Remington and Klein's Infectious Diseases of the Fetus and Newborn Infant

cover.pdf (p.1) a Front Matter.pdf (p.2) Remington and Klein’s Infectious Diseasesof the Fetus and Newborn Infant b Copyright.pdf (p.3) Copyright c Dedication.pdf (p.4) Dedication d Contributors.pdf (p.5-9) Contributors e Preface.pdf (p.10-11) Preface 1. Current Concepts of Infections of the Fetus and Newborn Infant.pdf (p.12-32) 1 - Current Concepts of Infections of the Fetus and Newborn Infant Overview Infections of the Fetus Pathogenesis Microbial Invasion of the Maternal Bloodstream .After reaching the intervillous spaces on the maternal side of the placenta, organisms can remain localized in the placenta wit... .Microorganisms may traverse the chorionic villi directly through pinocytosis, placental leaks, or diapedesis of infected matern... .Invasion of the bloodstream by microorganisms is common in pregnant women, yet in most cases, neither fetal nor placental infec... .Microorganisms disseminate from the infected placenta to the fetal bloodstream through infected emboli of necrotic chorionic ti... Infection of the Embryo and Fetus .Various organisms may infect the pregnant woman in the first few weeks of gestation and cause death and resorption of the embry... .The earliest recognizable effects of fetal infection are seen after 6 to 8 weeks of pregnancy and include abortion and stillbir... .Prematurity is defined as the birth of a viable infant before week 37 of gestation. Premature birth may result from almost any ... .Infection of the fetus may result in birth of an infant who is small for gestational age. Although many maternal infections are... .CMV, rubella virus, and VZV cause developmental anomalies in the human fetus. Coxsackieviruses B3 and B4 have been associated w... .Clinical evidence of intrauterine infections, resulting from tissue damage or secondary physiologic changes caused by the invad... .Most newborn infants infected in utero by rubella virus, T. gondii, CMV, HIV, or Treponema pallidum have no signs of congenital... .Microbial agents may continue to survive and replicate in tissues for months or years after in utero infection. Rubella virus a... Efficiency of Transmission of Microorganisms from Mother to Fetus Diagnosis of Infection in the Pregnant Woman Clinical Diagnosis .In many instances, infection in the pregnant woman and congenital infection in the newborn infant can be suspected on the basis... .Many infectious diseases with serious consequences for the fetus are difficult or impossible to diagnose in the mother solely o... .Some microorganisms can infect a susceptible person more than once, and when such reinfections occur in a pregnant woman, the o... .The occurrence of acute infection immediately before conception may result in infection of the fetus, and the association may g... Isolation and Identification of Infectious Agents .Diagnostic tests for microorganisms or infectious diseases are part of routine obstetric care; special care is warranted for se... .Isolation of CMV and rubella virus97 and demonstration of HBsAg98 from amniotic fluid obtained by amniocentesis have been repor... .Histologic review of cytologic preparations and tissue sections is no longer used as the primary method of diagnosing maternal ... .The serologic diagnosis of infection in the pregnant woman most often requires demonstration of elevated antibody titer against... .Routine skin tests for diagnosis of tuberculosis should be considered a part of prenatal care. Tuberculin skin tests can be adm... Universal Screening Diagnosis of Infection in the Newborn Infant Prevention and Management of Infection in the Pregnant Woman Prevention of Infection Infections Acquired by the Newborn Infant During Birth Pathogenesis Microbiology Diagnosis Management Prevention Immunoprophylaxis Chemoprophylaxis Infections of the Newborn Infant in the First Month of Life Pathogenesis and Microbiology Congenital Infections Infections Acquired During Delivery Nursery-Acquired Infections Community-Acquired Infections Infections That Indicate Underlying Abnormalities References 2. Neonatal Infections A Global Perspective.pdf (p.33-62) 2 - Neonatal Infections: A Global Perspective Global Burden of Neonatal Infections Infection as A Cause of Neonatal Death Incidence of Neonatal Sepsis, Bacteremia, and Meningitis and Associated Mortality Bacterial Pathogens Associated with Infections in Different Geographic Regions Incidence of Group B Streptococcal Colonization and Infection Antimicrobial Resistance in Neonatal Pathogens Nosocomial Infections Hospital Infection Control Selected Neonatal Infections Acute Respiratory Infections/Pneumonia Diarrhea Omphalitis Tetanus Ophthalmia Neonatorum Human Immunodeficiency Virus (HIV) Infection Transmission: Reducing the Disparity Between Low- and High-Income Countries Breastfeeding and Human Immunodeficiency Virus Prevention of Human Immunodeficiency Virus Infection in Low- and Middle-Income Countries Prevention of Transmission From an Infected Mother to Her Infant .The era of antiretroviral therapy (ART) to reduce vertical transmission of HIV started in 1994 with publication of the Pediatri... .Meta-analyses of North American and European studies performed in the late 1990s found that elective cesarean section reduced t... Integrated Health Care Programs Human Immunodeficiency Virus and Child Survival Tuberculosis Malaria Malaria in Pregnancy Perinatal Outcome Congenital Malaria Prevention and Treatment of Malaria in Pregnancy Prophylaxis and Treatment Using Antimalarial Drugs Prevention Using Insecticide-Treated Nets Malaria Control Strategies and Challenges Indirect Causes of Neonatal Death Related to Infection Strategies to Prevent and Treat Infection in the Neonate Maternal Immunization to Prevent Neonatal Disease Neonatal Immunization Antenatal Care and Prevention of Neonatal Infection Intrapartum and Delivery Care and Prevention of Neonatal Infection Postnatal Care and Prevention of Neonatal Infection Breastfeeding Management of Neonatal Infection Identification of Neonates with Infection Antibiotic Treatment of Neonates with Infection Integrated Management of Neonatal Illness Maternal Education and Socioeconomic Status Conclusion Acknowledgment References 3. Obstetric Factors Associated with Infections of the Fetus and Newborn Infant.pdf (p.63-89) 3 - Obstetric Factors Associated with Infections of the Fetus and Newborn Infant Overview Infection as a Cause of Preterm Birth Pathogenesis Histologic Chorioamnionitis Animal Models Microbiology Diagnosis of Intraamniotic Infection Amniotic Fluid Testing Proteomics Treatment of Intraamniotic Infection Antenatal Antibiotics to Prevent Intraamniotic Infection Prevention of Postpartum Endometritis After Intraamniotic Infection Diagnosis Antibiotic Choice Timing of Antibiotic Therapy Delivery as Therapy Neonatal Outcomes Fetal Lung Injury Fetal Brain Injury Magnesium Sulfate for Neuroprotection Premature Rupture of Membranes Natural History of Premature Rupture of the Membranes and Preterm Premature Rupture of the Membranes Biomechanical Strength of the Chorioamnion Pathogenesis Infection and Inflammation, Matrix Metalloproteinase Activation, and Oxidative Stress Abruption (Placental Bleeding) and Thrombin Genetic Predisposition Diagnosis Management of Premature Rupture of the Membranes and Preterm Premature Rupture of the Membranes Preterm Premature Rupture of the Membranes Before Fetal Viability Preterm Premature Rupture of the Membranes Between 24 and 34 Weeks Antenatal Corticosteroids and Tocolytics Determination of Fetal Lung Maturity Antenatal Surveillance Preterm Premature Rupture of the Membranes Between 34 to 37 Weeks Premature Rupture of the Membranes