Comparison of Oral and Intravenous Definitive Antibiotic Therapy for Beta-Hemolytic Streptococcus Species Bloodstream Infections from Soft Tissue Sources: a Propensity Score-Matched Analysis.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI. We conducted a retrospective study of adults with beta-hemolytic streptococcal BSI from a primary skin/soft tissue source from 2015 to 2020. Patients transitioned to oral antibiotics within 7 days of treatment initiation were compared to those who continued intravenous therapy, after propensity score matching. The primary outcome was 30-day treatment failure (composite of mortality, infection relapse, and hospital readmission). A prespecified 10% noninferiority margin was used for the primary outcome. We identified 66 matched pairs of patients treated with oral and intravenous antibiotics as definitive therapy. Based on an absolute difference in 30-day treatment failure of 13.6% (95% confidence interval 2.4 to 24.8%), the noninferiority of oral therapy was not confirmed (P = 0.741); on the contrary, the superiority of intravenous antibiotics is suggested by this difference. Acute kidney injury occurred in two patients who received intravenous treatment and zero who received oral therapy. No patients experienced deep vein thrombosis or other vascular complications related to treatment. In patients treated for beta-hemolytic streptococcal BSI, those who transitioned to oral antibiotics by day 7 showed higher rates of 30-day treatment failure than propensity-matched patients. This difference may have been driven by underdosing of oral therapy. Further investigation into optimal antibiotic choice, route, and dosing for definitive therapy of BSI is needed.

CLinician and patient characteristics effect on Antimicrobial Stewardship Interventions (CLASI) study.

OBJECTIVE: To determine whether the gender of clinicians making antimicrobial stewardship recommendations has an impact on intervention acceptance rate. DESIGN: A retrospective, multivariable analysis of antimicrobial stewardship prospective audit and feedback outcomes. SETTING: A multisite healthcare system including Mayo Clinic Rochester (MN), Mayo Clinic Arizona, Mayo Clinic Florida and 17 health-system hospital sites, where prospective audit and feedback is performed and documented within an electronic tool embedded in the medical record. PARTICIPANTS: The study included 143 Mayo Clinic clinicians (84 cisfemales and 59 cismales). METHODS: Outcomes were analyzed from July 1, 2017, to June 30, 2022, for intervention rates, communication methods, and intervention acceptance by clinician gender, profession, patient age, and intensive care unit (ICU) status of patient. RESULTS: Of 81,927 rules, 71,729 rules met study inclusion. There were 18,175 (25%) rules associated with an intervention. Most of the rules were reviewed by pharmacists (86.2%) and stewardship staff (85.5%). Of 10,363 interventions with an outcome documented, 8,829 (85.2%) were accepted and 1,534 (14.8%) were rejected. Female clinicians had 6,782 (86.5%) of 7,843 interventions accepted, and male clinicians had 2,047 (81.2%) of 2,520 interventions accepted (P = .19). Female patients had more interventions than male patients (female vs male: 25.9% vs 24.9%; OR, 1.04; 95% CI, 1.02-1.08; P = .001). Patients in the ICU had a significantly lower intervention acceptance rate (ICU vs non-ICU: 78.2% vs 86.7%; OR, 0.56; 95% CI, 0.45-0.7; P < .001). CONCLUSIONS: Female and male clinicians were equally effective at prospective audit and feedback in a multisite antimicrobial stewardship program. Patients in the ICU were less likely to have stewardship interventions accepted.

Pharmacist-led improvement in perioperative antibiotic selection for patients with a penicillin allergy label.

