Streptococcus spp. and related bacteria: Their identification and their pathogenic potential for chronic mastitis - A molecular approach

Streptococcus spp. and related bacteria form a large group of organisms which are associated with bovine intramammary Infections (IMI). Some of them are the well-known mastitis pathogens Streptococcus uberis and Streptococcus agalactiae. In addition, there are a considerable number of these gram-positive, catalase-negative cocci (PNC) with unclear mastitic pathogenicity such as Aerococcus viridans which make the conventional diagnostics of PNC difficult. One diagnostic, API 20 Strep (API, Biomerieux) is recommended which, as a phenotypic assay, involves a series of miniaturized biochemical tests. Recently, preference is given to genotypic identification methods. In particular, sequencing of the 16S rRNA gene allows highly reproducible and accurate identification of bacteria and permits discovery of novel, clinically relevant bacteria. As a consequence, the aim of the present study was to compare identification of IMI-associated PNC by the API method as well as by sequencing of their 16S rRNA gene (16S). Furthermore, the correlation of these bacteria to bovine chronic mastitis and their phylogeny was investigated. 102 PNC isolated from single quarter milk samples were identified by API and 16S sequencing. Considering Streptococcus uberis, Streptococcus dysgalactiae subsp. dysgalactiae and Streptococcus agalactiae, both methods generated fully concordant results. In contrast, a very high disconcordance was observed for most of the other PNC, in particular Enterococcus spp., Aerococcus viridans and the viridans streptococci were shown as apathogenic. Lactococcus garvieae was found to be an opportunistic pathogen causing IMI during late lactation. In addition, PNC isolated from milk were frequently observed together with other bacteria, in particular with Staphylococcus spp. In these cases, the levels of somatic cell counts (SCC) were determined by the specific PNC present in the sample. Considering PNC phylogeny based on 16S sequencing, 3 major clusters were observed. They included all the common mastitis pathogens (cluster I), the Lactococcus spp., Enterococcus spp. and Aerococcus spp. (cluster II) and all the viridans streptococci (cluster III).

Elimination of local abnormal ventricular activities: a new end point for substrate modification in patients with scar-related ventricular tachycardia

Catheter ablation of ventricular tachycardia (VT) is effective and particularly useful in patients with frequent defibrillator interventions. Various substrate modification techniques have been described for unmappable or hemodynamically intolerable VT. Noninducibility is the most frequently used end point but is associated with significant limitations, so the optimal end point remains unclear. We hypothesized that elimination of local abnormal ventricular activities (LAVAs) during sinus rhythm or ventricular pacing would be a useful and effective end point for substrate-based VT ablation. As an adjunct to this strategy, we used a new high-density mapping catheter and frequently used epicardial mapping.

[Guidance of interventions in subintimal recanalization and fenestration of dissection membranes using a novel dual-lumen intravascular ultrasound catheter]

PURPOSE: To evaluate the feasibility and effectiveness of IVUS-guided puncture for gaining controlled target lumen reentry in subintimal recanalization of chronic iliac/femoral artery occlusions and in fenestration of aortic dissections. MATERIALS AND METHODS: Between 5/2004 and 12/2005 12 consecutive patients (7 male, 5 female; mean age 64.6 +/- 12.0 years) with chronic critical limb ischemia and ischemic complications of aortic dissection were treated using the Pioneer catheter. This 6.2-F dual-lumen catheter combines a 20-MHz IVUS transducer with a pre-shaped extendable, hollow 24-gauge nitinol needle. This coaxial needle allows real-time IVUS-guided puncture of the target lumen and after successful reentry a 0.014" guidewire may be advanced through the needle into the target lumen. 7 patients were treated for aortic dissection and 5 patients (with failed previous attempts at subintimal recanalization) for chronic arterial occlusion. Patients with aortic dissection (5 type A dissections, 2 type B dissections) had developed renal ischemia (n = 2), renal and mesenteric ischemia (n = 2), or low extremity ischemia (n = 3). Patients with chronic arterial occlusions (2 common iliac artery occlusions, 3 superficial femoral artery occlusions) experienced ischemic rest pain (n = 4), and a non-healing foot ulcer (n = 1). RESULTS: The technical success rate using the Pioneer catheter was 100%. The recanalization/fenestration time was 37 +/- 12 min. Procedure-related complications did not occur. In 10 cases a significant improvement of clinical symptoms was evident. One patient with aortic dissection and ischemic paraplegia required subsequent surgical intervention. One patient had persistent ischemic rest pain despite successful recanalization of a superficial femoral artery occlusion. CONCLUSION: The Pioneer catheter is a reliable device which may be helpful for achieving target lumen reentry in subintimal recanalization of chronic occlusions and in fenestration of aortic dissections.

