Antimicrobial Susceptibility Survey of Invasive Haemophilus influenzae in the United States in 2016.

Antibiotics are important for the treatment and prevention of invasive Haemophilus influenzae disease. Reduced susceptibility to clinically relevant drugs, except ampicillin, has been uncommon in the United States. Susceptibility of 700 invasive H. influenzae isolates, collected through population-based surveillance during 2016, was assessed for 15 antibiotics using broth microdilution, according to the CLSI guidelines; a subset of 104 isolates were also assessed for rifampin susceptibility using Etest. Genomes were sequenced to identify genes and mutations known to be associated with reduced susceptibility to clinically relevant drugs. A total of 508 (72.6%) had reduced susceptibility to at least one antibiotic and more than half of the isolates exhibited reduced susceptibility to only one (33.6%) or two (21.6%) antibiotic classes. All tested isolates were susceptible to rifampin, a chemoprophylaxis agent, and <1% (n = 3) of isolates had reduced susceptibility to third generation cephalosporins, which are recommended for invasive disease treatment. In contrast, ampicillin resistance was more common (28.1%) and predominantly associated with the detection of a ß-lactamase gene; 26.2% of isolates in the collection contained either a TEM-1 or ROB-1 ß-lactamase gene, including 88.8% of ampicillin-resistant isolates. ß-lactamase negative ampicillin-resistant (BLNAR) isolates were less common and associated with ftsI mutations; resistance to amoxicillin-clavulanate was detected in <2% (n = 13) of isolates. The proportion of reduced susceptibility observed was higher among nontypeable H. influenzae and serotype e than other serotypes. US invasive H. influenzae isolates remain predominantly susceptible to clinically relevant antibiotics except ampicillin, and BLNAR isolates remain uncommon. IMPORTANCE Antibiotics play an important role for the treatment and prevention of invasive Haemophilus influenzae disease. Antimicrobial resistance survey of invasive H. influenzae isolates collected in 2016 showed that the US H. influenzae population remained susceptible to clinically relevant antibiotics, except for ampicillin. Detection of approximately a quarter ampicillin-resistant and ß-lactamase containing strains demonstrates that resistance mechanisms can be acquired and sustained within the H. influenzae population, highlighting the continued importance of antimicrobial resistance surveillance for H. influenzae to monitor susceptibility trends and mechanisms of resistance.

A 'Natural' thyroid storm!

WHAT IS KNOWN AND OBJECTIVE: Over the counter supplements are often taken for granted during medication reconciliation in the emergency department. Supplements are not regulated by FDA, and some can be potentially dangerous. CASE SUMMARY: We report a case of thyrotoxicosis secondary to over the counter bovine thyroid supplements. Our patient presented with atrial fibrillation with rapid ventricular response refractory to calcium channel blockers. Had we not known about the supplement, the course of treatment would have been different with potential adverse outcome. WHAT IS NEW AND CONCLUSION: Natural thyroid supplements are marketed as over the counter products and are largely unregulated. Thyroid extracts have been found to have disparaging inconsistencies in composition, delivering anywhere from non-existent to supratherapeutic doses. Thyroid supplements should be regulated considering the potential side effects.

Neuroprotective effects of the second generation antipsychotics.

