What is Antimicrobial Stewardship (AMS)? Why are WHO and Other Organizations Pushing so Hard?

Introduction

Antimicrobial resistance (AMR) is one of the leading global public health threats. In 2019, it is anticipated that resistant bacteria were responsible for 1.27 million deaths globally and contributed to 4.95 million deaths. The economic consequences of AMR are considerably more severe. As per the World Bank, AMR might lead to an extra US$ 1 trillion in healthcare costs by 2050, along with yearly GDP losses ranging from US$ 1 trillion to US$ 3.4 trillion by 2030.1 AMR undermines the advantages of medical progress in complex robotic surgery, organ transplantation, cancer treatment, and critical care for ICU patients.

Every clinician should spare 15 minutes to read this article and then think about how they can contribute to the AMS campaign?

So, coming to the first question, what is AMS?

AMS is an effort to measure and improve antibiotic utilization by clinicians. Improving antibiotic utilization by clinicians is critical to the patient’s management. Improving antibiotic utilization not only effectively treats the infections, but also protects patients from harm caused by unnecessary antibiotic use and minimizes the likelihood of antibiotic resistance development.

Most of the antimicrobial usage occurs in outpatient care. Inappropriate use of antimicrobials in outpatient settings is common. In the USA, the CDC estimates that up to 30% of antibiotics prescribed in clinics are unnecessary, and many more prescriptions are suboptimal. (i.e. wrong choice, wrong dose, wrong duration).2,3 I didn't find comparable studies from India, nonetheless our figures may be worse than those in the United States. Therefore, it is imperative for every practitioner to take on responsibility prior to prescribing antibiotics to our patients. 

Before prescribing antibiotics, we should have clear answers to the following questions: 

Does this patient require antibiotics for his or her treatment?

·         Is this illness caused by a bacterial infection?

·         If yes, which is the site of the infection?

·         What are the likely organisms causing this site infection?

·         As per textbooks, which is the drug of choice for the treatment of this bacterial infection and available in-vitro drug susceptibilities results?

We should remember that antibiotics can’t work for viral infections, and patients with leukocytosis and fever is not an indication for the antibiotics. Systemic inflammatory conditions can cause fever and leukocytosis. Empiric antimicrobials may be justified in such cases, but it should be stopped once a systemic inflammatory condition such as adult onset stills disease is diagnosed. The choice of an appropriate antibiotic is crucial when treating bacterial infections. Clinicians should be aware of the spectrum, site of penetration, and recommended dosage of antibiotics. On multiple occasions, I was called to opine that the patient is not responding to the antimicrobials selected based on in-vitro drug susceptibility. The most prevalent reason I discovered for this scenario was a suboptimal antibiotic dosage. So, when I receive a call from a doctor stating that the patient is not responding to 5 days on XYZ antibiotics, I simply ask for the site of infection, diagnostic tests performed, renal-liver functions, and the antibiotic dosage used for the treatment. The site of infection will inform me about drug penetration, while the diagnostic test will tell me whether the patient is being treated for colonizers or genuine pathogens, and whether dosage adjustments are required for renal or liver function. Most of the time, I get the answer "no response to treatment" from these questions, and invariably, suboptimal dose is responsible for the non-responder state, followed by unnecessary antimicrobials for colonizers in cases of asymptomatic bacteriuria or endotracheal/tracheostomy tube secretions repeatedly growing MDR gram negative organisms in a stable patient breathing on a T-piece.

In a patient with bacterial infections, clinician should be clear about following two questions at the time of initiating antibiotic treatment. 

·         What is the duration of antibiotic therapy in this condition? 

·         How do I monitor the response to the prescription for antibiotic treatment? Clinical or some laboratory markers.

Another major issue in antimicrobial treatment is the extended length of antibiotics used for treatment. Evidence suggests that most of the infections are better treated with a shorter course of antimicrobial treatment of 5-7 days. Only a few deep-seated infections, bone and joint infections, and infective endocarditis required a longer course of antimicrobials. Implementation of AMS coupled with comprehensive infection control program has shown to reduces the risk of treatment failure, hospital stay and cost of therapy, adverse drug reactions, clostridium difficille infection, and the emergence of antimicrobial resistance.4,5 

AMS Structure:

The core elements of an AMS program include of effective leadership from hospital administration, as well as from clinicians, preferably an infectious diseases specialist, who are trusted and esteemed by their peers. Other elements include hospital pharmacist and microbiologist who are aware of shifting resistance patterns, antimicrobial consumption, and outbreaks of certain organisms in the hospital. Periodic audits of antimicrobial usage, as well as educating consultants in other disciplines, are other important components of AMS. Medicines prescribed out of the formulary require prior authorization from the hospital's medical administration. This will prevent the misuse of restricted medications. 

Diagnostic Stewardship:

Improving the appropriate and timely use of microbiological diagnostics to guide therapy decisions can significantly improve antimicrobial usage practices. In this area, multiplex PCR and point-of-care testing for various infectious diseases can assist doctors in making an early, confirmed diagnosis, limiting the usage of antimicrobials on an empiric basis.

