[Optimization of microbial diagnostics by introduction of a blood culture standard operating procedure in the emergency department]. / Optimierung der mikrobiellen Diagnostik durch Einführung einer Standard Operating Procedure "Blutkulturen" in der zentralen Notaufnahme.

INTRODUCTION: The emergency department (ED) is the main port of entry for patients with infectious diseases, the place where a number of diagnostic procedures are performed and treatment is often initiated. The aim of this retrospective study was to estimate the influence of the establishment and introduction of a blood culture standard operating procedure (BC-SOP) and of the subsequent training of microbial diagnostics in an ED. METHODS: In a before and after study over a study period of 3 months each (November 2017-January 2018 and November 2018-January 2019), the number of blood cultures taken, the rate of blood cultures per 1000 patients, the number of positive blood cultures and the frequency of typical skin pathogens were evaluated. In the interim time between the two study periods, a BC-SOP was developed in collaboration with the hospital's antibiotic stewardship team and subsequently introduced with staff training in the ED. The study was approved by the local ethics committee of the medical faculty of the Heinrich Heine University (2019-392-RetroDEuA). RESULTS: In total 92% of the nursing personnel and 93% of the medical personnel received training. The total number of blood cultures increased from 1757 to 2872 (64% increase) and the rate of blood cultures per 1000 patients from 287 to 481 (68% increase). The number of positive blood cultures decreased from 18.6% to 13.7% (p < 0.05). Typical skin pathogens were found in 34.4% and 26.4% of the cases, respectively (p < 0.05). CONCLUSION: The development, introduction and training of a BC-SOP in the ED can make a relevant contribution to the microbial diagnostics and increase the quantity as well as the quality.

Severe pulmonary haemorrhage syndrome in leptospirosis in a returning traveller.

Clinical presentation of leptospirosis ranges from asymptomatic infection to fulminant, life-threatening disease. Pulmonary involvement in terms of severe pulmonary haemorrhage syndrome (SPHS) has recently become a more frequently reported facet of leptospirosis and correlates with high mortality rates. It has not yet been described in returning German travellers. We present a case of a healthy young man developing massive pulmonary haemorrhage and severe ARDS requiring mechanical ventilation and high-dose catecholamines after travelling to Indonesia. Leptospirosis was verified by blood PCR as well as serology and treated with high-dose, intravenous penicillin. Outcome was favourable, the patient recovered completely. Leptospirosis and SPHS should be taken into account as an emerging infectious disease in patients with fever and lung involvement.

Photoreactivation and subsequent solar disinfection of Escherichia coli in UV-disinfected municipal wastewater under natural conditions.

Photoreactivation of ultraviolet (UV)-disinfected wastewater of different qualities was experimentally assessed. Photoreactivation ability of secondary effluent and microstrained inflow was analyzed in different samples of 50 mL (Petri dish) and 7,000 mL volume to describe open channel effluent situations of wastewater treatment plants in a more realistic approach. The small sample of secondary effluent revealed a total log10 inactivation of 1.8 units and the small sample of microstrained inflow a total log10 inactivation of 3.2, with an applied UV-254 fluence of 84 and 253 J/m², respectively. Maximum net photoreactivation for secondary effluent and microstrained inflow was in the order of 1.2 log10 and 0.37 log10 units, respectively, for both sample sizes. However, significantly faster photoreactivation performance was generally determined for small sample volumes. The photoreactivation processes were completely compensated for by solar disinfection within a 120 min exposure time. Solar disinfection processes were negligible in the larger sample volumes of microstrained inflow. For municipal wastewater treatment systems with open channel effluents, it is essential to take into consideration the dependence of solar UV-365 fluence rate on water depth and wastewater characteristics.

In vitro characterization of representative clinical South African Staphylococcus aureus isolates from various clonal lineages.

