Questions raised over childhood antibiotics

Medical Tribune August 2009 SFV

David Brill

Using antibiotics to treat acute otitis media (AOM) in young children could increase their risk of recurrent infection, a recent study suggests.

Children who received amoxicillin for AOM were 2.5 times more likely to have a recurrent episode within the following 3.5 years, reported Dutch researchers, who are calling for more conservative use of antibiotics in this setting.

Senior author Dr. Maroeska Rovers said that up to 80 percent of children with mild, uncomplicated AOM will recover spontaneously, and that a 2 to 3 day “wait and see” policy is justified in such cases. Close observation by parents is required, since acute mastoiditis can result if AOM worsens and goes untreated, she said.

The British Medical Journal study included follow-up surveys from 168 children who had presented to Dutch GPs with AOM between the ages of 6 months and 2 years, and been randomized to amoxicillin or placebo. It is one of the first studies to look at the long-term effects of antibiotics in pediatric AOM, the authors say. [2009 Jun 30;338:b2525]

Sixty three percent of antibiotic-treated children had an AOM recurrence, compared to 43 percent of placebo-treated children (risk difference 20 percent; 95% CI 5-35%). Antibiotic-treated children were, however, less likely to undergo ear, nose and throat (ENT) surgery (21 percent versus 30 percent; risk difference 9 percent; 95% CI 4-23%).

Singapore expert Associate Professor Lynne Lim cautioned that more research is needed before practice should be changed, particularly given the small size of the study, the width of the reported confidence intervals and the different ethnicity and geographical location of patients.

“The debate on antibiotics use in AOM is continuing worldwide. It is definitely important to use antibiotics judiciously to avoid bacterial resistance and worse outcomes, if any, but until we are able to comcommitantly answer in the same study the complication rates and other problems associated with no antibiotic use, we cannot answer the question fully,” said Lim, head of the pediatric ENT service and senior consultant ENT surgeon at the National University Health System Singapore.

“The study suggests that more large, population-based, randomized clinical trials should be done to determine the cost-benefit of antibiotic use in AOM. I will continue treating as normal until more data are out,” she said, adding that that she typically follows US guidelines when treating AOM, and prescribes high-dose oral amoxicillin or amoxicillin/clavulanate potassium (80-90 mg/kg per day) for 7 to 10 days for children under 2.

Rovers, a clinical epidemiologist at University Medical Center Utrecht in the Netherlands, stressed that the “wait and see” policy should only apply to mild, unilateral AOM. Children under 2 years who have bilateral AOM or AOM with otorrhea should receive antibiotics without delay, she said, citing a meta-analysis of 1,643 children which found that antibiotics were of greatest benefit in these subgroups. [Lancet 2006 Oct 21;368(9545):1429-35]

“We now know which children benefit most from antibiotics but we also know that there is some harm. The next step for me will be to try to study the benefit and risk. Then we can say whether the guidelines should be changed or should not be changed,” she said.

Rovers and Lim both added that analgesics should be given to all children with AOM, regardless of whether antibiotics are prescribed.

Preventive antibiotics cut ICU death rates

Medical Tribune March 2009 P10
David Brill

Adopting a widespread preemptive approach with antibiotics could save lives in the Intensive Care Unit (ICU), Dutch researchers have recently reported.

Absolute mortality at 28 days was reduced by 3.5 percent in patients who received intravenous cefotaxime along with a cocktail of antibiotics applied topically to the stomach and orophyarynx. A simpler regimen – applying antibiotics only to the oropharynx – reduced mortality by 2.9 percent, as compared with standard care.

The findings are likely to prove contentious in the era of rising antibiotic resistance rates and hospital-associated infections. A Singapore infectious disease expert, who recently called for tighter regulation of the nation’s antibiotic usage, said that a similar approach could be adopted here but expressed his concern that resistance levels would increase in the long term.

The study, conducted across 13 ICUs in the Netherlands, randomized 5,939 patients to standard care or one of the two antibiotic regimens. Patients were only eligible if they were expected to be intubated for more than 48 hours or to remain in the ICU for more than 72 hours. [N Engl J Med 2009 Jan 1;360(1):20-31]

Lead researcher Dr. Anne Marie de Smet, of the University Medical Center Utrecht, said that the trial demonstrates that the benefits of preventive antibiotics outweigh the disadvantages.

“There are very few interventions in the ICU which can lower mortality on their own. These are not patients who come in for surgery and leave the next day – these people are really ill,” she said.

Antibiotic resistance rates did not rise significantly over the course of the 6-month study but longer follow-up data are needed, said de Smet. She added that The Netherlands has unusually low rates of resistance due to its strict regulations on antibiotic usage.

Dr. Hsu Li Yang, an infectious disease consultant at National University Hospital, Singapore, said that he would be “very concerned that resistance rates would increase” were the strategy to be adopted here, but added that is “for society as a whole to decide” whether such a move would be beneficial given the obvious short-term advantages.

