Bacterial Sepsis Differential Diagnoses

Updated: Feb 03, 2023
  • Author: Amber Mahmood Bokhari, MBBS; Chief Editor: Michael Stuart Bronze, MD  more...
  • Print
DDx

Diagnostic Considerations

Sepsis often is associated with or preceded by other conditions (see Table 2 below). [41, 42, 43] Noninfectious conditions that present in a manner similar to that of sepsis must also be considered, as should the host's immunocompetence. Early diagnosis with rapid initiation of appropriate therapy is the cornerstone of reducing mortality and morbidity associated with sepsis. Diagnostic studies should be sent within the first 3 hours of suspected sepsis, and antibiotics should be initiated within the first 45 minutes after appropriate cultures are collected. If the blood pressure remains less than 65 mm Hg despite initial fluid resuscitation of 30 mL/kg or if the initial lactate level is 4 mmol/L (36 mg/dl) or higher within 6 hours, further hemodynamic assessments should be performed to ensure adequate organ perfusion. It is essential to reach a preliminary diagnosis within the first 12 hours of presentation to decrease the likelihood of adverse clinical outcomes.

Table 2. Clinical Conditions Associated With Sepsis (Open Table in a new window)

System 

Associated With Sepsis

Not Typically Associated With Sepsis 

GI tract

Liver

Gallbladder

Colon

Abscess

Intestinal obstruction

Instrumentation

Esophagitis

Gastritis

Pancreatitis (may have multiorgan dysfunction but not infectious in origin)

Small bowel disorders

GI bleeding

GU tract 

Pyelonephritis

Intra- or perinephric abscess

Renal calculi

Urinary tract obstruction

Acute prostatitis/abscess

Renal insufficiency

Instrumentation in patients with bacteriuria

Urethritis

Cystitis

Cervicitis

Vaginitis

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

Pelvis

Peritonitis

Abscess

 

 

Upper respiratory tract

Deep neck space infection

Abscess

Pharyngitis

Sinusitis

Bronchitis

Otitis

Lower respiratory tract

Community-acquired pneumonia (with asplenia)

Empyema

Lung abscess

Community-acquired pneumonia (in otherwise healthy host)

 

 

 

Intravascular

IV line sepsis

Infected prosthetic device

Acute bacterial endocarditis

 

Cardiovascular

Acute bacterial endocarditis

Myocardial/perivalvular ring abscess

Subacute bacterial endocarditis

 

CNS

Bacterial meningitis

Aseptic meningitis

Skin/soft-tissue

 

Necrotizing fasciitis

 

Osteomyelitis

Uncomplicated wound infections

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. [41]

Pseudosepsis

A common medicolegal error is failure to consider pseudosepsis as a cause of the presenting syndrome. Most causes of pseudosepsis are readily treatable if recognized and managed early.

Thus, before embarking on a workup for sepsis or beginning empiric antibiotic therapy, it is vital 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 and differentiate between the distributive presentation versus septic shock (see Table 3 below). The causes of pseudosepsis must be identified because they require supportive, rather than antimicrobial, therapy.

Table 3. Noninfectious Conditions Mimicking Clinical and Hemodynamic Parameters of Sepsis (Open Table in a new window)

Clinical Presentations Mimicking Sepsis

Hemodynamic Parameters Mimicking Sepsis

Myocardial infarction

Spinal cord injury

Pancreatitis

Adrenal insufficiency

Diabetic ketoacidosis

Acute pancreatitis

Systemic lupus erythematosus flare with abdominal crisis

Hemorrhage

Ventricular pseudoaneurysm

Pulmonary embolism

Massive aspiration/atelectasis

Anaphylaxis

Systemic vasculitis

 

Hypovolemia (eg, due to diuretics, dehydration)

 

Pseudosepsis is a common cause of misdiagnosis in hospitalized patients, particularly in the emergency department (ED) and ICU. 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. Many causes of pseudosepsis produce pulmonary artery catheter readings that are compatible with sepsis (ie, increased cardiac output and decreased peripheral resistance), which could misdirect the unwary clinician (see Table 4 below).

Table 4. 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 several positive blood culture results with a pathogenic organism

Hemodynamic

⇓ PVR

⇑ CO

⇓ PVR

⇑ CO

Left ventricular dilatation

Laboratory

⇑ WBC count (with left shift)

Normal platelet count

⇑ FSP

⇑ Lactate

⇑ D-dimers

⇑ PT/PTT

⇓ Albumin

⇓ Fibrinogen

⇓ Globulins

⇑ WBC count (with left shift)

⇓ Platelets

⇑ FSP

⇑ Lactate

⇑ D-dimers

⇑ PT/PTT

⇓ Albumin

Clinical

≤102°F ±

Tachycardia ±

Respiratory alkalosis ±

Hypotension

≥102°F OR

Hypothermia ±

Mental status changes ±

Hypotension

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