INFECTIOUS DISEASE CONSULT
From Masters of Pediatrics 2008 Leadership Conferences, presented by the University of Miami Miller School of
Medicine
Russell W. Steele, MD, Clinical Professor, Department of Pediatrics, Tulane University School of Medicine, Staff
Physician, Ochsner Children’s Health Center, and Division Head, Pediatric Infectious Diseases, Oshsner Health
System, New Orleans, LA
Educational Objectives
| The goal of this program is to improve diagnosis and treatment of infectious diseases and to optimize the use of
vaccines to prevent them. After hearing and assimilating this program, the participant will be better able to:
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 | 1. Recognize the potential for technique-related errors in pediatric blood culture results.
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| 2. Describe the pathogens that most often cause osteomyelitis.
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| 3. Identify risk factors for sexual transmission of Epstein-Barr virus.
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| 4. Interpret current vaccination schedules, anticipate vaccines in development, and appraise safety profiles of
available vaccines.
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| 5. Detect and appropriately treat cases of infant botulism.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, Dr. Steele and the planning
committee reported nothing to disclose.
Acknowledgements
Dr. Steele’s lectures were recorded at the Masters of Pediatrics 2008 Leadership Conferences, held February 20-25,
2008, in Miami Beach, FL, and sponsored by the University of Miami Miller School of Medicine, Department of Pediatrics,
and Department of Dermatology and Cutaneous Surgery. The Audio-Digest Foundation thanks Dr. Steele
and the University of Miami Miller School of Medicine for their cooperation in the production of this program.
| RECENT INFECTIOUS DISEASE PUBLICATIONS THAT HAVE OR SHOULD HAVE CHANGED YOUR
PRACTICE
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| Issues with pediatric blood culture for bacteremia: errors in sample volume or culture bottle —correct volume
of blood depends on child’s age or size; must use pediatric (not adult) culture bottle; study in children’s hospital
showed laboratories did not always perform pediatric blood culture correctly; also, sample volume adequate in
<50% of cases; excess heme (ie, sample too large) prevents organisms from growing; too little sample volume also
prevents detection; use of incorrect bottle (adult vs pediatric) occurred in one-third of cases; even after educational
intervention, improvement marginal (64% of specimens had adequate volume, vs baseline of 46%); consequences
of errors—blood culture positivity rate reduced from 5.2% to less than one-half of that if too little sample volume
used; therefore, improving program could increase positivity rate; positivity rate decreased similarly if incorrect
bottle used; level of bacteremia influences impact of errors—in past, when Haemophilus influenzae type b (Hib) often
caused high-grade bacteremia, 0.2-mL specimen from neonates produced positive culture; however, pneumococcus
(Streptococcus pneumoniae) causes lower-grade bacteremia; study of significant isolates found 40% of
children had <10 organisms/mL of blood; detection depends on obtaining maximum volume possible; Escherichia
coli can cause high-grade bacteremia in neonates, but if level only 0 to 4 organisms/mL, rate of positive blood cultures
only 23% (therefore clinician must draw multiple bottles or use more blood); in study, when sample volumes
from young children <10 mL, only 67% of bacteremia cases detected; in vitro study of 0.5-mL samples containing
<4 spiked organisms/mL showed organisms undetectable
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| Osteomyelitis: most common organisms—study of positive culture rates in joint and bone infections, and polymerase
chain reaction (PCR) results from culture-negative specimens; bone samples obtained by drilling or from
surgical procedure; among culture-positive specimens, Staphylococcus aureus found most often, with Kingella kingae
second most common; 50% of bone and joint infections produced negative culture results (of these, 17% tested
positive for K kingae by PCR, and 5 more tested positive for other organisms); among 27 total septic arthritis cases,
7 patients with osteomyelitis and 5 patients with discitis had K kingae; K kingae now recognized as most common
pathogen in osteoarticular infections because PCR can identify organisms from culture-negative infections; K kingae
sensitive to β-lactam antibiotics
