- Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD more...
Bacterial sepsis refers to symptomatic bacteremia, with or without organ dysfunction. Sepsis is commonly defined as the presence of infection in conjunction with the systemic inflammatory response syndrome (SIRS); severe sepsis, as sepsis complicated by organ dysfunction; and septic shock, as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone (identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean blood pressure of 65 mm Hg or greater and having a serum lactate level >2 mmol/L after adequate fluid resuscitation ).
Sepsis is not a random occurrence and is usually associated with other conditions, such as perforation, compromise, or rupture of an intra-abdominal or pelvic structure. Intrarenal infection (pyelonephritis), renal abscess (intrarenal or extrarenal), acute prostatitis, or prostatic abscess may cause urosepsis in immunocompetent hosts. Urosepsis has also been reported after prostatic biopsy. An abdominal wall abscess is present on the CT scan shown below.
Signs and symptoms
The history and physical examination may suggest the likely source of the septic process and thereby help determine the appropriate antimicrobial therapy. General signs and symptoms may include the following:
Fever, with or without shaking chills
Impaired mental status (in the setting of fever or hypoperfusion)
Increased breathing rate resulting in respiratory alkalosis
Warm or cold skin, depending on the adequacy of organ perfusion and dilatation of the superficial vessels of the skin
The following factors suggest an IV line infection:
An infected central line site; peripheral venous lines are almost never involved, and arterial lines are rarely associated with bacteremia
Elimination of other potential sources, in conjunction with long-term IV line placement
The following factors suggest a gastrointestinal (GI) or genitourinary (GU) infection:
History of antecedent conditions predisposing to perforation or abscess
Abdominal pain – Diffuse pain (suggesting pancreatitis or generalized peritonitis), right upper quadrant (RUQ) tenderness (gallbladder etiology), right lower quadrant (RLQ) tenderness (appendicitis or Crohn disease), or discrete left lower quadrant (LLQ) tenderness (diverticulitis)
Abnormalities on rectal examination – Exquisite tenderness (suggesting a prostatic abscess) or an enlarged noninflamed prostate (benign prostatic hyperplasia)
Pertinent GU findings – Antecedent history of pyelonephritis, stone disease, congenital abnormal collecting system, prostate enlargement, or prostatic or renal operations or procedures; costovertebral angle tenderness (suggesting pyelonephritis)
Special considerations include the following:
Elderly patients may present with peritonitis and may not experience rebound tenderness of the abdomen
An acute surgical abdomen in a pregnant patient may be difficult to diagnose; the most common cause of sepsis in pregnancy is urosepsis due to an obstructed urinary tract
Sepsis is usually associated with other conditions, such as the following:
GI tract – Liver disease, gallbladder disease, colon disease, abscess, intestinal obstruction, and GI instrumentation
GU tract – Pyelonephritis, intra- or perinephric abscess, renal calculi, urinary tract obstruction, acute prostatitis or abscess, renal insufficiency, and GU instrumentation
Pelvis – Peritonitis and pelvic abscess
Lower respiratory tract – Community-acquired pneumonia (with asplenia), empyema, and lung abscess
Vascular system – Infected IV line or prosthetic device
Heart and cardiac vasculature – Acute bacterial endocarditis and myocardial or perivalvular ring abscess
See Clinical Presentation for more detail.
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
Bacterial cultures – Blood cultures at admission; culture of the catheter tip (for suspected central IV line sepsis); urine culture if urinary tract source is suspected
Stained buffy coat smears or Gram staining of peripheral blood (may be helpful in certain infections)
Urine studies (Gram stain, urinalysis, and urine culture)
Certain biomarkers, such as procalcitonin and presepsin, may be useful in diagnosis of early sepsis and determining prognosis
Imaging modalities that may be helpful include the following:
Chest radiography (to rule out pneumonia and diagnose other causes of pulmonary infiltrates)
Abdominal ultrasonography (for suspected biliary tract obstruction)
Abdominal CT or MRI (for assessing a suspected nonbiliary intra-abdominal source of infection or delineating intrarenal and extrarenal pathology)
The following cardiac studies may be useful if acute myocardial infarction (MI) is likely:
Cardiac enzyme levels
Invasive diagnostic procedures that may be considered include the following:
Thoracentesis (in patients with substantial pleural effusion)
Paracentesis (in patients with gross ascites)
Swan-Ganz catheterization (for helping manage fluid status and assessing left ventricular dysfunction in MI; not for diagnosis of sepsis per se)
See Workup for more detail.
