Systemic Infections

Septic Arthritis

Septic arthritis, also known as infectious arthritis, may be caused by any number of different microorganisms and results in erythematous, painful, swollen joints. Synovial (joint) fluid analysis is the cornerstone of diagnosis and should be performed before beginning antibiotic therapy. Blood or joint fluid culture may also be used to identify the microorganism causing the infection and guide subsequent treatment.

Diagnosis

Indications for Testing

  • Acute mono- or oligoarticular arthritis
  • Loosening of prosthesis

Laboratory Testing

  • CBC with differential – expect mild to moderate leukocytosis and left shift of cell composition (immature band forms)
    • Results that increase likelihood ratio (LR) for septic arthritis
      • White blood cell (WBC) count >10,000/µL = LR 1.4
      • Neutrophils >90% = LR 3.4
  • Joint aspiration (arthrocentesis) with synovial specimen (when possible) – cornerstone of diagnosis and should be performed prior to antibiotic administration
    • Aspiration should not be performed through overlying cellulitis
    • Macroscopic assessment – viscosity, color, clarity
      • Inflammatory fluid
        • Color – ranges from yellow to greenish
        • Consistency – turbid
    • WBC count with differential
      • Usually >50,000/µL with predominance of neutrophils
        • Same degree of leukocytosis may be noted in gout and pseudogout
      • WBC count >50,000/µL increases likelihood of septic arthritis (LR 7.7 positive; LR 0.42 negative)
        • At least 90% leukocytes (LR 3.4 positive; LR 0.34 negative)
        • <50,000/µL does not rule out septic arthritis
        • Low WBC count common in immunosuppressed patients
      • Prosthetic joints – cell count cutoffs are much lower   
        • Knee – WBC >1,700/µL or differential >65% neutrophils
        • Any other joint – WBC >4,200/µL or differential >80% neutrophils
    • Gram stain – low sensitivity; diagnostic if organisms are identified
    • Culture – moderately high sensitivity if positive
      • <50% positive in gonococcal arthritis – recommend diagnosis of gonococcal arthritis be made based on clinical presentation and cultures of cervix, rectum, urethra, or oropharynx
    • Crystal scan with polarized microscope – evaluate for crystalline arthritis
      • Monosodium urate demonstrates negative birefringence
      • Calcium pyrophosphate dehydrate (CPPD) crystals have weak birefringence
    • Not recommended
      • Glucose, lactate dehydrogenase (LD), and protein – neither sensitive nor specific
      • Polymerase chain reaction (PCR) for specific organisms
  • C-reactive protein (CRP)
    • Usually elevated; absence of increased concentrations does not exclude septic arthritis
    • CRP >10 mg/L (>1.0 mg/dL) increases likelihood of septic arthritis (LR 1.6)
      • CRP ≥13.5 mg/L (≥1.35 mg/dL) in prosthetic joints – sensitivity 73-91%, specificity 81-86%
      • CRP remains elevated up to 2 months postarthroplasty, then becomes normal
    • Inflammatory parameters may remain high for up to 2 weeks postsurgery
  • Cultures
    • Blood cultures
      • Positive in 50-70% of patients with nongonococcal bacterial arthritis
        • Diagnostic if positive
        • Limited usefulness but may be helpful when ruling out other diseases, particularly in children
      • Lower rate of positivity in prosthetic joints
    • Tissue cultures – prosthetic joints
      • Multiple intraoperative tissue samples should be sent for culture (ideal is 5-6)
      • Antimicrobial susceptibility testing may help guide therapy
    • Other site cultures dependent on patient history – skin ulcer, urine, throat, genitourinary
  • Other testing – serologic testing for Lyme disease in patient with negative cultures and who resides in an endemic area

Histology

Prosthetic joints – intraoperative frozen sections often show >5-10 polymorphonuclear neutrophils per high-power field (PMNs/hpf) which indicates acute inflammation.

