Acute Bacterial Sinusitis: The latest treatment recommendations. Objectives Having completed the learning activities, the participant will be able to:

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1 Acute Bacterial Sinusitis: The latest treatment recommendations Presented by: Monica Tombasco, MS, MSNA, FNP-BC, CRNA Senior Lecturer Fitzgerald Health Education Associates, Inc., North Andover, MA Emergency Medicine Nurse Practitioner Huggins Hospital, Wolfeboro, NH Certified Registered Nurse Anesthetist, Catholic Medical Center, Manchester, NH Content contributor Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC President, Fitzgerald Health Education Associates, Inc., North Andover, MA Objectives Having completed the learning activities, the participant will be able to: Identify factors influencing the choice of an antimicrobial. Recognize the efficacy of select antimicrobials for the ABRS. 2 Are the bugs winning? Is this a new problem? 3

2 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 4 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 5 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 penicillinresistant organism. I hope this evil can be averted. 6

3 Empiric Antimicrobial Therapy The decisionmaking process where the clinician chooses the agent based on patient characteristics and site of infection. 7 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? 8 The Beta-lactam Ring: Vulnerable or Not? Penicillin Cephalosporin 9

4 Without antibiotic: 1 a 1 b 2b 2x 3 Alteration in Target Site Altered Penicillin-binding Proteins (PBPs) 2z Actively growing S. pneumoniae: PBPs facilitate cell wall formation for new cell Antibiotic binds to PBPs Pn Pn 1 a 1 b 2b 2x 3 2z Susceptible S. pneumoniae Cannot make adequate cell wall, growth stops Pn Pn 2b 1 2x a1 2z b 3 DRSP Antibiotic cannot bind to altered PBPs, growth continues (antibiotic resistance) 10 Alteration in Ribosomal Target Sites S. pneumoniae vs. Macrolides: Methylation of Ribosomes Ribosomes Macrolide M M Protein Normal Macrolide MOA: Macrolide binds to ribosome of S. pneumoniae and inhibits bacterial protein synthesis M M CH3 CH3 Macrolide unable to bind to ribosome Protein Macrolide Resistance: S. pneumoniae acquires gene that results in methylation of the ribosomes. Macrolide unable to bind to altered ribosomes and cannot interfere with protein synthesis 11 Predictors of Bacterial Eradication: PK/PD Profiles Time-Dependent Agents Concentration-Dependent Agents Includes: Penicillins Cephalosporins Clinical and bacteriologic success correlates with length of time bacteria are exposed to agent at concentration that exceeds MIC Peric M, et al. Clin Ther. 2003;25: Includes: Quinolones Macrolides Telithromycin Doxycycline TMP-SMX Successful therapy correlates with parameters that involve blood concentration of agent and MIC 12

5 True or false? The macrolides, fluoroquinolones, and tetracyclines do not contain a betalactam ring and are therefore stable in the presence of beta-lactamase. 13 True or false? S. pneumoniae occasionally exhibits resistance via betalactamase production. 14 What facilitates resistance? Time Exposure Unnecessary doses Long tx period Under dosing Leaves behind more resistant bugs 15

6 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). 16 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 Patient_Care/PDF_Library/IDSA%20Clinical%20Practice%20G uideline%20for%20acute%20bacterial%20rhinosinusitis%20 in%20children%20and%20adults.pdf 17 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 18

7 Bacterial Pathogens Associated with ABRS Streptococcus pneumoniae Gram-positive diplococci DRSP rate nationally=25% Adults=38% Children=21 33% Source: Chow, A., et al., IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults 19 Bacterial Pathogens Associated with ABRS Haemophilus influenzae Gram-negative rod-shaped bacterium ~30% beta-lactamase production rate nationwide Nontypable 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 20 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 21

8 Acute Rhinosinusitis Syndrome (ARS): Defining the terms Inflammation of the mucosal lining of nasal passage and paranasal sinuses lasting up to 4 weeks, caused by allergens, environmental irritants, and/or infection (viruses {majority}, bacteria and fungi). 22 Acute bacterial rhinosinusitis (ABRS or ABS) Acute Rhinosinusitis (ARS): Defining the terms Secondary bacterial infection of paranasal sinuses usually following viral URI, relatively uncommon in adults and children. Less than 2% of viral URIs are complicated by ABRS. 23 Empiric Antimicrobial Therapy in ABRS: Gram-positive with DRSP risk Gram-negative with beta-lactamase production risk 24

