Risk Stratifi cation Prevention of Bacterial
14.2.2 Antimicrobial Approaches
14.2.2.1 Adult Data
Antibacterial prophylaxis for afebrile patients receiving myelosuppressive chemotherapy is widely adopted in adult oncology practice based on data from trials preformed over the last 30 years with more than 100 published studies evaluating various antibiotic regimens. Two large contemporary studies in adult solid tumor, lym- phoma and leukemia patients compared levofl ox- acin to placebo using a double-blind, randomized, controlled design Bucaneve et al. 2005 , Cullen et al. 2005 . Although neither study was able to show a signifi cantly decreased rate of death in the levofl oxacin arm, both studies showed that pro- phylaxis signifi cantly decreased episodes of fever, clinically documented infection and hospi- talization. In solid tumor and lymphoma patients, Cullen et al. 2005 reported a 34.2 rate of infection with levofl oxacin compared to 41.5 in the placebo arm RR 0.82, 95 CI 0.73–0.94, p = 0.004 while Bucaneve et al. 2005 reported 22 infection rate in the levofl oxacin arm versus 39 with placebo absolute risk difference –0.17, 95 CI –0.24 to –0.10 in patients with leukemia, lymphoma and solid tumors. Meta-analysis of randomized controlled trials has shown that prophylaxis has an impact on incidence of infection and, more important, is associated with a decreased risk of death Gafter- Gvili et al. 2012 . All-cause mortality was reduced in patients receiving prophylaxis RR 0.66, 95 CI 0.55–0.79, with the number of patients needed to treat to prevent death from any cause being 34 95 CI 26–56. The most sub- stantial effect was found in studies that used fl uo- roquinolones FQs as prophylaxis with the greatest benefi t in those at the highest risk.14.2.2.2 Pediatric Data Data regarding the utility of bacterial prophylaxis
in neutropenic children are very limited. Early studies using trimethoprim-sulfamethoxazole, erythromycin, and amoxicillin-clavulanate were hampered by diffi culties with patient accrual and compliance with oral therapies Pizzo et al. 1983 ; van Eys et al. 1987 ; Castagnola et al. 2003 . Studies which have documented benefi t are lim- ited by small patient numbers at single institu- tions. For instance, a single arm pilot trial of ciprofl oxacin prophylaxis in children receiving a reinduction block of therapy for ALL showed a decreased incidence of hospitalization, bactere- mia and intensive care unit admissions compared to historical controls Yousef et al. 2004 . Specifi cally, hospitalization was 90 in the con- trols versus 58 in the study group p 0.001, the overall rate of proven bacteremia was 22 in the controls versus 9 in the ciprofl oxacin group p = 0.028, and there were no Gram-negative bacteremias in this group as compared to 7.7 in the controls p 0.001 Yousef et al. 2004 . Similarly, a retrospective study in pediatric AML patients of prophylactic cefepime, or pro- phylactic vancomycin with ciprofl oxacin or a cephalosporin, showed decreased rates of septi- cemia and hospital days compared to historical controls while patients who received only an oral cephalosporin as prophylaxis had no signifi cant decrement in bacterial sepsis or hospital days compared with controls Kurt et al. 2008 . A recent survey by the Children’s Oncology Group COG of institutional standards for sup- portive care during AML trial AAML0531 found that antibacterial prophylaxis signifi cantly reduced Gram-positive sterile site infection inci- dence rate ratio [IRR] 0.71, 95 CI 0.57–0.90, p = 0.004 with a trend toward reducing all bacte- rial infection IRR 0.85, 95 CI 0.72–1.01, p = 0.058 Sung et al. 2013 .14.2.3 Risks of Prophylaxis
The main concern when considering prophylactic antibiotics is the potential development of bacte- rial resistance. Any exposure to antibiotics increases the risk of colonization and possible subsequent infection with resistant pathogens. Resistance can be acquired by selection of previ- ously undetectable but present bacteria or de novo in a previously susceptible organism. Resistant pathogens can be transmitted from patient to patient. Studies performed in the 1980s in patients with leukemia and in those undergo- ing hematopoietic stem cell transplant HSCT documented that surveillance stool cultures could often detect pathogens preceding the develop- ment of bacteremia Schimpff et al. 1972 ; Tancrede and Andremont 1985 ; Wingard et al. 1986 . Patients identifi ed as having a resistant organism in their stool were much more likely to have a subsequent infection with a resistant pathogen. Systematic studies evaluating the impact of FQ prophylaxis on the bacterial resis- tance profi les from sterile site cultures in oncol- ogy patients are limited. As anticipated with any broad antibacterial use, centers with extensive use of FQs have documented increased rates of clinically relevant FQ-resistant pathogens Razonable et al. 2002 ; Kern et al. 2005 ; Prabhu et al. 2005 . The two large contemporary double- blind studies of levofl oxacin prophylaxis, which combined included 2,325 patients, did not note increased rates of resistant organisms from sterile site cultures; however, the studies were not pow- ered to detect this outcome Bucaneve et al. 2005 ; Cullen et al. 2005 . Specifi cally, Bucaneve et al. 2005 noted 3 of patients in the levofl oxacin group had FQ-resistant Gram-negative bacilli as compared to 1 in the placebo group absolute risk difference 2 , 95 CI –0.4 to 3 , p = 0.10 while Cullen et al. 2005 did not rou- tinely test for FQ sensitivity. The use of antibacterial prophylaxis also has potential risk for other infectious complications. Exposure to FQs in adult oncology patients has been associated with increased incidence of Clostridium diffi cile -associated diarrhea CDAD von Baum et al. 2006 . Rates of CDAD in hospi- talized pediatric patients remain signifi cantly lower than their adult counterparts although has increased in the last decade Kim et al. 2008a . Additionally, there is theoretical concern that antibacterial prophylaxis may increase the rate of invasive fungal infection IFI though the data available do not support this concern Gafter- Gvili et al. 2012 . FQs are the class of antibiotic most intensively investigated for antibacterial prophylaxis in adult oncology patients; in meta-analysis, FQs are the agents associated with the greatest benefi t Gafter-Gvili et al. 2012 . As a class their safety profi le is similar to other antibiotics with unique toxicities including rare but consistent associa- tion with tendonitis and tendon rupture with those 60 years of age and receiving concomitant steroids at greatest risk, as well as possible asso- ciation with retinal detachment Owens and Ambrose 2005 ; Etminan et al. 2012 . Concern regarding potential FQ toxicity in children arose from early preclinical data that associated FQ exposure to articular cartilage damage in young animals although there is now signifi cant litera- ture describing the safety in children Hampel et al. 1997 ; Jick 1997 ; Redmond 1997 ; Bradley et al. 2007 ; Schaad 2007 , Noel et al. 2008 . Toxicity analysis in more than 2,500 pediatric patients reported that levofl oxacin exposure was associated with an increased rate 3.4 vs. 1.8 , p = 0.025 of musculoskeletal complaints primarily arthralgia at 12 months postexposure though the quality of symptoms was not different in the exposed and unexposed groups Noel et al. 2007 . Some concern remains that the results were biased by the open-label study design. Currently only ciprofl oxacin is approved in theParts
» 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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