Susan C. Bleasdale

The Empirical Combination of Vancomycin and a β-Lactam for Staphylococcal Bacteremia

The high prevalence of methicillin resistance among Staphylococcus aureus bacteremias leads to common use of vancomycin as empirical therapy. However, investigators have reported poor outcomes with vancomycin treatment for methicillin-susceptible Staphylococcus aureus bacteremia. We review the evidence supporting empirical combination of both vancomycin and a β-lactam agent for Staphylococcus aureus bacteremia. Vancomycin therapy for methicillin-susceptible Staphylococcus aureus bacteremia is associated with 2-3 times the risk of morbidity and mortality compared to an antistaphylococcal penicillin (oxacillin and nafcillin) or first-generation cephalosporin (cefazolin). De-escalation of empirical vancomycin to definitive β-lactam therapy still appears inferior to initial β-lactam therapy. Although there is no clinical trial supporting combination therapy, a scientific rationale for benefit exists and should be weighed against the risks (adverse events, antibiotic resistance, and cost) of additional pharmacotherapy. The empirical combination of vancomycin and a β-lactam (either nafcillin, oxacillin, or cefazolin) for staphylococcal bacteremia may improve infection-related clinical outcomes.

Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial

Importance Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections. Objective To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis. Design, Setting, and Participants Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region. Interventions Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment. Main Outcomes and Measures Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was −15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated. Results Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, −0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, −4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam. Conclusions and Relevance Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage. Trial Registration clinicaltrials.gov Identifier: NCT02166476

Predictors of Hospital Readmission in Patients Receiving Outpatient Parenteral Antimicrobial Therapy.

Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used, and unfortunately, readmissions during OPAT are common. The purpose of this study was to identify predictors of hospital readmission among patients receiving OPAT.

Electronic Algorithmic Prediction of Central Vascular Catheter Use

OBJECTIVE To develop prediction algorithms for the presence of a central vascular catheter in hospitalized patients with use of data present in an electronic health record. Such algorithms could be used for measurement of device utilization rates and for clinical decision support rules. DESIGN Criterion standard. SETTING John H. Stroger, Jr, Hospital of Cook County, a 464-bed public hospital in Chicago, Illinois. PARTICIPANTS Patients admitted to the medical intensive care unit from May 31, 2005 through June 26, 2006 (derivation data set, May 31, 2005-September 28, 2005; validation data set, September 29, 2005-June 28, 2006). METHODS Covariates were collected from the electronic medical record for each patient; the outcome variable was presence of a central vascular device. Multivariate models were developed using the derivation set and the generalized estimating equation. Three models, each with increasing database requirements, were validated using the validation set. Device utilization ratios and performance characteristics were calculated. RESULTS Although Charlson score and duration of intensive care unit stay were significant predictors in all models, factors that indicated use or presence of a central line were also important. Device utilization rates derived from the algorithmic models were as accurate as those obtained using manual sampling. CONCLUSIONS Automated calculation of central vascular catheter use is both feasible and accurate, providing estimates statistically similar to those obtained using manual surveillance. Prediction modeling of central vascular catheter use may enable automated surveillance of bloodstream infections and enhance important prevention interventions, such as timely removal of unnecessary central lines.

The Effect of a Piperacillin/Tazobactam Shortage on Antimicrobial Prescribing and Clostridium difficile Risk in 88 US Medical Centers

