Use of Novel Antibiograms to Determine the Need for Earlier Susceptibility Testing and Administration for New ß-Lactam/ß-Lactamase Inhibitors in the United States.

Antimicrobial resistance is a global public health threat, and gram-negative bacteria, such as Enterobacterales and Pseudomonas aeruginosa, are particularly problematic with difficult-to-treat resistance phenotypes. To reduce morbidity and mortality, a reduction in the time to effective antimicrobial therapy (TTET) is needed, especially among critically ill patients. The antibiogram is an effective clinical tool that can provide accurate antimicrobial susceptibility information and facilitate early antimicrobial optimization, decrease TTET, and improve outcomes such as mortality, hospital length of stay, and costs. Guidance is lacking on how to validate the susceptibility to new antibacterial agents. Commonly used traditional and combination antibiograms may not adequately assist clinicians in making treatment decisions. Challenges with the current susceptibility testing of new ß-lactam/ß-lactamase inhibitor combinations persist, impacting the appropriate antibacterial choice and patient outcomes. Novel antibiograms such as syndromic antibiograms that incorporate resistant gram-negative phenotypes and/or minimum inhibitory concentration distributions may assist in determining the need for earlier susceptibility testing or help define an earlier optimal use of the new ß-lactam/ß-lactamase inhibitors. The purpose of this review is to emphasize novel antibiogram approaches that are capable of improving the time to susceptibility testing and administration for new ß-lactam/ß-lactamase inhibitors so that they are earlier in a patient's treatment course.

The antibiogram: key considerations for its development and utilization.

The antibiogram is an essential resource for institutions to track changes in antimicrobial resistance and to guide empirical antimicrobial therapy. In this Viewpoint, data and examples from literature are presented that suggest institutions have not completely adopted the standardized approach in developing antibiograms, as variations in the development methodologies of antibiograms exist despite consensus guidelines (M39) published by CLSI. We emphasize developing antibiograms in line with the M39 recommendations will help ensure that they are accurate, reliable and valid, and highlight that understanding the limitations of antibiogram data is critical to ensuring appropriate interpretation and application to clinical decision-making. We also stress the importance of easy accessibility and education on antibiogram use, to allow for prescribers to select the most optimal empirical treatment regimens and propose the creation of an abbreviated antibiogram for frontline users. Multidisciplinary antimicrobial stewardship programmes are vital to accomplishing these goals.

Antimicrobial stewardship and antibiograms: importance of moving beyond traditional antibiograms.

The rapid evolution of resistance, particularly among Gram-negative bacteria, requires appropriate identification of patients at risk followed by administration of appropriate empiric antibiotic therapy. A primary tenet of antimicrobial stewardship programs (ASPs) is the establishment of empiric antibiotic recommendations for commonly encountered infections. An important tool in providing empiric antibiotic therapy recommendations is the use of an antibiogram. While the majority of institutions use a traditional antibiogram, ASPs have an opportunity to enhance antibiogram data. The authors provide the rationale for why ASPs should implement alternative antibiograms, and the importance of incorporating an antibiogram into clinical decision support systems with the goal of providing effective empiric antibiotic therapy.

A pilot assessment on perceived stress among working pharmacist moms.

OBJECTIVE: To assess perceptions of stress among working pharmacist moms. METHODS: Members of the then 1000-member Facebook Pharmacist Moms group were invited to complete an 18-question online survey. The survey included questions related to stress and demographics. RESULTS: Ninety-three pharmacist moms responded to the survey. The majority (82%) of respondents graduated more than 5 years ago. Most (81%) had at least 2 children; 44% had at least 1 child younger than 5 years. The largest proportion (58%) of respondents practiced in a community pharmacy, whereas nonretail respondents included those working in a hospital (25%) or in academia (12%). Retail pharmacist moms felt more nervous or stressed about work than nonretail pharmacist mothers (70% vs. 49%; P < 0.01) and were more likely to feel difficulties were piling up so high they could not overcome them (48% vs. 15%; P < 0.01). Moms who worked in retail also felt more upset because of something that happened at work compared with nonretail pharmacist moms (63% vs 28%; P < 0.01). CONCLUSION: Women have become a major force in pharmacy and will continue to play a considerable role in the future of the profession. Pharmacist moms working in retail report higher stress levels compared with their nonretail counterparts. These results indicate a need to educate future female pharmacists on coping skills and life management techniques that foster healthy work-life balances. Employers should be aware of the underlying stressors that pharmacist moms are coping with in the workplace. These findings suggest the need for a more comprehensive survey to determine whether the stress perceived by pharmacist moms is warranted.

