Antimicrobial Stewardship in the ICU.

Increasing rates of infection and multidrug-resistant pathogens, along with a high use of antimicrobial therapy, make the intensive care unit (ICU) an ideal setting for implementing and supporting antimicrobial stewardship efforts. Overuse of antimicrobial agents is common in the ICU, as practitioners are challenged daily with achieving early, appropriate empiric antimicrobial therapy to improve patient outcomes. While early antimicrobial stewardship programs focused on the financial implications of antimicrobial overuse, current goals of stewardship programs align closely with those of critical care providers-to optimize patient outcomes, reduce development of resistance, and minimize adverse outcomes associated with antibiotic overuse and misuse such as acute kidney injury and Clostridioides difficile-associated disease. Significant opportunities exist in the ICU for critical care clinicians to support stewardship practices at the bedside, including thoughtful and restrained initiation of antimicrobial therapy, use of biomarkers in addition to rapid diagnostics, Staphylococcus aureus screening, and traditional microbiologic culture and susceptibilities to guide antibiotic de-escalation, and use of the shortest duration of therapy that is clinically appropriate. Integration of critical care practitioners into the initiatives of antimicrobial stewardship programs is key to their success. This review summarizes key components of antimicrobial stewardship programs and mechanisms for critical care practitioners to share the responsibility for antimicrobial stewardship.

Effectiveness of fidaxomicin versus oral vancomycin in the treatment of recurrent clostridioides difficile.

WHAT IS KNOWN AND OBJECTIVE: The 2017 IDSA/SHEA Clinical Practice Guidelines for Clostridioides difficile infection (CDI) recommend treating recurrent episodes with fidaxomicin or oral vancomycin, but there is little evidence to support one strategy over another, particularly beyond the first recurrence. The aim of this study was to compare clinical outcomes in patients with recurrent CDI treated with vancomycin vs. fidaxomicin. METHODS: This retrospective study evaluated inpatients with recurrent CDI treated with vancomycin or fidaxomicin between 1 January 2013 and 1 May 2019. The primary outcome was CDI recurrence. Secondary outcomes included re-infection, treatment failure, infection-related length of stay (IRLOS) and in-hospital all-cause mortality (IHACM). The Wilcoxon rank-sum test, Pearson's chi-square test or Fisher's exact test was utilized, as appropriate. A multivariable logistic regression (MLR) model was used to estimate the adjusted odds ratio and 95% confidence interval assessing recurrence while adjusting for confounding variables. A survival analysis was also conducted. RESULTS: 135 patients met the inclusion criteria (35 fidaxomicin vs. 100 vancomycin). There was no difference in CDI recurrence [7 (20%) fidaxomicin vs. 11 (11%) vancomycin, p = 0.18]; this persisted in the MLR model (OR: 0.85 [95% CI 0.27-2.7]) and survival analysis (p = 0.1954). Additionally, there was no difference in re-infection rate (p = 0.73), treatment failure (p = 0.13), IRLOS (p = 0.19) or IHACM (p = 0.65). WHAT IS NEW AND CONCLUSION: This represents the first analysis of CDI recurrence that included patients with >2 prior episodes of CDI. The study found no difference in additional recurrences when patients were treated with oral vancomycin vs fidaxomicin for recurrent CDI. However, the current study is limited by the small sample size available for inclusion. Prospective randomized studies with larger sample sizes are needed to confirm this study's conclusions.

Efficacy of combination therapy versus monotherapy in the treatment of Stenotrophomonas maltophilia pneumonia.

