Infectious Disease Update: The latest adult treatment recommendations

Infectious Disease Update: The latest adult treatment recommendations Margaret Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC President, Fitzgerald Health Education Associates, Inc. North Andover, MA Family Nurse Practitioner Greater Lawrence (MA) Family Health Center Editorial Board Member The Nurse Practitioner Journal, Prescriber s Letter, American Nurse Today Objectives Having completed the learning activities, the participant will be able to: Discuss factors influencing the development of antimicrobial resistance. Identify factors influencing the choice of an antimicrobial for the treatment of community-acquired bacterial sinusitis. 2 Objectives Having completed the learning activities, the participant will be able to: (cont.) Recognize the efficacy of standard and newer antimicrobials for the treatment of community-acquired bacterial sinusitis. 3

Are the bugs winning? Is this a new problem? 4 In Late 1920s Sir Alexander Fleming 1 st to suggest that penicillium mold must secrete antibacterial substance. 1 st to isolate active substance which he named penicillin. 5 Sir Alexander Fleming June 26, 1945, New York Times the microbes are educated to resist penicillin and a host of penicillin-fast (resistant) organisms is bred out 6

Sir Alexander Fleming June 26, 1945, New York Times In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted. 7 The decisionmaking process where the clinician chooses the agent based on patient characteristics and site of infection. Empiric Antimicrobial Therapy 8 Questions to Ask Prior to Choosing an Antimicrobial What is/are the most likely pathogen(s) causing this infection? What is the spectrum of a given antimicrobial s activity? What is the likelihood of resistant pathogen? What is the danger if there is treatment failure? 9

What facilitates resistance? Time Exposure Unnecessary doses Long tx period Under dosing Leaves behind more resistant bugs 10 True or false? In a study of antimicrobial prescribing among primary care providers, physicians in high-volume practices and those who were in practice longer were more likely to prescribe antibiotics inappropriately. Source- CMAJ October 9, 2007; 177(8). 11 What determines antibiotic dose? The pharmacological absorption and distribution of the antibiotic will influence the dose, route and frequency of administration of the antibiotic in order to achieve an effective dose at the site of infection. Source- http://pathmicro.med.sc.edu/mayer/antibiot.htm, accessed 3.14.13. 12

Minimum Inhibitory Concentration (MIC) Defined Lowest concentration of an antimicrobial that will inhibit visible growth of a microorganism after overnight incubation under standard conditions Source: http://jac.oxfordjournals.org/content/48/suppl_1/5.sh ort, accessed 3.14.13. 13 Minimum Bactericidal Concentration (MBC) Defined Lowest concentration of antimicrobial that will prevent growth of 99.9% of an organism after subculture on to antibiotic-free media Sourcehttp://jac.oxfordjournals.org/content/48/suppl_1/5.sho rt, accessed 3.14.13. 14 Recommended Antibiotic Doses Usually dosed at level to 2-4 times MIC Overkill amount to allow for variations in absorption, distribution 15

Updated Treatment Guidelines for ABRS in Children and Adults Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults, available at http://www.idsociety.org/uploadedfiles/idsa/guidelines- Patient_Care/PDF_Library/IDSA%20Clinical%20Practice%20G uideline%20for%20acute%20bacterial%20rhinosinusitis%20 in%20children%20and%20adults.pdf, accessed 3.14.13. 16 Is antimicrobial needed in ABRS therapy? Meta-analyses of antibiotic treatment vs placebo in ABRS Number needed to treat (NNT) (95% CI) In adults=13 (9 22) In children=5 (4 15) Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 17 Streptococcus pneumoniae Gm pos diplococci DRSP rate nationally=25% Adults=38% Children=21 33% Bacterial Pathogens Associated with ABRS Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 18

