Antibiotic Resistance

Mechanisms and New Antimicrobial Approaches

Kateryna Kon,Mahendra Rai

• Publisher: Academic Press
• Year: 2016
• ISBN:
  9780128036686
• Topic: Medicina
• Subtopic: Farmacología

Antibiotic Resistance: Mechanisms and New Antimicrobial Approaches discusses up-to-date knowledge in mechanisms of antibiotic resistance and all recent advances in fighting microbial resistance such as the applications of nanotechnology, plant products, bacteriophages, marine products, algae, insect-derived products, and other alternative methods that can be applied to fight bacterial infections.

Understanding fundamental mechanisms of antibiotic resistance is a key step in the discovery of effective methods to cope with resistance. This book also discusses methods used to fight antibiotic-resistant infection based on a deep understanding of the mechanisms involved in the development of the resistance.

• Discusses methods used to fight antibiotic-resistant infection based on a deep understanding of mechanisms involved in the development of the resistance
• Provides information on modern methods used to fight antibiotic resistance
• Covers a wide range of alternative methods to fight bacterial resistance, offering the most complete information available
• Discusses both newly emerging trends and traditionally applied methods to fight antibiotic resistant infections in light of recent scientific developments
• Offers the most up-to-date information in fighting antibiotic resistance
• Includes involvement of contributors all across the world, presenting questions of interest to readers of both developed and developing countries

Chapter 1

Antimicrobial Stewardship

Hospital Strategies to Curb Antibiotic Resistance

L. Hsieh¹ and A. Amin², ¹Hospitalist Program and Division of Infectious Diseases, University of California, Irvine Medical Center, Irvine, CA, United States, ²Hospitalist Program, University of California, Irvine Medical Center, Irvine, CA, United States

Abstract

The use of potent broad-spectrum antibiotics has led to the growing challenge of antibiotic resistance and Clostridium difficile infections worldwide. Multidrug-resistant infections account for a significant portion of hospital-acquired infections, having a major impact on clinical outcomes and costs. It has been reported that a large proportion of antimicrobial use in acute care hospitals is inappropriate or suboptimal. Antimicrobial stewardship promotes the judicious use of antimicrobials to improve patient care while minimizing unintended consequences such as antibiotic resistance, C. difficile infections, and antibiotic-related toxicities. Core stewardship interventions include formulary restriction, prospective auditing with feedback, and antibiotic time-outs. Several supplemental strategies are also effective, including education, pharmacy-driven interventions, and early laboratory diagnostics. The transition to electronic medical records has also made stewardship efforts more efficient. As the world proceeds to meet the urgent problem of antimicrobial resistance by implementing more comprehensive antimicrobial stewardship programs, better ways to measure results are essential.

Keywords

Antimicrobial stewardship; antibiotic resistance; hospital strategies; stewardship interventions

Introduction

The discovery of antibiotics may be one of the greatest achievements in medicine. Antibiotic treatments have improved clinical outcomes from infections, leading to the reduction of morbidity and mortality in surgical, transplant, cancer, and critical care patients. With the use of potent broad-spectrum antibiotics, selective pressures have made antibiotic resistance an urgent worldwide concern. Increasing numbers of hospital-acquired infections are now caused by multidrug-resistant pathogens, making treatment progressively difficult and antibiotic choice increasingly limited. The Centers for Disease Control and Prevention (CDC) data showed that in 2010, 55.7% of patients discharged from 325 hospitals received antibiotics during their hospital stay, and 37.2% of those antibiotic prescriptions were unnecessary or could be improved, which is in line with previous studies in the literature on antibiotic utilization in acute care hospitals.¹ Inappropriate antimicrobial use can lead to the selection of resistant pathogens, Clostridium difficile infections, antibiotic-induced toxicities, and adverse drug reactions, all of which have a significant negative impact on patient morbidity, mortality, and health-care costs. It has been recognized that reduction of antibiotic use would slow the growth of or alleviate the problem of antibiotic resistance and C. difficile infections. In 1997, the Society for Healthcare Epidemiology of America (SHEA) and Infectious Diseases Society of America (IDSA) published guidelines for the prevention of antimicrobial resistance in hospitals, coining the term antimicrobial stewardship.² In addition to a comprehensive infection control program and surveillance of bacterial resistance, these guidelines advocated for the judicious use of antimicrobials in order to slow or prevent the development of antimicrobial resistance.

