01Approach to the Critical Patient/attcp55

Immediate stabilization

›Airway and breathing

›Respiratory failure pattern

›SpO2 < 90% on room air

›ARDS development in severe cases

›If unable to protect airway, proceed to intubation

›Rapid sequence intubation preparation

›ARDS ventilation strategy if applicable

›Circulatory and sepsis threats

›Shock physiology

›SBP < 90 mmHg

›MAP < 65 mmHg

›Septic shock-like syndrome recognition

›Fluid resuscitation with 30 ml/kg crystalloid

›Vasopressor initiation if refractory to fluids

›Lactate >= 2 mmol/l as organ hypoperfusion marker

›Repeat within 2 hours if elevated

›Doxycycline initiation on clinical suspicion

›Do NOT wait for confirmatory testing

›Treatment delay strongly associated with adverse outcomes

›Fever typically resolves within 24 to 48 hours if treated early

›IV route for critically ill, vomiting, or obtunded patients

›Doxycycline 100 mg IV every 12 hours

›Switch to oral when tolerating PO

Alarm features and escalation triggers

›Critical complication recognition

›Altered mental status or meningoencephalitis

›Neurological ehrlichiosis occurs in ~20% of cases

02History/hx62

Presentation pattern

›Core syndrome

›Acute onset high fever

›Often > 38.5 degrees C

›Incubation 5 to 14 days after tick bite (median 9 days)