Imaging Studies

  • X-ray/ultrasound – useful in detecting the presence of fluid; not useful in diagnosis of osteomyelitis unless late in course of disease
    • Prosthetic joints – periprosthetic lucency, osteolysis, or prosthesis migration may be seen
  • Bone scan or magnetic resonance imaging (MRI) – may be necessary to rule out osteomyelitis
    • Sensitive for detecting failed implants but not specific for infection
    • Artifact from implants may obscure information

Differential Diagnosis

  • Adult noninfectious inflammatory arthritis
  • Pediatric inflammatory arthritis
    • Kawasaki disease
    • Toxic (or transient) synovitis
    • Slipped capital femoral epiphysis
    • Acute rheumatic fever
    • Legg-Calvé-Perthes disease (LCPD)
    • Osteochondrosis
    • Sickle cell disease
  • Intra-articular injury
    • Fracture
    • Meniscal tear
    • Osteonecrosis
    • Traumatic effusion
    • Hemarthrosis
  • Other
    • Malignancy (eg, synovial sarcoma)
    • Osteomyelitis
    • Cellulitis overlying joint

Monitoring

C-reactive protein (CRP) levels – nonspecific, but often elevated during infection.

Background

Epidemiology

  • Incidence – 2-10/100,000 in the U.S.
    • 30-40/100,000 in patients with rheumatoid arthritis
    • 40-70/100,000 in patients with prosthetic joints
  • Transmission
    • Most cases are hematogenously acquired
    • Other mechanisms for infection
      • Surgery
      • Trauma
      • Percutaneous puncture
      • Spread from contiguous structure infection

Commonly Involved Organisms 

  • Bacteria
    • Children
    • Adults
      • S. aureus – most common (50% of cases)
      • Streptococcus spp (groups A and B)
      • Neisseria gonorrhoeae – almost exclusively in sexually active patients
      • Gram-negative bacilli – elderly, intravenous (IV) drug abusers, immunocompromised persons
        • E. coli
        • Pseudomonas aeruginosa
        • Salmonella – sickle cell disease, immunocompromised
      • Coagulase-negative staphylococci – prosthetic joint
      • Listeria (rare) – rheumatoid arthritis, immunosuppression
      • Anaerobes (rare) – prosthetic joints, bite victims
      • Polymicrobial – up to 20% of arthroplasty patients; most commonly methicillin-resistant S. aureus (MRSA) or anaerobes plus other organisms
      • Borrelia burgdorferi – areas where tick is endemic
  • Virus – rare; most common is parvovirus B19
  • Fungi – uncommon
    • Endemic dimorphic fungi
    • Candida spp – immunocompromised persons
  • Parasites – rare
    • Helminths
    • Filaria

Risk Factors

  • Nonprosthetic joint
  • Prosthetic joint
    • Patient related
      • Previous arthroplasty
      • Tobacco abuse
      • Obesity
      • Rheumatoid arthritis
      • Diabetes mellitus
      • Immunosuppression
      • Bacteremia, endocarditis
    • Surgery related
      • Simultaneous bilateral arthroplasty
      • Operative time >2.5 hours
      • Allogenic blood transfusion
      • Postoperative complications
        • Delayed wound healing
        • Atrial fibrillation
        • Myocardial infarction
        • Urinary tract infection (UTI)
        • Prolonged hospital stay

Pathophysiology

  • Organism accesses joint space either directly or hematogenously
  • Organisms cause release of inflammatory cell cytokines, proteases
    • Leads to destruction of cartilage, inhibition of new cartilage synthesis, and bone loss

Clinical Presentation

  • Fever
  • Warm, swollen, erythematous, painful joint
  • Prosthetic joint
    • Draining sinus
    • Loosening of prosthesis
    • Pain in the area around the prosthesis
  • Infection may disseminate systemically

ARUP Lab Tests

Initial screening test in septic arthritis

May assist in evaluating for joint disease, systemic disease, or inflammation

Detect white blood cells (WBCs) and presence and type of microorganisms in specimen

Identify bacteria in normally sterile body fluids

May assist in differentiating gout from septic arthritis

Anaerobe culture is recommended for body fluids, tissue, and deep wound/surgical culture; refer to anaerobe culture and gram stain

For CSF specimens, order CSF culture and gram stain

For blood specimens, order blood culture or blood culture, AFB and fungal

Anaerobe culture is NOT included with this order

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Detect presence of bacteria in blood

Time-sensitive test

Important informationTesting is limited to the University of Utah Health Sciences Center only

Identify bacteria in tissues

Anaerobe culture is recommended for body fluids, tissue, and deep wound/surgical cultures; refer to anaerobe culture and gram stain

