Antibiotics on Demand: Advances in Asynchronous Telemedicine Call for Increased Antibiotic Surveillance.

The rapid growth of telehealth services has brought about direct-to-consumer telemedicine platforms, enabling patients to request antibiotics online without a virtual or face-to-face consultation. While telemedicine aims to enhance accessibility, this trend raises significant concerns regarding appropriate antimicrobial use and patient safety. In this viewpoint, we share our first-hand experience with 2 direct-to-consumer platforms, where we intentionally sought inappropriate antibiotic prescriptions for nonspecific symptoms strongly indicative of a viral upper respiratory infection. Despite the lack of clear necessity, requested antibiotic prescriptions were readily transmitted to our local pharmacy following a simple monetary transaction. The effortless acquisition of patient-selected antibiotics online, devoid of personal interactions or consultations, underscores the urgent imperative for intensified antimicrobial stewardship initiatives led by state and national public health organizations in telehealth settings. By augmenting oversight and regulation, we can ensure the responsible and judicious use of antibiotics, safeguard patient well-being, and preserve the efficacy of these vital medications.

Advancements in Novel Live Biotherapeutic Products for Clostridioides difficile Infection Prevention.

The profound impact of the human microbiome on health and disease has captivated the interest of clinical and scientific communities. The human body hosts a vast array of microorganisms collectively forming the human microbiome, which significantly influences various physiological processes and profoundly shapes overall well-being. Notably, the gut stands out as an exceptional reservoir, harboring the most significant concentration of microorganisms, akin to an organ in itself. The gut microbiome's composition and function are influenced by genetics, environment, age, underlying conditions, and antibiotic usage, leading to dysbiosis and pathogenesis, such as Clostridioides difficile infection (CDI). Conventional CDI treatment, involving antibiotics like oral vancomycin and fidaxomicin, fails to address dysbiosis and may further disrupt gut microbial communities. Consequently, emerging therapeutic strategies are focused on targeting dysbiosis and restoring gut microbiota to advance CDI therapeutics. Fecal microbiota transplantation (FMT) has demonstrated remarkable efficacy in treating recurrent CDI by transferring processed stool from a healthy donor to a recipient, restoring gut dysbiosis and enhancing bacterial diversity. Moreover, 2 newer Food and Drug Administration (FDA)-approved live biotherapeutic products (LBP), namely, Fecal Microbiota Live-JSLM and Fecal Microbiota Spores Live-BRPK, have shown promise in preventing CDI recurrence. This review explores the role of the gut microbiota in preventing and treating CDI, with an emphasis on gut-based interventions like FMT and fecal microbiota-based products that hold potential for gut restoration and prevention of CDI recurrence. Understanding the microbiome's impact on CDI prevention and treatment offers valuable insights for advancing future CDI therapeutics.

Penicillin-Binding Proteins and Alternative Dual-Beta-Lactam Combinations for Serious Enterococcus faecalis Infections with Elevated Penicillin MICs.

Ampicillin-ceftriaxone has become a first-line therapy for Enterococcus faecalis endocarditis. We characterized the penicillin-binding protein (PBP) profiles of various E. faecalis strains and tested for synergy to better inform beta-lactam options for the treatment of E. faecalis infections. We assessed the affinity of PBP2B from elevated-MIC strain E. faecalis LS4828 compared to type strain JH2-2 using the fluorescent beta-lactam Bocillin FL. We also characterized pbp4 and pbpA structures and PBP4 and PBP2B expression and used deletion and complementation studies to assess the impact of PBP2B on the levels of resistance. We tested penicillin-susceptible and -resistant E. faecalis isolates against ceftriaxone or ceftaroline combinations with other beta-lactams in 24-h time-kill studies. Two penicillin-susceptible strains (JH2-2 and L2052) had identical pbp sequences and similar PBP expression levels. One reduced-penicillin-susceptibility strain (L2068) had pbp sequences identical to those of the susceptible strains but expressed more PBP4. The second decreased-penicillin-susceptibility strain (LS4828) had amino acid substitutions in both PBP4 and PBP2B and expressed increased quantities of both proteins. PBP2B did not appear to contribute significantly to the elevated beta-lactam MICs. No synergy was demonstrable against the strains with both mutated PBPs and increased expression (L2068 and LS4828). Meropenem plus ceftriaxone or ertapenem plus ceftriaxone demonstrated the most consistent synergistic activity. PBP2B of strain LS4828 does not contribute significantly to reduced penicillin susceptibility. Neither the MIC nor the level of PBP expression correlated directly with the identified synergistic combinations when tested at static subinhibitory concentrations.

