Systematic Review of the Clinical Utility of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screening for MRSA Pneumonia.

OBJECTIVE: To describe the diagnostic performance characteristics of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening for patients with pneumonia. DATA SOURCES: PubMed and Scopus were searched from 1 January 1990 to 12 December 2018 using terms methicillin-resistant Staphylococcus aureus AND (screening OR active surveillance OR surveillance culture OR targeted surveillance OR chromogenic OR PCR OR polymerase chain reaction OR rapid test) AND (nares OR nasal) AND (pneumonia OR respiratory). STUDY SELECTION AND DATA EXTRACTION: Relevant studies in humans and English were considered. DATA SYNTHESIS: In all, 19 studies, including 21 790 patients, were included. Nasal screening for MRSA had a high negative predictive value (NPV; 76% to 99.4% for relevant studies) across all types of pneumonia. Time from nasal screening to culture varied across studies. Relevance to Patient Care and Clinical Practice: MRSA nasal screening has a high NPV for MRSA involvement in pneumonia. Utilizing this test for antimicrobial stewardship program (ASP) purposes can provide a valuable tool for reducing unwarranted anti-MRSA agents and may provide additional cost benefits. A cutoff of 7 days between nasal swab and culture or infection onset seems most appropriate for use of this test for anti-MRSA agent de-escalation for ASP purposes. CONCLUSIONS: Consideration for the inclusion of the utility of MRSA nasal screening in MRSA pneumonia should be made for future pneumonia and ASP guidelines. Additional studies are warranted to fully evaluate specific pneumonia classifications, culture types, culture timing, and clinical outcomes associated with the use of this test in patients with pneumonia.

Bacteremias following autologous stem cell transplantation for multiple myeloma: Risk factors and outcomes.

BACKGROUND: Autologous stem cell transplantation (ASCT) is a commonly used treatment for multiple myeloma (MM). This retrospective cohort study characterizes the risk factors and outcomes associated with bacteremia following ASCT at a single center. METHODS: We conducted a retrospective analysis in subjects who underwent ASCT for multiple myeloma and other malignancies from May 2014 to March 2015 at a single center. The control cohort included all subjects undergoing ASCT in the same time period who did not develop bacteremia. RESULTS: During the study period, 363 ASCTs were completed in 282 discrete patients. Bacteremia was documented in 13% of all transplants. Enterococcus faecium was the most frequent species overall (14/62, 23%). Vancomycin resistance was present in 93% of E faecium isolates. Bacteremia was associated with a significantly decreased survival in patients who received their transplant after the first year of myeloma treatment. Overall survival (OS) was not significantly different in the two cohorts among patients undergoing ASCT within the first year of myeloma treatment. Survival analysis showed a significantly decreased OS in patients who developed Enterococcus bacteremia as compared to the non-bacteremia cohort. Enterococcal bacteremia was associated with significantly longer duration of neutropenia (mean 14 vs 9.7 days, P = 0.01), hospitalization (mean 61.7 vs 20.4 days, P = 0.0006), and higher mortality (69% vs 25%, P = 0.01) as compared to other bacteremias. CONCLUSION: We found a high incidence of E faecium and a low incidence of MRSA and Pseudomonas bacteremias following ASCT in our patient population. Survival analysis in our cohort suggests that the effect of underlying disease status and cumulative chemotherapy is critically important in determining outcomes related to bacteremia. Enterococcal bacteremias following ASCT were associated with significantly higher morbidity and mortality than non-enterococcal bacteremias.

Systematic Review and Meta-Analysis of Acute Kidney Injury Associated with Concomitant Vancomycin and Piperacillin/tazobactam.

