minocycline and Alcoholism

Raoultella planticola has been considered a relatively harmless Gram-negative bacteria, rarely associated with clinical infection. However, in recent years, the frequency at which severe infection by R. planticola and drug-resistant strains are reported in literature has increased. Here, we present one case of acute cholecystitis caused by R. planticola, and review all previously reported cases of the infection in an attempt to identify new trends in biological and clinical features of R. planticola infections.

Topics: Abdominal Pain; Aged; Aged, 80 and over; Alcoholism; Anti-Bacterial Agents; Cholecystitis, Acute; Communicable Diseases, Emerging; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Minocycline; Tigecycline

Alcohol has both acute and chronic effects on neuroimmune signaling, including triggering pro-inflammatory cytokine release by microglia. Minocycline, a second-generation tetracycline antibiotic, inhibits microglial activation and reduces neuroinflammation in preclinical studies. In mice, minocycline also reduces ethanol intake, attenuates ethanol-induced conditioned place preference, and inhibits ethanol-induced microglial activation and pro-inflammatory cytokine release.. Here, for the first time, we tested the effects of minocycline on subjective response to ethanol and acute ethanol-induced inflammation in humans.. Forty-eight heavy drinkers participated in a double-blind, placebo-controlled trial in which they were randomized to receive placebo, 100 mg, or 200 mg of minocycline for 10 days. Each subject then underwent two experimental sessions in which they were given a fixed dose of intravenous ethanol using a "clamp" procedure (100 mg%) or placebo (normal saline) on days 8 and 10 of treatment.. Minocycline was well tolerated, but there was no effect of either dose of minocycline on subjective response to ethanol or ethanol-induced craving; minocycline effects on cognitive function seem to interact with age. Minocycline treatment did not alter serum cytokine levels at baseline or during ethanol-exposure, although certain baseline cytokine levels predict sedative response to ethanol.. These findings indicate that a short-term treatment with minocycline may not alter ethanol-related inflammation or subjective response to ethanol in humans. Further research is needed to identify pharmacological agents with robust effects on ethanol-induced inflammation to determine whether neuroimmune modulation represents a viable treatment strategy for alcohol use disorder.

Topics: Adult; Alcoholic Intoxication; Alcoholism; Animals; Anti-Bacterial Agents; Cytokines; Double-Blind Method; Drug Delivery Systems; Ethanol; Humans; Infusions, Intravenous; Male; Mice; Microglia; Middle Aged; Minocycline; Young Adult

Anxiety and negative sensations due to alcohol withdrawal are factors leading to alcohol relapse and addiction. Minocycline, an antibiotic, can decrease alcohol consumption in rats, however, its effects on alcohol withdrawal anxiety and relapse have not been studied.. Part 1: Forced alcohol drinking in gradually increasing concentration was administered till day 22 in rats. Effect of drugs on anxiety was assessed using elevated plus maze (EPM) and two-chambered box apparatus, after removal of alcohol. Part 2: For relapse, an alcohol deprivation effect model was used, rats were continuously offered alcohol and water for 4 consecutive weeks in a two-bottle choice paradigm, followed by 2 weeks of alcohol deprivation. Effect of drugs on alcohol consumption during the first hour of alcohol reintroduction was assessed. Animals were sacrificed and whole brain Tumor Necrosis Factor (TNF) α was estimated.. Part 1: Anxiety at 3 hours was significantly lower following minocycline (20 mg/kg i.p.) or diazepam compared to vehicle control. Part 2: Acute administration of minocycline (5,10 and 20 mg/kg, i.p.) suppressed alcohol consumption significantly (p value<0.05) as compared to vehicle control. A significant decrease in whole brain TNF α was observed in animals treated with minocycline compared to untreated animals.. Minocycline attenuates alcohol withdrawal anxiety and disrupts alcohol relapse.

Topics: Alcohol Drinking; Alcoholism; Animals; Anti-Bacterial Agents; Anxiety; Diazepam; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Maze Learning; Minocycline; Rats; Rats, Wistar; Recurrence; Substance Withdrawal Syndrome; Tumor Necrosis Factor-alpha

