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.

Inappropriate Doses of Intravenous Polymyxin B after Renal Adjustment Lead to Treatment Failure

Sub-therapeutic doses, shorter duration of therapy, female gender, bacteremia, and renal impairment were among independent predictors of polymyxin B treatment failure. In this study, we found an association between inappropriate doses of polymyxin B (<15000 or >25000 unit/kg/day) and renal impairment. Inappropriate doses of polymyxin B were significantly associated with CrCl 20-50 mL/min (p = 0.021, ORadj 6.660, 95% CI 1.326, 33.453) and CrCl <20 mL/min (p = 0.001, ORadj 22.200, 95% CI 3.481, 141.592). By conducting sub-group analysis only using subjects with appropriate dosage, renal impairment was not associated with polymyxin B treatment failure, thus indicating that treatment failure was due to an inappropriate dose of polymyxin B, rather than renal impairment. In conclusion, renal impairment was not directly associated with treatment failure but was due to an inappropriate dosage of polymyxin B after renal adjustment

Antifungal Properties of Malaysian Tualang Honey and Stingless Bee Propolis against Candida albicans and Cryptococcus neoformans.

Candida albicans and Cryptococcus neoformans can cause life-threatening infections, especially in immune-compromised patients. Treatment with currently available antifungal agents may lead to severe side-effects and emergence of resistant strains. The objective of this study was to evaluate the antifungal properties of MTH and SBP against C. albicans and C. neoformans. Broth dilution method was used to assess the antifungal properties of the MTH and propolis. Different concentrations of the MTH and propolis (0.78 mg/mL – 50.00 mg/mL) in two-fold dilutions were tested against each fungus to determine the Minimum Inhibitory Concentration (MIC) which was done by visual inspection and spectrophotometric (MIC95) reading at 620 nm. Minimum Fungicidal Concentration (MFC) was obtained by culturing on Sabouraud Dextrose Agar. Total phenolic acids and flavonoids contents were also determined by Folin-Ciocalteu and colorimetric assay respectively. The MICs of the MTH against C. albicans and C. neoformans by visual inspection were 6.25 mg/mL and 1.56 mg/mL respectively, meanwhile 6.25 mg/mL and 3.13 mg/mL by spectrophotometric reading. The MFCs of the MTH against C. albicans and C. neoformans were 12.50 mg/mL and 6.25 mg/mL respectively. The MICs of SBP against C. albicans and C. neoformans by visual inspection were both 1.56 mg/mL whereas spectrophotometric reading recorded MICs of 3.13 mg/mL and 1.56 mg/mL respectively. The MFCs of SBP against C. albicans was 6.25 mg/mL and 3.13 mg/mL for C. neoformans. The total phenolic acids and flavonoids contents of MTH were 275.6 mg gallic acid/kg and 71.8 mg quercetin/kg respectively whereas for SBP, the phenolic acids content was 1754.2 mg gallic acid/kg and the flavonoids content was 82.6 mg quercetin/kg. MTH and SBP exhibited significant antifungal activities against C. albicans and C. neoformans. Their antifungal activities might be attributed to the high phenolic acids and flavonoids. This result suggests that MTH and SBP could potentially be used as alternative therapeutic agents against these fungi.

Risk factors and outcomes of imipenem-resistant Acinetobacter bloodstream infection in North-eastern Malaysia

Objective: To determine the risk factors and outcomes of imipenem-resistant Acinetobacterbaumannii (IRAB) bloodstream infection (BSI) cases, since there is very little publication on Acinetobacter baumannii infections from Malaysia. Methods: A cross sectional study of 41 cases (73.2%) of imipenem-sensitive Acinetobacter baumanii (ISAB) and 15 cases (26.8%) of IRAB was conducted in a teaching hospital which was located at North-Eastern state of Malaysia. Results:There was no independent risk factor for IRAB BSI identified but IRAB BSI was significantly associated with longer bacteraemic days [OR 1.23 (95% CI 1.01, 1.50)]. Although prior use of carbepenems and cephalosporin were higher among IRAB than ISAB group, statistically they were not significant. There was no significant difference in term of outcomes between the two groups. Conclusions: Although statistically not significant, this analysis compliments previous publication highlighting the importance of appropriate empiric antibiotic usage in hospital especially carbepenems and need further evaluation with bigger subjects.

Outcomes and appropriateness of management of nosocomial Acinetobacter bloodstream infections at a teaching hospital in northeastern Malaysia.

Acinetobacter spp is a known nosocomial pathogen causing a wide range of clinical diseases such as pneumonia, wound infection and bloodstream infections (BSI). The clinical outcomes of acinetobacter BSI were determined by a 1:1 case control study involving 58 confirmed cases of acinetobacter BSI who were compared to other gram-negative infections. The crude mortality of acinetobacter BSI was 47.2%, which was significantly greater than other gram-negative BSI (OR 1.89, 95% CI 1.10-3.24) but there were no significant differences in attributed mortality between the two groups. We found that patients treated in intensive care units (ICU), who had longer ICU stays, who presented with shock or coagulopathy, had prior exposure to carbapenems, had mechanical ventilation, were on a ventilator for longer periods, had a nasogastric tube, had an arterial catheter or had parenteral nutrition at a significantly greater risk of mortality due to acinetobacter BSI. Patients presenting with septic shock (OR 17.95, 95% CI 3.36-95.84) or having a central venous catheter (OR 12.48, 95% CI 1.09-142.68) were independently at higher risk for mortality. Appropriateness of therapy reduced the mortality attributes of acinetobacter BSI (OR 0.197, 95% CI 0.040-0.967) but did not significantly reduce crude mortality in acinetobacter BSI patients. This study shows the importance of preventing acinetobacter BSI and the appropriate use of antimicrobial agents to reduce mortality.