Mixed methods evaluation of handshake antimicrobial stewardship on adult inpatient medicine floors.

Objective: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital. Design: Retrospective observational study. Setting: 1,278-bed academic hospital. Patients: Adults admitted to non-ICU medicine services. Interventions: A handshake stewardship team consisting of an infectious diseases (ID) physician and pharmacist reviewed charts of patients receiving antimicrobials on medicine floors without a formal ID consult. Recommendations were communicated in-person to providers and acceptance rates were examined with descriptive statistics. Additional data regarding program perception among providers were obtained via surveys. Antibiotic usage trends were extracted from National Healthcare Safety Network Antimicrobial Use option data and evaluated using an interrupted time-series analysis pre- and post-intervention. Results: The overall acceptance rate of interventions was 80%, the majority being recommendations either to discontinue (37%) or de-escalate therapy (28%). Medical residents and hospitalists rated the intervention favorably with 90% reporting recommendations were helpful all or most of the time. There was a statistically significant decrease in vancomycin (78 vs 70 DOT/1,000 d present (DP), p = 0.002) and meropenem (24 vs 17 DOT/1,000 DP, p = 0.007) usage and a statistically significant increase in amoxicillin-clavulanate usage (11 vs 15 DOT/1,000 DP, p < 0.001). Overall antibiotic usage remained unchanged by the intervention, though pre-intervention there was a nonsignificant overall increasing trend while post-intervention there was a nonsignificant decreasing trend in overall usage. There was no change in in-hospital mortality. Conclusion: The addition of handshake stewardship with adult medicine services was favorably viewed by participants and led to shifts in antibiotic usage.

Spectrum scores: Toward a better definition of de-escalation.

Spectrum scores measure antimicrobial utilization while also quantifying the spectrum of activity. Accordingly, changes in spectrum score can be used to identify antimicrobial de-escalation. We show that spectrum-score-based de-escalation has a 95.7% positive percentage agreement and 81.6% negative percentage agreement versus de-escalation defined as stopping either antistaphylococcal or antipseudomonal agents.

Assessment of Antibiotic De-escalation by Spectrum Score in Patients With Nosocomial Pneumonia: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant mortality. Guidelines recommend empiric broad-spectrum antibiotics followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure. METHODS: This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016 to 2019. Patients were enrolled if they met predefined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). The primary outcome was composite treatment failure, defined as all-cause mortality or readmission for pneumonia within 30 days of diagnosis. RESULTS: Of 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs 1026 NDE). Groups were well matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs 50.6%, P = .011). There was no difference in composite treatment failure (35.0% DE vs 33.8% NDE, P = .604). De-escalation was not associated with treatment failure on multivariable Cox regression analysis (hazard ratio, 1.13; 95% confidence interval, 0.96-1.33). Patients receiving DE had fewer antibiotic days (median 9 vs 11, P < .0001), episodes of Clostridioides difficile infection (2.2% vs 3.8%, P = .046), and hospital days (median 20 vs 22 days, P = .006). CONCLUSIONS: De-escalation and NDE resulted in similar rates of 30-day treatment failure; however, DE was associated with fewer antibiotic days, episodes of C difficile infection, and days of hospitalization.

Evaluation of Total Body Weight versus Adjusted Body Weight Liposomal Amphotericin B Dosing in Obese Patients.

Liposomal amphotericin B (LAmB) is used for various fungal infections, but it is unclear which dosing weight to use in obese patients. The purpose of this study was to compare clinical outcomes of adjusted body weight (adjBW) versus total body weight (TBW) dosing of LAmB. This single-center, retrospective cohort study included patients who received LAmB for definitive therapy and whose TBW exceeded 120% of their ideal body weight (IBW). Analyses were conducted for 3 mg/kg for adjBW versus TBW and 5 mg/kg for adjBW versus TBW. A total of 238 patients were included. For the 68 patients who received LAmB at 3 mg/kg, there were no differences in safety or efficacy outcomes. For the 170 patients who received LAmB at 5 mg/kg, significantly more patients in the TBW group experienced the primary outcome of nephrotoxicity (57% versus 35% [P value of 0.016]) and had significantly higher rates of early discontinuation of LAmB due to toxicity (33% versus 17% [P = 0.030]). There was a trend toward increased 90-day mortality in the adjBW group (60% versus 45% [P = 0.079]); however, adjBW dosing was not associated with increased mortality in an adjusted model. Given the lower rates of nephrotoxicity but a possible trend toward increased mortality in patients whose TBW exceeds 120% of their IBW, dosing LAmB by adjBW may be reasonable in patients who are not critically ill and who have lower-risk infections. In critically ill patients or those with fungal pathogens or sites of infection associated with higher mortality risk, dosing by TBW can be considered.

