline; Nocardia; Nocardia Infections; Oxazolidinones; Respiratory Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination

Prion diseases are fatal and at present there are neither cures nor therapies available to delay disease onset or progression in humans. Inspired in part by therapeutic approaches in the fields of Alzheimer's disease and amyotrophic lateral sclerosis, we tested five different drugs, which are known to efficiently pass through the blood-brain barrier, in a murine prion model. Groups of intracerebrally prion-challenged mice were treated with the drugs curcumin, dapsone, ibuprofen, memantine and minocycline. Treatment with antibiotics dapsone and minocycline had no therapeutic benefit. Ibuprofen-treated mice showed severe adverse effects, which prevented assessment of therapeutic efficacy. Mice treated with low- but not high-dose curcumin and mice treated with memantine survived infections significantly longer than untreated controls (P<0.01). These results encourage further research efforts to improve the therapeutic effect of these drugs.

Topics: Animals; Central Nervous System Diseases; Curcumin; Evaluation Studies as Topic; Ibuprofen; Memantine; Mice; Minocycline; Prion Diseases

Initial studies conducted on the neuroprotective effects of minocycline, a second-generation tetracycline, in experimental models of neurodegeneration gave promising results. However, more recently, minocycline has clearly been shown to have variable and even contradictory (beneficial or detrimental) effects in different species and models of neurological disorders, and its "neuroprotective" mechanisms remain to be clarified. Although its anti-inflammatory properties are likely to contribute to its neuroprotective effects observed in several animal models, a body of recent evidence indicates that our community should proceed with caution in the clinical use of minocycline for central nervous system disorders.

Topics: Animals; Central Nervous System Diseases; Clinical Trials as Topic; Disease Models, Animal; Humans; Minocycline; Neuroprotective Agents

Topics: Adult; Alveolitis, Extrinsic Allergic; Anti-Bacterial Agents; Central Nervous System Diseases; Female; Humans; Minocycline

Nocardia species is a well-known pathogen in immunocompromised hosts, including renal transplant recipients. Primary pulmonary infection can disseminate to other organs and recommended first-line therapy is high-dose trimethoprim/sulfamethoxazole (TMP/SMX). We report two cases of primary pulmonary Nocardia sp. in immunosuppressed patients who were treated with minocycline, a second-line drug. During treatment with minocycline, both patients developed central nervous system (CNS) lesions of Nocardia sp. and were then treated with TMP/SMX with resolution of disease. The literature on Nocardia and treatment with minocycline is reviewed. Treatment of pulmonary Nocardia sp. with 200 mg minocycline daily is not adequate to prevent disseminated CNS disease.

Topics: Anti-Bacterial Agents; Brain; Central Nervous System Diseases; Female; Humans; Immunocompromised Host; Kidney Transplantation; Middle Aged; Minocycline; Nocardia; Nocardia Infections; Trimethoprim, Sulfamethoxazole Drug Combination

A 32-year-old woman developed myalgia, fever, consciousness disturbance, mental disorder, pyramidal tract signs and meningeal irritation signs at about 2 months after a normal labor. Laboratory examination showed hypopituitarism (decreased ACTH, TSH), renal dysfunction and hypercalcemia. A variety of antibiotics, acyclovir and gamma-globulin failed to improve her symptoms. A diagnosis of Chlamydia trachomatis infection was considered from the elevated antibody titers. In this case, minocycline was very effective. Rarely Chlamydia trachomatis infection involved general organs, including the central nervous system. It was interesting that she had endocrine disorders. We must take a look for Chlamydia trachomatis infection because this infection infrequently involves general organs, including the central nervous system and minocycline is very effective for this infection.

Topics: Adult; Central Nervous System Diseases; Chlamydia Infections; Chlamydia trachomatis; Female; Humans; Minocycline

Topics: Abnormalities, Severe Teratoid; Central Nervous System Diseases; Communicable Diseases; Congenital Abnormalities; Diseases in Twins; Female; Foot Diseases; Hand Deformities; Humans; Infant; Infant, Newborn; Minocycline; Pregnancy; Pregnancy Complications, Infectious; Rubella