Latest Research on Treating Common Bacterial Infections in Kids: A Short Summary

William T. Basco, Jr, MD, MS

Disclosures

May 29, 2020

William T. Basco, Jr, MD, MS

In a world consumed by fear of a virus, the damage done as a result of inappropriate antibiotic use and the subsequent increase in antimicrobial resistance has taken a back seat.

But that does not mean that the need for good antibiotic stewardship has gone away. Here are a few key studies published in the past few months about antibiotic use in kids that should affect our decision-making.

Treating UTIs

The initial choice of an antibiotic to treat a child with a suspected urinary tract infection (UTI) based on history, clinical picture, and screening labs is empirical. And sometimes the first choice is wrong. Are children who receive a "discordant" antibiotic (one to which the isolate was not ultimately deemed sensitive) ultimately hurt?

A recent study analyzed data from over 300 children (mostly outpatients) with UTIs with bacterial isolates later determined to be resistant to third-generation cephalosporins. Although over 90% of these children were initially treated with cephalexin (narrow-spectrum approach), only 2.2% of them required escalation of care. In addition to the very low rate of treatment failure overall, the large majority (85%) improved clinically. It's worth emphasizing that children with complex medical conditions other than urologic conditions were excluded, and the majority of these patients were well enough to not be admitted in the first place. However, the results demonstrate that even when concerned about a UTI in a patient, we can still begin narrow-spectrum antibiotics while awaiting culture results.

The 2011 clinical practice guideline from the American Academy of Pediatrics emphasizes beginning narrow-spectrum antibiotics in patients with no recent UTIs, while also taking local sensitivities into account. Because most UTIs in children are due to Escherichia coli, the practice guideline recommends either a cephalosporin, amoxicillin plus clavulanic acid, or trimethoprim-sulfamethoxazole.

An editorial published in conjunction with this new study reminds us not to assume that all of these children will improve regardless of empirical antibiotic begun. In fact, changing antibiotics to better match the sensitivities of a bacterial isolate may help prevent relapse of infection or may limit consequences of the UTI.

Treating Kids With Community-Acquired Pneumonia (CAP)

Another recent study compared outcomes in children seen in an emergency department (ED) with suspected CAP who were sent home with antibiotics versus those discharged without. These children were all 3 months to 18 years of age, had a diagnosis of CAP, and had chest x-rays done as part of their evaluations. The children discharged with antibiotics were propensity matched to a comparison group of patients with CAP who were discharged without antibiotics. The investigators then called families at 1 and 2 weeks post-ED visit to ask about treatment failure (a pneumonia hospitalization within 30 days of the ED visit, any visit that required change of antibiotics for CAP within 30 days, or a parental report that another provider changed antibiotics).

Treatment failure occurred in equivalent numbers of children (8.8%) in both groups.

The study authors are careful to emphasize several points:

  • This was not a randomized trial.

  • The average age of the group was very young (3.4 years on average).

  • They were not fully able to adjust for the differences between the two groups.

  • And most important, they are not saying that kids with suspected CAP should not be treated.

Previous research suggests that it is difficult to demonstrate different outcomes in treated versus untreated children with CAP. This is undoubtedly because most febrile lower respiratory tract disease in children is viral. I do think we can conclude, however, that nothing in this study suggests that broad-spectrum antibiotics would do better than narrow-spectrum antibiotics.

The current guidelines for diagnosis and treatment of CAP in children have a lot to say about empirical antibiotic choice.

For children younger than 5 years, treating for Steptococcus pneumoniae drives empirical choices. Amoxicillin dosed at 80-90 mg/kg/day (ie, "high dose") is recommended. Three-times-daily dosing allows amoxicillin to achieve more effective serum concentrations compared with cephalosporins, especially if those are dosed less frequently.

For children aged 5 years or older, atypical bacteria play more of a role, and empirical therapy must be driven by clinical picture. Macrolides, the therapy of choice for atypical bacterial CAP, do not have the same degree of pneumococcal coverage as amoxicillin or cephalosporins. Broadening coverage to better account for pneumococcus in an ambulatory patient with CAP who is not responding to macrolide therapy should remain a consideration.
 

The end result of this study is similar to that of the UTI study reviewed in this summary. Both support one of the primary goal of antibiotic stewardship: Use antibiotics with as narrow a spectrum as possible.

Beyond Resistance: Other Harms of Antibiotics

Two other recent studies remind us of the potential harms of antibiotic therapy, even when indicated. A study that utilized Department of Defense pediatric data evaluated associations between repeat antibiotic courses and later development of allergic/atopic conditions by looking at the effects of antibiotic exposure in the first 6 months of life in otherwise healthy children. An encouraging picture of our general caution with antibiotics in these young infants emerged; Four out of five of the children (83.3%) had received no antibiotics. However, any exposure to antibiotics, even a single treatment episode, in the first 6 months of life raised the adjusted hazard ratio (in the range of 1.06-1.30) for development of an allergic condition. In fact, antibiotic exposure was associated with a greater risk across the board for all of the allergic conditions studied, including food allergies, anaphylaxis, asthma, and atopic dermatitis, among others. Exposure to more than one class of antibiotic during that first 6 months of life further increased the risk of developing an allergic condition.

Another study utilizing comprehensive health data from New Zealand children looked at the effect of antibiotic exposure in the first 4 years of life on body mass index. A related study using the same database examined effect of maternal use of antibiotics during pregnancy. A less reassuring picture of antibiotic use overall emerged with this study, which found that, on the basis of pharmacy records, over one third of women were dispensed at least one round of antibiotics during their pregnancy. And a huge percentage of their children, 82.3%, received at least one course of antibiotics in the first 2 years of life.

The correlation between antibiotic use and weight was profound: Four or more courses of antibiotics before age 4 years correlated with a body mass index (BMI) in the obese range. Surprisingly, though, it did not correlate with a BMI that indicated overweight. The exposure risk seemed most concentrated in the first 12 months of life; exposure before 1 year of age, but not after, correlated with BMI-for-age z-score. Of note, although maternal treatment with antibiotics during pregnancy increased the risk for an elevated BMI z-score, it did not correlate with obesity or overweight.
 

Both the study that looked at development of allergic phenomena and the study that evaluated later weight and risk for obesity were observational cohort studies. So it must be kept in mind that both run the risk that the association is just that—an association between two factors that are related to another (unmeasured) factor, and not that antibiotics lead to either allergic phenomena or obesity. However, there are theoretical reasons to be concerned about possible relationships between antibiotic exposure and untoward outcomes, on the basis of disturbance of the gut microbiome.

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