International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

The risk of stroke and death in patients with aortic and mitral valve endocarditis.

BACKGROUND: Previous studies have generated inconsistent results when attempting to define predictors of stroke and death in patients with endocarditis. We sought to examine the relationship between vegetation 2-dimensional size and stroke in those with infective endocarditis (IE) and to identify differences between aortic valve (AV) and mitral valve (MV) IE with regard to clinical characteristics, echocardiographic findings, stroke, and death. METHODS: We used the Duke Endocarditis Database to examine 145 episodes of definite IE involving the AV, n = 62, or MV, n = 83. A logistic regression model was developed to analyze important variables in predicting stroke, and a Cox proportional hazards model was used in predicting mortality. RESULTS: The mitral valve was infected in 57% of the cases. Vegetations were more commonly detected in patients with MV IE (92.8% vs 66.1%, P =.001) and these MV vegetations were significantly larger (P <.05). Thirty-four of 145 episodes (23.4%) were complicated by stroke. MV IE was associated with a greater stroke rate, 32.5% versus 11.3% (P =.003). Strokes tended to occur early in the course of illness, particularly in MV IE. In the multivariable model, the independent predictors of stroke were MV IE (P =.04) and vegetation length (P =.03). Independent predictors of 1-year mortality were age (P =.02) and vegetation area (P =.048). CONCLUSION: Stroke is more common in patients with MV IE. Vegetation 2-dimensional size and characteristics are important predictors of stroke and mortality. These findings may lead to predictive models that allow physicians to identify high-risk patients who need aggressive treatment strategies to prevent long-term morbidity and mortality.

Oral microflora as a cause of endocarditis and other distant site infections.

Bacteremia originating from the oral cavity is common, but the role of bacteremia in the genesis of infective endocarditis and other distant site infections is unclear. Only a small percentage of oral flora have been associated with distant site infection. Important issues remain unresolved concerning the identification of patients at risk, the relative risk from invasive dental procedures versus naturally occurring bacteremia, and the impact of prophylactic antibiotics on the incidence, nature, magnitude, and duration of bacteremia from the oral cavity. This article addresses the controversies in infection management in patients at risk for distant site infection.

Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group.

This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis.

Negative predictive value of the Duke criteria for infective endocarditis.

With use of new Duke criteria, 405 episodes of suspected endocarditis were previously classified as "definite," "possible," or "rejected" endocarditis. To determine the negative predictive value of the Duke clinical criteria for the classification of suspected endocarditis, chart review and follow-up were performed for the 52 episodes in which the diagnosis of endocarditis was rejected. Three of 52 episodes were reclassified to possible endocarditis; 49 episodes in 48 patients met the criteria for rejected endocarditis. Of these 49 episodes, 31 (63%) had a firm alternate diagnosis other than endocarditis, 17 (35%) had resolution of the clinical syndrome leading to the suspicion of endocarditis with < or = 4 days of antibiotics, and 1 patient had no evidence of endocarditis at surgery. Echocardiograms recorded in 3 patients with rejected endocarditis had evidence of oscillating valvular masses, and blood cultures were positive in 13 episodes; none of these patients had evidence of endocarditis at follow-up. Follow-up or outcome information was available in all 49 episodes. Excluding the 5 in-hospital deaths, mean duration (+/- SD) of follow-up was 39.9 +/- 28.8 months (range 0.5 to 108.0); in living patients, mean time to final follow-up was 56.2 +/- 25.2 months (range 25.0 to 108.0). One patient had possible infective endocarditis at autopsy. No patient in our series whose diagnosis of endocarditis had been rejected had proven endocarditis. Therefore, the negative predictive value of the Duke clinical criteria for endocarditis is at least 92%.

Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association.

OBJECTIVE: To provide guidelines for the treatment of endocarditis in adults caused by the following microorganisms: viridans streptococci and other streptococci, enterococci, staphylococci, and fastidious gram-negative bacilli of the HACEK group. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young. EVIDENCE: Published studies of the treatment of patients with endocarditis and the collective clinical experience of this group of experts. CONSENSUS PROCESS: The recommendations were formulated during meetings of the working group and were prepared by a writing committee after the group had agreed on the specific therapeutic regimens. The consensus statement was subsequently reviewed by standing committees of the American Heart Association and by a group of experts not affiliated with the working group. CONCLUSIONS: Sufficient evidence has been published that recommendations regarding treatment of the most common microbiological causes of endocarditis (viridans streptococci, enterococci, Streptococcus bovis, staphylococci, and the HACEK organisms) are justified. There are insufficient published data to make a strong statement regarding the efficacy of specific therapeutic regimens for cases of endocarditis due to microorganisms that uncommonly cause endocarditis. As a useful aid to the practicing clinician, the writing group developed a consensus opinion regarding management of endocarditis caused by the most commonly encountered microorganisms and regarding those cases due to infrequent causes of endocarditis.

