Letter to the Editor

LETFERS

TO

THE

EDITOR

349

AARON

L.

CARREL,

MD

University

of Wisconsin

Hospital

and

Clinics

Madison,

WI

53792

REFERENCES

1. Baraff U, Bass JW, Fleisher CR, et al. Practice guideline for the man-agement of infants and children 0 to 36 months of age with fever

without source. Pediatrics. 199392:1-12

2. Baraff U, Oslund SA, Schriger DL, Stephen ML. Probability of bacterial infections in infants less than 3 months of age: a meta-analysis. Pediatr

Infect Dis

I.

1992;1I:257-265

3. Powell KR. Evaluation and management of febrile infants younger than

60 days of age. Pediatr Infect Dis J.19909:153-157

4. Dagan R, Powell KR, Hall CB, Menagus MA. Identification of infants unlikely to have serious bacterial infection although hospitalized for

presumed sepsis. I Pediatr. 1985;107:855-860

5. Bonadio WA. Evaluation and management of serious bacterial

infec-tions in the febrile young infant. Pediatr Infect Dis J.1990;9:905-912

6. Klassen TP, Rowe PC. Selecting diagnostic tests to identify febrile

in-fants less than 3 months of age as being at low risk for serious bacterial infection: a scientific overview. J Pediatr. 1992;121:671-676

7. Jaskiewicz JA, McCarthy CA, Richardson AC, Powell KR. Reevaluation

of criteria to identify infants evaluated for possible sepsis at low risk for

serious bacterial infection. ADJC. 1992;146:483

In

Reply.-We are pleased at the interest the publication of the Practice

Guideline created among the readers of Pediatrics and to have an

opportunity to respond to the reader’s comments.

Mefa-analysis. We appreciate the thoughtful comments of Drs Lehmann and Andrews, Hupert, and Kokx regarding the methods

of meta-analysis. The Medline search strategies were: (1) febrile (tw) or bacteremia (tw) and child (tw) or infant (tw) and not

foreign language with subheadings of therapy, diagnosis, or epi-demiology; (2) children (MESH) and explode fever (MESH) and

not foreign language. The primary author (L.J.B.) and a research

associate reviewed all studies identified by the literature search and classified them as addressing the questions of interest and determined their validity based on predetermined criteria. We did

consider intrastudy effects related to internal and external validity

of the individual studies. Although FAST*PRO software does al-low for explicit adjustment of individual studies for a variety of biases, we chose not to do this. We excluded from our analyses all

studies which we considered methodologically flawed and as-signed all other studies equal quality scores. All the studies were

of prospectively enrolled cohorts of children in the age groups of interest with fever without source treated as outpatients whose

evaluation included at least a blood culture. We utilized a consis-tent definition of serious bacterial infection: cerebrospinal fluid, blood, bone, joint, urine or stool culture positive for a known

bacterial pathogen. We acknowledge that there were differences in

other inclusion criteria, ie, temperature, age group, and laboratory tests. These differences were explicitly discussed in the text and

noted in Table 2 and are part of the basis for the treatment options noted. All the panel members were familiar with the studies on

which the meta-analysis and decisions were based. The more re-cent large prospective series were afforded special mention

be-cause they were specifically designed to determine the utility of antimicrobial therapy. The data from the unpublished studies

were available to the panelists, all of whom are qualified to de-termine the quality of these investigations. We do not contend that

practice guidelines should be based solely on this type of evi-dence. The expert panel considered the individual studies, the

results of the meta-analysis, and their own experience and opin-ions in the development of the Guideline.

Drs Lehmann and Andrews question the mean value for the

probability of bacteremia in Table 2, specifically, Streptococcus

pneumoniae bacteremia and make the general comment that the methods were not sufficiently detailed to allow the reader to

rep-licate the analyses.’ The omission of some details from the meth-ods reflects space considerations and the clinical orientation of the

majority of the journal’s readers. The specific values that were questioned were derived using hierarchical Bayesian beta-bino-mial model for the posterior probability for the true mean. When

this model is used, the resulting mean probability is higher than one would expect based on the results of the individual studies.

