FEVER AND PROSTHETIC HEART VALVES
Fever occurring in a patient with a prosthetic heart valve may signal infective endocarditis or numerous other conditions. It is estimated that an infection will develop in 1% to 4% of patients with prosthetic devices during the life span of the device.
In diagnosis, it is helpful to note how long after the operation the fever developed. Any major surgical procedure can be associated with a low-grade fever (100°F or 37.8°C) for a few days. Possibilities during the initial 24-hour period include a transfusion reaction, atelectasis, aspiration pneumonia, or wound infection, especially with group A hemolytic streptococci or Clostridium species. Fever developing after the first 24 hours may be caused by an anesthetic. Fever with lymphadenopathy and atypical lymphocytes, called the postperfusion syndrome, usually occurs 2 to 4 weeks after surgery. It is caused by the transfusion of fresh blood with cytomegalovirus or Epstein-Barr virus. Hepatitis C and, rarely, malaria may develop after blood transfusions. Other infectious complications to consider are phlebitis related to numerous IV lines, infusion of contaminated fluids, drug fever, abscesses secondary to IM injections, bacterial pneumonia, pulmonary infarction, urinary tract infection, wound infection, deep-vein thrombophlebitis, sternal osteomyelitis, and mediastinitis. A syndrome of unknown etiology, the postcardiotomy syndrome, occurs 10 days to 3 months after surgery and is characterized by fever, chest pain, and often a pericardial friction rub. Reactivation of rheumatic fever also may be responsible for fever.
It is important to obtain blood cultures from patients with fever and a prosthetic heart valve. Infective endocarditis occurring within 60 days after valve insertion is called early endocarditis; infection after that time is called late endocarditis. Some authors consider endocarditis as early if it occurs within the first 12 months of surgery and late if it is seen after a year. The source of organisms responsible for early-onset infections may be contamination of the prosthetic valve or bloodstream at the time of operation or an infectious complication developing during the postoperative period, such as a sternal wound infection, pneumonia, or an infected IV line. The same organism can often be isolated from a peripheral site (a wound), sputum, or the blood. The prosthetic valve, like any other foreign body, is at high risk for becoming infected as a consequence of bacteremia. Late-onset infections may be caused by a transient bacteremia associated with either a dental, skin, or genitourinary tract procedure or an infection. Other organisms responsible for late-onset infections may be acquired at the time of operation and have a long incubation period.
The organisms causing prosthetic valve infections differ from those producing classic endocarditis. Certain bacteria, such as diphtheroids and, especially, coagulase-negative staphylococci, usually considered blood culture contaminants, account for about one third of all infections in these patients. Of the early-onset cases, half are caused by Staphylococcus aureus or Staphylococcus epidermidis, 20% are caused by gram-negative bacilli, and 10% are produced by fungi such as Candida or, rarely, Aspergillus. The major causative organisms in late-onset infections are streptococci (36%), staphylococci (38%), gram-negative bacilli (10%), and other pathogens (10%). However, any organism can infect a prosthetic valve, and when blood cultures are positive for unusual pathogens or so-called nonpathogens, these should not be dismissed as contaminants. Approximately 5% to 10% of patients have culture-negative endocarditis.
The clinical features of early-onset infections are often dominated by other, concomitant infectious complications, such as pneumonia, wound infection, suppurative phlebitis, or urinary tract infection. Symptoms and signs include fever (90% to 100%), new insufficiency murmurs (60%), splenomegaly (20%), and shock (33%). The presence of petechiae, hematuria, or anemia is difficult to interpret during the early postoperative period, as these conditions may relate to the operation. A more fulminant clinical course often occurs in patients with early-onset prosthetic valve endocarditis (PVE). The manifestations of late-onset infection caused by streptococci are similar to those in patients without a prosthetic heart valve. Fever, a new aortic or mitral insufficiency murmur, splenomegaly, anemia, and peripheral stigmata such as petechiae and splinter hemorrhages are often present in late-onset infections.
