In general, antidiarrheal preparations are not recommended for infants or children
because they have little effect on acute diarrhea, are associated with side effects, and
direct attention away from the use of oral hydration therapy.
loperamide that alter GI motility should be avoided, especially in children with high
fever, toxemia, or bloody mucoid stools, because they may worsen the clinical
course of the bacterial infection. Bismuth subsalicylate preparations, which possess
antisecretory and antimicrobial effects, have not been shown to provide clinical
benefit and are not recommended.
45 Adsorbents, such as kaolin-pectin or attapulgite,
adsorb bacterial toxins and water and lessen the symptoms of diarrhea by producing
more formed stools, but there is no evidence of effectiveness, and they are not
45 Zinc supplementation (10–20 mg for 10–14 days) has been
recommended by the WHO for the treatment and prevention of diarrheal disease in
children in developing countries; however, its mechanism of action, best method of
administration, and efficacy in different populations are not yet well understood.
Probiotics, live microbial products containing species of Lactobacillus,
Bifidobacterium, Saccharomyces, and Streptococcus, can improve the balance of
intestinal flora and diminish the effect of enteric pathogens. These microbes are
thought to exert their beneficial effects through various mechanisms, including
producing antibacterial chemicals, competing with enteric pathogens, inhibiting the
adhesive capabilities of pathogens, altering toxins or toxin receptors, and
upregulating interleukin-mediated T-cell response.
48,49 Probiotics are most useful in
infectious gastroenteritis when used early in the course of disease. Lactobacilli are
the most well-studied species and have been the most consistently effective in
clinical trials. It appears that efficacy of the different species may depend on the
specific strain, the dose, and the timing of administration, although it is generally
accepted that dosage forms with at least 10
9 colony-forming units and above
45,48 The manufacture of probiotics is not regulated by the FDA;
therefore, the organism count per dose might be based on the number present at the
time of production and not at time of expiration, and the labeling might incorrectly
identify the species of organism. Probiotics are not recommended for use in
immunocompromised individuals because systemic infections after the use of these
43 For J.R., a Lactobacillus preparation administered for
5 days may provide some modest clinical benefit, although the benefit is most
pronounced in rotavirus diarrhea, which has not been documented in his case.
GER is a common disorder, with 50% to 67% of infants experiencing recurrent
vomiting and regurgitation during the first 4 months of life.
by transient relaxations of the lower esophageal sphincter (LES). Infants might also
be predisposed to reflux because of their body positioning (e.g., slumped over in a
car seat or lying supine), their consumption of a liquid feeding that exceeds the
volume capacity of the stomach, and in premature infants, a decrease in peristaltic
Infants and young children might also have undiagnosed underlying
conditions that predispose them to reflux (e.g., neurologic disorders, hiatal hernia,
hypertrophic pyloric stenosis, and cow’s milk protein allergy).
infants, 80% are benign and resolve by 18 months of age,
children resolves in a timeframe similar to that of adults. If untreated, GER can result
in esophageal strictures, GI hemorrhage, or chronic respiratory disease from the
aspiration of GI contents. Studies evaluating the relationship between GER disease
(GERD) and asthma or Helicobacter pylori have shown mixed results.
In infants, the vomiting and regurgitation of GER occur frequently, and other
symptoms often are nonspecific (e.g., failure to thrive [FTT], recurrent pneumonia,
apnea, dysphagia, reactive airway disease, apparent life-threatening events [ALTE],
58,59 A thorough diagnostic workup is generally not
necessary in a healthy infant with functional GER presenting as recurrent vomiting.
Empiric drug therapy can be initiated after the diagnosis is made based on clinical
findings and after other causes of vomiting have been eliminated.
evaluations, however, are indicated for infants and children presenting with
additional symptoms of GERD (e.g., FTT, irritability, ALTE, and respiratory
Because uncomplicated GER usually resolves spontaneously in infants, therapy
should focus on providing symptom relief and maintaining normal growth.
goals of therapy are to lessen symptoms, heal esophagitis, and prevent complications
in infants and children with pathologic GER, so that surgery can be avoided.
and young children with underlying neurologic problems (e.g., cerebral palsy) are
unlikely to have spontaneous resolutions of GER and frequently require aggressive
antireflux therapies and surgical intervention.
POSITIONAL AND DIETARY MEASURES
should S.B. be treated initially?
S.B. can be treated conservatively because he does not present with lifethreatening complications.
