minocycline and Lung-Diseases

We report four cases of the side effects of minocycline seen during the last two years in our department. There was one case of drug-related lupus and three cases of hypersensitivity reactions, including one eosinophilic pneumopathy with pericarditis, one nephropathy and one severe, pseudo-infectious episode of high fever, rash, lympadenopathy, hepatitis and eosinophilia. Minocycline is a tetracycline agent widely used for acne therapy in France and all over the world. During the last few years, there has been an increasing number of reports concerning systemic adverse reactions to minocycline, with on the one hand auto-immune disorders (lupus, autoimmune hepatitis, vascularitis with ANCA), occurring after a prolonged course of therapy and reported recently in the last few years, and on the other hand, hypersensitivity reactions (eosinophilic pneumopathies, hepatitis, nephropathies, myocarditis, serum sickness or pseudo-infectious reactions), occurring precociously in the course of therapy, and potentially severe. Although these side effects are uncommon in the context of the high number of patients who have been prescribed the drug, the first-line antibiotic therapy in acne must probably be reconsidered.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Drug Hypersensitivity; Eosinophilia; Female; Humans; Kidney Diseases; Lung Diseases; Lupus Vulgaris; Male; Minocycline

Iatrogenic lung disease in man is generated by very different and often complex pathology. This explains the great clinical diversity of these disorders which may manifest as eosinophilic pneumonia, intra-alveolar haemorrhage, bronchiolitis obliterans and diffuse interstitial pneumonia even with pulmonary fibrosis. The causes are also very varied such as direct cellular toxicity, cellular oedema, an alteration of the alveolar capillary membrane, the activation of inflammatory and/or immune cells, which are responsible for the production of soluble mediators whose effects are sometimes harmful to the pulmonary parenchyma. Rather than reporting on the different clinical types of iatrogenic lung disease and indicating for each one the hypothetical or known physiopathogenic mechanism, we have chosen to examine certain fundamental lesional mechanisms and to indicate the principal nosological groups which they cover. We have centered this review on the physiopathogenic models which are the most coherent and most fully elaborated based on observations made on man or on experimental animal models. Among those we have reported here is a case of bleomycin toxicity, with its direct toxic mechanism on the epithelial or endothelial cellular targets, amiodarone lung disease and with its associated alveolar oedema, inflammatory reactions and immunological reactions whose specificity is poorly understood; also there are some alveolitides whose specificity has been demonstrated, such as those to minocycline and to BCG and finally a complex model which is both inflammatory and disturbed immunology in radiation pneumonia.

Topics: Adjuvants, Immunologic; Amiodarone; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; BCG Vaccine; Bleomycin; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Humans; Lung Diseases; Minocycline

Mycobacterium abscessus causes chronic pulmonary infections that are extremely difficult to cure. The currently recommended combination therapy is associated with high failure rates and relapse. Tigecycline has been explored in salvage regimens, with a response rate of 43% in those who received at least a month of therapy. We performed a dose-response study in a hollow-fiber system model of pulmonary M. abscessus infection in which we recapitulated tigecycline human pulmonary concentration-time profiles of 8 different doses for 21 days. We identified the maximal kill or efficacy in CFU per milliliter and the ratio of the 0- to 24-h area under the concentration-time curve to MIC (AUC/MIC) associated with 80% efficacy (EC80). The tigecycline efficacy was 5.38 ± 2.35 log10 CFU/ml, and the drug achieved the unprecedented feat of a bacterial level of 1.0 log10 CFU/ml below the pretreatment inoculum (1-log kill) of M. abscessus in the hollow-fiber system. The EC80 AUC/MIC ratio was 36.65, while that for a 1-log kill was 44.6. Monte Carlo experiments with 10,000 patients were used to identify the clinical dose best able to achieve the EC80 or 1-log kill. The standard dose of 100 mg/day had a cumulative fraction of response of 51% for the EC80 and 46% for 1-log kill. For both the EC80 target and 1-log kill, the optimal tigecycline clinical dose was identified as 200 mg/day. The susceptibility breakpoint was ≤0.5 mg/liter. Tigecycline is the most active single agent evaluated to date, and we propose that 200 mg/day be examined as the backbone of new combination therapy regimens to replace current treatment.