This model may not be appropriate to combine studies with

prob-abilities close to zero. When pure Bayesian analysis is used, the probability of S pneumoniae bacteremia is 2.55%, as suggested by Drs Lehmann and Andrews.

Composition

of the Expert Panel.

Dr Toll is correct in stating that 90% of decisions regarding the management of febrile children are

made by community physicians not academicians. All panel mem-bers were aware of the differences in practice styles of academi-cians and community practitioners alluded to by Drs Lehmann

and Andrews and as reported by Green et al in 1981.2 All panel

members are practicing clinicians and are cognizant of the differ-ences between community and academic practice. Most have the

additional qualification of being actively involved in research in this area. We attempted to make the Guideline practical for corn-munity practitioners, hence the inclusion of the different manage-ment options for each of the clinical scenarios. We would be fas-cinated to see the results of a Guideline produced using the same

data by a panel of nonacademic practicing physicians.

Effect of “Prior Beliefs” or Practice Styles. The concept proposed by Drs Lehmann and Andrews that one must explicitly publish

one’s prior beliefs is intriguing. We did not specifically record the

opinions of panel members before their review of the evidence and

the panel meeting. There were substantial differences among

panel members regarding specific aspects of the Guideline, most notably the management of low-risk infants <28 days of age. Drs

Isaacman and Rogers note the inconsistency in the recommended management strategies for low-risk infants <28 days of age versus

infants 28 to 90 days of age whose risk of serious bacterial infection

is essentially identical. Dr Carrell has done an excellent job of

calling attention to the shifting paradigm of managing “low-risk” young infants as outpatients with a minimal laboratory evalua-tion, no antibiotic therapy, and careful observation by reliable

parents. This is a dramatic change from the almost universal prac-tice of a “full septic work-up” and hospitalization for parenteral

antibiotic therapy.3 At the time of the panel meeting, the evidence

that younger infants could be safely managed as outpatients was limited, and none was accepted for publication as noted by Dr

Hubert. Several panel members believed that careful observation

was an appropriate approach for all febrile infants <90 days of age,

and that this could be conducted by reliable parents in the outpa-tient setting with close physician supervision. The panel’s decision

was no doubt partly influenced by prior beliefs as suggested by

Drs Lehmann and Andrews and partly due to the limited data supporting this approach.

Young Infants With Otitis Media. Drs Isaacman and Andrews question the need for laboratory evaluation in febrile infants <90

days of age with otitis media. The original “Rochester criteria” excluded all children with focal bacterial infections from the

low-risk group. No child excluded from the low-risk group only

be-cause of otitis media has gone on to have a systemic bacterial infection (personal communication, Jaskiewicz). These data sup-port the findings presented by Avner et al, but neither data set has

been published following peer review.

Parent’s Preferences. One group not represented in the devel-opment of the guidelines was parents of children for whom the

Guideline was intended. Although it seems logical to incorporate patients’ preferences (or as in this case their surrogates) when

developing a guideline, in our opinion, the methods for doing so have not been adequately defined. Ideally, patients or their

prox-ies should be involved in the process of health care decision mak-ing. There has been a movement toward incorporating flexibility for patient preferences into guideline, as evidenced by the work of the Urinary Incontinence in Adults Guidelines Panel for the

Agency for Health Care Policy and Research.4 Wennberg et al have developed a method of incorporating patient preferences into

medical decision making using interactive videodisc technology.5 However, to our knowledge, no one has actually incorporated

patient preference in specific clinical management algorithms. We chose, as have others, to emphasize physician judgement. One of

us (L.J.B.), has conducted a study of patient preferences for each of the two management options for each of the two clinical scenarios using both panel meetings and individual parent interviews.6 We found that most but not all parents were substantially more will-ing than physicians to accept the small risk of serious bacterial infection and generally preferred option 2 for both scenarios for three primary reasons: (1 ) they reasoned that they could return for