Concomitant vancomycin and piperacillin/tazobactam may be associated with increased acute kidney injury (AKI) compared to vancomycin without piperacillin/tazobactam. A systematic search of Medline, Cochrane Library, and Scopus through October 2016 using ["vancomycin" and "piperacillin" and "tazobactam"] and ["AKI" or "acute renal failure" or "nephrotoxicity"] and registered meta-analysis (PROSPERO: CRD42016041646) with relevant scenarios was performed. From 307 results, fourteen observational studies totaling 3549 patients were analyzed. Concomitant vancomycin and piperacillin/tazobactam was associated with AKI in unadjusted (odds ratio (OR) 3.12, 95% confidence interval (CI) 2.04-4.78) and adjusted (aOR 3.11, 95% CI 1.77-5.47) analyses. Similar findings were seen assessing studies in adults (aOR 3.15, 95% CI 1.72-5.76), children (OR 4.55, 95% CI 2.71-10.21), and when <50% of patients received care in an intensive care unit (aOR 3.04, 95% CI 1.49-6.22) but not ≥50% (aOR 2.83, 95% CI 0.74-10.85). Increased AKI with concomitant vancomycin and piperacillin/tazobactam should be considered when determining beta-lactam therapy.

Assessing appropriateness of antimicrobial therapy: in the eye of the interpreter.

To address the increase of drug-resistant bacteria and widespread inappropriate use of antimicrobials, many healthcare institutions have implemented antimicrobial stewardship programs to promote appropriate use of antimicrobials and optimize patient outcomes. However, a consensus definition of appropriate use is lacking. We conducted a multicenter observational study to compare 4 definitions of appropriateness--a study site-specific definition, use supported by susceptibility data, use supported by electronic drug information resources (Clinical Pharmacology/Micromedex), or study site principal investigator (PI) opinion-among patients receiving 1 or more of 13 identified antimicrobials. Data were collected for 262 patients. Overall, appropriateness with the 4 definitions ranged from 79% based on PI opinion to 94% based on susceptibility data. No single definition resulted in consistently high appropriate use for all target antimicrobials. For individual antimicrobials, the definitions with the highest rate of appropriate use were Clinical Pharmacology/Micromedex support (6 of 7 antimicrobials) and susceptibility data (5 of 7 antimicrobials). For specific indications, support from susceptibility data resulted in the highest rate of appropriate use (4 of 7 indications). Overall comparisons showed that appropriateness assessed by PI opinion differed significantly compared with other definitions when stratified by either target antimicrobial or indication. The significant variability in the rate of appropriate use highlights the difficulty in developing a standardized definition that can be used to benchmark judicious antimicrobial use.

Breaking down the barriers: challenges with development and implementation of an industry-sponsored antimicrobial stewardship data collection and analysis tool.

Partnership between clinicians and the pharmaceutical industry with a focus on antimicrobial stewardship research initiatives is a necessary step toward meeting the shared goals of combating inappropriate antimicrobial use, improving patient outcomes, and minimizing resistance development. Achieving these goals requires outcomes-focused data collection and monitoring tools for antimicrobial stewardship programs (ASP) that consider real-world data about how antimicrobials are used to treat patients. Here we highlight the experiences and challenges associated with the development and implementation of an industry-sponsored electronic antimicrobial stewardship data collection and analysis tool (AS-DCAT). The benefits and risks of the industry-sponsored AS-DCAT from the perspectives of the sponsoring company and participating sites are discussed. Barriers encountered as well as general considerations and recommendations for preventing or overcoming those barriers for future studies and tool development are provided.

Development of VRE meningitis due to haematogenous spread while on high-dose daptomycin therapy.

Introduction: Vancomycin-resistant Enterococcus faecium (VRE) meningitis accounts for only 0.3%-4.0% of bacterial meningitis cases and typically occurs following neurosurgical intervention. We describe a rare case of a patient without neurological devices in situ or a recent neurological procedure who developed VRE meningitis via haematogenous spread. Optimal treatment for VRE meningitis is unknown. Case presentation: A 67-year-old male with end-stage liver failure underwent liver transplantation complicated by VRE bacteraemia and subsequently developed VRE meningitis while on high-dose daptomycin therapy (12 mg/kg/day). Due to clinical and microbiological failure with daptomycin, he was switched to linezolid and symptoms resolved rapidly. He completed 2 weeks of linezolid, fully recovered, and continued to do well without complications at the 5 month follow-up. Conclusions: This case highlights the severity of VRE infections in solid organ transplant recipients and raises concerns about daptomycin penetration into the CNS. Linezolid could be considered the preferred treatment for VRE CNS infections rather than high-dose daptomycin.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2019.

