• Contents

Etiology

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

Pathogenesis

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

Clinical Manifestations

Microbemias may be asymptomatic, symptomatic, transient, continuous, orintermittent. Microbemias due to small numbers of relatively nonpathogenicmicroorganisms are usually asymptomatic. Larger inocula or more pathogenicorganisms 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 withpatients and avoidance of unnecessary urinary and intravenous catheterization.After samples are taken for culturing, treatment with intravenous broad-spectrumantimicrobial agents is usually begun, based on an estimate of the most likelyorganisms and their usual antimicrobial susceptibility patterns. This empiricaltherapy is modified if necessary when the pathogen and its susceptibilitypattern are identified.

Etiology

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

Pathogenesis

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

Clinical Manifestations

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

Microbiologic Diagnosis

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

Prevention and Treatment

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

Etiology

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

Pathogenesis

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

Clinical Manifestations

Infective endocarditis may affect native or abnormal cardiac valves, prostheticvalves, and, secondarily, other intravascular sites. Manifestations includefever, malaise, fatigue, weight loss, skin petechiae, embolic infarction ofvital organs, and valve dysfunction with congestive failure. Metastaticinfection 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 valveswho are undergoing dental and other procedures known to produce bacteremia.Therapy consists of prolonged intravenous treatment with bactericidalantibiotics to eradicate bacteria within the protective clot. Surgicalreplacement of infected valves may be required to cure prosthetic valveinfections.

Asymptomatic Microbemia

Microbes enter the circulatory system via lymphatic drainage from localizedsites of infection or mucosal surfaces that are subject to trauma and arecolonized with members of the normal bacterial flora. Organisms may also beintroduced directly into the bloodstream by infected intravenous needles orcatheters or contaminated intravenous infusions. A number of disseminatedviral infections are also spread through the body via the bloodstream.Viremias are discussed inChapter45. Small numbers of organisms or nonvirulent microbes areremoved from the circulation by fixed macrophages in the liver, spleen, andlymph nodes. The phagocytes are assisted by circulating antibodies andcomplement factors present in serum. Under certain conditions, antibodiesand complement factors may kill Gram-negative bacteria by lysis of the cellwall. Also, they may promote phagocytosis by coating bacteria (opsonization)with antibody and complement factors that have receptor sites forneutrophils and macrophages.

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

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

Symptomatic Microbemia

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

Symptomatic microbemias are most commonly caused by the organisms listed inFigure 94-1. In recent years,the incidence of Gram-positive coccal bacteremias resulting fromintravascular access infections in debilitated patients with seriousunderlying conditions has increased steadily, but Gram-negative bacillaryinfection still predominates. Hospitalized patients frequently have hadsurgery, severe trauma, or neoplasms that predispose to complicated localinfections; also, these individuals' host defenses have been compromised bymalnutrition, age, or corticosteroid or cancer chemotherapy.Granulocytopenia due to leukemia, cancer, or cancer chemotherapy is afrequent predisposing cause of microbemia and a reason for poor response toantimicrobial therapy. Gram-negative bacteremia is frequently due topulmonary infections in intubated patients receiving ventilator therapy orto urinary tract infections caused by indwelling urinary catheters.Table 94-1 lists a number ofconditions predisposing to symptomatic microbemia and the organisms mostcommonly associated with those conditions. Organisms other than those listedinTable 94-1 may producemicrobemia in severely compromised hosts. Skin contaminants, such asStaphylococcus epidermidis and diphtheroid species, maycause significant microbemias (indicated by isolation from multiple bloodcultures). Bacteremias of this type are associated with intravenouscatheters or prosthetic heart valves.

Figure 94-1

Common causes of symptomatic microbemia.

Table 94-1

Conditions Predisposing to Symptomatic Microbemia.

