Monotherapy Versus Combination Therapy
1.5.2.2 Which Monotherapy to Choose A Cochrane review of antipseudomonal beta-
lactams for initial management of FN compared studies with ceftazidime, cefepime, piperacillin tazobactam, meropenem and imipenem Paul et al. 2010 . Cefepime monotherapy was shown to have a signifi cantly higher all-cause mortality which had been previously reported Yahav et al. 2007 . The Cochrane meta-analysis reported a nonsignifi cant higher rate of bacterial superinfection with cefepime which has been a reported concern due to its limited anaerobic profi le and poor coverage for skin infections Yahav et al. 2007 ; Paul et al. 2010 ; Kalil 2011 . A follow-up meta-analysis did not fi nd a statisti- cally signifi cant increased mortality with cefepime and current pediatric consensus guide- lines consider cefepime a reasonable choice for monotherapy Kim et al. 2010 ; Lehrnbecher et al. 2012 . Ceftazidime is not a good fi rst-line choice for monotherapy due to reduced Gram- positive coverage as well as induction of β-lactamase production leading to subsequent emergence of resistant pathogens and inferior clinical outcomes in pediatric patients Mebis et al. 1998 ; Ariffi n et al. 2000 ; Greenberg et al. 2005 . Paul et al. 2010 additionally noted that carbapenem monotherapy had similar all- cause mortality as other monotherapy regimens but was associated with higher rates of antibiotic- and Clostridium diffi cile -associated diarrhea. Pediatric meta-analyses have shown similar effectiveness between antipseudomonal cepha- losporins, antipseudomonal penicillins and car- bapenems as monotherapy but without the noted increase in Clostridium diffi cile -associated diar- rhea Manji et al. 2012b , c .1.5.2.3 Alterations in Initial Empiric FN Antibiotic Management
Once empiric therapy has been initiated, altera- tions in FN antibiotic management may be required to optimize treatment; these changes occur at the discretion of the practitioner or institution without signifi cant evidence basis. For instance, Lehrnbecher et al. 2012 recom- mend discontinuing combination therapy if initiated at presentation after 24–72 h in the stable patient without microbiologic evidence to continue both agents. Similarly, patients who are stable but with persistent fever should not have their initial regimen escalated. Those who become unstable should have additional coverage for potential resistant Gram-negative, Gram-positive and anaerobic causes initi- ated with consideration for fungal and viral etiologies.1.5.2.4 Outpatient Management of FN Although there remains a lack of one uniform
pediatric oncology risk stratifi cation system, many institutions have begun to utilize outpa- tient management of low-risk FN which can include outpatient oral or parenteral therapy as either initial management or as step-down to outpatient treatment after initial inpatient man- agement; such options and the evidence surrounding them are reviewed by Chisholm and Dommett 2006 . This differs from previ- ous studies in which low- risk patients were discharged early ANC 0.5 × 10 9 L but only after defervescence Mullen and Buchanan 1990 ; Aquino et al. 1997 ; Wacker et al. 1997 . Meta-analyses of effi cacy and safety from adult and pediatric studies found no signifi cant dif- ference in treatment failure in the inpatient ver- sus outpatient setting and no signifi cant difference in the effi cacy of outpatient oral ver- sus parenteral therapy in low-risk FN Teuffel et al. 2011b . Studies were extremely heterog- enous in terms of choice of antibiotics both oral and parenteral as well as timing of step- down making generalizations diffi cult. A recent Cochrane review of randomized controlled tri- als comparing oral versus intravenous anti- biotic therapy for FN found no significant difference in treatment failure or mortality Vidal et al. 2013 . The utilization of outpatient oral therapy specifi cally for pediatric patients either at FN presentation or as step-down after initial inpa- tient management was most recently reviewed by Manji et al. 2012a . Sixteen prospective tri- als were reviewed in the meta-analysis with no signifi cant difference between oral and paren- teral regimens and no outpatient infection- related mortality. None of the trials were randomized controlled trials specifi cally com- paring inpatient versus outpatient management and outcomes of low-risk FN Manji et al. 2012a . The types of oral agents utilized in pediatric studies are quite heterogenous and include amoxicillinclavulanate, cefi xime, fl uo- roquinolones ciprofl oxacin, gatifl oxacin and combination therapy ciprofl oxacin plus amoxi- cillin Mullen et al. 1999 ; Aquino et al. 2000 ; Paganini et al. 2000 , 2001 ; Shenep et al. 2001 ; Park et al. 2003 ; Petrilli et al. 2007 ; Dommett et al. 2009 ; Brack et al. 2012 . Ciprofl oxacin plus amoxicillinclavulanate is recommended as the oral regimen of choice in adult patients Freifeld et al. 2011 . Brack et al. 2012 recently reported on an RCT comparing contin- ued inpatient treatment versus oral outpatient management and found non- inferiority for effi cacy but lack of power to prove non-inferi- ority for safety. Many centers are continuing to initially admit all pediatric oncology FN patients with the poten- tial for early discharge with or without continued antibiotic support depending on the clinical con- text Gibson et al. 2013 . The United Kingdom recommends such a management strategy after 48 inpatient hours in patients 1 year of age, without medical or social comorbidities, not receiving extremely intensive therapy, appearing clinically well without a source of infection, with some marrow recovery i.e., ANC 0.1 × 10 9 L, and with fever improvement but not full defer- vescence necessary, for outpatient oral antibiotics to complete a 5-day course Gibson et al. 2013 . A recent survey of Canadian pediatric oncology centers found heterogenous treatment strategies from full inpatient care, to step-down care, to full outpatient care exemplifying the perceived lack of suffi cient data to uniformly modify practice Boragina et al. 2007 . Sung et al. 2004 reported in a survey of parents that only 53 supported initial FN outpatient management as compared to 71 of practitioners due to perceived increased fear and anxiety balanced with increased comfort, while early discharge and outpatient intravenous management are reportedly associated with improved health-related quality of life Cheng et al. 2011 . Finally, Teuffel et al. 2011a cal- culated that the most cost-effective model is one in which low-risk FN patients are treated entirely at home but through a parenteral rather than oral route. The risk of nosocomial infection NI with inpatient management must also be consid- ered and was reported to be 5.2 NI per 100 admissions by one group Simon et al. 2000 . The recent pediatric FN expert consensus guide- lines allow for consideration of initial or step- down outpatient management for the low- risk patient in the appropriate setting although as a weak recommendation Lehrnbecher et al. 2012 .1.5.2.5 Choice of Empiric Antifungal Therapy
The use of empiric antifungal therapy in neutro- penic children is also based upon limited data Pizzo et al. 1982 . Despite the low incidence ofParts
» 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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