Criteria for the diagnosis of endocarditis and the role of echocardiography.

When infective endocarditis is a diagnostic possibility, echocardiography permits noninvasive imaging of cardiac structures. As involvement of the endocardium is a sine qua non of endocarditis, echocardiography may assist in its diagnosis by demonstrating such involvement. The ability of echocardiography to detect the intracardiac manifestations of infective endocarditis has continued to improve, especially with the introduction of transesophageal imaging. This article will discuss some of the echocardiographic findings in endocarditis and elucidate the incorporation of these findings in the new Duke criteria for the diagnosis of endocarditis.

International health and internal medicine residency training: the Duke University experience.

OBJECTIVE: To evaluate the impact of the Duke University Medicine Residency International Health Program (IHP) on program participants and to evaluate the relationship of the IHP to the residency program. SUBJECTS AND METHODS: The Duke University Medicine Residency Program classes of 1988 to 1996 participated in a questionnaire-based survey. All program participants (n = 59), a group of nonparticipants (n = 138), and residents who had not yet had an opportunity to participate (preparticipants; n = 106). RESULTS: The overall response rate to the questionnaire was 93%. Participation exceeded expectations and had a strongly positive impact on personal and professional lives of the majority of the participants. Participants reported a significant positive impact on their training in internal medicine and their knowledge of tropical medicine. A minority of nonparticipants identified a positive effect in these areas due to conferences and interactions with their participating colleagues. Participants who changes career plans during residency tended to move toward areas of general internal medicine or public health, in contrast to nonparticipants who tended to change areas of subspecialty or chose private practice. The IHP was identified as a significant factor for selection of the Duke Medicine Residency by 42% of the preparticipant group. Nearly all of the respondents (99%) indicated that the IHP should be continued. CONCLUSION: The IHP has a measurable positive impact on the participants, as well as on the Medicine Residency Program.

Detection of antibodies to avian leukosis/sarcoma viruses (ALSV) and reticuloendotheliosis viruses (REV) in humans by ELISA.

We used a modified commercial ELISA kit to test for antibodies to avian leukosis/sarcoma and reticuloendotheliosis viral antigens in the sera of 45 poultry workers and their matched controls. We found that 42% of sera from poultry workers had anti-avian leukosis Sarcoma viruses (anti-ALSV) and 20% had anti-reticuloendotheliosis viruses (anti-REV), antibody titers that were higher than the highest titer recorded in control subjects, and hence were regarded as positive. To determine the specificity of these reactions, selected sera were absorbed with ALSV or REV antigens alone, or with chick embryo fibroblasts (CEF) alone, or with both CEF and ALSV/REV, and then retested. In each case, absorption resulted in a statistically significant reduction in absorbance, which was greatest for the combined CEF and ALSV/REV absorption, thus suggesting that the reactions involved viral as well as chicken antigens. However, definitive tests such as Western Blot analyses are needed to confirm whether indeed antibodies to these viruses were specifically elicited in human sera.

Infective endocarditis.

Endocarditis continues to be a popular subject among medical authors. A steady stream of new papers describes evolving aspects of epidemiology, clinical manifestations, natural history, and management. Significant developments include refinements in echocardiography and diagnostic criteria, and the introduction of improved surgical techniques for dealing with the complications of endocarditis. Here we review recent publications that present useful or interesting observations.

New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service.

