33-16: Gram-Negative Bacteremia & Sepsis

Gram-negative bacteremia can originate in a number of sites, the most common being the genitourinary system, hepatobiliary tract, gastrointestinal tract, and lungs. Less common sources include intravenous lines, infusion fluids, surgical wounds, drains, and pressure injuries.

Patients with potentially fatal underlying conditions in the short term such as neutropenia or immunoparesis have a mortality rate of 40–60%; those with serious underlying diseases likely to be fatal in 5 years, such as solid tumors, cirrhosis, and aplastic anemia, die in 15–20% of cases; and individuals with no underlying diseases have a mortality rate of 5% or less.

A. Symptoms and Signs

Most patients have fevers and chills, often with abrupt onset. However, 15% of patients are hypothermic (temperature 36.4°C or less) at presentation, and 5% never develop a temperature above 37.5°C. Hyperventilation with respiratory alkalosis and changes in mental status are important early manifestations. Hypotension and shock, which occur in 20–50% of patients, are unfavorable prognostic signs.

B. Laboratory Findings

Neutropenia or neutrophilia, often with increased numbers of immature forms of polymorphonuclear leukocytes, is the most common laboratory abnormality in septic patients. Thrombocytopenia occurs in 50% of patients, laboratory evidence of coagulation abnormalities in 10%, and overt disseminated intravascular coagulation in 2–3%. Both clinical manifestations and the laboratory abnormalities are nonspecific and insensitive, which accounts for the relatively low rate of blood culture positivity (approximately 20–40%). If possible, three blood cultures from separate sites should be obtained in rapid succession before starting antimicrobial therapy. The chance of recovering the organism in at least one of the three blood cultures is greater than 95%. The false-negative rate for a single culture of 5–10 mL of blood is 30%. This may be reduced to 5–10% (albeit with a slight false-positive rate due to isolation of contaminants) if a single volume of 30 mL is inoculated into several blood culture bottles. Blood cultures may be falsely negative; when a patient with presumed septic shock, negative blood cultures, and inadequate explanation for the clinical course responds to antimicrobial agents, therapy should be continued for 10–14 days.

Several factors are important in the management of patients with sepsis.

A. Removal of Predisposing Factors

This usually means decreasing or stopping immunosuppressive medications and, in certain circumstances, giving granulocyte colony-stimulating factor (filgrastim; G-CSF) to the neutropenic patient.

B. Identifying the Source of Bacteremia

By simply finding the source of bacteremia and removing it (central venous catheter) or draining it (abscess), a fatal disease becomes easily treatable.

C. Supportive Measures

The use of fluids and vasopressors in septic shock is discussed in Chapter 14; corticosteroids have not been shown to be helpful in this setting. Management of disseminated intravascular coagulation is discussed in Chapter 13.

D. Antibiotics

Antibiotics should be given as soon as the diagnosis is suspected, since delays in therapy have been associated with increased mortality rates, particularly once hypotension develops. In general, bactericidal antibiotics should be used and given intravenously to ensure therapeutic serum levels. Penetration of antibiotics into the site of primary infection is critical for successful therapy—ie, if the infection originates in the CNS, antibiotics that penetrate the blood-brain barrier should be used—eg, third- or fourth-generation cephalosporin—but not first-generation cephalosporins or aminoglycosides, which penetrate poorly. Sepsis caused by gram-positive organisms cannot be differentiated on clinical grounds from that due to gram-negative bacteria. Therefore, initial therapy should include antibiotics active against both types of organisms.

The number of antibiotics necessary remains controversial and depends on the cause. Table 30–4 provides a guide for empiric therapy. Although a combination of antibiotics is often recommended for “synergism,” combination therapy has not been shown to be superior to a single-drug regimen with any of several broad-spectrum antibiotics (eg, a third-generation cephalosporin, piperacillin-tazobactam, carbapenem). If multiple drugs are used initially, the regimen should be modified and coverage narrowed based on the results of culture and sensitivity testing.

Directed therapy for gram-negative bacteremia may be treated with as few as 7 days of antibiotic therapy.