Amikacin [HRP]

Background: There is limited information on amikacin pharmacokinetics (PK) and dose requirements in patients with mycobacterial infections. Objectives: To conduct a population PK analysis of amikacin data from patients with mycobacterial infections and compare predicted concentrations from standard and modified dosage guidelines with recommended target ranges. Methods: A population PK model was developed using NONMEM. C-max, C-min, concentration 1h post-infusion (C-1h) and AUC(0-24) using 15mg/kg daily (once daily), the WHO table, 25mg/kg three times weekly (TTW) and modified guidelines were compared using Monte Carlo simulations of 1000 patients. Results: Data were available from 124 patients (684 concentrations) aged 16-92years. CL was 4.64L/h per 100mL/min CLCR; V was 0.344L/kg. With once-daily regimens, C-max was 35-45mg/L in 30%-35% of patients and 35-50mg/L in 46%-48%; C-1h was 25-40mg/L in 53%-59%. The WHO table produced high C-max values in patients <60kg and low in patients >75kg. With TTW dosing, around 30% of C-max values were 65-80mg/L, 40% were 60-80mg/L, and 48% of C-1h were 45-65mg/L. Increasing the dosage interval for patients with CLCR <50mL/min reduced C-min values >2mg/L from 34% to 25% for once-daily dosing and from 18% to 13% for TTW. In patients whose C-min was <2mg/L, 82% of AUC(0-24) values were 100-300mg.h/L. Conclusions: Standard amikacin dosing guidelines achieve low percentages of target concentrations for mycobacterial infections. Extending the dosing interval in renal impairment and widening target ranges would reduce the need for dose adjustment.

Introduction Listeria monocytogenes is one of the most pathogenic bacteria related to the consumption of contaminated food. This study aims to determine the prevalence of L. monocytogenes in raw beef meat in Meknes city of Morocco, to evaluate its pathogenicity and resistance to antimicrobials. Methods During four seasons, a total of 140 samples were collected from supermarkets, butcheries and Souk (weekly traditional market). The PCR method was used to examine the presence of specific and virulence genes in the isolated strains, and also to identify their serotypes. The antimicrobial resistance was determined. Results The results show a prevalence of 7.14% which depends on retail sites and also on the season's variation. The majority of the strains were detected in butcheries (6 strains), and supermarkets (4 strains). Moreover, the majority of strains were detected during summer (50%). Concerning virulence genes, the seven researched genes were detected in 100% of isolated strains. The majority of strains were of the (1/2a, 1/2c, 3a and 3c) serogroup (70%), while two of them were of the (1/2b, 3b, 4b and 4d) serogroup (20%). All isolates were resistant to at least one antimicrobial, while three strains were resistant to nine tested antimicrobials. However, they were highly susceptible to amikacin, imipenem, gentamicin, sulfamethoxazole and chloramphenicol. Conclusions According to results, isolated L. monocytogenes from analyzed beef meat shows a high level of pathogenicity and resistance to the most used antimicrobials in listeriosis therapy, which calls for the severe application of quality systems at the slaughterhouses and retail sites level.