BACKGROUND: Stenotrophomonas maltophilia is intrinsically resistant to several antibiotics, making it potentially challenging to treat. Studies have demonstrated treatment failures and resistance development with monotherapy (MT); however, clinical data are limited with combination therapy (CT). OBJECTIVES: To compare clinical outcomes with CT versus MT for S. maltophilia pneumonia. METHODS: This was a retrospective cohort study of patients admitted between November 2011 and October 2017 with S. maltophilia pneumonia who received at least 48 h of effective therapy. The primary outcome was clinical response after 7 days of effective therapy with CT versus MT. Secondary outcomes included development of a non-susceptible isolate, 30 day microbiological cure, infection recurrence, infection-related mortality and all-cause mortality. The Wilcoxon rank sum test, the Pearson χ2 test and Fisher's exact test were utilized for univariate analyses. A multivariable logistic regression model was used to assess clinical response while adjusting for confounding variables. RESULTS: Of 252 patients with S. maltophilia pneumonia included, 38 received CT and 214 received MT. There was no difference in 7 day clinical response with CT versus MT (47.4% versus 39.7%, P = 0.38), even after controlling for immune status, APACHE II score and polymicrobial pneumonia (adjusted OR 1.51, 95% CI 0.63-3.65). Thirty day microbiological cure (P = 0.44), recurrence (P = 0.53), infection-related mortality (P = 0.19) and isolation of a non-susceptible isolate during or after therapy (P = 1.00 each) were also similar between both groups; however, 30 day all-cause mortality was greater with CT (P = 0.03). CONCLUSIONS: CT had similar rates of clinical efficacy and resistance development compared with MT for S. maltophilia pneumonia.

Methicillin-resistant Staphylococcus aureus in Ohio EMS Providers: A Statewide Cross-sectional Study.

The objective was to determine the nasal carriage prevalence of methicillin-resistant Staphylococcus aureus (MRSA) among emergency medical service (EMS) personnel and the associated risk factors. A cross-sectional study was conducted among Ohio EMS personnel randomly sampled from 84 urban and rural agencies. Surveys assessing demographics, occupational history, health, cohabitation status, and hygiene practice were collected with nasal swabs from those who enrolled. Survey weight adjusted analysis was performed (1) to estimate MRSA nasal carriage prevalence of Ohio EMS providers, and (2) to identify variables associated with MRSA. MRSA was detected in 4.6% (13/280) EMS personnel sampled. After employing a survey-weighted analysis the following risk factors associated with MRSA carriage were identified: those who did not practice frequent hand hygiene after glove use (OR, 10.51; 95% CI, 2.54-43.45; P = 0.0012), living with someone with a recent staphylococcal infection (OR, 9.02; 95% CI, 1.03-78.98; P = 0.0470), and individuals with low frequency of hand washing (< 8 times per shift) (OR, 4.20; 95% CI 1.02-17.27; P = 0.0468). An additional risk factor identified through the logistic regression analysis on the study population was EMS workers with an open wound or skin infection (OR, 6.75; 95% CI, 1.25-36.36; P = 0.0262). However, this was not significant in the survey-weighted analysis. The high prevalence of MRSA in Ohio EMS personnel is both an occupational hazard and patient safety concern. Implementing methods to reinforce CDC guidelines for proper hygiene could decrease MRSA found in the EMS setting. Previous literature suggests that a reduction in MRSA colonization can lead to decreases in transmission and improved health for both patients and personnel.

Molecular and clinical characteristics of hospital and community onset methicillin-resistant Staphylococcus aureus strains associated with bloodstream infections.

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are classified epidemiologically as health care-associated hospital onset (HAHO)-, health care-associated community onset (HACO)-, or community-associated (CA)-MRSA. Clinical and molecular differences between HAHO- and HACO-MRSA BSI are not well known. Thus, we evaluated clinical and molecular characteristics of MRSA BSI to determine if distinct features are associated with HAHO- or HACO-MRSA strains. Molecular genotyping and medical record reviews were conducted on 282 MRSA BSI isolates from January 2007 to December 2009. MRSA classifications were 38% HAHO-, 54% HACO-, and 8% CA-MRSA. Comparing patients with HAHO-MRSA to those with HACO-MRSA, HAHO-MRSA patients had significantly higher rates of malignancy, surgery, recent invasive devices, and mortality and longer hospital stays. Patients with HACO-MRSA were more likely to have a history of renal failure, hemodialysis, residence in a long-term-care facility, long-term invasive devices, and higher rate of MRSA relapse. Distinct MRSA molecular strain differences also were seen between HAHO-MRSA (60% staphylococcal cassette chromosome mec type II [SCCmec II], 30% SCCmec III, and 9% SCCmec IV) and HACO-MRSA (47% SCCmec II, 35% SCCmec III, and 16% SCCmec IV) (P < 0.001). In summary, our study reveals significant clinical and molecular differences between patients with HAHO- and HACO-MRSA BSI. In order to decrease rates of MRSA infection, preventive efforts need to be directed toward patients in the community with health care-associated risk factors in addition to inpatient infection control.