›Severe headache

›Present in majority of cases

›Retroorbital component possible

›Myalgias and malaise

›Prominent early features

›Arthralgias may accompany

›Gastrointestinal symptoms

›Nausea 57% of cases

›Vomiting 47% of cases

›Diarrhea 25% of cases

›Abdominal pain more prominent in children

›Rash

›Present in approximately 30% of patients

›More common in children than adults

›Maculopapular or petechial morphology

›Typically appears 5 days after illness onset

›Neurologic symptoms

›Confusion and altered mental status

›Neck stiffness in meningoencephalitis pattern

›Seizures or focal deficits in neuro-ehrlichiosis

›Respiratory symptoms

›Cough present in ~28% of cases

›Dyspnea with ARDS development

03Physical Exam/exam74

Vitals and general appearance

›Vital signs snapshot

›Temperature

›Fever often > 38.5 degrees C

›Hypothermia possible in severe sepsis

›Heart rate

›Tachycardia expected with fever and sepsis physiology

›Bradycardia uncommon unless cardiac complication

›Blood pressure

›Hypotension in toxic shock-like presentations

›SBP < 90 mmHg as severity marker

›Respiratory rate

›Tachypnea with ARDS or pneumonia complication

›>= 30 per minute as severity marker

›General appearance

›Toxic appearance

›Diaphoresis, pallor

›Ill appearance out of proportion to initial vitals

›Mental status

›Agitation or somnolence in neuro-ehrlichiosis

›GCS assessment

Skin examination

›Rash characterization

›Maculopapular or petechial morphology

›Distributed on trunk and extremities

›May involve palms, soles, and face

›Absent in approximately 70% of adults

›Rash visibility considerations

04Differential Diagnosis/ddx53

Life-threatening mimics

›Immediate threats requiring parallel evaluation

›Rocky Mountain Spotted Fever

›ICD-10 A77.0

›Rash more common; petechial with centripetal spread to palms and soles

›Higher untreated mortality; same empiric treatment with doxycycline

›Meningococcemia

›ICD-10 A39.4

›Petechial or purpuric rash

›Blood cultures and empiric cephalosporin coverage

›Sepsis from bacterial source

›ICD-10 A41.9

›Blood cultures and broad-spectrum antibiotics

›Thrombotic thrombocytopenic purpura

›ADAMTS13 activity level

›Microangiopathic hemolytic anemia pattern

›Hemophagocytic lymphohistiocytosis

›ICD-10 D76.1

›Ferritin, triglycerides, soluble IL-2 receptor evaluation

Tick-borne disease mimics

›Other tick-borne illnesses

›Anaplasmosis

›ICD-10 A77.49

›Similar presentation; granulocytes affected not monocytes

›Northeastern and upper Midwest distribution

›Rash uncommon; same doxycycline treatment

›Lyme disease

›ICD-10 A69.20

05Laboratory Tests/lt65

Core diagnostic labs

›Complete blood count with differential

›Leukopenia

›Present in 57.8% of cases

›Left shift may be present in severe infection

›Thrombocytopenia

›Present in 79.1% of cases

›Platelet count < 100 x10^9/L in severe disease

›Anemia

›Later in disease course

›Microangiopathic pattern if HLH developing

›Comprehensive metabolic panel

›Elevated transaminases

›Present in 68.1% of cases

›ALT and AST elevation proportional to disease severity

›Creatinine elevation

›Renal involvement marker

›Acute kidney injury in severe cases

›Electrolyte disturbances

›Hyponatremia common with systemic infection

›Renal function guides fluid and drug dosing

Inflammatory and coagulation markers

›Inflammatory markers

›LDH

›Often elevated

›Markedly elevated in HLH

›Ferritin

›If HLH suspected

06Diagnostic Tests/dt71

Scoring Systems

›Tick-borne illness severity assessment

›No validated disease-specific scoring tool for ehrlichiosis

›Clinical severity stratification used instead

›Mild: Fever and myalgias with mild cytopenias tolerating PO

›Moderate: Significant cytopenias, transaminitis, GI symptoms limiting PO

›Severe: AMS, ARDS, renal failure, DIC, HLH, or shock

›Sepsis screening tools as adjuncts

›qSOFA: RR >= 22, SBP <= 100 mmHg, altered mental status

›Screening tool only; not validated for ehrlichiosis specifically

›HLH-2004 diagnostic criteria

›5 of 8 criteria required

›Fever, splenomegaly, bicytopenia, hypertriglyceridemia or hypofibrinogenemia

›Hemophagocytosis on marrow biopsy, low NK activity, ferritin > 500 mcg/L, elevated soluble CD25

›Treatment response as clinical marker

›Defervescence within 24 to 48 hours of doxycycline is expected

›Failure to defervesce by 48 hours prompts diagnostic reassessment

MRI

›MRI indications in ehrlichiosis

›Neuro-ehrlichiosis evaluation

›White matter T2 signal changes in meningoencephalitis

›MRI brain often unremarkable despite significant neurological symptoms

›Most sensitive imaging for posterior fossa involvement

›Acute brain imaging

›CT head first for rapid exclusion of hemorrhage or mass lesion

›MRI for further characterization if CT non-diagnostic

›Spinal cord involvement

›MRI spine if myelopathy suspected

07Disposition/dispo59

Admission indications

›Hospital admission criteria

›Organ dysfunction

›Acute kidney injury with elevated creatinine

›Transaminase elevation > 3x upper limit of normal

›Respiratory compromise

›Severe cytopenias

›Platelet count < 50 x10^9/L

›WBC < 2.0 x10^9/L

›Altered mental status or meningoencephalitis

›Any change from baseline cognitive status

›Focal neurological findings

›Inability to tolerate oral medications

›Persistent vomiting

›GI symptoms limiting PO intake

›Hemodynamic instability

›SBP < 90 mmHg

›Heart rate > 120 with fever and signs of poor perfusion

›Immunocompromised host with moderate to severe disease

›Higher complication rate and mortality

›26.7% of reported cases are immunocompromised

ICU indications

›Critical care escalation

›Ventilatory support requirement

›ARDS meeting Berlin criteria

›Intubation or HFNC with escalating oxygen requirement

›Septic shock

›Vasopressor requirement after fluid resuscitation

08Treatment/t85

Empiric antibiotic therapy

›First-line treatment

›Doxycycline

›Adults: 100 mg PO or IV every 12 hours

›Children under 45 kg: 2.2 mg/kg PO or IV every 12 hours (max 100 mg per dose)

