Azithromycin Shortens 'Preschool Wheeze' Episodes


Azithromycin significantly shortens the duration of asthma-like episodes in young children, according to a new randomized controlled trial.

"We've shown in the new study that taking out the bacteria has a very dramatic effect," Dr. Hans Bisgaard of the Copenhagen Prospective Studies of Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, told Reuters Health in a telephone interview.

"Preschool viral wheeze" is a leading cause of hospital admission among young children, and current treatments are largely ineffective. As the name suggests, these episodes are generally considered to be viral. But in the COPSAC cohort, Dr. Bisgaard and colleagues had previously identified an association between airway bacteria and wheezing episodes.

To investigate whether antibiotic treatment might be beneficial, the researchers randomly assigned children one to three years old who had been diagnosed with recurrent asthma-like symptoms to receive a three-day course of azithromycin (10 mg/kg/day) or placebo when they had episodes of "troublesome lung symptoms" lasting at least three days. A total of 158 episodes in 72 children were randomized.

The findings were published online December 17 in The Lancet Respiratory Medicine.

On average, episodes lasted 3.4 days for children who received the antibiotic, versus 7.7 days for children who received placebo, shortening the episode by 63.3%. When treatment was initiated before day six of the episode, duration was reduced by 83%, versus 36% if treatment was initiated on or after the sixth day.

While antibiotics are not recommended for children experiencing these symptoms, they are frequently prescribed, Dr. Bisgaard noted. "It is in clinical practice actually used very extensively, there's just been no evidence to document why, and the international guidelines recommend not to use antibiotics," he said. Nevertheless, he added, "it's in effect reducing symptoms by half, which is more than you can do with any other treatment."

Dr. Bisgaard said he hopes to see others attempt to replicate the findings, and also to investigate whether simpler antibiotics would also be effective.

In an editorial accompanying the study, Dr. Jonathan Grigg of Queen Mary University of London in the U.K. notes that the use of "troublesome lung symptoms" as a primary outcome means the results should be interpreted with caution.

"The normal primary outcome in community-based trials of preschool wheeze is one that reflects clinically severe disease - eg. the need for unscheduled medical attention and hospital admission for physician-diagnosed wheeze," he writes.

"We need to know if azithromycin really reduces clinically significant wheeze," Dr. Grigg told Reuters Health by email. "We need to test this in a trial of children with severe wheeze attending hospital and use validated scoring for wheeze severity."

For now, antibiotics should not be used in children with preschool wheeze, he added. "Wheeze episodes in children six months to five years are virtually all triggered by viral colds and antibiotics have no effect," he said. "The study opens up a new area of research for this common condition. It is important that funders such as the MRC and NIHR support further research in this area."

However, he added, "it is too early to say that this type of therapy will be clinically useful. Azithromycin should not be used to treat preschool wheeze without further evidence from large trials."

The study was supported by the Lundbeck Foundation and others.

SOURCE: Lancet Respir Med 2015 Available from: ly/22PHrPr and


Medscape Medical News

Broad-Spectrum Antibiotics Prescribed Too Often, Despite Guidelines

Beth Skwarecki

October 27, 2016

Narrow-spectrum antibiotics such as amoxicillin are recommended as first-line treatment for otitis media, sinusitis, and pharyngitis, but a new survey of prescriptions shows that clinicians prescribe the recommended drugs only 52% of the time (95% confidence interval [CI], 49% - 55%).

"These findings indicate that the problem of inappropriate antibiotic prescribing includes not only prescriptions that are unnecessary altogether, but also selection of inappropriate agents," Adam L. Hersh, MD, PhD, from the Division of Pediatric Infectious Diseases at the University of Utah, Salt Lake City, and colleagues write. They report their findings in a research letter published online October 24 in JAMA Internal Medicine. The same team also published findings earlier this year that 30% of antibiotic prescriptions prescribed in outpatient settings may be unnecessary.

Guidelines from the American Academy of Pediatrics, the Infectious Diseases Society of America, and others recommend amoxicillin or penicillin as the first-line treatment for pharyngitis, and amoxicillin with or without clavulanate for otitis media and sinusitis. Clinicians should consider different antibiotics when first-line treatment fails or when the patient is allergic. The authors cite estimates that 10% of the population is allergic to penicillin and 10% of visits for sinusitis and otitis media are for failed first-line therapy. An important limitation of this study is that the team was not able to determine how often these factors were involved in their study sample.

On the basis of those previous estimates, they hypothesize that 80% of antibiotic prescriptions should be for the recommended antibiotics. Instead, prescribing rates for first-line drugs ranged from 37% (95% CI, 32% - 43%) for adults with sinusitis to 67% (95% CI, 63% - 71%) for pediatric patients with otitis media. Children received first-line antibiotics more often than adults, and the most common class of drugs prescribed, other than those recommended, was macrolides.