Application of conventional and real-time fluorescent ITS1 rDNA PCR for detection of Besnoitia besnoiti infections in bovine skin biopsies

Besnoitia besnoiti, an apicomplexan protozoan parasite, is the causative agent of bovine besnoitiosis. This infection may dramatically affect body condition, and, in males, lead to irreversible infertility. While identification of clinical cases and their histopathological confirmation is relatively simple to carry out, finding subclinical forms of infection is more difficult, thus a more sensitive test for the identification of the etiological agent may be an appropriate diagnostic tool. We have developed the ITS1 rDNA-sequence-based conventional and real-time PCR which are highly sensitive and specific for the detection of B. besnoiti infection in cattle. A recombinant internal positive control was introduced to assess possible sample-related inhibitory effects during the amplification reaction and, in order to prevent false-positive results, a pre-PCR treatment of potentially contaminating dU-containing PCR product with uracil-DNA-glycosylase (UDG) was followed.

[Transfusion-associated LAV/HTLV-III infections in Switzerland. Report of 2 cases]

Two patients developed signs of LAV/HTLV-III infection one and two years respectively after a blood transfusion. The leading symptom in one patient was generalized lymphadenopathy, while the other patient presented with Candida stomatitis. In both cases, blood transfusions administered in 1983 were found to be the only possible source of infection; one blood donor of each patient was anti-LAV/HTLV-III positive. Family members and sexual partners of the two were negative for antibodies against LAV/HTLV-III. Our findings document the first two cases of LAV/HTLV-III associated disease most probably related to blood transfusions in Switzerland.

[Integration process and organ-related fantasies in patients undergoing organ transplantation]

This review deals with an important aspect of organ transplantation, namely the process of psychic organ integration and organ-related fantasies. The body schema and body self are two important concepts in the integration of a transplanted organ. Different models and theories on organ integration are presented and will be discussed. There is evidence that beside the emotional impact and the influence on well-being, organ integration depends closely on psychic processes involving in the incorporation of the transplanted organ and the respective organ-related fantasies. Therefore, these organ fantasies - whether unconscious or conscious - may play an important role in the future development of the instinctive and highly individual relation the patients elaborate with the new organ. Beside the concern with the new organ, a bereavement to the lost old and sick organ may also influence the patients thoughts. Moreover, the good resolving of all these issues evokes the "good practice" patients develop towards the new situation. This will bring up issues as compliance, infections, rejection episodes and - most important - also organ survival.

Taurolidine-citrate lock solution (TauroLock) significantly reduces CVAD-associated grampositive infections in pediatric cancer patients

BACKGROUND: Taurolidin/Citrate (TauroLock), a lock solution with broad spectrum antimicrobial activity, may prevent bloodstream infection (BSI) due to coagulase-negative staphylococci (CoNS or 'MRSE' in case of methicillin-resistant isolates) in pediatric cancer patients with a long term central venous access device (CVAD, Port- or/Broviac-/Hickman-catheter type). METHODS: In a single center prospective 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 (group 1, heparin lock with 200 IU/ml sterile normal saline 0.9%; Canusal Wockhardt UK Ltd, Wrexham, Wales) and all patients from April 2005 to March 2007 (group 2; taurolidine 1.35%/Sodium Citrate 4%; TauroLock, Tauropharm, Waldbüttelbrunn, Germany). RESULTS: In group 1 (heparin), 90 patients had 98 CVAD in use during the surveillance period. 14 of 30 (47%) BSI were 'primary Gram positive BSI due to CoNS (n = 4) or MRSE (n = 10)' [incidence density (ID); 2.30 per 1000 inpatient CVAD-utilization days].In group 2 (TauroLock), 89 patients had 95 CVAD in use during the surveillance period. 3 of 25 (12%) BSI were caused by CoNS. (ID, 0.45). The difference in the ID between the two groups was statistically significant (P = 0.004). CONCLUSION: The use of Taurolidin/Citrate (TauroLock) significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients.

Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis

Antimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF. We next characterized the expression, secretion, and bactericidal properties of rat cathelin-related antimicrobial peptide, the homologue of the human LL-37, in rat astrocytes and microglia after incubation with different bacterial components. Using real-time polymerase chain reaction and Western blotting, we determined that supernatants from both astrocytes and microglia incubated with bacterial component supernatants had antimicrobial activity. The expression of rat cathelin-related antimicrobial peptide in rat glial cells involved different signal transduction pathways and was induced by the inflammatory cytokines interleukin 1beta and tumor necrosis factor. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae, and rat cathelin-related antimicrobial peptide was localized in glia, choroid plexus, and ependymal cells by immunohistochemistry. Together, these results suggest that cathelicidins produced by glia and other cells play an important part in the innate immune response against pathogens in central nervous system bacterial infections.

Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy

BACKGROUND: Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (G-CSF) or granulocyte-macrophage colony stimulating factors (GM-CSF); and antibiotics, frequently quinolones or cotrimoxazole. Important current guidelines recommend the use of colony stimulating factors when the risk of febrile neutropenia is above 20% but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken. OBJECTIVES: To compare the effectiveness of G-CSF or GM-CSF with antibiotics in cancer patients receiving myeloablative chemotherapy with respect to preventing fever, febrile neutropenia, infection, infection-related mortality, early mortality and improving quality of life. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to 2007). We planned to include both full-text and abstract publications. SELECTION CRITERIA: Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus antibiotics in cancer patients of all ages receiving chemotherapy or bone marrow or stem cell transplantation were included for review. Both study arms had to receive identical chemotherapy regimes and other supportive care. DATA COLLECTION AND ANALYSIS: Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. MAIN RESULTS: We included two eligible randomised controlled trials with 195 patients. Due to differences in the outcomes reported, the trials could not be pooled for meta-analysis. Both trials showed non-significant results favouring antibiotics for the prevention of fever or hospitalisation for febrile neutropenia. AUTHORS' CONCLUSIONS: There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.

Bailout revascularization of chronic femoral artery occlusions with the new outback catheter following failed conventional endovascular intervention

PURPOSE: To report the application of a true lumen re-entry device in the bailout treatment of chronic total occlusions (CTO) of the superficial femoral artery (SFA) after failed angioplasty. METHODS: Nineteen patients (12 men; mean age 81 years, range 61-97) with 20 SFA CTOs and Rutherford category 2 to 5 ischemia were prospectively evaluated. All CTOs had unsuccessful recanalization using conventional techniques and were subsequently treated with the Outback LTD catheter. Follow-up at 3, 6, and 12 months included ankle/toe pressure measurement and pulse volume recordings. Endpoints were revascularization rate, target lesion revascularization, and limb salvage. RESULTS: Revascularization was achieved in 95% of the cases. There were 2 (10%) periprocedural complications unrelated to the re-entry device, which were resolved by endovascular or surgical treatment. The target lesion revascularization rate was 10%, with the 2 events occurring at 3 and 6 months, respectively, in patients with Rutherford category 4-5 ischemia. There was one below-the-knee amputation in the patient with failed revascularization. CONCLUSION: The acute failure of endovascular treatment of SFA CTOs is most often due to an inability to re-enter the true lumen after the occlusion is crossed in a subintimal plane. Bailout revascularization with the Outback LTD catheter is highly successful and shows a low device-related complication rate. This needle- and fluoroscopic-based re-entry device increases the endovascular success rate and is therefore expanding the minimally invasive treatment options for surgically unfit patients.

Prospective population-based study of RSV-related intermediate care and intensive care unit admissions in Switzerland over a 4-year period (2001-2005)

OBJECTIVES: Respiratory syncytial virus (RSV) infections are a leading cause of hospital admissions in small children. A substantial proportion of these patients require medical and nursing care, which can only be provided in intermediate (IMC) or intensive care units (ICU). This article reports on all children aged < 3 years who required admission to IMC and/or ICU between October 1, 2001 and September 30, 2005 in Switzerland. PATIENTS AND METHODS: We prospectively collected data on all children aged < 3 years who were admitted to an IMC or ICU for an RSV-related illness. Using a detailed questionnaire, we collected information on risk factors, therapy requirements, length of stay in the IMC/ICU and hospital, and outcome. RESULTS: Of the 577 cases reported during the study period, 90 were excluded because the patients did not fulfill the inclusion criteria; data were incomplete in another 25 cases (5%). Therefore, a total of 462 verified cases were eligible for analysis. At the time of hospital admission, only 31 patients (11%) were older than 12 months. Since RSV infection was not the main reason for IMC/ICU admission in 52% of these patients, we chose to exclude this subgroup from further analyses. Among the 431 infants aged < 12 months, the majority (77%) were former near term or full term (NT/FT) infants with a gestational age > or = 35 weeks without additional risk factors who were hospitalized at a median age of 1.5 months. Gestational age (GA) < 32 weeks, moderate to severe bronchopulmonary dysplasia (BPD), and congenital heart disease (CHD) were all associated with a significant risk increase for IMC/ICU admission (relative risk 14, 56, and 10, for GA < or = 32 weeks, BPD, and CHD, respectively). Compared with NT/FT infants, high-risk infants were hospitalized at an older age (except for infants with CHD), required more invasive and longer respiratory support, and had longer stays in the IMC/ICU and hospital. CONCLUSIONS: In Switzerland, RSV infections lead to the IMC/ICU admission of approximately 1%-2% of each annual birth cohort. Although prematurity, BPD, and CHD are significant risk factors, non-pharmacological preventive strategies should not be restricted to these high-risk patients but also target young NT/FT infants since they constitute 77% of infants requiring IMC/ICU admission.

