Thoughts on the American Academy of Pediatrics/American Academy of Family Physicians Clinical Practice Guideline on Acute Otitis Media: A Different Perspective

REFERENCES

1. Lin HC, Su BH, Chen AC, et al. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants.

Pediatrics.2005;115:1– 4

2. Youssef RF, Darcy E, Barone A, Borja MT, Leggiadro RJ. Expressed breast milk as a source of neonatal sepsis.Pediatr Infect Dis J.2002;21:888 – 889 3. Ng PC, Lewindon PJ, Siu YK, Wong W, Cheung KL, Liu K. Bacterial contaminated breast milk and necrotizing enterocolitis in preterm twins.

J Hosp Infect.1995;31:105–110

4. Ng DK, Lee SYR, Leung LCK, Wong SK, Ho JCS. Bacteriological screen-ing of expressed breast milk revealed a high rate of bacterial contami-nation in Chinese women.J Hosp Infect.2004;58:146 –150

5. De Louvois J. Laboratory monitoring of banked human milk.Med Lab Sci.

1982;39:311–318

doi:10.1542/peds.2005-0146

In Reply.—

We appreciate the comment and suggestion by Ng et al, who believe that, as a Chinese society, Taiwan might share a similar cultural belief that accounted for the high bacterial colonization rate as Hong Kong.1_{This was the rationale to analyze the}

propor-tion of expressed breast milk (EBM) feeding versus banked breast milk feeding as the second confounding factor in our study.

EBM may be an underrecognized source of sepsis in susceptible infants. Human milk is a good culture medium and can be contam-inated with many pathogens includingSerratia marcescens2_{group B}

streptococcus,3_{methicillin-resistantStaphylococcus aureus,}4_Escherichia

coli,5_{and other microorganisms that have been shown to result in}

sepsis. Contamination with⬎1000 Gram-negative bacilli per mL is associated with feeding intolerance, whereas higher levels of contam-ination (⬎1 000 000/mL) can be associated with sepsis.6

We recognized in their report that bacteria in EBM might be associated with necrotizing enterocolitis (NEC) and sepsis because of the very high rate of contamination (63%)7,8_{; their findings only}

further emphasize that NEC is a multifactorial disease. However, we do not think their criticism of our study is appropriate. First of all, we did state in the results that 56 infants in the study group and 61 infants in the control group were fed with banked breast milk. In other words, there were 124 preterm infants in the study and 126 infants in the control group fed with EBM, initially because they couldn’t be nursed by oral sucking until 33 to 34 weeks’ gestational age. Obviously there was no difference in EBM feeding versus banked breast milk feeding. Second, we teach the mother how to properly handle and store breast milk. We screened the EBM randomly every 3 months for the last 5 years and cultured the EBM and the device if an infant developed sepsis twice. We did not find any association between sepsis or NEC and EBM. Third, Ng et al speculated that the high rate of bacterial contamination of EBM was because most of the mothers did not bath for 1 month after childbirth due to Chinese tradition. We did a very quick and simple survey of 600 pregnant woman; the results showed that 97.8% of the pregnant woman bathe within 7 days after delivery and that only 2.2% of the pregnant woman do not bathe until 28 days after delivery. All of them bathe every 1 to 2 days once they start bathing regularly again.

NEC is a complicated disease; the incidence of NEC varies from country to country and from nursery to nursery. Each unit needs to investigate the possible etiology independently and find the solution to improve quality of care. Nevertheless, according to our randomized, mask-control study, Infloran reduces the incidence and severity of NEC in very low birth weight preterm infants. We are going to initiate a multicenter collaborative study in Taiwan, and we hope that the results will further convince you of our results.

