Monitoring of antibiotic consumption and development of resistance by enterobacteria in a tertiary care hospital.

WHAT IS KNOWN AND OBJECTIVE: Antibiotics are the most frequently used drugs in hospitalized patients, but studies have shown that the prescribed antibiotics may be inappropriate and may contribute to antibiotic resistance. We carried out a survey of antibiotic consumption and antibiotic resistance in our tertiary care university hospital, from 2005 to 2013. We focus on cephalosporins, one of the most prescribed groups of antibiotics in the tertiary health care. The objective was to identify any relationship between ceftriaxone consumption and resistance by enterobacteria. METHODS: Antibiotics consumption and antimicrobial resistance were monitored in the tertiary care university hospital from 2005 to 2013. Data on the use of antibiotics in surgical inpatients were obtained and expressed as defined daily doses per 100 bed days. Bacterial resistances were given as percentages of resistant isolates. RESULTS AND DISCUSSION: There was an increasing trend in cephalosporins consumption from 9·56 DBD (2005) to 23·32 DBD (2013), with ceftriaxone as the most frequently used cephalosporin, 3·6 DBD (2005) to 10·78 DBD (2013). E. coli and P. mirabilis resistance to ceftriaxone increased significantly from 22% in 2005 to 47% in 2013 and from 31% in 2005 to 60% in 2013, respectively. We found a significant correlation between ceftriaxone consumption and E. coli resistance (r = 0·895, P < 0·05). WHAT IS NEW AND CONCLUSION: Our study shows that cephalosporin consumption increased from 2005 to 2013, with ceftriaxone as the most prescribed antibiotic. E. coli and P. mirabilis resistance to ceftriaxone increased significantly over the study period. E. coli resistance increased with ceftriaxone consumption.

Population pharmacokinetics of tacrolimus in kidney transplant patients.

OBJECTIVE: The purpose of this study was to derive population pharmacokinetics (PPK) model of tacrolimus clearance, identify and describe factors that influence it in Serbian kidney transplant patients. METHODS: Population pharmacokinetics analysis was performed using nonlinear mixed-effects model (NONMEM) program from Serbian adult kidney transplant patients receiving triple immunosuppressive therapy, including oral tacrolimus. Details of drug dosage history, sampling time and tacrolimus concentration in 63 patients (44 males and 19 females), 27 - 57 years old (age mean 40.88 +/- 7.01 years) were collected retrospectively. Effects of several covariates on tacrolimus clearance were tested: total body weight, gender, age, posttransplantation days, hemoglobin count, CRP, alanine aminotransferase/aspartate aminotransferase, total daily dose of tacrolimus, co-medication with cotrimoxasole, omeprazole, mycophenolate mofetil and prednisone (> 25 mg). RESULTS: Typical mean value of tacrolimus clearance, estimated by the base model (without covariates), in our population was 1.03 l h-1. The final model showed that tacrolimus clearance increased with total daily dose and concomitant administration of high-dose prednisone (> 25 mg). The magnitude of prednisone effect was + 1.16 l h-1. Final model was validated in a group of 17 patients, showing good predictive performance. CONCLUSIONS: The derived model describes well tacrolimus clearance in terms of characteristics of Serbian kidney transplant patients, offering basis for rational individualization of tacrolimus dosing regimens.