Bacterial Pathogens Associated with ABRS Haemophilus influenzae Gm negative rod-shaped bacterium ~30% beta-lactamase production rate nationwide Non-typable strains cause ABRS Adults=36% Children=31 32% Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 19 Bacterial Pathogens Associated with ABRS Moraxella catarrhalis Gram negative with =>90% betalactamase production rate Adults=16% Children=8 11% Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 20 Treatment of ABRS Antimicrobial with activity against: Gram positive organism S. pneumoniae with DRSP consideration Gram negative organisms H. influenzae and M. catarrhalis with propensity to produce beta-lactamase 21

Algorithm for the Management of Acute Bacterial Rhinosinusitis Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging Signs and symptoms either: Risk for antibiotic resistance a) Persistent and not improving ( 10 days); b) Severe ( 3-4 days); or Age <2 or >65, c) Worsening or double-sickening ( 3-4 days) daycare Prior antibiotics within Risk for Resistance the past month Prior hospitalization past 5 days No Yes Comorbidities Symptomatic Immunocompromised management Initiate first-line Initiate second-line antimicrobial therapy antimicrobial therapy Improvement after 3-5 days Worsening or no improvement after 3-5 days Improvement after 3-5 days Complete 5-7 days of antimicrobial therapy Improvement Complete 5-7 days of antimicrobial therapy Broaden coverage or switch to Complete 7-10 days of different antimicrobial class antimicrobial therapy Improvement Worsening or no improvement after 3-5 days Complete 7-10 days of Refer to specialist antimicrobial therapy CT or MRI to investigate noninfectious causes or Source- Clinical Infectious Diseases suppurative complications Advance, available at http://cid.oxfordjournals.org/, accessed Sinus or meatal cultures for pathogen-specific therapy 3.14.13 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults Indication First-line (Daily dose) Initial Amoxicillinclavulanate 500 empirical therapy mg/125 mg PO TID Or Amoxicillinclavulanate 875 mg/125 mg PO BID Second-line (Daily dose) Amoxicillinclavulanate 2000 mg/125 mg PO BID Or Doxycycline 100 mg PO BID or 200 mg PO QD Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 23 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults Risk for antibiotic resistance or failed initial therapy Amoxicillin-clavulanate 2000 mg/125 mg PO BID Or Levofloxacin 500 mg PO QD Or Moxifloxacin 400 mg PO QD Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 24

Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults β-lactam Doxycycline 100 mg PO BID allergy Or (Containing Doxycycline 200 mg PO QD β-lactam ring; penicillins, Or cephalosporins) Levofloxacin 500 mg PO QD Or Moxifloxacin 400 mg PO QD Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 25 Indication Initial empirical therapy Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Children First-line (Daily dose) Amoxicillinclavulanate 45 mg/kg/day PO BID Second-line (Daily dose) Amoxicillinclavulanate 90 mg/kg/day PO BID Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 26 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Children Risk for Amoxicillin-clavulanate 90 mg/kg/day antibiotic PO BID resistance Or or Clindamycin a 30 40 mg/kg/day PO TID failed initial plus cefixime 8 mg/kg/day PO BID or cefpodoxime 10 mg/kg/day PO BID therapy Or Levofloxacin 10 20 mg/kg/day PO every 12 24 h a Resistance to clindamycin (~31%) is found frequently among Streptococcus pneumoniae serotype 19A isolates in different regions of the United States [94]. Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults

Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Children β-lactam allergy Type I hypersensitivity Non type I hypersensitivity Levofloxacin 10 20 mg/kg/day PO every 12 24 h Or Clindamycin a (30 40 mg/kg/day PO TID) plus cefixime (8 mg/kg/day PO BID) or cefpodoxime (10 mg/kg/day PO BID) a Resistance to clindamycin (~31%) is found frequently among Streptococcus pneumoniae serotype 19A isolates in different regions of the United States [94]. Source- Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 28 Azithromycin and the Risk of Cardiovascular Death Wayne A. Ray, Ph.D., Katherine T. Murray, M.D., Kathi Hall, B.S., Patrick G. Arbogast, Ph.D., and C. Michael Stein, M.B., Ch.B. N Engl J Med Volume 366(20):1881-1890 May 17, 2012 29 Background Information Macrolide antibiotics Azithromycin, clarithromycin, erythromycin Clarithromycin, erythromycin Long known to have proarrhythmic potential, use increases risk of serious ventricular arrhythmias, associated with increased risk of sudden cardiac death 30

