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Red Book :
2003 REPORT OF THE COMMITTEE
ON INFECTIOUS DISEASES
Errata
(Revised 12/15/03)
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Page 26: Table 1.6: The minimum interval between Dose 2 and Dose 3 for HepB
should be changed from 3 wk (and 16 wk after first dose) to 8 wk (and 16 wk
after first dose). (See page 3 for revised table.)
Page 64: Table 1.11: Under the heading “Intravenous administration,” in the third
sentence, change 1 mg/kg or 0.01 mL/kg to 0.01 mg/kg or 0.1 mL/kg. (See
page 4 for revised table.)
Page 111: Within Viruses: Non-A Through -E Hepatitis Viruses: Second paragraph,
last sentence: crytogenic should be cryptogenic. (See page 5 for revised text.)
Page 215: Under Treatment: Fourth sentence: the dosage for clindamycin ovules
should be changed from 100 g to 100 mg. (See page 6 for revised text.)
Page 255: Under Treatment: Fifth sentence: flucytosine serum concentrations
should be changed from between 40 and 60 mg/mL to between 40 and
60 µg (micrograms)/mL. (See page 7 for revised text.)
Page 411: Table 3.32: Under Drug(s) and Dose for Meningitis or encephalitis,
the phrase but for 30–60 days and the preceding comma should be omitted.
(See page 8 for revised table.)
2
ERRATA
Page 474: Under Treatment, second bullet, fifth sentence: maximum dosage for
azithromycin dihydrate should be changed from 600 mg/day to 500 mg/day.
(See page 9 for revised text.)
Page 495: Table 3.45: In footnote 6, the following phrase should be omitted: is
not approved for use in patients younger than 12 years of age and. The sentence
should read: Drug is not recommended in patients with meningitis because of
its potential epileptogenic properties. (See page 10 for revised table.)
Page 495: Within Treatment: Otitis Media: Second paragraph, third sentence: the
ratio of amoxicillin to clavulanate should be changed from the 7:1 formulation to
the 14:1 formulation. (See page 10 for revised text.)
Page 601: Within Treatment: Congenital Syphilis: Newborn Infants: Second
sentence should be changed from If the mother’s titer is 4 times higher than
that of the infant, congenital syphilis still can be present to If the infant’s
titer is less than 4 times higher than that of the mother, congenital syphilis
still can be present. (See page 11 for revised text.)
Page 607: Within Treatment: Indications for Retreatment: Latent syphilis: Second
paragraph, first sentence: 2.4 U should be changed to 2.4 million U. (See page 12
for revised text.)
Page 659: Within Control Measures: BCG Vaccine, first sentence: The phrase livevirus vaccine should be changed to live vaccine. (See page 13 for revised text.)
Page 663: Under Treatment: Fourth paragraph, third sentence: younger than
17 years of age should be changed to younger than 18 years of age. (See
page 14 for revised text.)
Page 708: Table 4.2: Under Comments for Ampicillin-sulbactam (Unasyn),
the sentence should read Licensed for use in children 1 year of age and older.
(See page 15 for revised table.)
Page 733: Table 4.9: Under Drug (Abbreviation)/Trade Name for Abacavir (ABC)/
Ziagen, Component of Combivir should be changed to Component of Trizivir.
(See page 16 for revised table.)
Page 796: Under the heading “Assessment of immunization status,” the parentheses
in item 6 should read (see Precautions and Contraindications, p 45). (See page 17
for revised text.)
