{"product_id":"fever-of-unknown-origin-in-neutropenic-cancer-patients-a-patient-friendly-guide-to-the-2017-german-agiho-guidelines","title":"Fever of Unknown Origin in Neutropenic Cancer Patients: A Patient-Friendly Guide to the 2017 German AGIHO Guidelines","description":"\u003cp\u003eFever can be the only warning sign of a serious infection in cancer patients whose white blood cell counts have fallen sharply after chemotherapy. These updated German guidelines, issued by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO), explain how doctors should diagnose and treat \"fever of unknown origin\" (FUO) in adult neutropenic cancer patients. The guidelines stress that treatment must begin within 2 hours of fever onset, and they divide patients into standard-risk and high-risk groups to guide how aggressive the initial antibiotic therapy should be. High-risk patients need broad-spectrum antibiotics that cover dangerous bacteria such as \u003cem\u003ePseudomonas aeruginosa\u003c\/em\u003e, and if neutropenia is expected to last more than 7 days, antifungal therapy against \u003cem\u003eAspergillus\u003c\/em\u003e species may also be needed.\u003c\/p\u003e\n\n\u003ch1\u003eFever of Unknown Origin in Neutropenic Cancer Patients: A Patient-Friendly Guide to the 2017 German AGIHO Guidelines\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eWhy This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eHow the Guidelines Were Developed\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#definitions\"\u003eKey Definitions: Neutropenia and Fever\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#grading\"\u003eHow Doctors Grade Recommendations and Evidence\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#risk\"\u003eRisk Stratification: Standard-Risk vs. High-Risk Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#mascc\"\u003eThe MASCC Score: Identifying Standard-Risk Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#outpatient\"\u003eCriteria for Outpatient Management\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#epidemiology\"\u003eWhat Causes Fever in Neutropenic Patients?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#local-epidemiology\"\u003eLocal Resistance Patterns and Fluoroquinolone Prophylaxis\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#baseline\"\u003eBaseline Tests Before Starting Chemotherapy\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#fungal\"\u003eScreening for Fungal Infections in Asymptomatic Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#fever-onset\"\u003eDiagnostic Tests at the Moment Fever Begins\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#clinical-signs\"\u003eWhat Specific Symptoms Tell Doctors\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#first-line\"\u003eAntimicrobial Treatment: First-Line Antibacterial Therapy\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#combination\"\u003eAntibacterial Combination Therapy\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eClinical Implications for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of These Guidelines\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations for Patients and Caregivers\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"background\"\u003eWhy This Research Matters\u003c\/h2\u003e\n\u003cp\u003eCancer patients who develop neutropenia (a dangerously low count of neutrophils, the white blood cells that fight bacterial and fungal infections) are at high risk of infectious complications. The level of risk depends on how low the neutrophil count drops and how long it stays low, as well as on additional factors such as suppressed immunity and damage to skin and mucosal barriers. The duration and lowest point (nadir) of neutropenia are directly correlated with the incidence of fever and infections.\u003c\/p\u003e\n\u003cp\u003eThese infections cause significant illness and death, and they may also force doctors to delay or reduce further chemotherapy. When a neutropenic patient develops fever of unknown origin (FUO, meaning fever without an immediately obvious source), prompt and effective, evidence-based treatment is mandatory.\u003c\/p\u003e\n\u003cp\u003eOver the past decade, resistance among bacteria to widely used antibiotics, particularly beta-lactams (such as penicillins and cephalosporins) and fluoroquinolones (such as ciprofloxacin), has increased. At the same time, only a small number of newer antimicrobial drugs have become available. These include tigecycline, linezolid, moxifloxacin, cefozopran, telavancin, oritavancin, ceftazidime-avibactam, ceftolozan-tazobactam, and micafungin. However, data on using these newer agents empirically (without knowing the exact germ) in neutropenic patients are limited or do not exist.\u003c\/p\u003e\n\u003cp\u003eNew diagnostic tests and biomarkers (biological signs of infection or inflammation) also need careful evaluation. This guideline, which updates a 2003 version, focuses on risk-adapted diagnostic procedures and empirical antimicrobial treatment in neutropenic cancer patients with FUO. The goal is to tailor the approach according to each patient's likelihood of a complicated course of infection.