ABSTRACT
Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections. Minimum inhibitory concentration determination by Etest was performed for 205 Brazilian community urinary tract infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream strains recovered from a surveillance study. Pharmacodynamic exposure was modeled via a 5000 subject Monte Carlo simulation. All isolates were susceptible to ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%, 75.7% and 64.3% among inpatient isolates, respectively. Against outpatient isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in conservative scenarios) achieved high cumulative fraction of response: car-bapenems and piperacillin/tazobactam cumulative fraction of responses were close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar results were observed against inpatients isolates for carbapenems (100%) and piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9% bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive scenario) and 56.7% (conservative scenario) respectively. Based on this model, standard doses of beta-lactams were predicted to deliver sufficient pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided for inpatients and ciprofloxacin empirical prescription should be avoided in both inpatients and outpatients with complicated urinary tract infection.
Subject(s)
Humans , Anti-Bacterial Agents/pharmacology , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacokinetics , Ceftriaxone/pharmacokinetics , Ceftriaxone/pharmacology , Ciprofloxacin/pharmacokinetics , Ciprofloxacin/pharmacology , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology , Escherichia coli/isolation & purification , Monte Carlo Method , Microbial Sensitivity Tests/methods , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/pharmacokinetics , Penicillanic Acid/pharmacology , Piperacillin/pharmacokinetics , Piperacillin/pharmacology , Pyelonephritis/microbiology , Severity of Illness Index , Thienamycins/pharmacokinetics , Thienamycins/pharmacology , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiology , beta-Lactams/pharmacokinetics , beta-Lactams/pharmacologyABSTRACT
Tobramycin, an aminoglycoside, and piperacillin, an antipseudomonal penicillin, are widely used to treat Gram -ve infections. Their concurrent use is recommended because of their synergistic action and prevention of resistant strains against monotherapy. This experimental work was aimed to study the effects and interaction of these important drugs on rabbit kidney. Male rabbits were administered tobramycin, piperacillin, and tobramycin plus piperacillin for 21 days [n = 6 in each group]. Blood and urine samples were collected on day O, 11, and 21. Blood was analyzed for BUN, serum creatinine, serum potassium, and serum sodium while urine was analyzed for urine volume, creatinine, albumin and specific gravity. Renal creatinine clearance was calculated. Results showed some change in renal function with use of tobramycin but piperacillin neither changed the renal function nor did augment the toxic effect of tobramycin so it was concluded that combination of both drugs in safe
Subject(s)
Male , Animals , Tobramycin/adverse effects , Tobramycin , Piperacillin/pharmacokinetics , Urine/analysis , Kidney Function Tests/drug effects , Kidney Function Tests/pharmacology , Blood Urea Nitrogen , Glomerular Filtration Rate/drug effects , RabbitsABSTRACT
Recently, two new combinations of ß-lactam antibiotics with ß-lactamase inhibitors become commercially avaiable in Brazil: piperacillin/tazobactam and ampicillin/sulbactam. This study was designed to assess and compare the in-vitro activity of theses new compounds, as well as that of ticarcillin/clavulanic acid, against bacteria isolated in our environment. A total of 749 bacteria isolated at São Paulo Hospital were tested using the disk diffusion method, in compliance with NCCLS Standardization, using strict quality control. Only one sample per patient was included in the study. Oxacillin-resistant staphylococcus samples were not included in this study. Of the total samples tested 84.5 percent were susceptible to piperacillin/tazobactam, 81.2 percent to ticarcillin/clavulanic acid, and 77.6 percent to ampicillin/sulbactam. Piperacillin/tazobactam was also found to be the most active combination of the three against Enterobacteriaceae (n=312), inhibiting 91.7 percent of the bacteria tested. Ticarcillin/clavulanic acid was active against 85.8 percent of the Enterobacteriaceae, while ampicillin/sulbactam inhibited 83.2 percent of the samples...
Subject(s)
Clavulanic Acid/pharmacokinetics , Ampicillin/pharmacokinetics , beta-Lactamases , In Vitro Techniques , Cross Infection/epidemiology , Cross Infection/drug therapy , Piperacillin/pharmacokinetics , Sulbactam/pharmacokinetics , Sulbactam/therapeutic use , Ticarcillin/pharmacokinetics , Ticarcillin/therapeutic useABSTRACT
O estudo comparativo da atividade da azlocilina, da mezlocilina e da piperacilina sobre 123 cepas de bactérias Gram-negativas isoladas nos hospitais do Recife foi efetuado mediante a determinaçäo das CIM e das CBM pela microtécnica de diluiçäo em caldo. Estas três ureidopenicilinas apresentaram uma boa atividade contra E. coli, Salmonella, Shigella, Proteus indol positivo e Klebsiella. Todas as cepas de Pseudomonas foram sensíveis à Azlocilina e à Piperacilina