Anaerobe culture is NOT included with this order

Related Tests

May be helpful in initial diagnosis of septic arthritis

Normal erythrocyte sedimentation rate (ESR) does not rule out septic arthritis

Preferred reflex test to detect Lyme disease in individuals with ≤4 weeks of clinical symptoms or exposure to tick

Consider in patient with negative cultures and who resides in an endemic area

Reflex pattern: if enzyme-linked immunosorbent assay (ELISA) result is 1.00 LIV or greater, then IgG and IgM immunoblot will be added

Intended for use in suspected periprosthetic joint infection

Medical Experts

Contributor

Fisher

Mark A. Fisher, PhD, D(ABMM)

Associate Professor of Clinical Pathology, University of Utah

Medical Director, Bacteriology, and Special Microbiology, Antimicrobial Susceptibility Testing, at ARUP Laboratories

References

Additional Resources

Neonatal Sepsis - Sepsis in Newborns

Neonatal sepsis is a major cause of hospitalization and infant death and can result from meningitis, pneumonia, gastroenteritis, or other serious infections. Early detection and treatment can reduce morbidity and mortality, but nonspecific symptoms cause difficulty in differentiating bacterial and viral infections. Although there are no definitive confirmatory diagnostic tests for sepsis, laboratory tests including blood cultures, C-reactive protein (CRP), and procalcitonin (PCT) can contribute to the investigation of sepsis and help in determining when to discontinue treatment. 

Quick Answers for Clinicians

What are the risk factors for neonatal sepsis?

Major risk factors for neonatal sepsis include preterm birth, low birth weight, maternal colonization of group B streptococcus (GBS), the most common etiologic agent of sepsis,  and chorioamnionitis.   

Most infants with early-onset sepsis will exhibit abnormal signs in the first 24 hours after birth, although any critically ill infant should be immediately evaluated for sepsis and receive empirical broad-spectrum antimicrobial therapy after cultures, even if obvious risk factors for sepsis are absent.  

What role does laboratory testing play in diagnosing neonatal sepsis?

There is no definitive diagnostic test for sepsis. Along with clinical data, laboratory testing can provide clues that indicate the presence of or risk of developing sepsis. Blood culture is useful for investigating the severity of sepsis and for monitoring therapeutic response. The American Academy of Pediatrics (AAP) recommends that all newborn infants with suspected sepsis have a lumbar puncture if stable enough for the procedure.  Other tests, including CBC and chemistries, provide a baseline to assess therapeutic response.

What role do acute phase markers such as procalcitonin and C-reactive protein play in a neonatal sepsis workup?

Procalcitonin (PCT) is a proposed marker for early sepsis in infants and is more sensitive than C-reactive protein (CRP), but less specific; in addition, the interpretive cutoffs established for adults may not be transferable to the pediatric population.  CRP is helpful in ruling out neonatal sepsis in full-term infants; a cutoff of 2.0-2.5 ng/mL is moderately accurate in predicting neonatal sepsis.  Recent studies suggest similar efficacy in preterm infants. 

Indications for Testing

Most cases of neonatal sepsis (roughly 80-90%) present in the first 2 days of life. Manifestations range from nonspecific symptoms to multiorgan failure. Infants rarely present with fever unless born to a febrile mother, although some acquire fever immediately after delivery.  It is more common for an infant to be hypothermic or present with pneumonia, two nonspecific signs of sepsis.  Other presenting signs that warrant investigation include lethargy, irritability, poor feeding, respiratory symptoms (eg, apnea, grunting), and abdominal distention.

Clinical Definition

Neonatal sepsis is defined as a systemic infection occurring in infants ≤28 days old. Early-onset neonatal sepsis is defined as sepsis presenting within 72 hours of birth,   and late-onset sepsis as sepsis occurring after 72 hours in infants in the neonatal intensive care unit (NICU) and after 7 days of life in full-term infants. 

Laboratory Testing

Initial Workup of Suspected Neonatal Sepsis

Initial, nonspecific testing (eg, urine cultures, white blood cell counts) may prove useful for identifying infants with a low probability of developing sepsis, but not for identifying infants likely to be infected.  

Blood Culture

A single blood culture is used to determine the presence of bacterial infection. The culture should be obtained before beginning treatment. 