Use of an Anti-Infective Medication Review Process at Hospital Discharge to Identify Medication Errors and Optimize Therapy.

BACKGROUND: Medication reconciliation is a major patient safety concern, and the impact of a structured process to evaluate anti-infective agents at hospital discharge warrants further review. OBJECTIVE: The aim of this study was to (1) describe a structured, multidisciplinary approach to review anti-infectives at discharge and (2) measure the impact of a stewardship-initiated antimicrobial review process in identifying and preventing anti-infective-related medication errors (MEs) at discharge. METHODS: A prospective study to evaluate adult patients discharged on anti-infectives was conducted from October 2013 to May 2014. The antimicrobial stewardship program (ASP) classified interventions on anti-infective regimens into predefined ME categories. RESULTS: Forty-five patients who were discharged on 59 anti-infective prescriptions were included in the study. The most common indications for anti-infective regimens at discharge were pneumonia (22%, n = 10), bacteremia (18%, n = 8), and skin and soft tissue infections (16%, n = 7). An ME was identified in 42% (n = 19/45) of anti-infective regimens. Seventy percentage of ASP team recommendations were accepted which resulted in an avoidance of MEs in 68% (n = 13/19) of patients with an ME prior to discharge. CONCLUSION: This study describes the outcomes of a stewardship-initiated review process in preventing MEs at discharge. Developing a systematic process for a multidisciplinary ASP team to review all anti-infectives can be a valuable tool in preventing MEs at hospital discharge.

Preparing Students to Enter the Race for Postgraduate Training.

PURPOSE: Exposure of pharmacy students to postgraduate training prior to clinical practice is currently endorsed by national professional organizations. To meet this goal, colleges and schools of pharmacy are developing residency preparation programs. In this descriptive report, we review published studies of curricular activities and structured programs from academic institutions across the United States aimed at preparing students for residency training and promoting postgraduate education. Additionally, we discuss our experience developing a residency preparation program at Touro College of Pharmacy (TCOP). SUMMARY: A literature search yielded 15 residency preparation programs. While the format, content, and length of programs varied, there were common components such as curriculum vitae critique, mock interviews, and focused sessions on the residency application process. At TCOP, a 5-themed residency preparation workshop series was implemented during the third and fourth academic year. The workshops were modeled after existing programs and included several of the core components. One feature unique to the TCOP program was the addition of multiple mock interviews. CONCLUSION: The growing focus on residency training has led to increased competition among applicants. To better prepare students for this rigorous application and interview process, development of structured residency preparation programs, similar to TCOP's, should be encouraged.

Management of skin and soft-tissue infections at a community teaching hospital using a severity-of-illness tool.

