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Precision daptomycin dosing faces clinical implementation barriers despite known exposure-safety concerns with the use of twice the regulatory-approved doses. We propose achieving a single 7–11-hour post-dose plasma target concentration of 30 mg/L to 43 mg/L to be a practical starting point to facilitate precision daptomycin dosing. [ABSTRACT FROM AUTHOR]

Background In this study, we investigated the risk factors for daptomycin-associated creatine phosphokinase (CPK) elevation and established a risk score for CPK elevation. Methods Patients who received daptomycin at our hospital were classified into the non-elevated or elevated CPK group based on their peak CPK levels during daptomycin therapy. Univariable and multivariable analyses were performed, and a risk score and prediction model for the incidence probability of CPK elevation were calculated based on logistic regression analysis. Results The non-elevated and elevated CPK groups included 181 and 17 patients, respectively. Logistic regression analysis revealed that concomitant statin use (odds ratio [OR], 4.45 [95% confidence interval {CI}, 1.40–14.47]; risk score 4), concomitant antihistamine use (OR, 5.66 [95% CI, 1.58–20.75]; risk score 4), and trough concentration (Cmin) between 20 and <30 µg/mL (OR, 14.48 [95% CI, 2.90–87.13]; risk score 5) and ≥30.0 µg/mL (OR, 24.64 [95% CI, 3.21–204.53]; risk score 5) were risk factors for daptomycin-associated CPK elevation. The predicted incidence probabilities of CPK elevation were <10% (low risk), 10%–<25% (moderate risk), and ≥25% (high risk) with total risk scores of ≤4, 5–6, and ≥8, respectively. The risk prediction model exhibited a good fit (area under the receiver operating characteristic curve, 0.85 [95% CI,.74–.95]). Conclusions These results suggested that concomitant use of statins with antihistamines and Cmin ≥20 µg/mL were risk factors for daptomycin-associated CPK elevation. Our prediction model might aid in reducing the incidence of daptomycin-associated CPK elevation. [ABSTRACT FROM AUTHOR]

Introduction: Rhabdomyolysis is often encountered in austere environments where the diagnosis can be challenging due to the expense or unavailability of creatine phosphokinase (CPK) testing. CPK concentration ≥5,000 U/L has previously been found to be a sensitive marker for progression to renal failure. This study sought to propose a model utilizing an alternate biomarker to allow for the diagnosis and monitoring of clinically significant rhabdomyolysis in the absence of CPK.Materials and Methods: We performed a retrospective chart review of 77 patients admitted to a tertiary medical center with a primary diagnosis of rhabdomyolysis. A linear regression model with aspartate aminotransferase (AST) as the independent variable was developed and used to predict CPK ≥5,000 U/L on admission and CPK values on subsequent hospital days. The study was approved and monitored by the Institutional Review Board at Walter Reed National Military Medical Center.Results: Ln(AST) explained over 80% of the variance in ln(CPK) (adjusted R2 = 0.802). The diagnostic accuracy to predict CPK ≥5,000 U/L was high (AUC 0.959; 95% CI: 0.921-0.997, P < 0.001). A cut point of AST ≥110 U/L in our study population had a 97.1% sensitivity and an 85.7% specificity for the detection of a CPK value ≥5,000 U/L. The agreement between actual CPK and predicted CPK for subsequent days of hospitalization was fair with an intraclass correlation coefficient of 0.52 (95% CI: 0.38-0.63). The developed model based on day 1 data tended to overpredict CPK values on subsequent hospital days.Conclusions: We propose a threshold concentration of AST that has an excellent sensitivity for detecting CPK concentration ≥5,000 U/L on day of admission in a patient population with a diagnosis of rhabdomyolysis. A formula with a fair ability to predict CPK levels based on AST concentrations on subsequent hospital days was also developed. [ABSTRACT FROM AUTHOR]

