Pediatric Transplant and Oncology Infectious Diseases

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Ifc
Pediatric Transplant and Oncology Infectious Diseases
Copyright
Dedication
Contributors
Preface
Foreword
	References
Contents
SECTION 1 General Immunocompromised Host Infection Principles
1 The surgical and immunosuppressive basis for infections in the pediatric solid organ transplant recipient
	Surgical considerations
		Superficial surgical site infections
			Deep surgical site infections.
				Heart transplantation.
				Lung transplantation.
				Kidney transplantation.
				Liver transplantation.
				Multivisceral and intestinal transplantation.
	Immunologic overview
	Components of the immune system
	Rejection
		Hyperacute rejection
		Acute rejection
		Chronic rejection
	Current outcomes
	Immunosuppressive medications
		Induction therapies
			Biologic agents.
			Corticosteroids.
		Maintenance therapies
			Calcineurin inhibitors.
			Mammalian target of rapamycin inhibitors.
			Antimetabolites.
			Biologic agents.
			Standard approach to maintenance therapy.
		Rejection therapies
			Biologic agents.
			Other therapies.
			Standard approach to rejection therapy.
			New therapies.
	Conclusion
	References
2 Immunologic recovery and basis for infections in the pediatric hematopoietic stem cell transplant recipient
	Infection risk by fixed time periods after transplantation
		Pre-engraftment period
		Early post-engraftment period
		Late post-engraftment period
		Approaches to prophylaxis relative to infectious risk periods
	Timing of immune reconstitution after hematopoietic stem cell transplantation
		Innate immune recovery after transplantation
		Adaptive cellular immune recovery after transplantation
		Adaptive humoral immune recovery after transplantation
	Autologous hsct as a model for immune reconstitution
	Factors affecting immune reconstitution, autoreactivity, and alloreactivity
		HLA matching
		Stem cell source
			Bone marrow.
			Peripheral blood stem cells.
			Umbilical cord blood.
		Stem cell dose
		Pretransplant conditioning
		Recipient- and donor-specific factors
			Donor age.
			Recipient age.
			Sex and parity.
			Cytomegalovirus status.
		Graft-versus-host disease.
			Impact of graft-versus-host disease prophylaxis on immune reconstitution.
			Impact of graft versus host disease on immune reconstitution.
			Graft-versus-leukemia effect.
	Assessment of immune reconstitution
	Improving immune reconstitution after HSCT
	Summary
	References
3 Cancer and antineoplastic therapies and the risk of infection in the pediatric cancer patient
	Infectious risk assessment in oncology patients
	Disease-specific infectious risks
		Hematologic malignancies
			Acute lymphoblastic leukemia.
			Acute myelogenous leukemia.
			Chronic myeloid leukemia.
			Down syndrome.
			Infant leukemia.
			Lymphoma.
		Solid tumors
			Central nervous system tumors.
			Neuroblastoma.
			Sarcoma.
			Wilms tumor.
			Hepatoblastoma.
	Infectious risks associated with anticancer therapies
		Conventional chemotherapeutic agents
			Alkylating agents.
			Platinum analogs.
			Antimetabolites.
			Natural products.
		Autologous stem cell transplant
		Novel chemotherapeutics
			Immunotherapy: Biologic agents.
			Cellular-based immunotherapy.
			Small-molecule inhibitors.
	References
SECTION 2 Common Immunocompromised Host Infection Situations
4 Infectious disease evaluation of infants and children awaiting solid organ or hematopoietic stem cell transplant
	Basic principles of the infectious disease pretransplant evaluation
		Infectious disease screening of the pediatric solid organ transplant candidate
		HIV and hepatitis screening
		Herpesvirus screening
		Approach to infectious disease evaluation of the pediatric hematopoietic stem cell transplant candidate
		Approach to tuberculosis screening in the pediatric transplant candidate
		Additional screening measures for pediatric transplant candidates
	General approach to pretransplant immunization
	Special considerations for extremes of age
		Future directions
	References
5 Donor screening and donor-derived infections
	Anticipated and unanticipated donor-derived infections
	Regulatory oversite of donor screening and reporting of donor-derived infections
	Lessons learned
		Lessons from donor-derived infections in HSCT and SOT recipients
		Lessons from the ad hoc disease transmission advisory committee
	Educating candidates about donor-derived infections before transplant
		The importance of recognizing donor-derived infections
	Summary
	References
6 Prevention of infections in the hematopoietic stem cell transplant recipient
	Pretransplant evaluation
		Recipient evaluation
			History.