After 37 Weeks Maternal and Neonatal Outcomes Maternal Outcomes Neonatal Outcomes Conclusion References 4. Developmental Immunology and Role of Host Defenses in Fetal and Neonatal Susceptibility to Infec.pdf (p.90-197) 4 - Developmental Immunology and Role of Host Defenses in Fetal and Neonatal Susceptibility to Infection Epithelial Barriers Antimicrobial Peptides and Proteins Skin The Gastrointestinal Tract The Respiratory Tract Summary Complement and Other Humoral Mediators of Innate Immunity Collectins, Pentraxins, and Ficolins Complement Classical and Mannose-Binding Lectin Pathways Alternative Pathway Terminal Components, Membrane Attack Complex, and Biologic Consequences of Complement Activation Complement in the Fetus and Neonate Summary Phagocytes Hematopoiesis Phagocyte Production by the Bone Marrow Innate Immune Pattern Recognition Receptors Used by Leukocytes Toll-like Receptors Nucleotide-Binding Domain– and Leucine-Rich Repeat–Containing Receptors (NLRs) Retinoic Acid–Inducible Gene-I–Like Receptors C-Type Lectin Receptors Cytoplasmic DNA Receptors Decoding the Nature of the Threat Through Combinatorial Receptor Engagement Neutrophils Production Migration to Sites of Infection or Injury Migration of Neonatal Neutrophils Phagocytosis Killing Activation by Innate Immune Receptors Neutrophil Clearance and Resolution of Neutrophilic Inflammation Effects of Immunomodulators Eosinophils Mononuclear Phagocytes Production and Differentiation of Monocytes and Resident Tissue Macrophages Migration to Sites of Infection and Delayed Hypersensitivity Responses Antimicrobial Properties of Monocytes and Macrophages .Monocytes from human neonates and adults ingest and kill S. aureus, E. coli, and GBS with similar efficiency.207-211 Consistent... Mononuclear Phagocytes Produce Cytokines and Other Mediators That Regulate Inflammation and Immunity Cytokine Production, Toll-like Receptors, and Regulation of Innate Immunity and Inflammation by Neonatal Monocytes and Macrophag... .Levy and colleagues240,261 identified adenosine as a factor in cord blood plasma that inhibited TNF-α production but preserved ... Resolution of Mononuclear Phagocytic Inflammation SUMMARY Dendritic Cells: the Link between Innate and Adaptive Immunity OVERVIEW Conventional Dendritic Cells Neonatal Conventional Dendritic Cells Plasmacytoid Dendritic Cells Neonatal Plasmacytoid Dendritic Cells Langerhans Cells Inflammatory and Monocyte-Derived Dendritic Cells Summary Natural Killer Cells and Innate Lymphoid Cells Natural Killer Cells Overview and Development Natural Killer Cell Receptors Natural Killer Cell Cytotoxicity Natural Killer Cell Cytokine Responsiveness and Dependence Natural Killer Cell Cytokine and Chemokine Production Natural Killer Cells of the Maternal Decidua and Human Leukocyte Antigen G Natural Killer–Cell Numbers and Surface Phenotype in the Fetus and Neonate Fetal and Neonatal Natural Killer Cell–Mediated Cytotoxicity and Cytokine Production Innate Lymphoid Cells Summary T Cells and Antigen Presentation Overview Antigen Presentation by Classic Major Histocompatibility Complex Molecules Major Histocompatibility Complex Class Ia Major Histocompatibility Complex Class II Major Histocompatibility Complex Molecule Expression and Antigen Presentation in the Fetus and Neonate Nonclassic Antigen-Presentation Molecules Human Leukocyte Antigen E Human Leukocyte Antigen G Major Histocompatibility Class I–Related Chains A and B CD1 Prothymocytes and Early Thymocyte Differentiation Thymic Ontogeny Intrathymic Generation of T-Cell Receptor Diversity Overview Fetal and Neonatal T-Cell Receptor Repertoire T-Cell Receptor Excision Circles Thymocyte Selection and Late Maturation Positive and Negative Selection Thymocyte Growth and Differentiation Factors Thymocyte Postselection Maturation NaÏve T Cells CD4 and CD8 Recent Thymic Emigrants Naïve T-Cell Entry into Lymphoid Tissue, Recirculation, and Survival Ontogeny of NaÏve T-Cell Surface Phenotype CD31 CD38 CD45 Isoforms Homeostatic Proliferation Spontaneous Naïve Peripheral T-Cell Proliferation Antigen-Independent Naïve T-Cell Proliferation in Response to IL-7 and IL-15 NaÏve T-Cell Activation, Anergy, and Co-stimulation Neonatal T-Cell Activation, Co-Stimulation, and Anergy Differentiation of Activated NaÏve T Cells into Effector and Memory Cells Effector CD4 T-Cell Subsets Are Defined by Their Patterns of Cytokine Production Regulation of CD4 Effector T-Cell Subset Differentiation CD4 T-Cell Help for Antibody Production Overview of Memory T Cells Memory T-Cell Activation Postnatal Ontogeny of Memory CD4 T-Cell Subsets Production of Cytokines, Chemokines, and Tumor Necrosis Factor–Ligand Proteins by Neonatal T Cells CD4 T-Cell Cytokine Production CD8 T-Cell Cytokine and Chemokine Production Postnatal Ontogeny of Cytokine Production CD40 Ligand Other Tumor Necrosis Factor Family Ligands Mechanisms for Decreased Cytokine, Chemokine, and TNF Ligand Production by Neonatal T Cells Cytokine Production by Neonatal T Cells after Short-Term In Vitro Differentiation Cytokine Production After Long-Term In Vitro Generation of Effector CD4 T Cells T Cell–Mediated Cytotoxicity Effector T-Cell Migration Termination of the T-Cell Effector Response Regulation of T-Cell Expansion by Apoptosis Unique Phenotype and Function of the Fetal T-Cell Compartment Fetal Extrathymic T-Cell Differentiation Regulatory T Cells Overview Fetal and Neonatal Tregs Natural Killer and Mucosal-Associated Invariant T Cells Overview of Natural Killer T Cells NKT Cells of the Fetus and Neonate Mucosal-Associated Invariant T Cells Gamma-Delta T Cells Phenotype and Function Ontogeny of Gamma-Delta T-Cell Production and T-Cell Receptor Gene Rearrangements Ontogeny of Gamma-Delta T-Cell Function Antigen-Specific T-Cell Function in the Fetus and Neonate Delayed Cutaneous Hypersensitivity, Graft Rejection, and Graft-versus-Host Disease T-Cell Reactivity to Environmental Antigens Fetal T-Cell Sensitization to Maternally Administered Vaccines and Maternally Derived Antigens Maternal Transfer of T-Cell Immunity to the Fetus T-Cell Response to Congenital Infection CD4 T Cells CD8 T Cells Gamma-Delta T Cells T-Cell Response to Postnatal Infections and Vaccination in Early Infancy CD4 T-Cell Responses to Postnatal Infection CD4 T-Cell Responses to Postnatal Immunization with Inactivated Vaccines CD4 T-Cell Responses to Postnatal Immunization with Live-Attenuated Vaccines CD8 T Cells Summary B Cells and Immunoglobulin Overview Early B-Cell Development and Immunoglobulin Repertoire Formation Pro–B-Cell and Pre–B-Cell Maturation V(D)J Recombination of the Immunoglobulin Gene Loci V(D)J Segment Usage in the Fetus and Neonate CDR3 Length and Terminal Deoxytransferase B-Cell Maturation, PreImmune Selection, and Activation Receptor Editing, Clonal Deletion, and Clonal Anergy New Emigrant (Transitional) versus Fully-Mature Naïve B Cells Follicular B-Cell Maturation Fetal and Neonatal B-Cell Frequency and Surface Phenotype B-Cell Activation and Immune Selection Negative Regulation of B-Cell Signaling CD4 T-Cell Help for Naïve B-Cell Activation B-Cell Selection in Germinal Centers of the Follicle Somatic Hypermutation Memory B Cells B Cells as Antigen-Presenting Cells Switching of Immunoglobulin Isotype and Class and Antibody Production Isotype Switching Generation of Plasma Cells and the Molecular Basis for Immunoglobulin Secretion Isotype Switching and Immunoglobulin Production by Fetal and Neonatal B Cells The Marginal Zone and Marginal Zone B Cells Marginal Zone B Cells of the Fetus and Neonate B-1 Cells and Natural Immunoglobulin M Regulatory B Cells T-CELL–Dependent and T-CELL–Independent Responses by B Cells Overview Response to T-Cell