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| Scrofula (formerly tuberculous cervical lymphadenitis): treatment recommendations—previous texts recommended
surgical excision for scrofula caused by nontuberculous (formerly atypical) mycobacteria; now pharmacotherapy
recommended, due to excellent activity of clarithromycin and azithromycin; study in children showed 10%
lower cure rate with 12-wk regimen of clarithromycin plus rifabutin, than with surgical excision (96% cure rate; noncompliance
and in vitro antibiotic resistance ruled out as causes of poorer antibiotic cure rate); antibiotics caused minimal
adverse events (gastrointestinal), and only 4 in 50 discontinuations; surgical complications included facial nerve
branch dysfunction, secondary staphylococcal infections, and hematoma; speaker recommends trying pharmaceutical
management first (especially if multiple nodes involved), then performing surgical excision if antibiotics fail
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| Epstein-Barr virus (EBV) infections: risk factors for infection—2006 study found EBV more common in
women, older students, those with siblings at home, and students from tropical countries; higher incidence of infection
in sexually active students, and incidence correlated with number of sexual partners and nonuse of condoms or
use of oral contraceptives (marker for nonuse of condoms); sexual transmission—75% overall seroconversion rate
(63% in sexually inactive participants, 83% in sexually active individuals); type 1 more prevalent in Europe and
United States, whereas type 2 more prevalent in Africa; no difference between types in association with, eg, Burkitt’s
lymphoma; with EBV type 2, no sex-related risk factors for infection, and infection not correlated with number of
sex partners; study provides first documentation that sexual transmission of EBV similar to transmission of other
herpes group viruses (ie, Kaposi’s sarcoma-associated herpes virus, herpes simplex virus types 1 and 2, cytomegalovirus
[CMV])
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| Methicillin-resistant S aureus (MRSA): 7 in 8 studies of abscesses and/or cellulitis in pediatric literature found no
difference in success of incision and drainage, with or without antibiotics; however, one retrospective study in adults
found overall failure rate 8%, with 8% difference between success rates for treatments with and without antibiotics;
therefore, when using antibiotics, number needed to treat, 12 patients; individual practitioner’s judgment whether this
justifies antibiotic prescription; in analysis, patients receiving ineffective antibiotics (eg, penicillin, erythromycin) included
with no antibiotic group; too few patients in groups to compare antibiotics and their effectiveness (eg, clindamycin
vs trimethoprim-sulfamethoxazole); study quoted often, but not conclusive for use of antibiotics for abscesses
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| Cytomegalovirus: most common congenital infection (1% incidence); study tested infants with hearing loss for genetic
defect (GJB2 mutation) or presence of CMV DNA (by PCR) in preserved umbilical cord; 15% of deaf babies
had CMV, and 25% had GJB2 gene; concluded CMV second leading cause of hearing loss in children; almost half
of CMV-associated deafness detected only after 6 mo, as infection progresses; higher the viral load, greater the
likelihood of hearing loss; speaker’s conclusion that vaccine development better overall option than antiviral therapy
for infants with CMV
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| Lyme disease: controversial guideline from Infectious Disease Society of America (IDSA)—published in 2006; recommended
against prolonged (1-2 mo) therapy with ceftriaxone (Rocephin) for patients in whom initial therapy
failed; some physicians disagreed and sued IDSA because guideline prevents reimbursement; recent paper in Neurology
discusses and supports guideline
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| VACCINES IN 2008 AND BEYOND
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| Challenges in incorporating vaccine schedule recommendations: conjugated meningococcal vaccine
(Menactra)—approved in 2005 for children 11 to 12 yr of age; now recommended for high-risk children ≥2 yr of
age, and use in 7-mo-olds being studied; all children <4 yr of age at high risk; current recommendation to consider
giving Menactra to high-risk children 2 to 10 yr of age; Advisory Committee on Immunization Practices (ACIP)
defines high-risk children as those 1) traveling to developing countries, 2) with complement deficiency, and 3) with
anatomic or functional asplenia [eg, sickle cell disease]); ACIP now considering recommendation of universal vaccination