Sustained bacteremia is characteristic of endocarditis, and blood cultures are positive in 95% of patients with prosthetic valve infections. Blood cultures may be negative in patients with Candida or Aspergillus endocarditis. Emboli occluding major arteries are common in fungal endocarditis. Culture and histologic examination of the clot may be useful for establishing the cause. Fastidious microorganisms such as members of the HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) and Legionella should be considered. Noninvasive cardiac procedures such as transesophageal echocardiography, cinefluoroscopy, and electrocardiography may be helpful. Cardiac cinefluoroscopy, although used less often now than in the past, may show an abnormal rocking motion of the prosthesis. A new murmur of aortic insufficiency or large vegetations on a valve may be detected on an echocardiogram. Selective cardiac catheterization with quantitative blood cultures may be useful for determining the site of infection if the patient has more than one prosthetic valve.
A diagnostic dilemma occurs in the interpretation of positive blood cultures during the postoperative period. Although the presence of a sustained bacteremia may indicate bacterial endocarditis, it is important not to assume that the positive blood cultures confirm the diagnosis of endocarditis. Other criteria that help to establish the diagnosis are the presence of a new or changing heart murmur or of embolic phenomena, and the absence of an extracardiac source for the bacteremia. However, no criterion will absolutely distinguish bacterial endocarditis from a sustained bacteremia without endocarditis. If the blood cultures are positive during this period, remove the IV and arterial lines, drain any focus of pus, and begin antimicrobials. If during the next 2 to 3 weeks no new murmur develops, the peripheral stigmata of endocarditis are absent, and the repeated blood cultures are sterile, discontinue therapy. If a new murmur develops, peripheral manifestations of endocarditis appear, or the blood cultures remain positive after the source has been eliminated, continue therapy for 4 to 6 weeks.
A bactericidal antimicrobial given in high doses parenterally is the cornerstone of therapy for prosthetic valve infections. Peak serum bactericidal levels should be present at a dilution of at least 1:8. Commonly accepted indications for surgery along with high-dose antimicrobial agents include a significant valvular leak or congestive heart failure, or both; persistent or recurrent bacteremia after 1 to 2 weeks of optimal treatment; multiple peripheral emboli; new-onset conduction abnormalities; and endocarditis caused by fungi. Recurrent emboli are a controversial indication for surgery. Surgery combined with antimicrobials may be indicated for infections caused by S. aureus and S. epidermidis, as well as for early-onset prosthetic valve infections caused by gram-negative bacilli. Late-onset infections caused by streptococci usually respond to antimicrobial therapy alone and do not require valve replacement.
The mortality in early-onset infection is 60% to 80%, and in late-onset endocarditis it is 40%. Congestive heart failure secondary to valve dehiscence or myocardial abscesses and cerebral arterial emboli are the leading causes of death. Because the effects of a prosthetic valve infection can be devastating, prevention is important. A prophylactic antistaphylococcal agent should be administered just before operation and during the perioperative period while the long lines are present (usually for 2 to 3 days postoperatively). Prophylaxis is indicated as well for procedures associated with transient bacteremias, such as dental work, genitourinary manipulations, or any surgery through a contaminated area. Antimicrobial prophylaxis for other procedures, such as sigmoidoscopy or gastrointestinal roentgenography, is controversial. (N.M.G.)
Alsip SG, et al. Indications for cardiac surgery in patients with infective endocarditis. Am J Med 1985;78(Suppl 6B):138.
Use a point system to determine the need for surgery. Surgery is indicated for moderate-to-severe heart failure, fungal etiology, persistent bacteremia, or unstable prosthesis.
Blumberg EA, et al. Persistent fever in association with infective endocarditis. Clin Infect Dis 1992;15:983.
Causes of fever in patients with endocarditis and persistent fever included myocardial abscess (27%), drug fever (19%), other nosocomial infections (19%), persistent infection (24%), other (8%), and unknown (15%).
Calderwood SD. Risk factors for the development of prosthetic valve endocarditis. Circulation 1985;72:31.
