01Approach to the Critical Patient/attcp51

Red flags requiring urgent evaluation

›Alarm features mandating escalation

›Encephalitis presentation

›Seizures including status epilepticus

›Altered mental status or confusion

›Focal neurologic deficits

›Disseminated disease pattern

›High fever >39 C persisting >2 weeks

›Hepatosplenic involvement with abdominal pain

›Bone pain suggesting osteomyelitis

›Ocular emergency

›Acute visual loss

›Neuroretinitis with macular star pattern

›Immunocompromised host with systemic features

›HIV/AIDS, transplant, or biologic therapy

›Risk of bacillary angiomatosis or peliosis hepatis

Immediate stabilization

›Stabilization priorities for severe CSD

›Airway protection in encephalitis

›GCS < 13 triggers immediate airway assessment

›RSI preparation if unable to protect airway

›Seizure management

›Benzodiazepine first-line for active seizures

›Lorazepam 0.1 mg/kg IV up to 4 mg per dose

›Status epilepticus protocol if seizures persist >5 minutes

›Hemodynamic assessment

›SBP < 90 mmHg or MAP < 65 mmHg triggers resuscitation

›Isotonic fluid bolus 30 ml/kg if septic physiology

02History/hx59

Exposure and inoculation history

›Feline exposure

›Cat scratch, bite, or lick to broken skin

›92% of patients report cat contact

›Kittens <1 year old are highest-risk vectors

›Cat flea status

›Flea infestation facilitates B. henselae transmission between cats

›Flea bite on human is not required for transmission

›Dog exposure in ~22% of cases

›Less common vector than cats

›Occupational exposure

›Veterinarians, animal shelter workers at elevated risk

Symptom timeline

›Inoculation site papule

›Develops 3–30 days after scratch or bite

›Small papule or pustule at wound site

›May be missed or overlooked by patient

›Lymphadenopathy onset

›Regional lymph node enlargement ~3 weeks after inoculation

›Proximal to scratch site

›Typically unilateral and tender

›Systemic symptoms

›Low-grade fever and malaise

›Fatigue and anorexia common

›Headache reported in subset

›Seasonality peak August–September

Classic and atypical presentations

›Classic presentation

03Physical Exam/exam66

Vital signs

›Vital sign assessment

›Temperature

›Low-grade fever typical in uncomplicated CSD

›Fever >39 C or persisting >2 weeks suggests disseminated disease

›Blood pressure and heart rate

›Hypotension rare in immunocompetent patients

›Tachycardia in febrile or septic presentations

›Respiratory rate

›Elevated with pulmonary or systemic involvement

›Weight

›Weight loss may indicate lymphoma or chronic disseminated infection

Lymph node exam

›Lymphadenopathy characterization

›Location relative to scratch site

›Axillary nodes most common

›Cervical, epitrochlear, inguinal nodes less common

›Node characteristics

›Tender and mobile favor CSD

›Fixed, hard, non-tender favor malignancy

›Size 1–5 cm typical range

›Suppuration assessment

›Fluctuance in ~10% of nodes

›Overlying skin erythema or warmth

Skin and inoculation site

›Inoculation site findings

›Papule or pustule on hand, forearm, or face

›May be partially healed at presentation

04Differential Diagnosis/ddx49

Life-threatening mimics

›Lymphoma

›Hodgkin lymphoma

›ICD-10: C81

›Fixed, non-tender, mediastinal or cervical lymphadenopathy

›B symptoms, LDH elevation, CT confirms

›Non-Hodgkin lymphoma

›ICD-10: C82–C86

›Rapidly progressive, painless lymphadenopathy

›Biopsy required for diagnosis

›Bacterial endocarditis

›Bartonella endocarditis is culture-negative

›ICD-10: I33.0

›Serology and echocardiography differentiate

›Persistent fever with new murmur mandates echocardiogram

Infectious mimics

›Mycobacterial lymphadenitis

›Tuberculosis (ICD-10: A18.2)