Background Information Azithromycin Thought relatively free of cardiotoxic effects The FDA s Adverse Event Reporting System includes at least 20 reports of torsades de pointes associated with azithromycin use. 31 For Additional Information, www.qtdrugs.org True or false? The risk of torsades de pointe with erythromycin or clarithromycin is greater in females than in males. 32 Torsades de Ponte 33

Study Conclusion In conclusion, during 5 days of azithromycin therapy, there was a small absolute increase in cardiovascular deaths. 34 Study Conclusion As compared with amoxicillin, there were 47 additional cardiovascular deaths per 1 million courses of azithromycin therapy. For patients in the highest decile of baseline risk of cardiovascular disease, there were 245 additional cardiovascular deaths per 1 million courses. 35 What about treating the older adult with COPD exacerbation, typically a group with significant cardiovascular risk, in need of antimicrobial therapy? 36

Sanford Guide Recommendation for Antimicrobial Therapy Mild to moderate COPD exacerbation/ acute exacerbation of chronic bronchitis Antimicrobial therapy usually not indicated. If prescribed, consider using the following agents: Amoxicillin Cephalosporin TMP-SMX Doxycycline Source- Gilbert, D., Moellering R., Eliopoulos, G., Chambers, H., Saag, M. (2012) The Sanford Guide to Antimicrobial Therapy (42nd ed.). Sperryville, VA: Antimicrobial Therapy, Inc. 37 Sanford Guide Recommendation for Antimicrobial Therapy More severe COPD exacerbation/ acute exacerbation of chronic bronchitis One of the following: Amoxicillin-clavulanate Cephalosporin Azithromycin Clarithromycin Fluoroquinolone with activity against DRSP (Moxi-, gemi-, levofloxacin) Source- Gilbert, D., Moellering R., Eliopoulos, G., Chambers, H., Saag, M. (2012) The Sanford Guide to Antimicrobial Therapy (42nd ed.). Sperryville, VA: Antimicrobial Therapy, Inc. 38 FDA News Release Sourcehttp://www.fda.gov/bbs/topics/NEWS/2008/ NEW01858.html, accessed 3.14.13. 39

FDA Requests Boxed Warnings on Fluoroquinolone Antimicrobial Drugs The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in people older than 60, in those taking corticosteroid drugs, and in kidney, heart, and lung transplant recipients. 40 FDA Requests Boxed Warnings on Fluoroquinolone Antimicrobial Drugs Patients experiencing pain, swelling, inflammation of a tendon or tendon rupture should be advised to stop taking their fluoroquinolone medication and to contact their healthcare professional promptly about changing their antimicrobial therapy. 41 FDA Requests Boxed Warnings on Fluoroquinolone Antimicrobial Drugs Patients should also avoid exercise and using the affected area at the first sign of tendon pain, swelling, or inflammation. 42

And last but not least on antibiotic sparing behavior Acute bronchitis 43 True or false? In otherwise healthy patients, purulent sputum usually indicates the presence of sloughed tracheobronchial epithelium and inflammatory cells, not bacterial burden. Source- Gonzales R, Sande MA. Uncomplicated acute bronchitis. Ann Intern Med 2000;133:981-991. 44 True or false? In a study involving 2781 healthy adults, the median duration of cough from acute bronchitis due to all causes was 18 days. Source- Ward JI., Cherry JD., Chang S-J., et al. Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med 2005; 353:1555-1563. 45

