Comparison of pharmacodynamics of azithromycin and erythromycin in vitro and in vivo

In this study, we determined the efficacy of various dosing regimens for erythromycin and azithromycin against four pneumococci with different susceptibilities to penicillin in an in vitro pharmacokinetic model and in a mouse peritonitis model. The MIC was 0.03 microg/ml, and the 50% effective doses (determined after one dose) of both drugs were comparable for the four pneumococcal strains and were in the range of 1.83 to 6.22 mg/kg. Dosing experiments with mice, using regimens for azithromycin of one to eight doses/6 h, showed the one-dose regimen to give the best result; of the pharmacodynamic parameters tested (the maximum drug concentration in serum [Cmax], the times that the drug concentration in serum remained above the MIC and above the concentration required for maximum killing, and the area under the concentration time curve), Cmax was the best predictor of outcome. The bacterial counts in mouse blood or peritoneal fluid during the first 24 h after challenge were not correlated to survival of the mice. The serum concentration profiles obtained with mice for the different dosing regimens were simulated in the in vitro pharmacokinetic model. Here as well, the one-dose regimen of azithromycin showed the best result. However, the killing curves in vivo in mouse blood and peritoneal fluid and in the vitro pharmacokinetic model were not similar. The in vitro killing curves showed a decrease of 2 log10 within 2 and 3 h for azithromycin and erythromycin, respectively whereas the in vivo killing curves showed a bacteriostatic effect for both drugs. It is concluded that the results in terms of predictive pharmacodynamic parameters are comparable for the in vitro and in vivo models and that high initial concentrations of azithromycin favor a good outcome

Immunohaematological reference values in human immunodeficiency virus-negative adolescent and adults in rural northern Tanzania

<p>Abstract</p> <p>Background</p> <p>The amount of CD4 T cells is used for monitoring HIV progression and improvement, and to make decisions to start antiretroviral therapy and prophylactic drugs for opportunistic infections. The aim of this study was to determine normal reference values for CD4 T cells, lymphocytes, leucocytes and haemoglobin level in healthy, HIV negative adolescents and adults in rural northern Tanzania.</p> <p>Methods</p> <p>A cross sectional study was conducted from September 2006 to March 2007 in rural northern Tanzania. Participants were recruited from voluntary HIV counselling and testing clinics. Patients were counselled for HIV test and those who consented were tested for HIV. Clinical screening was done, and blood samples were collected for CD4 T cell counts and complete blood cell counts.</p> <p>Results</p> <p>We enrolled 102 participants, forty two (41.2%) males and 60 (58.8%) females. The mean age was 32.6 ± 95% CI 30.2–35.0. The mean absolute CD4 T cell count was 745.8 ± 95% CI 695.5–796.3, absolute CD8 T cells 504.6 ± 95% CI 461.7–547.5, absolute leukocyte count 5.1 ± 95% CI 4.8–5.4, absolute lymphocyte count 1.8 ± 95% CI 1.7–1.9, and haemoglobin level 13.2 ± 95% CI 12.7–13.7. Females had significantly higher mean absolute CD4 T cell count (p = 0.008), mean absolute CD8 T cell count (p = 0.009) and significantly lower mean haemoglobin level than males (p = 0.003)</p> <p>Conclusion</p> <p>Immunohaematological values found in this study were different from standard values for western countries. Females had significantly higher mean CD4 T cell counts and lower mean haemoglobin levels than males. This raises the issue of the appropriateness of the present reference values and guidelines for monitoring HIV/AIDS patients in Tanzania.</p

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24&nbsp;h. In both studies, patients were followed for outcome until death, hospital discharge or for 60&nbsp;days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24&nbsp;h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (&gt; 29 cmH2O) and driving pressure (&gt; 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (&gt; 8&nbsp;ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure &gt; 29 cmH2O and driving pressure &gt; 14 cmH2O on the first day of mechanical ventilation but not tidal volume &gt; 8&nbsp;ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies