Transcript Document
Guidelines for Prevention and
Treatment of Opportunistic Infections
among HIV-Infected Children
Bacterial Infections
Recommendations from Centers for Disease Control and Prevention,
the National Institutes of Health, the HIV Medicine Association of
the Infectious Diseases Society of America, the Pediatric Infectious
Diseases Society, and the American Academy of Pediatrics
About This Presentation
These slides were developed using the April 2008
Guidelines. The intended audience is clinicians
involved in the care of patients with HIV.
Users are cautioned that, because of the rapidly
changing field of HIV care, this information could
become out of date quickly. Finally, it is intended that
these slides be used as prepared, without changes
in either content or attribution. Users are asked to
honor this intent. Expert opinion should be sought
for complex treatment regimens.
– AETC NRC
2
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Epidemiology
Most common infection in pre-HAART era
(15/100 child years)
Because of difficulties in obtaining appropriate
diagnostic specimens, bacterial pneumonia is
often a presumptive diagnosis in a child with
fever, pulmonary symptoms, and an abnormal
chest radiogram
Bacteremia more common in HIV-infected
children with pneumonia
3
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Epidemiology (2)
Bacteria isolated include Streptococcus
pneumoniae, Haemophilus influenzae type B,
Staphylococcus aureus, Escherichia coli,
Pseudomonas aeruginosa, nontyphoid
Salmonella
S pneumoniae accounts for >50% of
bacteremia
Incidence of S pneumoniae and H influenzae
may be lower in regions where vaccines are
administered
4
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Epidemiology (3)
Increased risk of Haemophilus influenzae B,
invasive meningococcal disease
Gram-negative bacteremia more common in
children with advanced disease
Case mortality with gram-negative bacteremia
>40%
Central venous catheter increases risk of
bacterial infections
5
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Clinical Manifestations
Clinical presentation dependent on type of
bacterial infection
(eg, bacteremia, sepsis, vasculitis, septic
arthritis, pneumonia, meningitis, sinusitis)
Presentation similar to that of HIV-uninfected
children
Classical signs, symptoms, and laboratory tests
may be missing in many HIV-infected children
6
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Diagnosis
Isolation of pathogenic organism from normally
sterile sites: blood, bone marrow, CSF
Diagnosis of pneumonia by radiograph and
physical findings
Culture of catheter tips
Sputum cultures may be difficult to obtain
Additional studies such as ultrasound should be
considered
Assays for detection of bacterial antigens when
available may be helpful
7
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Prevention
Routine use of conjugated pneumococcal and
Haemophilus influenzae B vaccine (not
routinely available in resource-poor countries)
Avoid raw and undercooked foods, unsterilized
water, unpasteurized milk products
Hand washing and other precautions
Avoid pets
Caution with all foods when traveling
8
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Prevention – H influenza B
Children <5 years of age should be given H
influenza B (Hib) conjugate vaccine
Consider use in children >5 years
Incompletely immunized children should
receive 2 doses >8 weeks apart
Pneumococcal conjugate vaccines (A II)
>5 years: consider Hib conjugate vaccine 2
doses 1-2 months apart
Children 2-59 months should receive the
heptavalent pneumococcal vaccine (PCV) at
2, 4, 6, and 12-15 months
9
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Prevention – S pneumoniae
Previously unimmunized children aged 7-23
months should receive 2-3 doses of PCV
Incompletely immunized children should
receive 2 doses of PCV >8 weeks apart
Children >2 years of age should receive 23
valent PCV (>2 months after last conjugate
vaccine)
Reimmunize with PCV in 3-5 years in children
aged <10 years or after 5 years in children
aged >10 years
10
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Prevention
Trimethoprim sulfamethoxazole (TMP-SMX)
prophylaxis reduces bacterial infection and new
and recurrent episodes of malaria
Atovaquone plus azithromycin provides
prophylaxis for MAC as well as PCP
Discontinue prophylaxis in children on ART with
CD4 percentage >15% with caution
11
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Treatment
Patients with suspected serious bacterial
