Treatment outcomes with benzylpenicillin and non-benzylpenicillin antibiotics, and the performance of the penicillin zone-edge test versus molecular detection of blaZ in penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia.

OBJECTIVES: The blaZ gene encodes penicillinase, which inactivates penicillin. As there were reports on suboptimal sensitivity for the penicillin zone-edge test, a phenotypic method for blaZ detection, we investigated treatment outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia (phenotypically negative for penicillinase), subjecting isolates to molecular testing for blaZ retrospectively. PATIENTS AND METHODS: A retrospective cohort study was conducted on 121 patients with a first episode of PSSA bacteraemia from 1 January 2012 to 31 October 2015 at Tan Tock Seng Hospital (TTSH), Singapore. Patients were grouped into IV benzylpenicillin and non-benzylpenicillin groups. The primary outcome was overall treatment failure, defined as either 30 day all-cause mortality and/or 90 day relapse. The penicillin (P10) zone-edge test was repeated on archived PSSA isolates, concurrently with penicillin MIC determination via gradient diffusion and PCR for blaZ. RESULTS: Among 121 patients, 57 patients (47.1%) received IV benzylpenicillin as the predominant antibiotic. There was no significant difference in overall treatment failure between treatment with the benzylpenicillin [7/57 (12.3%)] versus non-benzylpenicillin groups [12/64 (18.8%)] (P = 0.33) or cloxacillin/cefazolin [6/37 (16.2%)] (P = 0.59). For 112 PSSA isolates available for testing, repeat penicillin zone-edge testing was negative for penicillinase production, corroborating previous results. A single PSSA isolate with a negative penicillin zone-edge test was found to be positive for blaZ. CONCLUSIONS: We found no differences in overall treatment failure between patients with PSSA bacteraemia treated with benzylpenicillin, anti-staphylococcal ß-lactams cefazolin/cloxacillin and other antimicrobials, when using the penicillin zone-edge test as the phenotypic method for blaZ screening.

Sustaining Antimicrobial Stewardship in a High-Antibiotic Resistance Setting.

Importance: There is a lack of studies comparing the intended and unintended consequences of prospective review and feedback (PRF) with computerized decision support systems (CDSS), especially in the longer term in antimicrobial stewardship. Objective: To examine the outcomes associated with the sequential implementation of PRF and CDSS and changes to these interventions with long-term use of antibiotics for and incidence of multidrug resistant organisms (MDROs) and other unintended outcomes. Design, Setting, and Participants: This cohort study used an interrupted time series with segmented regression analysis of data from January 2007 to December 2018. Data were extracted from the electronic medical records of patients admitted at a large university teaching hospital with high rates of antibiotic resistance in Singapore. Data were analyzed from June 2019 to June 2020. Exposures: PRF of piperacillin-tazobactam and carbapenems (intervention 1, April 2009), with the addition of hospital-wide CDSS (intervention 2, April 2011), and lifting of CDSS for half of the hospital wards for 6 months (intervention 3, March 2017). Main Outcomes and Measures: Monthly antimicrobial use was measured in defined daily doses (DDDs) per 1000 patient-days. The monthly incidence of MDROs was calculated as number of clinical isolates detected per 1000 inpatient-days over a 6-month period. Unintended outcomes examined included in-hospital mortality and age-adjusted length of stay (LOS). Results: The number of inpatients increased from 56 263 in 2007 to 63 572 in 2018. During the same period, the mean monthly patient days increased from 33 929 in 2007 to 45 603 in 2018, and the proportion of patients older than 65 years increased from 45.5% in 2007 to 56.6% in 2018. After intervention 1, there were 0.33 (95% CI, 0.18 to 0.48) more DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and -11.05 (95% CI, -15.55 to -6.55) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 2, there were -0.22 (95% CI, -0.33 to -0.10) fewer DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and -2.10 (95% CI, -3.13 to -1.07) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 3, use of piperacillin-tazobactam and carbapenem increased by 0.28 (95% CI, 0.02 to 0.55) DDDs per 1000 patient-days per month. After intervention 2, incidence of Clostridioides difficile decreased (estimate, -0.02 [95% CI, -0.03 to -0.01] cases per 1000 patient-days per month). Conclusions and Relevance: In this cohort study, concurrent PRF and CDSS were associated with limiting the use of piperacillin-tazobactam and carbapenems while reducing use of other antibiotics.

