A multi-center blinded study on the efficiency of phenotypic screening methods to detect glycopeptide intermediately susceptible Staphylococcus aureus (GISA) and heterogeneous GISA (h-GISA)

Contains fulltext : 52338.pdf (publisher's version ) (Open Access)BACKGROUNDS: To determine the true incidence of hGISA/GISA and its consequent clinical impact, methods must be defined that will reliably and reproducibly discriminate these resistant phenotypes from vancomycin susceptible S. aureus (VSSA). METHODS: This study assessed and compared the ability of eight Dutch laboratories under blinded conditions to discriminate VSSA from hGISA/GISA phenotypes and the intra- and inter-laboratory reproducibility of agar screening plates and the Etest method. A total of 25 blinded and unique strains (10 VSSA, 9 hGISA and 6 GISA) were categorized by the PAP-AUC method and PFGE typed to eliminate clonal duplication. All strains were deliberately added in quadruplets to evaluate intra-laboratory variability and reproducibility of the methods. Strains were tested using three agar screening methods, Brain Heart Infusion agar (BHI) + 6 microg/ml vancomycin, Mueller Hinton agar (MH) + 5 microg/ml vancomycin and MH + 5 microg/ml teicoplanin) and the Etest macromethod using a 2 McFarland inoculum. RESULTS AND DISCUSSION: The ability to detect the hGISA/GISA phenotypes varied significantly between methods and phenotypes. BHI vancomycin and MH vancomycin agar screens lacked the ability to detect hGISA. The MH teicoplanin agar screen was more sensitive but still inferior to Etest that had a sensitivity of 98.5% and 99.5%, for hGISA and GISA, respectively. Intra- and inter-laboratory reproducibility varied between methods with poorest performance seen with BHI vancomycin. CONCLUSION: This is the first multi-center blinded study to be undertaken evaluating various methods to detect GISA and hGISA. These data showed that the ability of clinical laboratories to detect GISA and hGISA varied considerably, and that screening plates with vancomycin have a poor performance in detecting hGISA

Reduced costs with bisoprolol treatment for heart failure - An economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II)

Background Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II). Methods Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS . These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per them (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K. Results Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions perpatient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per them analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound 4987 vs pound 4722 in the U.K. The diagnosis related group analysis gave similar results. Interpretation Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This `win-win' situation of positive health benefits associated with cost savings is Favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure

Predicting bacterial cause in infectious conjunctivitis: cohort study on informativeness of combinations of signs and symptoms

Objective To find an efficient set of diagnostic indicators that are optimally informative in. the diagnosis of a bacterial origin of acute infectious conjunctivitis. Design Cohort study involving consecutive patients. Results of index tests and reference standard were collected independently from each other. Setting 25 Dutch health centres. Participants 184 adults presenting with a red eye and either (muco)purulent discharge or glued eyelid(s), not wearing contact lenses. Main outcome measures Probability of a positive bacterial culture, given different combinations of index test results; area under receiver operating characteristics curve. Results Logistic regression analysis showed optimal diagnostic discrimination for the combination of early morning glued eye(s), itch, and a history of conjunctivitis. The first of these indicators increased the likelihood of a bacterial cause, whereas the other two decreased it. The area under the receiver operating characteristics curve for this combination of symptoms was 0.74 (95% confidence interval 0.63 to 0.80). The overall prevalence of bacterial involvement of 32% could be lowered to 4% or raised to 77%, depending on the pattern of index test results. Conclusion A bacterial origin of complaints indicative of acute infectious conjunctivitis can be made much more likely or unlikely by the answers to three simple questions posed during clinical history taking (possibly by telephone). These results may have consequences for more targeted prescription of ocular antibiotic

Diagnosis of conjunctivitis in primary care: comparison of two different culture procedures

Background: In general practice, infectious conjunctivitis is a common and mostly (64%) self-limiting disorder. In case of an aberrant course or severe symptoms, a general practitioner may take a culture. Direct inoculation is considered the reference standard, but usually a swab is sent to a laboratory. Objectives: To compare the diagnostic performance of the swab, transported by surface mail with direct inoculation. Methods: 19 general practitioners took two samples of the conjunctiva from 88 patients with symptoms suggestive of infectious conjunctivitis by rolling a cotton swab across the conjunctiva of the lower fornix. One swab was used to inoculate three agar plates directly, while the other was sent in a Stuart medium to the laboratory and inoculated at the time of arrival. The numbers of positive cultures of both methods were compared. Results: A pathogen was found in 31 of 88 samples (35% (95% CI 26 to 46)). Surprisingly, the number of positive cultures was higher for the Stuart medium (27/88) than for direct inoculation (23/88). The difference was 4.5% (90% CI 0 to 12, p = 0.388; one-sided McNemar test for paired proportions). In five of the 19 samples that were positive in both tests, the cultured pathogens were different. Conclusions: The Stuart medium detected more bacteria than direct inoculation. The lower 90% CI, testing non-inferiority at p = 0.05, indicates that it is unlikely that the Stuart medium misses any positive cultures compared with direct inoculatio

The effect of shock duration on trauma-induced coagulopathy in a murine model

Background: Trauma-induced coagulopathy (TIC) is a life-threatening condition associated with high morbidity and mortality. TIC can present with different coagulation defects. In this study, the aim was to determine the effect of shock duration on TIC characteristics. We hypothesized that longer duration of shock leads to a more hypocoagulable rotational thromboelastometry (ROTEM) profile compared to a shorter duration of shock. Methods: Male B57BL/6J(c) mice (n = 5–10 per group) were sedated and mechanically ventilated. Trauma was induced by bilateral lower limb fractures and crush injuries to the liver and small intestine. Shock was induced by blood withdrawals until a mean arterial pressure of 25–30 mmHg was achieved. Groups reflected trauma and shock for 30 min (TS30) and trauma and shock for 90 min (TS90). Control groups included ventilation only (V90) and trauma only (T90). Results: Mice in the TS90 group had significantly increased base deficit compared to the V90 group. Mortality was 10% in the TS30 group and 30% in the TS90 group. ROTEM profile was more hypocoagulable, as shown by significantly lower maximum clot firmness (MCF) in the TS30 group (43.5 [37.5–46.8] mm) compared to the TS90 group (52.0 [47.0–53.0] mm, p = 0.04). ROTEM clotting time and parameters of clot build-up did not significantly differ between groups. Conclusions: TIC characteristics change with shock duration. Contrary to the hypothesis, a shorter duration of shock was associated with decreased maximum clotting amplitudes compared to a longer duration of shock. The effect of shock duration on TIC should be further assessed in trauma patients