Whole-genome sequencing reveals two prolonged simultaneous outbreaks involving Pseudomonas aeruginosa high-risk strains ST111 and ST235 with resistance to quaternary ammonium compounds.

OBJECTIVE: Water-bearing systems are known as frequent Pseudomonas aeruginosa (PA) outbreak sources. However, many older buildings continue to have sanitary facilities in high-risk departments such as the ICU. We present two simultaneous prolonged multi-drug-resistant (MDR) PA outbreaks detected at the ICU of a pulmonology hospital, which were resolved by whole-genome sequencing (WGS). METHODS: Outbreak management and investigations were initiated in August 2019 after detecting two patients with nosocomial VIM-2-positive MDR PA. The investigations involved weekly patient screenings for four months and extensive environmental sampling for 15 months. All patient and environmental isolates were collected and analysed by WGS. RESULTS: From April to September 2019, we identified 10 patients with nosocomial MDR PA, including five VIM-2-positive strains. VIM-2-positive strains were also detected in nine sink drains, two toilets, and a cleaning bucket. WGS revealed that of 16 VIM-2-positive isolates, 14 were ST111 that carried qacE, or qacEΔ1 genes, whereas 13 isolates clustered (difference of ≤11 alleles by cgMLST). OXA-2 (two toilets), and OXA-2, OXA-74, PER-1 (two patients, three toilets) qacEΔ1-positive ST235 isolates dominated among VIM-2-negative isolates. The remaining seven PA strains were ST17, ST233, ST273, ST309 and ST446. Outbreak containment was achieved by replacing U-bends, and cleaning buckets, and switching from quaternary ammonium compounds (QUATs) to oxygen-releasing disinfectant products. CONCLUSION: Comprehension and management of two simultaneous MDR PA outbreaks involving the high-risk strains ST111 and ST235 were facilitated by precise control due to identification of different outbreak sources per strain, and by the in-silico detection of high-level QUATs resistance in all isolates.

Concerning emergence of a new vancomycin-resistant Enterococcus faecium strain ST1299/CT1903/vanA at a tertiary university centre in South Germany.

BACKGROUND: vanB-carrying vancomycin-resistant Enterococcus faecium (VREfm) of the sequence types 80 (ST80) and ST117 have dominated Germany in the past. In 2020, our hospital witnessed a sharp increase in the proportion of vanA-positive VREfm. AIM: To attempt to understand these dynamics through whole-genome sequencing (WGS) and analysis of nosocomial transmissions. METHODS: At our hospital, the first VREfm isolate per patient, treated during 2020, was analysed retrospectively using specific vanA/vanB PCR, WGS, multi-locus sequence typing (MLST), and core-genome (cg) MLST. Epidemiologic links between VRE-positive patients were assessed using hospital occupancy data. FINDINGS: Isolates from 319 out of 356 VREfm patients were available for WGS, of which 181 (56.7%) fulfilled the ECDC definition for nosocomial transmission. The high load of nosocomial cases is reflected in the overall high clonality rate with only three dominating sequence (ST) and complex types (CT), respectively: the new emerging strain ST1299 (100% vanA, 77.4% CT1903), and the well-known ST80 (90.0% vanB, 81.0% CT1065) and ST117 (78.0% vanB, 65.0% CT71). The ST1299 isolates overall, and the subtype CT1903 in particular, showed high isolate clonality, which demonstrates impressively high spreading potential. Overall, 152 out of 319 isolates had an allelic cgMLST difference of ≤3 to another, including 91 (59.6%) ST1299. Occupancy data identified shared rooms (3.7%), shared departments (6.2%), and VRE-colonized prior room occupants (0.6%) within 30 days before diagnosis as solid epidemiological links. CONCLUSION: A new emerging VREfm clone, ST1299/CT1903/vanA, dominated our institution in 2020 and has been an important driver of the increasing VREfm rates.