Cerebrospinal Fluid Studies

Cerebrospinal fluid (CSF) studies provide optimal diagnostic sensitivity for detecting sepsis. The American Academy of Pediatrics (AAP) recommends that all newborn infants with suspected sepsis have a lumbar puncture if stable enough for the procedure.  CSF studies are not necessary in all infants with suspected sepsis; if there are no obvious maternal risk factors or there is suspicion that a noninfectious etiology may be involved, CSF studies can be deferred.  However, if blood cultures are positive or infants fail to respond to therapy, a lumbar puncture should be obtained and tested. 

C-Reactive Protein

CRP is a nonspecific marker of acute inflammation. Evidence supports the use of CRP to help rule out neonatal sepsis in full-term infants, and recent studies suggest similar efficacy in preterm infants.  CRP increases within 6-8 hours of infection and peaks at 24 hours. CRP sensitivity is initially low, but improves 6-12 hours after birth. Two normal readings provide strong evidence that bacterial sepsis is unlikely and that any antibiotic treatment can be discontinued.   There is no evidence to support repetition of CRP testing to determine duration of treatment in an infant with an elevated CRP (≥1.0 mg/dL). 

Procalcitonin

PCT is another acute phase reactant that is used as a marker for the early detection of sepsis, and although it is more sensitive than CRP for identifying early sepsis, it is less specific.  A physiologic increase in PCT occurs within the first 24 hours after birth and may appear in the presence of noninfectious conditions (eg, respiratory distress syndrome). The interpretive cutoffs established for adults may not be transferable to the pediatric population, but a cutoff of 2.0-2.5 ng/mL is moderately accurate in predicting neonatal sepsis. 

ARUP Lab Tests

Initial, nonspecific testing

May be used as a marker for early detection of sepsis

May aid in ruling out neonatal sepsis in full-term infants

May be used to identify pathogens before treatment

May be used to evaluate suspected sepsis

Medical Experts

Contributor

Pearson

Lauren N. Pearson, DO, MPH

Assistant Professor of Clinical Pathology, University of Utah

Medical Director, University of Utah Health Hospital Clinical Laboratory

References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Sepsis

Sepsis is a severe illness characterized by a systemic, whole-body response to infection and is a frequent cause of morbidity and mortality in hospitalized patients. Sepsis is most common in older individuals and infants, and can be difficult to diagnose due to its variable presentation. Because there is no confirmatory diagnostic test, sepsis diagnosis requires clinical judgment based on evidence of infection and organ dysfunction. 

The clinical practice guideline issued by the Surviving Sepsis Campaign (SSC) emphasizes the importance of early identification and immediate management of infection, including obtaining cultures and measuring serum lactate as soon after patient presentation as possible. The SSC recently released a 1-hour bundle that combines the SSC’s previous 3-hour and 6-hour bundles and recommends beginning sepsis management and treatment immediately at the point of presentation. 

Quick Answers for Clinicians

Who is at risk of developing sepsis?

While anyone can develop sepsis, certain individuals are at higher risk, including the following  :

  • Adults ≥65 years
  • Children ≤1 year
  • Individuals with weakened immune systems
  • Individuals with chronic medical conditions (eg, diabetes, cancer, lung or kidney disease)
  • Those who have undergone surgery or other invasive procedures within the past 6 weeks
What role does laboratory testing play in diagnosing and monitoring sepsis?

There is no definitive diagnostic test for sepsis. Along with clinical data, laboratory testing can provide clues that indicate the presence of or risk of developing sepsis. Serum lactate may indicate the severity of sepsis and is used to monitor therapeutic response. Peripheral blood cultures are useful for investigating the infectious etiology of sepsis and managing appropriate antimicrobial treatment. Other tests, including CBC and chemistries, provide a baseline to assess therapeutic response.

What role does procalcitonin play in a sepsis workup?

Procalcitonin (PCT) provides supportive evidence that systemic inflammation is due to bacterial infection. As such, it can be useful in decreasing the unnecessary use of antibiotics. It may also be used to predict 28-day cumulative mortality risk for patients diagnosed with sepsis. A PCT concentration that has not declined by 80% or more between day 1 and 4 of admission is consistent with a higher cumulative mortality risk.  

Indications for Testing

Individuals with one or more risk factors and relevant clinical presentation (eg, possible source of infection and systemic signs of inflammation or organ dysfunction) should be screened for sepsis.