›IV route for critically ill, obtunded, or vomiting patients

›Switch to oral when tolerating PO

›Duration

›Minimum 5 to 7 days total

›At least 3 days after defervescence

›Extend to 10 to 14 days if neurological involvement

›Pediatric doxycycline safety

›Safe in children under 8 years old

›No evidence of dental staining at recommended doses and duration

›CDC and AAP recommend doxycycline as only first-line agent for children

›Expected response

›Fever typically resolves within 24 to 48 hours of initiation

›If no defervescence by 48 hours, reconsider diagnosis or evaluate for coinfection

Alternative therapy

›When doxycycline is contraindicated

›Rifampin

›Adults: 300 mg PO twice daily

›Children: 10 mg/kg PO twice daily

›Indications: mild illness only with true doxycycline allergy

›No clinical trial data supporting rifampin efficacy

›Infectious disease consultation recommended

›Pregnancy

›Consult infectious disease early

›Rifampin may be considered for mild illness

›Doxycycline preferred for life-threatening disease even in pregnancy

›Ineffective and contraindicated agents

›Chloramphenicol

›In vitro resistance demonstrated

›NOT effective for ehrlichiosis

›Sulfonamides including TMP-SMX

›Associated with increased disease severity

›Absolutely contraindicated

›Beta-lactams

›Penicillins, cephalosporins, carbapenems: all ineffective

›Macrolides

›Azithromycin, clarithromycin: ineffective

›Fluoroquinolones

›Ciprofloxacin, levofloxacin: ineffective

›Aminoglycosides

›Gentamicin, tobramycin: ineffective

›Pearl: Using antibiotics other than doxycycline increases risk of death per CDC

Supportive care

›Hemodynamic support

›IV fluid resuscitation

›0.9% NaCl or lactated Ringer 30 ml/kg for septic shock

›Reassess after initial bolus with clinical and ultrasound assessment

›Vasopressor therapy

›Norepinephrine 0.01 to 3 mcg/kg/minute

›Titrate to MAP >= 65 mmHg

›Add vasopressin 0.03 units/minute if refractory

›Respiratory support

›Supplemental oxygen

›Nasal cannula titration to SpO2 >= 92%

›HFNC for moderate ARDS

›Mechanical ventilation for severe ARDS (PaO2/FiO2 < 200 mmHg)

›Lung-protective ventilation if intubated

›Tidal volume 6 ml/kg ideal body weight

›Plateau pressure < 30 cmH2O

›Hematologic support

›Platelet transfusion

›Threshold < 10 x10^9/L for prophylactic transfusion

›Threshold < 50 x10^9/L for invasive procedures

›Packed red blood cells

›Threshold hemoglobin < 70 g/L in stable patients

›Higher threshold (< 80 g/L) in cardiac disease or active bleeding

›Fresh frozen plasma

›DIC with active bleeding and INR > 1.5

›Fibrinogen replacement with cryoprecipitate if < 1.5 g/L

HLH-directed therapy

›HLH treatment when confirmed or highly suspected

›Dexamethasone

›10 mg/m2 per day orally for 8 weeks with taper

›Immunosuppression to control hyperactivated immune response

›Etoposide

›150 mg/m2 IV weekly for first 2 weeks then biweekly

›Hematology-guided dosing and monitoring

›HLH protocol per HLH-2004 or HLH-94 guidelines

›Consider IVIG as adjunct

›Cyclosporine addition per specialist guidance

›Doxycycline must continue throughout HLH treatment

›Treat the underlying infection simultaneously

›Bone marrow transplant

›For familial or refractory HLH

›Specialist decision

09Special Populations/sp56

Pregnancy

›Pregnancy-specific considerations

›Physiological vulnerability

›Immune modulation of pregnancy may alter presentation

›High fever risks fetal harm and preterm labor

›Fever management with acetaminophen is important

›Antibiotic selection dilemma

›Doxycycline: tetracycline class; teratogenicity concern second and third trimester

