Antibiotic stewardship: The FP’s role

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Applied Evidence

Antibiotic stewardship: The FP’s role

J Fam Pract. 2016 December;65(12):876-878,880-885

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References

1. Fridkin S, Baggs J, Fagan R, et al. Vital signs: improving antibiotic use among hospitalized patients. MMWR Morb Mortal Wkly Rep. 2014;63:194-200.

2. Hicks DO, Taylor TH. US outpatient antibiotic prescribing, 2010. N Engl J Med. 2013;368:1461-1462.

3. Fleming-Dutra KE, Hersh, A, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016;315:1864-1873.

4. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. Available at: www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Accessed October 31, 2016.

5. Dantes R, Mu Y, Belflower R, et al. National burden of invasive methicillin-resistant Staphylococcus aureus infections, United States, 2011. JAMA Intern Med. 2013;173:1970-1978.

6. Chambers HF. Methicillin-resistant Staphylococcus aureus: mechanisms of resistance and implications for treatment. Postgrad Med. 2001;109:43-50.

7. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011;5:285-292.

8. Couch KA, Geide T. ASHP therapeutic position statement on strategies for identifying and preventing pneumococcal resistance. Am J Health-Syst Pharm. 2014;71:417-424.

9. Centers for Disease Control and Prevention (2010) ABCs report: Streptococcus pneumoniae. Available at: www.cdc.gov/abcs/reports-findings/survreports/spneu10.html. Accessed October 28, 2016.

10. Pallares R, Fenoll A, Linares J for the Spanish Pneumococcal Infection Study Network. The epidemiology of antibiotic resistance in Streptococcus pneumoniae and the clinical relevance of resistance to cephalosporins, macrolides, and fluoroquinolones. Int J Antimicrob Agents. 2003;22(suppl):S15-S24.

11. US Food and Drug Administration. 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). 2015. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM467383.pdf. Accessed October 28, 2016.

12. Nuorti JP, Butler JC, Farley NM, et al. Cigarette smoking and invasive pneumococcal disease. N Engl J Med. 2000;342:681-689.

13. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(suppl):S27-S72.

14. Gwaltney JM Jr, Wiesinger BA, Patrieb JT. Acute community-acquired bacterial sinusitis: the value of antimicrobial treatment and the natural history. Clin Infect Dis. 2004;38:227–233.

15. Diekema DJ, Brueggemann AB, Doern GV. Antimicrobial-drug use and changes in resistance in Streptococcus pneumoniae. Emerg Infect Dis. 2000;6:552-556.

16. Hicks LA, Chien YW, Taylor TH Jr, et al. Outpatient antibiotic prescribing and nonsusceptible Streptococcus pneumoniae in the United States, 1996–2003. Clin Infect Dis. 2011;53:631-639.

17. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54:e1-e41.

18. Lieberthal AS, Caroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media. Pediatrics. 2013;131:e964-e999.

19. Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53:e25-e76.

20. Sanchez GV, Adams SJ, Baird AM, et al. Escherichia coli antimicrobial resistance increased faster among geriatric outpatients compared with adult outpatients in the USA, 2000–10. J Antimicrob Chemother. 2013:68:1838-1841.

21. Gupta K, Scholes D, Stamm WE. Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women. JAMA. 1999;281:736-738.

22. Gupta K, Hooten TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52:e103-e120.

23. Ben-Ami R, Rodrıguez-Bano J, Arslan H, et al. A multinational survey of risk factors for infection with extended-spectrum beta-lactamase–producing Enterobacteriaceae in nonhospitalized patients. Clin Infect Dis. 2009;49:682–690.

24. Walker E, Lyman A, Gupta K, et al. Clinical management of an increasing threat: outpatient urinary tract infections due to multidrug-resistant uropathogens. Clin Infect Dis. 2016;63:960-965.

25. Hooton TM. Uncomplicated urinary tract infection. N Engl J Med. 2012;366:1028-1037.

26. Gupta K, Bhadelia N. Management of urinary tract infections from multidrug-resistant organisms. Infect Dis Clin N Am. 2014;28:49-59.

