In the associated editorial (MT Melia, PG Auwaeter, NEJM 2016; 374: 1277-8), it is noted that 10-20% of treated patients (after initial antibiotics) “may have lingering symptoms of fatigue, musculoskeletal pains…The plausible idea that additional antimicrobial therapy for potentially persistent bacterial infection would foster improvement has been a touchstone of hope in the 40 years since discovery of the disease in the mid-1970s.”
My take (from editorial): “Prolonged antibiotic therapy is not the answer” for lingering symptoms after Lyme disease. “We do not know what is truly helpful”
A recent study (Rogawski ET, et al. J Pediatr 2015; 167: 1096-102) examined a prospective observational cohort of 497 children in India (from “semi-urban slums”). The authors found that early exposure to antibiotics were not associated with increased or decreased growth.
“There are several potential explanations for the lack of a growth-promoting effect. Most of the previous studies showing increased weight gain or risk of obesity associated with antibiotics were conducted in high-income countries with Western diets.”
My take: This was a negative study on antibiotics and obesity. This suggests that the effects of antibiotics with regard to weight gain may be limited and/or modified by diet.
Also noted: Wakamoto H, et al. J Pediatr 2015; 167: 1136-42. This study showed that Krebs von den Lungen-6 (KL-6) which is abundant on type II alveolar pneumoctyes and respiratory epithelial cells is a fairly good serum biomarker for chronic aspiration in this study of children with severe motor and intellectual disabilities. Figure 1 shows the distribution of KL-6 among the 37 with aspiration and the 29 without aspiration. The median in the former was 344 vs 207 in the later, though there was overlapping results.
The topic of antibiotics and obesity has been discussed several times on this blog (see links below). More information on this topic has been published and is summarized by the NY Times: Frequent Antibiotics May Make Children Fatter
Children who regularly use antibiotics gain weight faster than those who have never taken the drugs, according to new research that suggests childhood antibiotics may have a lasting effect on body weight well into adulthood.
The study, published in the International Journal of Obesity, examined the electronic medical records of 163,820 children ages 3 to 18, counting antibiotic prescriptions, body weight and height. The records, which covered pediatric exams from 2001 through 2012, showed that one in five — over 30,000 children — had been prescribed antibiotics seven or more times. By the time those children reached age 15, they weighed, on average, about 3 pounds more than children who had received no antibiotics.
While earlier studies have suggested a link between antibiotics and childhood weight gain, they typically have relied on a mother’s memories of her child’s antibiotic use. The new research is significant because it’s based on documented use of antibiotics in a child’s medical record.
A recent study indicates that a fairly high number of adults with appendicitis could avoid surgery (JAMA 2015 June 15 [doi:10.1001/jama.2015.6154]).
In this study, patients with CT-confirmed acute uncomplicated appendicitis were randomly assigned to either immediate surgery (n=273) or a 1-day of IV ertapenem followed by 7 days of levofloxacin and metronidazole.
The primary endpoint for the antibiotic group – resolution of acute appendicitis with no recurrences for a full year – occurred in 73%. The remaining 27% of patients in this group underwent appendectomy during follow-up, at a median of 102 days after initial presentation. None of these patients developed abscesses or serious infections, “suggesting that the decision to delay appendectomy … can be made with a low likelihood of major complications,” the investigators said
And commentary from Edward Livingston, M.D., is deputy editor of JAMA. Corrine Vons, M.D., Ph.D., is in the digestive surgery department at Jean-Verdier Hospital, Bondy, France. :
The study findings dispel the notion that appendectomy is always an emergency and suggest instead that, given our current precise diagnostic capabilities and effective wide-spectrum antibiotics, a trial of antibiotic therapy is reasonable. However, it’s important to note that children, adolescents, pregnant women, and patients with complications were excluded from this trial so the findings do not apply to those patient groups.
Dr. Livingston and Dr. Vons made these remarks in an editorial accompanying Dr. Salminen’s report (JAMA 2015;313:2327-8).
My Take: This study indicates, at least in adults with uncomplicated appendicitis, that antibiotic treatment is an option. I think resolving the problem definitively would be my preference. If you had appendicitis, which therapy would you choose? Take the poll.
A recent study (Arboleya, S et al. J Pediatr 2015; 166: 538-44) provide sequential data regarding the intestinal microbiome in preterm infants in comparison to full-term infants; in addition, this study offers some insight into the changes that occur with perinatal antibiotics.
The researchers examined fecal samples at approximately 2 days of life, and then days 10, 30, and 90 in 27 preterm infants and 13 full-term babies. The study figures show the progression and changes of the microbiota over the first 90 days. In Figures 1, the profiles are the most similar between the full-term and preterm infants but there remains significant differences.
Key findings:
Preterm infants had higher initial percentage of Lactobacillaceae and reduced Bacteroidacease.
Perinatal antibiotics (including intrapartum antimicrobial prophylaxis) were noted to affect gut microbiota with increased Enterobacteriaceae organisms in these infants.
There were many confounding variables noted, including different diets, which make interpretation of the data difficult. The full-term infants received exclusive breast milk whereas the preterm infants received mixed feedings.
A recent review (Houghteling, PD, Walker, WA.”Why Is Initial Bacterial Colonization of the Intestine Important to Infants’ and Children’s Health?” JPGN 2015; 60: 294-307) had a relevant figure:
From NASPGHAN Twitter Feed
Bottomline: Overall, Arboleya et al provide some additional baseline data but much more is needed to ascertain what factors will make children healthier –starting from before birth. The understanding of the microbiome is truly in its infancy.
