De-escalation Of Antimicrobial Therapy Research Articles

Development of antibiotic metrics for hospitalists via multi-institutional modified Delphi survey.

Closing the gap between evidence-supported antibiotic use and real-world prescribing among clinicians is vital for curbing excessive antibiotic use, which fosters antimicrobial resistance and exposes patients to antimicrobial side effects. Providing prescribing information via scorecard improves clinician adherence to quality metrics. We aimed to delineate actionable, relevant antimicrobial prescribing metrics extractable from the electronic health record in an automated way. We used a modified Delphi consensus-building approach. Our study entailed two iterations of an electronic surveydisseminated to hospital medicine physicians at 10 academic medical centers nationwide. Main outcomes comprised consensus metrics describing the quality of antibiotic prescribing to hospital medicine physicians. Twenty-eight participants from 10 United States institutions completed the first survey version containing 38 measures. Sixteen respondents completed the second survey, which contained 37 metrics. Sixteen metrics, which were modified based on qualitative survey feedback, met criteria for inclusion in the final scorecard. Metrics considered most relevant by hospitalists focused on the appropriate de-escalation of antimicrobial therapy, selection of guideline-concordant antibiotics, and appropriate duration of treatment for common infectious syndromes. Next steps involve prioritization and implementation of these metrics based on quality gaps at our institution, focus groups exploring impressions of clinicians who receive a scorecard,and analysis of antibiotic prescribing patterns before and after metric implementation. Other institutions may be able to implement metrics from this scorecard based on their own quality gaps to provide hospitalists with automated feedback related to antibiotic prescribing.

O03 Rapid Infection Diagnostics in Cirrhosis (RIDiC): a novel molecular-based approach to address the ever increasing challenge of antimicrobial resistant infections in decompensated cirrhosis and acute-on-chronic liver failure

Abstract Background Global prevalence of MDR infections in cirrhotic patients has risen to 34% and associates with worsening clinical trajectory and mortality (Fernandez J et al. 2019). A major unmet need in addressing the challenge of antimicrobial resistance (AMR) in cirrhosis is rapid pathogen diagnosis and antimicrobial resistance (AMR) (Patel VC et al. 2019). These can facilitate selection of more effective antibiotic therapy, reducing selection for MDR organisms. The Curetis Unyvero™ platform (CUp) employs multiplex PCR technology for pathogen and AMR gene detection from multiple bodily tissues and fluids requiring minimal pre- processing. The investigator-initiated pilot study aimed to assess the utility of this platform for hospitalized cirrhotic patients. Methods Ascitic fluid, bronchoalveolar lavage (BAL) and blood culture samples were obtained from hospitalized cirrhotic patients with acute decompensation (AD) or acute-on-chronic liver failure (ACLF), in whom there was clinical suspicion of infection. Samples were tested using the IAI (intra-abdominal infection) panel, HPN (hospital pneumonia) panel and BCU (blood culture) panel based on sample type available. Results were not shared with clinicians for decision-making. Data were compared with standard microbiology diagnostics. Results 31 samples from 21 patients were tested: ascites (25), BAL (4), blood culture (2). Time to positive culture result of all samples was reduced with CUp compared with standard microbiology (4.59 versus 73.5 h). CUp showed 100% specificity (12/12) and detected the same organism in 100% of cases (10/12). In 6 samples, CUp identified pathogens which were consistent with clinical evidence of spontaneous bacterial peritonitis and previous positive isolates which standard microbiological diagnostics failed to identify. AMR genes identified by the CUp correlated with AMR patterns reported by standard diagnostics in 100% (5/5) of cases. In 2 patients, broad-spectrum antibiotic therapy continued although the CUp supported infection resolution. Four patients in whom CUp screening was negative continued to receive antibiotics whilst awaiting negative standard cultures that arrived 72 h later. CUp did not identify an Aspergillus species in one BAL sample as this is not part of the BAL panel. Conclusions These preliminary data suggest CUp results are compatible with standard laboratory diagnostics. The CUp may be utilized for earlier infection diagnosis and improve the targeting and de-escalation of antimicrobial therapy in AD and ACLF. These are crucial components in enhancing antibiotic stewardship strategies and to reduce MDR infections (Figure 1). Further work is however required to evaluate cost implications, validation and impact on clinical outcomes and mortality in cirrhosis.

