Risk Stratifi cation Prevention of Pneumocystis
14.4.2 Approaches to PCP Prophylaxis
PCP reactivation or infection is generally thought preventable in patients with cancer with adminis- tration of classical prophylaxis with trimethoprim- sulfamethoxazole TMP-SMX. However, in the setting of alternative prophylaxis agents or TMP- SMX noncompliance, episodes of PCP do still occur beginning about 2 months following initia- tion of chemotherapy and continuing through recovery of T-cell functional immunity. TMP acts by interfering with dihydrofolate reductase, inhib- iting synthesis of tetrahydrofolic acid and thus nucleic acid synthesis. TMP-SMX administration in conjunction with antifolates for ALL treatment can lead to marrow suppression and may require lowering of chemotherapy doses Levinsen et al. 2012 . The necessary amount of TMP-SMX required to prevent PCP has not been well stud- ied, and a variety of dosing regimens exist, with 2 or 3 days per week administration being the most common Agrawal et al. 2011 . Generally, TMP- SMX is continued for at least 3 months following chemotherapy, though this recommendation is not evidence-based as studies have shown a variable rate of T-cell recovery after chemotherapeutic regimens, potentially dependent on patient age and chemotherapeutic intensity Mackall et al. 1995 ; Azuma et al. 1998 ; Mazur et al. 2006 . In addition to possible bone marrow sup- pression, many patients have allergies or other reactions to TMP-SMX that induce clinicians to prematurely discontinue its use. However, the optimal second-line prophylactic agent is not well defi ned and all options appear to be potentially less effective than TMP-SMX. Agents that have been used include oral dapsone, intravenous or inhaled pentamidine and oral atovaquone. Dapsone is inexpensive but has a high incidence Table 14.5 Graded recommendations for interventions to prevent fungal infections in pediatric oncology patients Grade Comments References Data from studies of adult or adolescent patients a Data from studies of or including pediatric patients a Antifungal prophylaxis should generally not be utilized for patients with newly diagnosed ALL None Antifungal prophylaxis with fl uconazole should be considered for patients undergoing reinduction for relapsed ALL b None Antifungal prophylaxis with a minimum of fl uconazole can be considered for patients undergoing chemotherapy for AML although pediatric evidence is mixed 1A 1B b Antifungal prophylaxis with an echinocandin or posaconazole can also be considered; there is no accepted dose of posaconazole for children 13 years of age Mattiuzzi et al. 2006 ; Cornely et al. 2007 ; Robenshtok et al. 2007 ; Lehrnbecher et al. 2009 ; Sung et al. 2013 ; Science et al. 2014 Antifungal prophylaxis should generally not be utilized for patients with solid tumors 2B Science et al. 2014 ALL acute lymphoblastic leukemia, AML acute myelogenous leukemia a Level of evidence per Guyatt et al. 2006 ; see Preface b Area in urgent need of further investigation 14 of adverse events, especially in patients with glucose- 6-phosphate dehydrogenase G6PD defi ciency Sangiolo et al. 2005 . Intravenous pentamidine every 4 weeks has also been used, though inadequate protection has been noted in children 2 years of age and in those undergo- ing HSCT, who may require more frequent dos- ing Kim et al. 2008 b . Aerosolized pentamidine is generally well tolerated other than occasional bronchospasm, but its effectiveness has been questioned and it requires a compliant patient, generally 6 years of age and older Vasconcelles et al. 2000 . Atovaquone is also well tolerated, but absorption can be limited in patients not eating diets containing fatty foods. In vitro, the echino- candin class of antifungal agents appears to have some activity against the cyst form of P. jiroveci . To date, no study has evaluated an echinocandin as a solitary prophylactic agent; however, a few case reports have described their potential utility in combination with TMP-SMX for the treatment of PCP Annaloro et al. 2006 ; Beltz et al. 2006 .14.4.3 Summary of the Recommendations
from Guidelines for PCP Prophylaxis Perhaps because PCP prophylaxis is near- universal and of little controversy, the IDSA does not have guidelines for PCP prophylaxis in patients receiving chemotherapy. The joint guidelines of the American Society for Blood and Marrow Transplantion ASBMT, IDSA and others list TMP- SMX as fi rst choice, with dapsone, atovaquone and both forms of pentamidine as acceptable alternatives in pediatric HSCT patients Tomblyn et al. 2009 .14.4.4 Future Directions
Although questions remain regarding the dosing schedule and toxicities of TMP-SMX as well as the optimal second-line agents, the relative rarity of PCP infection today except in the setting of medication noncompliance makes the perfor- mance of future prospective trials a daunting endeavor, as the power required to show differ- ences in outcome would require enormous num- bers of patients. In this unique infection, large retrospective analyses may be the only way to obtain useful information on how to standardize approaches to optimal PCP prophylaxis.14.5 Prevention of Viral Infections
