Hospital Infection Control

Antimicrobial stewardship

How does antimicrobial stewardship impact infection control?

Antimicrobial stewardship efforts work hand in hand with infection control practices. Antimicrobial stewardship efforts are focused on decreasing unnecessary and inappropriate antibiotic use (either antimicrobial selection, dosing, route, or duration), a driver of antimicrobial resistance. Curtailing inappropriate use of antimicrobials in a hospital may also aid in decreasing rates of hospital-acquired Clostridium difficile infection, and the occurrence of adverse drug events to antimicrobials.

What elements of antimicrobial stewardship are necessary for infection prevention and control?

There is a lack of data regarding the most effective elements of a stewardship program that lead to decreased antimicrobial resistance. The Guideline on the Development of an Institutional Antimicrobial Stewardship Program, developed by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America, states that the two main core strategies of any program are the prospective review of antimicrobial use with direct feedback to the prescriber and formulary restriction and preauthorization. These activities should be conducted by an infectious diseases physician and clinical pharmacist with infectious diseases training. Other elements of a program, but not considered core strategies, include education, guidelines and clinical pathways, streamlining or de-escalation of therapy, dose optimization, and parenteral to oral conversion. Further, the guideline states that collaboration between members of the antimicrobial stewardship program and hospital infection control is essential.

What research supports antimicrobial stewardship?

Numerous single-center studies have been performed that demonstrate cost savings from antimicrobial stewardship programs, but there is a lack of well-conducted, rigorous studies that demonstrate a causal relationship between stewardship interventions and outcomes such as antimicrobial resistance reduction. A published systematic review of studies from 1980 to 2003, assessing antimicrobial prescribing to incidences of antimicrobial drug resistance and healthcare-associated infections, found that four studies provided strong evidence that antimicrobial prescribing interventions decreased resistance. Data most strongly support decreases in the incidence of Clostridium difficile infection following changes in antimicrobial prescribing.

Summary of current controversies.

Most experts agree that focusing on broad-spectrum antimicrobial use is an important element in the selection for multidrug-resistant organisms. However, there is no consensus on the approach of instituting and conducting antimicrobial stewardship programs within an institution. There is a great need for further well-defined studies that utilize well-defined interventions to define the optimal elements of a stewardship program.

Some controversies concerning the implementation of antimicrobial stewardship programs include the following: possible antagonism of other physicians by infectious diseases specialists; perceived challenge to physician autonomy with restrictive antibiotic policies; high-level of concern among clinicians with risks of not treating or under-treating patients. In order to be successful, stewardship programs need to have an element in their framework that addresses the cognitive biases that underlie prescribing behaviors. There is also a need for well-designed decision support systems to aid in helping clinicians choose appropriate antibiotic agents.

Another controversial area regarding antimicrobial stewardship is the concept known as “squeezing the balloon.” Restricting use of a certain antibiotic or antibiotic class to decrease resistance may result in inducing resistance to the antibiotic, or antibiotic class that was substituted.

What is the impact of antimicrobial stewardship relative to the impact of other infection control methods?

It is currently not known what the additional benefits are of certain antimicrobial stewardship efforts to infection control practices such as isolation and hand hygiene.

Overview of important clinical trials, meta-analyses, case control studies, case series, and individual case reports related to infection control and antimicrobial stewardship.

There is a general lack of relevant clinical trials or meta-analyses regarding this topic. Many single-center, quasi-experimental studies have been published demonstrating cost benefits of stewardship programs, and improvements in patient outcomes, including a reduced incidence of healthcare-associated infections such as C. difficile.

A review of these studies has been conducted by MacDougall, and in late 2010, the CDC established the Get Smart for Healthcare Web site that provides a toolkit for stewardship programs, including supportive references. However, most of these studies are hampered by inadequate control group selection and improper study design.

A review of 306 studies of prescribing interventions, published in 2003 by Ramsay, found that 70% of these did not meet minimum criteria of the Cochrane Collaboration’s Effective Practice and Organization of Care Group. The most common reasons were use of uncontrolled before-and-after design (46%) and inadequate interrupted time series analysis (24%). A more recent review (2006) of prescribing interventions on reduction in antimicrobial resistance or healthcare-associated infection by Davey, found that of 66 studies with interpretable data, only four studies showed strong evidence that the prescribing intervention resulted in a change in microbial outcomes. These four studies are summarized in Table I, and two studies that demonstrate the benefit of prescribing interventions in addition to infection control practices on the reduction in antimicrobial resistance or healthcare-associated infections are described in Table II.

Table I.

Published studies with strong evidence of antimicrobial drug prescribing interventions and reduction in antimicrobial resistance or healthcare-associated infections according to systematic review by Davey
Study Setting Intervention Findings
Carling P, 2003 University-affiliated teaching hospital Review of use of broad-spectrum antimicrobials with feedback to provider 22% decrease in broad-spectrum antibiotic use; significant decrease in C. difficile infections and infections due to resistant Enterobacteriaceae
Bradley SJ, 1999 Oncology unit Restriction of ceftazidime use Decrease in glycopeptide-resistant Enterococcus spp. colonization
de Man P, 2000 Two neonatal intensive care units Two different empiric antimicrobial regimens used in two identical NICUs: Penicillin G and tobramycin (for early onset septicemia) and flucloxacillin and tobramycin (late onset septicemia) vs. amoxicillin and cefotaxime The risk was 18 times higher for neonates exposed to amoxicillin and cefotaxime for colonization with gram negative bacilli resistant to empiric therapy. Isolation of Enterobacter vs. E. coli was more common among neonates receiving amoxicillin and cefotaxime.
Singh N, 2000 Surgical and medical intensive care units Implementation of a clinical pulmonary infection score as criteria for decision making regarding continuation and duration of antibiotics for pulmonary infiltrates Antimicrobial resistance or superinfections developed less commonly among patients randomized to shorter course of antibiotics

Table II.