Impact of Positive Culture Reports of E. coli or MSSA on De-Escalation of Antibiotic Use in a Teaching Hospital in Pakistan and the Implications

Antibiotic de-escalation is a key element of antimicrobial stewardship programs that restrict the spread and emergence of resistance. This study was performed to evaluate the impact of positive culture sensitivity reports of E. coli or Methicillin sensitive Staphylococcus aureus (MSSA) on de-escalation of antibiotic therapy. This prospective observational study was performed on 256 infected patients. The samples were obtained principally from the pus of infected sites for the identification of pathogens and culture-sensitivity testing. The data were collected from patient medical files, which included their demographic data, sample type, causative microbe and antimicrobial treatment as empiric or definitive treatment based on cultures. Data were analyzed using SPSS. Of 256 isolated microbes, 138 (53.9%) were MSSA and 118 were E. coli (46.1%). MSSA showed 100% sensitivity to cefoxitin, oxacillin, vancomycin, fosfomycin, colistin and more than 90% to linezolid (95.3%), tigecycline (93.1%), chloramphenicol (92.2%) and amikacin (90.2%). E. coli showed 100% sensitivity to only fosfomycin and more than 90% to colistin (96.7%), polymyxin-B (95.1%) and tigecycline (92.9%). The high use of cefoperazone+sulbactam (151), amikacin (149), ceftriaxone (33), metronidazole (30) and piperacillin + tazobactam (22) was seen with empiric prescribing. Following susceptibility testing, the most common antibiotics prescribed for E. coli were meropenem IV (34), amikacin (34), ciprofloxacin (29) and cefoperazone+sulbactam (25). For MSSA cases, linezolid (48), clindamycin (30), cefoperazone+ sulbactam IV (16) and amikacin (15) was used commonly. Overall, there was 23% reduction in antibiotic use in case of E. coli and 43% reduction in MSSA cases. Culture sensitivity reports helped in the de-escalation of antimicrobial therapy, reducing the prescribing of especially broad-spectrum antibiotics. Consequently, it is recommended that local hospital guidelines be developed based on local antimicrobial susceptibility patterns while preventing the unnecessary use of broad-spectrum antibiotics for empiric treatment.

Evaluating the impact of de-escalating antimicrobial therapy in burn patients: a retrospective cohort study.

Antimicrobials should be used appropriately to minimise the risk of resistant strains arising in association with overuse. De-escalation of antimicrobial therapy is one strategy used to ensure appropriate use, but its safety and efficacy in burn patients are unclear. The aim of this study was to evaluate the safety and efficacy of de-escalation therapy for treating infections in burn patients. This retrospective cohort study investigated patients admitted to our intensive care unit with burns and treated for infection between October 1, 2013, and September 30, 2020. Patients were classified into a de-escalation group (Group D) comprising patients treated with empiric antimicrobial therapy followed by de-escalation and a non-de-escalation group (Group ND) comprising patients who did not undergo de-escalation. Characteristics and outcomes were compared between groups. Forty-three patients met the inclusion criteria, including 15 patients in Group D and 28 patients in Group ND. Bacterial species commonly detected in these patients were Corynebacterium spp. (17.3%), Pseudomonas aeruginosa (16.1%), and Staphylococcus aureus (9.6%) . No inter-group difference was seen in 28-day mortality (6.7% vs 21.4%, p =0.391). Multidrug-resistant strains were detected significantly less frequently in Group D (13.0%) than in Group ND (26.1%, p =0.003). De-escalation was associated with use of two or more antimicrobials as empiric antimicrobial therapy. As the use of de-escalation in infection treatment did not impact 28-day mortality, de-escalation might be safe for treating infections in burn patients.

Empirical antimicrobial therapy for bloodstream infections not compliant with guideline was associated with discordant therapy, which predicted poorer outcome even in a low resistance environment

