AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• The Child with Frequent Infections
• Immune-compromising Conditions
• Differential Diagnoses
• Infections
• Evaluation
• Therapeutics For Initial Use
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• The Child with Frequent Infections
• Immune-compromising Conditions
• Differential Diagnoses
• Infections
• Evaluation
• Therapeutics For Initial Use
• References

Much of the practice of pediatric infectious diseases now focuses on the treatment of the fetus, neonate, infant, child, and adolescent who have infections in the context of immunocompromise. Because of the vast scope of this topic, the interested reader is referred to appropriate reviews for exhaustive treatment of specific immunologic and immune-compromising disorders and infections (see Differential Diagnoses). Further information is also available in textbooks of pediatric infectious diseases (some of which are devoted exclusively to this topic) as cited in the bibliography. This review focuses on evaluation of the child with frequent infections (who likely has no immunocompromise), conditions leading to immunocompromise (congenital, acquired, and iatrogenic in broad terms), and the particular infections associated with these conditions.

Most children examined in the office because of frequent infections have a series of benign, self-limited, largely viral infections in the context of parental or familial concern for an underlying immune problem or perception that the child is sickly. The patient often seems to get sick more frequently than siblings and others. However, most children with frequent infections are immunologically healthy.

Careful questioning and evaluation frequently reveals antecedent events or problems that predispose the patient to such concerns (eg, the vulnerable child syndrome). Thorough history taking and physical examination, with a review of laboratory and radiographic results (which generally accompany the patient) almost always help in excluding clinically significant immunologic disorders (see The Child with Frequent Infections). In rare cases, Münchhausen syndrome or Münchhausen syndrome by proxy manifests as frequent or obscure infections (or suspicion of such infections). Secondary, or acquired, immunodeficiency is more common than primary immunodeficiency.

Although the well child with frequent infections is seen in the outpatient office more often than one with immunocompromise, most hospitalized children have some immune-compromising condition.

THE CHILD WITH FREQUENT INFECTIONS

Section 3 of 9  

• Authors and Editors
• Introduction
• The Child with Frequent Infections
• Immune-compromising Conditions
• Differential Diagnoses
• Infections
• Evaluation
• Therapeutics For Initial Use
• References

History

• For the outpatient with frequent infections, a thorough history should be obtained. In particular, the following should be identified:¹
   
  • More than 10 episodes of acute otitis media in a year
  • More than 2 episodes of consolidated pneumonia in a year
  • More than 2 life-threatening infections
  • Infections with unusual pathogens
  • Unusual response to usual pathogens
  • Recurrent autoimmune phenomena
  • Exacerbation of chronic disorders by infections
  • Infections with vaccine pathogens despite adequate vaccination
  • Family history of recurrent infections or immunodeficiency
  • Chronic eczema, diarrhea, or thrush
  • Developmental delay
  • Growth problems
• A complete history should be obtained on all patients, with attention to the following:
• • Travel history
  • Dietary and medication history (including nonprescription medications and supplements)
  • Animal, insect, and tick exposure
  • Other exposures or risk factors

Physical

• For the outpatient with frequent infections, a thorough physical examination should be performed, with particular attention to the following:
• • Plot growth.
  • Evaluate development.
  • Evaluate for dysmorphology.
  • Seek evidence of normal physiology and functioning between episodes of fever.
• Thorough physical examination often provides clues to the presence and etiology of infectious complications of immunocompromise.

IMMUNE-COMPROMISING CONDITIONS

Section 4 of 9  

• Authors and Editors
• Introduction
• The Child with Frequent Infections
• Immune-compromising Conditions
• Differential Diagnoses
• Infections
• Evaluation
• Therapeutics For Initial Use
• References

Congenital conditions

These most commonly affect the fetus and newborn.