58,59 First, caregiver feedings should be observed to rule
out regurgitation caused either by overfeeding or by inappropriate feeding
techniques. Sometimes infants with milk protein allergies can have a similar clinical
presentation; therefore, a change to a soy protein formula or hypoallergenic formula
Interventions to modify an infant’s body positioning or to modify
infant feedings with milk thickeners are not proven to be effective, but are reasonable
60,61 Maintaining S.B. at a 60-degree angle during the day while sitting
and at a 30-degree position at night should be implemented in an effort to promote
clearance of acid from the esophagus and to minimize reflux after meals. Milk
thickeners (most commonly rice cereal in the United States) and more frequent,
smaller feedings are also worthwhile interventions, although thickened formula could
lead to increased coughing during feeding. Mild cases of GER often can be treated
successfully by dietary measures alone, as well as by propping infants in an upright
position during, and 1 hour after, feedings.
59 Although the placement of infants in a
face-down prone position during sleep can reduce reflux, the greater risk of sudden
infant death syndrome (SIDS) in infants younger than 12 months of age outweighs the
58 Older children and adolescents should follow the
recommended dietary guidelines (i.e., avoidance of caffeine, chocolate, and spicy
The efficacy of pharmacologic therapy in altering the course of uncomplicated GER
in infants has not been proved.
In infants or children who present with nonspecific
symptoms or complications, such as S.B., acid-suppression therapy or prokinetic
therapy is warranted even in the absence of documented esophagitis.
esophagitis is present, acid suppression is always recommended to aid in the healing
process; however, these agents alone do not rectify the causes of the GER.
various agents to treat infant GER are listed in Table 104-3.
Chronic antacid therapy is generally not recommended for the treatment of GER in
infants and young children, because infants treated with aluminum-containing antacids
can accumulate sufficient aluminum to cause osteopenia and neurotoxicity.
addition, information on other antacids in infants is limited; nevertheless, antacids
can provide short-term relief of symptoms in older children and adults.
Proton-pump inhibitors (PPIs) are superior to histamine-2 receptor antagonists
(H2RA) in relieving symptoms and in promoting healing of significant esophagitis
from GER in infants, young children, and adults.
58,73,74 PPIs control both basal and
meal-stimulated acid secretion, which may in part explain their superior efficacy.
The incidence of adverse effects in children from PPI is similar to that reported in
64,75 Despite concerns about the long-term use of PPI, untoward effects have not
been observed from their use for up to 11 years.
In children, increased metabolism
and decreased bioavailability necessitate larger milligram per kilogram doses to
maintain acid suppression than adults; thus, titration of dose to response is necessary,
particularly for treatment of esophageal erosions.
60,77 Although most clinicians dose
PPI once a day, multiple, divided daily doses can prevent acid breakthrough and
73 Omeprazole, lansoprazole, and esomeprazole are available
in extended-release capsules, which can be separated, opened, and sprinkled on soft
foods. Omeprazole and esomeprazole are also available as granules for an oral
suspension. Suspension formulations for both omeprazole and lansoprazole have
been extemporaneously compounded and evaluated for stability. Esomeprazole has
also been recently approved for use in children with GERD aged 1 to 11 years and
has been studied and reviewed extensively.
Histamine-2 Receptor Antagonists
H2RA reduce histamine-stimulated acid secretion, but have limited effects on acid
secretion by other chemical mediators and other stimuli. In randomized, controlled
trials, H2RA in infants and children relieved symptoms and facilitated the healing of
65,66 Tolerance to the acid-suppressant activity of H2RA for a
relatively short time (<30 days), however,
67,68 can limit their use for long-term
treatment of esophagitis. Oral liquid formulations are available for most H2RA.
Ranitidine is also available in an effervescent tablet.
Oral Drugs Used to Treat Gastroesophageal Reflux in Infants
Agent Mode of Action Oral Dosage
Neutralizes acid 0.5–1.0 mL/kg/dose before and after feeding
Omeprazole Decrease acid secretion via
inhibition of gastric hydrogenpotassium adenosine
Alternate dosing: 1 mg/kg daily or twice daily
Esomeprazole 1–11 years: 10 mg daily
(>1 mg/kg/day or therapy >8 weeks has not been
Lansoprazole Infants ≥3 months: 7.5 mg twice daily or 15 mg once
1–11 years: 15 mg (<30 kg)–30 mg (>30 kg) daily
Pantoprazole <5 years: 1.2 mg/kg/day once daily
>5 years: 20 or 40 mg once daily
Famotidine 1 mg/kg/day divided BID
Nizatidine 10 mg/kg/day divided BID
Ranitidine 5–10 mg/kg/day divided BID or TID
Bethanechol Cholinergic agent; stimulates
0.1–0.2 mg/kg/dose QID given 30–60 minutes before
Metoclopramide Dopamine antagonist 0.1–0.2 mg/kg/dose QID given 30 minutes before
Erythromycin Motilin agonist stimulates
3 mg/kg/dose QID; maximum dose: 10 mg/kg or 250
Sucralfate Forms paste and adheres to
Metoclopramide, a dopamine antagonist with cholinergic and serotonergic effects,
accelerates gastric emptying, increases LES pressure, enhances esophageal
clearance, and accelerates transit time in the small bowel; however, its effects on
vomiting and esophageal pH in children with GER has been equivocal.
