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Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996.

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Medical Microbiology. 4th edition.

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Chapter 94Microbiology of the Circulatory System

General Concepts



Gram-negative enteric bacilli, Staphylococcus aureus, and Streptococcus pneumoniae are the most common pathogens in the United States. Of these, the most likely agent of a given case of microbemia depends on host characteristics (age, granulocyte count, associated conditions, prior antimicrobial therapy) and epidemiologic setting (community vs. hospital-acquired, travel, animal exposure, etc.).


Microbes generally enter the circulatory system via the lymphatics from areas of localized infection or from diseased skin and mucous membranes colonized by members of the normal bacterial flora.

Clinical Manifestations

Microbemias may be asymptomatic, symptomatic, transient, continuous, or intermittent. Microbemias due to small numbers of relatively nonpathogenic microorganisms are usually asymptomatic. Larger inocula or more pathogenic organisms may produce systemic signs and symptoms: fever, chills, rigors, sweating, malaise, sleepiness, and fatigue.

Microbiologic Diagnosis

Techniques used in diagnosis include cultures of localized sites of infection, multiple blood cultures, and (rarely) blood serology.

Prevention and Treatment

Prevention in hospitals consists of hand-washing by personnel in contact with patients and avoidance of unnecessary urinary and intravenous catheterization. After samples are taken for culturing, treatment with intravenous broad-spectrum antimicrobial agents is usually begun, based on an estimate of the most likely organisms and their usual antimicrobial susceptibility patterns. This empirical therapy is modified if necessary when the pathogen and its susceptibility pattern are identified.

Septic Shock


Gram-negative enteric bacilli are the most common causes of septic shock, but the syndrome may be produced by a wide range of microorganisms.


Vascular injury from the microbes and release of inflammatory mediators cause local circulatory failure and multiorgan failure.

Clinical Manifestations

Manifestations of septic shock are widespread; they include hypotension, hypoxia, respiratory failure, lactic acidosis, renal failure, disseminated intravascular coagulation, and bleeding.

Microbiologic Diagnosis

Diagnosis is made by culturing local infections thought to be the source of microbemia and by culturing the blood.

Prevention and Treatment

Preventive measures are the same as for microbemia. Treatment consists of high-dose intravenous broad-spectrum antimicrobial agents, intravenous fluids, supplemental oxygen therapy, mechanical ventilation, hemodialysis, and transfusions of blood products and clotting factors, as needed.

Infective Endocarditis


Staphylococcus aureus, viridans streptococci, and enterococci are the most common causes of endocarditis.


Microbes that enter the blood lodge on heart valves. Previously damaged heart valves are more susceptible. Bacterial colonies become covered with fibrin and platelets, which protect the organisms from phagocytes and complement. Clots may dislodge as infected emboli.

Clinical Manifestations

Infective endocarditis may affect native or abnormal cardiac valves, prosthetic valves, and, secondarily, other intravascular sites. Manifestations include fever, malaise, fatigue, weight loss, skin petechiae, embolic infarction of vital organs, and valve dysfunction with congestive failure. Metastatic infection in acute endocarditis is caused by virulent organisms.

Microbiologic Diagnosis

Infective endocarditis is diagnosed through blood cultures.

Prevention and Treatment

Antimicrobial prophylaxis is administered to patients with defective heart valves who are undergoing dental and other procedures known to produce bacteremia. Therapy consists of prolonged intravenous treatment with bactericidal antibiotics to eradicate bacteria within the protective clot. Surgical replacement of infected valves may be required to cure prosthetic valve infections.


The circulatory system, consisting of the blood, blood vessels, and the heart, is normally free of microbial organisms. Isolation of bacteria or fungi from the blood of ill patients usually signifies serious and uncontrolled infection that may result in death. The presence of bacteria (bacteremia) and fungi (fungemia) in the blood occurs in more than 250,000 individuals per year in the United States and causes at least 50,000 deaths annually. Because rapid isolation, identification, and performance of antimicrobial susceptibility tests may lead to initiation of lifesaving measures, the culturing of blood to detect microbemia is one of the most important clinical microbiology laboratory procedures. Bacteremia may be prevented in some instances by the early recognition of localized infection and initiation of appropriate treatment with antimicrobial agents and surgical drainage of abscesses.

Clinical Syndromes


Asymptomatic Microbemia

Microbes enter the circulatory system via lymphatic drainage from localized sites of infection or mucosal surfaces that are subject to trauma and are colonized with members of the normal bacterial flora. Organisms may also be introduced directly into the bloodstream by infected intravenous needles or catheters or contaminated intravenous infusions. A number of disseminated viral infections are also spread through the body via the bloodstream. Viremias are discussed in Chapter 45. Small numbers of organisms or nonvirulent microbes are removed from the circulation by fixed macrophages in the liver, spleen, and lymph nodes. The phagocytes are assisted by circulating antibodies and complement factors present in serum. Under certain conditions, antibodies and complement factors may kill Gram-negative bacteria by lysis of the cell wall. Also, they may promote phagocytosis by coating bacteria (opsonization) with antibody and complement factors that have receptor sites for neutrophils and macrophages.

