SPECIAL CONTRIBUTION endocarditis

Endocarditis in the Emergency Department Clinical presentations and pathogeneses of endocarditis and aspects of its diagnosis and management relevant to emergency department practice are reviewed. Guidelines for admission, laboratory evaluation, and decisions regarding the initiation of therapy in the ED are offered. Also discussed are the role of the emergency physician in the prevention of iatrogenic infection and current recommendations regarding administration of prophylactic antibiotics for ED procedures. [Delaney KA: Endocarditis in the emergency department. Ann Emerg Med April 1991;20:405-414.] INTRODUCTION Endocarditis is a serious medical diagnosis. Mortality rates as high as 50% are reported when the aortic valve is involved. 1 Significant neurologic and cardiopulmonary disabilities may complicate the recovery of survivors. There is good evidence that early diagnosis and treatment reduce the incidence of complications and lower mortality rates. 2 Despite the ominous nature of this disease, the diagnosis is easily overlooked in the emergency department. The initial manifestations may be so subtle that the emergency physician may fail to consider the possibility of a serious infection. Alternatively, the physician may not recognize that the patient with renal failure, a painful rash, congestive heart failure, or a stroke has a complicatiofi of ~6~docarditis. To facilitate earlier diagnosis and treatment, emergency physicians must identify patients at risk and be familiar with the various clinical presentations of endocarditis. Although a definitive diagnosis of endocarditis cannot be made in the ED, knowledge of how the diagnosis is made will ensure sufficient evaluation and appropriate decisions regarding the timing and choice of antibiotic therapy in ED patients with possible endocarditis. Presentation, clinical diagnosis, and management of the patient with endocarditis in the ED are discussed. In addition, the role of the emergency physician in the prevention of iatrogenic infection in patients who are at risk of endocarditis is reviewed.

Kathieen A Delaney, MD Dallas, Texas From the Division of Emergency Medicine, Department of Surgery, The University of Texas Southwestern Medical School, Dallas. Received for publication March 14, 1990. Revision received September 4, 1990. Accepted for publication September 25, 1990. Presented at the American College of Emergency Physicians Winter Symposium in Tucson, Arizona, March 1990. Address for reprints: Kathleen A Delaney, Division of Emergency Medicine, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-8579.

CLINICAL PRESENTATION OF E N D O C A R D I T I S There are two distinct groups of patients who are at considerably greater risk of developing endocarditis than the general population: patients who abuse IV drugs and patients with structural heart disease. Members of the first risk group can be readily identified by an astute or persistent clinician. The second at-risk group may not have clinical evidence of valvular abnormalities and may not be readily identified before presentation with endocarditis. The incidence of endocarditis in the general population is one in 20,000. 3 Cases occur in IV drug abusers at a rate of one and one half to two cases per 1,000 IV drug abusers per year. 4 What this means to the emergency physician was illustrated by several recent ED studies. A retrospective evaluation of febrile IV drug abusers admitted to San Francisco General Hospital before 1987 demonstrated that 20% were diagnosed with endocarditis. 5 T h i r t e e n p e r c e n t of febrile IV drug abusers followed prospectively in a New York City hospital in 1986 and 6% of 283 febrile IV drug abusers collected prospectively in Boston in 1988 were ultimately diagnosed with endocarditis.6, 7 Endocarditis was diagnosed in 41% of 180

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bacteremic IV drug abusers evaluated in Detroit. s Studies of febrile IV drug abusers do not yet reflect the impact that acquired immunodeficiency syndrome (AIDS) would be expected to have on the percentage of patients with endoearditis in this population. Only six of 283 patients in the most recent study from Boston had fever attributed to h u m a n immunodeficiency virus or AIDS-related infection. 7 Risk figures for structural cardiac lesions are defined for only a few readily identifiable groups. For example, the risk in patients with mitral valve prolapse associated with a holosystolic murmur is estimated to be one in 1,920. 3 Patients with a prosthetic valve develop endocarditis at a rate of ten to 20 per 1,000 per year. 9 Several large, unselected case series are r e p e a t e d l y r e f e r e n c e d throughout this review. It is useful to briefly describe them here. First, Pelletier and Petersdorf reported 125 cases from Seattle occurring between 1963 and I972.1° Fifteen percent of these patients were IV drug abusers, and 13% had prosthetic valves. Second, Garvey and Neu reported 165 episodes of endocarditis in New York City occurring between 1968 and 1973.11 Twelve episodes occurred in 1V drug abusers, and 34 episodes involved prosthetic valves. Third, yon Reyn et al reported 104 cases occurring in Boston between 1970 and 1977. 2 Six of these patients were IV drug abusers, and 13 had cardiac prostheses. Finally, Levine et al reported 74 cases occurring in Detroit in 1982.12 All of these patients were IV drug abusers, and two had prosthetic valves. The primary disease process in endocarditis is a destructive bacterial or fungal infection of the endocardium, which usually originates in the valve leaflets. The patient with endocarditis may present with general constitutional signs and symptoms of infection or with a specific complication. Complications of endocarditis are of four general types: 1) Structural injury to the valve causes mechanical insufficiency and the development of congestive cardiac failure; 2) local abscesses invade the myocardium and c o n d u c t i n g s y s t e m , r e s u l t i n g in blockade of atrioventricular conduction or rupture of the aortic root; 3) immune complex deposition result20:4 April 1991

ing from chronic antigenic stimulation causes vasculitis, which is associated with glomerulonephritis, aseptic meningitis, and characteristic skin rashes; and 4J microembolic and macroembolic events cause vascular injury and result in the formation of myocotic aneurysms, metastatic infection, bleeding, and local ischemic injury. Vasculitis and emboli may cause injury to any organ system. Neurologic complications related to aseptic meningoencephalitis and cerebral vascular emboli account for a substantial number of ED presentations of endocarditis. Meningeal signs, focal deficits, and mental status abnormalities were noted on admission in 29% of patients reported by Garvey and Neu. 11 A focal neurologic deficit was detected on admission in 9%, 18%, and 4% of cases reported by von Reyn et al, Pelletier and Petersdorf, and Levine et al, respectively.%1°, ~ Delirium or coma was present on admission in 19% of the patients reported by yon Reyn et al and Pelletier and Petersdorf.~, lo Twenty percent of Lev i n e et al's p a t i e n t s w i t h S t a phylococcus aureus endocarditis were encephalopathic at the time of admission. 12 Despite the high incidence of neurologic abnormalities in patients with infective endocarditis, bacterial meningitis was diagnosed in only 3%, 6%, and 2% of patients in the von Reyn et al, Pelletier and Petersdorf, and Garvey and Neu series, respectively.% lo, u Spinal fluid examinations in patients with neurologic complications may be entirely normal or demonstrate mild-to-moderate increases in protein and polymorphonuclear leukocytes.11,1a Of 42 lumbar punctures done to evaluate neurologic abnormalities in Garvey and Neu's study, eight (19%} were completely normal, 20 (48%) had abnormal cell counts, and 29 (69%) had elevations of cerebral spinal fluid protein.11 Only three of 42 cultures were positive for the infecting organism. 11 Two of 13 of von Reyn et al's cases with pleocytosis and one of five cases of meningoencephalitis with cerebral spinal fluid pleocytosis described by Dryer and Fields had positive cerebral spinal fluid cultures.2A 3 One case of intracerebral abscess occurred in each series reported by yon Reyn et al, Pelletier and Petersdorf, and Levine et al.2,1o,~2 Intracerebral or subAnnals of Emergency Medicine

