At a Glance

Infective endocarditis (IE) is a specific bloodstream infection resulting from infection of the endocardium with a microorganism. The diagnosis is based on a constellation of clinical findings and other criteria in the presence of positive blood cultures and endocardial involvement. A predisposing cardiac lesion is not evident in one-third to one-fourth of patients. Blood cultures in some patients with IE are negative.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Three or more blood culture sets drawn from three different venipuncture sites are suggested for suspicion of IE. The cultures should be drawn before antibiotics are administered. The additional diagnostic yield of more than three blood culture sets is not appreciable in patients who have not recently been treated with antimicrobials. However, if a patient has recently received antibiotics, additional blood culture sets may be necessary to recover the organism.

In the past, the Microbiology Laboratory was notified to extend the blood culture bottle incubation time beyond the usual 5 days, if the HACEK group of organisms was suspected. However, current blood bottle media formulations permit adequate growth of these organisms within the 5-day time frame. Although Candida spp. and occasionally Fusarium spp. grow adequately in routine blood culture bottles, lysis centrifugation tubes should be inoculated if other fungi, such as molds, are considered. Bartonella spp. can be isolated using lysis centrifugation.

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Coxiella burnetii, the etiologic agent of Q fever, is an intracellular organism that cannot grow on routine culture plates in the laboratory. Serologic testing is the most commonly used diagnostic method for Q fever diagnosis. A single positive phase I IgG titer of greater than or equal to 1:800 is predictive of chronic infection. Other relatively nonspecific findings of IE include normochromic normocytic anemia, an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein, thrombocytopenia, and leukocytosis.

ESR is elevated in approximately 60% of endocarditis cases. Laboratory findings of hyperglobulinemia, cryoglobulins, circulating immune complexes, low complement levels, and elevated rheumatoid titers may also be associated with IE. Culture and Gram staining of valve tissue demonstrate poor sensitivity and are not suggested for routine diagnosis.

Follow-up blood cultures may demonstrate clearance of the organism once appropriate treatment is initiated. Susceptibilities of repeat-positive blood culture isolates should be performed every 3 days, as organisms may acquire resistance within that time period. Some authors argue that minimal bactericidal concentrations with or without serum bactericidal titers should be monitored in cases of IE. Synergy studies of resistant bacteria may be performed using broth microdilution, time-kill curves, or checkerboard assays, but such tests are not routinely performed in the majority of Clinical Microbiology Laboratories.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

The method of obtaining blood cultures is very important for accurate results. The technique of the blood draw, number of sets drawn, and the timing of blood cultures are important determinants. Studies of skin cleansing solutions, including alcohol, chlorhexidine, iodine tincture, and povidone-iodine, have been compared in a recent meta-analysis. If the vein must be palpated after skin preparation, a disinfected or sterile glove should be worn. Blood for cultures should not be drawn solely through in-dwelling intravascular catheters, as these lines are frequently colonized with common skin contaminants. Blood drawn from arteries yields the same results as that drawn from veins.

In most instances, there is no scientific basis for obtaining separate blood cultures from various ports of triple-lumen catheters. Needles should not be changed after the venipuncture and before inoculation of the blood culture bottles. Such practices increase the risk of fingerstick injury to the person handling the needles.

Ideally, 10 mL of blood should be injected into each blood culture bottle for adults, with 0.5-5 mL per bottle for infants and children. Although the bacteremia in IE is continuous, rather than random, occasionally, a low grade bacteremia of 1-10 colony-forming units (CFUs) per blood impedes diagnosis. Therefore, the yield of blood culture increases with a higher volume of blood submitted.

The timing of blood cultures drawn in relation to a febrile episode is not significant, particularly in IE, as the bacteria are released from cardiac vegetations at a relatively constant rate. There is no difference in yield between blood cultures drawn simultaneously versus hours apart. Blood culture draws on an acutely ill patient may be performed at three separate sites within minutes of each other, provided antibiotics have not yet been administered.

What Lab Results Are Absolutely Confirmatory?

A variety of microorganisms can cause IE, but streptococci and staphylococci comprise the majority. Typical causes of IE include Staphylococcus aureus, viridans streptococci, Streptococcus bovis, nutritionally variant streptococci, enterococci, and the HACEK organisms. The risk of endocarditis in a patient with S. aureus bacteremia is high. Other organisms highly associated with IE include Streptococcus sanguis, group G streptococcus, and Enterococcus faecalis. Positive blood cultures must be interpreted in the context of the clinical scenario and the number of sets submitted. Proprionibacterium acnes, Corynebacterium spp., Bacillus spp., and coagulase-negative staphylococci (excluding Staphylococcus lugdunensis) are usually considered contaminants when recovered singly or in a minority of the blood culture sets.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Water-based povidone products must remain on the skin long enough to dry and release the active ingredient, 1% iodine. As opposed to the alcohol-based products, aqueous products can take up to 5 minutes to dry. In addition, iodine and alcohol-based products lack the longer-term sterilization activity of chlorhexidine, which persists on the skin surface. For the reasons previously mentioned, a chlorhexidine-based approach may result in fewer false positives and more appropriate therapy.

Although most institutions define one blood culture set as an aerobic bottle plus an anaerobic bottle, the incidence of IE due to anaerobes is extremely low. Anaerobic bottles more often grow facultative anaerobesthan strict anaerobes. To obtain the recommended blood volume draw, a second aerobic bottle should be inoculated if an anaerobic bottle is not available. One study showed higher organism recovery with the aerobic-anaerobic bottle pair than with the aerobic-aerobic bottle pair.