Clinical Definition

Sepsis

Sepsis was redefined in the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) as “life threatening organ dysfunction caused by dysregulated host response to infections.” This definition was endorsed by the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM).  For clinical purposes, organ dysfunction is represented by an increase in the Sequential (Sepsis-related) Organ Failure Assessment (SOFA) Score of 2 points or more, which is associated with an in-hospital mortality greater than 10%.  A baseline SOFA score of 0 is used unless the patient has preexisting organ dysfunction before the onset of current infection.  Sepsis inflammatory response syndrome (SIRS) criteria are no longer considered in the identification of sepsis and septic shock.

Adult patients outside of intensive care units (ICUs) (ie, in the inpatient or outpatient setting) with suspected infection are at risk of sepsis development if they meet two or more quick SOFA (qSOFA) Score criteria. 

Septic Shock

Septic shock is a subset of sepsis characterized by circulatory, cellular, and metabolic abnormalities that are associated with a greater risk of mortality than sepsis alone. Septic shock can be identified by the presence of sepsis in addition to the following :

  • Persistent hypotension requiring vasopressors to maintain mean arterial pressure of ≥65 mmHg
  • Serum lactate level >2 mmol/L in the absence of hypovolemia

Laboratory Testing

Initial Workup of Suspected Sepsis

Although there is no definitive confirmatory diagnostic test for sepsis, the following laboratory tests can help assess organ dysfunction and contribute to the clinical diagnosis and appropriate medical management of sepsis.

Serum Lactate

Sepsis-induced hypoperfusion may manifest with acute organ dysfunction and/or decreased blood pressure and increased serum lactate. Lactate >2 mmol/L is considered abnormal and levels >4 mmol/L often suggest occult hypoperfusion and should trigger resuscitation.  Increases in serum lactate levels are associated with a higher risk of developing overt septic shock and with poor outcome in general.  

Blood Culture

Two sets of blood cultures (aerobic and anaerobic) should be obtained from two different sites before beginning antibiotics to ensure accurate identification of pathogens and proper medical management of infection. 

Procalcitonin

Procalcitonin (PCT) is an acute phase reactant that is used as a biomarker for the diagnosis of sepsis and as a guide for antibiotic stewardship.   Refer to the Monitoring section below.

C-Reactive Protein

C-reactive protein (CRP) is a nonspecific marker of acute inflammation. CRP does not peak for up to 48 hours from the onset of sepsis and does not correlate with severity or prognosis. However, there is good evidence that the use of CRP testing may help rule out neonatal sepsis in full-term infants. Recent studies suggest similar efficacy in preterm infants. 

Other Testing

CBC, bilirubin, and creatinine tests are also used in calculating SOFA scores and may help identify patients with sepsis. 

Monitoring

Serum Lactate

Lactate levels >2 mmol/L should be remeasured within 2-4 hours to guide resuscitation and normalization of lactate.  The American College of Emergency Physicians (ACEP) suggests remeasuring lactate at least 1-2 hours after starting resuscitation in patients with initially abnormal lactate concentrations; remeasuring lactate levels sooner than this does not appear to be helpful. 

Procalcitonin

The SSC suggests that PCT measurements can be used to support shortening the duration of antimicrobial therapy in some patients with sepsis, such as those with bacterial pneumonia or lower respiratory tract infections. 

PCT measurements also provide supportive evidence that systemic inflammation is due to bacterial infection and can be used to predict 28-day cumulative mortality risk for patients diagnosed with sepsis. Decreased PCT levels are independent predictors of mortality in patients with sepsis. The multicenter Procalcitonin Monitoring Sepsis (MOSES) study found that a PCT concentration that has not declined by 80% or more between day 1 and 4 of admission is consistent with a higher cumulative mortality risk.  