Hung-Chih Lin, MD

Department of Pediatrics

China Medical Children’s Hospital China Medical University

Taichung 404, Taiwan

Bai-Horng Su, MD, PhD

Department of Pediatrics

China Medical University Hospital China Medical University

Taichung 404, Taiwan

Chang-Hai Tsai, MD, PhD

Department of Pediatrics

China Medical Children’s Hospital China Medical University

Taichung 404, Taiwan

Healthcare and Management University Taichung 413, Taiwan

REFERENCES

1. Ng DK, Lee SYR, Leung LCK, Wong SK, Ho JCS. Bacteriological screen-ing of expressed breast milk revealed a high rate of bacterial contami-nation in Chinese women.J Hosp Infect.2004;58:146 –150

2. Drazin PB. Contamination in expressed breast milk.J Hum Lact.1998;14: 100

3. Olver WJ, Bond DW, Boswell TC, Watkin SL. Neonatal group B strep-tococcal disease associated with infected breast milk.Arch Dis Child Fetal Neonatal Ed.2000;83:F48 –F49

4. Lemoine L. Possible transmission of methicillin-resistantStaphylococcus aureusby expressed human breast milk.J Hosp Infect.1987;9:93–94 5. Graham JC, Morgan S, Ford M, Gould FK, Bolton DT. Sepsis and ECMO:

beware the breast milk.J Hosp Infect.1999;43:75–76

6. Botsford KB, Weinstein RA, Boyer KM, Nathan C, Carman M, Paton JB. Gram-negative bacilli in human milk feedings: quantitation and clinical consequences for premature infants.J Pediatr.1986;109:707–710 7. Youssef RF, Darcy E, Barone A, Borja MT, Leggiadro RJ. Expressed breast

milk as a source of neonatal sepsis.Pediatr Infect Dis J.2002;21:888 – 889 8. Ng PC, Lewindon PJ, Siu YK, Wong W, Cheung KL, Liu K. Bacterial contaminated breast milk and necrotizing enterocolitis in preterm twins.

J Hosp Infect.1995;31:105–110

doi:10.1542/peds.2005-0245

Thoughts on the American Academy of

Pediatrics/American Academy of Family

Physicians Clinical Practice Guideline on Acute

Otitis Media: A Different Perspective

To the Editor.—

In the May 2004 issue ofPediatrics, the Subcommittee on Man-agement of Acute Otitis Media published its long-awaited clinical practice guideline,1_{updating our understanding of this complex}

process.

The guideline is very helpful in pointing out the importance of pain management and reviewing strategies for more effective pain relief. Adopting preventive strategies to reduce the frequency of acute otitis media (AOM) is another important contribution. The most difficult and contentious recommendations made by the subcommittee involve criteria necessary for the accurate diagnosis and treatment of AOM.

An important stated mission of the diagnostic component of the guideline is to reduce overdiagnosis of AOM. The first guideline recommendation concerns the elements of the history and physi-cal examination needed to diagnose AOM accurately. The guide-line co-chair, Allan S. Lieberthal, MD, is quoted in the September 2004 issue ofInfectious Diseases in Childrenas stating: “The most important aspect of managing acute otitis media (AOM) is diag-nosing the disease…You must make an accurate diagnosis.”2_As

the authors correctly state, otitis media with effusion (OME) is often misdiagnosed as AOM.3_{The guideline states: “Clinicians}

should strive to avoid a false-positive diagnosis in children with middle-ear discomfort…A major challenge for the practitioner is to discriminate between OME and AOM.” In other words, the authors want the diagnostic component of the guideline to stress specificity over sensitivity. “Specificity” means that it would be okay to miss a few cases of AOM as long as almost every ear diagnosed as AOM really had AOM. “Sensitivity” means that no

LETTERS TO THE EDITOR 1443 at Viet Nam:AAP Sponsored on August 29, 2020

case of AOM would be missed at the expense of mislabeling many ears with OME or other diagnoses as AOM.

However, evidence has shown that many of the elements listed in the complex diagnostic table in the guideline are nonspecific and of limited value in separating AOM from OME. Guideline element 2 suggests that decreased mobility of the tympanic mem-brane (TM) and the presence of an air-fluid level behind the TM are as important in differentiating AOM from OME as are bulging of the tympanic membrane and otorrhea. Element 3 lists distinct erythema as a key finding in AOM.