arachnoid hemorrhage resulting from rupture of a mycotic aneurysm is unusual but occasionally reported. 12-14 The cardiac complications of endocarditis are also multifactorial. Coronary artery emboli resulting in acute myocardial infarction were clinically evident in 6% of Pelletier and Petersdorf's and 13% of Garvey and Neu's patients.lO, ~1 Myocardial abscess that involved the conducting system caused atrioventricular nodal dissociation, axis shift, or complete heart block in 9% of Garvey and N e u ' s patients.ll N e w congestive heart failure secondary to valve failure develops in 20% to 40% of patients with endocarditis, most frequently in patients with infections of the mitral or aortic valves.~,l°, 11A3,1s Twenty-five percent of Garvey and Neu's patients had congestive heart failure on admission31 The incidence of detectable murmurs in any series is also related to the site of the valvular infection. In Levine et al's series, 69% of the patients had isolated right-sided disease, and only 35% had murmurs detected on admission. 12 In Garvey and yon Reyn et al's and Garvey and Neu's series, 5% had isolated tricuspid valve disease and 95% to 97% of patients had murmurs noted on admission.2,11 This inverse association of the frequency of detection of a murmur with the incidence of isolated infection of both the pulmonic or tricuspid valves has been demonstrated repeatedly. 2,1s,16 Maneuvers that augment right-sided murmurs such as the hepatojugular reflux and deep inspiration may increase the frequency of detection.17 Emboli that result in clinically evident ischemia, metastatic infection, or aneurysm formation also occur in the extremities, spleen, eye, and gut. Major organ emboli precipitated the admission of 20% of patients with native valve infection in Garvey and Neu's series.11 Pulmonary symptoms such as cough, chest pain, hemoptysis, and dyspnea attributed to septic emboli constitute the most frequent presenting complaints of patients with tricuspid valve infection. ~1,~2,~s,16 Septic arthritis or osteomyelitis also may be a manif e s t a t i o n of m e t a s t a t i c i n f e c tion %11,t2 Splenomegaly is noted in approximately 25% of patients in all series and appears to be related to the c h r o n i c i t y of i n f e c t i o n . 1°,11A3,16 406/107

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Splenic abscess has been reported in as m a n y as 4% of patients.lO, 12 Pleural effusion and empyema associated with splenic abscess rupture also have been reported.18,19 The kidney is affected in a number of ways that are demonstrated pathologically. Bland and septic infarcts, abscesses, and focal, proliferative, and suppurative glomerulonephritis have been described.11,16 Clinically evident effects of these multiple processes are generally manifested as pyuria, hematuria, and renal insufficiency. Microscopic hematuria was noted in 25% of von Reyn et al's and in more than 50% of Garvey and Neu's patients.2, ~1 Renal failure attributed to acute glomerulonephritis occurred in 20% of Levine et al's patients with S a u r e u s endocarditis. ~2 In addition to aseptic meningitis and g l o m e r u l o n e p h r i t i s , i m m u n e complex deposition leads to useful diagnostic signs of vasculitis in the skin and optic fundi. Skin and conjunctival petechiae and subungual splinter hemorrhages are nonspecific clinical signs of vasculitis. Osler's nodes are tender nodules found most frequently on the tips of the fingers and toes. They are sterile and demonstrate perivasculitis on biopsy. 2,2° Janeway lesions are painless hemorrhagic lesions that occur in an acral distribution and contain bacteria, s u g g e s t i n g m i c r o e m b o l i . 2~ R o t h spots are small retinal hemorrhages with central clearing. Roth spots, Janeway lesions, and Osler's nodes are regarded as relatively specific although not pathognomonic for endocarditis.2,2o, zl Patients with endocarditis may present with painful Osler's nodes as their sole initial complaint, m Patients who present acutely with highly virulent infections appear to have a lower incidence of these specific findings.lZ, 2z Sixty percent of Levine et al's patients had S a u r e u s infections; only 3% exhibited Osler's nodes, Janeway lesions, or Roth spots on presentationJ 2 In contrast, 21% of von Reyn et al's patients had one or more findings specific for endocarditis, z The incidence of S a u r e u s infection was 25% in this group. 2 A low incidence of skin abnormalities also has been associated with patients with isolated pulmonic or tricuspid valve infection.~3,~5,16 When the information is recorded, almost all unselected series report the iden108/407

tification of nonspecific signs of vasculitis in more than 50% of patients.t,2,to,13 The majority of patients with endocarditis present to the ED with complaints of fever and nonspecific c o n s t i t u t i o n a l s y m p t o m s such as malaise, anorexia, or weight loss. Systemic manifestations of the primary infection depend on the type of infecting organism. Acute dramatic presentations are associated with highly virulent organisms such as S aureus, whereas subtle indolent courses occur in patients infected w i t h o r g a n i s m s of low v i r u l e n c e such as S t r e p t o c o c c u s v i r i d a n s . The absence of fever does not exclude the diagnosis. Although fever was documented in 98% of Levine et al's patients, 12 only 73% to 77% of von Reyn et al's and Pelletier and Petersdorf's patients manifested fever in the ED.2,10 The median duration of symptoms before the initiation of diagnostic studies and appropriate antibiotic therapy reflects primarily on the acuity and severity of the infection and somewhat on the acuity of the physician. More recent studies report much shorter durations of symptoms before diagnosis. This is p r e s u m a b l y because of improved recognition of the disease. Pelletier and Petersdorf reported a mean duration of symptoms of 68 clays for streptococcal species in 1963 through 1972 compared with 28 days for streptococcal species in von Reyn et al's study in 1970 through 1977. The much more virulent staphylococcal infections presented with median symptom duration of 14 days in the Pelletier and Petersdorf study versus nine days in the yon Reyn et al study. The clinical presentation of any individual patient with endocarditis is determined by the type of infecting organism and the location of the infection. When IV drug abusers and non-IV drug abusers are examined separately, their clinical presentations are distinguished by the incidence of underlying heart disease, site of valvular infection, and nature of the infecting organism. IV drug abusers with endocarditis have a high incidence of infection of previously normal valves, whereas non-IV drug abusers have a high incidence of infection of previously abnormal valves. The incidence of clinically demonstrated structural heart Annals of Emergency Medicine

disease in non-IV drug abusers with endocarditis has increased during the years, possibly as a result of the more sophisticated methods of detection. Only 36% of non-IV drug abusers in Garvey and Neu's study who presented with infected native valves had any documented history of valvular heart disease, although many without such history "had been told of a m u r m u r in the past. ''11 The prevalence of known structural disease was 72% in Pelletier and Petersdorf's study, m In von Reyn et al's more recent series, only 17% of nonIV drug abusers had no discernible general risk factors (including atherosclerotic disease) for endocarditis, whereas 66% had a clear history of known predisposing structural disease. 2 A collection of 249 nonselected cases in IV drug abusers reviewed by Reisberg revealed an overall prevalence of underlying heart disease of 26%. 1 Levine et al's study of IV drug abusers in the Detroit area demonstrated a 6% prevalence of underlying heart disease as evidenced by a history of murmur, rheumatic fever, or previous history of endocarditis. ~a Before the widespread use of IV drugs, endocarditis involving the right side of the heart accounted for less than 5% of cases.~,2,16 Sixty percent of infections in IV drug abusers involve the right side of the heart, with 80% of these resulting from S a u r e u s . 1 In Levine et al's series, 90% of the S a u r e u s infections affected a previously normal tricuspid valve. 1~ The majority of streptococcal infections (67%) and almost all enterococcal infections affect previously abnormal mitral or aortic valves.l,2,1° The incidence of S a u r e u s infections in IV drug abusers was 60% in both Levine et al's series and Reisberg's review of cases in IV drug abusers compared with 14% to 25% in non-IV drug abusers.l,2A1, lz In an old series of non-IV drug abusers (New York Hospital, 1944 through 1960), streptococcal infections occurred in 86% of patients with endocarditis, and staphylococcal infections occurred in 8%. ~3 More recent experience demonstrates that streptococcal infections account for 50% and enterococci account for 6% to 10% of infections in non-IV drug abusers, compared with 14% and 8% in IV drug a b u s e r s , r e s p e c t i v e ly.1,2,1o, ll 20:4 April 1991

