A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial.

OBJECTIVES: Intestinal carriage with extended spectrum ß-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. METHODS: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48 days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7). RESULTS: Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT). CONCLUSIONS: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.

Signs of stigma and poor mental health among carriers of MRSA.

BACKGROUND: Many countries have implemented guidelines to prevent transmission of meticillin-resistant Staphylococcus aureus (MRSA). Important contextual factors of stigma can be identified in the context of MRSA. Over the past decade, concerns have been raised over a possible stigmatizing effect of these actions. AIM: To identify and quantify the occurrence of MRSA-associated stigma, and to explore its association with mental health in a country with an MRSA 'search and destroy' policy. METHODS: In 2014, a questionnaire study among 57 Dutch MRSA carriers (people that carry MRSA without signs of MRSA infection) was performed. Stigma was measured with an adjusted version of the Berger HIV Stigma Scale. Mental health was measured with the five-item RAND Mental Health Inquiry. FINDINGS: Thirty-two (56%) MRSA carriers reported stigma; of these, eight (14%) reported 'clear stigma' (Berger score >110) and 24 (42%) reported 'suggestive for stigma' (Berger score 76-110). Educational level, female sex and intensive MRSA eradication therapy were associated with higher stigma scores. Poor mental health (RAND score <60) was reported by 33% of MRSA carriers. Stigma and mental health scores were inversely correlated. Stigma was experienced most frequently in healthcare settings, and was seldom experienced in the religious community or at sport facilities. CONCLUSION: A substantial proportion of MRSA carriers reported stigma due to MRSA, and stigma was associated with poor mental health. Anticipation of MRSA-associated stigma is warranted, both in the way that care is delivered by hospital staff and in the way that care is organized within the hospital.

Diagnosis and treatment of tuberculous uveitis in a low endemic setting.

OBJECTIVE: To determine factors associated with the diagnosis of tuberculous uveitis and the response to anti-tuberculous treatment (ATT). METHODS: A retrospective case study was performed at the University Medical Centre Utrecht between October 2007 and December 2009. Patients with possible tuberculous uveitis (TBU) were selected from all patients with an unexplained uveitis. Demographics, ethnicity, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tuberculin skin test (TST), QuantiFERON (QFT) test, and ocular findings were evaluated. An interdisciplinary panel discussed if there was a presumed TBU and decided to start treatment. When there was a decrease in intraocular cell count and/or improvement in visual acuity after ATT, the confirmation of presumed TBU was made. RESULTS: Of 585 patients with unexplained uveitis, 66 (11.3%) fulfilled the definition of possible TBU. Ten (15.4%) patients were regarded as having presumed TBU and received ATT. All of them had latent tuberculosis (LTB). The ocular situation improved in seven patients (70%). A history of TB contact, abnormalities on chest radiology, and extraocular manifestations of TB were associated with a good response to ATT in the case of presumed tuberculous uveitis. CONCLUSIONS: Tuberculous uveitis remains difficult to diagnose. No clearly correlating factors that predicted the response to ATT, including ocular parameters, could be identified.

Rapid diagnostic testing of methicillin-resistant Staphylococcus aureus carriage at different anatomical sites: costs and benefits of less extensive screening regimens.

Multiple body site screening and pre-emptive isolation of patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage are considered essential for control of nosocomial spread. The relative importance of extranasal screening when using rapid diagnostic testing (RDT) is unknown. Using data from a multicentre study evaluating BD GeneOhm™ MRSA PCR (IDI), Xpert MRSA (GeneXpert) and chromogenic agar, added to conventional cultures, we determined cost-effectiveness assuming isolation measures would have been based on RDT results of different hypothetical screening regimes. Costs per isolation day avoided were calculated for regimes with single or less extensive multiple site RDT, regimes without conventional back-up cultures and when PCR would have been performed with pooling of swabs. Among 1764 patients at risk, MRSA prevalence was 3.3% (n = 59). In all scenarios the negative predictive value is above 98.4%. With back-up cultures of all sites as a reference, the costs per isolation day avoided were €15.19, €30.83 and €45.37 with 'nares only' screening using chromogenic agar, IDI and GeneXpert, respectively, as compared with €19.95, €95.77 and €125.43 per isolation day avoided when all body sites had been screened. Without back-up cultures costs per isolation day avoided using chromogenic agar would range from €9.24 to €76.18 when costs per false-negative RDT range from €5000 up to €50 000; costs for molecular screening methods would be higher in all scenarios evaluated. In conclusion, in a low endemic setting chromogenic agar screening added to multiple site conventional cultures is the most cost-effective MRSA screening strategy.