In fact, well-conducted studies support different (and simpli-fied) diagnostic criteria for a more specific diagnosis of AOM. Of 15 patients that had distinct redness without bulging of the TM, none had fluid or bacteria when tympanocentesis was performed by Halsted et al.4_{In contrast, 61 of 67 patients with bulging and}

opaque eardrums yielded pus and pathogenic bacteria when tapped regardless of TM color. In fact, their summary states that “[w]ith few exceptions, the drums that showed definite bulging and total absence of landmarks yielded pus when aspirated and bacteria when cultured, while the diffusely red but not bulging membranes yielded no fluid and negative cultures.”

Harrison5_{states: “Contrary to what many clinicians are taught}

during training, erythema of the TM is the least specific finding for AOM.” Pelton’s review,6_{referenced in the guideline, showed that}

TM bulging and opacification had a high predictive value (83– 99%) of AOM, whereas distinct TM redness alone had a very low predictive value (7–15%) of AOM.

Schwartz,7_{in a well-conducted tympanocentesis study, was}

able to demonstrate that “a diffusely red, nonbulging, dull tym-panic membrane, mobile to negative and positive pressure, must be considered nonpathologic. A completely bulging yellow, opac-ified tympanic membrane…was the most frequently observed sign of acute otitis media.” In addition, Schwartz found that fever was only present in 61% of patients with confirmed AOM. Symp-toms of pain, including tugging of the ear, were absent in 20% of young patients. Finally, “segmental AOM should be considered as representing AOM with effusion” and “all three major effusion types, namely purulent, serous, and mucoid, can occur acutely.” The above-mentioned findings are all in conflict with the complex criteria listed in the American Academy of Pediatrics/American Academy of Family Physicians diagnostic table. Continuing to promote a red TM as one of the important findings of AOM is incorrect and misleading.

Listing the diagnostic criteria as a bulging, opaque TM, con-firmed by pneumatic otoscopy or otomicroscopy, would both simplify the diagnostic criteria in the guideline and confer the greater diagnostic specificity needed to reduce the problem of overdiagnosis of AOM. A small number of evolving or resolving AOM infections would not fit into this diagnostic guideline. Clin-ical decisions should be made by the practitioner in patients with atypical findings.

Guideline recommendation 3A deals with “the observation option.” For studies to reflect the role of antimicrobial therapy accurately, only patients with proven AOM should be enrolled (enrolling patients without proven AOM biases the results toward a nontreatment option), and the antibiotic used must be the best one available and dosed optimally (using a less effective antibiotic also biases the results toward the nontreatment option).

The studies selected by the guideline authors had very nonspe-cific diagnostic criteria for AOM and therefore included a signif-icant number of enrollees without AOM. This was confirmed by the low rates of positive tympanocentesis cultures on those studies that used myringotomies. A study by Kaleida et al8_only

con-firmed AOM in 71.4% of “severe” and 64.8% of “nonsevere” AOM-diagnosed children when myringotomies were performed. Despite this bias toward the nontreatment arm, antibiotic treat-ment still reduced failures, children with middle-ear effusion (MEE), and the length of time with MEE.

Two important goals of therapy that should be considered are improving quality of life and preventing suppurative complica-tions. Other studies cited by the guideline authors that had similar shortcomings still confirmed more rapid pain relief, less crying, shorter fever duration, and less analgesic use. It is reasonable to infer that the results would have been even better with a more accurately diagnosed AOM study population and the use of highly effective antibiotics.

It has been shown that children with a definite diagnosis of AOM (confirmed by tympanocentesis) who are treated with an

appropriate antibiotic will sterilize their middle-ear fluid rapidly, whereas children treated with placebo will continue to harbor pathogens9,10_{(eg, Howie and Ploussard’s}9_{pooled data for}

strep-tococcus pneumonia,Haemophilus influenza, andMoraxella: a 2- to 4-day sterilization rate with antibiotics of 97% and with placebo 17.5%).

