The sepsis syndrome: The sepsis syndrome: Differential diagnosis of the flu-like Differential diagnosis of the flu-like

illnessillnessDivya Ahuja, M.D.

November , 2008

Med Micro 2008 Clinical Correlations #5

Traditional definitionsTraditional definitions Bacteremia (or fungemia): presence of

microorganisms in the blood Sepsis: Harmful consequences of microbes or their

toxins in blood or tissues Septicemia (or bloodstream infection): bacteremia

with clinical manifestations Septic shock: shock due to sepsis, often with

bloodstream infection

Revised definitionsRevised definitions

Systemic inflammatory response syndrome (SIRS)

Sepsis Severe sepsis Septic shock

Systemic Inflammatory Response Systemic Inflammatory Response Syndrome (SIRS)Syndrome (SIRS)

Two or more of the followingTwo or more of the following – temperature > 38 degrees C (100.4 F)– respirations > 20/minute– Heart rate > 90 beats per minute– leukocyte count > 12,000/cmm or <

4000/cmm or with > 10% band forms

Sepsis and Severe SepsisSepsis and Severe Sepsis

Sepsis: SIRS plus a documented infection (culture proven or identified by visual inspection)

Severe sepsis: Sepsis associated with organ dysfunction, abnormalities due to hypoperfusion (such as lactic acidosis, oliguria, or acute alteration in mental status), ARDS, DIC, low platelets

Septic shockSeptic shock

Definition: Sepsis-induced hypotension despite fluid resuscitation and/or inotropic support, plus hypoperfusion abnormalities

The hallmark of septic shock is low systemic vascular resistance, which distinguishes it from hemorrhagic shock and cardiogenic shock.

Multiple Organ Failure

Some physiologic descriptors– Serum creatinine– Platelet count– pO2/FiO2 ratio– Serum bilirubin– Glasgow coma score

Sepsis

Sepsis has a 20-50% mortality Severity has increased recently Hospital case-fatality has declined Incidence is greatest in winter Risk factors for sepsis

– Bacteremia– Advanced age– Impaired immune system– Community acquired pneumonia

Continuum of severity

Incidence of positive blood cultures increases along the continuum

Increased mortality rate Severe organ dysfunction manifested as

– Acute respiratory distress syndrome– Acute renal failure– Disseminated intravascular coagulation

Disseminated intravascular coagulopathy

Case #1

20-year-old college student in ER General malaise, low-grade fever, and rapid

development of purplish discoloration on his face. (from when he left his house to the time he arrived at the emergency room).

Blood cultures were drawn and he was admitted to the intensive care unit

Presentation

Febrile, tachycardic, systolic BP-70 Creatinine- 3.6, poor urine output Platelets-46000 INR- 2.6 Obtunded mental status Needing maximum ventilatory support

Case # 1

Meningococcemia with Waterhouse-Friderichsen Syndrome and DIC

Treat with penicillin, ceftriaxone or chloramphenicol.

Family members and hospital employees in contact with respiratory secretions should receive prophylaxis. Attack rates for household contacts is 0.3-1%, 300-1000 times the rate in the general population (rifampin x 4 doses or cipro x 1 dose)

Epidemiology of meningococcal diseaseEpidemiology of meningococcal disease About 1 to 2 cases/100,000 in temperate areas;

occurs especially in the winter and spring Serogroups A and C are known as “epidemic

strains”; group B is major cause of sporadic disease in the U.S

Patients with deficiencies of late-acting complement components (C5 to C9) may repeat episodes of invasive meningococcal disease

Correlation of traditional and Correlation of traditional and revised definitionsrevised definitions

Severe sepsis: Blood cultures are positive in 20% to 40% of cases

Septic shock: Blood cultures are positive in 40% to 70% of cases

Evaluation of blood culturesEvaluation of blood cultures

True-positive versus false-positive (contamination; pseudobacteremia)

Transient versus intermittent versus continuous

Polymicrobial versus unimicrobial Primary versus secondary

Clues to contaminationClues to contamination

Microorganisms that are usually not pathogenic, unless isolated from multiple cultures (e.g., coagulase-negative staphylococci; Bacillus species)

< 2 positive cultures and/or delayed growth and/or < 1 cfu/ml

Doesn’t “fit” the clinical picture

Patterns of bacteremiaPatterns of bacteremia

Transient: caused by manipulation of a flora-containing body surface

Intermittent: typical of most infections giving rise to positive blood cultures

Sustained (or continuous): characteristic of intravascular infections--endocarditis, endarteritis, suppurative thrombophlebitis, infected AV fistula

Number of microorganismsNumber of microorganisms

Unimicrobial (or “monomicrobial”) bacteremia: one isolate

Polymicrobial bacteremia: more than one microorganism; typical of complicated situations often with surgical implications

Epidemiology of sepsisEpidemiology of sepsis

Contributes to > 100,000 deaths in the United States each year.

