minocycline and Brain-Abscess

Minocycline exerts beneficial immune modulatory effects in several noninfectious neurodegenerative disease models; however, its potential to influence the host immune response during central nervous system bacterial infections, such as brain abscess, has not yet been investigated. Using a minocycline-resistant strain of Staphylococcus aureus to dissect the antibiotic's bacteriostatic versus immune modulatory effects in a mouse experimental brain abscess model, we found that minocycline significantly reduced mortality rates within the first 24 hours following bacterial exposure. This protection was associated with a transient decrease in the expression of several proinflammatory mediators, including interleukin-1beta and CCL2 (MCP-1). Minocycline was also capable of protecting the brain parenchyma from necrotic damage as evident by significantly smaller abscesses in minocycline-treated mice. In addition, minocycline exerted anti-inflammatory effects when administered as late as 3 days following S. aureus infection, which correlated with a significant decrease in brain abscess size. Finally, minocycline was capable of partially attenuating S. aureus-dependent microglial and astrocyte activation. Therefore, minocycline may afford additional therapeutic benefits extending beyond its antimicrobial activity for the treatment of central nervous system infectious diseases typified by a pathogenic inflammatory component through its ability to balance beneficial versus detrimental inflammation.

Topics: Animals; Anti-Bacterial Agents; Brain Abscess; Chemokine CCL2; Encephalitis; Interleukin-1beta; Mice; Mice, Inbred C57BL; Minocycline; Neuroglia; Staphylococcal Infections; Staphylococcus aureus; Toll-Like Receptor 2

A 60-year-old man with surgically treated nocardia pyothorax was referred to our hospital since he became drowsy. Brain MRI revealed multiple brain abscesses. His cerebrospinal fluid (CSF) showed increase in polymorphonuclear cells and decrease in glucose. Since he was allergic to sulfamethoxazole * trimethoprim, ceftriaxone and then minocycline were given. Minocycline resulted in dramatic improvement of neurological symtoms, MRI findings and CSF cell count. PCR analysis of 16S ribosomal DNA using his resected thoracic wall revealed that nocardia from his tissue was strain IFM0860. Strain IFM0860 nocardia was found to be sensitive to minocycline but not to sulfamethoxazole * trimethoprim and ceftriaxone. Intravenous administration of minocycline was followed by three-year per os administration of minocycline during which he had no recurrence of brain abscess. Thus, brain nocardiosis could be successfully treated with appropriate antibiotics. The lesson from the present case is that identification of the type of nocardia by PCR analysis of 16S ribosomal DNA could help accomplish tailor-made antibiotic therapy.

Topics: Anti-Bacterial Agents; Brain; Brain Abscess; Empyema, Pleural; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Minocycline; Nocardia Infections

Nocardial infections in an immunocompromised host have been increasingly reported. Nocardial brain abscess, the most common presentation of nocardiosis in the central nervous system, is associated with a high mortality rate because of its delayed diagnosis and its unresponsiveness to the usual antibiotic therapy. We report four patients who experienced a long-term cure of nocardial brain abscess due to treatment by a combination of surgery and postoperative antibiotic therapy; 1 man and 3 women, ages ranging from 43 to 67 years old. Two patients were associated with systemic lupus erythematosus and two with autoimmune hemolytic anemia. Patients underwent surgical aspiration and drainage of brain abscess. Nocardia was identified from the aspirated specimen and postoperative antibiotic therapy for 5-6 weeks was performed using effective antibiotic agents; sulfamethoxazole/trimethoprim (ST), imipenem/cilastatin and minocycline (MINO) in Case 1, ST and MINO in Case 2, erythromycin in Case 3, and panipenem/betamipron and cefotaxime in Case 4. Case 3 and Case 4 with multilobulated brain abscess underwent total excision of the brain abscess. All patients showed successful cure of nocardial brain abscess with no recurrence for the period of 1-8 years. The combination of surgery and postoperative antibiotic therapy provides a good prognosis for nocardial brain abscess.

Topics: Adult; Aged; Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; beta-Alanine; Brain Abscess; Cefotaxime; Cilastatin; Cilastatin, Imipenem Drug Combination; Drainage; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Immunocompromised Host; Lupus Erythematosus, Systemic; Male; Middle Aged; Minocycline; Nocardia Infections; Postoperative Care; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Abscess; Aged; Anti-Bacterial Agents; Brain Abscess; Focal Infection; Humans; Immunocompetence; Male; Minocycline; Nocardia asteroides; Nocardia Infections; Seizures; Skin Diseases, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Brain Abscess; Ceftriaxone; Humans; Male; Minocycline; Nocardia asteroides; Nocardia Infections