Initial management may include the following:
Bed rest or admission to the ICU for monitoring and treatment
Transfer if requisite facilities are not available at the admitting hospital
Initiation of empiric antibiotic therapy, to be followed by focused treatment
Supportive therapy as necessary to maintain organ perfusion and respiration
Appropriate antimicrobial therapy depends on adequate coverage of the resident flora of the organ system presumed to be the source of the septic process and potential antimicrobial resistance patterns as follows:
IV line infections – Meropenem or cefepime plus additional coverage for staphylococci; if MRSA is prevalent, addition of linezolid, vancomycin, or daptomycin; if methicillin-sensitive staphylococci are recovered, avoidance of vancomycin if possible; line removal
Biliary tract infections – Imipenem, meropenem, piperacillin-tazobactam, or ampicillin-sulbactam
Intra-abdominal and pelvic infections – Imipenem, meropenem, piperacillin-tazobactam, ampicillin-sulbactam, or tigecycline; clindamycin or metronidazole plus aztreonam, levofloxacin, or an aminoglycoside
Urosepsis – Aztreonam, levofloxacin, a third- or fourth-generation cephalosporin, or an aminoglycoside; for enterococci, ampicillin or vancomycin; for vancomycin-resistant enterococcal urosepsis, linezolid or daptomycin; for community-acquired urosepsis, levofloxacin, aztreonam, or an aminoglycoside plus ampicillin; for nosocomial urosepsis, piperacillin, imipenem, or meropenem
Pneumococcal sepsis – Certain third-generation cephalosporins, carbapenem, or vancomycin if resistance is suspected
Sepsis of unknown origin – Meropenem, imipenem, piperacillin-tazobactam, or tigecycline; metronidazole plus either levofloxacin, aztreonam, cefepime, or ceftriaxone
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.
Bacterial sepsis is a clinical term used to describe symptomatic bacteremia, with or without organ dysfunction. Currently, sepsis is commonly defined as the presence of infection in conjunction with the systemic inflammatory response syndrome (SIRS), with severe sepsis understood as sepsis complicated by organ dysfunction and septic shock understood as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone (identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean blood pressure of 65 mm Hg or greater and having a serum lactate level >2 mmol/L after adequate fluid resuscitation).[2, 3]
The term sepsis is often misused and misapplied to patients with fever, leukocytosis, and hypotension due to other causes (pseudosepsis). True sepsis is a common cause of hospitalization in the United States, including in elderly men who are more likely to develop urosepsis as a result of benign urinary tract obstruction caused by prostatic hypertrophy. Patients who have diabetes, systemic lupus erythematosus (SLE), or alcoholism or who are taking steroids are also at increased risk for bacteremia.
Sustained bacteremia, in contrast to transient bacteremia, may result in a sustained febrile response that may be associated with organ dysfunction. The term septicemia refers to the active multiplication of bacteria in the bloodstream that results in an overwhelming infection; the term bloodstream infection (BSI) is also commonly used.
The most important medicolegal concerns regarding sepsis treatment include the following:
Ensuring that the patient indeed does have sepsis
Rapidly identifying its source
Implementing effective treatments
Etiology and Pathophysiology
Sepsis is not a random occurrence and is usually associated with other conditions, such as perforation, compromise, or rupture of an intra-abdominal or pelvic structure. Intrarenal infection (pyelonephritis), renal abscess (intrarenal or extrarenal), acute prostatitis, or prostatic abscess may cause urosepsis in immunocompetent hosts. Urosepsis has also been reported after prostatic biopsy. An abdominal wall abscess is depicted on the CT scan depicted below.
