Impact of removing ESBL designation from culture reports on the selection of antibiotics for the treatment of infections associated with ESBL-producing organisms

2020 ◽  
Vol 41 (5) ◽  
pp. 604-607 ◽  
Author(s):  
Mark D. Lesher ◽  
Cory M. Hale ◽  
Dona S. S. Wijetunge ◽  
Matt R. England ◽  
Debra S. Myers ◽  
...  
Keyword(s):  
Antimicrobial Stewardship ◽  
Antibiotic Prescribing ◽  
The Impact ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor ◽  
Selection Of

AbstractWe characterized the impact of removal of the ESBL designation from microbiology reports on inpatient antibiotic prescribing. Definitive prescribing of carbapenems decreased from 48.4% to 16.1% (P = .01) and β-lactam–β-lactamase inhibitor combination increased from 19.4% to 61.3% (P = .002). Our findings confirm the importance of collaboration between microbiology and antimicrobial stewardship programs.

scholarly journals 229. Hospitalists Antimicrobial Scorecard Improves Antibiotic Prescribing at a Community Teaching Hospital

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S116-S116
Author(s):  
Julia Sessa ◽  
Helen Jacoby ◽  
Bruce Blain ◽  
Lisa Avery
Keyword(s):  
Patient Care ◽  
Teaching Hospital ◽  
Antimicrobial Stewardship ◽  
Rank Order ◽  
Antibiotic Use ◽  
Outpatient Setting ◽  
Antibiotic Prescribing ◽  
Full Time ◽  
Days Of Therapy ◽  
The Impact

Abstract Background Measuring antimicrobial consumption data is a foundation of antimicrobial stewardship programs. There is data to support antimicrobial scorecard utilization to improve antibiotic use in the outpatient setting. There is a lack of data on the impact of an antimicrobial scorecard for hospitalists. Our objective was to improve antibiotic prescribing amongst the hospitalist service through the development of an antimicrobial scorecard. Methods Conducted in a 451-bed teaching hospital amongst 22 full time hospitalists. The antimicrobial scorecard for 2019 was distributed in two phases. In October 2019, baseline antibiotic prescribing data (January – September 2019) was distributed. In January 2020, a second scorecard was distributed (October – December 2019) to assess the impact of the scorecard. The scorecard distributed via e-mail to physicians included: Antibiotic days of therapy/1,000 patient care days (corrected for attending census), route of antibiotic prescribing (% intravenous (IV) vs % oral (PO)) and percentage of patients prescribed piperacillin-tazobactam (PT) for greater than 3 days. Hospitalists received their data in rank order amongst their peers. Along with the antimicrobial scorecard, recommendations from the antimicrobial stewardship team were included for hospitalists to improve their antibiotic prescribing for these initiatives. Hospitalists demographics (years of practice and gender) were collected. Descriptive statistics were utilized to analyze pre and post data. Results Sixteen (16) out of 22 (73%) hospitalists improved their antibiotic prescribing from pre- to post-scorecard (χ 2(1)=3.68, p = 0.055). The median antibiotic days of therapy/1,000 patient care days decreased from 661 pre-scorecard to 618 post-scorecard (p = 0.043). The median PT use greater than 3 days also decreased significantly, from 18% pre-scorecard to 11% post-scorecard (p = 0.0025). There was no change in % of IV antibiotic prescribing and no correlation between years of experience or gender to antibiotic prescribing. Conclusion Providing antimicrobial scorecards to our hospitalist service resulted in a significant decrease in antibiotic days of therapy/1,000 patient care days and PT prescribing beyond 3 days. Disclosures All Authors: No reported disclosures

scholarly journals 1138. Script for Pediatrics: Creating a Smartphone Application to Improve Antimicrobial Prescribing

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S405-S405
Author(s):  
Sarah Primhak ◽  
Natasha Pool ◽  
Gayl Humphrey ◽  
Lesley Voss ◽  
Rachel H Webb ◽  
...  
Keyword(s):  
Decision Making ◽  
Antimicrobial Stewardship ◽  
Point Of Care ◽  
Smartphone Application ◽  
Antibiotic Prescribing ◽  
Oral Antibiotic ◽  
Duration Of Treatment ◽  
Antibiotic Allergy ◽  
Alternative Agent ◽  
The Impact

