Recommendations from Centers for Disease Control and Prevention,

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

Bacterial InfectionsBacterial 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

July 20092 www.aidsect.org

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Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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: Serious Recurrent Bacterial Infections: EpidemiologyEpidemiology

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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:Epidemiology Epidemiology (2)(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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:Epidemiology Epidemiology (3)(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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:Clinical ManifestationsClinical 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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:DiagnosisDiagnosis

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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:PreventionPrevention

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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:Prevention Prevention – H influenzaH influenza B 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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:Prevention Prevention – S pneumoniaeS 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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:PreventionPrevention

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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:TreatmentTreatment

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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:Treatment Treatment (2)(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


Serious Recurrent Bacterial Infections:Serious Recurrent Bacterial Infections:Treatment FailureTreatment 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


Bartonellosis: Bartonellosis: EpidemiologyEpidemiology

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


Bartonellosis: Bartonellosis: Epidemiology Epidemiology (2)(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


Bartonellosis: Bartonellosis: Clinical ManifestationsClinical 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


Bartonellosis: Bartonellosis: Clinical Manifestations Clinical Manifestations – Bacillary angiomatosisBacillary 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


Bartonellosis: Bartonellosis: Clinical Manifestations Clinical Manifestations – Bacillary peliosisBacillary 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


Bartonellosis: Bartonellosis: DiagnosisDiagnosis

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


Bartonellosis: Bartonellosis: PreventionPrevention

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


Bartonellosis: Bartonellosis: TreatmentTreatment

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


Bartonellosis: Bartonellosis: Treatment Treatment (2)(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


Bartonellosis: Bartonellosis: Treatment FailureTreatment 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 <200 cells/µL

There are no data for children


Syphilis: Syphilis: EpidemiologyEpidemiology

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


Syphilis: Syphilis: Clinical ManifestationsClinical 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


Syphilis: Syphilis: Clinical Manifestations Clinical Manifestations (2)(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


Syphilis: Syphilis: DiagnosisDiagnosis

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)


Syphilis: Syphilis: Diagnosis Diagnosis (2)(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


Syphilis: Syphilis: Prevention Prevention – Congenital Congenital SyphilisSyphilis

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


Syphilis: Syphilis: Prevention Prevention – Acquired Syphilis 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


Syphilis: Syphilis: Treatment Treatment – Congenital Syphilis 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)


Syphilis: Syphilis: Treatment Treatment – Congenital Syphilis Congenital Syphilis (2)(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


Syphilis: Syphilis: Treatment Treatment – Acquired Syphilis 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)


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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Documents

Recommendations from Centers for Disease Control and Prevention,