17:I[462708,["/_next/static/chunks/3yo3kiro3bmlp.js","/_next/static/chunks/3vr2wvd8f2efb.js","/_next/static/chunks/2vtmb68_vu-9t.js","/_next/static/chunks/2s8mt6_8wrpfo.js","/_next/static/chunks/3vkulz2i3l61y.js","/_next/static/chunks/1cqw2i1silz0i.js","/_next/static/chunks/14dbm3lm_t629.js","/_next/static/chunks/335_v2mb569ld.js","/_next/static/chunks/1jvnwmb7jnkpz.js","/_next/static/chunks/3cmavum774kjt.js","/_next/static/chunks/3th-0-a2xf9qs.js","/_next/static/chunks/0p0xpwde6kzmv.js","/_next/static/chunks/401-sxxnzbtf_.js","/_next/static/chunks/0wywtv698a1v0.js","/_next/static/chunks/2botzqwpnrzyj.js"],"ArticleReader"] 18:T6868,## Summary **Febrile neutropenia (FN)** is an oncologic emergency because bacterial infection can progress rapidly while local inflammatory findings are muted. A widely used definition is a single oral temperature **≥38.3°C**, or **≥38.0°C sustained for approximately 1 hour**, with an absolute neutrophil count (ANC) **<500/µL** or expected to fall below 500/µL.[1,2] Neutropenic patients can also have life-threatening infection without fever; hypotension, hypoxemia, confusion, abdominal pain, or other organ dysfunction requires an infection/sepsis pathway even when temperature is normal. Start effective empiric antibacterial therapy promptly after focused cultures and essential baseline testing, without waiting for a source. The current ASCO/IDSA outpatient guideline recommends the first empiric antibacterial dose **within 1 hour of triage**.[2] High-risk or hospitalized adults generally receive an antipseudomonal beta-lactam such as cefepime, piperacillin-tazobactam, meropenem, or imipenem-cilastatin, selected according to allergy phenotype, renal function, prior cultures, recent antimicrobial exposure, local resistance, and the suspected source.[1,3] Routine empiric vancomycin or equivalent resistant gram-positive coverage is not indicated unless there is a specific reason such as hemodynamic instability, pneumonia with credible MRSA risk, serious catheter infection, skin/soft-tissue infection, or a resistant gram-positive organism identified or strongly suspected.[1,3] Risk assessment determines site of care. Hemodynamic instability, organ dysfunction, pneumonia or hypoxemia, severe mucositis, major abdominal/perianal disease, acute leukemia, hematopoietic cell transplantation, prolonged profound neutropenia, inability to take oral therapy, or unreliable follow-up generally requires admission. MASCC and CISNE can support—but never replace—clinical judgment. Selected low-risk adults may receive outpatient treatment after an initial supervised dose and **at least 4 hours of observation**, provided rapid access to reassessment and dependable logistics exist.[2] A common low-risk oral regimen is **ciprofloxacin 500–750 mg orally twice daily plus amoxicillin-clavulanate 875/125 mg orally twice daily**, provided fluoroquinolone prophylaxis was not used before fever and local susceptibility makes this strategy reasonable.[1,2] Dose adjustment and alternative regimens may be required for renal dysfunction, allergy, drug interaction, prior resistant organisms, or local epidemiology. Persistent fever by itself is not an automatic reason to broaden therapy in a clinically stable patient. Reassess for occult source, resistant bacteria, catheter infection, neutropenic enterocolitis, pneumonia, and invasive fungal disease. The 2024 AGIHO update, published in 2025, recommends that high-risk patients without mold-active prophylaxis who have persistent or recurrent fever after **72–96 hours** of appropriate antibacterial therapy be considered for empiric mold-active antifungal therapy; a diagnostic-driven strategy is appropriate where rapid fungal testing and imaging are available.[3] Stopping therapy must be criteria-based rather than a clock rule. Contemporary AGIHO guidance supports discontinuing empiric antibacterial therapy after sustained apyrexia and clinical recovery in stable patients even before neutrophil recovery in selected settings, while the older North American IDSA framework is more conservative for unexplained fever.[1,3] Document the source, microbiology, stability, marrow trajectory, and follow-up plan before narrowing or stopping treatment. > **Caution:** Severe neutropenia can erase the expected signs of infection. A normal chest radiograph, absent pyuria, minimal erythema, or lack of pus does not reliably exclude serious infection. ## Definitions | Term | Practical definition | |---|---| | Neutropenia | ANC <1500/µL; infection risk increases as ANC falls | | Severe neutropenia | ANC <500/µL | | Profound neutropenia | ANC <100/µL | | Febrile neutropenia | Fever with ANC <500/µL or expected decline below that threshold | | Prolonged neutropenia | Commonly >7 days; markedly increases invasive fungal risk | | Neutropenic sepsis | FN or suspected infection with sepsis/organ dysfunction | The **depth and expected duration** of neutropenia matter more than a single isolated ANC. ## Causes and microbiology ### Common settings - cytotoxic chemotherapy; - acute leukemia; - hematopoietic cell transplantation; - cellular therapies; - marrow failure or marrow infiltration; - selected targeted or immune-modulating therapies; - drug-induced neutropenia; - severe autoimmune or infectious marrow suppression. ### Host factors that increase risk - profound/prolonged neutropenia; - severe mucositis; - central venous catheter; - corticosteroid or other immunosuppression; - recent hospitalization; - recent broad-spectrum antibiotics; - prior multidrug-resistant colonization/infection; - uncontrolled malignancy; - gastrointestinal barrier injury. ### Pathogens Important bacterial groups include: - *Pseudomonas aeruginosa* and other gram-negative bacilli; - Enterobacterales including ESBL-producing and carbapenem-resistant strains; - *Staphylococcus aureus*; - viridans streptococci; - enterococci; - coagulase-negative staphylococci in catheter-associated contexts. In prolonged profound neutropenia, invasive molds and yeasts become increasingly important, especially with acute leukemia, transplantation, corticosteroid exposure, or broad antibacterial pressure. ## Clinical presentation Ask specifically about: - rigors or temperature change; - cough, dyspnea, pleuritic pain; - sore throat, odynophagia, oral ulcers, mucositis; - headache, confusion, focal neurologic symptoms; - dysuria or flank pain; - abdominal pain, diarrhea, vomiting, distention; - perianal pain or drainage; - skin pain, erythema, wounds, or line-site symptoms; - new focal bone or joint pain. Document: - cancer diagnosis and treatment phase; - date of last cytotoxic therapy and expected nadir; - prior FN; - previous culture and susceptibility data; - antibacterial/antifungal prophylaxis; - central venous access; - hematopoietic cell transplant or cellular therapy status; - corticosteroid exposure; - drug allergy phenotype; - recent hospitalization and antimicrobial exposure. ### Focused physical assessment Assess: - full vital-sign trend and oxygen saturation; - mental status and perfusion; - oral mucosa; - lungs; - abdomen; - skin and wounds; - central-line sites; - perineum externally when anorectal disease is suspected. Avoid rectal thermometers, enemas, and traumatic digital rectal procedures in profound neutropenia. Use imaging and surgical input when deep anorectal infection is suspected. ## Red flags | Finding | Concern | Immediate action | |---|---|---| | Hypotension, poor perfusion, rising lactate | Septic shock | Sepsis