Since 2006, the CDC has launched multiple campaigns to target antibiotic resistance and improve health care. In each of these campaigns, the CDC emphasized the need for judicious antibiotic utilization in acute care hospitals. In 2007, the IDSA and SHEA published guidelines for developing antimicrobial stewardship programs (ASPs) at an institutional level.³ In this document, IDSA and SHEA define the primary goal of ASPs to be the improvement of clinical outcomes while minimizing the unintended consequences of antimicrobial use, including emergence of resistance, toxicity, and selection of pathogenic organisms such as C. difficile. SHEA and IDSA, along with the Pediatric Infectious Disease Society (PIDS), issued a policy statement in 2012 recommending that ASPs be mandated through regulatory channels.⁴ Specifically, this policy statement advocated for the Centers for Medicare and Medicaid Services (CMS) to require participating institutions to implement ASPs. This document further detailed the minimum requirements for an effective ASP and made recommendations on expansion of stewardship efforts to the ambulatory setting, education, and research. In 2014, the CDC recommended that all acute care hospitals implement ASPs to combat the worsening problems of antibiotic resistance and C. difficile infections and released a document called “Core Elements of Hospital Antibiotic Stewardship Programs” to aid hospitals in this goal.⁵

In the United States, California remains the first and only state to pass legislation on antimicrobial stewardship. In 2008, Senate Bill 739 (SB 739) mandated California acute care hospitals to put processes in place to monitor the judicious use of antibiotics. It was left to each institution to develop its own procedures to comply with this mandate. The regulatory conditions were vague, and hospitals made various efforts to fulfill these requirement. In a web-based survey of 422 California acute care hospitals in 2010–11, 50% of the 223 respondents had a current ASP, and 30% reported planning to implement an ASP.⁶ This survey was subject to reporting bias, however, as those hospitals with active ASPs were more likely to respond. It was reported that SB 739 encouraged some of these hospitals to initiate an ASP. Those that did not adopt ASPs were likely to be smaller or rural hospitals, and lack of resources and administrative support were the most frequently cited barriers to doing so. Interestingly, many hospitals that reported not having an official ASP did have some stewardship processes in place, such as formulary restriction and antimicrobial oversight by pharmacists. In Sep. 2014, California Senate Bill 1311 (SB 1311) further required hospitals to implement an official policy on antimicrobial stewardship and to establish a multidisciplinary stewardship committee by Jul. 2015.⁷ This bill was much more prescriptive in its requirements than its predecessor, driving home the minimum requirements for an effective stewardship program in acute care hospitals. In Mar. 2015, the White House released the National Action Plan for Combating Antibiotic-Resistant Bacteria. This 63-page action plan aims to guide programs of the US government, public health, health care, and agriculture in a common effort to address the urgent challenge of mounting antibiotic resistance. The plan sets 1-, 3-, and 5-year milestones for each of five goals, the first of which is to slow the emergence of resistant bacteria and prevent the spread of infections. By 2020, the action plan seeks to establish ASPs in all acute care hospitals and improved antibiotic stewardship across all health-care settings, with a reduction of inappropriate antibiotic use by 20% in inpatient settings.⁸ This illustrates the commitment of the United States to meet the critical problem of antimicrobial resistance.