\u003c\/p\u003e\n\u003cp\u003eThe AGIHO has published separate guidelines for related topics, including sepsis, prevention of bacterial and fungal infections, prevention of infections after allogeneic stem cell transplantation, invasive fungal infections, pulmonary infiltrates, abdominal complications, venous catheter infections, central nervous system infections, infections after autologous stem cell transplantation, and community respiratory viral infections.\u003c\/p\u003e\n\n\u003ch2 id=\"methods\"\u003eHow the Guidelines Were Developed\u003c\/h2\u003e\n\u003cp\u003eA group of hematologists, oncologists, and infectious disease specialists was formed within the AGIHO. The team performed a thorough literature search that included only full publications and excluded studies of allogeneic hematopoietic stem cell transplant (a stem cell transplant from a donor) recipients.\u003c\/p\u003e\n\u003cp\u003eThe experts created a set of core slides with statements and recommendations. These were discussed in face-to-face meetings, telephone conferences, and electronic correspondence. The final version was approved at an AGIHO plenary meeting on 10 February 2017, and the manuscript was reviewed by all co-authors. A detailed methodological report is available in the online supplementary material of the original article.\u003c\/p\u003e\n\n\u003ch2 id=\"definitions\"\u003eKey Definitions: Neutropenia and Fever\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eNeutropenia\u003c\/strong\u003e is defined as a neutrophil count (segments and bands) below 500\/μl (microliter), or below 1000\/μl with a predicted decline to below 500\/μl within the next 2 days. There is no single cut-off value that clearly separates patients with and without increased risk of infections, but this definition matches most recommendations and risk stratifications used in clinical trials.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eFever\u003c\/strong\u003e in neutropenia is defined as one of the following:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eA temperature measured orally (in the mouth) of 38.3°C (101°F) or higher on one occasion, OR\u003c\/li\u003e\n  \u003cli\u003eA temperature of 38.0°C (100.4°F) or higher lasting for at least 1 hour, OR\u003c\/li\u003e\n  \u003cli\u003eA temperature of 38.0°C or higher measured twice within 12 hours, OR\u003c\/li\u003e\n  \u003cli\u003eAny other method shown to be equivalent to these results\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eWhen no definite non-infectious cause is found, fever must be regarded as a sign of an infectious complication. Possible non-infectious causes include a febrile reaction to cytokines (immune-signaling proteins), cytotoxic drugs (chemotherapy agents such as cytarabine or bleomycin), or a transfusion of blood products.\u003c\/p\u003e\n\u003cp\u003eDoctors must also remember that fever can be hidden by antipyretic drugs (fever-reducing medicines) used for pain or cancer treatment. These include prednisone (a corticosteroid), non-steroidal anti-inflammatory drugs (NSAIDs such as ibuprofen), and metamizole (dipyrone).\u003c\/p\u003e\n\n\u003ch2 id=\"grading\"\u003eHow Doctors Grade Recommendations and Evidence\u003c\/h2\u003e\n\u003cp\u003eThe guidelines use a grading system adapted from the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). This system tells clinicians how strongly a recommendation is supported and how good the underlying evidence is.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrength of recommendation:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGrade A:\u003c\/strong\u003e Strongly supports a recommendation for use\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGrade B:\u003c\/strong\u003e Moderately supports a recommendation for use\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGrade C:\u003c\/strong\u003e Marginally supports a recommendation for use\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGrade D:\u003c\/strong\u003e Supports a recommendation against use\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003e\u003cstrong\u003eQuality of evidence:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLevel I:\u003c\/strong\u003e Evidence from at least 1 properly designed randomized, controlled trial\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLevel IIa:\u003c\/strong\u003e Evidence from at least 1 well-designed clinical trial without randomization; from cohort or case-controlled analytic studies (preferably from more than 1 center); from multiple time series; or from dramatic results of uncontrolled experiences\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLevel III:\u003c\/strong\u003e Evidence from opinions of respected authorities, based on clinical experience, descriptive case studies, or reports of expert committees\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eAn added index letter is used in some recommendations. The letter \"r\" means a meta-analysis or systematic review of randomized controlled trials; \"t\" means transferred evidence from different patient cohorts or similar immune-status situations; \"h\" means the comparator group is a historical control; and \"u\" means an uncontrolled trial. For example, a recommendation labeled \"BIIr\" is a moderately strong recommendation supported by evidence from meta-analyses of randomized trials.