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350

LE1TERS

TO

THE

EDITOR

reevaluation if their child’s condition deteriorated, (2) they did not

wish to subject their child to painful and/or time-consuming

di-agnostic procedures, and (3) they did not want their child to receive unnecessary antibiotics. Drs Lehmann and Andrews

sug-gest the use of utility assessments to measure patient and

physi-cian preferences. This technique, although well defined, is subject to framing bias.7 No doubt most parents whose child suffers

seri-ous sequelae of bacterial meningitis in retrospect would prefer to

have had their physician adopt a management strategy which

minimized the risk of this outcome. Although concerns about medicolegal liability undoubtedly play a role in physicians’ desire to chose patient management options with the lowest risks, there

is also a fundamental difference in the risks to physicians and

patients. This disparity relates to the frequency with which

pa-tients and physicians confront various clinical situations. A parent

may have only one or two experiences with a child with fever

without source at risk for serious bacterial infection, thus their child’s risk of a serious bacterial infection is approximately I .4%. For physicians who see hundreds of “at-risk” children, the

prob-ability of a child developing a serious bacterial infection including meningitis is much greater, ie, a 75% chance of encountering at

least one serious bacterial infection per 100 children evaluated.

Definition of a Fever and Risk of Bactenemia. We do not think, as Isaacman suggests, that the definition of fever is conservative but

rather that it truly defines a febrile infant. Dr Kokx correctly notes that antipyretic administration will affect the child’s measured

temperature and, therefore, the child’s treatment using the

algo-rithm. We suggest that the highest measured temperature be used to determine patient management. Numerous studies have

dern-onstrated that the risk of occult bacteremia is higher in infants and children with higher fevers.”’4 This is best demonstrated by the difference in rates of occult bacteremia in the two recent multi-center prospective randomized control trials of Fleisher et al and

Bass et al noted in Table 2.’ The choice of 39.0#{176}Cwas arbitrary and in keeping with most of the studies to which we referred.

Indi-vidual practitioners may choose a high temperature as did Bass et

al to initiate a diagnostic evaluation and empiric antibiotic treat-ment. We chose to take a conservative approach and to

recom-mend evaluation and treatment of young infants with temperature 38.0#{176}C and older infants and children with temperatures

39.0#{176}C. Using a higher temperature criteria will increase the

probability of serious infection. Dr Kokx’s suggestion that the

duration of fever should be a decision point in the Practice

Guide-line is an interesting one. Although this may seem reasonable, there is no evidence regarding the duration of a febrile illness and the risk of occult bacteremia.

Sensitivity and Specificity of Physicians’ Evaluation. With regard to Dr Falik’s question, the sensitivity and specificity of clinical

examination as defined by McCarthy et al refers to detection of serious bacterial infection using clinical assessment alone. Ill-ap-pearing infants and children are more likely to be seriously ill and

to have serious bacterial infections and abnormal nonspecific

screening test results. The Practice Guideline was specifically

in-tended for children who are nontoxic appearing, because clinical appearance alone cannot be used to eliminate the risk of occult

bacteremia. All children included in the publications which served as the basis of the Guideline, except that of Schwartz et al,’6 were

nontoxic appearing. None were judged sufficiently ill-appearing to be hospitalized. The probability of bacteremia in such children

with fever of 39.0#{176}C is approximately 3% to 4%. There is no

substantial difference in the probabilities of occult bacteremia in children 3 to 24 months of age and those 25 to 36 months of age. The use of WBC criteria allows clinicians to further divide children with fever of this degree into groups with substantially different

probabilities of occult bacteremia (2.6% vs 13.0%). The panel pos-tulated that the majority of children with S pneumoniae bacteremia would have a leukocytosis and, therefore, that as illness due to

