Table 3. Overview on externally validated clinical decision rules (CDRs): Inclusion and exclusion criteria, characteristics and outcomes.
| CDR | Inclusion criteria | Exclusion criteria | High risk criteria | High risk outcome |
|---|---|---|---|---|
| Rackoff 1996* | Cancer or hematologic malignancy; fever ≥ 38.5°C once or ≥38.0°C 3× during a 24-h period*; ANC < 0.5 G/l; outpatient |
Inpatient onset FN | High risk = AMC < 0.1 G/l and temperature ≥39°C Intermediate risk = AMC < 0.1 G/l and temperature < 39°C Low risk = AMC ≥ 0.1 G/l |
Bacteremia (defined as a positive blood culture) |
| Klaassen 2000* | Cancer or hematologic malignancy, fever > 38.5°C once or >38.0°C during 12 hour period*; ANC ≤ 0.5 or between 0.5 and 1.0 G/l and expected to fall, outpatient |
New diagnosis cancer, HSCT within 6 months, comorbidity on presentation including severe mucositis and pneumonia |
AMC < 0.1 G/l |
Significant bacterial Infection—defined as blood or urine culture positive for bacteria, interstitial or lobar consolidation on chest x-ray, or unexpected death from infection (patient not palliative) |
| Baorto 2001* | Cancer or hematologic malignancy, fever ≥ 38.0°C; ANC ≤ 0.5 G/l |
Age < 1 y, previous HSCT |
AMC < 0.155 G/l | Bacteremia (not defined)† |
| Madsen 2002* | Cancer or hematologic malignancy; fever ≥ 38.5°C once or ≥38.0°C 3× during a 24-h period*; ANC ≤ 0.5 G/l; outpatient |
Inpatient onset of FN, HSCT, AML patients in intensive timing theraoy | Temperature > = 39.5°C and AMC ≤0.01G/l | positive blood culture † |
| Rondinelli 2006* | Cancer or hematologic Malignancy; fever ≥ 38.1°C once or > 37.8°C on 3 separate occasions measured within a period of 24 hours*; ANC (segmented granulocytes and rods) < 0.5 G/l or 0.5–1.0 that tended to drop in 72 hours, outpatient, first episode of FN |
HSCT (autolog and allogenic), not the first episode of FN; inpatient onset of FN | Score 2.5–5 = low risk Score 5.5–9 = intermediate risk Score ≥ 9 = high risk Age ≤5 y = 1, 2. CVAD = 2, Clinical site = 4.5, Fever >38.5°C = 1, Hemoglobin ≤ 70g/l = 1, upper respiratory tract infection = 2.5 |
Severe infection complication was defined as the presence of sepsis and/or shock and/or bacteremia or fungemia from blood sample, and/or death from an infectious process during a FN episode. The presence of any infectious agent in a blood sample was considered as bacteremia. Septicemia was defined as a syndrome of systemic inflammatory response (involving ≥ 2 of the following characteristics: tachycardia, tachypnea, hypothermia,or hyperthermia, with positive blood culture or clinical and laboratorial infection detected and adequate peripheral perfusion). Patients were considered in septic shock when severe sepsis was observed, with clinical signs of hypoperfusion and blood hypotension, who no longer answered to fluids and who needed inotropic doses to maintain hemodynamic balance. |
| SPOG-AE (Ammann) 2010* | Cancer or hematologic malignancy; fever ≥ 38.5°C once or ≥38.0°C during ≥2 hours*; ANC ≤ 0.5 G/l; outpatient |
Myeloablative chemotherapy; AE known at presentation | Applied after 24 hours‡ Total score ≥ 9 = high risk of AE. Score for preceding chemotherapy more intensive than ALL maintenance = 4; Hb ≥ 90 g/l = 5; leukocyte count < 0.3 G/L = 3; platelet count < 50 G/L = 3 |
Adverse outcome, defined as a SMC (death, complication requiring ICU and potentially life-threatening complication as judged by the treating physician) as a result of infection, MDI (positive bacterial or fungal culture from a normally sterile site and detection of a viral antigen by PCR) and radiologically confirmed pneumonia. Bacteremia not defined† |
| Hakim 2010* | Cancer or hematologic malignancy; fever ≥ 38.3°C or ≥38.0°C for ≥1 hour*; ANC ≤ 0.5 G/l; outpatient |
HSCT; inpatient onset FN |
Total score ≥ 24 = high risk of invasive bacterial infection. Score for cancer diagnosis: AML = 20, ALL/lymphoma = 7, solids = 0 points; Clinical presentation serious unwell or toxic = 14 points; Fever ≥ 39°C at presentation = 11 points; ANC < 0.1 G/l = 10 points |
Proven invasive bacterial Infection, defined as isolation of a pathogen from a sterile body site or as proven by histology. Culturenegative Sepsis, defined as a systemic response to a possible infection because of hemodynamic instability, focal or multiple organ involvement or altered mental status or lethargy. Bacteremia defined as a recognized pathogen cultured from one or more blood cultures or common commensals cultured from two or more blood cultures. |
| Suttitossatam 2020* | fever ≥ 38.3°C or ≥ 38.0°C persisting >1 hour*; ANC < 0.5 G/l or ANC < 1.0 G/l with a predicted decrease to < 0.5 G/l | Age < 1 year | Age ≥ 10 years |
Severe adverse outcomes as hypotension (is determined by age and systolic blood pressure, in line with Pediatric Advanced Life Support (PALS) Guidelines) or shock; respiratory failure (the need for noninvasive respiratory support or mechanical ventilation); death |
| AUS (Haeusler) 2020* | Cancer or hematologic Malignancy; fever ≥ 38°C; ANC < 1.0 G/l; in- and outpatient |
HSCT in last 3 months; treatment commenced at a non-participating site already receiving concurrent intravenous or oral antibiotics (excluding prophylaxis) |
Score ≥ 1 = High risk preceding chemotherapy more intensive than ALL maintenance = 1; WCC < 0.3 G/l = 1; platelet <50 g/L = 1 |
Three outcomes were analyzed: • Likely bacterial infectionI (any infection with a microbiologically documented bacterial cause or that was clinically documented in categories typically attributed to bacterial infection, including pneumonia, skin and soft-tissue infection, osteomyelitis or myositis, enterocolitis, otitis media or externa, sinusitis, epididymoorchitis, centralvenous catheter pocket or tunnel infection, pharyngitis, perianal abscess or cellulitis, peritonitis or lymphadenitis) • Bacteremia (recognised pathogen (including organisms associated with mucosal barrier injury in the setting of mucositis or neutropenia) from ≥ 1 blood culture set or common commensals from ≥ 2 blood culture sets drawn on separate occasions) • ICU-Admission |
* for external crossvalidation with restricted dataframe these definitions were modified for validation because of available data (inclusion of all events which reached the lower temperature limit once).
† if not otherwise specified, international consensus definition was used for validation (Haeusler GM, 2015, Pediatr Blood Cancer).
‡ Application at FN presentation for external cross-validation.
Abbreviations: AE, adverse event; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; AMC, absolute monocyte count; ANC, absolute neutrophil count; FN, fever in neutropenia; HSCT, hematopoietic stem cell transplantation; ICU, intensive care unit; MDI, microbiological defined infection; PCR, polymerase chain reaction; SMC, serious medical complication, WCC, white cell count.