Purpose This article evaluates the musculoskeletal safety of concomitant therapy with daptomycin and Hydroxymethylglutaryl-coenzyme A (HMG CoA) reductase inhibitors (statins). Summary Often indicated for severe gram-positive infections, daptomycin is commonly administered with statins but there is limited guidance on the appropriate management of concomitant therapy with daptomycin and statins. A narrative review was conducted to review contemporary clinical evidence of the safety of concomitant therapy with daptomycin and statins. A total of 5 studies were identified comparing daptomycin monotherapy versus daptomycin and statin concomitant therapy for the primary outcome of creatine phosphokinase (CPK) elevations in a variety of patient populations with systemic, skin/soft tissue, and bone/joint infections. Of these studies, 4 also compared myalgia or myopathy as a secondary outcome. Case studies, the case–control study and 1 prospective registry comparing statin alone versus daptomycin and statin concomitant therapy were excluded. These studies showed that concomitant therapy with daptomycin and statin was not significantly associated with CPK elevation or higher event rate of myalgia or myopathy, compared to daptomycin monotherapy. Conclusion Published cohort studies do not demonstrate a statistically significant difference in the rate of CPK elevations or musculoskeletal toxicities between patients receiving daptomycin monotherapy and daptomycin plus a statin. Patients receiving statins who start daptomycin therapy should continue statin but with weekly monitoring of CPK levels. Continuation of statins is especially important in high-risk patients receiving statins for secondary prevention for atherosclerotic cardiovascular diseases. If myalgia develops, it is reasonable to evaluate the degree of CPK elevation and reassess the need for statin use during daptomycin treatment. [ABSTRACT FROM AUTHOR]

Ractopamine is a ß-adrenergic agonist used as an energy repartitioning agent in the diets of finishing pigs. Most ractopamine studies are limited to evaluations of growth performance and meat quality, and there is little information on the effects of this additive on the behavior and welfare of pigs. Therefore, the objective of this study was to evaluate various indicators of stress caused by feeding diets containing ractopamine. One hundred seventy barrows and 170 gilts weighing 107.3 kg were allocated to 30 pens with 10 to 12 barrows or gilts per pen. Pigs were offered 1 of the 3 dietary treatments (0, 5, or 10 mg ractopamine/kg) for 28 d with 5 barrow pens and 5 gilt pens per treatment. Pigs were evaluated for behavior 3 d per week 1 wk before the initiation of the experiment and throughout the experiment. Each pig was classified into 1 of the 13 activities (drinking water, lying alone, lying in clusters, standing, nosing pig, sitting, feeding, biting pig, walking, exploring, running away, playing, and mounting pen mates) and also grouped into 1 of the 3 categories (calm, moving, and feeding themselves) based on those activities. At the end of the experiment, 3 pigs from each pen were slaughtered, and blood samples were collected during exsanguination to determine physiological indicators of stress (cortisol, lactate, and creatine-kinase enzymes). The incidence of skin and carcass lesions was determined at shoulder, loin, and ham. Ractopamine had no effect (P > 0.05) on pig behavior, total number of skin and carcass lesions, or blood concentrations of cortisol or lactate. However, there was an increase (P < 0.05) of creatine kinase concentrations in pigs receiving ractopamine-supplemented feed. This finding is consistent with the concept that ractopamine may cause muscular disorders, and this warrants further investigation. [ABSTRACT FROM AUTHOR]