Neuroimmune cytokines are increased with alcohol withdrawal and may mediate clinical responses associated with alcoholism. Because minocycline regulates the level of cytokines, it has been suggested as a therapeutic for disorders associated with alcohol. Male Wistar rats were exposed to chronic intermittent alcohol (CIA) comprising three 5-day cycles of ethanol liquid diet separated by 2 days of withdrawal. Rats were tested on social interaction, a measure of anxiety-like behavior, followed immediately by collection of amygdala tissue to measure CCL2 and TNFα or collection of the blood to measure corticosterone (CORT). One group received a single minocycline injection 3 h into the final CIA withdrawal and was tested 2 h later. A second group received injections during each of the three withdrawals and was similarly tested during the final acute withdrawal. A third group received a single injection at 23 h into withdrawal (extended withdrawal) and was tested 6 h later. Results showed that CIA withdrawal increased anxiety-like behavior. A single injection of minocycline during the final acute withdrawal increased anxiety-like behavior in rats that consumed liquid diet with or without alcohol, but this effect disappeared with repeated injections of minocycline. Differences in alcohol intake, blood alcohol level, and plasma CORT levels did not explain results. Only repeated injections of minocycline decreased TNFα mRNA levels in rats that consumed liquid diet with or without alcohol. When a single injection of minocycline was given during extended withdrawal, it decreased CCL2 mRNA levels, but did not reverse the elevation of CCL2 protein. These results suggest that minocycline has actions in brain and on behavior, but minocycline does not significantly impact these actions in relation to alcohol withdrawal.

Topics: Alcoholism; Amygdala; Animals; Anti-Bacterial Agents; Anxiety; Chemokine CCL2; Corticosterone; Drug Administration Schedule; Drug Interactions; Male; Minocycline; Rats, Wistar; RNA, Messenger; Substance Withdrawal Syndrome; Tumor Necrosis Factor-alpha

Medical management for alcohol abuse has limitations. Alcohol consumption activates N-methyl-d-aspartate receptors and release of nitric oxide which can be inhibited by minocycline as it readily crosses blood brain barrier and may have effect on alcohol consumption. Thus, study objective is to evaluate the effect of minocycline on rewarding property, extinction and the reinstatement phenomenon induced by alcohol in a model of conditioned place preference (CPP) in mice.. To evaluate rewarding effects of alcohol, CPP procedure consisted of 4 parts, including adaptation (day 1), pre-conditioning test (day 2), conditionings with alcohol (days 3, 5, 7 and 9) or saline (days 4, 6, 8 and 10) and postconditioning test (day 11) conducted on 11 consecutive days. The groups included were saline treated group (alcohol control), naltrexone - 1mg/kg (positive control), and minocycline in the doses of 10, 30 and 50mg/kg. To evaluate the effect of minocycline on alcohol relapse, CPP procedure consisted 6 parts, the first 4 were the same as enumerated above followed by extinction (days 12-16) and reinstatement phase (day 17).. The time spent in alcohol paired compartment by different groups, revealed that minocycline and naltrexone significantly attenuated alcohol-induced place preference compared to alcohol control (p<0.05). Pretreatment with minocycline and naltrexone blocked reinstatement of extinguished CPP.. Minocycline may have a role in attenuating the rewarding property of alcohol and prevent alcohol relapse.

Topics: Alcohol Drinking; Alcoholism; Animals; Conditioning, Classical; Conditioning, Operant; Disease Models, Animal; Ethanol; Extinction, Psychological; Male; Mice; Minocycline; Naltrexone; Reward; Secondary Prevention

The chronic intermittent ethanol (CIE) paradigm is valuable for screening compounds for efficacy to reduce drinking traits related to alcohol use disorder (AUD), as it measures alcohol consumption and preference under physical dependence conditions. Air control-treated animals allow simultaneous testing of similarly treated, nondependent animals. As a consequence, we used CIE to test the hypothesis that tigecycline, a semisynthetic tetracycline similar to minocycline and doxycycline, would reduce alcohol consumption regardless of dependence status.. Adult C57BL/6J female and male mice were tested for tigecycline efficacy to reduce ethanol (EtOH) consumption using a standard CIE paradigm. The ability of tigecycline to decrease 2-bottle choice of 15% EtOH (15E) versus water intake in dependent (CIE vapor) and nondependent (air-treated) male and female mice was tested after 4 cycles of CIE vapor or air exposure using a within-subjects design and a dose-response. Drug doses of 0, 40, 60, 80, and 100 mg/kg in saline were administered intraperitoneally (0.01 ml/g body weight) and in random order, with a 1-hour pretreatment time. Baseline 15E intake was re-established prior to administration of subsequent injections, with a maximum of 2 drug injections tested per week.. Tigecycline was found to effectively reduce high alcohol consumption in both dependent and nondependent female and male mice.. Our data suggest that tigecycline may be a promising drug with novel pharmacotherapeutic characteristics for the treatment of mild-to-severe AUD in both sexes.