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Although this discussion has emphasized the most common infecting species, there are a number of cases of infection with coagulase-negative Staphylococcus, Gram-negative organisms, Candida, and other fungi reported in each case series. In addition, a significant number of cases of fulminant Serratia and Pseudomonas endocarditis in IV drug abusers have been reported r e c e n t l y from San Francisco a n d D e t r o i t , r e s p e c tively.J2,15,24 The literature abounds with individual case reports of infection resulting from very unusual organisms. 25-3o These rarer cases are important with regard to inpatient management but not particularly relevant to the presentation of the patient with endocarditis in the ED. The bacteriology of infection will be further discussed in the sections on pathogenesis and management of end0carditis.

LABORATORY E V A L U A T I O N With the exception of blood cultures, routine ED laboratory studies are not very helpful in diagnosing end0carditis. The longer a patient has been ill, the more likely he is to have a mild anemia and elevation of the erythrocyte sedimentation rate (ESR). Patients who present acutely frequently have a normal hematocrit and normal ESR. The white count may be low, normal, or elevated. Microscopic hematuria has been noted in 25% to 50% of cases.~, t°-I~ Although the chest radiograph is usually normal, it may show multiple septic emboli when the tricuspid valve is infected. Radiographic findings consistent with septic emboli are occasionally seen in patients with septic thrombophlebitis, mycotic aneurysms, and other causes of bacteremia. 12 Levine et al noted a specificity of 91% for the diagnosis of endocarditis w h e n septic e m b o l i were seen on the chest radiograph. 12 Echocardiographic techniques are used frequently in attempts to diagnose endocarditis. Predictions of sensitivity range from 45% to 60% for the demonstration of valvular vegetations.2,12, 31 There are few studies that compare autopsy or surgically proven vegetations with their detection by echocardiography; therefore, the specificity of the technique is not well defined. Levine et al noted that vegetations demonstrated by echocardiography in three of 13 of his pa20:4 April 1991

FIGURE 1. Cardiac abnormalities for which prophylaxis is recommended by the AHA.

Very-High-Risk Lesions Surgical systemic-pulmonaryshunts Prosthelic valves Relative High Risk Congenital cardiac malformations Acquired valvular disease Previous history of endocarditis Mitral valve prolapse with insufficiency Risk Unclear Asymmetric septal hypertrophy Prophylaxis Not Recommended in Secundum atrial septal defect Repaired secundum ASH (more than six months postoperativewith graft) Ligated patent ductus arteriosus (more than six months postoperative) Postoperativecoronary artery bypass Transvenous pacemaker Adaptedfrom References32 and 60,

tients with multiple valve involvement were not confirmed at surgery or autopsy, suggesting a specificity of 77% for this group of patients when the gold standard of direct histological d e m o n s t r a t i o n of disease was used. They reported an overall sensitivity of 45% and specificity of 96% when the test was compared against the clinical diagnosis. 12

PATHOGENESIS OF ENDOCARDITIS IV drug abuse constitutes a likely source of bacteremia in this population. In non-IV drug abusers, transient bacteremias frequently occur during activities that traumatize mucosal surfaces, such as brushing the teeth or moving the bowels. They are also frequently associated with primary infections such as skin abscesses, infected IV catheter sites, cellulitis, p n e u m o n i a , or u r i n a r y tract infections. Iatrogenic bacteremias occur during investigative or therapeutic medical procedures that cause mucosal trauma. 32-34 In the n o r m a l host, t h e s e b a c t e r i a are cleared rapidly by the immune system, and d i s s e m i n a t e d i n f e c t i o n rarely occurs. Patients with abnormal i m m u n e f u n c t i o n such as severe granulocytopenia are at risk of sepsis from these bacteremias. 23 Patients with abnormalities that impair local immune defenses or with a damaged joint surface, cardiac valve, or intravascular prosthesis may develop a localized infection.32, 34 The high incidence of infective endocarditis in IV drug abusers and the low prevalence of underlying heart disease has been discussed previously. Although valvular infection may be a consequence of frequent, high-grade b a c t e r e m i a a s s o c i a t e d with IV injection, many investigators believe that establishment of infection necessitates predisposing valvular injury. Continuous irritation of the endothelial surface by injected particulate matter has been proposed as the cause of this injury.lZ, t5 An important animal study demonstrated that cardiac infection could be induced in rabbits by injection of streptococci only at sites at which previous injury had been produced. It Annals of Emergency Medicine

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could not be demonstrated in control animals. 35 The use of IV cocaine has been associated with a higher risk of endocarditis than the use of IV heroin alone. 5 Factors that may explain this observation include more frequent injections by cocaine users, more significant soft-tissue infections at injection sites because of the vasoconstrictive properties of cocaine, and a greater propensity of cocaine to cause injury to the myocardial surface. In addition, unlike heroin, cocaine dissolves readily and does not need to be boiled before injection, s Evidence for an identifiable predisposing source of bacteremia in patients with endocarditis who do not abuse IV drugs varies among different series; 34%, 42%, and 61% of patients have been reported to have prior histories of infection or instrumentation that were thought to be related to the development of endocarditis.2,1o,11 Overall, less than 20% of cases of infective endocarditis can be related specifically to prior medical instrumentation. 32 The origins of specific infecting organisms have been determined with variable success. Clinically, in nonIV drug abusers, staphylococcal endocarditis has been associated with skin and IV catheter infections. S viridans is classically seen after dental manipulation or oral infection. Gastrointestinal and genitourinary instrumentations and infections are associated with Gram-negative and enterococcal bacteremia. 2,1o,1],36 Among IV drug abusers, regional 408/109