\u003c\/p\u003e\n\n\u003ch2 id=\"risk\"\u003eRisk Stratification: Standard-Risk vs. High-Risk Patients\u003c\/h2\u003e\n\u003cp\u003eThe incidence of infections in cancer patients is directly related to the lowest point (nadir) and duration of neutropenia. However, predicting the exact course in an individual patient is difficult. Clinical trials on treating fever in patients with short periods of neutropenia (below 5 or 7 days) are limited, and some patients with neutropenia lasting more than 5 days have been enrolled in studies involving oral therapy and outpatient care.\u003c\/p\u003e\n\u003cp\u003eAfter reviewing the literature, the expert panel agreed on stratifying patients into two risk groups:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eStandard risk:\u003c\/strong\u003e expected duration of neutropenia of up to 7 days\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHigh risk:\u003c\/strong\u003e expected duration of neutropenia of at least 8 days\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eAll patients with neutropenia lasting 8 or more days are considered high-risk patients with respect to a complicated course of a febrile episode. However, patients assigned to the standard-risk group may have individual characteristics that justify classifying them as high-risk as well. These individual factors can be identified using the Multinational Association of Supportive Care in Cancer (MASCC) criteria, which have been repeatedly validated.\u003c\/p\u003e\n\n\u003ch2 id=\"mascc\"\u003eThe MASCC Score: Identifying Standard-Risk Patients\u003c\/h2\u003e\n\u003cp\u003eStandard-risk patients with a MASCC score of 21 or higher make up a group with a high likelihood of a non-complicated course of infection. The maximum theoretical score is 26 points. Here is how the score is calculated:\u003c\/p\u003e\n\u003ctable\u003e\n  \u003ctr\u003e\n\u003cth\u003eCharacteristic\u003c\/th\u003e\n\u003cth\u003ePoints (weight)\u003c\/th\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eBurden of febrile neutropenia with no or mild symptoms\u003c\/td\u003e\n\u003ctd\u003e5\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eNo hypotension (systolic blood pressure above 90 mmHg)\u003c\/td\u003e\n\u003ctd\u003e5\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eNo chronic obstructive pulmonary disease (COPD)\u003c\/td\u003e\n\u003ctd\u003e4\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eSolid tumor or hematologic malignancy with no previous fungal infection\u003c\/td\u003e\n\u003ctd\u003e4\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eNo dehydration requiring parenteral (intravenous) fluids\u003c\/td\u003e\n\u003ctd\u003e3\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eBurden of febrile neutropenia with moderate symptoms\u003c\/td\u003e\n\u003ctd\u003e3\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eOutpatient status (the patient was not hospitalized when fever developed)\u003c\/td\u003e\n\u003ctd\u003e3\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eAge under 60 years\u003c\/td\u003e\n\u003ctd\u003e2\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/table\u003e\n\u003cp\u003eThe points for the \"burden of febrile neutropenia\" variable are not cumulative, which is why the maximum theoretical score is 26.\u003c\/p\u003e\n\u003cp\u003eIf a patient meets all individual criteria listed below, primary outpatient management (home treatment) of neutropenic fever is possible. The strength of this recommendation is BIIr — a moderate recommendation supported by evidence from randomized trials.\u003c\/p\u003e\n\n\u003ch2 id=\"outpatient\"\u003eCriteria for Outpatient Management\u003c\/h2\u003e\n\u003cp\u003eNot every patient can be treated at home. The guidelines list specific criteria that must all be met before primary outpatient management is considered. These fall into three categories:\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eGeneral medical criteria:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eNo signs of central nervous system (CNS, brain or spinal cord) infection, severe pneumonia, or venous catheter infection\u003c\/li\u003e\n  \u003cli\u003eNo signs of sepsis (a life-threatening whole-body reaction to infection) or shock\u003c\/li\u003e\n  \u003cli\u003eNone of the following: associated organ failure, pronounced abdominal pain (with or