New Perspectives on Antimicrobial Agents: Ceftolozane-Tazobactam.

Ceftolozane-tazobactam (C/T) is a new fifth-generation cephalosporin/beta-lactamase inhibitor combination approved by the Food and Drug Administration and the European Medicines Agency for treatment of complicated intraabdominal infections, complicated urinary tract infections, and hospital-acquired pneumonia in adult patients. This review will briefly describe the pharmacology of C/T and focus on the emerging clinical trial and real-world data supporting its current utilization. Additionally, our synthesis of these data over time has set our current usage of C/T at Barnes-Jewish Hospital (BJH). C/T is primarily employed as directed monotherapy at BJH when Pseudomonas aeruginosa isolates are identified with resistance to other beta-lactams. C/T can also be used empirically in specific clinical situations at BJH prior to microbiological detection of an antibiotic-resistant P. aeruginosa isolate. These situations include critically ill patients in the intensive care unit (ICU) setting, where there is a high likelihood of infection with multidrug-resistant (MDR) P. aeruginosa; patients failing therapy with a carbapenem; specific patient populations known to be at high risk for infection with MDR P. aeruginosa (e.g., lung transplant and cystic fibrosis patients); and patients know to have previous infection or colonization with MDR P. aeruginosa.

Evaluation of a hybrid antimicrobial restriction process at a large academic medical center.

We conducted a retrospective review of a hybrid antimicrobial restriction process demonstrating adherence to appropriate use criteria in 72% of provisional-only orders, in 100% of provisional orders followed by ID orders, and in 97% of ID-initiated orders. Therapy interruptions occurred in 24% of provisional orders followed by ID orders.

Intraparenchymal extravasation of gadolinium mimicking an enhancing brain tumor.

Gadolinium (Gd)-enhanced magnetic resonance imaging plays an essential role in the detection, characterization, and staging of intracranial neoplasms and vascular abnormalities. Although Gd is helpful in a majority of situations, it can lead to diagnostic misinterpretation in the setting of active vascular extravasation. Scarce reports of intracranial extravasation of Gd are present in the literature. Here, we report the first case of surgically proven spontaneous intraparenchymal extravasation of Gd mimicking an enhancing intra-axial neoplasm in a pediatric patient. Early and accurate recognition of Gd extravasation is critical in obtaining the accurate diagnosis and triaging patients expeditiously into proper avenues of care.

Intraductal papillary mucinous neoplasm of the biliary tract: A precursor lesion to cholangiocarcinoma.

Intraductal papillary mucinous neoplasm of the biliary tract (IPMN-B) is an increasingly recognized pathologic entity characterized by intraluminal papillary masses and increased mucin secretion, resulting in obstruction and dilation of the biliary tree. These lesions, rarely seen in clinical practice in the United States, are now considered to be important precursors for the development of cholangiocarcinoma. Therefore, it is critical that radiologists become familiar with the radiographic manifestations of IPMN-B in order to diagnosis these lesions at a time when surgical resection may be curative. Here we report a pathologically confirmed case of IPMN-B in a patient with chronic ulcerative colitis and subsequently discuss the main radiographic manifestations of this rare condition across multiple imaging modalities.

Outcomes Associated With De-escalating Therapy for Methicillin-Resistant Staphylococcus aureus in Culture-Negative Nosocomial Pneumonia.

BACKGROUND: In culture-positive nosocomial pneumonia, de-escalation (DE) from broad-spectrum empirical antimicrobials to narrower-spectrum agents has shown to decrease broad-spectrum antibiotic use without compromising patient outcomes. However, uncertainty exists regarding the safety of anti-methicillin-resistant Staphylococcus aureus (MRSA) agent DE in culture-negative nosocomial pneumonia. This study aimed to determine if anti-MRSA agent DE in culture-negative nosocomial pneumonia affects 28-day and hospital mortality, ICU and hospital length of stay (LOS), treatment failure, and safety. METHODS: This single-center retrospective cohort study included adult patients admitted from 2012 to 2017 with nosocomial pneumonia and a negative respiratory culture. DE was defined as anti-MRSA agent discontinuation within 4 days of initiation. Secondary outcomes included hospital mortality, hospital and ICU LOS, treatment failure, and occurrence of acute kidney injury (AKI). RESULTS: Of 279 patients included, 92 were in the DE group and 187 were in the no DE (NDE) group. Patients who were not de-escalated received 5 more days of MRSA coverage than patients who were de-escalated; however, there was no difference in 28-day mortality (NDE group, 28% vs DE group, 23%; difference, -5.5%; 95% CI, -16.1 to 6.5). Patients who were de-escalated had shorter hospital (DE group, 15 days vs NDE group, 20 days; difference, 3.2 days; 95% CI, 0.1-6.4) and ICU (DE group, 10 days vs NDE group, 13 days; difference, 2.2 days; 95% CI, -0.3 to 4.9) LOSs after the index date. The incidence of AKI was significantly higher in patients who were not de-escalated (DE group, 36% vs NDE group, 50%; difference, -13.8%; 95% CI, -26.9 to -0.4). CONCLUSIONS: Although anti-MRSA agent DE in culture-negative nosocomial pneumonia did not affect 28-day mortality, it was associated with a shorter hospital LOS and lower incidence of AKI.