For the minority (<10%) of acute bronchitis cases not caused by virus Likely causative pathogens Bordetella pertussis Chlamydophila (Chlamydia) pneumoniae Mycoplasma pneumoniae Source- Macfarlane J., Holmes W., Gard P., et al. Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community. Thorax 2001;56:109-114. 46 Therefore, if you are going to use an antibiotic in acute bronchitis (Which is a huge if!), you prescribe: A. Amoxicillin. B. Cefprozil. C. Doxycycline. D. Levofloxacin. 47 UTI Therapies Source- Gilbert, D., Moellering, R., Eliopoulos, G., Chambers, H., Saag, M. (2012) The Sanford Guide to Antimicrobial Therapy (42nd ed.). Sperryville, VA: Antimicrobial Therapy, Inc. 48

Type of infection Acute, uncomplicated urinary tract infection (cystitis, urethritis) in nonpregnant women Usual pathogens E. coli (Gm neg, most common pathogen), S. saprophyticus (Gm pos), Enterococci (Gm pos) Regimens Primary If local E. coli resistance to TMP/SMX<20% and no allergy, then TMP/SMX-DS BID x 3 days If local E. coli resistance to TMP/ SMX>20% or sulfa allergy, nitrofurantoin X 5 d or fosfomycin X 1 dose, all plus phenazopyridine (Pyridium ) 49 Type of infection Acute, uncomplicated urinary tract infection (cystitis, urethritis) in nonpregnant women (cont.) Usual pathogens E. coli (Gm neg, most common pathogen), S. saprophyticus (Gm pos), Enterococci (Gm pos) Regimens Alternative If local E. coli resistance to TMP/ SMX>20% or sulfa allergy, ciprofloxacin 250 mg BID, ciprofloxacin ER 500 mg QD, levofloxacin 250 mg QD, or moxifloxacin 400 mg QD, all for 3 days, all plus phenazopyridine (Pyridium ) Gemifloxacin not labeled for use in UTI, likely effective. Nitrofurantoin 100 mg BID X 5 d or fosfomycin 3 g X 1 dose, all plus phenazopyridine (Pyridium ) 200 mg TID X 2 d 50 Type of infection Acute, uncomplicated urinary tract infection (cystitis, urethritis) in nonpregnant women (cont.) Usual pathogens E. coli (Gm neg, most common pathogen), S. saprophyticus (Gm pos), Enterococci (Gm pos) Regimens Alternative (cont,) Amoxicillin-clavulanate 875/125 mg BID x 5-7 days or an oral cephalosporin (e.g., cephalexin 500 mg qid x 5-7 days or cefpodoxime proxetil 100 mg BID x 3 days) Beta-lactams generally less efficacious than fluoroquinolones or TMP-SMX and should be reserved for cases where other agents cannot be used. 51

Per Sanford Guide Fosfomycin 3 G taken as a 1 time dose Spectrum of antimicrobial activity Less effective vs. E. coli when compared to multiple doses of TMP- SMX Active again E. faecalis, poor activity against other coliforms 52 Fosfomycin (Monurol ) Indications Treatment of uncomplicated UTIs in women due to susceptible strains of Escherichia coli and Enterococcus faecalis Not indicated for the treatment of pyelonephritis or perinephric abscess 53 Fosfomycin (Monurol ) Pregnancy risk category B based largely on lab animal studies Cost 1 packet=1 dose=~$45 on drugstore.com 54

Fosfomycin (Monurol ) per PI Do not use more than one single dose of Monurol to treat a single episode of acute cystitis. Repeated daily doses of Monurol did not improve the clinical success or microbiological eradication rates compared to single dose therapy, but did increase the incidence of adverse events. 55 Per Up To Date Fosfomycin- A single-dose 3 gram sachet is an acceptable agent for women with mild to moderate infections who cannot take TMP-SMX or nitrofurantoin. Source- http://www.uptodate.com/contents/acute-uncomplicatedcystitis-and-pyelonephritis-inwomen?source=search_result&search=fosfomycin+cystitis&selectedtit le=1%7e49, accessed 3.15.13. 56 Extended Spectrum Beta Lactamase-producing Strains AKA ESBL-producing strains Most often K. pneumoniae, E. coli, Acinetobacter Usually effective antimicrobials include nitrofurantoin, fosfomycin, or amoxicillin-clavulanate plus cefdinir Source- 2012 Sanford Guide 57

