Effect of Concomitant 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor Therapy on Creatine Phosphokinase Levels and Mortality Among Patients Receiving Daptomycin: Retrospective Cohort Study.

IntroductionThe prescribing information for daptomycin recommends discontinuing statin therapy during receipt of daptomycin. The literature supporting this recommendation is sparse. The objectives of this study were to examine the impact of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) on creatine phosphokinase (CPK) elevations and mortality among patients receiving daptomycin therapy.MethodsA retrospective cohort study was performed among daptomycin recipients in the Upstate New York Veterans' Healthcare Administration from September 15, 2003 to July 1, 2013. Inclusion criteria were: (1) daptomycin for ≥48 h, (2) availability of baseline CPK value and (3) >1 CPK level measurement taken while on therapy. The following were extracted from medical records: demographics, comorbidities, laboratory data, medication history (daptomycin, statins and concomitant drugs known to increase CPK), Acute Physiology and Chronic Health Evaluation (APACHE)-II score and vital status at 30 days. The exposure of interest was use of statins. The primary outcome was CPK elevation defined as a CPK value ≥3 times the upper limit of normal (ULN) if baseline CPK was normal, and ≥5 times ULN if baseline CPK was elevated. The secondary outcome was death within 30 days of commencing daptomycin.ResultsA total of 233 patients were included in this analysis. Among these patients, 53 received concomitant statin therapy. Most baseline clinical characteristics were similar between statin recipients and non-recipients. Five (2.1%) patients experienced a CPK elevation; 3/53 (5.7%) were statin recipients and 2/180 (1.1%) received daptomycin alone (p = 0.08). All patients with CPK elevations had normal baseline CPK values. No effect modification was observed by use of other concomitant medications known to increase CPK values. Death was observed more frequently among statin non-recipients (17.2%) than recipients (9.4%).ConclusionsAmong patients receiving daptomycin, no significant difference was observed in frequency of CPK elevation between statin recipients and non-recipients

Antimicrobial Susceptibility Trends Observed in Urinary Pathogens Obtained From New York State

International guidelines recommend using local susceptibility data to direct empiric therapy for acute uncomplicated cystitis. We evaluated outpatient urinary isolate susceptibility trends in New York State. Nitrofurantoin had the lowest resistance prevalence whereas trimethoprim-sulfamethoxazole and fluoroquinolones had higher prevalences. This study highlights the need for local outpatient antimicrobial stewardship programs

Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter

In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter.The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports.The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice.All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines.Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria.Overall, higher troughs ( >15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of >15 mg/liter.The relationship between a trough of >15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37).The relationship between troughs of >15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event.An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration.Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes.The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists.The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy

Effect of prior receipt of antibiotics on the pathogen distribution and antibiotic resistance profile of key Gram-negative pathogens among patients with hospital-onset urinary tract infections

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Clinicians should critically assess prior antibiotic exposure when selecting empirical therapy for patients with hospital-onset urinary tract infections caused by Gram-negative pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2270-7) contains supplementary material, which is available to authorized users

Individualization of piperacillin dosing for critically ill patients: Dosing software to optimize antimicrobial therapy

Piperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. The aim of this study was to establish a population PK model for piperacillin in critically ill patients and then analyze the performance of the model in the dose optimization software program BestDose. Linear, with estimated creatinine clearance and weight as covariates, Michaelis-Menten (MM) and parallel linear/MM structural models were fitted to the data from 146 critically ill patients with nosocomial infection. Piperacillin concentrations measured in the first dosing interval, from each of 8 additional individuals, combined with the population model were embedded into the dose optimization software. The impact of the number of observations was assessed. Precision was assessed by (i) the predicted piperacillin dosage and by (ii) linear regression of the observed-versus-predicted piperacillin concentrations from the second 24 h of treatment. We found that a linear clearance model with creatinine clearance and weight as covariates for drug clearance and volume of distribution, respectively, best described the observed data. When there were at least two observed piperacillin concentrations, the dose optimization software predicted a mean piperacillin dosage of 4.02 g in the 8 patients administered piperacillin doses of 4.00 g. Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated an r2 of > 0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required. Copyrigh

Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥ 400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P373, derived using classification and regression tree analysis, was associated with reduced mortality (P=0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods. Copyrigh

Pharmacokinetic and pharmacodynamic profiling of minocycline for injection following a single infusion in critically ill adults in a phase IV open-label multicenter study (ACUMIN)

Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR

Quantitative evaluation of antibiotic exposure-response relationships among patients with serious staphylococcal infections

This dissertation advances our understanding of antimicrobial exposure-response relationships among patients with serious infections due to Staphylococcus aureus. The need is pressing as treatment of this invasive pathogen has been complicated by the development of antibiotic resistance. One antibiotic resistant phenotype of particular concern is methicillin-resistant S. aureus (MRSA). Due to the multi-drug resistant nature of most MRSA strains, vancomycin emerged as the cornerstone of therapy. Although widely used for serious MRSA infections, many clinicians now question its continued utility due to the emergence of MRSA strains with reduced vancomycin susceptibility phenotypes (rVSPs). The literature is developing rapidly, but characterization of the outcomes associated with these rVSPs remains largely incomplete. The paucity of clinical exposure-response evaluations also makes it difficult to determine whether outcomes can be improved by optimizing the vancomycin concentration-time profile. The emerging concerns with vancomycin have prompted clinicians to consider alternate agents. Linezolid is one the more promising antibiotics with MRSA activity. However, concerns over its potential to cause serotonin toxicity have tempered its use despite limited clinical data to substantiate an increased risk. To address these voids in the literature, the first specific aim was to critically evaluate the relationships between rVSPs and assess their individual and combined effects on outcomes among patients who received vancomycin for a MRSA bloodstream infection. The second specific aim was to quantitatively evaluate the relationship between vancomycin exposure and outcomes among patients with MRSA bloodstream infections. The third specific aim was to delineate the risk of serotonin toxicity associated with linezolid relative to vancomycin among hospitalized patients. There were several notable findings across the studies. The first study strongly suggested that rVSPs contribute to deleterious treatment outcomes in concert. The second study highlighted the critical importance of daily area under the curve (AUC) profiles during the first two days of vancomycin therapy. The collective findings from the third study failed to establish an increased risk of serotonin toxicity with linezolid relative to vancomycin. The investigations presented here have important implications for clinical practice and provide clear directions for future research

Reappraisal of Contemporary Pharmacokinetic and Pharmacodynamic Principles for Informing Aminoglycoside Dosing

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147085/1/phar2193.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147085/2/phar2193_am.pd

La realidad a través del humor

La realidad a través del humor es una tesis mediante la cual se pretende informar sobre temas de impacto social utilizando como mecanismo el humor y así mismo atraer al usuario a que se mantenga informado de una manera diferente a la usual.Reality trough humor s web is a space that pretends to cause in user s attention to reality in a different way from the others news websites using humor as a way to tell about the most important success in the world.Comunicador (a) SocialPregrad