Medical Grand Rounds

Antibiotic stewardship: Why we must, how we can

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ABSTRACT

Improving our antibiotic use is critical to the safety of our patients and the future of medicine. This can improve patient outcomes, save money, reduce resistance, and help prevent negative consequences such as Clostridium difficile infection. The US Centers for Disease Control and Prevention (CDC) is undertaking a nationwide effort to appropriately improve antibiotic use in inpatient and outpatient settings.

KEY POINTS

  • Antibiotics are fundamentally different from other medications, posing special challenges and needs for improving their use.
  • Antibiotic usage in the United States varies widely among healthcare settings.
  • Antibiotic stewardship efforts should focus on optimizing appropriate use rather than simply reducing use.
  • Effective interventions include timely consultation on appropriate prescribing, targeting specific infections, and providing feedback to physicians.

 

References

Antibiotic stewardship has always been a good idea. Now it is also required by the Joint Commission and the Center for Medicare and Medicaid Services (CMS). This article reviews the state of antibiotic use in the United States and efforts to improve antibiotic stewardship in practice. 

ANTIBIOTICS ARE DIFFERENT FROM OTHER DRUGS

Their efficacy wanes over time. Antibiotics are the only medications that become less useful over time even if used correctly. Although other types of drugs are continuously being improved, the old ones work as well today as they did when they first came out. But antibiotics that were in use 50 years ago are no longer as effective.

They are a shared resource. Antibiotics are regularly used by many specialties to deliver routine and advanced medical care. Surgeries, transplantation, and immunosuppressive therapy would be unsafe without antibiotics to treat infections. Some patients awaiting lung transplant are not considered good candidates if they have evidence of colonization by antibiotic-resistant organisms.

Individual use may harm others. Even people who are not exposed to an antibiotic can suffer the consequences of how others use them.

In a retrospective cohort study, Freedberg et al1 analyzed the risk of hospitalized patients developing Clostridium difficile infection and found that the risk was higher if the previous occupant of the bed had received antibiotics. The putative mechanism is that a patient receiving antibiotics develops altered gut flora, leading to C difficile spores released into the environment and not eradicated by normal cleaning. The next patient using the bed is then exposed and infected.

ANTIBIOTIC USE IS HIGH

The US Centers for Disease Control (CDC) monitors antibiotic prescriptions throughout the United States. In the outpatient setting, enough antibiotics are prescribed nationwide for 5 out of every 6 people to get 1 course of antibiotics annually (835 prescriptions per 1,000 people). Rates vary widely among states, with the lowest rate in Alaska (501 prescriptions per 1,000 people) and the highest in West Virginia (1,285 prescriptions per 1,000 people).2 In comparison, Scandinavian countries prescribe about 400 courses per 1,000 people, about 20% less than our lowest-prescribing state.3

Antibiotics are probably the most frequently prescribed drugs in US hospitals. Data from 2006 to 2012 showed that 55% of hospitalized patients received at least 1 dose of an antibiotic and that overall about 75% of all hospital days involved an antibiotic.4 Rates did not vary by hospital size, but nonteaching hospitals tended to use antibiotics more than teaching hospitals. Antibiotic use is much more common in intensive care units than in hospital wards (1,092 and 720 days of antibiotic treatment per 1,000 patient-days, respectively).

Although overall antibiotic use did not change significantly over the years of the survey, use patterns did: fluoroquinolone use dropped by 20%, possibly reflecting rising resistance or increased attention to associated side effects (although fluoroquinolones remain the most widely prescribed inpatient antibiotic class), and use of first-generation cephalosporins fell by 7%. A cause for concern is that the use of broad-spectrum and “last-resort” antibiotics increased: carbapenem use by 37%, vancomycin use by 32%, beta-lactam/beta-lactamase inhibitor use by 26%, and third- and fourth-generation cephalosporin use by 12%.4

About one-third of use is unnecessary

Many studies have tried to measure the extent of inappropriate or unnecessary antibiotic use. The results have been remarkably consistent at 20% to 40% for both inpatient and outpatient studies. One study of hospitalized patients not in the intensive care unit found that 30% of 1,941 days of prescribed antimicrobial therapy were unnecessary, mostly because patients received antibiotics for longer than needed or because antibiotics were used to treat noninfectious syndromes or colonizing microorganisms.5  

ANTIBIOTIC EXPOSURE HAS NEGATIVE CONSEQUENCES

Any exposure to a medication involves the potential for side effects; this is true for antibiotics whether or not their use is appropriate. An estimated 140,000 visits to emergency departments occur annually for adverse reactions to antibiotics.6 In hospitalized patients, these reactions can be severe, including renal and bone marrow toxicity. As with any medications, the risks and benefits of antibiotic therapy must be weighed patient by patient.

Disturbance of gut microbiome

Antibiotics’ disruptive effects on normal gut flora are becoming better understood and are even believed to increase the risk of obesity and asthma.7,8 

Animal models provide evidence that altered flora is associated with sepsis, which is attributed to the gut microbiome’s role in containing dissemination of bacteria in the body.9 An ecological study provides further evidence. Baggs et al10 retrospectively studied more than 9 million patients discharged without sepsis from 473 US hospitals, of whom 0.6% were readmitted for sepsis within 90 days. Exposure to a broad-spectrum antibiotic was associated with a 50% increased risk of readmission within 90 days of discharge because of sepsis (odds ratio 1.50, 95% confidence interval 1.47–1.53).

Increase of C difficile infections

Antibiotics exert selective pressure, killing susceptible bacteria and allowing resistant bacteria to thrive.

The risk of C difficile infection is 7 to 10 times higher than at baseline for 1 month after antibiotic use and 3 times higher than baseline in the 2 months after that.11 Multiple studies have found that stewardship efforts to reduce antibiotic use have resulted in fewer C difficile infections.

A nationwide effort in England over the past decade to reduce C difficile infections has resulted in 50% less use of fluoroquinolones and third-generation cephalosporins in patients over age 65. During that time, the incidence of C difficile infection in that age group fell by about 70%, with concomitant reductions in mortality and colectomy associated with infection. No increase in rates of hospital admissions, infection complications, or death were observed.12–14

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