Accuracy of a Rapid Multiplex Polymerase Chain Reaction Plus a Chromogenic Phenotypic Test Algorithm for Detection of Extended-Spectrum ß-Lactamase and Carbapenemase-Producing Gram-Negative Bacilli in Positive Blood Culture Bottles.

We studied the performance of an algorithm combining multiplex polymerase chain reaction with phenotypic detection of extended-spectrum ß-lactamases and carbapenemases directly from positive blood culture bottles in patients with gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time to optimal therapy in patients with gram-negative bacteremia.

Use of Erector Spinae Fascial Plane Blocks in Enhanced Recovery for Open Abdominal Surgery.

BACKGROUND: Bilateral erector spinae fascial plane blocks (ESPB) offers a novel, alternative method of regional post-operative pain control to thoracic epidural analgesia (TEA). The aim of this study was to compare rates of postoperative hypotension, and other standard enhanced recovery after surgery (ERAS) endpoints, in patients receiving ESPB versus TEA for open hepatopancreaticobiliary (HPB) surgery. MATERIALS AND METHODS: This retrospective analysis compared historical controls of ERAS patients undergoing open HPB surgery with TEA versus ESPB. The incidence of postoperative hypotension and clinical outcomes, including opioid requirements, were compared. RESULTS: Forty patients receiving TEA were compared to 27 ESPB patients. Return of bowel function and length of stay (mean 7.2 versus7.4 days; P = 0.83) were similar. ESPB patients received less intraoperative colloid (142cc versus 340cc; P = 0.01) and had less postoperative hypotension versus TEA (22% versus 55%; P = 0.03). No ESPB patient required patient-controlled analgesia (versus 32.5% TEA; P< 0.001). ESPB MME requirements decreased over time, while TEA MME requirements increased over 72 hours (P = 0.019). CONCLUSIONS: ESPB is a novel method that shows promising outcomes in improving enhanced recovery parameters and minimizing opioid administration in open HPB surgery.

Content analysis of child user and carer perspectives of ankle-foot orthoses.

BACKGROUND: The evaluation of ankle-foot orthoses is primarily focused on biomechanical performance, with comparatively less studies pertaining to users' quality of life and experiential factors. OBJECTIVES: To investigate how child users regard acquisition and use of ankle-foot orthoses through the perspectives of child users, parents/carers and practitioners. STUDY DESIGN: Inductive content analysis of secondary data. METHODS: Child user and parent/carer perspectives, as communicated by them and by practitioners, were collected from online platforms and formal publications. Data and themes were analysed through an inductive approach. Investigator triangulation was used to increase trustworthiness and reduce bias. RESULTS: We found and analysed 223 data points from 30 informal online platforms and 15 formal publications. These data clustered into five key themes relating to user experience with ankle-foot orthoses, including materials, structure, aesthetics, service and impact. Child users had mixed opinions about ankle-foot orthoses, reporting satisfaction with the functional improvements resulting from ankle-foot orthosis wear, while noting negative feelings from the experience of acquiring and using the device. CONCLUSION: This research suggests that considering the five themes in ankle-foot orthosis provision could improve the child user experience, inform future ankle-foot orthosis design, and improve clinical outcomes.

Effects of coronavirus disease 2019 (COVID-19) pandemic on antimicrobial prevalence and prescribing in a tertiary hospital in Singapore.