			Transplant information.
			Physical examination.
			Pathogen-specific testing.
			Imaging.
			Additional evaluations.
		Donor evaluation
			History.
			Pathogen-specific testing.
			Active infections.
			Special considerations and contraindications to donation.
			Imaging.
	Vaccination
	Prevention of bacterial infections
	Prevention of invasive fungal disease
	Prevention of viral infections
	Prevention of other infections
		Pneumocystis jirovecii (formerly pneumocystis carinii) pneumonia
		Tuberculosis
			Active infection.
			Preventing infection.
		Toxoplasma gondii
			Active infection.
			Preventing infection.
		Strongyloides stercolaris
	References
7 Prevention of infections in the solid organ transplantation recipient
	Pretransplant evaluation
	Vaccination
	Perioperative antimicrobial prophylaxis
	Posttransplant prophylaxis and monitoring
	Summary
	References
8 Management principles for patients with neutropenia
	Epidemiology
		Bacterial pathogens
		Fungal pathogens
		Viral pathogens
	Evaluation
		Initial risk stratification
		Initial investigations
	Management of bacterial infections
		Initial antibiotic therapy
		Consideration for patients with high-risk fever and neutropenia
		Considerations for patients with low-risk fever and neutropenia
		Modification of empiric antibacterial therapy
		Cessation of empiric antibacterial therapy
	Invasive fungal disease management
		Evaluation for invasive fungal disease
		Empiric antifungal therapy
	Prophylactic strategies
		Antibacterial prophylaxis
		Antifungal prophylaxis
	References
9 Vaccination issues for transplantation and chemotherapy
	General considerations
		Vaccination history
		Vaccine administration before immunosuppression
		Protective titer levels
		Window of time between intravenous immunoglobulins, blood products, and vaccine administration
		Donors and contacts of immunocompromised host
	Solid organ transplantation
		Pretransplantation vaccination
		Posttransplant vaccination
			General considerations.
			Inactivated vaccines.
		Pneumococcal vaccine
		Influenza vaccine
		Hepatitis B vaccine
		Hepatitis A vaccine
		Pertussis vaccine
		Human papillomavirus vaccine
		Meningococcal vaccine
			Live attenuated vaccines.
		Measles-mumps-rubella vaccine
		Varicella-zoster vaccine
		Rotavirus vaccine
	Oncology patients
		Inactivated vaccines
		Pneumococcal vaccines
		Influenza vaccines
		Human papillomavirus vaccines
		Hepatitis A and B vaccines
		Live vaccines
	Hematopoietic stem cell transplantation
		Timing to start vaccination
		Pneumococcal vaccine
		Influenza vaccination
		Tetanus toxoid, diphtheria toxoid, pertussis, and poliovirus
		Meningococcal vaccine
		Human papilloma virus
		Live vaccines
		Vaccines in special circumstances
	Conclusion and future directions
	References
10 Microbiome implications in transplantation and oncology
	Microbiome and hematopoietic stem cell transplantation
		Graft-versus-host disease
		Infections
		Microbiome therapeutics
	Microbiome and oncology
	Microbiome and solid organ transplantation
		Allograft rejection
		Microbiome therapeutics
	Knowledge limitations
	Future directions
	References
11 Antimicrobial stewardship in immunocompromised hosts
	Goals of stewardship in immunocompromised hosts
	Barriers to antimicrobial stewardship programs in immunocompromised children
		Paucity of evidence for prevention and management of infections
		Diagnostic uncertainty
		Concerns for polymicrobial or multiple infections
		Provider autonomy and the stewardship team
		End-of-life care
		Antimicrobial stewardship programs
	Strategies and tactics for stewardship in immunocompromised hosts
	Stewardship metrics in the transplant population
	Conclusion and future research
	References
12 Hospital infection prevention for pediatric transplant recipients and oncology patients
	General principles
	Importance of healthcare-associated infections surveillance
	Pathogen-specific infection prevention strategies
		Legionella
		Staphylococcus aureus and vancomycin-resistant enterococci
