01Approach to the Critical Patient/attcp57

Immediate priorities

›Airway and breathing threats

›Inhalational glanders with severe pneumonia

›Rapid respiratory failure possible

›ARDS pattern may develop

›Oxygenation failure criteria

›SpO2 < 90% on room air

›PaO2 < 60 mmHg

›If unable to protect airway, proceed to definitive airway control

›Rapid sequence intubation preparation

›ARDS ventilation strategy: low tidal volume 6 ml/kg IBW

›Circulation and sepsis threats

›Septic shock physiology

›SBP < 90 mmHg or MAP < 65 mmHg

›Lactate >= 2 mmol/l

›Broad-spectrum antibiotics within 1 hour of recognition

›Ceftazidime or meropenem as initial backbone

›Infectious disease consultation immediately

›30 ml/kg crystalloid bolus for sepsis-induced hypoperfusion

›Reassess after each bolus

›Vasopressor if refractory to fluids

›Bioterrorism recognition

›Multiple unexplained cases in non-endemic setting

›Immediate public health notification

›Tier 1 select agent reporting requirements

›Laboratory biosafety level 3 (BSL-3) precautions for cultures

›Alert microbiology lab before specimen submission

›Standard contact precautions for clinical staff

02History/hx53

Exposure history

›Occupational and environmental contacts

›Direct equine contact

›Horses, mules, donkeys

›Veterinary or farriery work

›Laboratory exposure

›Burkholderia mallei culture work

›Biodefense or military research setting

›Geographic context

›Travel to or from endemic regions (Middle East, Asia, Africa)

›Areas with infected animal populations

Symptom characterization

›Route-specific symptom patterns

›Inhalational exposure

›Febrile pneumonia within 10 to 14 days

›Cough, dyspnea, pleuritic chest pain

›Cutaneous inoculation

›Local nodule or ulcer at entry site within 1 to 5 days

›Ascending lymphangitis

›Ingestion route

›Gastrointestinal symptoms with systemic spread

›Less common route

›Constitutional symptoms

›Fever and rigors

›Onset within days to weeks of exposure

›High-grade sustained fever

›Malaise and myalgias

›Weight loss with prolonged course

03Physical Exam/exam57

Vitals and general appearance

›Stability snapshot

›Temperature

›High-grade fever >= 38.5 C typical

›Hypothermia in severe sepsis

›Respiratory rate

›>= 30 per minute as severity marker

›Accessory muscle use

›Blood pressure

›SBP < 90 mmHg or MAP < 65 mmHg indicates shock

›Pulse pressure narrowing in distributive shock

›Oxygen saturation

›Room air value priority

›Rapid desaturation pattern

Skin and lymph node exam

›Dermatological findings

›Cutaneous form lesions

›Papule or nodule at inoculation site

›Ulceration with raised edges

›Pustular lesions

›Single or multiple pustules

›Nasal or facial distribution possible

›Subcutaneous abscesses

›Fluctuant nodules along lymphatics

›Cord-like lymphangitis pattern

›Lymphadenopathy

›Regional to entry site

›Suppurative nodes

04Differential Diagnosis/ddx50

Life-threatening mimics

›Immediate threats requiring differentiation

›Melioidosis (Burkholderia pseudomallei)

›ICD-10 A24.4

›Nearly identical clinical syndrome

›Different geographic distribution: Southeast Asia and northern Australia

›Pneumonic plague (Yersinia pestis)

›ICD-10 A22.1

›Rapid fulminant pneumonia

›Bioterrorism agent overlap

›Inhalational anthrax (Bacillus anthracis)

›ICD-10 A22.1

›Widened mediastinum on chest imaging

›Bioterrorism agent overlap

Zoonotic and infectious mimics

›Overlapping zoonoses

›Tularemia (Francisella tularensis)

›ICD-10 A21.9

›Similar zoonotic acquisition

›Lymphadenopathy pattern similar

›Tuberculosis (Mycobacterium tuberculosis)

