Detroit Receiving Hospital

Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

Abstract A direct method for the quantitative determination of total serum cholesterol is described. The procedure consists of adding a reagent containing sulfuric acid, acetic acid, and ferric chloride to a 0.1 ml. sample of serum. The sensitivity achieved is several times that of current procedures and the time required for a single determination is in the order of minutes. Precision and reproducibility are demonstrated as well as the absorption characteristics of the purple color produced through the spectral range of 400 to 700 mμ. Finally, the method is compared with samples in which total cholesterol is determined by the Kingsley-Schaffert and Schoenheimer-Sperry procedures.

Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400-600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.

Practice guidelines for therapeutic monitoring of vancomycin treatment for Staphylococcus aureus infection in adult patients were reviewed by an expert panel of the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. A literature review of existing evidence regarding vancomycin dosing and monitoring of serum concentrations, in addition to patient outcomes combined with expert opinion regarding the drug's pharmacokinetic, pharmacodynamic, and safety record, resulted in new recommendations for targeting and adjustment of vancomycin therapy.

The objective of this study was to determine the effect of delayed therapy on morbidity and mortality associated with nosocomial Staphylococcus aureus bacteremia. The study included all episodes of S. aureus bacteremia that developed >2 days after hospital admission during 1999 to 2001. Classification and regression tree analysis (CART) was used to select the mortality breakpoint between early and delayed treatment. During the 25-month study period, 167 patients met the inclusion criteria. The breakpoint between delayed and early treatment derived using CART was 44.75 hours. On multivariate analysis, delayed treatment was found to be an independent predictor of infection-related mortality (odds ratio, 3.8; 95% confidence interval, 1.3-11.0; P=.01) and was associated with a longer hospital stay than was early treatment (20.2 days versus 14.3 days; P=.05). These findings support the notion that delay of therapy has deleterious effects on clinical outcomes, and efforts should be made to ensure that appropriate therapy is initiated promptly.

Journal Article Simple Rapid Microtechnic for Serum Total Cholesterol Get access Bennie Zak, Ph.D. Bennie Zak, Ph.D. Laboratories of the Departments of Pathology, Wayne State University College of Medicine, and Detroit Receiving Hospital, Detroit, Michigan Dr. Zak is Medical Laboratory Analyst. Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 27, Issue 5_ts, May 1957, Pages 583–588, https://doi.org/10.1093/ajcp/27.5_ts.583 Published: 01 May 1957 Article history Received: 01 November 1956 Accepted: 17 January 1957 Published: 01 May 1957

Journal Article Rapid Estimation of Free and Total Cholesterol Get access B. Zak, Ph.D., B. Zak, Ph.D. Departments of Pathology, Wayne University College of Medicine, Detroit Receiving Hospital and Detroit Memorial Hospital, Detroit, Michigan Dr. Zak is Medical Laboratory Analyst and Junior Associate in Pathology, Wayne University College of Medicine and Detroit Receiving Hospital; Drs. Dickenman and Cherney are Residents in Pathology at Detroit Receiving Hospital; Mrs. White is Research Technician, Department of Pathology, Wayne University Medical School and Mr. Burnett was Bacteriologist at Detroit Memorial Hospital. Search for other works by this author on: Oxford Academic Google Scholar R. C. Dickenman, M.D., R. C. Dickenman, M.D. Departments of Pathology, Wayne University College of Medicine, Detroit Receiving Hospital and Detroit Memorial Hospital, Detroit, Michigan Search for other works by this author on: Oxford Academic Google Scholar E. G. White, M.S., M.T. (ASCP), E. G. White, M.S., M.T. (ASCP) Departments of Pathology, Wayne University College of Medicine, Detroit Receiving Hospital and Detroit Memorial Hospital, Detroit, Michigan Search for other works by this author on: Oxford Academic Google Scholar H. Burnett, M.S., H. Burnett, M.S. Departments of Pathology, Wayne University College of Medicine, Detroit Receiving Hospital and Detroit Memorial Hospital, Detroit, Michigan Search for other works by this author on: Oxford Academic Google Scholar P. J. Cherney, M.D. P. J. Cherney, M.D. Departments of Pathology, Wayne University College of Medicine, Detroit Receiving Hospital and Detroit Memorial Hospital, Detroit, Michigan Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 24, Issue 11_ts, November 1954, Pages 1307–1315, https://doi.org/10.1093/ajcp/24.11_ts.1307 Published: 01 November 1954 Article history Published: 01 November 1954 Received: 12 December 1954