Abstract Background When considering antimicrobial stewardship (AMS) interventions, pediatrics is an important and often overlooked group. By 5 years of age, 97% of New Zealand (NZ) children have received antibiotics (median 8 antibiotic courses/child). Prescribing is complex due to age and weight-based adjustments, unpalatable oral preparations and inappropriate allergy labeling. Our tertiary Children’s Hospital has >250 web-based nationally utilized guidelines, 15% including antimicrobials. A point prevalence audit showed only 63% guideline adherence for inpatient antimicrobial prescriptions. We designed an accessible app to bring antibiotic prescribing and antibiotic allergy decision-making to prescribers at point of care. Methods Using local hospital and community guidelines, the national formulary and in consultation with subspecialist teams, 31 algorithms were developed. Each algorithm asked questions including diagnosis, age, antibiotic allergy history and known colonization with-resistant organisms. Results The smartphone app (Script) uses the algorithms to advise on appropriate antimicrobial, dose, route and duration of treatment. Advice regarding IV-oral switch parameters and oral antibiotic choice is provided. If allergy is suspected symptom-based decision-making enables the user to choose an alternative agent or encourages allergy de-labeling. Further AMS occurs in some algorithms when advice is given not to prescribe antimicrobials. Conclusion Script for Pediatrics launched in NZ in March 2019 with >1000 users in the first 6 weeks. The most frequently accessed guidelines are otitis media, pneumonia and meningitis. Smartphone applications with local relevance and the ability to update in real-time may prove important tools, by providing easily accessible and intuitive advice to help support antimicrobial stewardship activities. This intervention has been rapidly adopted by pediatric hospital prescribers. The impact on prescribing in concordance with guidelines, timely intravenous to oral antibiotic switch and allergy de-labeling will be assessed. Disclosures All authors: No reported disclosures.

scholarly journals Development of an Electronic Algorithm to Target Outpatient Antimicrobial Stewardship Efforts for Acute Bronchitis

2020 ◽  
Vol 41 (S1) ◽  
pp. s32-s32
Author(s):  
Ebbing Lautenbach ◽  
Keith Hamilton ◽  
Robert Grundmeier ◽  
Melinda Neuhauser ◽  
Lauri Hicks ◽  
...  
Keyword(s):  
Antimicrobial Stewardship ◽  
Predictive Value ◽  
Gold Standard ◽  
Chart Review ◽  
Acute Bronchitis ◽  
Antibiotic Use ◽  
Antibiotic Prescribing ◽  
Diagnostic Codes ◽  
Icd 10 ◽  
The Impact

Background: Antibiotic resistance has increased at alarming rates, driven predominantly by antibiotic overuse. Although most antibiotic use occurs in outpatients, antimicrobial stewardship programs have primarily focused on inpatient settings. A major challenge for outpatient stewardship is the lack of accurate and accessible electronic data to target interventions. We sought to develop and validate an electronic algorithm to identify inappropriate antibiotic use for outpatients with acute bronchitis. Methods: This study was conducted within the University of Pennsylvania Health System (UPHS). We used ICD-10 diagnostic codes to identify encounters for acute bronchitis at any outpatient UPHS practice between March 15, 2017, and March 14, 2018. Exclusion criteria included underlying immunocompromising condition, other comorbidity influencing the need for antibiotics (eg, emphysema), or ICD-10 code at the same visit for a concurrent infection (eg, sinusitis). We randomly selected 300 (150 from academic practices and 150 from nonacademic practices) eligible subjects for detailed chart abstraction that assessed patient demographics and practice and prescriber characteristics. Appropriateness of antibiotic use based on chart review served as the gold standard for assessment of the electronic algorithm. Because antibiotic use is not indicated for this study population, appropriateness was assessed based upon whether an antibiotic was prescribed or not. Results: Of 300 subjects, median age was 61 years (interquartile range, 50–68), 62% were women, 74% were seen in internal medicine (vs family medicine) practices, and 75% were seen by a physician (vs an advanced practice provider). On chart review, 167 (56%) subjects received an antibiotic. Of these subjects, 1 had documented concern for pertussis and 4 had excluding conditions for which there were no ICD-10 codes. One received an antibiotic prescription for a planned dental procedure. Thus, based on chart review, 161 (54%) subjects received antibiotics inappropriately. Using the electronic algorithm based on diagnostic codes, underlying and concurrent conditions, and prescribing data, the number of subjects with inappropriate prescribing was 170 (56%) because 3 subjects had antibiotic prescribing not noted based on chart review. The test characteristics of the electronic algorithm (compared to gold standard chart review) for identification of inappropriate antibiotic prescribing were the following: sensitivity, 100% (161 of 161); specificity, 94% (130 of 139); positive predictive value, 95% (161 of 170); and negative predictive value, 100% (130 of 130). Conclusions: For outpatients with acute bronchitis, an electronic algorithm for identification of inappropriate antibiotic prescribing is highly accurate. This algorithm could be used to efficiently assess prescribing among practices and individual clinicians. The impact of interventions based on this algorithm should be tested in future studies.Funding: NoneDisclosures: None

scholarly journals Impact of the COVID-19 pandemic on community antibiotic prescribing in Scotland

