minocycline and Respiratory-Insufficiency

Opioid treatment of pain is generally safe with 0.5% or less events from respiratory depression. However, fatalities are regularly reported. The only treatment currently available to reverse opioid respiratory depression is by naloxone infusion. The efficacy of naloxone depends on its own pharmacological characteristics and on those (including receptor kinetics) of the opioid that needs reversal. Short elimination of naloxone and biophase equilibration half-lives and rapid receptor kinetics complicates reversal of high-affinity opioids. An opioid with high receptor affinity will require greater naloxone concentrations and/or a continuous infusion before reversal sets in compared with an opioid with lower receptor affinity. The clinical approach to severe opioid-induced respiratory depression is to titrate naloxone to effect and continue treatment by continuous infusion until chances for renarcotization have diminished. New approaches to prevent opioid respiratory depression without affecting analgesia have led to the experimental application of serotinine agonists, ampakines, and the antibiotic minocycline.

Topics: Buprenorphine; Humans; Minocycline; Naloxone; Narcotic Antagonists; Postoperative Complications; Respiratory Insufficiency; Serotonin Agents

A previously healthy 40-year-old woman was admitted with severe dyspnea, cough and slight fever. Chest X-ray film revealed bilateral widespread opaque infiltration with ground glass shadows around it. The laboratory examination showed moderate hepatic and muscular injury with disseminated intravascular coagulation. In addition her arterial blood gas showed severe hypoxemia (PaO2: 25 Torr under room air). Moreover, about 1 week prior to admission, 2 baby budgerigars she had been raising for half a year died. Because of this history and multi-organ injuries, this disease was considered to be acute pneumonia owing to fulminant psittacosis causing acute respiratory failure. On the first day of admission, she was intubated and ventilated mechanically with an oxygen concentration (FIO2) of 100%. Subsequently, treatment with intravenous minocycline (400 mg/day), heparin for D.I.C. and corticosteroid were started. Abnormal findings in both chest X-ray and several laboratory parameters improved gradually though fever continued for a week. On the 14th day of her hospital stay, she was weaned from the ventilator successfully and the administration of corticosteroid and heparin tapered. On the 41st day, she was discharged without any symptoms. Results of complement fixation (CF) antibodies against chlamydia on paired sera showed a significant rise from 1:32 to 1:256. Moreover, both IgG and IgM antibodies for Chlamydia psittaci with microplate immunofluorescent antibody technique (MFA) showed an 8 times' rise during 10 days after admission. The definitive diagnosis was made with positive isolation of C. psittaci from both the throat swab of this patient and the spleen and liver of the dead budgerigar by the cell culture method. Psittacosis should always be borne in mind as a possible cause of fulminant pneumonia with acute respiratory failure, and such a situation can be handled successfully if emergency care including mechanical ventilation is available.

Topics: Acute Disease; Adult; Chlamydophila psittaci; Emergencies; Female; Heparin; Humans; Minocycline; Pneumonia; Psittacosis; Respiration, Artificial; Respiratory Insufficiency; Tetracyclines

Bronchiolitis obliterans is a small-airway obstructive lung disease for which immunologically mediated pathogenesis is supposed. Frequent association of bronchiolitis obliterans with paraneoplastic pemphigus is well known, but its association with other autoimmune bullous diseases has not been reported except for a case of anti-laminin-332-type mucous membrane pemphigoid in a patient with chronic graft-versus-host disease. We report a case of non-paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans in a patient without transplantation. Although the patient's serum contained immunoglobulin (Ig)A antibodies to the 180-kDa bullous pemphigoid antigen/type XVII collagen and IgG antibodies to laminin-332, diagnosis of either linear IgA bullous dermatosis or mucous membrane pemphigoid could not be made because of the failure to detect linear IgA deposition at the basement membrane zone by direct immunofluorescence and the lack of mucous membrane lesions. Physicians should be aware that autoimmune bullous diseases other than paraneoplastic pemphigus can also associate with this rare but potentially fatal lung disease.