		Clostridium difficile
		Multidrug-resistant gram-negative organisms
		Mycobacteria
		Opportunistic mold
		Viruses
	Good practice recommendations
		Policies regarding sick providers
		Vaccinations of healthcare workers and close contacts
		Visitation policies
		Animal safety
		Good bathing practices: Showers and wipes
		Toys
		Food safety
		Mask use in patients during ambulation or transportation within hospitals
		Environmental impact on medical care of immunocompromised patients
		Air quality
		Construction and renovation
		Furnishings
		Care of linens and healthcare worker attire
		Plants
		Water quality
		Water damage
		Cleaning and disinfecting environmental surfaces within hospital units
	Infection prevention practices in specific immunocompromised pediatric populations
		Hematopoietic stem cell transplantation
		Solid organ transplantation
		Oncology
		Future areas of research in standardizing infection prevention practices
	References
13 Safe living after transplantation or chemotherapy
	Prevention of infections by direct contact
	Prevention of respiratory infections
	Water safety/exposure to cryptosporidium
	Food safety
	Animal contact and pet safety
	Returning to school
	Recreational activities including travel
		Sports
		Travel
		Sexual activity
	References
SECTION 3 Specific Infections in Transplant Recipients and Oncology Patients
14 Multidrug-resistant gram-negative infections in transplant and oncology patients
	Common mechanisms of gram-negative resistance
	Epidemiology and risk factors
		Heart and lung transplant recipients
		Liver and intestinal transplant recipients
		Renal transplant recipients
		Oncology patients
	Clinical manifestations of mdrgn infection
		Solid organ transplant patients
		Oncology and hematopoietic stem cell transplant patients
		Disease prophylaxis and prevention
		Diagnosis
		Treatment
			Extended-spectrum β-lactamase-producing enterobacteriaceae.
			Carbapenem-resistant enterobacteriaceae.
			Carbapenem-resistant pseudomonas aeruginosa.
		Infection prevention and anticipatory guidance
			Infection prevention.
			Anticipatory guidance.
	References
15 Bartonella, legionella, mycoplasma, and ureaplasma
	Bartonella
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis/prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Legionella
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis/prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Mycoplasma and ureaplasma
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis/prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	References
16 Nontuberculous and tuberculous mycobacterium
	Mycobacterium tuberculosis infection
		Epidemiology, risk factors, and pathogenesis
		Clinical manifestations
		Diagnosis
		Treatment
		Prevention and screening practices
		Epidemiology, risk factors, and pathogenesis
		Clinical manifestations
		Diagnosis
		Treatment
		Disease prophylaxis and infection prevention
	References
17 Cytomegalovirus
	Epidemiology and risk factors
	Clinical manifestations
	Disease prophylaxis and prevention
		Solid organ transplant–specific strategies
		HSCT-specific strategies
		Oncology-specific strategies
		Emerging prevention therapies and strategies
	Diagnosis
		Testing for antiviral resistance
		Cellular assays to document CMV-specific immunity
	Treatment
		Emerging cellular treatment strategies
	Infection prevention and anticipatory guidance
	Conclusions
	References
18 Epstein-barr virus and posttransplant lymphoproliferative disorder
	Epidemiology and risk factors
		Epstein-Barr virus in solid organ transplant recipients
		Epstein-Barr virus in hematopoietic stem cell transplantation
		Epstein-Barr virus in cancer
		Clinical manifestations
	Prevention of Epstein-Barr virus infection and PTLD
	Immunoprophylaxis
		Chemoprophylaxis
		Viral load monitoring and preemptive prevention strategies
	Diagnosis
	Therapy for posttransplant lymphoproliferative disorders
		Ptld treatment in solid organ transplant recipients
			Reduction of immunosuppression.