Dependent Antigens Response to T-Cell–Independent Antigens Specific Antibody Response by the Fetus to Maternal Immunization and Congenital Infection Response to Fetal Immunization in Animal Models Response to Maternal Immunization Response to Intrauterine Infection PostNatal Specific Antibody Responses Specific Antibody Responses by the Neonate and Young Infant to Protein Antigens Specific Antibody Responses by the Term Neonate to Polysaccharide and Polysaccharide-Protein Conjugates Antibody Responses by the Premature Infant to Immunization Maternally Derived Immunoglobulin G Antibody Placental Transfer of Specific Antibodies .Maternal antibody also may inhibit the production by the fetus or newborn of antibodies of the same specificity. This inhibition... Immunoglobulin Synthesis by the Fetus and Neonate Immunoglobulin G Immunoglobulin M Immunoglobulin A Immunoglobulin D Immunoglobulin E Summary Immunologic Approaches to Prevent or Treat Fetal and Neonatal Infections Overview U.S. Food and Drug Administration–approved Uses of Passive Immunization in the Mother and Newborn Infant Exploratory Evaluation of Passive Immunization for Other Indications Prevention or Treatment of Neonatal Sepsis with Intravenous Immunoglobulin Cytomegalovirus Hyperimmune Intravenous Immunoglobulin Neutrophil Transfusions Colony-Stimulating Factors References 5. Human Milk.pdf (p.198-222) 5 - Human Milk Developmental Anatomy of the Mammary Gland Anatomy and Development Postnatal Development Physiology of Lactation Endocrine Control of Mammary Gland Function Initiation and Maintenance of Lactation Milk Secretion Lactation Performance Components of Human Milk and Their Potential Benefits for the Breastfed Infant Proteins, Peptides, and Nonprotein Nitrogen Nutritional Proteins Bioactive Proteins and Peptides .A number of nutrients are supplied to the neonate bound to proteins found in human milk. This binding may play an important rol... .The activity of several dozen enzymes has been detected in human milk.44 Most of these enzymes appear to originate from the blo... .Human milk contains several growth factors with potential effects on the intestine, vasculature, nervous system, and endocrine ... .As observed in other peripheral mucosal sites, the major class of immunoglobulin in human colostrum and milk is the 11S secreto... .In the 1990s, several cytokines, chemokines, and growth factors that mediate the effector phases of natural and specific immunit... Protein-Derived Peptides Nonprotein Nitrogen Lipids Carbohydrates Lactose Oligosaccharides Vitamins Vitamin D Vitamin E Vitamin K Vitamin B Minerals Cells Leukocytes Epithelial Cells Stem Cells Bacteria Benefits and Risks of Human Milk Benefits Gastrointestinal Homeostasis Prevention of Diarrhea Necrotizing Enterocolitis Neonatal Sepsis Prevention of Atopy and Allergy Special Considerations for the Premature Neonate Other Benefits Noninfectious Risks Infectious Risks Bacterial Infections Viral Infections .Cytomegalovirus infection is a common perinatal infection. The virus is shed in the milk in about 25% of infected mothers. Alth... .Hepatitis B surface antigen (HBsAg) has been detected in milk of HBV-infected mothers. Nevertheless, breastfeeding does not inc... .The RNA of HCV and antibody to HCV have been detected in the milk from infected mothers. Transmission by means of breastfeeding... .Herpes simplex virus transmission directly from maternal breast lesions to their infants has been demonstrated. Women with lesi... .A number of studies have demonstrated HIV in milk.317-321 The findings include isolation of HIV from milk supernatants collected... .Human T-lymphotropic virus type 1 is endemic in Japan, the Caribbean, and parts of South America. This infection can be transmi... .Rubella virus has been recovered from milk after natural as well as vaccine-associated infection. It has not been associated wi... .The RNA of West Nile virus has been detected in human milk, and seroconversion in breastfeeding infants also has been observed.... Current Trends in Breastfeeding Summary and Conclusions References 6. Bacterial Sepsis and Meningitis.pdf (p.223-277) 6 - Bacterial Sepsis and Meningitis Bacteriology Group B Streptococci Group A Streptococci Streptococcus Pneumoniae Other Streptococci Enterococcus Species Staphylococcus Aureus and Coagulase-Negative Staphylococci Listeria Monocytogenes Escherichia Coli Klebsiella Species Enterobacter and Cronobacter Species Citrobacter Species Serratia Marcescens Pseudomonas Aeruginosa Salmonella Species Neisseria Meningitidis Haemophilus Influenzae Anaerobic Bacteria Neonatal Tetanus Mixed Infections Uncommon Bacterial Pathogens Epidemiology Incidence of Sepsis and Meningitis Characteristics of Infants who Develop Sepsis Birth Weight Risk Factors of Infant and Mother Ethnicity Gender Geographic Factors Socioeconomic Factors Procedures Nursery Outbreaks or Epidemics Pathogenesis Host Factors Predisposing to Neonatal Bacterial Sepsis Infection in Twins The Umbilical Cord as a focus of Infection Administration of Drugs to the Mother Before Delivery Administration of Drugs other than Antibiotics to the Neonate Pathology Clinical Manifestations Fever and Hypothermia Respiratory Distress Jaundice Organomegaly Gastrointestinal Signs Skin Lesions Neurologic Signs Diagnosis Maternal History Microbiologic Techniques Culture of Blood .Technology has evolved from manually read, broth-based methods to continuously monitored, automated blood-culture systems that ... .Bacterial growth is evident in most cultures of blood from neonates within 48 hours.495-497 With use of conventional culture te... .The optimal number of cultures to obtain for the diagnosis of bacteremia in the newborn remains uncertain. A single blood cultu... .The optimal volume of blood needed to detect bacteremia in neonates has not been determined. Neal and colleagues500 evaluated t... Buffy-Coat Examination Culture of Urine Cultures of Tracheal Aspirates and Pharynx Diagnostic Needle Aspiration and Tissue Biopsy Autopsy Microbiology Rapid Techniques for Detection of Bacterial Antigens in Body Fluid Specimens Lumbar Puncture and Examination of Cerebrospinal Fluid .Lumbar puncture is more difficult to perform in the neonate than in the older child or adult; traumatic LPs resulting in blood i... .Is it sufficient to culture only blood and urine for the diagnosis of neonatal bacterial meningitis Visser and Hall561 demonstra... .The cell content and chemistry of the CSF of healthy newborn infants differ from those of older infants, children, and adults (... .A traumatic LP can result in blood in the CSF and can complicate the interpretation of the results for CSF white blood cell cou... .Brain abscess is a rare entity in the neonate, usually complicating meningitis caused by certain gram-negative bacilli. The CSF... Laboratory Aids Management Choice of Antimicrobial Agents Initial Therapy for Presumed Sepsis Role of Third-Generation Cephalosporins and Carbapenems Current Practice Continuation of Therapy when Results of Cultures are Available Management of the Infant whose Mother Received Intrapartum Antimicrobial Agents Treatment of the Infant whose Bacterial Culture Results are Negative Management of the Infant with Catheter-Associated Infection Treatment of Neonatal Meningitis Management of the Infant with a Brain Abscess Treatment of the Infant with Meningitis whose Bacterial Culture Results are Negative Treatment of Anaerobic Infections Adjunctive Therapies for Treatment of Neonatal Sepsis Prognosis Prevention Obstetric Factors Chemoprophylaxis Maternal Factors Immunoprophylaxis Decontamination of Fomites Epidemiologic Surveillance Endemic Infection Epidemic Infection Sepsis in the Newborn