Wednesday, September 26, 2012

Childhood Antibiotics Linked to Inflammatory Bowel Disease

Childhood Antibiotics Linked to Inflammatory Bowel Disease

September 24, 2012 — Children who received antianaerobic antibiotics in the first year of life had a 5.5-fold increased risk of developing inflammatory bowel disease (IBD) compared with those who were never exposed, according to a retrospective cohort study of more than 1 million children.
Matthew P. Kronman, MD, MSCE, an assistant professor of pediatric infectious diseases in the Division of Infectious Diseases at Seattle Children's Hospital and the University of Washington in Seattle, and colleagues presented their findings in an article published online September 24 in Pediatrics.
"We sought to examine the association between childhood antianaerobic antibiotic exposure and subsequent IBD development using a large population-based cohort, hypothesizing that exposure to antibiotics with anaerobic activity would be associated with the development of IBD," the authors write.
They analyzed data from 464 ambulatory practices in the United Kingdom that were participants in the Health Improvement Network. All children with at least 2 years of data from 1994 to 2009 were followed up between practice enrollment and IBD development, practice deregistration, 19 years of age, or death. The investigators excluded children with previous IBD.
A total of 1,072,426 patients provided 6.6 million person-years of follow-up. Of those patients, 748 (0.07%) developed IBD, for an overall incidence rate of 1.2/10,000 person-years. Of the 225,100 patients followed from birth, only 30 developed IBD, so meaningful analyses were not possible in this subgroup.
Among the 748 children who developed IBD, the median latency period between the first healthcare visit with a gastrointestinal diagnosis suspicious for IBD and the first IBD diagnosis was 3.9 months (interquartile range [IQR], 0.5 - 17.9 months), and 68.2% had latencies of 1 year or less. Fewer than 25% of the other children had diagnoses consistent with possible IBD within 5 years before censorship.
Exposure to Antibiotics
More than half (57.7%) of the patients received at least 1 antianaerobic antibiotic, defined as penicillin, amoxicillin, ampicillin, penicillin/b-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin.
The patients took antianaerobic antibiotics for a median of 1 week (IQR, 0 - 2 weeks), with 42.3% receiving none, 31.9% receiving them for 1 to 2 weeks, and 25.8% receiving them for more than 2 weeks.
In both the unexposed and exposed groups, 0.07% of children developed IBD; however, the IBD incidence rates were 0.83/10,000 person-years in the unexposed group and 1.52/10,000 person-years in the exposed group, for an absolute risk increase of 0.69 cases/10,000 person-years and an 84% relative risk increase.
In univariate analysis, any antianaerobic antibiotic exposure was associated with developing IBD (P < .001, log-rank test), there was a dose-response effect (P < .001, log-rank test), and this association remained significant throughout childhood.
In their multivariate analysis, the investigators adjusted for family history of IBD, gender, chronic granulomatous disease, primary sclerosing cholangitis, and socioeconomic deprivation. They found that exposure by 1 year of age was associated with a 5.5-fold increased IBD risk (adjusted hazard ratio [aHR], 5.51; 95% confidence interval [CI], 1.66 - 18.28) compared with those never exposed, with IBD risks decreasing every 5 (aHR, 2.62; 95% CI, 1.61 - 4.25) and 15 (aHR, 1.57; 95% CI, 1.35 - 1.84) years.
Each course of antianaerobic antibiotics was associated with a 6% increased IBD hazard (aHR, 1.06; 95% CI, 1.04 - 1.08), and each week of exposure was associated with a 1% increase in hazard (aHR, 1.01; 95% CI, 1.00 - 1.02).
Exposure to more than 2 courses of antianaerobic antibiotics in the first year of life had a higher association with IBD development than exposure to 1 to 2 courses, with an aHR of 4.77 (95% CI, 2.13 - 10.68) vs 3.33 (95% CI, 1.69 - 6.58).
Exposure to any antibiotic, penicillins, broad-spectrum penicillins, and cephalosporins was associated with development of IBD, but exposure to macrolide, sulfonamide, and tetracycline were not.
Exposure to metronidazole or fluoroquinolones (2 potential IBD treatments) was associated with IBD development.
"[T]hese class-specific findings remained significant after re-setting the IBD outcome at the first metronidazole or fluoroquinolone prescription in the year before IBD diagnosis, suggesting that outcome misclassification was not significantly present," the authors write. Exposure to any fluoroquinolone (aHR, 2.09; 95% CI, 1.10 - 3.98]) and any metronidazole (aHR, 186.25; 95% CI, 10.86 - 3193.65) by 1 year of age.
Results were similar for the 2 IBD subgroups, Crohn's disease, and ulcerative colitis, but they did not vary with age. The primary outcome was not changed when sensitivity analysis was conducted by assigning all missing Townsend scores first in the highest and then in the lower deprivation category.
When sensitivity analysis was conducted using a 1-year latency period, the primary outcome's precision and magnitude were altered, but not its direction: any antianaerobic antibiotic exposure in the first year of life (aHR, 3.73; 95% CI, 1.17 - 11.84), each course of antibiotics (aHR, 1.03; 95% CI, 0.99 - 1.06), exposure to 1 to 2 courses of antibiotics (aHR, 2.18; 95% CI, 1.07 - 4.50), and exposure to more than 2 courses of antibiotics (aHR, 4.14; 95% CI, 1.74 - 9.87).
"Our study suggests that reduction in childhood antianaerobic antibiotic use may have the potential to help curb the rising incidence of childhood IBD. Many unanswered questions remain, however, such as whether specific difficult-to-culture organisms could play roles in either IBD pathogenesis or protection against IBD, and whether alteration of flora through antibiotic exposure alters the immune system directly," the authors write.
Sonia Michail, MD, an investigator at the Saban Research Institute of Children's Hospital Los Angeles, California, and an associate professor of clinical pediatrics at the Keck School of Medicine of the University of Southern California, commented on the study in an email interview with Medscape Medical News.
Dr. Michail was not surprised by the association between antibiotics and the development of IBD, but she was surprised by the strength of the association.
"This work further confirms the strong contribution of the gut microbiome towards the development of disease and suggests that perturbations of the gut microbiome at an early stage in life when the immune system is still developing may have an impact on disease incidence several years later. These findings fit well with what we now know about the effect of antimicrobial therapy on the gut microbiome," Dr. Michail said.
"This study highlights the importance of judicial use of antibiotics, especially in young infants and children at higher risk for developing [IBD] such as those with a strong family history of IBD. It adds yet another depth to the potential risk of using antimicrobial therapy in infants and children," Dr. Michail said.
Dr. Kronman received support for this study from a National Research Service Award Institutional Research Training grant at the Children's Hospital of Philadelphia in Pennsylvania, as well as a University of Pennsylvania Center for Education and Research on Therapeutics grant from the Agency for Healthcare Research and Quality. This work was also supported by a National Institutes of Health Clinical and Translational Science Award and was funded by the National Institutes of Health. One author has received research support from Merck and Company Inc for other projects and has served as a consultant for Pfizer Inc, HemoCue Inc, Merck and Company Inc, Cubist Pharmaceuticals, and Astellas Pharma US Inc. He has also received a lecture honorarium from Merck and Company Inc. Another author previously received research support from Sage Pharmaceuticals Inc for other projects. The remaining authors and Dr. Michail have disclosed no relevant financial relationships.
Pediatrics. Published online September 24, 2012. Abstract

