Vancomycin and Linezolid dosing in Obese and Overweight Patients: Is There a Universally Accepted Dosing Protocol to Improve their Efficacy?

@#Vancomycin is used to manage methicillin-resistant Staphylococcus aureus (MRSA) and other bacterial infections that are Gram-positive in nature. Linezolid belongs to the oxazolidinone class of antibiotics, which is primarily used to treat vancomycin-resistant Enterococcus (VRE), MRSA, diabetic foot, soft tissue, and skin infections. Here, we discuss vancomycin and linezolid dosing in obese patients, their mechanism of actions, pharmacokinetics, problems with dosing and evaluation of several dosing protocols in the obese patient population. There is no generally accepted dosing protocol for linezolid and vancomycin. Evidence suggests that using trough concentrations alone is insufficient for estimating vancomycin and linezolid exposure accurately as many researchers have revised protocol guidelines, developed more rigorous dosing and monitoring guidelines, or developed novel dosage strategies to meet the needs of overweight patients. Peaks and troughs measurement should be considered because it improves precision and reduces the area under the curve (AUC) estimate bias. To provide better dosing guidelines in this vulnerable group, obese patients must be included in all phases of drug design.

Linezolid-resistant Enterococcus casseliflavus and Enterococcus gallinarum isolated from poultry farms in Kelantan, Malaysia

Aims@#Linezolid has become a decisive therapy in treating infections with vancomycin-resistant Enterococcus (VRE). Currently, the emergence of linezolid-resistant Enterococcus further complicates the therapeutic options and leads to global health threat not only in hospital setting but in the community. The study aimed at antimicrobial pattern of Enterococcus isolated from 6 poultry farms in Kelantan, Malaysia.@*Methodology and results@#Between February and December 2019, 300 broiler cloacal swab sample (Gallus gallus domesticus) were collected and screened for linezolid-resistant enterococci (LRE) using a standard biochemical and antimicrobial susceptibility tests. Among all the samples, 32.3% (n=97/300) grew Enterococcus, 71.1% (n=69/97) of it were identified Enterococcus casseliflavus by molecular identification, whilst remaining isolates 28.9% (n=28/97) were further identified as Enterococcus gallinarum by 16S rRNA sequencing. None of the isolates were found to exhibit high-level resistance to vancomycin. However, 3/97 (3.1%) were exhibit resistance to high-level gentamicin based on Kirby-Bauer disk diffusion test. Whereas 48/97 (49.5%) of isolates were observed to be resistant to ampicillin, 28/97 (28.9%) were resistant to penicillin. Surprisingly, among the two strains isolated, 18.6% (n=18/97) of it were resistant to linezolid. Isolates showed resistance to linezolid by disk diffusion test were verified by VITEK-2 automated system (bioMérieux, USA) with MIC ≥8 µg/mL. All antimicrobial susceptibility test and minimal inhibitory concentration (MIC) results were interpreted according to Clinical and Laboratory Standard Institute (CLSI). @*Conclusion, significance and impact of study@#In conclusion, this study has reported the prevalence of linezolid resistant Enterococcus (LRE) in highly intrinsic antibiotic resistant of E. casseliflavus and E. gallinarum in Malaysia poultry farms, alongside with the truancy of vanA strains. The emergence of LRE strains is an alarming problem to the animal husbandry and healthcare setting worldwide. This could lead to potentially untreatable and life-threatening enterococcal infections. Even more worrying is the spread of LRE to geographical regions where these strains were previously unreported, which may pose a global health threat. Antimicrobial surveillance in poultry husbandry is thus, dimly necessary to prevent wide spread of multidrug-resistant bacteria.

Prevalence of Clostridium difficile toxin in diarhoeal stool samples of patients from a tertiary hospital in North Eastern Penisular Malaysia

This study describes the prevalence of Clostridium difficile toxin (CDT) in loose stool samples from inpatients aged more than two years of a tertiary hospital. A total of 175 samples that had been examined were from stool samples that were sent to the Medical Microbiology & Parasitology Laboratory for various clinical indications. The toxin was detected by a commercial immunochromatograhic test, and the patients’ demography, clinical features, treatment and outcomes were analyzed from their medical records. Clostridium difficile toxin was positive in 24 (13.7%) of the stool samples. Male and female were 11 (45.8 %) and 13 (54.2 %) respectively, with the majority of them aged more than 50 years. Most were from medical wards (n=21, 87.5%), with the rest from surgical wards (n=2, 8.3%) and intensive care units (n=1, 3.4%). All the CDT positive patients had history of prior antibiotic usage within 6 weeks before the detection of the toxin. The mean duration of antibiotics usage was 17.75 (±13.75) days, while the mean duration of diarrhea was 5.21((± 5.85) days. Eighteen patients had underlying medical illnesses that were diabetes mellitus, chronic renal disease, hypertension, ischaemic heart disease, cerebrovascular disease and malignancy; with seven of them being CDT positive while on chemotherapy. Stool occult blood test was positive in 15 patients whereas presence of pus cells in the CD positive stool samples were detected in 21 patients. The duration of hospitalization among the patients was 27.96 (± 23.22) days.