Objectives To characterise all bloodstream infections (BSIs) in a low antimicrobial resistance (AMR) prevalence setting with regard to the appropriateness of empirical antimicrobial therapy, compliance with the national clinical practice guideline, de-escalation practice and outcome. Methods A retrospective observational study including patients aged 18 years admitted to a university hospital in central Norway with positive blood culture in 2019. Results We included 756 BSI episodes in our analysis. Empirical antimicrobial therapy was in accordance with the national guideline in 534 (70.6%), and not in accordance in 190 (25.1%) of the BSI episodes. There was a statistically significant association between compliance with the national guideline and concordant empirical antimicrobial therapy (p = .001). De-escalation of antimicrobial therapy was possible but not done in 217 (31.1%) of the BSI episodes. Variables identified as independent predictors of discordant empirical antimicrobial therapy included hospital department, type of empirical antimicrobial regimen, bacterial species, and AMR. Independent predictors of intra-hospital case fatality rate were coverage of empirical antimicrobial therapy, CCI-score, SAPS-II score, site of infection, and type of empirical antimicrobial regimen. Furthermore, the intra-hospital and long-term unadjusted all-cause case fatality rates were increased (p < .001, log-rank test for overall difference in survival) for the patients who received discordant empirical antimicrobial therapy. Conclusion Our study shows that empirical antimicrobial therapy initiated in accordance with national guideline recommendations increases the likelihood of receiving concordant therapy. Discordant empirical antimicrobial therapy was associated with poorer outcomes, even in a setting with low AMR prevalence.

The impact of GenMark Dx ePlex blood-culture identification on the treatment and outcomes of gram-positive bacteremia

Background: In the treatment of bloodstream infections, the identification of the causal pathogen, and the evaluation of its susceptibility to antibiotics, often serve as the rate-limiting steps of the patient’s hospital stay. The GenMark Dx ePlex blood culture identification gram-positive (BCID-GP) panel aims to alleviate this bottleneck, thereby reducing the risk of severe complications and the spread of resistance, using electrowetting technology to detect the most common causes of GP bacteremia (20 targets) and 4 antimicrobial resistance (AMR) genes. We hypothesized that implementation of the ePlex BCID-GP panel would improve antimicrobial choice and de-escalation where appropriate. Methods: A mixed blinded and unblinded study was conducted to assess the effect of the BCID-GP panel on the outcomes and antibiotic stewardship of GP bacteremic patients before ePlex results were made clinically available (before implementation, N = 73) and once they accompanied the standard-of-care work-up (after implementation, N = 82). Differences in time to different benchmarks between the 2 modalities and the effect on patient outcomes were analyzed using null-hypothesis significance testing. Results: During the study, the BCID-GP panel identified 63 (42%) Staphylococcus epidermidis isolates, 31 (21%) Staphylococcus spp, 24 (16%) Staphylococcus aureus isolates, 12 (8%) Streptococcus spp, and 7 (5%) Enterococcus spp, and results were similar in the pre- and postimplementation groups (P = .13). The panel saved an average of 32.0 ± 24.2 hours in pathogen identification over standard-of-care methods, with no statistical difference made by the clinical availability of the data (Table 1). In terms of susceptibility testing, the panel saved an average of 70.1 ± 58.2 hours but with less unity between the 2 cohorts (P = .005). Of the 66 cases with follow-up, identification via ePlex indicated an escalation of therapy in 20 (30%) and a narrowing of coverage in 31 (47%). In patients identified to have Staphylococcus aureus, BCID-GP could change antimicrobial therapy in 79%; the need for escalation of antibiotics was identified in 58% of cases. In patients with Staphylococcus epidermidis bacteremia, implementation of BCID-GP panel could have resulted in de-escalation of antimicrobial therapy in 67% of patients. The implementation of the BCID-GP panel was correlated with no significant change of in-hospital mortality (P = .72) but was correlated with a significantly decreased death-censored total length of stay (LOS) (P &lt; .001) and LOS after culture (P = .001). Conclusions: Our study has demonstrated that nonculture identification of bacteria and susceptibility can result in major improvements in antimicrobial therapy in patients, particularly those with contaminants identified.Funding: GenMark DXDisclosures: None

Clinical impact of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay on treatment decisions: a single-center retrospective study

BackgroundMetagenomic next-generation sequencing of microbial cell-free DNA (mcfDNA) allows for non-invasive pathogen detection from plasma. However, there is little data describing the optimal role for this assay in real-world clinical decision making.MethodsWe performed a single-center retrospective cohort study of adult patients for whom a mcfDNA (Karius©) test was sent between May 2019 and February 2021. Clinical impact was arbitrated after review and discussion of each case.ResultsA total of 80 patients were included. The most common reason for sending the assay was unknown microbiologic diagnosis (78%), followed by avoiding invasive procedures (14%). The test had a positive impact in 34 (43%), a negative impact in 2 (3%), and uncertain or no impact in 44 (55%). A positive impact was observed in solid organ transplant recipients (SOTR, 71.4%, p = 0.003), sepsis (71.4%, p = 0.003), and those receiving antimicrobial agents for less than 7 days prior to mcfDNA testing (i.e., 61.8%, p = 0.004). Positive impact was driven primarily by de-escalation of antimicrobial therapy.ConclusionClinical impact of mcfDNA testing was highest in SOTR, patients with sepsis and patients who had been on antimicrobial therapy for less than 7 days. Positive impact was driven by de-escalation of antimicrobial therapy which may highlight a potential role for mcfDNA in the realm of stewardship.

