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Description of Medical Condition

The systemic response to infection; it encompasses a broad array of clinical manifestations and overlaps with inflammatory reactions to other clinical insults (e.g., severe trauma or burn)

  • Bacteremia: Bacteria in the blood; may have no accompanying symptoms
  • Systemic inflammatory response syndrome (SIRS) inflammatory reaction to different clinical insults manifest by two of the following: (1) temperature >38°C or<36°C, (2) heart rate >90/min; (3) respiratory rate >20/min or PaC02 <32 mm Hg, and (4) WBC count >12,000/mm3, <4,000/mm3 or >10% immature forms (bands)
  • Sepsis: SIRS with documented infection (typically bacterial)
  • Septic shock: Sepsis induced hypotension (systolic BP <90 mmHg or >40 mmHg drop from baseline) despite adequate fluid resuscitation plus hypoperfusion abnormalities (oliguria, lactic acidosis, acute change in mental status)
  • Multiple organ dysfunction syndrome (MODS): altered organ function in an acutely ill patient — requires intervention to maintain homeostasis

System(s) affected: Cardiovascular, Endocrine/ Metabolic, Hemic/Lymphatic/lmmunologic, Renal/Urologic, Nervous, Pulmonary, Gastrointestinal Genetics: Single nucleotide polymorphisms i.e., cytokine and cytokine receptor genes influence risk for development of sepsis and risk of mortality from sepsis Incidence/Prevalence in USA: 300/100,000 persons/year Predominant age: All ages Predominant sex: Male> Female (1.28:1)

Medical Symptoms and Signs of Disease

  • Fever
  • Chills, rigors
  • Myalgias
  • Changes in mental status — restlessness, agitation, confusion, delirium, lethargy, stupor, coma
  • Tachycardia
  • Tachypnea
  • Hypotension
  • Skin lesions — erythema, petechiae, ecthyma gangrenosum, embolic lesions
  • Signs and symptoms related to site of primary infection
    • Respiratory tract — cough, sputum production, dyspnea, chest pain
    • Urinary tract — dysuria, flank pain, frequency, urgency
    • Intra-abdominal source — nausea, vomiting, diarrhea, constipation, abdominal pain
    • Central nervous system — stiff neck, headache. photophobia, focal neurologic signs
  • Signs and symptoms related to end organ failure
    • Pulmonary — cyanosis
    • Renal — oliguria, anuria
    • Hepatic — jaundice
    • Cardiac — congestive heart failure


What Causes Disease?

Specific etiologic agents include:

  • Gram positive organisms — most commonly Staphylococcus spp, Streptococcus spp. Enterococcus spp
  • Gram negative organisms — most commonly Escherichia coli, Klebsiella spp, Proteus spp.,Pseudomonas spp
  • Fungi — most commonly Candida spp
  • Other agents — anaerobes. Also, see Differential diagnosis.

Common sources of septicemia include

  • Lungs
  • Urinary tract
  • Intra-abdominal focus — biliary tree, abscess, peritonitis
  • Intravascular catheters
  • Skin — cellulitis, decubitus ulcer, gangrene
  • Heart valves

Risk Factors

  • Age extremes (very old and very young)
  • Impaired host (see associated conditions)
  • Indwelling catheters- intravascular, urinary, biliary, etc.
  • Complicated labor and delivery — premature and/or prolonged rupture of membranes, etc.
  • Certain surgical procedures

Diagnosis of Disease

Differential Diagnosis

  • Viral diseases (influenza, dengue and other hemorrhagic viruses, Coxsackie B virus)
  • Rickettsial diseases (Rocky Mountain spotted fever, endemic typhus)
  • Spirochetal diseases (leptospirosis, relapsing fever [Borrelia sp], Jarisch-Herxheimer reaction in syphilis)
  • Protozoal diseases (Toxoplasma gondii, Trypanosoma cruzi, Pneumocystis carinii, Plasmodium falciparum)
  • Collagen vascular diseases, vasculitides, myocardial infarction, pulmonary embolus, thromboticthrombocyto-penic purpura/hemolytic-uremic syndrome, thyrotoxico-sis, adrenal insufficiency (Addison disease), dissecting aortic aneurysm, multiple trauma, third-degree burn


  • Positive blood cultures
  • Positive cultures from other sites (sputum, urine, cerebrospinal fluid [CSF], etc.)
  • Gram stain of clinical specimens (sputum, urine, CSF. etc.)
  • Common:
    • Leukocytosis
    • Proteinuria
    • Hypoxemia
    • Eosinopenia
    • Hypoferremia
    • Hyperglycemia
    • Hypocalcemia
    • Mild hyperbilirubinemia
  • Less common:
    • Lactic acidosis
    • Leukopenia
    • Azotemia
    • Thrombocytopenia
    • Prolonged prothrombin time
    • Anemia
    • Hypoglycemia

Drugs that may alter lab results: Prior antibiotic use Disorders that may alter lab results: N/A

Pathological Findings

  • Inflammation at primary site of infection
  • Disseminated intravascular coagulation
  • Non-cardiogenic pulmonary edema

Special Tests

  • Antigen detection systems — counterimmunoelectrophoresis (CIE) and latex agglutination tests (pneumococcus, H. influenzae type B, group B streptococcus, meningococcus)
  • Gram stain of buffy coat smears occasionally useful


  • X-rays (e.g., chest)
  • Ultrasound, CT scan, or MRI may be useful in delineating sites of infection

Diagnostic Procedures

  • Aspiration of potentially infected body fluids (pleural. peritoneal, CSF) when appropriate
  • Biopsy, drainage of potentially infected tissues (abscess, biliary tree, etc.) when appropriate