• Hemoglobinopathy
• Syndromes
• • Partial albinism with immunodeficiency (Griscelli) syndrome^{2, 3}
  • Hemorrhagic hereditary telangiectasia (Rendu-Osler disease)⁴
  • Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome
  • Kabuki syndrome
  • Partial albinism, immunodeficiency, and progressive white matter disease (PAID) syndrome
  • Autoimmune polyendocrinopathy syndrome type 1
  • Rubinstein-Taybi syndrome⁵
  • Other dysmorphology or immunodeficiency syndromes
• B-cell defects
• • Antibody deficiency with transcobalamin II deficiency
  • Antibody deficiency with normal or high immunoglobulin (Ig) levels
  • Common variable immunodeficiency
  • Hyper-IgE (Job) syndrome (STAT3 mutation)
  • IgG heavy-chain deletion
  • IgG subclass deficiency
  • Kappa-chain deficiency
  • Organic cation transporter 2 deficiency
  • Selective IgA deficiency
  • Selective IgM deficiency
  • Selective antipolysaccharide antibody deficiency
  • Transient hypogammaglobulinemia of infancy or early childhood
  • Thymoma with agammaglobulinemia
  • X-linked (Bruton) agammaglobulinemia
  • X-linked hyper-IgM syndrome
  • X-linked hypogammaglobulinemia with growth hormone deficiency
• Combined B- and T-cell defects
• • Adenosine deaminase deficiency
  • Artemis deficiency
  • Ataxia-telangiectasia syndrome
  • Bare lymphocyte syndrome (major histocompatability complex class I/II deficiency)
  • Interleukin (IL)-2R alpha or gamma deficiency
  • Intestinal lymphangiectasia
  • Janus kinase 3 (JAK3) deficiency
  • Nuclear factor-kappaB essential modifier (NEMO) deficiency
  • Nijmegen breakage syndrome
  • Omenn syndrome
  • Purine nucleoside phosphorylase deficiency
  • Recombination activation gene (RAG) 1 or 2 deficiency
  • Reticular dysgenesis
  • Swiss-type severe combined immunodeficiency
  • T-cell receptor deficiency
  • Wiskott-Aldrich syndrome
  • X-linked lymphoproliferative syndrome
  • X-linked severe combined immunodeficiency
  • Zeta-associated protein of 70 kDa (ZAP-70) tyrosine kinase deficiency
• T-cell defects
• • Biotin-dependent multiple carboxylase deficiency
  • Chronic mucocutaneous candidiasis
  • DiGeorge (velocardiofacial) syndrome
  • Fas defect
  • Nezelof syndrome
  • Short-limbed dwarfism or cartilage-hair hypoplasia
• Macrophage, cytokine, and miscellaneous defects
• • Mendelian susceptibility to mycobacterial diseases (MSMD)
  • • Interferon-gamma deficiency
    • Interferon-gamma receptor I or II deficiency
    • IL-12 deficiency
    • IL-12 receptor deficiency
    • STAT1 mutations
    • NEMO
    • CYBB
  • IL-1 receptor–associated kinase 4 (IRAK4) deficiency
  • Toll-like receptor 5 mutations
  • Apolipoprotein L-I deficiency
  • UNC-93B deficiency
  • Toll-like receptor 3 mutations
  • Plasminogen activator inhibitor-1 4G/4G promoter genotype
  • Anti-interferon-gamma antibodies
  • IL-18 polymorphisms
  • RANTES promoter gene polymorphisms⁶
  • Deficiency of chemokine receptor CCR5^{7, 8}
• Phagocyte deficiency or dysfunction
• • Chediak-Higashi syndrome
  • Chronic granulomatous disease
  • Chronic idiopathic neutropenia
  • Cyclic neutropenia
  • Glycogen storage disease 1b
  • Hyper-IgE syndrome
  • Kostmann syndrome
  • Leukocyte adhesion deficiency (including CD11 or CD18 deficiency)
  • Myeloperoxidase deficiency
  • Neutrophil actin dysfunction
  • Papillon-Lefèvre syndrome
  • Specific granule deficiency
  • Shwachman-Diamond syndrome
• Complement deficiencies
• • Mannose-binding lectin (Mannan-binding protein) deficiency
  • Deficiencies of C1q, C1r, C1rs, C4, C2, C3, or C5-9
  • Deficiencies of factor D, factor P, factor I, factor H, or properdin
• Other conditions
• • Asplenia
  • Ciliary dyskinesia, Kartagener syndrome, and other disorders
  • Galactosemia and other metabolic conditions
  • Lymphedema (congenital)
  • Trisomy 21 and other genetic disorders
  • Other anatomic defects (eg, midline dermal sinus, Mondini defect of the inner ear, fistulae, cysts, duplications, meningeal defects, iron overload, decreased sensation)