9 Algorithm for the Management of Acute Bacterial Rhinosinusitis Signs and symptoms either: Risk for antibiotic resistance a) Persistent and not improving ( 10 days); Abbreviations: CT, computed b) Severe ( 3-4 days); or Age <2 y or >65 y, tomography; MRI, magnetic c) Worsening or double-sickening ( 3-4 days) daycare resonance imaging Prior antibiotics within the past month Risk for Resistance 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 suppurative complications Diseases Advance Sinus or meatal cultures for pathogen-specific therapy Evidence-based Practice: Symptomatic treatment in ABRS Saline nasal irrigations Intranasal corticosteroids when ABRS is accompanied by allergic rhinitis Topical or systemic decongestants for patient sense of congestion relief 26 Indication Initial empiric therapy Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults First-line (Daily dose) Second-line (Daily dose) Amoxicillinclavulanate Amoxicillin-clavulanate mg/125 mg mg/125 mg PO TID PO BID Amoxicillinclavulanate Doxycycline 100 mg 875 PO BID or 200 mg PO mg/125 mg PO BID daily 27

10 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults High dose (HD, 3-4 g/d) amoxicillin needed against DRSP Clavulanate as a beta-lactamase inhibitor, allows amoxicillin to have activity against beta-lactamase producing organisms such as H. influenzae, M. catarrhalis 28 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults Doxycycline- DRSP treatment failure risk, activity against gm negative organisms, stable in presence of beta-lactamase Pregnancy risk category D 29 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults β-lactam allergy (Allergy to antimicrobials with beta-lactam ring such as penicillins, cephalosporins) Doxycycline 100 mg PO BID Doxycycline 200 mg PO daily Levofloxacin 500 mg PO daily Moxifloxacin 400 mg PO daily 30

11 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults Respiratory fluoroquinolones (FQ)- Activity against DRSP, gramnegative organisms, stable in presence of beta-lactamase 31 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults Risk for antibiotic resistance or failed initial therapy Amoxicillin-clavulanate 2000 mg/125 mg PO BID Levofloxacin 500 mg PO daily Moxifloxacin 400 mg PO daily 32 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults All options with activity against DRSP, gram-negative organisms, stable in presence of and/or active against beta-lactamase 33

12 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Children Indication Initial empirical therapy 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 34 Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Children Risk for antibiotic resistance or failed initial therapy Amoxicillin-clavulanate 90 mg/kg/day PO BID Clindamycin a mg/kg/day PO TID plus cefixime 8 mg/kg/day PO BID or cefpodoxime 10 mg/kg/day PO BID Levofloxacin mg/kg/day PO every 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 mg/kg/day PO every h 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 36

13 Where are the $4 drugs? Amoxicillin Clinical limitations? Ciprofloxacin Clinical limitations? TMP-SMX Clinical limitations? Cephalexin Clinical limitations? 37 Antimicrobials Not Recommended Azithro-, clarithromycin DRSP treatment failure risk 38 Safe products General Rule with Peds Antibiotic Dosing Easily metabolized Prescribe up to but do not exceed adult doses Source- Prescriber's Letter 2008; 15(4):

14 Cross Allergy of PCN to Cephalosporins? How would you Prescribe Cephalosporins to Patients with Penicillin Allergies? FHEA News, Volume XII, Issue VIII, Page 13 Available at er/fheanews_volume12_issue8.pdf 40 Type I Hypersensitivity Reaction AKA immediate or anaphylactic hypersensitivity Reaction involves preferential production of IgE in response to certain antigens (allergens) 41 Type I Hypersensitivity Reaction Usually involves skin (urticaria eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (wheeze, cough) and/or GI tract (gastroenteritis) 42

15 Type II Hypersensitivity AKA cytotoxic hypersensitivity Antigens normally endogenous Primarily mediated by IgM or IgG antibodies Reaction time Minutes to hours 43 Clinical manifestations Type II Hypersensitivity Drug-induced hemolytic anemia, granulocytopenia, thrombocytopenia 44 Conclusion 45

16 End of Presentation Thank you for your time and attention. Monica Tombasco, MS, MSNA, FNP-BC, CRNA 46 All websites listed active at the time of publication. 47