Oksana M. Korzeniowski

Dental and Cardiac Risk Factors for Infective Endocarditis: A Population-Based, Case-Control Study

Infective endocarditis is uncommon but potentially fatal. Administration of antibiotic prophylaxis is conventional [1], but data supporting its effectiveness derive solely from anecdotal reports, studies of bacteremia after dental and other procedures, and animal models. The low incidence of disease [2] has made randomized human trials of antibiotic effectiveness impractical. Even if effective, antibiotic prophylaxis should be reserved for patients at increased risk, such as those with cardiac abnormalities who are undergoing dental procedures. However, controlled human studies of risk factors are lacking. Previous case series indicate that approximately 15% of patients with infective endocarditis caused by mouth organisms had undergone a recent dental procedure [3], but the comparable percentage from a general population is unknown. The single hospital-based casecontrol study did not find an elevated risk associated with dental therapy, except for a borderline increase with dental scaling [4]. We are unaware of controlled human studies that quantify the risk for infective endocarditis associated with cardiac valve abnormalities other than mitral valve prolapse. We therefore conducted a population-based casecontrol study to evaluate and quantify risk factors for infective endocarditis, especially those considered by the American Heart Association (AHA) to be indications for antibiotic prophylaxis [1]. Methods Participants From August 1988 to November 1990, we maintained surveillance for infective endocarditis in 54 hospitals of the Delaware Valley Case-Control Network, a population-based network of hospitals in the eight counties that constitute the Philadelphia Metropolitan Statistical Area and the county of New Castle, Delaware. Patients with a putative diagnosis of infective endocarditis were identified by hospital personnel and were reported to study nurses, who also actively sought cases. To assess the completeness of ascertainment, five high-yield hospitals and three low-yield hospitals were asked to list all patients discharged with a diagnosis of endocarditis over 3 months. These lists were compared with those obtained from our surveillance; charts were reviewed when differences were identified. We obtained informed consent from physicians and case-patients, then used structured forms to abstract medical records, including echocardiographic reports and hospital laboratory information on the infecting organism. We deleted information on purported risk factors for infective endocarditis and submitted these records for review by three of the authors, who are consultants in infectious diseases recognized for their expertise in infective endocarditis [5, 6]. These experts used their own global clinical judgment to classify potential cases as definite, probable, or possible cases or probable noncases. Agreement of two of the three reviewers was required to make the determination of a case or a noncase [6]. One control from the community was selected for each case-patient by using a modification of the Waksberg random-digit dialing method [7]. Controls and case-patients were matched for age (in 5-year strata), sex, and neighborhood of residence (by using area code, telephone exchange, and the first subsequent digit of the case-patients telephone number). We excluded from these analyses patients with infective endocarditis who were younger than 18 years of age, intravenous drug users, and patients who developed endocarditis in the hospital. This study received separate institutional review board approval at the University of Pennsylvania and all 54 participating hospitals. Data Collection Information was obtained from case-patients by conducting a structured telephone interview after hospital discharge. The date of hospital admission served as the study date for case-patients; for controls, the date of the telephone interview was used. Telephone interviewers collected information on demographic characteristics; diagnostic and therapeutic medical and dental procedures in the year before the study date; potential host risk factors, including preexisting cardiac lesions, preexisting local infection, risk factors for oral or dental disease, diabetes mellitus, immune deficiencies, family history of endocarditis, alcoholism, malignant conditions, and autoimmune disease; previous antibiotic use; and other recent illnesses. For each host risk factor, we requested the date of diagnosis, diagnostic method (for example, echocardiography for mitral valve prolapse), and the name of the practitioner who made the diagnosis. For each medical and dental procedure, we sought information about the procedure, the month and year in which it was performed, and the practitioner. We requested medical and dental records describing procedures and validating individual diagnoses. Study Variables Case-patients were considered infected with dental flora if the organism found was viridans streptococci; nutritionally variant streptococci; Actinobacillus species; Cardiobacterium hominis; anaerobes; -hemolytic streptococci (not group D); unspecified streptococci; or Haemophilus, Eikenella, Kingella, or Neisseria species. Because this study focused on indications for antibiotic prophylaxis, we examined host characteristics reported by patients as the primary risk factor variables, reflecting the information that would be available to a practitioner about to perform a procedure for which prophylaxis might be indicated. A variable called any valvular heart abnormality was defined as the presence of any of the following self-reported, preexisting conditions: mitral valve prolapse, congenital heart disease, history of rheumatic fever with heart involvement, prosthetic heart valve, previous episode of endocarditis, or other valvular heart disease. Dental visit information was obtained solely from dental records. Dental hygiene care was defined as preventive oral health services and therapeutic services, including coronal scaling and polishing. Consistent with AHA guidelines, invasive dental procedures were defined to include dental hygiene care, extractions, periodontal treatment (including scaling and root planing), endodontic treatment, mouth or gingival surgery, and treatment of tooth abscess. Noninvasive dental procedures were simple restorations, prosthetic and restorative dentistry, fluoride treatment, and other procedures (prosthetic services, including adjustments and suture removal). Unless otherwise specified, dental treatment refers to all dental treatment and is not limited to invasive procedures. Initial analyses focused on dental procedures performed at any time in the 3 months before the study date. Analyses were then narrowed to 2 months and 1 month before the study date. Time frames are approximate because the onset of infective endocarditis is often difficult to determine with certainty. We therefore chose the date of hospital admission as the study date, collected procedural data based on month rather than on a specific date, and calculated time frames under the assumption that procedures were performed on the 15th of the month. Statistical Analysis Frequencies and cross-tabulations between casecontrol status and potential risk factors were obtained. Conditional logistic regression was used to determine the independent effects of the various potential risk factors and the possibility of any interactions among factors [8]. Variables were included in multiple regression models if they were significant (P < 0.2) in unadjusted (matched) analyses (such as kidney disease and diabetes), if their inclusion had a substantial effect (>15% change) on coefficients for variables already in the model (such as insurance status) [9], or if they were strongly suspected a priori of being confounders (such as ethnicity). For analyses specific to participants with known cardiac valvular abnormalities, odds ratios and CIs were calculated from a model that included main effects for cardiac valvular abnormalities and dental treatment and the interaction between those variables. The odds ratio for various dental therapy variables among participants with cardiac valvular abnormalities was estimated by combining coefficients for the dental therapy variable and the interaction term. The CI for this combination of coefficients was estimated by using the appropriate variance and covariance terms [8]. With the interaction terms, participants with and those without valvular abnormalities were included in these analyses. Exact odds ratios and CIs, stratified on the matching variables, were calculated when data were too sparse for conditional logistic regression [10]. We used SAS statistical software (SAS Institute Inc, Cary, North Carolina) for data management and to obtain frequencies and cross-tabulations. We used EGRET (Epidemiological Graphics, Estimation and Testing software, version 0.25.1, Cytel Software Corp., Cambridge, Massachusetts) for conditional logistic regressions and exact analyses. All CIs are 95%, and all P values are two-sided. The sample size for the study was chosen so that by assuming an level of 0.05 (two-sided) and a power of 80%, we would be able to detect associations with an odds ratio of 2.0 or more for risk factors with a prevalence between 0.1 and 0.8. Results Participants We identified and recruited 416 potential case-patients (Figure 1). Our assessment process confirmed that more than 90% of true cases of infective endocarditis had been identified. The expert panel judged 379 patients to have definite, probable, or possible infective endocarditis; 37 (9%) were judged to be probable noncases and were excluded. Agreement among judgments was high, ranging from 92% to 96% [6]. Figure 1. Enrollment of case-patients. Of these 379 patients, 287 had community-acquired infective endocarditis not associated with intravenous drug use (248 on native valves and 39 on prosthetic valves), 27 had nosocomial infective endocarditis (18 on nativ