H

influenzae type B becomes less prevalent due to the widespread use of HIB vaccine, an even smaller proportion of children with occult

bacteremia will not be detected by this screening laboratory test. Office Laboratory Tests. The panel proposed two alternative management strategies recognizing that it is difficult and

expen-sive for office-based pediatricians to routinely perform a veni-puncture to obtain blood cultures from children with fever

with-out source 39.0#{176}C and because many physicians may not want to treat all such children with empiric antibiotics. We agree with the

Dr Hyrnan and his colleagues that undue restrictions should not be placed on practitioners which prevent them from performing

laboratory

tests in their offices and that the American Academy of

Pediatrics should lobby for the changes necessary to simplify the

procedures so that pediatricians may continue to perform simple laboratory tests in their offices. We hope that the publication of the

guideline will justify the use of the recommended tests and serve

as evidence that they should be reimbursed by insurers, including

health maintenance organizations.

“Oventreatment” With Antibiotics. As Dr Falik suggests, the Guideline will lead to the “overtreatment” of fever, if by that one means prescribing antibiotics for children without bacterial

infec-tions. This is necessary to prevent the rare event (approximately I /200 in children with WBC counts of 15 000) of occult bactere-mia progressing to bacterial meningitis if untreated. Dr Kokx

raises the issue of what degree of risk is acceptable or “low.” He suggests that a risk of bacterial meningitis of 0.5% is not low

enough and that a lumbar puncture should be performed on every febrile low-risk infant to exclude this possibility. Ultimately we

must come to grips with the concept that we cannot reduce risk to zero and that attempting to do so is not appropriate. As noted above, most parents are more willing to take these risks than are

practicing physicians.

Consideration of Other Clinical Variables. We agree with Dr Kokx that there are a variety of factors that should influence the

clinician’s decision regarding the type of diagnostic evaluation and empiric antibiotic therapy such as the presence of other ill

children in the home or community, parenteral reliability, and

practice setting. Children with sickle cell disease are a subpopu-lation at much higher risk of occult pneumococcal bacteremia and meningitis.’7 When febrile black children <5 years of age are not

know to have sickle cell disease, a complete blood cell count,

examination of the peripheral smear, and reticulocyte count should be used to screen for this disease. The absence of abnormal red blood cell counts and a reticulocyte <2% makes the presence of sickle cell disease unlikely.’8 All febrile black children in whom

this diagnosis cannot be excluded should at least have a blood culture and empiric antibiotic therapy, preferably with

ceftriax-one, because of the emergence of penicillin resistance among pneumococci.

Credibility of Investigations. We believe that Dr Kokx’s sugges-tion that the fact that the two publications had the same principal

investigator and funding source substantially influenced the

re-sults is unwarranted. The panel members were chosen because they were respected as independent minded and knowledgeable

experts in this clinical area and played a substantial role in the development of the practice guideline. There is no doubt that

infants and children with untreated bacteremia may progress to develop serious bacterial infections including meningitis as is documented in the 20 reports to which we referred.’ None of these

studies was funded by the same research grant, and none was conducted by the principal investigator.

The authors acknowledge that this guideline is not based solely on the evidence and that the opinions of the experts influenced the

guideline. Like all clinical guidelines, it is a document in evolution that will change in response to new knowledge and enhanced methods for organizing and interpreting that knowledge.

How-ever, we hope that the readers will recognize that this guideline is more firmly based on the evidence than any previous collection of

recommendations on the subject, and hope that it will stimulate

further clinical research in this area.

LARRY

J.

BARAFF,

MD

JAMES

W.

BASS,

MD

GARY

R.

FLEISHER,

MD

JEROME

0.

KLEIN, MD

GEORGE

H.

MCCRACKEN, JR.,

MD

KEITH

R.

POWELL,

MD

DAVID

L.