			Local disease control.
			Systemic therapy
				Chemotherapy.
				Anti-CD20 monoclonal antibody.
				Adoptive immunotherapy.
		PTLD of “true” lymphoma
		PTLD therapy in HSCT
		Exceptional clinical situations
		Other treatment modalities
		Prognostic indicators of treatment outcomes
		Infection prevention and anticipatory guidance
	References
19 Herpes simplex and varicella-zoster viruses
	Herpes simplex virus in transplant and oncology
		Epidemiology and risk factors
		Clinical manifestations
		Diagnosis
		Suppressive therapy and treatment
			Suppressive therapy.
			Treatment.
		Infection prevention
		Active or passive immunization
	Varicella-zoster virus in transplant and oncology
		Epidemiology and risk factors
		Clinical manifestations
		Diagnosis
		Treatment, prophylaxis, and prevention
			Treatment.
			Prophylaxis.
		Infection prevention
			Exposure avoidance and immunization of contacts.
		Vaccination
			Pretransplant vaccination.
			Vaccination after chemotherapy or transplant.
			Vaccines for zoster.
	Summary and future directions
	References
20 Human herpesvirus 6, 7, and 8
	Epidemiology and risk factors
		Human herpesvirus 6
		Human herpesvirus 7
		Human herpesvirus 8
	Clinical manifestations
		Hematopoietic stem cell transplant
		Solid organ transplant
		Oncology
		Disease prophylaxis/prevention
	Diagnosis
		Human herpesvirus 6
		Human herpesvirus 7
		Human herpesvirus 8
	Treatment
		Human herpesvirus 6
		Human herpesvirus 7
		Human herpesvirus 8
	Infection prevention and anticipatory guidance
	References
21 Respiratory viruses
	Epidemiology and risk factors
	Clinical manifestations
	Disease prophylaxis/prevention
		Influenza vaccination
			HCT recipients.
			SOT recipients.
			Oncology patients.
		Influenza chemoprophylaxis
		Other vaccines in development
		Prophylaxis for other viruses
	Diagnosis
		Sample type and handling
		Nucleic acid detection
	Treatment
		Supportive treatment
		Antiviral treatment
			Respiratory syncytial virus.
			Influenza.
			Parainfluenza.
			Other respiratory viruses.
		New therapeutics under investigation
	Infection prevention and anticipatory guidance
		Nosocomial outbreaks
		Infections in HCT candidates
		Infections in SOT candidates
	References
22 Adenoviruses
	Adenoviruses
	Epidemiology and risk factors
		Solid organ transplantation
		Hematopoietic stem cell transplantation
	Clinical manifestations
		Solid organ transplantation
		Hematopoietic stem cell transplantation
	Disease prophylaxis/prevention
	Diagnosis
	Treatment
		Antiviral agents
			Cidofovir.
			Brincidofovir.
			Ribavirin.
			Ganciclovir.
			Nitazoxanide.
		Immunotherapy
	Infection prevention and anticipatory guidance
	References
23 Bk and other polyomavirus associated diseases in children
	Viral structure and life cycle
	Epidemiology and risk factors
		General population
		Kidney transplantation
		Nonrenal solid organ transplantation
		Hematopoietic cell transplantation
	Clinical manifestations
		Nephropathy
		Hemorrhagic cystitis
	Disease prophylaxis/prevention
		Pretransplant approaches to prevent infection
		Posttransplant screening to prevent infection
	Diagnosis
		Nephropathy
		Hemorrhagic cystitis
	Treatment
	Infection prevention and anticipatory guidance
	References
24 Aspergillosis
	Epidemiology and risk factors
		Hematopoietic stem cell transplant
		Solid organ transplant
		Oncology
		Pediatric-specific invasive aspergillosis epidemiology
	Clinical manifestations
		Invasive pulmonary aspergillosis
		Invasive aspergillus sinusitis
		Cerebral aspergillosis
		Cutaneous aspergillosis
	Disease prophylaxis/prevention
	Diagnosis
		Cultures
		Radiology
			Pulmonary imaging.
