Thomas F. Keys

Neurologic complications of endocarditis A 12‐year experience

We reviewed the neurologic complications in 113 patients with native and 62 patients with prosthetic valve endocarditis. Neurologic complications occurred with the same frequency (35.3% vs 38.7%) and distribution among the two groups. Death occurred in 20.6% of patients with neurologic complications and in 13.6% of patients without neurologic complications (p = 0.23). Staphylococcus aureus endocarditis correlated statistically with the development of neurologic complications (p < 0.01) and death (p < 0.01). Among 50 patients discharged from the hospital after receiving only medical treatment for native valve endocarditis, and followed for a mean period of 48 months, there was one patient with mitral valve prolapse and stroke. We conclude that (1) neurologic complications occur with the same frequency in native and prosthetic valve endocarditis, (2) S aureus endocarditis increases the risk of neurologic complications and death, (3) mortality is not significantly increased in patients with neurologic complications, and (4) an episode of treated native valve endocarditis does not increase the natural history of stroke in valvular disease.

Prosthetic Valve Endocarditis Resulting from Nosocomial Bacteremia: A Prospective, Multicenter Study

More than 100 000 artificial heart valves are implanted annually in the United States, and the number is increasing [1]. Because the number of invasive therapeutic and diagnostic procedures done during hospitalization is also increasing, the risk for bacteremia is correspondingly greater. A common dilemma for the clinician is determining the optimal therapeutic approach to a patient with a prosthetic valve who develops bacteremia. There has been controversy regarding the optimal duration of antibiotic therapy for bacteremic patients with prosthetic valves. An informal survey of infectious disease and cardiology specialists revealed that the recommended duration of therapy ranged widely, from 10 days to 8 weeks. To clarify this issue, we conducted a prospective, observational, multicenter study during a 3-year period in six university teaching hospitals with high-volume cardiac surgery. Our objectives were to determine 1) the incidence of endocarditis in bacteremic patients with an implanted heart valve, 2) the risk factors for development of subsequent prosthetic valve endocarditis, and 3) the optimal duration of antibiotic therapy in this select group of patients who experience bacteremia. We also report mortality rates. Methods We did a prospective, observational study at six university teaching hospitals: The Cleveland Clinic, Cleveland, Ohio; St. Lukes Episcopal Hospital, Houston, Texas; Rush-Presbyterian-St. Lukes Medical Center, Chicago, Illinois; St. Vincent Hospital and Medical Center, Portland, Oregon; Hunter-McGuire Veterans Affairs Medical Center, Richmond, Virginia; and Presbyterian University Hospital and Veterans Affairs Medical Center, Pittsburgh, Pennsylvania. The study lasted approximately 2 years at each hospital and was conducted in the period from 1986 to 1989; start dates differed among hospitals. Bacteremic patients were identified through a daily review of blood culture results in the microbiology laboratory; these patients were then screened by the infection control practitioner for presence of a prosthetic heart valve. The study group comprised bacteremic patients with a prosthetic valve who were prospectively monitored during the hospitalization and after discharge for 1 year. All treatment decisions were made by the attending physicians without intervention by the investigators. Bacteremia was considered to be present if one or more blood cultures yielded an organism. Endocarditis was classified as definitive, presumptive, and suspicious. Definitive endocarditis was defined by 1) culture positivity or proven pathology [demonstration of vegetations or isolation of the organism from a prosthetic valve obtained at autopsy or during open heart surgery] or 2) vegetations documented on echocardiogram. Presumptive endocarditis was defined by peripheral embolic signs, including Osler nodes, Janeway lesions, Roth spot, petechiae, splenomegaly, acute cerebrovascular accident; or a new or changing murmur. The criterion for suspicious endocarditis was sustained bacteremia (defined by three positive blood cultures of three or the occurrence of at least four positive blood cultures within 72 hours) with no identified portal of entry. Thus, four positive cultures obtained within 72 hours fulfilled the criterion for suspicious endocarditis, whereas two positive of two or three positive of four blood cultures obtained within 72 hours did not. Demonstration of vegetations by transthoracic echocardiography in a bacteremic patient with a prosthetic valve was arbitrarily considered as definitive evidence for endocarditis; transesophageal echocardiography was not routinely done at the time of study. Patients were classified as having bacteremia only, as having bacteremia with endocarditis at the outset, or as having bacteremia with subsequent development of new endocarditis (Table 1). Patients who were identified as having endocarditis at the time the initial blood culture was obtained were classified as having endocarditis at the outset. Patients in whom bacteremia led to the subsequent development of prosthetic valve endocarditis were classified as having new endocarditis. Table 1. Criteria for Diagnosis of Endocarditis The portal of entry for bacteremic infection was defined by isolation of the same organism from a source other than blood or