Sex, drugs, bugs, and age: rational selection of empirical therapy for outpatient urinary tract infection in an era of extensive antimicrobial resistance

BackgroundOptimal empirical therapy of urinary tract infection requires accurate knowledge of local susceptibility patterns, which may vary with organism and patient characteristics.MethodsAmong 9,798 consecutive, non-duplicate, community-source urine isolates from ambulatory patients ≥ 13 years old, from clinical laboratory and an academic medical center in Curitiba, Brazil (May 1^st to December 1^st, 2009), susceptibility data for ampicillin, nitrofurantoin, trimethoprim-sulfamethoxazole, gentamicin, fluoroquinolones, and ceftriaxone/cefotaxime were compared with organism and patient gender and age.ResultsThe female-to-male ratio decreased with age, from 28.1 (among 20–29 year-olds) to 3.3 (among > 80 year-olds). Overall, susceptibility prevalence varied widely by drug class, from unacceptably low levels (53.5% and 61.1%: ampicillin and trimethoprimsulfamethoxazole) to acceptable but suboptimal levels (81.2% to 91.7%: fluoroquinolones, ceftriaxone, nitrofurantoin, and gentamicin). E. coli isolates exhibited higher susceptibility rates than other isolates, from 3–4% higher (fluoroquinolones, gentamicin) to ≥ 30% (nitrofurantoin, ceftriaxone). Males exhibited lower susceptibility rates than females. Within each gender, susceptibility declined with increasing age. For females, only nitrofurantoin and gentamicin were suitable for empirical therapy (≥ 80% susceptibility) across all age cohorts; fluoroquinolones were suitable only through age 60, and ceftriaxone only through age 80. For males, only gentamicin yielded ≥ 80% susceptibility in any age cohort.ConclusionFew suitable empirical treatment options for community-source urinary tract infection were identified for women aged over 60 years or males of any age. Empirical therapy recommendations must consider the patient's demographic characteristics. Site-specific, age and gender-stratified susceptibility surveillance involving all uropathogens is needed.     

Effect of initial combination therapy with sitagliptin and metformin on β-cell function in patients with type 2 diabetes

Aim: To examine the effect of sitagliptin and metformin, alone and in combination, on modelled parameters of β‐cell function in patients with type 2 diabetes. Methods: The data used in the present analyses are from a 104‐week study, which included a 24‐week, placebo‐ and active controlled phase followed by a 30‐week, active controlled, continuation phase and an additional 50‐week, active controlled extension phase. Patients were randomised to one of six blinded treatments: sitagliptin 50 mg + metformin 1000 mg b.i.d., sitagliptin 50 mg + metformin 500 mg b.i.d., metformin 1000 mg b.i.d., metformin 500 mg b.i.d., sitagliptin 100 mg q.d. or placebo. Patients on placebo were switched in a blinded manner to metformin 1000 mg b.i.d. at week 24. Subsets of patients volunteered to undergo frequently sampled meal tolerance tests at baseline and at weeks 24, 54 and 104. β‐cell responsivity was assessed with the C‐peptide minimal model. The static component (Φ_s) estimates the rate of insulin secretion related to above‐basal glucose concentration. The dynamic component (Φ_d) is related to the rate of change in glucose. The total index (Φ_total) represents the overall response to a glycaemic stimulus and is calculated as a function of Φ_s and Φ_d. Insulin sensitivity was estimated with the Matsuda index (ISI). The disposition index, which assesses insulin secretion relative to the prevailing insulin sensitivity, was calculated based on the Φ_total and ISI. Results: At week 24, substantial reductions in postmeal glucose were observed with all active treatment groups relative to the placebo group. Φ_s, Φ_total and the disposition index were significantly improved from baseline at week 24 with all active treatments relative to placebo. Generally larger effects were observed with the initial combination of sitagliptin and metformin relative to the monotherapy groups. When expressed as median percent change from baseline, Φ_s increased from baseline by 137 and 177% in the low‐ and high‐dose combination groups and by 85, 54, 73 and ?9% in the high‐dose metformin, low‐dose metformin, sitagliptin monotherapy and placebo groups, respectively. At weeks 54 and 104, the combination treatment groups continued to demonstrate greater improvements in β‐cell function relative to their respective monotherapy groups. Conclusions: After 24 weeks of therapy, relative to placebo, initial treatment with sitagliptin or metformin monotherapy improved β‐cell function; moreover, initial combination therapy demonstrated larger improvements than the individual monotherapies. Improvements in β‐cell function were found with treatments for up to 2 years.     

Macular microhole and foveal red spot syndrome: a critical review of the literature

Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose of this article is to review the literature on nomenclature, natural history, clinical features, diagnosis,...     

Economic Evaluation of Chlorhexidine Cloths on Healthcare Costs due to Surgical Site Infections Following Total Knee Arthroplasty

The purpose of this study was to evaluate the overall annual healthcare cost savings of adding a pre-operative chlorhexidine cloth preparation protocol. We used reports from the National Healthcare Safety Network and previously published reports to determine a range of surgical site infection rates following total knee arthroplasty and the cost per revision procedure. The savings listed are potential, but may be less. The cost benefit of using chlorhexidine at our institution per 1,000 total knee arthroplasty patients was a net savings of approximately $2.1 million. The annual healthcare savings ranged from $0.78 to $3.18 billion. This epidemiologic evaluation of using chlorhexidine prior to undergoing total knee arthroplasty has demonstrated the potential to decrease healthcare costs primarily by decreasing the incidence of surgical site infections.     

Results of Primary Total Knee Arthroplasty in Jehovah's Witness Patients

Total knee arthroplasty can be challenging in Jehovah's Witnesses, as these patients do not accept blood transfusions. We reported our experiences with a special blood management protocol for these patients who underwent total knee arthroplasty. There were 124 self-reported Jehovah's Witnesses who had a mean age of 64 years and who underwent total knee arthroplasties between 1998 and 2009. Mean follow-up was 60 months (range, 24-120 months). Implant survivorship, with revision for aseptic component failure as an end point, was 98%. At the final follow-up, mean Knee Society objective and function score improved to 91and 81 points, respectively. The authors believe that this blood management protocol was responsible for performing safe and transfusion-free total knee arthroplasties that can ultimately lead to excellent outcomes.