Rapid MRSA PCR on respiratory specimens from ventilated patients with suspected pneumonia: a tool to facilitate antimicrobial stewardship.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of pneumonia in ventilated patients. Our objective was to evaluate the GeneXpert MRSA/SA SSTI Assay (Xpert MRSA/SA) (Cepheid, Sunnyvale, CA) for use in lower respiratory tract (LRT) specimens for rapid MRSA detection and to determine the potentially saved antibiotic-days if a culture-based identification method was replaced by this assay. Remnant LRT samples from ventilated patients submitted to the microbiology laboratory for routine culture were tested using conventional culture and Xpert MRSA/SA. One hundred of 310 LRT specimens met the inclusion criteria. Ten samples were positive for MRSA by Xpert MRSA/SA, while six were positive by routine culture methods. Xpert MRSA/SA correctly identified 5/6 positive and 89/94 negative MRSA specimens, for a sensitivity of 83.3%, specificity of 94.7%, positive predictive value of 45.6%, and negative predictive value of 98.9%. The assay also correctly detected 3/3 positive and 90/97 negative methicillin-susceptible S. aureus (MSSA) specimens, for a sensitivity of 100%, specificity of 92.8%, positive predictive value of 30%, and negative predictive value of 100%. A total of 748 vancomycin and 305 linezolid antibiotic-days were associated with the enrolled specimens. Vancomycin and linezolid utilization could decrease by 68.4% and 83%, respectively, if discontinued 1 day after negative polymerase chain reaction (PCR) results. The Xpert MRSA/SA SSTI rapid MRSA PCR assay performed well in respiratory samples from ventilated patients with suspected pneumonia and has the potential to facilitate stewardship efforts such as reducing empiric vancomycin and linezolid therapy.

Baseline hypovitaminosis D is not associated with poor clinical outcomes in osteoarticular infections.

OBJECTIVES: Although vitamin D is recognized as an important factor in bone health, its role in osteoarticular infections is unclear. We hypothesized that low vitamin D (25-hydroxycholecalciferol) levels are associated with a lower likelihood of treatment success in osteoarticular infections. METHODS: This was a retrospective cohort study of patients with orthopedic infections who had a 25-hydroxycholecalciferol level drawn when their infection was diagnosed. Outcomes were determined at early (3-6 months) and late (≥ 6 months) follow-up after completing intravenous antibiotics. RESULTS: We included 223 patients seen during an 11-month period with osteoarticular infections and baseline 25-hydroxycholecalciferol levels. During the initial inpatient management of the infection, hypovitaminosis D was identified and treated. The mean 25-hydroxycholecalciferol level was 23 ± 14 ng/ml; 167 (75%) patients had levels <30 ng/ml. Overall, infection treatment success was 91% (159/174) at early follow-up and 88% (145/164) at late follow-up. 25-Hydroxycholecalciferol baseline levels were similar in those with and without successful clinical outcomes, both at early (25 ± 15 vs. 21 ± 9 ng/ml; p=0.3) and late follow-up (25 ± 15 vs. 23 ± 16 ng/ml; p=0.6). CONCLUSIONS: To our knowledge this is the first report on hypovitaminosis D and its impact on outcomes of osteoarticular infections. Hypovitaminosis D was frequent in this cohort. With vitamin D repletion, there was no difference in treatment success whether patients had baseline hypovitaminosis or not.

Daptomycin versus vancomycin for osteoarticular infections due to methicillin-resistant Staphylococcus aureus (MRSA): a nested case-control study.

Vancomycin is the standard antibiotic for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. While daptomycin is approved for MRSA bacteremia, its effectiveness in osteoarticular infections (OAIs) has not been established. A 1:2 nested case-control study of adult patients with MRSA OAIs admitted to an academic center from 2005 to 2010 was carried out. Clinical outcomes and drug toxicity in patients treated with daptomycin versus vancomycin were compared. Twenty patients with MRSA OAIs treated with daptomycin were matched to 40 patients treated with vancomycin. The median age of the patients was 52 years (range, 25-90), and 40 (67%) were male. Most patients had osteomyelitis (82%), predominantly from a contiguous source (87%). Forty percent were diabetics. Diabetic patients were more likely to receive vancomycin than daptomycin [20 (50%) vs. 4 (20%); p = 0.03]. Vancomycin was more often combined with antibiotics other than daptomycin [22 (55%) vs. 5 (25%); p = 0.03]. The median total antibiotic treatment duration was 48 (daptomycin) vs. 46 days (vancomycin) (p = 0.5). Ninety percent of daptomycin-treated patients had previously received vancomycin for a median of 14.5 days (range, 2-36). Clinical success rates were similar between daptomycin and vancomycin at 3 months [15 (75%) vs. 27 (68%); p = 0.8] and 6 months [14 (70%) vs. 23 (58%); p = 0.5], even after propensity score-based adjustment for antibiotic assignment. The frequency of adverse events was similar between treatment groups [1 (5%) vs. 7 (18%); p = 0.2]. Daptomycin and vancomycin achieved similar rates of clinical success and drug tolerability. Daptomycin is a reasonable alternative for treating MRSA OAIs, particularly in patients where therapy with vancomycin has not been well tolerated.