Background Anti-infective shortages are a pervasive problem in the United States. The objective of this study was to identify any associations between changes in prescribing of antibiotics that have a high risk for CDI during a piperacillin/tazobactam (PIP/TAZO) shortage and hospital-onset Clostridium difficile infection (HO-CDI) risk in 88 US medical centers. Methods We analyzed electronically captured microbiology and antibiotic use data from a network of US hospitals from July 2014 through June 2016. The primary outcome was HO-CDI rate and the secondary outcome was changes in antibiotic usage. We fit a Poisson model to estimate the risk of HO-CDI associated with PIP/TAZO shortage that were associated with increased high-risk antibiotic use while controlling for hospital characteristics. Results A total of 88 hospitals experienced PIP/TAZO shortage and 72 of them experienced a shift toward increased use of high-risk antibiotics during the shortage period. The adjusted relative risk (RR) of HO-CDI for hospitals experiencing a PIP/TAZO shortage was 1.03 (95% confidence interval [CI], .85-1.26; P = .73). The adjusted RR of HO-CDI for hospitals that both experienced a shortage and also showed a shift toward increased use of high-risk antibiotics was 1.30 (95% CI, 1.03-1.64; P < .05). Conclusions Hospitals that experienced a PIP/TAZO shortage and responded to that shortage by shifting antibiotic usage toward antibiotics traditionally known to place patients at greater risk for CDI experienced greater HO-CDI rates; this highlights an important adverse effect of the PIP/TAZO shortage and the importance of antibiotic stewardship when mitigating drug shortages.

Pharmacokinetics of telavancin at fixed doses in normal- body-weight and obese (classes I, II, and III) adult subjects

ABSTRACT A recommended total-body-weight (TBW) dosing strategy for telavancin may not be optimal in obese patients. The primary objective of this study was to characterize and compare the pharmacokinetics (PK) of telavancin across four body size groups: normal to overweight and obese classes I, II, and III. Healthy adult subjects (n = 32) received a single, weight-stratified, fixed dose of 500 mg (n = 4), 750 mg (n = 8), or 1,000 mg (n = 20) of telavancin. Noncompartmental PK analyses revealed that subjects with a body mass index (BMI) of ≥40 kg/m2 had a higher volume of distribution (16.24 ± 2.7 liters) than subjects with a BMI of <30 kg/m2 (11.71 ± 2.6 liters). The observed area under the concentration-time curve from time zero to infinity (AUC0–∞) ranged from 338.1 to 867.3 mg · h/liter, with the lowest exposures being in subjects who received 500 mg. AUC0–∞ values were similar among obese subjects who received 1,000 mg. A two-compartment population PK model best described the plasma concentration-time profile of telavancin when adjusted body weight (ABW) was included as a predictive covariate. Fixed doses of 750 mg and 1,000 mg had similar target attainment probabilities for efficacy as doses of 10 mg/kg of body weight based on ABW and TBW, respectively. However, the probability of achieving a target area under the concentration-time curve from time zero to 24 h of ≥763 mg · h/liter in association with acute kidney injury was highest (19.7%) with TBW-simulated dosing and lowest (0.4%) at the 750-mg dose. These results suggest that a fixed dose of 750 mg is a safe and effective alternative to telavancin doses based on TBW or ABW for the treatment of obese patients with normal renal function and Staphylococcus aureus infections. (This study has been registered at ClinicalTrials.gov under identifier NCT02753855.)

The Impact of Recurrent Clostridium difficile Infection on Patients’ Prevention Behaviors

OBJECTIVE To determine the impact of recurrent Clostridium difficile infection (RCDI) on patient behaviors following illness. METHODS Using a computer algorithm, we searched the electronic medical records of 7 Chicago-area hospitals to identify patients with RCDI (2 episodes of CDI within 15 to 56 days of each other). RCDI was validated by medical record review. Patients were asked to complete a telephone survey. The survey included questions regarding general health, social isolation, symptom severity, emotional distress, and prevention behaviors. RESULTS In total, 119 patients completed the survey (32%). On average, respondents were 57.4 years old (standard deviation, 16.8); 57% were white, and ~50% reported hospitalization for CDI. At the time of their most recent illness, patients rated their diarrhea as high severity (58.5%) and their exhaustion as extreme (30.7%). Respondents indicated that they were very worried about getting sick again (41.5%) and about infecting others (31%). Almost 50% said that they have washed their hands more frequently (47%) and have increased their use of soap and water (45%) since their illness. Some of these patients (22%-32%) reported eating out less, avoiding certain medications and public areas, and increasing probiotic use. Most behavioral changes were unrelated to disease severity. CONCLUSION Having had RCDI appears to increase prevention-related behaviors in some patients. While some behaviors are appropriate (eg, handwashing), others are not supported by evidence of decreased risk and may negatively impact patient quality of life. Providers should discuss appropriate prevention behaviors with their patients and should clarify that other behaviors (eg, eating out less) will not affect their risk of future illness. Infect Control Hosp Epidemiol. 2017;38:1351-1357.