BACKGROUND: The deployment of antimicrobial stewardship (AMS) teams to deal with the COVID-19 pandemic can lead to a loss of developed frameworks, best practices and leadership resulting in adverse impact on antimicrobial prescribing and resistance. We aim to investigate effects of reduction in AMS resources during the COVID-19 pandemic on antimicrobial prescribing. METHODS: One of 5 full-time equivalent AMS pharmacists was deployed to support pandemic work and AMS rounds with infectious disease physicians were reduced from 5 to 2 times a week. A survey in acute inpatients was conducted using the Global Point Prevalence Survey methodology in July 2020 and compared with those in 2015 and 2017-2019. RESULTS: The prevalence of antimicrobial prescribing (55% in 2015 to 49% in 2019 and 47% in 2020, p = 0.02) and antibacterials (54% in 2015 to 45% in 2019 and 42% in 2020, p < 0.01) have been reducing despite the pandemic. Antimicrobial prescribing in infectious disease wards with suspected or confirmed COVID-19 cases was 29% in 2020. Overall, antimicrobial prescribing quality indicators continued to improve (e.g. reasons in notes, 91% in 2015 to 94% in 2019 and 97% in 2020, p < 0.01) or remained stable (compliance to guideline, 71% in 2015 to 62% in 2019 and 73% in 2020, p = 0.08). CONCLUSION: During the COVID-19 pandemic, there was no increase in antimicrobial prescribing and no significant differences in antimicrobial prescribing quality indicators.

A point prevalence survey to assess antibiotic prescribing in patients hospitalized with confirmed and suspected coronavirus disease 2019 (COVID-19).

BACKGROUND: Earlier studies have reported high antibiotic use in patients hospitalised for coronavirus disease 2019 (COVID-19), resulting in concerns of increasing antimicrobial resistance with increase antibiotic use in this pandemic. Point prevalence survey (PPS) can be a quick tool to provide antibiotic prescribing information to aid antimicrobial stewardship (AMS) activities. OBJECTIVES: To describe antibiotic utilization and evaluate antibiotic appropriateness in COVID-19 patients using PPS. METHODS: Adapting Global-PPS on antimicrobial use, the survey was conducted in COVID-19 wards at 2 centres in Singapore on 22 April 2020 at 0800h. Patients on systemic antibiotics were included and evaluated for antibiotic appropriateness. RESULTS: Five hundred and seventy-seven patients were screened. Thirty-six (6.2%) patients were on antibiotics and which were started at median of 7 days (inter-quartile rate (IQR), 4, 11) from symptom onset. Fifty-one antibiotics were prescribed in these patients. Overall, co-amoxiclav (26/51, 51.0%) was the most often prescribed antibiotic. Thirty-one out of 51 (60.8%) antibiotic prescriptions were appropriate. Among 20 inappropriate prescriptions, 18 (90.0%) were initiated in patients with low likelihood of bacterial infections. Antibiotic prescriptions were more appropriate when reviewed by infectious diseases physicians (13/31 [41.9%] versus 2/20 [10.0%], p=0.015), and if reasons for use were stated in notes (31/31 [100.0%] versus 16/20 [80.0%], p=0.019). CONCLUSIONS: Despite low prevalence of antibiotic use among confirmed and suspected COVID-19 patients at 2 centres in Singapore, there was significant proportion of inappropriate antibiotics use where bacterial infections were unlikely. AMS teams can tailor stewardship strategies using PPS results.

Effective Antimicrobial StewaRdship StrategIES (ARIES): Cluster Randomized Trial of Computerized Decision Support System and Prospective Review and Feedback.

BACKGROUND: Prospective review and feedback (PRF) of antibiotic prescriptions and compulsory computerized decision support system (CDSS) are 2 strategies of antimicrobial stewardship. There are limited studies investigating their combined effects. We hypothesized that the use of on-demand (voluntary) CDSS would achieve similar patient outcomes compared with automatically triggered (compulsory) CDSS whenever broad-spectrum antibiotics are ordered. METHODS: A parallel-group, 1:1 block cluster randomized crossover study was conducted in 32 medical and surgical wards from March to August 2017. CDSS use for piperacillin-tazobactam or carbapenem in the intervention clusters was at the demand of the doctor, while in the control clusters CDSS use was compulsory. PRF was continued for both arms. The primary outcome was 30-day mortality. RESULTS: Six hundred forty-one and 616 patients were randomized to voluntary and compulsory CDSS, respectively. There were no differences in 30-day mortality (hazard ratio [HR], 0.87; 95% CI, 0.67-1.12), re-infection and re-admission rates, antibiotic duration, length of stay, or hospitalization cost. The proportion of patients receiving PRF recommendations was not significantly lower in the voluntary CDSS arm (62 [10%] vs 81 [13%]; P = .05). Appropriate indication of antibiotics was high in both arms (351/448 [78%] vs 330/433 [74%]; P = .18). However, in geriatric medicine patients where antibiotic appropriateness was <50%, prescription via compulsory CDSS resulted in a shorter length of stay and lower hospitalization cost. CONCLUSIONS: Voluntary broad-spectrum antibiotics with PRF via CDSS did not result in differing clinical outcomes, antibiotic duration, or length of stay. However, in the setting of low antibiotic appropriateness, compulsory CDSS may be beneficial.