Topics: Anti-Bacterial Agents; Area Under Curve; Humans; Lung Diseases; Microbial Sensitivity Tests; Minocycline; Monte Carlo Method; Mycobacterium; Tigecycline

Topics: Amikacin; Anti-Bacterial Agents; Cefoxitin; Diabetes Complications; Drug Therapy, Combination; Female; Humans; Lung Diseases; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Tigecycline

A 65-year-old-woman complained of lumbago from the end of March 2008. Three weeks later, she visited a local clinic because of high fever, and she was given a diagnosis of urinary tract infection. Although levofloxacin was given, her condition did not improve and she was referred to the urology department of our hospital. Two days after hospitalization, she rapidly developed respiratory failure. Chest CT revealed bilateral pleural effusion, interlobular septal thickening, diffuse ground-glass opacities and mediastinal lymphadenopathy. We suspected scrub typhus because we noticed a localized necrotic skin lesion on her left lower leg. When minocycline was administered, both her clinical condition and radiographic imaging promptly improved. Because lung involvement with scrub typhus is very rare in Japan, we report this case of scrub typhus with various lung findings.

Topics: Aged; Female; Humans; Lung Diseases; Minocycline; Scrub Typhus

A 53-year-old man was treated for hypoxic pneumonia. Alveolar lavage revealed neutrophilic alveolitis and search for an infectious agent was negative. Lung biopsy revealed discrete endo-alveolar edema and polymorphous infiltration in moderately thickened alveolar walls. After 17 days, an ineffective antibiotic regimen was replaced by corticosteroids. Clinical and radiological signs improved in a few days and pneumonia did not recur after corticosteroid withdrawal. The most likely causal agent was minocycline which the patient had received for two Years for the treatment of rhinophyma. Minocycline had been interrupted several weeks when the pulmonary disorder developed after re-introduction of minocycline. Different clinical manifestations of minocycline-induced lung disease have been described including eosinophilic pneumopathy, bronchiolitis obliterans with organized pneumonitis, and hypersensitivity pneumonitis. There has only been one report of polymorphonuclear neutrophils observed in the lavage fluid.

Topics: Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Humans; Lung Diseases; Male; Middle Aged; Minocycline; Neutrophil Infiltration; Pulmonary Alveoli

A 62-year-old woman was admitted with fever and bloody sputum. A mass shadow in the left S3 and obstruction of the left B3 were seen on a chest radiograph and CT. Obstructive pneumonia was suspected, and cefotiam and imipenem/cilastatin were administered. However, this treatment did not show adequate efficacy. Bronchoscopy demonstrated a yellowish-white polypoid lesion in the left B3, but histopathological findings with HE staining yielded no definite diagnosis. Subsequently, Nocardia asteroides was detected in sputum test. A sulfamethoxazole-trimethoprim combination and minocycline were administered, and the clinical findings improved. Gram-positive microfilaments were confirmed retrospectively in the pathologic specimen, and a diagnosis of pulmonary nocardiosis was made.

Topics: Anti-Bacterial Agents; Bronchial Diseases; Female; Humans; Lung Diseases; Middle Aged; Minocycline; Nocardia asteroides; Nocardia Infections; Polyps; Trimethoprim, Sulfamethoxazole Drug Combination

A 32-year-old patient taking corticosteroid therapy for 10 months for autoimmune hemolytic anemia developed Hodgkin's disease and concomitant acute pulmonary nocardiosis. After treatment with imipenen and amikacin for 15 days, which was adapted to susceptibility tests, multiple-drug chemotherapy using the ABVD protocol (doxorubicin, bléomycin, vinblastine, dacarbazine) was given without recurrence of the pulmonary infection. Antibiotic prophylaxis using a minocycine-erythromycin combination was continued for 8 months. We discuss the importance of long-term treatment based on data in the literature.

Topics: Adult; Amikacin; Anemia, Hemolytic; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Erythromycin; Hodgkin Disease; Humans; Imipenem; Long-Term Care; Lung Diseases; Male; Minocycline; Nocardia Infections

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Fever; Hemoptysis; Hemorrhage; Humans; Kidney; Leg; Leptospirosis; Liver; Lung Diseases; Male; Minocycline; Muscle, Skeletal; Pain; Radiography, Thoracic; Respiratory Distress Syndrome; Tomography, X-Ray Computed

Minoeycline, a semisynthetic tetracycline, is often used to treat acne and rheumatoid arthritis. It has been considered an unlikely drug to be associated with systemic lupus erythematosus; however, many cases of drug-induced lupus related to minocycline have been reported. Some of those reports included pulmonary lupus, but none of the patients described developed respiratory distress. We describe a patient treated with minocycline for 2 years who presented with progressive dyspnea, severe hypoxia, and pulmonary infiltrates necessitating hospitalization and oxygen supplementation.