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variations in the type of infecting organisms are common and often unexplained. A large number of cases of P s e u d o m o n a s endocarditis, particularly involving the tricuspid valve, have been reported from the Detroit metropolitan area.12,15 In 1982, they constituted 13% of cases of endocarditis. 12 Predominantly left-sided Serratia m a r c e s c e n s infection was described in 14% of cases of endocarditis in IV drug abusers reported in the San Francisco Bay area from 1969 through 1974. 24 Infections with Serratia and Pseud o m o n a s are rarely reported on the East Coast. 24 The clustering of cases of Pseudomonas endocarditis in the Detroit area has not been adequately explained. Epidemiologic investigation d e m o n s t r a t e d that t h e y are linked to the practice of crushing and injecting pentazocine and tripelennamine tablets. These are dissolved in tap (or toilet) water and injected without prior boiling.* Crane et al believe that the infections are related to this practice. 8 Alternatively, Levine et al postulated that the skin flora of patients with P s e u d o m o n a s endocarditis was altered by adherence to the local practice of taking prophylactic antibiotics to avoid hospitalization. 12 Attempts to explain the unusual clustering of Serratia cases in the San Francisco Bay area have been unrevealing. It has been suggested that the US Army practice of monitoring wind and water currents in the bay by releasing and tracing aerosolized Serratia altered the microflora of the environment. Cultures of the local drug supply and local water did not support this theory. 24 Staphylococcal infections in IV drug abusers have been traced to the patient's own flora. Epidemiologic studies during an outbreak of methicillin-resistant S t a p h y l o c o c c u s infection in the Detroit area demonstrated colonization of the patient with the infecting organism in 70% to 100% of cases.22,37, 3s The high incidence of methicillin-resistant S aureus in this area may also be related to the common practice of self-prophylaxis with antibiotics. 8 *The practice of using toilet water is not uncommon, nor is the motivation bizarre. Persons wishing to inject themselves in a public area will often resort to the privacy of a toilet stall. 110/409

The source of the infecting organism in the IV drug abuser is also related to the site of injection. Women who inject into the groin area have a higher incidence of streptococcal infection, which may be related to colonization of this area with vaginal flora. 8 Rarely, an unusual outbreak of infection has been traced to the drug supply itself. A contaminated supply of heroin was the probable source of an outbreak of disseminated candidiasis in heroin abusers in the United Kingdom in 1982. 39 A large number of isolated case reports suggest that almost any organism not normally associated with serious infection in human beings can cause endocarditis in the IV drug abuser. These include c o m m e n s a l fungi, diphtheroids, saphrophytes, and moderately pathogenic bacteria such as Bacillus cereus and Clostridium perf rin g ens. 27,29,30,40-42

DIAGNOSIS OF ENDOCARDITIS von Reyn et al's criteria for the diagnosis of endocarditis are particularly useful to the emergency physician because they rely on strictly clinical criteria. 2 The gold standard for the diagnosis of endocarditis is the demonstration at surgery or autopsy of direct histologic evidence of infected valve leaflets or positive Gram stain or culture of a vegetation obtained from an involved valve or peripheral embolus. Patients w i t h these findings have definite endocarditis. All other clinical diagnostic evidence is indirect and leads to the probable or possible diagnosis of endocarditis. 2 The probability or possibility of endocarditis is inferred from combinations of three different types of clinical data: the incidence of blood culture positivity; clinical evidence of valvular damage, either preexisting or progressive; and clinical evidence of vascular phenomena suggestive of vasculitis or embolic events. The echocardiogram is not used by von Reyn et al in their definition of endocarditis, although others include it as an adjunct to the diagnosis when supported by additional clinical factors. 2,8,22,31 Persistently positive blood cultures are the rule in the patient with endocarditis because of the presence of an intravascular infection that is continuously seeding the bloodstream.23, 36 Annals of Emergency Medicine

(See the excellent review by Aronson and Gor. 34) yon Reyn et al define "persistently positive" as two of two, three of three, or 70% when four or more cultures are taken. 2 Continuous bacteremia also occurs in other intravascular infections such as septic thrombophlebitis and mycotic aneurysms and in the early stages of typhoid fever and brucellosis. 34 Bacteremia from other types of localized infection tends to be transient or intermittent so that a lower percentage of blood cultures will be positive. 36 A gold standard for the demonstration of bacteremia would involve continuous bloodstream sampling, which of course is not possible. The likelihood of a positive blood culture in the setting of bacteremia is directly related to the frequency of bacteremia, frequency, and volume of the samples, and ability to culture the organism. 34 In Werner et al's classic study of 206 patients with endocarditis, all blood cultures were positive in 91% of patients. 23 Barritt and Gillespie demonstrated a 99% incidence of overall positivity (164 of 166 cultures) in 65 cases of endocarditis in which no previous antibiotics had been administered. 43 In Pelletier and Petersdorf's patients, all blood cultures were positive in 68% of patients: 85% of patients with S aureus endocarditis and 75% of patients with streptococcal endocarditis, lo The failure to demonstrate a 100% incidence of blood culture positivity in patients with continuous bacteremia from endocarditis is attributed to a number of factors: suppression of the infection by previous antibiotic therapy, inadequate blood sample volume, infection with fastidious organisms, and infection of a prosthetic valve.2,23, 34 Previous antibiotic therapy decreased the overall incidence of positive blood cultures in penicillin-sensitive streptococcal endocarditis from 93% to 63% in von Reyn et al's study of 104 patients. 2 The presence of a prosthetic valve was associated with a significant decrease in the incidence of blood culture positivity in several large series.2,1o, 11 The reason for this was not apparent. The low incidences of positivity in some case series have been attributed to the use of 5-mL blood samples rather than the 10-mL blood samples used in the Werner et al and Barritt and Gillespie studies 23,43

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Cases of "culture-negative" endocarditis have been reported in every series. Thirteen of Pelletier and Petersdorf's and Garvey and Neu's patients had negative cultures. Of Garvey and N e u ' s 20 c u l t u r e - n e g a t i v e cases, two had fungal infections, two had received antibiotics, eight had prosthetic valves, and eight were unexplained.l~ von Reyn et al reported a 5% incidence of culture-negative cases, which they attributed to more rigid criteria for defining endocarditis and i m p r o v e d l a b o r a t o r y c u l t u r e techniques. 2 M a n y culture-negative cases are caused by infection with a fastidious or slow-growing organism such as Haemophilus parainfluenzae, Brucella sp, anaerobes, fungi, diphtheroids, or rickettsia. Others are related to exposure to poorly selected or noncurative doses of antibiotics. In some cases, the clinical diagnosis of infective endocarditis is not confirmed a t autopsy.2,10,34,44, 45 The demonstration of persistently positive blood cultures and a new regurgitant m u r m u r or the presence of pre-existing valvular heart disease and vascular phenomena support the clinical diagnosis of probable endocarditis by von Reyn et al's criteria. 2 The demonstration of negative or intermittently positive cultures plus fever, a new regurgitant murmur, and vascular phenomena also support the diagnosis of probable endocarditis. "Vascular p h e n o m e n a " are defined here as central and peripheral emboli, aseptic meningitis, glomerulonephritis, Roth spots, and other specific and nonspecific skin lesions. 2 As isolated findings, the presence of septic arthritis or osteomyelitis does not constitute strong evidence for endocarditis. 31,46-5° Of 15 s u c h i n f e c t i o n s noted in Levine et al's study, four were metastatic infections associated with endocarditis, and 11 occurred as primary c o n s e q u e n c e s of transient bacteremia. 12 The diagnosis of possible endocarditis is made when persistently positive blood cultures occur in the setting of predisposing heart disease or vascular phenomena. 2 Possible endocarditis is also diagnosed when negative or intermittently positive blood cultures occur in conjunction with fever, predisposing heart disease, and vascular phenomena. Fever and positive blood cultures for S viridans without evidence of another source also constitute criteria for possible 20:4 April 1991