ARUP Lab Tests

May indicate severity of sepsis; can be used to monitor therapeutic response

May be used as a marker for early detection of sepsis and to assess risk of progression to severe sepsis and septic shock in critically ill patients upon admission to ICU

Nonspecific marker of acute inflammation; may aid in ruling out neonatal sepsis in full-term infants

May be used to identify pathogens before treatment

May be used to assess therapeutic response

Medical Experts

Contributor

Fisher

Mark A. Fisher, PhD, D(ABMM)

Associate Professor of Clinical Pathology, University of Utah

Medical Director, Bacteriology, and Special Microbiology, Antimicrobial Susceptibility Testing, at ARUP Laboratories

Contributor

Pearson

Lauren N. Pearson, DO, MPH

Assistant Professor of Clinical Pathology, University of Utah

Medical Director, University of Utah Health Hospital Clinical Laboratory

References

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Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®

Necrotizing Soft Tissue Infections - Complicated Skin Infections

Aggressive, necrotizing soft tissue infections can cause extensive local tissue damage as well as systemic toxicity. These infections require prompt recognition to prevent severe morbidity and mortality. Laboratory testing includes gram stain of aspirates or tissue biopsies for simple infections; complicated infections may require CBC, culture, and surgical exploration of the site.

Diagnosis

Indications for Testing

Redness, warmth, tenderness, crepitus, and induration or purulent drainage indicating infection in underlying structures, including skin, dermis, muscle, and bone

Laboratory Testing

  • Simple infections – abscesses, furuncles, carbuncles
    • Culture
      • Tissue
      • Wound
    • Gram stain of aspirates or tissue biopsies – may not be as helpful as culture, depending on organism involved and quality of specimen
  • Complicated infections – fever, tachycardia, immunocompromised state
    • CBC
    • Culture
      • Tissue
      • Wound
      • Blood – infrequently positive
    • C-reactive protein (CRP)
    • Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score
      • Use to differentiate cellulitis from more serious infection and need for surgical referral
      • ≥6 points has positive predictive value of 92% and negative predictive value of 96% for diagnosis of necrotizing fasciitis
      • If above studies do not confirm necrotizing fasciitis, surgical exploration of the site may confirm the disease

Imaging Studies

  • X-ray – subcutaneous air in tissue noted in about 25% of patients with complicated infections
    • May reveal foreign body in infected wounds
  • Ultrasound (US)/computed tomography (CT)/magnetic resonance imaging (MRI)
    • Choose imaging study based on suspected location of infection and usefulness for site infected
    • Imaging frequently used for localized drainage of identified site

Differential Diagnosis

Background

Epidemiology

  • Incidence – 500-1,500 cases per year in the U.S. (Anaya, 2007)
  • Age – increased frequency in older patients
  • Sex – M:F, equal
    • Exception in Vibrio vulnificus, M>F
  • Transmission – skin entry via break in dermis

Classification

  • Type I – polymicrobial infection with aerobes, anaerobes, and facultative bacterial species
  • Type II – monomicrobial, generally, with gram-positive streptococci or staphylococci, especially
    • Group A beta-hemolytic streptococci, or
    • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Type III – infection with gram-negative rods, especially Clostridium perfringens
  • Other generally recognized types outside of this Type I-III classification system are caused by V. vulnificus or fungal infection
  • Additional subclassifications formerly known by other terms are now described using general term “necrotizing soft tissue infections” (NSTIs)
    • Necrotizing fasciitis – necrotizing infection of the deep fascia
    • Fournier’s gangrene – necrotizing soft tissue infection of the perineum
    • Clostridial myonecrosis/gangrene/gas gangrene – necrotizing infection of muscle due to C. perfringens or related gas-producing organisms

Organisms

  • Monomicrobial infection – one third of infections
  • Polymicrobial infection more common – about two thirds of infections
  • Most common organisms
    • Staphylococcus spp (including MRSA)
    • Streptococcus spp
  • Other common organisms
    • Enterococci
    • Pseudomonas aeruginosa
    • Enterobacteriaceae
    • Bacteroides spp
    • Proteus spp
    • Clostridium spp

Risk Factors

  • Approximately 30% of NSTIs occur in healthy individuals with no risk factors (Mishra, 2013)
  • Risk factors include (Anaya, 2007; Mishra, 2013)
    • Diabetes mellitus
    • Intravenous drug use
    • Alcohol abuse
    • Cancer or other immunocompromised state
    • Peripheral vascular disease
    • Obesity or malnutrition
    • Trauma
    • Postoperative infection
    • Burns

Clinical Presentation

  • General symptoms
    • Cutaneous – erythema, tense edema, vesicles or bullae, necrosis ulcers, crepitus, gray or discolored wound drainage, pain extending past margin of skin infection
    • Constitutional – fever, diaphoresis, delirium, tachycardia, tachypnea
    • Most common locations – extremities (50-55%), perineum/buttocks (20%), trunk (18-20%), head and neck (8-10%)
  • Clinical markers that may help differentiate necrotizing infection from localized infection include
    • Pain disproportionate to appearance of infection
    • Crepitus
    • High fever
    • Rapidly spreading erythema