PURPOSE: Surgical patients with a penicillin allergy label (PAL) are less likely to receive ß-lactams for surgical site infection (SSI) prophylaxis and more likely to receive second-line antibiotics, which may increase the risk of SSI, drug toxicities, and associated costs. We assessed the impact of implementing a pharmacist-led quality improvement project to increase the use of cefazolin as a first-line agent in this population. SUMMARY: After implementation of a pilot project in December 2021, all patients with a PAL and orders for preoperative antibiotics were risk stratified into high- or low-risk categories by a pharmacist. For the low-risk group, cefazolin was recommended. For the high-risk group, cefazolin was avoided and a second-line agent was administered. Our analysis compared 422 preintervention patients (August 15 to November 15, 2021) to 492 postintervention patients (December 15 to March 15, 2022). During the postintervention period, ß-lactam usage increased (from 12.6% to 37.8%, P < 0.001), while usage of vancomycin (45.5% vs 29.5%, P < 0.001) and other second-line antibiotics (87.4% vs 62.2%, P < 0.001) declined. There were no adverse reactions reported in the preintervention cohort, with 2 potential adverse reactions reported after the intervention (0% vs 0.4%, P = 0.190). Medication costs based on claims data were 50% to 80% lower for patients receiving cefazolin. CONCLUSION: In our cohort, a pharmacy-led antibiotic selection algorithm for patients with a PAL receiving perioperative antimicrobial prophylaxis resulted in increased use of ß-lactam antibiotics, decreased use of second-line antibiotics, and decreased costs without a significant change in the incidence of adverse reactions.

Effectiveness of an electronic health system-based best-practice advisory to enhance the time to de-escalation of vancomycin for respiratory indications.

Objective: Methicillin-resistant Staphylococcus aureus (MRSA) infection is highly unlikely when nasal-swab results are negative. We evaluated the impact of an electronic prompt regarding MRSA nasal screening on the length of vancomycin therapy for respiratory indications. Design: Retrospective, single-center cohort study. Setting: Tertiary-care academic medical center (Mayo Clinic) in Jacksonville, Florida. Patients: Eligible patients received empiric treatment with vancomycin for suspected or confirmed respiratory infections from January through April 2019 (preimplementation cohort) and from October 2019 through January 2020 (postimplementation cohort). Intervention: The electronic health system software was modified to provide a best-practice advisory (BPA) prompt to the pharmacist upon order verification of vancomycin for patients with suspected or confirmed respiratory indications. Pharmacists were prompted to order a MRSA nasal swab if it was not already ordered by the provider. Methods: We reviewed patient records to determine the time from vancomycin prescription to de-escalation. The secondary end point was incidence of acute kidney injury. Results: The study included 120 patients (preimplementation, n = 61; postimplementation, n = 59). Median time to de-escalation was significantly shorter for the postimplementation cohort: 76 hours (interquartile range [IQR], 52-109) versus 42 hours (IQR, 37-61; P = .002). Acute kidney injury occurred in 11 patients (18%) in the preimplementation cohort and in 3 patients (5%) in the postimplementation cohort (P = .01; number needed to treat, 8). Conclusions: Implementation of a BPA notification for MRSA nasal screening helped decrease the time to de-escalation of vancomycin.

A Framework for Outpatient Infusion of Antispike Monoclonal Antibodies to High-Risk Patients with Mild-to-Moderate Coronavirus Disease-19: The Mayo Clinic Model.

The administration of spike monoclonal antibody treatment to patients with mild to moderate COVID-19 is very challenging. This article summarizes essential components and processes in establishing an effective spike monoclonal antibody infusion program. Rapid identification of a dedicated physical infrastructure was essential to circumvent the logistical challenges of caring for infectious patients while maintaining compliance with regulations and ensuring the safety of our personnel and other patients. Our partnerships and collaborations among multiple different specialties and disciplines enabled contributions from personnel with specific expertise in medicine, nursing, pharmacy, infection prevention and control, electronic health record (EHR) informatics, compliance, legal, medical ethics, engineering, administration, and other critical areas. Clear communication and a culture in which all roles are welcomed at the planning and operational tables are critical to the rapid development and refinement needed to adapt and thrive in providing this time-sensitive beneficial therapy. Our partnerships with leaders and providers outside our institutions, including those who care for underserved populations, have promoted equity in the access of monoclonal antibodies in our regions. Strong support from institutional leadership facilitated expedited action when needed, from a physical, personnel, and system infrastructure standpoint. Our ongoing real-time assessment and monitoring of our clinical program allowed us to improve and optimize our processes to ensure that the needs of our patients with COVID-19 in the outpatient setting are met.

State of the art in cystic fibrosis pharmacology optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: III. Executive summary.

