Archive for September 20, 2012

Plasma protein binding may reduce antimicrobial activity by preventing intra-bacterial uptake of antibiotics, for example clindamycin

Journal of Antimicrobial Chemotherapy Jan. 2011 V.66 N.1 P.134-137

A. Burian1, C. Wagner1, J. Stanek1, M. Manafi2, M. Böhmdorfer3, W. Jäger3 and M. Zeitlinger1,*

1Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria

2Institute of Hygiene and Medical Microbiology, Medical University Vienna, Vienna, Austria

3Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria


Although plasma protein binding (PPB) is accepted to be an essential factor in reducing antimicrobial activity, little is known about the underlying mechanisms. One possibility includes impaired penetration of an antimicrobial into bacterial cells in the presence of PPB. As a prerequisite for testing this hypothesis an optimized medium displaying high protein binding without impairing bacterial growth had to be identified for our model compound clindamycin.


Determination of PPB, bacterial growth and antimicrobial killing was performed in Mueller—Hinton broth (MHB) containing various amounts of human albumin or serum. [3H] clindamycin was used to investigate clindamycin penetration into Staphylococcus aureus.


Of all investigated media only MHB50%serum and MHB70%serum achieved protein binding comparable to pure serum. In contrast, MHB20%serum and most media containing only albumin demonstrated considerably lower protein binding. Pure serum resulted in bacterial growth inhibition compared with MHB while MHB16%albumin and MHB50%serum did not result in significant differences in bacterial count after 24 h. However, in both MHB16%albumin and MHB50%serum the antimicrobial activity of clindamycin was reduced by >2 log10 cfu/mL compared with pure MHB. The radioactive signal after administration of [3H]clindamycin to S. aureus was significantly decreased in pure serum as well as in MHB16%albumin and MHB50%serum, while no significant difference was observed for MHB4%albumin and MHB20%serum.


Reduction of the intracellular radioactive signal in the presence of serum proteins correlated both with the degree of protein binding and reduction of antimicrobial activity supporting the hypothesis of impairment of activity by PPB by reducing intra-bacterial antimicrobial concentrations.


September 20, 2012 at 2:49 pm

Oxygen Saturations Less than 92% Are Associated with Major Adverse Events in Outpatients with Pneumonia: A Population-Based Cohort Study

Clin Infect Dis  Feb. 2011 V.52 N.3 P.325-331

Sumit R. Majumdar1,2, Dean T. Eurich2, John-Michael Gamble2, A. Senthilselvan2, and Thomas J. Marrie3

1Department of Medicine, Faculty of Medicine and Dentistry

2Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada

3Department of Medicine, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada


Patients with hypoxemia (blood oxygen saturation <90%) are usually hospitalized, although validated criteria (eg, the Pneumonia Severity Index [PSI]) suggest outpatient treatment is safe. We sought evidence to support or refute the practice.


All patients in Edmonton, Alberta, Canada with pneumonia assessed at any of 7 emergency departments (EDs) and then discharged were enrolled in a population-based cohort study. The independent variable of interest was oxygen saturation; the outcome was the composite endpoint of 30-day mortality or hospitalization.


The study evaluated 2923 individuals with pneumonia who were treated as outpatients at any of 7 EDs. The patients’ mean age (standard deviation [SD])was 52 (20) years; 47% were women; 74% were low risk (PSI Class I–II). The mean blood oxygen saturation (SD) was 95% (3%); 126 patients (4%) had blood oxygen saturations <90%, and 201 patients (7%) had blood oxygen saturations of 90%–92%. Over 30 days, 39 patients (1%) died and 252 (9%) reached the composite endpoint. Compared with patients with higher blood oxygen saturations, those discharged with saturations <90% had significantly (P < .001) higher rates of 30-day mortality (7 [6%] vs 32 [1%]), hospitalization (23 [18%] vs 201 [7%]), and composite endpoints (27 [21%] vs 225 [8%]). Blood oxygen saturation <90% was independently associated with 30-day mortality or hospitalization (adjusted odds ratio (OR), 1.7; 95% confidence interval (CI) 1.1–2.8; P = .032). If the saturation threshold for hospitalization was 92%, then there was no association with adverse events (adjusted OR 1.1, 95% CI 0.8–1.7, P = .48). Raising the admission threshold to 92% entails 1 additional hospitalization for every 14 patients discharged.


Among outpatients with pneumonia, oxygen saturations <90% were associated with increased morbidity and mortality. Our results indicate a hospital admission threshold of <92% would be safer and clinically better justified.


September 20, 2012 at 2:48 pm


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