Evaluation of Opportunities for Oral Antibiotic Therapy in Bone and Joint Infections.

BACKGROUND: The OVIVA trial suggests oral antibiotics are an alternative to intravenous antibiotics to treat bone and joint infections (BJI). A shift in practice to treatment with oral antibiotics would eliminate the need for central vascular access, improve patient satisfaction, and reduce overall healthcare costs. OBJECTIVE: The primary objective was to identify the proportion of patients treated for BJIs with outpatient parenteral antimicrobial therapy (OPAT) who would have qualified for oral antibiotics based on microbiological data. The secondary objective was to conduct a cost-analysis to estimate potential cost-savings had eligible patients been treated with oral antibiotics. METHODS: This was a single-center, retrospective study of adult patients in the United States treated with intravenous antibiotics for BJIs from January 2018 to April 2020. Inclusion and exclusion criteria matched the OVIVA trial. Patients with Staphylococcus aureus bacteremia, endocarditis, or other high-risk features were excluded. RESULTS: 281 patients met the inclusion criteria. Most had prosthetic joint infections (56%). Infections caused by coagulase-negative staphylococci (25%) were most common, followed by S. aureus (23%) and polymicrobial infections (22%). 69 (25%) patients required a switch during their OPAT course to an alternate antibiotic agent. Thirteen patients (5%) experienced vascular access complications, and 6 patients (2%) developed Clostridiodes difficile infections. Oral therapy could have resulted in an estimated average savings per patient of $3,270.69 USD. CONCLUSION AND RELEVANCE: Most patients treated with OPAT for BJIs were candidates for oral antibiotics. A change in practice would result in cost-savings to the U.S. healthcare system.

Delabeling penicillin and other antibiotic allergies in solid organ transplantation patients.

BACKGROUND: Immunocompromised populations including solid organ transplant (SOT) recipients have a high likelihood of need for antibiotic therapy for treatment of infection as well as for prophylaxis. Antibiotic allergy is commonly reported and often leads to the use of alternative, second-line antibiotics, which have been associated with poor outcomes, increased adverse effects, and higher cost. Formal allergy assessment and allergy testing can serve as an important antimicrobial stewardship tool in optimizing antibiotic regimens for this patient population. METHODS: A PubMed search with relevant keywords was performed. Review of relevant professional society guidelines was also performed. RESULTS: Documented penicillin and sulfonamide allergies are common impediments to the treatment and prophylaxis of immunocompromised populations, but are rarely formally evaluated in practice; however, there is evidence that most patients with documented allergy to these antibiotics can, in fact, tolerate penicillins and sulfonamide antibiotics. Implementation of an antibiotic allergy evaluation and testing program has been shown to increase the use of first-line antibiotics and can be cost saving. CONCLUSION: Antibiotic allergies have significant clinical consequences, especially in immunocompromised populations. Evaluation of these allergies to prevent the avoidance of first-line antibiotics should be a standard part of the workflow for these patients, prior to transplant. Programs can be tailored to the available personnel and resources of the organization.

Safety and efficacy of direct two-step penicillin challenges with an inpatient pharmacist-driven allergy evaluation.

Background: Penicillin allergy is commonly reported and has clinical and financial consequences for patients and hospitals. A penicillin evaluation program can safely delabel patients and optimize antibiotic therapy. Pharmacists who perform this task have focused on a detailed interview or penicillin skin testing (PST). Antibiotic graded challenge after PST requires more resources and is more costly than going directly to a two-step challenge. Objective: To determine whether a pharmacist-driven penicillin allergy evaluation and a testing protocol that primarily uses direct oral challenges can safely delabel patients. Methods: Adult patients (ages >18 years) with a penicillin allergy in their electronic medical record (EMR) who were admitted between September 2019 and June 2020 were eligible. Although all patients with penicillin allergy were eligible, priority was given to patients who required antibiotics. Patients were interviewed, and, if indicated, based on an institutional protocol, were tested by using PST and/or two-step oral challenge. If the patient passed the challenge, then the penicillin allergy label was removed in the EMR and the patient counseled. Demographic information, allergy questionnaire results, testing results, and changes in antimicrobial therapy were collected. Results: Fifty patients were evaluated from September 2019 to June 2020. Ninety-six percent of the patients were delabeled, and antibiotic therapy changed for 54%. Twenty patients were delabeled with an interview alone, and 30 patients underwent oral two-step challenge. Only one patient required PST. Conclusion: A pharmacist-driven penicillin allergy evaluation program focused on direct oral graded challenges and bypassing PST can effectively delabel admitted patients. However, more safety data are needed before implementation of similar programs to optimize antibiotic treatment.

