Are histopathological findings of diagnostic value in native valve endocarditis?

BACKGROUND: Optimal management of infective endocarditis (IE) depends on the early detection of IE-causing pathogens and on appropriate antimicrobial and surgical therapy. The current guidelines of the European Society of Cardiology (ESC) recommend histopathological examination as the gold standard for diagnosing IE Habib et al. (Eur Heart J 30:2369-2413, 2005). We hypothesize that histopathological findings do not provide additional information relevant to clinical decision-making. METHODS: We retrospectively reviewed a cohort of patients who had undergone surgery for native valve endocarditis (NVE) at the University Hospital Regensburg between September 1994 and February 2005. All episodes of intraoperatively confirmed endocarditis during this period were included in the study. Data were retrieved from surgical records, microbiological and histopathological reports, and medical files of the treating as well as admitting hospital. Pathogens were correlated with the site of manifestation of the affected heart valve and with clinical and histopathological findings. RESULTS: A total of 163 episodes of NVE were recorded and entered into our study for analysis. The valves affected were the aortic valve (45 %), the mitral valve (28 %), the aortic and mitral valve (22 %), and other valves (5 %). IE-causing pathogens were Staphylococcus aureus (22 %), viridans streptococci (18 %), enterococci (10 %), streptococci other than Streptococcus viridans (9 %), coagulase-negative staphylococci (5 %), miscellaneous pathogens (4 %), and culture-negative endocarditis (33 %). Infection with S. aureus was associated with high rates of sepsis, septic foci, and embolic events, while patients with enterococcal IE showed the highest rate of abscesses. Mortality rate in all subgroups was low without significant differences. However, histopathological findings correlated poorly with the pathogen involved and showed only few significant associations that were without clinical relevance. CONCLUSIONS: The clinical presentation of IE depends on the pathogen involved. Among the episodes of NVE examined, the histopathological examination of resected heart valves did not show any pathogen-specific morphological patterns and therefore did not provide any additional information of clinical value. Based on our findings, we recommend complementary cultures of the resected materials (valve tissue, thrombotic material, pacer wire) and implementation of molecular diagnostic methods (e.g., broad-range PCR amplification techniques) instead of histopathological analyses of resected valve tissue.

[Suspected borreliosis - what's behind it?]. / Verdacht auf Borreliose - Was hat der Patient?

BACKGROUND AND OBJECTIVE: Borreliosis may be associated with unspecific symptoms and thus not only cause difficulties in diagnosis but also lead to overdiagnosis. PATIENTS AND METHODS: Data on 134 patients (mean age 47 [12 - 78] years, 51.5 % male) with suspected borreliosis presenting at the university hospital Regensburg were analyzed retrospectively. RESULTS: The majority of patients had been adequately treated for borreliosis previously. 34 patients (25.4 %) had proven or possible borreliosis, 20 patients (14.9 %) presented for consultation only. Regarding the remaining 80 patients (59.7 %), in 36 (45 %) a rheumatologic, orthopedic or neurologic disease was found as causal for the presenting symptoms, in 44 (55 %) no somatic disease could be diagnosed. CONCLUSION: A careful differential diagnosis seems mandatory in patients with suspected borreliosis and persistent complaints.

[Rare viral infections during immunosuppressive therapy: a "normal" side effect?]. / Seltene virale Infektionen unter Immunsuppression: Eine "Normale" Nebenwirkung?

The use of biologicals in the therapy of rheumatic diseases allows more effective treatment of patients with very active disease. Such regimens, however, can induce a more severe treatment-related immunosuppression and, as a consequence, opportunistic infections that are rarely seen with conventional immunosuppressive therapy appear to occur more frequently. The majority of these opportunistic infections are common viral infections which become latent and only cause severe disease if they are reactivated in a severely immunocompromised host. However, some of the newer biologicals, especially natalizumab, efalizumab or rituximab, appear to carry a special risk for the reactivation of JC polyoma virus manifesting as progressive multifocal leukoencephalopathy, a severe, untreatable and often fatal encephalitis. Therefore, such treatments should be used with caution in patients who have been or are being treated with combined immunosuppressive therapy including corticosteroids. Elderly patients are specifically at risk for this "normal" side effect.

Vaccination in patients with chronic rheumatic or autoimmune diseases.