Comparative incidence of acute kidney injury in patients on vancomycin therapy in combination with cefepime, piperacillin-tazobactam or meropenem

Recent studies have shown that the incidence of nephrotoxicity increases when vancomycin is combined with a beta-lactam antibiotic. The objective of this study was to compare the incidence of acute kidney injury (AKI) in adult patients who received vancomycin with either piperacillin-tazobactam (VPT), cefepime (VC), or meropenem (VM). This was a single center retrospective chart review. Patients were included if they were 18 years or older, received 48 hours of combination therapy and antibiotics were started within 24 hours of each other. Exclusion criteria were receiving more than one combination of antibiotics, serum creatinine > 1.2 mg/dL, AKI at the time of inclusion, or any form of renal replacement therapy. Two hundred patients met inclusion criteria. A total of 27 (13%) patients experienced AKI. The incidence of AKI was 21.6%, 9%, and 7.4% in the VPT, VC and VM groups, respectively. A patient who received VPT was 5 times more likely to develop AKI when compared to a patient who received VC (adjusted OR 5.09 95% CI (1.51–17.08), p = 0.008) and 7 times more likely to develop AKI when compared to VM (adjusted OR 7.03 95% CI (1.97–28.08), p = 0.002). This study found a statistically significant difference in the incidence of AKI in patient receiving VPT when compared to VC or VM. This finding supports the need for careful monitoring of renal function in patients receiving VPT therapy and routine evaluation for de-escalation of antimicrobial therapy.

De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock.

De-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance. To assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance. Multicentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation. A total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11-0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14-0.70, P = 0.005). In ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality.

The impact of diagnostic microbiology on de-escalation of antimicrobial therapy in hospitalised adults

BackgroundMinimising antimicrobial overuse is needed to limit antimicrobial resistance. There is little evidence on how often microbiological testing informs antimicrobial de-escalation (e.g. stopping, shortening duration, switching to narrower spectrum or intravenous to oral switch) at 48–72 h “review and revise”. We performed a patient level analysis of diagnostic microbiology and antimicrobial prescribing to determine the impact of microbiology results on antimicrobial review outcomes.MethodsAntimicrobial prescribing data were collected for hospitalised adults from across Brighton and Sussex University Hospitals NHS Trust using routine monthly audits of prescribing practice from July 2016 to April 2017. Microbiology testing data for cultures of blood, urine, sputum and cerebrospinal fluid (CSF) were gathered from the hospital pathology database and linked to prescriptions with matching patient identification codes. Antimicrobial prescriptions were grouped into “prescription episodes” (PEs), defined as one or more antimicrobials prescribed to the same patient for the same indication. Medical records were reviewed for all PEs with positive microbiology and a randomised sample of those with negative results to assess the impact of the microbiology result on the antimicrobial prescription(s).ResultsAfter excluding topical and prophylactic prescriptions, data were available for 382 inpatient antimicrobial prescriptions grouped into 276 prescription episodes. 162/276 (59%) had contemporaneous microbiology sent. After filtering likely contaminants, 33/276 (12%) returned relevant positive results, of which 20/33 (61%) had antimicrobials changed from empiric therapy as a result with 6/33 (18%) prompting de-escalation. Positive blood and CSF tended to have greater impact than urine or sputum cultures. 124/276 (45%) PEs returned only negative microbiology, and this was documented in the medical notes less often (9/40, 23%) than positive results (28/33, 85%). Out of 40 reviewed PEs with negative microbiology, we identified just one (~ 3%) in which antimicrobials were unambiguously de-escalated following the negative result.ConclusionsThe majority of diagnostic microbiology tests sent to inform clinical management yielded negative results. However, negative microbiology contributed little to clinical decision making about antimicrobial de-escalation, perhaps reflecting a lack of trust in negative results by treating clinicians. Improving the negative predictive value of currently available diagnostic microbiology could help hospital prescribers in de-escalating antimicrobial therapy.