Prevention

  • Vibrio – do not eat raw seafood; avoid exposing open wounds to seawater
  • Pasteurella – begin prophylaxis at time of bite for serious bite wounds

ARUP Lab Tests

Help differentiate aggressive (systemic) infection from local infection

May not be elevated in spite of aggressive disease

Identify bacteria in tissues

Anaerobe culture is recommended for body fluids, tissue, and deep wound/surgical cultures; refer to anaerobe culture and gram stain

Anaerobe culture is NOT included with this order

Identify bacteria in wounds

Anaerobe culture is recommended for body fluids, tissue, and deep wound/surgical cultures; refer to anaerobe culture and gram stain

Anaerobe culture is NOT included with this order

Detect presence of bacteria in blood

Important informationTesting is limited to the University of Utah Health Sciences Center only

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Component of Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score

Component of LRINEC score

Related Tests

ARUP recommends contacting your local or state health department in suspected botulism cases

If local and state officials are not available, the Centers for Disease Control and Prevention (CDC) can be contacted

Clostridium botulinum culture

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)

Associate Professor of Clinical Pathology, University of Utah

Medical Director, Microbial Immunology, Parasitology and Fecal Testing, and Infectious Disease Antigen Testing at ARUP Laboratories

Contributor

Fisher

Mark A. Fisher, PhD, D(ABMM)

Associate Professor of Clinical Pathology, University of Utah

Medical Director, Bacteriology, and Special Microbiology, Antimicrobial Susceptibility Testing, at ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®

Endocarditis

Endocarditis is an infection of the endocardium that is usually associated with infection of the cardiac valve leaflets. Blood cultures are generally used for diagnosis, and are very sensitive for most organisms.

Diagnosis

Indications for Testing

Risk factors and appropriate clinical presentation

Criteria for Diagnosis

To establish final diagnosis, use the modified Duke Criteria for Infective Endocarditis (2009).

Laboratory Testing

  • CBC – frequently shows leukocytosis and left shift toward immature cell forms
  • Blood cultures – three sets from separate venipuncture sites; first and last set at least 1 hour apart
    • Perform prior to antibiotic administration
    • Very sensitive for most organisms
  • C- reactive protein (CRP)
  • For blood culture-negative disease, consider
    • Coxiella – antibody testing
    • Bartonella – polymerase chain reaction (PCR)
    • Brucellaculture, antibody testing
    • HACEK organisms (Haemophilus spp, Aggregatibacter spp [A. aphrophilusA. actinomycetemcomitans], Cardiobacterium hominisEikenella corrodens, Kingella kingae)
      • Cardiobacterium hominis
      • Eikenella corrodens
      • Kingella kingae
    • Antinuclear antibodies (ANA)/rheumatoid arthritis (RA) testing
    • Unusual causes – Tropheryma whipplei, fungi (yeastsmolds)
  • Urine analysis – may demonstrate hematuria, proteinuria, pyuria, red cell casts

Imaging Studies

  • Transthoracic echocardiogram (TTE) or transesophageal echocardiogram (TEE) is the gold standard for visualization of vegetations, but negative study does not rule out endocarditis
    • TTE
      • Recommended first test
      • Sensitivity dependent on vegetation size – if >10 mm, test is 100% sensitive
      • Prosthetic values may be better visualized with TTE
    • TEE
      •  Use in patients with negative TTE and high clinical suggestion of endocarditis
      •  Very sensitive – negative study has negative predictive value of 90%

Differential Diagnosis

Background

Epidemiology

  • Incidence – 3-10/100,000; incidence increases with age (up to 20/100,000)
  • Age – mean 30-60 years, depending on population
  • Sex – M>F, 3:1 to 9:1