Topics: Aged; Anti-Bacterial Agents; Autoantibodies; Autoantigens; Basement Membrane; Biopsy; Bronchiolitis Obliterans; Cell Adhesion Molecules; Collagen Type XVII; Fatal Outcome; Fluorescent Antibody Technique, Direct; Glucocorticoids; Humans; Immunoglobulin A; Immunoglobulin G; Kalinin; Male; Minocycline; Niacinamide; Non-Fibrillar Collagens; Paraneoplastic Syndromes; Pemphigoid, Bullous; Prednisolone; Respiratory Insufficiency; Vitamin B Complex

We report the first case of Mycoplasma hominis periaortic abscess after heart-lung transplantation. The absence of sternal wound infection delayed the diagnosis, but the patient successfully recovered with debridement surgeries and long-term antibiotic therapy. Owing to the difficulty in detection and the intrinsic resistance to beta-lactams, M. hominis infections are prone to being misdiagnosed and undertreated. M. hominis should be suspected in cases where conventional microbiological identification and treatment approaches fail.

Topics: Abscess; Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Bronchoscopy; Cardiomyopathy, Restrictive; Debridement; Dyspnea; Glucocorticoids; Graft Rejection; Heart-Lung Transplantation; Humans; Hypertension, Pulmonary; Levofloxacin; Male; Methylprednisolone; Minocycline; Mycoplasma hominis; Nausea; Plasmapheresis; Postoperative Complications; Respiratory Insufficiency; Sternum; Surgical Wound Infection; Tomography, X-Ray Computed; Young Adult

Opioids activate glia in the central nervous system in part by activating the toll-like receptor 4 (TLR4)/myeloid differentiation 2 (MD2) complex. TLR4/MD2-mediated activation of glia by opioids compromises their analgesic actions. Glial activation is also hypothesized as pivotal in opioid-mediated reward and tolerance and as a contributor to opioid-mediated respiratory depression. We tested the contribution of TLR4 to opioid-induced respiratory depression using rhythmically active medullary slices that contain the pre-Bötzinger Complex (preBötC, an important site of respiratory rhythm generation) and adult rats in vivo. Injection with DAMGO (μ-opioid receptor agonist; 50 μM) or bath application of DAMGO (500 nM) or fentanyl (1 μM) slowed frequency recorded from XII nerves to 40%, 40%, or 50% of control, respectively. This DAMGO-mediated frequency inhibition was unaffected by preapplication of lipopolysaccharides from Rhodobacter sphaeroides (a TLR4 antagonist, 2,000 ng/ml) or (+)naloxone (1-10 μM, a TLR4-antagonist). Bath application of (-)naloxone (500 nM; a TLR4 and μ-opioid antagonist), however, rapidly reversed the opioid-mediated frequency decrease. We also compared the opioid-induced respiratory depression in slices in vitro in the absence and presence of bath-applied minocycline (an inhibitor of microglial activation) and in slices prepared from mice injected (ip) 18 h earlier with minocycline or saline. Minocycline had no effect on respiratory depression in vitro. Finally, the respiratory depression evoked in anesthetized rats by tail vein infusion of fentanyl was unaffected by subsequent injection of (+)naloxone, but completely reversed by (-)naloxone. These data indicate that neither activation of microglia in preBötC nor TLR4/MD2-activation contribute to opioid-induced respiratory depression.

Topics: Analgesics, Opioid; Animals; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Female; Fentanyl; Male; Medulla Oblongata; Minocycline; Naloxone; Neuroglia; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Respiration; Respiratory Insufficiency; Signal Transduction; Toll-Like Receptor 4

Topics: Anti-Bacterial Agents; Extracorporeal Membrane Oxygenation; Humans; Infusions, Intravenous; Minocycline; Plasma; Pneumonia, Staphylococcal; Pneumonia, Ventilator-Associated; Respiratory Insufficiency; Tigecycline; Young Adult