without diarrhea), dehydration, recurrent vomiting, need for intravenous supportive therapy, or need for permanent or close monitoring (for example, due to metabolic decompensation or hypercalcemia)\u003c\/li\u003e\n  \u003cli\u003eNo new electrocardiogram (ECG, heart tracing) abnormalities requiring treatment\u003c\/li\u003e\n  \u003cli\u003eNo new severe organ impairment\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003e\u003cstrong\u003eOral antibiotic criteria:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eNo fluoroquinolone prophylaxis (preventive antibiotic treatment) or therapy within the last 7 days\u003c\/li\u003e\n  \u003cli\u003eOral medication is feasible\u003c\/li\u003e\n  \u003cli\u003eGood compliance with oral medication is expected\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003e\u003cstrong\u003eOutpatient management criteria:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eMedical care is ensured (different options available)\u003c\/li\u003e\n  \u003cli\u003eThe patient does not live alone; the patient or a helper has a telephone; the patient can reach a clinic skilled in treating neutropenic patients within 1 hour\u003c\/li\u003e\n  \u003cli\u003eThe patient is conscious, knows the risks, and understands them\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"epidemiology\"\u003eWhat Causes Fever in Neutropenic Patients?\u003c\/h2\u003e\n\u003cp\u003eAt the onset of fever, antibiotic therapy must be started immediately. Because microbiological tests take time, the initial treatment is empirical (chosen based on the most likely germs) in patients who do not show a suspected clinical focus of infection. In about half of patients with febrile neutropenia (roughly 1 in 2), the antibiotic therapy remains empirical, because no relevant pathogen or focus of infection can be identified during the following days.\u003c\/p\u003e\n\u003cp\u003eThe selection of empirical antimicrobial agents is based on two things: (a) the results of prospective, randomized clinical studies, and (b) the microorganisms identified by analogy in patients with microbiologically documented infections. The most frequent and relevant pathogens are:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\u003cem\u003eStaphylococcus aureus\u003c\/em\u003e\u003c\/li\u003e\n  \u003cli\u003e\n\u003cem\u003eStreptococcus\u003c\/em\u003e species\u003c\/li\u003e\n  \u003cli\u003eEnterococci\u003c\/li\u003e\n  \u003cli\u003eCoagulase-negative staphylococci\u003c\/li\u003e\n  \u003cli\u003eGram-negative enterobacteria (intestinal bacteria)\u003c\/li\u003e\n  \u003cli\u003e\u003cem\u003ePseudomonas aeruginosa\u003c\/em\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eCoagulase-negative staphylococci are numerically the most frequent microbial isolates in many institutions. However, a single blood culture positive for these commensal skin pathogens (bacteria that normally live harmlessly on the skin) should be considered contamination if there is no corresponding clinical focus of infection. The same is true for other potential contaminants such as \u003cem\u003eCorynebacterium\u003c\/em\u003e, \u003cem\u003eBacillus cereus\u003c\/em\u003e, \u003cem\u003ePropionibacterium\u003c\/em\u003e, and \u003cem\u003eMicrococcus\u003c\/em\u003e species.\u003c\/p\u003e\n\u003cp\u003eAmong fungal pathogens, \u003cem\u003eCandida\u003c\/em\u003e species and \u003cem\u003eAspergillus\u003c\/em\u003e species are predominant. \u003cem\u003eAspergillus\u003c\/em\u003e is typically associated with a prolonged duration of neutropenia in high-risk patients.\u003c\/p\u003e\n\n\u003ch2 id=\"local-epidemiology\"\u003eLocal Resistance Patterns and Fluoroquinolone Prophylaxis\u003c\/h2\u003e\n\u003cp\u003eA recent history of antibiotic prophylaxis or therapy increases the risk of infections due to bacterial pathogens resistant to the antibiotic used. After ciprofloxacin prophylaxis, a relative predominance of infections caused by gram-positive cocci (round bacteria that stain positive in lab tests) compared with gram-negative bacteria has been observed.\u003c\/p\u003e\n\u003cp\u003eQuinolone antibiotics (a class that includes ciprofloxacin) have been linked to several problems:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eAn increased rate of colonization (germs living in or on the body without causing disease) by vancomycin-resistant enterococci (VRE, bacteria resistant to the antibiotic vancomycin)\u003c\/li\u003e\n  \u003cli\u003eAn increased rate of colonization by methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c\/em\u003e (MRSA)\u003c\/li\u003e\n  \u003cli\u003eA higher prevalence of multidrug resistance among enterobacteria via extended-spectrum beta-lactamases (ESBL, enzymes that make bacteria resistant to many beta-lactam antibiotics)\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eColonization by ESBL, VRE, or MRSA has been associated with an increased rate of bacteremia (bacteria in the bloodstream) caused by these same pathogens. As a result, the use of quinolones for interventional treatment in febrile neutropenic patients should be limited to microbiologically documented infections caused by microorganisms that are susceptible to these drugs in laboratory testing.