Adolescent with osteomyelitis after intramuscular administration of a vaccine: A case report.

OBJECTIVE: To emphasize adverse outcomes associated with applying adult immunization protocols to the pediatric population. CASE SUMMARY: A 15-year-old female with no past medical history developed severe pain in her left arm and decreased range of motion 11 days after receiving an intramuscular injection of the human papillomavirus vaccine. Over the following month, she was treated with a short course of steroids for frozen shoulder and gabapentin for Parsonage-Turner syndrome. During the third visit to a specialist for severe pain and loss of left arm mobility, she was sent to the emergency department for further workup. An x-ray and magnetic resonance imaging of the left arm were suspicious for osteomyelitis. The diagnosis was confirmed by incision and drainage of the abscess and a bone biopsy. A 6-week course of antibiotic therapy was initiated after the biopsy results. The injury was attributed to overpenetration by the needle during the intramuscular injection she had received in the previous month. PRACTICE IMPLICATIONS: As the number of states allowing pharmacists to vaccinate patients of all ages grows, pharmacists must be prepared to safely provide vaccinations to patients of varying sizes. Assessing body habitus while balancing the constant responsibilities of a community pharmacy will be a challenge. Introduction of a guidance document with specific needle lengths based on weight, age, and sex can address potential errors before they occur.

Meropenem-Vaborbactam (Vabomere™): Another Option for Carbapenem-Resistant Enterobacteriaceae.

Meropenem-Vaborbactam (Vabomere) for carbapenem-resistant Enterobacteriaceae.

Bezlotoxumab (Zinplava) for Clostridium Difficile Infection: The First Monoclonal Antibody Approved to Prevent the Recurrence of a Bacterial Infection.

Bezlotoxumab (Zinplava) to prevent the recurrence of Clostridium difficile infection.

Risk factors for nephrotoxicity onset associated with polymyxin B therapy.

OBJECTIVES: Polymyxin B is an active agent against many MDR Gram-negative bacteria, but nephrotoxicity is a major hindrance to its widespread use. To guide its optimal use, we determined the risk factors for nephrotoxicity onset associated with polymyxin B. METHODS: In a multicentre, retrospective, cohort study, we evaluated adult patients with normal renal function who received ≥72 h of polymyxin B therapy. Pertinent information was retrieved from medical records; patients were followed for up to 30 days after therapy was started. The primary endpoint of this study was the onset of nephrotoxicity. A Cox proportional hazards model was used for analysis. RESULTS: A total of 192 patients (52.1% male, 67.7% Caucasian) were evaluated. The mean ±â€ŠSD age, actual body weight (ABW) and daily dose by ABW were 68.3 ±â€Š17.2 years, 71.5 ±â€Š20.4 kg and 1.5 ±â€Š0.5 mg/kg, respectively. The median duration of therapy was 9.5 days. The overall prevalence rate of nephrotoxicity was 45.8% and the median onset of nephrotoxicity was 9 days. Independent risk factors for the onset of nephrotoxicity included daily dose by ABW (HR = 1.73; P = 0.022), concurrent use of vancomycin (HR = 1.89; P = 0.005) and contrast media (HR = 1.79; P = 0.009). Nephrotoxicity was seen earlier in the high-risk group (P = 0.003). CONCLUSIONS: Risk factors for nephrotoxicity onset associated with polymyxin B were identified. In conjunction with susceptibility and other pharmacokinetic/pharmacodynamic data, our results can be used to optimize treatment for MDR Gram-negative infections.

In vitro assessment and multicenter cohort study of comparative nephrotoxicity rates associated with colistimethate versus polymyxin B therapy.