Table 1.6. Catch-up Immunization Schedules for Children and Adolescents Who Start Late or Who Are >1 Month Behind*
Children 4 Months Through 6 Years of Age
Minimum Interval Between Doses
Dose 1
(Minimum Age)
Dose 3 to Dose 4
Dose 4 to Dose 5
4 wk
4 wk
8 wk (and 16 wk after first dose)
6 mo
4 wk2
6 mo1
4 wk: if first dose given at
younger than 12 mo of age
8 wk (as final dose): if first dose
given at 12 to 14 mo of age
No further doses needed: if first
dose given at 15 mo of age
or older
PCV 7: (6 wk)
4 wk: if first dose given at
younger than 12 mo of age
and current age younger
than 24 mo
8 wk (as final dose): if first dose
given at 12 mo of age or older
or current age 24 to 59 mo
No further doses needed: for
healthy children if first dose
given at 24 mo of age or older
4 wk6: if current age younger
8 wk (as final dose): this dose
than 12 mo
only necessary for children
12 mo to 5 y of age who
8 wk (as final dose)6: if current
age 12 mo or older and second
received 3 doses before 12 mo
dose given at younger than
of age
15 mo of age
No further doses needed: if
previous dose given at 15 mo
of age or older
4 wk: if current age younger
8 wk (as final dose): this dose
than 12 mo
only necessary for children
8 wk (as final dose): if current
12 mo to 5 y of age who
age 12 mo or older
received 3 doses before
No further doses needed: for
12 mo of age
healthy children if previous dose
given at 24 mo of age or older
3
Dose 2 to Dose 3
4 wk
4 wk
4 wk
4 wk4
ERRATA—REVISED TABLE
Dose 1 to Dose 2
DTaP (6 wk)
IPV (6 wk)
HepB3 (birth)
MMR (12 mo)
Varicella (12 mo)
Hib5 (6 wk)
4
ERRATA—REVISED TABLE
Table 1.11. Epinephrine in the Treatment of Anaphylaxis1
Intramuscular administration
Epinephrine 1:1000 (aqueous): 0.01 mL/kg per dose, up to 0.5 mL, repeated every
10–20 min up to 3 doses.2
Intravenous administration
An initial bolus of intravenous epinephrine is given to patients not responding to intramuscular epinephrine using a dilution of 1:10 000 rather than a dilution of 1:1000.
This dilution can be made using 1 mL of the 1:1000 dilution in 9 mL of physiologic
saline solution. The dose is 0.01 mg/kg or 0.1 mL/kg of the 1:10 000 dilution. A continuous infusion should be started if repeated doses are required. One milligram (1 mL)
of 1:1000 dilution of epinephrine added to 250 mL of 5% dextrose in water, resulting in
a concentration of 4 µg/mL, is infused initially at a rate of 0.1 µg/kg per minute and
increased gradually to 1.5 µg/kg per minute to maintain blood pressure.
1
2
In addition to epinephrine, maintenance of the airway and administration of oxygen are critical.
If agent causing anaphylactic reaction was given by injection, epinephrine can be injected into the
same site to slow absorption.
ERRATA—REVISED TEXT
5
can be found in blood donors and can be transmitted by transfusion, neither agent
has been found to be associated with development of post-transfusion hepatitis and,
hence, are not “hepatitis” viruses.
The SEN virus also is being evaluated as an agent of non-A through -E hepatitis.
In one study, tests of stored sera from blood donors and cardiac surgery patients
revealed that approximately 2% of donors tested positive for SEN virus DNA,
and the proportion of cardiac surgery patients with evidence of new infection with
SEN virus was 10 times higher among those who had received transfusions, compared with those who had not. Of 12 recipients with non-A through -E hepatitis,
11 (92%) became SENV positive after transfusion. Extending this early work will
be essential to prove that SENV replicates inside hepatocytes. There are no data to
date showing that SENV is a cause of fulminant liver failure, and its roles in chronic
cryptogenic hepatitis and cirrhosis are uncertain.
6
ERRATA—REVISED TEXT
TREATMENT: The principal goal of treatment is to relieve vaginal symptoms and
signs of infection and decrease the risk of infectious complications. All nonpregnant
patients who are symptomatic require treatment. Nonpregnant patients with symptoms should be treated with metronidazole (1.0 g/day, orally, in 2 divided doses)
for 7 days; or metronidazole gel, 0.75%, 5 g (1 applicator), intravaginally, once a
day for 5 days; or clindamycin cream, 2%, 1 applicator (5 g), intravaginally, at bedtime for 7 days. Alternative regimens that have a lower efficacy for BV are metronidazole, 2 g, orally, in a single dose; clindamycin, 600 mg/day, orally, in 2 divided
doses for 7 days; or clindamycin ovules, 100 mg, intravaginally, once at bedtime for
3 days. Clindamycin cream is oil-based and may weaken latex condoms for up to
72 hours after completion of therapy.