Transient microbemias are self:limited and often due to manipulation ofinfected tissues, such as incision and drainage of an abscess; early phasesof localized infection, such as pneumococcal bacteremia in pneumococcalpneumonias; or bacteremias associated with trauma to mucosal surfacescolonized by the normal host flora. When multiple blood cultures arepositive over a period of 12 hours or more, a continuous microbemia ispresent. The presence of continuous microbemia suggests a severe spreadinginfection that has overwhelmed host defenses. A continuous microbemia mayoriginate from an intravascular site of infection in which organisms areshed directly into the bloodstream (e.g., infective endocarditis or aninfected intravascular catheter), or from an early phase of a specificinfection characterized by a continuous microbemia (e.g., typhoidfever).

Microbemias may persist despite treatment with antimicrobial agents to whichthe organisms are susceptible. Therefore, repeated blood cultures should beperformed in patients who do not appear to respond to sustainedantimicrobial treatment. During the first 3 days of treatment, positiveblood cultures often are associated with inadequate antimicrobial dosage.Microbemias that persist longer than 3 days may be caused by organismsresistant to multiple antimicrobial agents, by undrained abscesses, or byintravascular foci of infection. When positive blood cultures with the sameorganism are separated by negative cultures, an intermittent microbemia ispresent.

Septic Shock

Septic shock occurs in approximately 40 percent of patients withGram-negative bacillary bacteremia and 5 percent of patients withGram-positive bacteremia. The septic shock syndrome consists of a fall insystemic arterial blood pressure with resultant decreased effective bloodflow to vital organs. Septic shock patients frequently develop renal andpulmonary insufficiency and coma as part of a generalized metabolic failurecaused by inadequate blood flow. Survival depends on rapid institution ofbroad-spectrum antimicrobial therapy, intravenous fluids, and othersupportive measures. Elderly patients and those with severe underlyingsurgical or medical diseases are less likely to survive. Mortality fromGram-negative septic shock ranges from 40 to 70 percent. Septic shock mayalso occur with rickettsial, viral, and fungal infections .

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

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 areuntreated, these infections are fatal. With treatment, mortality averages 30percent; it is higher in acute and prosthetic valve infections.

Acute endocarditis usually occurs when heart valves are colonized by virulentbacteria in the course of microbemia (Fig.94-3). The most common cause of acute endocarditis isStaphylococcus aureus; other less common causes areStreptococcus pneumoniae, Neisseria gonorrhoeae, Streptococcuspyogenes, and Enterococcusfaecalis. Patientswith acute endocarditis usually have fever, marked prostration, and signs ofinfection at other sites. Infected heart valves may be destroyed rapidly,leading to heart failure from valve leaflet perforation and acute valvularinsufficiency. Infected pieces of fibrin and platelet vegetations on thevalves may break loose into the circulation and lodge at distant sites,producing damage to target organs. Metastatic infection due to emboli mayinvolve arterial walls (mycotic aneurysm) or produce abscesses.

Figure 94-3

Infective endocarditis: metastatic infections due toemboli.

Patients with subacute endocarditis usually have underlying valvular heartdisease and are infected by less virulent organisms such as viridansstreptococci, enterococci, nonenterococcal group D streptococci,microaerophilic streptococci, andHaemophilus species.Frequently, the source and onset of infection are not clear, and patientsconsult physicians with complaints of fever, weight loss, or symptomsrelated to embolic phenomenon and congestive heart failure.

Prosthetic valvular endocarditis may present either acute or subacute inonset, and the infecting organisms differ, depending on whether endocarditisdevelops within 2 months of surgery or later (Table 94-1). Whereas infections on nonprostheticvalves usually are eradicated by antimicrobial therapy alone, prostheticvalve infections frequently require surgical removal of the infected valvebefore the infection is eliminated. Antimicrobial therapy of endocarditis isprolonged and should be guided by susceptibility studies. Fungalendocarditis is rare, butCandida infections occur in thosewith prosthetic valves and in drug addicts.Aspergillusendocarditis may occur after cardiac valve surgery.