A Point Prevalence Study of Antimicrobial Use and Practice Among Nursing Homes in Singapore.

BACKGROUND: Inappropriate antimicrobial use is a major cause for the development of antimicrobial resistance in nursing homes (NHs); however, little is known about antimicrobial use at NHs in Singapore compared with NHs in other countries. OBJECTIVES: The aim of this study was to determine the prevalence, practice and challenges of antimicrobial prescribing in Singapore NHs compared with those in other countries. METHODS: A point prevalence survey (PPS) was conducted from August to October 2017. Data on antimicrobial use and the quality of documentation were retrieved from medical and/or medication records of NH residents. Informed consent was obtained from the NH management. RESULTS: Nine of 73 NHs in Singapore, with a total of 1760 residents, participated in the PPS. The prevalence of oral antibiotic and topical antimicrobial use was 2% and 11%, respectively, and the worldwide point prevalence of antimicrobial prescribing in NHs ranged from 1-17% (median 8%). The key challenges identified locally were different from those of overseas NHs, including incomplete documentation of antimicrobial duration and indication of use, as well as the high prevalence of topical antimicrobial use. CONCLUSIONS: The prevalence of oral antibiotic use in NHs in Singapore was lower, while topical antimicrobial use was higher, compared with NHs in other countries. Variability in antimicrobial prescribing and challenges in practice among local and overseas NHs implied that a comprehensive PPS could be beneficial to aid in the design of effective and practicable antimicrobial stewardship strategies appropriate for the NH.

Drug-related problems associated with community-dwelling older persons living alone in Singapore.

Background Older persons living alone have been associated with poorer health outcomes and higher mortality rate. However, little is known about the drug related problems (DRPs) faced by this population group in Singapore. Objectives This study aims to elucidate the prevalence and type of DRPs associated with older persons living alone. Setting Eleven Senior Activity Centers in Singapore. Method Individuals aged above 55 years, taking at least one oral chronic medication and living in the housing estate served by the Senior Activity Centers were recruited to participate in an individual interviewer-administered cross-sectional survey. Those who were unable to comprehend the survey or communicate their responses fully were excluded. DRPs were identified by the interviewers and reported using a modified DOCUMENT system. Main outcome measure The main outcome measure was the difference in prevalence and types of DRPs between survey participants with different living arrangements. Results Among 360 respondents, 152 (42.2%) were older persons living alone. A higher prevalence (61.2% vs. 47.6%, adjusted OR = 1.86 [1.12-3.10], p = 0.016) and mean number of DRPs (1.23 ± 1.4 vs. 0.95 ± 1.33, p = 0.018) were observed among older persons living alone in comparison with those who were not living alone. Specifically, those living alone were more likely to have DRP related to the category 'Taking too little' (adjusted OR = 2.32 [1.28-4.20], p = 0.006) and which involved the use of HMG-CoA reductase inhibitors (adjusted OR = 2.78 [1.16-6.69], p = 0.022). Conclusion Besides having a significantly higher prevalence of DRP, older persons living alone were more likely to be non-adherent to their medications, particularly statins. Targeted interventions to reduce these DRPs and ensure appropriate management of chronic conditions should be derived, especially for those who lack the ability to help themselves.

Clinical and Molecular Correlates of Escherichia coli Bloodstream Infection from Two Geographically Diverse Centers in Rochester, Minnesota, and Singapore.