Topics: Adolescent; Anti-Bacterial Agents; Female; Humans; Lung; Lung Diseases; Lupus Erythematosus, Systemic; Minocycline; Radiography; Respiratory Insufficiency

Pathological changes were seen in the lungs of ddY mice one week after repeated intraperitoneal injections of lipopolysaccharide (LPS) of Klebsiella pneumoniae. The infiltration of polymorphonuclear cells (PMN), mainly neutrophils, and lymphocytes into the alveolar septum, the infiltration of PMN into perivascular areas and microthrombi were recognized in this murine model. The blood levels of TNF alpha and IL-1 alpha did not rise at this time, suggesting that the most important cytokine promoting inflammation one week after LPS stimulation was neither TNF alpha nor IL-1 alpha. In the lungs of mice administered minocycline together with LPS, lymphocyte infiltration of alveoli and perivascular areas as well as microthrombi were suppressed. The blood levels of TNF alpha, IL-1 alpha, IL-4 and IL-6 were elevated in these groups, suggesting the suppression of pathological changes to be associated with the anti-inflammatory effect of IL-6 and/or persistent elevation of TNF alpha and/or IL-1 alpha levels. In conclusion, subacute pathological changes in the lung were induced by repeated intraperitoneal injections of LPS to mice. These pathological changes were suppressed by minocycline, suggesting the anti-inflammatory effects of this antibiotic to be the result of stimulating certain cytokines.

Topics: Animals; Anti-Bacterial Agents; Cytokines; Disease Models, Animal; Injections, Intraperitoneal; Klebsiella pneumoniae; Lipopolysaccharides; Lung Diseases; Mice; Minocycline

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cartilage; Cartilage, Articular; Horses; Humans; Lung Diseases; Minocycline; Rheumatic Diseases; Steroids; Surface Properties; Surface-Active Agents; Synovial Fluid

A 55-year-old man was admitted to our department one month after resection of rectal carcinoma, with complaints of fever and general malaise. Shock developed rapidly after admission. The chest X-ray film and computed tomography showed diffuse small nodular shadows and bilateral pleural effusion. Septic lung caused by Methicillin-resistant Staphylococcus epidermidis (MRSE) was diagnosed from the results of a bacteriological study. This bacteria is a Coagulase Negative Staphylococcus (CNS). Chemotherapy with Minocycline and Cefotiam was effective. Characteristic radiologic features of this case may be related to the early stage of adult respiratory distress syndrome (ARDS) and septic pulmonary microembolism.

Topics: Anti-Bacterial Agents; Bacteremia; Cefotiam; Cephalosporins; Humans; Lung Diseases; Male; Methicillin Resistance; Middle Aged; Minocycline; Staphylococcal Infections; Staphylococcus epidermidis

Minocycline hydrochloride was used to treat pulmonary infections with Nocardia asteroides in five cardiac allograft recipients. In three patients, minocycline was successfully used as the only antinocardial agent. Two other patients were found to have leukopenia after initial therapy with sulfisoxazole. These two patients were subsequently treated with minocycline. The clinical success with minocycline in these highly immunosuppressed patients suggests that minocycline is an effective antinocardial agent. These data did not allow any conclusion regarding which drug, minocycline or sulfisoxazole, is superior in the treatment of this disease.

Topics: Adult; Drug Resistance, Microbial; Female; Heart Transplantation; Humans; Immunosuppression Therapy; Lung Diseases; Male; Middle Aged; Minocycline; Nocardia asteroides; Nocardia Infections; Sulfisoxazole; Tetracyclines

Topics: Aged; Albumins; Bronchial Diseases; Female; Humans; Lung Diseases; Male; Middle Aged; Minocycline; Oxytetracycline; Respiratory Tract Infections; Sputum; Tetracyclines; Time Factors; Transferrin

Topics: Adult; Ampicillin; Aspergillus fumigatus; Drug Synergism; Erythromycin; Humans; Kidney Transplantation; Lung Diseases; Male; Minocycline; Nocardia asteroides; Nocardia Infections; Postoperative Complications; Sputum; Tetracycline; Transplantation, Homologous

Topics: Acute Disease; Aged; Bacterial Infections; Bronchitis; Bronchopneumonia; Female; Humans; Lung Diseases; Male; Middle Aged; Minocycline; Respiratory Tract Infections; Tetracycline