In addition, the use of the arbitrary categories of “severe” and “nonsevere” AOM in decision-making does not seem to be helpful and is not based on evidence. The designations made by Kaleida et al8_{were based on height of fever and severity of pain. However,}

fever is frequently absent in AOM,7_{and high fever is frequently}

present in the viral infections that are so common in children. In fact, the positive tympanocentesis rates between the 2 Kaleida et al categories (71.4% for the “severe” groups and 64.8% for the “non-severe” groups) were so similar that this designation should not be part of the decision-making process.

Although the guideline has provided an important tool for pediatricians, an open forum on some of the guideline recommen-dations is necessary to clarify some of the discrepancies with the available evidence.

Harry Pellman, MD

Edinger Medical Group and Research Center Fountain Valley, CA 92708

REFERENCES

1. American Academy of Pediatrics, Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media.

Pediatrics.2004;113:1451–1465

2. Rosenthal M. Guideline for AOM: controversy where there shouldn’t be?Infect Dis Child.2004:35

3. Pichichero ME, Poole MD. Assessing diagnostic accuracy and tympa-nocentesis skills in the management of otitis media.Arch Pediatr Adolesc Med.2001;155:1137–1142

4. Halsted C, Lepow ML, Balassanian N, Emmerich J, Wolinsky E. Otitis media. Clinical observations, microbiology, and evaluation of therapy.

Am J Dis Child.1968;115:542–551

5. Harrison CJ. The laws of acute otitis media.Prim Care.2003;30:109 –135 6. Pelton SI. Otoscopy for the diagnosis of otitis media.Pediatr Infect Dis J.

1998;17:540 –543

7. Schwartz RH, Stool SE, Rodriguez WJ, Grundfast KM. Acute otitis media: toward a more precise definition.Clin Pediatr (Phila).1981;20: 549 –554

8. Kaleida PH, Casselbrant ML, Rockette HE, et al. Amoxicillin or myrin-gotomy or both for acute otitis media: results of a randomized clinical trial.Pediatrics.1991;87:466 – 474

9. Howie VM, Ploussard JH. Efficacy of fixed combination antibiotics versus separate components in otitis media. Effectiveness of erythro-mycin estrolate, triple sulfonamide, ampicillin, erythroerythro-mycin estolate-triple sulfonamide, and placebo in 280 patients with acute otitis media under two and one-half years of age.Clin Pediatr (Phila).1972;11:205–214 10. Ruohola A, Heikkinen T, Meurman O, Puhakka T, Lindblad N, Ruus-kanen O. Antibiotic Treatment of acute otorrhea through tympanos-tomy tube: randomized double-blind placebo-controlled study with daily follow-up.Pediatrics.2003;111:1061–1067

doi:10.1542/peds.2005-0064

In Reply.—

We thank Dr Pellman for his comments on the clinical practice guideline “Diagnosis and Management of Acute Otitis Media.”1

As he notes, accurate diagnosis is the key to appropriate manage-ment of this common condition. The debate as to the place of bulging in the diagnosis of acute otitis media (AOM) is important, and many commentators have stated that significant bulging is the most reliable sign of AOM.

Issues related to the articles by Halsted et al2_{and Schwartz et}

al,3_{as well as the studies by Karma et al}4_{that served as the basis}

for Pelton’s review,5_{have been addressed previously in a letter}6_to

the editor ofPediatricsand its reply.7_{To summarize, each of the}

quoted studies has flaws that result in the true relationship of bulging in the diagnosis of AOM being inconclusive. A well-conducted study to clarify the situation would be welcome.