Recently Discharged From the Hospital Congenital Infection Late-Onset Disease Infections in the Household Fever in the First Month of Life Acknowledgment References 7. Bacterial Infections of the Respiratory Tract.pdf (p.278-296) 7 - Bacterial Infections of the Respiratory Tract Infections of the Oral Cavity and Nasopharynx Pharyngitis, Retropharyngeal Cellulitis, and Retropharyngeal Abscess Noma Epiglottitis Laryngitis Infection of the Paranasal Sinuses Diphtheria Pertussis Otitis Media Pathogenesis and Pathology Epidemiology Microbiology Diagnosis Treatment Prognosis Mastoiditis Pneumonia Pathogenesis and Pathology Congenital or Intrauterine Pneumonia Pneumonia Acquired During the Birth Process and in the First Month of Life Microbiology Epidemiology Incidence Race and Socioeconomic Status Epidemic Disease Developing Countries Clinical Manifestations Diagnosis Clinical Diagnosis Radiologic Diagnosis Microbiologic Diagnosis Histologic and Cytologic Diagnosis Immunologic Diagnosis Differential Diagnosis Management Prognosis References 8. Bacterial Infections of the Bones and Joints.pdf (p.297-312) 8 - Bacterial Infections of the Bones and Joints Osteomyelitis Microbiology Pathogenesis Clinical Manifestations Prognosis Diagnosis Differential Diagnosis Therapy Primary Septic Arthritis Osteomyelitis of the Maxilla References 9. Bacterial Infections of the Urinary Tract.pdf (p.313-324) 9 - Bacterial Infections of the Urinary Tract Epidemiology Microbiology Pathogenesis Anatomic and Physiologic Abnormalities Bacterial Virulence Pathology Clinical Manifestations Diagnosis Culture of Urine Culture of Blood and Cerebrospinal Fluid Examination of Urine Sediment Examination of Blood Chemical Determinations Imaging of the Urinary Tract Management and Prevention Prognosis References 10. Focal Bacterial Infections.pdf (p.325-355) 10 - Focal Bacterial Infections Infections of the Liver Microbiology Pathogenesis Clinical Manifestations Diagnosis Prognosis Treatment Splenic Abscess Infections of the Biliary Tract Infections of the Adrenal Glands Appendicitis Microbiology Pathogenesis Clinical Manifestations Diagnosis Prognosis Treatment Peritonitis Microbiology Pathogenesis Clinical Manifestations Diagnosis Prognosis Treatment Necrotizing Enterocolitis Pathology and Pathogenesis Microbiology Clinical Manifestations Diagnosis Treatment Prevention Prognosis Endocarditis Pericarditis Mediastinitis Esophagitis Infections of Endocrine Organs Infections of the Salivary Glands Infections of the Skin and Subcutaneous Tissue Pathogenesis Microbiology Epidemiology Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prevention Conjunctivitis and Other Eye Infections References 11. Microorganisms Responsible for Neonatal Diarrhea.pdf (p.356-416) 11 - Microorganisms Responsible for Neonatal Diarrhea Enteric Host Defense Mechanisms Protective Factors in Human Milk Bacterial Pathogens Enterotoxigenic Escherichia coli .Although early work on the recognition of E. coli as a potential enteric pathogen focused on biochemical or serologic distincti... .The two types of enterotoxins produced by enterotoxigenic E. coli146-148 have been found to be plasmid-encoded but genetically ... .ETEC are important diarrheal pathogens among infants in developing countries, predominantly affecting children younger than 2 y... .The clinical manifestations of ETEC diarrhea tend to be mild and self-limited except in small or undernourished infants, in who... .As in cholera, the pathologic changes associated with ETEC infection are minimal. From animal experiments in which intestinal l... .The preliminary diagnosis of ETEC diarrhea can be suspected by the epidemiologic setting and the noninflammatory nature of stoo... .The cornerstone of treatment for any diarrheal infection is rehydration.199 This principle especially pertains to ETEC diarrhea... Enteroinvasive Escherichia coli .Entero­invasive E. coli is similar genetically, pathogenetically, epidemiologically, and clinically to shigellosis, although th... .Little is known about the epidemiology and transmission of this organism in newborns and infants; it is more frequently found i... .Symptoms often include watery diarrhea, although a dysentery-like syndrome with an inflammatory exudate in stool, invasion and ... .Enteroinvasive E. coli should be suspected in infants who have an inflammatory diarrhea, as evidenced by fecal neutrophils or b... .The management and prevention of EIEC diarrhea should be similar to that of acute Shigella or other E. coli enteric infections.... Enteropathogenic Escherichia coli .Based on the molecular identification of two virulence factors, EPEC is now classified as either typical, usually associated wi... .Bacterial cultures of the meconium and feces of newborns indicate that EPEC can effectively colonize the intestinal tract in th... .The principal pathologic lesion in EPEC infection is the A/E lesion, manifest by electron microscopy but not light microscopy. ... .The incubation period after EPEC exposure is quite variable. Its duration has been calculated mostly from evidence in outbreaks... .In 1987, the WHO came to a consensus that O serogroups of E. coli should be classified as EPEC: O26, O55, O86, O111, O114 O119,... .The mortality rate recorded previously in epidemics of typical EPEC gastroenteritis is impressive for its variability. During t... .The management of EPEC gastroenteritis should be directed primarily toward prevention or correction of problems caused by loss ... .The transmission for EPEC is fecal-oral. Therefore strict adherence to infection control and appropriate hygiene can help preve... Enterohemorrhagic Escherichia coli Enteroaggregative Escherichia coli .The mode of transmission of EAEC is not well established. In adult volunteer studies, the infectious dose is high (>108 CFU), s... .Descriptions from outbreaks and volunteer studies suggest that EAEC diarrhea is most often watery, with mucus and accompanied b... .Diagnosis of EAEC requires identification of the organism in the patient’s feces. The HEp-2 adherence assay can be used for thi... Other Escherichia coli Pathotypes Salmonella Nature of the Organism Epidemiology and Transmission Clinical Manifestations Diagnosis Therapy Prevention Shigella Nature of the Organism Epidemiology Clinical Manifestations Diagnosis Therapy Prevention Campylobacter Virulence Factors and Pathogenic Mechanisms Epidemiology and Transmission Clinical Manifestations Pathology Diagnosis Therapy and Prevention Clostridium Difficile Virulence Factors and Pathogenic Mechanisms Epidemiology Clinical Manifestations Diagnosis Therapy Prevention Vibrio Cholerae Nature of the Organism Virulence Factors and Pathogenic Mechanisms Epidemiology and Transmission Clinical Manifestations Diagnosis Therapy and Preventio cover.pdf (p.1) a Front Matter.pdf (p.2) Remington and Klein’s Infectious Diseasesof the Fetus and Newborn Infant b Copyright.pdf (p.3) Copyright c Dedication.pdf (p.4) Dedication d Contributors.pdf (p.5-9) Contributors e Preface.pdf (p.10-11) Preface 1. Current Concepts of Infections of the Fetus and Newborn Infant.pdf (p.12-32) 1 - Current Concepts of Infections of the Fetus and Newborn Infant Overview Infections of the Fetus Pathogenesis Microbial Invasion of the Maternal Bloodstream .After reaching the intervillous spaces on the maternal side of the placenta, organisms can remain localized in the placenta wit... .Microorganisms may traverse the chorionic villi directly through pinocytosis, placental leaks, or diapedesis of infected matern... .Invasion of the bloodstream by microorganisms is common in pregnant women, yet in most cases, neither fetal nor placental infec... .Microorganisms disseminate from the infected