OBJECTIVES: Skin and soft-tissue infections (SSTIs) encompass a diverse range of infections of varying severity. The Clinical Resource Efficiency Support Team (CREST) scoring system stratifies patients into four classes (I = least severe to IV = most severe) based on the Standardized Early Warning Score (SEWS). The objective of this study was to apply CREST to hospitalized patients with SSTIs in order to quantify disease severity and evaluate appropriateness of antibiotic management. METHODS: This was a retrospective, hypothesis-generating, single-centre evaluation of hospitalized patients with SSTIs admitted in 2011. Based on CREST classification, the empirical antimicrobial choices were categorized as appropriate, over-treatment or under-treatment. RESULTS: A total of 369 patients were screened and 200 met the inclusion criteria. The majority of patients were classified as either CREST class I (n = 68) or class II (n = 102). Over-treatment was more common in the less severe classes (88% and 32% in class I and class II, respectively; P < 0.05). Sixty-three percent of class I (n = 43) were over-treated due to both the use of intravenous antibiotics when oral therapy was sufficient and use of unnecessarily broad-spectrum antibiotics. In contrast, 25% (n = 26) of class II were over-treated due to use of unnecessarily broad-spectrum antibiotics. Overall clinical failure rates remained low with only 1%, 4% and 17% of patients unable to achieve initial response in class II, class III and class IV. CONCLUSIONS: Retrospective application of CREST identified opportunities to improve the management of SSTIs. CREST can be of great value in discriminating less-severe SSTIs, which can be treated on an outpatient basis.

Administration of a survey to evaluate the attitudes of house staff physicians towards antimicrobial resistance and the antimicrobial stewardship programme at a community teaching hospital.

Antimicrobial stewardship programmes (ASPs) are used in numerous institutions in an effort to promote safe and effective antimicrobial use. The objectives of this study were to (i) assess physicians' perceptions, attitudes and knowledge about antimicrobial use, resistance and the ASP at The Brooklyn Hospital Center (TBHC) and (ii) measure physicians' beliefs and attitudes to the current system of prior authorisation of antimicrobials. A 75-item, anonymous, voluntary, traditional paper and pencil survey was distributed to resident physicians at TBHC. Multiple-choice, 5-point Likert scale and knowledge-based questions were utilised. Of the 261 residents, 129 (49%) completed the survey. The respondents significantly believed that antibiotics are overused more frequently nationally vs. locally [117/129 (91%) vs. 91/129 (71%); P=0.0001]. Although 49% (63/129) felt that other providers overprescribe antibiotics, only 26% (34/129) agreed that they themselves were contributing to the current problem (P=0.0003). Fifty-seven percent of respondents agreed that individual patient care is improved by having an antibiotic approval programme; however, 45% of respondents reported that the antibiotic approval programme limits their autonomy in choosing antibiotics. Compared with surgical residents, medical residents were more likely (33% vs. 13%; P=0.02) to feel that the antibiotic approval programme forced them to choose an inappropriate antibiotic. On the antibiotic knowledge assessment segment of the survey, there was no difference in score when stratified by specialty or years of postgraduate training. Based on the survey results, house staff are supportive of antimicrobial stewardship and feel that the ASP is valuable for patient care.

Active-learning implementation in an advanced elective course on infectious diseases.

OBJECTIVES: To describe the development, implementation, and assessment of an advanced elective course on infectious diseases using active-learning strategies. DESIGN: Pedagogy for active learning was incorporated by means of mini-lecture, journal club, and debate with follow-up discussion. Forty-eight students were enrolled in this 4-week elective course, in which 30% of course time was allocated for active-learning exercises. All activities were fundamentally designed as a stepwise approach in complementing each active-learning exercise. ASSESSMENT: Achievement of the course learning objectives was assessed using a 5-point Likert scale survey instrument. Students' awareness of the significance of antimicrobial resistance was improved (p ≤ 0.05). Students' ability to critically evaluate the infectious-disease literature and its application in informed clinical judgments was also enhanced through these active-learning exercises (p ≤ 0.05). Students agreed that active learning should be part of the pharmacy curriculum and that active-learning exercises improved their critical-thinking, literature-evaluation, and self-learning skills. CONCLUSION: An elective course using active-learning strategies allowed students to combine information gained from the evaluation of infectious-disease literature, critical thinking, and informed clinical judgment. This blended approach ultimately resulted in an increased knowledge and awareness of infectious diseases.

Pharmacy student absenteeism and academic performance.