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

Improving quality of life (QoL) is a major goal in ALS palliative care. Previous studies performed on the general ALS population showed no relationship between QoL and disease progression. ALS subjects participating in clinical trials may differ from those in the general ALS population. We explored the relationship between QoL and disease progression in 412 subjects enrolled in a minocycline trial. We examined correlations between Single Item McGill Quality of Life Scale (MQoL-SIS) score and disease duration, ALS Functional Rating Scale Revised (ALSFRS-R) score, FVC, and survival rate. We also analyzed how NIV and PEG affect QoL. Within subjects, MQoL-SIS scores correlated with ALSFRS-R and FVC (p<0.001). MQoL-SIS declined over time (p<0.001) and correlated with the decline of ALSFRS-R (p<0.001). MQoL-SIS tended to improve after initiation of NIV (p=0.07). There was a significant reduction in the rate of MQoL-SIS decline (p<0.001) after initiation of PEG. Subjects with slower QoL decline survived seven months longer than those with faster QoL decline (p<0.01). Our study demonstrated that QoL does decline with advancing ALS in subjects who participated in a minocycline trial, that the slope of QoL predicts survival, and that both NIV and PEG have beneficial impacts on QoL.

Topics: Amyotrophic Lateral Sclerosis; Anti-Bacterial Agents; Clinical Trials, Phase III as Topic; Disease Progression; Humans; Minocycline; Outcome Assessment, Health Care; Palliative Care; Predictive Value of Tests; Quality of Life; Randomized Controlled Trials as Topic; Respiratory Insufficiency; Survival Analysis

Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here, we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force, and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation.

Topics: Analgesia; Analysis of Variance; Animals; Cell Line; Cells, Cultured; Conditioning, Operant; Cyclooxygenase 1; Dose-Response Relationship, Drug; Drug Interactions; Male; Microglia; Minocycline; Morphine; Narcotics; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Respiratory Insufficiency; Reverse Transcriptase Polymerase Chain Reaction; Reward; RNA, Messenger; Spatial Behavior

The antibiotic minocycline, which is used in the treatment of acne, has been associated with various pulmonary complications such as pulmonary lupus and hypersensitivity pneumonitis. We now report a particularly severe case of minocycline-related pulmonary toxicity that was characterized by a relapsing form of hypersensitivity eosinophilic pneumonia complicated by acute respiratory failure.

Topics: Acne Vulgaris; Acute Disease; Administration, Oral; Anti-Bacterial Agents; Female; Humans; Middle Aged; Minocycline; Pulmonary Eosinophilia; Recurrence; Respiratory Insufficiency

A previously healthy 48-year-old man presented to his primary care physician with high fever, dry cough and dyspnea. Pneumonia was diagnosed and intravenous administration of imipenem/cilastatin was begun, but his respiratory condition worsened and he was admitted to our hospital with severe hypoxia. A chest radiograph showed reticular opacity and consolidation in both lung fields. The case was complicated with disseminated intravascular coagulation. Analysis of the bronchoalveolar lavage fluid showed increases in the total cell counts and an elevated percentage of lymphocytes. Sputum, blood and bronchoalveolar lavage examinations failed to reveal etiology to explain his severe respiratory illness. Treatment consisted of mechanical ventilation and administration of steroid pulse-therapy and gabexate mesilate. On the basis of his clinical course, we suspected possible atypical pneumonia, and began therapy with intravenous minocyclin and oral erythromycin administration. On the third hospital day, the arterial blood gas data improved and the bilateral pulmonary infiltration on the chest radiographs disappeared. Using paired sera, we detected increases of 1.35 in ID for anti-Chlamydia pneumoniae IgG antibodies by ELISA, and arrived at a diagnosis of Chlamydia pneumoniae pneumonia.

Topics: Acute Disease; Chlamydophila Infections; Chlamydophila pneumoniae; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Erythromycin; Gabexate; Humans; Male; Methylprednisolone; Minocycline; Pneumonia, Bacterial; Respiration, Artificial; Respiratory Insufficiency; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Drug Eruptions; Female; Humans; Minocycline; Respiratory Insufficiency

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