ABSTRACT
Los antibióticos betalactámicos son los que más se usan en el tratamientoy profilaxis de las infecciones odontogénicas. Con frecuenciaes necesario prescribir un segundo antibiótico que incremente el efectodel primero. Debido a ello se hizo una revisión de los antibióticos y otros medicamentos que administrados simultáneamente o en forma secuencial con betalactámicos producen efectos deseados (sinergismo, potenciación) o indeseados (antagonismo) o provocan efectos adversos en el organismo.
Beta-lactams are the most commonly used antibiotics in the treatmentand prophylaxis of odontogenic infections. It is often necessary toprescribe a second antibiotic to increase the eff ect of the fi rst. For thisreason, we performed a review of antibiotics and other medicationswhich, when administered simultaneously or sequentially with betalactams,produce desirable (synergism, potentiation) or undesirable(antagonism) eff ects or provoke adverse eff ects in the organism.
Subject(s)
Humans , beta-Lactams/administration & dosage , beta-Lactams/pharmacokinetics , beta-Lactams/pharmacology , Drug Interactions , beta-Lactams/adverse effects , Cephalosporins/pharmacology , Drug Antagonism , Drug Synergism , Food-Drug InteractionsABSTRACT
ABSTRACTINTRODUCTION: Monte Carlo simulations have been used for selecting optimal antibiotic regimens for treatment of bacterial infections. The aim of this study was to assess the pharmacokinetic and pharmacodynamic target attainment of intravenous β-lactam regimens commonly used to treat bloodstream infections (BSIs) caused by Gram-negative rod-shaped organisms in a Brazilian teaching hospital.METHODS: In total, 5,000 patients were included in the Monte Carlo simulations of distinct antimicrobial regimens to estimate the likelihood of achieving free drug concentrations above the minimum inhibitory concentration (MIC; fT > MIC) for the requisite periods to clear distinct target organisms. Microbiological data were obtained from blood culture isolates harvested in our hospital from 2008 to 2010.RESULTS: In total, 614 bacterial isolates, including Escherichia coli, Enterobacterspp., Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, were analyzed Piperacillin/tazobactam failed to achieve a cumulative fraction of response (CFR) > 90% for any of the isolates. While standard dosing (short infusion) of β-lactams achieved target attainment for BSIs caused by E. coliand Enterobacterspp., pharmacodynamic target attainment against K. pneumoniaeisolates was only achieved with ceftazidime and meropenem (prolonged infusion). Lastly, only prolonged infusion of high-dose meropenem approached an ideal CFR against P. aeruginosa; however, no antimicrobial regimen achieved an ideal CFR against A. baumannii.CONCLUSIONS:These data reinforce the use of prolonged infusions of high-dose β-lactam antimicrobials as a reasonable strategy for the treatment of BSIs caused by multidrug resistant Gram-negative bacteria in Brazil.
Subject(s)
Humans , Anti-Bacterial Agents/administration & dosage , Drug Resistance, Multiple, Bacterial/drug effects , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/drug therapy , beta-Lactams/administration & dosage , Administration, Intravenous , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Brazil , Gram-Negative Bacteria/classification , Gram-Negative Bacterial Infections/metabolism , Gram-Negative Bacterial Infections/microbiology , Hospitals, Teaching , Microbial Sensitivity Tests , Monte Carlo Method , Time Factors , beta-Lactams/pharmacokinetics , beta-Lactams/pharmacologyABSTRACT
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.