Staphylococcal and enterococcal infections are very prominent in hospital settings, especially prevalent in patients with inserted devices such as catheters. The bacteria that cause these infections are hard to get rid of and can lead to more serious infections.
In this study, a central venous catheter model was utilized to evaluate lock solutions and their efficacy against bacterial in-line growth. The experiment was done in vitro. Lock solutions containing vancomycin (5 mg/mL) or telavancin (5 mg/mL), with and without preservative containing heparin sodium (2,500 units/mL), heparin, and normal saline solution. The solutions were put into the catheters after the bacteria was given a 24-hour growth period. After 72 hours of exposure to the lock solutions, the catheters were flushed, segmented, and analyzed for bacterial colony growth. In order to establish a baseline, catheters were processed after 24 hours of incubation with any lock solution.
The examined catheter and lock solutions revealed that vancomycin and telavancin (with or without heparin) had similar activity against S. epidermidis and that vancomycin alone was more effective that telavancin against E. faecalis. Against S. aureus, vancomycin plus heparin had activity similar to that of vancomycin alone; both lock agents had greater activity than telavancin. However, addition of heparin to vancomycin decreased efficacy against E. faecalis and S. epidermidis.
Am J Health-Syst Pharm. 2016;73(5):315-21.
Piperacillin-tazobactam and vancomycin are two of the most commonly used antibiotics in a hospital setting. They are often the go-to first line therapies for numerous indications, including hospital-acquired and ventilation-associated pneumonias, severe hospital-acquired intraabdominal infections, and severe skin and soft issue infections such as necrotizing fasciitis. Extended infusion (EI) dosing schemes have been developed for piperacillin-tazobactam in order to improve patient outcomes. EI dosing of piperacillin-tazobactam is commonly administered as 3.375 g (piperacillin 3 g and tazobactam 0.375 g) every 8 hours as a 4-hour infusion, while there is limited data to support compatibility of coinfusion.
O’Donnell et al. conducted a compatibility study to test the compatibility of vancomycin and piperacillin-tazobactam in concentrations typically used in extended-infusion dosing schemes. In order to test this, various concentrations of piperacillin-tazobactam specifically 33.75, 45, 50, 60, 67.5, 80, and 90 mg/mL were reconstituted and diluted. Vancomycin was diluted to concentrations of 4–8, 10, and 12 mg/mL. Frozen formulations of each medication and brand name Zosynâ were also studied. The mixtures were visually observed from hours 1-4 and after 24 hours for abnormalities or precipitates. Each concentration combination of each product was tested for precipitation as well as microscopic analyses were performed to discern less perceptible incompatibilities that did not result in clear visual precipitation.
Visual analyses resulted in observed compatibility for all concentrations of piperacillin-tazobactam when combined with vancomycin 4-7mg/mL. Also, at higher doses when piperacillin-tazobactam 80 or 90 mg/mL was added to vancomycin 8 mg/mL, a transient and reversible precipitate had formed lasting less than 30 seconds. Most notably of the results observed was the formation of an irreversible precipitate between vancomycin 10 mg/mL and all concentrations of piperacillin-tazobactam. Absorbance and microscopic analyses resulted in findings that did not differ significantly between the controls (0.9% sodium chloride) and the solutions that exhibited reversible visual precipitation. From these results, O’Donnell et al. was able to show through visual, microscopic, and absorbance analyses that no evidence of incompatibility was observed when piperacillin-tazobactam 33.75-90 mg/mL was combined with vancomycin ≤7 mg/mL. Reversible and irreversible precipitates formed when piperacillin–tazobactam was combined with vancomycin ≥8 mg/mL.
Am J Health-Syst Pharm. 2016; 73:241-46.
Although this article is from 2009, I thought it would be an interesting read considering it was one of the most viewed articles listed on the American Journal of Health Systems Pharmacists’ website. The article explores vancomycin monitoring in hospitalized patients to treat gram-positive infections, typically MRSA. It was found that earlier formulations of vancomycin might have been the reason for some serious adverse effects including nephrotoxicity and ototoxicity (toxicity to the ear). These formulations possibly contained impurities. The study found that the AUC, or area under the curve, is the most useful pharmacokinetic parameter to monitor vancomycin administration. Various other methods of monitoring are recommended when obtaining vancomycin serum concentration is not possible, but more clinical data would be necessary.
The article mentioned a lack of clinical data hindering the results of this study. It was stated that due to vancomycin being a generic formulation that very few newer clinical trials had actually been conducted. It was also noted that pediatric monitoring was beyond the scope of the article. Now that we are learning a lot about the drug development process it was interesting to read about a case where this process actually hindered further research for companies.
While a lot of the pharmacokinetic terms were familiar thanks to the Principles of Drug Action course material, it was definitely a newer concept to learn that vancomycin metabolism differed significantly for diabetic patients. Drug dosing, especially with a drug like vancomycin with such a narrow therapeutic index, should be done strategically. A patient’s medical history needs to be carefully reviewed when deciding how to dose a patient, which should be a very individualized process.
Rybak M, Lomaestro B, Rotschafer JC et al. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases. Am J Health-Syst Pharm. 2009; 66:887-98.