The prescribing data come from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, which cover office-based physicians and hospital outpatient and emergency departments.

Dr Hersh has received funding from the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, Pfizer/Joint Commission, and Merck. The other authors have disclosed no relevant financial relationships.

JAMA Intern Med. Published online October 24, 2016. Letter extract


Caffeine for the Treatment of Apnea in Bronchiolitis: A Randomized Trial




To evaluate the efficacy and safety of caffeine citrate in the treatment of apnea in bronchiolitis.


Study design

Eligible infants aged ≤4 months presenting to the main pediatric emergency service with apnea associated bronchiolitis were stratified by gestational age (<34 weeks or longer) and randomized to receive a single dose of intravenous 25 mg/kg caffeine citrate or saline placebo. The primary efficacy outcome was a 24-hour apnea-free period beginning after completion of the blinded study drug infusion. Secondary outcomes were frequency of apnea by 24, 48, and 72 hours after study medication, need for noninvasive/invasive ventilation, and length of stay in the hospital's pediatric intensive care/step-down unit.



A total of 90 infants diagnosed with viral bronchiolitis associated with apnea (median age, 38 days) were enrolled. The rate of respiratory virus panel positivity was similar in the 2 groups (78% for the placebo group vs 84% for the caffeine group). The geometric mean duration to a 24-hour apnea-free period was 28.1 hours (95% CI, 25.6-32.3 hours) for the caffeine group and 29.1 hours (95% CI, 25.7-32.9 hours) for the placebo group (P = .88; OR, 0.99; 95% CI, 0.83-1.17). The frequency of apnea at 24 hours, 24-48 hours, and 48-72 hours after enrollment and the need for noninvasive and invasive ventilation were similar in the 2 groups. No safety issues were reported.



A single dose of caffeine citrate did not significantly reduce apnea episodes associated with bronchiolitis.


Khalid Alansari, et al.  DOI:



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November 2016

Influenza Prophylaxis in Children: Could a Single Dose of One Drug Be an Option?

Flor M. MunozHenry H. Bernstein

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During annual influenza epidemics, the highest illness rates occur among children, who are also known to play substantial roles in influenza transmission among households and communities. The Centers for Disease Control and Prevention recommend postexposure chemoprophylaxis with neuraminidase inhibitors for close contacts at elevated risk for influenza complications who have not been vaccinated or are unlikely to be protected through vaccination or other contact precautions at the time of exposure.1 The effectiveness of postexposure prophylaxis with neuraminidase inhibitors is estimated to be 68% to 90%. The American Academy of Pediatrics recommends oral oseltamivir prophylaxis in infants starting at 3 months of age and in high-risk children, and inhaled zanamivir prophylaxis is recommended only in children ≥5 years old.1,2 Intravenous peramivir is not approved for children or for prophylaxis in the United States. The recommended duration of prophylaxis currently is 7 to 10 days from last exposure or ≤1 weeks after vaccination. Similar to treatment, antiviral prophylaxis is recommended preferably within 48 hours of exposure. Its use is limited by concerns for antiviral availability, development of resistance, and …

Address correspondence to Flor M. Munoz, MD, FAAP, Associate Professor of Pediatrics, Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, BCM-280, Houston, TX 77030. E-mail:

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Linezolid is Associated with Improved Early Outcomes of Childhood Tuberculous Meningitis 


Linezolid serves as an important component for the treatment of drug-resistant tuberculosis, while there are few published data about linezolid use in children, especially in childhood tuberculous meningitis (TBM).


In this study, we retrospectively reviewed records of childhood TBM patients who started treatment between January 2012 and August 2014. A total of 86 childhood TBM patients less than15 years old were enrolled. Of 86 children, 36 (41.9%) received the regimen containing linezolid.


32 (88.9%) of 36 linezolid-treated cases had favorable outcomes, and 35 (70.0%) cases were successfully treated in the control group. The frequency of favorable outcome of linezolid group was significantly higher than that of control group (P=0.037). In addition, compared with cases with fever clearance time of <1 week, the control group had more cases with fever clearance time of 1-4 weeks (P=0.010) and >4 weeks (P=0.000) than linezolid group. Furthermore, there was no significant difference in the frequency of adverse events between the two regimens (P=0.896). The patients with adverse events were more likely to have treatment failure, the P value of which was 0.008.





Our data demonstrate that linezolid improves early outcome of childhood TBM. The low frequency of linezolid-associated adverse effects highlights the promising prospects for its use for treatment of childhood TBM.

Source: Li, Huimin et al. Pediatr Infect Dis J. 2016 Jun;35(6):607-10.