Acquired conditions

These conditions may interfere directly with the immune system or may disrupt barrier function.

• Malnutrition
• HIV infection: Although human immunodeficiency virus (HIV) infection is a considerable cause of immunodeficiency worldwide, immunocompromise is most likely to result from common problems, including asthma, diabetes, malnutrition, and cancer, among others.
• Trauma
• • Burns
  • Lacerations and abrasions
• Medical conditions
• • Collagen vascular
  • GI tract
  • Hematologic or oncologic
  • Hepatic
  • Metabolic
  • Pregnancy
  • Pulmonary, particularly asthma and cystic fibrosis (CF)
  • Renal
  • Skin and mucous membrane
  • Viral infections (eg, cytomegalovirus [CMV] infection,⁹ measles)
  • Other anatomic or physiologic problems (eg, fistulae, cysts, obstructions, iron overload, decreased sensation)
• Acquired asplenia
• Acquired lymphedema
• Other conditions that injure or bypass barrier function
• • Parasitic infections
  • Animal and insect bites or scratches

Iatrogenic or self-inflicted conditions

These conditions may interfere directly with the immune system or may disrupt barrier function.

• Use of drugs and/or therapies (eg, radiation therapy), which may interfere with normal flora, decrease gastric acidity and ciliary motility, and be directly immunomodulating
• Trauma
• • Injections (eg, insulin injections, intravenous [IV] drug use, others)
  • Operative and other incisions
  • Vascular, osseous, tracheal, gastric, bladder, joint, peritoneal, wound, or ventricular access or drainage devices
  • Internal foreign bodies
• Treatment
• • For leukemia or lymphoma
  • Bone marrow or stem-cell transplantation
  • Solid organ transplantation
  • Therapy for autoimmune or inflammatory disorders

DIFFERENTIAL DIAGNOSES

Section 5 of 9  

• Authors and Editors
• Introduction
• The Child with Frequent Infections
• Immune-compromising Conditions
• Differential Diagnoses
• Infections
• Evaluation
• Therapeutics For Initial Use
• References

INFECTIONS

Section 6 of 9  

• Authors and Editors
• Introduction
• The Child with Frequent Infections
• Immune-compromising Conditions
• Differential Diagnoses
• Infections
• Evaluation
• Therapeutics For Initial Use
• References

In general, infectious complications can be seen with almost any immune-compromising condition. However, the following discussion includes the infections most frequently associated with the immunocompromising conditions enumerated above, with particular attention to the distinctive infections. Refer to the reviews of the specific infections for further details (see Differential Diagnoses).