Student pharmacists delivering academic detailing on adult pneumococcal vaccination to community pharmacists.

BACKGROUND: Academic detailing is an educational outreach approach to disseminate evidence-based information to health care professionals and improve clinical decision making. Pharmacists and physicians are recognized as the most qualified individuals to perform academic detailing; however, trained student pharmacists may also serve as suitable academic detailers. OBJECTIVES: To describe our academic detailing intervention that used trained student pharmacists to disseminate an updated pneumococcal vaccination clinical pathway (i.e., decision-support tool) and education to community pharmacists in Rhode Island and Massachusetts. METHODS: We updated an academic detailing initiative that included a pneumococcal vaccination clinical pathway and education for community pharmacists in 2021. Two University of Rhode Island (URI) College of Pharmacy pharmacist faculty members trained 6 student pharmacists to perform academic detailing. Student pharmacists visited URI-affiliated community pharmacies throughout Rhode Island and Massachusetts. After each session, each participant received a 6-question anonymous paper survey to assess the effectiveness of the updated pathway and academic detailing session. The survey used a 5-point Likert-type scale. We assessed the percentage agreement with each question. RESULTS: Academic detailing was delivered to 76 community pharmacists from May to August 2021. Most respondents agreed (89.2%, 58/65) that their knowledge of which patient populations met eligibility for the pneumococcal conjugate vaccine or pneumococcal polysaccharide vaccine improved. Respondents were confident they could apply the knowledge gained (93.8%, 61/65) and intended to apply the pathway (93.8%, 61/65) to clinical practice. Most respondents expected vaccination practices to change because of the academic detailing and education materials received (83.6%, 51/61). Almost all respondents (95.4%, 62/65) found the educational materials easy to understand. CONCLUSION: Trained student pharmacists can deliver academic detailing regarding adult pneumococcal vaccination to community pharmacists. Enlisting the help of student pharmacists may be a sustainable approach to academic detailing and provides students with valuable opportunities to practice delivering educational outreach to community pharmacists.

Antimicrobial Prescribing in the Telehealth Setting: Framework for Stewardship During a Period of Rapid Acceleration Within Primary Care.

Antibiotic resistance is a global public health threat. The use of telehealth in primary care presents unique barriers to antimicrobial stewardship, including limited physical examination and changes to the patient-provider relationship. Since the coronavirus disease 2019 (COVID-19) pandemic, there is a need to identify novel antimicrobial stewardship strategies with an explosion in the use of telehealth within primary care. Our review proposes a tailored, sustainable approach to antimicrobial prescribing in the telehealth setting based on the Centers for Disease Control and Prevention's Core Elements of Outpatient Antibiotic Stewardship: commitment, action for policy and practice; tracking and reporting; and education and expertise. The rapid growth of telehealth for all types of primary care visits (not just antibiotic use) is outpacing knowledge associated with strategies for antimicrobial stewardship. Improving antibiotic use within primary care settings is critical as telehealth will remain a priority whether the COVID-19 pandemic recedes, particularly within patient populations with limited access to healthcare.

Treatment, Clinical Outcomes, and Predictors of Mortality among a National Cohort of Admitted Patients with Acinetobacter baumannii Infection.

