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Antibiotic Prescribing Trends Following Suppression of Fluoroquinolone Susceptibilities

Corrie Black, Pharm D Candidate

Angharad Ratliff, PharmD, BCPS, BCCCP

Idaho State University/University of Alaska-Anchorage

Alaska Regional Hospital

Authors have no disclosures or

conflicts of interest to report.

IRB exemption received from

Idaho State University IRB.

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Objective

– Describe the implementation of an antibiotic

stewardship strategy, it’s effectiveness, potential

benefits, and limitations

Q: In 2018, the FDA issued safety

warnings around fluoroquinolone

(FQ) use because of ?

Blood sugar disturbances, including reports of

hypoglycemic comas

Increased risk of agitation, nervousness, memory

impairment, and/or disturbances in attention

Increased incidence of tendonitis or tendon rupture

Increased incidence of aortic rupture or aneurysm

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Answer: In 2018, the FDA issued safety

warnings around FQ use because of:

Blood sugar disturbances, including reports of hypoglycemic comas2

Increased risk of agitation, nervousness, memory

impairment, and/or disturbances in attention2

Increased incidence of tendonitis or tendon rupture

(Blackbox warning added in 2008)

Increased incidence of aortic rupture or aneurysm1

Background

• Extensive and serious adverse effects

• Clostridium difficile infections3-5

• Increasing resistance6

Increasing motivation to limit FQ use:

• Protocols within microbiology reporting system

• “Passive” tool for Antimicrobial Stewardship

• Improves antibiotic selection, data limited9-17

IDSA & CLSI guidelines endorse Cascade

Reporting to influence prescribing practices7,8

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Background continued

January 2018, cascade reporting protocols were implemented with FQ

susceptibilities suppressed if narrower, more appropriate agent susceptible

Purpose of this study was to:

– Identify if FQ use decreased over a six month period after implementing

– Identify alternative antibiotic use during this intervention

Susceptibility

Reporting

Enterobacteriaceae cultures

Antibiotic SYSTEMIC Sample URINE Sample

Ampicillin/Sulbactam REPORT REPORT

Aztreonam REPORT REPORT

Cefazolin (CZ) DO NOT REPORT REPORT

Cefepime (FEP) DO NOT REPORT DO NOT REPORT

Ceftazidime (CAZ) REPORT WHEN CRO I OR R REPORT WHEN CRO I OR R

Ceftriaxone (CRO) REPORT REPORT WHEN CXM I OR R

Cefuroxime (CXM) REPORT REPORT WHEN CZ I OR R

Ciprofloxacin REPORT ON REQUEST REPORT ON REQUEST

Gentamicin REPORT REPORT

Levofloxacin REPORT WHEN CRO I/R REPORT WHEN CXM I/R

Meropenem REPORT ON REQUEST OR IF I OR R REPORT ON REQUEST OR IF I

OR R

Piperacillin/Tazobactam REPORT WHEN CRO IS I OR R REPORT WHEN CXM IS I OR R

Tobramycin REPORT IF GENT R REPORT IF GENT R

Sulfamethoxazole/Trimethoprim REPORT REPORT

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Methods

– Pre-post cohort comparison matched on antibiotic administration time accounting

for seasonality

– Intervention data: included antibiotic use for first six months of 2018

– Control data: included antibiotic use for first six months of 2017

– Total DDD per 1,000 patient days

– Antibiotic use normalized, defined as defined daily dose (DDD) per 1,000 patient days

– Percent change calculated and analyzed for statistical significance using student’s T test

– Antibiotics grouped based on spectrum of activity in secondary analysis

Results

Between 2017 (control data) and 2018 (intervention data)

there was a 32.6% reduction in FQ use, P=0.018

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P=0.484

[CATEGORY NAME], [VALUE]

1st/2nd Gen Cef, -5.26%

3rd Gen Cef, -16.55%

AminoPNC, -31.17%

AminoPNC βLI, 3.52%

Clindamycin, -22.05%

Macrolides, 13.36%

SMX-TMP, -9.36%

Nitrofurantoin, 33.22%

Pip-Tazo/ Cefepime , [VALUE]

-40.00%

-30.00%

-20.00%

-10.00%

0.00%

10.00%

20.00%

30.00%

40.00%

% Difference between 2017-2018

P=0.018

P=0.301

P=0.869

P=0.158

P=0.441

P=0.196

P=0.637

P=0.619

Limitations

– Patient level data with indications was unavailable to incorporate into analysis