Combination Antimicrobial Therapy for Staphylococcus aureus Endocarditis in Patients Addicted to Parenteral Drugs and in Nonaddicts: A Prospective Study

Single (nafcillin for 6 weeks) and combined (nafcillin for 6 weeks plus gentamicin for 2 weeks) drug regimens were compared in two separate multicenter prospective randomized trials. Forty-eight parenteral drug addicts and 30 nonaddicts with clinically and bacteriologically documented Staphylococcus aureus endocarditis were studied. In the addicts, combined therapy effected a more rapid mean clinical response (defervescence and normalization of leukocyte count) and a reduced duration of bacteremia in patients with right-sided endocarditis. In the nonaddicts, combined therapy effected more rapid clearance of bacteremia, but was associated with a higher incidence of azotemia. The addition of gentamicin did not alter morbidity or mortality in either group.

Risk Factors for Infective Endocarditis Oral Hygiene and Nondental Exposures

Background—The risks of infective endocarditis (IE) associated with various conditions and procedures are poorly defined. Methods and Results—This was a population-based case-control study conducted in 54 Philadelphia, Pa–area hospitals from 1988 to 1990. Community-acquired IE cases unassociated with intravenous drug use were compared with matched community residents. Subjects were interviewed for risk factors. Diagnoses were confirmed by expert review of medical record abstracts with risk factor data removed. Cases were more likely than controls to suffer from prior severe kidney disease (adjusted OR [95% CI]=16.9 [1.5 to 193], P =0.02) and diabetes mellitus (adjusted OR [95% CI]=2.7 [1.4 to 5.2], P =0.004). Cases infected with skin flora had received intravenous fluids more often (adjusted OR [95% CI]=6.7 [1.1 to 41], P =0.04) and had more often had a previous skin infection (adjusted OR [95% CI]=3.5 [0.7 to 17], P =0.11). No association was seen with pulmonary, gastrointestinal, cardiac, or genitourinary procedures or with surgery. Edentulous patients had a lower risk of IE from dental flora than patients who had teeth but did not floss. Daily flossing was associated with a borderline decreased IE risk. Conclusions—Within the limits of the available sample size, the data showed that IE patients differ from people without IE with regard to certain important risk factors but not regarding recent procedures.

Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts.

Data collected from a prospective multicenter study of endocarditis caused by S. aureus were analyzed to contrast the clinical presentation of the disease between a group of 46 intravenous drug addicts and a group of 35 nonaddicts. Two-thirds of the patients in each group were men. The duration of illness before diagnosis was similar (mean, 9.3 days). Intravenous-drug addicts were younger and had less underlying disease (30% versus 80%) than the non-addicts. When first seen, the drug addicts had signs and symptoms of sepsis and pulmonary embolism, but only 40% had pathologic murmurs. Seventy-six percent had evidence of tricuspid valve infection only. Congestive heart failure and neurologic manifestations were uncommon in addicts. Nonaddicts had infection involving predominantly the left side of the heart (14 mitral valves, 8 aortic valves, 4 both aortic and mitral valves) and 80% had underlying medical diseases. Only half of these patients had pathologic murmurs when first examined, but another 30% developed them later. Congestive heart failure, involvement of the central nervous system, and peripheral embolic or septic complications each occurred in over half of the nonaddicts. Eighty percent of these patients had peripheral stigmas of endocarditis. One intravenous drug addict (2%) and seven nonaddicts (20%) died. Six patients required cardiac valve replacement either during or after a course of antibiotics. Outcome was not related to the titer of peak serum bactericidal tests. Endocarditis caused by S. aureus presents as two distinct clinical syndromes depending on the patient population (intravenous drug user or nonaddict) and the location of infection (right-sided or left-sided). The disease is distinguished from endocarditis due to other causes by its acute onset and its fulminant course manifested by a multitude of septic and embolic complications and its ability to cause heart failure. Medical management alone is often successful but in certain subsets of patients, notably those with infection of aortic or multiple valves, early operation may be necessary.

An Assessment of the Usefulness of the Duke Criteria for Diagnosing Active Infective Endocarditis

We evaluated the usefulness of the Duke criteria for diagnosing cases of active infective endocarditis (IE). Patients were identified prospectively over a 3-year period at 54 hospitals in the Philadelphia metropolitan area. Three of us independently reviewed abstracted hospital records and classified 410 patients as definite, probable, or possible cases of IE or as probable noncases. We then applied the Duke criteria to this sample to assess the degree of agreement between our diagnoses and the diagnoses based on these new criteria. Agreement was good to excellent, ranging from 72% to 90%, depending on the case definition used. The sensitivity of the Duke criteria was also good to excellent, varying from 71% to 99%, again depending on case definition used. Specificity was lower (0-89%). We conclude that use of the Duke criteria will result in little underdiagnosis of IE but that it may result in overdiagnosis of IE; therefore, these criteria should be applied prospectively to determine their clinical usefulness.

Leprosy, Hypercalcemia, and Elevated Serum Calcitriol Levels

Excerpt Increased calcitriol levels have been reported in patients who have hypercalcemia with sarcoid and other granulomatous diseases, which suggests that calcidiol 1-alpha-hydroxylase is produce...

Penicillin-netilmicin synergism against Streptococcus faecalis.

The combination of penicillin plus netilmicin was synergistic in vitro against 28 strains of Streptococcus faecalis and compared favorably with penicillin in combination with gentamicin. Similarly, penicillin plus netilmicin was as effective as penicillin plus gentamicin in the therapy of 67 rabbits with enterococcal endocarditis produced with a streptomycin-susceptible (S) or a streptomycin-resistant (R) strain of S. faecalis. After 5 days of infection, control rabbits had bacterial titers of 10(10) colony-forming units (CFU)/g of vegetation. Those treated with penicillin plus netilmicin had mean titers of 10(5.2) and 10(5.1) CFU/g for S and R strains, respectively, and those treated with penicillin plus gentamicin had mean valve titers of 10(5.8) CFU/g for both strains. After 10 days of therapy, mean valve titers with penicillin plus netilmicin were 10(3.8) and 10(4.7) CFU/g, and with penicillin plus gentamicin they were 10(4.5) and 10(5.4) CFU/g for S and R strains, respectively. Thus, if netilmicin proves to be less toxic than other aminoglycoside antibiotics, it may have potential usefulness in the therapy of enterococcal endocarditis.

In Vitro Antibiotic Susceptibility of Salmonellae

In vitro antibiotic susceptibilities were determined for 101 strains of salmonellae. Resistance to chloramphenicol and ampicillin was low. Cefamandole was active against the majority of strains and deserves further evaluation.