Data concerning the virulence and pathogenesis of South African strains of Staphylococcus aureus are limited. We investigated host-pathogen interactions of randomly selected clinical S. aureus isolates representing various clones. We characterized the ability of isolates to adhere to fibronectin, fibrinogen, collagens IV and VI, to invade host cells and to induce cell death in vitro. We analysed the possible association of these results with characteristics such as methicillin resistance, Panton-Valentine leucocidin (PVL) positivity and clonality. The S. aureus isolates displayed diversity in their abilities to adhere to various human ligands. All isolates were highly invasive except for ST121. PVL-negative isolates were significantly more invasive than the PVL-positive isolates (p 0.004). Isolates of CC5, CC30 and CC121 were non-cytotoxic, whereas isolates of CC22, CC8, CC15, CC45 and CC88 were very cytotoxic. No statistical association was identified between cell death and methicillin resistance, bacterial PVL status, clonality or patient HIV status. The vast majority of isolates were invasive and induced significant cell death. PVL-negative isolates were more invasive than PVL-positive isolates, while methicillin-resistant isolates were not found to be more invasive or cytotoxic than methicillin-susceptible isolates.

Population structure analyses of Staphylococcus aureus at Tygerberg Hospital, South Africa, reveals a diverse population, a high prevalence of Panton-Valentine leukocidin genes, and unique local methicillin-resistant S. aureus clones.

Studies reporting on the population structure of Staphylococcus aureus in South Africa have focused only on methicillin-resistant S. aureus (MRSA). This study describes the population structure of S. aureus, including methicillin-susceptible S. aureus (MSSA) isolated from patients at Tygerberg Academic Hospital, Western Cape province. Pulsed-field gel electrophoresis (PFGE), detection of Panton-Valentine leukocidin (PVL), spa typing, multilocus sequence typing (MLST), agr typing and SCCmec typing were used to characterize strains. Of 367 non-repetitive S. aureus isolates collected over a period of 1 year, 56 (15.3%) were MRSA. Skin and soft tissue infections were the most frequent source (54.8%), followed by bone and joint (15.3%) and respiratory tract infections (7.7%). For strain typing, PFGE was the most discriminative method, and resulted in 31 pulsotypes (n = 345, 94.0%), as compared with 16 spa clonal complexes (CCs) (n = 344, 93.4%). Four MLST CCs were identified after eBURST of sequence types (STs) of selected isolates. One hundred and sixty isolates (MSSA, n = 155, 42.2%) were PVL-positive, and agr types I-IV and SCCmec types I-V were identified. Our S. aureus population consisted of genotypically diverse strains, with PVL being a common characteristic of MSSA. MSSA and MRSA isolates clustered in different clones. However, the dominant MRSA clone (ST612) also contained an MSSA isolate, and had a unique genotype. Common global epidemic MRSA clones, such as ST239-MRSA-III and ST36-MRSA-II, were identified. A local clone, ST612-MRSA-IV, was found to be the dominant MRSA clone.

Plasmodium knowlesi infection imported to Germany, January 2013.

Plasmodium knowlesi was known as a plasmodium of macaques until P. knowlesi transmission to humans was recognised in Borneo and later throughout South-East Asia. We describe here a case of a P. knowlesi infection imported to Germany from Thailand. The patient had not taken antimalarial chemoprophylaxis and suffered from daily fever attacks. Microscopy revealed trophozoites and gametocytes resembling P. malariae. P. knowlesi malaria was confirmed by PCR.

Superior Detection of Pathogens in Synovial Fluid by the Bactec 9240 Peds Plus/F System Compared to the Conventional Agar-based Culture Method

To improve culture yield in cases of possible septic arthritis; we compared culture of joint fluid aspirates on conventional agar-based media to culture in Bactec 9240 Peds/Plus F blood culture bottles with and without the addition of fastidious organism supplement (FOS). Over a period of 21 months; we analysed 123 synovial fluid samples and isolated 20 pathogens. The Bactec methods proved superior by yielding more pathogens than the conventional culture method (p=0.074). However; this method also yielded more contaminants within the first three days of incubation (p=0.027). All contaminants detected after three days of incubation were the result of overgrowth on conventional method agar plates. The Bactec methods provided clinicians with a positive pathogen result one day earlier than the conventional counterpart (p=0.001). Four isolates of Neisseria gonorrhoeae were only cultured with the Bactec method. No significant benefit was demonstrated by supplementing blood culture bottles with FOS. We recommend that whenever infection by fastidious organisms is suspected; synovial fluid aspirates should be cultured using automated blood culture systems to increase the culture yield and to decrease the time to detection

Isotopic dependence of the nuclear caloric curve.