ERRATA—REVISED TEXT
7
TREATMENT: Amphotericin B (see Drugs for Invasive and Other Serious Fungal
Infections, p 725), in combination with oral flucytosine, is indicated for patients
with meningeal and other serious cryptococcal infections. Combination antifungal
therapy with flucytosine probably is superior to amphotericin B alone. Flucytosine
can induce bone marrow suppression, which often necessitates discontinuation of
the medication, especially in HIV-infected patients. Other flucytosine adverse effects
are hepatic and renal dysfunction, rash, diarrhea, ulcerative colitis, and gastrointestinal tract bleeding, especially in patients with azotemia. When flucytosine is
used, serum concentrations should be monitored and maintained between 40 and
60 µg (micrograms)/mL. Patients with meningitis should receive combination
therapy for at least 2 weeks or until CSF culture results are negative; at least
6 weeks of total treatment should be completed with amphotericin B or 10 weeks
if fluconazole alone is used for therapy. Lipid formulations of amphotericin B can
be substituted for conventional amphotericin B in children with renal impairment.
Patients with HIV infection should be treated for longer periods than should
non–HIV-infected patients, as should patients who are immunosuppressed as a
result of organ transplantation. Patients with less severe disease may be treated
with fluconazole or itraconazole, but data on use of these drugs for children with
C neoformans infection are limited. Another potential treatment option for HIVinfected patients with less severe disease is combination therapy with fluconazole
and flucytosine; the toxicity associated with this regimen often limits its usefulness.
8
ERRATA—REVISED TABLE
Table 3.32. Recommended Treatment of Lyme Disease in Children
Disease Category
Drug(s) and Dose1
disease1
Early localized
8 y of age or older
All ages
Doxycycline, 100 mg, orally, twice a day for 14–21 days
Amoxicillin, 25–50 mg/kg per day, orally, divided into
2 doses (maximum 2 g/day) for 14–21 days
Early disseminated and late disease
Multiple erythema migrans
Same oral regimen as for early disease but for 21 days
Isolated facial palsy
Same oral regimen as for early disease but for
21–28 days2,3
Arthritis
Same oral regimen as for early disease but for 28 days
Persistent or recurrent arthritis4 Ceftriaxone sodium, 75–100 mg/kg, IV or IM, once a
day (maximum 2 g/day), for 14–21 days; or
penicillin, 300 000 U/kg per day, IV, given in
divided doses every 4 h (maximum 20 million
U/day) for 14–28 days OR same oral regimen as
for early disease
Carditis
Ceftriaxone or penicillin: see persistent or recurrent
arthritis
Ceftriaxone or penicillin: see persistent or recurrent
Meningitis or encephalitis
arthritis
1
2
3
4
IV indicates intravenously; IM, intramuscularly.
For patients who are allergic to penicillin, cefuroxime axetil and erythromycin are alternative drugs.
Corticosteroids should not be given.
Treatment has no effect on the resolution of facial nerve palsy; its purpose is to prevent late disease.
Arthritis is not considered persistent or recurrent unless objective evidence of synovitis exists at least 2
months after treatment is initiated. Some experts administer a second course of an oral agent before
using an IV-administered antimicrobial agent.
ERRATA—REVISED TEXT
9
TREATMENT:
• Infants younger than 6 months of age and other patients with severe disease
commonly require hospitalization for supportive care to manage apnea,
hypoxia, feeding difficulties, and other complications. Intensive care facilities
may be required.
• Antimicrobial agents given during the catarrhal stage may ameliorate the
disease. After the cough is established, antimicrobial agents may have no
discernible effect on the course of illness but are recommended to limit the
spread of organisms to others. The drug of choice is erythromycin estolate
(40–50 mg/kg per day, orally, in 4 divided doses; maximum 2 g/day). The
recommended duration of therapy to prevent bacteriologic relapse is 14 days.
Studies have documented that the newer macrolides, azithromycin dihydrate
(10–12 mg/kg per day, orally, in 1 dose for 5 days; maximum 500 mg/day)
or clarithromycin (15–20 mg/kg per day, orally, in 2 divided doses; maximum
1 g/day for 7 days), may be as effective as erythromycin and have fewer
adverse effects and better compliance. Resistance to erythromycin (and
other macrolide antimicrobial agents) by B pertussis has been reported rarely.