\u003c\/p\u003e\n\u003cp\u003eLocal epidemiology must be taken into account when choosing empirical antimicrobial therapy. Microbiological findings from patients treated in a given hematology-oncology institution should be discussed on a regular basis, at least once a year, with infection-control and antimicrobial stewardship (antibiotic management) experts. Baseline screening of newly or re-admitted patients for multidrug-resistant pathogens should be considered: screening for MRSA is grade BIII, for VRE grade BIII, and for ESBL grade BIIt.\u003c\/p\u003e\n\n\u003ch2 id=\"baseline\"\u003eBaseline Tests Before Starting Chemotherapy\u003c\/h2\u003e\n\u003cp\u003eBefore starting myelosuppressive chemotherapy (treatment that suppresses bone marrow function), patients must be thoroughly evaluated for relevant previous or prevalent infections that might become important during treatment-induced neutropenia. This recommendation is grade AIII, meaning it is strongly supported by expert opinion.\u003c\/p\u003e\n\u003cp\u003eClinical examination should pay special attention to the skin, mucosa (moist linings of the body), puncture sites, vascular catheter exit sites, paranasal sinuses, lungs, and the perianal (area around the anus) region. This too is a strong, expert-opinion recommendation (AIII).\u003c\/p\u003e\n\u003cp\u003eIn patients with a self-reported penicillin allergy, skin testing is recommended (BIIt). A negative result — which is expected in the vast majority of cases — helps avoid unnecessary first-line use of carbapenems, aztreonam, or vancomycin. Baseline laboratory tests include:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eBlood count\u003c\/li\u003e\n  \u003cli\u003eLiver enzymes (ASAT\/SGPT, ALAT\/SGOT, gGT)\u003c\/li\u003e\n  \u003cli\u003eTotal bilirubin, alkaline phosphatase, and LDH (lactate dehydrogenase)\u003c\/li\u003e\n  \u003cli\u003eCreatinine and blood urea nitrogen (kidney function tests)\u003c\/li\u003e\n  \u003cli\u003eCoagulation tests (INR, aPTT, which measure blood clotting)\u003c\/li\u003e\n  \u003cli\u003eC-reactive protein (CRP, a marker of inflammation)\u003c\/li\u003e\n  \u003cli\u003eUrinalysis (urine test)\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eAll of these recommendations are graded BIII. Except for urinalysis, it is recommended to repeat these tests regularly, for example twice a week, during long-lasting neutropenia (BIII).\u003c\/p\u003e\n\u003cp\u003eProcalcitonin or cytokine levels (such as interleukin-6) are not recommended for routine baseline diagnostics (grade DIII, a recommendation against use). If neither computed tomography (CT) nor magnetic resonance imaging (MRI) of the chest and abdomen has been done for staging of the underlying disease, chest radiographs (X-rays, two views) and abdominal ultrasound may be considered as a baseline examination before the first chemotherapy (CIII). This helps check for pre-existing abnormalities and makes it easier to compare with later studies.\u003c\/p\u003e\n\u003cp\u003eParticularly in high-risk patients, a thoracic CT scan before chemotherapy appears desirable to document the baseline status of the lungs. However, because there are no prospective studies, no formal recommendation can be made. In patients with a history of an invasive infection, appropriate imaging is recommended even when there are no clinical symptoms of recurrence (BIII).\u003c\/p\u003e\n\n\u003ch2 id=\"fungal\"\u003eScreening for Fungal Infections in Asymptomatic Patients\u003c\/h2\u003e\n\u003cp\u003eFor high-risk patients with an expected duration of profound neutropenia longer than 7 days, serial monitoring for \u003cem\u003eAspergillus\u003c\/em\u003e galactomannan in serum has been recommended. Galactomannan is a molecule released by \u003cem\u003eAspergillus\u003c\/em\u003e fungi that can be detected in the blood. Monitoring should be done at least twice weekly.\u003c\/p\u003e\n\u003cp\u003eMonitoring patients with 1,3-beta-D-glucan (a component of fungal cell walls) in blood samples is discussed as an alternative, but it is rarely used because of higher costs. A sensitive, validated \u003cem\u003eAspergillus\u003c\/em\u003e PCR (polymerase chain reaction, a test that detects fungal DNA) may also be helpful (CIII) for screening blood samples in specific high-risk populations.\u003c\/p\u003e\n\u003cp\u003eHowever, the sensitivity of these tests is strongly reduced in patients taking systemic mold-active antifungals (drugs that treat mold infections). False-positive results can be caused by beta-lactam antibiotics, parenteral nutrition (intravenous feeding), severe intestinal mucositis (inflammation of the gut lining), or transfusion of blood products. Therefore, screening of afebrile (fever-free) and asymptomatic patients should be restricted to those NOT receiving systemic mold-active prophylaxis (BIIu). These non-culture-based procedures do not replace clinical, imaging, endoscopic, or other microbiological diagnostics (BIII).