Transmissibility of livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch hospitals.

We quantified nosocomial transmission rates of sequence type (ST) 398 methicillin-resistant Staphylococcus aureus (MRSA) (an emerging livestock-associated MRSA clone) and non-ST398 MRSA isolates in patients hospitalized without infection control measures in 51 Dutch hospitals. Identification of 174 index patients initiated 139 post-exposure screenings of 9925 persons. There were 65 genotype-confirmed secondary cases (three and 62 for ST398 and non-ST398 MRSA, respectively), yielding a relative transmission risk for ST398 MRSA of 0.28 (95% CI 0.09-0.90), which was not sensitive to adjustment for duration of hospitalization at time of detection. Nosocomial transmission of ST398 MRSA is 72% less likely than that of non-ST398 MRSA strains.

Psychological impact of short-term isolation measures in hospitalised patients.

Unintended negative effects, such as anxiety and depression, have been demonstrated in patients subjected to infection control strategies, such as isolation for long periods. Yet isolation precautions are mostly short-term. We therefore determined levels of anxiety, depression and quality of life in patients exposed to short-term isolation. In a cross-sectional matched cohort study, performed in a single university hospital, patients isolated for infection control were evaluated with the Hospital Anxiety and Depression Scale [HADS-A (Anxiety) and HADS-D (Depression)], Visual Analogue Scale of EQ-5D (EQ VAS) and an isolation evaluation questionnaire within 24-48 h after start of isolation. Two matched controls were selected for each isolated patient. Isolated patients (N=42) and control patients (N=84) had comparable HADS-A (4.5 vs 5.0), HADS-D (4.0 vs 5.0) and EQ VAS (65 vs 62) scores. In multiple regression analysis comorbidity was associated with EQ VAS outcome (P=0.005), whereas all other variables, including being in isolation, were unrelated to HADS and EQ VAS scores. Patients reported positive associations with isolation measures. The quality of care provided by physicians and nurses, as perceived by isolated patients, was not negatively affected in 74% and 71% of patients, respectively. In conclusion, short-term infection control measures do not influence hospitalised patients' levels of anxiety and depression and quality of life. Isolated patients had a positive attitude towards the precautions taken.

Rapid screening of methicillin-resistant Staphylococcus aureus using PCR and chromogenic agar: a prospective study to evaluate costs and effects.

Pre-emptive isolation of suspected methicillin-resistant Staphylococcus aureus (MRSA) carriers is considered essential for controlling the spread of MRSA, but noncolonized patients will be isolated unnecessarily as a result of a delay in diagnosis of 3-5 days with conventional cultures. We determined costs per isolation day avoided, and incremental costs of rapid MRSA screening tests when added to conventional screening, but with decisions on isolation measures based on PCR results. A prospective multicentre study evaluating BD GeneOhm MRSA PCR (`IDI') (BD Diagnostics, San Diego, CA, USA), Xpert MRSA (`GeneXpert') (Cepheid, Sunnyvale, CA, USA) and chromogenic agar (MRSA-ID) (bioMérieux, Marcy-l'Etoile, France) was performed in 14 Dutch hospitals. Among 1764 patients at risk, MRSA prevalence was 3.3% (n=59). Duration of isolation was 19.7 and 16.1 h with IDI and GeneXpert, respectively, and would have been 30.0 and 76.2 h when based on chromogenic agar and conventional cultures, respectively. Negative predictive values (at a patient level) were 99.5%, 99.1% and 99.5% for IDI, GeneXpert and chromogenic agar, respectively. Numbers of isolation days were reduced by 60% and 47% with PCR-based and chromogenic agar-based screening, respectively. The cost per test was €56.22 for IDI, €69.62 for GeneXpert and €2.08 for chromogenic agar, and additional costs per extra isolation day were €26.34. Costs per isolation day avoided were €95.77 (IDI) and €125.43 (GeneXpert). PCR-based decision-making added €153.64 (IDI) and €193.84 (GeneXpert) per patient to overall costs and chromogenic testing would have saved €30.79 per patient. Rapid diagnostic testing safely reduces the number of unnecessary isolation days, but only chromogenic screening, and not PCR-based screening, can be considered as cost saving.