BACKGROUND: High rates of vancomycin failure in methicillin-resistant Staphylococcus aureus (MRSA) infections have been increasingly reported over time. The primary objective of our study was to determine the impact of vancomycin exposure and outcomes in patients with MRSA bacteremia initially treated with vancomycin. METHODS: This was a single-center retrospective analysis of 320 patients with documented MRSA bacteremia initially treated with vancomycin from January 2005 through April 2010. Two methods of susceptibility, Etest and broth microdilution, were performed for all isolates to determine the correlation of susceptibility testing to patient outcomes. RESULTS: Among a cohort of 320 patients, more than half (52.5%) experienced vancomycin failure. Independent predictors of vancomycin failure in logistic regression included infective endocarditis (adjusted odds ratio [AOR], 4.55; 95% confidence interval [CI], 2.26-9.15), nosocomial-acquired infection (AOR, 2.19; 95% CI, 1.21-3.97), initial vancomycin trough <15 mg/L (AOR, 2.00; 95% CI, 1.25-3.22), and vancomycin minimum inhibitory concentration (MIC) >1 mg/L by Etest (AOR, 1.52; 95% CI, 1.09-2.49). With use of Classification and Regression Tree (CART) analysis, patients with vancomycin area under the curve at 24 h (AUC(24h)) to MIC ratios <421 were found to have significantly higher rates of failure, compared with patients with AUC(24h) to MIC ratios >421 (61.2% vs 48.6%; P = .038). CONCLUSIONS: In light of the high failure rates associated with this antimicrobial, optimizing the pharmacokinetic/pharmacodynamic properties of vancomycin by targeting higher trough values of 15-20 mg/L and AUC(24h)/MIC ratios ≥400 in selected patients should be considered.

RATIONALE: Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown. OBJECTIVES: To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes. METHODS: Prospective cohort study at 28 sites. MEASUREMENTS AND MAIN RESULTS: We used standard criteria to define CAP and the National Death Index to determine all-cause and cause-specific 1-year mortality. At hospital discharge, 1,799 subjects (77.5%) were alive and vital signs had returned to normal in 1,512 (87%) subjects. The geometric means (+/-SD) for circulating IL-6 and IL-10 concentrations were 6.9 (+/-1) pg/ml and 1.2 (+/-1.1) pg/ml. At 1 year, 307 (17.1%) subjects had died. Higher IL-6 and IL-10 concentrations at hospital discharge were associated with an increased risk of death, which gradually fell over time. Using Gray's survival model, the associations were independent of demographics, comorbidities, and severity of illness (for each log-unit increase, the range of adjusted hazard ratios [HRs] for IL-6 were 1.02-1.46, P < 0.0001, and for IL-10 were 1.17-1.44, P = 0.01). The ranges of HRs for each log-unit increase in IL-6 and IL-10 concentrations among subjects who did and did not develop severe sepsis were 0.95-1.27 and 1.07-1.55, respectively. High IL-6 concentrations were associated with death due to cardiovascular disease, cancer, infections, and renal failure (P = 0.008). CONCLUSIONS: Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death.

