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Bacterial Sepsis

Practice Essentials

Definitions

Sepsis  is a life-threatening syndrome usually caused by bacterial infection. Sepsis is a response of the body’s immune system that results in organ dysfunction or failure. The systemic inflammatory response syndrome (SIRS) criteria were recently replaced by the quick Sequential Organ Failure Assessment (qSOFA) in 2016, allowing for quick bedside analysis of organ dysfunction in patients with suspected or documented infection. The qSOFA score includes a respiratory rate of 22 breaths/minute or more, systolic blood pressure of 100 mm Hg or less, and altered level of consciousness.
For completeness, severe sepsis is defined as sepsis complicated by organ dysfunction.

Multiple organ dysfunction syndrome (MODS)  is characterized by progressive organ dysfunction in a severely ill patient, with failure to maintain homeostasis without intervention. It is the end stage in infectious conditions (sepsis, septic shock) and noninfectious conditions (eg, SIRS due to pancreatitis). The greater the number of organ failures, the higher the mortality risk, with the greatest risk associated with respiratory failure requiring mechanical ventilation. MODS can be classified as primary or secondary.

Primary MODS is the direct result of identifiable injury or insult with early organ dysfunction (eg, renal failure due to a nephrotoxic agent or liver failure due to a hepatotoxic agent).

Secondary MODS is organ failure that has no attributable cause and is a consequence of the host’s response (eg, acute respiratory distress syndrome [ARDS] in individuals with pancreatitis).

The following parameters are used to assess individual organ dysfunction:

Respiratory system: Partial pressure of arterial oxygen (PaO
2)/fraction of inspired oxygen (FiO
2) ratio

Hematology: Platelet count, coagulation panel (prothrombin time and partial thromboplastin time)

Liver: Serum bilirubin

Renal: Serum creatinine (or urine output)

Brain: Glasgow coma score

Cardiovascular: Hypotension and vasopressor requirement

Septic shock  is defined as sepsis with hypotension requiring vasopressor therapy to maintain a mean blood pressure of more than 65 mm Hg and a serum lactate level exceeding 2 mmol/L (18 mg/dL) after adequate fluid resuscitation.
This has a greater risk of mortality and long-term morbidity.

Pseudosepsis is defined as fever, leukocytosis, and hypotension due to causes other than sepsis. Examples might include the clinical picture seen with salicylate intoxication, methamphetamine overdose, or bilateral adrenal hemorrhage.

Etiology

Sepsis can be caused by an obvious injury or infection or a more complicated etiology such as perforation, compromise, or rupture of an intra-abdominal or pelvic structure.
Other etiologies can include meningitis, head and neck infections, deep neck space infections, pyelonephritis, renal abscess (intrarenal or extrarenal), acute prostatitis/prostatic abscess, severe skin or skin structure infections (eg, necrotizing fasciitis), postsurgical infections, or systemic infections such as rickettsial infection. A more detailed discussion of sepsis etiology in various organ systems is provided in Etiology.

Clinical Presentation

Individuals with sepsis may present with localizing symptoms related to a specific site or source of infection or may present with nonspecific symptoms. Individuals with nonspecific symptoms are usually acutely ill with fever and may present with or without shaking chills. Mental status may be impaired in the setting of fever or hypotension. Patients with bacteremia from any source often display an increased breathing rate resulting in respiratory alkalosis. The skin of patients with sepsis may be warm or cold, depending on the adequacy of organ and skin perfusion. A detailed history and physical examination is essential in determining the likely source of the septic process (See History and Physical Examination). This helps the clinician to determine the appropriate treatment and antimicrobial therapy (see Treatment for further detail).

See Clinical Presentation for more detail.

Diagnosis

A diagnosis of sepsis is based on a detailed history, physical examination, laboratory and microbiology testing, and imaging studies.