cardiac vegetation and by review of the patient record by the investigators. Subtyping of the isolates was not done. We assessed severity of illness for each patient at the time of bacteremia using an index based on mental status, vital signs, the need for respiratory support, and the occurrence of cardiac arrest; previous investigators have found this index to be highly predictive of outcome [2-4]. All bacteremic patients with prosthetic valves were prospectively studied for up to 1 year after the onset of bacteremia. Outcome and cardiac status were assessed 1, 2, 6, and 12 months after the detection of bacteremia. Discharged patients had telephone follow-up on chart review at 6 and 12 months. Clinical and laboratory data for analysis were entered into a computer database (Prophet Systems, Division of Research Resources, National Institutes of Health, Bethesda, Maryland). Categorical data were analyzed using a chi-square or Fisher exact test. Continuous variables (age, days hospitalized, and laboratory values) were compared using the t-test or Newman-Keuls test. A multiple regression model was used to examine the effects of several factors on the development of endocarditis. The regression model was also used to evaluate the risk factors for death. Factors used in the regression model were those found to be significant by univariate analysis and those hypothesized to seriously affect outcome. Results One hundred seventy-one patients with bacteremia and a prosthetic heart valve constituted the study group. The mean number of positive blood cultures per patient was 3.0 and the median number was 3.6 (range, 1 to 14 blood cultures). All patients had fever, which was usually the motivating factor for obtaining the blood culture. At 6 months, follow-up data were complete for all 171 study patients. By 12 months, 4 patients with bacteremia had been lost to follow-up, but follow-up data were obtained on all 74 patients with endocarditis. Patient age ranged from 23 to 89 years (mean age, 65 years). Bacteremic patients were significantly older (mean age, 69 years) than those with endocarditis (mean age, 60 years) (P < 0.001). Other clinical and demographic characteristics are shown in Table 2. Table 2. Demographic and Clinical Characteristics of 171 Patients with Bacteremia Who Had Prosthetic Valves Endocarditis Seventy-four of 171 patients (43%) were classified as having prosthetic valve endocarditis. Of these 74 patients, 42 (57%) were classified as having definitive endocarditis, 22 (30%) as having presumptive endocarditis, and 10 (13%) as having suspicious endocarditis. Of the 171 study patients, 56 (33%) were classified as having endocarditis at the time bacteremia occurred (endocarditis at the outset) and 18 (10%) as having endocarditis that developed after bacteremia (new endocarditis). The remaining 97 patients (57%) with bacteremia had no evidence of endocarditis (see Table 2). Twenty-three patients had vegetations detectable by transthoracic echocardiography: Seven patients were classified as having definitive prosthetic valve endocarditis based solely on echocardiographic demonstration of vegetations; another 6 patients had abnormal echocardiographic findings but also showed other objective evidence of endocarditis (including new or changing murmur and peripheral stigmata); and 10 patients with abnormal echocardiographic findings had the diagnosis confirmed at open heart surgery or at autopsy. Transesophageal echocardiography was not routinely used at the time of our study. Of the 74 patients with prosthetic valve endocarditis, 2 (3%) had peripheral embolism (cerebral emboli or cerebrovascular accident), 15 (20%) had stigmata (Osler nodes, Janeway lesions, Roth spot, petechiae), 4 (5%) had splenomegaly, and 23 (31%) had new or changing murmur. No significant difference was found regarding the presence of these signs between patients with new endocarditis and those with endocarditis at the outset (data not shown). Location and Type of Valvular Prosthesis Eighty-seven of the 171 study patients (51%) had prosthetic mitral valves, 102 (60%) had prosthetic aortic valves, and 8 (5%) had prosthetic tricuspid valves (the number of patients totals more than 171 because 25 patients [15%] had more than one prosthetic valve) (Table 3). Presence of a prosthetic mitral valve was seen significantly more often in patients with new endocarditis (P = 0.005), whereas prosthetic aortic valves were seen significantly more often in patients with endocarditis at outset (P < 0.001) (Table 3). Of the 171 study patients, 82 (48%) had mechanical valves and 87 (51%) had biological valves (including 5 patients with both mechanical and biologic valves). In seven cases (4%), the exact valve type was not known because the operation had been done elsewhere and past medical records were not available (see Table 3). No association was observed between type of valve and the occurrence of endocarditis. Table 3. Valvular Location and Type in 171 Bacteremic Patients with Prosthetic Valves Timing of Endocarditis Prosthetic valve endocarditis has been arbitrarily classified as early when it occurs within 60 days of valve insertion and late when it occurs more than 60 days after valve insertion [5]. Of the 74 patients with prosthetic valve endocarditis, 23 (31%) were classified as having early endocarditis and 51 (69%) as having late endocarditis. Twelve of the 18 patients (67%) with new endocarditis were classified as having early onset disease compared with 11 of 56 patients with endocarditis at the outset (difference, 48%; 95% CI, 19 to 75; P < 0.001). Cause of Bacteremia As shown in Table 4, 206 o