endocarditis. S viridans is rarely associated with sustained bacteremia from a source other than cardiac. ~ The identification of a noncardiac source of bacteremia puts the patient in a group at lower risk for the presence of endocarditis. In a review of 105 patients w i t h S aureus bacteremia, two cases of endocarditis were f o u n d a m o n g 63 p a t i e n t s w i t h an identifiable primary skin or catheter infection. Twenty-six cases of endocarditis were detected in 42 patients in w h o m no identifiable skin source was noted. 5~ Bayer et al reviewed the cases of 72 patients with S aureus bacteremia. 42 Twenty-nine of these patients had endocarditis. The findings of no identifiable primary infection, c o m m u n i t y acquisition, and the presence of metastatic infection to spleen, kidney, brain, or skin identified the patients w i t h endocarditis with 70% sensitivity and 100% specificity. In this study, septic osteomyelitis and arthritis were regarded as primary infections. 3~ Finally, Barg et al reported 40 IV drug abusers w i t h group A streptococcal bacteremia. 5o Five cases of endocarditis were f o u n d a m o n g 32 patients with an identifiable focus of infection (including septic arthritis and osteomyelitis), whereas six cases were identified in eight patients who lacked such a primary source. The message from these studies is clear. A drainable or removable skin or intravascular source of bacteremia puts the patient in a lower-risk group for endocarditis w h e n the infection is appropriately identified and treated. A site of infection in the bone or a joint that is a source of bacteremia also puts the patient in a lower risk group, although endocarditis m a y occur. P a t i e n t s w i t h c o m m u n i t y - a c quired bacteremia who have no evidence of localized infection are at high risk of having endocarditis as a source of the bacteremia.

M A N A G E M E N T I N T H E ED Because the most important diagnostic laboratory e v a l u a t i o n is the blood culture series, the decision to admit a patient and initiate evaluation of possible endocarditis must be made on clinical grounds. Patients with highly virulent infections are critically ill. Although they m a y lack specific findings suggestive of endocarditis, the need for hospitalization is evident. A thorough history and Annals of Emergency Medicine

e x a m i n a t i o n of t h e p a t i e n t w i t h extracardiac complications of endocarditis will u s u a l l y provide some evidence that suggests the possibility of a cardiac infection. When faced with a less obviously ill, febrile IV drug abuser, the physician must only recall that the incidence of endocarditis in this population is very high and that the present a t i o n of e n d o c a r d i t i s in IV drug abusers m a y be as subtle as it can be dramatic. In a large, prospective ED study of 283 febrile IV drug abusers, the examining physicians were asked to predict whether each patient had a trivial or serious illness. Eleven of 103 patients who were predicted to h a v e t r i v i a l i l l n e s s e s on c l i n i c a l grounds alone a c t u a l l y had occult major illnesses. Seven of these patients had endocarditis. 7 Because of the high incidence of endocarditis, the unreliability of this population, and the difficulty in clinically predicting the absence of significant illness, any febrile IV drug abuser warrants admission to exclude serious infection. The most difficult admission decisions o c c u r w h e n the e m e r g e n c y physician is faced with a patient who has vague, prolonged constitutional symptoms and is not by history in a risk group for endocarditis. The decision to pursue an evaluation for possible endocarditis is based on the history of the preceding illness, risk factors (including recent infection or instrumentation), and findings on the physical examination. The physical examination should include a thorough inspection of the skin, nailbeds, and conjunctiva for vascular lesions; a f u n d u s c o p i c e x a m i n a t i o n ; a focused a u s c u l t a t o r y e x a m i n a t i o n of the heart, listening carefully during deep i n s p i r a t i o n to a u g m e n t a n y right-sided murmur; and an attempt to palpate the spleen. A n y positive finding should increase the physician's suspicion for the diagnosis of endocarditis. The demonstration of hematuria, mild anemia, or elevation of the ESR will support the diagnosis. The following additional guidelines will help in decision making with regard to these patients and should increase the detection of this disease in the ED. First, in the a b s e n c e of a clear source, this diagnosis should be considered in any elderly patient with a fever. Febrile elderly patients have a 410/111

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Oral Cavity All dental procedures likely to cause gingival bleeding Incision and drainage of abscesses Rigid bronchoscopy Flexible bronchoscopy Genitourinary and Gastrointestinal Tracts Foley catheter placement (especially when infection is present) Consider in patients with very-high-risk lesions Proctosigmoidoscopy Upper gastrointestinal endoscopy" Uncomplicated vaginal delivery Urethral in-and-out catheterization with sterile urine Skin incision and drainage of abscesses Adapted from References32, 60, and 61.

greater risk for a bacterial etiology of fever, and t h e y have a h i g h e r incid e n c e of u n d e t e c t e d d e g e n e r a t i v e h e a r t disease. Second, p r o l o n g e d fever (more than two weeks) w i t h o u t a clear etiology is u n u s u a l for m o s t benign illnesses. The diagnosis of endocarditis should be considered in these cases. Third, a patient who has a n e w m u r m u r or change in an old m u r m u r , w i t h evidence of vasculitis or embolization, should be admitted. Fourth, the diagnosis should be considered in febrile patients with known heart disease or m u r m u r s , no clear source, and a history of recent i n s t r u m e n t a tion. Fifth, because of the grave c o n sequences of valvular infection, any p a t i e n t w i t h a cardiac prosthesis and fever of a n y d u r a t i o n or p e r s i s t e n t malaise, vasculitis, or a n e w m u r m u r should be hospitalized for evaluation. Finally, all 1V drug abusers w i t h fever should be hospitalized for evaluation. M o r e e x p l i c i t g u i d e l i n e s are difficult to formulate. Clearly, the judgm e n t of the physician who has considered t h e diagnosis w i l l be b e t t e r t h a n t h a t of the p h y s i c i a n w h o has not considered the diagnosis. T h e p a t i e n t w i t h s u s p e c t e d endoc a r d i t i s w h o is n o t c r i t i c a l l y ill is best served if a n t i b i o t i c s are w i t h held until adequate n u m b e r s of cultures can be drawn and the diagnosis established. A d m i n i s t r a t i o n of antibiotics before the a c c o m p l i s h m e n t of an adequate series of blood cultures m a y obscure the diagnosis. A l t h o u g h h i g h blood c u l t u r e p o s i t i v i t y r a t e s are the norm, low blood culture posi t i v i t y rates are associated w i t h re112/411

FIGURE 2. Procedures related to ED patients w h o are r e c o m m e n d e d for prophylaxis by A H A guidelines.

