Antimicrobial resistance – A global concern

Antimicrobial resistance (AMR) has emerged as a major public health problem all over the world. Infections caused by resistant microbes fail to respond to treatment, resulting in prolonged illness and greater risk of death. Treatment failures also lead to longer periods of infectivity, with increased numbers of infected people moving in the community. This in turn exposes the general population to the risk of contracting a resistant strain of microorganisms. Most alarming of all are the diseases caused by multidrug-resistant microbes, which are virtually non-treatable and thereby create a post-antibiotic era scenario. Unlike other medications, the potential for spread of resistant organisms means that the misuse of antibiotics can adversely impact the health of patients who are not even exposed to them. The CDC estimates more than two million people are infected with antibiotic-resistant organisms, resulting in approximately 23,000 deaths annually.

Hospital antibiotic stewardship programs

• Leadership commitment. Dedicating necessary human, financial, and information technology resources;
• Accountability. Appointing a single leader responsible for program outcomes;
  Drug expertise. Appointing a single pharmacist leader responsible for working to improve antibiotic use;
• Action. Implementing at least one recommended action, such as systemic evaluation of ongoing treatment need after a set period of initial treatment;
• Tracking. Monitoring antibiotic prescribing and resistance patterns;
  Reporting. Regular reporting information on antibiotic use and resistance to doctors, nurses, and relevant staff; and
• Education. Educating clinicians about resistance and optimal prescribing.

Policies that support optimal antibiotic use

• Document dose, duration, and indication. Specify the dose, duration and indication for all courses of antibiotics so they are readily identifiable. Make this information accessible to ensure that antibiotics are modified as needed and/or discontinued in a timely manner.
• Develop and implement facility-specific treatment recommendations. Facility-specific treatment recommendations, based on national guidelines and local susceptibilities and formulary options can optimize antibiotic selection and duration.

Interventions to improve antibiotic use
Antibiotic time outs. Antibiotics are often started empirically in hospitalized patients while diagnostic information is being obtained. An antibiotic time out prompts a reassessment of the continuing need and choice of antibiotics when the clinical picture is clearer and more diagnostic information is available. All clinicians should perform a review of antibiotics 48 hours after antibiotics are initiated to answer these key questions:

• • Does this patient have an infection that will respond to antibiotics?
  • If so, is the patient on the right antibiotic(s), dose, and route of administration?
  • Can a more targeted antibiotic be used to treat the infection (de-escalate)?
  • How long should the patient receive the antibiotic(s)?

Prior authorization. Some facilities restrict the use of certain antibiotics based on the spectrum of activity, cost, or associated toxicities to ensure that use is reviewed with an antibiotic expert before therapy is initiated.

Prospective audit and feedback. External reviews of antibiotic therapy by an expert in antibiotic use have been highly effective in optimizing antibiotics in critically ill patients, and in cases where broad spectrum or multiple antibiotics are being used.

Pharmacy-driven interventions

• Automatic changes from intravenous to oral antibiotic therapy in appropriate situations and for antibiotics with good absorption, which improves patient safety by reducing the need for intravenous access;
• Dose adjustments in cases of organ dysfunction (e.g., renal adjustment);
• Dose optimization including dose adjustments based on therapeutic drug monitoring, optimizing therapy for highly drug-resistant bacteria, achieving central nervous system penetration, extended-infusion administration of beta-lactams, and the like;
• Automatic alerts in situations where therapy might be unnecessarily duplicative including simultaneous use of multiple agents with overlapping spectra, e.g., anaerobic activity, atypical activity, Gram-negative activity, and resistant Gram-positive activity ;
• Time-sensitive automatic stop orders for specified antibiotic prescriptions, especially antibiotics administered for surgical prophylaxis; and
• Detection and prevention of antibiotic-related drug-drug interactions, e.g., interactions between some orally administered fluoroquinolones and certain vitamins.