Organisms

  • Variety of organisms – Staphylococcus and Streptococcus spp account for most cases
  • Specific medical condition associations
    • Intravenous (IV) drug use – Staphylococcus spp, Streptococcus anginosus group
    • Rheumatic heart disease – Streptococcus anginosus group
    • Gastrointestinal neoplasm in elderly – Streptococcus bovis
    • Healthcare-associated infection – Enterococcus spp, Staphylococcus spp
    • Prosthetic valves – Staphylococcus spp
    • Culture-negative disease – CoxiellaBartonella, BrucellaHACEK organisms
    • Fungi – yeastsmolds
      • Usually 2-3 months after left ventricular assist device (LVAD) implantation
      • Immunocompromised patients

Risk Factors

  • IV drug use
  • Structural heart disease – rheumatic carditis, valvular stenosis, congenital heart disease
  • Hemodialysis
  • Cardiovascular prostheses, intravascular devices
  • Poor dentition
  • HIV
  • Prior episode of infective endocarditis (IE)
  • ​Age >60 years

Pathophysiology

  • Classification
    • Native valve endocarditis, prosthetic valve endocarditis, and nonvalvular device endocarditis (eg, pacemaker, LVAD)
    • Right- versus left-sided valves
    • Community versus healthcare acquired
  • Turbulent blood flow produced by abnormalities on valvular leaflets
    • In patients with rheumatic heart disease, mitral valve most commonly involved; aortic valve second most commonly involved
    • Right-sided endocarditis more common with IV drug use
  • Transient bacteremia occurs
    • Bacteria naturally adhere to abnormal tissue and form vegetations on the valve
    • Bacteria proliferate within the vegetations

Clinical Presentation

  • Constitutional – fever, anorexia, night sweats, weight loss
  • Cardiovascular – new-onset murmur, congestive heart failure, dysfunctional prosthetic valve
  • Renal – glomerulonephritis
  • Embolic phenomena
  • Osler nodes – painful blue or purple nodules on the fingers, toes, palms, and soles (rare)
  • Roth spots – retinal hemorrhages with central white spots (rare)
  • Janeway lesions – nontender nodules on hands and feet (rare)
  • Splinter hemorrhages – subungual linear hemorrhages on the long axis of the distal third of nail
  • Complications
    • Valvular collapse with heart failure
    • Periannular extension of the infection into the adjacent myocardium
    • Rupture of the myocardium from extension
    • Embolization (highest with left-sided lesions); stroke
    • Mycotic aneurysm
    • Splenic/hepatic abscesses
    • Intracardiac abscesses

Pediatrics

Epidemiology

Incidence – lower than in adult population

Risk Factors

  • Congenital heart disease
    • Highest risk in cyanotic heart disease, endocardial cushion defects, high-velocity jets
  • Indwelling catheters
  • Rarely – malignancy, osteomyelitis

Organisms

  • Streptococcus anginosus group – rheumatic heart disease
  • Staphylococcus epidermidis – nosocomial infection

Clinical Presentation

  • Constitutional – lethargy, fever, malaise
  • Cardiovascular – new-onset murmur
  • Adult manifestations such as Osler nodes and Janeway lesions uncommon
  • Complications

ARUP Lab Tests

Aid in diagnosis of bacterial process

Detect presence of bacteria in blood

Testing is limited to the University of Utah Health Sciences Center only

Low volume will result in decreased recovery of pathogens

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, RA, infection, or sepsis)

Related Tests

Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases

Confirm infectious agent as C. burnetii (Q-fever) in symptomatic patients

Detect Bartonella species in blood, cerebrospinal fluid (CSF), or tissue

Identify Brucella in blood, CSF, body fluids, and abscesses

Recommended serology test to detect recent infection from Brucella in the context of a clinically compatible illness and exposure history

Reference method for identification of most bacterial species

Aid in initial diagnosis of connective tissue disease

Preferred panel for the workup of suspected RA or undifferentiated inflammatory arthritides

Panel includes cyclic citrullinated peptide (CCP) antibody, IgG; rheumatoid factor

Medical Experts

Contributor

Fisher

Mark A. Fisher, PhD, D(ABMM)

Associate Professor of Clinical Pathology, University of Utah

Medical Director, Bacteriology, and Special Microbiology, Antimicrobial Susceptibility Testing, at ARUP Laboratories

Contributor

Genzen

Jonathan R. Genzen, MD, PhD

Associate Professor of Clinical Pathology, University of Utah

Chief Operations Officer, Medical Director of Automated Core Laboratory and Farmington Health Center Clinical Laboratory, at ARUP Laboratories

References

Additional Resources
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    American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council

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