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
William Malcolm ◽  
Ronald A Seaton ◽  
Gail Haddock ◽  
Linsey Baxter ◽  
Sarah Thirlwell ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Age Groups ◽  
Antibiotic Use ◽  
Antibiotic Prescribing ◽  
Prescription Data ◽  
National Data ◽  
Time Data ◽  
Electronic Messaging ◽  
The Impact ◽  
Selection Of

Abstract Background Following concerns about increased antibiotic use during the COVID-19 pandemic, trends in community antibiotic prescriptions in Scotland were evaluated. Methods The primary care prescription electronic messaging system used in GP practices with NHS contracts provided near real-time data analysis of national data. The main outcome measures were the weekly number of prescriptions for antibiotics generated by prescribers in GP practices in 2020 compared with 2019. Results At end of Week 12 2020 (22 March), after a sharp increase, the number of prescriptions commonly used for respiratory infections was 44% higher than the corresponding week in 2019. The number of prescriptions for respiratory antibiotics reduced through April and May 2020, with 34% fewer prescriptions issued by end of Week 22 (31 May) than in the corresponding week in 2019. Reductions were pronounced in all age groups but particularly apparent for prescriptions for children aged 0–4 years. These data were compared with weekly prescriptions for a selection of non-respiratory antibiotics and no difference was seen between 2020 and 2019. Conclusions Trends in antibiotic prescription data show that after an initial surge, and following ‘lockdown’ in Scotland, the total number of prescriptions for antibiotics commonly used for respiratory infections fell. We believe this is the first published national evaluation of the impact of COVID-19 on community use of antibiotics. Further analysis of national data is planned to provide a greater understanding of the reasons behind these trends.

scholarly journals 1043. Love Thy Steward – Who Does Not Love Antimicrobial Stewardship?

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S367-S368
Author(s):  
Aamir S Kazi ◽  
Sarah Sansom ◽  
Christy Varughese ◽  
Hayley A Hodgson ◽  
Sarah Y Won
Keyword(s):  
Infectious Disease ◽  
Antimicrobial Stewardship ◽  
Service Providers ◽  
Medical Center ◽  
General Medicine ◽  
Immunocompromised Host ◽  
Antibiotic Prescribing ◽  
Alternative Communication ◽  
Physician Perception ◽  
The Impact

Abstract Background The impact of antimicrobial stewardship programs (ASPs) depends on physician perception of antimicrobial stewardship and institutional antibiotic prescribing culture. At Rush University Medical Center (RUMC), we conducted an antimicrobial stewardship study targeting inpatient levofloxacin (FQ) use and assessed rates of implementation of recommendations (IORs) by general medicine (GM), vs. surgical services (SS) (general surgery, urology, orthopedics and neurosurgery), vs. transplant surgery-immunocompromised host (T-ICH) teams when made by either infectious disease pharmacists (IDPharmD) or infectious disease fellows (IDMDF). Methods Between August 13, 2018 and January 15, 2019 at RUMC, IDPharmDs reviewed 251 inpatients on FQ, and made ASP recommendations on 36 (14%) that were communicated via telephone. No scripted discussion or note was utilized. From January 15, 2019 to April 19, 2019, an IDMDF reviewed 207 inpatients on FQ, and made ASP recommendations on 47 (22%). IDMDF’s recommendations were communicated via a scripted discussion describing the role of ASP, highlighting the importance of optimizing FQ use due to toxicity, low rates of RUMC’s FQ susceptibilities and to decrease rates of resistance. Telephone recommendations were made to the primary team house staff or attending followed by a templated electronic note left in the medical chart. Rates of IORs were assessed during each period and by each group. Results In 20 out of 83 recommendations (24%), no antibiotic was indicated (Figure 1). GM teams had the highest overall (IDPharmD + IDMDF) IOR (76%), compared with 40% IOR for both SS and T-ICH groups. For all groups, the scripted IDMDF recommendations had higher IOR compared with the nonscripted IDPharmD recommendations (GM 89% vs. 61%; SS 50% vs. 29%; T-ICH 50% vs. 0%). Conclusion ASP interventions using scripted discussions and notes by an IDMDF were more effective than nonscripted IDPharmD interventions across all service lines. Both interventions were less successful with SS or T-ICH compared with GM services. These findings demonstrate the need for further research to understand the importance of scripted vs. nonscripted communication methods by pharmacists and ID physicians, and to develop alternative communication models for nongeneral medicine service providers. Disclosures All authors: No reported disclosures.