Globally, antimicrobial stewardship is gaining momentum as the challenge of antibiotic resistance became an urgent worldwide concern. In a 2012 international survey of 660 hospitals from 67 countries from 6 continents on inpatient antimicrobial stewardship, 58% of respondents had an ASP and 22% planned to implement one.⁹ Academic medical centers accounted for almost 50% of respondents. Reducing antimicrobial resistance was the most frequently cited goal for ASPs across all continents. Formulary restriction was practiced in 81% of hospitals, while 64% had postprescription review as part of the stewardship strategy. Two-thirds of hospitals in North America and Europe had ASPs, with 80% of European countries having antimicrobial stewardship standards at the national level. It was noted that ASPs were more established in Sweden (100%), United States (88%), France (81%), and the United Kingdom (77%) than other countries.¹⁰ However, it should be noted since hospitals with active ASPs were more likely to participate in this survey, the results are subject to selection bias. Progress is being made in the implementation and expansion of stewardship programs across the United States and Europe. The degree of legislative requirements differ significantly among countries, their primary objectives are different as well. In France, the primary goal is to reduce antibiotic resistance. Reduction of health-care-associated infections is the main impetus in the United Kingdom. For the United States, the principal driver is to improve clinical outcomes. The utilization of electronic medical records, physician order entry, and data warehousing as part of antimicrobial stewardship is much more common in the United States than in France or the United Kingdom.

Moving From Cost to Quality and Patient Safety

The CDC estimates that at least 2 million patients each year acquire serious infections with drug-resistant bacteria in the United States, accounting for at least 23,000 deaths and significant morbidity and health-care costs.¹¹ In addition, the CDC estimates that 150,000 cases per year go to US Emergency Departments for antimicrobial-related adverse events.¹² Effective ASPs can improve patient care and be cost effective. They have shown reductions in antimicrobial use with annual savings of $200,000–900,000, making the programs self-supporting.^13,14 Most of the data from the literature measured direct pharmacy acquisition costs. When taken together with the impact on length of stay, readmission rates, and avoidance of potential adverse drug reactions, the financial impact of ASPs is even greater. The cost effectiveness of ASPs is often cited to garner administration support in a climate of cost-conscious medical care. However, the main goal of antimicrobial stewardship should be to improve patient care and optimize clinical outcomes. More and more, antimicrobial stewardship has become the focus of quality and patient safety improvement efforts.

Appropriate antimicrobial utilization is tied to quality patient care. In a cohort study of 500 randomly selected hospitalized patients with an antimicrobial course, Filice et al. found that diagnostic accuracy correlated to optimal antimicrobial use.¹⁵ Diagnostic accuracy in turn was closely tied to the quality of clinical evidence at the time of initial diagnosis. Accuracy was generally poor for the diagnoses of pneumonia and urinary tract infection, which are extremely common in the inpatient setting. In this study, the appropriateness of antibiotics was judged by a group of four infectious disease physicians. It should be noted that each reviewer’s responses was compared with those of the other three reviewers, and agreement was 69–72%.

It is generally accepted that routine treatment of asymptomatic bacteriuria is inappropriate.¹⁶ It is a substantial contributor to antibiotic overuse in hospitalized and nursing home patients, particularly among patients with urinary catheters. In a study at two Veterans Affairs health-care systems, Trautner et al. introduced a streamlined diagnostic algorithm for catheter-associated urinary tract infection versus asymptomatic bacteriuria.¹⁷ This intervention significantly decreased the inappropriate ordering of urine cultures, thereby decreasing the inappropriate treatment of asymptomatic bacteriuria. At the same time, the study did not find undertreatment of true catheter-associated urinary tract infections during the intervention period.

Regardless of appropriateness, all antibiotic use exerts selective pressures that contribute to the development of resistance and other unintentional consequences. It is apparent that not only is the choice of antibiotics important, the duration of therapy may be equally important. In a retrospective cohort study of 7792 hospitalized adult patients who received 2 or more days of antibiotics, dose-dependent increases in the risk of C. difficile infection was associated with the cumulative dose, number of antibiotics, and days of antibiotic exposure.¹⁸ These studies illustrate that ...