The nephrotoxicity and ototoxicity associated with once-daily versus twice-daily administration of aminoglycosides was assessed in patients with suspected or proven gram-negative bacterial infections in a randomized, double-blind clinical trial. Patients who received therapy for >/=72 h were evaluated for toxicity. Patients also received concomitant antibiotics as deemed necessary for treatment of their infection. Plasma aminoglycoside concentrations, prospective aminoglycoside dosage adjustment, and serial audiologic and renal status evaluations were performed. The probability of occurrence of a nephrotoxic event and its relationship to doses and daily aminoglycoside exposure served as the main outcome measurement. One hundred twenty-three patients were enrolled in the study, with 83 patients receiving therapy for at least 72 h. For 74 patients plasma aminoglycoside concentrations were available for analysis, and the patients formed the group evaluable for toxicity. The primary infectious diagnosis for the patients who were enrolled in the study were bacteremia or sepsis, respiratory infections, skin and soft tissue infections, or urosepsis or pyelonephritis. Of the 74 patients evaluable for toxicity, 39 received doses twice daily and 35 received doses once daily and a placebo 12 h later. Nephrotoxicity occurred in 6 of 39 (15.4%) patients who received aminoglycosides twice daily and 0 of 35 patients who received aminoglycosides once daily. The schedule of aminoglycoside administration, concomitant use of vancomycin, and daily area under the plasma concentration-time curve (AUC) for the aminoglycosides were found to be significant predictors of nephrotoxicity by multivariate logistic regression analysis (P </= 0.001). The time to a nephrotoxic event was significantly influenced by vancomycin use and the schedule of administration, as assessed by Cox proportional hazards modeling (P </= 0.002). The results of the multivariate logistic regression analysis and the Cox proportional hazards modeling demonstrate that both the probability of occurrence and the time to occurrence of aminoglycoside nephrotoxicity are influenced by the schedule on which the aminoglycoside is administered as well as by the concomitant use of vancomycin. Furthermore, this risk of occurrence is modulated by the daily AUC for aminoglycoside exposure. These data suggest that once-daily administration of aminoglycosides has a predictably lower probability of causing nephrotoxicity than twice-daily administration.

BACKGROUND: The effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear. METHODS: In 14 U.S. hospitals with high adherence to quality measures for the treatment of pneumonia, we provided guidance for clinicians about national clinical practice recommendations for the treatment of lower respiratory tract infections and the interpretation of procalcitonin assays. We then randomly assigned patients who presented to the emergency department with a suspected lower respiratory tract infection and for whom the treating physician was uncertain whether antibiotic therapy was indicated to one of two groups: the procalcitonin group, in which the treating clinicians were provided with real-time initial (and serial, if the patient was hospitalized) procalcitonin assay results and an antibiotic use guideline with graded recommendations based on four tiers of procalcitonin levels, or the usual-care group. We hypothesized that within 30 days after enrollment the total antibiotic-days would be lower - and the percentage of patients with adverse outcomes would not be more than 4.5 percentage points higher - in the procalcitonin group than in the usual-care group. RESULTS: A total of 1656 patients were included in the final analysis cohort (826 randomly assigned to the procalcitonin group and 830 to the usual-care group), of whom 782 (47.2%) were hospitalized and 984 (59.4%) received antibiotics within 30 days. The treating clinician received procalcitonin assay results for 792 of 826 patients (95.9%) in the procalcitonin group (median time from sample collection to assay result, 77 minutes) and for 18 of 830 patients (2.2%) in the usual-care group. In both groups, the procalcitonin-level tier was associated with the decision to prescribe antibiotics in the emergency department. There was no significant difference between the procalcitonin group and the usual-care group in antibiotic-days (mean, 4.2 and 4.3 days, respectively; difference, -0.05 day; 95% confidence interval [CI], -0.6 to 0.5; P=0.87) or the proportion of patients with adverse outcomes (11.7% [96 patients] and 13.1% [109 patients]; difference, -1.5 percentage points; 95% CI, -4.6 to 1.7; P<0.001 for noninferiority) within 30 days. CONCLUSIONS: The provision of procalcitonin assay results, along with instructions on their interpretation, to emergency department and hospital-based clinicians did not result in less use of antibiotics than did usual care among patients with suspected lower respiratory tract infection. (Funded by the National Institute of General Medical Sciences; ProACT ClinicalTrials.gov number, NCT02130986 .).

Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400-600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.

The effects of increased intra-abdominal pressure (IAP) on hepatic perfusion were studied in five anesthetized pigs. Doppler flow probes were used to measure hepatic artery blood flow (HABF) and portal venous blood flow (PVBF), and laser Doppler flowmetry was used to assess changes in hepatic microvascular blood flow (HMVBF). Hepatic blood flow responses to 10, 20, 30 and 40 mm Hg increases in IAP were assessed while the mean arterial BP (MAP) was maintained at baseline levels with IV crystalloid infusions. Although cardiac output and MAP were normal, HABF and HMVBF fell significantly with 10 mm IAP, and at 20 mm Hg IAP, HABF was 45% of the control value, PVBF was 65% of the control value, and HMVBF was 71% of the control value (p less than 0.05). At 30 and 40 mm Hg, hepatic blood flow was reduced even more. Thus, modest increases in IAP can cause significant impairment of hepatic perfusion despite a normal BP and cardiac output.

UNLABELLED: The concept of "learning by doing" has become less acceptable, particularly when invasive procedures and high-risk care are required. Restrictions on medical educators have prompted them to seek alternative methods to teach medical knowledge and gain procedural experience. Fortunately, the last decade has seen an explosion of the number of tools available to enhance medical education: web-based education, virtual reality, and high fidelity patient simulation. This paper presents some of the consensus statements in regard to these tools agreed upon by members of the Educational Technology Section of the 2004 AEM Consensus Conference for Informatics and Technology in Emergency Department Health Care, held in Orlando, Florida. FINDINGS: Web-based teaching: 1) Every ED should have access to medical educational materials via the Internet, computer-based training, and other effective education methods for point-of-service information, continuing medical education, and training. 2) Real-time automated tools should be integrated into Emergency Department Information Systems [EDIS] for contemporaneous education. Virtual reality [VR]: 1) Emergency physicians and emergency medicine societies should become more involved in VR development and assessment. 2) Nationally accepted protocols for the proper assessment of VR applications should be adopted and large multi-center groups should be formed to perform these studies. High-fidelity simulation: Emergency medicine residency programs should consider the use of high-fidelity patient simulators to enhance the teaching and evaluation of core competencies among trainees. CONCLUSIONS: Across specialties, patient simulation, virtual reality, and the Web will soon enable medical students and residents to... see one, simulate many, do one competently, and teach everyone.

Vancomycin is a commonly used antibiotic due to its effectiveness in treating serious gram-positive infections caused by methicillin-resistant Staphylococcus aureus. As commercial drug assays and a multitude of pharmacokinetic data from a variety of patient populations are widely available, therapeutic monitoring of serum vancomycin concentrations is frequently performed by clinicians, with the expectation that targeting the concentrations within a relatively narrow range can minimize toxicity yet still achieve therapeutic success. Much debate exists, however, over the value of routine therapeutic monitoring of vancomycin levels because of conflicting evidence regarding the ability of serum concentrations to predict effectiveness or prevent toxicity. In addition, studies have suggested that the potential for nephrotoxicity or ototoxicity with vancomycin monotherapy is minimal at conventional dosages of 1 g (15 mg/kg) every 12 hours. However, increased rates of nephrotoxicity have recently been reported with doses of 4 g/day or higher. The American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists published a consensus statement on therapeutic monitoring of serum vancomycin levels in adults. These organizations established an expert panel to review the scientific data and controversies associated with vancomycin monitoring and to make recommendations based on the available evidence. As the members of this panel, we summarize the conclusions and highlight the recommendations from the consensus statement. We determined that the area under the concentration-time curve (AUC): minimum inhibitory concentration (MIC) ratio is the most useful pharmacodynamic parameter to predict vancomycin effectiveness and suggested a target ratio of 400 or greater to eradicate S. aureus. In addition, trough serum concentration monitoring is the most accurate and practical method to monitor vancomycin serum levels. Increasing trough concentrations to 15-20 mg/L to attain the target AUC:MIC ratio may be desirable but is currently not supported by clinical trials. Alternative therapies should be considered in patients with S. aureus infections that demonstrate a vancomycin MIC of 2 mg/L or greater because the target AUC:MIC ratio ( 400) is unlikely to be achieved in this setting. Increasing the dosage to result in higher trough concentrations may increase the potential for toxicity; however additional clinical experience is required to determine the extent.