cent a n t i b i o t i c therapy, a less t h a n 10-mL t o t a l b l o o d c u l t u r e i n n o c u lure, and the presence of a prosthetic valve. In addition, a large n u m b e r of b l o o d c u l t u r e s m a y be r e q u i r e d to confirm the diagnosis of endocarditis w h e n the infecting organism is one that is m o r e often encountered as a c o n t a m i n a n t t h a n as a p a t h o g e n . This m i g h t occur in a patient w i t h S epidermidis infection of a prosthetic valve, for example, or a native valve infection w i t h a diphtheroid in an IV drug abuser.42,4s, 52 A l l of the b l o o d c u l t u r e s will be p o s i t i v e in the m a j o r i t y of p a t i e n t s w i t h n a t i v e v a l v e i n f e c t i o n s . In W e r n e r et al's 206 cases, t h r e e cultures were sufficient to diagnose all patients w h o had n o t received antibiotics in the two weeks before admission. 23 W h e n all cases were considered, one blood c u l t u r e y i e l d e d the infecting organism in 95% of cases, t w o c u l t u r e s diagnosed 98%, three diagnosed 99%, five diagnosed 99.5%, and seven diagnosed 100%. The two difficult cases were indolent i n f e c t i o n s w i t h Enterococcus (one) and S viridans (one) in p a t i e n t s recently on antibiotics. A l l S aureus infections were diagnosed with two blood cultures. 23 Based on these data, a m i n i m u m of three blood c u l t u r e s s h o u l d be obt a i n e d before t h e a d m i n i s t r a t i o n of a n t i b i o t i c s to t h e p a t i e n t w i t h suspected native valve endocarditis who has n o t received prior antibiotics, a3 A patient with subacute symptoms who has recently been exposed to antibiotics should not be treated u n t i l at least seven cultures are drawn or o n e or m o r e c u l t u r e s a r e d e m o n strated to be growing. Such detailed d a t a are n o t r e p o r t e d for t h e diagn o s i s of p a t i e n t s w i t h p r o s t h e t i c v a l v e e n d o c a r d i t i s . Because of t h e significantly lower p o s i t i v i t y of cult u r e s in p a t i e n t s w i t h p r o s t h e t i c valves, it is prudent to obtain at least six cultures before i n i t i a t i o n of treatment. In the critically ill patient who requires a d m i n i s t r a t i o n of antibiotics in the ED, these cultures should be drawn over a short period of t i m e before i n s t i t u t i o n of antibiotic therapy. T h e m a j o r i t y of p a t i e n t s w h o are so acutely and seriously ill w i t h enAnnals of Emergency Medicine

docarditis that they require initiation of antibiotic therapy in the ED have S aureus infection. The choice of ant i b i o t i c s for e m p i r i c a l t r e a t m e n t of t h e IV drug a b u s e r w i t h suspected native valve endocarditis is dictated by regional variation in the incidence of m e t h i c i l l i n - r e s i s t a n t S aureus and the l i k e l i h o o d of Pseudomonas or Serratia infection. Also, t h e poss i b i l i t y of a r e s i s t a n t o r g a n i s m s h o u l d be c o n s i d e r e d in the patient w h o c h r o n i c a l l y t a k e s oral antibio t i c s or h a s r e c e n t l y b e e n hospitalized.8,22,24,53 For all patients w i t h suspected native valve e n d o c a r d i t i s w h o are not in an area in w h i c h community-acquired Pseudomonas or Serratia inf e c t i o n is seen and m e t h i c i l l i n res i s t a n c e is n o t e x p e c t e d , e m p i r i c a l therapy w i t h a penicillinase-resistant p e n i c i l l i n s u c h as n a f c i l l i n 1.5 g every four hours w i t h an aminoglycoside is a r e a s o n a b l e regiinen.S3, 54 The adjunctive use of an aminoglycoside in the initial t r e a t m e n t of S aureus i n f e c t i o n h a s b e e n s h o w n in both in vitro and a n i m a l studies to be m o r e r a p i d l y b a c t e r i c i d a l t h a n w h e n a penicillin is used alone.SS, 56 Although recent studies have failed to d e m o n s t r a t e a clinical benefit from the early use of an aminoglycoside w h e n a f o u r - w e e k course of antibiotics is used, the t i m e course of b a c t e r e m i a is d e c r e a s e d w h e n an a m i n o g l y c o s i d e is added during initial therapy.S7, s8 T h e cure rate in a recent study of a t w o - w e e k course of nafcillin and t o b r a m y c i n in patients w i t h S aureus endocarditis compared favorably w i t h cure rates w i t h fourw e e k regimens of a penicillin alone. H o w e v e r , t w o - w e e k c o u r s e s of n a f c i l l i n a l o n e h a v e s i g n i f i c a n t relapse rates. 54 W h e n Pseudomonas or Serratia is a possibility in a very ill p a t i e n t , an a n t i - P s e u d o m o n a s penicillin and an aminoglycoside should be used in addition to v a n c o m y c i n or nafcillin.SAS,24 In areas in w h i c h there is a high inc i d e n c e of m e t h i c i l l i n - r e s i s t a n t Staphylococcus or in a recently hospitalized patient or a chronic antibiotic user, v a n c o m y c i n is the drug of choice for e m p i r i c a l therapy.~2, 53 In prolonged therapy of native valve endoearditis, the c o m b i n a t i o n of vanc o m y c i n w i t h an aminoglycoside results in i n c r e a s e d r e n a l and ototoxicity with no improvement in outcome. 53 In patients w i t h prosthe20:4 April 1991

ENDOCARDITIS Delaney

tic valve endocarditis, methicillin-resistant S epidermidis is a common infecting organism. These infections are difficult to eradicate, and the combination of vancomycin with an aminoglycoside is the therapy of choice.S3,S9

PREVENTION OF NOSOCOMIAL ENDOCARDITIS The role of the emergency physician in the prevention of endocarditis emerges in several areas: identification of patients at risk and institution of appropriate prophylactic antibiotic coverage before invasive ED procedures, appropriate surgical and antibiotic treatment of localized infections, and prevention of localized infections in p a t i e n t s at risk by changing urgently placed IV catheters as soon as possible. Nosocomial endocarditis accounts for 13% to 29% of reported cases. ~,1o,ll yon Reyn et al provided a detailed analysis of 14 cases of endocarditis that followed hospital-related procedures. Twelve of these patients had known valvular heart disease (mean age, 62 years). The predisposing iatrogenic events were abscess drainage in one of 14, infected IV devices in ten of 14, and Foley catheter placement in three of 14.~ None of these patients received appropriate antibiotic therapy before the diagnosis of endocarditis. Mortality in this group was 43% compared with 15% for the entire group. The researchers believed that most of these cases would have been prevented by appropriate antibiotic therapy of local infections, changing of emergently placed lines, and prophylactic antibiotics in patients recognized to be at risk. 2 GUIDELINES FOR A N T I B I O T I C PROPHYLAXIS IN T H E ED The administration of prophylactic antibiotics before the instrumentation of patients with structural cardiac disease in an attempt to prevent bacterial endocarditis is controversial. It is most controversial when the cardiac risk factor is c o m m o n and the risk is very low (eg, mitral valve prolapse without a regurgitant murmur). It is least controversial when the risk is very high and the morbidity of infection is enormous, as in the patient with a prosthetic cardiac valve. 3~ 20:4 April 1991

Some of the controversy regarding routine prophylaxis for prevention of endocarditis comes from determinations of its efficacy. The use of prop h y l a c t i c a n t i b i o t i c s before procedures prevents very few cases of e n d o c a r d i t i s . As p r e v i o u s l y discussed, approximately 50% of patients who develop endocarditis do not have a recognizable cardiac lesion and would not be considered for prophylaxis. In patients who are not IV drug abusers, less than 20% of cases occur after a procedure for which prophylaxis would be indicated.2, 32 Prophylactic antibiotic regimens are chosen to cover those organisms most likely to cause bacteremia after a specific procedure, such as streptococci associated with oral and upper gastrointestinal instrumentation and enterococci after genitourinary and lower bowel instrumentation. These bacteria account for only two thirds of cases. Based on these c o n s i d e r a t i o n s , Kaye estimates that less than 10% of cases could be prevented by prophylactic antibiotics. 32 The incision and drainage of skin abscesses in IV drug abusers, a c o m m o n ED procedure, was not considered in the above calculations. 61 The contribution of this procedure to the incidence of cases in this population would be difficult to determine. The considerations that guide the use of prophylactic antibiotics include a number of unproven but reasonable assumptions. Trauma to mucosal surfaces increases the risk of bacteremia and subsequent endocarditis; antibiotics decrease the intensity of the bacteremia and prevent adherence to the valve; S viridans infection m o s t often follows dental procedures; Enterococcus most often follows genitourinary and lower gastrointestinal procedures; staphylococcal endocarditis follows skin infections; and persons with valvular heart disease are at increased risk of developing endocarditis. 32 No clinical trials have been accomplished to prove that prophylaxis is of benefit. In addition, it has not been demonstrated that p r o p h y l a x i s has decreased the occurrence of endocarditis in the general population.g2, 6o The American Heart Association (AHA} has established guidelines for the administration of prophylactic antibiotics before procedures.g2, 6° These are subject to the judgment of