OBJECTIVES: To assess the association of pharmacy students' personal characteristics with absenteeism and academic performance. METHODS: A survey instrument was distributed to first- (P1) and second-year (P2) pharmacy students to gather characteristics including employment status, travel time to school, and primary source of educational funding. In addition, absences from specific courses and reasons for not attending classes were assessed. Participants were divided into "high" and "low" performers based on grade point average. RESULTS: One hundred sixty survey instruments were completed and 135 (84.3%) were included in the study analysis. Low performers were significantly more likely than high performers to have missed more than 8 hours in therapeutics courses. Low performers were significantly more likely than high performers to miss class when the class was held before or after an examination and low performers were significantly more likely to believe that participating in class did not benefit them. CONCLUSIONS: There was a negative association between the number of hours students' missed and their performance in specific courses. These findings provide further insight into the reasons for students' absenteeism in a college or school of pharmacy setting.

GFR estimates using cystatin C are superior to serum creatinine in adult patients with cystic fibrosis.

BACKGROUND: Accurate assessment of renal function in patients with cystic fibrosis (CF) is vital for determining the appropriate dose of medications and for early detection of renal disease. Cystatin C (CysC) is a new marker of GFR with reportedly improved accuracy and precision compared to methods incorporating serum creatinine. The purpose of this study is to evaluate the predictive performance of cystatin C in estimating GFR in adult patients with CF. METHODS: Iothalamate was administered to enable measurement of GFR in 38 adult patients with CF and control subjects. Creatinine clearance (C&G) and GFR estimates (cystatin C clearance [Cys C] and abbreviated modified diet in renal disease [aMDRD]) were compared using Bland-Altman and receiver operating characteristic (ROC) analysis. GFR cutoff values of 80 and 90 mL/min-1.73 m(2) were used in the analysis. RESULTS: The measured GFR was similar in both the CF and healthy volunteers 104 (32.2) and 105 (29.9), P=0.969 respectively. No significant difference in mean bias was noted between the predictive methods within the CF population. Cys C provided the most precise estimates of GFR in both populations. ROC curves demonstrated that CysC provided greater sensitivity and specificity compared to the aMDRD (AUC 0.93 vs. 0.54, P=0.003) and C&G (AUC 0.93 vs. 0.56, P=0.005) in CF at a cutoff GFR of 90 mL/min-1.73 m(2). CONCLUSION: Cystatin C clearance provides an improved marker of glomerular filtration rate in CF patients.

Comparison of method-specific vancomycin minimum inhibitory concentration values and their predictability for treatment outcome of meticillin-resistant Staphylococcus aureus (MRSA) infections.

The objectives of this study were to examine the predictive value of method-specific vancomycin (VAN) minimum inhibitory concentration (MIC) results on treatment outcomes of meticillin-resistant Staphylococcus aureus (MRSA) infections. VAN MIC values for MRSA strains were determined using Etest, VITEK-1, MicroScan (MScan) and broth microdilution (BMD), with additional screening for heterogeneous glycopeptide-intermediate S. aureus (hGISA) phenotype. Patients' charts were reviewed for outcome correlation. Performance characteristics of method-specific VAN MICs in predicting outcome were compared. Most (76%) of the 92 strains tested caused pneumonia or bacteraemia. The majority of strains tested (>70%) had a VAN MIC >1mg/L by Etest or MScan compared with 41% by Vitek and 7% by BMD. Agreement between test methods for high versus low MICs (>1mg/L vs. < or = 1mg/L) ranged from 36% to 71%. High versus low VAN MICs by Etest differentiated response of invasive strains to VAN. Performance characteristics (sensitivity/specificity/positive predictive value/negative predictive value) were: Etest, 55/81/89/38%; and Vitek, 56/62/81/32/%, respectively. Eight strains (9%) demonstrated a hGISA phenotype; more yielded high MICs by Etest, MScan and Vitek than BMD (87%, 87% and 75% vs. 50%). In conclusion, VAN MIC testing methods produce highly variable results. The Etest method appears to be relatively more reliable in predicting treatment response and yielded higher MICs for strains with a hGISA phenotype.

Lack of effect of P-glycoprotein inhibition on renal clearance of dicloxacillin in patients with cystic fibrosis.

