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During the pre-HAART era, serious bacterial infections were the most commonly diagnosed OIs in HIV-infected children, with an event rate of 15 per 100 child-years (1Dankner WM, Lindsey JC, Levin MJ, et al. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J 2001;20:40-8.). Pneumonia was the most common bacterial infection (11 per 100 child-years), followed by bacteremia (3 per 100 child-years), and urinary tract infection (2 per 100 child-years). Other serious bacterial infections, including osteomyelitis, meningitis, abscess, and septic arthritis, occurred at rates <0.2 per 100 child-years. More minor bacterial infections such as otitis media and sinusitis were particularly common (17-85 per 100 child-years) in untreated HIV-infected children (45Mofenson LM, Korelitz J, Pelton S, et al. Sinusitis in children infected with human immunodeficiency virus: clinical characteristics, risk factors, and prophylaxis. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group. Clin Infect Dis 1995;21:1175-81.).

With the advent of HAART, the rate of pneumonia has decreased to 2.2-3.1 per 100 child-years (3Gona P, Van Dyke RB, Williams PL, et al. Incidence of opportunistic and other infections in HIV-infected children in the HAART era. JAMA 2006;296:292-300., 46Nachman S, Gona P, Dankner W, et al. The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis. Pediatrics 2005;115:e488-94.), similar to the rate of 3-4 per 100 child-years in HIV-uninfected children (47Murphy TF HF, Clyde WA, Jr, Collier AM, Denny FW. Pneumonia: an eleven-year study in a pediatric practice. Am J Epidemiol 1981;113: 12-21., 48Jokinen C, Heiskanen L, Juvonen H, et al. Incidence of communityacquired pneumonia in the population of four municipalities in eastern Finland. Am J Epidemiol 1993;137:977-88.). The rate of bacteremia/sepsis during the HAART era also has decreased dramatically to 0.35-0.37 per 100 childyears (3Gona P, Van Dyke RB, Williams PL, et al. Incidence of opportunistic and other infections in HIV-infected children in the HAART era. JAMA 2006;296:292-300., 4Nesheim SR, Kapogiannis BG, Soe MM, et al. Trends in opportunistic infections in the pre- and post-highly active antiretroviral therapy eras among HIV-infected children in the Perinatal AIDS Collaborative Transmission Study, 1986-2004. Pediatrics 2007;120:00 100–9., 46Nachman S, Gona P, Dankner W, et al. The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis. Pediatrics 2005;115:e488-94.), but this rate remains substantially higher than the rate of <0.01 per 100 child-years in HIV-uninfected children (49Zangwill KM, Vadheim CM, Vannier AM, et al. Epidemiology of invasive pneumococcal disease in southern California: implications for the design and conduct of a pneumococcal conjugate vaccine efficacy trial. J Infect Dis 1996;174:752-9., 50CDC. Active bacterial core surveillance of the Emerging Infections Program Network, Streptococcus pneumoniae, 2003. Available at: www. cdc.gov/ncidod/dbmd/abcs. Accessed February 11, 2005.). Sinusitis and otitis rates among HAART-treated children are substantially lower (2.9-3.5 per 100 child-years) but remain higher than rates in children who do not have HIV infection (46Nachman S, Gona P, Dankner W, et al. The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis. Pediatrics 2005;115:e488-94.).

Acute pneumonia, often presumptively diagnosed in children, was associated with increased risk for long-term mortality among HIV-infected children in one study during the pre-HAART era (51Mofenson LM, Yogev R, Korelitz J, et al. Characteristics of acute pneumonia in human immunodeficiency virus-infected children and association with long term mortality risk. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group. Pediatr Infect Dis J 1998;17:872-80. Vol. 58 / RR-11 Recommendations and Reports 101). HIV-infected children with pneumonia are more likely to be bacteremic and to die than are HIV-uninfected children with pneumonia (52Madhi SA, Petersen K, Madhi A, et al. Increased disease burden and antibiotic resistance of bacteria causing severe community-acquired lower respiratory tract infections in human immunodeficiency virus type 1-infected children. Clin Infect Dis 2000;31:170-6.). Chronic lung disease might predispose persons to development of acute pneumonia; in one study, the incidence of acute lower respiratory tract infection in HIV-infected children with chronic lymphoid interstitial pneumonitis was approximately 10-fold higher than in a community-based study of HIV-uninfected children (53Sharland M, Gibb DM, Holland F. Respiratory morbidity from lymphocytic interstitial pneumonitis (LIP) in vertically acquired HIV infection. Arch Dis Child 1997;76:334-6.). Chronically abnormal airways probably are more susceptible to infectious exacerbations (similar to those in children and adults with bronchiectasis or cystic fibrosis) caused by typical respiratory bacteria (Streptococcus pneumoniae,, nontypeable Haemophilus influenzae) and Pseudomonas spp.