The objectives were to analyze treatment, clinical outcomes, and predictors of mortality in hospitalized patients with Acinetobacter baumannii infection. This was a retrospective cohort study of inpatients with A. baumannii cultures and treatment from 2010 to 2019. Patients who died during admission were compared to those who survived, to identify predictors of inpatient mortality, using multivariable unconditional logistic regression models. We identified 4,599 inpatients with A. baumannii infection; 13.6% died during admission. Fluoroquinolones (26.8%), piperacillin-tazobactam (24%), and carbapenems (15.6%) were used for treatment. Tigecycline (3%) and polymyxins (3.7%) were not used often. Predictors of inpatient mortality included current acute respiratory failure (adjusted odds ratio [aOR] 3.94), shock (aOR 3.05), and acute renal failure (aOR 2.01); blood (aOR 1.94) and respiratory (aOR 1.64) infectious source; multidrug-resistant A. baumannii (MDRAB) infection (aOR 1.66); liver disease (aOR 2.15); and inadequate initial treatment (aOR 1.30). Inpatient mortality was higher in those with MDRAB versus non-MDRAB (aOR 1.61) and in those with CRAB versus non-CRAB infection (aOR 1.68). Length of stay >10 days was higher among those with MDRAB versus non-MDRAB (aOR 1.25) and in those with CRAB versus non-CRAB infection (aOR 1.31). In our national cohort of inpatients with A. baumannii infection, clinical outcomes were worse among those with MDRAB and/or CRAB infection. Predictors of inpatient mortality included several current conditions associated with severity, infectious source, underlying illness, and inappropriate treatment. Our study may assist health care providers in the early identification of admitted patients with A. baumannii infection who are at higher risk of death.

Meropenem plus Ceftaroline Is Active against Enterococcus faecalis in an In Vitro Pharmacodynamic Model Using Humanized Dosing Simulations.

The standard of care for serious Enterococcus faecalis infections is ampicillin plus ceftriaxone. Ampicillin's inconvenient dosing schedule, drug instability, allergy potential, along with ceftriaxone's high risk for Clostridioides difficile infection and its promotion of vancomycin-resistant enterococci (VRE), led our team to explore alternative options. This work aimed to understand the role of carbapenems in combination with cephalosporins in these infections. We selected two ampicillin and penicillin susceptible E. faecalis strains (AMP-MIC 0.5-2 µg/mL; PCN-MIC 2 µg/mL) and simulated human therapeutic dosing regimens in a 48-h in vitro pharmacodynamic model (IVPD) with ampicillin (2g q4h), ertapenem (1g q24h), meropenem (2g q8h), ceftriaxone (2g q12h), and ceftaroline (600 mg q8h). As expected, ampicillin plus ceftriaxone demonstrated enhanced activity compared with ampicillin monotherapy with no MIC increases in either isolate. Meropenem and ceftaroline demonstrated significant kill against both isolates, with no regrowth or MIC increases occurring. Meropenem plus ceftriaxone also demonstrated significant kill, and while no MIC increases were identified for meropenem, there was minor regrowth and larger standard deviations. Ertapenem combined with either ceftriaxone or ceftaroline enhanced activity at 24 h, but at 48 h, regrowth occurred, and ertapenem MIC increases were noted. Meropenem-based combination therapy against E. faecalis may provide clinicians with another regimen to treat severe E. faecalis infections. Meropenem plus ceftaroline was as active as the standard of care treatment (ampicillin plus ceftriaxone) and may serve as an alternative for serious E. faecalis infections. Further studies are warranted to determine the clinical efficacy.

Impact of Clopidogrel on Clinical Outcomes in Patients with Staphylococcus aureus Bacteremia: a National Retrospective Cohort Study.

Activated platelets have known antimicrobial activity against Staphylococcus aureus. Accelerated clearance of platelets induced by S. aureus can result in thrombocytopenia and increased mortality in patients. Recent studies suggest that P2Y12 inhibition protects platelets from accelerated clearance. We therefore evaluated the effect of P2Y12 inhibition on clinical outcomes in patients with S. aureus bacteremia across a large national cohort. Our retrospective cohort (2010 to 2018) included patients admitted to Veterans Affairs (VA) hospitals with blood cultures positive for S. aureus and treated with standard-of-care antibiotics. Employing propensity score-matched Cox proportional hazards regression models, we compared clinical outcomes in patients treated with clopidogrel for at least the 30 days prior to admission and continuing for at least 5 days after admission to patients without any P2Y12 inhibitor use in the year preceding admission. Mortality was significantly lower among clopidogrel users than P2Y12 inhibitor nonusers (n = 147 propensity score-matched pairs): the inpatient mortality hazard ratio (HR) was 0.11 (95% confidence interval [CI], 0.01 to 0.86), and 30-day mortality HR was 0.43 (95% CI, 0.19 to 0.98). There were no differences in 30-day readmission, 30-day S. aureus reinfection, microbiological clearance, or thrombocytopenia. Clopidogrel use at the time of infection reduced in-hospital mortality by 89% and 30-day mortality by 57% among a cohort of patients with S. aureus bacteremia. These results support the need to further study the use of P2Y12 inhibitors as adjunctive therapy in S. aureus bloodstream infections.