Length of Therapy in Select Populations For patients with DM, symptoms greater than 7 days, recently used antimicrobials, =>age 65 yr, or male 7-day regimen Oral TMP-SMX Fluoroquinolone Cefixime 400 mg QD Cefpodoxime 100-200 mg QD Other cephalosporin as appropriate Source- Gupta, K, Stamm, W. Best Dx/Best Tx, Urinary Tract Infection, available http://www.acpmedicine.com/bcdecker/newrxdx/rxdx/dxrx0723.htm#4, accessed 3.1.13. 58 Per Sanford Guide 2012 If failure on 3- day course, culture and treat for 2 weeks 59 Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections Available at http://www.cdc.gov/mmwr/preview/m mwrhtml/mm6131a3.htm?s_cid=mm61 31a3_w, accessed 3.14.13. 60

ceftriaxone the last antimicrobial that is recommended and known to be highly effective in a single dose for treatment of gonorrhea at all anatomic sites of infection. Sourcehttp://www.cdc.gov/mmwr/preview/mmwrht ml/mm6131a3.htm?s_cid=mm6131a3_w, accessed 3.14.13. 61 Uncomplicated Gonococcal Infections of the Cervix, Urethra, and Rectum CDC recommendations as of August 2012 Ceftriaxone 250 mg IM as 1 X dose Plus Azithromycin 1 g PO X 1 dose or doxycycline 100 mg PO BID X 7 d 62 Uncomplicated Gonococcal Infections of the Cervix, Urethra, and Rectum Option 1 Alternative when ceftriaxone unable to be used Return 1 week after treatment for TOC at site of infection Cefixime 400 mg orally plus either azithromycin 1 g PO X 1 or doxycycline 100 mg PO BID X 7 d 63

Uncomplicated Gonococcal Infections of the Cervix, Urethra, and Rectum Option 2 Azithromycin 2 g orally in a single dose if ceftriaxone cannot be given because of severe allergy Return 1 week after treatment for TOC at site of infection 64 Neisseria gonorrhoeae Pharyngeal Infection Ceftriaxone 250 mg IM X 1 dose Plus Azithromycin 1 g PO X 1 in or doxycycline 100 mg PO BID X 7 d Plus TOC in 1 week 65 Expedited Partner Therapy (EPT) Defined Clinical practice of treating the sex partners of patients diagnosed with certain STI by providing prescriptions or medications to the patient to take to his/her partner without the health care provider first examining the partner. Source- http://www.cdc.gov/std/ept/default.htm, accessed 3.14.13. 66

EPT Q and A According to the CDC s recommendations, EPT can be use in the treatment of: A. Chlamydia. B. Gonorrhea. C. Chlamydia and gonorrhea. D. All clinically documented STIs. 67 EPT: Allowed or not? Permissible in 32 states All New England states, NY Potentially allowable in 11 states, DC, and Puerto Rico Sourcehttp://www.cdc.gov/std/ ept/legal/default.htm, accessed 3.14.13. Prohibited Arkansas Florida Kentucky Michigan Ohio Oklahoma West Virginia 68 True or false? For all patients with gonorrhea, every effort should be made to ensure that the patients' sex partners from the preceding 60 days are evaluated and treated for N. gonorrhoeae with a recommended regimen. 69

With All STIs Concomitant testing Syphilis HIV HBV, consider HCV Immunization considerations HAV, HBV HPV 70 End of Presentation! Thank you for your time and attention. Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC www.fhea.com, E-mail: cs@fhea.com 71