Since the 1970s, outpatient parenteral antimicrobial therapy (OPAT) has been a viable option for patients who require intravenous antibiotics when hospitalization is not warranted. While the benefits ...of OPAT as a measure to improve the efficiency of healthcare delivery (i.e., reduced hospital days) and patient satisfaction are well-documented, OPAT is associated with a number of challenges, including line complications and reliance on daily healthcare interactions in some cases at home or in a clinic. To minimize the continued need for intensive healthcare services in the outpatient setting, there is trend toward patients self-administering antibiotics at home without the presence of healthcare workers, after adequate training. In most cases, patients administer the antibiotics through an established intravenous catheter. While this OPAT practice is becoming more accepted as a standard of care, the potential for line complications still exists. Outpatient subcutaneous antimicrobial therapy (OSCAT) has become an increasingly accepted alternative route of administration of antibiotics to IV by French infectious diseases physicians and geriatricians; however, currently, no antibiotics are approved to be administered subcutaneously. Antibiotics with longer half-lives that are completely absorbed and have a favorable local tolerability profile are ideal candidates for OSCAT and have the potential to maximize the quality and efficiency of parenteral antibiotic delivery in the outpatient setting. The increasing development of wearable, on-body subcutaneous delivery systems make OSCAT even more viable as they increase patient independence while avoiding line complications and potentially removing the need for direct healthcare professional observation.
Questions on Vancomycin Dosing Rybak, Michael J; Le, Jennifer; Lodise, Thomas P ...
Clinical infectious diseases,
10/2021, Letnik:
73, Številka:
7
Journal Article
Iclaprim is a bacterial dihydrofolate reductase inhibitor that is currently being evaluated in two phase 3 trials for the treatment of patients with acute bacterial skin and skin structure infections ...(ABSSSI). Prior animal infection model studies suggest that the pharmacokinetic/pharmacodynamic (PK/PD) drivers for efficacy are area under the concentration-time curve from 0 to 24 h at steady state (AUC
), AUC/MIC, and time above the MIC during the dosing interval (
> MIC), while QTc prolongation was associated with the maximal concentration at steady state (
) in a thorough QTc phase 1 study. Using PK data collected from 470 patients from the previously conducted phase 3 complicated skin and skin structure infection (cSSSI) trials, population PK modeling and Monte Carlo simulation (MCS) were used to identify a fixed iclaprim dosage regimen for the ongoing phase 3 ABSSSI studies that maximizes AUC
, AUC/MIC, and
> MIC while minimizing the probability of a
of ≥800 ng/ml relative to the values for the previously employed cSSSI regimen of 0.8 mg/kg of body weight infused intravenously over 0.5 h every 12 h. The MCS analyses indicated that administration of 80 mg as a 2-h infusion every 12 h provides 28%, 28%, and 32% increases in AUC
, AUC/MIC, and
> MIC, respectively, compared to values for the 0.8-mg/kg cSSSI regimen, while decreasing the probability of a
of ≥800 ng/ml, by 9%. Based on PK/PD analyses, 80 mg iclaprim administered over 2 h every 12 h was selected as the dosing scheme for subsequent phase 3 clinical trials.
Very-near-surface ocean currents are dominated by wind and wave
forcing and have large impacts on the transport of buoyant materials in the
ocean. Surface currents, however, are under-resolved in ...most operational
ocean models due to the difficultly of measuring ocean currents close to, or
directly at, the air–sea interface with many modern instrumentations. Here,
observations of ocean currents at two depths within the first meter of the
surface are made utilizing trajectory data from both drogued and undrogued
Consortium for Advanced Research on Transport of Hydrocarbon in the Environment
(CARTHE) drifters, which have draft depths of 60 and 5 cm, respectively.
Trajectory data of dense, colocated drogued and undrogued drifters were
collected during the Lagrangian Submesoscale Experiment (LASER) that took
place from January to March of 2016 in the northern Gulf of Mexico.
Examination of the drifter data reveals that the drifter velocities become
strongly wind- and wave-driven during periods of high wind, with the
pre-existing regional circulation having a smaller, but non-negligible,
influence on the total drifter velocities. During these high wind events, we
deconstruct the total drifter velocities of each drifter type into their
wind- and wave-driven components after subtracting an estimate for the
regional circulation, which pre-exists each wind event. In order to capture
the regional circulation in the absence of strong wind and wave forcing, a
Lagrangian variational method is used to create hourly velocity field
estimates for both drifter types separately, during the hours preceding each
high wind event. Synoptic wind and wave output data from the Unified Wave
INterface-Coupled Model (UWIN-CM), a fully coupled atmosphere, wave and
ocean circulation model, are used for analysis. The wind-driven component of
the drifter velocities exhibits a rotation to the right with depth between
the velocities measured by undrogued and drogued drifters. We find that the
average wind-driven velocity of undrogued drifters (drogued drifters) is
∼3.4 %–6.0 % (∼2.3 %–4.1 %) of the wind
speed and is deflected ∼5–55∘
(∼30–85∘) to the right of the wind, reaching higher
deflection angles at higher wind speeds. Results provide new insight on the
vertical shear present in wind-driven surface currents under high winds,
which have vital implications for any surface transport problem.