Clinical epidemiology of carbapenem-resistant gram-negative sepsis among hospitalized patients: Shifting burden of disease?

BACKGROUND: Infections caused by carbapenem-resistant gram-negative bacilli are an emerging public health threat. However, there is a paucity of data examining comparative incidence rates, risk factors, and outcomes in this population. METHODS: This single-center retrospective cohort study was conducted at an urban tertiary-care academic medical center. We included patients admitted from 2012 to 2015 who met the following criteria: i) age ≥ 18 years; and ii) culture positive for carbapenem-resistant Enterobacteriaceae (CRE) or carbapenem-resistant non-Enterobacteriaceae (CRNE) from any site. Exclusion criteria were: i) < 2 systemic inflammatory response criteria; ii) cystic fibrosis; and iii) no targeted treatment. We evaluated hospital survival by Cox regression and year-by-year differences in the distribution of cases by the Cochran-Armitage test. RESULTS: 448 patients were analyzed (CRE, n = 111 [24.8%]; CRNE, n = 337 [75.2%]). CRE sepsis cases increased significantly over the study period (P <.001), driven primarily by increasing incidence of Enterobacter spp. infection (P = .004). No difference was observed in hospital survival between patients with CRE versus CRNE sepsis (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.83-2.02; P = .285), even after adjusting for confounding factors (adjusted HR, 1.08; 95% CI, 0.62-1.87; P = .799). CONCLUSIONS: Clinical outcomes did not differ between patients with CRE versus CRNE sepsis. Dramatic increases in CRE, particularly Enterobacter spp., appear to be causing a shift in the burden of clinically significant carbapenem-resistant gram-negative infection.

Importance of Site of Infection and Antibiotic Selection in the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Sepsis.

In a retrospective analysis of 215 patients with carbapenem-resistant Pseudomonas aeruginosa sepsis, we observed a significantly higher risk of mortality associated with respiratory tract infection (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.04 to 1.39; P = 0.010) and lower risk with urinary tract infection (RR, 0.80; 95% CI, 0.71 to 0.90; P = 0.004). Aminoglycoside monotherapy was associated with increased mortality, even after adjusting for confounders (adjusted RR, 1.72; 95% CI, 1.03 to 2.85; P = 0.037), consistent across multiple sites of infection.

Telavancin for refractory MRSA bacteraemia in intermittent haemodialysis recipients.

Background: Patients with end-stage renal disease (ESRD) requiring intermittent haemodialysis (IHD) are at high risk of MRSA bacteraemia (MRSA-B) and often fail first-line therapy. The safety, effectiveness and optimal dosing of telavancin for MRSA-B in this patient population are unclear. Objectives: We aimed to describe clinical outcomes of telavancin in the treatment of refractory MRSA-B in patients with ESRD requiring IHD. Patients and methods: This was a retrospective study of hospitalized patients at two tertiary care academic medical centres with recurrent or persistent (≥3 days) MRSA-B treated with telavancin monotherapy. Outcomes included duration of MRSA-B (pre-telavancin versus post-telavancin) and microbiological failure (duration of MRSA-B ≥3 days after initiation of telavancin). Results: Telavancin dosed 10 mg/kg three times weekly post-IHD or 10 mg/kg every 48 h resulted in microbiological cure in 7/8 (87.5%) refractory MRSA-B cases. Telavancin monotherapy was associated with a significant reduction in median duration of bacteraemia [16 days pre-telavancin (IQR 8-19 days) versus 1 day post-telavancin (IQR 0-2 days); P = 0.018]. Telavancin was well tolerated by all patients and no adverse events were reported. Conclusions: Telavancin was very safe and highly effective in the treatment of refractory MRSA-B in a cohort of patients with ESRD requiring IHD. These data support the utility of telavancin in the armamentarium against refractory MRSA-B, particularly in the high-risk IHD-dependent population.