resuscitation, immediate effective antibacterials, critical care | | New oxygen need or respiratory distress | Pneumonia, ARDS, fungal disease, alternative chest process | Oxygen/ventilatory support and urgent imaging | | Severe abdominal pain, distention, diarrhea | Neutropenic enterocolitis, perforation, abscess | CT abdomen/pelvis, broad intra-abdominal coverage, surgical/oncology input | | Perianal pain or swelling | Deep anorectal infection | Cross-sectional imaging; surgical review | | Rigors with line pain/erythema | Catheter-related bloodstream infection | Paired cultures, directed coverage, source-control assessment | | Persistent/recurrent fever in prolonged profound neutropenia | Invasive fungal disease or occult source | Repeat source search; CT/biomarkers; antifungal strategy | | Confusion, seizure, meningism | CNS infection or severe sepsis | Stabilize and pursue urgent CNS pathway | ## Initial investigations Do not postpone the first effective antibacterial dose for completion of every test. ### Typical initial laboratory testing - CBC with differential and ANC; - creatinine and electrolytes; - liver biochemical tests; - lactate when instability or sepsis is suspected; - blood cultures before antibiotics when obtainable without meaningful delay; - urinalysis/culture when urinary infection is plausible; - respiratory viral molecular testing when symptoms or exposure warrant it; - stool testing for clinically significant diarrhea. Inflammatory markers can support trend assessment but do not reliably rule infection in or out. ### Blood cultures A practical approach is: - at least one peripheral set when feasible; - cultures from each lumen of an indwelling central line when catheter infection is plausible or required by local protocol. Do not delay antibiotics in an unstable patient to obtain ideal cultures. ### Imaging - chest CT is more sensitive than plain radiography for pulmonary infection in prolonged neutropenia; - CT abdomen/pelvis is preferred for major abdominal pain, suspected neutropenic enterocolitis, obstruction, abscess, or perforation; - cross-sectional imaging is useful for deep perianal disease; - CNS imaging and lumbar-puncture decisions depend on neurologic findings, platelet count, coagulation status, and urgency. ## Risk stratification ### High-risk features Admission is generally appropriate for: - hemodynamic instability or organ dysfunction; - pneumonia, hypoxemia, or new oxygen requirement; - significant abdominal pain or suspected neutropenic enterocolitis; - severe mucositis preventing oral intake; - neurologic abnormality; - serious catheter, skin, or soft-tissue infection; - acute leukemia or hematopoietic cell transplantation; - expected profound neutropenia for >7 days; - major renal, hepatic, cardiac, or pulmonary comorbidity; - known resistant-organism colonization with compatible severe illness; - inability to absorb oral drugs; - unreliable transport, communication, housing, or follow-up. ### MASCC risk index The MASCC score can help identify lower-risk FN. | Variable | Points | |---|---:| | Burden of illness: none/mild | 5 | | Burden of illness: moderate | 3 | | No hypotension | 5 | | No active COPD | 4 | | Solid tumor or hematologic malignancy without prior fungal infection | 4 | | No dehydration requiring parenteral fluids | 3 | | Outpatient at fever onset | 3 | | Age <60 years | 2 | A score **≥21** identifies a lower-risk group but does not by itself establish outpatient suitability.[2] ### CISNE CISNE is designed for **apparently stable adults with solid tumors**, not for unstable patients. | Variable | Points | |---|---:| | ECOG performance status ≥2 | 2 | | Stress-induced hyperglycemia | 2 | | COPD | 1 | | Chronic cardiovascular disease | 1 | | Grade ≥2 mucositis | 1 | | Monocytes <200/µL | 1 | - 0: lower risk; - 1–2: intermediate risk; - ≥3: higher risk. The 2024 AGIHO update favors CISNE for stratification of apparently stable patients with solid tumors while emphasizing that instability overrides any score.[3] ## Immediate management pathway 1. Assess airway, breathing, circulation, mental status, and perfusion. 2. Establish IV access and initiate sepsis resuscitation when indicated. 3. Obtain blood cultures and focused laboratory tests if this will not materially delay treatment. 4. Give empiric antipseudomonal antibacterial therapy promptly. 5. Identify high-risk features and likely source. 6. Review prior cultures, colonization, prophylaxis, allergies, and local resistance. 7. Decide inpatient versus carefully selected outpatient treatment. 8. Reassess frequently during the first hours. ## Empiric antibacterial therapy ### High-risk or hospitalized adults One antipseudomonal beta-lactam is standard initial therapy for many patients.[1,3] | Agent | Typical adult dose with normal renal function | Clinical notes | |---|---:|---| | Cefepime | 2 g IV every 8 h | Antipseudomonal; add anaerobic coverage when a relevant abdominal source is suspected | | Piperacillin-tazobactam | 4.5 g IV every 6 h | Antipseudomonal and anaerobic activity | | Meropenem | 1 g IV every 8 h | Reserve according to resistance risk/stewardship; broad anaerobic and ESBL activity | | Imipenem-cilastatin | 500 mg IV every 6 h | Broad spectrum; adjust for renal function; consider seizure risk | Adjust for kidney function, infusion strategy, allergy, local susceptibility, and patient-specific factors. ### Resistant gram-negative risk Broaden or alter empiric therapy when justified by: - prior ESBL or carbapenem-resistant organism; - prior resistant *Pseudomonas*; - recent broad-spectrum antibacterial exposure; - severe sepsis with credible resistant-pathogen risk; - local antibiogram showing poor susceptibility to standard monotherapy. Prior microbiology is often more useful than generic risk labels. ### Additional gram-positive coverage Do **not** add vancomycin routinely.[1,3] Add targeted resistant gram-positive therapy when there is: - hemodynamic instability; - pneumonia with credible MRSA risk; - serious catheter-related infection; - skin/soft-tissue infection; - known MRSA or resistant gram-positive colonization with compatible illness; - a clinically important gram-positive blood-culture result pending identification. De-escalate when the indication disappears. ### Abdominal or perianal focus Ensure anaerobic coverage for suspected neutropenic enterocolitis, perforation, intra-abdominal abscess, or deep anorectal infection. Piperacillin-tazobactam or a carbapenem provides anaerobic activity; cefepime-based regimens may require an additional anaerobic agent. ## Low-risk outpatient therapy ASCO/IDSA recommends initial empiric therapy within **1 hour of triage** and **≥4 hours observation** before outpatient discharge.[2] A suitable outpatient candidate generally has: - stable vital signs and no organ dysfunction; - no major focal infection requiring admission; - anticipated short neutropenia duration; - ability to take and absorb oral therapy; - no recent fluoroquinolone prophylaxis if a fluoroquinolone regimen is planned; - reliable phone access, transport, home support, and rapid return capability; - structured oncology follow-up. A common regimen is:[1,2] - **ciprofloxacin 500–750 mg PO twice daily**, plus - **amoxicillin-clavulanate 875/125 mg PO twice daily**. Use a local alternative when beta-lactam allergy, fluoroquinolone prophylaxis, renal impairment, resistance, or drug interaction makes this regimen unsuitable. > **Caution:** A low-risk score does not make an unstable patient appropriate for discharge. ## Reassessment at 24–96 hours Review: - hemodynamics and oxygen requirement; - fever trajectory; - new focal symptoms; - culture and susceptibility results; - line findings; - abdominal/perianal symptoms; - renal and hepatic function; - ANC trend and expected duration of neutropenia; - antimicrobial toxicity. Narrow therapy when a pathogen/source is identified and the patient is stable. ### Persistent fever Fever alone does not require automatic antibacterial broadening. Median time to defervescence can be several days.