Escherichia coli bacteremia is caused mainly by sequence type complex 131 (STc131) and two clades within its fluoroquinolone-resistance-associated H30 subclone, H30R1 and H30Rx. We examined clinical and molecular correlates of E. coli bacteremia in two geographically distinct centers. We retrospectively studied 251 unique E. coli bloodstream isolates from 246 patients (48 from the Mayo Clinic, Rochester, MN [MN], and 198 from Tan Tock Seng Hospital, Singapore [SG]), from October 2013 through March 2014. Isolates underwent PCR for phylogroup, STc, blaCTX-M type, and virulence gene profiles, and medical records were reviewed. Although STc131 accounted for 25 to 27% of all E. coli bacteremia isolates at each site, its extended-spectrum-ß-lactamase (ESBL)-associated H30Rx clade was more prominent in SG than in MN (15% versus 4%; P = 0.04). In SG only, patients with STc131 (versus other E. coli STc isolates) were more likely to receive inactive initial antibiotics (odds ratio, 2.8; P = 0.005); this was true specifically for patients with H30Rx (odds ratio, 7.0; P = 0.005). H30Rx comprised 16% of community-onset bacteremia episodes in SG but none in MN. In SG, virulence scores were higher for H30Rx than for H30R1, non-H30 STc131, and non-STc131 isolates (P < 0.02 for all comparisons). At neither site did mortality differ by clonal status. The ESBL-associated H30Rx clade was more prevalent and more often of community onset in SG, where it predicted inactive empirical treatment. The clonal distribution varies geographically and has potentially important clinical implications. Rapid susceptibility testing and clonal diagnostics for H30/H30Rx might facilitate earlier prescribing of active therapy.

Antimicrobial use and drug-drug interactions among nursing home residents in Singapore: a multicentre prevalence study.

Background With the Ministry of Health's projected increase in nursing home beds and optimization of antimicrobial use in health care settings, it is therefore timely to consider baseline prevalence and patterns of antimicrobial use at nursing homes in Singapore as well as to evaluate the prevalence of potential clinically significant drug-drug interactions involving antimicrobials. Objective The primary objective was to determine the prevalence and patterns of antimicrobial use at nursing homes in Singapore. The secondary objective was to evaluate the prevalence of potential clinically significant drug-drug interactions involving antimicrobials. Setting Four nursing homes in Singapore. Method A retrospective cross-sectional study was conducted among nursing home residents. The antimicrobial prevalence, defined daily doses, days of therapy, and potential drug-drug interactions were determined using data from archived resident medication prescribing and administration records. Main outcome measure Prevalence and patterns of antimicrobial use, drug-drug interactions involving antimicrobials. Results Among 707 residents (mean age: 80.7 ± 8.8 years, female: 57.1%), 10% used antimicrobials during the study month, with a 1-day point prevalence of 3%. The utilization rates of antimicrobials were 28.9 defined daily doses/1000 resident-days and 24.8 days of therapy/1000 resident-days. Potential drug-drug interactions involving antimicrobials were identified among 32 of the 70 (46%) residents who were prescribed antimicrobials. Of these, 26 (81%) residents had 43 potential clinically significant drug-drug interactions. Conclusions The prevalence and utilization rates of antimicrobial use in Singapore nursing homes appear to be low. Yet, potential clinically significant drug-drug interactions are prevalent.

Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.

Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.

Pharmacokinetic/Pharmacodynamic Determinants of Vancomycin Efficacy in Enterococcal Bacteremia.

While pharmacokinetic-pharmacodynamic targets for vancomycin therapy are recognized for invasive methicillin-resistant Staphylococcus aureus infections, scant data are available to guide therapy for other Gram-positive infections. A retrospective single-center cohort of patients with Enterococcus bacteremia hospitalized between 1 January 2009 and 31 May 2015 were studied. The average vancomycin AUC0-24 was computed using a Bayesian approach. The MIC was determined by gradient diffusion (Etest; bioMérieux), and the average AUC0-24/MIC value over the initial 72 h of therapy was calculated. We assessed 30-day all-cause mortality as the primary outcome. Classification and regression tree analysis (CART) was used to identify the vancomycin AUC0-24/MIC value associated with 30-day mortality. Fifty-seven patients with enterococcal bacteremia (32 E. faecium, 21 E. faecalis, and 4 other Enterococcus spp.) were studied. The median vancomycin MIC was 0.75 mg/liter (range, 0.38 to 3 mg/liter). All-cause 30-day mortality occurred in 10 of 57 patients (17.5%). A CART-derived vancomycin AUC/MICEtest value of ≥389 was associated with reduced mortality (P = 0.017); failure to achieve this independently predicted 30-day mortality (odds ratio, 6.83 [95% confidence interval = 1.51 to 30.84]; P = 0.01). We found that a vancomycin AUC/MICEtest value of ≥389 achieved within 72 h was associated with reduced mortality. Larger, prospective studies are warranted to verify the vancomycin pharmacodynamic targets associated with maximal clinical outcomes and acceptable safety.