Despite concerns of nephrotoxicity, polymyxin antibiotics often remain the only susceptible agents for multidrug-resistant (MDR) Gram-negative bacteria. Colistin has been more commonly used clinically due to a perceived safety benefit. We compared the nephrotoxicity of colistin to polymyxin B. The in vitro cytotoxicity of colistin was compared to polymyxin B in two mammalian renal cell lines. To validate the clinical relevance of the findings, we evaluated adult patients with normal renal function who received a minimum of 72 h of polymyxin therapy in a multicenter study. The primary outcome was the prevalence of nephrotoxicity, as defined by the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. Colistin exhibited an in vitro cytotoxicity profile similar to polymyxin B. A total of 225 patients (121 receiving colistimethate, 104 receiving polymyxin B) were evaluated. Independent risk factors for colistimethate-associated nephrotoxicity included age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00 to 1.07; P = 0.03), duration of therapy (OR 1.08; 95% CI, 1.02 to 1.15; P = 0.02), and daily dose by ideal body weight (OR 1.40; 95% CI, 1.05 to 1.88; P = 0.02). In contrast, cystic fibrosis was found to be a protective factor in patients who received colistimethate (OR, 0.03; 95% CI, 0.001 to 0.79; P = 0.04). In a matched analysis based on the risk factors identified (n = 76), the prevalence of nephrotoxicity was higher with colistimethate than with polymyxin B (55.3% versus 21.1%; P = 0.004). Polymyxin B was not found to be more nephrotoxic than colistin and may be the preferred polymyxin for MDR infections. A prospective study comparing the two polymyxins directly is warranted.

Antimicrobial Stewardship Practices in a Subset of Community Pharmacies across the United States.

BACKGROUND: Antimicrobial stewardship in the community is essential as most antibiotic prescribing occurs in the outpatient setting. Pharmacists are recognized as co-leaders for implementing efforts to improve antimicrobial use. OBJECTIVES: the purpose of this study is to evaluate current antimicrobial stewardship practices in community pharmacies across the United States and identify perceptions and challenges faced by community pharmacists. METHODS: a survey based on the Center of Disease Control and Prevention (CDC) Core Elements of Outpatient Antibiotic Stewardship was created and distributed. RESULTS: Sixty-one community pharmacists participated in the survey. The majority of pharmacists practiced in chain pharmacies. Based on the responses, a minority of pharmacies met the requirements of the CDC core elements: commitment (27.9%), action (24.6%), tracking and reporting (14.8%), and education and expertise (23% for providing pharmacist resources and 9.8% for providing patient resources). Regarding perception, 67.9% felt antimicrobial stewardship is important in the community and would participate in antimicrobial stewardship activities if the opportunity was provided (88.5%). Challenges faced by community pharmacists include the lack of time, staff, training, and technology support; pushback from prescribers and patients; and the lack of leadership, financial incentives, funding, and legal requirements. CONCLUSIONS: many challenges exist in community pharmacies inhibiting the full potential of pharmacists in implementing antimicrobial stewardship.

Assessment of the Implementation of AUC Dosing and Monitoring Practices With Vancomycin at Hospitals Across the United States.

INTRODUCTION: The latest vancomycin therapeutic drug monitoring guidelines for serious MRSA infections have made a pivotal change in dosing, switching from targeting trough levels to AUC dosing. Because of these new recommendations, antimicrobial stewardship programs across the country are tasked with implementing AUC based dosing. OBJECTIVES: To assess plans for institutional adoption of vancomycin AUC dosing programs and perceptions of currently used programs in hospitals across the US. METHODS: An electronic survey was distributed to members of the American College of Clinical Pharmacy IDprn Listserv and American Society of Health-System Pharmacists between May and June 2020 to assess current institutional vancomycin dosing. Institutional program use and multiple software user parameters were analyzed using descriptive statistics. RESULTS: Two hundred two pharmacists responded to the survey with the majority practicing in institutions with 251-500 beds. Most respondents have yet to implement AUC dosing (142/202, 70.3%) with many of them planning to do so in the next year (81/142, 57.0%). Of those that already implemented AUC dosing programs, purchased Bayesian software (23/60, 38.3%) and homemade software (21/60, 35.0%) were the 2 methods most frequently utilized. Purchased Bayesian software users were more likely to recommend their software to other institutions and ranked user friendliness higher compared to non-purchased software. CONCLUSION: Most respondents have not made the switch to vancomycin AUC dosing, but there is a growing interest with many institutions looking to adopt a program within the next year.