Nanosilver/DCOIT-containing surface coating effectively and constantly reduces microbial load in emergency room surfaces.

BACKGROUND: Colonization of near-patient surfaces in hospitals plays an important role as a source of healthcare-associated infections. Routine disinfection methods only result in short-term elimination of pathogens. AIM: To investigate the efficiency of a newly developed antimicrobial coating containing nanosilver in long-term reduction of bacterial burden in hospital surfaces to close the gap between routine disinfection cycles. METHODS: In this prospective, double-blinded trial, frequently touched surfaces of a routinely used treatment room in an emergency unit of a level-I hospital were treated with a surface coating (nanosilver/DCOIT-coated surface, NCS) containing nanosilver particles and another organic biocidal agent (4,5-dichloro-2-octyl-4-isothiazolin-3-one, DCOIT), whereas surfaces of another room were treated with a coating missing both the nanosilver- and DCOIT-containing ingredient and served as control. Bacterial contamination of the surfaces was examined using contact plates and liquid-based swabs daily for a total trial duration of 90 days. After incubation, total microbial counts and species were assessed. FINDINGS: In a total of 2880 antimicrobial samples, a significant reduction of the overall bacterial load was observed in the NCS room (median: 0.31 cfu/cm2; interquartile range: 0.00-1.13) compared with the control coated surfaces (0.69 cfu/cm2; 0.06-2.00; P < 0.001). The nanosilver- and DCOIT-containing surface coating reduced the relative risk of a critical bacterial load (defined as >5 cfu/cm2) by 60% (odds ratio 0.38, P < 0.001). No significant difference in species distribution was detected between NCS and control group. CONCLUSION: Nanosilver-/DCOIT-containing surface coating has shown efficiency for sustainable reduction of bacterial load of frequently touched surfaces in a clinical setting.

[Hygiene during otorhinolaryngological examinations : Prevention of nosocomial infections]. / Hygiene bei der HNO-Untersuchung : Vermeidung nosokomialer Infektionen.

Awareness of the importance of working as aseptically as possible first emerged in the 19th century. In the meantime, there is an obligation to prevent transmission and further spread of pathogens, including adherence to the Infection Protection Act. Pathogens can also survive for a long time on inanimate surfaces, from where they can be transferred via the hands of personnel and thus lead to infections. Studies have shown that even contamination of untouched instruments after an otorhinolaryngological examination is not a rare occurrence. The Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) of the Robert Koch Institute gives recommendations for general hygiene measures (basic or standard hygiene). These must be adapted and implemented accordingly for the otorhinolaryngological examination. Due to the increasing development of resistance of nosocomial pathogens and the current pandemic, consistent implementation of these infection-prevention measures is important.

[Epidemiology of SARS-CoV-2/COVID-19]. / Epidemiologie von SARS-CoV-2/COVID 19: Aktueller Stand.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta coronavirus, which first appeared in 2019 and rapidly spread causing a worldwide pandemic. Here we present a nonsystematic review of the current knowledge on its epidemiological features. The SARS-CoV­2 replicates mainly in the upper and lower respiratory tract and is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The estimate for the basic reproduction number (R0) is between 2 and 3 and the median incubation period is 6 days (range 2-14 days). Similar to the related coronaviruses SARS and Middle East respiratory syndrome (MERS), superspreading events play an important role in spreading the disease. The majority of infections run an uncomplicated course but 5-10% of those infected develop pneumonia or a systemic inflammation leading to hospitalization, respiratory and potentially multiorgan failure. The most important risk factors for a complicated disease course are age, hypertension, diabetes, chronic cardiovascular and pulmonary diseases and immunodeficiency. The current infection fatality rate over all age groups is between 0.5% and 1% and the rate rises after the sixth decade of life. Nosocomial transmission and infections in medical personnel have been reported. A drastic reduction of social contacts has been implemented in many countries with outbreaks of SARS-CoV­2, leading to rapid reductions in R0. Most interventions have used bundles and which of the measures have been more effective is still unknown. Using mathematical models an incidence of 0.4%-1.8% can be estimated for the first wave in Germany.