The A/Z dependence of projectile fragmentation at relativistic energies has been studied with the ALADIN forward spectrometer at SIS. A stable beam of (124)Sn and radioactive beams of (124)La and (107)Sn at 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z of the produced spectator sources, consistent with predictions for expanded systems. Small Coulomb effects (DeltaT approximately 0.6 MeV) appear for residue production near the onset of multifragmentation.

Rehabilitation of therapy-related cognitive deficits in patients after hematopoietic stem cell transplantation.

Neuropsychological deficits are potential side effects of hematopoietic stem cell therapy (HSCT). Systematic data on the long-term course of and therapeutic options for these consequences are limited. One hundred fifty-seven patients were screened for cognitive deficits following HSCT for malignant diseases at an in-patient oncologic rehabilitation clinic. Patients showing evidence of impairment were randomly assigned to one of two training groups: individualized PC-supported training or neuropsychological group therapy. The control group consisted of patients who received no specific training. During in-patient rehabilitation, the results of a comprehensive neuropsychological test battery improved significantly in all three groups, and no specific intervention effects were identified. Neuropsychological deficits were still evident in a subgroup of patients 6 months later. Correlation between neuropsychological testing and patients' self-evaluation of cognitive functioning in daily life was generally low. Sustained attention and verbal-semantic memory played the main role for self-appraisal and in the designation as 'neuropsychologically impaired'. In conclusion, a substantial number of patients revealed evidence of cognitive deficits a long time after HSCT. There is a need for more studies and for the development of differentiated rehabilitative measures for such therapeutic consequences.

Centralised versus decentralised wastewater systems?

A host of centralised and decentralised systems are available for wastewater disposal purposes. Consequently, selecting the right system calls for a comprehensive and, above all, unbiased assessment of the alternatives. Costs and unsettled ecological issues can be adduced to show that total rejection of one system or the other is not warranted. An ecological assessment that, for example, also covers hygienic aspects is only in its infancy and an intensification of research work is necessary. The example of a conurbation is used to illustrate the interplay of centralised and decentralised elements.

Clinical rotation in pathology: description of a case based approach.

BACKGROUND: The implementation of a system based, integrated curriculum at the Faculty of Health Sciences of Stellenbosch University, Western Cape, South Africa, resulted in less contact time for the pathology disciplines during theoretical modules, while a weekly rotation in pathology was introduced during clinical training in the fourth and fifth years. OBJECTIVE: To describe a problem based approach for this rotation. METHODS: Students are presented with a clinical "paper" case daily, integrating as many of the pathology disciplines as possible to demonstrate the interdependence of the various disciplines. They receive chemical pathology tutorials, visit the various laboratories, and receive practical training in fine needle aspiration biopsy. On the final day, the case studies are assessed and discussed. RESULTS: Most students appreciated all activities. This rotation enhanced student interactivity and autonomy and guaranteed immediate feedback. On evaluation of the rotation it was found that the students enjoyed the rotation, learnt something new, and realised the value of group work. CONCLUSIONS: This innovation integrates pathology with clinical practice and illustrates the use of laboratory medicine in the management of common diseases seen in this country. Students appreciate learning practical skills and having to request special investigations under a pathologist's supervision changes their approach to pathology requests. Familiarity with the pathology environment empowers the student to use pathology with greater ease. A bank of case studies that can be expanded to include all medical disciplines will facilitate the application of a problem based approach and enhance communication between the basic science disciplines and the clinical and pathology disciplines.

Isotopic scaling and the symmetry energy in spectator fragmentation.