Impact of a Cost Visibility Tool in the Electronic Medical Record on Antibiotic Prescribing in an Academic Medical Center.

BACKGROUND: Studies evaluating the impact of passive cost visibility tools on antibiotic prescribing are lacking. OBJECTIVE: The objective of this study was to evaluate whether the implementation of a passive antibiotic cost visibility tool would impact antibiotic prescribing and decrease antibiotic spending. METHODS: An efficiency and effectiveness initiative (EEI) was implemented in October 2012. To support the EEI, an antibiotic cost visibility tool was created in June 2013 displaying the relative cost of antibiotics. Using an observational study of interrupted time series design, 3 time frames were studied: pre EEI, post EEI, and post cost visibility tool implementation. The primary outcome was antibiotic cost per 1,000 patient days. Secondary outcomes included case mix index (CMI)-adjusted antibiotic cost per 1,000 patient days and utilization of the cost visibility tool. RESULTS: Initiation of the EEI was associated with a $4,675 decrease in antibiotic cost per 1,000 patient days (P = .003), and costs continued to decrease in the months following EEI (P = .009). After implementation of the cost visibility tool, costs remained stable (P = .844). Despite CMI increasing over time, adjustment for CMI had no impact on the directionality or statistical significance of the results. CONCLUSION: Our study demonstrated a significant and sustained decrease in antibiotic cost per 1,000 patient days when focused medication cost reduction efforts were implemented, but passive cost visibility tool implementation was not associated with additional cost reduction. Antibiotic cost visibility tools may be of most benefit when prior medication cost reduction efforts are lacking or when an active intervention is incorporated.

Nephrotoxicity Risk Factors and Intravenous Vancomycin Dosing in the Immediate Postoperative Period Following Antibiotic-Impregnated Cement Spacer Placement.

BACKGROUND: Several case reports have documented acute kidney injury (AKI) attributable to antibiotic-impregnated cement (AIC) spacers. OBJECTIVES: To identify AKI risk factors among patients who underwent AIC placement and determine whether vancomycin-AIC placement affects systemic vancomycin dosing. METHODS: Phase 1 was a case-control study to identify AKI risk factors among patients who underwent AIC placement. Cases experienced AKI; controls had unchanged renal function. Phase 2 was a retrospective cohort study. Patients who received ≥72 hours of intravenous (IV) vancomycin were divided into 2 groups according to whether they underwent vancomycin-AIC placement. Primary outcome was number of vancomycin dosing changes. RESULTS: Phase 1: Among 26 cases and 74 controls AKI risk factors on univariate and multivariable analysis included exposure to angiotensin-converting-enzyme (ACE) inhibitor exposure within 7 days of AIC placement (42% vs 20%, P = 0.03) and piperacillin-tazobactam within 7 days following AIC placement (31% vs 12%, P = 0.03). Phase 2: Among 53 patients who underwent vancomycin-AIC placement and 104 who underwent another surgery type, vancomycin was adjusted more frequently in patients who underwent vancomycin-AIC placement (28% vs 15%, P = 0.06). CONCLUSIONS: Among patients who undergo AIC placement with vancomycin and/or tobramycin, exposure to ACE inhibitors and piperacillin-tazobactam are associated with increased risk of AKI in the immediate postoperative period. No empirical adjustments to IV vancomycin dosing are necessary in patients undergoing vancomycin-AIC placement.