placenta to the fetal bloodstream through infected emboli of necrotic chorionic ti... Infection of the Embryo and Fetus .Various organisms may infect the pregnant woman in the first few weeks of gestation and cause death and resorption of the embry... .The earliest recognizable effects of fetal infection are seen after 6 to 8 weeks of pregnancy and include abortion and stillbir... .Prematurity is defined as the birth of a viable infant before week 37 of gestation. Premature birth may result from almost any ... .Infection of the fetus may result in birth of an infant who is small for gestational age. Although many maternal infections are... .CMV, rubella virus, and VZV cause developmental anomalies in the human fetus. Coxsackieviruses B3 and B4 have been associated w... .Clinical evidence of intrauterine infections, resulting from tissue damage or secondary physiologic changes caused by the invad... .Most newborn infants infected in utero by rubella virus, T. gondii, CMV, HIV, or Treponema pallidum have no signs of congenital... .Microbial agents may continue to survive and replicate in tissues for months or years after in utero infection. Rubella virus a... Efficiency of Transmission of Microorganisms from Mother to Fetus Diagnosis of Infection in the Pregnant Woman Clinical Diagnosis .In many instances, infection in the pregnant woman and congenital infection in the newborn infant can be suspected on the basis... .Many infectious diseases with serious consequences for the fetus are difficult or impossible to diagnose in the mother solely o... .Some microorganisms can infect a susceptible person more than once, and when such reinfections occur in a pregnant woman, the o... .The occurrence of acute infection immediately before conception may result in infection of the fetus, and the association may g... Isolation and Identification of Infectious Agents .Diagnostic tests for microorganisms or infectious diseases are part of routine obstetric care; special care is warranted for se... .Isolation of CMV and rubella virus97 and demonstration of HBsAg98 from amniotic fluid obtained by amniocentesis have been repor... .Histologic review of cytologic preparations and tissue sections is no longer used as the primary method of diagnosing maternal ... .The serologic diagnosis of infection in the pregnant woman most often requires demonstration of elevated antibody titer against... .Routine skin tests for diagnosis of tuberculosis should be considered a part of prenatal care. Tuberculin skin tests can be adm... Universal Screening Diagnosis of Infection in the Newborn Infant Prevention and Management of Infection in the Pregnant Woman Prevention of Infection Infections Acquired by the Newborn Infant During Birth Pathogenesis Microbiology Diagnosis Management Prevention Immunoprophylaxis Chemoprophylaxis Infections of the Newborn Infant in the First Month of Life Pathogenesis and Microbiology Congenital Infections Infections Acquired During Delivery Nursery-Acquired Infections Community-Acquired Infections Infections That Indicate Underlying Abnormalities References 2. Neonatal Infections A Global Perspective.pdf (p.33-62) 2 - Neonatal Infections: A Global Perspective Global Burden of Neonatal Infections Infection as A Cause of Neonatal Death Incidence of Neonatal Sepsis, Bacteremia, and Meningitis and Associated Mortality Bacterial Pathogens Associated with Infections in Different Geographic Regions Incidence of Group B Streptococcal Colonization and Infection Antimicrobial Resistance in Neonatal Pathogens Nosocomial Infections Hospital Infection Control Selected Neonatal Infections Acute Respiratory Infections/Pneumonia Diarrhea Omphalitis Tetanus Ophthalmia Neonatorum Human Immunodeficiency Virus (HIV) Infection Transmission: Reducing the Disparity Between Low- and High-Income Countries Breastfeeding and Human Immunodeficiency Virus Prevention of Human Immunodeficiency Virus Infection in Low- and Middle-Income Countries Prevention of Transmission From an Infected Mother to Her Infant .The era of antiretroviral therapy (ART) to reduce vertical transmission of HIV started in 1994 with publication of the Pediatri... .Meta-analyses of North American and European studies performed in the late 1990s found that elective cesarean section reduced t... Integrated Health Care Programs Human Immunodeficiency Virus and Child Survival Tuberculosis Malaria Malaria in Pregnancy Perinatal Outcome Congenital Malaria Prevention and Treatment of Malaria in Pregnancy Prophylaxis and Treatment Using Antimalarial Drugs Prevention Using Insecticide-Treated Nets Malaria Control Strategies and Challenges Indirect Causes of Neonatal Death Related to Infection Strategies to Prevent and Treat Infection in the Neonate Maternal Immunization to Prevent Neonatal Disease Neonatal Immunization Antenatal Care and Prevention of Neonatal Infection Intrapartum and Delivery Care and Prevention of Neonatal Infection Postnatal Care and Prevention of Neonatal Infection Breastfeeding Management of Neonatal Infection Identification of Neonates with Infection Antibiotic Treatment of Neonates with Infection Integrated Management of Neonatal Illness Maternal Education and Socioeconomic Status Conclusion Acknowledgment References 3. Obstetric Factors Associated with Infections of the Fetus and Newborn Infant.pdf (p.63-89) 3 - Obstetric Factors Associated with Infections of the Fetus and Newborn Infant Overview Infection as a Cause of Preterm Birth Pathogenesis Histologic Chorioamnionitis Animal Models Microbiology Diagnosis of Intraamniotic Infection Amniotic Fluid Testing Proteomics Treatment of Intraamniotic Infection Antenatal Antibiotics to Prevent Intraamniotic Infection Prevention of Postpartum Endometritis After Intraamniotic Infection Diagnosis Antibiotic Choice Timing of Antibiotic Therapy Delivery as Therapy Neonatal Outcomes Fetal Lung Injury Fetal Brain Injury Magnesium Sulfate for Neuroprotection Premature Rupture of Membranes Natural History of Premature Rupture of the Membranes and Preterm Premature Rupture of the Membranes Biomechanical Strength of the Chorioamnion Pathogenesis Infection and Inflammation, Matrix Metalloproteinase Activation, and Oxidative Stress Abruption (Placental Bleeding) and Thrombin Genetic Predisposition Diagnosis Management of Premature Rupture of the Membranes and Preterm Premature Rupture of the Membranes Preterm Premature Rupture of the Membranes Before Fetal Viability Preterm Premature Rupture of the Membranes Between 24 and 34 Weeks Antenatal Corticosteroids and Tocolytics Determination of Fetal Lung Maturity Antenatal Surveillance Preterm Premature Rupture of the Membranes Between 34 to 37 Weeks Premature Rupture of the Membranes After 37 Weeks Maternal and Neonatal Outcomes Maternal Outcomes Neonatal Outcomes Conclusion References 4. Developmental Immunology and Role of Host Defenses in Fetal and Neonatal Susceptibility to Infec.pdf (p.90-197) 4 - Developmental Immunology and Role of Host Defenses in Fetal and Neonatal Susceptibility to Infection Epithelial Barriers Antimicrobial Peptides and Proteins Skin The Gastrointestinal Tract The Respiratory Tract Summary Complement and Other Humoral Mediators of Innate Immunity Collectins, Pentraxins, and Ficolins Complement Classical and Mannose-Binding Lectin Pathways Alternative Pathway Terminal Components, Membrane Attack Complex, and Biologic Consequences of Complement Activation Complement in the Fetus and Neonate Summary Phagocytes Hematopoiesis Phagocyte Production by the Bone Marrow Innate Immune Pattern Recognition Receptors Used by Leukocytes Toll-like Receptors Nucleotide-Binding Domain– and Leucine-Rich Repeat–Containing Receptors (NLRs) Retinoic Acid–Inducible