Novel photodynamic coating reduces the bioburden on near-patient surfaces thereby reducing the risk for onward pathogen transmission: a field study in two hospitals.

BACKGROUND: Near-patient surfaces are recognized as a source for hospital-acquired infections. Such surfaces act as reservoirs for microbial contamination by which pathogens can be transmitted from colonized or infected patients to susceptible patients. Routine disinfection of surfaces only results in a temporal elimination of pathogens, and recontamination inevitably occurs shortly between disinfections. AIM: A novel antimicrobial coating based on photodynamics was tested under laboratory conditions and subsequently in a field study in two hospitals under real-life conditions. METHODS: Identical surfaces received a photodynamic or control coating. Bacterial counts [colony-forming units (cfu)/cm2) were assessed regularly for up to 6 months. FINDINGS: The laboratory study revealed a mean reduction of several human pathogens of up to 4.0 ± 0.3 log10. The field study in near-patient environments demonstrated mean bacterial values of 6.1 ± 24.7 cfu/cm2 on all control coatings. Photodynamic coatings showed a significantly lower mean value of 1.9 ± 2.8 cfu/cm2 (P<0.001). When considering benchmarks of 2.5 cfu/cm2 or 5 cfu/cm2, the relative risk for high bacterial counts on surfaces was reduced by 48% (odds ratio 0.38, P<0.001) or 67% (odds ratio 0.27, P<0.001), respectively. CONCLUSION: Photodynamic coatings provide a significant and lasting reduction of bacterial counts on near-patient surfaces, particularly for high bacterial loads, in addition to routine hygiene. The promising results of this proof-of-concept study highlight the need for further studies to determine how this novel technology is correlated with the frequency of hospital-acquired infections.

[Microbiological diagnosis of periprosthetic joint infections]. / Mikrobiologische Diagnostik periprothetischer Gelenkinfektionen.

BACKGROUND: Prosthetic joint infection is a rare but serious complication after arthroplasty, leading to prolonged hospitalization and repeated surgical intervention. THEME: In this article, successful strategies for the rapid and accurate microbiological diagnosis of infection are reviewed. In the case of clinical suspicion of a prosthetic joint infection, at least a comprehensive clinical review of the patient's postoperative history, a physical examination, routine blood tests including white cell count, erythrocyte sedimentation rate, and C-reactive protein, and further investigation of the synovial-fluid leukocyte count and microbial culture are needed. Depending of the clinical signs of infection additional blood culture samples should be taken. RESULTS: The gold standard to confirm infection is a surgical procedure with at least 5-6 biopsies from suspected areas for both microbial culture and histopathological examination. Culture results may be negative because of previous antimicrobial therapy, a low number of culturable organisms in biofilm formations, inappropriate culture medium, and prolonged transport time. CONCLUSION: In any of these conditions, diagnosis with highly sensitive diagnostic techniques such as polymerase chain reaction should be considered for the identification of the causative agent in order to establish the most appropriate antimicrobial treatment options.

[Ophthalmomyiasis externa]. / Ophthalmomyiasis externa.

Ophthalmomyiasis refers to infestation of the eye by fly larvae. Although rare, cases have been reported from all over the world. Patients with ophthalmomyiasis suffer from itching, foreign body sensation and epiphora. Ophthalmomyiasis is mostly caused by larvae of Oestrus ovis, the common sheep botfly. Larvae of Oestrus ovis are photophobic and hide in the upper and lower fornix. First line treatment consists of mechanical removal of the larvae.

Fatal anthrax infection in a heroin user from southern Germany, June 2012.

Blood cultures from a heroin user who died in June 2012, a few hours after hospital admission, due to acute septic disease, revealed the presence of Bacillus anthracis. This report describes the extended diagnosis by MALDI-TOF and real-time PCR and rapid confirmation of the anthrax infection through reference laboratories. Physicians and diagnostic laboratories were informed and alerted efficiently through the reporting channels of German public health institutions, which is essential for the prevention of further cases.