›Chronic, painless cervical lymphadenopathy

›PPD, IGRA, and chest imaging differentiate

›Non-tuberculous mycobacteria (NTM)

›Submandibular nodes in children

›Violaceous overlying skin; culture and PCR confirm

›Toxoplasmosis

›ICD-10: B58.1

›Cat exposure overlap

›Cervical lymphadenopathy; Toxoplasma IgG/IgM serology differentiates

›EBV or CMV mononucleosis

05Laboratory Tests/lt48

Serology

›Bartonella henselae serology (IFA)

›IgG titer >=1:256 highly suggestive of active or recent infection

›Sensitivity ~88%, specificity ~94%

›Cross-reactivity with B. quintana and Chlamydia

›IgM positive in early acute infection

›May be negative if tested >4 weeks after symptom onset

›Paired acute and convalescent titers for equivocal results

›Fourfold rise in IgG confirms diagnosis

›ACEP Level B: serology recommended as initial diagnostic test

PCR and molecular testing

›PCR for B. henselae

›Specimen sources

›Lymph node aspirate or biopsy — highest yield

›Blood PCR — positive in bacteremia or immunocompromised host

›Tissue from biopsied node

›Performance

›Higher sensitivity than serology alone in early infection

›Combined serology + PCR increases diagnostic yield from ~28% to ~44%

›mNGS (metagenomic next-generation sequencing)

›Emerging tool for diagnostically challenging cases

›Useful when conventional methods inconclusive or biopsy declined

Routine laboratory tests

›Complete blood count

›Usually normal in uncomplicated CSD

›Mild leukocytosis possible

›Eosinophilia occasionally reported

›Thrombocytopenia or anemia raises concern for disseminated disease

06Diagnostic Tests/dt55

Scoring Systems

›Severity stratification (clinical framework)

›Mild CSD

›Isolated regional lymphadenopathy

›No systemic symptoms

›Immunocompetent host

›Moderate CSD

›Persistent fever >1 week

›Large or suppurative lymph nodes

›Significant malaise or functional limitation

›Severe/disseminated CSD

›Encephalitis, hepatosplenic disease, osteomyelitis

›Endocarditis or bacillary angiomatosis

›Atypical CSD carries 8.8x increased hospitalization risk

›Immunocompromised risk tier

›Any systemic symptom in HIV+ or transplant patient warrants full workup

›CD4 count guides dissemination risk in HIV

MRI

›MRI indications in CSD

›CNS involvement

›MRI brain with and without contrast for encephalitis

›Neuroimaging normal in ~79% of CSD encephalitis cases

›When abnormal: T2 hyperintensities in cortex or white matter

›Osteomyelitis assessment

›MRI spine or affected bone for detailed soft tissue and marrow evaluation

›T1 hypointense, T2 hyperintense bone marrow signal suggests osteomyelitis

›Superior to CT for early marrow edema detection

›Hepatosplenic lesion characterization

07Disposition/dispo40

Discharge criteria

›Safe for outpatient management

›Uncomplicated lymphadenopathy in immunocompetent host

›No systemic toxicity

›Tolerating oral medications

›Reliable follow-up within 2–4 weeks

›Classic presentation with confirmed or suspected CSD

›Cat exposure with regional lymphadenopathy

›No alarm features

Admission criteria

›Indications for inpatient management

›Neurologic involvement

›Encephalitis or active seizures

›Status epilepticus requiring IV anticonvulsants

›Hepatosplenic CSD

›Significant abdominal pain or hemodynamic concern

›Markedly elevated transaminases

›Endocarditis

›Culture-negative endocarditis with Bartonella serology

›Requires prolonged IV and oral antibiotic therapy

›Immunocompromised host with systemic features

›Bacillary angiomatosis requiring IV erythromycin

›HIV patient with disseminated disease

›Inability to tolerate oral medications

›Persistent vomiting

›Severe systemic toxicity

Observation and monitoring

›Indications for observation unit or extended ED stay

08Treatment/t80

First-line antibiotic therapy

›Azithromycin (IDSA first-line recommendation)

›Adult dosing (>=45 kg)

›500 mg PO on day 1

›250 mg PO daily on days 2–5

›Total 5-day course

›Pediatric dosing (<45 kg)

›10 mg/kg PO on day 1 (max 500 mg)

›5 mg/kg PO daily on days 2–5 (max 250 mg)

›Evidence: accelerates lymph node regression; does not shorten total illness duration

›Randomized placebo-controlled trial evidence

›IDSA skin/soft tissue guidelines Class I recommendation

Disseminated and severe disease therapy

›Doxycycline-based regimens

›Doxycycline 100 mg PO BID

›First-line for disseminated, hepatosplenic, and CNS disease in adults

›Duration 2 weeks to 2 months depending on severity

›Doxycycline + rifampin combination

›Rifampin 300 mg PO BID added for severe or refractory cases

›Combination preferred for hepatosplenic CSD

›Duration 2–4 weeks for hepatosplenic; up to 2 months for osteomyelitis

›Endocarditis regimen

›Doxycycline 100 mg BID + rifampin 300 mg BID x 6 weeks

›Followed by doxycycline alone for >=3 months

›Gentamicin 3 mg/kg IV daily for first 14 days in native valve endocarditis

Immunocompromised host therapy

›Bacillary angiomatosis and peliosis hepatis

›Erythromycin 500 mg PO QID as first-line

›Duration: minimum 2 months

›HIV patients may require lifelong suppressive therapy

›Doxycycline 100 mg PO BID as alternative

›Equivalent efficacy to erythromycin

›Duration minimum 2 months; indefinite if CD4 <100 cells/mcL

›Azithromycin 250 mg PO daily as alternative

›DHHS/IDSA HIV OI guidelines support use

Alternative antibiotics

›TMP-SMX (trimethoprim-sulfamethoxazole)

›Comparable effectiveness shown in pediatric studies

›One DS tablet PO BID for 5–7 days

›Useful when azithromycin is contraindicated or unavailable

›Rifampin monotherapy or combination

›Rifampin 10–20 mg/kg/day (pediatric); 300 mg BID (adult)

›Used as adjunct in disseminated disease

›Hepatotoxicity monitoring required

Contraindicated and ineffective antibiotics

›Antibiotics without efficacy against Bartonella

›First-generation cephalosporins (cephalexin) — lack efficacy

›Do not use as empiric therapy for suspected CSD

›Second-generation cephalosporins — lack efficacy

›Doxycycline avoided in children <8 years for prolonged courses

›Dental enamel dysplasia risk with extended use

›Single short course (5–7 days) may be acceptable

Supportive care

›Symptomatic management

›Analgesics for lymph node pain

›Acetaminophen 500–1000 mg PO Q6-8h PRN

›Ibuprofen 400–600 mg PO Q6-8h PRN in adults

›Antipyretics for fever

›Acetaminophen preferred in hepatosplenic disease

›Avoid NSAIDs if hepatic involvement with elevated transaminases

›Hydration support

›Oral hydration encouraged during febrile illness

›IV fluids if unable to tolerate PO

Lymph node aspiration

›Procedure for suppurative lymph nodes

›Needle aspiration preferred over incision and drainage

›Avoids chronic fistula formation

›Ultrasound guidance recommended

›Send aspirate for

›PCR for B. henselae

›Bacterial culture

›Histopathology if malignancy concern

›Provides symptomatic relief and diagnostic material

›Do not perform surgical excision for typical CSD nodes

Encephalitis management

›CSD encephalitis

›Antibiotic therapy

›Doxycycline 100 mg BID + rifampin 300 mg BID for adults

›Duration 4–6 weeks for CNS involvement

›Anticonvulsant therapy

›Levetiracetam 500–1000 mg IV/PO BID as first-line

›Valproic acid as alternative if levetiracetam unavailable

›Corticosteroid role

›Corticosteroid use remains investigational in CSD encephalitis

›Consider dexamethasone 0.15 mg/kg IV Q6h if cerebral edema suspected

›Prognosis

›Generally favorable; most patients recover fully

›~42% report persistent cognitive complaints at follow-up

09Special Populations/sp59

Pregnancy

›CSD in pregnancy

›Epidemiology and risk

›Cat ownership common in pregnancy

›Bartonella henselae in utero transmission is rare but reported

›Immunologic changes of pregnancy may alter presentation

›Antibiotic safety

›Azithromycin is Category B (generally considered safe in pregnancy)

