Performance of a divided-load intravenous vancomycin dosing strategy for obese patients.

BACKGROUND: Current guidelines recommend vancomycin trough concentrations of 15 to 20 µg/mL in complicated infections and all trough concentrations >10 µg/mL to avoid developing microbial resistance. To date, no published protocol reliably meets these recommendations for obese patients. OBJECTIVE: We assessed the performance of a novel, obese-specific, divided-load vancomycin protocol for attaining target trough concentrations within 12 to 24 hours of dosing initiation, and during maintenance dosing, in obese patients. METHODS: The protocol was evaluated through prospective medical record review in 54 consecutive obese patients. Vancomycin serum concentrations were drawn before the third and fifth dose after initiation. Steady-state concentrations were drawn after the third dose once maintenance dosing was achieved and periodically thereafter. RESULTS: Within 12 hours after dosing initiation, 48 (89%) study patients exhibited trough concentrations of 10 to 20 µg/mL averaging 14.5 ± 3.2 µg/mL; 51 (94%) study patients exhibited trough concentrations >10 µg/mL within 12 hours after dosing initiation, and 3 (6%) had trough concentrations >20 µg/mL. Thirty-one participants had second trough concentrations drawn within 24 hours of dosing initiation, averaging 15.0 ± 3.1 µg/mL; 24 patients had a total of 32 trough concentrations drawn during maintenance dosing, averaging 15.1 ± 2.5 µg/mL. CONCLUSION: Obese-specific, divided-load dosing achieved trough concentrations of 10 to 20 µg/mL for 89% of obese patients within 12 hours of initial dosing and 97% of obese patients within 24 hours of initial dosing while preventing doses given during supratherapeutic trough levels; 97% of troughs measured during steady state were within target range.

Successful treatment of ventriculostomy-associated meningitis caused by multidrug resistant coagulase-negative Staphylococcus epidermidis using low-volume intrathecal daptomycin and loading strategy.

OBJECTIVE: To report successful use of low-volume intrathecal (IT) daptomycin and loading strategy for the treatment of ventriculostomy-associated meningitis. CASE SUMMARY: A 23-year-old man with a history of multiple ventriculoperitoneal shunt revisions resulting from multidrug-resistant Staphylococcus epidermidis shunt infection presented with meningitis despite suppressive antibiotic therapy. After source control surgery, the patient improved with intravenous daptomycin plus IT vancomycin. Then, 4 days later, significant ventriculostomy output occurred, and the S epidermidis was confirmed to be intermediately sensitive to vancomycin (MIC = 8 µg/mL) and susceptible to daptomycin (MIC = 2 µg/mL). IT vancomycin was changed to IT daptomycin 5 mg in 3 mL normal saline (NS) every 24 hours for 3 days, then every 72 hours for 18 days. The cerebrospinal fluid (CSF) was sterile after 1 day of IT daptomycin and remained so. Creatine kinase remained normal throughout the course of treatment. The patient was discharged on hospital day 50 without antibiotics. DISCUSSION: IT daptomycin has been reported for adult doses ranging from 5 to 10 mg once every 24 to 72 hours in volumes ranging from 5 to 10 mL; drug accumulation has been seen after the third dose of once every 24 hours dosing, and delayed improvement has been seen with once every 72 hours dosing. We planned for rapid load and CSF sterilization and extended the dosing interval once drug accumulation was expected to have occurred. CONCLUSIONS: IT daptomycin 5 mg diluted to 3 mL in NS and dosed in a loading strategy was effective and without adverse sequelae.

Needs analysis for educating community pharmacists to interface with prehospital stroke chain of survival.

BACKGROUND: Awareness of the American Heart Association's Stroke Chain of Survival, and willingness to learn and share this information with the public, was assessed for community pharmacists practicing near a primary stroke center. METHODS: Twenty-three community pharmacies local to a primary stroke center were identified and surveyed. The surveyor showed each pharmacist a flier with a mnemonic for assessing stroke symptoms, briefly explained steps in the Stroke Chain of Survival, and noted if the pharmacist was available, listened to the entire presentation, read the information on the flier, agreed to post the flier, and if the pharmacist made any comments. The surveyor also assessed whether the Stroke Chain of Survival was new information to each pharmacist. RESULTS: All subjects read the information on the flier. Twenty-two (95.7%) listened to the entire presentation, and 23 (100%) were willing to post the flier. Two (11%) indicated that the parent company does not allow public posting of noncorporate information but agreed to post the flier internally. Twenty-one (91%) expressed appreciation for receiving the information. Seventeen (74%) indicated that the Stroke Chain of Survival was new information to them, 14 (61%) spontaneously remarked on the importance of the information, and 4 (17%) asked for additional information. CONCLUSIONS: Community pharmacists surveyed were willing to interface with the prehospital phase of the Stroke Chain of Survival; nearly 75% of them required education to do so. Community pharmacies are potentially a venue for educating the public on the Stroke Chain of Survival. It may be necessary to approach community pharmacy corporate leadership to partner with such efforts.

