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

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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.

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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.

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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.

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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.

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How to respond to drug-resistant S pneumoniae

CASE 1 › Daniel

Daniel’s physician recommends observation, analgesics, and follow-up in 24 to 48 hours if his symptoms do not improve. Two days later, his mother brings him back to the office with worsening upper respiratory symptoms. Within the last 24 hours, she reports, Daniel’s axial temperatures have ranged from 101.5 to 102.9°F. He is drinking water and eating popsicles, she adds, but refusing to eat solid food. An otoscopic exam reveals moderately bulging tympanic membranes and poor mobility, with purulent fluid behind the membranes. The rest of the physical exam is non-contributory.

S pneumoniae is a gram-positive diplococcus frequently implicated in sinusitis, acute otitis media, and community-acquired pneumonia among outpatients and in meningitis among hospitalized patients. S pneumoniae is a virulent strain of streptococcus associated with increased morbidity and mortality in both young children and the elderly.⁸

The emergence of drug resistance

For years, penicillins, cephalosporins, and macrolides were used to treat community-acquired S pneumoniae infections, but penicillin-resistant S pneumoniae (PRSP) emerged in the 1990s. It results from alterations in penicillin-binding proteins, with the degree of resistance dependent on the particular proteins affected and the binding affinity of the beta-lactam agent used. S pneumoniae resistance to macrolides and clindamycin has also emerged.⁸

In 2010, a report on a large registry of S pneumoniae isolates revealed antibiotic resistance rates of approximately 5% for penicillin, 3% for cephalosporins, 30% for macrolides, and 20% for TMP/SMX. Levofloxacin resistance in S pneumoniae is rare (<1%).⁹

Penicillin resistance has been associated with poor clinical outcomes in patients with PRSP meningitis who were treated with standard doses of penicillin or cephalosporins.¹⁰ The impact of penicillin resistance on clinical outcomes in non-meningeal infections, however, is less clear.⁸ Macrolide and fluoroquinolone resistance has been associated with worse clinical outcomes and treatment failures.⁹ Fluoroquinolone use has been linked to an increased risk for adverse events and to Clostridium difficile (C difficile)-associated diarrhea.¹¹ Recent antibiotic use is a major risk factor for developing a drug-resistant S pneumoniae infection. Additional risk factors are listed in TABLE 2.^8,12,13

Is it bacterial? Distinguishing viral from bacterial etiologies in upper respiratory tract infections is challenging but critical in determining whether antibiotics are indicated. Use rapid diagnostic assays, whenever possible, to differentiate between them and to identify resistant bacteria.¹⁴ Prescribing antibiotics for respiratory infections only when necessary is crucial, as high rates of antimicrobial use is correlated with increasing resistance to S pneumoniae.^15,16

What the societies call for

Practice guidelines from the Infectious Diseases Society of America (IDSA) for acute bacterial rhinosinusitis recommend starting antibiotics only when the following criteria are met:

persistent symptoms that have not improved for ≥10 days
severe symptoms have been present for ≥3 to 4 days
“double sickening,” in which symptoms initially improve, but subsequently worsen.¹⁷

The acute otitis media guideline, developed by the American Academy of Pediatricians and the American Academy of Family Physicians, takes a similar approach. The guideline recommends observation with close follow-up in patients ≥24 months of age without severe signs or symptoms (eg, otalgia lasting >48 hours, temperature ≥102.2°F in the past 48 hours).¹⁸ When antibiotics are needed for respiratory tract infections, the selection of agents should be based on the site of infection, the latest evidence, and an assessment of patient-specific factors, including risk for PRSP (TABLE 3).^13,17-19

High-dose amoxicillin has become the mainstay when PRSP is a concern, as the high doses have been found to overcome this type of penicillin resistance. Fluoroquinolones and cephalosporins are typically reserved for selected cases in which drug allergies or resistance to first-line agents is a concern.

CASE 1 › Daniel

The physician prescribes high-dose amoxicillin (80 mg/kg/d taken in 2 divided doses for 5 days) for Daniel, whose exposure at day care and recent antibiotic use put him at increased risk for PRSP. The doctor stresses the importance of giving the medication to Daniel for the full 5 days, even if his symptoms resolve. He encourages the patient’s mother to give him bedtime analgesics and yogurt with active cultures while he takes the amoxicillin to reduce the likelihood of diarrhea. He also schedules a follow-up visit in a week.

Treating drug-resistant UTIs

The vast majority of community-acquired UTIs are caused by E coli, followed by other Enterobacteriaceae such as Klebsiella pneumoniae and Proteus mirabilis.¹ Since 2000, E coli resistance to commonly used outpatient antimicrobials has increased, particularly to ciprofloxacin, TMP/SMX, and narrow spectrum beta-lactams (amoxicillin and cephalexin).^20-22 The prevalence of extended-spectrum-beta-lactamase (ESBL)-producing Enterobacteriaceae among urinary pathogens is also rising.¹