scholarly journals 43. Impact of a Five-Year Intervention of an Antimicrobial Stewardship Program on the Optimal Antibiotic Prophylaxis Selection in Surgery in a Hospital without Restrictions on Antibiotics Prescription in Costa Rica

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S143-S143
Author(s):  
José P Díaz-Madriz ◽  
Esteban Zavaleta-Monestel ◽  
Jorge A Villalobos-Madriz ◽  
Alison V Meléndez-Alfaro ◽  
Priscilla Castrillo-Portillo ◽  
...  
Keyword(s):  
Antibiotic Prophylaxis ◽  
Antimicrobial Stewardship ◽  
Bacterial Resistance ◽  
Positive Impact ◽  
Surgical Site Infections ◽  
Antimicrobial Stewardship Program ◽  
Defined Daily Doses ◽  
Stewardship Program ◽  
The Impact ◽  
Selection Of

Abstract Background In a private hospital without restrictions on antibiotic prescription, the success of an Antimicrobial Stewardship Program (ASP) depends mainly on prospective feedback and education. Previously, the ASP of this hospital (PROA-HCB) managed to achieve a positive impact on the antibiotic prophylaxis in cesarean delivery. The purpose of this study is to characterize the impact after implementing the PROA-HCB on the optimal prophylaxis selection of all the procedures included in the clinical guideline for surgical antibiotic prophylaxis in adult patients. Methods A retrospective observational study that compares the selection, duration, antibiotic consumption, bacterial resistance profiles and patient’s safety outcomes regarding antibiotic use for all surgical prophylaxis prescription over six months for the periods before (pre-ASP) and after a five-year intervention of PROA-HCB (post-ASP). Results After a five-year intervention, the percentage of optimal selection of antibiotic prophylaxis in Surgery was 21.0% (N=1598) in the pre-ASP period and 80.0% (N=841) in the post-ASP period (59% absolute improvement, p < 0.001). Percentage of optimal duration was 69,1% (N=1598) in the pre-ASP period and 78.0% (N=841) in the post-ASP period (8.9% absolute improvement, p < 0.001). Mean ceftriaxone utilization was 217.7 defined daily doses (DDD) per 1,000 patient days DDD for the pre-ASP period and 139.8 DDD per 1,000 patient days for the ASP period (35.8% decrease; p = 0.019). Mean cefazolin utilization was 14.9 DDD per 1,000 patient days for the pre-ASP period and 153.3 DDD per 1,000 patient days for the ASP period (928.6% increase; p = 0.021). Regarding percentage of bacterial resistance, there was detected an improvement in some isolates like Escherichia coli with a decrease of ESBL detection (11% decrease; p = 0.007). In addition, no serious adverse reactions or an increase in surgical site infections were detected after the intervention. Conclusion The implementation of an ASP in the surgical ward showed an overall positive impact on selection and duration of antibiotic prophylaxis. Furthermore, this intervention could have had a positive impact on antimicrobial resistance and at the same time had no negative effects on the patients. Disclosures All Authors: No reported disclosures

scholarly journals 2075. Transforming Outpatient Antimicrobial Stewardship Through a Clinical Surveillance System

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S699-S700
Author(s):  
David B Portman ◽  
Victoria M Pattison
Keyword(s):  
Antimicrobial Stewardship ◽  
Surveillance System ◽  
Chart Review ◽  
Performance Metrics ◽  
Outpatient Setting ◽  
Direct Approach ◽  
Antibiotic Prescribing ◽  
Clinical Surveillance ◽  
The Impact