Frequency and Predictors of Suboptimal Prescribing Among a Cohort of Older Male Residents with Urinary Tract Infections.

BACKGROUND: Unnecessary antibiotic treatment of suspected urinary tract infections (UTI) is common in long-term care facilities (LTCFs). However, less is known about the extent of suboptimal treatment, in terms of antibiotic choice, dose, and duration, after the decision to use antibiotics has been made. METHODS: We described the frequency of potentially suboptimal treatment among residents with an incident UTI (the first during the study with none in the year prior) in Department of Veterans Affairs (VA) community living centers (CLCs; 2013-2018). Time trends were analyzed using Joinpoint regression. Residents with UTIs receiving potentially suboptimal treatment were compared with those receiving optimal treatment, to identify resident characteristics predictive of suboptimal antibiotic treatment, using multivariable unconditional logistic regression models. RESULTS: We identified 21 938 residents with an incident UTI treated in 120 VA CLCs, of whom 96.0% were male. Potentially suboptimal antibiotic treatment was identified in 65.0% of residents and decreased 1.8% annually (P < .05). Potentially suboptimal initial drug choice was identified in 45.6% of residents, suboptimal dose frequency in 28.6%, and longer than recommended duration in 12.7%. Predictors of suboptimal antibiotic treatment included prior fluoroquinolone exposure (adjusted odds ratio, 1.38), chronic renal disease (1.19), age ≥85 years (1.17), prior skin infection (1.14), recent high white blood cell count (1.08), and genitourinary disorder (1.08). CONCLUSION: Similar to findings in non-VA facilities, potentially suboptimal treatment was common but improving in CLC residents with an incident UTI. Predictors of suboptimal antibiotic treatment should be targeted with antibiotic stewardship interventions to improve UTI treatment.

Minocycline Alone and in Combination with Polymyxin B, Meropenem, and Sulbactam against Carbapenem-Susceptible and -Resistant Acinetobacter baumannii in an In Vitro Pharmacodynamic Model.

Acinetobacter baumannii is recognized as an urgent public health threat by the Centers for Disease Control and Prevention (CDC). Current treatment options are scarce, particularly against carbapenem-resistant Acinetobacter baumannii (CRAB). We simulated the impact of minocycline standard (200 mg load + 100 mg Q12h) and high (700 mg load + 350 mg Q12h) doses, polymyxin B (2.5 mg/kg Q12h), sulbactam (1 g Q6h and 9 g/24 h as continuous infusion), and meropenem (intermittent 1 or 2 g Q8h and 6 g/24 h as continuous infusion) alone or in combination against CRAB and non-CRAB isolates by simulating human therapeutic dosing regimens in a 72-h, in vitro pharmacodynamic (IVPD) model. There were no monotherapy regimens that demonstrated bactericidal activity against the tested non-CRAB and CRAB strains. Resistance development was common in monotherapy regimens. Against the CRAB isolate, the triple combination of high-dose minocycline (fAUC/MIC 21.2), polymyxin B (fAUC/MIC 15.6), and continuous-infusion sulbactam (67% T>MIC) was the most consistently active regimen. Against non-CRAB, the triple therapy regimen of high-dose minocycline (fAUC/MIC 84.8) with continuous-infusion meropenem (100% T>MIC) and continuous-infusion sulbactam (83% T>MIC), as well as the double therapy of high-dose minocycline (fAUC/MIC 84.8) with continuous-infusion meropenem (100% T>MIC), resulted in persistently bactericidal activity. In conclusion, triple therapy with high-dose minocycline, continuous-infusion sulbactam, and polymyxin B produced the most significant kill against the carbapenem-resistant Acinetobacter baumannii, with no regrowth and minimal resistance development.

Poor clinical outcomes associated with suboptimal antibiotic treatment among older long-term care facility residents with urinary tract infection: a retrospective cohort study.