Although signifi cant questions are yet to be answered, the foundation for preventing bacterial and fungal infections has been established. This foundation includes a logical approach of strati- fying patients by risk of infection and then insti- tuting prophylactic therapy for high-risk patients. For many reasons, this preventative model can- not be easily adapted to viral pathogens. First, children with cancer are at risk of infection from a wide variety of viruses with various modes of transmission including from close contacts and the surrounding environment or from reactiva- tion within the patient. Second, establishing risk strata that can be generically applied to all viral infections is extremely challenging; host fac- tors, such as prolonged lymphopenia in a well- appearing child with ALL that increases the risk for certain viral infections, are not traditionally considered risk factors and the course of infec- tion can be extremely variable from benign in one immunosuppressed patient to fatal in another. Third, there are limited effective antiviral thera- peutic options that can be employed in a prophy- lactic manner; the few antiviral options that do exist often have activity against specifi c viruses, thus limiting their impact as broad-spectrum pro- phylactic options. Therefore, in order to effectively prevent viral infections, a more comprehensive approach that targets the patient, close contacts of the patient and the patient’s environment is necessary. Despite these challenges some important strate- gies have been developed including preexposure prophylaxis i.e., vaccination, postexposure pas- sive prophylaxis i.e., immunoglobulin, chemo- prophylaxis, suppressive therapy i.e., prevention of viral reactivation, hospital infection control practices and anticipatory guidance to be applied in the home or school setting. Here, suppressive therapy, chemoprophylaxis and hospital infectionParts
» Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Introduction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» History and Physical Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Defi ning the Risk for Serious
» Initial Laboratory Evaluation Diagnostic Evaluation
» Chest Radiography CXR A supine CXR may identify pleural effusions,
» Computed Tomography CT Radiographic Imaging
» Magnetic Resonance Imaging MRI
» Positron Emission Tomography PET
» Aspergillus Galactomannan GMN Biomarkers for Invasive
» 1,3-β- Biomarkers for Invasive
» Polymerase Chain Reaction PCR
» Viral Studies Diagnostic Evaluation
» Invasive Procedures: Diagnostic Evaluation
» Adult FN Guidelines Empiric Management
» Monotherapy Versus Combination Therapy
» Which Monotherapy to Choose A Cochrane review of antipseudomonal beta-
» Alterations in Initial Empiric FN Antibiotic Management
» Outpatient Management of FN Although there remains a lack of one uniform
» Choice of Empiric Antifungal Therapy
» Duration of Antimicrobial Empiric Management
» Endovascular Sources Empiric Management
» Adjunctive Treatment Empiric Management
» Emergence of Resistant Empiric Management
» Red Blood Cell Administration
» Granulocyte Transfusion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hemolytic Transfusion Risks of Blood Product
» Infection and Sepsis Risks of Blood Product
» Allergic Reactions Risks of Blood Product
» Febrile Nonhemolytic Risks of Blood Product
» Transfusion-Related Acute Risks of Blood Product
» Transfusion-Associated Risks of Blood Product
» Iron Overload Risks of Blood Product
» Laboratory Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» General Management Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Alkalinization Urinary alkalinization has been a long-standing
» Allopurinol Allopurinol inhibits xanthine oxidase, an enzyme
» Rasburicase Rasburicase, recombinant urate oxidase, converts
» Renal Interventions Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pathophysiology Superior Vena Cava
» History and Physical Exam SVCSSMS should be suspected in a patient
» Imaging Studies The diagnosis of SVCSSMS is often made on
» Other Studies Tissue is required to make a defi nitive diagnosis
» Treatment Superior Vena Cava
» History and Physical Exam Small pericardial effusions are frequently asymp-
» Imaging and Other Studies The presence of a pericardial effusion can be
» History and Physical Exam Many patients with small pleural effusions are
» Imaging Studies When a pleural effusion is suspected, a chest
» History and Physical Exam Patients with pheochromocytoma typically have
» Laboratory Studies The diagnosis of pheochromocytoma is best made
» Imaging Studies Clinical Presentation