Infection and syndrome-specific interventions
Community-acquired pneumonia. Interventions for community-acquired pneumonia have focused on correcting recognized problems in therapy, including improving diagnostic accuracy, tailoring of therapy to culture results and optimizing the duration of treatment to ensure compliance with guidelines.

Urinary tract infections (UTIs). Interventions for UTIs focus on avoiding unnecessary urine cultures and treatment of patients, who are asymptomatic, and ensuring that patients receive appropriate therapy based on local antibiogram.

Skin and soft-tissue infections. Interventions for skin and soft-tissue infections have focused on ensuring patients do not get antibiotics with overly broad spectra and ensuring the correct duration of treatment.

Empiric coverage of methicillin-resistant Staphylococcus aureus (MRSA) infections. In many cases, therapy for MRSA can be stopped if the patient does not have an MRSA infection, or changed to a beta-lactam if the cause is methicillin-sensitive S. aureus.

Clostridium difficile infections. Reviewing antibiotics in patients with new diagnoses of CDI can identify opportunities to stop unnecessary antibiotics, which improves the clinical response of CDI to treatment and reduces the risk of recurrence.

Treatment of culture-proven invasive infections. Invasive infections (e.g. blood stream infections) present good opportunities for interventions to improve antibiotic use because they are easily identified from microbiology results.

Tracking and reporting antibiotic use and outcomes
Monitoring antibiotic prescribing. Measurement is critical to identify opportunities for improvement and assess the impact of improvement efforts. For antibiotic stewardship, measurement may involve evaluation of both process (are policies and guidelines being followed as expected?) and outcome (have interventions improved antibiotic use and patient outcomes?).

Antibiotic-use measures. Measure antibiotic use as either days of therapy (DoT) or defined daily dose (DDD). DoT is an aggregate sum of days for which any amount of a specific antimicrobial agent is administered or dispensed to a particular patient (numerator) divided by a standardized denominator (e.g. patient days, days present, or admissions). If a patient is receiving two antibiotics for 10 days, the DoT numerator would be 20. An alternative measure of antibiotic use is defined daily dose (DDD). This metric estimates antibiotic use in hospitals by aggregating the total number of grams of each antibiotic purchased, dispensed, or administered during a period of interest divided by the World Health Organization-assigned DDD.

Outcome measures. Stewardship programs can result in significant annual drug cost savings, and even larger savings when other costs are included. These savings have been helpful in garnering support for antibiotic stewardship programs. If hospitals monitor antibiotic costs, consideration should be given to assessing the pace at which antibiotic costs were rising before the start of the stewardship program. After an initial period of marked cost savings, antibiotic-use patterns and savings often stabilize; so continuous decreases in antibiotic use and cost should not be expected. However, it is important to continue support for stewardship to maintain gains as costs can increase if programs are terminated.

Education. Antibiotic stewardship programs should provide regular updates on antibiotic prescribing, antibiotic resistance, and infectious-disease management that address both national and local issues. Sharing facility-specific information on antibiotic use is a tool to motivate improved prescribing, particularly if wide variations in the patterns of use exist among similar patient-care locations. There are many options for providing education on antibiotic use such as didactic presentations, which can be done in formal and informal settings, messaging through posters and flyers and newsletters, or electronic communication to staff groups.

Emerging developments in antibiotic stewardship. Strategies for improving antibiotic use and evidence for best practices in antibiotic stewardship are evolving. The integration of IT into the clinical data presentation and decision making for antibiotic use will expand with increased uptake and capabilities of electronic health records. The role of diagnostic laboratory testing is another area of evolution. Rapid diagnostic tests, such as procalcitonin, fluorescence in situ hybridization using peptide nucleic acid probes (PNA FISH), and matrix-assisted laser-desorption/ionization time of flight (MALDI-TOF) mass spectrometric analysis have been successfully incorporated by some stewardship programs and may become important additions to stewardship efforts. The use of these diagnostic tools on patient care is an area of great interest, and further research is needed to determine how they can best be applied to stewardship efforts.