			Brain imaging.
			Sinus imaging.
		Galactomannan antigen
			Serum galactomannan testing.
			Bronchoalveolar lavage.
		(1,3)-β-D-glucan
		Polymerase chain reaction
	Treatment
		Primary antifungal therapy for invasive aspergillosis
		Alternative antifungal therapy for invasive aspergillosis
		Salvage antifungal therapy for invasive aspergillosis
		Combination antifungal therapy for invasive aspergillosis
		Adjunctive therapies for invasive aspergillosis
	Infection prevention and anticipatory guidance
	References
25 Mucormycosis, fusariosis, scedosporiasis, and other invasive mold diseases
	Mucormycosis
		Epidemiology and risk factors
			Increasing incidence and breakthrough infections.
			Hematopoietic stem cell transplant.
			Solid organ transplant.
			Oncology.
			Prognosis and modifying factors.
		Clinical manifestations
			Pulmonary mucormycosis.
			Rhinocerebral mucormycosis.
			Cutaneous mucormycosis.
			Other forms of mucormycosis.
		Disease prophylaxis
		Diagnosis
			Diagnostic sampling.
			Primary diagnostic tests.
			Adjunctive and emerging diagnostic tests.
		Treatment
			Primary antifungal therapy
				Amphotericin B–based monotherapy.
				Triazole monotherapy.
				Combination antifungal therapy.
			Salvage antifungal therapy.
				Salvage therapy because of intolerance of primary therapy.
				Salvage therapy because of refractory or progressive disease.
			Step-down therapy and duration.
			Surgical management.
			Reversal of predisposing conditions and adjunctive therapy.
		Infection prevention and anticipatory guidance
	Fusariosis and Scedosporiasis
		Epidemiology and risk factors
			Hematopoietic stem cell transplant.
			Solid organ transplant.
			Oncology.
			Prognosis and modifying factors.
		Clinical manifestations
			Fusariosis.
			Scedosporiasis.
		Disease prophylaxis
		Diagnosis
		Treatment
			Antifungal therapy for fusariosis.
			Antifungal therapy for S. apiospermum species complex.
			Antifungal therapy for L. prolificans.
			Surgical management of fusariosis and scedosporiasis.
			Adjunctive therapy.
		Infection prevention and anticipatory guidance
	Other invasive mold diseases
		Epidemiology and risk factors
			Hematopoietic stem cell transplant.
			Solid organ transplant.
			Oncology.
		Clinical manifestations
			Localized manifestations.
			Invasive manifestations.
		Disease prophylaxis
		Diagnosis
		Treatment
			Antifungal therapy.
			Surgical management and other source control measures.
			Adjunctive therapy.
		Infection prevention and anticipatory guidance
	References
26 Candidiasis
	Epidemiology and risk factors
		Hematopoietic stem cell transplant
		Solid organ transplant
		Oncology
		Clinical manifestations
		Superficial and mucosal infections
			Dermatitis.
			Mucosal infections.
	Invasive candidiasis
		Candidemia.
		Genitourinary and renal candidiasis.
		Hepatosplenic (chronic disseminated) candidiasis.
		Intraabdominal candidiasis.
		Osteoarticular candidiasis.
		Endovascular candidiasis.
		Ocular candidiasis.
		Central nervous system candidiasis.
		Pulmonary candidiasis.
	Disease prophylaxis and prevention
		Hematopoietic stem cell transplant
		Solid organ transplant
		Oncology
	Diagnosis
		Laboratory findings
		Culture
		Non-culture detection methods
		Non-culture dna-based diagnostic tests
		Non-dna and non-culture diagnostic tests
	Treatment
		Definitive therapy based on candida species
		Definitive therapy based on location of infection
			Superficial candidiasis.
			Invasive candidiasis: Candidemia.
			Invasive candidiasis: Focal disease.
