01Approach to the Critical Patient/attcp60

Immediate priorities

›Airway and breathing threats

›Rapid respiratory failure risk

›Progression from symptom onset to ARDS within 24-48 hours

›Hemoptysis with pulmonary hemorrhage pattern

›Oxygenation failure

›SpO2 < 90% on room air

›PaO2 < 60 mmHg

›Ventilation failure

›Rising PaCO2

›Respiratory fatigue with accessory muscle use

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

›Rapid sequence intubation preparation

›ARDS-protective ventilation strategy

›Circulatory and sepsis threats

›Septic shock physiology

›MAP < 65 mmHg

›SBP < 90 mmHg

›DIC recognition

›Petechiae and purpura

›Coagulation panel abnormalities

›Initiate broad-spectrum antibiotics within 1 hour of recognition

›Do not delay for confirmatory culture results

›Class I recommendation

Isolation and public health

›Immediate isolation requirements

›Droplet precautions for all suspected pneumonic plague cases

›Minimum 48 hours of effective antimicrobial therapy before discontinuing precautions

02History/hx51

Exposure and epidemiology

›Geographic and travel history

›Endemic region travel

›Western United States (New Mexico, Arizona, Colorado)

›Madagascar, Democratic Republic of Congo, Tanzania

›Central Asia (marmot exposure zones)

›Animal exposures

›Rodents (rats, prairie dogs, squirrels)

›Cats (known vector amplifier)

›Marmots in Central Asia

›Contact history

›Close contact with confirmed or suspected pneumonic plague patient

›Contact within 2 metres for > 1 hour

›Attendance at funerals with ill contacts

›Occupational exposure

›Veterinarians and animal handlers

›Hunters and trappers

›Laboratory workers handling Yersinia pestis

›Incubation context

›Symptom onset 1-6 days after exposure

›Most commonly 2-4 days

›Inhalation exposure may be shorter: few hours to 2 days

Presenting symptoms

›Respiratory syndrome

›Cough onset and character

›Initially dry, progressing to productive

›Hemoptysis: bloody, watery, or purulent sputum

›Chest pain

03Physical Exam/exam62

Vital signs and general

›Stability snapshot

›Temperature

›High fever typically > 38.5 C

›Hypothermia as severe sepsis marker

›Respiratory rate

›>= 30 per minute as severity marker

›Rising trend indicating fatigue

›Blood pressure

›SBP < 90 mmHg

›MAP < 65 mmHg

›Heart rate

›Tachycardia correlated with fever and sepsis

›Oxygen saturation

›Room air value at presentation

›Ambulatory desaturation test

›General appearance

›Toxicity and prostration

›Severely ill appearance

›Inability to speak full sentences

›Mental status

›Altered mental status or agitation from hypoxemia

›Progressive obtundation in severe disease

Pulmonary and airway exam

›Chest exam findings

›Bilateral rales and crackles

›Diffuse distribution

›Bilateral infiltrates pattern

04Differential Diagnosis/ddx42

Life-threatening differentials

›Must-not-miss diagnoses

›Bioterrorism-related pneumonic plague

›ICD-10 A20.2 (pneumonic plague)

›Cluster presentation without natural exposure

›Anthrax pneumonia (inhalation)