Published studies that demonstrated the effect of antimicrobial use and infection control efforts on reduction in antimicrobial resistance or healthcare-associated infections
Study Setting Intervention Findings
Valiquette L, 2007 Secondary/tertiary care hospital Implementation of antimicrobial guidelines for empiric treatment of common infections aimed to decrease use of antibiotics associated with C. difficile infection (2nd/3rd generation cephalosporins, ciprofloxacin, clindamycin, and macrolides) Reduction in targeted antibiotics was congruent with a reduction in C. difficile occurrence, which was not seen when infection control practices were upgraded
Aldeyab MA, 2008 General teaching hospital Variationsin certain antimicrobial use and infection control activities were assessed in relation to the incidence of healthcare-associated MRSA over a 5-year period Certain antimicrobial use (3rdgeneration cephalosporins, macrolides, amoxicillin/clavulanic acid) was associated with variations in MRSA incidence and also certain infection control practices (such as number of patients screened for MRSA) were associated with decreased incidence of healthcare-associated MRSA

Controversies in detail.

The membership of the Society of Healthcare Epidemiology of America (SHEA) has identified the defining of effective approaches to antimicrobial stewardship as one of the most important clinical problems for Healthcare Epidemiology. Also, the SHEA/IDSA Institutional Antimicrobial Stewardship Program Guideline has identified the defining of the incremental role of antimicrobial stewardship programs combined with infection control practices, such as hand hygiene and isolation, to prevent secondary spread of resistant organisms, as an area for future research. There is also a need for education and training programs for infectious diseases fellows and pharmacists in the area of antimicrobial stewardship.

What national and international antimicrobial stewardship guidelines exist?

The SHEA/IDSA Guideline for Developing an Institutional Program to Enhance Antimicrobial Stewardship

References

Dellit, TH, Owens, RC, McGowan, JE. "Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship". Clin Infect Dis. vol. 44. 2007. pp. 159-77.

Davey, P, Brown, E, Fenelon, L. "Systematic review of antimicrobial drug prescribing in hospitals". Emerg Infect Dis. vol. 12. 2006. pp. 211-216.

Drew, RH, White, R, MacDougall, C, Hermsen, ED. "Owens RC on behalf of the Society of Infectious Diseases Pharmacists. Insights from the Society of Infectious Diseases Pharmacists on antimicrobial stewardship guidelines from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America". Pharmacotherapy. vol. 29. 2009. pp. 593-607.

MacDougall, C, Polk, RE. "Antimicrobial stewardship programs in health care systems". Clinical Microbiology Reviews. vol. 18. 2005. pp. 638-56.

Ramsay, C, Brown, E, Hartman, G, Davey, P. "Room for improvement: a systematic review of the quality of evaluations of interventions to improve hospital antibiotic prescribing". J Antimicrob Chemother. vol. 52. 2003. pp. 764-71.

"The Research Committee of the Society of Healthcare Epidemiology of America. Enhancing patient safety by reducing healthcare-associated infections: the role of discovery and dissemination". Infect Control Hosp Epidemiol. vol. 31. 2010. pp. 118-23.

Carling, P, Fung, T, Killion, A, Terrin, N, Barza, M. "Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years". Infect Control Hosp Epidemiol. vol. 24. 2003. pp. 699-706.

Bradley, SJ, Wilson, ALT, Allen, MC, Sher, HA, Goldstone, AH, Scott, GM. "The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic usage". J Antimicrob Chemother. vol. 43. 1999. pp. 261-6.

de Man, P, Verhoeven, BAN, Berbrugh, HA, Bos, MC, van den Anker, JN. "An antibiotic policy to prevent emergence of resistant bacilli". Lancet. vol. 355. 2000. pp. 973-8.

Singh, N, Rogers, P, Atwood, CW, Wagener, MM, Yu, VL. "Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription". Am J Respir Crit Care Med. vol. 162. 2000. pp. 505-11.

Valiquette, L, Cossette, B, Garant, MP, Diab, H, Pepin, J. "Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain". Clin infect Dis. vol. 45. 2007. pp. S112-21.

Aldeyab, MA, Monnet, DL, Lopez-Lozano, JM. "Modelling the impact of antibiotic use and infection control practices on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus: a time-series analysis". J Antimicrob Chemother. vol. 62. 2008. pp. 593-600.

Burke, JP. "Antibiotic resistance—squeezing the balloon?". JAMA. vol. 14. 1998. pp. 1270-1.

Charani, E, Cooke, J, Homes, A. "Antibiotic stewardship programmes—what’s missing?". J Antimicrob Chemother. vol. 65. 2010. pp. 2275-77.

"Centers for Disease Control and Prevention: Get Smart for Healthcare".

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