The results of the present study demonstrate that in septic shock patients, piperacillin concentrations in the interstitial space may be subinhibitory, even though effective concentrations are attained in plasma. The lack of success of antimicrobial therapy in these patients thus might be attributable to inadequate target site penetration of antibiotics.

Background-Platelet activation is a hallmark of acute coronary syndromes. Numerous lines of evidence suggest a mechanistic link between von Willebrand factor or platelet hyperfunction and myocardial damage in patients with acute coronary syndromes. Thus, we assessed whether platelet function under high shear rates (collagen adenosine diphosphate closure times [CADP-CTs]) measured with the platelet function analyzer (PFA-100) may be enhanced in patients with myocardial infarction (MI) and whether it may predict the extent of myocardial damage as measured by creatine kinase (CK-MB) or troponin T (TnT) levels. Methods and Results-Patients with acute chest pain or symptoms suggestive of acute coronary syndromes (nϭ216) were prospectively examined at an emergency department. CADP-CT was significantly shorter in patients with MI, particularly in those with an ST-segment-elevation MI (STEMI) compared with the other patient groups (unstable angina, stable coronary artery disease, or controls). Furthermore, CADP-CT and collagen epinephrine-CT at presentation were independent predictors of myocardial damage as measured by CK-MB or TnT. Patients with MI whose CADP-CT values fell in the first quartile had 3-fold higher CK-MB and TnT levels than those in the fourth quartile. Conclusions-Patients with STEMI have significantly enhanced platelet function when measured under high shear rates.CADP-CT is an independent predictor of the severity of MI, as measured by markers of cardiac necrosis. Measurement of platelet function with the PFA-100 may help in the risk stratification of patients presenting with MI. (Circulation.

See also Boos CJ, Lip GYH. Platelet activation and cardiovascular outcomes in acute coronary syndromes. This issue, pp 2542-3. Harrison P, Keeling D. Platelet hyperactivity and risk of recurrent thrombosis. This issue, pp 2544-6. Summary. Background: Platelet hyperfunction contributes to acute coronary syndromes (ACS). Thus, we hypothesized that platelet function under high shear stress predicts recurrent ACS during long-term follow-up of ACS patients. Patients and methods: Consecutive ACS patients (n ¼ 208) were prospectively followed-up for an average of 28 months. Platelet function was measured with the platelet function analyzer (PFA-100 Ò ; Dade Behring, Marburg, Germany) at baseline for collagen/adenosine diphosphate closure times (CADP-CT) and for collagen/epinephrine closure times (CEPI-CT) after infusion of a uniform dose of 250 mg aspirin. Results: Of the conventional risk factors, only the prevalence of diabetes was higher in ACS patients with re-events. However, use of clopidogrel and use of beta blockers were also slightly lower in patients with reevents (P < 0.05). The unadjusted risk hazard ratio (HR) for re-events was 3.3 [95% confidence interval (95% CI): 1.4-7.4; P ¼ 0.005] in those patients with the shortest CADP-CT values (lowest quartile). Similarly, the risk was 2.0-fold higher (95% CI: 1.1-3.6; P ¼ 0.02) in ACS patients with CEPI-CT < 300 s as compared with CEPI-CT ‡ 300 s. Inclusion of diabetes, clopidogrel and beta blockers in a multivariate Cox regression model enhanced the predictive value of CEPI-CT (HR: 2.7). Inclusion of von Willebrand factor levels did not alter the HR for recurrent ACS (HR: 2.1; 95% CI: 1.1-5.2; P ¼ 0.03) for CEPI-CT < 300 s, but reduced the HR for CADP-CT (HR: 2.8, 95% CI: 0.8-9.8; P ¼ 0.11). Conclusion: Shortened CT values reflect biologically relevant platelet hyperfunction in patients with ACS because they predict recurrent ACS.

No abstract

Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus, Enterobacter cloacae, and Serratia marcescens for which MICs were 16 g/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.

In summary there is a substantial transcapillary insulin gradient in healthy human skeletal muscle under baseline and glucose-stimulated conditions. Our findings support the hypothesis of a saturable transcapillary insulin transport representing a partly rate-limiting step for insulin action.

Background and Purpose-The prediction of neurological outcome in comatose cardiac arrest survivors has enormous ethical and socioeconomic implications. The purpose of the present study was to investigate the prognostic relevance of the time course of serum neuron-specific enolase (NSE) as a biochemical marker of hypoxic brain damage. Methods-Serial analysis of serum NSE levels was performed in 56 patients resuscitated from witnessed, nontraumatic, normothermic, in-or out-of-hospital cardiac arrest. The neurological outcome was evaluated with the use of the cerebral performance category (CPC) within 6 months after restoration of spontaneous circulation (ROSC). The Mann-Whitney U test was used to compare patients with good (CPC 1 to 2) and bad (CPC 3 to 4) neurological outcome. The diagnostic performance at different time points after ROSC was described in terms of areas under receiver operating characteristic curves according to standard methods. Results-Patients with a bad neurological outcome (CPC 3 to 4) had significantly higher NSE levels than those with a good neurological outcome at 12 (Pϭ0.004), 24 (Pϭ0.04), 48 (PϽ0.001), and 72 hours (PϽ0.001) after ROSC. The maximum NSE level measured within 72 hours after ROSC was also significantly higher in patients with a bad neurological outcome (PϽ0.001). The NSE value at 72 hours after ROSC was the best predictor of neurological outcome (area under the curveϭ0.92Ϯ0.04). In addition, we also found a significant difference in the time course of NSE concentrations during the first 3 days after ROSC. Conclusions-Serum NSE levels are valuable adjunctive parameters for assessing neurological outcome after cardiac arrest. (Stroke. 1999;30:1598-1603.)

We investigated the distribution of the broad-spectrum antibiotic fosfomycin in infected soft tissue of patients with uncomplicated cellulitis of the lower extremities or diabetic foot infection using in vivo microdialysis. Our findings suggest that fosfomycin exhibits good and similar penetration into the fluid in the interstitial space in inflamed and noninflamed soft tissue in patients.