Is the "low-hanging fruit" worth picking for antimicrobial stewardship programs?

A new antimicrobial stewardship program can be overwhelmed at the breadth of interventions and education required to conduct a successful program. The expression "low-hanging fruit," in reference to stewardship, refers to selecting the most obtainable targets rather than confronting more complicated management issues. These targets include intravenous-to-oral conversions, batching of intravenous antimicrobials, therapeutic substitutions, and formulary restriction. These strategies require fewer resources and less effort than other stewardship activities; however, they are applicable to a variety of healthcare settings, including limited-resource hospitals, and have demonstrated significant financial savings. Our stewardship program found that staged and systematic interventions that focus on obvious areas of need, that is, low hanging fruit, provided early successes in our expanded program with a substantial cumulative cost savings of $832,590.

Methicillin-resistant Staphylococcus aureus sequence type 239-III, Ohio, USA, 2007-2009.

Methicillin-resistant Staphylococcus aureus (MRSA) is a human pathogen that has diverse molecular heterogeneity. Most MRSA strains in the United States are pulsed-field gel electrophoresis USA100 sequence type (ST) 5 and USA300 ST8. Infections with MRSA ST239-III are common and found during health care-associated outbreaks. However, this strain has been rarely reported in the United States. As part of a study supported by the Prevention Epicenter Program of the Centers for Disease Control and Prevention (Atlanta, GA, USA), which evaluated transmission of MRSA among hospitals in Ohio, molecular typing identified 78 (6%) of 1,286 patients with MRSA ST239-III infections. Ninety-five percent (74/78) of these infections were health care associated, and 65% (51/78) of patients had histories of invasive device use. The crude case-fatality rate was 22% (17/78). Identification of these strains, which belong to a virulent clonal group, emphasizes the need for molecular surveillance.

Case-case-control study of risk factors for carbapenem-resistant Enterobacterales infections among hospitalized patients.

Objective: To identify important risk factors for carbapenem-resistant Enterobacterales (CRE) infections among hospitalized patients. Design: We utilized a case-case-control design that compared patients with CRE infections to patients with carbapenem-susceptible Enterobacterales (CSE) infections and randomly selected controls during the period from January 2011 through December 2016. Setting: The study population was selected from patients at a large metropolitan tertiary-care and instructional medical center. Patients: Cases of CRE were defined as initial admission of adults diagnosed with a bacterial infection of an Enterobacterales species resistant clinically or through sensitivity testing to carbapenems 48 hours or more after admission. Cases of CSE were selected from the same patient population as the CRE cases within a 30-day window for admission, with diagnostic pathogens identified as susceptible to carbapenems. Controls were defined as adult patients admitted to any service within a 30-day window from a CRE case for >48 hours who did not meet either of the above case definitions during that admission. Results: Antibiotic exposure within 90 days prior to admission and length of hospital stay were both associated with increased odds of CRE and CSE infections compared to controls. Patients with CRE infections had >18 times greater odds of prior antibiotic exposure compared to patients with CSE infections. Conclusions: Antibiotic exposure and increased length of hospital stay may result in increased patient risk of developing an infection resistant to carbapenems and other ß-lactams.

Market withdrawal of new molecular entities approved in the United States from 1980 to 2009.

