Guidelines for Prevention and Treatment of Opportunistic Infections among HIV-Infected Children Bacterial Infections

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Guidelines for Prevention and Treatment of
Opportunistic Infections among HIV-Infected
ChildrenBacterial 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

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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could become out of date quickly.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 InfectionsEpidemiolo
gy (2)

• Bacteria isolated include Streptococcus
  pneumoniae, Haemophilus influenzae type B,
  Staphylococcus aureus, Escherichia coli,
  Pseudomonas aeruginosa, nontyphoid Salmonella
• S pneumoniae accounts for gt50 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 InfectionsEpidemiolo
gy (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 gt40
• Central venous catheter increases risk of
  bacterial infections

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Serious Recurrent Bacterial InfectionsClinical
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 InfectionsDiagnosis

• 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 InfectionsPrevention

• 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 InfectionsPrevention
H influenza B

• Children lt5 years of age should be given H
  influenza B (Hib) conjugate vaccine
• Consider use in children gt5 years
• Incompletely immunized children should receive 2
  doses gt8 weeks apart
• Pneumococcal conjugate vaccines (A II)
• gt5 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 InfectionsPrevention
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 gt8 weeks apart
• Children gt2 years of age should receive 23 valent
  PCV (gt2 months after last conjugate vaccine)
• Reimmunize with PCV in 3-5 years in children aged
  lt10 years or after 5 years in children aged gt10
  years

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Serious Recurrent Bacterial InfectionsPrevention

• 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 gt15 with caution

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Serious Recurrent Bacterial InfectionsTreatment

• 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 InfectionsTreatment
(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 InfectionsTreatment
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 HIV-infected
  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 re-treated 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 lt200 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 100,000-150,000
  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