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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