– DDD does not provide total number of courses prescribed

– Additional stewardship efforts during intervention time including:

– Increased pharmacy stewardship presence and recommendations

– Order sets updated to recommend cefepime over piperacillin/tazobactam (agents grouped together to account for this)

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Conclusions

– Suppression of FQ susceptibilities resulted in a reduction in FQ use that was

statistically significant over six months

– Increased use of narrower spectrum agents observed during intervention that

were consistent with stewardship recommendations in place of FQ’s:

– Nitrofurantoin in uncomplicated cystitis

– Macrolides in community acquired pneumonia

– Increase use of broader spectrum agents did not appear during intervention

– Required minimal implementation time and daily maintenance

References 1. Safety Announcement FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain

patients, December 20, 2018. Retrieved from https://www.fda.gov/Drugs/DrugSafety/ucm628753.htm.

2. Safety Announcement FDA reinforces safety information about serious low blood sugar levels and mental health side effects with

fluoroquinolone antibiotics; requires label changes, July 10, 2018. Retrieved from https://www.fda.gov/Drugs/DrugSafety/ucm611032.htm.

3. McDonald LC, Gerding DN, Johnson S, et al. (2018). Clinical Practice Guidelines for Clostridium difcile Infection in Adults and Children: 2017

Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis; 66(7),

e1–e48.

4. McDonald LC, Killgore GE, Thompson A, et al (2005). An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med; 353:2433–41.

5. Wilcox MH, Shetty N, Fawley WN, et al. Changing epidemiology of Clostridium difficile infection following the introduction of a national

ribotyping-based surveillance scheme in England. Clin Infect Dis 2012; 55:1056–63.

6. White House (2015). National action plan for combating antibiotic-resistant bacteria. Washington, DC, 62.

7. Barlam TF, Cosgrove SE, Abbo LM, et al. (2016). Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of

America and the Society for Healthcare Epidemiology of America. Clin Infect Dis; 62(10):e51-e77.

8. Clinical and Laboratory Standards Institute (2010). Performance standards for antimicrobial susceptibility testing. Twentieth informational

supplement. CLSI document M100-S20. Wayne, PA: Clinical and Laboratory Standards Institute.

9. Leis JA, Rebick GW, Daneman N et al (2014). Reducing antimicrobial therapy for asymptomatic bacteriuria among noncatheterized inpatients: a

proof-ofconcept study. Clin Infect Dis; 58: 980–3.

10. Coupat C, Pradier C, Degand N et al (2013). Selective reporting of antibiotic susceptibility data improves the appropriateness of intended

antibiotic prescriptions in urinary tract infections: a case-vignette randomised study. Eur J Clin Microbiol Infect Dis; 32: 627–36.

11. Davey P, Marwick CA, Scott CL et al (2017). Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database

Syst Rev; issue 2.

12. Steffee CH, Morrell RM, Wasilauskas BL (1997). Clinical use of rifampicin during routine reporting of rifampicin susceptibilities: a lesson in

selective reporting of antimicrobial susceptibility data. J Antimicrob Chemother; 40: 595–8.

13. Maryza Graham, Debra A Walker, Elizabeth Haremza, Arthur J Morris (2018). RCPAQAP audit of antimicrobial reporting in Australian and New

Zealand laboratories: opportunities for laboratory contribution to antimicrobial stewardship. J Antimicrob Chemother; 74(1), 251–5.

14. Pulcini C, Tebano G, Mutters NT et al (2017). Selective reporting of antibiotic susceptibility test results in European countries: an ESCMID cross-

sectional survey. Int J Antimicrob; 49: 162–6.

15. Al-Tawfiq JA, Momattin H, Al-Habboubi F, Dancer S (2015). Restrictive reporting of selected antimicrobial susceptibilities influences clinical

prescribing. Journal of Infection and Public Health, 8(3), 234-241.

16. Johnson LS, Patel D., King EA et al (2016). Eur J Clin Microbiol Infect Dis; 35: 1151.

17. Langford BJ, Seah J, Chan A et al (2016). Antimicrobial stewardship in the microbiology laboratory: impact of selective susceptibility reporting on

ciprofloxacin utilization and susceptibility of Gram-negative isolates to ciprofloxacin in a hospital setting. J Clin Microbiol; 54: 2343–7.

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Questions?