Topics: Alcohol Drinking; Alcoholism; Animals; Case-Control Studies; Dose-Response Relationship, Drug; Female; Male; Mice; Mice, Inbred C57BL; Minocycline; Tigecycline

Use of in silico bioinformatics analyses has led to important leads in the complex nature of alcoholism at the genomic, epigenomic, and proteomic level, but has not previously been successfully translated to the development of effective pharmacotherapies. In this study, a bioinformatics approach led to the discovery of neuroimmune pathways as an age-specific druggable target. Minocycline, a neuroimmune modulator, reduced high ethanol (EtOH) drinking in adult, but not adolescent, mice as predicted a priori.. Age and sex-divergent effects in alcohol consumption were quantified in FVB/NJ × C57BL/6J F1 mice given access to 20% alcohol using a 4 h/d, 4-day drinking-in-dark (DID) paradigm. In silico bioinformatics pathway overrepresentation analysis for age-specific effects of alcohol in brain was performed using gene expression data collected in control and DID-treated, adolescent and adult, male mice. Minocycline (50 mg/kg i.p., once daily) or saline alone was tested for an effect on EtOH intake in the F1 and C57BL/6J (B6) mice across both age and gender groups. Effects of minocycline on the pharmacokinetic properties of alcohol were evaluated by comparing the rates of EtOH elimination between the saline- and minocycline-treated F1 and B6 mice.. Age and gender differences in DID consumption were identified. Only males showed a clear developmental increase difference in drinking over time. In silico analyses revealed neuroimmune-related pathways as significantly overrepresented in adult, but not in adolescent, male mice. As predicted, minocycline treatment reduced drinking in adult, but not adolescent, mice. The age effect was present for both genders, and in both the F1 and B6 mice. Minocycline had no effect on the pharmacokinetic elimination of EtOH.. Our results are a proof of concept that bioinformatics analysis of brain gene expression can lead to the generation of new hypotheses and a positive translational outcome for individualized pharmacotherapeutic treatment of high alcohol consumption.

Topics: Aging; Alcoholism; Animals; Anti-Bacterial Agents; Central Nervous System Depressants; Computational Biology; Ethanol; Female; Male; Mice; Mice, Inbred C57BL; Minocycline; Neuroimmunomodulation; Sex Characteristics

Phymas (swellings, masses, or bulbs) are considered the end-stage of rosacea and mostly affect the nose (rhinophyma), and rarely involve the chin (gnatophyma), the cheek (metophyma), eyelids (blepharophyma), or ears (otophyma). Herein, we report the case of a 57-year-old man who developed unilateral enlargement of his left ear over 2 years. Biopsy revealed changes of rosaceous lymphedema associated with Demodex infestation. Corticosteroid and minocycline therapies resulted in partial reduction of the ear enlargement. Literature review examining for cases of lymphedema (elephantiasis) of the ear revealed that chronic inflammatory disorders (rosacea (most frequent), psoriasis, eczema), bacterial cellulitis (erysipelas), pediculosis, trauma, and primary (congenital) lymphedema can all lead to localized, lymphedematous enlargement of the ear. Depending on the severity, medical treatment directed at the inflammatory condition for mild, diffuse enlargement to surgical debulking for extensive diffuse enlargement or tumor formation can improve the signs and symptoms of otophyma. Decreased immune surveillance secondary to rosaceous lymphedema may explain why Demodex infestation is common in rosacea and support the suspicion that phymatous skin is predisposed to skin cancer development.

Topics: Adrenal Cortex Hormones; Alcoholism; Anti-Infective Agents; Anti-Inflammatory Agents; Antidepressive Agents, Second-Generation; Antihypertensive Agents; Dapsone; Doxycycline; Ear Deformities, Acquired; Elephantiasis; Fenofibrate; Fluoxetine; Humans; Hydrochlorothiazide; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Hypolipidemic Agents; Insecticides; Male; Middle Aged; Minocycline; Mite Infestations; Mood Disorders; Permethrin; Prednisone; Rosacea; Triamcinolone

Currently preferred therapy for CNS Nocardia infection is high-dose sulfonamide coupled with surgical drainage. Neither of these could be used in our patient; this led to therapy with minocycline alone. Several months after completion of minocycline therapy, the patient apparently is cured. His favorable outcome probably resulted from a combination of susceptibility of the organism to minocycline coupled with good CNS penetration of the agent resulting in CNS levels of drug 16 to 22 times higher than the Nocardia inhibitory concentration.

Topics: Alcoholism; Brain Diseases; Humans; Male; Middle Aged; Minocycline; Nocardia asteroides; Nocardia Infections; Tetracyclines

Two patients had community-acquired Acinetobacter calcoaceticus var anitratus pneumonia. Both patients were alcoholic and one was cirrhotic. One patient died and the other received two weeks of gentamicin therapy and survived. Misinterpretation of the sputum Gram stain delayed diagnosis and institution of proper therapy in both cases. In addition to organisms sensitive to penicillins such as Neisseria or Haemophilus, Acinetobacter must be considered in the differential diagnosis of community-acquired Gram-negative coccobacillary pneumonia.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Alcoholism; Amikacin; Diagnostic Errors; Drug Resistance, Microbial; Female; Gentamicins; Humans; Liver Cirrhosis; Male; Middle Aged; Minocycline; Pneumonia; Sputum; Staining and Labeling; Tobramycin