[3] Broaden or change therapy when there is: - clinical deterioration; - new focus; - resistant organism; - inadequate source control; - microbiology showing ineffective initial therapy. The AGIHO update advises hospitalization/reassessment for persistent fever around 96 hours in patients who are not already admitted and emphasizes that time alone should not trigger an arbitrary antibacterial change.[3] ## Invasive fungal disease Risk is highest with prolonged profound neutropenia, acute leukemia, allogeneic transplantation, corticosteroids, and prior fungal disease. ### Diagnostic reassessment For persistent or recurrent fever, consider: - chest CT; - sinus imaging when symptoms suggest; - serum galactomannan where validated and relevant; - beta-D-glucan where locally used, recognizing limited specificity; - bronchoscopy/BAL for pulmonary infiltrates when safe; - fungal blood culture or tissue diagnosis for selected syndromes. ### Empiric versus diagnostic-driven antifungal treatment For **high-risk patients without mold-active prophylaxis**, AGIHO recommends empiric mold-active antifungal therapy when fever persists **>72–96 hours** or recurs despite appropriate antibacterial therapy.[3] A diagnostic-driven strategy can reduce unnecessary antifungal exposure when the center can provide rapid CT, fungal biomarkers, bronchoscopy, and close monitoring. Choice of agent depends on: - prior antifungal prophylaxis; - likely pathogen; - renal/hepatic function; - drug interactions; - local epidemiology; - pulmonary versus disseminated disease. If the patient was already receiving mold-active prophylaxis, involve infectious diseases because breakthrough infection requires a different diagnostic and therapeutic approach. ## Neutropenic enterocolitis Suspect with neutropenia plus fever and abdominal pain, particularly right-sided pain, diarrhea, distention, or ileus. Management generally includes: - bowel rest individualized to severity; - IV fluids/hemodynamic support; - broad antipseudomonal and anaerobic antibacterial coverage; - CT abdomen/pelvis; - correction of thrombocytopenia/coagulopathy as needed; - surgical consultation for perforation, uncontrolled bleeding, necrosis, or clinical deterioration. Avoid routine colonoscopy in acute severe disease because of perforation risk. ## Catheter-related infection Obtain paired central/peripheral blood cultures when feasible. Source control depends on organism, tunnel/pocket infection, persistent bacteremia, hemodynamic status, and line necessity. Organisms such as *S. aureus*, *Pseudomonas*, or fungi generally lower the threshold for line removal. ## De-escalation and stopping criteria ### Documented infection Treat according to: - organism; - source; - source control; - clinical response; - immune status; - standard syndrome-specific duration. Neutropenia alone does not mandate indefinite broad-spectrum therapy when a documented infection has been adequately treated and the patient is stable. ### Unexplained fever Guidelines differ. - The older IDSA framework is conservative and historically continued the initial regimen through neutrophil recovery for unexplained fever in high-risk patients.[1] - The 2024 AGIHO update supports stopping empiric antibacterial therapy after **≥72 hours of apyrexia plus clinical recovery** in selected stable patients regardless of neutrophil recovery and cites trial/cohort data supporting this strategy.[3] A criteria-based stopping decision should confirm: - sustained clinical stability; - meaningful period without fever off antipyretic masking; - no untreated documented infection; - no new focal findings; - cultures reviewed; - no uncontrolled source; - clear plan for recurrent fever; - ability to monitor closely if discharged. > **Current practice:** European stewardship-oriented guidance permits earlier cessation than older North American recommendations in carefully selected stable patients. Follow local policy and resistance ecology while documenting why continuation or cessation is safe. ## Growth factors Granulocyte colony-stimulating factor is primarily used for **prevention** in patients whose chemotherapy carries sufficient FN risk or whose patient-specific factors increase risk. Routine therapeutic G-CSF for every episode of established FN is not indicated, but it may be considered in selected severe high-risk cases according to oncology guidance. ## Special scenarios ### Hematopoietic cell transplantation Transplant recipients may have prolonged neutropenia, mucosal barrier injury, graft-versus-host disease, viral reactivation, and prior mold-active prophylaxis. Empiric and preemptive strategies should follow the transplant program’s protocol and recent colonization data. ### Cellular therapy Fever after CAR-T or other cellular therapy can reflect infection, cytokine release syndrome, or both. Do not attribute fever to cytokine release syndrome until bacterial infection has been addressed with an appropriate initial pathway when neutropenia or instability is present. ### Severe beta-lactam allergy Clarify the reaction phenotype. Many reported penicillin allergies do not represent immediate hypersensitivity, but a credible severe immediate or severe delayed reaction changes therapy substantially. Use local allergy and antimicrobial guidance; avoid unnecessarily inferior broad-spectrum combinations when the allergy label can be safely clarified. ### Renal dysfunction Adjust renally eliminated antimicrobials and reassess dosing as kidney function changes. Under-dosing early in sepsis can also be harmful; loading and extended-infusion strategies should follow institutional pharmacokinetic protocols. ## Disposition ### Admit Admission is indicated for: - instability or organ dysfunction; - high-risk neutropenia; - pneumonia/hypoxemia; - significant abdominal/perianal disease; - uncontrolled pain/vomiting; - severe mucositis; - resistant organism requiring IV therapy; - unreliable outpatient logistics. ### Outpatient discharge Requires: - clinical stability after observation; - low-risk profile; - oral regimen tolerated; - medication access; - reliable transportation and communication; - close follow-up; - explicit return pathway for fever recurrence or deterioration. ### Return immediately for - recurrent/persistent fever; - rigors; - dyspnea; - confusion; - syncope; - worsening abdominal or perianal pain; - inability to take medication; - new rash/line changes; - hypotension or profound weakness. ## Acute management checklist - [ ] Assess perfusion, oxygenation, and organ dysfunction. - [ ] Confirm ANC and expected neutropenia duration. - [ ] Obtain blood cultures without delaying therapy. - [ ] Review prior cultures, prophylaxis, recent antibiotics, and allergy phenotype. - [ ] Give effective empiric antibacterial therapy promptly. - [ ] Ensure antipseudomonal coverage for high-risk disease. - [ ] Add resistant gram-positive coverage only for a defined indication. - [ ] Search actively for