• The fetal and neonatal immune systems are immature and the aggressive measures frequently needed to care for young patients predispose them to various infections with the following agents:
• • Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Chlamydia trachomatis, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Ureaplasma urealyticum, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Chryseobacterium meningosepticum, Mycobacterium tuberculosis, viridans streptococci, other gram-negative bacilli, other gram-positive organisms, syphilis, lactobacilli, and anaerobes
  • Herpes simplex virus (HSV), HIV, CMV, and varicella zoster virus (VZV)
  • Candida albicans and other fungi
  • Pneumocystis jiroveci
• Hemoglobinopathies predispose patients to infections that are also seen with congenital or acquired asplenia. Some infectious agents are encapsulated organisms, particularly Streptococcus pneumoniae. Others are Salmonella species, E coli, Haemophilus influenzae, K pneumoniae, Edwardsiella species, and Neisseria species.
• Asplenia (congenital or acquired) predisposes patients to malaria, babesiosis, and infection by encapsulated organisms, including the following: S pneumoniae, H influenzae, E coli, K pneumoniae, Neisseria meningitidis, and Capnocytophaga canimorsus.
• Disorders of ciliary function predispose patients to frequent sinopulmonary infections.
• Galactosemia predisposes patients to infections with E coli.
• Congenital or acquired lymphedema predisposes patients to infections with Streptococcus pyogenes.
• Trisomy 21 and other genetic disorders are linked to otitis media and upper respiratory infections, as well as to infections with Candida organisms.
• Midline dermal sinuses, Mondini defects of the inner ear, and meningeal defects predispose patients to recurrent meningitis.
• Iron overload predisposes patients to Yersinia, Vibrio, and Capnocytophaga infections.
• Decreased sensation can contribute to recurrent skin and soft tissue infections.
• Hemorrhagic hereditary telangiectasia (Rendu-Osler disease) predisposes patients to brain abscess and S aureus extracerebral infections.
• Rubinstein-Taybi syndrome predisposes to recurrent respiratory tract infections, apparently because of deficient polysaccharide antibody responses.
• B-cell defects predispose patients to frequent sinopulmonary and respiratory tract infections and infections with nonenveloped viruses, parvovirus B19, and rotavirus. They are also at risk for infections with S pneumoniae; H influenzae; S aureus; Pseudomonas aeruginosa; M pneumoniae; Giardia lamblia; and Salmonella, Shigella, and Campylobacter species. Specific B-cell defects and their associated pathogens, signs, and symptoms are listed below:
• • Antibody deficiency with transcobalamin II deficiency - S aureus infection, failure to thrive, severe diarrhea
  • Antibody deficiency with normal or high Ig levels - Recurrent sinopulmonary infections, recurrent pneumococcal septicemia
  • Common variable immunodeficiency - Respiratory tract infections; infections with Giardia, Salmonella, or Campylobacter species; infections with Cryptosporidium parvum and P jiroveci; enteroviral infections
  • Hyper-IgE (Job) syndrome (STAT3 mutations) - Recurrent S aureus infections
  • IgG heavy-chain deletion
  • IgG subclass deficiency - S pneumoniae, H influenzae, and other encapsulated bacteria
  • Kappa-chain deficiency
  • Organic cation transporter 2 deficiency - Recurrent respiratory tract infections
  • Selective IgA deficiency - Sinopulmonary and GI infections with bacteria, including Giardia; more common with associated IgG2 subclass deficiency
  • Selective IgM deficiency
  • Selective antipolysaccharide antibody deficiency - Encapsulated organisms, especially pneumococcus
  • Transient hypogammaglobulinemia of infancy/early childhood - Respiratory tract infections
  • Thymoma with agammaglobulinemia - Sinusitis and respiratory tract infections
  • X-linked (Bruton) agammaglobulinemia - Sinopulmonary, pneumococcal, and enteroviral (nonenveloped) infections (especially with echovirus) and S pneumoniae, S aureus, G lamblia, P jiroveci, and rotaviral infections