PURPOSE: Economic factors, market dynamics, and safety issues are largely responsible for decisions to withdraw pharmaceutical products from the market. In this study, new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) were examined in the USA from 1980 to 2009. METHODS: Data were obtained from the FDA, Micromedex, Medline, and Lexis-Nexis. Descriptive analyses were used to classify product discontinuations by therapeutic category, time frame for discontinuation, and reason for withdrawal. RESULTS: There were 740 NMEs approved by the FDA during the study period. As of 1 December 2010, the number of drugs discontinued was 118 (15.9%). Discontinuations were the highest for antiparasitic products, insecticides, and repellents (6, 33.3% of approvals), systemic hormonal preparations excluding sex hormones and insulins (5, 33.3%), musculo-skeletal system (11, 32.4%), diagnostic agents (16, 28.1%), and anti-infectives for systemic use (27, 25.2%). Safety was the primary reason for withdrawing 26 drugs (3.5% of approvals). CONCLUSIONS: Approximately one in seven approved NMEs were discontinued from the market in the period of 1980-2009. Less than one-quarter (22%) of the total withdrawals were attributed to safety reasons. An ongoing evaluation of new drugs throughout their product life cycle is important to determine their efficacy, safety, and value to society.

Synovial Fluid-Induced Aggregation Occurs across Staphylococcus aureus Clinical Isolates and is Mechanistically Independent of Attached Biofilm Formation.

Rapid synovial fluid-induced aggregation of Staphylococcus aureus is currently being investigated as an important factor in the establishment of periprosthetic joint infections (PJIs). Pathogenic advantages of aggregate formation have been well documented in vitro, including recalcitrance to antibiotics and protection from host immune defenses. The objective of the present work was to determine the strain dependency of synovial fluid-induced aggregation by measuring the degree of aggregation of 21 clinical S. aureus isolates cultured from either PJI or bloodstream infections using imaging and flow cytometry. Furthermore, by measuring attached bacterial biomass using a conventional crystal violet assay, we assessed whether there is a correlation between the aggregative phenotype and surface-associated biofilm formation. While all of the isolates were stimulated to aggregate upon exposure to bovine synovial fluid (BSF) and human serum (HS), the extent of aggregation was highly variable between individual strains. Interestingly, the PJI isolates aggregated significantly more upon BSF exposure than those isolated from bloodstream infections. While we were able to stimulate biofilm formation with all of the isolates in growth medium, supplementation with either synovial fluid or human serum inhibited bacterial surface attachment over a 24 h incubation. Surprisingly, there was no correlation between the degree of synovial fluid-induced aggregation and quantity of surface-associated biofilm as measured by a conventional biofilm assay without host fluid supplementation. Taken together, our findings suggest that synovial fluid-induced aggregation appears to be widespread among S. aureus strains and mechanistically independent of biofilm formation. IMPORTANCE Bacterial infections of hip and knee implants are rare but devastating complications of orthopedic surgery. Despite a widespread appreciation of the considerable financial, physical, and emotional burden associated with the development of a prosthetic joint infection, the establishment of bacteria in the synovial joint remains poorly understood. It has been shown that immediately upon exposure to synovial fluid, the viscous fluid in the joint, Staphylococcus aureus rapidly forms aggregates which are resistant to antibiotics and host immune cell clearance. The bacterial virulence associated with aggregate formation is likely a step in the establishment of prosthetic joint infection, and as such, it has the potential to be a potent target of prevention. We hope that this work contributes to the future development of therapeutics targeting synovial fluid-induced aggregation to better prevent and treat these infections.

Implementation of an antimicrobial stewardship program in a veterinary medical teaching institution.

Widespread use of antimicrobials in human and veterinary medicine drives the emergence and dissemination of resistant bacteria in human, animal, and environmental reservoirs. The AVMA and FDA Center for Veterinary Medicine have both taken public positions emphasizing the importance of incorporating antimicrobial stewardship in veterinary clinical settings; however, a model for implementing a comprehensive antimicrobial stewardship program in veterinary practice is not readily available. In 2015, The Ohio State University College of Veterinary Medicine began developing a veterinary antimicrobial stewardship program modeled on existing programs in human health-care institutions and the 7 core elements of a successful hospital antimicrobial stewardship program, as defined by the CDC. The program includes comprehensive antimicrobial use guidelines, active environmental surveillance, and enhanced infection control procedures in The Ohio State University Veterinary Medical Center, along with routine monitoring and reporting of antimicrobial prescribing practices and antimicrobial susceptibility patterns of common pathogens isolated from patients and the hospital environment. Finally, programs have been developed to educate clinicians, staff, and students on antimicrobial resistance and appropriate antimicrobial prescribing practices. The antimicrobial stewardship program has been designed to help clinicians and students confidently make judicious antimicrobial use decisions and provide them with actionable steps that can help them act as strong stewards while providing the best care for their patients. This report describes our program and the process involved in developing it, with the intent that the program could serve as a potential model for other veterinary medical institutions.

