Kathleen Steger Craven

Consultant in Infectious Diseases and Public Health, Wellesley, Massachusetts, U.S.A.

Clinical medicine seems to consist of a few things we think we know and lots of things we don't know.

INTRODUCTION

The population in the United States in the 21st century is at greater risk for infections due to increased longevity coupled with more chronic underlying diseases, aggressive medical and surgical procedures, solid organ transplantation, immunosuppressive therapy, and a highly mobile modern society. The current population is also at greater risk of infection from obesity, diabetes mellitus, and cardiovascular diseases. Therapies for various diseases may include antibiotics, steroids, chemotherapy, and a spectrum of monoclonal immune modulators that may increase colonization with antibiotic-resistant bacteria or alter the host immune system. As the result of these pressures, there have been well-documented increases in infections caused by multidrug-resistant (MDR) pathogens both in the community and healthcare settings (2). Some of the more common MDR pathogens include methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, extended-spectrum beta-lactamase-positive (ESBL+) Klebsiella pneumoniae, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus faecalis (VRE). The widespread use and frequent misuse of antibiotics provide persistent selection pressure for expansion and transmission of MDR pathogens both within and outside of healthcare settings (3-5).

Prevention strategies for reducing antibiotic resistance and improving patient outcomes should focus on reducing inappropriate initiation of antibiotics as well as on using shorter course antibiotic therapy (SCAT) (6). Significant progress has been made in our understanding of SCAT for treating outpatient infections such as sexually transmitted diseases (STDs), urinary tract infections (UTIs), surgical prophylaxis, and selected gastrointestinal and respiratory tract infections (6). Perhaps the best example of the success of SCAT has been the use of combination therapy regimens containing rifampin for the treatment of Mycobacterium tuberculosis (TB). The length of treatment for TB in immunocompetent individuals has decreased from 18 to 24 months to 4 to 6 months and also has included the use of directly observed therapy (DOT) administered three times per week. These changes underscore the importance and impact of SCAT for improving quality of life, adherence, and reducing the plague of MDR disease pathogens, toxicity, and cost (Fig. 1) (7,8). Although sufficient data supporting the use of SCAT for many other infectious diseases or for defining populations that would be most likely to benefit from SCAT is lacking, there is potential to save enormous resources, reduce healthcare costs, and improve clinical outcomes. The lack of compelling data to support SCAT is related, in part, to a lack of funds to support randomized clinical trials. Unfortunately, pharmaceutical companies may lack the incentives to support the conduct of such trials, but perhaps a federal-government administered and pharmaceutical-supported collaborative group, similar to the AIDS clinical trials group (ACTG) model should be established to evaluate a broader spectrum of optimal infectious disease management. Important considerations regarding the use of SCAT include host variables, the specific pathogen(s), site and type of infection, antibiotic pharmacokinetics, and antibiotic sensitivity of the infecting organism(s) (Fig. 2). Effective use of SCAT should decrease the number and amount of antibiotics prescribed, improve outcomes, particularly in terms of better adherence, and reduce adverse effects, complications, and selection of antibiotic-resistant pathogens (Table 1). SCAT also provides enormous economic benefits related to reduced costs for drug acquisition and administration and fewer office visits for laboratory tests and treatments for adverse events, and reduced complications secondary to more prolonged antibiotic use. Potential disadvantages of SCAT may include reduced treatment efficacy related to incomplete therapy that could result in complications and prolonged carriage or potential transmission of the pathogen (9).

This chapter provides an overview of the background and available evidence for the use of SCAT for selected infectious diseases. Our primary focus is the use of SCAT in adults with bacteremia, genitourinary, gastrointestinal, and respiratory tract infections acquired in both the community and healthcare settings. A summary of key points with references is included at the end of each section.

FIGURE 1 Advantages of shorter course antimicrobial therapy (SCAT) are numerous. These advantages must be balanced by the potential disadvantages of complications related to untreated infection, the possibility of prolonged carriage, or colonization with the potential spread to others.

FIGURE 2 Considerations for the use of shorter course antimicrobial therapy (SCAT) involve host factors, specific type and extent of the infection, the infecting pathogen, and the characteristics and efficacy of the antimicrobial agent prescribed.

SCAT Variables

FIGURE 2 Considerations for the use of shorter course antimicrobial therapy (SCAT) involve host factors, specific type and extent of the infection, the infecting pathogen, and the characteristics and efficacy of the antimicrobial agent prescribed.

BACKGROUND ISSUES

Since antibiotics were first introduced nearly 70 years ago, there have been a number of antimicrobial agents developed to inhibit or kill bacteria causing human infections. Sulfonamides were the first modern antimicrobials used, but it was Fleming's observation that a mold (penicillin) could inhibit bacterial growth, that ushered in the antibiotic era that is such an integral part of modern medicine. The use of penicillin and other antibiotics has had an enormous effect on reducing patient morbidity and mortality, but these successes have been countered, in part, by the widespread misuse of antimicrobial agents, resulting in the sustained emergence of MDR bacteria. It is estimated that 40% to 50% of antibiotic use in hospitals is inappropriate in terms of timing, indications, and proper dosing (10,11). Solutions to this problem include wiser and more effective use and monitoring of antibiotics, coupled with better primary and secondary prevention strategies (12,13).

Strategies to Reduce Antibiotic Use

Appropriate antibiotic therapy should target bacterial pathogens rather than viruses, treating individuals who are symptomatic or have evidence of infection rather than those with colonization, streamlining, or de-escalating antibiotic therapy when possible, and discontinuing antibiotics in patients with undocumented infection (14,15). Implementing such strategies will require better education of healthcare providers and consumers about the risks of antibiotic misuse, along

TABLE 1 General Principles of Antibiotic Therapy and for the Use of Shorter-Course Antibiotic Therapy (SCAT)

Identify the site of infection, pathogen, and the antibiotic sensitivity pattern Evaluate host factors: age, pregnancy, drug allergies, renal, hepatic, and immune status Assess antibiotic dose, route, synergy, antagonism, pharmacokinetics, drug interactions, and adverse events

Assess the patient's response to therapy and need to alter, streamline, or stop antibiotic therapy Assess for SCAT as recommended in guidelines and follow patient for relapse, reinfection, or complications with more effective systems to monitor and control antibiotic use. Use of a computerized pharmacy surveillance system or the use of targeted surveillance by pharmacists have also been cost-effective intervention strategies (16).

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