» Pulmonary Leukostasis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Presentation Spinal Cord Compression
» Differential Diagnosis Spinal Cord Compression
» Imaging MRI of the spine can help narrow the differential
» Surgery Surgery in spinal cord compression can be uti-
» Radiation Therapy The advantages of external beam radiation ther-
» Outcomes Spinal Cord Compression
» Presentation Altered Mental Status
» Initial Management Altered Mental Status
» Metabolic The metabolic causes of AMS or seizure in pedi-
» Chemotherapy-Associated Neurotoxicity Differential Diagnosis
» Posterior Reversible Encephalopathy Syndrome
» Outcomes Altered Mental Status
» Initial Management Increased Intracranial
» Soft Tissue A large meta-analysis of published data suggests
» Cerebrospinal Fluid Hydrocephalus is an excess of CSF within the
» Hemorrhage and Thrombosis Differential Diagnosis
» Idiopathic Intracranial Hypertension Differential Diagnosis
» Presentation of Stroke Cerebrovascular Disease
» Differential Diagnosis Cerebrovascular Disease
» Etiology of Stroke in Pediatric
» Ischemic Stroke After an ischemic stroke is diagnosed, the patient
» Hemorrhagic Stroke Hematomas can expand over several hours from
» Acute Lymphoblastic Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Myelogenous Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Promyelocytic Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Chronic Myelogenous Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Tumor Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Leukapheresis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hyperhydration Other Treatment Modalities
» Hydroxyurea Other Treatment Modalities
» Cranial Irradiation Other Treatment Modalities
» Pseudohyperkalemia Hyperleukocytosis has been noted to cause pseudo-
» Pseudohypoxemia Due to the rapid consumption of oxygen by leu-
» Pseudohypoglycemia Consumption of glucose by excess leukocytes
» Pseudothrombocytosis Leukemic blast lysis can lead to cell fragmenta-
» Transfusion Practice with Other Supportive Care
» Anesthetic Procedures Other Supportive Care
» Neutropenic Enterocolitis Gastrointestinal Infection
» Perirectal Abscess Gastrointestinal Infection
» Gastrointestinal Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pancreatitis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Bowel Obstruction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Abdominal Compartment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» ALL Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Other Malignancies Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Central Venous Catheters Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diagnosis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nociceptive Pain Types of Pain
» Neuropathic Pain Types of Pain
» World Health Organization Pharmacologic Treatment
» Intermittent Opioid Use Pharmacologic Treatment
» Long-Acting Opioids Pharmacologic Treatment
» Breakthrough Dosing Pharmacologic Treatment
» Opioid Rotation Pharmacologic Treatment
» Patient-Controlled Analgesia Pharmacologic Treatment
» Constipation Side Effects of Opioids
» Nausea and Vomiting Nausea and vomiting are rare opioid side effects
» Pruritus Pruritus is a common side effect of opioid use
» Sedation Side Effects of Opioids
» Confusion and Agitation Renal and hepatic function should be checked
» Respiratory Depression When dosed appropriately, opioids rarely result
» Myoclonus Patients receiving very high doses of opioids for
» Urinary Retention Urinary retention can be caused by any opioid but
» Calcium Channel Blockers Neuropathic Pain
» Serotonin and Norepinephrine Neuropathic Pain
» Tricyclic Antidepressants Neuropathic Pain
» Interventional Techniques Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vincristine-Related Peripheral Oncology-Specifi c Pain
» Osteonecrosis Oncology-Specifi c Pain
» Post-lumbar Puncture Oncology-Specifi c Pain
» Mucositis Pain Oncology-Specifi c Pain
» Pathophysiology of Emesis Chemotherapy-Induced
» Principles of Emesis Control in the Cancer Patient
» Emetogenicity of Chemotherapy Chemotherapy-Induced
» Dopamine Receptor Antagonists Classes of Antiemetics
» Corticosteroids Classes of Antiemetics
» Cannabinoids The plant Cannabis contains more than 60 differ-
» Other Antiemetic Agents Antihistamines
» Alternative Therapies Ginger Classes of Antiemetics
» Management of CINV Management of CINV Table
» Special Considerations Anticipatory Nausea and Vomiting
» Radiation-Induced Nausea Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Initiation The initiation stage occurs immediately following
» Primary Damage Response Pathophysiology of Oral Mucositis
» Signal Amplifi cation Pathophysiology of Oral Mucositis
» Ulceration Ulceration is the phase with the most clinical sig-
» Healing Pathophysiology of Oral Mucositis
» Clinical Course of Oral Mucositis
» Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Palifermin Prevention and Treatment