Empirical antimicrobial therapy of purulent-septic complications in surgical coloproctology

Object. to optimize antibacterial therapy in patients with coloproctological profile with purulent-septic complications.Materials and methods. A one-center intervention study with historical control was conducted. The intervention began in January 2017, when in the hospital FSBI «N. I. Pirogov National Medical Surgical Center» Russian Ministry of Health introduced strict monitoring of compliance with the protocols of empirical antimicrobial therapy. The study included 62 patients who underwent antibacterial therapy after operations on the colon and rectum in 2016–2017. Patients were divided into two groups with respect to the beginning of the intervention: 2016 – comparison group (A), 2017 – main group (B).Results. There was a slight decrease in the total consumption of antibacterial drugs in coloproctological patients from 823.0 to 691.0 Defined Daily Dose (DDD, established daily dose), as well as the average consumption of antibiotics per patient from 26.5 to 22.3 DDD. An increase in the number of cases of compliance with the approved protocol of empirical antimicrobial therapy (AMT) was revealed from 32.3 % in group A to 67.7 % in group B, p = 0.01. The frequency of adequate empirical antibiotic prescribing increased from 71.0 to 93.5 %, p = 0.042. A significant increase in the frequency of de-escalation of AMT was revealed from 3.2 % in group A to 25.8 % in group B, p = 0.026.Conclusion. Monitoring compliance with empirical AMT protocols allowed to increase the number of cases of adherence to approved protocols, which positively affected the frequency of adequate appointment of empirical AMT, and also led to increase the number of cases of de-escalation of AMT.

Confounding by indication of the safety of de-escalation in community-acquired pneumonia: Asimulation study embedded in a prospective cohort.

Observational studies have demonstrated that de-escalation of antimicrobial therapy is independently associated with lower mortality. This most probably results from confounding by indication. Reaching clinical stability is associated with the decision to de-escalate and with survival. However, studies rarely adjust for this confounder. We quantified the potential confounding effect of clinical stability on the estimated impact of de-escalation on mortality in patients with community-acquired pneumonia. Data were used from the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA). The primary outcome was 30-day mortality. We performed Cox proportional-hazards regression with de-escalation as time-dependent variable and adjusted for baseline characteristics using propensity scores. The potential impact of unmeasured confounding was quantified through simulating a variable representing clinical stability on day three, using data on prevalence and associations with mortality from the literature. Of 1,536 included patients, 257 (16.7%) were de-escalated, 123 (8.0%) were escalated and in 1156 (75.3%) the antibiotic spectrum remained unchanged. Crude 30-day mortality was 3.5% (9/257) and 10.9% (107/986) in the de-escalation and continuation groups, respectively. The adjusted hazard ratio of de-escalation for 30-day mortality (compared to patients with unchanged coverage), without adjustment for clinical stability, was 0.39 (95%CI: 0.19–0.79). If 90% to 100% of de-escalated patients were clinically stable on day three, the fully adjusted hazard ratio would be 0.56 (95%CI: 0.27–1.12) to 1.04 (95%CI: 0.49–2.23), respectively. The simulated confounder was substantially stronger than any of the baseline confounders in our dataset. Quantification of effects of de-escalation on patient outcomes without proper adjustment for clinical stability results in strong negative bias. This study suggests the effect of de-escalation on mortality needs further well-designed prospective research to determine effect size more accurately.

Implications of culture collection after the first antimicrobial dose in septic emergency department patients