BACKGROUND: Antibiotic use is associated with several antibiotic-related harms in vulnerable, older long-term care (LTC) residents. Suboptimal antibiotic use may also be associated with harms but has not yet been investigated. The aim of this work was to compare rates of poor clinical outcomes among LTC residents with UTI receiving suboptimal versus optimal antibiotic treatment. METHODS: We conducted a retrospective cohort study among residents with an incident urinary tract infection (UTI) treated in Veterans Affairs LTC units (2013-2018). Potentially suboptimal antibiotic treatment was defined as use of a suboptimal initial antibiotic drug choice, dose frequency, and/or excessive treatment duration. The primary outcome was time to a composite measure of poor clinical outcome, defined as UTI recurrence, acute care hospitalization/emergency department visit, adverse drug event, Clostridioides difficile infection (CDI), or death within 30 days of antibiotic discontinuation. Shared frailty Cox proportional hazard regression models were used to compare the time-to-event between suboptimal and optimal treatment. RESULTS: Among 19,701 LTC residents with an incident UTI, 64.6% received potentially suboptimal antibiotic treatment and 35.4% experienced a poor clinical outcome. In adjusted analyses, potentially suboptimal antibiotic treatment was associated with a small increased hazard of poor clinical outcome (aHR 1.06, 95% CI 1.01-1.11) as compared with optimal treatment, driven by an increased hazard of CDI (aHR 1.94, 95% CI 1.54-2.44). CONCLUSION: In this national cohort study, suboptimal antibiotic treatment was associated with a 6% increased risk of the composite measure of poor clinical outcomes, in particular, a 94% increased risk of CDI. Beyond the decision to use antibiotics, clinicians should also consider the potential harms of suboptimal treatment choices with regards to drug type, dose frequency, and duration used.

Delay in Antibiotic Administration Is Associated With Mortality Among Septic Shock Patients With Staphylococcus aureus Bacteremia.

OBJECTIVES: The relationship between the timing of antibiotics and mortality among septic shock patients has not been examined among patients specifically with Staphylococcus aureus bacteremia. DESIGN: Retrospective analysis of a Veterans Affairs S. aureus bacteremia database. SETTING: One-hundred twenty-two hospitals in the Veterans Affairs Health System. PATIENTS: Patients with septic shock and S. aureus bacteremia admitted directly from the emergency department to the ICU from January 1, 2003, to October 1, 2015, were evaluated. INTERVENTIONS: Time to appropriate antibiotic administration and 30-day mortality. MEASUREMENTS AND MAIN RESULTS: A total of 506 patients with S. aureus bacteremia and septic shock were included in the analysis. Thirty-day mortality was 78.1% for the entire cohort and was similar for those participants with methicillin-resistant S. aureus and methicillin-sensitive S. aureus bacteremia. Our multivariate analysis revealed that, as compared with those who received appropriate antibiotics within 1 hour after emergency department presentation, each additional hour that passed before appropriate antibiotics were administered produced an odds ratio of 1.11 (95% CI, 1.02-1.21) of mortality within 30 days. This odds increase equates to an average adjusted mortality increase of 1.3% (95% CI, 0.4-2.2%) for every hour that passes before antibiotics are administered. CONCLUSIONS: The results of this study further support the importance of prompt appropriate antibiotic administration for patients with septic shock. Physicians should consider acting quickly to administer antibiotics with S. aureus coverage to any patient suspected of having septic shock.

Science-based communication to decrease disparities in adult pneumococcal vaccination rates.