Gene-I–Like Receptors C-Type Lectin Receptors Cytoplasmic DNA Receptors Decoding the Nature of the Threat Through Combinatorial Receptor Engagement Neutrophils Production Migration to Sites of Infection or Injury Migration of Neonatal Neutrophils Phagocytosis Killing Activation by Innate Immune Receptors Neutrophil Clearance and Resolution of Neutrophilic Inflammation Effects of Immunomodulators Eosinophils Mononuclear Phagocytes Production and Differentiation of Monocytes and Resident Tissue Macrophages Migration to Sites of Infection and Delayed Hypersensitivity Responses Antimicrobial Properties of Monocytes and Macrophages .Monocytes from human neonates and adults ingest and kill S. aureus, E. coli, and GBS with similar efficiency.207-211 Consistent... Mononuclear Phagocytes Produce Cytokines and Other Mediators That Regulate Inflammation and Immunity Cytokine Production, Toll-like Receptors, and Regulation of Innate Immunity and Inflammation by Neonatal Monocytes and Macrophag... .Levy and colleagues240,261 identified adenosine as a factor in cord blood plasma that inhibited TNF-α production but preserved ... Resolution of Mononuclear Phagocytic Inflammation SUMMARY Dendritic Cells: the Link between Innate and Adaptive Immunity OVERVIEW Conventional Dendritic Cells Neonatal Conventional Dendritic Cells Plasmacytoid Dendritic Cells Neonatal Plasmacytoid Dendritic Cells Langerhans Cells Inflammatory and Monocyte-Derived Dendritic Cells Summary Natural Killer Cells and Innate Lymphoid Cells Natural Killer Cells Overview and Development Natural Killer Cell Receptors Natural Killer Cell Cytotoxicity Natural Killer Cell Cytokine Responsiveness and Dependence Natural Killer Cell Cytokine and Chemokine Production Natural Killer Cells of the Maternal Decidua and Human Leukocyte Antigen G Natural Killer–Cell Numbers and Surface Phenotype in the Fetus and Neonate Fetal and Neonatal Natural Killer Cell–Mediated Cytotoxicity and Cytokine Production Innate Lymphoid Cells Summary T Cells and Antigen Presentation Overview Antigen Presentation by Classic Major Histocompatibility Complex Molecules Major Histocompatibility Complex Class Ia Major Histocompatibility Complex Class II Major Histocompatibility Complex Molecule Expression and Antigen Presentation in the Fetus and Neonate Nonclassic Antigen-Presentation Molecules Human Leukocyte Antigen E Human Leukocyte Antigen G Major Histocompatibility Class I–Related Chains A and B CD1 Prothymocytes and Early Thymocyte Differentiation Thymic Ontogeny Intrathymic Generation of T-Cell Receptor Diversity Overview Fetal and Neonatal T-Cell Receptor Repertoire T-Cell Receptor Excision Circles Thymocyte Selection and Late Maturation Positive and Negative Selection Thymocyte Growth and Differentiation Factors Thymocyte Postselection Maturation NaÏve T Cells CD4 and CD8 Recent Thymic Emigrants Naïve T-Cell Entry into Lymphoid Tissue, Recirculation, and Survival Ontogeny of NaÏve T-Cell Surface Phenotype CD31 CD38 CD45 Isoforms Homeostatic Proliferation Spontaneous Naïve Peripheral T-Cell Proliferation Antigen-Independent Naïve T-Cell Proliferation in Response to IL-7 and IL-15 NaÏve T-Cell Activation, Anergy, and Co-stimulation Neonatal T-Cell Activation, Co-Stimulation, and Anergy Differentiation of Activated NaÏve T Cells into Effector and Memory Cells Effector CD4 T-Cell Subsets Are Defined by Their Patterns of Cytokine Production Regulation of CD4 Effector T-Cell Subset Differentiation CD4 T-Cell Help for Antibody Production Overview of Memory T Cells Memory T-Cell Activation Postnatal Ontogeny of Memory CD4 T-Cell Subsets Production of Cytokines, Chemokines, and Tumor Necrosis Factor–Ligand Proteins by Neonatal T Cells CD4 T-Cell Cytokine Production CD8 T-Cell Cytokine and Chemokine Production Postnatal Ontogeny of Cytokine Production CD40 Ligand Other Tumor Necrosis Factor Family Ligands Mechanisms for Decreased Cytokine, Chemokine, and TNF Ligand Production by Neonatal T Cells Cytokine Production by Neonatal T Cells after Short-Term In Vitro Differentiation Cytokine Production After Long-Term In Vitro Generation of Effector CD4 T Cells T Cell–Mediated Cytotoxicity Effector T-Cell Migration Termination of the T-Cell Effector Response Regulation of T-Cell Expansion by Apoptosis Unique Phenotype and Function of the Fetal T-Cell Compartment Fetal Extrathymic T-Cell Differentiation Regulatory T Cells Overview Fetal and Neonatal Tregs Natural Killer and Mucosal-Associated Invariant T Cells Overview of Natural Killer T Cells NKT Cells of the Fetus and Neonate Mucosal-Associated Invariant T Cells Gamma-Delta T Cells Phenotype and Function Ontogeny of Gamma-Delta T-Cell Production and T-Cell Receptor Gene Rearrangements Ontogeny of Gamma-Delta T-Cell Function Antigen-Specific T-Cell Function in the Fetus and Neonate Delayed Cutaneous Hypersensitivity, Graft Rejection, and Graft-versus-Host Disease T-Cell Reactivity to Environmental Antigens Fetal T-Cell Sensitization to Maternally Administered Vaccines and Maternally Derived Antigens Maternal Transfer of T-Cell Immunity to the Fetus T-Cell Response to Congenital Infection CD4 T Cells CD8 T Cells Gamma-Delta T Cells T-Cell Response to Postnatal Infections and Vaccination in Early Infancy CD4 T-Cell Responses to Postnatal Infection CD4 T-Cell Responses to Postnatal Immunization with Inactivated Vaccines CD4 T-Cell Responses to Postnatal Immunization with Live-Attenuated Vaccines CD8 T Cells Summary B Cells and Immunoglobulin Overview Early B-Cell Development and Immunoglobulin Repertoire Formation Pro–B-Cell and Pre–B-Cell Maturation V(D)J Recombination of the Immunoglobulin Gene Loci V(D)J Segment Usage in the Fetus and Neonate CDR3 Length and Terminal Deoxytransferase B-Cell Maturation, PreImmune Selection, and Activation Receptor Editing, Clonal Deletion, and Clonal Anergy New Emigrant (Transitional) versus Fully-Mature Naïve B Cells Follicular B-Cell Maturation Fetal and Neonatal B-Cell Frequency and Surface Phenotype B-Cell Activation and Immune Selection Negative Regulation of B-Cell Signaling CD4 T-Cell Help for Naïve B-Cell Activation B-Cell Selection in Germinal Centers of the Follicle Somatic Hypermutation Memory B Cells B Cells as Antigen-Presenting Cells Switching of Immunoglobulin Isotype and Class and Antibody Production Isotype Switching Generation of Plasma Cells and the Molecular Basis for Immunoglobulin Secretion Isotype Switching and Immunoglobulin Production by Fetal and Neonatal B Cells The Marginal Zone and Marginal Zone B Cells Marginal Zone B Cells of the Fetus and Neonate B-1 Cells and Natural Immunoglobulin M Regulatory B Cells T-CELL–Dependent and T-CELL–Independent Responses by B Cells Overview Response to T-Cell Dependent Antigens Response to T-Cell–Independent Antigens Specific Antibody Response by the Fetus to Maternal Immunization and Congenital Infection Response to Fetal Immunization in Animal Models Response to Maternal Immunization Response to Intrauterine Infection PostNatal Specific Antibody Responses Specific Antibody Responses by the Neonate and Young Infant to Protein Antigens Specific Antibody Responses by the Term Neonate to Polysaccharide and Polysaccharide-Protein Conjugates Antibody Responses by the Premature Infant to Immunization Maternally Derived Immunoglobulin G Antibody Placental Transfer of Specific Antibodies .Maternal antibody also may inhibit the production by the fetus or newborn of antibodies of the same specificity. This inhibition... Immunoglobulin Synthesis by the Fetus and Neonate Immunoglobulin G Immunoglobulin M Immunoglobulin A Immunoglobulin D Immunoglobulin E Summary Immunologic Approaches to Prevent or Treat Fetal and Neonatal Infections Overview U.S. Food and Drug