Keith S. Kaye

Strategies to Prevent Central Line-Associated Bloodstream Infections in Acute Care Hospitals

Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections. The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their central line–associated bloodstream infection (CLABSI) prevention efforts. Refer to the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America “Compendium of Strategies to Prevent Healthcare-Associated Infections” Executive Summary and Introduction and accompanying editorial for additional discussion.1. Patients at risk for CLABSIs in acute care facilitiesa. Intensive care unit (ICU) population: The risk of CLABSI in ICU patients is high. Reasons for this include the frequent insertion of multiple catheters, the use of specific types of catheters that are almost exclusively inserted in ICU patients and associated with substantial risk (eg, arterial catheters), and the fact that catheters are frequently placed in emergency circumstances, repeatedly accessed each day, and often needed for extended periods.b. Non-ICU population: Although the primary focus of attention over the past 2 decades has been the ICU setting, recent data suggest that the greatest numbers of patients with central lines are in hospital units outside the ICU, where there is a substantial risk of CLABSI.2. Outcomes associated with hospital-acquired CLABSIa. Increased length of hospital stayb. Increased cost; the non-inflation-adjusted attributable cost of CLABSIs has been found to vary from 29,000 per episode

Strategies to Prevent Catheter‐Associated Urinary Tract Infections in Acute Care Hospitals

Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections. The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their catheter-associated urinary tract infection (CAUTI) prevention efforts. Refer to the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America “Compendium of Strategies to Prevent Healthcare-Associated Infections” Executive Summary and Introduction and accompanying editorial for additional discussion. 1. Burden of CAUTIs a. Urinary tract infection is the most common hospital-acquired infection; 80% of these infections are attributable to an indwelling urethral catheter. b. Twelve to sixteen percent of hospital inpatients will have a urinary catheter at some time during their hospital stay. c. The daily risk of acquisition of urinary infection varies from 3% to 7% when an indwelling urethral catheter remains in situ. 2. Outcomes associated with CAUTI a. Urinary tract infection is the most important adverse outcome of urinary catheter use. Bacteremia and sepsis may occur in a small proportion of infected patients. b. Morbidity attributable to any single episode of catheterization is limited, but the high frequency of catheter use in hospitalized patients means that the cumulative burden of CAUTI is substantial. c. Catheter use is also associated with negative outcomes other than infection, including nonbacterial urethral inflammation, urethral strictures, and mechanical trauma.

Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals

Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections. The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their ventilator-associated pneumonia (VAP) prevention efforts. Refer to the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America “Compendium of Strategies to Prevent Healthcare-Associated Infections” Executive Summary and Introduction and accompanying editorial for additional discussion.1. Occurrence of VAP in acute care facilities.a. VAP is one of the most common infections acquired by adults and children in intensive care units (ICUs).i. In early studies, it was reported that 10%-20% of patients undergoing ventilation developed VAP. More-recent publications report rates of VAP that range from 1 to 4 cases per 1,000 ventilator-days, but rates may exceed 10 cases per 1,000 ventilator-days in some neonatal and surgical patient populations. The results of recent quality improvement initiatives, however, suggest that many cases of VAP might be prevented by careful attention to the process of care.2. Outcomes associated with VAPa. VAP is a cause of significant patient morbidity and mortality, increased utilization of healthcare resources, and excess cost.i. The mortality attributable to VAP may exceed 10%.ii. Patients with VAP require prolonged periods of mechanical ventilation, extended hospitalizations, excess use of antimicrobial medications, and increased direct medical costs.

A compendium of strategies to prevent healthcare-associated infections in acute care hospitals.

Preventable healthcare-associated infections (HAIs) occur in US hospitals. Preventing these infections is a national priority, with initiatives led by healthcare organizations, professional associations, government and accrediting agencies, legislators, regulators, payers, and consumer advocacy groups. To assist acute care hospitals in focusing and prioritizing efforts to implement evidence-based practices for prevention of HAIs, the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America Standards and Practice Guidelines Committee appointed a task force to create a concise compendium of recommendations for the prevention of common HAIs. This compendium is implementation focused and differs from most previously published guidelines in that it highlights a set of basic HAI prevention strategies plus special approaches for use in locations and/or populations within the hospital when infections are not controlled by use of basic practices, recommends that accountability for implementing infection prevention practices be assigned to specific groups and individuals, and includes proposed performance measures for internal quality improvement efforts.

Strategies to prevent clostridium difficile infections in acute care hospitals.

Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections. The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their Clostridium difficile infection (CDI) prevention efforts. Refer to the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America “Compendium of Strategies to Prevent Healthcare-Associated Infections” Executive Summary and Introduction and accompanying editorial for additional discussion. 1. Increasing rates of CDI C. difficile now rivals methicillin-resistant Staphylococcus aureus (MRSA) as the most common organism to cause healthcare-associated infections in the United States. a. In the United States, the proportion of hospital discharges in which the patient received the International Classification of Diseases, Ninth Revision discharge diagnosis code for CDI more than doubled between 2000 and 2003, and CDI rates continued to increase in 2004 and 2005 (L. C. McDonald, MD, personal communication, July 2007). These increases have been seen in pediatric and adult populations, but elderly individuals have been disproportionately affected. CDI incidence has also increased in Canada and Europe. b. There have been numerous reports of an increase in CDI severity. c. Most reports of increases in the incidence and severity of CDI have been associated with the BI/NAP1/027 strain of C. difficile . This strain produces more toxins A and B in vitro than do many other strains of C. difficile , produces a third toxin (binary toxin), and is highly resistant to fluoroquinolones.