Patients who have chronic rheumatic or autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, or vasculitides, show a risk of infection that is at least 2-fold greater than that for healthy individuals. This increased risk is not only a result of the aberrant immunologic reaction itself but also can be attributed to the immunosuppressive therapy required to control the activity of the underlying disease and the associated organ complications. Vaccination is an option for a substantial number of these infections. In this context, pneumococcal and influenza vaccines are the best evaluated and are recommended by standard vaccination guidelines. Some studies have found mildly impaired immune responses to vaccines among patients receiving long-term immunosuppressive therapy, but postvaccination antibody titers are usually sufficient to provide protection for the majority of immunized individuals. The accumulated data on the safety and effectiveness of vaccines warrant immunization with the majority of vaccines for patients with chronic autoimmune or rheumatic diseases, especially vaccination against influenza and pneumococci. Vaccination protocols for this population should be better implemented in daily clinical practice.

Comparison of the pharmacokinetics of piperacillin and sulbactam during intermittent and continuous intravenous infusion.

BACKGROUND: The antibacterial effect of piperacillin/sulbactam depends on the time of drug concentration above the minimal inhibitory concentration (MIC). Therefore, continuous infusion (CI) may be a more rational approach than standard intermittent short-term infusion (SI). The study investigated whether CI achieves effective drug concentrations comparable with SI. METHODS: Seven intensive care unit patients received either piperacillin/sulbactam as 4/1 g intravenous infusion over 15-20 min every 8 h or as 4/1 g intravenous loading dose (15-20 min) followed by 8/2 g intravenous CI per 24 h. After 2 days, regimes were crossed over. RESULTS: Pharmacokinetic parameters (mean +/- SD) for SI piperacillin/sulbactam were: (1) peak serum concentration: piperacillin 231 +/- 66 mg/l, sulbactam 53.1 +/- 15.0 mg/l; (2) minimum serum concentration: piperacillin 11.5 +/- 14.8 mg/l, sulbactam 4.2 +/- 3.5 mg/l; (3) clearance: piperacillin 197 +/- 72 ml/min (CI 269 +/- 123 ml/min), sulbactam 167 +/- 61 ml/min (CI 212 +/- 109 ml/min); (4) half-life: piperacillin 2.4 +/- 1.2 h, sulbactam 3.1 +/- 1.6 h. Steady-state concentrations during CI were 25.5 +/- 14.5 mg/l for piperacillin and 8.0 +/- 3.7 mg/l for sulbactam. Average serum concentrations were comparable in both regimens. CONCLUSION: A large German survey demonstrated that approximately 89% of Pseudomonas aerugionsa have an MIC < or =16 mg/l and approximately 82% have an MIC < or =8 mg/l. According to this threshold, appropriate anti-bacterial concentrations of piperacillin/sulbactam were achievable with CI. CI dosing has the additional advantage that less drug is necessary. Further prospective studies are warranted to compare the clinical efficacy of CI and SI regimens in bacterial infections.

Reduced TH-1 cytokine release in an adult patient with chronic relapsing Mycobacterium malmoense infection.

An unusual course of infection with Mycobacterium malmoense is described in a patient receiving chronic but mild immunosuppressive therapy for rheumatoid arthritis. Symptoms mimicking Crohn's disease deteriorated under intensified immunosuppression and surgery. Judging from the patient's course under treatment specific for M. malmoense, the gastrointestinal symptoms were rather manifestations of a chronic relapsing mycobacterial infection. Detailed immunological investigation of the patient revealed a severely impaired TH-1 cytokine response as the immunological background for this uncommon course.

Vasculitis of the aortic arch and cardiac valves as the cause of relapsing fever of unknown origin in an elderly, white man.

Here, we report the case of fever of unknown origin (FUO) in a 77-year-old white man. The patient presented with a 3-week history of fever (between 38.5 and 39 degrees C) and general malaise. These symptoms had occurred about five to seven times during the past 30 years, and despite repeated hospitalizations, no diagnosis was made. Physical examination did not reveal any specific signs of infection nor did the patient fulfill the criteria for any rheumatic disease including vasculitides. Blood chemistry showed a greatly elevated C-reactive protein (CRP; 158.2 mg/l) and an erythrocyte sedimentation rate >100 mm, indicating an active inflammatory process, and leukocytes were significantly elevated (20,000/mul). Rheumatological parameters showed only nonspecific changes. Finally, a 2-[(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography was performed, revealing a markedly enhanced glucose uptake in the ascending aorta and the cardiac valves, indicating vasculitis as the cause of FUO in this patient. Based on this finding, treatment was started with corticosteroids, and 2 days after the initiation of treatment, the patient had normal body temperature, and after 5 days, CRP values had returned to normal. After tapering and final complete removal of steroid treatment, the patient was still free of symptoms, hence no disease-modifying antirheumatic drug therapy was necessary.