Treatment (Medical Therapy)


Appropriate Health Care

  • Hospitalization
  • Intensive care treatment of patients with shock, respiratory failure

General Measures

  • Removal or drainage of septic foci
  • Correction of metabolic abnormalities (hypoxemia, hyperglycemia, hypoglycemia, severe acidemia [pH < 7.10])
  • Mechanical ventilation for respiratory failure
  • Transfusion of RBC, platelets, and/or fresh frozen plasma for bleeding
  • Volume replacement followed by pressors for hypotension
  • Stress ulcer and deep venous thrombosis prophylactic measures
  • Insulin therapy to keep serum glucose < 150 mg/dl

Surgical Measures

Drainage of infected sites, debridement of necrotic tissues




NPO initially; intravenous hyperalimentation appropriate in some severely malnourished patients and in patients who will be unable to receive enteral alimentation within the week

Patient Education


Medications (Drugs, Medicines)

Drug(s) of Choice

  • Antibiotic coverage should be broad initially and directed against organisms associated with identified septic foci. After culture results are available, treatment should be more organism-specific. Knowledge of the antibiotic susceptibility patterns of local pathogens extremely important.
  • Neonatal (< 7 days old) sepsis — ampicillin 300 mg/kg/d in 3 divided doses and gentamicin (Garamycin) 5 mg/kg/d in 2 divided doses
  • Non-immunocompromised child — cefotaxime (Claforan) 200 mg/kg/d in 4 divided doses
  • Non-immunocompromised adult — cefotaxime (Claforan) 1-2 gm q8-12 orticarcillin-clavulanate (Timentin) 3.1 g q6h plus gentamicin 5 mg/kg/day in 1 -3 divided doses
  • Neutropenic host — cefepime (Maxipime) 1 -2 gm q12h, and gentamicin (Garamycin) ortobramycin 3-5 mg/kg/d in 2-3 divided doses; vancomycin (Vancocin) is added when there is an obvious catheter-related infection or a known gram positive bacteremia or if there is an increased likelihood of infection with resistant gram positive organisms.

Contraindications: History of anaphylaxis or other allergic reaction to the antibiotic Precautions: Dose adjustments required in renal failure Significant possible interactions:

  • Aminoglycosides — increased nephrotoxicitywith enflurane, cisplatin and possibly vancomycin; increased ototoxidty with loop diuretics; increased paralysis with neuromuscular blocking agents
  • Ampicillin — increased frequency of rash with allopurinol

Alternative Drugs

  • Intravenous hydrocortisone, 200-300 mg/day in 3-4 divided doses may benefit patients who require vasopressor therapy to maintain an adequate blood pressure. Higher doses of corticosteroids should not be used.
  • Many other drug combinations are possible to get adequate coverage
  • Antifungals
  • Antimicrobials for anaerobic infections
  • Antipseudomonals
  • Drotrecogin alfa (Xigris) — 24 mcg/kg/hr for 96 hrs in patients with severe sepsis (APACHE score >24). Do not use in patients with increased risk of bleeding, thrombocytopenia with platelets < 30,000, sepsis-induced organ dysfunction for >24 hours, hypercoagu-lable states, chronic renal or hepatic failure, children or pregnancy. Very expensive.

Patient Monitoring

  • Depends upon source of infection, underlying disease(s)
  • Peak and trough drug levels for aminoglycosides
  • BUN, creatinine, electrolytes and complete blood counts at least twice weekly; more frequently if unstable

Prevention / Avoidance

  • Vaccination — pneumococcal (geriatric patients, patients with certain chronic diseases), Haemophilus influ-enzae type B (infants, young children)
  • Gamma globulin (for hypo- or agammaglobulinemic patients)
  • Hand washing by hospital personnel, appropriate catheter care, etc., for hospitalized patients

Possible Complications

  • Death
  • Adult respiratory distress syndrome (ARDS)
  • Multi-organ failure (cardiac, pulmonary, renal, hepatic)
  • Disseminated intravascular coagulation (DIC)
  • Gastrointestinal hemorrhage

Expected Course / Prognosis

Even with optimal care, mortality will be 10-50% overall; this is increased in patients with neutropenia, diabetes, alcoholism, renal failure, respiratory failure, hypogammaglobulinemia, certain etiologic agents (e.g., Pseudomonas aeruginosa), a delay in appropriate antimicrobial therapy, and those patients at the age extremes


Associated Conditions

  • Neutropenia
  • Diabetes mellitus
  • Alcoholism
  • Leukemia, lymphoma, and solid tumors
  • Cirrhosis
  • Burns
  • Multiple trauma
  • Intravenous drug abuse
  • Malnutrition
  • Complement deficiencies
  • Hypo-oragammaglobulinemia
  • Spienectomy
  • HIV infection

Age-Related Factors

Pediatric: Screen newborns for infection due to prolonged rupture of membranes (> 24 h), maternal fever, prematurity Geriatric:

  • Often more difficult to diagnose clinically in the elderly
  • Change in mental status/behavior may be only early manifestation


Beta lactam antibiotics, aminoglycosides, erythromycin are considered safe


  • Septicemia
  • Sepsis neonatorum

International Classification of Diseases

038.9 Unspecified septicemia

See Also

  • Pneumonia, bacterial
  • Pyelonephritis
  • Meningitis, bacterial
  • Endocarditis, infective
  • Toxic shock syndrome
  • Rocky Mountain spotted fever
  • Candidiasis
  • Listeriosis
  • Tularemia

Other Notes

High dose steroids of no benefit

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