Isotopic effects in the fragmentation of excited target residues following collisions of 12C on (112,124)Sn at incident energies of 300 and 600 MeV per nucleon were studied with the INDRA 4pi detector. The measured yield ratios for light particles and fragments with atomic number Z < or = 5 obey the exponential law of isotopic scaling. The deduced scaling parameters decrease strongly with increasing centrality to values smaller than 50% of those obtained for the peripheral event groups. Symmetry-term coefficients, deduced from these data within the statistical description of isotopic scaling, are near gamma = 25 MeV for peripheral and gamma < 15 MeV for central collisions.

Infective endocarditis: improving the diagnostic yield.

INTRODUCTION: Isolating aetiological agents in patients with infective endocarditis (IE) remains problematical. We postulated that the high local incidence of culture-negative IE resulted from antibiotic exposure prior to blood cultures and that a structured delay in therapy in the subacute presentation would improve the diagnostic yield. AIM: We aimed to prospectively observe the diagnostic approach and give an overview of supplementary laboratory tests. STUDY DESIGN: Patients with suspected IE were enrolled into this analytical observational study and followed up for six months (n = 92). We compared the diagnostic yield and outcome in cases where antibiotics were withheld for 72 hours, with those cases who received early antimicrobials, despite being deemed safe for delayed therapy. RESULTS: Definitive diagnoses (definite or excluded IE) were made in 92.8% of patients where antibiotics were delayed, compared to 60% of patients who received empirical treatment (p = 0.08). The mortality rates were 18.4% and 30.0% (p = 0.18). Twenty-three of 26 patients with definite culture-negative IE received antibiotics during the 48 hours preceding cultures, compared to eight of 21 culture-positive patients (P < 0.001). Screening for atypical bacteria did not improve the yield. C-reactive protein (CRP) had a sensitivity of 97.0% (negative predictive value 87.5%), whereas a positive rheumatoid factor (RF) had a specificity of 93.8% (positive predictive value 91.7%). CONCLUSIONS: We observed tendencies towards a greater diagnostic yield and lower mortality where antibiotics were initially withheld. Antibiotic prior to blood cultures were an important cause of culture-negative IE. A normal CRP proved useful in excluding IE; a positive RF strongly favoured IE.

Infective endocarditis in the Western Cape Province of South Africa: a three-year prospective study.

BACKGROUND: The last 50 years have seen major changes in the epidemiology of infective endocarditis (IE). AIM: To evaluate local patient characteristics, risk factors, clinical sequelae, microbiology, morbidity and mortality in patients with definite IE. DESIGN: Prospective observational study. METHODS: Over a three-year period, patients referred with probable IE were prospectively enrolled. All received a standardized diagnostic evaluation. Epidemiological data were documented; underlying risk factors for IE were sought. Initial evaluation and follow-up (to 6 months) included the documentation of vascular or immunological phenomena, morbidity and mortality. RESULTS: Of 92 patients referred with probable IE, 47 had definite IE. These patients had a mean age of 37.7 years with a male predominance (1.6:1). Rheumatic heart disease was present in 36 (76.6%). Eight had prosthetic valves. Three had congenital heart disease, mitral valve prolapse or multiple central intravascular catheters, respectively. All denied the use of intravenous recreational drugs and only one tested seropositive for HIV. Renal involvement (59.6%) and clubbing (29.8%) were commonly observed. The 6-month mortality rate was 35.6%, while 44.7% needed valvular replacement. An aetiological diagnosis was made in 21, with viridans streptococci the most common isolate. DISCUSSION: Infective endocarditis in the Western Cape of South Africa is a disease of younger adults, with a male predominance. Rheumatic heart disease is the major predisposing factor. Degenerative heart disease and intravenous drug abuse are not important risk factors. Our data do not support the notion that HIV infection is an independent risk factor for IE. Local mortality rates are much higher than recent international figures, as is the proportion of 'culture-negative' IE.

Control measures for wastewater treatment plants during storm flow.