Penicillins and first- and second-generation cephalosporins are not effective
against B pertussis.
10
ERRATA—REVISED TABLE
Table 3.45. Dosages of Intravenous Antimicrobial Agents for Invasive
Pneumococcal Infections in Infants and Children1
Antimicrobial
Agent
Dose, kg/day
Penicillin G
250 000–
400 000 U2
225–300 mg
100 mg
60 mg
20 mg
75–100 mg
Not indicated
120 mg
…
Cefotaxime
Ceftriaxone
Vancomycin
Rifampin3
Chloramphenicol4
Clindamycin4
Meropenem5
Imipenemcilastatin6
1
2
3
4
5
6
Meningitis
Nonmeningeal Infections
Dose Interval
4–6 h
8h
12–24 h
6h
12 h
6h
…
8h
…
Dose, kg/day
250 000–
400 000 U2
75–100 mg
50–75 mg
40–45 mg
Not indicated
75–100 mg
25–40 mg
60 mg
60 mg
Dose Interval
4–6 h
8h
12–24 h
6h
…
6h
6–8 h
8h
6h
Doses are for children 1 month of age or older.
Because 1 U = 0.6 µg/mL, this range is equal to 150 to 240 mg/kg per day.
Indications for use are not defined completely.
Drug should be considered only for patients with life-threatening allergic response after
administration of β-lactam antimicrobial agents.
Drug is approved for pediatric patients 3 months of age and older.
Drug is not recommended in patients with meningitis because of its potential epileptogenic
properties.
duration of therapy is 10 days, but uncomplicated cases among children older than
2 years of age can be treated for 5 days. On the basis of concentrations in middle
ear fluid and in vitro activity, no currently available oral antimicrobial agent has
better activity than amoxicillin against nonsusceptible S pneumoniae.
For patients with clinically defined treatment failures when assessed after
3 to 5 days of initial therapy, suitable alternative agents should be active against
penicillin-nonsusceptible pneumococci as well as β-lactamase–producing Haemophilus influenzae and Moraxella catarrhalis. Such agents include oral cefdinir, cefuroxime axetil, intramuscular ceftriaxone, and high-dose oral amoxicillin-clavulanate
potassium. Amoxicillin-clavulanate should be given at 80 mg/kg per day of the
amoxicillin component (eg, the 14:1 formulation) to decrease the incidence of diarrhea. Erythromycin-sulfisoxazole acetyl, clarithromycin, and azithromycin dihydrate
are appropriate alternatives for penicillin-allergic patients.
ERRATA—REVISED TEXT
11
result is available and should be performed in a hospital setting.* Oral desensitization
is regarded as safer and easier to perform. Desensitization usually can be completed
in approximately 4 hours, after which the first dose of penicillin can be given.
Congenital Syphilis: Newborn Infants (see Table 3.59, p 602). Infants should
be treated for congenital syphilis if they have proven or probable disease demonstrated by one or more of the following: (1) physical, laboratory, or radiographic
evidence of active disease; (2) positive placenta or umbilical cord test results for
treponemes using DFA-TP staining or darkfield test; (3) a reactive result on VDRL
testing of CSF; or (4) a serum quantitative nontreponemal titer that is at least
fourfold higher than the mother’s titer using the same test and preferably the same
laboratory. If the infant’s titer is less than 4 times higher than that of the mother,
congenital syphilis still can be present. When an infant warrants evaluation for
congenital syphilis (see Evaluation of Newborn Infants for Congenital Infection, p
598), the infant should be treated if test results cannot exclude infection, if the
infant cannot be evaluated fully, or if adequate follow-up cannot be ensured.
12
ERRATA—REVISED TEXT
• Signs or symptoms attributable to syphilis develop
In all these instances, retreatment, when indicated, should be performed
with 3 weekly injections of penicillin G benzathine, 2.4 million U, intramuscularly,
unless CSF examination indicates that neurosyphilis is present, at which time treatment for neurosyphilis should be initiated. Retreated patients should be treated
with the schedules recommended for patients with syphilis for more than 1 year.