›ICD-10 A15.0

›Chronic pulmonary infection

›Cavitary lesions overlap

›Nocardiosis (Nocardia spp)

›ICD-10 A43.9

›Abscess formation pattern similar

›Immunocompromised host overlap

05Laboratory Tests/lt63

Core infection workup

›Haematological tests

›Complete blood count

›Leukocytosis with left shift typical

›Thrombocytopenia in severe sepsis

›Inflammatory markers

›C-reactive protein elevated

›Erythrocyte sedimentation rate elevated

›Procalcitonin

›Bacterial sepsis support

›Not specific for glanders

Microbiological diagnosis

›Culture and identification

›Blood cultures

›Positive in disseminated or septicemic disease

›Obtain before antibiotic initiation when feasible

›Wound or lesion culture

›Swab of ulcer or pustule

›Alert BSL-3 lab before submission

›Sputum culture

›Respiratory specimen in pulmonary form

›Sensitivity variable; PCR preferred

›Culture caution

›Slow growth on standard media

›May be misidentified by automated systems

›Molecular diagnostics

›PCR testing

›More sensitive than culture

06Diagnostic Tests/dt73

Scoring Systems

›Severity and sepsis stratification tools

›Sequential Organ Failure Assessment (SOFA)

›Six organ domains scored

›Score >= 2 indicates organ dysfunction in sepsis

›Tracks treatment response

›qSOFA

›Respiratory rate >= 22 per minute

›SBP <= 100 mmHg

›Altered mental status

›Bedside screening tool; not diagnostic

›Pneumonia Severity Index

›Respiratory form severity stratification

›Not validated specifically for glanders

›CURB-65

›Confusion

›Urea > 7 mmol/l

›Respiratory rate >= 30 per minute

›BP SBP < 90 mmHg or DBP <= 60 mmHg

›Age >= 65 years

›Adjunct only; all glanders cases require admission

MRI

›MRI indications for glanders

›Central nervous system involvement

›Meningitis or brain abscess concern

›Altered mental status without clear cause

›Soft tissue abscess characterization

›Deep tissue extension assessment

07Disposition/dispo31

Admission criteria

›All suspected glanders require hospitalization

›No outpatient management appropriate

›Rapid progression risk

›Select agent reporting requirements

›ICU admission indications

›Septic shock

›Respiratory failure or ARDS

›Multi-organ dysfunction

›Step-down or general admission

›Stable vital signs with localized infection

›IV antibiotic administration requirement

Transfer and consultation criteria

›Transfer indications

›Tertiary center with infectious disease expertise

›Complex antibiotic management

›Rare disease experience

›Reference laboratory access

›CDC Laboratory Response Network confirmation required

›Specialized diagnostics not locally available

›Surgical intervention requirement

›Large abscess drainage

›Empyema management

Isolation and public health

›Infection control precautions

›Standard contact precautions

›Not transmitted person to person under standard care

›Wound secretions potentially infectious

08Treatment/t78

Initial intensive therapy

›Induction phase antibiotics

›Ceftazidime IV

›2 g IV every 8 hours

›Preferred initial agent based on in vitro and animal data

›Renal dose adjustment required

›Meropenem IV

›1 g IV every 8 hours

›Alternative when ceftazidime unavailable or suspected resistance

›Extended infusion protocol considered for severe disease

›Imipenem IV

›500 mg to 1 g IV every 6 hours

›Used in combination with doxycycline in published cases

›Seizure risk monitoring in renal impairment

Combination therapy

›Combination regimen options

›Imipenem plus doxycycline

›Successful documented case report (Van Zandt et al. 2013)

›Imipenem 500 mg IV every 6 hours

›Doxycycline 100 mg PO or IV every 12 hours

›Ceftazidime plus trimethoprim-sulfamethoxazole

›Eradication phase component

›TMP-SMX 8 to 10 mg/kg/day TMP component divided every 12 hours

›Duration of induction phase

›Minimum 10 to 14 days intensive IV therapy

›Longer if slow clinical response or complications

Eradication therapy

›Oral step-down eradication phase

09Special Populations/sp40

Pregnancy

›Pregnancy-specific considerations

›Antibiotic safety profile

›Ceftazidime: generally considered safe in pregnancy (category B)