S.pneumoniae was the most prominent invasive bacterial pathogen in HIV-infected children both in the United States and worldwide, accounting for >50% of bacterial bloodstream infections in HIV-infected children (1Dankner WM, Lindsey JC, Levin MJ, et al. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J 2001;20:40-8., 4Nesheim SR, Kapogiannis BG, Soe MM, et al. Trends in opportunistic infections in the pre- and post-highly active antiretroviral therapy eras among HIV-infected children in the Perinatal AIDS Collaborative Transmission Study, 1986-2004. Pediatrics 2007;120:00 100–9., 54Intravenous immune globulin for the prevention of bacterial infections in children with symptomatic human immunodeficiency virus infection. The National Institute of Child Health and Human Developments Intravenous Immunoglobulin Study Group. N Engl J Med 1991;325:73-80., 55Spector SA, Gelber RD, McGrath N, et al. A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. Pediatric AIDS Clinical Trials Group. N Engl J Med 1994;331:1181-7., 56Madhi SA, Petersen K, Madhi A, et al. Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children. Pediatr Infect Dis J 2000; 19:1141-7., 57). HIV-infected children have a markedly higher risk for pneumococcal infection than do HIV-uninfected children (58Farley JJ, King JC Jr, Nair P, et al. Invasive pneumococcal disease among infected and uninfected children of mothers with human immunodeficiency virus infection. J Pediatr 1994;124:853-8., 59Andiman WA, Simpson J, Holtkamp C, et al. Invasive pneumococcal infections in children infected with HIV are not associated with splenic dysfunction. AIDS Patient Care STDS 1996;10:336-41.). In the absence of HAART, the incidence of invasive pneumococcal disease was 6.1 per 100 child-years among HIV-infected children through age 7 years (60Mao C, Harper M, McIntosh K, et al. Invasive pneumococcal infections in human immunodeficiency virus-infected children. J Infect Dis 1996;173:870-6.), whereas among children treated with HAART, the rate of invasive pneumococcal disease decreased by about half, to 3.3 per 100 child-years (46Nachman S, Gona P, Dankner W, et al. The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis. Pediatrics 2005;115:e488-94.). This is consistent with the halving of invasive pneumococcal disease rates in HIV-infected adults receiving HAART compared with rates in those not receiving HAART (61Klugman KP, Madhi SA, Feldman C. HIV and pneumococcal disease. Curr Opin Infect Dis 2007;20:11-5.). Among children with invasive pneumococcal infections, study results vary on whether penicillin-resistant pneumococcal strains are more commonly isolated from HIV-infected than HIV-uninfected persons (56Madhi SA, Petersen K, Madhi A, et al. Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children. Pediatr Infect Dis J 2000; 19:1141-7., 60Mao C, Harper M, McIntosh K, et al. Invasive pneumococcal infections in human immunodeficiency virus-infected children. J Infect Dis 1996;173:870-6., 62Crewe-Brown HH, Karstaedt AS, Saunders GL, et al. Streptococcus pneumoniae blood culture isolates from patients with and without human immunodeficiency virus infection: alterations in penicillin susceptibilities and in serogroups or serotypes. Clin Infect Dis 1997; 25:1165-72., 63Klugman KP, Madhi SA, Huebner RE, et al. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med 2003;349:1341-8., 64Frankel RE, Virata M, Hardalo C, et al. Invasive pneumococcal disease: clinical features, serotypes, and antimicrobial resistance patterns in cases involving patients with and without human immunodeficiency virus infection. Clin Infect Dis 1996;23:577-84.). Reports among children without HIV infection have not demonstrated a difference in the case-fatality rate between those with penicillin-susceptible and those with nonsusceptible pneumococcal infections (case-fatality rate was associated with severity of disease and underlying illness) (65Gímez-Barreto D, Calderín-Jaimes E, Rodríguez RS, et al. Clinical outcome of invasive infections in children caused by highly penicillinresistant Streptococcus pneumoniae compared with infections caused by penicillin-susceptible strains. Arch Med Res 2000;31:592-8.). Invasive disease caused by penicillin-nonsusceptible pneumococcus was associated with longer fever and hospitalization but not with greater risk for complications or poorer outcome in a study of HIV-uninfected children (66Rowland KE, Turnidge JD. The impact of penicillin resistance on the outcome of invasive Streptococcus pneumoniae infection in children. Aust N Z J Med 2000;30:441-9.). Since routine use of seven-valent pneumococcal conjugate vaccine (PCV) in 2000, the overall incidence of drug-resistant pneumococcal infections has stabilized or decreased.