When defense mechanisms effectively remove small numbers of organisms, clinical signs or symptoms of microbemia may not occur (asymptomatic microbemia). Asymptomatic bacteremias caused by members of the endogenous bacterial flora have been observed in normal individuals after vigorous chewing, dental cleaning or tooth extraction, insertion of urinary bladder catheters, colon surgery, and other manipulative procedures. Asymptomatic bacteremias may occur if localized infections are subjected to trauma or surgery.

Most asymptomatic bacteremias are of no consequence; however, occasionally, virulent organisms that cause a localized infection (such as a Staphylococcus aureus skin boil) may produce infection at a distant site (e.g., bone infection) by means of asymptomatic bacteremia. Similarly, artificial or damaged heart valves may be colonized by viridans streptococci during asymptomatic bacteremia induced by dental manipulation. Infection of the heart valve (infective endocarditis) is fatal if not treated. Therefore, individuals with known valvular heart disease who undergo dental work or other procedures that produce asymptomatic bacteremias are given antibiotics to prevent colonization of the heart.

Symptomatic Microbemia

When a sufficient number of organisms are introduced into the bloodstream, an individual will develop fever, chills, shivering (rigors), and sweating (diaphoresis). Patients with symptomatic microbemias usually look and feel ill. As macrophages and polymorphonuclear leukocytes phagocytose microbes, they synthesize and release interleukin-1 into the circulation. This small protein acts on the temperature-regulatory center in the brain and sets the body thermostat at a higher level. The thermoregulatory center acts to decrease heat loss by reducing peripheral blood flow to the skin (pale appearance) and increases heat production by muscular activity (shivering), resulting in a rise in body temperature. When either a high body temperature level is attained or the microbemia terminates, the central nervous system thermostat becomes reset at a lower level and acts to reduce body temperature by increased peripheral blood flow to the skin (flushed appearance) and by sweating.

Symptomatic microbemias are most commonly caused by the organisms listed in Figure 94-1. In recent years, the incidence of Gram-positive coccal bacteremias resulting from intravascular access infections in debilitated patients with serious underlying conditions has increased steadily, but Gram-negative bacillary infection still predominates. Hospitalized patients frequently have had surgery, severe trauma, or neoplasms that predispose to complicated local infections; also, these individuals' host defenses have been compromised by malnutrition, age, or corticosteroid or cancer chemotherapy. Granulocytopenia due to leukemia, cancer, or cancer chemotherapy is a frequent predisposing cause of microbemia and a reason for poor response to antimicrobial therapy. Gram-negative bacteremia is frequently due to pulmonary infections in intubated patients receiving ventilator therapy or to urinary tract infections caused by indwelling urinary catheters. Table 94-1 lists a number of conditions predisposing to symptomatic microbemia and the organisms most commonly associated with those conditions. Organisms other than those listed in Table 94-1 may produce microbemia in severely compromised hosts. Skin contaminants, such as Staphylococcus epidermidis and diphtheroid species, may cause significant microbemias (indicated by isolation from multiple blood cultures). Bacteremias of this type are associated with intravenous catheters or prosthetic heart valves.

Figure 94-1. Common causes of symptomatic microbemia.

Figure 94-1

Common causes of symptomatic microbemia.

Table 94-1. Conditions Predisposing to Symptomatic Microbemia.

Table 94-1

Conditions Predisposing to Symptomatic Microbemia.

Transient microbemias are self:limited and often due to manipulation of infected tissues, such as incision and drainage of an abscess; early phases of localized infection, such as pneumococcal bacteremia in pneumococcal pneumonias; or bacteremias associated with trauma to mucosal surfaces colonized by the normal host flora. When multiple blood cultures are positive over a period of 12 hours or more, a continuous microbemia is present. The presence of continuous microbemia suggests a severe spreading infection that has overwhelmed host defenses. A continuous microbemia may originate from an intravascular site of infection in which organisms are shed directly into the bloodstream (e.g., infective endocarditis or an infected intravascular catheter), or from an early phase of a specific infection characterized by a continuous microbemia (e.g., typhoid fever).

Microbemias may persist despite treatment with antimicrobial agents to which the organisms are susceptible. Therefore, repeated blood cultures should be performed in patients who do not appear to respond to sustained antimicrobial treatment. During the first 3 days of treatment, positive blood cultures often are associated with inadequate antimicrobial dosage. Microbemias that persist longer than 3 days may be caused by organisms resistant to multiple antimicrobial agents, by undrained abscesses, or by intravascular foci of infection. When positive blood cultures with the same organism are separated by negative cultures, an intermittent microbemia is present.

Septic Shock

Septic shock occurs in approximately 40 percent of patients with Gram-negative bacillary bacteremia and 5 percent of patients with Gram-positive bacteremia. The septic shock syndrome consists of a fall in systemic arterial blood pressure with resultant decreased effective blood flow to vital organs. Septic shock patients frequently develop renal and pulmonary insufficiency and coma as part of a generalized metabolic failure caused by inadequate blood flow. Survival depends on rapid institution of broad-spectrum antimicrobial therapy, intravenous fluids, and other supportive measures. Elderly patients and those with severe underlying surgical or medical diseases are less likely to survive. Mortality from Gram-negative septic shock ranges from 40 to 70 percent. Septic shock may also occur with rickettsial, viral, and fungal infections .