One third of the cases had an early onset, and two thirds occurred late.
Chen TT, Schapiro JM, Loutit J. Prosthetic valve endocarditis due to Legionella pneumophila. J Cardiovasc Surg 1996;37:631–633.
A rare cause of culture-negative endocarditis.
Conte JE, et al. Antibiotic prophylaxis and cardiac surgery. Ann Intern Med 1972; 76:943.
Compared a single dose of intraoperative cephalothin with preoperative plus intraoperative and postoperative cephalothin. There was no difference in infection rates.
Daniel WG, et al. Improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography. N Engl J Med 1991;324:795.
The transesophageal approach was superior to transthoracic echocardiography, but a negative study result does not exclude a complication in a patient with a prosthetic valve.
Dismukes WE, et al. Prosthetic valve endocarditis: analysis of 38 cases. Circulation 1973;48:365.
Staphylococci (both S. aureus and S. epidermidis) are the most common organisms causing early-onset infections; streptococci are the leading causes among late-onset cases.
Douglas JL, Cobbs CG. Prosthetic valve endocarditis. In: Kaye D, ed. Infective endocarditis, 2nd ed. New York: Raven Press, 1992.
A review emphasizing an approach to diagnosis and management.
Durack DT, Lukes AS, Bright DK, Duke Endocarditis Service. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med 1994;96:200–209.
Criteria to improve accuracy of diagnosis.
Everett ED, Hirschmann JV. Transient bacteremia and endocarditis prophylaxis. A review. Medicine (Baltimore) 1977;56:61.
An extensive review of the incidence of and organisms associated with bacteremia secondary to various procedures or manipulations. The authors favor prophylactic antimicrobials for patients with prosthetic valves who undergo dental procedures, urologic manipulations, upper gastrointestinal endoscopy, sigmoidoscopy, liver biopsy, or barium enema.
Fang G, et al. Bacteremia in patients with prosthetic cardiac valves. Ann Intern Med 1993;119:560.
The most frequent source of bacteremia for a patient with nosocomial endocarditis was an intravascular catheter, wound, or skin infection.
Giladi M, et al. Microbiological cultures of heart valves and valve tags are not valuable for patients without infective endocarditis who are undergoing valve replacement. Clin Infect Dis 1997;24:884–888.
When endocarditis is not suspected, cultures of heart valves or prosthetic valve tags are not indicated.
John MDV, et al. Staphylococcus aureus prosthetic valve endocarditis: optimal management and risk factors for death. Clin Infect Dis 1998;26:1302–1309.
In patients with S. aureus infection, valve replacement during the treatment of infection was associated with reduced mortality.
Karchmer AW, Archer GL, Dismukes WE. Staphylococcus epidermidis causing prosthetic valve endocarditis: microbiologic and clinical observations as guides to therapy. Ann Intern Med 1983;98:447.
Most (87%) isolates of S. epidermidis were methicillin-resistant. Therapy of choice consists of vancomycin, plus rifampin with or without an aminoglycoside.
Karchmer AW, Gibbons GW. Infections of prosthetic heart valves and vascular grafts. In: Bisno AL, Waldvogel FA, eds. Infections associated with indwelling medical devices, 2nd ed. Washington, DC: American Society for Microbiology, 1994:213–249.
Karchmer AW, et al. Late prosthetic valve endocarditis. Clinical features influencing therapy. Am J Med 1978;64:199.
The occurrence of any two of three features (nonstreptococcal etiology, a new regurgitant murmur, and moderate-to-severe congestive heart failure) carried a high mortality. Surgery should be strongly considered.
Kluge RM, et al. Sources of contamination in open heart surgery. JAMA 1974;230:1415.
A variety of organisms, including diphtheroids and S. epidermidis, were frequently (71%) isolated in cultures obtained from the operative sites.
Lytle BW, et al. Surgery for acquired heart disease. Surgical treatment of prosthetic valve endocarditis. J Thorac Cardiovasc Surg 1996;111:198–210.