[Methicillin-resistant Staphylococcus aureus of livestock origin in Dutch hospitals: high-risk patients need only to be investigated if admitted to hospital]. / Meticillineresistente Staphylococcus aureus afkomstig uit de veestapel in Nederlandse ziekenhuizen: risicopatiënten alleen controleren bij eventuele ziekenhuisopname.

OBJECTIVE: To determine the incidence and prevalence of carriage of methicillin-resistent Staphylococcus aureus (MRSA) in patients and hospital personnel, and to examine the consequences of the revised Dutch MRSA guideline with respect to patients who have frequent contact with pigs or calves (in the course of their work). DESIGN: Retrospective and prospective observational study using questionnaires. METHOD: Since July 2006 patients who have contact with living pigs or calves have been regarded as a high-risk group for MRSA carriage, after it was established that this occupational group had an increased chance of carriage of the so-called non-typable MRSA (NT-MRSA). An inventory was made of incidence and prevalence of MRSA carriage in patients and hospital personnel, and of the consequences of the new MRSA policy, for the period July-December 2006. RESULTS: Information was obtained from 58 Dutch hospitals. On January 1 2007, 37 (64%) hospitals had changed their MRSA policy; 22% of the hospitals it was applied in accordance with the MRSA guideline. The new guideline resulted in an increase of MRSA screenings by 15% and of detected MRSA carriers by 44%. 73% of all MRSA screenings took place in the out-patients department. In regions with high pig-density the incidence of NT-MRSA was 12% in patients with risk factors for carriage. In 49% of the hospitals one or more NT-MRSA carriers were detected (range 1-19 carriers). Possible transmission of NT-MRSA in hospital was shown in 3 of 1,007 (0.3%) hospital personnel, but in none of the 183 fellow-patients, examined. In the same period transmission of typable MRSA was demonstrated in 41 of 2,019 (2.0%) patients and 33 of 5,190 (0.6%) of hospital personnel examined. Prevalence of NT-MRSA carriage in 6,197 screened hospital personnel was 0.05% (n = 3). CONCLUSION: The revised Dutch MRSA guideline lead to an increase in the number of MRSA screenings by 15%, particularly in the out-patients department, and to an increase in the number of detected MRSA carriers by 44%. During 306 months of observation no patient-to-patient transmission ofNT-MRSA was demonstrated.

Hypertension management in primary care: standard care and attitude towards a disease management model.