Risk Factors for Recovery of Ampicillin-Sulbactam-Resistant Escherichia coli in Hospitalized Patients

ABSTRACT Ampicillin-sulbactam resistance in Escherichia coli is an emerging problem. This study determined risk factors for the recovery of ampicillin-sulbactam-resistant E. coli in hospitalized patients. A case-control design was used to compare two groups of case patients with control patients. The first group of case patients consisted of patients from whom nosocomially acquired ampicillin-sulbactam-resistant E. coli strains were isolated, and the second group of case patients consisted of patients from whom ampicillin-sulbactam-susceptible E. coli strains were isolated. Control patients were a random selection among 5% of all patients admitted during the same time period. Risk factors analyzed included antimicrobial drug exposure, comorbid conditions, and demographics. Univariate and multivariate analyses were performed. Ampicillin-sulbactam-resistant E. coli strains were isolated from 175 patients, and ampicillin-sulbactam-susceptibleE. coli strains were isolated from 577 patients. Nine hundred thirty-four control patients were selected. Exposure to penicillin antibiotics as a class and to ampicillin and ampicillin-sulbactam individually were the only significant, independent risk factors associated with the isolation of ampicillin-sulbactam-resistant E. coli (odds ratio [OR] = 2.32 [P < 0.001], OR = 3.04 [P = 0.02], and OR = 1.72 [P= 0.04], respectively), but they were not associated with the isolation of ampicillin-sulbactam-susceptible E. coli. Interestingly, exposure to piperacillin-tazobactam tended to protect against the isolation of E. coli strains resistant to ampicillin-sulbactam, but this did not reach statistical significance (OR = 0.13; P = 0.11).

Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae

BackgroundnThe efficacy of ceftazidime-avibactam-a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown.nnnMethodsnPatients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW).nnnResultsnThirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin.nnnConclusionsnCeftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections. These findings require confirmation in a randomized controlled trial.

Gram-negative bacterial infections: Research priorities, accomplishments, and future directions of the Antibacterial Resistance Leadership Group

Antimicrobial resistance in pathogenic gram-negative bacteria is one of the most pressing challenges in the field of infectious diseases and is one of 4 key areas of unmet medical need identified by the Antibacterial Resistance Leadership Group (ARLG). The mission of the Gram-Negative Committee is to advance our knowledge of these challenging infections and implement studies to improve patient outcomes. Studies have fallen primarily into 2 broad categories: prospective cohort studies and interventional trials. Among the observational studies, CRACKLE (Consortium on Resistance Against Carbapenems in Klebsiella pneumoniae and Other Enterobacteriaceae) has contributed seminal multicenter data describing risk factors and clinical outcomes of carbapenem-resistant Enterobacteriaceae (CRE) in sentinel US hospitals. Building on this success, CRACKLE II will expand the network to hospitals across the United States and Colombia. Similar protocols have been proposed to include Acinetobacter baumannii and Pseudomonas aeruginosa (SNAP and POP studies). In addition, the CREST study (Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplant Patients) has provided pivotal data on extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and CRE carriage among solid organ transplant recipients to inform management of this vulnerable patient population. Two clinical trials to define novel ways of using an existing antibiotic, fosfomycin, to treat ESBL-producing Enterobacteriaceae (one that has completed enrollment and the other in late protocol development) will determine the clinical efficacy of fosfomycin as step-down oral therapy to treat complicated urinary tract infections. Additional clinical studies and trials using immunotherapeutic or newly approved agents are also in the planning stage, with the main goals of generating actionable data that will inform clinical decision making and facilitate development of new treatment options for highly resistant gram-negative bacterial infections.

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; nu2009=u2009274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; nu2009=u2009276) 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%]; Pu2009<u2009.001 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%]; Pu2009<u2009.001 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%]; Pu2009<u2009.001 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

Old antibiotics for multidrug-resistant pathogens: from in vitro activity to clinical outcomes

Antimicrobial resistance is a major and emerging threat worldwide. New antimicrobials have been unable to meet the resistance challenge, and treatment options are limited for a growing number of resistant pathogens. More and more clinicians are relying on older antimicrobials for the treatment of multidrug-resistant (MDR) bacteria. Some older antimicrobials have maintained excellent in vitro activity against highly resistant pathogens. In some instances, use of older agents is limited by unfavourable pharmacokinetic/pharmacodynamic characteristics and/or toxicities. In general, clinical data pertaining to the use of older agents for the treatment of MDR pathogens are scarce. Research efforts should be focused on the evaluation of older agents for the treatment of MDR pathogens as well as evaluating how these agents perform in complex patient populations with various and multiple co-morbid conditions.