pulmonary, abdominal, perianal, skin, CNS, and line sources. - [ ] Decide inpatient versus outpatient care using physiology plus risk/logistics. - [ ] Reassess at least daily for culture results, source, toxicity, and de-escalation. - [ ] For persistent fever in high-risk prolonged neutropenia, initiate a fungal diagnostic/treatment pathway. - [ ] Use clinical recovery and source/microbiology criteria—not elapsed time alone—to stop or narrow therapy. ## Decision pathway ```text Fever or suspected infection + ANC <500/µL | +--> Unstable / organ dysfunction? | | | +--> cultures if no delay | +--> immediate IV antipseudomonal therapy | +--> sepsis/critical-care pathway | +--> Stable | +--> assess expected depth/duration + focal infection +--> MASCC/CISNE can support risk classification | +--> High risk -> inpatient IV therapy | +--> Carefully selected low risk -> first supervised dose -> observe ≥4 h -> oral regimen + reliable follow-up At 72–96 h if fever persists/recurs: -> repeat source search and cultures/imaging -> do not broaden solely because time elapsed -> high-risk prolonged neutropenia: fungal diagnostic strategy ± mold-active empiric therapy When improving: -> narrow to pathogen/source -> stop only when stability, fever resolution, source control, microbiology, and follow-up criteria are satisfied ``` ## Common pitfalls 1. Delaying antibacterial treatment until every culture or scan is complete. 2. Assuming lack of fever excludes infection. 3. Adding vancomycin routinely. 4. Using a risk score to discharge an unstable patient. 5. Failing to review prior resistant-organism data. 6. Missing neutropenic enterocolitis or anorectal infection because local inflammatory signs are subtle. 7. Broadening antibacterials solely because fever persists. 8. Ignoring invasive fungal disease in prolonged profound neutropenia. 9. Continuing broad-spectrum therapy without daily de-escalation review. 10. Stopping therapy solely because a fixed number of hours has passed without confirming clinical recovery and source control. ## Current practice changes The 2024 AGIHO update, published in 2025, places greater emphasis on CISNE in apparently stable solid-tumor patients, contemporary resistance-informed empiric therapy, structured fungal assessment, and criteria-based earlier antibacterial discontinuation in clinically recovered patients.[3] This differs from the more conservative older IDSA approach for unexplained fever and should be implemented within local antimicrobial stewardship and follow-up capacity.[1,3] ## Related library topics - [Sepsis and Septic Shock](../critical-care/sepsis-and-septic-shock.md) - [Neutropenic Enterocolitis](neutropenic-enterocolitis.md) - [Invasive Aspergillosis](../infectious-disease/invasive-aspergillosis.md) - [Central Line-Associated Bloodstream Infection](../infectious-disease/central-line-associated-bloodstream-infection.md) - [Penicillin Allergy in Adults](../allergy-immunology/penicillin-allergy-in-adults.md) ## References 1. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America. *Clin Infect Dis.* 2011;52(4):e56-e93. doi:10.1093/cid/cir073. PMID:21258094. https://www.idsociety.org/practice-guideline/neutropenic-patients-with-cancer/ 2. Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. *J Clin Oncol.* 2018;36(14):1443-1453. doi:10.1200/JCO.2017.77.6211. PMID:29461916. https://www.idsociety.org/practice-guideline/fever-and-neutropenia-in-adults-with-cancer/ 3. Sandherr M, Stemler J, Schalk E, et al. 2024 update of the AGIHO guideline on diagnosis and empirical treatment of fever of unknown origin in adult neutropenic patients with solid tumours and hematological malignancies. *Lancet Reg Health Eur.* 2025;51:101214. doi:10.1016/j.lanepe.2025.101214. PMID:39973942. https://pubmed.ncbi.nlm.nih.gov/39973942/19:T6868,## Summary **Febrile neutropenia (FN)** is an oncologic emergency because bacterial infection can progress rapidly while local inflammatory findings are muted. A widely used definition is a single oral temperature **≥38.3°C**, or **≥38.0°C sustained for approximately 1 hour**, with an absolute neutrophil count (ANC) **<500/µL** or expected to fall below 500/µL.[1,2] Neutropenic patients can also have life-threatening infection without fever; hypotension, hypoxemia, confusion, abdominal pain, or other organ dysfunction requires an infection/sepsis pathway even when temperature is normal. Start effective empiric antibacterial therapy promptly after focused cultures and essential baseline testing, without waiting for a source. The current ASCO/IDSA outpatient guideline recommends the first empiric antibacterial dose **within 1 hour of triage**.[2] High-risk or hospitalized adults generally receive an antipseudomonal beta-lactam such as cefepime, piperacillin-tazobactam, meropenem, or imipenem-cilastatin, selected according to allergy phenotype, renal function, prior cultures, recent antimicrobial exposure, local resistance, and the suspected source.[1,3] Routine empiric vancomycin or equivalent resistant gram-positive coverage is not indicated unless there is a specific reason such as hemodynamic instability, pneumonia with credible MRSA risk, serious catheter infection, skin/soft-tissue infection, or a resistant gram-positive organism identified or strongly suspected.[1,3] Risk assessment determines site of care. Hemodynamic instability, organ dysfunction, pneumonia or hypoxemia, severe mucositis, major abdominal/perianal disease, acute leukemia, hematopoietic cell transplantation, prolonged profound neutropenia, inability to take oral therapy, or unreliable follow-up generally requires admission. MASCC and CISNE can support—but never replace—clinical judgment. Selected low-risk adults may receive outpatient treatment after an initial supervised dose and **at least 4 hours of observation**, provided rapid access to reassessment and dependable logistics exist.[2] A common low-risk oral regimen is **ciprofloxacin 500–750 mg orally twice daily plus amoxicillin-clavulanate 875/125 mg orally twice daily**, provided fluoroquinolone prophylaxis was not used before fever and local susceptibility makes this strategy reasonable.[1,2] Dose adjustment and alternative regimens may be required for renal dysfunction, allergy, drug interaction, prior resistant organisms, or local epidemiology. Persistent fever by itself is not an automatic reason to broaden therapy in a clinically stable patient. Reassess for occult source, resistant bacteria, catheter infection, neutropenic enterocolitis, pneumonia, and invasive fungal disease. The 2024 AGIHO update, published in 2025, recommends that high-risk patients without mold-active prophylaxis who have persistent or recurrent fever after **72–96 hours** of appropriate antibacterial therapy be considered for empiric mold-active antifungal therapy; a diagnostic-driven strategy is appropriate where rapid fungal testing and imaging are available.[3] Stopping therapy must be criteria-based rather than a clock rule. Contemporary AGIHO guidance supports discontinuing empiric antibacterial therapy after sustained apyrexia and clinical recovery in stable patients even before neutrophil recovery in selected settings, while the older North American IDSA framework is more conservative for unexplained fever.