H. influenzae type b (Hib) also has been reported to have been more common in HIV-infected children before the availability of Hib vaccine. In a study in South African children who had not received Hib conjugate vaccine, the estimated relative annual rate of overall invasive Hib disease in children aged <1 year was 5.9 times greater among HIV-infected than HIV-uninfected children, and HIV-infected children were at greater risk for bacteremic pneumonia (67Madhi SA, Petersen K, Khoosal M, et al. Reduced effectiveness of Haemophilus influenzae type b conjugate vaccine in children with a high prevalence of human immunodeficiency virus type 1 infection. Pediatr Infect Dis J 2002;21:315-21.). However, Hib is unlikely to occur in HIV-infected children in most U.S. communities, where high rates of Hib vaccination result in very low rates of Hib nasopharyngeal colonization among contacts.

HIV-related immune dysfunction may increase the risk for invasive meningococcal disease in HIV-infected patients, but few cases have been reported (68Nelson CG, Iler MA, Woods CW, et al. Meningococcemia in a patient coinfected with hepatitis C virus and HIV. Emerg Infect Dis 2000;6:646-8., 69Nitta AT, Douglas JM, Arakere G, et al. Disseminated meningococcal infection in HIV-seropositive patients. AIDS 1993;7:87-90., 70Pearson IC, Baker R, Sullivan AK, et al. Meningococcal infection in patients with the human immunodeficiency virus and acquired immunodeficiency syndrome. Int J STD AIDS 2001;12:410-1., 71Kipp W, Kamugisha J, Rehle T. Meningococcal meningitis and HIV infection: results from a case-control study in western Uganda. AIDS 1992;6:1557-8., 70Pearson IC, Baker R, Sullivan AK, et al. Meningococcal infection in patients with the human immunodeficiency virus and acquired immunodeficiency syndrome. Int J STD AIDS 2001;12:410-1., 71Kipp W, Kamugisha J, Rehle T. Meningococcal meningitis and HIV infection: results from a case-control study in western Uganda. AIDS 1992;6:1557-8., 72Stephens DS, Hajjeh RA, Baughman WS, et al. Sporadic meningococcal disease in adults: results of a 5-year population-based study. Ann Intern Med 1995;123:937-40.). In a population-based study of invasive meningococcal disease in Atlanta, Georgia (72Stephens DS, Hajjeh RA, Baughman WS, et al. Sporadic meningococcal disease in adults: results of a 5-year population-based study. Ann Intern Med 1995;123:937-40.), as expected, the annual rate of disease was higher for 18- to 24-year-olds (1.17 per 100,000) than for all adults (0.5 per 100,000), but the estimated annual rate for HIV-infected adults was substantially higher (11.2 per 100,000). Risk for invasive meningococcal disease may be higher in HIV-infected adults. Specific data are not available on risk for meningococcal disease in younger HIV-infected children.