OBJECTIVES: The objective of our study was to determine the effects of science-based communications on the attitude toward pneumococcal vaccination and understand how nonwhite racial and ethnic populations respond to these messages. DESIGN: Our team tested several science-based communications using a nationally representative survey, and validated them in a local community pharmacy as a field experiment. SETTING AND PARTICIPANTS: The nationally representative sample phase was a survey of 3276 participants, conducted by YouGov, a leading online survey firm. The field experiment was conducted at a community pharmacy in the northeastern United States and included 86 participants. OUTCOME MEASURES: In the national survey, participants were assigned to treatment groups or a control group to determine the effects of messaging strategies on influencing favorable views of pneumococcal vaccination. In the field experiment, participants were assigned to treatment or control groups to determine if the messaging strategies affected intent to ask a medical professional about the vaccine. RESULTS: The nationally representative sample survey identified that messaging that focused on community and family duty had statistically significant treatment effects toward increasing individuals' perception of personal importance to have the vaccine in both the nonwhite (increase of 12.2% points relative to control) and white respondents (increase of 8.7% points relative to control). These results were validated through a field experiment, which showed that a combination message, emphasizing duty, increased the individual's intent to vaccinate by 25% points in a diverse ethnic population as compared with the control. CONCLUSIONS: Messaging focused on appeals to community and family duty produced statistically significant increases in favorable attitudes toward pneumococcal vaccines and behavioral intent to seek medical advice about the vaccine in white and nonwhite populations across both the nationally representative survey and the field experiment. Medical professionals should highlight the duty to family and community when communicating with patients, as it may motivate vaccination in all populations.

What Is the Role for Metronidazole in the Treatment of Clostridium difficile Infection? Results From a National Cohort Study of Veterans With Initial Mild Disease.

BACKGROUND: Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data are limited to guide clinicians in identifying these patients. METHODS: Our 2-stage study included a national cohort of Veterans with a first episode of mild CDI (2010-2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30 days posttreatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristics predictive of success identified in the first stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. RESULTS: Among 3656 patients treated with metronidazole, we identified 3282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI], 1.29-2.06) than age >65 years. Among 115 propensity score-matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR], 0.29 [95% CI, .06-1.38]), CDI recurrence (HR, 0.62 [95% CI, .26-1.49]), or failure (HR, 0.50 [95% CI, .23-1.07]). CONCLUSIONS: Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest that metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger.

Heterogeneity in the treatment of bloodstream infections identified from antibiotic exposure mapping.

PURPOSE: As changes in antibiotic therapy are common, intent-to-treat and definitive therapy exposure definitions in infectious disease clinical trials and observational studies may not accurately reflect all antibiotics received over the course of the infection. Therefore, we sought to describe changes in antibiotic therapy and unique treatment patterns among patients with bacteremia. METHODS: We conducted a retrospective cohort study of hospitalizations from Veterans Affairs (VA) Medical Centers (January 2002-September 2015) and community hospitals (de-identified Optum Clinformatics DataMart with matched Premier Hospital data; October 2009-March 2013). In the VA population, antibiotic exposures were mapped from the culture collection date among those with positive Staphylococcus aureus cultures. In the Optum-Premier population, exposures were mapped from the admission date among those with a primary diagnosis of bacteremia. RESULTS: Our study included 50 467 bacteremia admissions, with only 14% of admissions having the same treatment pattern as another admission. For every 100 bacteremia admissions, 89 had changes in antibiotic therapy. For every 100 bacteremia admissions with changes in therapy, 95 had unique antibiotic treatment patterns. These findings were consistent in both populations, over time, and among different facilities within study populations. The median time to first therapy change was 2 days after initial therapy, with a median of three changes. CONCLUSIONS: Changes in antibiotic therapy for bloodstream infections were nearly universal regardless of hospital setting. Based on our findings, common antibiotic exposure definitions of intent-to-treat and definitive therapy would misclassify exposure in 86% of admissions, which highlights the need for better operational definitions of exposure in infectious diseases research.

Facilitators and Barriers to Antibiotic Stewardship: A Qualitative Study of Pharmacists' Perspectives.