BACKGROUND: In contrast to over 30 studies reporting neurotoxicity associated with the first-generation antipsychotics (FGAs), several published studies have reported multiple neuroprotective effects associated with the second generation antipsychotics (SGAs). This prompted us to conduct a review of the reported neuroprotective mechanisms of the SGA class of antipsychotics compared to the FGAs. METHODS: A PubMed search was conducted using the keywords antipsychotic, neuroprotection, neuroplasticity, neurogenesis, neurotoxicity, toxicity, brain volume, neuroinflammation, oxidative stress, myelin, and oligodendrocyte. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. RESULTS: Animal, cell culture, and human clinical studies were identified. Twenty-four reports met the criteria for the search. All studies included at least one SGA (aripiprazole, clozapine, lurasidone, olanzapine, paliperidone, perospirone, quetiapine, risperidone, and/or ziprasidone). A few also included FGAs as a comparator (predominantly haloperidol). All studies demonstrated at least one neuroprotective mechanism of one or more SGAs, while some studies also showed that FGAs ranged from having no neuroprotective effects to actually exerting neurotoxic effects leading to neuronal death. CONCLUSIONS: A review of the literature suggests that in addition to their antipsychotic efficacy and low motoric side effects, SGAs exert measurable neuroprotective effects mediated via multiple molecular mechanisms and often in a dose-dependent manner. The neuroprotective effects of SGAs range from preventative to restorative and may play a salutary role in ameliorating the neurodegenerative effects of psychosis.

Body temperature rises following improvement of depression with ECT.

BACKGROUND: Recent studies have reported hyperthermia is an efficacious treatment for depression. Thus, we hypothesized that a proven depression therapy such as electroconvulsive therapy (ECT) would be associated with an increase in body temperature. METHODS: A retrospective chart analysis was conducted on 33 participants who recovered from depression after a course of ECT. All were hospitalized for recurrent, severe symptoms and had no previous ECT treatment. Oral temperature recordings before and after the first and last ECT treatments were collected for each participant. Statistical analysis was performed using paired t test. RESULTS: No significant change in mean oral temperature occurred after the first ECT, but a significant increase from baseline was observed after the final ECT treatment when depression symptoms had clinically remitted (P < .009). CONCLUSIONS: Improvement in clinical depression with ECT is correlated with an increase in body temperature. Body temperature may have potential as a biomarker for ECT efficacy, and possibly for antidepressant pharmacotherapies.

Allopurinol augmentation in acute mania: A meta-analysis of placebo-controlled trials.

BACKGROUND: Allopurinol is a xanthine oxidase inhibitor commonly used in the treatment of gout. Recent studies have also shown its promise as an adjunctive treatment for manic episodes in bipolar 1 disorder, possibly through mechanisms involving the purinergic pathway. However, its efficacy across studies has been inconsistent, so we conducted a meta-analysis of the published controlled studies with the goal of determining the efficacy profile of allopurinol as an adjunctive treatment for mania in bipolar disorder. METHODS: An online search was conducted using PubMed for placebo-controlled, randomized, double-blind, clinical trials (RCTs) using the terms "allopurinol," "bipolar," "mania," "manic," and "YMRS" and a meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. RESULTS: Five studies met the criteria for inclusion. Three of the five studies were inpatient treatments, one study was outpatient treatment, and one study had a mixture of both. All studies used allopurinol as an adjunct in treating acute mania in bipolar disorder subjects. Four of the studies showed efficacy in the primary outcome measure between allopurinol vs. placebo groups with significantly reduced YMRS scores while one showed no significant effect size between the allopurinol and placebo groups. The overall effect size for the four studies is d = 0.294. No significant difference in side effects were found between groups for any of the studies. CONCLUSION: The data suggest that allopurinol may have some efficacy as an adjunct in reducing mania symptoms during acute manic episodes in patients with bipolar disorder. Adjunctive allopurinol efficacy may be related to the mood stabilizer used. Additional controlled trials with greater sample sizes, homogenous dosing, and consistent treatment modalities are needed to determine optimal clinical application.

Multiple neurotoxic effects of haloperidol resulting in neuronal death.

