Modelagem farmacocinética/farmacodinâmica do florfenicol para o tratamento da adenite equina por meio da simulação de Monte Carlo / Pharmacokinetic/pharmacodynamic modeling of florfenicol for the treatment of equine adenitis using Monte Carlo simulation

O objetivo deste trabalho foi avaliar a eficácia do florfenicol na dose usualmente empregada em equinos de 22 mg/kg pelas vias intravenosa, intramuscular e oral para o tratamento de adenite equina por Streptococcus equi. subsp. equi, usando a modelagem farmacocinética/farmacodinâmica (PK/PD – Pharmacokinetic/Pharmacodynamic) e a simulação de Monte Carlo. Foi realizada uma simulação de Monte Carlo a partir dos parâmetros PK, logo depois, efetuou-se a modelagem PK/PD para determinar as taxas de eficácia do antimicrobiano para o tratamento dessa infecção bacteriana, de acordo com o valor da concentração inibitória mínima (CIM), em um intervalo de CIM de 0,125 – 4 μg/mL. Pela via intravenosa, a probabilidade de erradicação bacteriana foi de 100% para CIM até 0,5 μg/mL e efeito bacteriostático com probabilidades de 99% e 80% para CIMs de 2 e 4 μg/mL, respectivamente. Já pelas vias intramuscular e oral a probabilidade de se atingir o índice de erradicação bacteriológica foi de 100% para CIM de até 0,5 μg/mL, contudo, atinge valores de 80% e 81%, respectivamente, para CIM de 1 μg/mL considerando o efeito bactericida (p<0,01). Portanto, através desse estudo é evidenciado a eficácia do florfenicol até a CIM de 0,5 μg/mL para as três vias de administração citadas, entretanto, para CIMs superiores a esse valor, é imprescindível o ajuste da dose farmacológica, evitando falhas na terapêutica e possível resistência microbiana.

The objective of this study was to evaluate the efficacy of florfenicol at the dose usually used in horses of 22 mg/kg by intravenous, intramuscular and oral routes for the treatment of equine adenitis caused by Streptococcus equi. subsp. equi, using Pharmacokinetic/Pharmacodynamic (PK/PD) modeling and Monte Carlo simulation. A Monte Carlo simulation was performed from the PK parameters, then PK/PD modeling was performed to determine the antimicrobial efficacy rates for the treatment of this bacterial infection, according to the minimum inhibitory concentration (MIC) value, in a MIC range of 0.125 - 4 μg/mL. Intravenously, the probability of bacterial eradication was 100% for MICs up to 0.5 μg/mL, and the bacteriostatic effect was 99% and 80% for MICs of 2 and 4 μg/mL, respectively. However, for the intramuscular and oral routes, the probability of reaching the bacteriologic eradication index was 100% for MICs of up to 0.5 μg/mL, however, it reaches values of 80% and 81%, respectively, for MICs of 1 μg/mL considering the bactericidal effect (p<0.01). Therefore, through this study the efficacy of florfenicol is evidenced up to the MIC of 0.5 μg/mL for the three routes of administration cited, however, for MICs higher than this value, it is essential to adjust the pharmacological dose, avoiding failures in therapy and possible microbial resistance.

in vitro effect of chloramphenicol and salicylate on erythrocytes of patients with favism

Glucose 6-phosphate dehydrogenase [G6PD] deficiency is the most common of all clinically significant enzyme defects. A long list of drugs thought to cause haemolysis in patients with this enzyme defect. To determine whether chloramphenicol and salicylate can act as in vitro exogenous oxidizing agents and subsequently cause haemolysis of G6PD deficient erythrocytes and matching the result with the data obtained from the clinical observations which includes the intake of trimethoprim-sulfamethoxazole, salicylate or nalidixic acid by favic patient. Sixty six patients admitted to the hospital [Karbala teaching hospital for Children, Karbala, Iraq] with history of sudden onset of pallor and dark urine after fava beans ingestion were studied. Each patient was fully examined and his parents were asked about the type of fava beans ingested and the past drug history. Of the sixty six patients, ten were evaluated 1-3 months later and blood samples were taken from them along with blood samples from ten healthy volunteers. Blood samples from both groups were incubated in vitro with chloramphenicol and salicylate separately. Mean [SD] of methaemoglobin concentrations at baseline and after incubation with therapeutic and toxic concentrations of chloramphenicol [15 micro g/ml and 25 micro g/ml] and salicylate [150 micro g/ml and 300 micro g/ml] were calculated for both the control and the study groups. Paired t-test showed no significant differences [P> 0.05] in methaemoglobin concentrations at baseline and after incubation with therapeutic and toxic concentrations of these drugs. Mean percentage differences from baseline for G6PD deficient group were not significantly different from control group at both concentrations of these drugs as tested by student t-test. Hemolysis in G[6]PD deficient patients occurs mainly after fresh fava beans ingestion. chloramphenicol and acetylsalicylic acid do not cause significant hemolysis in G[6]PD deficient erythrocytes in vitro

Antimicrobial susceptibility and molecular detection of chloramphenicol and florfenicol resistance among Escherichia coli isolates from diseased chickens

Seventy Escherichia coli isolates recovered from diseasedchickens diagnosed with colibacillosis in Henan Province,China, between 2004 and 2005 were characterized forantimicrobial susceptibility profiles via a broth doublingdilution method. Overall, the isolates displayed resistanceto trimethoprim-sulfamethoxazole (100%), oxytetracycline(100%), ampicillin (83%), enrofloxacin (83%), and ciprofloxacin(81%), respectively. Among the phenicols, resistance wasapproximately 79% and 29% for chloramphenicol andflorfenicol, respectively. Molecular detection revealed thatthe incidence rates of the floR, cmlA, cat1, cat2 and cat3were 29, 31, 16, 13, and 0%, respectively. Additionally,10% of the isolates were positive for both floR and cmlA.As these antimicrobial agents may potentially inducecross-resistance between animal and human bacterialpathogens, their prudent use in veterinary medicine ishighly recommended.