		Therapeutic drug monitoring
	Infection prevention and anticipatory guidance
		Prevention of recurrent infections
	References
27 Cryptococcosis and other rare invasive yeasts infections
	Cryptococcosis
		Background
		Epidemiology and risk factors
		Transplant recipients
		Malignancies
		Other risk factors for cryptococcosis
		Clinical manifestations
			Meningoencephalitis.
			Pneumonia.
		Other forms of disease.
		Diagnosis
		Treatment
		Management of increased intracanial pressure
		Immune reconstitution inflammatory syndrome
		Disease prophylaxis/prevention
		Other invasive yeast infections
	Trichosporon species infection
		Epidemiology and risk factors
			Clinical manifestations
			Diagnosis
			Treatment
	Rhodotorula species infections
		Epidemiology and risk factors
		Clinical manifestations
		Diagnosis
		Treatment
	Saccharomyces species infections
		Epidemiology and risk factors
		Clinical manifestations
		Diagnosis
		Treatment
	Geotrichum spp. infections
		Epidemiology and risk factors
		Clinical presentation
		Diagnosis
		Treatment
	References
28 Histoplasmosis, blastomycosis, and coccidioidomycosis
	Epidemiology of endemic mycoses
	Histoplasmosis
		Epidemiology and risk factors
		Clinical manifestations
		Disseminated histoplasmosis
		Histoplasmosis in oncology patients
		Histoplasmosis in transplant patients
		Diagnosis
		Medical imaging
		Histopathology
		Culture
		Serology
		Antigen detection
		Molecular testing
		Other assays
		Treatment
		Disease prophylaxis and prevention
	Blastomycosis
		Epidemiology and risk factors
		Clinical manifestations
		Diagnosis
		Treatment
		Disease prophylaxis and prevention
	Coccidioidomycosis
		Epidemiology and risk factors
		Clinical manifestations
		Diagnosis
		Treatment
		Disease prophylaxis and prevention
	References
29 Toxoplasma gondii
	Epidemiology and risk factors
		Clinical manifestations
	Disease prophylaxis and prevention
		Pretransplant monitoring
		Posttransplant monitoring
		Chemoprophylaxis
	Diagnosis
	Treatment
	Infection prevention and anticipatory guidance
	References
30 Nocardia and actinomyces
	Nocardia
		Epidemiology and risk factors
		Microbiology of nocardia
		Nocardiosis in solid organ transplant recipients
		Nocardiosis in hematologic malignancy and stem cell transplant
		Clinical presentation
		Prevention and prophylaxis
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Actinomyces
		Epidemiology
		Clinical presentation
		Prevention and prophylaxis
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	References
31 Pneumocystis pneumonia
	Epidemiology and risk factors
	Clinical manifestations
		Imaging
	Disease prophylaxis and prevention
		Trimethoprim-sulfamethoxazole
		Alternative agents
		Duration of prophylaxis
	Diagnosis
	Treatment
	Infection prevention and anticipatory guidance
	References
32 Strongyloides, cryptosporidium, and other parasitic infections
	Strongyloidiasis
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis and prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Cryptosporidium species
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis and prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Chagas disease
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis and prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Other intestinal parasites
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis and prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	References
33 Gastrointestinal viruses
	Norovirus
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis and prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Rotavirus
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis and prevention:
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Astrovirus
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis and prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Sapovirus
		Epidemiology and risk factors
		Clinical manifestations
		Disease prophylaxis and prevention
		Diagnosis
		Treatment
		Infection prevention and anticipatory guidance
	Adenovirus
	Conclusion
	References
34 Clostridioides difficile infection
	Epidemiology and risk factors
		Definitions of C. difficile disease and colonization
		C. difficile infection in pediatric sot recipients
		C. difficile infection in pediatric HSCT recipients
		C. difficile disease in pediatric oncologic patients
	Clinical manifestations
		Toxin detection and clinicopathologic correlation
		C. difficile disease
		Severe C. difficile disease
		Clinical outcomes
		Recurrence of C. difficile disease
		Diagnosis
	Treatment
		Primary and secondary prevention
	Conclusion
	References
Index
	A
	B
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	D
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	L
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	N
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	U
	V
	W
	Y
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