BACKGROUND: Several published studies have reported an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume. This prompted us to review the possible neurotoxic mechanisms of first-generation antipsychotics (FGAs), especially haloperidol, which has been widely used over the past several decades. METHODS: A PubMed search was conducted using the keywords haloperidol, antipsychotic, neurotoxicity, apoptosis, oxidative stress, and neuroplasticity. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. RESULTS: Animal, cell culture, and human tissue studies were identified. Thirty reports met the criteria for the search. All studies included haloperidol; a few also included other FGAs (fluphenazine and perphenazine) and/or second-generation agents (SGAs) (aripiprazole, paliperidone, and risperidone). A neurotoxic effect of haloperidol and other FGAs was a common theme across all studies. Minimal (mainly at high doses) or no neurotoxic effects were noted in SGAs. CONCLUSIONS: A review of the literature suggests that haloperidol exerts measurable neurotoxic effects at all doses via many molecular mechanisms that lead to neuronal death. A similar effect was observed in 2 other FGAs, but the effect in SGAs was much smaller and occurred mainly at high doses. A stronger binding to serotonin 5HT-2A receptors than to dopamine D2 receptors may have a neuroprotective effect among SGAs. Further studies are warranted to confirm these findings.

Placebo-controlled augmentation trials of the antioxidant NAC in schizophrenia: A review.

BACKGROUND: Several studies have reported that schizophrenia is associated with mitochondrial abnormalities, glutathione deficit, and increased brain oxidative stress (free radicals). N-acetylcysteine (NAC) is a strong antioxidant with potential therapeutic benefit in schizophrenia, according to some reports. We conducted a review of the published controlled studies, with the goal of determining the efficacy profile of NAC as an adjunctive treatment for schizophrenia. METHODS: An online search was conducted for all placebo-controlled, double-blind, randomized clinical trials of NAC in schizophrenia, and a review was conducted. RESULTS: Two studies met the criteria for inclusion. Berk et al (2008) used NAC as an adjunctive treatment to atypical antipsychotics in subjects with chronic schizophrenia who were stable on antipsychotic medications. Treatment at 8 weeks was less efficacious than placebo, but at 24 weeks produced significant reductions vs placebo in Positive and Negative Syndrome Scale (PANSS) negative (d = 0.52), general (d = 0.46), and total (d = 0.57) scores. Farokhnia et al (2013) used NAC as an adjunctive treatment to risperidone in subjects with chronic schizophrenia who were experiencing an acute exacerbation episode. Eight weeks of treatment led to clinically significant reductions vs placebo in PANSS negative (d = 0.96), general (d = 0.59), and total (d = 0.88) scores. CONCLUSIONS: The data suggest that adjunctive NAC may be efficacious in reducing negative and general symptoms in schizophrenia.

A meta-analysis of placebo-controlled trials of omega-3 fatty acid augmentation in schizophrenia: Possible stage-specific effects.

BACKGROUND: Omega-3 fatty acids have shown promise as an adjunctive treatment for schizophrenia. However, efficacy across studies has been inconsistent. We conducted a meta-analysis of published controlled studies with the goal of detecting different efficacy profiles at various stages of schizophrenia. METHODS: An online search was conducted for randomized, double-blind, placebo-controlled clinical trials, and a meta-analysis was conducted. RESULTS: Ten studies met the criteria for inclusion. Among patients in the prodromal phase of schizophrenia, omega-3 supplementation reduced psychotic symptom severity and lowered conversion rates to first-episode psychosis. In patients with first-episode schizophrenia, omega-3 decreased nonpsychotic symptoms, required lower antipsychotic medication dosages, and improved early treatment response rates. Omega-3 had mixed results in patients with stable chronic schizophrenia, with only some patients experiencing significant benefits. Among patients with chronic schizophrenia, use of omega-3 fatty acids both by those experiencing acute exacerbations and those who had discontinued antipsychotic medications resulted in worsening of psychotic symptoms. CONCLUSIONS: The data suggest that omega-3 fatty acids may be efficacious in reducing clinical symptoms for patients in the earlier stages of schizophrenia (prodrome and first episode), while producing mixed results for patients in the chronic stages. Based on these results, omega-3 fatty acids would not be recommended for acute exacerbations in patients with chronic schizophrenia nor for relapse prevention after discontinuation of antipsychotics.