SCHRIGER,

MD,

MPH

UCLA

Medical

Center

Emergency

Medicine

Center

Los Angeles, CA 90024-1744

REFERENCES

1. Baraff U, Oslund 5, Prather M. Effect of antibiotic therapy and etiologic

microorganism on the risk of bacterial meningitis in children with occult bacteremia. Pediatrics. 1993;92:140-143

2. Greene JW, Hara C, O’Conner 5, Attemeier WA. Management of febrile

outpatient neonates. Clin Pediatr. 1981;20:375-380

3. Baraff U. Management of the febrile child: a survey of pediatric and

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LETFERS

TO

THE

EDITOR

351

emergency medicine residency directors. Pediatr Infect Dis

I.

1991;10:

795-800

4. Deleted in proof.

5. Kasper JF, Mulley AC Jr, Wennberg JE. Developing shared

decision-making programs to improve the quality of health care. QRB QRev Bull. 1992;18:183-190

6. Oppenheim P1, Sotiropoulos 5, Baraff U. Incorporating patient prefer-ences into practice guidelines: management of children with fever with-out source. Submitted for publication.

7. Redelmeier DA, Rozin P. Kahneman D. Understanding patient’s

decision: cognitive and emotional perspectives. JAMA. 1993;270:72-76

8. McCarthy PL, Dolan TF. The serious implications of high fever in in-fants during their first three months. Clin Pediatr. 1976;15:794-796

9. McCarthy PL, Jekel JF, Dolan iT. Temperature greater than or equal to

40#{176}Cin children less than 24 months of age: a prospective study.

Pedi-atnics. 197759:663-668

10. Waskerwitz S. Berkelhamer JE. Outpatient bacteremia: clinical findings

in children under two years with initial temperatures of 39.5#{176}Cor higher. I Pediatr. 1981;99:213-233

Ii. Wright PF, ThompsonJ, McKee KTJr, Vaughn WK, Sell SH, Karzon DT.

Patterns of illness in the highly febnle young child: epidemiologic,

clinical, and laboratory correlates. Pediatrics. 1981;67:694-700

12. Press S. Fawcett NP. Association of temperature greater than 41.1#{176}C

(106#{176}F)with serious illness. Clin Pediatr. 1985;24:21-25

13. Bonadio WA, Romine K, Cyuro J. Relationship of fever magnitude to rate of serious bacterial infections in neonates. I Pediatr. 1990;116:

733-735

14. Jaffe DM, Fleisher CR. Temperature and total white blood cell count as

indicators of bacteremia. Pediatrics. 1991;87:670-674

15. Baraff U, Bass JW, Fleisher CR, et al. Practice guideline for the

man-agement of infants and children with fever without source 0 to 36

months of age. Pediatrics. 1993;92:i-12

16. Schwartz RH, Wientzen RL. Occult bacteremia in toxic appearing,

fe-brile infants: a prospective dmical study in an office setting. Clin Pediatr.

1982;21:659-663

17. Overturf CD, Powars D, Baraff U. Bacterial meningitis and septicemia

in sickle cell disease. AJDC. 1977;131:784-778

18. Losek JD, Hellmich TR, Hoffman CM. Diagnostic value of anemia, red blood cell morphology, and reticulocyte count for sickle cell disease.

Ann Emerg Med. 1992;21:915-918

Does

Immunization

in

the

Buttocks

Cause

Sciatic

Nerve

Injury?

To the Edit

or.-Currently, US and Canadian authorities (Canadian Green Book,

US Red Book, and ACIP Recommendations) advise the anterolat-eral thigh or deltoid as the preferred site for immunization injec-tions in infants and children, and caution against using the buttock

because of the possibility of damaging the sciatic nerve. Curiously,

some authorities state that the buttock site can be considered “when large volumes must be given, eg, immune globulin.”

Re-view of the English language literature yields several reports of

direct nerve injury after injection into the buttocks of an infant or child of antibiotics or antiserum, but none associated with modern

childhood vaccines.

We are seeking brief reports of local, direct neurologic injury to the sciatic nerve, associated with administration of childhood

vac-dnes: DTP, DT, MMR, or the component vaccines IPV, Hib, or

hepatitis B in the buttocks of infants or children.

