Fluoroquinolone Restriction as an Effective Antimicrobial Stewardship Intervention
Purpose of review
Fluoroquinolones are a commonly prescribed antibiotic class that has come under scrutiny in recent years due to mounting evidence of association between adverse drug events, C. difficile infection and isolation of antibiotic-resistant bacteria.
Inpatient antimicrobial stewardship (AMS) programs have a toolbox of potential interventions to curb inappropriate antibiotic use, prevent antibiotic-associated adverse drug events, and avoid unnecessary costs of care. Fluoroquinolone restriction policies in the acute care setting have demonstrated beneficial effects, including decreased rates of C. difficile infection and ESBL-producing Enterobacteriaceae. However, a simple blanket restriction policy may “squeeze the antibiotic balloon” and will likely be insufficient if not implemented in conjunction with other AMS interventions.
There is a growing body of evidence to support formulary restriction of fluoroquinolones in the acute care setting to decrease rates of C. difficile infection and development of ESBL-producing organisms. Data on how to best implement these restrictions or how to implement outside of acute care settings is limited.
KeywordsAntibiotic restriction C. difficile Extended-spectrum beta-lactamase Fluoroquinolones
Compliance with Ethical Standards
Conflict of Interest
Kimberly C. Claeys, Teri L. Hopkins, Ana D. Vega, and Emily L. Heil declare they have no conflicts of interests.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.• Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51–77. Official IDSA/SHEA guidelines for antimicrobial stewardship. CrossRefPubMedPubMedCentralGoogle Scholar
- 2.•• Tamma PD, Avdic E, Keenan JF, Zhao Y, Anand G, Cooper J, et al. What Is the More Effective Antibiotic Stewardship Intervention: Preprescription Authorization or Postprescription Review With Feedback? Clin Infect Dis. 2017;64(5):537–43. Study comparing the efficacy of two common stewardship approaches; preprescription authorization versus post-prescription review with feedback that showed a larger impact on decreasing antibiotic DOTs with post-prescription review with feedback. PubMedGoogle Scholar
- 4.•• Pitiriga V, Vrioni G, Saroglou G, Tsakris A. The impact of antibiotic stewardship programs in combating quinolone resistance: a systematic review and recommendations for more efficient interventions. Adv Ther. 2017;34(4):854–65. Systematic review of antibiotic stewardship programs on fluoroquinolone resistance along with expert opinion recommendations for effective interventions including a focus on diagnostic stewardship CrossRefPubMedGoogle Scholar
- 6.Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together. 2017; Available at: https://www.fda.gov/Drugs/DrugSafety/ucm500143.htm. Accessed 08.10.2017, 2017.
- 7.Food and Drug Administration (FDA),. The Benefits and Risks of Systemic Fluoroquinolone Antibacterial Drugs for the Treatment of Acute Bacterial Sinusitis (ABS), Acute Bacterial Exacerbation of Chronic Bronchitis in Patients Who Have Chronic Obstructive Pulmonary Disease (ABECB-COPD), and Uncomplicated Urinary Tract Infections (uUTI). 2017; Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf. Accessed 09.27, 2017.
- 11.• Dingle KE, Didelot X, Quan TP, Eyre DW, Stoesser N, Golubchik T, et al. Effects of control interventions on Clostridium difficile infection in England: an observational study. Lancet Infect Dis. 2017;17(4):411–21. Retrospective study of prescribing data and whole-genome sequencing to demonstrate the importance of fluoroquinolone restriction as evidenced by significant declines in cases caused by fluoroquinolone-resistant isolates CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Lawes T, Lopez-Lozano JM, Nebot CA, Macartney G, Subbarao-Sharma R, Wares KD, et al. Effect of a national 4C antibiotic stewardship intervention on the clinical and molecular epidemiology of Clostridium difficile infections in a region of Scotland: a non-linear time-series analysis. Lancet Infect Dis. 2017;17(2):194–206.CrossRefPubMedGoogle Scholar
- 20.Kardas-Sloma L, Boelle PY, Opatowski L, Brun-Buisson C, Guillemot D, Temime L. Impact of antibiotic exposure patterns on selection of community-associated methicillin-resistant Staphylococcus aureus in hospital settings. Antimicrob Agents Chemother. 2011;55(10):4888–95.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Boel J, Andreasen V, Jarlov JO, Ostergaard C, Gjorup I, Boggild N, et al. Impact of antibiotic restriction on resistance levels of Escherichia coli: a controlled interrupted time series study of a hospital-wide antibiotic stewardship programme. J Antimicrob Chemother. 2016;71(7):2047–51.CrossRefPubMedGoogle Scholar