Annals of Emergency Medicine

the clinician in individual cases. Risk/benefit analyses consider not only the cost of treatment but also complications of antibiotic administration, i n c l u d i n g a n a p h y l a x i s to penicillin, renal toxicity from a m i n o g l y c o s i d e s , and o t o t o x i c i t y from vancomycin. Prophylaxis is most strongly recommended in two groups of patients who are at very high risk of endocarditis: patients with surgically constructed systemic-pulmonary shunts and patients with prosthetic cardiac valves. 3~ The patient with a prosthetic valve has a particularly high risk of a bad outcome (59% mortality and high incidence of valve dysfunction and need for replacement) if the valve becomes infected. 9 High-risk lesions r e c o m m e n d e d for prophylaxis are most congenital cardiac malformations and rheumatic and degenerative valvular abnormalities. Relatively high-risk patients also recommended for prophylaxis include those with mitral valve prolapse with a systolic murmur and those with a history of endocarditis. 32 The risk of endocarditis in patients with asymmetric septal hypertrophy (ASH, previously called idiopathic hypertrophic subaortic stenosis) is not well defined. However, because it is a rare lesion and known to be associated with endocarditis, prophylaxis is recommended. Unlike ASH, mitral valve prolapse is a very common problem that has been estimated to be present in 6% to 10% of the population. 32 Because of its very high prevalence, mitral valve prolapse has been implicated in a number of cases of reported endocarditis.5~, 62 Most c o m p l i c a t i o n s , such as endocarditis, need for valve replacement, and sudden death, occur in the 2% to 4% of patients with mitral valve prolapse who have significant mitral insufficiency. 3 The most conservative recommendations for prophylaxis of patients with mitral valve prolapse are found in the AHA guidelines, which recommend prophylaxis in any patient with a systolic murmur associated with mitral valve prolapse. 6o A recent report noted a somewhat increased incidence of endocarditis in men and patients more than 45 years with isolated clicks and recommended consideration of prophylaxis in these cases. 3 In other cases of mitral valve prolapse with isolated sys412/113

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AHA Standard for Oral Cavity Procedures

Penicillin allergy Very-high-risk cases

Penicillin allergy

FIGURE 3. Suggested antibiotic regimens.

2 g penicillin IV orally one hour before, then 1 g six hours postprocedure or 2 million units penicillin G IV or IM 30 to 60 minutes before, then 1 million units IV at six hours postprocedure Erythromycin 1 g orally one hour before, then 500 mg orally at six hours postprocedure Ampicitlin 1 2 g IM or IV plus gentamicin 1.5 mg/kg IV or IM 30 minutes before, then 1 g penicillin VK orally six hours (if IV or IM eight hours) postprocedure Vancomycin 1 g IV over one hour

indicated by the patient's condition. Most patients do not require treatment in the ED. Rationales for the use of prophylactic antibiotics and AHA guidelines for their use in the ED are discussed and outlined (Figures 1, 2, and 3).

REFERENCES AHA Standard for Gastrointestinal or Genitourinary Procedures Minor or repetitive procedures in lower-risk patients Penicillin allergy

Kaye Recommendation for Incision and Drainage of Skin Abscess Concerning methicillin-resistant S

2. von Reyn CF, Levy BS, Arbeit RD, et al: Infective endocarditis: An analysis based on strict case definitions. Ann Intern Med 198l;94:505-518. 3. Devereux RB, Kramer-Fox R, Kligfield P: Mitral valve prolapse: Causes, clinical manifestations, and management. Ann Intern Med i989;111:305-317. 4. Simberkoff MS: Narcotic associated infective endocarditis, in Kaplan EL, Taranta AV (eds): In[ective Endocarditis. Dallas, American Heart Association, 1977, p 46-50.

Cefazolin 1.0 g IM 30 minutes belore, then cephalexin 500 mg orally at six hours postprocedure

5. Chambers HF, Morris DL, Tauber MG, et ai: Cocaine use and the risk for endocarditis in intravenous drug users. Ann hltern Med i987;106:833-836.

Vancomycin 1.0 g IV over 60 minutes

aureus

tolic click, the incidence of endocarditis is estimated to be the same as in the general population. ,~ These recommendations are summarized (Figure 1). The risk of induced bacteremia varies with the type of procedure. For example, an in-and-out bladder catheterization when the urine is not infected carries much less risk of bacteremia than the placement of an indwelling Foley catheter in a patient with a urinary tract infection. Proctosigmoidoscopy without biopsy has a lower risk than proctosigmoidoscopy with biopsy. 32 Procedures that are recommended for coverage by the AHA that might be done in the ED or in the periadmission period are any procedures in the oral cavity likely to induce gingival bleeding; bronchoscopy, especially with a rigid scope; urethral catheterization, especially in the presence of infection; and incision and drainage of infected tissue. Other ED procedures that occasionally cause bacteremia should be considered for coverage in the patient with a prosthetic valve; these are upper gastrointestinal endoscopy and proctosigmoidoscopy (without biopsy), uncomplicated vaginal delivery, and in-and-out bladder catheterization with sterile urine 3~ (Figure 2). Antibiotic regimens suggested by 114/413

1. Reisberg BE: Infective endocarditis in the narcotic ~d- I dict. Prog Cardiow2sc Dis 1979~22:193-204. !

Ampicillin 2 g IV or IM plus gentamicin 1.5 mg/kg IV or IM 30 minutes before procedure; may repeat eight hours postprocedure Amoxicillin 3.0 g orally one hour before, then 1.5 g orally at six hours postprocedure Vancomycin 1.0 g IV over one hour plus gentamicin 1.5 mg/kg IV or IM one hour before procedure; may repeat at eight to 12 hours postprocedure

3 the AHA are listed (Figure 3). These are divided into regimens for oral, upper gastrointestinal and respiratory tract, and lower gastrointestinal and genitourologic procedures. These recommendations include more aggressive parental regimens for patients who fall into the very-high-risk categories.