infections should be treated empirically and
promptly without waiting for laboratory results
Consider local prevalence of resistance of
common infectious agents
Response of mildly immunodeficient children
is similar to that of HIV-uninfected children
12
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Treatment (2)
Treat HIV-infected children outside the neonatal
period with empiric therapy until cultures are
available (A III)
Use extended spectrum cephalosporin such as
ceftriaxone or cefotaxime
Consider addition of azithromycin for hospitalized
patients with pneumonia
Add clindamycin or vancomycin if MRSA is
suspected
13
July 2009
www.aidsect.org
Serious Recurrent Bacterial Infections:
Treatment Failure
Consider bacterial resistance if treatment
failure occurs
Consider nonbacterial cause such as TB,
PCP, meningitis (Cryptococcus or TB)
Look for catheter-related infections
Occult abscess
14
July 2009
www.aidsect.org
Bartonellosis: Epidemiology
Bartonella henselae and Bartonella quintana
are primary species causing bacillary
angiomatosis and peliosis
Bartonella bacteremia also occurs in HIVinfected individuals but is relatively uncommon
in HIV-infected children
Bartonella henselae is associated with cat
scratch disease in the general population
15
July 2009
www.aidsect.org
Bartonellosis: Epidemiology (2)
Household cat is the primary vector
Eradication of flea infestation may be important
in preventing infection, as contamination of cat
claws is a possible mechanism of human
infection
90% of patients with cat scratch disease have a
history of recent contact with cats
The vector for Bartonella quintana is the human
body louse
16
July 2009
www.aidsect.org
Bartonellosis: Clinical Manifestations
Clinical manifestations determined by host
response
Localized disease consisting of suppurative
regional lymphadenopathy is most common in
patients with an intact immune system
Systemic infection is more common among
immunocompromised individuals
17
July 2009
www.aidsect.org
Bartonellosis: Clinical Manifestations –
Bacillary angiomatosis
Rare disorder occurring in severely
immunocompromised individuals
Characterized by cutaneous and subcutaneous
angiomatous papules
Can be confused with Kaposi sarcoma
Nodules may be observed in the subcutaneous
tissue and can erode to the skin
18
July 2009
www.aidsect.org
Bartonellosis: Clinical Manifestations –
Bacillary peliosis
Characterized by angiomatous masses in the
visceral organs
The liver is most frequently infected
Individuals with bacillary peliosis and bacillary
angiomatosis may have relapsing fevers
Dissemination can result in osteomyelitis,
endocarditis, encephalopathy, seizures,
neuroretinitis, and transverse myelitis
Nonspecific symptoms include fever, chills,
night sweats, anorexia, weight loss, abdominal
pain, vomiting, and diarrhea
19
July 2009
www.aidsect.org
Bartonellosis: Diagnosis
Diagnosis usually made by means of a biopsy
with demonstration of small gram-negative
bacilli
Isolated with difficulty from blood and tissue
culture
Indirect fluorescent antibody and enzyme
immunoassay tests are available at some
laboratories
Cross-reactivity among Bartonella species and
other bacteria is common
PCR is the most sensitive means of diagnosis
20
July 2009
www.aidsect.org
Bartonellosis: Prevention
Reduce exposure to cats and cat fleas
Treat infestations of body lice
Consider risk of ownership of cats, especially
for individuals who are severely
immunocompromised
21
July 2009
www.aidsect.org
Bartonellosis: Treatment
Treatment of cat scratch disease in
immunocompetent individuals is mainly
supportive
In vitro and in vivo antibiotic susceptibilities do
not correlate well with efficacy
Drug of choice is erythromycin or doxycycline
Clarithromycin and azithromycin treatment has
been associated with clinical responses
22
July 2009
www.aidsect.org
Bartonellosis: Treatment (2)
Severe disease requires IV administration
Treatment should be given for 3 months for
bacillary angiomatosis and 4 months for
bacillary peliosis central nervous system
disease, osteomyelitis and other severe
systemic infections
Add rifampin to either erythromycin or
doxycycline for severely infected
immunocompromised individuals
23
July 2009
www.aidsect.org
Bartonellosis: Treatment Failure
Immunocompromised individuals who
experience treatment failure should be retreated for 4-6 months
Immunocompromised HIV-infected adults who
experience relapse have been treated with
long-term suppression with doxycycline or a