NONI MACDONALD,

MD,

FRCPC

Chair,

Infectious

Diseases

and

Immunization

Committee

Canadian

Pediatric

Society

Division

of Infectious

Diseases

Children’s Hospital of Eastern Ontario

401 Smyth

Rd

Ottawa, Ontario KIH 8L1, Canada

EDGAR K. MARCUSE,

MD,

MPH

Associate

Editor,

Red

Book

American

Academy

of Pediatrics

Children’s

Hospital

and

Medical

Center

P0

Box

5371

Seattle, WA 98105

Comparison

of

the

Number

of

Neonatologists

in

Different

Countries

Not

Valid

To the

Editor.-I read with dismay, Dr William A. Silverman’s “informal

sur-vey” purporting to demonstrate a disproportionate excess of

neo-natologists in the United States compared with six other devel-o_ countries. The fact that these “rough estimates” of physicians

providing neonatology services are totally incomparable makes all

subsequent manpower discussions purely judgmental, not factual. In fact, if one is really interested in the number of pediatricians

dedicated to neonatal care (neonatologist equivalents) as opposed to only “titled” neonatologists, then calculations using the data in

the footnotes triples the manpower figures for both Britain and

Japan, catapulting Japan above the United States with the highest density of neonatologist equivalents.

In fact, however, Dr Silverman never really addresses the issue

of numbers or types of doctors needed to provide neonatal care. He does not consider, for example, the financial imperatives that

increasingly bind US pediatricians to their offices, thereby shifting

responsibility for hospital-based newborn services and medical care to neonatologists. As a result, US neonatologists are not only newborn intensivists, they are also becoming the hospital primary

care physician for newborns! Surely health care delivery system differences like this must be factored into manpower assessments

and comparisons! Without such considerations, Dr Silverman’s personal biases may be misconstrued or misrepresented as justi-lying funding cuts for maternal child health and/or perinatal

training programs.

After presenting inconclusive manpower data, Dr Silverman

then speculates about the relative costs of neonatal intensive care. Without citing any data whatsoever, Dr Silverman speculates that

“the rest of the world (has) set more realistic financial limits on neonatal intensive care by controlling the number of neonatolo-gists and their compensation.” Finally, he suggests that US

neo-natologists somehow discard their altruistic pediatrician heritage, yielding to the lure of enormous financial rewards in the US

“market-driven ...laissez-faire medical system.” This last

allega-lion is both demeaning and totally unsubstantiated.

More useful than Dr Silverman’s speculation and innuendo would be careful studies of different models for practicing

neonatal/perinatal medicine. How can teams of health care pro-fessionals best serve patients and community? How can US

pe-diatricians and neonatologists, academicians and private practi-tioners, work together more effectively to deliver the least costly,

highest quality care? How can we accurately analyze manpower needs in the context of a defined health care system?

In these times of major health care reform, the American Acad-emy of Pediatrics and its representative constituency have a unique opportunity to constructively influence policy “towards

improving the outcome of pregnancy” by continuing to make

recommendations that are based on thoughtful analysis of reliable data. Let us do more than allow health care change, let us provide

the kind of pediatric leadership that will assure health care progress.

Ian

M. Ratner,

MD,

FAAP

North Texas Neonatal Associates

Dallas,

TX

75231

REFERENCE

I. Silverman, WA. Is neonatal medicine in the United States out of step? Pediatrics. 1993; 92:612-613

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1994;93;349

Pediatrics

Jr., Keith R. Powell and David L. Schriger

Larry J. Baraff, James W. Bass, Gary R. Fleisher, Jerome O. Klein, George H. McCracken,

Letter to the Editor

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1994;93;349

Pediatrics

Jr., Keith R. Powell and David L. Schriger

Larry J. Baraff, James W. Bass, Gary R. Fleisher, Jerome O. Klein, George H. McCracken,

Letter to the Editor

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