Laboratory studies that may be considered include the following:

Complete blood (CBC) count – May show elevated or low white blood cell count, anemia, and/or thrombocytopenia

Chemistry studies, such as markers of liver or kidney injury – May suggest organ dysfunction

Bacterial cultures – Blood cultures and site-specific cultures based on clinical suspicion (eg, wound culture, sputum culture, or urine culture)

Stained buffy coat smears or Gram staining of peripheral blood – May be helpful in certain infections

Urine studies (urinalysis, microscopy, urine culture)

Certain biomarkers, such as
procalcitonin

and presepsin

– May be useful in diagnosing early sepsis and in determining prognosis

Imaging modalities should be focused on areas of clinical concern, based on the history and physical examination, and may include the following:

Chest radiography (to rule out pneumonia and diagnose other causes of pulmonary infiltrates)

Chest CT scanning (to further evaluate for pneumonia or other lung pathology)

Abdominal ultrasonography (for suspected biliary tract obstruction)

Abdominal CT scanning or MRI (for assessing a suspected non-biliary intra-abdominal source of infection or delineating intrarenal and extrarenal pathology)

Site-specific soft tissue imaging, including ultrasonography, CT scanning, or MRI (to assess for possible abscess, fluid collection, or necrotizing skin infection)

Contrast-enhanced CT scanning or MRI of the brain/neck (to assess for possible masses, abscess, fluid collection, or necrotizing infection)

The following cardiac studies may be useful if cardiac involvement or disease is suspected as a cause or complication of infection:

Electrocardiography (ECG) to evaluate for conduction abnormalities or delays or arrhythmias; pericarditis may be a cause of “pseudosepsis”

Cardiac enzyme levels

Echocardiography to evaluate for structural heart disease

Invasive diagnostic procedures that may be considered include the following:

Thoracentesis (in patients with pleural effusion)

Paracentesis (in patients with ascites)

Drainage of fluid collections/abscesses

Bronchoscopy with washing, lavage, or other invasive sampling (in patients with suspected pneumonia)

See Workup for more detail.

Management

Initial management may include the following:

Inpatient admission or ICU admission for monitoring and treatment

Initiation of empiric antibiotic therapy, to be followed by focused treatment based on culture, laboratory, and imaging data

Supportive therapy as necessary to maintain organ perfusion and respiration; timely intervention with infection source control, hemodynamic stabilization, and ventilatory support

Transfer if requisite facilities are not available at the admitting hospital

Appropriate empiric antimicrobial therapy depends on adequate coverage of the presumed pathogen(s) responsible for the septic process, potential antimicrobial resistance patterns, and patient-specific issues such as drug allergies or chronic medical conditions. Tying sites of infection to specific pathogens should occur, as follows:

Intravenous line infections: Consider broad-spectrum coverage for gram-positive organisms, especially methicillin-resistant
Staphylococcus aureus (MRSA) (linezolid, vancomycin, or daptomycin) and gram-negative nosocomial pathogens (especially
Pseudomonas species and other Enterobacteriaceae [piperacillin-tazobactam, carbapenems, or cefepime]), and line removal. Some of these may be
Candida infections.

Biliary tract infections: Typical bacterial agents include Enterobacteriaceae, gut-associated anaerobes, and
Enterococcus. Consider carbapenems, piperacillin-tazobactam, cephalosporins, or quinolones in combination with an anaerobic agent such as metronidazole.

Intra-abdominal and pelvic infections: Typically Enterobacteriaceae, gut-associated anaerobes, or
Enterococcus (carbapenems, piperacillin-tazobactam, or cephalosporins or quinolones in combination with an anaerobic agent such as metronidazole)

Urosepsis: Typically Enterobacteriaceae or
Enterococcus (carbapenems, piperacillin-tazobactam, cephalosporins, quinolones, or aminoglycosides)

Pneumococcal sepsis: Third-generation cephalosporins, respiratory quinolone (levofloxacin or moxifloxacin), carbapenem, or vancomycin if resistance is suspected

Sepsis of unknown origin: Meropenem, imipenem, piperacillin-tazobactam, or tigecycline; metronidazole plus levofloxacin, cefepime, or ceftriaxone may be alternatives

Early surgical evaluation for presumed intra-abdominal or pelvic sepsis is essential. Procedures that may be warranted depend on the source of the infection, the severity of sepsis, and the patient’s clinical status, among other factors.

Once an etiologic pathogen is identified, typically via culture, narrowed antibiotic therapy against the identified pathogen is appropriate (eg, penicillin for penicillin-susceptible Streptococcus pneumoniae).

See Treatment and Medication for more detail.

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