27. Neuner EA, Sekeres J, Hall GS, et al. Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother. 2012;56:5744-5748.

28. Tasbakan MI, Pullukcu H, Sipahi OR, et al. Nitrofurantoin in the treatment of extended-spectrum beta-lactamase-producing Escherichia coli-related lower urinary tract infection. Int J Antimicrob Agents. 2012;40:554-556.

29. Rodriguez-Bano J, Alcala JC, Cisneros JM, et al. Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Arch Intern Med. 2008;268:1897-1902.

30. Guh AY, Bulens SN, Mu Y, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae in 7 US communities, 2012-2013. JAMA. 2015;314:1479-1487.

31. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR. 2015;64:1-137.

32. Kirkcaldy RD, Weinstock HS, Moore PC, et al. The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea. Clin Infect Dis. 2014;59:1083-1091.

33. Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. JAMA. 1997;278:901-904.

34. Belongia EA, Sullivan BJ, Chyou, PH, et al. A community intervention trial to promote judicious antibiotic use and reduce penicillin-resistant Streptococcus pneumoniae carriage in children. Pediatrics. 2001;108;575-583.

35. Gjelstad S, Hoye S, Straand J, et al. Improving antibiotic prescribing in acute respiratory tract infections: cluster randomised trial from Norwegian general practice (prescription peer academic detailing [Rx-PAD] study). BMJ. 2013;347:f4403.

36. Huttner B, Harbarth S. ‘Antibiotics are not automatic anymore’’—the French national campaign to cut antibiotic overuse. PLoS Med. 2009;6: e1000080.

37. Webber EC, Warhurst HM, Smith SS, et al. Conversion of a single-facility pediatric antimicrobial stewardship program to multi-facility application with computerized provider order entry and clinical decision support. Appl Clin Informatics. 2013;4:556-568.

38. Gonzales R, Anderer T, McCulloch CE, et al. A cluster randomized trial of decision support strategies for reducing antibiotic use in acute bronchitis. JAMA Intern Med. 2013;173:267-273.

39. Gerber JS, Prasad PA, Fiks AG, et al. Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial. JAMA. 2013;309:2345-2352.

40. Meeker D, Linder JA, Fox CR, et al. Effect of behavioral interventions on inappropriate antibiotic prescribing among primary care practices: a randomized clinical trial. JAMA. 2016;315:562-570.

41. Schwartz BS, Armstrong WS, Ohl CA, et al. Create allies, IDSA stewardship commitments should prioritize health professions learners. Clin Infect Dis. 2015; 61:1626-1627.

42. Barlam TF, Cosgrove SE, Abbo LM, 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;62:1-27.

How best to manage uncomplicated cystitis

Treating uncomplicated cystitis is challenging for a number of reasons, including increasing gram-negative resistance, a lack of surveillance data describing local outpatient resistance rates, and limited reliable oral options. UTIs caused by resistant organisms, such as ESBL-producing Enterobacteriaceae, are associated with recent antibiotic use, recurrent UTIs, recent hospitalization, advanced age, multiple comorbidities, hemodialysis, recent international travel, and urinary catheterization.^23,24 Urine cultures and susceptibilities should be included in an assessment of patients with any of these risk factors and used to inform antibiotic selection.²⁴ First-line treatment options for uncomplicated cystitis include nitrofurantoin, TMP/SMX (in regions where the uropathogen resistance is <20%), and fosfomycin.²⁵

Multidrug-resistant pathogens

Nitrofurantoin, fosfomycin, and in some instances, fluoroquinolones, are options for treating multidrug-resistant uropathogens, as guided by susceptibility results (TABLE 4).^24,26-28 IV antibiotics may be necessary for patients who have severe infections or live in long-term care facilities.^24,29 UTIs caused by carbapenem-resistant Enterobacteriaceae are fortunately still rare in outpatient settings.³⁰ There is a lack of high-quality evidence describing best practices for treating infections caused by ESBL-producing bacteria in the community; therefore, antimicrobial selection should be based on infection severity and patient-specific factors.¹

Neisseria gonorrhoeae is multidrug-resistant

CASE 2 › Jon F

Mr. F’s physician suspects gonorrhea, although chlamydia cannot be ruled out, and orders a urethral culture, first-catch urine test using nucleic acid amplification, syphilis, and HIV tests. The physician administers ceftriaxone 250 mg IM and azithromycin 1 g PO, instructs the patient to contact all sex partners within the last 60 days, and emphasizes the importance of using latex condoms consistently.

