Fever Without a Source Age: 0-28 Day Pathway - Emergency Department Evidence Based Outcome Center

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Age: 0-28 Day Pathway - Emergency Department EXCLUSION CRITERIA Toxic appearing No fever Born < 37 weeks gestational age INCLUSION CRITERIA Non-toxic with temperature > 38 C (100.4 F) < 36 C (96.5 F) measured in Emergency Department reported measurement at home.! ALERT Patient Toxic/Septic Appearance Full Sepsis Workup & treat as appropriate. (LINK TO SEPSIS PATHWAY/GUIDELINE) Consider HSV work up and empiric ED treatment for patients with any of the following conditions: Historical and Clinical Features Severe illness / Hypothermia / Lethargy Seizures Hepatosplenomegaly Postnatal HSV contact Vesicular rash Conjunctivitis Interstitial pneumonitis Laboratory Findings Thrombocytopenia CSF pleocytosis without clear bacterial infection Transaminitis Focal infection Complete Blood Count with differential Blood Culture Complete Metabolic Panel Urinalysis with Micro Urine Culture: Catheter or Suprapubic Cerebrospinal Fluid (Hold Tube # 4) Gram stain Culture Cell count with differential Glucose Protein Stool culture & Stool WBC(If patient has diarrhea) Herpes Simplex Virus (HSV) work-up indicated Start empiric antibiotic treatment: Ampicillin x1 + Gentamicin x1 Manage OFF-PATHWAY Contraindications for Ceftriaxone in patients < 28 days of age: Patient expected to or receiving calcium containing IV products. Total Bilirubin > 10 (See risk factors for hyperbilirubinemia) 1 HSV DNA PCR of Blood Meningitis/Encephalitis PCR Panel of CSF Swab/scraping of skin or mucous membrane lesions for HSV DFA AND HSV culture Surface HSV cultures in viral transport media tube Conjunctiva Throat Nasopharynx Rectum Skin vesicle (if present) ADD antiviral treatment: Acyclovir Normal CSF Values 0-20 WBC/mm 3 Protein 0-30 days: < 100 mg/dl Normal Gram Stain ADMIT to Inpatient Management Pathway Patient Age: 0-7 Days 1 Confirm meningitic dose of Ampicillin (Redose if needed) 2 Add Cefotaxime (Use Cefepime if supply unavailable) 3 Consider HSV testing and Acyclovir therapy Patient Age: 8-28 Days 1 Confirm meningitic dose of Ampicillin (Redose if needed) 2 Add Ceftriaxone Confirm meningitic dosing (Use Cefepime if contraindicated ❶) 3 Consider HSV workup and Acyclovir therapy

Age: 29-60 Day Pathway - Emergency Department EXCLUSION CRITERIA Toxic appearing No fever Born < 37 weeks gestational age Low Risk Criteria for Serious Bacterial Infection Historical and Clinical Features 29-60 days Full-term ( 37 weeks gestation) No prolonged NICU stay No chronic medical problems No systemic antibiotics within 72 hours Well-appearing and easily consolable No focal infections on exam Fecal Leucocytes Stool WBC 5 hpf Blood WBC 5,000 AND 15,000 Immature WBC/neutrophil Ratio < 0.2 Absolute Band Count < 1500/mm 3 Standard UA: WBC < 5/HPF Negative LE, Nitrite, Bacteria Chest X-ray (if obtained) No infiltrate Normal CSF Values 0-20 WBC/mm 3 Protein 0-30 days: < 100 mg/dl Normal Gram Stain DISCHARGE Home Follow-up in 24 hours No Antibiotics OPTION 1 ADMIT for Observation Manage OFF-PATHWAY Focal bacterial infection Complete Blood Count with differential Blood Culture Basic metabolic panel Urinalysis with Micro Urine Culture: Catheter or Suprapubic Stool culture & Stool WBC(If patient has diarrhea) INCLUSION CRITERIA Non-toxic with temperature > 38 C (100.4 F) < 36 C (96.5 F) measured in Emergency Department reported measurement at home. OPTION 2 OPTION 3 Meets Low Risk Criteria CSF Collected Empiric antibiotic treatment: Ceftriaxone DISCHARGE Home Follow-up in 24 hours Patient family & PCP must be in agreement! ALERT Patient Toxic/Septic Appearance Full Sepsis Workup & treat as appropriate. (LINK TO SEPSIS PATHWAY/GUIDELINE) Order Lumbar Puncture: Cerebrospinal Fluid (Hold Tube # 4) Gram stain Culture Cell count with differential Glucose Protein Empiric antibiotic treatment: Ceftriaxone + Vancomycin ADMIT to Inpatient Manage OFF-PATHWAY