Septic shock due to Gram-negative bacillary bacteremias constitutes the most common serious infectious disease problem in hospitalized patients. The high frequency of septic shock in Gram-negative bacillary infeHtion is attributed to the toxic effect on the circulatory system of lipopolysaccharides (endotoxin) found in the cell wall of Gram-negative organisms (Fig. 94-2). Endotoxin within the circulatory system has multiple and complex effects on neutrophils, platelets, complement, clotting factors, and inflammatory mediators in the blood. The symptoms of bacteremia and septic shock are reproduced when purified cell wall endotoxin is injected into the circulation.

Figure 94-2. Pathogenesis of septic shock.

Figure 94-2

Pathogenesis of septic shock.

Infective Endocarditis

Heart valve infections generally are classified as acute endocarditis, subacute endocarditis, and prosthetic valve endocarditis. If they are untreated, these infections are fatal. With treatment, mortality averages 30 percent; it is higher in acute and prosthetic valve infections.

Acute endocarditis usually occurs when heart valves are colonized by virulent bacteria in the course of microbemia (Fig. 94-3). The most common cause of acute endocarditis is Staphylococcus aureus; other less common causes are Streptococcus pneumoniae, Neisseria gonorrhoeae, Streptococcus pyogenes, and Enterococcus faecalis. Patients with acute endocarditis usually have fever, marked prostration, and signs of infection at other sites. Infected heart valves may be destroyed rapidly, leading to heart failure from valve leaflet perforation and acute valvular insufficiency. Infected pieces of fibrin and platelet vegetations on the valves may break loose into the circulation and lodge at distant sites, producing damage to target organs. Metastatic infection due to emboli may involve arterial walls (mycotic aneurysm) or produce abscesses.

Figure 94-3. Infective endocarditis: metastatic infections due to emboli.

Figure 94-3

Infective endocarditis: metastatic infections due to emboli.

Patients with subacute endocarditis usually have underlying valvular heart disease and are infected by less virulent organisms such as viridans streptococci, enterococci, nonenterococcal group D streptococci, microaerophilic streptococci, and Haemophilus species. Frequently, the source and onset of infection are not clear, and patients consult physicians with complaints of fever, weight loss, or symptoms related to embolic phenomenon and congestive heart failure.

Prosthetic valvular endocarditis may present either acute or subacute in onset, and the infecting organisms differ, depending on whether endocarditis develops within 2 months of surgery or later (Table 94-1). Whereas infections on nonprosthetic valves usually are eradicated by antimicrobial therapy alone, prosthetic valve infections frequently require surgical removal of the infected valve before the infection is eliminated. Antimicrobial therapy of endocarditis is prolonged and should be guided by susceptibility studies. Fungal endocarditis is rare, but Candida infections occur in those with prosthetic valves and in drug addicts. Aspergillus endocarditis may occur after cardiac valve surgery.

Blood Cultures

Because several commercial blood culture systems are used by clinical microbiology laboratories, blood culture specimens may be processed differently by different laboratories. Most clinical laboratories will give a preliminary report of a negative culture if no growth is detected after 4 days of incubation. A final negative report is made if there is no growth after 7 days of incubation.

Clinicians should know when it is necessary for the laboratory to use special or nonroutine blood culture techniques to detect microorganisms. Failure to tell the clinical laboratory about the need for special culture conditions may result in false-negative blood culture reports.

If the patient has received antimicrobial agents before the blood specimen was obtained, the clinical laboratory can add penicillinase to remove β-lactam antibiotics, use an antimicrobial removal device or special resin bottle to remove or inactivate the antimicrobial agent, or prolong blood incubation for 2 weeks to improve the chances of obtaining a positive culture. If infective endocarditis is suspected, the blood culture bottles should be incubated for 2 weeks to allow growth of slow-growing or fastidious microorganisms. When fungemia is suspected, special media and techniques are used to grow fungi. When Mycobacterium avium-intracellulare bacteremia is suspected in patients with human immunodeficiency virus (HIV) infection, the laboratory must be alerted to use special mycobacterium culture bottles and media. Special culture techniques or media are required for the isolation of brucellae, Listeria monocytogenes, leptospires, Francisella tularensis, and Mycoplasma hominis.

If a central venous catheter infection is suspected, blood should be drawn both from the line and from a peripheral vein, and the results of quantitative cultures compared. If the catheter blood culture has a 10-fold greater count than the peripheral blood culture or has more than 100 CFU/ml, the catheter is probably infected. Semi-quantitative culture of peripheral intravenous catheters may also help establish whether they are the portal of entry for bacteremia. When the results of blood cultures do not fit with the clinical condition of an infected patient, the clinician should review the situation with the clinical microbiology laboratory director or an infectious diseases specialist.


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Copyright © 1996, The University of Texas Medical Branch at Galveston.
Bookshelf ID: NBK8290PMID: 21413321


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