  • X-linked hyper-IgM syndrome - Oral ulcers, perirectal abscesses, infections with P jiroveci, recurrent abscesses, mycobacterial infections, infections with Cryptococcus and Salmonella species, Entamoeba histolytica infections, infections with Giardia and Cryptosporidium species, and CMV and adenovirus infections
  • X-linked hypogammaglobulinemia with growth hormone deficiency
• Almost any organism can cause infection in combined B- and T-cell defects. Patients often present with failure to thrive, thrush, and/or P jiroveci infection. Other commonly seen pathogens include S pneumoniae, P aeruginosa, Legionella pneumophila, L monocytogenes, Nocardia species, Mycobacterium species, fungi, VZV, HSV, CMV, Epstein-Barr virus (EBV), Toxoplasma species, cryptosporidia, Strongyloides species, and encapsulated bacteria. Types of combined B- and T-cell defects and their associated conditions and pathogens include the following:
• • Adenosine deaminase deficiency
  • Artemis deficiency
  • Ataxia-telangiectasia syndrome - Severe sinopulmonary infections and bronchiectasis
  • Bare lymphocyte syndrome (major histocompatability complex class I/II deficiency) - Overwhelming viral infection
  • IL-2R alpha/gamma deficiency
  • Intestinal lymphangiectasia - Encapsulated organisms
  • JAK3 deficiency
  • NEMO deficiency - Pyogenic bacteria, mycobacteria, herpesviruses
  • Nijmegen breakage syndrome - Recurrent pyogenic infections
  • Omenn syndrome
  • Purine nucleoside phosphorylase deficiency
  • RAG1 or RAG2 deficiency
  • Reticular dysgenesis - Overwhelming gram-negative infection
  • Swiss-type severe combined immunodeficiency
  • T-cell receptor deficiency
  • Wiskott-Aldrich syndrome - S pneumoniae, H influenzae, P jiroveci, Candida species, CMV, HSV, EBV
  • X-linked lymphoproliferative syndrome - EBV
  • X-linked severe combined immunodeficiency
  • ZAP-70 tyrosine kinase deficiency
• T-cell defects predispose to infections with Candida, Mycobacterium avium-intracellulare complex, herpesviruses, and P jiroveci infections. T-cell defects and associated conditions and pathogens are as follows:
• • Biotin-dependent multiple carboxylase deficiency
  • Chronic mucocutaneous candidiasis - Candida organisms
  • DiGeorge (velocardiofacial) syndrome - Recurrent chronic S pneumoniae, Candida species, and P jiroveci, infections; chronic diarrhea; CMV, HSV, and others
  • Fas defect - EBV, mycobacteria
  • Nezelof syndrome - Herpesviruses, mycobacteria
  • Short-limbed dwarfism or cartilage-hair hypoplasia - Enteric viruses
• Macrophage, cytokine, and miscellaneous defects are associated with mycobacterial infections and infections with Salmonella and Listeria species. Defects and associated conditions and pathogens are as follows:
• • Mendelian susceptibility to mycobacterial diseases (MSMD) - BCG and other mycobacterial infections, Salmonella, Histoplasma, Listeria, Legionella, HSV, VZV, respiratory syncytial virus (RSV), human herpesvirus (HHV)-8, CMV
  • • Interferon-gamma deficiency - Some viral infections; Cryptosporidia
    • Interferon-gamma receptor I or II deficiency - Some viral infections and histoplasmosis
    • IL-12 deficiency - Infections with intracellular organisms and paracoccidioidomycosis
    • IL-12 receptor deficiency - Recurrent leishmaniasis; mycobacterial osteomyelitis is typical
    • STAT1 mutations
    • NEMO
    • CYBB
  • IRAK4 deficiency - S aureus, S pneumoniae
  • Toll-like receptor 5 mutations - Legionella organisms
  • Apolipoprotein L-I deficiency - Trypanosoma evansi infection
  • UNC-93B deficiency - HSV encephalitis
  • Toll-like receptor 3 mutations - HSV encephalitis
  • Plasminogen activator inhibitor-1 4G/4G promoter genotype - Delayed healing following otitis media with increased risk for recurrence
  • Anti-interferon-gamma antibodies - Nontuberculous Mycobacteria
  • IL-18 polymorphisms - Severe RSV infection
  • RANTES promoter gene polymorphisms - Severe RSV infection
  • Deficiency of chemokine receptor CCR5 - Severe flaviviral infections, particularly West Nile virus and tick-borne encephalitis virus
• Phagocyte deficiency or dysfunction predisposes patients to infections with S aureus, Nocardia species, P aeruginosa, Serratia species, streptococci, other enteric organisms, and Candida, Burkholderia, Aspergillus, and Chromobacterium species. Immunocompromising conditions and associated pathogens and infections are as follows:
