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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 Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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