Archive for March 3, 2013

Effect of pravastatin and fosinopril on recurrent urinary tract infections.

J Antimicrob Chemother. 2013 Mar;68(3):708-14.

Pouwels KB, Visser ST, Hak E.


Unit of PharmacoEpidemiology and PharmacoEconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.



Recurrent urinary tract infections (UTIs) are a problem affecting both women and men. Animal experiments and in vitro studies indicate that statins might prevent recurrent UTIs. We assessed the effects of pravastatin on UTI antibiotic prescribing among adults.


A post hoc analysis was conducted with data from PREVEND IT, a trial among participants randomized to receive pravastatin, fosinopril or placebo in a 2 × 2 factorial design over 4 years. Trial data were linked to the pharmacy prescription database The primary outcome was the number of prescriptions with a nitrofuran derivate, a sulphonamide or trimethoprim as a proxy for UTI antibiotic prescribing. Generalized estimating equations were used to estimate the effect on the number of UTI antibiotic prescriptions. Cox regression was used to determine the effect on first and second (recurrent) UTI antibiotic prescriptions.


Of the 864 trial participants, 655 were eligible for analysis. During an average follow-up of 3.8 years, 112 (17%) participants received at least one UTI antibiotic prescription. Intention-to-treat analyses showed that pravastatin was associated with a reduced total number of UTI antibiotic prescriptions (relative risk, 0.43; 95% CI, 0.21-0.88) and occurrence of second UTI antibiotic prescriptions [hazard ratio (HR), 0.25; 95% CI, 0.08-0.77]. No significant effect on occurrence of first UTI antibiotic prescriptions was found (HR, 0.83; 95% CI, 0.57-1.20). Fosinopril was associated with an increased occurrence of first UTI antibiotic prescriptions (HR, 1.82; 95% CI, 1.16-2.88). Combination therapy with fosinopril and pravastatin did not significantly influence the number of UTI antibiotic prescriptions.


This study suggests that pravastatin can reduce the occurrence of recurrent UTIs. Larger studies among patients with recurrent UTIs are warranted.


March 3, 2013 at 10:46 am

Non-adherence to antimicrobial treatment guidelines results in more broad-spectrum but not more appropriate therapy

Eur J Clin Microbiol Infect Dis. 2012 July; 31(7): 1561–1568.

L. B. J. van der Velden,1 M. Tromp,2,3 C. P. Bleeker-Rovers,2,3 M. Hulscher,4 B. J. Kullberg,2,3 J. W. Mouton,1 P. D. J. Sturm,1 and P. Pickkers3,5

1Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands

2Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

3Nijmegen Institute for Infection, Inflammation, and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

4Scientific Institute for Quality of Healthcare, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

5Department of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Mortality in patients admitted with sepsis is high and the increasing incidence of infections with multiresistant bacteria is a worldwide problem. Many hospitals have local antimicrobial guidelines to assure effective treatment and limit the use of broad-spectrum antibiotics, thereby reducing the selection of resistant bacteria. We evaluated adherence to the antimicrobial treatment guidelines of our hospital in patients presenting to the emergency department (ED) with sepsis and assessed the in vitro susceptibility of isolated pathogens to the guideline-recommended treatment and the prescribed treatment. We included all adult patients with a known or suspected infection and two or more extended systemic inflammatory response syndrome (SIRS) criteria. Patients who did not receive antimicrobial treatment, presented with infections not included in the guidelines, or had more than one possible focus of infection were excluded. A total of 276 ED visits (262 patients) were included. Guideline-concordant treatment was prescribed in 168 visits (61%). In the case of guideline-disconcordant treatment, 87% was more broad-spectrum than guideline-recommended treatment. A microbiological diagnosis was established in 96 visits (35%). The susceptibility of the pathogens isolated from patients treated with guideline-concordant treatment (n=68) and guideline-disconcordant treatment (n=28) to guideline-recommended treatment (91% versus 89%) and to prescribed treatment (91% versus 93%) was similar (p=0.77 and p=0.79, respectively). In conclusion, non-adherence to the guidelines occurred frequently and resulted in more broad-spectrum empirical therapy. This did not result in a higher rate of susceptibility of the isolated pathogens to the prescribed empirical therapy.



March 3, 2013 at 10:45 am

Effect of clarithromycin in inflammatory markers of patients with ventilator-associated pneumonia and sepsis caused by Gram-negative bacteria: results from a randomized clinical study.

Antimicrob Agents Chemother. 2012 Jul;56(7):3819-25.

Spyridaki A, Raftogiannis M, Antonopoulou A, Tsaganos T, Routsi C, Baziaka F, Karagianni V, Mouktaroudi M, Koutoukas P, Pelekanou A, Kotanidou A, Orfanos SE, van der Meer JW, Netea MG, Giamarellos-Bourboulis EJ.


4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.


One recent, double-blind, randomized clinical trial with 200 patients showed that clarithromycin administered intravenously for 3 days in patients with ventilator-associated pneumonia (VAP) accelerated the resolution of pneumonia and decreased the risk of death from septic shock and multiple organ dysfunctions (MODS). The present study focused on the effect of clarithromycin on markers of inflammation in these patients. Blood was drawn immediately before the administration of the allocated treatment and on six consecutive days after the start of treatment. The concentrations of circulating markers were measured. Monocytes and neutrophils were isolated for immunophenotyping analysis and for cytokine stimulation. The ratio of serum interleukin-10 (IL-10) to serum tumor necrosis factor alpha (TNF-α) was decreased in the clarithromycin group compared with the results in the placebo group. Apoptosis of monocytes was significantly increased on day 4 in the clarithromycin group compared with the rate of apoptosis in the placebo group. On the same day, the expression of CD86 was increased and the ratio of soluble CD40 ligand (sCD40L) to CD86 in serum was unchanged. The release of TNF-α, IL-6, and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by circulating monocytes after stimulation was greater in the clarithromycin group than in the placebo group. The expression of TREM-1 on monocytes was also increased in the former group. These effects were pronounced in patients with septic shock and MODS. These results suggest that the administration of clarithromycin restored the balance between proinflammatory versus anti-inflammatory mediators in patients with sepsis; this was accompanied by more efficient antigen presentation and increased apoptosis. These effects render new perspectives for the immunotherapy of sepsis.


March 3, 2013 at 10:42 am


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