Staying current on literature related to antimicrobial stewardship can be challenging given the ever-increasing number of published articles. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an actionable intervention for 2019. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training and to identify potential intervention opportunities within one's institution.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2017.

With an increasing number of antimicrobial stewardship-related articles published each year, attempting to stay current is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an "actionable" intervention for 2017. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the "actionable" intervention used by antimicrobial stewardship programs to provide key stewardship literature for training and teaching and identify potential intervention opportunities within their institutions.

Changing the Time of Blood Collection to Determine Vancomycin Concentrations in Intensive Care Unit Patients.

BACKGROUND: Clinical practice guidelines for initiation and therapeutic drug monitoring, but not timing, of vancomycin dosing exist at many institutions. Scheduling vancomycin trough measurements and doses around the morning blood sample collection could yield more interpretable troughs and increase patient safety. OBJECTIVE: To evaluate the appropriateness of blood sample collection times for vancomycin trough measurements before and after an initiative to change the timing of blood sampling to determine vancomycin doses and trough levels in a medical intensive care unit. METHODS: A retrospective cohort study was conducted of patients in a medical intensive care unit who received intravenous vancomycin at a scheduled interval. Differences in continuous and categorical data were compared between pre- and postintervention groups. The primary outcome was proportion of blood samples collected for vancomycin trough measurements within 30 minutes of the next scheduled vancomycin dose. RESULTS: Baseline characteristics were similar between the preintervention (n = 68) and postintervention (n = 176) groups except for the percentage of blood samples drawn for trough measurements and morning laboratory tests (6% vs 81%; P < .001). Frequency of loading doses was similar between patients in the pre- and postintervention groups, as was weight-based maintenance dosing. There was no significant difference in the percentage of blood samples collected to measure vancomycin trough levels appropriately at 30, 60, or 75 minutes from the next scheduled dose. CONCLUSION: Measuring vancomycin trough levels in morning blood samples did not affect the percentage of inappropriately collected blood samples used to measure vancomycin trough levels.

Effects of staff education and standardizing dosing and collection times on vancomycin trough appropriateness in ward patients.

BACKGROUND: Many institutions have guidelines for initiation and monitoring, but not timing, of vancomycin. OBJECTIVE: Our objective was to evaluate vancomycin trough collection appropriateness before and after an initiative to change the dosing and trough collection times in ward patients. METHODS: A retrospective cohort study of ward patients from May 2014-16 who received scheduled intravenous vancomycin was performed. Nurse managers and pharmacists provided staff education. Differences between pre- and post-intervention groups were compared using student's t-test for continuous data and chi-square test for categorical data. RESULTS: Baseline characteristics were similar between the pre-intervention (n=124) and post-intervention (n=122) groups except for weight-based maintenance dose (15.3 mg/kg vs. 16.5 mg/kg, p=0.03) and percentage of troughs collected with morning labs (14% vs. 87%, p<0.001). Patients in the pre- and post-intervention groups received a similar frequency of loading doses (14.5% vs. 16%, p=0.68). There was no significant difference in percentage of vancomycin troughs collected appropriately at 30 (40% vs. 42%, p=0.72), 60 (57% vs. 63%, p=0.35), or 75 (60% vs. 68%, p=0.22) minutes from the scheduled time of the next dose. CONCLUSION: Staff education and standardizing collection of vancomycin troughs with morning blood collections did not affect the percentage of appropriately collected vancomycin troughs.

Comparative Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam or Cefepime: A Retrospective Cohort Study.