Although the frequency of gram-negative bacteremia is lower than that of gram-positive bacteremia among HIV-infected children, gram-negative bacteremia is more common among children with advanced HIV disease or immunosuppression and among children with central venous catheters. However, in children aged <5 years, gram-negative bacteremia also was observed among children with milder levels of immune suppression. In a study of 680 HIV-infected children in Miami, Florida, through 1997, a total of 72 (10.6%) had 95 episodes of gram-negative bacteremia; the predominant organisms identified in those with gram-negative bacteremia were P. aeruginosa (26%), nontyphoidal Salmonella (15%), Escherichia coli (15%), and H. influenzae (13%) (73Rongkavilit C, Rodriguez ZM, Gímez-Marín O, et al. Gram-negative bacillary bacteremia in human immunodeficiency virus type 1-infected children. Pediatr Infect Dis J 2000;19:122-8.). The relative frequency of the organisms varied over time, with the relative frequency of P. aeruginosa bacteremia increasing from 13% before 1984 to 56% during 1995-1997, and of Salmonella from 7% before 1984 to 22% during 1995-1997. However, H. influenzae was not observed after 1990 (presumably decreasing after incorporation of Hib vaccine into routine childhood vaccinations). The overall case-fatality rate for children with gram-negative bacteremia was 43%. Among Kenyan children with bacteremia, HIV infection increased the risk for nontyphoidal Salmonella and E. coli infections (74Berkley JA, Lowe BS, Mwangi I, et al. Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med 2005;352:39-47.).

The presence of a central venous catheter increases the risk for bacterial infections in HIV-infected children, and the incidence is similar to that for children with cancer. The most commonly isolated pathogens in catheter-associated bacteremia in HIVinfected children are similar to those in HIV-negative children with indwelling catheters, including coagulase-negative staphylococci, S. aureus, enterococci, P. aeruginosa,, gram-negative enteric bacilli, Bacillus cereus, and Candida spp. (57Lichenstein R, King JC Jr, Farley JJ, et al. Bacteremia in febrile human immunodeficiency virus-infected children presenting to ambulatory care settings. Pediatr Infect Dis J 1998;17:381-5.,75Roilides E, Marshall D, Venzon D, et al. Bacterial infections in human immunodeficiency virus type 1-infected children: the impact of central venous catheters and antiretroviral agents. Pediatr Infect Dis J 1991;10:813-9.).

Data conflict about whether infectious morbidity increases in children who have been exposed to but not infected with HIV. In studies in developing countries, uninfected infants of HIV-infected mothers had higher mortality (primarily because of bacterial pneumonia and sepsis) than did those born to uninfected mothers (76Kuhn L, Kasonde P, Sinkala M, et al. Does severity of HIV disease in HIV-infected mothers affect mortality and morbidity among their uninfected infants? Clin Infect Dis 2005;41:1654-61., 77Brahmbhatt H, Kigozi G, Wabwire-Mangen F, et al. Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda. J Acquir Immune Defic Syndr 2006;41:504-8.). Advanced maternal HIV infection was associated with increased risk for infant death (76Kuhn L, Kasonde P, Sinkala M, et al. Does severity of HIV disease in HIV-infected mothers affect mortality and morbidity among their uninfected infants? Clin Infect Dis 2005;41:1654-61., 77Brahmbhatt H, Kigozi G, Wabwire-Mangen F, et al. Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda. J Acquir Immune Defic Syndr 2006;41:504-8.). In a study in Latin America and the Caribbean, 60% of 462 uninfected infants of HIV-infected mothers experienced infectious disease morbidity during the first 6 months of life, with the rate of neonatal infections (particularly sepsis) and respiratory infections higher than rates in comparable community-based studies (78Mussi-Pinhata M, Freimanis L, Yamamoto AY, et al. Infectious disease morbidity among young HIV-1-exposed but uninfected infants in Latin American and Caribbean countries: the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study. Pediatrics 2007;119:e694-704.). Among other factors, infections in uninfected infants were associated with more advanced maternal HIV disease and maternal smoking during pregnancy. However, in a study from the United States, the rate of lower respiratory tract infections in HIV-exposed, uninfected children was within the range reported for healthy children during the first year of life (79Kattan M, Platzker A, Mellins RB, et al. Respiratory diseases in the first year of life in children born to HIV-1-infected women. Pediatr Pulmonol 2001;31:267-76.). In a separate study, the rate of overall morbidity (including but not specific to infections) decreased from 1990 through 1999 in HIV-exposed, uninfected children (80Paul ME, Chantry CJ, Read JS, et al. Morbidity and mortality during the first two years of life among uninfected children born to human immunodeficiency virus type 1-infected women: the women and infants transmission study. Pediatr Infect Dis J 2005;24:46-56.), although rates were not compared with an HIV-unexposed or community-based cohort.

