Choice of Empiric Antifungal Therapy
1.5.3 Duration of Antimicrobial
Therapy: Empiric Versus Therapeutic Intent In the absence of documented or clinical concern for infection, empiric antimicrobial therapy is often continued until resolution of FN in both low- and high-risk patients. As mentioned, in low-risk pediatric patients, discontinuing antibi- otics prior to attaining an ANC 0.5 × 10 9 L has been shown safe if afebrile ≥24 h and with nega- tive cultures ≥48 h Mullen and Buchanan 1990 ; Aquino et al. 1997 ; Wacker et al. 1997 ; Lehrnbecher et al. 2002 ; Hodgson-Viden et al. 2005 ; Lehrnbecher et al. 2012 . Risk stratifi ca- tion in these studies was heterogenous with no set ANC threshold for early discharge; therefore, consensus pediatric guidelines recommend evi- dence of bone marrow recovery i.e., post nadir ANC ≥0.1 × 10 9 L prior to antimicrobial discon- tinuation Lehrnbecher et al. 2012 . Santolaya et al. 1997 have also shown in a small low-risk carefully selected pediatric cohort that antimicro- bials can be discontinued on day 3 of hospital admission prior to defervescence or neutrophil recovery; thus, consensus guidelines suggest dis- continuation of antimicrobials after 72 h of intra- venous antibiotic therapy in the patient who is afebrile ≥24 h even without evidence of bone marrow recovery as long as close follow-up is ensured Lehrnbecher et al. 2012 . Again, the data to support this practice comes from small prospective trials with no uniform risk strati- fi cation system. In high-risk patients, empiric antifungal therapy is usually discontinued once fever has resolved for ≥48 h with an ANC 0.5 × 10 9 L. If the patient remains afebrile and clinically stable, antibiotic therapies are discon- tinued. Although defi nitive evidence is lacking, the usual clinical practice is to remove one anti- microbial agent per 24 h time interval to observe for fever recrudescence if the patient is on combi- nation antimicrobial therapy. No pediatric studies address the appropriate management strategy in high-risk pediatric FN patients and specifi c man- agement of these patients is not addressed in the pediatric consensus guidelines Lehrnbecher et al. 2012 . For documented infection, duration of ther- apy is determined by the site, pathogen and clin- ical response to therapy. Most bacterial infections with notable exceptions including CNS infection, abscess formation and endovas- cular focus require 10–14 days of appropriate therapy, assuming complete clinical and micro- biologic response. In general, duration of anti- microbial therapy should be continued through a time of neutrophil recovery i.e., at least 5 days beyond ANC 0.5 × 10 9 L, although there is little evidence to support the effi cacy of this practice. For established IFI, prolonged therapy 4–6 weeks is necessary and concomitant immune recovery is critical for favorable out- comes Nucci et al. 2003 . The role for combi- nation antifungal therapy, particularly in the context of mold infection, requires further investigation; potential utilization of combina- tion therapy must balance the signifi cant drug interactions and potential side effects with ques- tionable benefi t Vazquez 2008 ; Spellberg et al. 2012 . The interested reader is directed to recently published IDSA guidelines for a more extensive discussion of infections due to Aspergillus , Candida and Cryptococcus Walsh et al. 2008 ; Pappas et al. 2009 ; Perfect et al. 2010 .1.5.4 Endovascular Sources
of Infection: Catheter Removal Any central venous access device CVAD can cause central line-associated bloodstream infection CLABSI, including a peripherally inserted central catheter PICC Advani et al. 2011 . As mentioned, although DTP between peripheral and central cultures can allow for determination of line infection versus bacte- remia, such information rarely changes man- agement. Rather, CVAD removal is necessary in the following clinical contexts: any blood- stream infection in which the CVAD is no lon- ger required, tunneled catheter site infection, hemodynamic instabilitysepsis, endocarditis or other endovascular infection e.g., throm- bophlebitis, persistent positive blood culture despite appropriate antimicrobial therapy for 72 h, and CLABSI due to highly resistant pathogens e.g., MRSA, ESBL Gram- negative bacilli, VRE or pathogens that are diffi cult to eradicate, particularly due to adhesive biofi lm production e.g., fungi, Propionibacterium spp., Bacillus spp. Mycobacterium spp. Mermel et al. 2009 . Delay in catheter removal for less virulent pathogens increases the risk for recur- rent CLABSI Raad et al. 2009 . Antibiotic lock therapy, instilling high concentrations of susceptible antibiotic or ethanol into the CVAD lumen, has been successfully used in combina- tion with systemic antimicrobial therapy to both eradicate and prevent CLABSI and should be considered when the CVAD cannot be removed e.g., limited access sites in the patient Fortun et al. 2006 ; Flynn 2009 .Parts
» 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
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