›Preferred first-line agent in pregnancy

›Standard 5-day course appropriate

›Doxycycline is Category D — avoid in pregnancy

›Associated with fetal tooth discoloration and hepatotoxicity

›Use only if no alternative exists and benefits clearly outweigh risks

›Rifampin: Category C — use with caution

›Associated with vitamin K deficiency and hemorrhage in neonate if used near term

›Monitoring

›Obstetric consultation for any disseminated or febrile illness

›Ultrasound to monitor fetal well-being if systemic disease

Geriatric

›CSD in older adults

›Epidemiology

›Less common; peak incidence in children and young adults

›Older adults with cat contact or biologic therapy at risk

›Disseminated CSD reported during abatacept therapy for rheumatoid arthritis

›Clinical presentation differences

›Fever may be blunted; lower threshold for workup

›Polypharmacy increases drug interaction risk

›Valvular heart disease increases endocarditis risk

10Background/b69

Epidemiology

›Incidence and prevalence

›Estimated 12,000–22,000 cases diagnosed annually in the United States

›Actual incidence likely higher due to underdiagnosis

›Most common cause of chronic regional lymphadenopathy in children and adolescents

›Age distribution

›Peak incidence age 5–14 years

›Adults with cat exposure also affected

›Seasonal variation

›Peak incidence August–September in North America

›Correlates with kitten acquisition season

›Geographic distribution

›Worldwide distribution; endemic where cats and fleas coexist

›Higher incidence in Southern US states (warm climate, flea prevalence)

›Hospitalization risk

›Atypical CSD associated with 8.8x increased hospitalization risk

›Hepatosplenic CSD more common in school-age children

›Mortality

›Very low in immunocompetent hosts

›Elevated in immunocompromised patients with endocarditis or disseminated disease

Pathophysiology

›Causative organism

›Bartonella henselae — gram-negative intracellular bacterium

›Facultative intracellular pathogen

›Infects erythrocytes and endothelial cells

›Related organism: B. quintana causes trench fever and urban trench fever

›Transmission cycle

›Cats are reservoir hosts; typically asymptomatic

›Cat flea (Ctenocephalides felis) transmits B. henselae between cats via flea feces

›Humans infected via flea feces inoculated into skin during scratch or bite

›Direct flea bite to human is not required

›Disease mechanism

›Inoculation site reaction

›Local granulomatous inflammation at scratch site

›Papule or pustule develops within 3–30 days

›Lymph node pathology

›Bacteria spread to regional lymph nodes via lymphatics

›Stellate caseating granulomas and microabscesses form

›Follicular hyperplasia precedes granuloma formation

›Dissemination mechanism

›Bacteremic spread in 5–20% of cases

›Endothelial cell invasion leads to vascular proliferative lesions (bacillary angiomatosis)

›Hepatic and splenic macrophage seeding causes microabscesses

›CNS tropism mechanism incompletely understood; cytokine-mediated encephalitis proposed

›Histopathology

›Warthin-Starry silver stain demonstrates pleomorphic bacilli in tissue

›Cannot differentiate Bartonella species

›Stellate microabscesses with neutrophilic infiltration

›Surrounding palisading histiocytes

›Non-caseating granulomas in chronic phase

Therapeutic Considerations

›Treatment rationale

›Immunocompetent uncomplicated CSD

›Self-limited in 1–6 months; antibiotic shortens node regression time

›Azithromycin reduces node volume by ~80% at 30 days vs 54% placebo

›Antibiotic treatment does not always prevent suppuration

›Disseminated disease treatment rationale

›Bartonella has intracellular tropism; intracellular-penetrating antibiotics required