Utility of beta-lactam allergy assessment in patients receiving vancomycin for surgical prophylaxis.

Background: Beta-lactam antibiotics are first-line agents for most patients receiving antimicrobial prophylaxis in surgical procedures. Despite evidence showing low cross-reactivity between penicillins and cephalosporins, patients with beta-lactam allergies commonly receive vancomycin as an alternative to avoid allergic reaction. Methods: Adult patients receiving vancomycin for surgical prophylaxis with a reported beta-lactam allergy at our institution between August 2017 to July 2018 were retrospectively evaluated for potential eligibility for penicillin allergy testing and/or receipt of standard prophylaxis. Results: Among 830 patients who received vancomycin for surgical prophylaxis, 196 reported beta-lactam allergy and were included in the analysis. Approximately 40 % of surgeries were orthopedic. Of patients receiving vancomycin as first-line therapy, 189 (96.4 %) were potentially eligible for beta-lactam prophylaxis. Conclusions: Patients with beta-lactam allergies often qualify for receipt of a first-line antibiotic. An opportunity exists for improved allergy assessment as an antimicrobial stewardship intervention in surgical prophylaxis.

Dalba Got Back? Use of Dalbavancin for the Treatment of Vertebral Osteomyelitis.

Data evaluating dalbavancin use for vertebral osteomyelitis remain limited. In our retrospective cohort, 29 of 34 (85.3%) patients completed their dalbavancin course. Adverse reactions occurred for 6 (17.6%) and infection recurrence in 3 (8.8%) within 90 days. Dalbavancin appears to be safe and well-tolerated for vertebral osteomyelitis.

The hidden cost of dalbavancin: OPAT RN time required in coordination for persons who use drugs.

Background: Serious infections in persons who use drugs (PWUD) are rising. Dalbavancin, due to its extended half-life, offers an alternative treatment for patients in whom standard of care antibiotics are not feasible or practical, allowing for reduced hospital days and the avoidance of central line placement or the use of complex oral regimens. Objectives: We aim to describe the time and effort required for coordination of dalbavancin courses by outpatient registered nurses (RNs) and other outpatient parenteral antimicrobial therapy (OPAT) staff. Design and methods: We conducted a retrospective review of adult patients with documented substance use who received at least one dose of dalbavancin and quantified the number of interventions required by our OPAT RNs and other OPAT staff for coordination of dalbavancin courses. Additionally, detailed data on time spent per intervention were prospectively collected for a 1-month period. Results: A total of 52 patients with 53 dalbavancin courses were included. Most substance use was intravenous. Infectious diagnoses included bone and joint infections (61%) and endocarditis (7%), in addition to skin and soft tissue infections (19%). Infections were most commonly caused by Staphylococcus aureus (62%). RN intervention was required in the coordination of 60% of all courses and in 77% of courses in which at least one outpatient dose was needed. Adverse reactions occurred in one patient (2%) and 90-day readmissions due to infectious complications occurred in two patients (4%). Detailed time analysis was performed for seven consecutive patients, with a total of 179 min spent by OPAT RNs on coordination. Conclusions: The ease of dalbavancin administration does not eliminate the need for extensive RN coordination for successful administration of doses in the outpatient setting for PWUD. This need should be accounted for in program staffing to help increase successful dalbavancin course completion.

Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets.

Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT.

Case report: Persistent shedding of a live vaccine-derived rubella virus in a young man with severe combined immunodeficiency and cutaneous granuloma.

A young man with X-linked severe combined immunodeficiency developed a persistent vaccine-derived rubella virus (VDRV) infection, with the emergence of cutaneous granulomas more than fifteen years after receipt of two doses of measles-mumps-rubella (MMR) vaccine. Following nasopharyngeal swab (NP) collection, VDRV was detected by real-time polymerase chain reaction (RT-qPCR) and sequencing, and live, replication-competent VDRV was isolated in cell culture. To assess duration and intensity of viral shedding, sequential respiratory samples, one cerebrospinal fluid sample, and two urine samples were collected over 15 months, and VDRV RNA was detected in all samples by RT-qPCR. Live VDRV was cultured from nine of the eleven respiratory specimens and from one urine specimen. To our knowledge, this was the first reported instance of VDRV cultured from respiratory specimens or from urine. To assess potential transmission to close contacts, NP specimens and sera were collected from all household contacts, all of whom were immunocompetent and previously vaccinated with MMR. VDRV RNA was not detected in any NP swabs from the contacts, nor did serologic investigations suggest VDRV transmission to any contacts. This report highlights the need to understand the prevalence and duration of VDRV shedding in granuloma patients and to estimate the risk of VDRV transmission to immune and non-immune contacts.