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become out of date quickly.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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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)
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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
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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
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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
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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)
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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
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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)
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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
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