›For mild disease: rifampin 300 mg PO twice daily may be considered after infectious disease consultation

›For severe or life-threatening disease: doxycycline is indicated regardless of gestational age

›Risk of untreated ehrlichiosis exceeds drug risk in severe disease

›Maternal and fetal monitoring

›Fetal monitoring when viable gestation

›Obstetrics consultation for all pregnant patients with ehrlichiosis

›Outcomes

›Case reports of maternal death and fetal loss with untreated or delayed treatment

›Early treatment generally associated with good maternal and fetal outcome

Geriatric

›Older adult considerations

›Atypical presentation risk

›Attenuated febrile response; may present afebrile

›Delirium as primary presenting symptom

›Higher baseline comorbidity obscuring diagnosis

›Higher severity and mortality

›Case fatality rate higher in older adults

›Rapid deterioration to multi-organ failure

›Medication considerations

›Doxycycline dosing unchanged by age alone

10Background/b78

Epidemiology

›Incidence and distribution

›National case data

›Ehrlichiosis is a nationally notifiable disease in the United States

›Several thousand cases reported annually to CDC

›Cases concentrated in southeastern and south-central United States

›Missouri, Arkansas, North Carolina, and New York account for approximately 50% of cases

›Species distribution

›E. chaffeensis causes human monocytic ehrlichiosis (HME); most common

›E. ewingii causes ehrlichiosis primarily in immunocompromised hosts

›E. muris eauclairensis concentrated in Upper Midwest (Minnesota and Wisconsin)

›Tick vectors

›Lone star tick (Amblyomma americanum): primary vector for E. chaffeensis and E. ewingii

›Blacklegged tick (Ixodes scapularis): vector for E. muris eauclairensis

›Seasonality

›Peak transmission May through August corresponding to tick activity

›Mortality and outcomes

›Overall case fatality rate approximately 11.6%

›Immunocompromised patients: 16.3% fatality

›Immunocompetent patients: 9.9% fatality

›Death associated with delayed treatment

›Treatment within first 5 days of illness dramatically reduces mortality

›Using antibiotics other than doxycycline increases risk of death

›Immunocompromised overrepresentation

›26.7% of reported cases occur in immunocompromised patients

›Multi-organ failure in 26% of immunocompromised vs 14.9% in immunocompetent

Pathophysiology

›Intracellular infection mechanism

›Obligate intracellular bacteria

›E. chaffeensis infects monocytes and macrophages

›E. ewingii infects granulocytes (neutrophils)

›Bacteria replicate within membrane-bound vacuoles (morulae)