Saturday, September 22, 2012

Sore Throats Mostly Viral, Not Strep

Sore Throats Mostly Viral, Not Strep:

September 17, 2012 — The majority of throat infections are viral and should not be treated with antibiotics, according to new guidelines from the Infectious Diseases Society of America.
The recommendations, published online September 9 in Clinical Infectious Diseases, are aimed at limiting the antimicrobial treatment of viral infections and correctly identifying and treating cases of group A streptococcal pharyngitis ("strep throat"). Penicillin and amoxicillin are the drugs of choice for treating streptococcal infections, according to the recommendations.
Up to 70% of Americans with a sore throat receive antibiotics, according to a society news release. However, bacteria are responsible for only 20% to 30% of pediatric cases and 5% to 15% of adult cases.
"These important, timely guidelines provide guidance to physicians on when to test for, and how to treat, strep throat," Jesse T. Jacob, MD, assistant professor of medicine in the Division of Infectious Diseases at Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News. "Strep throat is a common disease, but viral infections are more common. It is important to differentiate them, so that patients do not get unnecessary antibiotics, which can carry side effects for the individual, and also increases the chance that the next infection (whether in the same person or the next) will become resistant to the antibiotic. It may also help kids avoid unnecessary surgery for recurrent sore throats." Dr. Jacob was not involved in writing the new guidelines.
Some Symptoms Overlap
Although bacterial and viral throat infections often have overlapping symptoms, other symptoms, such as cough, rhinorrhea, hoarseness, and oral ulcers, strongly suggest a viral infection, the authors write.
In contrast, a sore throat is more likely to be caused by group A strep if the onset of pain is sudden, swallowing hurts, and a fever is present. Such cases can be evaluated using a stand-alone rapid antigen detection test. Because children younger than 3 years are unlikely to have strep throat, testing is unnecessary, with the exception of certain circumstances such as an infected older sibling.
Throat cultures should only be used to confirm negative antigen tests in children and adolescents. They should be eschewed in adults because of their low risk for strep throat and even lower risk for complications such as rheumatic fever.
Once strep throat is confirmed, the treatment of choice remains a 10-day course of penicillin (or its congener amoxicillin), which has a narrow spectrum of activity, is cheaply available, and carries a low risk for adverse events.
"We recommend penicillin or amoxicillin for treating strep because they are very effective and safe in those without penicillin allergy, and there is increasing resistance of strep to the broader-spectrum — and more expensive — macrolides, including azithromycin," said lead author Stanford T. Shulman, MD, from the Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, in the news release.
The guidelines also recommend against tonsillectomy for children with repeated throat infection, except in very specific cases (eg, children with obstructive breathing), because the risks of surgery are generally not worth the transient benefit.
The 13 recommendations replace those issued in 2002 and are presented in a novel format designed to facilitate use.
"The Q&A format of the guideline parallels in large part how a clinician would think through a patient with suspected strep throat. They are written precisely to help clinicians work through this tough but common issue," Dr. Jacob said, noting that patients will need to be taught that not all infections are bacterial, that antibiotics do not treat viral infections, and that antibiotics, as an unintended consequence, can be harmful.
"Antibiotics will not help a viral infection, but there are other treatments for sore throats, regardless of need for antibiotics. Clinicians will need to work with patients to communicate all the information, reassure them, and provide them with appropriate care," Dr. Jacob concluded.
The study was funded by the Infectious Diseases Society of America. Dr. Shulman reports having served as a consultant to Novartis Vaccines and Merck Vaccines and received research support from Quidel. One of the other authors has served as a consultant for SPD Development, Cornerstone BioPharma, and Rib-X Pharmaceuticals. Dr. Jacob has disclosed no relevant financial relationships.
Clin Infect Dis. Published online September 9, 2012. Full text