Low rate of clinical consequences derived from results of blood cultures obtained in an internal medicine emergency department.

BACKGROUND: Blood cultures detect bacteremia in individual patients and help define local pathogen and resistance spectra. At the same time, the benefits of blood culture results in the management of individual patients -- and therefore their cost-effectiveness -- are disputed. PATIENTS AND METHODS: During 1 calendar year, we conducted a prospective study of emergency department admissions with blood culture draws and at least a 3-day hospitalization afterwards. We prospectively surveyed treating physicians on usefulness of blood culture results for patient management. RESULTS: 428 diagnostic episodes (emergency visits) involving 390 patients occurred during the study period from 10/2002 to 10/2003. The analysis included 188/428 (44%) episodes with blood culture draws performed according to the predefined clinical standard where patients were hospitalized with sufficient duration. Absence of therapeutic consequences in response to blood culture results was reported for 138/142 (97%) of episodes with negative blood culture results, for 16/21 (76%) with blood culture results positive only for skin flora, and for 14/25 (56%) of episodes with blood cultures positive for obligate pathogens. Treating physicians regarded the blood culture results necessary for clarifying the etiology in 34/188 (18%) episodes, and rated blood culture results necessary for their therapeutic decisions in 29/188 (15%) episodes. CONCLUSION: Negative blood culture results rarely changed the management of medical inpatients. Our study suggests that in settings with broad-spectrum empirical antibiotic therapy positive blood culture results for obligate pathogens trigger adjustment of the antibiotic therapy in only about half of instances. Many blood cultures drawn in the emergency department where considered unnecessary by ward physicians. Guidelines for preventing unnecessary blood culture draws are warranted in order to increase the rate of their meaningful clinical consequences for medical inpatients initially treated with broad-spectrum empirical antibiotics.

TLR-4 surface display on human monocytes is increased in septic patients.

BACKGROUND: Sepsis is a serious condition, most often occurring as a complication of bacterial infections. The Toll-like receptors (TLR)-2 and TLR-4 have been identified as key molecules in response to Gram-positive and Gram-negative bacteria. This study aimed to assess possible alterations of the surface display of TLR-2 and TLR-4 on monocytes and granulocytes derived from patients with sepsis in comparison with healthy controls. - METHODS: We have utilized flow-cytometry to determine the presence of TLR-2 and TLR-4 on the cell surface at baseline and in response to LPS (40 ng/ml) in vitro. - RESULTS: We found no significant differences of TLR-2 display on monocytes and granulocytes from septic patients compared to controls. Surface display of TLR-4 on monocytes from septic patients at baseline was significantly higher than in healthy controls but there was no further response to LPS, whereas controls showed a significant increase of TLR-4 display on the cell surface after LPS stimulation. In contrast, TLR-4 baseline cell surface display on granulocytes was significantly lower in septic patients than in controls and there was no response to LPS in both groups. - CONCLUSION: Our data suggest a complex relationship between TLR-4 display and bacterial challenge in vivo and in vitro.

Pericarditis as primary manifestation of Mycobacterium bovis SSP. caprae infection.

A 76-year-old white male presented with progressive malaise, weight loss and dyspnea at rest. Echocardiography revealed a circular pericardial effusion and global hypokinesia. Pericardiocentesis showed a purulent exudate and microbiologic examination revealed Mycobacterium bovis fully sensitive to isoniazid, streptomycin, ethambutol, rifampin, and pyrazinamide. By spoligotyping the isolate could be further differentiated to M. bovis ssp. caprae. Antimycobacterial therapy was initiated but 3 weeks later the patient's circulation and renal function deteriorated and he died with clinical signs of sepsis despite intensive care treatment. Pericarditis is a rare manifestation of tuberculosis and can be fatal even when diagnosed and treated appropriately. In low incidence countries diagnosis is often delayed and even overlooked.