STUDY OBJECTIVE: To determine whether upregulation of P-glycoprotein is responsible for the enhanced renal clearance of dicloxacillin in patients with cystic fibrosis. DESIGN: Single-center, prospective, open-label, randomized, three-part crossover pharmacokinetic study. SETTING: General clinical research center. SUBJECTS: Eleven patients with cystic fibrosis and 11 age-matched healthy volunteers. INTERVENTION: All subjects received a single oral dose of dicloxacillin 500 mg alone, dicloxacillin 500 mg plus probenecid (an organic anion transport inhibitor) 1 g, and dicloxacillin 500 mg plus cyclosporine (a P-glycoprotein inhibitor) 5 mg/kg; each treatment was separated by a washout period of 48 hours. A bolus dose of iothalamate meglumine 456 mg was administered on each study day as a marker of glomerular filtration. MEASUREMENTS AND MAIN RESULTS: Blood and urine samples were taken serially up to 6 hours after each dose. Pharmacokinetics of dicloxacillin and iothalamate were determined by using compartmental and noncompartmental methods. Quantitative polymerase chain reaction was performed on peripheral blood mononuclear cells to measure expression of multidrug resistance 1 (MDR1) messenger RNA (mRNA). Genotyping for ABCB1 was performed to determine the presence of single nucleotide polymorphisms (exons 21 and 26). In both healthy subjects and patients with cystic fibrosis, compared with dicloxacillin alone, coadministration with probenecid produced a significantly lower renal clearance of dicloxacillin, whereas coadministration with cyclosporine resulted in no significant change; renal clearance was not significantly different between the two study groups. No correlation was found between MDR1 mRNA expression and renal clearance of dicloxacillin. The renal excretion of dicloxacillin was significantly greater in subjects with the ABCB1 exon 26 TT polymorphism when compared with subjects with the CT genotype. CONCLUSION: We found no significant difference in the pharmacokinetics of dicloxacillin between patients with cystic fibrosis and healthy volunteers. Renal clearance of dicloxacillin was significantly reduced in the presence of probenecid but not with cyclosporine, suggesting that the rate-limiting step in tubular secretion of dicloxacillin is uptake mediated by the organic anion transporter, and not P-glycoprotein inhibition.

Probenecid, but not cystic fibrosis, alters the total and renal clearance of fexofenadine.

This study aims to evaluate renal P-glycoprotein (P-gp) activity in patients with cystic fibrosis. P-gp efflux activity in peripheral T cells was measured by flow cytometry in 10 cystic fibrosis and 15 healthy volunteers. Eight cystic fibrosis patients and 8 healthy volunteers were recruited into a crossover pharmacokinetic study in which participants received 180 mg fexofenadine with or without 1 g probenecid twice a day. Genotyping was performed for ABCB1 C1236T, G2677T, and C3435T. P-gp efflux activity in peripheral T cells was not significantly different between cystic fibrosis patients and healthy volunteers. No difference in fexofenadine pharmacokinetic parameters was observed between cystic fibrosis patients and healthy volunteers when fexofenadine was administered with or without probenecid. Coadministration of probenecid significantly increased fexofenadine AUC and decreased the cumulative urinary excretion, total body clearance, and renal clearance. ABCB1 3435 C/T carriers showed increased basal P-gp activity in CD4+ and CD8+ T cells, increased R123-induced efflux activity in CD4+ T cell, and decreased fexofenadine AUC. Fexofenadine disposition and P-gp efflux activity in peripheral T cells was similar between cystic fibrosis patients and healthy volunteers. Probenecid administration significantly reduced the total body and renal clearance of fexofenadine. ABCB1 3435 C/T was associated with an elevated efflux activity compared with C/C subjects.

High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity.

BACKGROUND: Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 microg/mL. METHODS: A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>/=2 vs <2 microg/mL) for efficacy and high vs low trough (>/=15 vs <15 microg/mL) for nephrotoxicity analyses. RESULTS: Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents. CONCLUSIONS: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 microg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.