The incidence of nephrotoxicity in patients receiving vancomycin alone or in combination with an aminoglycoside was prospectively evaluated. A total of 231 courses of antibiotic therapy in 224 patients were consecutively monitored over 28-month period. One hundred and sixty-eight patients received vancomycin alone, 63 patients received vancomycin with an aminoglycoside, and 103 patients received gentamicin. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a 50% increase above baseline, whichever was greater. Eight patients (5%) receiving vancomycin alone, 14 patients (22%) receiving vancomycin with an aminoglycoside, and 11 patients (11%) receiving gentamicin alone were found to have nephrotoxicity. Factors found to be associated with increased risk of nephrotoxicity in patients receiving vancomycin were concurrent therapy with an aminoglycoside, length of treatment with vancomycin (greater than 21 days), and vancomycin trough serum concentration (greater than 10 mg/l). Although the incidence of vancomycin nephrotoxicity is low, patients receiving vancomycin therapy with the above risk factors should be closely monitored.

OBJECTIVE: To compare the effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in patients with hyperdynamic sepsis. DESIGN: A randomized short-term, interventional study. SETTING: An intensive care unit of a university hospital. PATIENTS: Twenty septic patients with a cardiac index greater than 3.2 L-min-1.m-2 and either a mean arterial pressure (MAP) less than 60 mm Hg or a systemic vascular resistance index less than 1200 dyne.s.cm-5.m-2. METHODS AND INTERVENTIONS: Patients were randomized to receive an infusion of either dopamine or norepinephrine titrated to increase the MAP to greater than 75 mm Hg. The hemodynamic profile, oxygen delivery, oxygen consumption (determined by indirect calorimetry), and gastric intramucosal pH (pHi) (determined by gastric tonometry) were determined at baseline and after 3 hours of achieving the target MAP. RESULTS: Dopamine increased the MAP largely by increasing the cardiac index whereas norepinephrine increased the MAP by increasing the systemic vascular resistance index while maintaining the cardiac index. Although oxygen delivery and oxygen consumption increased in both groups of patients, the pHi increased significantly in those patients treated with norepinephrine whereas the pHi decreased significantly in those patients receiving dopamine (P < .001, for corrected 3-hour value). CONCLUSIONS: This study suggests that dopamine may cause an uncompensated increase in splanchnic oxygen requirements in septic patients. Norepinephrine, however, may have a more favorable hemodynamic profile and improve splanchnic tissue oxygen utilization in sepsis.

The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristin-dalfopristin against a variety (n = 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus (VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing > or =3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.

BACKGROUND: Thoracic ultrasound may rapidly diagnose pneumothorax when radiographs are unobtainable; the accuracy is not known. METHODS: We prospectively evaluated thoracic ultrasound detection of pneumothorax in patients at high suspicion of pneumothorax. The presence of "lung sliding" or "comet tail" artifacts were determined in patients by ultrasound before radiologic verification of pneumothorax by residents instructed in thoracic ultrasound. Results were compared with standard radiography. RESULTS: There were 382 patients enrolled; the cause of injury was blunt (281 of 382), gunshot wound (22 of 382), stab wound (61 of 382), and spontaneous (18 of 382). Pneumothorax was demonstrated on chest radiograph in 39 patients and confirmed by ultrasound in 37 of 39 patients (95% sensitivity); two pneumothoraces could not be diagnosed because of subcutaneous air; the true-negative rate was 100%. CONCLUSION: Thoracic ultrasound reliably diagnoses pneumothorax. Expansion of the focused abdominal sonography for trauma (FAST) examination to include the thorax should be investigated for terrestrial and space medical applications.