for as young as 2 yr of age (or younger); rotavirus vaccine (RotaTeq)—safety and efficacy data from hundreds
of thousands of recipients show no association with intussusception; human papillomavirus (HPV) vaccine
(Gardasil)—approved in United States for girls; generating data for boys (approved for boys in Australia); surveillance
ongoing for Guillain-Barré syndrome, but no evidence of association; varicella-zoster virus—Zostavax approved
for adults >60 yr of age; expensive and efficacy poor (protection against postherpetic neuralgia, 39%;
protection against shingles, 51%); ProQuad under development; Pentacel—quadrivalent vaccine similar to Pediarix
but covers Hib instead of hepatitis B virus (HBV); expected availability June 2008; hepatitis A virus (HAV)
vaccine—recommended for all children ≥1 and ≤2 yr of age; recommended, but not always reimbursed, for children
between 6 and 10 yr of age for “catch-up” vaccination; influenza vaccine—this year covers only 50% of
strains causing disease; varicella-zoster virus vaccine (second dose)—adults given single dose as children need
second dose; avian flu vaccine—5 million doses available; efficacy retained if diluted at ratio of 1:10
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| Status of developmental vaccines: Rotarix—trials show increased incidence of pneumonia-related deaths and
convulsions; FDA evaluating; may not come to market in United States; Cervarix—contains new adjuvant; approval
delayed by FDA request for more toxicity data; ProQuad —expected launch in early 2009; VAQTA for
HAV)—pediatric vaccine (expected availability, third quarter 2008); adult vaccine (expected availability, fourth
quarter 2008); Comvax and Pedvax HIB for Hib—expected to launch fourth quarter 2008; Pentacel—due June
2008; Menactra—as mentioned previously, recommendations changed recently but all children <4 yr of age at high
risk
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| Impact of vaccines: meningitis from Hib and polio nearly eradicated (no polio in United States since 1978); pneumococcal
invasive disease and meningococcal disease reduced; for every 1000 African children vaccinated against
measles, 3 lives saved; for every 100 Asian children vaccinated against HBV (3 doses required), 7 lives saved
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| Tracking vaccination status: new Internet tracking system developed in Louisiana after Hurricane Katrina; currently
16 vaccines to track for girls; introduction of 3 vaccines has compelled medical community to schedule routine health
care visit at age 11 to 12 yr to accomodate this requirement; some states require health and vaccination certificate for
middle school; annual (eg, child’s birth month, summer months) health visits recommended for all children to ensure
vaccinations current; if Pentacel used at 12-mo visit in future, speaker recommends use of diphtheria and tetanus toxoids
and acellular pertussis (DTaP), Hib, polio, and HBV vaccines given separately; combination vaccines anticipated
in future
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| Safety: modern vaccines very safe; no life-threatening anaphylactic reactions with any vaccines, including those for
acellular pertussis, HAV, and polio; pertussis—booster recommended for ages 11 to 65 yr (especially parents and
caregivers of young children); disease presents as prolonged cough; in 1940s, vaccine reduced incidence, but waning
immunity caused incidence to increase again in 1980s; antibody studies (against antigens not present in vaccine)
found 25% of patients (range, 12%-52%) with prolonged cough (>3 wk) had pertussis; estimated 3.3 million
cases/yr in United States; now realize immunity not lifelong (infection can occur 6 yr [or >15 yr if wild-type disease]
after immunization or infection); 14-yr study found cases of infection increasing in older people over time;
hypothesized that immunization of children removed organism from circulation, so adults not reexposed and immunity
waned; adults can transmit infection to children; infection in infant <3 mo old may cause death; transmission
from adult family member causes 75% of cases in infants; outbreak in 2006 caused 2 deaths (19-day-old and
5-wk-old infants) infected by breast-feeding mothers; booster emphasized by Centers for Disease Control and Prevention
(CDC) for all adults, especially postpartum women, those visiting emergency departments (DTaP vaccine),
and all health care personnel; chickenpox—disease breakthrough rate, 1% per year after immunization (usually
mild disease [<35 vesicles]); children must receive 2 doses of vaccine; postexposure vaccination can be given up to
96 hr after exposure; HAV—immunization important for young children because disease often asymptomatic, and