Abstract Background Multiple studies have highlighted the predominance of inappropriate antibiotic prescribing in the outpatient setting, thus making an area ripe for antimicrobial stewardship interventions. One way to identify intervention opportunities and monitor performance metrics is through utilization of a clinical surveillance system (CSS). Methods In October 2017, TheraDoc (DSS Inc.) was obtained which serves as a CSS. Upon installation, the antimicrobial stewardship committee designed the alerts found in Figure 1 that would be utilized to identify potential interventions. Alerts that were deemed to be of high value or time sensitive were to be emailed to pharmacists involved with antimicrobial stewardship. It was theorized that this method would help transform outpatient antimicrobial stewardship from a predominately retrospective approach, to a prospective approach. Outpatient stewardship metrics were compared for pre- and post-CSS implementation to evaluate the impact of a CSS. The pre-implementation group (PreCSS) represented outpatient stewardship interventions that occurred January 2017 through June 2017 where all antibiotic prescriptions were reviewed. The post-implementation group (PostCSS) represented outpatient stewardship interventions that occurred April 2018 through September 2018 which were predominantly driven by CSS alerts. Results The PostCSS group had substantially fewer charts reviewed compared with the PreCSS group (267 vs. 1,415). In addition, the PostCSS group completed 77.6% more interventions compared with the PreCSS group (87 vs. 49). Thirty-one less charts were reviewed per one intervention, which led to 469 less minutes of chart review per one intervention. See Figure 2 for list of interventions. The PostCSS group received a significant increase in consults due to the direct approach to interventions compared with the PreCSS group (45 vs. 11). Conclusion The use of a clinical surveillance system has demonstrated an efficient way to transition outpatient antimicrobial stewardship to a prospective, interventional approach. Disclosures All authors: No reported disclosures.

Interrupted Time-Series Analysis to Evaluate the Impact of a National Antimicrobial Stewardship Campaign on Antibiotic Prescribing: A Typical Practice in China’s Primary Care

2020 ◽  
Author(s):  
Hui Li ◽  
Yanhong Gong ◽  
Jing Han ◽  
Shengchao Zhang ◽  
Shanquan Chen ◽  
...  
Keyword(s):  
Primary Care ◽  
Time Series ◽  
Antimicrobial Stewardship ◽  
Broad Spectrum ◽  
Interrupted Time Series ◽  
Antibiotic Prescribing ◽  
Interrupted Time Series Analysis ◽  
Targeted Interventions ◽  
The Impact ◽  
Outpatient Prescriptions

Abstract Background After implementing the 2011 national antimicrobial stewardship campaign, few studies focused on evaluating its effect in China’s primary care facilities. Methods We randomly selected 11 community health centers in Shenzhen, China, and collected all outpatient prescriptions of these centers from 2010–2015. To evaluate the impact of local interventions on antibiotic prescribing, we used a segmented regression model of interrupted time series to analyze seven outcomes, i.e., percentage of prescriptions with antibiotics, and percentages of prescriptions with broad-spectrum antibiotics, with parenteral antibiotics, and with two or more antibiotics in all prescriptions or antibiotics-containing prescriptions. Results Overall, 1 482 223 outpatient prescriptions were obtained. The intervention was associated with a significant immediate change (–5.2%, P=.04) and change in slope (–3.1% per month, P<.01) for the percentage of prescriptions with antibiotics, and its relative cumulative effect at the end of the study was –74.0% (95% confidence interval, –79.0% to –69.1%). After the intervention, the percentage of prescriptions with broad-spectrum, and with parenteral antibiotics decreased dramatically by 36.7% and 77.3%, respectively, but their percentages in antibiotic-containing prescriptions decreased insignificantly. Percentage of prescriptions with two or more antibiotics in all prescriptions or antibiotics-containing prescriptions only showed immediate changes, but significant changes in slope were not observed. Conclusions A typical practice in Shenzhen, China, showed that strict enforcement of antimicrobial stewardship campaign could effectively reduce antibiotic prescribing in primary care with a stable long-term effect. However, prescribing of broad-spectrum and parenteral antibiotics was still prevalent. More targeted interventions are required to promote appropriate antibiotic use.

scholarly journals In VivoEfficacy of Humanized Exposures of Ceftazidime-Avibactam in Comparison with Ceftazidime against Contemporary Enterobacteriaceae Isolates

2014 ◽  
Vol 58 (11) ◽  
pp. 6913-6919 ◽  
Author(s):  
Shawn H. MacVane ◽  
Jared L. Crandon ◽  
Wright W. Nichols ◽  
David P. Nicolau
Keyword(s):  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Class D ◽  
Variable Activity ◽  
Resistant Strains ◽  
The Impact ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