›Avoid doxycycline: tetracycline class causes fetal bone and tooth effects

›Alternative agents in pregnancy

›Meropenem relatively safer than imipenem

›TMP-SMX avoided in first trimester and near term

›Consult infectious disease and maternal-fetal medicine

›Maternal oxygenation targets

›SpO2 >= 95% when feasible for fetal protection

›Fetal monitoring when at viable gestation

›Imaging considerations

›CT with fetal shielding when clinically required

›Ultrasound preferred where adequate

Geriatric

›Older adult considerations

›Atypical presentation risk

›Afebrile infection possible

›Delirium as primary manifestation

›Pharmacokinetic changes

›Renal dose adjustment critical for ceftazidime and meropenem

›Aminoglycoside nephrotoxicity risk increased

›Comorbidity interactions

›Diabetes mellitus as severity modifier

›Frailty limits tolerance of prolonged treatment

›Prolonged treatment course tolerance

›Monthly CBC monitoring with TMP-SMX

10Background/b76

Epidemiology

›Incidence and distribution

›Extremely rare human disease

›Only sporadic cases reported in modern era

›Fewer than 30 human cases documented in peer-reviewed literature since 1900 in developed countries

›Endemic animal reservoirs

›Equids (horses, mules, donkeys) primary reservoir

›Rare cases in camels, dogs, goats

›Geographic distribution

›Historically global; now endemic in parts of Middle East, Asia, Africa, and Latin America

›Eradicated from North America, Europe, and Australia by mid-20th century

›Occupational risk patterns

›Historically associated with military and veterinary settings

›World War I and II outbreaks in military horses

›US Army laboratory exposure case 2000 (Srinivasan et al. 2001)

›Bioterrorism potential

›CDC Tier 1 select agent classification

›Weaponization history during World War II

›Unusual cluster triggers bioterrorism investigation

›Mortality data

›Untreated septicemic form: approximately 95% mortality

›Untreated localized form: approximately 50% mortality

›With appropriate treatment: mortality significantly reduced

Pathophysiology

›Organism characteristics

›Burkholderia mallei

›Gram-negative aerobic bacillus

›Obligate pathogen; no environmental reservoir outside hosts

›Intracellular survival mechanism enables chronic infection

›Virulence mechanisms

›Intracellular survival evades humoral immunity

›Lipopolysaccharide and capsular polysaccharide virulence factors

›Type III and Type VI secretion systems

›Disease mechanism by route

›Inhalational route

›Aerosol exposure leads to alveolar infection

›Consolidation, necrosis, abscess formation in lungs

›Haematogenous spread to visceral organs

›Cutaneous inoculation

›Local papule progresses to ulcer

›Lymphangitic spread

›Bacteremia and systemic dissemination possible

›Septicemic dissemination

›Haematogenous seeding of liver, spleen, skin, and musculoskeletal system

›Multiple organ abscesses

›Necrosis of tracheobronchial tree in severe cases

›Chronic form pathophysiology

›Granuloma formation

›Suppurative granulomas in affected tissues

›Nodular skin lesions (farcy)

›Persistent intracellular reservoir

›Incomplete clearance without prolonged eradication therapy

Therapeutic Considerations

›Antibiotic susceptibility principles

›Intrinsic resistance pattern

›Resistance to penicillin, ampicillin, azithromycin, colistin

›Resistance to aminoglycosides at lower doses

›Reliable susceptibility agents

›Ceftazidime (in vitro and animal model data; Kenny et al. 1999)

›Carbapenems (imipenem and meropenem)

›TMP-SMX for eradication

›Variable susceptibility agents

›Tetracyclines (doxycycline)

›Fluoroquinolones (levofloxacin superior to ciprofloxacin; Judy et al. 2009)