• • Chediak-Higashi syndrome - Infections with S aureus and streptococci, recurrent skin and mucosal infections
  • Chronic granulomatous disease - Primarily catalase-positive organisms, including S aureus, S marcescens, Burkholderia cepacia, Granulibacter bethesdensis, Candida species, Aspergillus species, Nocardia species, Chromobacterium species
  • Chronic idiopathic neutropenia - Helicobacter pylori, CMV
  • Cyclic neutropenia - Gingivostomatitis, perirectal abscesses, fever of unknown origin
  • Glycogen storage disease 1b - Recurrent skin and soft tissue infections
  • Granulocyte colony-stimulating factor receptor mutation
  • Hyper-IgE syndrome - Recurrent staphylococcal furuncles; infections with streptococci or Candida or Aspergillus species
  • Kostmann syndrome - S agalactiae, S aureus, E coli, P aeruginosa, fungi
  • Leukocyte adhesion deficiency (including CD11/CD18 deficiency) - Recurrent necrotic skin and soft-tissue infection, poor wound healing, delayed separation of the umbilicus, omphalitis, gingivitis, periodontal disease, infections with P aeruginosa, S aureus, E coli, B cepacia, Serratia species, Klebsiella species, Candida species, and Aspergillus species
  • Leukocyte glucose-6-phosphate dehydrogenase deficiency - Toxoplasmosis
  • Myeloperoxidase deficiency - Disseminated candidiasis
  • Neutrophil actin dysfunction - Recurrent skin infections with S aureus and Candida infections
  • Papillon-Lefèvre syndrome - Herpesviruses, periodontic infection, pyogenic liver abscess
  • Specific granule deficiency - S aureus, P aeruginosa, streptococci
  • Shwachman-Diamond syndrome - P aeruginosa
• Complement deficiencies and associated conditions and infections are as follows:
• • Mannose-binding lectin (Mannan-binding protein) deficiency - Cryptosporidia or Burkholderia species, meningococcal infections, respiratory viruses
  • Deficiency of C1q, C1r, C1rs, C4, C2, C3, or C5-9 - Recurrent sinopulmonary infections, S pneumoniae, H influenzae, Neisseria species
  • Deficiency of factor D, factor P, factor I, factor H, or properdin - Meningococcal infections
• Malnutrition is a significant immunocompromising condition worldwide. Those affected are less able than others to tolerate infection. Infectious diarrhea, pneumonia, tuberculosis, measles, malaria, salmonellosis, P jiroveci infection, and HIV are common causes of death among malnourished infants and children.
• In immunosuppression due to HIV infection a myriad of infections occur, particularly as immune function deteriorates. Conditions and organisms related to HIV infection are as follows:
• • S pneumoniae, S aureus, M tuberculosis, M avium-intracellulare complex, other mycobacteria, P aeruginosa, Bartonella species, syphilis, Nocardia species, Rhodococcus equi, Tsukamurella species, other gram-positive organisms, other gram-negative organisms, anaerobes
  • Hepatitis C, CMV, VZV, HSV, molluscum contagiosum, human papilloma virus, EBV, measles, JC virus
  • Tinea and infections with Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, Candida species, and Blastomyces dermatitidis
  • Infections with Toxoplasma gondii, P jiroveci, C parvum, Cyclospora cayetanensis, and Isospora belli; amebiasis; scabies; leishmaniasis; microsporidiosis; and other protozoal infections
• Any break in the barrier function of skin and other epithelium predisposes to infection, including wound infections, tetanus, wound botulism, P aeruginosa infection, and infection with staphylococci, streptococci, gram-negative bacilli, and Mycobacterium marinum.
• Medical conditions lead to infectious complications as follows:
• • Collagen vascular complications - S aureus, P aeruginosa, Listeria species, Serratia species, Nocardia species, Candida species, Aspergillus species, Cryptococcus species, Mucor species, P jiroveci, diphtheroids, streptococci, Strongyloides species, CMV, VZV
  • GI tract - Enteric organisms, Leuconostoc species, Pediococcus species
  • Hematologic or oncologic complications
  • • Coagulase-negative staphylococci, viridans streptococci, S aureus, P aeruginosa, S pneumoniae, S pyogenes, Aeromonas species, mycobacteria, other gram-positive and gram-negative organisms