[1,3] Document the source, microbiology, stability, marrow trajectory, and follow-up plan before narrowing or stopping treatment. > **Caution:** Severe neutropenia can erase the expected signs of infection. A normal chest radiograph, absent pyuria, minimal erythema, or lack of pus does not reliably exclude serious infection. ## Definitions | Term | Practical definition | |---|---| | Neutropenia | ANC <1500/µL; infection risk increases as ANC falls | | Severe neutropenia | ANC <500/µL | | Profound neutropenia | ANC <100/µL | | Febrile neutropenia | Fever with ANC <500/µL or expected decline below that threshold | | Prolonged neutropenia | Commonly >7 days; markedly increases invasive fungal risk | | Neutropenic sepsis | FN or suspected infection with sepsis/organ dysfunction | The **depth and expected duration** of neutropenia matter more than a single isolated ANC. ## Causes and microbiology ### Common settings - cytotoxic chemotherapy; - acute leukemia; - hematopoietic cell transplantation; - cellular therapies; - marrow failure or marrow infiltration; - selected targeted or immune-modulating therapies; - drug-induced neutropenia; - severe autoimmune or infectious marrow suppression. ### Host factors that increase risk - profound/prolonged neutropenia; - severe mucositis; - central venous catheter; - corticosteroid or other immunosuppression; - recent hospitalization; - recent broad-spectrum antibiotics; - prior multidrug-resistant colonization/infection; - uncontrolled malignancy; - gastrointestinal barrier injury. ### Pathogens Important bacterial groups include: - *Pseudomonas aeruginosa* and other gram-negative bacilli; - Enterobacterales including ESBL-producing and carbapenem-resistant strains; - *Staphylococcus aureus*; - viridans streptococci; - enterococci; - coagulase-negative staphylococci in catheter-associated contexts. In prolonged profound neutropenia, invasive molds and yeasts become increasingly important, especially with acute leukemia, transplantation, corticosteroid exposure, or broad antibacterial pressure. ## Clinical presentation Ask specifically about: - rigors or temperature change; - cough, dyspnea, pleuritic pain; - sore throat, odynophagia, oral ulcers, mucositis; - headache, confusion, focal neurologic symptoms; - dysuria or flank pain; - abdominal pain, diarrhea, vomiting, distention; - perianal pain or drainage; - skin pain, erythema, wounds, or line-site symptoms; - new focal bone or joint pain. Document: - cancer diagnosis and treatment phase; - date of last cytotoxic therapy and expected nadir; - prior FN; - previous culture and susceptibility data; - antibacterial/antifungal prophylaxis; - central venous access; - hematopoietic cell transplant or cellular therapy status; - corticosteroid exposure; - drug allergy phenotype; - recent hospitalization and antimicrobial exposure. ### Focused physical assessment Assess: - full vital-sign trend and oxygen saturation; - mental status and perfusion; - oral mucosa; - lungs; - abdomen; - skin and wounds; - central-line sites; - perineum externally when anorectal disease is suspected. Avoid rectal thermometers, enemas, and traumatic digital rectal procedures in profound neutropenia. Use imaging and surgical input when deep anorectal infection is suspected. ## Red flags | Finding | Concern | Immediate action | |---|---|---| | Hypotension, poor perfusion, rising lactate | Septic shock | Sepsis resuscitation, immediate effective antibacterials, critical care | | New oxygen need or respiratory distress | Pneumonia, ARDS, fungal disease, alternative chest process | Oxygen/ventilatory support and urgent imaging | | Severe abdominal pain, distention, diarrhea | Neutropenic enterocolitis, perforation, abscess | CT abdomen/pelvis, broad intra-abdominal coverage, surgical/oncology input | | Perianal pain or swelling | Deep anorectal infection | Cross-sectional imaging; surgical review | | Rigors with line pain/erythema | Catheter-related bloodstream infection | Paired cultures, directed coverage, source-control assessment | | Persistent/recurrent fever in prolonged profound neutropenia | Invasive fungal disease or occult source | Repeat source search; CT/biomarkers; antifungal strategy | | Confusion, seizure, meningism | CNS infection or severe sepsis | Stabilize and pursue urgent CNS pathway | ## Initial investigations Do not postpone the first effective antibacterial dose for completion of every test. ### Typical initial laboratory testing - CBC with differential and ANC; - creatinine and electrolytes; - liver biochemical tests; - lactate when instability or sepsis is suspected; - blood cultures before antibiotics when obtainable without meaningful delay; - urinalysis/culture when urinary infection is plausible; - respiratory viral molecular testing when symptoms or exposure warrant it; - stool testing for clinically significant diarrhea. Inflammatory markers can support trend assessment but do not reliably rule infection in or out. ### Blood cultures A practical approach is: - at least one peripheral set when feasible; - cultures from each lumen of an indwelling central line when catheter infection is plausible or required by local protocol. Do not delay antibiotics in an unstable patient to obtain ideal cultures. ### Imaging - chest CT is more sensitive than plain radiography for pulmonary infection in prolonged neutropenia; - CT abdomen/pelvis is preferred for major abdominal pain, suspected neutropenic enterocolitis, obstruction, abscess, or perforation; - cross-sectional imaging is useful for deep perianal disease; - CNS imaging and lumbar-puncture decisions depend on neurologic findings, platelet count, coagulation status, and urgency. ## Risk stratification ### High-risk features Admission is generally appropriate for: - hemodynamic instability or organ dysfunction; - pneumonia, hypoxemia, or new oxygen requirement; - significant abdominal pain or suspected neutropenic enterocolitis; - severe mucositis preventing oral intake; - neurologic abnormality; - serious catheter, skin, or soft-tissue infection; - acute leukemia or hematopoietic cell transplantation; - expected profound neutropenia for >7 days; - major renal, hepatic, cardiac, or pulmonary comorbidity; - known resistant-organism colonization with compatible severe illness; - inability to absorb oral drugs; - unreliable transport, communication, housing, or follow-up. ### MASCC risk index The MASCC score can help identify lower-risk FN. | Variable | Points | |---|---:| | Burden of illness: none/mild | 5 | | Burden of illness: moderate | 3 | | No hypotension | 5 | | No active COPD | 4 | | Solid tumor or hematologic malignancy without prior fungal infection | 4 | | No dehydration requiring parenteral fluids | 3 | | Outpatient at fever onset | 3 | | Age <60 years | 2 | A score **≥21** identifies a lower-risk group but does not by itself establish outpatient suitability.[2] ### CISNE CISNE is designed for **apparently stable adults with solid tumors**, not for unstable patients. | Variable | Points | |---|---:| | ECOG performance status ≥2 | 2 | | Stress-induced hyperglycemia | 2 | | COPD | 1 | | Chronic cardiovascular disease | 1 | | Grade ≥2 mucositis | 1 | | Monocytes <200/µL | 1 | - 0: lower risk; - 1–2: intermediate risk; - ≥3: higher risk. The 2024 AGIHO update favors CISNE for stratification of apparently stable patients with solid tumors while emphasizing that instability overrides any score.[3] ## Immediate management pathway 1. Assess airway, breathing, circulation, mental status, and perfusion. 2. Establish IV access and initiate sepsis resuscitation when indicated. 3. Obtain blood cultures and focused laboratory tests if this will not materially delay treatment. 4. Give empiric antipseudomonal antibacterial therapy promptly. 