›ICD-10 A22.1

›Mediastinal widening on imaging

›Severe community-acquired pneumonia with sepsis

›ICD-10 J18.9 with A41.9

›Streptococcus pneumoniae, Staphylococcus aureus

Infectious mimics

›Respiratory infections

›Tularemia pneumonia

›Similar rodent exposure history

›Francisella tularensis

›Hantavirus pulmonary syndrome

›Rodent exposure in western US

›Bilateral infiltrates without hemoptysis

›Legionella pneumonia

›Water exposure history

›Gastrointestinal symptoms overlap

›Melioidosis

›Southeast Asia or tropical exposure

›Burkholderia pseudomallei

›Viral pneumonia

›Influenza with bacterial superinfection

›Seasonal pattern

05Laboratory Tests/lt60

Core infection labs

›Complete blood count

›Leukocytosis with left shift typical

›Toxic granulations on peripheral smear

›Leukopenia as severe sepsis marker

›Thrombocytopenia in DIC

›Platelet trend monitoring

›Comprehensive metabolic panel

›Aminotransferase elevation from hepatic involvement

›Azotemia from sepsis-related hypoperfusion

›Electrolyte derangements from gastrointestinal losses

›Inflammatory markers

›C-reactive protein elevation

›Procalcitonin elevation supports bacterial etiology

›Erythrocyte sedimentation rate

Coagulation and perfusion labs

›DIC panel

›Prothrombin time and activated partial thromboplastin time

›Prolonged PT/aPTT in severe disease

›Fibrinogen

›Decreased in consumptive coagulopathy

›D-dimer

›Markedly elevated with DIC

›Lactate

›>= 2 mmol/l as organ hypoperfusion marker

›Repeat within 2-4 hours if initially elevated

›Serial monitoring for treatment response

›Arterial blood gas

06Diagnostic Tests/dt58

Scoring Systems

›Severity assessment tools

›SOFA score for sepsis severity

›SOFA >= 2 associated with > 10% mortality in sepsis

›Six organ systems assessed: respiratory, coagulation, hepatic, cardiovascular, CNS, renal

›PSI/PORT score for pneumonia severity

›Not validated specifically for plague pneumonia

›Use to guide ICU disposition

›CURB-65 score

›Confusion, urea > 7 mmol/l, RR >= 30, BP < 90/60, age >= 65

›Score >= 3 warrants ICU consideration

›APACHE II score

›ICU prognostication tool

›Elevated score correlates with increased mortality in sepsis

MRI

›MRI indications

›Not first-line in acute pneumonic plague

›Limited utility in acute respiratory illness

›Reserved for neurological complications

›CNS complications evaluation

›Meningeal enhancement in plague meningitis

›Diffuse white matter changes with severe sepsis encephalopathy

›Musculoskeletal complications

›Septic arthritis or osteomyelitis if clinically suspected

CT

›CT chest indications

›Diagnostic utility

›Superior to plain chest X-ray for characterizing infiltrate pattern

07Disposition/dispo31

Admission criteria

›Inpatient admission indications

›All suspected pneumonic plague cases require hospitalization

›No outpatient management appropriate

›Mandatory isolation with droplet precautions

›ICU admission criteria

›Respiratory failure requiring supplemental oxygen > 6 L/min

›Mechanical ventilation requirement

›Septic shock

›Multiorgan dysfunction

›Hemodynamic instability

›Isolation requirements

›Droplet precautions minimum

›Minimum 48 hours of effective antimicrobial therapy before discontinuing

›N95 for aerosol-generating procedures

›Private room mandatory

›PPE for all healthcare workers entering room

Transfer criteria

›Transfer indications

›Facility without ICU capability and patient requires ICU care

›Stabilize before transfer

›Notify receiving facility of plague diagnosis

›Specialist consultation unavailable

›Infectious disease specialist

›Pulmonologist for refractory ARDS

Discharge criteria

›Discharge requirements

›Clinical improvement with decreased sputum production

08Treatment/t76

Immediate stabilization

›Resuscitation priorities

›Airway management

›Early intubation if respiratory failure worsening

›ARDS-protective lung ventilation: tidal volume 6 mL/kg ideal body weight

›Plateau pressure < 30 cmH2O

›Fluid resuscitation

›30 mL/kg crystalloid bolus for septic shock

›Reassess fluid responsiveness after each bolus

›Vasopressor initiation for refractory hypotension

›Norepinephrine first-line: 0.01-3 mcg/kg/min

›Vasopressin 0.03 units/min as adjunct if needed

First-line antibiotics

›Fluoroquinolone therapy (preferred for bioterrorism scenarios)

›Ciprofloxacin IV

›400 mg IV every 8 hours

›Transition to 750 mg PO every 12 hours when able

›Duration: 10-14 days total

›Levofloxacin IV/PO

›750 mg IV or PO once daily

›Duration: 10-14 days

›Preferred in bioterrorism response scenarios (MMWR 2021 recommendation)