Annual incidence is probably between 300,000 and 500,000 cases.

About 2/3rds of cases occur in patients hospitalized for another illness (nosocomial infection).

Risk factors for nosocomial sepsisRisk factors for nosocomial sepsis

Gram-negative bacilli: diabetes mellitus; tumors; cirrhosis; burns; invasive procedures; neutropenia

Gram-positive cocci: vascular access lines, devices

Fungi: immunosuppression; broad-spectrum antibiotic therapy

Host factors in sepsisHost factors in sepsis

Mortality is directly related to severity of underlying disease: rapidly-fatal> ultimately fatal (i.e., within 5 years)>nonfatal.

Elderly have increased mortality. Mortality is higher in patients with

subnormal temperatures than in those with fever.

Clinical findings in sepsisClinical findings in sepsis

Early: apprehension, hyperventilation, altered mental status

Complications: hypotension, bleeding, leukopenia, thrombocytopenia, organ failure

Lungs: cyanosis, acidosis, full-blown ARDS

Clinical findings in sepsis (2)Clinical findings in sepsis (2)

Kidneys: oliguria, anuria, tubular necrosis Liver: jaundice and transaminitis Heart: heart failure, stunned myocardium Gastrointestinal: nausea, vomiting, diarrhea, stress

ulceration Systemic: lactic acidosis

Clinical findings in sepsis (3)Clinical findings in sepsis (3)

Petechiae early in course: suspect especially meningococcemia, RMSF

Ecthyma gangrenosum: Ps. aeruginosa Generalized erythroderma: Toxic Shock Syndrome

Petechiae Ecthyema gangrenosum

Skin lesions in septicemias (1)Skin lesions in septicemias (1)

Neisseria meningitidis: erythematous macules or petechiae and purpura

Rocky Mountain spotted fever: petechiae, purpura

Staphylococcus aureus: “purulent purpura” Pseudomonas aeruginosa: ecthyma

gangrenosum

Skin lesions in septicemia (2)Skin lesions in septicemia (2)

Salmonella typhi: “Rose spots” Hemophilus influenzae: cellulitis Endocarditis: petechiae; Osler’s nodes (painful

lesions of finger and toe pads); Janeway lesions (painless lesions of palms or soles)

Anthrax: papules-->vesicles-->eschar Fungemias

A 50 yo man presents to emergency room with severe pain A 50 yo man presents to emergency room with severe pain and swelling of LLE. On exam, temperature is 40.0 and swelling of LLE. On exam, temperature is 40.0 ºC, ºC,

pulse rate is 135/min, respiration rate is 35/min, and blood pulse rate is 135/min, respiration rate is 35/min, and blood pressure is 80/40pressure is 80/40

Which of the following is the most Which of the following is the most appropriate initial therapy?appropriate initial therapy?

1. LLE elevation

2. X-ray of LLE

3. Surgical consultation

4. Oral antibiotics

Necrotizing fasciitis Necrotizing fasciitis

Necrotizing fasciitis usually results from an initial break in skin (trauma or surgery)

It is deep: may involve the fascial and/or muscle compartments

The initial presentation is that of cellulitis

Necrotizing fasciitis: Red flagsNecrotizing fasciitis: Red flags

1. Severe pain (out of proportion of skin findings)

2. Bullae (due to occlusion of deep blood vessels)

3. Skin necrosis or ecchymosis

4. Gas in soft tissue (palpation or imaging)

5. Systemic toxicity

6. Rapid spread during antibiotic therapy

Necrotizing fasciitisNecrotizing fasciitis

Monomicrobial: S. pyogenes, S. aureus, anaerobic streptococci,…. Most are community acquired and present in the limbs in patients with DM or vascular insufficiency

Polymicrobial: aerobic and anaerobic (bowel flora), Usually associated with abdominal surgical procedures, decubitus ulcer, perianal ulcer, bartholin abscess, IV drug injection