›Immune evasion strategies

›Inhibits phagosome-lysosome fusion

›Downregulates host immune signaling

›Modulates apoptosis to survive within host cells

›Tick transmission

›Tick must be attached and feeding; transmission risk increases after 24 hours

›Saliva contains immunomodulatory factors facilitating infection

›Pathological mechanisms

›Direct cellular injury

›Monocyte and macrophage dysfunction

›Hepatocyte involvement causing transaminase elevation

›Endothelial dysfunction contributing to vascular complications

›Immune-mediated tissue damage

›Cytokine storm in severe cases

›HLH as extreme immune dysregulation

›Cytopenias partly from bone marrow suppression

›Organ-specific effects

›CNS: Direct meningeal involvement with lymphocytic pleocytosis

›Liver: Hepatitis pattern with transaminase elevation

›Bone marrow: Hemophagocytosis in HLH

›Kidney: Acute tubular injury in severe disease

Therapeutic Considerations

›Antibiotic rationale

›Mechanism of doxycycline

›Tetracycline class antibiotic

›Inhibits bacterial protein synthesis at 30S ribosomal subunit

›Effective against intracellular organisms including Ehrlichia species

›Why other antibiotics fail

›Beta-lactams cannot penetrate intracellular compartments

›Chloramphenicol: in vitro resistance documented for E. chaffeensis

›Sulfonamides paradoxically increase disease severity; absolute contraindication

›Macrolides and fluoroquinolones: insufficient intracellular activity

›Empiric treatment principle

›Clinical suspicion alone is sufficient to start treatment

›Do not wait for PCR or serology confirmation

›Treatment should be initiated in the ED or clinic

›Diagnostic testing strategy

›PCR as gold standard for acute illness

›Whole blood PCR sensitivity > 95% during first 10 days of illness

›Sensitivity decreases after doxycycline initiation

›EDTA or heparin tube; transport on ice within 1 hour

›Serology limitations

›IFA IgG antibody titers frequently negative in first 7 to 10 days

›Requires paired sera with fourfold rise in titer

›Acute serology alone cannot be used to rule out diagnosis

›IgG titer >= 1:128 supports diagnosis in later presentations

›Treatment response as diagnostic confirmation

›Defervescence within 24 to 48 hours strongly supports diagnosis

›Used as clinical confirmation when PCR result pending

11Patient Discharge Instructions/pdi38

copy discharge instructions

›Ehrlichiosis home care instructions

›Medications

›Take doxycycline exactly as prescribed; complete the full course

›Do not stop early even if feeling better

›Take with a full glass of water; avoid lying down for 30 minutes after each dose

›Avoid dairy, antacids, iron, and calcium supplements within 2 hours of each dose

›Activity and diet

›Rest as needed; activity as tolerated

›Drink plenty of fluids to stay well hydrated

›Light diet initially if nausea is present

›Sun exposure

›Doxycycline increases sensitivity to sunlight

›Use sunscreen and protective clothing outdoors

›Return to emergency department immediately for

›Warning signs requiring urgent care

›Fever that is not improving after 48 hours of antibiotics

›Confusion, unusual drowsiness, or difficulty waking

›Neck stiffness or severe headache not relieved by pain medication

›Shortness of breath or chest pain

›Unusual bruising, bleeding, or petechiae (pinpoint red spots)

›Inability to keep medications down due to vomiting

›Any new rash or rapidly spreading skin changes

›Weakness in arms or legs, or difficulty speaking

›Follow-up plan

›Clinic or doctor follow-up

›Within 48 to 72 hours of leaving the emergency department

›Repeat blood tests to confirm lab values are improving

12References/r35

Guidelines and key sources

›Primary guidelines and references

›CDC Tickborne Diseases of the United States Reference Manual (6th ed, 2022)

›Comprehensive clinical and epidemiological data

›Case fatality rates and demographic data

›MMWR Recommendations and Reports: Diagnosis and Management of Tickborne Rickettsial Diseases (Biggs et al., 2016)

›Diagnostic and treatment recommendations for ehrlichiosis and anaplasmosis

›CDC Level guidance for empiric doxycycline treatment

›Wilderness Medical Society Clinical Practice Guidelines for Tick-Borne Illness (Ho et al., 2021)

›Prevention and management guidance

›Doxycycline dosing recommendations including pediatric use

›IDSA/ASM Guide to Microbiology Laboratory Utilization 2024 Update (Miller et al., 2024)

›PCR and serological testing guidance

›Specimen handling requirements

Key clinical studies

›Evidence base

›Gygax et al. PLoS NTD 2024: Systematic review of human monocytotropic ehrlichiosis

›Comprehensive analysis of clinical features and outcomes

›Iyamu et al. BMC Infectious Diseases 2024: Neurological manifestations of ehrlichiosis

›Prevalence and clinical features of neuro-ehrlichiosis

›Otrock et al. Blood Cells Mol Dis 2019: Ehrlichiosis in transplant patients and HLH

›Outcomes data for immunocompromised populations

›Cheng et al. Pediatrics 2016: ECMO use in HLH secondary to ehrlichiosis

›Pediatric severe disease management

›Dumler et al. Clin Infect Dis 2007: Ehrlichioses in humans epidemiology and treatment

›Foundational clinical reference

›Stone et al. JAMA 2004: Human monocytic ehrlichiosis

›Classic clinical description and management framework

Evidence & Review