Skin and soft tissue infections, such as cellulitis, are commonly diagnosed in the emergency department and these patients are often admitted to the hospital for intravenous antibiotic therapy. Oritavancin is a novel antibiotic approved for the treatment of skin and soft tissue infections that is administered as a one-time infusion. While oritavancin has demonstrated comparable efficacy with multi-dose parenteral antibiotics in clinical trials and has been proposed as an alternative to admission for emergency department patients, there is a paucity of available real world effectiveness data. In this case series, we describe the characteristics and outcomes of ten patients with high-risk skin and soft tissue infections who received oritavancin and were discharged from the emergency department.

Osteomyelitis remains difficult to treat, typically requiring a prolonged course of intravenous (i.v.) antibiotics. The optimal route and duration of antibiotics remains ill-defined due to limited prospective clinical trials. Oritavancin is a long-acting, semisynthetic lipoglycopeptide antibiotic with rapid concentration-dependent bactericidal activity against many Gram-positive organisms. Favourable pharmacokinetics makes oritavancin an appealing alternative to currently available antibiotics requiring daily infusion to decrease the risk of vascular access complications associated with outpatient antimicrobial therapy. The purpose of this study was to report the outcomes of nine patients with chronic osteomyelitis receiving multidose oritavancin. Using electronic medical records, patients aged ≥18 years treated with i.v. oritavancin between September 2015 and April 2018 at Downtown Dublin Wound Center, a hospital-owned outpatient wound care clinic and infusion centre affiliated with Meadows Regional Health System in Dublin, GA, were identified. Of 12 cases reviewed, 9 patients received at least two doses of i.v. oritavancin for the treatment of chronic osteomyelitis. All nine patients experienced clinical cure at 6-month follow-up after the last dose of oritavancin. Multidose oritavancin was found to be a safe and efficacious option for chronic osteomyelitis when treatment options are limited by patient complexities or barriers in their ability to access healthcare services.

The most common pathogen in pediatric cystic fibrosis (CF) patients is Staphylococcus aureus, and drug-resistant species are associated with negative outcomes. Methicillin-resistant Staphylococcus aureus (MRSA) is notoriously hard to treat because many antibiotics are not FDA approved for children and drug allergies or intolerances can prohibit the use of others. Telavancin is currently indicated for hospital-acquired pneumonia and ventilator-associated pneumonia caused by MRSA, but it has not been studied in patients with CF or in pediatrics. As a semi-synthetic derivative of vancomycin, it is unknown if cross-reactivity with telavancin occurs in patients with vancomycin hypersensitivity or intolerance. In this case series, we describe three adolescent patients with CF and previous intolerance to vancomycin who received telavancin for bronchopulmonary exacerbations.

Infective endocarditis (IE) one-year mortality rates approach 40%. Here, we report two native valve Enterococcus faecalis IE cases in patients successfully treated with telavancin. An 88-year-old with mitral valve endocarditis and a penicillin allergy, initially treated with intravenous vancomycin, was switched to telavancin. A 69-year-old, who previously received amoxicillin and intravenous vancomycin for presumed enterococcal bacteraemia, was diagnosed with dual valve endocarditis for which he received telavancin. Both received six weeks of telavancin. Neither had telavancin-related adverse events, evidence of infection at six months, nor required telavancin dosing adjustments. Documented use of novel treatments for serious enterococcal infections is needed.

Gram-positive bacterial infections are an important cause of morbidity and death among cancer patients, despite current therapy. In this case-control study, we evaluated the clinical outcomes and safety of telavancin in cancer patients with uncomplicated Gram-positive bloodstream infections (BSIs). Between March 2011 and May 2013, we enrolled cancer patients with uncomplicated Gram-positive BSIs to receive intravenous telavancin therapy for at least 14 days for Staphylococcus aureus and 7 days for other Gram-positive cocci. Patients with baseline creatinine clearance (CLCR) values of >50 ml/min received 10 mg/kg/day of telavancin, and those with CLCR values between 30 and 49 ml/min received 7.5 mg/kg/day. Patients were compared with a retrospective cohort of 39 historical patients with Gram-positive BSIs, matched for underlying malignancy, infecting organism, and neutropenia status, who had been treated with vancomycin. A total of 78 patients were analyzed, with 39 in each group. The most common pathogen causing BSIs was S. aureus (51%), followed by alpha-hemolytic streptococci (23%), Enterococcus spp. (15%), coagulase-negative staphylococci (8%), and beta-hemolytic streptococci (3%). Sixty-two percent of patients had hematological malignancies, and 38% had solid tumors; 51% of the patients were neutropenic. The overall response rate determined by clinical outcome and microbiological eradication at 72 h following the initiation of therapy, in the absence of relapse, deep-seated infections, and/or infection-related death, was better with telavancin than with vancomycin (86% versus 61%; P = 0.013). Rates of drug-related adverse events were similar in the two groups (telavancin, 31%; vancomycin, 23%; P = 0.79), with similar rates of renal adverse events. Telavancin may provide a useful alternative to standard vancomycin therapy for Gram-positive BSIs in cancer patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01321879.).

Results of pharmacometric analyses influence high-level decisions such as clinical trial design, drug approval, and labeling. Key challenges for timely delivery of pharmacometric analyses are the data assembly process and tracking and documenting the modeling process and results. Since clinical efficacy and safety data typically reside in the biostatistics computing area, an integrated computing platform for pharmacometric and biostatistical analyses would be ideal. A case study is presented integrating a pharmacometric modeling platform into an existing statistical computing environment (SCE). The feasibility and specific configurations of running common PK/PD programs such as NONMEM and R inside of the SCE are provided. The case study provides an example of an integrated repository that facilitates efficient data assembly for pharmacometrics analyses. The proposed platform encourages a good pharmacometrics working practice to maintain transparency, traceability, and reproducibility of PK/PD models and associated data in supporting drug development and regulatory decisions.

BACKGROUND: Methicillin-resistant Staphylococcus aureus infections are a well-documented risk of surgery and are becoming increasingly difficult to treat owing to continued acquired resistance. A new antibiotic for treatment of Staphylococcus aureus is telavancin.
METHODS: A patient at our institution was prescribed telavancin for multiple spinal abscesses before spinal surgery. Routine preoperative testing revealed an international normalized ratio (INR) of 2.05 with no clear cause. Careful review of the patient\'s medication history and prescriber information revealed that telavancin may interfere with prothrombin time (PT/INR) testing. In vitro testing by our laboratory confirmed an association between telavancin dose and an increase in PT/INR. An alternative reagent for PT/INR testing unaffected by telavancin dose revealed a PT/INR of 0.97.
METHODS: Telavancin interacts with artificial phospholipid surfaces used to monitor coagulation while having no actual effect on coagulation.
CONCLUSIONS: All physicians, especially orthopaedic surgeons, should be aware of the effects of telavancin and ensure proper measures are taken to acquire the true INR by switching the reagent used to test PT/INR or ensuring the PT/INR is drawn before telavancin dosing.