BackgroundPrevious research has illustrated the importance of collection of microbiologic cultures prior to first antimicrobial dose (FAD) in septic patients to avoid sterilization of pathogens and thus allowing confirmation of infection, identification of pathogen(s), and de-escalation of antimicrobial therapy. There is currently a lack of literature characterizing the implications and clinical courses of patients who have cultures collected after FAD. MethodsIn this single-center, retrospective chart review of 163 sepsis cases in the emergency department, the primary outcome was positive-cultures from appropriate sources. Secondary outcomes included time to FAD (TFAD); ICU and hospital lengths of stay (LOS); rate of antibiotic restart; secondary infection rate; readmission; and mortality. Cases were divided based on culture timing relative to FAD: culture-first (CF) or antimicrobial-first (AF) cohorts. ResultsCultures were more frequently positive in the CF cohort vs. AF cohort overall (80.4% vs. 46.7%, p < 0.005). TFAD was greater in the CF cohort (202 min vs. 153 min, p = 0.036) and these cases trended toward shorter ICU and hospital LOS (6.8 days vs. 8.4 days, p = 0.122; 11.5 days vs. 13.5 days, p = 0.218). Antibiotic restart was less frequent in the CF cohort (10.7% vs. 17.8%, p < 0.005). C. difficile infection and mortality trended toward lower incidence in the CF cohort, and readmission rates were similar. ConclusionsSepsis patients who have cultures obtained after FAD (represented in the AF cohort) had less positive-cultures, shorter TFAD, a trend toward longer ICU and hospital LOS, and perhaps higher risk of C. difficile infection, and mortality.

Knowledge, Attitudes, and Practices Regarding Antimicrobial Use and Stewardship Among Prescribers at Acute-Care Hospitals.

OBJECTIVE To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing. DESIGN Cross-sectional survey. SETTING Online survey. PARTICIPANTS A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network. INTERVENTION The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing. RESULTS In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some "usually" or "always" preferred using the most broad-spectrum empiric antimicrobials possible (32%). Nearly all (99%) reported reviewing antimicrobial appropriateness at 48-72 hours, but only 55% reported "always" doing so. Furthermore, 45% of respondents felt that they had not received adequate training regarding antimicrobial prescribing. Some respondents lacked confidence selecting empiric therapy using antibiograms (30%), interpreting susceptibility results (24%), de-escalating therapy (18%), and determining duration of therapy (31%). Postprescription review and feedback (PPRF) was the most commonly cited AS intervention (79%) with potential to improve patient care. CONCLUSIONS Barriers to appropriate antimicrobial selection and de-escalation of antimicrobial therapy were identified among front-line prescribers in acute-care hospitals. Prescribers desired more AS-related education and identified PPRF as the most helpful AS intervention to improve patient care. Educational interventions should be preceded by and tailored to local assessment of educational needs. Infect Control Hosp Epidemiol 2018;39:316-322.

Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial

IntroductionWithin the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of...

Successful Implementation of BCID Across Large Healthcare System Using a Central Testing Laboratory and Multidisciplinary Pharmacy Team

BackgroundMolecular testing has been shown to improve turnaround time (TAT) for identifying bloodborne pathogens. Early results can inform directed escalation or de-escalation of antimicrobial therapy. Paired with antibiotic stewardship, rapid pathogen identification has been shown to reduce antibiotic utilization and improve patient outcomes. However, many of these studies were in single site institutions. We evaluated implementation of the BioFireÒ FilmArray Blood Culture Identification System (BCID) across 3 acute care facilities utilizing a central testing laboratory at Carolinas Healthcare.MethodsBCID testing was implemented over a 2-month period. A multidisciplinary team developed standard protocols for processing, transport and testing, with communication of results across teams of stewardship pharmacists. Standard algorithms were used across all facilities to guide antibiotic prescribing. Data were collected between January and May 2017 from three sources (BacTec, Theradoc and Cerner EMR). Positive bottles were tracked from the time of the positive bottle alert through pharmacist intervention. We evaluate rates of interventions and consistency using variance comparison tests.Results708 positive blood cultures were identified at 3 acute care facilities and tested using BCID. TAT from positive bottle to BCID result was 4.6 (95% CI 4.4–4.8) hours. 86.7% (614/708) were on appropriate empiric antimicrobials at the time of the BCID result. 28.0% (198/708) required a recommendation by a pharmacist. 39.6% (78/197) had an escalation recommendation while 26.4% (52/197) had a de-escalation recommendation. There was no significant variation across shifts or sites except with de-escalation where variation was greater than 10% across sites (P = 0.02).ConclusionBCID testing was successfully implemented across a large integrated healthcare system using central testing laboratory paired with a team of stewardship and virtual care pharmacists. Our strategy provided timely and reproducible results across facilities and shifts. Implementation of BCID allowed for more pathogen directed therapy at all facilities with variability in need for escalation and de-escalation of therapy between facilities.Disclosures All authors: No reported disclosures.