Successful treatment of Scedosporium apiospermum soft tissue abscess with caspofungin and voriconazole in a severely immunocompromised patient with acute myeloid leukemia.

We report the case of a 53-year-old female patient with refractory acute myeloid leukemia developing a necrotic, soft tissue abscess on the right forearm caused by Scedosporium apiospermum during prolonged severe neutropenia (absolute white blood cell count <500/µL for 49 days). In the context of the severely immunocompromised state of the patient and her need for allogeneic hematopoietic stem cell transplantation (HSCT), surgical treatment options were not favored. Therefore, combined antifungal therapy with voriconazole and caspofungin was started, based on the results of the in vitro testing (minimum inhibitory concentrations of voriconazole, posaconazole, and amphotericin B: 1, 4, and >2mg/L, respectively). The local site of infection slowly improved clinically and no spread of S. apiospermum infection to other sites was observed. After HSCT, the soft tissue abscess resolved completely and the patient has remained free of S. apiospermum infection since then. We successfully demonstrate that the use of combined antifungal therapy with voriconazole and casopfungin may further improve the clinical course and provides a promising therapeutic option to treat Scedosporium infections in such patients.

[Anaplastic astrocytomas of the medulla oblongata. A rare differential diagnosis in orthostatic hypotension]. / Anaplastisches Astrozytom der Medulla oblongata. Eine seltene Differentialdiagnose bei orthostatisch bedingter Hypotonie.

HISTORY AND PHYSICAL EXAMINATION: A 39-year-old women was admitted for evaluation of dizziness and hypotension. During standing the blood pressure dropped from 130/80 to 80/40 mmHg. Ten weeks before admission she had recurrent cerebral convulsions. Neurological evaluation showed a slight left hemiparesis. Computed tomography of the brain revealed a 1.5 +/- 1 cm cyst in the left tempral region. It was thought that the cause of the recurrent convulsions was alcohol abuse. During the next few weeks orthostatic hypotension increased and she was not able to work. INVESTIGATIONS: At admission abnormal findings included hypotension, horizontal nystagmus, and deviation of the soft palate to the right. After the patient was brought to an upright position during standardized passive tilt testing she showed a defect in the sympathetic limb of the baroreceptor reflex arc. Head magnetic resonance tomography showed a signal-enhancing tumour in the cervicomedullary region. TREATMENT AND CLINICAL COURSE: Before a planned biopsy could be performed the patient died of respiratory arrest. Postmortem examination revealed an anaplastic grade III astrocytoma extending form the pons to the medulla oblongata. CONCLUSION: Upright tilting leads to pooling of blood in the legs. One of the normal compensatory responses is a reflex tachycardia which our patient did not show as a sign of an afferent defect. Patients with orthostatic hypotension as a prominent symptom should be investigated with a standardized tilt test. In special patients, additional neurological investigations are necessary.

Transgenic and knock out mice in skeletal research. Towards a molecular understanding of the mammalian skeleton.

Our understanding of the biology of the skeleton, like that of virtually every other subject in biology, has been transformed by recent advances in human and mouse genetics. Among mammals, mice are the most promising animals for this experimental work. Because extensive genetic information exists, many mouse mutations are known, and cells from early mouse developmental stages are accessible, scientists have developed transgenic mice - mice in which a gene is introduced or ablated in the germ line. Thus far, we have analyzed more than 100 different transgenic and knock out models with various skeletal phenotypes, covering the major aspects of both skeletal development and skeletal maintenance. Based on these results we here present a first perspective on transgenic and gene knock out animals in skeletal research, including insights in signaling pathways controlling endochondral bone formation, in the regulation of osteoblast function, osteoclastic bone resorption and in bone tumorigenesis, as well as the central control of bone formation. The use of transgenic mice to dissect and analyze regulatory mechanisms in bone cell physiology and the pathogenesis of human bone diseases is an extremely powerful experimental tool. The data presented here demonstrate that the successful convergence of novel genetic approaches with the established and fundamental knowledge of bone biology has made a beginning.

Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses.

1,25-Dihydroxyvitamin D3 has been shown to play an important role in vitro in regulating osteoblast gene transcription and promoting osteoclast differentiation. To address the role of the vitamin D receptor (VDR) in skeletal homeostasis, formal histomorphometric analyses were performed in VDR null mice in the setting of impaired mineral ion homeostasis as well as in VDR null mice in whom normal mineral ion homeostasis had been preserved. In hypocalcemic VDR null mice, there was an increase in bone volume as a result of a dramatic increase in osteoid. There was also an increase in the number of osteoblasts without a significant change in the number of osteoclasts. Examination of the growth plate revealed marked disorganization, with an increase in vascularity and matrix. Biomechanical parameters demonstrated increased bone fragility in the hypocalcemic VDR null mice. In the VDR ablated mice in whom normal mineral ion homeostasis had been preserved, none of these measurements was significantly different from those in wild-type littermates raised under identical conditions. Notably, the morphology and width of the growth plate were indistinguishable from those in wild-type controls, demonstrating that a calcium/phosphorus/lactose-enriched diet started at 16 days of age in the VDR null mice permits the development of both normal morphology in the growth cartilage and adjacent metaphysis and normal biomechanical competence of cortical bone. Thus, the principle action of the VDR in skeletal growth, maturation, and remodeling is its role in intestinal calcium absorption. The skeletal consequences of VDR ablation are a result of impaired intestinal calcium absorption and/or the resultant secondary hyperparathyroidism and hypophosphatemia.

Dopamine D2 receptor occupancy measured by single photon emission computed tomography with 123I-Iodobenzamide in chronic schizophrenia.

Single photon emission computed tomography (SPECT) with 123I-iodobenzamide (123I-IBZM) was used to study 22 chronic schizophrenic patients. The patients, who were receiving maintenance therapy with typical neuroleptics, had not shown any significant improvement since their admission to the hospital. Basal ganglia/frontal cortex ratios of the uptake of 123I-IBZM did not show significant differences on the basis of neuroleptic dosage in chlorpromazine equivalents. There were, however, significant differences in 123I-IBZM uptake in the basal ganglia among patients characterized by negative, mixed, and positive symptoms of schizophrenia. Although only a small number of patients had shown a positive response to treatment by the time of discharge, D2 receptor blockade was significantly higher in responders than in nonresponders. In addition, there was an inverse correlation between reduced activation as measured by the Brief Psychiatric Rating Scale and the basal ganglia/frontal cortex ratio. These findings suggest a complex pathogenetic link between the blockade of dopamine D2 receptors and psychopathology in chronic schizophrenic patients. SPECT studies with 123I-IBZM appear to have prognostic value in identifying chronic schizophrenic patients who respond poorly to neuroleptic treatment.

[Foreign patients in inpatient treatment in a psychiatric university clinic with community service]. / Ausländische Patienten in stationärer Behandlung in einer psychiatrischen Universitätsklinik mit Versorgungsauftrag.

About one third (29.5%) of the population living within the area of Frankfurt, for which the psychiatric university clinic provides psychiatric service, are foreigners. For the better understanding of our foreign psychiatric inpatients treated in our clinic in in 1992, the diagnostic spectrum and the nationalities of these patients were analysed. More than half of them (58%) were raised up in former Yugoslavia, Turkey, Italy, Poland and Marocco. The other foreign patients came from 36 different countries. The diagnostic spectrum comparing german and foreign patients showed marked differences. Paranoid schizophrenia was more common in foreigners (31.5%) compared with german patients (16.8%), as well as female foreigners were admitted to the clinic because of psychoreactive disorders (65.2% of all turkish females) more often. The language barrier limited the treatment in many patients. In addition treatment was also hampered by family induced pressure on our patients. This was mainly due to differences and misunderstanding concerning the nature and treatment strategies. In spite of these difficulties, engagement of the therapeutic teams and treatment outcome did not differ between german and foreign patients. In order to improve treatment modalities, we quote for an increasing number of psychiatrists, who are capable of serbocroatic, turkish, italian, polish or arab language and culture, to work in clinical psychiatry.