Effective Antibiotic Conservation by Emergency Antimicrobial Stewardship During a Drug Shortage.

We present the first description of an antimicrobial stewardship program (ASP) used to successfully manage a multi-antimicrobial drug shortage. Without resorting to formulary restriction, meropenem utilization decreased by 69% and piperacillin-tazobactam by 73%. During the shortage period, hospital mortality decreased (P=.03), while hospital length of stay remained unchanged. Infect Control Hosp Epidemiol 2017;38:356-359.

New Gram-Positive Agents: the Next Generation of Oxazolidinones and Lipoglycopeptides.

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibit in vitro activity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstrate in vitro activity against VRE. These new Gram-positive agents are reviewed here.

Epidemiology, Co-Infections, and Outcomes of Viral Pneumonia in Adults: An Observational Cohort Study.

Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48  h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk.

Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship.

INTRODUCTION: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. RESULTS: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.

A review of intravenous minocycline for treatment of multidrug-resistant Acinetobacter infections.

Options for treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections are extremely limited. Minocycline intravenous is active against many MDR strains of Acinetobacter, and Clinical and Laboratory Standards Institute breakpoints exist to guide interpretation of minocycline susceptibility results with Acinetobacter. In addition, minocycline intravenous holds a US Food and Drug Administration indication for treatment of infections caused by Acinetobacter. There is an accumulating amount of literature reporting successful use of minocycline intravenous for treatment of serious MDR Acinetobacter infections, particularly for nosocomial pneumonia. These results, coupled with the generally favorable tolerability of minocycline intravenous, support its use as a viable therapeutic option for treatment of MDR Acinetobacter infections.

Health services management development: what formal knowledge should support the skills and experience required?

This study reports on an analysis of 17 postgraduate programs in health services management. Public information was collected from websites in February 2010. Data analysed included core subject abstracts, admission requirements and length and aims of each course. Findings indicate that only three out of 16 subjects identified as core are common to more than 50% of the programs, with the eight most common individual subjects appearing in only a third of programs. This suggests diversity in what is deemed core foundational knowledge in managing health services and the approach taken to management development. We believe there should be greater consensus on core subjects in a specialist health services management qualification. WHAT IS KNOWN ABOUT THE TOPIC? With changes in the organisational structure of health organisations in Australia over the past two decades, managerial positions and roles have also changed. The educational preparation for those managerial roles would also be expected to have changed but core foundational knowledge should remain similar between the various academic institutions.WHAT DOES THIS PAPER ADD? This paper indicates greater diversity in core knowledge areas in health services management education than expected despite a similar target audience.WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? There are differences in what are deemed to be core foundational areas of knowledge required in specialist management development between academic programs. Management development requires a balance between knowledge, skills and experience and intending st

Treatment and clinical outcomes of urinary tract infections caused by KPC-producing Enterobacteriaceae in a retrospective cohort.

BACKGROUND: Optimal treatment regimens for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are not well-defined. OBJECTIVES: This study describes the treatment and outcomes in patients with urinary tract infection (UTI) caused by KPC-producing Enterobacteriaceae. METHODS: This retrospective cohort study analyzed data from adult inpatients with bacteriuria caused by KPC-positive organisms treated at Barnes-Jewish Hospital from June 1, 2006, to February 1, 2008. KPC-positive isolates were identified utilizing disk-diffusion susceptibility testing and confirmed to contain bla(KPC) via molecular methods. RESULTS: Twenty-one patients met the inclusion criteria and all were classified as having symptomatic UTI. The majority of patients were female (15/21 [71%]), and the mean (SD) age was 62.4 (15.2) years. Successful clinical and microbiologic responses were observed in 16 patients (76%) for both outcomes. Patients with urinary catheters had them removed or replaced in 9 of 15 cases (60%). Antibiotics active against the isolated pathogen were provided in 14 of 21 cases (67%), often after considerable delay (median, 72.5 hours [range, 4-312 hours]). All 7 patients receiving aminoglycoside therapy had successful clinical and microbiologic responses, and in vitro testing of an extended antibiotic panel revealed high susceptibility rates for tigecycline (28/29 [97%]), minocycline (22/29 [76%]), and fosfomycin (25/29 [86%]) against the KPC-positive isolates. CONCLUSIONS: Although receipt of appropriate therapy was delayed in many cases, clinical outcomes investigated revealed [corrected] high rates of successful response in this defined group of patients Aminoglycosides and tetracycline derivatives suggested therapeutic promise in the treatment of KPC-producing Enterobacteriaceae UTI.