Differential diagnosis of the flu-like illness

The sepsis syndrome: Differential diagnosis of the flu-like illness
By:Divya Ahuja, M.D.

Med Micro 2008 Clinical Correlations #5
Traditional 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 definitions
* Systemic inflammatory response syndrome (SIRS)
* Sepsis
* Severe sepsis
* Septic shock

Systemic Inflammatory Response Syndrome (SIRS)
* Two or more of the following
o temperature > 38 degrees C (100.4 F)
o respirations > 20/minute
o Heart rate > 90 beats per minute
o leukocyte count > 12,000/cmm or < 4000/cmm or with > 10% band forms

Sepsis 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 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
o Serum creatinine
o Platelet count
o pO2/FiO2 ratio
o Serum bilirubin
o 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
o Bacteremia
o Advanced age
o Impaired immune system
o Community acquired pneumonia

Continuum of severity
* Incidence of positive blood cultures increases along the continuum
* Increased mortality rate
* Severe organ dysfunction manifested as
o Acute respiratory distress syndrome
o Acute renal failure
o 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
* 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 disease

Evaluation of blood cultures
* True-positive versus false-positive (contamination; pseudobacteremia)
* Transient versus intermittent versus continuous
* Polymicrobial versus unimicrobial
* Primary versus secondary

Clues 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 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 microorganisms
* Unimicrobial (or “monomicrobial”) bacteremia: one isolate
* Polymicrobial bacteremia: more than one microorganism; typical of complicated situations often with surgical implications

Epidemiology 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 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 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 sepsis
* Early: apprehension, hyperventilation, altered mental status
* Complications: hypotension, bleeding, leukopenia, thrombocytopenia, organ failure
* Lungs: cyanosis, acidosis, full-blown ARDS
* Kidneys: oliguria, anuria, tubular necrosis
* Liver: jaundice and transaminitis
* Heart: heart failure, stunned myocardium
* Gastrointestinal: nausea, vomiting, diarrhea, stress ulceration
* Systemic: lactic acidosis
* 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)
* Neisseria meningitidis: erythematous macules or petechiae and purpura
* Rocky Mountain spotted fever: petechiae, purpura
* Staphylococcus aureus: “purulent purpura”
* Pseudomonas aeruginosa: ecthyma gangrenosum
* 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 and swelling of LLE. On exam, temperature is 40.0 ºC, pulse rate is 135/min, respiration rate is 35/min, and blood pressure is 80/40

Which of the following is the most appropriate initial therapy?
* LLE elevation
* X-ray of LLE
* Surgical consultation
* Oral antibiotics

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 flags
* Severe pain (out of proportion of skin findings)
* Bullae (due to occlusion of deep blood vessels)
* Skin necrosis or ecchymosis
* Gas in soft tissue (palpation or imaging)
* Systemic toxicity
* Rapid spread during antibiotic therapy

Necrotizing 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 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 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 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 WM
* Presents with fever, hypotension, cellulitis with bullous skin lesions
* PMH: cirrhosis
* SH: recently returned from New Orleans, likes oysters

Vibrio vulnificus sepsis
* 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 WM
* Fever, “worst headache ever,” myalgias, rash
* Returned from family camping trip in Smoky Mountain National Park 1 week PTA

Rocky 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
* 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: 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 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 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 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

The sepsis syndrome: Differential diagnosis of the flu-like illness.ppt