By Philip R. Fischer, MD, DTM&H

Dr. Fischer is 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: Meningitis is very unlikely in otherwise healthy-appearing febrile infants older than 21 days of age. Thus, cerebrospinal fluid analysis might not be needed as part of a "routine" evaluation of these babies.

Source: Martinez E, Mintegi S, Vilar B, Martinez MJ, Lopez A, Catediano E, Gomez B. Prevalence and predictors of bacterial meningitis in young infants with fever without a source. Pediatr Infect Dis J published online 12-2014, doi: 10.1097/INF.0000000000000629.

Clinical investigators in Spain prospectively evaluated all infants with fever in whom its source was not evident after initial exam and laboratory testing from 2003 to 2013 in an emergency department of a tertiary teaching hospital. A total of 2362 infants younger than 90 days of age were included in the study.

Lumbar puncture was performed in 27% of febrile infants. However, in the subset of febrile infants who did not appear to be well, lumbar puncture was done in 61%. And cerebrospinal fluid analysis was done in 70% of the study subjects younger than 21 days of age.

Meningitis was identified in only 11 of the 639 children who underwent lumbar puncture. Nine of those 11 babies were younger than three weeks old, and five did not appear well on initial exam. Meningitis was diagnosed in zero of the 1975 well-appearing febrile infants more than 21 days of age.

Group B streptococcus, Escherichia coli, and Listeria monocytogenes were each responsible for three cases of meningitis. Pneumococcus (in a 23-day-old) and meningococcus (in a 49-day-old) accounted for the other two cases of meningitis.

The authors concluded that cerebrospinal fluid analysis should be "strongly considered in not well-appearing infants and in those less than or equal to 21 days of age" who presented with fever without apparent source. They suggested that the recommendation to systematically perform spinal fluid analysis in older well-appearing febrile infants be re-evaluated.

COMMENTARY

None of us is accurate enough with a physical exam to reliably determine if a febrile newborn who looks well has an underlying serious bacterial infection or not. For decades, the published standard of care has been to begin antibiotic therapy while waiting for results of microbiology testing of blood, urine, and cerebrospinal fluid.

However, the vast majority of otherwise healthy-appearing febrile infants have self-limited viral infections. "Routine" testing and presumptive treatment can lead to discomfort (such as from needles to obtain samples), cost (for testing as well as for hospitalization and treatment while waiting for definitive results), and confusion (and further unnecessary testing and treatment) when initial tests show "positive" results due to contaminants.

Thus, standards of care have shifted from hospitalizing and treating all febrile babies younger than two (or three) months of age toward being a bit more selective in the management of these children. Still, however, most American pediatricians would consider it good routine care to obtain samples of blood, urine, and cerebrospinal fluid from all infants who become febrile during at least the first month of life, and to hospitalize these patients for parenteral antibiotic therapy while waiting for culture results.

The new data from Spain provide helpful evidence to suggest that cerebrospinal fluid analysis is likely not necessary in otherwise healthy-appearing babies after the 21st day of life. Removing cerebrospinal fluid sampling and analysis from the routine care of older otherwise well-appearing febrile infants could save discomfort, cost, and some complications presumably without significantly adding risk for "missing" meningitis. But, are these results generalizable to sites outside of Spain? Perhaps not!

The Spanish investigators identified 11 younger babies who did have meningitis, and three of those were infected with Listeria, a germ that is decidedly uncommon among North American newborns with meningitis. (A total of 181 cases of bacteremia during the first three months of life in six U.S. hospital systems revealed no cases of Listeria.1 In Kenya, an even wider variety of microorganisms is associated with neonatal and infantile meningitis.2) Realizing that the microbial epidemiology is different in various parts of the world, testing and care of febrile infants might also need to vary. It could be the organisms and infections that are less common in Spain are more common in the United States and might be missed by omitting lumbar puncture from routine evaluation of febrile babies. (Interestingly, though, two of the three babies with Listeria meningitis were born at an "outside" maternity facility during an outbreak of Listeria infection. There was only one case of Listeria meningitis in the subsequent six years at the Spanish center.)

Interestingly, not all of the ill-appearing febrile infants and not all of the youngest febrile infants had cerebrospinal fluid analysis in the Spanish study. Despite recommendations for thorough evaluation of febrile infants, there is practice variation in other parts of the world as well.3 In the United States, for instance, pediatric clinicians often use clinical judgment rather than guidelines to decide on testing and treatment of febrile infants; with only about 0.4% of well-appearing febrile infants older than 25 days of age having bacteremia or meningitis, following guidelines would use more medical resources without altering outcomes.4

The management of febrile infants will continue to evolve as microbial epidemiology changes and as diagnostic measures improve.5 In the meantime, these new data from Spain contribute usefully to the practice of those caring for febrile newborns. First, they remind us that meningitis continues to occur, even in this era of good prenatal care and preventive treatment of mothers with known group B streptococcal colonization. Second, these data reassure us that meningitis is still uncommon but is more likely in ill-appearing babies than in otherwise well-appearing babies. Third, the Spanish report maintains our concern for possible meningitis in febrile infants younger than three weeks of age, even when those young infants do not look sick. Finally, though, these data call us to continue to seek data about risks and benefits of cerebrospinal fluid analysis in our own areas with varying illnesses and microbial epidemiology.

References

  1. Biondi E, et al. Epidemiology of bacteremia in febrile infants in the United States. Pediatrics 2013;132:990-996.
  2. Mwaniki MK, et al. Clinical indicators of bacterial meningitis among neonates and young infants in rural Kenya. BMC Infectious Diseases 2011;11:301.
  3. Mechan WP, et al. Adherence to guidelines for managing the well-appearing febrile infant. Pediatr Emerg Care 2010;26:
    875-880.
  4. Pantell RH, et al. Management and outcomes of care of fever in early infancy. JAMA 2004;291:1203-1212.
  5. Jhaveri R, et al. Management of the non-toxic-appearing acutely febrile child: A 21st century approach. J Pediatr 2011;159:181-185.