An antimicrobial stewardship program's impact with rapid polymerase chain reaction methicillin-resistant Staphylococcus aureus/S. aureus blood culture test in patients with S. aureus bacteremia.

Rapid organism detection of Staphylococcus aureus bacteremia and communication to clinicians expedites antibiotic optimization. We evaluated clinical and economic outcomes of a rapid polymerase chain reaction methicillin­resistant S. aureus/S. aureus blood culture test (rPCR). This single­center study compared inpatients with S. aureus bacteremia admitted from 1 September 2008 through 31 December 2008 (pre­rPCR) and those admitted from 10 March 2009 through 30 June 2009 (post­rPCR). An infectious diseases pharmacist was contacted with results of the rPCR; effective antibiotics and an infectious diseases consult were recommended. Multivariable regression assessed clinical and economic outcomes of the 156 patients. Mean time to switch from empiric vancomycin to cefazolin or nafcillin in patients with methicillin­susceptible S. aureus bacteremia was 1.7 days shorter post­rPCR (P = .002). In the post­rPCR methicillin­susceptible and methicillin­resistant S. aureus groups, the mean length of stay was 6.2 days shorter (P = .07) and the mean hospital costs were $21,387 less (P = .02). rPCR allows rapid differentiation of S. aureus bacteremia, enabling timely, effective therapy and is associated with decreased length of stay and health care costs.

Quality of traditional surveillance for public reporting of nosocomial bloodstream infection rates.

CONTEXT: Central line-associated bloodstream infection (BSI) rates, determined by infection preventionists using the Centers for Disease Control and Prevention (CDC) surveillance definitions, are increasingly published to compare the quality of patient care delivered by hospitals. However, such comparisons are valid only if surveillance is performed consistently across institutions. OBJECTIVE: To assess institutional variation in performance of traditional central line-associated BSI surveillance. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of 20 intensive care units among 4 medical centers (2004-2007). Unit-specific central line-associated BSI rates were calculated for 12-month periods. Infection preventionists, blinded to study participation, performed routine prospective surveillance using CDC definitions. A computer algorithm reference standard was applied retrospectively using criteria that adapted the same CDC surveillance definitions. MAIN OUTCOME MEASURES: Correlation of central line-associated BSI rates as determined by infection preventionist vs the computer algorithm reference standard. Variation in performance was assessed by testing for institution-dependent heterogeneity in a linear regression model. RESULTS: Forty-one unit-periods among 20 intensive care units were analyzed, representing 241,518 patient-days and 165,963 central line-days. The median infection preventionist and computer algorithm central line-associated BSI rates were 3.3 (interquartile range [IQR], 2.0-4.5) and 9.0 (IQR, 6.3-11.3) infections per 1000 central line-days, respectively. Overall correlation between computer algorithm and infection preventionist rates was weak (ρ = 0.34), and when stratified by medical center, point estimates for institution-specific correlations ranged widely: medical center A: 0.83; 95% confidence interval (CI), 0.05 to 0.98; P = .04; medical center B: 0.76; 95% CI, 0.32 to 0.93; P = .003; medical center C: 0.50, 95% CI, -0.11 to 0.83; P = .10; and medical center D: 0.10; 95% CI -0.53 to 0.66; P = .77. Regression modeling demonstrated significant heterogeneity among medical centers in the relationship between computer algorithm and expected infection preventionist rates (P < .001). The medical center that had the lowest rate by traditional surveillance (2.4 infections per 1000 central line-days) had the highest rate by computer algorithm (12.6 infections per 1000 central line-days). CONCLUSIONS: Institutional variability of infection preventionist rates relative to a computer algorithm reference standard suggests that there is significant variation in the application of standard central line-associated BSI surveillance definitions across medical centers. Variation in central line-associated BSI surveillance practice may complicate interinstitutional comparisons of publicly reported central line-associated BSI rates.