Parameters influencing membrane CD14 expression and soluble CD14 levels in sepsis.

INTRODUCTION: Membrane (mCD14) and soluble (sCD14) CD14 are pattern recognition receptors for bacterial cell wall fragments. They play an important role in the generation of the innate immune response against bacterial pathogens. Differential expression of these receptors may be relevant for the clinical course of patients with sepsis. PATIENTS AND METHODS: 32 patients with an early onset of sepsis (duration of symptoms < 24h) were examined repeatedly by flow cytometry for expression of mCD14, and by ELISA for levels of sCD14, leukocyte elastase and C-reactive Protein (CRP). RESULTS: At study entry, mCD14 expression was reduced in all patients with sepsis, but returned to normal levels during the course of the disease in survivors only. mCD14 was found to be inversely correlated with severity of disease, leukocyte elastase, and C-reactive protein. Among patients with severe disease and Apache II scores >or= 20, sCD14 levels at study entry were significantly higher in those who survived by day 28, as compared to non-survivors (p = 0.02). CONCLUSION: The data presented are compatible with a recently published hypothesis derived from in vitro experiments suggesting that leukocyte elastase may be responsible for cleavage of mCD14 from the monocyte surface. The data also suggest that higher sCD14 levels may be beneficial in sepsis. Persistently reduced mCD14 expression seems to be a marker for severity of disease in patients with sepsis.

Decreased T cell stimulatory capacity of monocyte-derived human macrophages following herpes simplex virus type 1 infection.

Macrophages play a central role in establishing a specific immune response by acting as professional antigen presenting cells (APC) for T cells leading to a vigorous immune response. In order to analyze if Herpes simplex Virus (HSV) type 1 infection might affect the macrophage APC-function, monocyte-derived human macrophages were infected with HSV-1 strain F in vitro. Cocultures with allogeneic T cells revealed a strongly impaired stimulatory capacity of HSV-infected macrophages compared to uninfected controls which was not owing to a productive viral infection in macrophages. An increased expression of Fas ligand (FasL/CD95L) was detected in HSV-infected macrophages by FACS analysis. Although the majority of the macrophages expressed high levels of Fas (CD95/Apo-1), the HSV-induced upregulation of FasL did not result in an increased autocrine apoptosis of macrophages which might be related to endogenous expression of the apoptosis inhibitor FLICE inhibitory protein (FLIP). However, substantial apoptosis occurred in peripheral T cells as well as Fas-sensitive Jurkat T cells when cocultured with HSV-infected macrophages. These findings suggest that the paracrine killing of activated T cells by FasL expressing APC might be a novel strategy of immune evasion by HSV.

[Fatal sinus vein thrombosis in a patient with mixed connective tissue disease and secondary antiphospholipid antibody syndrome]. / Letale Sinusvenenthrombose bei einer Patientin mit Mischkollagenose und sekundärem Antiphospholipid-Antikörper-Syndrom.

BACKGROUND: The antiphospholipid (Huges) syndrome is a complication of connective tissue diseases characterized by thromboembolic occlusions of arterial and venous blood vessels. CASE REPORT: At the age of 13, the patient developed connective tissue disease with arthritis and myositis. The course of her disease was characterized by frequent relapses despite immunosuppressive treatment. She developed deep venous thrombosis of her right leg as a manifestation of secondary antiphospholipid antibody syndrome at the age of 15 and was subsequently started on oral anticoagulation therapy. Approximately 10 months later, however, she decided to try alternative medicine and stopped both anticoagulation and immunosuppressive therapy. Only after 4 weeks she developed seizures followed by respiratory arrest with the need for cardiopulmonary resuscitation. Despite intensive care she died 2 days later with the signs of severe cerebral edema causing herniation of the brainstem. Autopsy confirmed the diagnosis of severe edema of the brain as a result of extensive thrombosis of all sinus veins. CONCLUSION: A complete sinus vein thrombosis is a rare manifestation of antiphospholipid antibody syndrome. The lethal thrombosis in this case occurred during a period of reactive hypercoagulability after termination of immunosuppressive and/or anticoagulation therapy. This case report underlines the need for long-term anticoagulation in patients with the antiphospholipid syndrome.