›Macrolides, tetracyclines, and rifamycins penetrate intracellularly

›Beta-lactams and first/second-generation cephalosporins do not penetrate intracellularly

›Immunocompromised patients

›Antibiotic suppression reduces relapse in HIV patients

›CD4 count <100 cells/mcL associated with highest relapse risk

›Immune reconstitution inflammatory syndrome (IRIS) may mimic worsening disease

›Antibiotic resistance

›In vitro resistance testing not standardized for Bartonella

›Clinical failures with macrolides are uncommon

›Fluoroquinolone efficacy variable; not first-line

›Prevention strategies

›Flea control on cats reduces B. henselae bacteremia in cats

›Avoiding rough play with kittens and prompt wound washing

›Immunocompromised patients: avoid scratches and bites; flea treatment of pets

11Patient Discharge Instructions/pdi33

copy discharge instructions

›Discharge instructions for Cat Scratch Disease

›Diagnosis explanation

›Cat scratch disease is a bacterial infection caused by Bartonella henselae

›It is spread by scratches or bites from cats, especially kittens

›It is not spread from person to person

›Medication instructions

›Take all prescribed antibiotics as directed until course is complete

›Azithromycin: take once daily with or without food

›Doxycycline: take with a full glass of water; remain upright 30 minutes after dose

›Do not stop antibiotics early even if you feel better

›Expected course

›Swollen lymph nodes may take 1–6 months to fully resolve

›Some swelling may persist for several months even with treatment

›Fever and fatigue should improve within 1–2 weeks

›Activity and wound care

›Wash any cat scratches or bites immediately with soap and water

›Avoid rough play with kittens to prevent further scratches

›No need to rehome your cat

›Flea prevention

›Apply monthly flea prevention to your cat to reduce transmission risk

›Flea control is important even for indoor cats

›Follow-up

›Follow up with your doctor in 2–4 weeks to check lymph node improvement

›If lymph node grows rapidly or does not begin to shrink within 6 weeks, return for evaluation

›Return to emergency department immediately for

›Seizures or loss of consciousness

›Confusion or difficulty speaking

12References/r33

Guidelines and key sources

›IDSA skin and soft tissue infection guidelines

›Stevens DL et al. IDSA Practice Guidelines for Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update

›Clinical Infectious Diseases 2014

›Azithromycin Class I recommendation for uncomplicated CSD

›URL: academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciu296

›IDSA/DHHS Guidelines for Prevention and Treatment of Opportunistic Infections in Adults with HIV (2025)

›Bartonella section covers bacillary angiomatosis and peliosis hepatis management

›URL: clinicalinfo.hiv.gov

›Key clinical studies

›Amin O et al. Cat Scratch Disease: 9 Years of Experience at a Pediatric Center. Open Forum Infectious Diseases 2022

›CSD encephalitis: seizures in 68%, ~79% normal MRI, ~42% persistent cognitive complaints

›PMID: 36072697

›Nawrocki CC et al. Atypical Manifestations of Cat-Scratch Disease, United States 2005-2014. Emerging Infectious Diseases 2020

›Atypical CSD 8.8x increased hospitalization risk

›PMID: 32568056

›Allizond V et al. Serological and Molecular Detection of B. henselae in Italy. PLoS One 2019

›Combined serology + PCR diagnostic yield ~44%

›PMID: 30735549

›Shorbatli LA et al. Effectiveness of Antibiotic Therapy in Pediatric CSD. International Journal of Clinical Pharmacy 2018

›TMP-SMX comparable efficacy to azithromycin in pediatrics

›PMID: 30446895

›Klotz SA et al. Cat-Scratch Disease. American Family Physician 2011

›ESR elevated ~47%, CRP elevated ~21%; clinical review

›PMID: 21243990

›Stroescu RF et al. Systemic Bartonella henselae Infection in Children. Microorganisms 2024

›Hepatosplenic CSD retrospective analysis

›PMID: 38674610

Evidence & Review

Evidence & Review