macrolides

Based upon this met-analysis and current guidelines, macrolide antibiotics alone (without the addition of narrow- or broad-spectrum antibiotics) are the best treatment for community-acquired pneumonia in children. James W. Mold, MD, MPH

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Objectives

To describe antibiotic prescribing patterns in ambulatory children with community acquired pneumonia, and to assess the relationship between antibiotic selection and clinical outcomes.

Study design

This was a retrospective cohort study of ambulatory Medicaid-enrolled children 0-18 years of age diagnosed with CAP from 2010-2016. The exposure was antibiotic class: narrow-spectrum (aminopenicillins), broad-spectrum (amoxicillin/clavulanate and cephalosporins), macrolide monotherapy, macrolides with narrow-spectrum antibiotics, or macrolides with broad-spectrum antibiotics. The associations between antibiotic selection and the outcomes of subsequent hospitalization and development of severe pneumonia (chest drainage procedure, intensive care admission, mechanical ventilation) were assessed, controlling for measures of illness severity.

Results

Among 252,177 outpatient pneumonia visits, macrolide monotherapy was used in 43.2%, narrow-spectrum antibiotics in 26.1%, and broad-spectrum antibiotics in 24.7%. A total of 1488 children (0.59%) were subsequently hospitalized and 117 (0.05%) developed severe pneumonia. Compared with children receiving narrow-spectrum antibiotics, the odds of subsequent hospitalization were higher in children receiving broad-spectrum antibiotics (aOR=1.34 [95%CI 1.17-1.52]) and lower in children receiving macrolide monotherapy (aOR=0.64 [95%CI 0.55-0.73]) and macrolides with narrow-spectrum antibiotics (aOR=0.62 [95%CI 0.39-0.97]). Children receiving macrolide monotherapy had lower odds of developing severe pneumonia than children receiving narrow-spectrum antibiotics (aOR=0.56, 95%CI 0.33-0.93). However, the absolute risk difference was <0.5% for all analyses.

Conclusions

Macrolides are the most commonly prescribed antibiotic for ambulatory children with CAP. Subsequent hospitalization and severe pneumonia are rare. Future efforts should focus on reducing broad-spectrum and macrolide antibiotic prescribing.

Author/s:

Lipsett, Susan C., Hall, Matthew, Ambroggio, Lilliam, Hersh, Adam L., Shah, Samir S., Brogan, Thomas V., Gerber, Jeffrey S., Williams, Derek J., Grijalva, Carlos G., Blaschke, Anne J., Neuman, Mark I.

Prophylactic antibiotic therapy effective for chronic obstructive pulmonary disease

Brian Desmarais — Thu, 18 Jun 2020 19:23:20 +0000

Date Added:

June 18, 2020

Journal/Publication:

Cochrane Systematic Review

Publisher:

Cochrane Library

Publication Date:

October 1, 2018

URL:

Prophylactic antibiotic therapy effective for chronic obstructive pulmonary disease

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1002/14651858. CD009764.pub3.

MeSH

Intention to Treat Analysis

Moxifloxacin

anti-bacterial agents

Use of continuous or intermittent macrolide antibiotics reduce COPD exacerbations and improved QOL over a one-year period. There were no serious adverse events. James W. Mold, MD, MPH

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Background

There has been renewal of interest in the use of prophylactic antibiotics to reduce the frequency of exacerbations and improve quality of life in chronic obstructive pulmonary disease (COPD).

Objectives

To determine whether or not regular (continuous, intermittent or pulsed) treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life.

Search methods

We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was performed on 27 July 2018.

Selection criteria

Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD.

Data collection and analysis

We used the standard Cochrane methods. Two independent review authors selected studies for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author.

Main results

We included 14 studies involving 3932 participants in this review. We identified two further studies meeting inclusion criteria but both were terminated early without providing results. All studies were published between 2001 and 2015. Nine studies were of continuous macrolide antibiotics, two studies were of intermittent antibiotic prophylaxis (three times per week) and two were of pulsed antibiotic regimens (e.g. five days every eight weeks). The final study included one continuous, one intermittent and one pulsed arm. The antibiotics investigated were azithromycin, erythromycin, clarithromycin, doxycyline, roxithromycin and moxifloxacin. The study duration varied from three months to 36 months and all used intention‐to‐treat analysis. Most of the pooled results were of moderate quality. The risk of bias of the included studies was generally low.

The studies recruited participants with a mean age between 65 and 72 years and mostly at least moderate‐severity COPD. Five studies only included participants with frequent exacerbations and two studies recruited participants requiring systemic steroids or antibiotics or both, or who were at the end stage of their disease and required oxygen. One study recruited participants with pulmonary hypertension secondary to COPD and a further study was specifically designed to asses whether eradication of Chlamydia pneumoniae reduced exacerbation rates.

The co‐primary outcomes for this review were the number of exacerbations and quality of life.

With use of prophylactic antibiotics, the number of participants experiencing one or more exacerbations was reduced (odds ratio (OR) 0.57, 95% CI 0.42 to 0.78; participants = 2716; studies = 8; moderate‐quality evidence). This represented a reduction from 61% of participants in the control group compared to 47% in the treatment group (95% CI 39% to 55%). The number needed to treat for an additional beneficial outcome with prophylactic antibiotics given for three to 12 months to prevent one person from experiencing an exacerbation (NNTB) was 8 (95% CI 5 to 17). The test for subgroup difference suggested that continuous and intermittent antibiotics may be more effective than pulsed antibiotics (P = 0.02, I² = 73.3%).