Changes in influenza vaccination rates among healthcare workers following a pandemic influenza year at a Japanese tertiary care centre.

BACKGROUND: Although influenza vaccination, which is a key part of a control plan to prevent nosocomial influenza transmission, is recommended for all healthcare workers (HCWs), the achievement of a high influenza vaccination rate among HCWs is a challenge. In Japan, there are limited data on influenza vaccination rates among HCWs. Moreover, the effect of pandemic influenza on influenza vaccination rates among HCWs following a pandemic year remains unclear. AIM: To determine influenza vaccination rates among HCWs at a tertiary medical centre in Japan, and to evaluate the need for further interventions to enhance the vaccination rate among HCWs. METHODS: The 2005-2010 influenza vaccination rates among HCWs at a 550-bed, tertiary care centre in Sapporo, Japan were reviewed retrospectively using the hospital's occupational health service database. FINDINGS: There was a gradual increase in the seasonal influenza vaccination rate in this population from 2005 to 2010, and a high vaccination rate among HCWs during the 2009-2010 pandemic H1N1 influenza season. However, the seasonal influenza vaccination rate in 2010-2011 was significantly lower than that for the pandemic vaccine in 2009-2010, with doctors having the lowest vaccination rate among all HCWs. CONCLUSION: Pandemic influenza may not have a sustained effect on the uptake of influenza vaccination in subsequent years. Thus, vaccination rates among HCWs after a pandemic year still need to be monitored, and the implementation of interventions such as a mandatory vaccination programme should be considered to maintain consistently adequate vaccination rates.

Successful treatment of vancomycin-resistant Enterococcus endocarditis with oral linezolid.

We report a case of vancomycin-resistant Enterococcus faecium endocarditis that failed to respond to sequential monotherapy with chloramphenicol and quinupristin/dalfopristin but was successfully treated with oral linezolid.

Relating the microscopic and macroscopic response of a polymeric fluid in a shearing flow.

The microscopic and macroscopic response of a polymer solution in start-up shear flow was investigated using fluorescence microscopy of single molecules, bulk viscosity measurements, and Brownian dynamics simulations. An overshoot in viscosity was observed upon flow inception and understood via the observed molecular extension and by simulation findings. Increasing the polymer concentration up to six times the overlap concentration ( C(*)) has no effect on the character of the dynamics of individual molecules.

A single-molecule study of RNA catalysis and folding.

Using fluorescence microscopy, we studied the catalysis by and folding of individual Tetrahymena thermophila ribozyme molecules. The dye-labeled and surface-immobilized ribozymes used were shown to be functionally indistinguishable from the unmodified free ribozyme in solution. A reversible local folding step in which a duplex docks and undocks from the ribozyme core was observed directly in single-molecule time trajectories, allowing the determination of the rate constants and characterization of the transition state. A rarely populated docked state, not measurable by ensemble methods, was observed. In the overall folding process, intermediate folding states and multiple folding pathways were observed. In addition to observing previously established folding pathways, a pathway with an observed folding rate constant of 1 per second was discovered. These results establish single-molecule fluorescence as a powerful tool for examining RNA folding.

Single-polymer dynamics in steady shear flow.

The conformational dynamics of individual, flexible polymers in steady shear flow were directly observed by the use of video fluorescence microscopy. The probability distribution for the molecular extension was determined as a function of shear rate, gamma;, for two different polymer relaxation times, tau. In contrast to the behavior in pure elongational flow, the average polymer extension in shear flow does not display a sharp coil-stretch transition. Large, aperiodic temporal fluctuations were observed, consistent with end-over-end tumbling of the molecule. The rate of these fluctuations (relative to the relaxation rate) increased as the Weissenberg number, gamma;tau, was increased.

The dynamics of partially extended single molecules of DNA.

The behaviour of an isolated polymer floating in a solvent forms the basis of our understanding of polymer dynamics. Classical theories describe the motion of a polymer with linear equations of motion, which yield a set of 'normal modes', analogous to the fundamental frequency and the harmonics of a vibrating violin string. But hydrodynamic interactions make polymer dynamics inherently nonlinear, and the linearizing approximations required for the normal-mode picture have therefore been questioned. Here we test the normal-mode theory by measuring the fluctuations of single molecules of DNA held in a partially extended state with optical tweezers. We find that the motion of the DNA can be described by linearly independent normal modes, and we have experimentally determined the eigenstates of the system. Furthermore, we show that the spectrum of relaxation times obeys a power law.

Effect of anisotropy of the bending rigidity on the supercoiling free energy of small circular DNAs.