The interpretation of test results is equally important in AMS. This can be explained using the example of evaluating and treating UTI in older people. Several patients, both outpatients and inpatients, were misdiagnosed with UTI due to the presence of pus cells or a positive urine culture and treated with antibiotics. Up to 50% of women in long-term care institutions will test positive for bacteria in their urine while not having a urinary tract infection. Experts advocate diagnosing and treating only people who exhibit specific signs and symptoms of a urinary tract infection. Although guidelines strongly advise against treatment, research suggests that up to 80% of people with asymptomatic bacteriuria receive antibiotics.6 Pyuria is commonly found with asymptomatic bacteriuria (ASB). 90% of elderly institutionalized residents7, 30-75% patients with short term (< 30 days) catheters. and 50-100% with long-term catheters have pyuria.8 

Treatment for ASB is not indicated in premenopausal, non-pregnant women, diabetic women, older persons living in the community, elderly people living in long term care facilities, persons with spinal cord injuries, or catheterized patients. Pregnant women and people undergoing urogenital intervention should be treated for ASB to prevent the risk of adverse outcomes and complications. Remember that routine screening for and treatment of ASB in older individuals in the community/ long-term care facilities is not recommended. 

Antibiotic misuse is also common in critical care department like outpatient care. Study revealed that 30-60% of antibiotics prescribed in ICU are unnecessary, inappropriate and sub-optimal.9. Fear and not knowledge deficit often drives excess antibiotic use in these settings.10                                                           

Summary:

Effective deployment of AMS requires strong leadership (at both the ID doctor and management levels). AMS is a collaborative endeavor; ongoing education of medical professionals will improve understanding and confidence in distinguishing colonizers from infections. Monitoring and auditing are two effective ways to enhance hospital AMS.

References:

1. https://www.who.int/news-room/fact sheets / detail / antimicrobial-resistance1.

2. Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM Jr, Finkelstein JA, Gerber JS, Hyun DY, Linder JA, Lynfield R, Margolis DJ, May LS, Merenstein D, Metlay JP, Newland JG, Piccirillo JF, Roberts RM, Sanchez GV, Suda KJ, Thomas A, Woo TM, Zetts RM, Hicks LA. Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011. JAMA. 2016 May 3;315(17):1864-73. doi: 10.1001/jama.2016.4151. PMID: 27139059.

3. Drekonja DM, Filice GA, Greer N, Olson A, MacDonald R, Rutks I, Wilt TJ. Antimicrobial stewardship in outpatient settings: a systematic review. Infect Control Hosp Epidemiol. 2015 Feb;36(2):142-52. doi: 10.1017/ice.2014.41. PMID: 25632996.

4. Karanika S, Paudel S, Grigoras C, Kalbasi A, Mylonakis E. Systematic Review and Meta-analysis of Clinical and Economic Outcomes from the Implementation of Hospital-Based Antimicrobial Stewardship Programs. Antimicrob Agents Chemother. 2016 Jul 22;60(8):4840-52. doi: 10.1128/AAC.00825-16. PMID: 27246783; PMCID: PMC4958232.

5. Baur D, Gladstone BP, Burkert F, Carrara E, Foschi F, Döbele S, Tacconelli E. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis. 2017 Sep;17(9):990-1001. doi: 10.1016/S1473-3099(17)30325-0. Epub 2017 Jun 16. PMID: 28629876.

6. Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, Eckert LO, Geerlings SE, Köves B, Hooton TM, Juthani-Mehta M, Knight SL, Saint S, Schaeffer AJ, Trautner B, Wullt B, Siemieniuk R. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2019 May 2;68(10):e83-e110. doi: 10.1093/cid/ciy1121. PMID: 30895288.

7. Nicolle LE. Asymptomatic bacteriuria in the elderly. Infect Dis Clin North Am. 1997 Sep;11(3):647-62. doi: 10.1016/s0891-5520(05)70378-0. PMID: 9378928.

8. Tambyah PA, Maki DG. Catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1,497 catheterized patients. Arch Intern Med. 2000 Mar 13;160(5):678-82. doi: 10.1001/archinte.160.5.678. PMID: 10724054.

9. Luyt CE, Bréchot N, Trouillet JL, Chastre J. Antibiotic stewardship in the intensive care unit. Crit Care. 2014 Aug 13;18(5):480. doi: 10.1186/s13054-014-0480-6. PMID: 25405992; PMCID: PMC4281952.

10. Wunderink RG, Srinivasan A, Barie PS, Chastre J, Dela Cruz CS, Douglas IS, Ecklund M, Evans SE, Evans SR, Gerlach AT, Hicks LA, Howell M, Hutchinson ML, Hyzy RC, Kane-Gill SL, Lease ED, Metersky ML, Munro N, Niederman MS, Restrepo MI, Sessler CN, Simpson SQ, Swoboda SM, Guillamet CV, Waterer GW, Weiss CH. Antibiotic Stewardship in the Intensive Care Unit. An Official American Thoracic Society Workshop Report in Collaboration with the AACN, CHEST, CDC, and SCCM. Ann Am Thorac Soc. 2020 May;17(5):531-540. doi: 10.1513/AnnalsATS.202003-188ST. PMID: 32356696; PMCID: PMC7193806.