    • Candida, Aspergillus, Mucor, Rhizopus, Fusarium, Pseudoallescheria, Alternaria, Scedosporium, and Trichosporon species
    • CMV, HSV, VZV, or community respiratory viruses
    • P jiroveci, Strongyloides species, Toxoplasma species
  • Hepatic complications - Enteric organisms, enterococci, streptococci, anaerobes, S aureus, P aeruginosa, Vibrio vulnificans, Aeromonas species
  • Metabolic complications - S aureus infection, candidiasis, mucormycosis
  • Pregnancy complications - S agalactiae, Candida species, Listeria species, hepatitis E virus
  • Pulmonary complications
  • • Asthma predisposes patients to invasive pneumococcal infections.
    • CF predisposes to infections with S aureus, H influenzae, P aeruginosa (mucoid in CF), S marcescens, B cepacia, Stenotrophomonas maltophilia, mycobacteria, and fungi.
    • Exposure to cigarette smoke predisposes patients to meningococcal carriage and infection, infection with nontuberculous mycobacteria, and respiratory tract infections.
  • Renal complications - S aureus, S pneumoniae, E coli, enterococci, viridans streptococci
  • Skin and mucous membrane complications - S aureus, S pyogenes, and corynebacteria, among others
• Various infections may complicate animal or insect bites or scratches.
• • Tick- and arthropod-borne infections
  • Pasteurella multocida, C canimorsus, Bartonella species, S aureus, S pyogenes, Eikenella corrodens, gram-negative bacilli, anaerobes, rabies virus
• Drugs that interfere with the normal flora may predispose patients to candidiasis and Clostridium difficile infection, among others.
• Drugs that decrease gastric acidity predispose to infections with Salmonella species and Vibrio cholerae.
• Other treatments and medications may interfere directly with immune function.
• • Neutropenic patients are particularly at risk for infections with bacteria such as E coli, K pneumoniae, Enterobacter species, Citrobacter species, P aeruginosa, S aureus, Clostridium septicum, coagulase-negative staphylococci, streptococci, enterococci, anaerobes, and a variety of yeasts and fungi (especially Candida and Aspergillus).
  • Corticosteroid therapy predisposes patients to infections many organisms, including S aureus, S pneumoniae, Legionella species, Listeria species, P jiroveci, Nocardia species, Strongyloides species, and VZV.
  • Inhibitors of tumor necrosis factor predispose to tuberculosis, atypical mycobacterial infections, and severe falciparum malaria.
• Injections predispose to skin and soft tissue infections. Intravascular infections may follow contaminated IV access. Organisms include P aeruginosa and Gemella species.
• Wound infections may complicate incisions and other breaks in the skin.
• Access or drainage devices predispose patients to infections with coagulase-negative staphylococci, S aureus, viridans streptococci, enteric organisms, Corynebacterium species, Bacillus species, Malassezia furfur, Acinetobacter species, P aeruginosa, Candida species, and mycobacteria.
• Internal foreign bodies predispose to infections with coagulase-negative staphylococci; diphtheroids; corynebacteria; and Leuconostoc, Tsukamurella, and Pediococcus species.
• Leukemia or lymphoma predisposes patients to infections with S aureus, coagulase-negative staphylococci, P aeruginosa, enteric organisms, fungi, S pneumoniae, H influenzae, mycobacteria, and viruses.
• Bone marrow or stem cell transplant predisposes to infections with the following:
• • Aerobic gram-negative rods, coagulase-negative staphylococci, streptococci, S aureus, C difficile
  • Candida, Aspergillus, Fusarium, and Pseudoallescheria species
  • P jiroveci, T gondii
  • Respiratory and enteric viruses, CMV, VZV, HSV, EBV, HHV 6 or 7, parvovirus B19, polyomaviruses, rotavirus
• Solid organ transplant predisposes to infections with the following:
• • P jiroveci, Toxoplasma species (heart or heart-lung transplant)
  • Nocardia, Listeria, mycobacteria, other bacteria (early posttransplant)
  • Respiratory viruses, CMV, VZV, HSV, EBV, BK virus, JC virus
  • Candida (early posttransplantation period)
  • Strongyloides species
• Autoimmune or inflammatory disorders predispose patients to infections with P jiroveci and Candida, Aspergillus, and Mucor species.