outbreaks possibly not detected until adults become symptomatic; incidence higher at young age but not recognized
because infected 1-yr-old may have only low-grade fever, crankiness, or adenopathy; older children diagnosed
more often because of jaundice; most mortality occurs in adults, so important to immunize children to protect
adults; rotavirus—causes decreased quality of life, with problems (eg, diarrhea, dehydration) for children, parents,
and pediatricians, some deaths, and many hospitalizations; 80% of children infected; vaccination difficult to justify
on cost basis, but keeping children healthy and parents at work important benefit; cumbersome vaccination schedule
(first dose before 12 wk of age, last dose before 32 wk), but these recommendations driven by design of studies;
judgment can override schedule in some cases, but insurance may not cover; recently recognized that children of
HIV-positive mothers can receive vaccine; association suspected between RotaShield and intussusception, but study
of 72,000 patients receiving RotaTeq showed safety; HPV vaccine (Gardasil)—expensive; 3 doses needed; covers 2
strains causing cancer and 90% of strains causing genital warts; one case of cervical cancer prevented for every 200
girls immunized; in vitro data show cross-antigenicity with some other HPV strains; vaccine protects against prodrome
to cervical cancer (cervical intraepithelial neoplasia), and covers 4 of approximately 40 HPV strains; efficacy
correlates with humoral response; seroconversion rate almost 100% in unexposed individuals; important to
vaccinate before exposure (vaccination after exposure to single strain gives no protection)
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| Case report: history—4-mo-old infant with suspected sepsis; exposed to river water; pediatrician consulted on use of
ceftazidime plus aminoglycoside to cover Vibrio vulnificus, Pseudomonas, Aeromonas, or Mycobacterium marinum;
examination results—normal complete blood cell count (white cell count 7x109 /L, 60% lymphocytes, no bands, normal
platelets), no fever; infant appeared toxic (poor response to environment, not eating or drinking well), and spinal
fluid clear; 8-day history of constipation; diagnosis of infant botulism; neurologic examination normal, except infant’s
arms and legs hung down when turned face-down; aminoglycoside therapy dangerous because it potentiates neuromuscular
blockade and caused deaths of infants during outbreak in California in 1970s; diagnosing infant botulism—
toxin in stool or blood (can also culture stool); repetitive electromyographic stimulation produces stair stepping; lumbar
puncture needed to rule out Guillain-Barré or polio syndromes; treatment—antitoxin recently developed; provide
supportive care; avoid aminoglycosides; prevention—disinfect toys, wash or peel fruits and vegetables, and avoid
honey; breast-feeding risk factor for infant botulism, but hypothesized that also possibly protective
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Suggested Reading
American Academy of Pediatrics committee on Infectious Diseases: Recommended immunization schedules
for children and adolescents—United States, 2007. Pediatrics 11:207, 2007; Chometon S et al: Specific real-
time polymerase chain reaction places Kingella kingae as the most common cause of osteoarticular infections in young
children. Pediatr Infect Dis J 26:377, 2007; Connell TG et al: How reliable is a negative blood culture result? Volume
of blood submitted for culture in routine practice in a children’s hospital. Pediatrics 119:891, 2007; Dempsey
AF, Freed GL: Human papillomavirus vaccination: expected impacts and unresolved issues. J Pediatr 152:305,
2008; Dennehy PH: Rotavirus vaccines: an overview. Clin Microbiol Rev 21:198, 2008; Halperin JJ et al: Practice
parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology 69:91, 2007; Ogawa H et al: Etiology of severe
sensorineural hearing loss in children: independent impact of congenital cytomegalovirus infection and GJB2 mutations.
J Infect Dis 195:782, 2007; Pagano JS: Is Epstein-Barr virus transmitted sexually? J Infect Dis 195:469, 2007;
Pierce VM, Vazquez M: New combination vaccines: integration into pediatric practice. Pediatr Infect Dis J
26:1149, 2007; Post JN: Immunizations, neonatal jaundice and animal-induced injuries. Curr Opin Pediatr 18:330,
2006; Ruhe JJ et al: Community-onset methicillin-resistant Staphylococcus aureus skin and soft-tissue infections:
impact of antimicrobial therapy on outcome. Clin Infect Dis 44:777, 2007; Tseng-Ong L, Mitchell WG: Infant
botulism: 20 years’ experience at a single institution. J Child Neurol 22:1333, 2007.
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