SUMMARY The majority of patients who present to the ED with endocarditis belong to one of two risk groups: IV drug abusers or patients with structural cardiac disease. The second group may be difficult to identify because of an absence of a known history, although a murmur is often detected on presentation. The complications of endocarditis have been reviewed because they might be encountered by the emergency physician. The clinical characteristics of endocarditis and their relation to the nature of the infecting organism and sites of infection were discussed for each risk group. Guidelines for evaluation and admission were offered. Management in the ED requires a decision about the need for early versus delayed antibiotic therapy and requires that adequate numbers of blood cultures be obtained to ensure the diagnosis if empirical therapy is Annals of Emergency Medicine

6. Marantz PR, Linzer M, Feiner CJ, et al: Inability to predict diagnosis in febrile intravenous drug abusers. Ann Intern Med 1987;106:823-828. 7. 8amet JH, Shevitz A, Fowle J, et al: Hospitalization decision in febrile intravenous drug abusers. A m J Med 1990;89:53~57. 8. Crane RC, Levine DP, Zervos MJ, et al: Bacteremia in narcotic addicts at the Detroit Medical Center: I. Microbiology, epidemiology, risk factors, and empiric therapy. Rev In~ect Dis 1986;8:364-373. 9. Wilson WR, Danielson GK, Giuliani ER, et al: Prosthetic valve endocarditis. Mayo Clin Proc 1982;57: 155-161. 10. Pelletier LL Jr, Petersdorf RG: Infective endocarditis: A review of 125 cases from the University of W a s h i n g t o n h o s p i t a l s , 1963-72. M e d i c i n e 1977; 56:287-813. 1I. Garvey GJ, Neu HC: Infective endocarditis evolving disease. Medicine 1978;57:105-127.

An

12. Levine DP, Cushing RD, fui J, et al: Bacteremia in narcotic addicts at the Detroit Medical Center: II. Infectious endocarditis: A prospective comparative study. Rev Infect Dis i986;8:374. 13. Dryer NP, Fields BN: Heroin-associated infective endoearditis: A report of 28 cases. Ann Intern Meal 1973;78:699-702. 14. Gilroy J, Andaya L, Thomas VJ: Intracranial mycotic aneurysms and subacute bacterial endocarditis in heroin addiction. Neurology 1973;23:i193-1198. 15. Reyes MP, Paiutke WA, Wylin RF, et al: Pseu domonas endocarditis in the Detroit Medical Center 1969 1972. Medicine 1973;52:173-194. 16. Bain RC, Edwards JE, Schiefley CH, et al: Rightsided bacterial endoearditis and endarteritis. A m J Med 1958;24:98-110. 17. Maisel AS, Atwood JE, Goldberger AL: HepatojuguIar reflux: Useful in the diagnosis of tricuspid regurgitation. A~n Intern Med 1984;101:78l. 18. Fry DE, Richardson JD, h i n t LM: Occult splenic ab~ scess: An unrecognized complication of heroin abuse. Surgery 1978;84:650-654. 19. Nallathambi MN, Ivatury RR, Lankin DH~ et al: Pyogenic splenic abscess in intravenous drug addiction. Am Surg 1987;53:342-346. 20. H o w a r d EJ: O s l e r ' s nodes. A m Heart ]" 1960~ 59:633-634. 21. Cross DF, Ellis JG: Occurrence of the Janeway Ie-

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si0n in mycotic aneurysm. Arch Intern Med 1966;118: 588-591. 22. Levine DP, Cushing RD, Jui J, et ah Communityacquired methicillin-resistant Staphylococcus aureus endocarditis in the Detroit Medical Center. Ann Intern Med 1982;97:330-338. 23. Werner AS, Cobbs CG, Kaye D, et al: Studies on the bscteremia of bacterial endocarditis. JAMA 1967;Z02: I99-203. 24. Mills J, Drew D: Serratia marcescens endocarditis: A regional illness associated with intravenous drug abuse. Ann Intern Med 1976;84:29-35. 25. Nohinek B, Zee-Cheng ZC, Barnes WG, et ah Infective endocarditis of a bicuspid aortic valve caused by Hansenula anomala. A m J Med 1987;82:165-168. 26. Vartian CV, Shlaes DM, Padhey AA, et ah Wan giefla dermatJtJdis endocarditis in an intravenous drug user. Am J Med 1985;78:703~707. 27. Kolander SA, Cosgrove EM, Molavi A: Clostridial endoearditis: Report of a case caused by CIostridium bL fsrmentans and review of the literature. Arch Intern Med 1989;149:455-456. 28. Raucher B, Dobkin J, Mandel L, et al: Occult polymicrobial e n d o c a r d i t i s w i t h Haemophilus para influenzas in intravenous drug abusers. A m J Med 1989;86:169-172. 29. Planthoh SJ, Trofa AF: Citrobacter freundii endocsrditis in an intravenous drug abuser. South Med f 1987;80:1439-1441. 30. Relman DA, Ruoff K, Ferraro MJ: Stomatococcus mucilagdnosus endocarditis in an intravenous drug abuser. J Infect Dis i987;155:1080-1082. 31. Bayer DS, Lain K, Ginzton L, et al: Staphylococcus aureus bacteremia: Clinical, serologic, and echocardiographic findings in patients with and without endocarditis. Arch Int Med I987;147:457-462. 32. Kaye D: Prophylaxis for infective endocarditis: An update. Ann Intern Med 1986;104:419-423. 33. Everett ED, Hirschmann JV: Transient bacteremia and endocarditis prophylaxis: A review. Medicine 1977;56:61-77.

34. Aronson ME), Gor DH: Blood cultures. Ann Intern Med 1987;106:246-253. 35. Durack DT, Beeson PBJ: Experimental bacterial endocarditis: I. Colonization of a sterile vegetation. Br J

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Exp Pathol 1972;53:44-49.

36. Weinstein MP, Relier LB, Murphy JR, et al: The clinical significance of positive blood cultures: A comprehensive analysis of 500 episodes of baeteremia and fungemia in adults: I. Laboratory and epidemiologic observations. Rev Infect Dis 1983;5:35~53. 37. Saravolatz LD, Markowitz N, Arking L, et ah Methicillin-resistant Staphylococcus aureus: Epidemiologic observations during a community-acquired outbreak. Ann Intern Med i982;96:11-16. 38. Tuazon C, Seagren JN: Staphylococcal endocarditis in parenteral drug abusers: Source of the organism. Ann Intern Mect 1975~82:788-790. 39. 8orrell TC, Dunlop C, .Gollignon PJ, et ah Exogenous ocular candidiasis associated with intravenous heroin abuse. Br J OphthalmoJ 1984;68:846845.

50. Barg NL, Kish MA, Kauffman CA, et ah Group A streptococcal bacteremia in intravenous drug abusers. A m J Med 1985;78:569-574. 51. Nolan CM: Staphylococcus aureus bacteremia. A m J Med 1976;60:495-500. 52. Baddour LM, Phillips TN, Bisno AL: Coagulase-neg~ a t i v e s t a p h y l o e o c c a l endocarditis. Arch l n t Med 1986;146:119d21. 53. Karchmer AW: Staphylococcal endocarditis: Laboratory and clinical basis for antibiotic therapy. A m J Med 1985;78(suppl 6B):116-127. 54. Chambers HF, Miller RT, N e w m a n MD: Rightsided Staphylococcus aureus endocarditis in intravenous drug abusers: Two-week combination therapy. Ann Intern Med 1988;109:619-624.

40. Alvarez-Elcoro 8, 8ifuentes-Osorio J: Clostridium perfringens bacteremia in prosthetic valve endoearditis. Arch Intern Med 1984;144:849-850.

55. Sands MA, Johnson MS: Antimicrobial therapy of experimental endocarditis caused by Staphylococcus aureus. J Infect Dis 1975;131:367-875.

41. Craig CP: Bacilhls cereus endocarditis in an addict. Ann Intern Med 1974;80:418.

56. Lambelin G: Evidence for the in vivo synergism between peniciliin and kanamycin. Chemotherapy 1972; 17:3564363.

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Annals of Emergency Medicine

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