Improved surveillance for surgical site infections after orthopedic implantation procedures: extending applications for automated data.

BACKGROUND: Screening methods that use automated data may streamline surgical site infection (SSI) surveillance and improve the accuracy and comparability of data on SSIs. We evaluated the use of automated inpatient diagnosis codes and pharmacy data to identify SSIs after arthroplasty. METHODS: This retrospective cohort study at 8 hospitals involved weighted, random samples of medical records from 2128 total hip arthroplasty (THA) procedures performed from 1 July 2002 through 30 June 2004, and 4194 total knee arthroplasty (TKA) procedures performed from 1 July 2003 through 30 June 2005. We compared routine surveillance with screening of inpatient pharmacy data and diagnoses codes followed by medical record review to confirm SSI status. RESULTS: Records from 696 THA and 1009 TKA procedures were reviewed. The SSI rates were nearly double those determined by routine surveillance (1.32% [95% confidence interval, 0.83%-1.81%] vs. 0.75% for THA; 1.83% [95% confidence interval, 1.43%-2.23%] vs. 0.71% for TKA). An inpatient diagnosis code for infection within a year after the operation had substantially higher sensitivity (THA, 89%; TKA, 81%), compared with routine surveillance (THA, 56%; TKA, 39%). Adding antimicrobial exposure of 7 days after the procedure increased the sensitivity (THA, 93%; TKA, 86%). Record review confirmed SSIs after 51% of THAs and 55% of TKAs that met diagnosis code criteria and after 25% of THAs and 39% of TKAs that met antimicrobial exposure and/or diagnosis code criteria. CONCLUSIONS: Focused surveillance among a subset of patients who met diagnosis code screening criteria with or without the addition of antimicrobial exposure-based screening was more sensitive than routine surveillance for detecting SSIs after arthroplasty and could be an efficient and readily standardized adjunct to traditional methods.

Nonspecific Symptoms Lack Diagnostic Accuracy for Infection in Older Patients in the Emergency Department.

OBJECTIVES: To determine if nonspecific symptoms and fever affect the posttest probability of acute bacterial infection in older patients in the emergency department (ED). DESIGN: Preplanned, secondary analysis of a prospective observational study. SETTING: Tertiary care, academic ED. PARTICIPANTS: A total of 424 patients in the ED, 65 years or older, including all chief complaints. MEASUREMENTS: We identified presence of altered mental status, malaise/lethargy, and fever, as reported by the patient, as documented in the chart, or both. Bacterial infection was adjudicated by agreement among two or more of three expert reviewers. Odds ratios were calculated using univariable logistic regression. Positive and negative likelihood ratios (PLR and NLR, respectively) were used to determine each symptom's effect on posttest probability of infection. RESULTS: Of 424 subjects, 77 (18%) had bacterial infection. Accounting for different reporting methods, presence of altered mental status (PLR range, 1.40-2.53) or malaise/lethargy (PLR range, 1.25-1.34) only slightly increased posttest probability of infection. Their absence did not assist with ruling out infection (NLR, greater than 0.50 for both). Fever of 38°C or higher either before or during the ED visit had moderate to large increases in probability of infection (PLR, 5.15-18.10), with initial fever in the ED perfectly predictive, but absence of fever did not rule out infection (NLR, 0.79-0.92). Results were similar when analyzing lower respiratory, gastrointestinal, and urinary tract infections (UTIs) individually. Of older adults diagnosed as having UTIs, 47% did not complain of UTI symptoms. CONCLUSIONS: The presence of either altered mental status or malaise/lethargy does not substantially increase the probability of bacterial infection in older adults in the ED and should not be used alone to indicate infection in this population. Fever of 38°C or higher is associated with increased probability of infection. J Am Geriatr Soc 67:484-492, 2019.