- 30.Wieczorkiewicz JT, Lopansri BK, Cheknis A, Osmolski JR, Hecht DW, Gerding DN, et al. Fluoroquinolone and macrolide exposure predict Clostridium difficile infection with the highly fluoroquinolone- and macrolide-resistant Epidemic C. Difficile strain BI/NAP1/027. Antimicrob Agents Chemother. 2015;60(1):418–23.CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Dancer SJ, Kirkpatrick P, Corcoran DS, Christison F, Farmer D, Robertson C. Approaching zero: temporal effects of a restrictive antibiotic policy on hospital-acquired Clostridium difficile, extended-spectrum beta-lactamase-producing coliforms and meticillin-resistant Staphylococcus aureus. Int J Antimicrob Agents. 2013;41(2):137–42.CrossRefPubMedGoogle Scholar
- 32.Aldeyab MA, Kearney MP, Scott MG, Aldiab MA, Alahmadi YM, Darwish Elhajji FW, et al. An evaluation of the impact of antibiotic stewardship on reducing the use of high-risk antibiotics and its effect on the incidence of Clostridium difficile infection in hospital settings. J Antimicrob Chemother. 2012;67(12):2988–96.CrossRefPubMedGoogle Scholar
- 34.•• Feazel LM, Malhotra A, Perencevich EN, Kaboli P, Diekema DJ, Schweizer ML. Effect of antibiotic stewardship programmes on Clostridium difficile incidence: a systematic review and meta-analysis. J Antimicrob Chemother. 2014;69(7):1748–54. Systematic review and meta-analysis of 16 quasi-experimental or observational studies demonstrated a significant risk reduction in C. difficile rate associated with restrictive efforts targeting cephalosporins and fluoroquinolones. CrossRefPubMedGoogle Scholar
- 35.•• Baur D, Gladstone BP, Burkert F, Carrara E, Foschi F, Dobele S, et al. 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. Systematic review and meta-analysis of 32 studies demonstrated significantly reduced incidence of infections and colonization with multi-drug resistant Gram-negative bacteria, and methicillin-resistance S. Aureus, as well as the incidence of C. Difficile infection with restriction. Google Scholar
- 36.Shea KM, Hobbs AL, Jaso TC, Bissett JD, Cruz CM, Douglass ET, et al. Effect of a healthcare-system respiratory fluoroquinolone restriction program to Alter utilization and impact rates of C. Difficile infection. Antimicrob Agents Chemother. 2017;61:e00125–17.CrossRefPubMedPubMedCentralGoogle Scholar
- 38.• Sarma JB, Marshall B, Cleeve V, Tate D, Oswald T, Woolfrey S. Effects of fluoroquinolone restriction (from 2007 to 2012) on Clostridium difficile infections: interrupted time-series analysis. J Hosp Infect. 2015;91(1):74–80. Interrupted time-series analysis that showed that fluoroquinolone use was significantly associated with incidence of CDI, which decreased in the setting of a fluoroquinolone restriction policy. CrossRefPubMedGoogle Scholar
- 42.Lafaurie M, Porcher R, Donay JL, Touratier S, Molina JM. Reduction of fluoroquinolone use is associated with a decrease in methicillin-resistant Staphylococcus aureus and fluoroquinolone-resistant Pseudomonas aeruginosa isolation rates: a 10 year study. J Antimicrob Chemother. 2012;67(4):1010–5.CrossRefPubMedGoogle Scholar
- 46.Aldeyab MA, Harbarth S, Vernaz N, Kearney MP, Scott MG, Darwish Elhajji FW, et al. The impact of antibiotic use on the incidence and resistance pattern of extended-spectrum beta-lactamase-producing bacteria in primary and secondary healthcare settings. Br J Clin Pharmacol. 2012;74(1):171–9.CrossRefPubMedGoogle Scholar
- 47.• Sarma JB, Marshall B, Cleeve V, Tate D, Oswald T, Woolfrey S. Effects of fluoroquinolone restriction (from 2007 to 2012) on resistance in Enterobacteriaceae: interrupted time-series analysis. J Hosp Infect. 2015;91(1):68–73. Interrupted time series analysis demonstrated a large decline in ciprofloxacin-resistant ESBL E. coli isolates in hospital and community settings during a fluoroquinolone restriction CrossRefPubMedGoogle Scholar
- 53.MELINTA THERAPEUTICS,. Melinta Therapeutics Announces U.S. FDAS Approval of Baxdela™ (Delafloxacin) for Acute Bacterial Skin And Skin Structure Infections (ABSSSI). Available at: http://melinta.com/melinta-therapeutics-announces-u-s-fda-approval-baxdela-delafloxacin-acute-bacterial-skin-skin-structure-infections-absssi/. Accessed 9.17, 2017.