“Doctors should not ‘allow’ patients to die so that future patients may be better or more easily treated. What we try to do is to retard the rise of resistance while preventing any increased mortality that may arise from inadequate use of antibiotics … minimize the use of antibiotics for those who do not need them and prescribe appropriate but not excessive antibiotics for those patients who do,” he said.

“Similar strategies might be adopted [here] in the future following the results of this study,” said Hsu, adding that the trial was very well conducted and one of the few in this field with adequate statistical power to demonstrate a significant mortality reduction.

The researchers used an antibiotic paste containing colistin, tobramycin and amphotericin B for both strategies. In the more comprehensive approach – selective digestive tract decontamination – the paste was applied topically to the stomach and oropharynx, and intravenous cefotaxime was given for the first 4 days. In the simpler strategy – selective orophyarygeal decontamination – the paste was just applied to the oropharynx.

Hsu added that that a different combination of antimicrobial agents would probably be necessary were the approach to be adopted in Singapore hospitals, where resistance rates are considerably higher than in the Netherlands.

Hsu recently co-authored a position paper calling for more data to be gathered on the use of antibiotics in Singapore and for the Ministry of Health to take a greater role in regulating usage. [Singapore Med J 2008 Oct;49(10):749-55]

Experts fear rise of drug-resistant superbug

Medical Tribune January 2009 P1&6
David Brill

Rising levels of drug resistance among Acinetobacter Baumannii are causing serious concern among infectious disease experts, who are calling for urgent international attention to the issue.

The bug is particularly prevalent in hospitals in Southeast Asia, with Taiwan and Korea seemingly the worst affected.

The rapidly dwindling number of treatment options could soon herald the dawn of the “post-antibiotic era,” according to a specialist from Singapore, where extensively drug-resistant strains have already been reported.

A. Baumannii resistance rates are increasing globally, with around half of strains presently thought to be resistant to at least one antibiotic. Nearly 20 percent of strains are resistant to all but one or two agents.

Reports have already emerged of pandrug resistant strains, which – although rare at present – will beome increasingly common if the problem is not addressed, said Professor Matthew Falagas, an international expert who published a recent high-profile review calling for more research into treatment options. [Lancet Infect Dis 2008 Dec;8(12):751-62]

“We should be worried because we have never heard before of bugs which affect humans where we do not have an antibiotic to provide,” he told Medical Tribune.

“The issue of pan-drug resistance needs international attention. Public health organizations and local infection controls at the country level should disseminate guidelines on this issue,” he said, adding that in some hospitals the significance of the bug is already on a par with methicillin-resistant S. Aureus (MRSA).

A. Baumannii mainly affects seriously ill patients in intensive care units and burn wards. Although less common than other hospital-based infections, the bug can cause significant morbidity and mortality, placing a heavy drain upon hospital resources through repeated hospitalizations and increased lengths of stay.

A Singapore study found that 69 percent of A. Baumannii strains in one intensive care unit were resistant to carbapenem. Nearly 20 percent of isolates from all the nation’s hospitals were resistant to everything except the polymixins, which can cause significant toxicity to the brain and kidneys. [Emerg Infect Dis 2007 Dec;13(12):1944-7]

“Its ability to acquire resistance is a big concern because there aren’t going to be many treatment options available,” said Dr. Tan Thuan Tong, an infectious diseases consultant at Singapore General Hospital.

“We foresee a time when you get strains that are not treatable and you just try your luck with various combinations that might act in a synergistic manner,” he said, adding that such a scenario could arise in Singapore within the next 5 years.

Around 30 to 40 percent of patients who get a multidrug-resistant A. Baumannii bloodstream infection may die, according to Tan, but he added that the directly attributable mortality is not clear-cut since patients are often critically ill for other reasons.

Falagas, meanwhile, called on hospitals worldwide to decrease the usage of antibiotics and promote stricter infection prevention and control measures, particularly with regard to hand hygiene. He added that research is now ongoing to find new antibiotics for Gram-negative bacteria, but said that the process has been too slow getting started.

“The scientific community and the pharmaceutical companies have focused attention on Gram-positives without understanding the significance of Gram-negatives as healthcare-associated infections, and especially A. Baumannii,” said Falagas, who is director of the Alfa Institute of Biomedical Sciences in Athens, Greece, and an adjunct associate professor at Tufts University
School of Medicine, Boston, US.

Singapore has already begun to acknowledge the growing problem of antimicrobial resistance, with a group of experts publishing a recent position paper advocating stricter controls on the use of antibiotics. [Singapore Med J 2008 Oct;49(10):749-55]

“In the 18th and 19th century, there were no antibiotics and treatment was with drainage of pus, amputation and other surgical approaches. If you have infections with these untreatable bugs, then you are back to the days when you can’t do anything,” added Tan.