In the context of the development of treatment plant control techniques, three measures for maintaining a high efficiency of treatment plants during rainfall events were tested. The three measures are increasing the nitrification volume by operating a facultative aeration, bypassing the primary sedimentation and adding flocculants before secondary sedimentation. Ammonia concentrations and ammonia loads were used in combination with rainfall forecasts as the criteria for putting the measures into operation. A simulation based on the Activated Sludge Model No. 1 and a pilot scale plant were used for testing the measures. The results show that all three measures may be suitable to cope with peak loads of treatment plants during rainfall events.

Isolation, purity analysis and stability of hyperforin as a standard material from Hypericum perforatum L.

In 1996 131.5 million daily doses of preparations containing extracts of Hypericum perforatum L. were prescribed in Germany for treating mild to moderately severe depressive disorders. New pharmacological and clinical results focus on hyperforin as the main active ingredient of the drug. Hyperforin (C35H52O4) is one of the main components (2-4%) of the dried herb Hypericum perforatum L. It was isolated after six consecutive steps: extraction of deep-frozen blossoms (-20 degrees C) with n-hexane by means of an Ultra Turrax at room temperature; separation of lipophilic substances on a silica gel column; purification of the relevant fraction by preparative HPLC; evaporation of the mobile phase under reduced pressure; removal of the remaining water by freeze-drying; and storage of hyperforin at -20 degrees C under nitrogen. The identity and purity of the isolated substance were determined by high-performance thin-layer chromatography (HPTLC), high-performance liquid chromatography (HPLC) with diode-array and ultraviolet detection (DAD and UV), Fourier-transformed infrared (FTIR) and proton nuclear magnetic resonance (1H NMR) spectroscopy, and liquid chromatography coupled with positive-ion electrospray-ionization tandem mass spectrometry (LC-ESI(+)-MS-MS). By use of these methods the purity of hyperforin was shown to be >99.9%. Peroxides present at each step of the isolation were detected by titration and by means of Merckoquant analytical peroxide test-strips. Elimination of the peroxides and stabilization of hyperforin was achieved by consistent protection from oxidation-the mobile phases were protected by use of ascorbic acid; evaporation and freeze-drying were performed under nitrogen; and the mobile phase used for preparative HPLC was sparged with helium. Stability testing was performed by HPLC-the samples were stored at -30 degrees C in a normal atmosphere and at -20, 4, and 20 degrees C in a normal atmosphere or under nitrogen. Results were compared with those obtained after storage under liquid nitrogen (-196 degrees C). Because of its high sensitivity to oxidation, hyperforin was more stable under nitrogen under all test conditions. There was no statistically significant difference between results obtained after 8 months at -20 degrees C under nitrogen or at -30 degrees C under a normal atmosphere and those from the reference sample stored under liquid nitrogen (-196 degrees C). Despite this, because of the tendency of hyperforin to degrade, long-term storage at -70 degrees C under nitrogen is recommended.

[Late idiopathic pneumopathy following bone marrow transplantation]. / Späte idiopathische Pneumopathie nach Knochenmarktransplantation.

4 of the 198 patients treated by bone marrow transplantation in Basel, Switzerland, with a follow-up of more than one year after therapy, developed a severe restrictive pneumopathy. In none of the 4 patients could an infectious pathogen be isolated, but all of them had signs of a chronic graft-versus-host disease. The 4 cases are described in detail.

[gamma-heavy chain production as an epiphenomenon in non-Hodgkin's lymphoma]. / gamma-Schwerketten-Produktion als Epiphänomen bei Non-Hodgkin-Lymphom.

A 46-year-old woman was found to have localized lymphoplasmocytic lymphoma (low-malignancy non-Hodgkin lymphoma). Repeated recurrences required various chemotherapy courses with different drugs. Gamma heavy chains in serum and urine, as well as in blast cells in bone marrow, were first found 3 years later as part of a follow-up examination. When the lymphoplasmocytic lymphoma subsequently changed into a highly malignant disseminated large-cell lymphoma, the monoclonal gamma heavy chain-producing components no longer occurred. During continuing treatment and presumably selection of different cell clones the now terminal chemotherapy-resistant lymphoma again produced biclonal IgG heavy chains. The gamma heavy chain production added little to the histomorphological characterization of the underlying lymphoma, as well as its treatment and prognosis.