\u003c\/p\u003e\n\n\u003ch2 id=\"fever-onset\"\u003eDiagnostic Tests at the Moment Fever Begins\u003c\/h2\u003e\n\u003cp\u003eWhen a neutropenic patient first develops fever, diagnostic measures have three aims: (a) rule out non-infectious causes of fever, (b) identify a clinical focus and\/or causative pathogens, and (c) assess the severity of the inflammatory response to identify early which patients need intensive care. These diagnostic steps must never delay the start of appropriate antibiotic therapy (AIIt). In a clinically unstable patient, possibly arriving in the emergency room, prompt antimicrobial therapy is required (AI), and immediate referral to an intensive care unit must be considered.\u003c\/p\u003e\n\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is neutropenia and why is it dangerous in cancer patients after chemotherapy?\u003c\/h3\u003e\n\u003cp\u003eNeutropenia is a dangerously low count of neutrophils, the white blood cells that fight bacterial and fungal infections. It is defined as a count below 500\/μl or below 1000\/μl with a predicted drop within 2 days. The lower and longer the neutropenia, the higher the risk of fever and serious infections, which can delay chemotherapy.\u003c\/p\u003e\n\u003ch3\u003eWhen must antibiotic treatment start for a neutropenic patient with fever?\u003c\/h3\u003e\n\u003cp\u003eTreatment must begin within 2 hours of fever onset. The guidelines emphasize that diagnostic tests must never delay starting appropriate antibiotic therapy. In a clinically unstable patient, prompt antimicrobial therapy is required, and immediate referral to an intensive care unit may be considered.\u003c\/p\u003e\n\u003ch3\u003eWhat is the difference between standard-risk and high-risk neutropenic patients?\u003c\/h3\u003e\n\u003cp\u003eStandard-risk patients have an expected duration of neutropenia of up to 7 days. High-risk patients have neutropenia expected to last at least 8 days. High-risk patients need broad-spectrum antibiotics covering bacteria like Pseudomonas aeruginosa, and possibly antifungal therapy against Aspergillus if neutropenia lasts more than 7 days.\u003c\/p\u003e\n\u003ch3\u003eWhat is the MASCC score and what does a score of 21 or higher mean?\u003c\/h3\u003e\n\u003cp\u003eThe MASCC score helps identify standard-risk patients likely to have a non-complicated course of infection. A score of 21 or higher (maximum 26) indicates a high likelihood of a non-complicated course. Points are given for factors like no hypotension, no COPD, solid tumor, outpatient status, and age under 60.\u003c\/p\u003e\n\u003ch3\u003eCan neutropenic fever be treated at home?\u003c\/h3\u003e\n\u003cp\u003ePrimary outpatient management is possible only if all criteria are met. These include no signs of serious infection or organ failure, no fluoroquinolone prophylaxis in the last 7 days, oral medication is feasible, good compliance expected, medical care ensured, the patient does not live alone, has a telephone, and can reach a skilled clinic within 1 hour.\u003c\/p\u003e\n\u003ch3\u003eWhat causes fever in neutropenic patients and how is treatment chosen?\u003c\/h3\u003e\n\u003cp\u003eIn about half of patients, no specific germ or infection focus is identified, so antibiotic therapy remains empirical. Common pathogens include Staphylococcus aureus, Streptococcus species, enterococci, gram-negative enterobacteria, and Pseudomonas aeruginosa. Fungal pathogens like Candida and Aspergillus are also considered, especially with prolonged neutropenia. Local resistance patterns guide antibiotic choice.\u003c\/p\u003e\n\u003ch3\u003eShould I seek a second opinion on the recommended antibiotic treatment for fever during neutropenia after chemotherapy?\u003c\/h3\u003e\n\u003cp\u003eThe guidelines divide patients into standard-risk and high-risk groups, and treatment differs accordingly: high-risk patients need broad-spectrum antibiotics covering Pseudomonas, and antifungal therapy may be added if neutropenia lasts more than 7 days. If your doctor's risk assessment or choice of antibiotics differs from these published recommendations, a second opinion could help confirm whether the treatment plan is appropriate. Additionally, if you have a penicillin allergy, skin testing is recommended to avoid unnecessary drugs. A second opinion can review your risk status and antibiotic plan. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47527660454044,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"url":"https:\/\/diagnosticdetectives.com\/ja\/products\/fever-of-unknown-origin-in-neutropenic-cancer-patients-a-patient-friendly-guide-to-the-2017-german-agiho-guidelines","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}