Duodenal fistula--a rare complication following the removal of an infected aortic graft: case report.

We present a rare case of fistulation from the duodenum into the prosthesis site of an aortic Y graft removed 8 months previously owing to infection. We have verified the topographical and anatomical location of the fistulation by fistula filling and CT and MR examination. To our knowledge such a postoperative complication has not been previously documented. In evaluating and comparing our observation we discuss their significance for topographical associations and prognosis and as an indication for surgical intervention.

[Pseudoexfoliation syndrome. Clinical and statistical studies]. / Pseudo-Exfoliations-Syndrom. Klinisch-statistische Untersuchungen.

Between July 1, 1980 and December 31, 1982, out of 26 825 patients treated in both the outpatient and inpatient departments at the University Eye Clinic of Erlangen-Nürnberg, 107 (i.e., 0.4%) were found to have pseudo-exfoliation syndrome. In 51 cases only one eye was affected, in 56 cases both. Of these patients 49 were male and 58 female. They were between 54 and 89 years old, the average age being 73.2 years. In 61.3% of the cases the initial symptom was ocular hypertension. In about 75% the most important finding on slit-lamp examination, with the pupil undilated, was atrophy of the pupillary margin. A central disc was only seen in 39.3%, while the peripheral band was present in all cases. Fistulating operations had to be performed in 43 out of 100 cases diagnosed as having capsular glaucoma. This corresponds to 18.5% of all fistulating procedures performed for primary chronic open-angle glaucoma.

[Clinical experiences in the use of lymphovenous anastomoses in secondary lymphedema]. / Klinische Erfahrungen in der Anwendung von lympho-venösen Anastomosen beim sekundären Lymphödem.

Secondary lymphedema of the arm after therapy for breast cancer has a frequency of about 30% in the Federal Republic of Germany. Many authors have performed lympho-venous anastomoses to release lymphostatic edema, most using microsurgical technique. In this paper the authors present microlympho-venous anastomoses done in a telescope-like manner and using fibrin glue. First this technique was applied to dogs, later to patients. Measurement of the limb and of the limb volume at different levels were done pre- and postoperatively. Investigations with radionucleides were undertaken in some cases to measure lymphatic clearance. The operations were performed under local anaesthesia with perioperative antibiotic prophylaxis. The procedure was well tolerated by the patients, achieving a reduction of the swelling of about 30%. Despite the short follow-up of only six months and the limited number of cases we feel that this type of therapy should be offered to patients with secondary lymphedema.

[Autologous vein grafts as artery replacement in microsurgery. An experimental study of micro- and macromorphologic changes 3 weeks to 12 months postoperatively]. / Autologe Veneninterponate als Arterienersatz in der Mikrogefässchirurgie. Eine experimentelle Studie der mikro- und makromorphologischen Veränderungen in Zeiträumen von 3 Wochen bis 12 Monate postoperativ.

In 45 rabbits we interposed autologous vein grafts of different length in equivalent defects of the femoral artery. After fixed intervals of six weeks to 12 months functional, histological and angiographic studies were done. Long grafts showed the same thrombus rate as short ones. The histological findings showed a marked thickening of the vessel wall with a maximum between six to eight weeks after operation. After this period this thickening was reduced but was after 12 months still noticeable. The angiography showed no signs of stenosis or narrowing of the lumen. Occasionally we saw bone formation or incrustation which might be induced by intima lesions.