Mycotic aneurysm, subarachnoid hemorrhage, and indications for cerebral angiography in infective endocarditis.

We compared the clinical course of 68 patients with infective endocarditis and mycotic aneurysm and 147 patients with infective endocarditis but no mycotic aneurysm. Among the patients with mycotic aneurysm, 57% had subarachnoid hemorrhage without warning. Forty-three percent had a neurologic prodrome 2 days to 18 months (median 17 days) prior to discovery of the mycotic aneurysm. A focal deficit consistent with embolism was the most common prodrome (23%). However, there was no significant difference in the frequency of neurologic symptoms between patients with and without mycotic aneurysm. During an average follow-up of 40 months, there were no instances of subarachnoid hemorrhage/mycotic aneurysm among 121 patients discharged after a full course of antibiotic therapy. Therefore, the risk of rupture of an unsuspected mycotic aneurysm following a full course of antibiotics is low. When a prodrome does precede a mycotic aneurysm, it most often is a focal deficit consistent with embolism. We favor angiography in all patients with infective endocarditis who experience a focal deficit with good recovery. The timing and other indications for angiography in infective endocarditis are discussed.

Fungal prosthetic valve endocarditis in 16 patients. An 11-year experience in a tertiary care hospital.

&NA; Abbreviations used in this article: NVE, native valve endocarditis; PVE, prosthetic valve endocarditis; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.

Hepatic abscess after liver transplantation: 1990-2000.

Background. Infections following solid-organ transplants are a major cause of morbidity and mortality. Few studies have reported the complications of hepatic abscesses. Methods. This investigation consisted of a retrospective chart review of all solid-organ transplant recipients from 1990 to 2000. Criteria for diagnosis included parenchymal hepatic lesions, positive cultures from liver aspirates or blood cultures, or both, and a compatible clinical presentation. Results. Of 2175 recipients of all organ transplants (heart, lung, kidney, liver, pancreas), we identified 12 patients who had experienced 14 episodes of hepatic abscess, all in liver transplant recipients. Median time from transplant to hepatic abscess was 386 days (range 25–4198). The most common predisposing factor was hepatic artery thrombosis (HAT), which occurred in eight patients, and was diagnosed at an average of 249 days (range 33–3215) after transplantation. Clinical presentation of hepatic abscess was similar to that described in non-immunosuppressed patients. All but one patient showed hypoalbuminemia (<3.5 g/dL); those with HAT also had significantly elevated lactate dehydrogenase. Liver aspirates grew gram-positive aerobic bacteria (50% of isolates), gram-negative aerobic bacteria (30%), and anaerobes and yeasts (10% each). Patients received an average of 6 weeks of intravenous antibiotic therapy. Catheter drainage was successful in 70% of cases; and five patients required retransplantation. Altogether, five of the patients died, yielding a mortality rate of 42%. Conclusions. Hepatic abscess, a rare complication after liver transplantation, was frequently associated with hepatic artery thrombosis. Mortality was higher than in patients who had not undergone transplantation. Prolonged antibiotic therapy, drainage, and even retransplantation may be required to improve the outcome in these patients.