In general, only 1 retreatment course is indicated. The possibility of reinfection or
concurrent HIV infection always should be considered when retreating patients
with early syphilis.
ERRATA—REVISED TEXT
13
BCG Vaccine. The BCG vaccine is a live vaccine prepared from attenuated
strains of M bovis. Use of BCG vaccine is recommended by the Expanded
Programme on Immunization of the World Health Organization for administration
at birth (see Table 1.3, p 8) and currently is used in more than 100 countries. Bacille
Calmette-Guérin vaccine is used to prevent disseminated and other life-threatening
manifestations of M tuberculosis infection in infants and young children. However,
BCG immunization does not prevent infection with M tuberculosis. The various
BCG vaccines used throughout the world differ in composition and efficacy.
14
ERRATA—REVISED TEXT
TREATMENT: Many NTM are relatively resistant in vitro to antituberculosis
drugs. In vitro resistance, however, does not necessarily correlate with clinical
response. Only limited controlled trials have been performed in patients with
NTM infections. The approach to therapy should be dictated by the following:
(1) the species causing the infection; (2) the results of drug-susceptibility testing;
(3) the site(s) of infection; (4) the patient’s underlying disease (if any); and (5) the
need to treat a patient presumptively for tuberculosis while awaiting culture reports
that subsequently reveal NTM.
For NTM lymphadenitis in otherwise healthy children, especially when the
disease is caused by MAC, complete surgical excision almost always is curative.
Antituberculosis chemotherapy offers no benefit. Therapy with clarithromycin
combined with ethambutol or rifabutin may be beneficial for children in whom
surgical excision is incomplete or for children with recurrent disease but has not
been studied in a clinical trial (see Table 3.74, p 664).
Isolates of rapidly growing mycobacteria (M fortuitum, M abscessus, and
M chelonae) should be tested in vitro against drugs (such as amikacin sulfate,
imipenem, sulfamethoxazole or trimethoprim-sulfamethoxazole, cefoxitin sodium,
ciprofloxacin, gatifloxacin, clarithromycin, linezolid, and doxycycline), to which
they commonly are susceptible and which have been used with some therapeutic
success. Clarithromycin and at least one other agent commonly is the treatment
of choice for cutaneous (disseminated) infections attributable to M chelonae. Details
about choice of drugs, dosages, and duration should be reviewed with a consultant
experienced in the management of NTM infections.
In patients with AIDS and in other immunocompromised people with disseminated MAC infection, multidrug therapy is recommended. Single-drug therapy with
a macrolide antimicrobial agent commonly results in development of antimicrobial
resistance. Clinical isolates of MAC usually are resistant to many of the approved
antituberculosis drugs, including isoniazid, but often are susceptible to clarithromycin,
azithromycin dihydrate, ethambutol hydrochloride, rifabutin, rifampin, amikacin,
streptomycin, and fluoroquinolones, which are not licensed for use in people
younger than 18 years of age. The optimal regimen has yet to be determined.
Treatment of disseminated MAC infection should be done in consultation with
an expert. In addition, the following treatment guidelines should be considered:
• Susceptibility testing to drugs other than the macrolides is not predictive
of in vivo response and should not be used to guide therapy.
• Unless there is clinical or laboratory evidence of macrolide resistance, treatment regimens should contain clarithromycin or azithromycin combined
with ethambutol.
• Many clinicians have added a third agent (rifampin, rifabutin), and in some
situations, a fourth agent (amikacin or streptomycin).
Table 4.2. Antibacterial Drugs for Pediatric Patients Beyond the Newborn Period, continued
Dosage per kg per Day
Drug, Generic
(Trade Name)
PENICILLINS2
Broad-spectrum
penicillins
Ampicillin
(numerous types)
Route
IV, IM
100–150 mg in 4 doses
(daily adult dose, 2–4 g)
50–100 mg in 4 doses
(daily adult dose, 2–4 g)
100–150 mg of ampicillin
in 4 doses
Severe
Infections
200–400 mg in 4 doses
(daily adult dose, 6–12 g)
Inappropriate
Larger dosage recommended for treatment
of meningitis.