PURPOSE: This study was designed to develop improved criteria for the diagnosis of infective endocarditis and to compare these criteria with currently accepted criteria in a large series of cases. PATIENTS AND METHODS: A total of 405 consecutive cases of suspected infective endocarditis in 353 patients evaluated in a tertiary care hospital from 1985 to 1992 were analyzed using new diagnostic criteria for endocarditis. We defined two "major criteria" (typical blood culture and positive echocardiogram) and six "minor criteria" (predisposition, fever, vascular phenomena, immunologic phenomena, suggestive echocardiogram, and suggestive microbiologic findings). We also defined three diagnostic categories: (1) "definite" by pathologic or clinical criteria, (2) "possible," and (3) "rejected." Each suspected case of endocarditis was classified using both old and new criteria. Sixty-nine pathologically proven cases were reclassified after exclusion of the surgical or autopsy findings, enabling comparison of clinical diagnostic criteria in proven cases. RESULTS: Fifty-five (80%) of the 69 pathologically confirmed cases were classified as clinically definite endocarditis. The older criteria classified only 35 (51%) of the 69 pathologically confirmed cases into the analogous probable category (p < 0.0001). Twelve (17%) pathologically confirmed cases were rejected by older clinical criteria, but none were rejected by the new criteria. Seventy-one (21%) of the remaining 336 cases that were not proven pathologically were probable by older criteria, whereas the new criteria almost doubled the number of definite cases, to 135 (40%, p < 0.01). Of the 150 cases rejected by older criteria, 11 were definite, 87 were possible, and 52 were rejected by the new criteria. CONCLUSION: Application of the proposed new criteria increases the number of definite diagnoses. This should be useful for more accurate diagnosis and classification of patients with suspected endocarditis and provide better entry criteria for epidemiologic studies and clinical trials.

Ethical issues in infectious diseases.

Ethical behavior is an essential component of professional life. Developments in medical science continually test society's concepts of right and wrong, of virtue and morality. Ethical conflicts will be played out in public with greater frequency and intensity. Physicians will be challenged to maintain high standards of ethical conduct despite the pressures that personal preference, society, and government may exert. We do not present neat solutions to ethical conflicts, but we describe a framework for understanding models of physician behavior and outline an approach to the analysis of problems.

Uptake of itraconazole by alveolar macrophages.

Itraconazole is a broad-spectrum potent triazole antifungal agent. Its efficacy in treatment cannot always be explained by body fluid drug levels. In this study, itraconazole was shown to accumulate into host cells. Its intracellular accumulation in cells is greater than that of the antibacterial agent clindamycin, which is known for intracellular localization, and the uptake process does not appear to be active. This ability to reach high concentrations intracellularly may be an important property for the in vivo efficacy of itraconazole.

Disseminated infection with rapidly growing mycobacteria.

Disseminated infection with the rapidly growing mycobacteria Mycobacterium chelonae and Mycobacterium fortuitum is uncommon. Only eight cases were diagnosed at Duke University Medical Center (Durham, NC) over the last 14 years. We identified 46 other cases by review of the medical literature since 1960. We categorized these 54 cases into three groups according to underlying disease and outcome. Group 1 comprised patients with no identified immune defect, a kidney transplant, collagen vascular disease, or chronic renal failure; these patients usually presented with skin involvement and responded well to antimicrobial therapy (survival rate, 90%). Group 2 comprised patients with cell-mediated immune deficiency, lymphoma, or leukemia; they presented with widespread, multiorgan involvement and severe illness. The survival rate in this group was only 10%. Patients in group 3 (who had other underlying diseases) had intermediately severe illnesses and intermediate responses to therapy. These groups provide the basis for an understanding of disseminated infection secondary to rapidly growing mycobacteria and of the profound effect that unresolved immunosuppression has on survival.

Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA.

A transformation scheme for Cryptococcus neoformans to yield high-frequency, integrative events was developed. Adenine auxotrophs from a clinical isolate of C. neoformans serotype A were complemented by the cryptococcal phosphoribosylaminoimidazole carboxylase gene (ade2) with a biolistic DNA delivery system. Comparison of two DNA delivery systems (electroporation versus a biolistic system) showed notable differences. The biolistic system did not require linear vectors and transformed each auxotrophic strain at similar frequencies. Examination of randomly selected transformants by biolistics showed that 15 to 40% were stable, depending on the recipient auxotroph, with integrative events identified in all stable transformants by DNA analysis. Although the ade2 cDNA copy transformed at a low frequency, DNA analysis found homologous recombination in each of these transformants. DNA analysis of stable transformants receiving genomic ade2 revealed ectopic integration in a majority of cases, but approximately a quarter of the transformants showed homologous recombination with vector integration or gene replacement. This system has the potential for targeted gene disruption, and its efficiency will also allow for screening of DNA libraries within C. neoformans. Further molecular strategies to study the pathobiology of this pathogenic yeast are now possible with this transformation system.

Diagnosis of infective endocarditis.

The diagnosis of IE is often difficult to establish with certainty. Current diagnostic criteria have several weaknesses, the most important being failure to utilize the results of echocardiography. This seems inconsistent with modern practice. In reality, the results of modern echocardiography, including appropriate use of transesophageal echocardiography, are critically important for diagnosis of infective endocarditis. New criteria are in the process of development which should prove more sensitive and more specific for disease classification, epidemiologic studies, and clinical trials.