Clinical Outcomes with Penicillin Versus Alternative ß-Lactams in the Treatment of Penicillin-Susceptible Staphylococcus aureus Bacteremia.

OBJECTIVES: To identify the impact of penicillin versus alternative ß-lactams on clinical outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Adult patients with PSSA bacteremia treated with a ß-lactam as definitive therapy. MEASUREMENTS: The primary outcome was a composite end point of 30-day clinical failure (change in PSSA therapy due to persistent or worsening signs and symptoms, PSSA bacteremia recurrence or persistence, and/or infection-related mortality) in patients treated with penicillin versus alternative ß-lactams. Secondary outcomes included infection-related and hospital length of stay (LOS), 90-day recurrence, 90-day infection-related readmission, 30-day all-cause mortality, adverse drug events (ADEs), and 30-day change in PSSA therapy due to ADEs. A subgroup analysis comparing penicillin, nafcillin, and cefazolin was also conducted. MAIN RESULTS: For the 122 patients who were included, the most common definitive therapies were nafcillin (37%), cefazolin (29%), and penicillin (21%). No difference was found in 30-day clinical failure (4% vs 11%, p=0.46), infection-related LOS (12 days vs 11 days, p=0.39), hospital LOS (12.5 days vs 12 days, p=0.69), 90-day recurrence (p=1.00), 90-day infection-related readmission (p=1.00), or 30-day all-cause mortality (p=0.45) between penicillin and other ß-lactams. The prevalence of ADEs was different among penicillin, nafcillin, and cefazolin (p=0.049), with nafcillin requiring more changes in therapy (p=0.005). CONCLUSIONS: Definitive therapy with penicillin had similar efficacy compared with alternative ß-lactams for the treatment of PSSA bacteremia. However, nafcillin was associated with more ADEs requiring a change in therapy.

Risk of acute kidney injury in critically ill surgical patients with presumed pneumonia is not impacted by choice of methicillin-resistant staphylococcus aureus therapy.

BACKGROUND: Vancomycin and linezolid are standard treatment options for nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. While acute kidney injury (AKI) is commonly attributed to vancomycin, existing data has not definitely confirmed vancomycin as an independent risk factor for AKI. AIMS: This study aimed to quantify the incidence of AKI in Surgical Intensive Care Unit (ICU) patients receiving empiric vancomycin or linezolid for nosocomial pneumonia and to identify risk factors for AKI with a focus on MRSA antibiotic therapy. MATERIALS AND METHODS: A retrospective cohort analysis of surgical ICU patients who received at least 48 h of vancomycin or linezolid for pneumonia was performed. Patients who received vancomycin were compared to those who received linezolid with a primary endpoint of AKI as defined by the risk/injury/failure/loss/end-stage renal disease (RIFLE) criteria. A modified RIFLE criteria assessing only changes in serum creatinine was also used. RESULTS: One hundred one patients were evaluated (63 vancomycin and 38 linezolid). AKI occurred in 51 (81.0%) and 32 (84.2%) patients in the vancomycin and linezolid groups (P = 0.79), respectively. Using the modified RIFLE criteria, AKI occurred in 19 (30.2%) and 14 (36.8%) patients in the vancomycin and linezolid groups (P = 0.448). After adjustment for age, diabetes mellitus, Charlson comorbidity index, and concomitant nephrotoxins, there was no difference in risk of AKI between groups (P = 0.773). CONCLUSIONS: Patients who received empiric vancomycin or linezolid for nosocomial pneumonia experienced high, but similar rates of AKI. The results suggest MRSA antibacterial therapy in this setting may not be independently indicative of AKI risk, rather the risk is likely multifactorial.