A Peer Educational Tool to Promote Antimicrobial Stewardship on a University Campus.

Antibiotic resistance is a major public health threat. Patient education on the appropriate use of antibiotics is a key component in combating antimicrobial resistance. The purpose of this study was to analyze the utility of an origami fortune teller as a novel peer educational tool in promoting antimicrobial stewardship on a university campus. An origami fortune teller, with various case scenarios to demonstrate key antibiotic principles, was developed and used by peer educators to educate students attending a university wellness fair. The case studies included: antibiotic indications; differentiation between viral vs. bacterial infection; proper use of antibiotics; non-pharmacologic measures to combat infection; and antibiotic resistance. Students were asked to take an assessment pre and post working with the tool. One hundred and forty-three students received education using the novel tool. A significant improvement in the assessment score was observed after education was completed using the novel tool (69.5 vs. 96.6 p ≤ 0.05).

A Review and Clinical Understanding of Tenofovir: Tenofovir Disoproxil Fumarate versus Tenofovir Alafenamide.

HIV is a serious chronic medical condition. Significant improvements in antiretroviral therapy have led to a transformation in its management. No curative treatment is available for HIV, and lifelong therapy is required with a combination of agents to control viral replication and prevent complications. Some of the older agents are notorious for many side effects, making patient compliance difficult, which is critical to preventing HIV resistance. Tenofovir is one of the newer, more tolerable, nucleotide reverse transcriptase inhibitors on the market; is a mainstay of many antiretroviral therapy combinations; and is now available in 2 different formulations, tenofovir disoproxil fumarate (TDF) and, the more recent, tenofovir alafenamide (TAF). These 2 formulations have very different pharmacokinetics, which seem to affect their efficacy and safety. This manuscript provides insight into the history of TDF and TAF development, their unique pharmacokinetics and pharmacology, clinically important adverse effects, monitoring, interactions, resistance, review of clinical studies, and guideline recommendations and clinical applications for tenofovir's various indications.

Practical Implications of New Antibiotic Agents for the Treatment of Carbapenem-Resistant Enterobacteriaceae.

OBJECTIVE: To provide insight into the practical implications of the use of ceftazidime/avibactam and meropenem/vaborbactam for the management of carbapenem-resistant Enterobacteriaceae (CRE) and to identify strategies for overcoming barriers to the use of these agents in clinical practice. DATA SOURCES: A literature search of PubMed was conducted using the following search terms: ceftazidime/avibactam, meropenem/vaborbactam, carbapenem-resistant Enterobacteriaceae, antimicrobial stewardship, and clinical laboratory standards institute. Abstracts from infectious diseases conferences, article bibliographies, and relevant drug monographs were also reviewed. STUDY SELECTION/DATA EXTRACTION: Relevant English-language studies were considered. DATA SYNTHESIS: Studies demonstrating the clinical utility of ceftazidime/avibactam and meropenem/vaborbactam over older agents for CRE were summarized. Laboratory challenges, including lack of widespread technology and delays in usable information, and formulary considerations were discussed. Insight was provided into overcoming these challenges and minimizing barriers using infectious diseases pharmacists, antimicrobial stewardship teams, and infection control teams. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review informs clinicians of the potential difficulties of the use of ceftazidime/avibactam and meropenem/vaborbactam in clinical practice and provides tools to overcome these difficulties, thus allowing clinicians to stay at the forefront of CRE treatment. CONCLUSIONS: Clinicians treating patients with CRE infections need to be aware of challenges they may face when using ceftazidime/avibactam and meropenem/vaborbactam. Infectious disease (ID) pharmacists and antimicrobial stewardship teams play an important role in minimizing barriers and ensuring appropriate use of these antibiotics.

Overview and Insights into Carbapenem Allergy.