Clinical presentation depends on the particular type of bacterial infection (e.g., bacteremia/sepsis, osteomyelitis/septic arthritis, pneumonia, meningitis, and sinusitis/otitis media) (81Abrams EJ. Opportunistic infections and other clinical manifestations of HIV disease in children. Pediatr Clin North AM 2000;47:79-108.). HIV-infected children with invasive bacterial infections typically have a clinical presentation similar to children without HIV infection, with acute presentation and fever (59Andiman WA, Simpson J, Holtkamp C, et al. Invasive pneumococcal infections in children infected with HIV are not associated with splenic dysfunction. AIDS Patient Care STDS 1996;10:336-41., 60Mao C, Harper M, McIntosh K, et al. Invasive pneumococcal infections in human immunodeficiency virus-infected children. J Infect Dis 1996;173:870-6., 82Gesner M, Desiderio D, Kim M, et al. Streptococcus pneumoniae in human immunodeficiency virus type 1-infected children. Pediatr Infect Dis J 1994;13:697-703.). HIV-infected children might be less likely than children without HIV infection to have leukocytosis (60Mao C, Harper M, McIntosh K, et al. Invasive pneumococcal infections in human immunodeficiency virus-infected children. J Infect Dis 1996;173:870-6.).

The classical signs, symptoms, and laboratory test abnormalities that usually indicate invasive bacterial infection (e.g., fever and elevated white blood cell count) are usually present but might be lacking among HIV-infected children who have reduced immune competence (59Andiman WA, Simpson J, Holtkamp C, et al. Invasive pneumococcal infections in children infected with HIV are not associated with splenic dysfunction. AIDS Patient Care STDS 1996;10:336-41., 81Abrams EJ. Opportunistic infections and other clinical manifestations of HIV disease in children. Pediatr Clin North AM 2000;47:79-108.). One-third of HIV-infected children not receiving HAART who have acute pneumonia have recurrent episodes (51Mofenson LM, Yogev R, Korelitz J, et al. Characteristics of acute pneumonia in human immunodeficiency virus-infected children and association with long term mortality risk. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group. Pediatr Infect Dis J 1998;17:872-80. Vol. 58 / RR-11 Recommendations and Reports 101). Resulting lung damage before initiation of HAART can lead to continued recurrent pulmonary infections, even in the presence of effective HAART.

In studies in Malawian and South African children with acute bacterial meningitis, the clinical presentations of children with and without HIV infection were similar (83Molyneux EM, Tembo M, Kayira K, et al. The effect of HIV infection on paediatric bacterial meningitis in Blantyre, Malawi. Arch Dis Child 2003;88:1112-8., 84Madhi SA, Madhi A, Petersen K, et al. Impact of human immunodeficiency virus type 1 infection on the epidemiology and outcome of bacterial meningitis in South African children. Int J Infect Dis 2001;5:119-25.). However, in the Malawi study, HIV-infected children were 6.4-fold more likely to have repeated episodes of meningitis than were children without HIV infection, although the study did not differentiate recrudescence from new infections (83Molyneux EM, Tembo M, Kayira K, et al. The effect of HIV infection on paediatric bacterial meningitis in Blantyre, Malawi. Arch Dis Child 2003;88:1112-8.). In both studies, HIV-infected children were more likely to die from meningitis than were children without HIV infection.

Attempted isolation of a pathogenic organism from normally sterile sites (e.g., blood, cerebrospinal fluid [CSF], and pleural fluid) is strongly recommended. This is particularly important because of an increasing incidence of antimicrobial resistance, including penicillin-resistant S. pneumoniae and communityacquired methicillin-resistant S. aureus (MRSA).