Age: 2-6 Months Pathway - Emergency Department EXCLUSION CRITERIA Toxic appearing No fever Born < 37 weeks gestational age INCLUSION CRITERIA Non-toxic with temperature > 39 C (102.2 F) < 36 C (96.5 F) measured in Emergency Department reported measurement at home.! ALERT Patient Toxic/Septic Appearance Full Sepsis Workup & treat as appropriate. (LINK TO SEPSIS PATHWAY/GUIDELINE) Treat with Supportive Care Defined Focal Bacterial Infection: Cellulitis, abscess, pneumonia, osteomyelitis, bacterial arthritis, omphalitis, meningitis Defined Viral Syndrome Croup Bronchiolitis Stomatitis Influenza Varicella Manage OFF-Pathway Consider Alternate Management Pathway Community Acquired Pneumonia Urinary Tract Infection Acute Osteomyelitis Prolonged fever >5 days: Consider Kawasaki Disease Patient received 2 or more doses of Pneumococcal Conjugate Vaccine (PCV) Continue UTI Assessment Complete Blood Count with differential WBC > 15,000/mm 3 < 5,000/mm 3 Influenza/ Bronchiolitis Meets Low Risk UTI Criteria? Order Blood Culture Urinalysis with Micro Urine Culture: Catheter or Suprapubic After UTI Assessment is Complete Empiric antibiotic treatment: Ceftriaxone UTI Management Guideline Urinalysis positive ED Discharge Criteria Tolerating liquids Reliable PCP or ED follow-up PCP and Caregiver comfortable with discharge Good social support Education complete ADMIT to Inpatient Management Pathway DISCHARGE Home Follow-up in 24 hours

EXCLUSION CRITERIA Toxic appearing No fever Born < 37 weeks gestational age Fever Without Source 0-89 Days of Age INCLUSION CRITERIA Non-toxic with temperature > 38 C (100.4 F) < 36 C measured in Emergency Department reported measurement at home. Normal CSF Values 0-20 WBC/mm 3 Protein 0-30 days: < 100 mg/dl Normal Gram Stain 0 7 Days of Age 8 28 Days of Age 29 89 Days of Age High Risk for Serious Bacterial Infection 1 Meningitic dose of Ampicillin 2 Cefotaxime (Use Cefepime if unavailable) ADD antiviral treatment: Acyclovir (If clinical suspicion of HSV) Continue antibiotic treatment: Ampicillin + Gentamicin Contraindication for Ceftriaxone? ❶ 1 Meningitic dose of Ampicillin 2 Add Ceftriaxone 1 Meningitic dose of Ampicillin 2 Cefotaxime (Use Cefepime if supply unavailable) ADD antiviral treatment: Acyclovir (If clinical suspicion of HSV) Continue antibiotic treatment: Ceftriaxone Observation 36 hours (Longer if ill-appearing) ADD antiviral treatment: Acyclovir (If clinical suspicion of HSV) Monitor Cultures: Blood Urine CSF GPC on CSF gram stain 1 Add Vancomycin 2 Continue Ceftriaxone/Cefotaxime 3 Continue Ampicillin Observation: 24-36 hours (Longer if ill-appearing) Monitor Cultures: Blood Urine CSF 1 Add Vancomycin 2 Continue Ceftriaxone Risk factors for hyperbilirubinemia ABO incompatibility HDN Lethargy Temperature instability Sepsis Acidosis Albumin < 3g/dL Dehydration Weight loss Poor feeding Irritability Jaundice Contraindications for Ceftriaxone in patients < 28 days of age: Patient expected to or receiving calcium containing IV products. Total Bilirubin > 10 (See risk factors for hyperbilirubinemia) 1 Inpatient Discharge Criteria Blood, urine, CSF, & HSV evaluation negative Clinically stable based on provider assessment Reliable PCP Follow-up Education complete Manage OFF-PATHWAY DISCHARGE Home Follow-up in 24 hours

Risk Factors for UTI and Screening Recommendations Probability of UTI > 1%: 2 or more risk factors Female Risk Factors* Non-black T 39 C Fever 2 days No apparent source of fever Age < 12 months *Recommend screening if prior history of UTI, fever 2 days > 2 months Not Toilet Trained Probability of UTI > 1%: Uncircumcised Circumcised with 3 or more Risk Factors Male Risk Factors* Non-black T 39 C Fever 2 days No apparent source of fever Age < 6 months Toilet Trained 18 years All Patients Symptoms referable to urinary tract Prior history of UTI, fever 2 days Prolonged fever ( 5 days) Recommend screening for any of the above factors

Serious Bacterial Infection Low Risk Criteria for Serious Bacterial Infection Historical and Clinical Features 29-60 days Full-term ( 37 weeks gestation) No prolonged NICU stay No chronic medical problems No systemic antibiotics within 72 hours Well-appearing and easily consolable No focal infections on exam Fecal Leucocytes Stool WBC 5 hpf Blood WBC 5,000 AND 15,000 Immature WBC/neutrophil Ratio < 0.2 Absolute Band Count < 1500/mm 3 Standard UA: WBC < 5/HPF Negative LE, Nitrite, Bacteria Chest X-ray (if obtained) No infiltrate