Understanding antibiotic allergies and the risk of cross-sensitivity between and within antibiotic classes can have a substantial impact on patient care. The purpose of this review article is to provide insight into carbapenem allergies, describing the overall incidence, risk factors, and in-class cross-sensitivity. A PubMed search was conducted using the following search terms: carbapenem, allergy, cross-sensitivity, incidence, imipenem/cilastatin, meropenem, ertapenem, and doripenem. Article bibliographies and relevant drug monographs were also reviewed. The overall reported incidence of carbapenem allergy is 0.3%-3.7%. Risk of cross-sensitivity between penicillins and carbapenems is less than 1% in patients with a positive penicillin skin test. Data on cross-sensitivity between cephalosporins and carbapenems are limited; however, the risk appears to also be low. No clinical studies have described cross-sensitivity between the carbapenem agents thus far. The limited data available from case reports demonstrates a lack of cross-sensitivity between the individual carbapenems, suggesting that an alternative carbapenem may cautiously be used in patients with a reported carbapenem allergy.

A rare fungus on the rise: Candida auris.

PURPOSE: An overview of the growing health threat posed by the fungus Candida auris is provided, including a review of the literature and Centers for Disease Control and Prevention recommendations on C. auris identification, treatment, and infection control. SUMMARY: Since C. auris was first identified in Japan in 2009, cases of C. auris infection have been on the rise in several parts of the world, including the United States, where the first case was reported in 2017; as of November 2017, a total of 206 U.S. cases in 10 states had been reported. Risk factors for C. auris infection have been difficult to identify. However, catheterization, hospitalization, and recent surgery appear to be common factors in patients with C. auris infection. Major challenges in the management of C. auris infections include the common misidentification of C. auris using conventional laboratory techniques and the pathogen's resistance profile, which includes resistance to commonly used antifungals. These challenges may lead to breakdowns in timely implementation of infection-control and prevention measures. Antimicrobial stewardship can play a key role in the management and prevention of C. auris infections. CONCLUSION: C. auris is an emerging fungus that has the potential for causing serious invasive infections. The organism is resistant to commonly used antifungals and is difficult to identify with conventional laboratory techniques. Echinocandins are currently recommended as initial therapy for the treatment of C. auris infections in adults and children at least 2 months of age.

Antimicrobial salvage therapy for persistent staphylococcal bacteremia using daptomycin plus ceftaroline.

PURPOSE: Guidelines recommend daptomycin combination therapy as an option for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia after vancomycin failure. Recent data suggest that combining daptomycin with a ß-lactam may have unique benefits; however, there are very limited clinical data regarding the use of ceftaroline with daptomycin. METHODS: All 26 cases from the 10 medical centers in which ceftaroline plus daptomycin was used for treatment of documented refractory staphylococcal bacteremia from March 2011 to November 2012 were included. In vitro (synergy studies, binding assays, cathelicidin LL-37 killing assays), and in vivo (virulence assays using a murine subcutaneous infection model) studies examining the effects of ceftaroline with daptomycin were also performed. FINDINGS: Daptomycin plus ceftaroline was used in 26 cases of staphylococcal bacteremia (20 MRSA, 2 vancomycin-intermediate S aureus, 2 methicillin-susceptible S aureus [MSSA], 2 methicillin-resistant S epidermidis). Bacteremia persisted for a median of 10 days (range, 3-23 days) on previous antimicrobial therapy. After daptomycin plus ceftaroline was started, the median time to bacteremia clearance was 2 days (range, 1-6 days). In vitro studies showed ceftaroline synergy against MRSA and enhanced MRSA killing by cathelicidin LL-37 and neutrophils. Ceftaroline also induced daptomycin binding in MSSA and MRSA to a comparable degree as nafcillin. MRSA grown in subinhibitory concentrations of ceftaroline showed attenuated virulence in a murine subcutaneous infection model. IMPLICATIONS: Ceftaroline plus daptomycin may be an option to hasten clearance of refractory staphylococcal bacteremia. Ceftaroline offers dual benefit via synergy with both daptomycin and sensitization to innate host defense peptide cathelicidin LL37, which could attenuate virulence of the pathogen.