Secular Trends in Nosocomial Bloodstream Infections in a 55-Bed Cardiothoracic Intensive Care Unit

BACKGROUND Although bloodstream infections (BSIs) occur more frequently in intensive care unit patients than in ward patients, most studies of nosocomial BSIs in critically ill patients have not distinguished between intensive care unit populations beyond surgical, medical, and pediatric patients. METHODS The primary objective of this study was to characterize the secular trends in rates of nosocomial BSIs for all pathogens among patients admitted to a busy cardiothoracic intensive care unit in a single tertiary care institution between January 1986 and December 1995. Patients with nosocomial BSIs were identified through continual prospective surveillance. RESULTS A total of 40,207 patients were admitted to the cardiothoracic intensive care unit during the 10-year study period, and 804 episodes of nosocomial BSIs among 681 patients were identified. The mean crude BSI infection rate was 6.0 per 1,000 patient-care days and increased linearly during the study period (range, 4.4 to 8.1 per 1000 patient-care days), and approached statistical significance (p value = 0.07). The most common organisms causing BSIs were Staphylococcus aureus (12%), coagulase-negative staphylococci (11%), Candida albicans (11%), Pseudomonas aeruginosa (10%), and Enterococci (9%). The leading sources of nosocomial BSIs were primary BSIs (33%), intravascular devices (27%), lower respiratory tract infections (17%), and surgical wound infections (12%). The etiologic fraction or the proportion of deaths in cardiothoracic intensive care unit patients with BSIs was 15-fold higher than those patients without BSIs (37% versus 2.5%, p < 0.001). CONCLUSIONS Rates of nosocomial BSIs among patients in our cardiothoracic intensive care unit have increased linearly during the past decade and patients with nosocomial BSIs have an increased risk of in hospital mortality.

Microbiology of liver abscesses and the predictive value of abscess gram stain and associated blood cultures.

Although rare, pyogenic liver abscesses are potentially fatal. We evaluated the predictive value of Gram stain of liver abscess aspirates and temporally associated blood cultures. Gram stains detected bacteria in 79% of the liver abscesses tested. The sensitivity and specificity of Gram stain of the liver abscesses were 90% and 100% for Gram-positive cocci (GPC) and 52% and 94% for Gram-negative bacilli (GNB). The sensitivities of the blood cultures for any GPC and GNB present in the liver abscess were 30% and 39%, respectively. Although, Gram stains and blood cultures offer incomplete detection of the microbial contents of pyogenic liver abscesses, both tests should always accompany liver abscess cultures.

Reactive hemophagocytic syndrome associated with disseminated histoplasmosis in a heart transplant recipient

We describe a patient who developed multi-organ failure with reactive hemophagocytic syndrome secondary to disseminated histoplasmosis 8 months after orthotopic heart transplantation. The patient responded fully to a prolonged course of therapy with amphotericin B and remains free of recurrence. Disseminated histoplasmosis and reactive hemophagocytic syndrome have rarely been described in the setting of cardiac transplantation and never before in combination.

A multivariate analysis of risk factors for pneumonia following cardiac transplantation

Fifty cardiac transplant recipients were followed over a 34-month period for evidence of pneumonia that developed in twelve patients. Potential risk factors evaluated fell into three categories: demographic (age, sex, race, and underlying cardiac disease); pretransplant status (hospitalized, intubated, pulmonary infiltrate, requirement for antibiotics, or the need for a ventricular assist device); and posttransplant therapy (amount and type of blood products, prolonged endotracheal intubation or reintubation, use of ventricular assist devices, immunosuppressive protocols, lymphocyte subset ratios, and occurrence of rejection, leukopenia, or CMV infection). The Cox proportional hazards model identified posttransplant reintubation (P = 0.009) and the use of protocols employing larger steroid dosages (P = 0.02) as significant risk factors for pneumonia. In a separate analysis, the occurrence of pneumonia was shown to be a significant risk factor for mortality (P = 0.018).

Cost of Cardiac Care in the Three Years After Coronary Catheterization in a Contained Care System: Critical Determinants and Implications

OBJECTIVES We sought to determine the clinical, angiographic, treatment and outcome correlates of the intermediate-term cost of caring for patients with suspected coronary artery disease (CAD). BACKGROUND To adequately predict medical costs and to compare different treatment and cost reduction strategies, the determinants of cost must be understood. However, little is known about the correlates of costs of treatment of CAD in heterogeneous patient populations that typify clinical practice. METHODS From a consecutive series of 781 patients undergoing cardiac catheterization in 1992 to 1994, we analyzed 44 variables as potential correlates of total (direct and indirect) in-hospital, 12- and 36-month cardiac costs. RESULTS Mean (+/-SD) patient age was 65+/-10 years; 71% were men, and 45% had multiple vessel disease. The initial treatment strategy was medical therapy alone in 47% of patients, percutaneous intervention (PI) in 30% and coronary artery bypass graft surgery (CABG) in 24%. The 36-month survival and event-free (death, infarction, CABG, PI) survival rates were 89.6+/-0.2% and 68.4+/-0.4%, respectively. Median hospital and 36-month costs were