A concise review (NJEM 2014; 371: 2526-28) quickly describes the latest science on microbiota, antibiotics, and obesity chiefly by summarizing the work of Cox LM et al (Cell 2014; 158: 705-21).
Key points:
In mice, studies have shown that low-dose penicillin in early life induces marked effects on body composition (eg. excessive weight gain) lasting into adulthood
Prenatally administered penicillin to the mother and high-fat diet also induced fat mass of male mice.
Gut microbiota transferred from penicillin-moderated flora mice (at 18 weeks) into the cecums of 3-week-old germ-free mice also resulted in excessive fat mass compared to controls who received gut microbiota transfer from control mice (who did not receive penicillin).
“These results suggest that immunologic and metabolic changes are not caused by direct effects of antibiotics but rather by derived changes in the gut microbiota.”
“It may even be speculated that in families in which obesity is a problem, specific antibiotic treatment at birth could reverse the adverse effect of obesogenic microbiota transferred from mother to infant during delivery.”
Take-home message: Understanding the microbes in our bodies may lead to much more than curing intestinal infections and intestinal maladies.
A recent JAMA Pediatrics study showed that early and frequent antibiotics were associated with an increase risk of obesity. Here’s a link to the LA Times summary of this article: Antibiotics and Obestiy (LA Times)
Here’s an excerpt:
Broad-spectrum antibiotics — including amoxicillin, tetracycline, streptomycin, moxifloxacin and ciprofloxacin — are intended for treatment of major systemic infections, in cases where the bacteria causing the illness has not been identified, or where a patient is under attack by a strain of bacteria resistant to standard antibiotics. While they can be highly effective, their antibiotic action is indiscriminate, and beneficial bacteria in the body are often killed off as collateral damage.
The latest study tapped the medical records of 64,580 babies and children in and around Philadelphia. It was published Monday [Sept 29, 2014] in the journal JAMA Pediatrics.
The heightened risk of obesity linked to antibiotic use was not huge: Babies who got wide-spectrum antibiotics in their first two years were about 11% more likely to be obese between 2 and 5 than were those who got no such drugs. Babies who had four or more courses of any antibiotics in the first two years were also 11% more likely to be obese in early childhood than those who’d had fewer exposures to antibiotics.
A recent study shows that Clostridium difficile infection (CDI) is identified frequently in young children and that approximately three-fourths had recent preceding antibiotics (Pediatrics 2014; 133: 651-58). Abstract link.
Methods: “Data from an active population- and laboratory-based CDI surveillance in 10 US geographic areas during 2010–2011 were used to identify cases.”
Key findings:
Of 944 pediatric CDI cases identified, 71% were community-acquired
CDI incidence per 100 000 children was highest among 1-year-olds (66.3)
Using a representative sample (n=84) who reported diarrhea on the day of stool collection, 73% received antibiotics during the previous 12 weeks.
Despite the frequency of CDI, understanding a couple of key diagnostic pearls is crucial. According to the American Academy of Pediatrics Committee on Infectious Disease policy guideline: (Link to AAP guideline PDF)
Recommends avoid routine testing in pediatric patients less than 1 year of age due to high carriage rates.
“Testing for C difficile can be considered in children 1 to 3 years of age with diarrhea, but testing for other causes of diarrhea, particularly viral, is recommended first>
“A common mistake is to… test for cure. C difficile, its toxins, and genome are shed for long periods after resolution of diarrheal symptoms.”
“An interval greater than 4 weeks since last testing should be used for testing with a recurrence.”
Bottomline: This most recent study reinforces the notion that about 1/4th of pediatric CDI occurs in the absence of recent antibiotics; nevertheless, understanding the limitations of testing for CDI could prevent a fair amount of aggravation.
A recent study (J Pediatr 2014; 165: 23-9) confirmed the obvious: “early empiric antibiotic use in preterm infants is associated with lower bacterial diversity.” That being said, you still need the data and the specific changes are of importance.
This study examined the stools from 74 preterm infants (≤32 weeks gestational age) and determined how the microbiota changed in relation to no antibiotics (18% of cohort), brief antibiotics (1-4 days) (64% of cohort), or ‘intensive’ antibiotics (5-7 days) (18% of cohort). Empiric antibiotics consisted of ampicillin and gentamicin. Stools were analyzed with the 16s ribosomal DNA community profiling.
The key findings are graphically shown in Figure 1 with pie charts showing the relative abundance of 10 bacterial genera at week 1, week 2, and week 3 in each of the three groups.
Those who received 5-7 days of antibiotics had the most changes in their microbiota with increased Enterobacter and lower bacterial diversity in the second and third weeks of life.
In those who received no empiric antibiotics there was increasing bacterial diversity noted sequentially. These changes were not seen in either of the antibiotic groups. However, the group with brief antibiotic exposure returned to their baseline diversity by week 3.
Infants receiving early antibiotics experienced more cases of necrotizing enterocolitis, sepsis and death than those who were not exposed to antibiotics (this was not proven to be casually-related).
Take-home message: This study proves that antibiotics change the microbiome in neonates and that neonates exposed to antibiotics may have complications as a result. Better biomarkers (with rapid turn around time) would allow more careful selection of which neonates need empiric antibiotics.
gutsandgrowth 