Following Guidelines May Prolong Neonatal Sepsis Treatment

Laurie Barclay, MD

May 05, 2014

Following clinical guidelines for infants who were exposed to chorioamnionitis (CAM) and who had sterile blood cultures led to prolonged antibiotic therapy, longer length of stay, and more interventions, according to a retrospective data analysis published online May 5 in Pediatrics.

As noted in an accompanying commentary, the Committee on the Fetus and Newborn (COFN) has recently changed their guidelines on the basis of these findings, and now antibiotic therapy for neonates with abnormal laboratory findings and those born to mothers with CAM does not have to extend for longer than 72 hours.

"[CAM] is a major risk factor for neonatal sepsis," write study author Courtney Kiser, MD, from Pediatrics/Neonatology, Thomas Jefferson University/Nemours in Philadelphia, Pennsylvania, and colleagues. "At our institution, neonates exposed to CAM and intrapartum antibiotics are treated with prolonged antimicrobial therapy if laboratory values are abnormal despite a sterile blood culture."

Therefore, Dr. Kiser and colleagues examined the frequency of abnormal laboratory testing in term and late-preterm neonates born to mothers with CAM and assessed the effects of following recent COFN guidelines.

"The management of infants born to mothers with CAM and treated with intrapartum antibiotics can be challenging," senior study author Zubair H Aghai, MD, associate professor, director of neonatology research, and attending neonatologist at Thomas Jefferson University/Nemours, told Medscape Medical News. "The COFN recommends extending the course of antibiotic therapy in neonates exposed to CAM if the mother received intrapartum antibiotics, even if the infant appears well with a sterile blood culture but has abnormal laboratory data."

Laboratory Findings Not Specific

Of 554 infants meeting inclusion criteria, 83 (14.9%) had an abnormal immature to total neutrophil ratio (>0.2), 121 (22%) had an abnormal C-reactive protein level (>1 mg/dL), and 153 (27.6%) had either or both of these abnormalities at 12 hours of age. Blood culture was positive in only 4 (0.7%) of the infants.

"A more specific test or tool is needed to guide therapy in asymptomatic neonates exposed to CAM and with sterile blood cultures," Dr. Aghai pointed out.

Of 134 infants (24.2%) who received prolonged antibiotic therapy, 112 (20.2%) were treated only because of abnormal laboratory findings. More than one fifth (21.6%; n = 120) underwent lumbar puncture.

"The take-home message for clinicians is that a large number of term and late-preterm infants exposed to CAM with sterile blood cultures will have abnormal laboratory data," Dr. Aghai said. "If we follow recent COFN recommendations, 1 in 4 healthy infants exposed to CAM will be treated with prolonged antibiotic therapy, will be subjected to additional invasive procedures, and will have prolonged hospitalization."

Limitations of this study include its retrospective design, use of a single center data, and lack of generalizability to premature neonates with early-onset sepsis or to infants with late-onset sepsis.

"The health care costs and risks associated with an extended course of antibiotics, prolonged hospitalization, lumbar puncture, intravenous access, and separation of infant from mother may be too high to justify such treatment," the study authors conclude. "The COFN should consider changing their recommendation on extending the course of antimicrobial therapy in asymptomatic late-preterm and term neonates exposed to CAM and intrapartum antibiotics with abnormal laboratory data and negative blood culture results."

Recommendations for Early-Onset Sepsis

"If the treatment of sepsis were completely benign, it would make no difference if every infant with the slightest chance of infection was treated," write Richard A. Polin, MD, from the College of Physicians and Surgeons, Columbia University, New York City, and colleagues in the commentary. "However, treating an uninfected infant for 5 to 7 days means disrupting maternal bonding for an extended period of time, exposing the infant to drugs with potential toxicities, fostering the development of antibiotic-resistant flora, and increasing the probability that the infant will experience a more serious morbidity later in the course of hospitalization."

They note the following:

  • Close monitoring, but not necessarily treatment, may be appropriate for symptomatic neonates without risk factors for infection who improve during the first 6 hours of life.

  • Although CAM significantly increases the risk of early-onset sepsis, the risk for sepsis is low in an infant who appears well at birth.

  • Intrapartum antibiotics may lower the risk for sepsis in infants born to mothers with CAM, but antibiotics may be less effective once CAM is established.

  • Intrapartum antibiotics lower the sensitivity of postnatal blood cultures.

  • In an otherwise healthy term infant aged 48 to 72 hours, commonly used laboratory tests should never be used as a rationale to continue antibiotics, as their positive predictive accuracy is limited.

  • To rule in or rule out sepsis, physical examination is at least as good as most laboratory tests.

On the basis of their conclusions, the commentators recommend the following:

  • Antibiotics may be discontinued by 48 hours of life in well-appearing term newborn infants who are born to women with CAM.

  • For infants with greater degrees of prematurity or abnormal screening results, antibiotic treatment for 72 hours may be considered.

  • Lumbar puncture is indicated in infants with a positive blood culture, with a high probability of sepsis based on clinical signs or laboratory findings, or with lack of clinical improvement when treated with appropriate antimicrobial therapy.

"I strongly agree with the commentary," Dr. Aghai said. "The COFN has changed the guidelines based on this paper, [and now] we do not have to extend antibiotic therapy for neonates born to mothers with CAM for longer than 72 hours if they have abnormal laboratory data. This will not only reduce the risks associated with an extended course of antibiotics, prolonged hospitalization, lumbar puncture, intravenous access, and separation of infant from mother but also significantly reduce the healthcare cost."

This study and commentary received no outside funding, and the authors and commentators have disclosed no relevant financial relationships.

Pediatrics. Published online May 5, 2014.

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