Administration–approved Uses of Passive Immunization in the Mother and Newborn Infant Exploratory Evaluation of Passive Immunization for Other Indications Prevention or Treatment of Neonatal Sepsis with Intravenous Immunoglobulin Cytomegalovirus Hyperimmune Intravenous Immunoglobulin Neutrophil Transfusions Colony-Stimulating Factors References 5. Human Milk.pdf (p.198-222) 5 - Human Milk Developmental Anatomy of the Mammary Gland Anatomy and Development Postnatal Development Physiology of Lactation Endocrine Control of Mammary Gland Function Initiation and Maintenance of Lactation Milk Secretion Lactation Performance Components of Human Milk and Their Potential Benefits for the Breastfed Infant Proteins, Peptides, and Nonprotein Nitrogen Nutritional Proteins Bioactive Proteins and Peptides .A number of nutrients are supplied to the neonate bound to proteins found in human milk. This binding may play an important rol... .The activity of several dozen enzymes has been detected in human milk.44 Most of these enzymes appear to originate from the blo... .Human milk contains several growth factors with potential effects on the intestine, vasculature, nervous system, and endocrine ... .As observed in other peripheral mucosal sites, the major class of immunoglobulin in human colostrum and milk is the 11S secreto... .In the 1990s, several cytokines, chemokines, and growth factors that mediate the effector phases of natural and specific immunit... Protein-Derived Peptides Nonprotein Nitrogen Lipids Carbohydrates Lactose Oligosaccharides Vitamins Vitamin D Vitamin E Vitamin K Vitamin B Minerals Cells Leukocytes Epithelial Cells Stem Cells Bacteria Benefits and Risks of Human Milk Benefits Gastrointestinal Homeostasis Prevention of Diarrhea Necrotizing Enterocolitis Neonatal Sepsis Prevention of Atopy and Allergy Special Considerations for the Premature Neonate Other Benefits Noninfectious Risks Infectious Risks Bacterial Infections Viral Infections .Cytomegalovirus infection is a common perinatal infection. The virus is shed in the milk in about 25% of infected mothers. Alth... .Hepatitis B surface antigen (HBsAg) has been detected in milk of HBV-infected mothers. Nevertheless, breastfeeding does not inc... .The RNA of HCV and antibody to HCV have been detected in the milk from infected mothers. Transmission by means of breastfeeding... .Herpes simplex virus transmission directly from maternal breast lesions to their infants has been demonstrated. Women with lesi... .A number of studies have demonstrated HIV in milk.317-321 The findings include isolation of HIV from milk supernatants collected... .Human T-lymphotropic virus type 1 is endemic in Japan, the Caribbean, and parts of South America. This infection can be transmi... .Rubella virus has been recovered from milk after natural as well as vaccine-associated infection. It has not been associated wi... .The RNA of West Nile virus has been detected in human milk, and seroconversion in breastfeeding infants also has been observed.... Current Trends in Breastfeeding Summary and Conclusions References 6. Bacterial Sepsis and Meningitis.pdf (p.223-277) 6 - Bacterial Sepsis and Meningitis Bacteriology Group B Streptococci Group A Streptococci Streptococcus Pneumoniae Other Streptococci Enterococcus Species Staphylococcus Aureus and Coagulase-Negative Staphylococci Listeria Monocytogenes Escherichia Coli Klebsiella Species Enterobacter and Cronobacter Species Citrobacter Species Serratia Marcescens Pseudomonas Aeruginosa Salmonella Species Neisseria Meningitidis Haemophilus Influenzae Anaerobic Bacteria Neonatal Tetanus Mixed Infections Uncommon Bacterial Pathogens Epidemiology Incidence of Sepsis and Meningitis Characteristics of Infants who Develop Sepsis Birth Weight Risk Factors of Infant and Mother Ethnicity Gender Geographic Factors Socioeconomic Factors Procedures Nursery Outbreaks or Epidemics Pathogenesis Host Factors Predisposing to Neonatal Bacterial Sepsis Infection in Twins The Umbilical Cord as a focus of Infection Administration of Drugs to the Mother Before Delivery Administration of Drugs other than Antibiotics to the Neonate Pathology Clinical Manifestations Fever and Hypothermia Respiratory Distress Jaundice Organomegaly Gastrointestinal Signs Skin Lesions Neurologic Signs Diagnosis Maternal History Microbiologic Techniques Culture of Blood .Technology has evolved from manually read, broth-based methods to continuously monitored, automated blood-culture systems that ... .Bacterial growth is evident in most cultures of blood from neonates within 48 hours.495-497 With use of conventional culture te... .The optimal number of cultures to obtain for the diagnosis of bacteremia in the newborn remains uncertain. A single blood cultu... .The optimal volume of blood needed to detect bacteremia in neonates has not been determined. Neal and colleagues500 evaluated t... Buffy-Coat Examination Culture of Urine Cultures of Tracheal Aspirates and Pharynx Diagnostic Needle Aspiration and Tissue Biopsy Autopsy Microbiology Rapid Techniques for Detection of Bacterial Antigens in Body Fluid Specimens Lumbar Puncture and Examination of Cerebrospinal Fluid .Lumbar puncture is more difficult to perform in the neonate than in the older child or adult; traumatic LPs resulting in blood i... .Is it sufficient to culture only blood and urine for the diagnosis of neonatal bacterial meningitis Visser and Hall561 demonstra... .The cell content and chemistry of the CSF of healthy newborn infants differ from those of older infants, children, and adults (... .A traumatic LP can result in blood in the CSF and can complicate the interpretation of the results for CSF white blood cell cou... .Brain abscess is a rare entity in the neonate, usually complicating meningitis caused by certain gram-negative bacilli. The CSF... Laboratory Aids Management Choice of Antimicrobial Agents Initial Therapy for Presumed Sepsis Role of Third-Generation Cephalosporins and Carbapenems Current Practice Continuation of Therapy when Results of Cultures are Available Management of the Infant whose Mother Received Intrapartum Antimicrobial Agents Treatment of the Infant whose Bacterial Culture Results are Negative Management of the Infant with Catheter-Associated Infection Treatment of Neonatal Meningitis Management of the Infant with a Brain Abscess Treatment of the Infant with Meningitis whose Bacterial Culture Results are Negative Treatment of Anaerobic Infections Adjunctive Therapies for Treatment of Neonatal Sepsis Prognosis Prevention Obstetric Factors Chemoprophylaxis Maternal Factors Immunoprophylaxis Decontamination of Fomites Epidemiologic Surveillance Endemic Infection Epidemic Infection Sepsis in the Newborn Recently Discharged From the Hospital Congenital Infection Late-Onset Disease Infections in the Household Fever in the First Month of Life Acknowledgment References 7. Bacterial Infections of the Respiratory Tract.pdf (p.278-296) 7 - Bacterial Infections of the Respiratory Tract Infections of the Oral Cavity and Nasopharynx Pharyngitis, Retropharyngeal Cellulitis, and Retropharyngeal Abscess Noma Epiglottitis Laryngitis Infection of the Paranasal Sinuses Diphtheria Pertussis Otitis Media Pathogenesis and Pathology Epidemiology Microbiology Diagnosis Treatment Prognosis Mastoiditis Pneumonia Pathogenesis and Pathology Congenital or Intrauterine Pneumonia Pneumonia Acquired During the Birth Process and in the First Month of Life Microbiology Epidemiology Incidence Race and Socioeconomic Status Epidemic Disease Developing Countries Clinical Manifestations Diagnosis Clinical Diagnosis Radiologic Diagnosis Microbiologic Diagnosis Histologic and Cytologic Diagnosis Immunologic Diagnosis Differential