Performance of a divided-load intravenous vancomycin dosing strategy for critically ill patients.

BACKGROUND: Current guidelines recommend vancomycin trough concentrations 15 to 20 µg/mL in complicated infections and all trough concentrations above 10 µg/mL. OBJECTIVE: We assessed the performance of a novel divided-load protocol designed to attain target trough concentrations within 24 hours of initiation and prevent doses given at concentrations above the target range, in critically ill patients. METHODS: The protocol was evaluated in 79 critically ill patients through retrospective medical record review. Vancomycin serum concentrations were drawn before the third dose after initiation and after any dosing change. Steady-state concentrations were drawn before the fifth or sixth doses. Vancomycin concentrations before the second dose were predicted using a nonparametric expectation maximization algorithm. RESULTS: Sixty-nine of 79 patients received scheduled doses, and 62 (90%) of the scheduled-dose patients attained therapeutic target concentrations 12 to 24 hours after therapy initiation. Eight scheduled-dose patients weighed > 150% of ideal body weight (IBW) and were significantly more likely to exhibit supratherapeutic trough concentrations before the fifth or sixth doses (P = .0004) compared with patients weighing ≤150% of IBW. Ten of 79 patients (8 dialysis dependent and 2 experiencing acute kidney injury) were dosed in response to measured serum drug concentrations drawn according to the divided-load protocol. All the 8 dialysis-dependent patients (100%) attained therapeutic concentrations 12 hours after therapy initiation. CONCLUSION: The divided-load vancomycin dosing strategy achieved measured trough concentrations 15 to 20 µg/mL for most critically ill patients within 24 hours of initial dosing, without allowing doses given during supratherapeutic concentrations.

Case Report: Apixaban-Associated Gluteal Artery Extravasation Reversed With PCC3 Without FFP.

Apixaban, an oral factor Xa inhibitor, has no commercially available assay to measure its activity and no specific antidote. To date, recommendations for managing bleeding associated with apixaban are based on studies with animal models and healthy volunteers (who do not have identified thrombogenic risk factors) and expert opinion. No clinical experience has been published in the literature. Ideally, apixaban would be reversed sufficiently to stop a perilous bleed without producing more thrombogenic risk than the patients' underlying risk factors. Three-factor prothrombin complex concentrate (PCC3) is the least thrombogenic among the suggested reversal agents. Fresh frozen plasma (FFP) is sometimes recommended to add to PCC3, but it adds considerable volume. We describe successful management of an active left gluteal arterial extravasation due to trauma and associated apixaban, in a patient with aortic stenosis and atrial fibrillation, by administration of PCC3 alone, without the added volume of FFP.

Managing Subdural Bleeding Associated With Rivaroxaban: A Series of 3 Cases.

OBJECTIVE: To report 3 cases of subdural bleeding associated with rivaroxaban managed by 3-factor prothrombin complex concentrate (PCC3). CASE SUMMARIES: Case 1 presented with a 1-cm thick subdural hematoma (SDH) 12 hours after her last dose of rivaroxaban. Case 2 presented with a right 1-cm acute right SDH with 2 to 3 mm of midline shift 24 hours after his last dose of rivaroxaban. Case 3 presented with a 1.8-cm thick right cerebral convexity hematoma 12 hours after her last dose of rivaroxaban. All patients received 23 to 35 units/kg PCC3 with 1 to 3 units of fresh frozen plasm (FFP) and demonstrated no progression in lesions measured by repeat computed tomography (CT). Two patients were discharged to rehabilitation facilities and 1 patient ultimately died due to the location of the lesion. DISCUSSION: Rivaroxaban has no specific antidote. Current bleeding management strategies are based on expert opinion. The risks and benefits for differing strategies are unclear, and no clinical experience has been reported to date. These cases begin to illuminate differences among choices for managing bleeding associated with Xa inhibitors. CONCLUSION: In this case series, 25 to 35 units/kilogram PCC3 and FFP 1 to 3 units ceased rivaroxaban-associated bleeding without thrombogenic complications.