» Low-Level Laser Therapy Prevention and Treatment
» Glutamine Prevention and Treatment
» Cryotherapy Prevention and Treatment
» Oral Care Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Infections Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nutrition Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Dietary Counseling Nutrition Intervention
» Appetite Stimulants Nutrition Intervention
» Enteral Tube Feeding Nutrition Intervention
» Parenteral Nutrition Nutrition Intervention
» Nutrition and Survivorship Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Neutropenia Hematologic Toxicity
» Management of Thrombocytopenia Hematologic Toxicity
» Management of Anemia Hematologic Toxicity
» Somnolence Syndrome Central Nervous System
» Lhermitte’s Sign Central Nervous System
» Skin Complications Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Mucositis Head and Neck
» Ear Complications Head and Neck
» Laryngeal Complications Head and Neck
» Dysphagia and Esophagitis Gastrointestinal
» Nausea, Vomiting and Anorexia
» Pneumonitis Major Organ Infl ammation
» Pericarditis Major Organ Infl ammation
» Hepatitis Major Organ Infl ammation
» Nephropathy Major Organ Infl ammation
» Cystitis Major Organ Infl ammation
» Risk Stratifi cation Prevention of Bacterial
» Adult Data Antimicrobial Approaches
» Pediatric Data Data regarding the utility of bacterial prophylaxis
» Risks of Prophylaxis Prevention of Bacterial
» Guidelines and Current Usage of Antibacterial Prophylaxis
» Protocols for Line Placement and Care
» Antibiotic and Ethanol Locks
» Chlorhexidine Cleansing Chlorhexidine gluconate CHG is a bactericidal
» Future Directions Prevention of Bacterial
» Risk Stratifi cation Prevention of Fungal
» Approaches to Antifungal Prophylaxis
» Guideline Recommendations for Antifungal Prophylaxis
» Limitations of Current Options for Antifungal Prophylaxis
» Risks of Prophylaxis Prevention of Fungal
» Biomarkers Prevention of Fungal
» Future Directions Prevention of Fungal
» Risk Stratifi cation Prevention of Pneumocystis
» Approaches to PCP Prophylaxis
» Summary of the Recommendations
» Future Directions Prevention of Pneumocystis
» Postexposure Chemoprophylaxis Prevention of Viral Infections
» Suppressive Therapy Prevention of Viral Infections
» Future Directions Prevention of Viral Infections
» Hand Hygiene Infection Control Practices
» Mandatory Vaccination Infection Control Practices
» Hospital Isolation Practices Infection Control Practices
» Visitor Screening Policies Infection Control Practices
» Work Restriction Infection Control Practices
» Cytomegalovirus CMV Status of Transfused Blood
» Treatment of Myelosuppression with
» Prevention of Febrile Neutropenia, Delay
» Treatment of Febrile Neutropenia
» Treatment of Myelosuppression Clinical Usage of Myeloid Growth Factors
» Comparison of Granulocyte Colony-Stimulating Factor
» Optimal Dosing Adult guidelines recommend dosing of 5 mcgkg
» Route of Administration Optimal Administration of Colony-Stimulating Factors
» Optimal Timing Optimal Administration of Colony-Stimulating Factors
» Erythropoietin Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Interleukin-11 Platelet Growth Factors
» Thrombopoietin Receptor Agonists Platelet Growth Factors
» Immune Status Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Status During Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Recovery After Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immunization Practice Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diphtheria, Tetanus, and Acellular Pertussis
» Pneumococcal Conjugate Vaccine Recommendations
» Hemophilus Infl uenzae Type b
» Inactivated Infl uenza Vaccine Although in a Cochrane review Goossen et al.
» 2009 H1N1 Pandemic Vaccine Seven studies have reported on effi cacy of the
» Live Attenuated Infl uenza Vaccine
» Meningococcal Conjugate Vaccine Recommendations
» Varicella Zoster Virus Recommendations
» Recommendations Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Treatment of Hypogammaglobulinemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vaccination of Household Contacts
» Peripherally Inserted Central Catheter
» External Tunneled Central Venous Catheter
» Implanted Port Types of Central Venous
» Catheter Insertion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Exit Site Infection Infection
» Prevention of Infection Infection
» Drug Precipitate or Lipid Residue Occlusion Thrombotic Occlusion
» Evaluation of Catheter- Related Thrombosis
» Treatment of Catheter- Related Thrombosis
» Special Considerations During Anticoagulation Therapy
» Contraindications of Anticoagulant Therapy
» Skin Antisepsis Catheter Maintenance
» Central Venous Catheter Dressings
» Hub Care Catheter Maintenance
» Central Venous Catheter Flushing and Locking
» Chlorhexidine Bathing Chlorhexidine has been shown to be effective in
» Antiseptic Needleless Connectors and Antiseptic
Show more