Background: The Veterans Affairs (VA) is a leader in the implementation and advancement of antibiotic stewardship programs throughout the nation. The Centers for Disease Control and Prevention (CDC) has also led national antibiotic stewardship efforts and has outlined core elements to improve antibiotic use in hospitals, long-term care, and outpatient settings. Many facilities still face challenges to the implementation and maintenance of successful programs, particularly in nonacute care settings. The objective of this study was to identify barriers and facilitators to antibiotic stewardship within the VA medical centers through qualitative interviews with pharmacists. Methods: Eight semi-structured telephone interviews were conducted with pharmacists from 6 VA medical centers within VA New England Healthcare System. Pharmacist respondents were either pharmacy champions (for medical centers with established programs) or pharmacists with responsibilities in making antibiotic recommendations (locations without established programs). All interviews were audio recorded and transcribed verbatim. NVivo 8 was used for data coding and analysis. Results: Pharmacists from all 8 medical centers were contacted for interviews and pharmacists from 6 medical centers agreed to interviews (75% VA New England medical center participation). Three main themes regarding antibiotic stewardship were identified from the interviews with pharmacists. Respondents described the importance of (1) a supportive organizational culture, (2) protected time for antibiotic stewardship, and (3) a cohesive organizational structure in the success of antibiotic stewardship programs. Conclusions: Our findings support the CDC core elements for antibiotic stewardship, in particular the importance of leadership commitment in the creation of a culture that supports antibiotic stewardship and in ensuring staff are given sufficient time for antibiotic stewardship efforts. Although a strong supportive culture has been built, strategies focused on fostering increased protected time for antibiotic stewardship and a cohesive organizational structure may be helpful in advancing and sustaining successful antibiotic stewardship programs that improve patient outcomes.

A Review of Combination Antimicrobial Therapy for Enterococcus faecalis Bloodstream Infections and Infective Endocarditis.

Enterococci, one of the most common causes of hospital-associated infections, are responsible for substantial morbidity and mortality. Enterococcus faecalis, the more common and virulent species, causes serious high-inoculum infections, namely infective endocarditis, that are associated with cardiac surgery and mortality rates that remained unchanged for the last 30 years. The best cures for these infections are observed with combination antibiotic therapy; however, optimal treatment has not been fully elucidated. It is the purpose of this review to highlight treatment options and their limitations, and provide direction for future investigative efforts to aid in the treatment of these severe infections. While ampicillin plus ceftriaxone has emerged as a preferred treatment option, mortality rates continue to be high, and from a safety standpoint, ceftriaxone, unlike other cephalosporins, promotes colonization with vancomycin resistant-enterococci due to high biliary concentrations. More research is needed to improve patient outcomes from this high-mortality disease.

Clinical and Genetic Risk Factors for Biofilm-Forming Staphylococcus aureus.

The molecular and clinical factors associated with biofilm-forming methicillin-resistant Staphylococcus aureus (MRSA) are incompletely understood. Biofilm production for 182 MRSA isolates obtained from clinical culture sites (2004 to 2013) was quantified. Microbiological toxins, pigmentation, and genotypes were evaluated, and patient demographics were collected. Logistic regression was used to quantify the effect of strong biofilm production (versus weak biofilm production) on clinical outcomes and independent predictors of a strong biofilm. Of the isolates evaluated, 25.8% (47/182) produced strong biofilms and 40.7% (74/182) produced weak biofilms. Strong biofilm-producing isolates were more likely to be from multilocus sequence typing (MLST) clonal complex 8 (CC8) (34.0% versus 14.9%; P = 0.01) but less likely to be from MLST CC5 (48.9% versus 73.0%; P = 0.007). Predictors for strong biofilms were spa type t008 (adjusted odds ratio [aOR], 4.54; 95% confidence interval [CI], 1.21 to 17.1) and receipt of chemotherapy or immunosuppressants in the previous 90 days (aOR, 33.6; 95% CI, 1.68 to 673). Conversely, patients with high serum creatinine concentrations (aOR, 0.33; 95% CI, 0.15 to 0.72) or who previously received vancomycin (aOR, 0.03; 95% CI, 0.002 to 0.39) were less likely to harbor strong biofilm-producing MRSA. Beta-toxin-producing isolates (aOR, 0.31; 95% CI, 0.11 to 0.89) and isolates with spa type t895 (aOR, 0.02 95% CI, <0.001 to 0.47) were less likely to produce strong biofilms. Patient outcomes also varied between the two groups. Specifically, patients with strong biofilm-forming MRSA were significantly more likely to be readmitted within 90 days (aOR, 5.43; 95% CI, 1.69 to 17.4) but tended to have decreased 90-day mortality (aOR, 0.36; 95% CI, 0.12 to 1.06). Patients that harbored t008 and received immunosuppressants were more likely to have strong biofilm-producing MRSA isolates. Clinically, patients with strong biofilm-forming MRSA were less likely to die at 90 days but five times more likely to be readmitted.