Sepsis or septic shock may be associated with the direct introduction of microbes into the bloodstream via intravenous (IV) infusion (eg, IV line infections and other device-associated infections). Meningococcemia from a respiratory source may also result in sepsis, with or without associated meningitis.
Bacteremia due to bacteriuria (urosepsis) may complicate cystitis in compromised hosts, and sepsis may be caused by overwhelming pneumococcal infection in patients with impaired or absent splenic function.
The pathophysiology of sepsis is complex and results from the effects of circulating bacterial products, mediated by cytokine release, caused by sustained bacteremia. Cytokines are responsible for the clinically observable effects of the bacteremia in the host.[5, 6, 7, 8] Impaired pulmonary, hepatic, or renal function may result from excessive cytokine release during the septic process.
Sepsis is a common cause of mortality and morbidity worldwide. The prognosis depends on underlying health status and host defenses, prompt and adequate surgical drainage of abscesses, relief of any obstruction of the intestinal or urinary tract, and appropriate and early empiric antimicrobial therapy with the drug spectrum appropriate to the presumed septic source. Thus, early and appropriate empiric antimicrobial therapy and surgical intervention are critical in decreasing mortality and morbidity.
The prognosis in most patients is good, except in those with intra-abdominal or pelvic abscesses due to organ perforation. The underlying physiologic condition of the host is the primary determinant of outcome.
A systematic review by Winters et al suggested that beyond the standard 28-day in-hospital mortality endpoint, ongoing mortality in patients with sepsis remains elevated up to 2 years and beyond. In addition, survivors consistently demonstrate impaired quality of life.
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|Associated With Sepsis (Fever ≥102°F)||Not Associated With Sepsis (Fever ≤102°F)|
|GI tract source
|GI tract source
Small bowel disorders
|GU tract source
Intra- or perinephric abscess
Urinary tract obstruction
Instrumentation in patients with bacteriuria
|GU tract source
Catheter-associated bacteriuria (in otherwise healthy hosts without genitourinary tract disease)
|Upper respiratory tract source
|Lower respiratory tract source
Community-acquired pneumonia (with asplenia)
|Lower respiratory tract source
Community-acquired pneumonia (in otherwise healthy host)
IV line sepsis
Infected prosthetic device
Acute bacterial endocarditis
Uncomplicated wound infections
Acute bacterial endocarditis
Myocardial/perivalvular ring abscess
Subacute bacterial endocarditis
|CNS = central nervous system; GI = gastrointestinal; GU = genitourinary; IV = intravenous.|
|Adapted from: Cunha BA, Shea KW. Fever in the intensive care unit. Infect Dis Clin North Am. Mar 1996;10(1):185-209.|
|Clinical Presentations Mimicking Sepsis||Hemodynamic Parameters Mimicking Sepsis|
|Myocardial infarction||Spinal cord injury|
|Diabetic (abdominal crisis) ketoacidosis|
|Systemic lupus erythematosus flare with abdominal crisis|
|Microbiologic||No definite source PLUS ≥1 abnormalities
Negative blood cultures excluding contaminants
|Proper identification/process/source PLUS ≥1 microbiologic abnormalities
Positive buffy coat smear result OR 2/3 or 3/3 positive blood cultures
Left ventricular dilatation
|Laboratory||⇑ WBC count (with left shift)
Normal platelet count
|⇑ WBC count (with left shift)
Respiratory alkalosis ±
Mental status changes ±
|CO = cardiac output; FSP = fibrin split products; GI = gastrointestinal; GU = genitourinary; PT/PTT = prothrombin time/partial thromboplastin time; PVR = peripheral vascular resistance; WBC = white blood cell.|