Three days later, Jon returns, complaining that his symptoms have not improved. The urethral culture shows a gram-negative oxidase-positive diplococcus and testing confirms N gonorrhoeae. The lab results also reveal a high cephalosporin minimal inhibitory concentration, negative tests for chlamydia and HIV, and a non-reactive rapid plasma reagin.

Gonococcal infections are the second most common communicable disease reported in the United States, with some 820,000 new cases annually.³¹ Sites of infection include the cervix, urethra, and rectum, and less commonly, the pharynx, conjunctiva, joints, meninges, and endocardium. Those at risk for gonorrhea are:³¹

women who are sexually active and <25 years of age
any woman with a new sex partner
any individual with multiple sex partners or a partner with concurrent partners and/or a known sexually transmitted infection (STI)
an individual who has a history of inconsistent condom use in non-monogamous relationships
sex workers.

SIDEBAR
Combatting antibiotic resistance: A call to action for FPs

Use the best available evidence to determine when antibiotics are indicated.
Develop and use “antibiograms”—tools that use data from patient specimens to identify patterns of antibiotic susceptibility and guide appropriate empiric antibiotic selection.
Use rapid diagnostic assays to differentiate between viral and bacterial infections and identify resistant bacteria.
Add antibiotic use to the list of metrics your practice uses to assess clinician performance.
Adopt standard, clear language to explain to patients and parents when—and why—antibiotics are not indicated.
Support public health surveillance efforts by learning and adhering to reporting requirements in your community.

The difficulty of treating gonorrhea

Cephalosporins are now the only class of antimicrobials with reliable activity against N gonorrhoeae. The Centers for Disease Control and Prevention (CDC) no longer recommends fluoroquinolones due to increasing resistance. However, cefixime-resistant strains of gonorrhea and treatment failures have been reported, and the drug is no longer recommended for gonorrhea treatment.³¹

Combination therapy with one dose of ceftriaxone 250 mg IM and one dose of azithromycin 1 g orally is recommended by the CDC,³² as combination therapy improves efficacy and delays the development of resistance. Azithromycin is preferred over doxycycline as the second agent. That’s both because of a higher prevalence of tetracycline resistance among circulating gonococci and azithromycin’s activity against Chlamydia trachomatis, as patients with gonococcal infections are frequently co-infected with this organism.³¹

Suspected treatment failures are more likely caused by re-infection than drug resistance. If resistance is suspected, however, physicians should seek guidance from an infectious diseases specialist or the CDC on repeat cultures, susceptibility testing, and antimicrobial therapy.

Two treatment regimens have demonstrated efficacy against cephalosporin-resistant N gonorrhoeae:^31,32

A single dose of gemifloxacin 320 mg PO plus azithromycin 2 g PO or
a single dose of gentamicin 240 mg IM plus azithromycin 2 g PO.

CASE 2 › Jon F

Mr. F’s physician consults with an infectious disease specialist at the local hospital, who confirms his suspicion that the patient has been infected with antibiotic-resistant N gonorrhoeae. The physician administers gentamicin 240 mg IM plus azithromycin 2 g orally, and warns the patient that he may experience gastrointestinal adverse effects. The physician reports the case, as required, to the local health department.

Antibiotic stewardship: What’s being done…

Efforts to improve antibiotic use in the community setting include a variety of strategies, including academic detailing (ie, evidence-based promotion of drug therapies rather than promotion by manufacturer representatives), patient education, clinical decision support, multi-faceted programs using a combination of interventions, and local and national campaigns.^33-36Recent examples of successful campaigns include the American Board of Internal Medicine Foundation’s Choosing Wisely initiative (choosingwisely.org) and the CDC’s Get Smart program (cdc.gov/getsmart/community/index.html).