Additionally, metoclopramide has been associated with significant CNS (i.e.,
restlessness, drowsiness, and extrapyramidal) effects, recently receiving a special
alert for a higher risk of extrapyramidal symptoms in those <1 year of age, and rare
reports of gynecomastia and galactorrhea.
59 Erythromycin increases GI motility by
increasing smooth muscle contractions through its motilin agonistic activity, and it
has been used as a prokinetic agent for GER in children, when acid suppression
therapy alone was ineffective.
80 Erythromycin-induced development of infantile
hypertrophic pyloric stenosis, arrhythmias, and potential changes in bacterial
resistance patterns, however, limit its use for GER. The cholinergic agonist,
bethanechol, reportedly reduces vomiting episodes in infants with GER
however, its role in treating GER in infants is limited because of its potential to
induce bronchospasm and to stimulate gastric acid secretion. The lack of a suitable
commercially available formulation of bethanechol for young infants necessitates its
extemporaneous compounding. Baclofen, which decreases transient LES relaxations
through its γ-aminobutyric acid agonist actions, could be a future therapeutic option
for GER, pending further study.
82 Generally, prokinetic agents only are marginally
effective in the management of GER.
Sucralfate was equally effective as cimetidine for use in esophagitis
use for GER is more limited because of concern about the adverse effects of
aluminum-containing products in infants.
wheezes; endoscopy rules out esophagitis. What would be the next step of therapy?
The treatment of S.B. can include acid-suppression therapy. Acid-suppression
therapy in children who have complications from GER can be implemented by a
step-up approach in which treatment is initiated with an H2RA followed by a PPI if
no improvement is noted, or through a step-down approach involving a PPI followed
by an H2RA for maintenance therapy. However, initial therapy with PPI is
58,59 and S.B. may be treated with omeprazole 5 mg daily. Granules for
suspension may be mixed in 10 mL of water and administered orally.
The effectiveness of acid suppression for managing symptoms of GER in children
is not as well documented as it is for healing esophagitis; however, acid suppression
is believed to play a useful role for symptom control, particularly for managing the
58 Treatment should be continued for at least 3 to 4 months,
although the optimal duration of therapy is unknown. If S.B. requires additional drug
therapy to control symptoms of GER beyond 18 months to 2 years of age, surgery
should be considered because GER is unlikely to resolve spontaneously after this
84 Surgery might be considered earlier if S.B. fails medical therapy or if he
develops an esophageal stricture, apnea, or recurrent respiratory disease.
Acute otitis media (AOM) is the most common reason for antimicrobial use in
children, and is associated with expenditures of $350 per episode and, cumulatively,
85 AOM is most common from the ages of 3 months to 3
years, although the highest incidence occurs between 6 and 9 months of age. Most
children will have had at least one episode by the time they reach 1 year of age.
Incidence is higher in the winter months, concurrent with viral upper respiratory
illnesses. Several risk factors for AOM have been identified and include age younger
than 2 years, early colonization of pathogens and onset of AOM, day-care attendance,
bottle propping, cleft palate, immune compromise, and Down syndrome. Other
factors such as smoke exposure, bottle feeding, pacifier use, and ethnicity have not
been consistently found to increase risk of AOM.
Eustachian tube dysfunction, either from intermittent causes such as upper
respiratory infections or permanent causes such as cleft palate, is the primary
condition required for the development of AOM. This results in a defect in the
eustachian tube’s ability to equilibrate middle ear pressure. Thus, nasopharyngeal
contents, including bacteria, may be aspirated into the middle ear. This process is
more likely in infants and young children who have shorter, flatter eustachian tubes.
Changes in pressure can also cause increased vascular permeability, resulting in an
effusion. Viral infections contribute by enhancing bacterial transfer from the
nasopharynx and adherence to the middle ear.
S. pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis
colonize the nasopharynx early in childhood, and thus, are the most common
87 Historically, these pathogens have been implicated in
28% to 54%, 32% to 59%, and up to 63% of cases of AOM, respectively.
introduction of the pneumococcal conjugate vaccine (PCV7) reduced the overall
incidence of AOM, the recurrence of AOM, and the need for tympanostomy tube
85–87 However, the incidence of AOM caused by non-PCV7 serotypes, H.
influenzae, and M. catarrhalis increased with the reduction in AOM cases caused by
85,86,90,91 These studies were used to guide the development of a 13-
valent PCV (PCV13), which was approved and licensed to replace the PCV7 in
2010. The PCV13 vaccine includes six of the serotypes that had been shown to
produce more than 60% of non-PCV7 vaccine strain invasive infections. The PCV13
vaccine has shown increased protective effects against AOM because of the
reduction in nasopharyngeal colonization by emerging serotypes.
have shown that PCV13 provides a reduction in pneumococcal disease, including
exhibit, which are consistent with AOM, and how should AOM be diagnosed?
Very often, as in this patient case, otitis media is preceded by an upper respiratory
tract infection. These viral infections often will produce otitis media with effusion
(OME), which typically will cause no more than temporary mild hearing loss. If
AOM develops, more signs and symptoms will usually arise. These symptoms can
include otalgia (pain causing infants to pull on or rub the ears), fever, irritability, and
89 Unfortunately, aside from otorrhea, these symptoms are nonspecific and
may be present in many children who do not have AOM. As a result, a definitive
diagnosis may not be easily obtained with symptoms alone. Diagnosis should be
confirmed on visualization of the middle ear.
In 2013, the American Academy of Pediatrics (AAP) published guidelines on the
diagnosis and management of AOM that stated that a diagnosis of AOM requires mild
bulging of the tympanic membrane and either recent onset of ear pain (<48 hours) or
intense erythema of the tympanic membrane.
89 Pneumatic otoscopy should be used to
confirm the presence of effusion. Middle ear effusion can be differentiated from
AOM in that, whereas both present with bulging tympanic membranes, in AOM, the
middle ear fluid is more often dark yellow or red.
87,89 Other diagnostic tools may be
used. Tympanometry uses sound waves to measure the compliance of the tympanic
membrane. In acoustic reflectometry, the absorption of sound waves by the tympanic
membrane provides information about the middle ear in that an effusion will cause
more sound to be reflected back than a normal ear.
87 C.D.’s fever and irritability
along with fluid in the middle ear and bulging, dark yellow tympanic membranes are
consistent with the diagnosis of AOM.
CASE 104-8, QUESTION 2: How should C.D.’s otitis media be treated?
The 2013 AAP recommendations provide for the option to observe without
treatment or to treat with antibiotics, depending on the age of the patient and
89 Generally, infants 6 months of age and younger should receive
antibiotic therapy in all cases. Infants and children 6 months to 2 years of age can be
managed with observation if there is a nonsevere unilateral AOM without otorrhea.
Children 2 years of age and older can be managed with observation in bilateral or
unilateral nonsevere AOM without otorrhea. Antibiotics are warranted in all cases of
AOM with otorrhea or in AOM cases with severe symptoms (e.g., temperature
C.D. appears to have bilateral AOM with severe symptoms based on his fever
greater than 39°C, so antibiotic therapy is indicated. Despite pneumococcal
penicillin resistance rates, initial therapy in most children who have not received
amoxicillin in the last 30 days, would still be amoxicillin at a dose of 80 to 90
89 Amoxicillin is effective against susceptible and intermediately resistant
pneumococcus, it is affordable and palatable, and it has a narrow spectrum of
86 Providers should prescribe amoxicillin/clavulanate in children who have
received amoxicillin in the last 30 days, have concurrent purulent conjunctivitis, or
have a history of recurrent AOM unresponsive to amoxicillin.
may be used in those with Type I allergies to penicillin.
Whichever treatment course is taken in a patient (observation or antibiotic therapy
with amoxicillin or amoxicillin/clavulanate), effectiveness is assessed for 48 to 72
hours. If the treatment is effective, the patient should defervesce, irritability should
decrease, and normal activity should resume (e.g., eating and sleeping). If the
observation is ineffective, treatment with amoxicillin or amoxicillin/clavulanate is
recommended. If amoxicillin or amoxicillin/clavulanate is ineffective for C.D.,
ceftriaxone 400 mg (50 mg/kg) intramuscularly for 1 or 3 days is an option.
CASE 104-8, QUESTION 3: How should C.D.’s otalgia be managed?
Ear pain is a common feature of AOM, and it should be addressed regardless of
the decision to use antibiotics or not. Acetaminophen 120 mg (15 mg/kg) or ibuprofen
80 mg (10 mg/kg) can provide adequate relief, and are first-line agents in the
89 Home remedies such as the application of heat or cold may
89 For example, a washcloth can be soaked with very warm water,
wrung out, and placed over the ear for comfort for 15 minutes several times per day.