macrolide when CD4 counts are <200 cells/µL
There are no data for children
24
July 2009
www.aidsect.org
Syphilis: Epidemiology
Perinatal transmission of Treponema pallidum at
any stage of pregnancy or during delivery
Illicit drug use during pregnancy increases risk
of maternal and congenital syphilis
Rate of congenital syphilis 50 times greater
among infants born to HIV-infected mothers
Half of new infections are in women 15-24 years
of age
25
July 2009
www.aidsect.org
Syphilis: Clinical Manifestations
Untreated early syphilis in pregnancy leads to
spontaneous abortion, stillbirth, hydrops,
preterm delivery, death in up to 40% of
pregnancies
47% of infants born to mothers with inadequately
treated syphilis have clinical, radiographic, or
laboratory findings consistent with congenital
syphilis
26
July 2009
www.aidsect.org
Syphilis: Clinical Manifestations (2)
60% of infants with congenital syphilis have
hepatomegaly, jaundice, skin rash, nasal
discharge, anemia, thrombocytopenia, osteitis,
periostitis, osteochondritis, or pseudoparalysis
Late manifestations include mental retardation,
keratitis, deafness, frontal bossing, Hutchinson
teeth, saddle nose, Clutton joints
27
July 2009
www.aidsect.org
Syphilis: Diagnosis
Use combination of physical, radiologic,
serologic, and direct microscopic results, as
standard serologic tests detect only IgG
All infants born to mothers with reactive
nontreponemal and treponemal tests should be
evaluated with a quantitative nontreponemal
test (eg, slide test, RPR, automated reagin test)
28
July 2009
www.aidsect.org
Syphilis: Diagnosis (2)
Darkfield microscopy or direct fluorescent
antibody staining
Presumptive diagnosis – any infant, regardless
of physical findings, born to an untreated or
inadequately treated mother with syphilis
29
July 2009
www.aidsect.org
Syphilis: Prevention – Congenital
Syphilis
Routinely screen all pregnant women with
serologic testing during first prenatal visit
Obtain information regarding the treatment of
sexual partners for sexually transmitted diseases
Serologic testing of mothers serum is preferable
Routine screening of newborns’ serum or
umbilical cord blood is not recommended
30
July 2009
www.aidsect.org
Syphilis: Prevention – Acquired Syphilis
Routine discussion of sexual behaviors that
place individuals at risk of syphilis and HIV
Routine serologic screening for syphilis annually
for all sexually active HIV-infected individuals
The occurrence of syphilis in an HIV infected
individual is an indication of high-risk behavior
Individuals undergoing screening or treatment
for syphilis should be evaluated for all sexually
transmitted diseases
31
July 2009
www.aidsect.org
Syphilis: Treatment – Congenital Syphilis
Treat all infants whose mothers have untreated or
inadequately treated syphilis; not treated or initiated
treatment 4 weeks prior to delivery
Treat if mother treated with penicillin but no 4-fold
decrease in nontreponemal antibody titer, or a 4-fold
increase suggesting relapse or reinfection
Treat infants regardless of maternal history if
examination suggests syphilis; darkfield or fluorescent
antibody test positive or nontreponemal serologic titer =
4-fold higher than maternal level (A II)
32
July 2009
www.aidsect.org
Syphilis: Treatment – Congenital Syphilis (2)
Aqueous crystalline penicillin G: 100,000150,000 units/kg/day given as 50,000
units/kg/dose IV Q12H for 7 days, followed by
Q8H for a total of 10 days (A II)
Diagnosis after 1 month of age, increase
dosage to 50,000 units/kg IV Q6H for 10 days
33
July 2009
www.aidsect.org
Syphilis: Treatment – Acquired Syphilis
Treat acquired syphilis with single dose of benzathine
penicillin G 50,000 units/kg IM
Treat late latent disease with benzathine penicillin G
50,000 units/kg IM once weekly for 3 doses (A III)
Alternative therapies among HIV-infected patients have
not been evaluated
Treat neurosyphilis with aqueous penicillin G 200,000
to 300,000 units/kg IV Q6H for 10-14 days
Follow up with examinations at 1, 2, 3, 6, and 12
months and serologic tests at 3, 6, and 12 months; if
titers continue to be positive or increase, consider
retreatment (A III)
34
July 2009
www.aidsect.org
About This Slide Set
This presentation was prepared by Arthur Ammann,
MD, Clinical Professor of Pediatrics University of
California and President of Global Strategies for HIV
Prevention for the AETC National Resource Center, in
July 2009
See the AETC NRC website for the most current
version of this presentation:
http://www.aidsetc.org
35
July 2009
www.aidsect.org