Similar in strength to hurricanes, Extratropical Cyclones (ECs) are responsible for innavigable sea states, coastal inundation and erosion, and subsequent destruction to coastal infrastructure. ...Across modern operational wave models, there exists a known systematic underestimation of wave heights during these extreme events. Using a global database of EC storm tracks and 36 years of satellite altimeter data, we examine EC structure and assess model performance through storm centered composite analyses of significant wave height ( Hs) and U10 wind speed ( |U10|). Through the collocation of satellite altimeter observations with a state-of-the-art reanalysis product (ERA5), we investigate model performance with respect to |U10| and Hs within ECs of varying intensities. By rotating our data reference frames, we align all storm directions to account for asymmetry in EC wind fields and subsequent increased wave growth This rotation results in the organization of the strongest wind speed and Hs, as well as trends in the ERA5 performance. A characteristic EC radii is calculated and used to normalize data coordinates in the storm centered reference frame, which highlights the organization of EC structures. Performance metrics are then compared within different EC quadrants to explore the relationship between wind forcing accuracy and underestimation of Hs.
This retrospective cohort study characterized the impact of prior antibiotic exposure on distribution and nonsusceptibility profiles of Gram-negative pathogens causing hospital-onset urinary tract ...infections (UTI).
Hospital patients with positive urine culture for Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and other Enterobacteriaceae ≥3 days after hospital admission were included. Assessment outcomes included the distribution of bacteria in urine cultures, antibiotic susceptibility patterns, and the effect of prior antibiotic exposure, defined as 0, 1, or ≥2 prior antibiotics, on the distribution and antibiotic susceptibility profiles of the Gram-negative organisms.
The most commonly isolated pathogens from 5574 unique UTI episodes (2027 with and 3547 without prior antibiotic exposure) were E. coli (49.5%), K. pneumoniae (17.1%), and P. aeruginosa (8.2%). P. aeruginosa was significantly more commonly isolated in patients with ≥2 prior antibiotic exposures (12.6%) compared with no exposure (8.2%; p = 0.036) or 1 prior exposure (7.9%; p = 0.025). Two or more prior antibiotic exposures were associated with slightly higher incidences of fluoroquinolone nonsusceptibility, multidrug resistance, and extended-spectrum β-lactamase phenotype compared with 0 or 1 exposure, suggesting an increased risk for resistant Gram-negative pathogens among hospital patients with urinary tract infections occurring ≥3 days after admission.
Clinicians should critically assess prior antibiotic exposure when selecting empirical therapy for patients with hospital-onset urinary tract infections caused by Gram-negative pathogens.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In 2014, the pharmacist’s role in the United States expanded to include prescribing hormonal contraception, and this practice is currently addressed by policy in 14 states and the District of ...Columbia. Training and education requirements for this expanded scope of practice vary between states and are changing rapidly. The objective of this review is to examine how student pharmacists are taught to provide contraceptive care, specifically for prescribing ongoing hormonal contraception and emergency contraception, and to identify potential gaps in the United States pharmacy curricula related to contraception. Despite steady adoption into community pharmacy practice, there is sparse literature assessing educational methods used to teach contraceptive care. This review offers recommendations to promote consistent and comprehensive student pharmacist education in providing contraceptive care across institutions, regardless of state policy status.
Infertility is a significant public health concern in the United States. As such, utilization of infertility services, including pharmacotherapeutic treatments, is prevalent, and the role of the ...pharmacist as part of the health care team is essential. Pharmacists can assist patients by providing education on infertility causes, risk factor mitigation, referrals, nonpharmacologic and pharmacologic management options, navigation of the prescription process, and resource availability for the significant financial burden accompanying infertility treatment. In-depth pharmacotherapeutic information may not be readily available to pharmacists dispensing and counseling on these medications, and infertility management regimens are often varied and complicated requiring more in-depth counseling on use and administration. Given the complexity of infertility management, pharmacists are a valuable patient support and education resource. This article provides an in-depth review of infertility management strategies, both nonpharmacologic and pharmacologic.
The statistics of submesoscale divergence and vorticity (kinematic properties, KPs) in the Alboran Sea (Mediterranean Sea) are investigated, using data from drifters released during two experiments ...in June 2018 and April 2019 in the framework of the Coherent Lagrangian Pathways from the Surface Ocean to Interior (CALYPSO) project. Surface drifters sampling the first meter of water (CARTHE and CODE) and 15 m drifters (SVP) are considered. The area of interest is dominated by processes of strong frontogenesis and eddy formation as well as mixing, related to the high lateral gradients between Mediterranean and Atlantic waters. Drifter coverage and distribution allow to investigate the dependence of KPs on horizontal scales in a range between 1 and 16 km, that effectively bridges submesoscale and mesoscale processes, and at two depths, of 1 and 15 m. For both experiments, the surface flow is highly ageostrophic at 1 km scale, with positive vorticity skewness indicating the presence of submesoscale features. Surface divergence quickly decreases at increasing scales with a slope compatible with a turbulent process with broadband wavenumber spectrum, suggesting the influence of surface boundary layer processes such as wind effects, waves and Langmuir cells at the smaller scales. Vorticity, on the other hand, has a significantly slower decay, suggesting interaction between submesoscale and mesoscale dynamics. Results at 15 m are characterized by reduced ageostrophic dynamics with respect to the surface, especially for divergence. Submesoscale processes are present but appear attenuated in terms of KP magnitude and skewness. The results are generally consistent for the two experiments, despite the observed differences in the mixed layer stratification, suggesting that submesoscale instabilities occur mostly at surface fronts associated with filaments of Atlantic and Mediterranean waters that are present in both cases. The results are compared with previous literature results in other parts of the world ocean and a synthesis is provided. Good agreement with previous surface results is found, suggesting some general properties for divergence and vorticity scale dependence. The importance of further investigating very high resolution frontal processes at scales of tens of meters, as well as processes of interaction with high wind effects is highlighted.
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