Utilizing Nanosphere's Verigene® Technology to Assist With Possible Rapid Pharmacologic De-escalation of Antimicrobial Therapy in A University Hospital Setting

Utilizing Nanosphere's Verigene® Technology to Assist With Possible Rapid Pharmacologic De-escalation of Antimicrobial Therapy in A University Hospital Setting

Ventilator-associated pneumonia: the influence of bacterial resistance, prescription errors, and de-escalation of antimicrobial therapy on mortality rates

Ventilator-associated pneumonia is the most prevalent nosocomial infection in intensive care units and is associated with high mortality rates (14–70%). AimThis study evaluated factors influencing mortality of patients with Ventilator-associated pneumonia (VAP), including bacterial resistance, prescription errors, and de-escalation of antibiotic therapy. MethodsThis retrospective study included 120 cases of Ventilator-associated pneumonia admitted to the adult adult intensive care unit of the Federal University of Uberlândia. The chi-square test was used to compare qualitative variables. Student's t-test was used for quantitative variables and multiple logistic regression analysis to identify independent predictors of mortality. FindingsDe-escalation of antibiotic therapy and resistant bacteria did not influence mortality. Mortality was 4 times and 3 times higher, respectively, in patients who received an inappropriate antibiotic loading dose and in patients whose antibiotic dose was not adjusted for renal function. Multiple logistic regression analysis revealed the incorrect adjustment for renal function was the only independent factor associated with increased mortality. ConclusionPrescription errors influenced mortality of patients with Ventilator-associated pneumonia, underscoring the challenge of proper Ventilator-associated pneumonia treatment, which requires continuous reevaluation to ensure that clinical response to therapy meets expectations.

Impact of antimicrobial strategies on clinical outcomes of adults with septic shock and community-onset Enterobacteriaceae bacteremia: de-escalation is beneficial

To investigate the clinical outcomes of patients with septic shock related to community-onset monomicrobial Enterobacteriaceae (CoME) bacteremia as categorized by the strategy of antimicrobial therapy, a retrospective and observational study was conducted. Clinical information on the patients was obtained from medical records. Antibiotic regimens were ranked according to their activity spectrum against Enterobacteriaceae (category IV, highest; I, lowest). De-escalation was defined as a switch to a category with a narrower spectrum of coverage within 5days after the bacteremic onset. Of the 189 eligible patients, 86 (45.5%) patients received de-escalation antibiotic therapy, and most (48, 55.8%) of the patients were empirically treated first with a category IV antibiotic. In a multivariate analysis for 28-day mortality, of several independent predictors, the de-escalation strategy was protective (odds ratio, 0.37; P=0.04). In conclusion, for patients with CoME bacteremia and available susceptibility data, de-escalation of antimicrobial therapy was beneficial for improving clinical outcome.

Point-Counterpoint: Quantitative Cultures of Bronchoscopically Obtained Specimens Should Be Performed for Optimal Management of Ventilator-Associated Pneumonia

ABSTRACT Ventilator-associated pneumonia (VAP) is a leading cause of health care-associated infection. It has a high rate of attributed mortality, and this mortality is increased in patients who do not receive appropriate empirical antimicrobial therapy. As a result of the overuse of broad-spectrum antimicrobials such as the carbapenems, strains of Acinetobacter , Enterobacteriaceae , and Pseudomonas aeruginosa susceptible only to polymyxins and tigecycline have emerged as important causes of VAP. The need to accurately diagnose VAP so that appropriate discontinuation or de-escalation of antimicrobial therapy can be initiated to reduce this antimicrobial pressure is essential. Practice guidelines for the diagnosis of VAP advocate the use of bronchoalveolar lavage (BAL) fluid obtained either bronchoscopically or by the use of a catheter passed through the endotracheal tube. The CDC recommends that quantitative cultures be performed on these specimens, using ≥10 4 CFU/ml to designate a positive culture ( http://www.cdc.gov/nhsn/TOC_PSCManual.html , accessed 30 October 2012). However, there is no consensus in the clinical microbiology community as to whether these specimens should be cultured quantitatively, using the aforementioned designated bacterial cell count to designate infection, or by a semiquantitative approach. We have asked Vickie Baselski, University of Tennessee Health Science Center, who was the lead author on one of the seminal papers on quantitative BAL fluid culture, to explain why she believes that quantitative BAL fluid cultures are the optimal strategy for VAP diagnosis. We have Stacey Klutts, University of Iowa, to advocate the semiquantitative approach.