Because of difficulties obtaining appropriate specimens (e.g., sputum) from young children, bacterial pneumonia is most often a presumptive diagnosis in a child with fever, pulmonary symptoms, and an abnormal chest radiograph unless an accompanying bacteremia exists. In the absence of a laboratory isolate, differentiating viral from bacterial pneumonia using clinical criteria can be difficult (85McIntosh K. Community-acquired pneumonia in children. N Engl J Med 2002;346:429-37.). In a study of intravenous immune globulin (IVIG) prophylaxis of bacterial infections, only a bacterial pathogen was identified in 12% of acute presumed bacterial pneumonia episodes (51Mofenson LM, Yogev R, Korelitz J, et al. Characteristics of acute pneumonia in human immunodeficiency virus-infected children and association with long term mortality risk. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group. Pediatr Infect Dis J 1998;17:872-80. Vol. 58 / RR-11 Recommendations and Reports 101). TB and PCP must always be considered in HIV-infected children with pneumonia. Presence of wheezing makes acute bacterial pneumonia less likely than other causes, such as viral pathogens, asthma exacerbation, "atypical" bacterial pathogens such as Mycoplasma pneumoniae, or aspiration. Sputum induction obtained by nebulization with hypertonic (5%) saline was evaluated for diagnosis of pneumonia in 210 South African infants and children (median age: 6 months), 66% of whom had HIV infection (86Zar HJ, Tannenbaum E, Hanslo D, et al. Sputum induction as a diagnostic tool for community-acquired pneumonia in infants and young children from a high HIV prevalence area. Pediatr Pulmonol 2003;36:58-62.). The procedure was well-tolerated, and identified an etiology in 63% of children with pneumonia (identification of bacteria in 101, M. tuberculosis in 19, and PCP in 12 children). Blood and, if present, fluid from pleural effusion should be cultured.

Among children with bacteremia, a source for the bacteremia should be sought. In addition to routine chest radiographs, other diagnostic radiologic evaluations (e.g., abdomen, ultrasound studies) might be necessary among HIV-infected children with compromised immune systems to identify less apparent foci of infection (e.g., bronchiectasis, internal organ abscesses) (87Selwyn PA, Pumerantz AS, Durante A, et al. Clinical predictors of Pneumocystis carinii pneumonia, bacterial pneumonia and tuberculosis in HIV-infected patients. AIDS 1998;12:885-93., 88Sheikh S, Madiraju K, Steiner P, et al. Bronchiectasis in pediatric AIDS. Chest 1997;112:1202-7., 89Midulla F, Strappini P, Sandstrom T, et al. Cellular and noncellular components of bronchoalveolar lavage fluid in HIV-1-infected children with radiological evidence of interstitial lung damage. Pediatr Pulmonol 2001;31:205-13.). Among children with central venous catheters, both a peripheral and catheter blood culture should be obtained; if the catheter is removed, the catheter tip should be sent for culture. Assays for detection of bacterial antigens or evidence by molecular biology techniques are important for the diagnostic evaluation of HIV-infected children in whom unusual pathogens might be involved or difficult to identify or culture by standard techniques. For example, Bordetella pertussis and Chlamydia pneumoniae can be identified by a polymerase chain reaction (PCR) assay of nasopharyngeal secretions (85McIntosh K. Community-acquired pneumonia in children. N Engl J Med 2002;346:429-37.).

HIV-infected children aged ≤5 years should receive the Hib conjugate vaccine (AII) (Figure 1). Clinicians and other health-care providers should consider use of Hib vaccine among HIV-infected children >5 years old who have not previously received Hib vaccine (AIII) (30CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006;55(No. RR-15)., 34CDC. Haemophilus b conjugate vaccines for prevention of Haemophilus influenzae type b disease among infants and children two months of age and older. Recommendations of the immunization practices advisory committee (ACIP). MMWR 1991;40(No. RR-1).). For these older children, the American Academy of Pediatrics recommends two doses of any conjugate Hib vaccine, administered at least 1-2 months apart (AIII) (90American Academy of Pediatrics. Red book: 2006 report of the Committee on Infectious Diseases. 27th ed. Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Elk Grove Village, IL;2006.).