›Moxifloxacin

›400 mg IV or PO once daily

›Alternative fluoroquinolone option

›Aminoglycoside therapy (traditional first-line for naturally acquired)

›Gentamicin

›5 mg/kg IV once daily (extended interval dosing)

09Special Populations/sp65

Pregnancy

›Pregnancy-specific risks

›Maternal and fetal outcomes

›High risk of maternal hemorrhage

›Risk of fetal demise and preterm birth

›Increased maternal mortality with severe disease

›Antibiotic selection

›Gentamicin preferred first-line

›5 mg/kg IV once daily with therapeutic drug monitoring

›Monitor fetal and neonatal hearing if exposed near delivery

›Streptomycin relatively contraindicated

›Risk of 8th cranial nerve damage to fetus

›Fluoroquinolones: theoretical fetal cartilage risk

›Use when benefit exceeds risk in severe disease

›Class C: acceptable in life-threatening infection

›Doxycycline: avoid if possible

›Tooth and bone development concerns

›Use in life-threatening cases after first trimester if no alternative

›Chloramphenicol: avoid near term

›Risk of gray baby syndrome

›Obstetric consultation mandatory

›Fetal monitoring throughout illness

›Delivery planning if near term

Geriatric

›Age-related considerations

›Atypical presentations

›Fever may be blunted or absent

›Altered mental status as primary presentation

10Background/b92

Epidemiology

›Global distribution

›Endemic regions

›Madagascar: highest global burden (>75% of global cases)

›Democratic Republic of Congo

›Tanzania and other sub-Saharan African countries

›Western United States (New Mexico, Colorado, Arizona, California)

›Central Asia (marmot reservoir zones)

›Annual global incidence

›Approximately 1,000-2,000 cases reported annually worldwide

›Under-reporting common in endemic areas

›United States cases

›1-17 cases per year historically

›Primarily in southwestern states (New Mexico, Arizona, Colorado)

›Last urban outbreak: Los Angeles 1924

›Mortality and morbidity

›Untreated pneumonic plague mortality

›Approaches 100% without treatment

›Treated pneumonic plague mortality

›25-50% case fatality rate even with appropriate antimicrobials

›Higher mortality than bubonic plague (untreated < 30-60%)

›Time to death

›2-6 days from symptom onset historically

›Modern ICU care extends survival but mortality remains high

›Forms of plague

›Bubonic: 80-85% of cases

›Flea bite transmission

›Bubo (lymphadenopathy) characteristic

›Septicemic: 10-15% of cases

›Blood stream dissemination

›May lack bubo

›Pneumonic: 1-4% of naturally acquired cases

›Most lethal form

›Only form transmissible person-to-person

Pathophysiology

›Causative organism

›Yersinia pestis

›Gram-negative coccobacillus

›Facultative intracellular organism

›Family Enterobacteriaceae

›Virulence factors

›F1 capsular antigen: antiphagocytic

›Plasminogen activator (Pla): promotes invasiveness

›LcrV (V antigen): immunosuppressive

›Yersiniabactin: iron acquisition siderophore

›Disease mechanism

›Transmission routes for pneumonic plague

›Primary: inhalation of respiratory droplets from infected person or animal

›Secondary: hematogenous spread from bubonic or septicemic plague

›Bioterrorism: deliberate aerosolization

›Pulmonary pathology

›Alveolar macrophage infection and dissemination

›Diffuse alveolar damage and pulmonary hemorrhage

›ARDS-pattern injury

›Bilateral pneumonia with pleural effusion

›Systemic dissemination

›Bacteremia with multiorgan involvement

›DIC from endotoxin and inflammatory cascade

›Hepatic, splenic, and renal involvement

›Meningeal involvement in severe disease

›Reservoir and transmission

›Natural reservoir

›Rodents (rats, prairie dogs, squirrels, marmots)

›Fleas (Xenopsylla cheopis) as primary vector

›Person-to-person transmission

›Only with pneumonic plague

›Droplet transmission requiring close contact

›No documented airborne transmission in natural outbreaks

Therapeutic Considerations

›Antibiotic evidence base

›Aminoglycoside evidence

›Streptomycin historically considered gold standard

›2025 NEJM RCT (Randremanana): ciprofloxacin non-inferior to aminoglycoside-ciprofloxacin for bubonic plague