INTRODUCTION: Cardiovascular risk control has become one of the hallmarks in the treatment of diabetes and coronary heart disease, yet assessment of individual risk factors is suboptimal. We have designed a new Hypertension Screening Facility (HSF) for the evaluation of cardiovascular risk in hypertensive patients, based on 1) systematic, protocol-driven (WHO/ISH-based) analysis by nurse practitioners, 2) computer-assisted reporting of results and advice, 3) risk assessment using a Decision Support System (DSS), 4) maintenance of the autonomy of the GP. In a pilot study we wanted to investigate this HSF. METHODS: Survey 1 addressed a. how general practitioners deal with hypertension, b. whether they intend to and do use existing clinical guidelines, c. what their opinions are towards changes in the current process of care. In survey 2, we evaluated the attitude of GPs using the HSF. Responses were 43% (51 out of 120) to the first survey and 100% (20 out of 20) to the second. RESULTS: The majority of physicians included lifestyle in their assessment of risk factors and management of hypertension. Consideration of age and a positive family history was extremely high. In contrast, vision disturbances, ECG and microalbuminuria were not often considered. In the absence of additional risk factors, drug treatment was initiated in patients with a mean systolic blood pressure of 162+/-6 over 99+/-4 mmHg. In the presence of risk factors (obesity, smoking and a positive family history of cardiovascular disease) treatment is started at an average blood pressure of 154+/-8 over 96+/-4 mmHg. Opinions towards a change in management of hypertensive patients were generally positive. The opinions about the new HSF and the cardiovascular risk were reported to the general practitioner and considered useful or very useful by 79%. CONCLUSION: The present study thus confirms that cardiovascular risk evaluation by GPs is suboptimal, but there is a positive attitude towards an improvement in their assessment by HSF. The novelty of the HSF is that it respects the autonomy of the GP and brings the expertise to the GP.

White matter lesions and encephalopathy in patients treated for primary central nervous system lymphoma.

A retrospective analysis of the clinical presentations and neuroimaging characteristics of 33 patients with a primary central nervous system lymphoma (PCNL) who received cranial radiotherapy was performed to assess incidence of and risk factors for radiation-induced encephalopathy. CT and MRI scans were revised by a neurologist and a radiologist in conference. White matter abnormalities before and after radiotherapy on the last scan before recurrence were quantified according to a semi-quantitative scale. All available medical records were retrieved and reviewed with respect to demographic and tumor-related variables, treatment modalities, disease-free and overall survival and clinical symptoms and signs of encephalopathy. CT and MRI scans showed severe white matter lesions in 75% of 20 patients and in 86% of patients aged more than 60 years. Forty percent of patients presented with new clinical signs of cognitive impairment a median of 14.5 months after initial diagnosis (8.5 months after radiotherapy). The risk of white matter lesions appeared greater in patients aged >60 (RR 1.2, 95% CI = 0.8-2.0), in patients with prior white matter lesions (RR 1.3, 95% CI = 0.8-2.1) and in patients with multifocal cerebral lymphoma (RR 1.5, 95% CI = 1.0-2.1). In conclusion, the risk of white matter lesions and clinical symptoms and signs of encephalopathy is high in patients treated by radiotherapy for PCNL. The risk appears to be greatest in older patients, patients with multifocal tumor and in those with prior white matter lesions on CT or MRI.

Tongue force in patients with myasthenia gravis.

OBJECTIVES: The aim was to study tongue force in patients with bulbar myasthenia gravis and compare it with that of patients with ocular myasthenia gravis, patients in clinical remission who previously suffered from bulbar myasthenia gravis, and healthy subjects. MATERIAL AND METHODS: Tongue force was measured with a tongue force transducer in cranial and lateral directions, which coincide with the directions in which the tongue exerts force during swallowing, speech, and mastication. RESULTS: Tongue force in lateral direction was significantly decreased in patients with bulbar myasthenia gravis. In addition, our findings suggest an incomplete recovery of lateral tongue force in the patients of the remission group. CONCLUSION: Our tongue force measurements may be useful for longitudinal evaluation of therapy in individual patients and also in studies of therapy efficacy in matched groups of patients if the influence of factors such as age, dental state, and sex is taken into account.

Oral functions of patients with myasthenia gravis.

With the use of the methods developed to quantify oral dysfunctions in bulbar MG patients, our results indicate that we can distinguish the patients from their matched controls. These results can add to our knowledge of myasthenia gravis and these methods may improve diagnosis and therapy evaluation in individual patients. In addition, these methods may be used in future pharmacological research.