HIV-infected children aged 2-59 months should receive the seven-valent PCV (AII). A four-dose series of PCV is recommended for routine administration to infants at ages 2, 4, 6, and 12-15 months; two or three doses are recommended for previously unvaccinated infants and children aged 7-23 months depending on age at first vaccination (36CDC. Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2000;49(No. RR-9).). Incompletely vaccinated children aged 24-59 months should receive two doses of PCV ≥8 weeks apart. Children who previously received three PCV doses need only one additional dose. Additionally, children aged >2 years should receive the 23-valent pneumococcal polysaccharide vaccine (PPSV) (≥2 months after their last PCV dose), with a single revaccination with PPSV 5 years later (CIII) (36CDC. Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2000;49(No. RR-9).) (see http://www.cdc.gov/vaccines/recs/ provisional/downloads/pneumo-Oct-2008-508.pdf for the most updated recommendations). Data are limited regarding efficacy of PCV for children aged ≥5 years and for adults who are at high risk for pneumococcal infection. Administering PCV to older children with high-risk conditions (including HIV-infected children) is not contraindicated. (Figures 1 and 2). One study reported that five-valent PCV is immunogenic among HIV-infected children aged 2-9 years (91CDC. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46(No. RR-8). Available at http://www.cdc.gov/mmwr/pdf/rr/ rr4608.pdf. Accessed June 13, 2009.). A multicenter study of pneumococcal vaccination in a group of HIV-infected children not administered PCV during infancy demonstrated the safety and immunogenicity of two doses of PCV followed by one dose of PPSV for HAART-treated HIVinfected children aged 2-19 years (including some who had previously received PPSV) (92Abzug MJ, Pelton SI, Song LY, et al. Immunogenicity, safety, and predictors of response after a pneumococcal conjugate and pneumococcal polysaccharide vaccine series in human immunodeficiency virusinfected children receiving highly active antiretroviral therapy. Pediatr Infect Dis J 2006;25:920-9.). In a placebo-controlled trial of a nine-valent PCV among South African children, although vaccine efficacy was somewhat lower among children with than without HIV infection (65% versus 85%, respectively), the incidence of invasive pneumococcal disease was substantially lower among HIV-infected vaccine recipients (63Klugman KP, Madhi SA, Huebner RE, et al. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med 2003;349:1341-8.).

HIV-infected children probably are at increased risk for meningococcal disease, although not to the extent they are for invasive S. pneumoniae infection. Although the efficacy of conjugated meningococcal vaccine (MCV) and meningococcal polysaccharide vaccine (MPSV) among HIV-infected patients is unknown, HIV infection is not a contraindication to receiving these vaccines (30CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006;55(No. RR-15).). MCV is currently recommended for all children at age 11 or 12 years or at age 13-18 years if not previously vaccinated and for previously unvaccinated college freshmen living in a dormitory (44CDC. Revised recommendations of the Advisory Committee on Immunization Practices to vaccinate all persons aged 11-18 years with men ingococcal conjugate vaccine.MMWR 2007;56:794-5.). A multicenter safety and immunogenicity trial of MCV in HIV-infected 11- to 24-year-olds is under way. In addition, children at high risk for meningococcal disease because of other conditions (e.g., terminal complement deficiencies, anatomic or functional asplenia) should receive MCV if aged 2-10 years (BIII) (41CDC. Notice to readers: Recommendation from the Advisory Committee on Immunization Practices (ACIP) for use of quadrivalent meningococcal conjugate vaccine (MCV4) in children aged 2-10 years at increased risk for invasive meningococcal disease. MMWR 2007:56:1265-6.). Although the efficacy of MCV among HIV-infected children is unknown, because patients with HIV probably are at increased risk for meningococcal disease, HIV-infected children who do not fit into the above groups may elect to be vaccinated. Revaccination with MCV is indicated for children who had been vaccinated ≥5 years previously with MPSV (CIII).

Because influenza increases the risk for secondary bacterial respiratory infections (93Madhi SA, Ramasamy N, Bessellar TG, et al. Lower respiratory tract infections associated with influenza A and B viruses in an area with a high prevalence of pediatric human immunodeficiency type 1 infection. Pediatr Infect Dis J 2002;21:291-7.), following guidelines for annual influenza vaccination for influenza prevention can be expected to reduce the risk for serious bacterial infections in HIV-infected children (BIII) (Figures 1 and 2) (35CDC. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR 2008;57(No. RR-7).).