5. Identify high-risk features and likely source. 6. Review prior cultures, colonization, prophylaxis, allergies, and local resistance. 7. Decide inpatient versus carefully selected outpatient treatment. 8. Reassess frequently during the first hours. ## Empiric antibacterial therapy ### High-risk or hospitalized adults One antipseudomonal beta-lactam is standard initial therapy for many patients.[1,3] | Agent | Typical adult dose with normal renal function | Clinical notes | |---|---:|---| | Cefepime | 2 g IV every 8 h | Antipseudomonal; add anaerobic coverage when a relevant abdominal source is suspected | | Piperacillin-tazobactam | 4.5 g IV every 6 h | Antipseudomonal and anaerobic activity | | Meropenem | 1 g IV every 8 h | Reserve according to resistance risk/stewardship; broad anaerobic and ESBL activity | | Imipenem-cilastatin | 500 mg IV every 6 h | Broad spectrum; adjust for renal function; consider seizure risk | Adjust for kidney function, infusion strategy, allergy, local susceptibility, and patient-specific factors. ### Resistant gram-negative risk Broaden or alter empiric therapy when justified by: - prior ESBL or carbapenem-resistant organism; - prior resistant *Pseudomonas*; - recent broad-spectrum antibacterial exposure; - severe sepsis with credible resistant-pathogen risk; - local antibiogram showing poor susceptibility to standard monotherapy. Prior microbiology is often more useful than generic risk labels. ### Additional gram-positive coverage Do **not** add vancomycin routinely.[1,3] Add targeted resistant gram-positive therapy when there is: - hemodynamic instability; - pneumonia with credible MRSA risk; - serious catheter-related infection; - skin/soft-tissue infection; - known MRSA or resistant gram-positive colonization with compatible illness; - a clinically important gram-positive blood-culture result pending identification. De-escalate when the indication disappears. ### Abdominal or perianal focus Ensure anaerobic coverage for suspected neutropenic enterocolitis, perforation, intra-abdominal abscess, or deep anorectal infection. Piperacillin-tazobactam or a carbapenem provides anaerobic activity; cefepime-based regimens may require an additional anaerobic agent. ## Low-risk outpatient therapy ASCO/IDSA recommends initial empiric therapy within **1 hour of triage** and **≥4 hours observation** before outpatient discharge.[2] A suitable outpatient candidate generally has: - stable vital signs and no organ dysfunction; - no major focal infection requiring admission; - anticipated short neutropenia duration; - ability to take and absorb oral therapy; - no recent fluoroquinolone prophylaxis if a fluoroquinolone regimen is planned; - reliable phone access, transport, home support, and rapid return capability; - structured oncology follow-up. A common regimen is:[1,2] - **ciprofloxacin 500–750 mg PO twice daily**, plus - **amoxicillin-clavulanate 875/125 mg PO twice daily**. Use a local alternative when beta-lactam allergy, fluoroquinolone prophylaxis, renal impairment, resistance, or drug interaction makes this regimen unsuitable. > **Caution:** A low-risk score does not make an unstable patient appropriate for discharge. ## Reassessment at 24–96 hours Review: - hemodynamics and oxygen requirement; - fever trajectory; - new focal symptoms; - culture and susceptibility results; - line findings; - abdominal/perianal symptoms; - renal and hepatic function; - ANC trend and expected duration of neutropenia; - antimicrobial toxicity. Narrow therapy when a pathogen/source is identified and the patient is stable. ### Persistent fever Fever alone does not require automatic antibacterial broadening. Median time to defervescence can be several days.[3] Broaden or change therapy when there is: - clinical deterioration; - new focus; - resistant organism; - inadequate source control; - microbiology showing ineffective initial therapy. The AGIHO update advises hospitalization/reassessment for persistent fever around 96 hours in patients who are not already admitted and emphasizes that time alone should not trigger an arbitrary antibacterial change.[3] ## Invasive fungal disease Risk is highest with prolonged profound neutropenia, acute leukemia, allogeneic transplantation, corticosteroids, and prior fungal disease. ### Diagnostic reassessment For persistent or recurrent fever, consider: - chest CT; - sinus imaging when symptoms suggest; - serum galactomannan where validated and relevant; - beta-D-glucan where locally used, recognizing limited specificity; - bronchoscopy/BAL for pulmonary infiltrates when safe; - fungal blood culture or tissue diagnosis for selected syndromes. ### Empiric versus diagnostic-driven antifungal treatment For **high-risk patients without mold-active prophylaxis**, AGIHO recommends empiric mold-active antifungal therapy when fever persists **>72–96 hours** or recurs despite appropriate antibacterial therapy.[3] A diagnostic-driven strategy can reduce unnecessary antifungal exposure when the center can provide rapid CT, fungal biomarkers, bronchoscopy, and close monitoring. Choice of agent depends on: - prior antifungal prophylaxis; - likely pathogen; - renal/hepatic function; - drug interactions; - local epidemiology; - pulmonary versus disseminated disease. If the patient was already receiving mold-active prophylaxis, involve infectious diseases because breakthrough infection requires a different diagnostic and therapeutic approach. ## Neutropenic enterocolitis Suspect with neutropenia plus fever and abdominal pain, particularly right-sided pain, diarrhea, distention, or ileus. Management generally includes: - bowel rest individualized to severity; - IV fluids/hemodynamic support; - broad antipseudomonal and anaerobic antibacterial coverage; - CT abdomen/pelvis; - correction of thrombocytopenia/coagulopathy as needed; - surgical consultation for perforation, uncontrolled bleeding, necrosis, or clinical deterioration. Avoid routine colonoscopy in acute severe disease because of perforation risk. ## Catheter-related infection Obtain paired central/peripheral blood cultures when feasible. Source control depends on organism, tunnel/pocket infection, persistent bacteremia, hemodynamic status, and line necessity. Organisms such as *S. aureus*, *Pseudomonas*, or fungi generally lower the threshold for line removal. ## De-escalation and stopping criteria ### Documented infection Treat according to: - organism; - source; - source control; - clinical response; - immune status; - standard syndrome-specific duration. Neutropenia alone does not mandate indefinite broad-spectrum therapy when a documented infection has been adequately treated and the patient is stable. ### Unexplained fever Guidelines differ. - The older IDSA framework is conservative and historically continued the initial regimen through neutrophil recovery for unexplained fever in high-risk patients.[1] - The 2024 AGIHO update supports stopping empiric antibacterial therapy after **≥72 hours of apyrexia plus clinical recovery** in selected stable patients regardless of neutrophil recovery and cites trial/cohort data supporting this strategy.