Acute pulmonary exacerbations are complications of cystic fibrosis (CF) and are associated with increased morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) and Aspergillus fumigatus are organisms that have been detected in the lungs of CF patients. The focus of this review is to provide an overview of the classes of antimicrobials used for MRSA and allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity reaction caused by A. fumigatus. The current anti-MRSA antibiotics and medications for ABPA dosing recommendations are discussed. This article also reviews the findings from the MRSA utilization surveys and the pharmacokinetic and pharmacodynamic differences between CF and non-CF patients. Antimethicillin S. aureus antibiotics include ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim, and tetracycline derivatives (doxycycline, minocycline, tigecycline). Medications used for ABPA include corticosteroids, amphotericin B, azole antifungals (isavuconazole, itraconazole, posaconazole, voriconazole), and a monoclonal antibody, omalizumab.

Optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations:  II. Therapies for allergic bronchopulmonary aspergillosis.

This review is the second article in the State-of-the-Art series and aims to evaluate medications used in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in pediatric and adult patients with cystic fibrosis (CF). ABPA is one of several organisms that are found in the airways of CF patients. This review provides an evidence-based summary of pharmacokinetic (PK)/pharmacodynamic (PD), tolerability, and efficacy studies of medications including corticosteroids, amphotericin B, azole antifungals (isavuconazole, itraconazole, posaconazole, and voriconazole), and a monoclonal antibody omalizumab in the treatment of ABPA and identifies areas where further study is warranted.

State of the art in cystic fibrosis pharmacology-Optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: I. Anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics.

Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated with morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is one of many organisms that has been detected in the airways of patients with CF. This review provides an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-MRSA antibiotics (ie, ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim (SMZ/TMP), and tetracycline derivatives (doxycycline, minocycline, tigecycline) in the treatment of APE and identifies areas where further study is warranted. A recent utilization study of antimicrobials for anti-MRSA has shown some CF Foundation accredited care centers and affiliate programs are using doses higher than the FDA-approved doses. Further studies are needed to determine the PK/PD properties in CF patients with clindamycin, minocycline, rifampin, SMZ/TMP, telavancin, and tigecycline; as well as, efficacy and tolerability studies with ciprofloxacin, clindamycin, doxycycline, levofloxacin, minocycline, rifampin, SMZ/TMP, in CF patients with MRSA.

Inpatient ß-lactam test-dose protocol and antimicrobial stewardship in patients with a history of penicillin allergy.

BACKGROUND: Penicillin allergy is the most commonly reported drug allergy in hospitalized patients, resulting in increased second-line antibiotic use, nosocomial infections, and health care use. Given that most patients are not truly allergic, a safe strategy that empowers the admitting physician is needed. OBJECTIVE: To assess the effect on antibiotic prescribing practices for hospitalized patients with penicillin allergy using a validated intervention. METHODS: An intervention was implemented to educate health care professionals on management of patients with penicillin allergy using a validated risk stratification algorithm to guide testing and antibiotic use. Thirty days of control data using current standard of care was compared with 60 days of postintervention data measuring documentation of penicillin allergy history and antibiotic selection. RESULTS: The relative use of cephalosporin and penicillin antibiotics increased by 121.2% (P = .03) and 256% (P = .04), respectively, without an increase in adverse drug reactions. There was a decrease in the use of broad-spectrum antibiotics: vancomycin, 67.2% (P = .04); quinolones, 33.3% (P = .31); carbapenems, 81.9% (P = .08); and aztreonam, 73.8% (P = .18). CONCLUSION: The antibiotic choice in patients admitted to the hospital with a reported penicillin allergy can be improved by better evaluation of the allergy history and the use of a risk stratification guideline.

Initiative to reduce aztreonam use in patients with self-reported penicillin allergy: Effects on clinical outcomes and antibiotic prescribing patterns.