Diarrhea occurs in approximately 20%
of recipients.
Licensed for use in children 1 year of
age and older.
IV
Amoxicillin
(numerous types)
PO
25–50 mg in 3 doses
(daily adult dose,
750 mg–1.5 g)
PO
45 mg of amoxicillin in
2 doses
90 mg of amoxicillin in
2 doses
Inappropriate
…
Inappropriate
2 g, twice a day (total
4000 mg)
100–150 mg in 4 doses
(daily adult dose, 6–8 g)
100–150 mg in 4 doses
(daily adult dose, 6–8 g)
Inappropriate
For multidrug-resistant pneumococcal otitis
media and β-lactamase-positive
H influenzae.
Oral extended-release formulation licensed
for adults.
…
PO
PO
Mezlocillin (Mezlin)
IV, IM
Piperacillin5 (Pipracil)
IV, IM
200–300 mg in 4–6 doses
(daily adult dose, 12–18 g)
200–300 mg in 4–6 doses
daily adult dose, 12–18 g)
Larger dosage (80–90 mg in 2 doses) for
otitis media caused by penicillin-resistant
pneumococci.
…
15
Ampicillin-sulbactam
(Unasyn)
Amoxicillin-clavulanic
acid
(Augmentin,
7:1 ratio)
(Augmentin
ES-600;
14:1 ratio)
(Augmentin XR)
200–400 mg of ampicillin in
4 doses (daily adult dose,
6–12 g)
Inappropriate
Comments
ERRATA—REVISED TABLE
PO
Mild to
Moderate
Infections
Drug (Abbreviation)/
Trade Name
Abacavir (ABC)/Ziagen
Component of Trizivir
Lamivudine (3TC)/Epivir
Component of Combivir,
Trizivir.
Stavudine (d4T)/Zerit
Special Instructions
An abacavir warning card, which lists signs and sympNeonatal: 1 to 3 mo of age: 8 mg/kg, twice daily,
toms of abacavir hypersensitivity, should be provided
is under study.
with each prescription of abacavir.
Pediatric and adolescent: 8 mg/kg, twice daily; maximum dosage 300 mg, twice daily
Adult: 300 mg, twice daily
All formulations except Videx EC contain buffering
Usual pediatric range: 90–120 mg/m2, every 12 h
agents or antacids.
Neonatal (<90 days of age): 100 mg/m2 age 14 days Food decreases absorption; administer ddI on an empty
to 6 wk
stomach (1 h before or 2 h after meal).
Adolescent and adult:
Concomitant therapy with quinolones: ddI should
Weight >60 kg: 200 mg, twice daily
be given 2 h after or 6 h before the quinolone dose.
Weight <60 kg: 125 mg, twice daily
For oral solution: shake well and keep refrigerated;
Videx EC, adolescent and adult:
admixture stable for 30 days.
Weight >60 kg: 400 mg, once daily
Weight <60 kg: 250 mg, once daily
Pediatric: 4 mg/kg, every 12 h
Can be administered with or without food.
Neonatal (<30 days of age): under study in clinical
For oral solution: store at room temperature.
trials: 2 mg/kg, every 12 h
Decrease dosage for patients with impaired renal
Adolescent and adult: 150 mg, twice daily
function.
Pediatric: 1 mg/kg, every 12 h (up to weight of
Can be administered with food.
30 kg)
For oral solution: shake well and keep refrigerated;
Neonatal: birth to 13 days: 0.5 mg/kg, every 12 h,
solution stable for 30 days.
>13 days of age: 1 mg/kg, every 12 h
Adolescent and adult:
Weight >60 kg: 40 mg, twice daily
Weight 30–60 kg: 30 mg, twice daily
ERRATA—REVISED TABLE
Didanosine (ddI)/Videx
Dosage1
16
Table 4.9. Characteristics of Antiretroviral Drugs:
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors
ERRATA—REVISED TEXT
17
Assessment of immunization status
5. Health care professionals review the immunization and health status of patients
at every encounter to determine which vaccines are indicated (see Fig 1.1, p 24).
6. Health care professionals assess for and follow only medically accepted contraindications (see Precautions and Contraindications, p 45).