The frequency of exacerbations per patient per year was also reduced with prophylactic antibiotic treatment (rate ratio 0.67; 95% CI 0.54 to 0.83; participants = 1384; studies = 5; moderate‐quality evidence). Although we were unable to pool the result, six of the seven studies reporting time to first exacerbation identified an increase (i.e. benefit) with antibiotics, which was reported as statistically significant in four studies.

There was a statistically significant improvement in quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) with prophylactic antibiotic treatment, but this was smaller than the four unit improvement that is regarded as being clinically significant (mean difference (MD) ‐1.94, 95% CI ‐3.13 to ‐0.75; participants = 2237; studies = 7, high‐quality evidence).

Prophylactic antibiotics showed no significant effect on the secondary outcomes of frequency of hospital admissions, change in forced expiratory volume in one second (FEV1), serious adverse events or all‐cause mortality (moderate‐quality evidence). There was some evidence of benefit in exercise tolerance, but this was driven by a single study of lower methodological quality.

The adverse events that were recorded varied among the studies depending on the antibiotics used. Azithromycin was associated with significant hearing loss in the treatment group, which was in many cases reversible or partially reversible. The moxifloxacin pulsed study reported a significantly higher number of adverse events in the treatment arm due to the marked increase in gastrointestinal adverse events (P < 0.001). Some adverse events that led to drug discontinuation, such as development of long QTc or tinnitus, were not significantly more frequent in the treatment group than the placebo group but pose important considerations in clinical practice.

The development of antibiotic resistance in the community is of major concern. Six studies reported on this, but we were unable to combine results. One study found newly colonised participants to have higher rates of antibiotic resistance. Participants colonised with moxifloxacin‐sensitive pseudomonas at initiation of therapy rapidly became resistant with the quinolone treatment. A further study with three active treatment arms found an increase in the degree of antibiotic resistance of isolates in all three arms after 13 weeks treatment.

Authors' conclusions

Use of continuous and intermittent prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. All studies of continuous and intermittent antibiotics used macrolides, hence the noted benefit applies only to the use of macrolide antibiotics prescribed at least three times per week. The impact of pulsed antibiotics remains uncertain and requires further research.

The studies in this review included mostly participants who were frequent exacerbators with at least moderate‐severity COPD. There were also older individuals with a mean age over 65 years. The results of these studies apply only to the group of participants who were studied in these studies and may not be generalisable to other groups.

Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse. Monitoring of significant side effects including hearing loss, tinnitus, and long QTc in the community in this elderly patient group may require extra health resources.

Author/s:

Herath, S.

Drug interactions with cannabinoids

John Bayhi — Mon, 02 Mar 2020 18:41:14 +0000

Date Added:

March 2, 2020

Journal/Publication:

CMAJ: Canadian Medical Association Journal = journal de l'Association medicale canadienne

Publisher:

Joule Inc.

Publication Date:

March 2, 2020

Issue:

Volume:

192

Pages:

E206

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

Keywords

MeSH

Cytochrome P-450 CYP1A2

cannabinoids

Cytochrome P-450 CYP3A Inhibitors

Cytochrome P-450 CYP3A

Tacrolimus

Trimethoprim

Sulfamethoxazole Drug Combination

Cytochrome P-450 CYP2C9

Cytochrome P-450 CYP2C9 Inhibitors

CYP2C19 protein

Cytochrome P-450 CYP2C19

Benzodiazepines

International Normalized Ratio

Marijuana Use

cholinergic antagonists

A nice one-page review of drug interactions with cannabinoids. James W. Mold, MD, MPH

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No abstract available

Author/s:

Antoniou, T, Bodkin, J, Ho, JMW

Chapter 16: Pertussis

Tracy Ashby — Fri, 07 Dec 2018 06:00:00 +0000

Date Added:

December 7, 2018

Journal/Publication:

Epidemiology and Prevention of Vaccine-Preventable Diseases, aka "Pink Book"

Publisher:

Centers for Disease Control and Prevention

Publication Date:

January 1, 2015

Pages:

261-278

URL:

Epidemiology and Prevention of Vaccine-Preventable Diseases

Type:

Meta-analyses, Reviews, and Guidelines, Meta-analyses, Reviews, and Guidelines

Keywords

MeSH

trimethoprim, sulfamethoxazole drug combination

This is a chapter on Bordetella pertussis from the Pink Book on infectious diseases. Several key points regarding pertussis in adults:

Immunization is not 100% effective but usually diminishes disease severity
In immunized adults, pertussis causes URI symptoms plus cough that can last for weeks
Antibiotics (macrolides or Bactrim) reduce contagion but have little effect on symptoms

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Pertussis, or whooping cough, is an acute infectious disease caused by the bacterium Bordetella pertussis. Outbreaks of pertussis were first described in the 16th century, and the organism was first isolated in 1906.

In the 20th century, pertussis was one of the most common childhood diseases and a major cause of childhood mortality in the United States. Before the availability of pertussis vaccine in the 1940s, more than 200,000 cases of pertussis were reported annually. Since widespread use of the vaccine began, incidence has decreased more than 80% compared with the prevaccine era.

Pertussis remains a major health problem among children in developing countries, with 195,000 deaths resulting from the disease in 2008 (World Health Organization estimate).

Author/s:

Hamborsky, Jennifer, Kroger, Andrew, Wolfe, Charles S.