The risk for PVE is about 3% after the first year and 1% per year thereafter. Mortality with surgery for PVE has declined, with a survival rate of 82% at 5 years and 60% at 10 postoperative years.
Mayer KH, Schoenbaum SC. Evaluation and management of prosthetic valve endocarditis. Prog Cardiovasc Dis 1982;25:43.
Early surgical intervention is recommended in most cases of PVE, except for late-onset streptococcal disease.
Melgar GR, et al. Fungal prosthetic valve endocarditis in 16 patients. Medicine 1997; 76:94–103.
Amphotericin B plus surgery resulted in a 67% survival rate, but relapse may occur that requires long-term suppression therapy.
Meyer DJ, Gerding DN. Favorable prognosis of patients with prosthetic valve endocarditis caused by gram-negative bacilli of the HACEK group. Am J Med 1988;85:104.
A group of fastidious gram-negative rods that includes Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species.
Mugge A, et al. Echocardiography in infective endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and transesophageal approach. J Am Coll Cardiol 1989;14:631.
Vegetations were detected in 86% of patients by means of transesophageal echocardiography, compared with only 36% by the transthoracic technique.
Mullany CJ, et al. Early and late survival after surgical treatment of culture-positive active endocarditis. Mayo Clin Proc 1995;70:517–525.
Overall mortality was 26%. A higher mortality was seen in patients with an abscess at surgery (40%) and with an increased serum creatinine (40%).
Nasser RM, et al. Incidence and risk of developing fungal prosthetic valve endocarditis after nosocomial candidemia. Am J Med 1997;103:25–32.
Among patients with candidemia and a prosthetic heart valve, evidence of PVE never developed in 75%, 16% had endocarditis at the time of the fungemia, and 9% had a late onset of endocarditis.
Nettles RE, et al. An evaluation of the Duke criteria in 25 pathologically confirmed cases of prosthetic valve endocarditis. Clin Infect Dis 1997;25:1401–1403.
The Duke diagnostic criteria had a sensitivity of 76% in cases of endocarditis that were confirmed pathologically.
Nguyen MH, et al. Candida prosthetic valve endocarditis: prospective study of six cases and review of the literature. Clin Infect Dis 1996;22:262–267.
In patients unable to tolerate surgery, antifungal therapy followed by chronic suppression may be effective (46%).
Pazin GJ, et al. Determination of site of infection in endocarditis. Ann Intern Med 1975; 82:746.
Quantitative blood cultures from various cardiac chambers may indicate the site of infection.
Sande MA, et al. Sustained bacteremia in patients with prosthetic cardiac valves. N Engl J Med 1972;286:1067.
Discusses the diagnostic dilemma of sustained bacteremia without endocarditis versus endocarditis.
Schulz R, et al. Clinical outcome and echocardiographic findings of native and prosthetic valve endocarditis in the 1990s. Eur Heart J 1996;17:281–288.
Vegetations were detected by transesophageal echocardiography in 80% of episodes of PVE. This finding compares with a yield of only 15% for transthoracic echocardiography.
Tornos P, et al. Clinical outcome and long-term prognosis of late prosthetic valve endocarditis: a 20-year experience. Clin Infect Dis 1997;24:381–386.
Staphylococcus aureus infection had a mortality rate of 67%; streptococcal infection, 6%; other causes, 23%.
Weinstein L, Rubin RH. Infective endocarditis 1973. Prog Cardiovasc Dis 1973;16:239.
Wilson WR, et al. Prosthetic valve endocarditis. Ann Intern Med 1975;82:751.
The incidence of prosthetic valve infections was low. In this series, most infections occurred more than 2 months after surgery.
Wilson WR, et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. JAMA 1995; 274:1706–1713.
Guidelines for therapy.
Wolff M, et al. Prosthetic valve endocarditis in the ICU. Prognostic factors of overall survival in a series of 122 cases and consequences for treatment decision. Chest 1995;108:688–694.
In patients with S. aureus PVE, survival was higher (45%) in those who received medical-surgical therapy compared with only antibiotics (0).