EVALUATION

Section 7 of 9  

• Authors and Editors
• Introduction
• The Child with Frequent Infections
• Immune-compromising Conditions
• Differential Diagnoses
• Infections
• Evaluation
• Therapeutics For Initial Use
• References

Laboratory studies at initial presentation

• Obtain a CBC count, chemistry profile, erythrocyte sedimentation rate and/or C-reactive protein, and others, as directed by presentation and underlying condition
• Blood cultures may be needed, depending on the patient's illness. Initial and/or serial cultures might be performed by using samples obtained from peripheral sites and from an access device.
• Routine aerobic and anaerobic, fungal, viral, and mycobacterial stains and cultures of samples of various sources or locations: blood, urine, cerebrospinal fluid (CSF), throat, wound, synovial fluid, pleural fluid, peritoneal fluid, genitourinary tract, conjunctivae, nares, or skin. The patient's presenting infection and underlying immunocompromise dictate the tests and samples needed.
• Order rapid antigen testing, as appropriate. This may include tests for group A streptococci, pneumococci, C difficile, Cryptococcus species, RSV, influenza virus, adenovirus, parainfluenza, human metapneumovirus, and/or rotavirus.

Laboratory studies of immune function

• Evaluation of numbers and function of B cells
• • Ig levels
  • IgG subclass levels
  • Isohemagglutinins
  • Lymphocyte subpopulations (CD19 or CD20)
  • Antibody production after vaccination (eg, diphtheria, meningococcus, pneumococcus, tetanus)
• Evaluation of numbers and function T cells
• • Lymphocyte subpopulations
  • Assessment of delayed-type hypersensitivity reactions
  • Mitogen-stimulation assays
• Evaluation of phagocyte numbers and function
• • Absolute neutrophil count
  • Numbers of CD11a, CD11b, CD11c, CD18 beta receptor
  • Assay for chronic granulomatous disease (formerly nitroblue tetrazolium and Oil red O testing)
• Evaluation of complement status
• • Total hemolytic complement
  • Measurements of specific components as needed

Imaging studies at initial presentation

• Chest radiography may demonstrate infiltrates or other pulmonary disease
• Other radiographic studies should be performed as warranted.

Imaging studies of immune system anatomy and/or function

• Chest radiography or CT of the chest can be used to identify a thymus and/or lymphoid tissue.
• Other imaging studies are indicated by the particular immunocompromising conditions and infectious complications

THERAPEUTICS FOR INITIAL USE

Section 8 of 9  

• Authors and Editors
• Introduction
• The Child with Frequent Infections
• Immune-compromising Conditions
• Differential Diagnoses
• Infections
• Evaluation
• Therapeutics For Initial Use
• References

Empiric Antimicrobials for Common Pathogens in Immunocompromised Children

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• The Child with Frequent Infections
• Immune-compromising Conditions
• Differential Diagnoses
• Infections
• Evaluation
• Therapeutics For Initial Use
• References

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