Despite the strides made toward understanding cardiac abnormalities in obesity-induced hypertension, the composition and concentration of cardiac extracellular matrix (ECM) components resulting from diet-induced obesity are largely unknown. Previous studies from our laboratory have demonstrated differential expression of collagens, growth factors, and homocysteine (Hcy) in pressure overload models of cardiac hypertrophy. The hypothesis of the present study was that left ventricular hypertrophy (LVH) from the combined pressure and volume overload of obesity induced cardiac fibrosis in part by increasing Hcy, increasing transforming growth factor-β1 (TGF-β1), and decreasing decorin. Using the rabbit model, we examined the changes in cardiac collagen accumulation, plasma Hcy, left ventricular (LV) TGF-β1, and LV decorin after 12 weeks of developing obesity. Cardiac fibrosis was analyzed by trichrome stain for collagens. Total collagens types I and III, TGF-β1, and decorin were analyzed in tissue homogenates by immunoblots and quantitated with a densitometer. After 12 weeks, rabbits eating a high-fat diet had greater body weight (5.38 ± 0.3 kg v 3.73 ± 0.6 kg) and greater LV weight (5.08 ± 0.05 g v 3.86 ± 0.17 g) compared with lean rabbits. Heart rate was also significantly higher in obese than in lean rabbits (221 ± 8 v 173 ± 5 beats/min). Plasma concentrations of circulating Hcy were 16.9 ± 2.4 μmol/L and 24.3 ± 1.8 μmol/L in lean and obese rabbits, respectively. Compared with lean rabbits, obese rabbits had increased interstitial and perivascular collagen, a 4-fold increase in the medial/lumen ratio of coronary vessels, a 1.75-fold increase in cardiac collagen I, and a 1.5-fold increase in cardiac collagen III levels. Levels of TGF-β1 were increased 1.75-fold, whereas decorin levels were significantly reduced in obese compared with lean rabbits. In conclusion, a high-fat diet, even over a period as short as 12 weeks, causes fibrosis in coronary vessels as well as accumulation of collagen in the cardiac interstitium. The accumulation of cardiac collagen was associated with induction of Hcy and TGF-β1 and with suppression of decorin. [Copyright &y& Elsevier]

Background Vibrio vulnificus infection causes rapidly progressive skin lesions and sepsis in compromised hosts with liver cirrhosis, and is often fatal. Early diagnosis and rapid treatment are important. Objectives To clarify the characteristics of V. vulnificus infection that distinguish it from other cutaneous and soft-tissue bacterial infections and to confirm that serum creatine phosphokinase (CPK) levels are useful in early diagnosis, and are a prognostic factor for, V. vulnificus infection. Methods We analysed the clinical and laboratory findings (especially serum CPK levels) in eight patients with V. vulnificus infection who were treated at the Saga Medical School Hospital between January 1989 and December 1999. Results All eight patients had liver dysfunction and typical skin manifestations. Six had eaten raw seafood before onset. Seven patients had initial skin manifestations in their legs or feet and eventually died, despite prompt therapy in the intensive care unit. CPK levels of six of these seven patients were already elevated at their initial presentation. Only one patient, with skin manifestations solely on his left hand, showed and maintained a normal CPK level and survived. In 23 patients with cutaneous and soft-tissue infections (10 with necrotizing fasciitis, three with erysipelas, 10 with cellulitis), only three patients with necrotizing fasciitis and streptococcal toxic shock syndrome (STSS) showed CPK elevation. Conclusions A high level of serum CPK in cutaneous or soft-tissue bacterial infection is considered useful for an early diagnosis of V. vulnificus infection and STSS. A history of eating raw seafood, underlying liver disease and multiple lesions suggest a diagnosis of V. vulnificus infection, rather than STSS. [ABSTRACT FROM AUTHOR]

1-Bromopropane has been newly introduced as an alternative to ozone layer-depleting solvents. We aimed to clarify the dose-dependent effects of 1-bromopropane on the nervous system. Forty-four Wistar male rats were randomly divided into 4 groups of 11 each. The groups were exposed to 200, 400, or 800 ppm of 1-bromopropane or only fresh air 8 h per day for 12 weeks. Grip strength of forelimbs and hind limbs, maximum motor nerve conduction velocity (MCV), and distal latency (DL) of the tail nerve were measured in 9 rats of each group every 4 weeks. The other 2 rats of each group were perfused at the end of the experiment for morphological examinations. The rats of the 800-ppm group showed poor kicking and were not able to stand still on the slope. After a 12-week exposure, forelimb grip strength decreased significantly at 800 ppm and hind limb grip strength decreased significantly at both 400 and 800 ppm or after a 12-week exposure. MCV and DL of the tail nerve deteriorated significantly at 800 ppm. Ovoid or bubble-like debris of myelin sheaths was prominent in the unraveled muscular branch of the posterior tibial nerve in the 800-ppm group. Swelling of preterminal axons in the gracile nucleus increased in a dose-dependent manner. Plasma creatine phosphokinase (CPK) decreased dose-dependently with significant changes at 400 and 800 ppm. 1-Bromopropane induced weakness in the muscle strength of rat limbs and deterioration of MCV and DL in a dose-dependent manner, with morphological changes in peripheral nerve and preterminal axon in the gracile nucleus. 1-Bromopropane may be seriously neurotoxic to humans and should thus be used carefully in the workplace. [ABSTRACT FROM PUBLISHER]