[3] A criteria-based stopping decision should confirm: - sustained clinical stability; - meaningful period without fever off antipyretic masking; - no untreated documented infection; - no new focal findings; - cultures reviewed; - no uncontrolled source; - clear plan for recurrent fever; - ability to monitor closely if discharged. > **Current practice:** European stewardship-oriented guidance permits earlier cessation than older North American recommendations in carefully selected stable patients. Follow local policy and resistance ecology while documenting why continuation or cessation is safe. ## Growth factors Granulocyte colony-stimulating factor is primarily used for **prevention** in patients whose chemotherapy carries sufficient FN risk or whose patient-specific factors increase risk. Routine therapeutic G-CSF for every episode of established FN is not indicated, but it may be considered in selected severe high-risk cases according to oncology guidance. ## Special scenarios ### Hematopoietic cell transplantation Transplant recipients may have prolonged neutropenia, mucosal barrier injury, graft-versus-host disease, viral reactivation, and prior mold-active prophylaxis. Empiric and preemptive strategies should follow the transplant program’s protocol and recent colonization data. ### Cellular therapy Fever after CAR-T or other cellular therapy can reflect infection, cytokine release syndrome, or both. Do not attribute fever to cytokine release syndrome until bacterial infection has been addressed with an appropriate initial pathway when neutropenia or instability is present. ### Severe beta-lactam allergy Clarify the reaction phenotype. Many reported penicillin allergies do not represent immediate hypersensitivity, but a credible severe immediate or severe delayed reaction changes therapy substantially. Use local allergy and antimicrobial guidance; avoid unnecessarily inferior broad-spectrum combinations when the allergy label can be safely clarified. ### Renal dysfunction Adjust renally eliminated antimicrobials and reassess dosing as kidney function changes. Under-dosing early in sepsis can also be harmful; loading and extended-infusion strategies should follow institutional pharmacokinetic protocols. ## Disposition ### Admit Admission is indicated for: - instability or organ dysfunction; - high-risk neutropenia; - pneumonia/hypoxemia; - significant abdominal/perianal disease; - uncontrolled pain/vomiting; - severe mucositis; - resistant organism requiring IV therapy; - unreliable outpatient logistics. ### Outpatient discharge Requires: - clinical stability after observation; - low-risk profile; - oral regimen tolerated; - medication access; - reliable transportation and communication; - close follow-up; - explicit return pathway for fever recurrence or deterioration. ### Return immediately for - recurrent/persistent fever; - rigors; - dyspnea; - confusion; - syncope; - worsening abdominal or perianal pain; - inability to take medication; - new rash/line changes; - hypotension or profound weakness. ## Acute management checklist - [ ] Assess perfusion, oxygenation, and organ dysfunction. - [ ] Confirm ANC and expected neutropenia duration. - [ ] Obtain blood cultures without delaying therapy. - [ ] Review prior cultures, prophylaxis, recent antibiotics, and allergy phenotype. - [ ] Give effective empiric antibacterial therapy promptly. - [ ] Ensure antipseudomonal coverage for high-risk disease. - [ ] Add resistant gram-positive coverage only for a defined indication. - [ ] Search actively for pulmonary, abdominal, perianal, skin, CNS, and line sources. - [ ] Decide inpatient versus outpatient care using physiology plus risk/logistics. - [ ] Reassess at least daily for culture results, source, toxicity, and de-escalation. - [ ] For persistent fever in high-risk prolonged neutropenia, initiate a fungal diagnostic/treatment pathway. - [ ] Use clinical recovery and source/microbiology criteria—not elapsed time alone—to stop or narrow therapy. ## Decision pathway ```text Fever or suspected infection + ANC <500/µL | +--> Unstable / organ dysfunction? | | | +--> cultures if no delay | +--> immediate IV antipseudomonal therapy | +--> sepsis/critical-care pathway | +--> Stable | +--> assess expected depth/duration + focal infection +--> MASCC/CISNE can support risk classification | +--> High risk -> inpatient IV therapy | +--> Carefully selected low risk -> first supervised dose -> observe ≥4 h -> oral regimen + reliable follow-up At 72–96 h if fever persists/recurs: -> repeat source search and cultures/imaging -> do not broaden solely because time elapsed -> high-risk prolonged neutropenia: fungal diagnostic strategy ± mold-active empiric therapy When improving: -> narrow to pathogen/source -> stop only when stability, fever resolution, source control, microbiology, and follow-up criteria are satisfied ``` ## Common pitfalls 1. Delaying antibacterial treatment until every culture or scan is complete. 2. Assuming lack of fever excludes infection. 3. Adding vancomycin routinely. 4. Using a risk score to discharge an unstable patient. 5. Failing to review prior resistant-organism data. 6. Missing neutropenic enterocolitis or anorectal infection because local inflammatory signs are subtle. 7. Broadening antibacterials solely because fever persists. 8. Ignoring invasive fungal disease in prolonged profound neutropenia. 9. Continuing broad-spectrum therapy without daily de-escalation review. 10. Stopping therapy solely because a fixed number of hours has passed without confirming clinical recovery and source control. ## Current practice changes The 2024 AGIHO update, published in 2025, places greater emphasis on CISNE in apparently stable solid-tumor patients, contemporary resistance-informed empiric therapy, structured fungal assessment, and criteria-based earlier antibacterial discontinuation in clinically recovered patients.[3] This differs from the more conservative older IDSA approach for unexplained fever and should be implemented within local antimicrobial stewardship and follow-up capacity.[1,3] ## Related library topics - [Sepsis and Septic Shock](../critical-care/sepsis-and-septic-shock.md) - [Neutropenic Enterocolitis](neutropenic-enterocolitis.md) - [Invasive Aspergillosis](../infectious-disease/invasive-aspergillosis.md) - [Central Line-Associated Bloodstream Infection](../infectious-disease/central-line-associated-bloodstream-infection.md) - [Penicillin Allergy in Adults](../allergy-immunology/penicillin-allergy-in-adults.md) ## References 1. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America. *Clin Infect Dis.* 2011;52(4):e56-e93. doi:10.1093/cid/cir073. PMID:21258094. https://www.idsociety.org/practice-guideline/neutropenic-patients-with-cancer/ 2. Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. *J Clin Oncol.* 2018;36(14):1443-1453. doi:10.1200/JCO.2017.77.6211. PMID:29461916. https://www.idsociety.org/practice-guideline/fever-and-neutropenia-in-adults-with-cancer/ 3. Sandherr M, Stemler J, Schalk E, et al. 2024 update of the AGIHO guideline on diagnosis and empirical treatment of fever of unknown origin in adult neutropenic patients with solid tumours and hematological malignancies. *Lancet Reg Health Eur.