ABSTRACTCeftazidime-avibactam is a β-lactam β-lactamase inhibitor combination under investigation for the treatment of serious Gram-negative infections. When combined with avibactam, a novel non-β-lactam β-lactamase inhibitor, ceftazidime has activity against isolates that produce Ambler class A, class C, and some class D β-lactamases. However, little is known of thein vivoefficacy of the combination against these targeted ceftazidime- and carbapenem-resistantEnterobacteriaceae. Using humanized exposures in the murine thigh model, we evaluated the efficacy of ceftazidime-avibactam againstEnterobacteriaceaeexhibiting MICs of ≥8 μg/ml to aid in the assignment of interpretive susceptibility criteria. Eighteen clinicalEnterobacteriaceaeisolates, including nine carbapenem-resistant strains, were evaluated against ceftazidime-avibactam (2,000 mg/500 mg) as a 2-h infusion every 8 h. To highlight the impact of avibactam, 13 select isolates were tested in the neutropenic model against a humanized regimen of 2,000 mg ceftazidime every 8 h (2-h infusion). Additionally, nine isolates were evaluated in immunocompetent animals. The efficacy was evaluated as the change in log10CFU compared with that of 0-h controls after 24 h. The vast majority (17/18, 94%) of the isolates were resistant to ceftazidime alone. The ceftazidime monotherapy failed to have activity against 10 of 13 isolates, while ceftazidime-avibactam produced reductions in bacterial density against 16 of 18 isolates. Ceftazidime-avibactam (2,000 mg/500 mg) every 8 h (2-h infusion) displayed dependable activity against theEnterobacteriaceaeisolates, exhibiting MICs of ≤16 μg/ml (free drug concentration above the MIC [fT>MIC] of ≥62%) and variable activity was noted at an MIC of 32 μg/ml (fT>MICof 34%). The presence of a functioning immune system enhanced the efficacy for both regimens against all tested isolates. These data support further examination of the use of ceftazidime-avibactam as an effective therapy against infections due to Gram-negative infections, including carbapenem-resistantEnterobacteriaceae.

scholarly journals Pharmacokinetics-Pharmacodynamics of Tazobactam in Combination with Piperacillin in anIn VitroInfection Model

2016 ◽  
Vol 60 (4) ◽  
pp. 2075-2080 ◽  
Author(s):  
Anthony M. Nicasio ◽  
Brian D. VanScoy ◽  
Rodrigo E. Mendes ◽  
Mariana Castanheira ◽  
Catharine C. Bulik ◽  
...  
Keyword(s):  
Genetically Engineered ◽  
Dose Fractionation ◽  
Infection Model ◽  
Content Type ◽  
Study Results ◽  
High Level ◽  
The Impact ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

ABSTRACTWe have previously demonstrated the pharmacokinetic-pharmacodynamic (PK-PD) index best associated with the efficacy of tazobactam when used in combination with ceftolozane to be the percentage of the dosing interval during which tazobactam concentrations remained above a threshold value (%time>threshold). Using anin vitroinfection model and the same isogenic CTX-M-15-producingEscherichia colitriplet set genetically engineered to transcribe different levels ofblaCTX-M-15, herein we describe dose fractionation studies designed to evaluate the PK-PD index associated with tazobactam efficacy, when given in combination with piperacillin, and the impact of the presence of a different β-lactam agent, or differentblaCTX-M-15transcription levels, on the magnitude of the tazobactam PK-PD index necessary for efficacy. The recombinant strains demonstrated piperacillin MIC values of 128, >256, and >256 μg/ml for the low-, moderate-, and high-level CTX-M-15-producingE. colistrains, respectively. The MIC value for piperacillin in the presence of 4 μg/ml of tazobactam was 2 μg/ml for all three strains. The PK-PD index associated with tazobactam efficacy was confirmed to be %time>threshold, regardless of β-lactamase transcription (r2= 0.839). The tazobactam concentration thresholds, however, changed with the CTX-M-15 transcription level and were 0.25, 0.5, and 2 μg/ml for the low-, moderate-, and high-level CTX-M-15-producing strains, respectively (r2= 0.921, 0.773, and 0.875, respectively). The %time>threshold values for tazobactam necessary for net bacterial stasis and a 1- and 2-log10-unit CFU/ml decrease from baseline at 24 h were 44.9, 62.9, and 84.9%, respectively. In addition to verifying our previous study results, these results also demonstrated that the magnitude of bacterial-cell killing associated with a β-lactam–β-lactamase inhibitor combination is dependent on the amount of β-lactamase produced. These data provide important information for the development of β-lactam–β-lactamase inhibitor combination agents.

Sign in / Sign up

Export Citation Format

Share Document