“Option,” as defined by the American Academy of Pediatrics’ Steering Committee on Quality Improvement and Management, “…means either that the evidence quality that exists is suspect or

that well-designed, well-conducted studies have demonstrated little clear advantage to one approach versus another. Options offer clinicians flexibility in their decision-making regarding ap-propriate practice…”8

Observation (recommendation 3A) has been categorized as an option for the exact reasons stated by Dr Pellman. The studies on which it is based have limitations including a significant number of patients who do not have AOM. Despite these deficiencies the studies consistently show that observation in selected children is safe as demonstrated by the very low incidence of mastoiditis or other suppurative complications. Pain and fever may be present longer (1/2 and 1 day, respectively) in the observed child as opposed to one treated with antibacterial medication.9,10 _Both

symptoms are readily relieved with analgesic/antipyretic medi-cines. The potential to reduce the duration of symptoms must be weighed against the risk of adverse effects from antibiotics in 16% of patients11_{and the concern for increasing resistance of common}

bacteria resulting from excessive antibiotic use.

The study by Kaleida et al12 _{showed greater likelihood of}

failure of observation in younger children and in those who were severely ill (defined in the study as moderate or severe pain or fever

ⱖ39°C [102.6°F]). Based on this study the clinical practice guideline states that the observation option should only be considered in chil-dren⬎24 months old with certain AOM or⬎6 months old if the diagnosis is uncertain and only if the child is not severely ill.

The observation option provides an alternative approach to the management of AOM and is not a mandated mode of therapy. The clinician and the parent should jointly decide if this option is appropriate for the individual child on the basis of diagnostic certainty, age, illness severity, assurance of follow-up, and per-sonal preference.

Allan S. Lieberthal, MD, FAAP

Kaiser Permanente Panorama City, CA 91402

Theodore G. Ganiats, MD

Department of Family Medicine University of California, San Diego San Diego, CA 92093

REFERENCES

1. American Academy of Pediatrics, Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media.

Pediatrics.2004;113:1451–1465

2. Halsted C, Lepow ML, Balassanian N, Emmerich J, Wolinsky E. Otitis media: clinical observations, microbiology, and evaluation of therapy.

Am J Dis Child.1968;115:542–551

3. Schwartz RH, Stool SE, Rodriguez WJ, Grundfast KM. Acute otitis media: toward a more precise definition.Clin Pediatr (Phila).1981;20:549–554 4. Karma PH, Penttila MA, Sipila MM, Kataja MJ. Otoscopic diagnosis of

middle ear effusion in acute and non-acute otitis media. I. The value of different otoscopic findings.Int J Pediatr Otorhinolaryngol.1989;17:37– 49 5. Pelton SI. Otoscopy for the diagnosis of otitis media.Pediatr Infect Dis J.

1998;17:540 –543

6. Hoover H, Roddey OF. The overlooked importance of tympanic mem-brane bulging [letter].Pediatrics.2005;115:513

7. Lieberthal AS, Ganiats TG. The overlooked importance of tympanic membrane bulging: in reply [letter].Pediatrics.2005;115:513–514 8. American Academy of Pediatrics, Steering Committee on Quality

Im-provement and Management. Classifying recommendations for clinical practice guidelines.Pediatrics.2004;114:874 – 877

9. Damoiseaux RA, van Balen FA, Hoes AW, Vaerheij TJ, de Melker RA. Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years.BMJ.

2000;320:350 –354

10. Burke P, Bain J, Robinson D, Dunleavey J. Acute red ear in children: controlled trial of non-antibiotic treatment in general practice.BMJ.