In principle, the supercoiling free energy of a small circular DNA will be enhanced by increasing the anisotropy of its bending potential at constant persistence length. The magnitude of this effect is investigated by Monte Carlo simulation using an extension of a previously proposed algorithm. The supercoiling free energy at 298 K is simulated for circular DNAs containing N = bp with torsion constant alpha = 5.8 X 10(-12) dyne cm, persistence lengths P = 500 A and 10,000 A, and a range of anisotropies of the bending potential from rho = 1.0 to 16.0. The apparent torsion constants, reckoned from these supercoiling free energies by assuming an isotropic bending potential, are found to increase by less than 3% as the input anisotropy increases from 1.0 to 16.0 When P = 500 A, the apparent torsion constant never rises significantly above the input value over the entire range of input anisotropies. When P = 10,000 A, the apparent torsion constant rises only about 3% above the input value for anisotropies rho = 8.0 and 16.0. Evidently, anisotropy of the bending potential cannot account for the fact that the torsion constants reported for small circular DNAs exceed those reported for long linear DNAs by a factor of 1.6 or more.

Changes in presence of a segmental dysfunction pattern associated with hypertension: Part 1. A short-term longitudinal study.

A statistically significant pattern of segmental components of somatic dysfunction associated with a history of high blood pressure was investigated for change after an interval of 4 to 8 months. The volunteer subjects, from an inner-city ambulatory clinic, included normotensive, borderline hypertensive, and hypertensive persons. A standardized palpatory examination determined whether there were specific motion asymmetries centered at spinal segments C6, T2, and T6 and confirmed by mirror-image motion asymmetries in adjacent segments. Blood pressure measurements and diagnosis of hypertension followed American Heart Association standards. The repeated presence of the pattern in subjects with a history of hypertension was statistically significant. Presence of the pattern in normotensive subjects, however, appeared to be random. The subjects' histories during the study period revealed no influence of antihypertensive medications, major accidents, or illness on the patterns' continuing presence in subjects requiring medical control of their hypertension.

A test of the model-free formulas. Effects of anisotropic rotational diffusion and dimerization.

The effects of anisotropy of rotational diffusion and extent of dimerization on the performance of the simple and extended model-free formulas are investigated. Numerically exact 15N NMR R1, R2, and NOE data are simulated for cylindrically symmetric species and also for mixtures of spherical monomers and dimers with the same internal dynamics. The relevant internuclear vectors are assumed to move in isotropic deflection potentials fixed at different orientations in the molecule and to exhibit a single relaxation time in their internal correlation functions. The simple model-free formula is fitted to these simulated data in order to obtain the best-fit order parameter and internal relaxation time for each nucleus. Fitting is accomplished by the standard data-analysis protocol, in which a single common global correlation time is adjusted, and also by an alternative protocol, in which the global correlation time is adjusted separately for each nucleus. The extended model-free formula is likewise fitted to these same data. With noise-free data, the simple model-free formula and standard protocol yield remarkably good best-fit internal motion parameters up to moderate anisotropies (r = D parallel/D perpendicular = 2.0), but some or many of the NMR relaxation data are not fitted well even for quite modest anisotropies (r = 1.3). The extended model-free formula yields an improved fit to the NMR data, but predicts substantial amplitudes of nonexistent slow internal motions (tau approximately greater than 0.2 ns) for many of the nuclei for all r > or = 1.3. The simple model-free formula with the alternate protocol yields even better internal motion parameters than the standard protocol and also an excellent fit to the NMR relaxation data. The best-fit global correlation time for each nucleus corresponds very closely to the theoretical correlation time defined herein. Knowledge of these times would allow one not only to estimate the anisotropy of diffusion but also in favorable cases to infer the existence of slow internal motions. Inclusion of typical statistical errors in R1, R2, and NOE, or modest exchange contributions to R2, seriously degrades the performance of the simple model-free formula with either protocol, especially in regard to the internal relaxation times, which can exhibit very large deviations from their input value even for spherical diffusors. When the fraction of monomers existing as dimers lies in the range 0.1 < or = fd < or = 0.8, none of the three model-free approaches tested yields reliable internal motion parameters.

Children with cancer and medical students teach each other.

A medical student group and a pediatric oncology staff have united resources to provide a unique opportunity for patients and students. This article describes a program that matches first- and second-year medical students with individual children who have cancer or another chronic illness. Modeled after the traditional "Big Brother/Big Sister" programs, this program has two purposes: (1) to provide medical students with a better understanding of the issues concerning patients with chronic illness and their families, and (2) to provide individual emotional support for young patients while, coincidentally, offering some relief for their parents. Students in the early academic years of medical school are given an opportunity to develop a relationship with a patient, and patients can develop a relationship with a responsible adult who is concerned as much about friendship and companionship as about a patient and illness.

Adaptive optics revisited.

From the earliest days and nights of telescopic astronomy, atmospheric turbulence has been a serious detriment to optical performance. The new technology of adaptive optics can overcome this problem by compensating for the wavefront distortion that results from turbulence. The result will be large gains in resolving power and limiting magnitude, closely approaching the theoretical limit. In other words, telescopic images will be very significantly sharpened. Rapid and accelerating progress is being made today by several groups. Adaptive optics, together with the closely related technology of active optics, seems certain to be utilized in large astronomical telescopes of the future. This may entail significant changes in telescope design.