Diagnosis Management Prognosis References 8. Bacterial Infections of the Bones and Joints.pdf (p.297-312) 8 - Bacterial Infections of the Bones and Joints Osteomyelitis Microbiology Pathogenesis Clinical Manifestations Prognosis Diagnosis Differential Diagnosis Therapy Primary Septic Arthritis Osteomyelitis of the Maxilla References 9. Bacterial Infections of the Urinary Tract.pdf (p.313-324) 9 - Bacterial Infections of the Urinary Tract Epidemiology Microbiology Pathogenesis Anatomic and Physiologic Abnormalities Bacterial Virulence Pathology Clinical Manifestations Diagnosis Culture of Urine Culture of Blood and Cerebrospinal Fluid Examination of Urine Sediment Examination of Blood Chemical Determinations Imaging of the Urinary Tract Management and Prevention Prognosis References 10. Focal Bacterial Infections.pdf (p.325-355) 10 - Focal Bacterial Infections Infections of the Liver Microbiology Pathogenesis Clinical Manifestations Diagnosis Prognosis Treatment Splenic Abscess Infections of the Biliary Tract Infections of the Adrenal Glands Appendicitis Microbiology Pathogenesis Clinical Manifestations Diagnosis Prognosis Treatment Peritonitis Microbiology Pathogenesis Clinical Manifestations Diagnosis Prognosis Treatment Necrotizing Enterocolitis Pathology and Pathogenesis Microbiology Clinical Manifestations Diagnosis Treatment Prevention Prognosis Endocarditis Pericarditis Mediastinitis Esophagitis Infections of Endocrine Organs Infections of the Salivary Glands Infections of the Skin and Subcutaneous Tissue Pathogenesis Microbiology Epidemiology Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prevention Conjunctivitis and Other Eye Infections References 11. Microorganisms Responsible for Neonatal Diarrhea.pdf (p.356-416) 11 - Microorganisms Responsible for Neonatal Diarrhea Enteric Host Defense Mechanisms Protective Factors in Human Milk Bacterial Pathogens Enterotoxigenic Escherichia coli .Although early work on the recognition of E. coli as a potential enteric pathogen focused on biochemical or serologic distincti... .The two types of enterotoxins produced by enterotoxigenic E. coli146-148 have been found to be plasmid-encoded but genetically ... .ETEC are important diarrheal pathogens among infants in developing countries, predominantly affecting children younger than 2 y... .The clinical manifestations of ETEC diarrhea tend to be mild and self-limited except in small or undernourished infants, in who... .As in cholera, the pathologic changes associated with ETEC infection are minimal. From animal experiments in which intestinal l... .The preliminary diagnosis of ETEC diarrhea can be suspected by the epidemiologic setting and the noninflammatory nature of stoo... .The cornerstone of treatment for any diarrheal infection is rehydration.199 This principle especially pertains to ETEC diarrhea... Enteroinvasive Escherichia coli .Entero­invasive E. coli is similar genetically, pathogenetically, epidemiologically, and clinically to shigellosis, although th... .Little is known about the epidemiology and transmission of this organism in newborns and infants; it is more frequently found i... .Symptoms often include watery diarrhea, although a dysentery-like syndrome with an inflammatory exudate in stool, invasion and ... .Enteroinvasive E. coli should be suspected in infants who have an inflammatory diarrhea, as evidenced by fecal neutrophils or b... .The management and prevention of EIEC diarrhea should be similar to that of acute Shigella or other E. coli enteric infections.... Enteropathogenic Escherichia coli .Based on the molecular identification of two virulence factors, EPEC is now classified as either typical, usually associated wi... .Bacterial cultures of the meconium and feces of newborns indicate that EPEC can effectively colonize the intestinal tract in th... .The principal pathologic lesion in EPEC infection is the A/E lesion, manifest by electron microscopy but not light microscopy. ... .The incubation period after EPEC exposure is quite variable. Its duration has been calculated mostly from evidence in outbreaks... .In 1987, the WHO came to a consensus that O serogroups of E. coli should be classified as EPEC: O26, O55, O86, O111, O114 O119,... .The mortality rate recorded previously in epidemics of typical EPEC gastroenteritis is impressive for its variability. During t... .The management of EPEC gastroenteritis should be directed primarily toward prevention or correction of problems caused by loss ... .The transmission for EPEC is fecal-oral. Therefore strict adherence to infection control and appropriate hygiene can help preve... Enterohemorrhagic Escherichia coli Enteroaggregative Escherichia coli .The mode of transmission of EAEC is not well established. In adult volunteer studies, the infectious dose is high (>108 CFU), s... .Descriptions from outbreaks and volunteer studies suggest that EAEC diarrhea is most often watery, with mucus and accompanied b... .Diagnosis of EAEC requires identification of the organism in the patient’s feces. The HEp-2 adherence assay can be used for thi... Other Escherichia coli Pathotypes Salmonella Nature of the Organism Epidemiology and Transmission Clinical Manifestations Diagnosis Therapy Prevention Shigella Nature of the Organism Epidemiology Clinical Manifestations Diagnosis Therapy Prevention Campylobacter Virulence Factors and Pathogenic Mechanisms Epidemiology and Transmission Clinical Manifestations Pathology Diagnosis Therapy and Prevention Clostridium Difficile Virulence Factors and Pathogenic Mechanisms Epidemiology Clinical Manifestations Diagnosis Therapy Prevention Vibrio Cholerae Nature of the Organism Virulence Factors and Pathogenic Mechanisms Epidemiology and Transmission Clinical Manifestations Diagnosis Therapy a **__Infectious Diseases of the Fetus and Newborn Infant__**, written and edited by Drs. Remington, Klein, Wilson, Nizet, and Maldonado, remains the definitive source of information in this field. The 8^th^ edition of this authoritative reference provides the most **up-to-date and complete guidance on infections found in utero**, during delivery, and in the neonatal period in both premature and term infants. Special attention is given to the **prevention** and **treatment** of these diseases found in developing countries as well as the latest findings about new antimicrobial agents, gram-negative infections and their management, and recommendations for immunization of the fetus/mother. **Nationally and internationally recognized in immunology and infectious diseases**, new associate editors Nizet and Maldonado bring new insight and fresh perspective to the book. *** Explore what’s changing in key areas**such as: - emerging problems and concepts in maternal, fetal, and neonatal infectious diseases - anticipation and recognition of infections occurring in utero, during delivery, and in the neonatal period * Stay on the cutting edge of your field with **new** and **improved chapters** including: obstetric factors associated with infections of the fetus and newborn infant; human milk; borella infections; tuberculosis; bordetella pertussis and other bordetella sp infections; herpes simplex; toxoplasmosis; pneumocystis and other less common fungal infections; and healthcare-associated infections in the nursery * Keep up with the most relevant topics in fetal/neonatal infectious disease including new antimicrobial agents, gram- negative infections and their management, and recommendations for immunization of the fetus/mother. * Overcome clinical challenges in developing countries where access to proper medical care is limited. * Expert Consult eBook version included with purchase. 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