PURPOSE: Evaluation of the clinical impact of a pharmacist led-penicillin allergy assessment initiative to enhance antibiotic selection is reported. METHODS: A retrospective analysis was conducted on patients with a self-reported penicillin allergy (SRPA) at a 529-bed community teaching hospital and compared clinical response rate before and after implementation of a penicillin allergy assessment initiative, consisting of pharmacy staff education and pocket card development. Patients admitted with SRPA who received antibiotics with gram-negative coverage for at least 48 hours were included. The primary outcome was the clinical response rate of penicillin-allergic patients determined preimplementation and postimplementation of the initiative and was based upon improvement in signs and symptoms of infection. Secondary outcomes included antibiotics used, antibiotic durations, length of stay, survival rate, antibiotic discontinuation rate, and Clostridium difficile infection rate. RESULTS: A total of 280 patients were reviewed. Clinical response rate improved after implementation of the initiative (p = 0.047). There were significant differences in the type of antibiotics prescribed between the preimplementation group and the postimplementation group: increased cephalosporin use (p < 0.001), decreased aztreonam use (p = 0.017), and lower fluoroquinolone use (p = 0.008). Median length of stay (p = 0.943), in-hospital mortality rate (p = 0.173), and C. difficile infection rate (p = 0.426) were similar before and after implementation of the initiative. CONCLUSION: After implementation of an initiative to encourage the use of cephalosporins rather than aztreonam in patients with SRPA, the rate of clinical response and cephalosporin use increased and rates of exposure to aztreonam and fluoroquinolones decreased.

Impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus surveillance protocol.

PURPOSE: Results of a study to evaluate the impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus (MRSA) surveillance screening protocol are reported. METHODS: A retrospective single-center, quasi-experimental, pre-post cohort study was conducted to assess medication-use and clinical outcomes before and after implementation of a protocol allowing pharmacists to order nasal swabs and polymerase chain reaction (PCR) testing for MRSA in selected patients receiving vancomycin for pneumonia or acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Negative assay results were used to guide de-escalation of vancomycin therapy. The primary outcome was vancomycin days of therapy (DOT). Secondary outcomes included hospital length of stay, the rate of vancomycin-associated acute kidney injury, and in-hospital mortality. RESULTS: A total of 300 patients were identified for inclusion in the preprotocol group (n = 150) or postprotocol group (n = 150) through medical records review. Compared with patients in the preprotocol group, those in the postprotocol group had a median 2.1-day reduction in vancomycin DOT (2.1 days versus 4.2 days, p < 0.0001). Protocol implementation was also associated with a decrease in the median number of vancomycin serum levels obtained per patient but did not have a significant impact on other secondary outcomes. CONCLUSION: Among patients with suspected or confirmed pneumonia or an AECOPD, the expansion of pharmacists' traditional scope of practice to include a surveillance protocol using a MRSA PCR nares assay to guide vancomycin de-escalation resulted in a reduction in vancomycin utilization without compromising clinical outcomes.

Vancomycin Dosing and Monitoring in the Treatment of Cystic Fibrosis: Results of a National Practice Survey.

OBJECTIVES: Vancomycin is commonly used in patients with cystic fibrosis (CF) to treat acute pulmonary exacerbations, but few guidelines exist to help dose and monitor patients. The objective of this study was to assess vancomycin use and monitoring strategies at Cystic Fibrosis Foundation (CFF)-accredited centers in hopes of developing and implementing vancomycin dosing and monitoring standards. METHODS: An anonymous national cross-sectional survey of pharmacists affiliated with CFF-accredited pediatric and/or adult centers was performed by using Surveymonkey.com. The survey consisted of 3 sections: (1) CF Center Demographic Information (10 questions); 2) vancomycin use in pediatric CF patients (31 questions); and 3) vancomycin use in adult CF patients (29 questions); it was administered from March 9, 2015, to April 13, 2015. RESULTS: The survey was completed by 31/69 (45%) pharmacists and 28 (90.3%) reported using vancomycin in the pediatric population. The most common initial starting dose for pediatric patients was 15 mg/kg/dose (57.1%) and every 6 hours was the most common dosing frequency (67.9%). The most common monitoring strategy was collection of a trough concentration (92.9%) with 57.7% of pharmacist targeting a range of 15 to 20 mg/L. The most common initial starting vancomycin dose in adults with CF was 15 mg/kg/dose (61.5%), and initial frequency of every 8 hours (73.1%). The most common monitoring strategy was a trough concentration (96.2%) with 83.3% of pharmacists reporting a goal trough range of 15 to 20 mg/L. CONCLUSIONS: The most common vancomycin dosing reported was 15 to 20 mg/kg/dose every 6 hours (pediatric) and 15 to 20 mg/kg/dose every 8 to 12 hours (adults). Serum concentrations measured to meet monitoring parameters of trough concentrations of 15 to 20 mg/L, or area under the curve to minimum inhibitory concentration ratio > 400, were the same in both pediatric and adult patients.

Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach.

OBJECTIVES: Survey suggests that recommended doses and dosage regimens for antipseudomonal antibiotics for the treatment of acute pulmonary exacerbations in cystic fibrosis (CF) patients are not used, and one way to address these disparities is the involvement of pharmacists who are dedicated to CF. This is the first survey specifically designed for pharmacists at Cystic Fibrosis Foundation (CFF)-accredited centers to identify how tobramycin and antipseudomonal beta-lactams are being used. The purpose of this survey is to quantify this information and to promote future study to allow for implementation of tobramycin and beta-lactam dosage and monitoring standardization. METHODS: An anonymous national cross-sectional survey of pharmacists that are affliated with CFF-accredited programs was performed using Qualtrics.com. RESULTS: The survey had a 48.5% response rate. Most pediatric pharmacists (78.6%) report using extended-interval tobramycin dosage. The most common reported starting dosage was 10 mg/kg every 24 hours; most centers aim for a maximum serum concentration (Cmax) between 20 and 40 mg/L (78.6%). A total of 26 adult pharmacists reported using extended-interval dosage (96%), using an initial dosage of 10 mg/kg/day. The most common parameters used to adjust dosage were Cmax and area under the curve (AUC; 31%); the Cmax goal was 20 to 40 mg/L (84.2%). Most respondents (79%) report using beta-lactams in combination with tobramycin. Extended-infusion and continuous-infusion beta-lactams were used more in adults than pediatric patients. CONCLUSIONS: Most CF pharmacists report using extended-interval tobramycin. With the information from this survey, the establishment of future consensus recommendations by pharmacists for optimal and consistent tobramycin and antipseudomonal beta-lactam dosage and monitoring strategies needs to be considered.

Utilization of antibiotics for methicillin-resistant Staphylococcus aureus infection in cystic fibrosis.

OBJECTIVES: The purpose of this study was to characterize the utilization of antibiotics for chronic methicillin-resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis (CF) patients with acute pulmonary exacerbations (PEx). METHODS: An anonymous national cross-sectional survey of CF Foundation accredited care programs was performed using an electronic survey tool. RESULTS: Fifty-eight percent (152/261) CF Foundation accredited programs completed the survey. Ninety-eight percent (149/152) of respondents reported using antibiotics (oral or intravenous) against MRSA. Variability exists in the use of antibiotics amongst the programs and in the dosages utilized. For oral outpatient treatment, sulfamethoxazole/trimethoprim was the most commonly utilized antibiotic by both pediatric (109/287, 38%) and adult (99/295, 34%) respondents, of which, ten percent of reported to use it in combination with rifampin. For inpatient treatment, linezolid (both intravenous (IV) and oral) was most commonly utilized in both pediatric (IV 35/224, 16%; oral 41/224, 18%), and adult (IV 44/235, 19%; oral 38/235, 16%) respondents for inpatient treatment. IV vancomycin was the second most commonly utilized antibiotic by pediatric (70/224, 31%) and adult (71/235, 30%) respondents. Most respondents reported dose titration to achieve a vancomycin trough level of 15-20 mg/L (150/179, 84%). Topical or inhaled antibiotic utilization was reported to be an uncommon practice with approximately 70% of pediatric and adult respondents reporting to use them either rarely or never. The concomitant use of anti-MRSA and anti-pseudomonal antibiotics was common with 96% of pediatric and 99% of adult respondents answering in the affirmative. CONCLUSION: We conclude that anti-MRSA antibiotics are utilized via various dosage regimens by a majority of CF Foundation accredited care programs for the treatment of chronic MRSA in PEx, and there is no consensus on the best treatment approach.