To determine whether exercise training in animals with normal coronary arteries has a salutary effect on ischaemic myocardium, 24 dogs were randomly assigned to be either trained or confined to cages for three months. All dogs then underwent left thoracotomy for placement of indwelling right and left atrial and aortic catheters and a loose snare ligature around the proximal left circumflex coronary artery. Three days after operation control scintigrams were recorded after injection of thallous chloride-201 in animals running on a treadmill to achieve exercise heart rates of 220 beats·min−1. Four days later the snares were pulled to occlude the left circumflex artery and infarct size determined by measuring venous activity of creatine phosphokinase. Three days after infarction the first post-ligation scintigram was performed after thallium-201 injection in exercising animals. Exercise scans were repeated at 10 days and 2, 4, and 6 weeks after coronary ligation. During the final exercise study collateral blood flow was measured with radioactive microspheres. There was no difference in mean creatine phosphokinase appearance time, peak creatine phosphokinase activity, or measured infarct size between the trained and sedentary dogs. The ratio of thallium-201 activity in left circumflex artery or ischaemic area to left anterior descending artery or normally perfused myocardium fell from 100% before occlusion to 86.6% in the sedentary animals and 80.6% in the trained dogs three days after coronary ligation. Although these falls were significant (p<0.025 and p<0.005 respectively), there was no difference between groups. Over the next five and a half weeks the scintigraphic defect shrank as the thallium-201 ratio gradually increased, but changes were again similar in both groups. At six weeks there was little difference in exercise collateral flow to left circumflex artery myocardium and flow to normal myocardial tissue in cage confined and trained dogs. Therefore, no beneficial effect of exercise training in dogs with normal hearts could be seen on ischaemic or infarcting myocardium or coronary collateral development after coronary ligation. [ABSTRACT FROM PUBLISHER]

The incidence, causes and complications of severe rhabdomyolysis (creatine phosphokinase (CK) ≥5000 U/l) were studied during a 7-year study period in a large university hospital population. This condition was present in 0.074% of all admitted patients. The mortality in the study group (=93) was 32% and the incidence of acute renal failure (ARF) 51%. Ischaemia was the most frequent cause, and drugs, alcohol and/or coma were the second most common cause of severe rhabdomyolysis. Patients with rhabdomyolysis due to ischaemia were older, had ARF more often, and also had the highest mortality. Hyperkalaemia (potassium ≥5.5 mmol/1) occurred in 13% of the patients, and all of them had or developed an impaired renal function. Hypocalcaemia (calcium ≤2.00 mmol/1) was found in 41%. The incidence of ARF and electrolyte disturbances was higher in patients with CK levels exceeding 15 000 U/l. Mortality was significantly higher in patients with ARF. Plasma concentrations of potassium and calcium correlated better with the severity of renal failure than with the maximal height of plasma CK. [ABSTRACT FROM PUBLISHER]

The diagnosis of polymyositis is made on the basis of clinical features, muscle enzymes, EMG studies and muscle biopsy. Treatment requires corticosteroids often m combination with immunosuppressive agents, and relapse in spite of treatment may render management difficult. The case described below appeared to demonstrate features from which the diagnosis could be made, but in which the almost complete resistance to conventional therapy led to a correct reappraisal of the diagnosis. This illustrates an unusual cause for diagnostic confusion and the value of diagnosis reassessment under such circumstances. [ABSTRACT FROM PUBLISHER]