STUDY OBJECTIVE: The combination of vancomycin and piperacillin-tazobactam has been associated with an increased risk of acute kidney injury (AKI) in non-critically ill patient populations, but it is still unknown if this association exists in critically ill patients. The objective of this study was to compare the incidence of AKI development during therapy or within 72 hours after completion of therapy in adult critically ill patients who received vancomycin with concomitant piperacillin-tazobactam or cefepime. DESIGN: Retrospective cohort study. SETTING: Medical, surgical, and neuroscience intensive care units (ICUs) within a single tertiary care hospital. PATIENTS: A total of 122 critically ill patients who received at least 48 hours of combination therapy with vancomycin and piperacillin-tazobactam (49 patients) or vancomycin and cefepime (73 patients) during an ICU admission between September 2012 and December 2014. MEASUREMENTS AND MAIN RESULTS: The primary outcome was AKI development, as determined by the Acute Kidney Injury Network criteria, during combination therapy or within 72 hours of completion of combination therapy. The inverse probability of the treatment-weighting (IPTW) approach was used to account for potential treatment selection bias. AKI incidence was assessed in the unadjusted and propensity score-weighted cohorts. Of the 122 patients, 37 patients (30.3%) developed AKI. In the unadjusted analysis, the incidence of AKI was similar in the piperacillin-tazobactam group compared with the cefepime group (32.7% vs 28.8%, p=0.647). The average treatment effect between the groups was not significant, showing no association between ß-lactam choice and AKI (ß = -0.004, p=0.958). Secondary outcomes were ICU length of stay, hospital length of stay, AKI duration, and need for renal replacement therapy. The choice of ß-lactam was not a significant predictor of any of these outcomes: ICU length of stay (ß = 0.436, p=0.780), hospital length of stay (ß = 3.819, p=0.125), AKI duration (ß = -4.027, p=0.283), and need for renal replacement therapy (ß = 2.828, p=0.161). CONCLUSION: After adjusting for propensity to receive each of the treatment choices, no significant difference was found in the incidence of AKI development or other outcomes between the groups. The previously described finding that concomitant vancomycin and piperacillin-tazobactam increases AKI in non-critically ill patients may not be generalizable to the critically ill population. Prospective evaluation of this hypothesis is warranted.

A multi-center study of fidaxomicin use for Clostridium difficile infection.

PURPOSE: Fidaxomicin use in real-world clinical practice, especially for severe Clostridium difficile infection (CDI), is mainly based on single-center observational studies. The purpose of this pharmacoepidemiology study was to assess outcomes of patients given fidaxomicin based on episode number and use of concomitant antibiotics. METHODS: Fidaxomicin use over time across included hospitals in the United States was assessed using a large inpatient drug utilization database. A multicenter retrospective chart review was also conducted of hospitalized patients with CDI that received fidaxomicin between 2011 and 2013. Fidaxomicin utilization and clinical outcomes were stratified by use of fidaxomicin for first or second episode (early episodes) versus greater than or equal to episodes (later episodes). RESULTS: The overall fidaxomicin use rate was 2.16 % which increased from 0.22 % in the last two quarters of 2011 to 3.16 % in the first two quarters of 2013. A total of 102 hospitalized patients that received fidaxomicin from 11 hospitals were identified in the multicenter study. Sixty-nine patients received fidaxomicin for early (68 % with severe CDI) and 33 received for later episodes. The majority of patients received other CDI therapy including 61 patients (88 %) for early episodes and 27 (82 %) for later episodes. Concomitant non-CDI antibiotics were received by 48 patients (47 %). Rates of clinical outcomes were similar regardless of CDI episode. CONCLUSION: This study demonstrated a slow but steady increase in fidaxomicin utilization over time; most of which was combined with other systemic antibiotics. Antimicrobial stewardship teams should provide guidance on appropriate use of fidaxomicin to optimize therapy and assess the need to continue other antibiotics during CDI treatment.