By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: Although standard treatment of late-onset neonatal group B Streptococcus bacteremia includes intravenous antibiotic therapy for 10 days, shorter courses seem safe and effective.

SOURCE: Coon ER, Srivastava R, Stoddard G, et al. Shortened IV antibiotic course for uncomplicated, late-onset group B streptococcal bacteremia. Pediatrics 2018;142:e20180345.

During the first three months of life, group B Streptococcus is a leading cause of serious bacterial infection. The use of intrapartum antibiotics in mothers colonized by group B Streptococcus has reduced the risk of neonatal infection during the first week of life, but it has not significantly altered the risk of subsequent infection. In the United States, 0.03% of newborns become ill with late-onset group B Streptococcus infection.

Although current recommendations are that babies with uncomplicated late-onset group B Streptococcus infection be treated with intravenous antibiotics for 10 days, there are no actual data suggesting that this duration of treatment is better than shorter-course treatment. Anecdotally, babies treated for less than 10 days sometimes do well and sometimes experience recurrent infection. Of course, longer courses of intravenous antibiotics also are associated with increased costs and, especially with the placement of central catheters, potentially more complications.

Thus, Coon and colleagues reviewed treatment and outcomes data from the Pediatric Health Information System database, which includes patients at 49 stand-alone children’s hospitals in the United States. Included patients had been dismissed from a participating hospital prior to 4 months of age with a diagnosis of group B streptococcal disease and bacteremia sometime between January 2000 and September 2015. Patients were identified as having “uncomplicated” disease by the absence of a concurrent diagnosis of meningitis, osteomyelitis, septic arthritis, or a significant co-infection and by the absence of marked prematurity (< 29 weeks of gestation), a prolonged hospital course (more than 14 days), or receipt of intensive care services. Patients who received a peripherally placed central catheter were assumed to have received longer antibiotic courses (even if post-discharge home intravenous antibiotics were not identified in the database). Only patients admitted after 7 days of age were included.

A total of 1,369 infants were identified as potential study participants. Of them, 594 were excluded based on exclusion criteria, leaving 775 babies to be evaluated. Of those, 612 (79%) had received more than eight days of antibiotic therapy, and 163 (21%) received eight or fewer days of intravenous antibiotic treatment. The infection occurred at a median age of 48 days. Shorter courses of treatment were more likely in older children, in the later years of the study, and in infants with concurrent urinary tract infection. The source of payment was not statistically significantly associated with the duration of antibiotic treatment, nor was race or ethnicity.

Among patients treated with shortened intravenous courses, 16% were discharged with an oral antibiotic. The use of shortened antibiotic courses varied by hospital, with 14 of the participating 49 hospitals never using shortened courses and five hospitals using shorter courses in more than half of their patients.

Overall, 2.2% of studied infants had subsequently repeated group B streptococcal infection, 1.8% of those with longer treatment and 2.3% of those with shortened courses of treatment (the rates were not statistically different). None of the children receiving oral antibiotics at discharge had recurrent infection. One percent of patients experienced complications of central line use.

The authors pointed out that prolonged antibiotic courses can be complicated with adverse outcomes. They summarized their novel findings about management of uncomplicated late-onset group B Streptococcus bacteremia by saying that shortened courses of intravenous antibiotics are prescribed, with low rates of recurrence.

COMMENTARY

This new study points out several features of common evidence-based medicine practice. First, the evidence for the duration of antibiotic treatment is limited to what has been studied, and there is a dearth of comparative studies on the effectiveness of shorter durations. Second, as time goes on, physicians increasingly are switching to shorter courses of treatment, even without published evidence and guidelines to support such a practice. Third, the application of evidence-based medicine varies with the habits of peers as seen by the variation between hospitals in using shorter antibiotic courses. Fourth, despite the common adage to “do no harm,” this new paper shows that longer intravenous antibiotic courses do not necessarily help outcomes and it adds concrete data about the frequency of significant complications (“harm”) of intravenous lines used for antibiotic treatment.

Clearly, there has been a move over recent years to use shorter courses of antibiotics, and supportive data sometimes follow the early adaptation of practice change. Uncomplicated urinary tract infections, even in children, are treated for fewer days than when some of us were in training. More recently, serious bone and joint infections have been treated with shorter intravenous courses. Resources do affect practice (but not necessarily outcomes), and the World Health Organization was recommending five-day antibiotic courses for pneumonia when most American physicians still were treating for 10 days.

In addition, there are newer data to guide treatment decisions. In a prospective study of 29 infants with early-onset group B streptococcal bacteremia, conversion from intravenous to oral treatment (amoxicillin 200-300 mg/kg/day) after 48 hours of therapy yielded highly bactericidal concentrations (> 5 mg/L) of the antibiotic in the blood of treated babies after 48 hours of oral therapy.1

Recurrent infection has been used often as an adverse outcome suggesting the inadequacy of initial treatment. However, infants colonized and infected with group B Streptococcus often live with family members who are similarly colonized. Many mothers who are colonized with group B Streptococcus during pregnancy still are colonized with the same clonal strain of bacteria one year later.2 In addition, women transmit group B Streptococcus in their breast milk.3 Thus, some subsequent infection after successful treatment of the initial bout of bacteremia could be due to re-colonization and re-infection rather than to failure of the initial treatment.

Finally, prior to rushing to uniformly short courses of intravenous antibiotics for bacteremic babies, readers of this study should remember that these data are based on the practices of clinicians. It is possible that the clinicians judged the patients who received longer courses to be sicker and to need longer courses (and not to have decided on antibiotic duration simply based on protocol or habit). The babies who were treated with shorter courses tended to be older. It might be premature to apply shorter courses to sick, younger babies.

As we await more data, pediatricians treating newborns with bacteremia can be aware of the possibility of shorter courses and the risks of longer intravenous courses. These data can help guide thoughtful practice.

REFERENCES

  1. Gras-Le Guen C, Boscher C, Godon N, et al. Therapeutic amoxicillin levels achieved with oral administration in term neonates. Eur J Clin Pharmacol 2007;63:657-662.
  2. Hansen SM, Uldbjerg N, Kilian M, Sorensen UB. Dynamics of Streptococcus agalactiae colonization in women during and after pregnancy and in their infants. J Clin Microbiol 2004;42:83-89.
  3. Filleron A, Lombard F, Jacquot A, et al. Group B streptococci in milk and late neonatal infections: An analysis of cases in the literature. Arch Dis Child Fetal Neonatal Ed 2014;99:F41-F47.