›Treatment phase rationale

›Induction phase goal

›Rapid bacterial load reduction

›Prevention of seeding and abscess expansion

›Eradication phase goal

›Clearance of intracellular bacterial reservoir

›Prevention of relapse

›6 months for disseminated disease (Lipsitz et al. 2012)

›Evidence base limitations

›No controlled clinical trials in humans

›All recommendations from case reports and animal models

›Expert consensus workshop (Lipsitz et al. 2012) primary guidance

›Bioterrorism preparedness framework

›Post-exposure prophylaxis protocols established

›TMP-SMX or doxycycline for 21 days post-exposure

11Patient Discharge Instructions/pdi27

copy discharge instructions

›Glanders home care instructions

›This is a rare serious bacterial infection; complete full antibiotic course

›Do not stop antibiotics without physician approval

›Treatment may last 6 months or longer

›Take all oral medications exactly as prescribed

›TMP-SMX with plenty of fluids

›Doxycycline with food to reduce stomach upset

›Follow all infection control instructions

›Cover any skin wounds or draining lesions

›Wash hands thoroughly after touching wounds

›Return to emergency department immediately for

›Difficulty breathing or worsening shortness of breath

›Fever not improving or spiking higher on treatment

›New skin wounds, swellings, or draining lesions

›Confusion, severe headache, or neck stiffness

›Signs of allergic reaction to antibiotics

›Rash, hives, swelling of face or throat

›Inability to keep oral medications down

›Yellowing of skin or eyes (jaundice)

›Follow-up plan

›Infectious disease specialist within 1 week of discharge

›Repeat blood work at scheduled intervals

›Repeat imaging at 2 to 4 weeks to assess treatment response

›Public health follow-up as directed

›Animal contact restriction

›Avoid equine contact until cleared by physician

›Report any additional sick animals to veterinary authorities

12References/r17

Guidelines and key sources

›Primary guideline references

›Lipsitz R et al. Workshop on Treatment of and Postexposure Prophylaxis for Burkholderia pseudomallei and B. mallei Infection 2010. Emerging Infectious Diseases 2012. PMID 23171644

›Van Zandt KE, Greer MT, Gelhaus HC. Glanders: An Overview of Infection in Humans. Orphanet Journal of Rare Diseases 2013. PMID 24004906

›Srinivasan A et al. Glanders in a Military Research Microbiologist. New England Journal of Medicine 2001. PMID 11474078

›Antimicrobial susceptibility references

›Kenny DJ et al. In Vitro Susceptibilities of Burkholderia mallei in Comparison to Those of Other Pathogenic Burkholderia SPP. Antimicrobial Agents and Chemotherapy 1999. PMID 10543761

›Judy BM et al. Comparison of the in Vitro and in Vivo Susceptibilities of Burkholderia mallei to Ceftazidime and Levofloxacin. BMC Microbiology 2009. PMID 19426516

›Diagnostic references

›Wagner GE et al. Protein Microarray-Guided Development of a Highly Sensitive and Specific Dipstick Assay for Glanders Serodiagnostics. Journal of Clinical Microbiology 2023. PMID 36541753

›Wernery U et al. Development of a Sensitive Competitive Enzyme-Linked Immunosorbent Assay for Serodiagnosis of Burkholderia mallei. PLoS Neglected Tropical Diseases 2021. PMID 34932554

›He G et al. A Case Report of Infection Leading to Pneumonia. Combinatorial Chemistry and High Throughput Screening 2022. PMID 35579163

›Animal model and pathogenesis references

›Yingst SL et al. Pathological Findings and Diagnostic Implications of a Rhesus Macaque Model of Aerosol Exposure to Burkholderia mallei. Journal of Medical Microbiology 2015. PMID 25850696

›Coding standards

›ICD-10 A24.0 glanders

›ICD-10 A24.4 melioidosis for differential coding

›SNOMED CT glanders disorder concept

Evidence & Review

Evidence & Review