1991;303:558 –562

11. Ruben RJ. Sequelae of antibiotic therapy. In: Rosenfeld RM, Bluestone CD, eds.Evidence-Based Otitis Media. Hamilton, ON, Canada: BC Decker Inc; 1999:303–314

12. Kaleida PH, Casselbrant ML, Rockette HE, et al. Amoxicillin or myrin-gotomy or both for acute otitis media: results of a randomized clinical trial.Pediatrics.1991;87:466 – 474

doi:10.1542/peds.2005-0284

Misinterpretation of Liver-Function Tests and

West Nile Virus Infection in Children

To the Editor.—

I write to add several comments about the recent report in

Pediatricson 4 cases of West Nile virus (WNV) infection in chil-dren.1_{With regard to the first patient, the authors comment}

nu-merous times about the unusual presentation of a “fulminant hepatitis.” In addition, they use the term “hepatic failure” to describe the marked elevation of transaminases along with a mild coagulopathy. Based on my careful reading, I conclude that this patient had neither fulminant hepatitis nor hepatic failure. Fur-thermore, I think the assertion that this child’s liver injury is causally related to WNV is misleading.

Among hepatologists, the most widely accepted definition of fulminant hepatic failure includes the onset of hepatic encepha-lopathy⬍8 weeks after the beginning of liver disease. Failure of the liver and loss of hepatocyte function results in the inability to remove neurotoxins and synthesize vital proteins that are needed to sustain life. This patient did have a prolonged seizure, but it is unlikely that it was a result of hepatic dysfunction. In fact, this patient had normal transaminases on arrival to the hospital. The presence of a coagulopathy caused by liver dysfunction is a wor-risome sign but does not indicate liver failure.

The fact that the initial transaminases were normal also casts doubt on the possibility of WNV involvement of the liver. It is counterintuitive to hypothesize that liver involvement would oc-cur rapidly 24 hours after the onset of the illness. Moreover, marked elevation of transaminases is seen most often when there is a hepatotropic virus such as hepatitis A or B or in circumstances that can cause centrilobular necrosis. This latter condition can be seen when there is a perfusion injury or with certain hepatotoxins such as acetaminophen. My interpretation of the abnormal transaminases is that they are most likely secondary to the pro-longed seizure resulting in ischemic hepatitis. The rapid resolu-tion of the transaminases over 8 days would be typical in this scenario and very atypical for most viral hepatitis cases. Support-ing evidence includes the increased creatine kinase levels and transiently increased the creatinine level. In addition, a coagulopa-thy is seen in 25% to 50% of cases of ischemic hepatitis.2_Certainly

the high fever, the coexistent use of anticonvulsants, and the administration of antipyretics may have contributed to the hepatic injury.

In summary, this case of WNV infection highlights 2 important points. First, the degree of transaminase elevation frequently does not correlate with the severity of liver disease; therefore, it is a mistake to interpret transaminases as a measure of liver function. Second, temporal elevation of liver enzymes is often seen in many infections. Many factors need to be considered before assigning causality.

Jay A. Hochman, MD

Children’s Center for Digestive Health Care Atlanta, GA 30342

REFERENCES

1. Yim R, Posfay-Barbe KM, Nolt D, Fatula G, Wald ER. Spectrum of clinical manifestations of West Nile virus infection in children.Pediatrics.2004; 114:1673–1675

2. Farrell MK, Bucuvalas JC. Systemic disease and the liver. In: Suchy FJ, Sokol R, Balistreri WF, eds.Liver Disease in Children. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:870 –71

doi:10.1542/peds.2004-2756

In Reply.—

We thank Dr Hochman for his thoughtful comments on our recent case report.1_{Dr Hochman asserts that patient 1 had neither}

a fulminant hepatitis nor hepatic failure causally related to infec-tion with West Nile virus (WNV). He correctly points out, and we agree, that transaminases may become markedly elevated with hepatotropic viruses, perfusion injuries, or hepatotoxins. As Dr Hochman states, temporal elevations of liver enzymes can be seen in many infections. However, as we have described previously, patient 1 tested negative for several of the infectious agents that

LETTERS TO THE EDITOR 1445 at Viet Nam:AAP Sponsored on August 29, 2020

DOI: 10.1542/peds.2005-0064

2005;115;1443

Pediatrics

Harry Pellman

Perspective

Physicians Clinical Practice Guideline on Acute Otitis Media: A Different

Thoughts on the American Academy of Pediatrics/American Academy of Family

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