›Gentamicin widely preferred due to availability

›Fluoroquinolone evidence

›MMWR 2021 (Nelson et al.) recommends fluoroquinolones as preferred for bioterrorism response

›Ciprofloxacin and levofloxacin both effective in animal models and human data

›Treatment duration

›Minimum 10 days for plague

›Extended to 14 days for severe or complicated cases

›Timing impact on survival

›Antibiotic delay beyond 24 hours significantly increases mortality

›Empiric treatment must not await culture confirmation

›Clinical and epidemiological grounds sufficient for initiation

›Drug resistance

›Natural resistance rare

›Most strains remain susceptible to standard agents

›Engineered resistance concern

›Bioterrorism scenario may involve drug-resistant strains

›Broad coverage and dual therapy prudent in bioterrorism context

›ICD-10 classification

›A20.2: Pneumonic plague

›A20.0: Bubonic plague

›A20.7: Septicaemic plague

›A20.9: Plague, unspecified

11Patient Discharge Instructions/pdi24

copy discharge instructions

›Discharge instructions for Plague (Pneumonic)

›Medication instructions

›Complete the full course of antibiotics as prescribed (10-14 days total)

›Do not stop antibiotics even if you feel better

›Take doxycycline with a full glass of water and remain upright for 30 minutes

›Activity and precautions

›Droplet isolation precautions until 48 hours of effective antibiotic therapy completed

›Avoid close contact (within 2 metres) with others until cleared by infectious disease

›All household contacts must be evaluated by public health for prophylaxis

›Return to emergency department immediately if

›Difficulty breathing or worsening shortness of breath

›Return of high fever despite antibiotics

›Coughing up blood

›Confusion or altered mental status

›Inability to keep medications down

›Any new symptoms suggesting clinical deterioration

›Follow-up requirements

›Infectious disease follow-up within 48-72 hours of discharge

›Weekly follow-up until antibiotic course completed

›Public health contact tracing coordination

›Public health obligations

›All household and close contacts must receive prophylactic antibiotics

›Notify public health of any new contacts identified

›Do not travel or return to work until cleared by infectious disease and public health

12References/r11

Guidelines and key sources

›Primary guidelines and landmark references

›Nelson CA, Meaney-Delman D, Fleck-Derderian S, et al. Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response. MMWR Recomm Rep. 2021

›Inglesby TV, Dennis DT, Henderson DA, et al. Plague as a Biological Weapon: Medical and Public Health Management. JAMA. 2000;283(17):2281-2290

›Randremanana RV, Raberahona M, Bourner J, et al. Ciprofloxacin versus Aminoglycoside-Ciprofloxacin for Bubonic Plague. N Engl J Med. 2025

›Godfred-Cato S, Cooley KM, Fleck-Derderian S, et al. Treatment of Human Plague: A Systematic Review of Published Aggregate Data on Antimicrobial Efficacy, 1939-2019. Clin Infect Dis. 2020

›Jullien S, Dissanayake HA, Chaplin M. Rapid Diagnostic Tests for Plague. Cochrane Database Syst Rev. 2020

›Prentice MB, Rahalison L. Plague. Lancet. 2007;369(9568):1196-1207

›Adalja AA, Toner E, Inglesby TV. Clinical Management of Potential Bioterrorism-Related Conditions. N Engl J Med. 2015;372(10):954-962

›Ratsitorahina M, Chanteau S, Rahalison L, et al. Epidemiological and Diagnostic Aspects of the Outbreak of Pneumonic Plague in Madagascar. Lancet. 2000;355(9198):111-113

›Wang W, Li X, Wu J, et al. Imaging Analysis of Pneumonic Plague Infection in Xizang, China. BMC Pulm Med. 2024

›Apangu T, Acayo S, Atiku LA, et al. Intervention to Stop Transmission of Imported Pneumonic Plague - Uganda, 2019. MMWR Morb Mortal Wkly Rep. 2020

Evidence & Review

Evidence & Review