Clinical impact of non-antibiotic recommendations by a multi-disciplinary antimicrobial stewardship team.

INTRODUCTION: The multi-disciplinary antimicrobial stewardship team at the study hospital conducts prospective review and feedback on all inpatient orders of piperacillin-tazobactam and carbapenems. In addition, the team provides non-antibiotic recommendations (i.e. additional investigations and infectious disease reviews). This study aimed to describe the impact of these recommendations on patient outcomes. METHODS: Patients on carbapenem and piperacillin-tazobactam who received at least one non-antibiotic recommendation between January 2012 and August 2014 were included in this study. Acceptance and rejection of non-antibiotic recommendations by the managing physician were compared. The primary outcome was 30-d mortality. RESULTS: Non-antibiotic recommendations were made in 166 patients. There were no differences in baseline characteristics between patients for whom recommendations were accepted and patients for whom recommendations were rejected. Thirty-day mortality (18.0% vs. 34.5%, P = 0.02) was significantly lower in patients who had at least one non-antibiotic recommendation accepted. Multi-variate analysis found that Charlson's comorbidity score [odds ratio (OR) 1.20, 95% confidence interval (CI) 1.03-1.42, P = 0.03], APACHE II score (OR 1.10, 95% CI 1.01-1.19, P < 0.01), hepatobiliary source of infection (OR 10.19, 95% CI 1.44-72.13, P = 0.02) and acceptance of at least one non-antibiotic recommendation (OR 0.39, 95% CI 0.17-0.88, P = 0.02) were independently associated with 30-d mortality. CONCLUSIONS: During prospective review and feedback of piperacillin-tazobactam and carbapenems, acceptance of non-antibiotic recommendations was found to be associated with a reduction in 30-d mortality.

Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing.

BACKGROUND: The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs. METHODS: A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost. RESULTS: Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum ß-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost. CONCLUSIONS: rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation. CLINICAL TRIALS REGISTRATION: NCT01898208.

Safety and effectiveness of improving carbapenem use via prospective review and feedback in a multidisciplinary antimicrobial stewardship programme.

INTRODUCTION: Antimicrobial stewardship programmes (ASP) can reduce antibiotic use but patient safety concerns exist. We evaluated the safety of prospective carbapenem review and feedback and its impact on carbapenem use and patient outcomes. MATERIALS AND METHODS: After 3 months implementation of our ASP, we compared patients with and without acceptance of ASP recommendations on the use of carbapenems. Primary outcome was 30-day mortality. Secondary outcomes included duration of carbapenem use, length of hospitalisation, clinical response, microbiological clearance, 30-day readmission and mortality at discharge. RESULTS: Of 226 recommendations for 183 patients, 59.3% was accepted. De-escalation, switching to oral antibiotics and antibiotic cessation comprised 72% of recommendations. Patients with acceptance of ASP recommendations had lower 30-day mortality and higher end-of-therapy clinical response despite shorter carbapenem duration (P <0.05). Predictors of 30-day mortality were Pitt bacteraemia score (adjusted odds ratio [aOR] 1.39, 95% confidence interval [CI], 1.11 to 1.74; P = 0.004) and non-acceptance of ASP recommendations (aOR 2.84, 95% CI, 1.21 to 6.64; P = 0.016). CONCLUSION: Our prospective carbapenem review and feedback mainly comprising of reducing carbapenem use is safe.