Herpes Simplex Virus Patiens with any of the following conditions should be considered for a Herpes Simplex Virus work up and empiric treatment: Historical and Clinical Features Severe illness / Hypothermia / Lethargy Seizures Hepatosplenomegaly Postnatal HSV contact Vesicular rash Conjunctivitis Interstitial pneumonitis Laboratory Findings Thrombocytopenia CSF pleocytosis without clear bacterial infection Transaminitis Herpes Simplex Virus Workup Consists of the following labs: HSV DNA PCR of Blood Meningitis/Encephalitis PCR Panel of CSF Swab/scraping of skin or mucous membrane lesions for HSV DFA AND HSV culture Surface HSV cultures in viral transport media tube Conjunctiva Throat Nasopharynx Rectum Skin vesicle (if present)

UTI Definition and Urinalysis DCMC Positive Urinalysis (UA) Definition: The presence of Leukocyte Esterase Nitrites microscopic analysis results positive for leukocytes or bacteria is suggestive of an active UTI. When more than one of these findings is present at the same time, the sensitivity and specificity increase significantly. Dell Children s and Seton Family of Hospitals does not currently perform an enhanced urinalysis on urine specimens routinely. The following criteria are guide in diagnosing a UTI in young children using the standard method of collection and processing. Diagnostic Interpretation Nitrites Poor sensitivity: Conversion of nitrates to nitrites by bacteria takes approximately 4 hours and not all bacteria reduce nitrate levels combined with frequency of infants voiding. Helpful when positive. Few false positives and high specificity. Leukocyte Esterase Positive leukocyte esterase is suggestive of a UTI. However, children may have WBC present in their urine in conditions other than a UTI (e.g. Kawasaki Disease) White Blood Cells Positive if: (WBC) - Pyuria 5 WBC per HBF via standard method Pyuria is absent in approximately 10% of children with a UTI Bacteriuria Presence of bacteriuria alone in the absence of other findings does not define a UTI. Culture Method Definite* Indeterminant Contaminant Suprapubic Any growth Growth of non-pathogens, Mixed culture Catheter 50,000 CFU/ML 10,000 CFU/ML Growth of non-pathogens, Mixed culture, < 10,000 CFU/ml * If also with presence of pyuria or bacteriuria Consider obtaining repeat specimen Mixed Culture = uropathogen + non-pathogen or two uropathogens Bag UA specimens should never be sent for urine culture. Only catheter or suprapubic methods are appropriate for culture collection in this age. Uropathogens Gram Negative Escherichia coli (~80%) Klebsiella Proteus Enterobacter Citrobacter Gram Positive Staphylococcus saprophyticus Enterococcus Staphylococcus aureus Non-pathogens Lactobacillus Coagulase-negative Staph Corynebacterium

Antimicrobial and Antiviral Dose Recommendations Drug a,b,c,d Dose Duration e N-MENINGITIC 7 days of age: 50 mg/kg/dose IV q8h 5 doses Ampicillin N-MENINGITIC > 7days of age: 50 mg/kg/dose IV q6h 6 doses MENINGITIC 7 days of age: 100 mg/kg/dose IV q8h 5 doses MENINGITIC > 7days of age: 100 mg/kg/dose IV q6h 6 doses Cefepime 50 mg/kg/dose IV q8h 5 doses Cefotaxime 7 days of age: 50 mg/kg/dose q8h 5 doses > 7days of age: 50 mg/kg/dose q6h 6 doses Ceftriaxone d If to be admitted: 50 mg/kg/dose IV q12h 3 doses If to be discharged: 50-100 mg/kg/dose IV (ED ONLY) 1 dose Gentamicin b 4 mg/kg/dose IV q24h 2 doses Vancomycin c 7 days of age: 20 mg/kg/dose IV q8h > 7days of age: 20 mg/kg/dose IV q6h Recommended Dose for UTI a Dosing in this table is for patients with normal renal function. Please contact pharmacy for assistance with dosing in renal insufficiency. b For gentamicin, serum drug levels are not necessary unless treatment is anticipated or continued for more than 2 doses, SCr is increased more than 0.3 mg/dl from normal value for age, or UOP less than 1 ml/kg/hr. c For vancomycin, serum drug levels are not necessary unless treatment is anticipated or continued for more than 2 doses, SCr is increased more than 0.3 mg/dl from normal value for age, or UOP less than 1 ml/kg/hr. d Ceftriaxone is contraindicated with calcium containing IV products or hyperbilirubinemia. Meningitic dosing of ceftriaxone is 80-100 mg/kg/day divided every 12-24 hours but CSF concentrations are optimal when dosed at 50mg/kg/dose IV q12h; once daily dosing should be reserved for patients to be discharged from the ED. e If cultures become positive at any time, treat specific condition, narrow agent and lengthen antibiotic duration as appropriate. 5 doses 6 doses Drug Dose Duration Cefazolin 17 mg/kg/dose q8h 7 Days Recommended Dose for Antiviral Drug Dose Duration Acyclovir 20 mg/kg/dose IV q8h 5 doses until HSV surface cultures AND PCR Blood & CSF negative Exceptions: Seizures, Lethargy, or ongoing Fever