Outbreak Response and Incident Management: SHEA Guidance and Resources for Healthcare Epidemiologists in United States Acute-Care Hospitals

David B. Banach, MD, MPH, MS; B. Lynn Johnston, MD, MS, FRCPC; Duha Al-Zubeidi, MD; Allison H. Bartlett, MD, MS; Susan Casey Bleasdale, MD; Valerie M. Deloney, MBA; Kyle B. Enfield, MD, MS; Judith A. Guzman-Cottrill, DO; Christopher Lowe, MD, MSc; Luis Ostrosky-Zeichner, MD; Kyle J. Popovich, MD, MS; Payal K. Patel, MD; Karen Ravin, MD, MS; Theresa Rowe, DO, MS; Erica S. Shenoy, MD, PhD; Roger Stienecker, MD; Pritish K. Tosh, MD; Kavita K. Trivedi, MD; and the Outbreak Response Training Program (ORTP) Advisory Panel

Pharmacokinetics and Dialytic Clearance of Ceftazidime-Avibactam in a Critically Ill Patient on Continuous Venovenous Hemofiltration

ABSTRACT Ceftazidime-avibactam administered at 1.25 g every 8 h was used to treat multidrug-resistant Pseudomonas aeruginosa bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Prefiltration plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 h along with postfiltration and ultrafiltrate concentrations at h 2 and h 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were as follows: maximum plasma concentration (Cmax), 61.10 and 14.54 mg/liter; minimum plasma concentration (Cmin), 31.96 and 8.45 mg/liter; half-life (t1/2), 6.07 and 6.78 h; apparent volume of distribution at the steady state (Vss), 27.23 and 30.81 liters; total clearance at the steady state (CLss), 2.87 and 2.95 liters/h; area under the concentration-time curve from 0 to 8 h (AUC0–8), 347.87 and 85.69 mg · h/liter. Concentrations of ceftazidime in plasma exceeded the ceftazidime-avibactam MIC (6 mg/liter) throughout the 8-h dosing interval. Mean CVVH extraction ratios for ceftazidime and avibactam were 14.44% and 11.53%, respectively, and mean sieving coefficients were 0.96 and 0.93, respectively. The calculated mean clearance of ceftazidime by CVVH was 1.64 liters/h and for avibactam was 1.59 liters/h, representing 57.1% of the total clearance of ceftazidime and 54.3% of the total clearance of avibactam. Further data that include multiple patients and dialysis modes are needed to verify the optimal ceftazidime-avibactam dosing strategy during critical illness and CVVH.

Contact patterns during cleaning of vomitus: A simulation study

HighlightsCleaning of simulated vomitus was relatively quick.Cleaners infrequently touched their own bodies while cleaning.Cleaners touched the cleaning cart more often than other surfaces, on average.Each participant used different cleaning practices, but used similar cleaning practices each time he or she cleaned.Few cleaners followed the recommended protocol for cleaning bodily fluids.Following the recommended protocol for cleaning bodily fluids was associated with fewer surface contacts and improved cleaning quality. Background: Environmental service workers cleaning bodily fluids may transfer pathogens through the environment and to themselves through contacts. Methods: Participants with experience in cleaning of hospital environments were asked to clean simulated vomitus using normal practices in a simulated patient room while being videorecorded. Contacts with environmental surfaces and self were later observed. Results: In 21 experimental trials with 7 participants, environmental surfaces were contacted 26.8 times per trial, at a frequency of 266 contacts per hour, on average. Self‐contact occurred in 9 of 21 trials, and involved 1‐18 contacts, mostly to the upper body. The recommended protocol of cleaning bodily fluids was followed by a minority of participants (2 of 7), and was associated with fewer surface contacts, improved cleaning quality, and different tool use. Participants used different cleaning practices, but each employed similar practices each time they performed an experimental trial. Conclusions: Training in the use of the recommended protocol may standardize cleaning practices and reduce the number of surface contacts.