To prevent serious bacterial infections among HIV-infected children who have hypogammaglobulinemia (IgG <400 mg/dL), clinicians should use IVIG (AI). During the pre-HAART era, IVIG was effective in preventing serious bacterial infections in symptomatic HIV-infected children (54Intravenous immune globulin for the prevention of bacterial infections in children with symptomatic human immunodeficiency virus infection. The National Institute of Child Health and Human Developments Intravenous Immunoglobulin Study Group. N Engl J Med 1991;325:73-80.), but this effect was most clearly demonstrated only in those not receiving prophylaxis (55Spector SA, Gelber RD, McGrath N, et al. A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. Pediatric AIDS Clinical Trials Group. N Engl J Med 1994;331:1181-7.). Thus, IVIG is no longer recommended for primary prevention of serious bacterial infections in HIV-infected children unless hypogammaglobulinemia is present or functional antibody deficiency is demonstrated by either poor specific antibody titers or recurrent bacterial infections (CII).

TMP-SMX administered daily for PCP prophylaxis is effective in reducing the rate of serious bacterial infections (predominantly respiratory) in HIV-infected children who do not have access to HAART (AII) (55Spector SA, Gelber RD, McGrath N, et al. A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. Pediatric AIDS Clinical Trials Group. N Engl J Med 1994;331:1181-7., 94Mulenga V, Ford D, Walker AS, et al. Effect of cotrimoxazole on causes of death, hospital admissions and antibiotic use in HIV-infected children. AIDS 2007;21:77-84.) . Atovaquone combined with azithromycin, which provides prophylaxis for MAC as well as PCP, has been shown in HIV-infected children to be as effective as TMP-SMX in preventing serious bacterial infections and is similarly tolerated (95Hughes WT, Dankner WM, Yogev R, et al. Comparison of atovaquone and azithromycin with trimethoprim-sulfamethoxazole for the prevention of serious bacterial infections in children with HIV infection. Clin Infect Dis 2005;40:136-45.). However, indiscriminate use of antibiotics (when not indicated for PCP or MAC prophylaxis or other specific reasons) might promote development of drug-resistant organisms. Thus, antibiotic prophylaxis is not recommended solely for primary prevention of serious bacterial infections (DIII).

In developing countries, where endemic deficiency of vitamin A and zinc is common, supplementation with vitamin A and zinc conferred additional protection against bacterial diarrhea and/or pneumonia in HIV-infected children (96Bobat R, Coovadia H, Stephen C, et al. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial. Lancet 2005;366:1862-7., 97Irlam JH, Visser ME, Rollins N, et al. Micronutrient supplementation in children and adults with HIV infection. Cochrane Database Syst Rev 2005;Oct 19(4):CD003650.). However, in the United States, although attention to good nutrition including standard daily multivitamins is an important component of care for HIV-infected children, additional vitamin supplementation above the recommended daily amounts is not recommended (DIII).

A clinical trial, PACTG 1008, demonstrated that discontinuation of MAC and/or PCP antibiotic prophylaxis in HIV-infected children who achieved immune reconstitution (CD4 >15%) while receiving ART did not result in excessive rates of serious bacterial infections (46Nachman S, Gona P, Dankner W, et al. The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis. Pediatrics 2005;115:e488-94.).

The response to appropriate antibiotic therapy should be similar in HIV-infected and HIV-uninfected children, with a clinical response usually observed within 2-3 days after initiation of appropriate antibiotics; radiologic improvement in patients with pneumonia may lag behind clinical response. Fatal hemolytic reaction to ceftriaxone has been reported in an HIV-infected child with prior ceftriaxone treatment (102Moallem HJ, Garratty G, Wakeham M, et al. Ceftriaxone-related fatal hemolysis in an adolescent with perinatally acquired human immunodeficiency virus infection. J Pediatr 1998;133:279-81.). Whereas HIV-infected adults experience high rates of adverse and even treatment-limiting reactions to TMP-SMX, in HIV-infected children, serious adverse reactions to TMP-SMX appear to be much less of a problem (103Chintu C, Bhat GJ, Walker AS, et al. Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial. Lancet 2004;364:1865-71.).IRIS has not been described in association with treatment of bacterial infections in children.

As noted earlier, PACTG 1008, demonstrated that discontinuation of MAC and/or PCP antibiotic phylaxis in HIV-infected children who achieved immune reconstitution (CD4 >15%) while receiving antiretroviral therapy did not result in excessive rates of serious bacterial infections (46Nachman S, Gona P, Dankner W, et al. The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis. Pediatrics 2005;115:e488-94.).