* 2025;51:101214. doi:10.1016/j.lanepe.2025.101214. PMID:39973942. https://pubmed.ncbi.nlm.nih.gov/39973942/7:["$","$L17",null,{"article":{"id":"medical-febrile-neutropenia","title":"Febrile Neutropenia","slug":"febrile-neutropenia","description":"Febrile neutropenia (FN) is an oncologic emergency because bacterial infection can progress rapidly while local inflammatory findings are muted. A widely used definition is a single oral temperature ≥38.3°C, or ≥38.0°…","aliases":[],"category":"Hematology & Oncology","tags":["Hematology & Oncology","Infectious Diseases"],"updatedAt":"$undefined","body":"$18","headings":[{"id":"summary","text":"Summary","level":2},{"id":"definitions","text":"Definitions","level":2},{"id":"causes-and-microbiology","text":"Causes and microbiology","level":2},{"id":"common-settings","text":"Common settings","level":3},{"id":"host-factors-that-increase-risk","text":"Host factors that increase risk","level":3},{"id":"pathogens","text":"Pathogens","level":3},{"id":"clinical-presentation","text":"Clinical presentation","level":2},{"id":"focused-physical-assessment","text":"Focused physical assessment","level":3},{"id":"red-flags","text":"Red flags","level":2},{"id":"initial-investigations","text":"Initial investigations","level":2},{"id":"typical-initial-laboratory-testing","text":"Typical initial laboratory testing","level":3},{"id":"blood-cultures","text":"Blood cultures","level":3},{"id":"imaging","text":"Imaging","level":3},{"id":"risk-stratification","text":"Risk stratification","level":2},{"id":"high-risk-features","text":"High-risk features","level":3},{"id":"mascc-risk-index","text":"MASCC risk index","level":3},{"id":"cisne","text":"CISNE","level":3},{"id":"immediate-management-pathway","text":"Immediate management pathway","level":2},{"id":"empiric-antibacterial-therapy","text":"Empiric antibacterial therapy","level":2},{"id":"high-risk-or-hospitalized-adults","text":"High-risk or hospitalized adults","level":3},{"id":"resistant-gram-negative-risk","text":"Resistant gram-negative risk","level":3},{"id":"additional-gram-positive-coverage","text":"Additional gram-positive coverage","level":3},{"id":"abdominal-or-perianal-focus","text":"Abdominal or perianal focus","level":3},{"id":"low-risk-outpatient-therapy","text":"Low-risk outpatient therapy","level":2},{"id":"reassessment-at-2496-hours","text":"Reassessment at 24–96 hours","level":2},{"id":"persistent-fever","text":"Persistent fever","level":3},{"id":"invasive-fungal-disease","text":"Invasive fungal disease","level":2},{"id":"diagnostic-reassessment","text":"Diagnostic reassessment","level":3},{"id":"empiric-versus-diagnostic-driven-antifungal-treatment","text":"Empiric versus diagnostic-driven antifungal treatment","level":3},{"id":"neutropenic-enterocolitis","text":"Neutropenic enterocolitis","level":2},{"id":"catheter-related-infection","text":"Catheter-related infection","level":2},{"id":"de-escalation-and-stopping-criteria","text":"De-escalation and stopping criteria","level":2},{"id":"documented-infection","text":"Documented infection","level":3},{"id":"unexplained-fever","text":"Unexplained fever","level":3},{"id":"growth-factors","text":"Growth factors","level":2},{"id":"special-scenarios","text":"Special scenarios","level":2},{"id":"hematopoietic-cell-transplantation","text":"Hematopoietic cell transplantation","level":3},{"id":"cellular-therapy","text":"Cellular therapy","level":3},{"id":"severe-beta-lactam-allergy","text":"Severe beta-lactam allergy","level":3},{"id":"renal-dysfunction","text":"Renal dysfunction","level":3},{"id":"disposition","text":"Disposition","level":2},{"id":"admit","text":"Admit","level":3},{"id":"outpatient-discharge","text":"Outpatient discharge","level":3},{"id":"return-immediately-for","text":"Return immediately for","level":3},{"id":"acute-management-checklist","text":"Acute management checklist","level":2},{"id":"decision-pathway","text":"Decision pathway","level":2},{"id":"common-pitfalls","text":"Common pitfalls","level":2},{"id":"current-practice-changes","text":"Current practice changes","level":2},{"id":"related-library-topics","text":"Related library topics","level":2},{"id":"references","text":"References","level":2}],"readingMinutes":16},"linkedMarkdown":"$19","backlinks":[],"related":[],"previewBySlug":{"abcde-approach":{"title":"ABCDE Approach","description":"The ABCDE approach is a structured method for the immediate assessment and treatment of a deteriorating or critically ill patient: Airway, Breathing, Circulation, Disability, Exposure. The central rule is treat life-t…","category":"Emergency Medicine"},"acute-asthma-exacerbation":{"title":"Acute Asthma Exacerbation","description":"An asthma exacerbation is an acute or subacute worsening of dyspnea, wheeze, cough or chest tightness with a fall in expiratory airflow compared with the patient’s usual state. The attack is caused by variable airflow…","category":"Pulmonology"},"bacterial-meningitis":{"title":"Acute Bacterial Meningitis","description":"Acute bacterial meningitis is infection-driven inflammation of the leptomeninges and cerebrospinal fluid (CSF). It can progress over hours to sepsis, shock, cerebral edema, seizures, raised intracranial pressure, hern…","category":"Infectious Disease"},"acute-coronary-syndrome":{"title":"Acute Coronary Syndrome","description":"Acute coronary syndrome (ACS) is the clinical spectrum caused most often by acute coronary atherothrombosis after plaque rupture or erosion and includes ST-elevation myocardial infarction (STEMI), non-ST-elevation myo…","category":"Cardiology"},"acute-ischemic-stroke":{"title":"Acute Ischemic Stroke","description":"Acute ischemic stroke (AIS) is sudden neurological dysfunction caused by focal cerebral, retinal, or spinal cord ischemia, most often from arterial occlusion. The practical emergency question is not simply “is this a…","category":"Neurology"},"acute-kidney-injury":{"title":"Acute Kidney Injury","description":"Acute kidney injury (AKI) is an abrupt decline in kidney function identified by a rise in serum creatinine and/or reduced urine output. The current established international definition remains the KDIGO 2012 definitio…","category":"Nephrology"},"acute-pulmonary-embolism":{"title":"Acute Pulmonary Embolism","description":"Acute pulmonary embolism (PE) is obstruction of the pulmonary arterial circulation by thrombus, usually arising from deep veins of the legs or pelvis. The immediate threat is acute right-ventricular (RV) pressure over…","category":"Pulmonology"},"atrial-fibrillation":{"title":"Atrial Fibrillation","description":"Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by chaotic atrial electrical activation and ineffective atrial contraction. On ECG it produces irregularly irregular RR intervals (when AV c…","category":"Cardiology"},"diabetic-ketoacidosis":{"title":"Diabetic Ketoacidosis","description":"Diabetic ketoacidosis (DKA) is an acute metabolic emergency caused by insufficient effective insulin activity together with excess counterregulatory hormones, producing ketogenesis, metabolic acidosis, osmotic diuresi…","category":"Endocrinology"},"dyslipidemia-in-adults":{"title":"Dyslipidemia in Adults","description":"Dyslipidemia is an abnormal concentration or composition of circulating lipoproteins that increases atherosclerotic cardiovascular disease (ASCVD) risk or, when triglycerides are very high, pancreatitis risk. LDL-cont…","category":"Cardiology"},"sepsis-and-septic-shock":{"title":"Sepsis and Septic Shock","description":"Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Operationally, Sepsis-3 identifies organ dysfunction as an acute increase in SOFA score ≥2 points attributable to infec…","category":"Critical Care"},"upper-gastrointestinal-bleeding":{"title":"Upper Gastrointestinal Bleeding","description":"Upper gastrointestinal bleeding (UGIB) is bleeding arising proximal to the ligament of Treitz. It most commonly presents with hematemesis, coffee-ground emesis, melena, or—when brisk—hematochezia with hemodynamic inst…","category":"Gastroenterology"}},"categories":["Cardiology","Critical Care","Emergency Medicine","Endocrinology","Gastroenterology","Infectious Disease","Nephrology","Neurology","Pulmonology"]}]