Infection prevention strategies in a stem cell transplant unit: impact of change of care in isolation practice and routine use of high dose intravenous immunoglobulins on infectious complications and transplant related mortality

OBJECTIVE: Nursing in 'live islands' and routine high dose intravenous immunoglobulins after allogeneic hematopoietic stem cell transplantation were abandoned by many teams in view of limited evidence and high costs. METHODS: This retrospective single-center study examines the impact of change from nursing in 'live islands' to care in single rooms (SR) and from high dose to targeted intravenous immunoglobulins (IVIG) on mortality and infection rate of adult patients receiving an allogeneic stem cell or bone marrow transplantation in two steps and three time cohorts (1993-1997, 1997-2000, 2000-2003). RESULTS: Two hundred forty-eight allogeneic hematopoetic stem cell transplantations were performed in 227 patients. Patient characteristics were comparable in the three cohorts for gender, median age, underlying disease, and disease stage, prophylaxis for graft versus host disease (GvHD) and cytomegalovirus constellation. The incidence of infections (78.4%) and infection rates remained stable (rates/1000 days of neutropenia for sepsis 17.61, for pneumonia 6.76). Cumulative incidence of GvHD and transplant-related mortality did not change over time. CONCLUSIONS: Change from nursing in 'live islands' to SR and reduction of high dose to targeted IVIG did not result in increased infection rates or mortality despite an increase in patient age. These results support the current practice.

Mastitis-related subtypes of bovine Staphylococcus aureus are characterized by different clinical properties

Based on a former study from our group, one subtype of Staphylococcus aureus was associated with high within-herd prevalence of mastitis, whereas the other subtypes were associated with a low prevalence (sporadic intramammary infection). To confirm this hypothesis, a prospective study was done in 29 Swiss dairy herds. In particular, milk samples were collected from 10 herds with Staph. aureus herd problems (cases) and compared with samples from 19 herds with only sporadic cases of with Staph. aureus intramammary infection (controls). The isolates were tested for their virulence gene pattern and genotyped by PCR amplification of the 16S-23S rRNA intergenic spacer. The patterns and genotypes were then associated and compared with epidemiological and clinical data. Confirming the hypothesis, one particular subtype (genotype B) was associated with high within-herd and within-cow prevalence of intramammary infection, whereas the other subtypes were associated with low within-herd prevalence and infected single quarters. The gene patterns and genotypes were highly related, demonstrating the genetic diversity of the genotypes. The somatic cell counts were clearly increased in herds with a genotype B problem compared with herds with infections of other genotypes. Based on the different clinical properties and treatment consequences associated with these different genotypes found in Switzerland, we recommend subtyping Staph. aureus in other countries to determine if this finding is universally applicable.

Valuing the Health States Associated with Chlamydia trachomatis Infections and Their Sequelae: A Systematic Review of Economic Evaluations and Primary Studies

OBJECTIVES Economic evaluations of interventions to prevent and control sexually transmitted infections such as Chlamydia trachomatis are increasingly required to present their outcomes in terms of quality-adjusted life-years using preference-based measurements of relevant health states. The objectives of this study were to critically evaluate how published cost-effectiveness studies have conceptualized and valued health states associated with chlamydia and to examine the primary evidence available to inform health state utility values (HSUVs). METHODS A systematic review was conducted, with searches of six electronic databases up to December 2012. Data on study characteristics, methods, and main results were extracted by using a standard template. RESULTS Nineteen economic evaluations of relevant interventions were included. Individual studies considered different health states and assigned different values and durations. Eleven studies cited the same source for HSUVs. Only five primary studies valued relevant health states. The methods and viewpoints adopted varied, and different values for health states were generated. CONCLUSIONS Limitations in the information available about HSUVs associated with chlamydia and its complications have implications for the robustness of economic evaluations in this area. None of the primary studies could be used without reservation to inform cost-effectiveness analyses in the United Kingdom. Future debate should consider appropriate methods for valuing health states for infectious diseases, because recommended approaches may not be suitable. Unless we adequately tackle the challenges associated with measuring and valuing health-related quality of life for patients with chlamydia and other infectious diseases, evaluating the cost-effectiveness of interventions in this area will remain problematic.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.