Antimicrobial Resistance: Problem Pathogens and Clinical Countermeasures PDF

Preface

With more than two million infections occurring in the United States alone each year, and a substantial proportion of them being caused by antimicrobial resistant organisms, interventions are desperately needed. Antimicrobial resistance has the potential to impact everyone. In fact, antimicrobials are the only category of drugs that have "societal" consequences. In other words, antihypertensives or lipid lowering agents only impact the person receiving these drugs. With antimicrobials, in contrast, an individual can receive these drugs, develop resistance to them, and then pass along the newly created resistant organism to individuals that have never been exposed to the antimicrobial(s) administered. This so-called "societal" impact of antimicrobials can be seen with not only traditional antibiotics used to treat bacteria and fungal pathogens (both of which this book will focus on), but also antivirals used to treat human immunodeficiency virus, influenza A, avian flu virus, and anti-tuberculosis agents to treat tuberculosis. The latter examples have received considerable press attention due to the fact that multiple antiviral-resistant human immunodeficiency virus strains can be transmitted to an individual who is treatment naïve, with the same being true for extrapulmonary tuberculosis , or extensively drug-resistant tuberculosis. The examples of highly resistant human immunodeficiency virus and extrapulmonary tuberculosis portray the societal consequences well to the general public because of the therapeutic challenges they create and the poor associated outcomes. For bacteria and fungi, there does not yet seem to be a public eruption about bacteria and fungi that are resistant to multiple drugs and are in part responsible for numerous deaths in the developed world each day.

Sometimes these resistant organisms occur as a consequence of treatment that has been suboptimally selected, dosed, and/or given for an appropriate duration (usually too long). However, a significant proportion of resistance is created in patients who are receiving antimicrobial therapy that is not optimized in terms of its selection, dose, and duration, and/or the adherence to the regimen by the patient is poor or non-existent. In the spirit that this book, Antimicrobial Resistance: Problem Pathogens and Clinical Countermeasures, was developed, our intentions were to focus on the more common pathogens that are causing significant disease and pathogens that have also developed multiple drug resistance, and, perhaps most importantly, to discuss interventions to minimize the development, spread, and impact of antimicrobial resistance.

This book is divided into three sections. The first section tackles several background subjects germane to antimicrobial resistance, including the subject of measuring the cost of resistance from the healthcare and clinician's perspective. The intention of this is to enable administrators, clinician administrators, as well as clinicians themselves to understand the direct and indirect costs of antimicrobial resistance. It is in the hope that, as more administrators understand (and more clinicians are able to speak to) these issues, more progress will be made in the investment of programs designed to prevent infection and use antimicrobials more judiciously in the healthcare setting. Other chapters in this section deal with quantifying escalating resistance rates through national and international surveillance projects, their limitations, and ultimately quantifying and benchmarking resistance at the local level through the use of modified antibiograms. A chapter is also dedicated to tackling the troubling issues surrounding why we have seen a seventy five percent reduction in new antimicrobials for human use over the last two decades. What is driving this reduction in antimicrobial development? Why are large pharmaceutical companies who have brought more than ninety percent of our current antimicrobial arsenal to the market leaving anti-infective development? Finally, a chapter is included that addresses the types of methodologies used by investigators to understand the impact of antimicrobial resistance compared with infections caused by antimicrobial-susceptible organisms. This section is designed to help the reader understand the general methodologies currently in use, when to use certain methodologies, and the strengths and limitations of each.

The next section deals with clinically important pathogens ranging from community- to healthcare-associated bacteria, as well as the troubling developments in Clostridium difficile and fungi. The topic of Staphlyococcus aureus is covered nicely, addressing both community-acquired methicillin-resistant staphylococci as well as healthcare-associated methicillin-resistant staphylococci in terms of both virulence characteristics and treatment. Streptococcus pneumoniae, the leading community-acquired pathogen is discussed, as are enterococci. In addition, the most common and refractory healthcare-associated pathogens are discussed, including Pseudomonas aeruginosa and Acinetobacter spp. The chapters are designed to give the clinician a general overview of the organism, including resistance mechanisms and recent trends as well as potential treatment options. In the case of C. difficile, this chapter focuses on a novel aspect of resistance, that is, resistance to certain antimicrobials has lead to an increased risk of developing C. difficileinfection. Recent and historical data are reviewed in an effort to simplify this complex association between antimicrobial use and risk for C. difficileinfection. Furthermore, an up-to-date C. difficile treatment algorithm is proposed that has been in clinical use since the time of the BI/NAP1/027 outbreak strain. A chapter on emerging beta-lactamases was developed, in part, due to the overwhelming changes that have occurred with this sophisticated mechanism of resistance. Within this chapter, a variety of organisms are discussed as well as the types of beta-lactamases they are most associated with.

The final section is one that may separate it from traditional books on antimicrobial resistance. The intention is to discuss clinically relevant options to minimize the development of resistance, ranging from a nicely written chapter overviewing infection control interventions, to a chapter discussing the merits and practical implementation issues related to antimicrobial stewardship programs. Some components of antimicrobial stewardship programs require their own chapter. These include the a review of antimicrobial de-escalation/streamlining, use of computer assisted technology to optimize antimicrobial use, employing shorter courses of therapy when appropriate, and using guidelines to drive appropriate antimicrobial use, as examples.

This book has an appeal to all who are involved in the ordering and oversight of antimicrobial agents or are responsible for antimicrobial policy or guideline creation in both community and healthcare practice venues. Also, with the advancing era of computerization and physician order entry, this book provides an ideal perspective on the use of computerized decision support to optimize the use of antimicrobials.