Acute pharyngitis is most common in children 5 to 15 years of age and is rare before
3 years of age. The etiology is typically viral, but bacteria such as group A
streptococci (GAS, Streptococcus pyogenes), groups C and G streptococci,
Neisseria gonorrhoeae, Mycoplasma pneumoniae, and Chlamydia pneumoniae may
also cause pharyngitis in children.
94 The majority of attention is directed toward the
detection and management of GAS infections as, untreated, they may lead to
rheumatic fever, a complication progressing to permanent heart disease.
node. Are P.J.’s symptoms more consistent with GAS or viral pharyngitis?
Findings suggestive of GAS tonsillopharyngitis include sudden onset of throat
pain, fever, headache, abdominal pain, nausea, vomiting, tonsillopharyngeal edema,
enlarged anterior cervical lymph nodes, soft palate petechiae, and a scarlatiniform
94 Symptoms that increase the likelihood of a viral cause include rhinorrhea,
cough, conjunctivitis, and viral rash.
94 P.J. is lacking associated symptoms that would
suggest a viral cause and has more symptoms of GAS pharyngitis, but confirmatory
Because clinical and physical findings are not definitive for GAS pharyngitis,
confirmatory testing is important to determine the need for antibiotic therapy. A rapid
antigen detection test is recommended, and, if positive, treatment is initiated. If
negative, a throat culture should also be obtained and treatment initiated if the culture
grows GAS. Rheumatic fever can be effectively prevented if treatment is started
within 9 days from the start of the illness.
What treatment should be initiated at this time?
Penicillins remain the agents of choice for GAS pharyngitis. Either oral penicillin,
oral amoxicillin, or intramuscular benzathine penicillin may be used. Amoxicillin
suspension is more palatable than penicillin and has the advantage of a once-daily
dosing regimen. Intramuscular penicillin is a one-time dose that is helpful in those at
risk for nonadherence. In patients with a Type I hypersensitivity to penicillins,
azithromycin, clarithromycin, or clindamycin may be used. In those with a non-Type I
allergy to penicillin, a first-generation cephalosporin may be considered.
Recommended regimens are summarized in Table 104-4.
94,95 Although there is little
reported GAS resistance to penicillin, some patients have a decreased clinical
response and may respond better to cephalosporins. This is often seen in patients
who are GAS carriers and those who may have other bacteria causing infection.
Patients are no longer contagious 24 hours after the first antibiotic dose.
Medication Regimens for the Treatment of Streptococcal Pharyngitis and
Amoxicillin 50 mg/kg once a day or 25 mg/kg twice a day (maximum 1 g/day) 10 days
Penicillin VK Children ≤27 kg: 250 mg 2 or 3 times a day
Children >27 kg, adolescents: 500 mg 2 or 3 times a day or 250 mg 4
Benzathine penicillin G ≤27 kg: 600,000 units IM
For Patients with Penicillin Allergy
Cephalexin 20 mg/kg (up to 500 mg) twice a day 10 days
Cefadroxil 30 mg/kg (up to 1 g) once a day 10 days
Clindamycin 7 mg/kg 3 times a day (maximum 300 mg/dose) 10 days
Azithromycin 12 mg/kg once a day (maximum 500 mg) 5 days
Clarithromycin 7.5 mg/kg twice a day (maximum 250 mg/dose) 10 days
Medication Regimens for the Prevention of Recurrent Rheumatic Fever
Benzathine penicillin G ≤27 kg: 600,000 units IM
Penicillin V 250 mg oral Twice a day
Sulfadiazine ≤27 kg: 0.5 g oral
P.J. should receive amoxicillin (400 mg/5 mL), 12.5 mL (1,000 mg) every 24
hours for 10 days. For pain relief, he may also receive as-needed doses of
acetaminophen (160 mg/5 mL), 10 mLevery 6 hours, or ibuprofen (100 mg/5 mL), 10
Those with a history of rheumatic fever, characterized by acute generalized
inflammation of the heart, joints, brain, or skin, should receive long-term antibiotic
prophylaxis to prevent further complications from streptococcal infections.
Recommended medications and dosing regimens are summarized in Table 104-5.
Patients with acute carditis and residual heart disease should receive treatment for 10
years or until 40 years of age, whichever is longer.
95 Patients with an episode of
carditis but without residual heart disease should receive treatment for 10 years or at
95 Patients who had rheumatic fever without carditis should
receive treatment for 5 years or at least until 21 years of age.
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