Bacterial Sepsis Differential Diagnoses

Updated: May 22, 2017
  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Diagnostic Considerations

Sepsis is not a random occurrence and is usually associated with other conditions (see Table 1 below). [18, 19, 20] Noninfectious conditions that present similarly to sepsis must also be considered, as should the host's immunocompetence.

Table 1. Clinical Conditions Associated With Sepsis (Open Table in a new window)

Associated With Sepsis (Fever ≥102°F) Not Associated With Sepsis (Fever ≤102°F)
GI tract source





Intestinal obstruction


GI tract source




Small bowel disorders

GI bleeding

GU tract source


Intra- or perinephric abscess

Renal calculi

Urinary tract obstruction

Acute prostatitis/abscess

Renal insufficiency

Instrumentation in patients with bacteriuria

GU tract source





Catheter-associated bacteriuria (in otherwise healthy hosts without genitourinary tract disease)

Pelvic source



Upper respiratory tract source





Lower respiratory tract source

Community-acquired pneumonia (with asplenia)


Lung abscess

Lower respiratory tract source

Community-acquired pneumonia (in otherwise healthy host)

Intravascular source

IV line sepsis

Infected prosthetic device

Acute bacterial endocarditis

Skin/soft-tissue source


Uncomplicated wound infections

Cardiovascular source

Acute bacterial endocarditis

Myocardial/perivalvular ring abscess

Cardiovascular source

Subacute bacterial endocarditis

  CNS source

Bacterial meningitis

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. [18]


The most common medicolegal error is failure to consider pseudosepsis as a cause of the presenting syndrome complex. Most causes of pseudosepsis are readily treatable and reversible if recognized and treated early.

Thus, before embarking on a workup for sepsis or beginning empiric antibiotic therapy, it is vital first to rule out the treatable causes of pseudosepsis early in the disease process. Consider other causes or conditions that mimic the clinical and hemodynamic parameters of sepsis (see Table 2 below). The causes of pseudosepsis must be identified because they require supportive, rather than antimicrobial, therapy.

Table 2. Noninfectious Conditions Mimicking Clinical and Hemodynamic Parameters of Sepsis (Open Table in a new window)

Clinical Presentations Mimicking Sepsis Hemodynamic Parameters Mimicking Sepsis
Hemorrhage Acute pancreatitis
Pulmonary embolism Anaphylaxis
Myocardial infarction Spinal cord injury
Pancreatitis Adrenal insufficiency
Diabetic (abdominal crisis) ketoacidosis  
Systemic lupus erythematosus flare with abdominal crisis  
Ventricular pseudoaneurysm  
Massive aspiration/atelectasis  
Systemic vasculitis  
Diuretic-induced hypovolemia  

Pseudosepsis is a common cause of misdiagnosis in hospitalized patients, particularly in the emergency department (ED) and in medical and surgical intensive care units (ICUs). The most common causes of pseudosepsis include gastrointestinal (GI) hemorrhage, pulmonary embolism, acute myocardial infarction (MI), acute pancreatitis (edematous or hemorrhagic), diuretic-induced hypovolemia, and relative adrenal insufficiency.

Patients with pseudosepsis may have fever, chills, leukocytosis, and a left shift, with or without hypotension. All causes of pseudosepsis produce Swan-Ganz catheter readings that are compatible with sepsis (eg, increased cardiac output and decreased peripheral resistance), which could misdirect the unwary clinician (see Table 3 below).

Table 3. Characteristics of Pseudosepsis and Sepsis (Open Table in a new window)

Parameters Pseudosepsis Sepsis
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

Hemodynamic ⇓ PVR

⇑ CO


⇑ CO

Left ventricular dilatation

Laboratory ⇑ WBC count (with left shift)

Normal platelet count


⇑ Lactate

⇑ D-dimers


⇓ Albumin

⇓ Fibrinogen

⇓ Globulins

⇑ WBC count (with left shift)

⇓ Platelets


⇑ Lactate

⇑ D-dimers


⇓ Albumin

Clinical ≤102°F ±

Tachycardia ±

Respiratory alkalosis ±


≥102°F OR

Hypothermia ±

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.

Host immunocompetence

Otherwise healthy hosts with community-acquired pneumonia virtually never present with hypotension or sepsis; however, patients with decreased or absent splenic function may present with overwhelming pneumococcal sepsis. If an otherwise healthy patient with community-acquired pneumonia presents with shock and all of the other causes of pseudosepsis are ruled out, then it must be assumed that the patient is a compromised host with impaired or absent splenic function.

Differential Diagnoses