Staphylococcal bacteremiaStaphylococcal bacteremia

Complications: endocarditis; metastatic infection; sepsis syndrome

Staphylococci adhere avidly to endothelial cells and bind through adhesin-receptor interactions

Fulminant onset; high fever, erythematous rash with subsequent desquamation, and multiorgan damage

DDx: Rocky Mountain spotted fever, streptococcal scarlet fever, leptospirosis

Streptococcal toxic shock syndromeStreptococcal toxic shock syndrome Early onset of shock and organ failure associated

with isolation of group A streptococci Necrotizing fasciitis present in about 50% of cases Early symptoms: Myalgias, malaise, chills, fever,

nausea, vomiting, diarrhea Pain at minor trauma site may be first symptom

Sepsis in the asplenic patientSepsis in the asplenic patient

Frequently fulminant with massive bacteremia Streptococcus pneumoniae accounts for 50%

to 90% of infections and 60% of deaths Other pathogens: Haemophilus influenzae,

Neisseria meningitidis, Capnocytophaga canimorsus (after dog bites), Babesia microti (babesiosis)

64 year old WM64 year old WM

Presents with fever, hypotension, cellulitis with bullous skin lesions

PMH: cirrhosis SH: recently returned

from New Orleans, likes oysters

Vibrio vulnificusVibrio vulnificus sepsissepsis

Organism found in warm seawater and in shellfish (90% of deaths due to seafood in U.S.)

Cirrhosis a major risk factor to sepsis, with rapid onset

Chills, fever, characteristic skin lesions (bullae with hemorrhagic fluid; necrotizing fasciitis, other)

Also causes wound infection after exposure to salt water

41 year old WM41 year old WM

Fever, “worst headache ever,” myalgias, rash

Returned from family camping trip in Smoky Mountain National Park 1 week PTA

Rocky Mountain spotted feverRocky Mountain spotted fever

Generalized infection of vascular endothelium

Headache typically severe. Fever may be low-grade and rash may be absent (“spotless fever”) when patient first seen

Suspect with flu-like illness and severe headache in endemic areas!

65 year old woman 65 year old woman

PMH diabetes During influenza epidemic, presents with

fever, chills, aching all over (myalgia) PE: bibasilar rales; no murmur Admitted to hospital for treatment of heart

failure

Infective endocarditis: definitionsInfective endocarditis: definitions

Septic vegetations of the endocardium usually involving the heart valves or other areas of turbulent flow

Acute endocarditis occurs on normal heart valves, is caused by highly virulent bacteria and leads to death in < 6 weeks

Subacute endocarditis is caused by less virulent bacteria and has a more indolent course.

Pathogenesis of endocarditisPathogenesis of endocarditis

Sterile vegetations arise downstream of high-flow areas of the heart

Damaged endothelium and foreign bodies increase turbulent flow

Microorganisms implant on the sterile vegetations during transient bacteremia

Septic vegetations become a source of infection elsewhere

Diagnosis of endocarditisDiagnosis of endocarditis

Revised Duke Criteria : positive blood cultures plus echocardiography with or without minor criteria

Heart murmurs (especially regurgitant) Splinter hemorrhages (nail beds) Osler nodes (finger pulps; painful) Petechiae; “pustular purpura” (Staph) Roth spots (fundi)

Etiologies of endocarditisEtiologies of endocarditis Viridans streptococci most common (30-40%) Other streptococci include enterococci and

Streptococcus bovis Staphylococci cause 20-30%) Less common: aerobic gram-negative rods; HACEK

organisms; fungi; anaerobic bacteria; Brucella; Coxiella burnetti; Chlamydia psittaci

“Culture-negative” (<5% to 24%)

Case

42 year male Previously healthy, non smoker 2 week history of progressive cough,

dyspnea, fever Intubated within 48 hours of admission

Case

Hamman-Rich syndrome

Also known as acute interstitial pneumonia, is a rare, severe lung disease which usually affects otherwise healthy individuals

Cough, fever, dyspnea Hamman-Rich syndrome progresses rapidly, with

hospitalization and mechanical ventilation within days to weeks after initial symptoms

Sepsis-summary

Look at the host (age, immunedeficiency,-HIV, cancer, steroids, cirrhosis, dialysis,

Clinical assessment for MOD (vitals, perfusion, mental status, urine output)

Lab parameters-platelets, creatinine, coags, leukocytosis vs. leukopenia

Hemodyanamic, ventilatory support, antibiotics Hit hard and hit early and then deescalate based on

emerging microbiological data