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Acute Bacterial Sinusitis: The latest treatment recommendations Presented by:Monica Tombasco, MS, MSNA, FNP-BC, CRNASenior LecturerFitzgerald Health Education Associates, Inc., North Andover, MAEmergency Medicine Nurse Practitioner Huggins Hospital, Wolfeboro, NHCertified 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 Fitzgerald Health Education Associates, Inc.

Are the bugs winning?Is this a new problem?


In Late 1920sSir Alexander Fleming• 1st to suggest that penicillium mold must secrete antibacterial substance; 1st to isolate active substance which he named penicillin


Sir Alexander FlemingJune 26, 1945, New York Times • “…the microbes are educated to resist penicillin and a host of penicillin-fast (resistant organisms is bred out…


Sir Alexander FlemingJune 26, 1945, New York Times (continued) • 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.”


Empiric Antimicrobial Therapy• The decision-making process where the clinician chooses the agent based on patient characteristics and site of infection.


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?


The Beta-lactam Ring:Vulnerable or Not?Penicillin Cephalosporin


Alteration in Target SiteAltered Penicillin-binding Proteins (PBPs)

3

2b1a1b

2x2z

Actively growing S. pneumoniae: PBPs facilitate cell wall formation for new cell

Cannot makeadequate cellwall, growth

stops

Antibiotic bindsto PBPs

3

2b1a1b

2x2z

3

2b1a1b

2x2z

Antibiotic cannotbind to altered PBPs, growthcontinues (antibiotic resistance)

Withoutantibiotic:

DRSPSusceptible

S. pneumoniae

PnPn Pn Pn


Alteration in Ribosomal Target SitesS. pneumoniae vs. Macrolides:

Methylation of Ribosomes

Normal Macrolide MOA:Macrolide binds to ribosome ofS. pneumoniae and inhibitsbacterial protein synthesis

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

Ribosomes MacrolideProteinMM

MM

ProteinCH3 CH3

Macrolide unableto bind to ribosome


Includes: Quinolones Macrolides

Time-Dependent Agents Concentration-Dependent Agents

Predictors of Bacterial Eradication: PK/PD Profiles

Includes: Penicillins CephalosporinsClinical and bacteriologic success correlates with length of time bacteria are exposed to agent at concentration that exceeds MIC

Telithromycin Doxycycline TMP-SMXSuccessful therapy correlates with parameters that involve blood concentration of agent and MICPeric M, et al. Clin Ther. 2003;25:169-177.


True or false?• The macrolides, fluoroquinolones, and tetracyclines do not contain a beta-lactam ring and are therefore stable in the presence of beta-lactamase.


True or false?• S. pneumoniae occasionally exhibits resistance via beta-lactamase production.


What facilitates resistance?• Time• Exposure

–Unnecessary doses– Long tx period

• Under dosing–Leaves behind more resistant bugs


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).


Updated Treatment Guidelines for ABRS in Children and AdultsChow, A., et al.,

IDSA Clinical Practice Guideline for AcuteBacterial Rhinosinusitis in Children and Adults, available at http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/IDSA%20Clinical%20Practice%20Guideline%20for%20Acute%20Bacterial%20Rhinosinusitis%20in%20Children%20and%20Adults.pdf

Fitzgerald Health Education Associates, Inc. 17

Is antimicrobial neededin 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


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


Bacterial Pathogens Associated with ABRS (continued) • Haemophilus influenzae

• Gram-negative rod-shaped bacterium• ~30% beta-lactamase production rate nationwide• Nontypable strains cause ABRS

– Adults=36% – Children=31–32%



Bacterial Pathogens Associated with ABRS (continued) • Moraxella catarrhalis

• Gram-negative with =>90% beta-lactamase production rate –Adults=16%–Children=8–11%



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 Fitzgerald Health Education Associates, Inc.

Acute Rhinosinusitis (ARS): Defining the termsAcute bacterial rhinosinusitis (ABRS or ABS)

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.


Empiric Antimicrobial Therapy in ABRS:Gram-positive with DRSP riskGram-negative with beta-lactamase production risk


Signs and symptoms either:a) Persistent and not improving (≥10 days);b) Severe (≥3-4 days); orc) Worsening or “double-sickening” (≥3-4 days)

Risk for Resistance

Risk for antibiotic resistance Age <2 y or >65 y, daycare Prior antibiotics within the past month Prior hospitalization past 5 days Comorbidities ImmunocompromisedSymptomatic

managementNo Yes

Initiate first-line antimicrobial therapy

Initiate second-line antimicrobial therapy

CT or MRI to investigate noninfectious causes or suppurative complications

Sinus or meatal cultures for pathogen-specific therapy

Refer to specialist

Improvement

Complete 5-7 days of antimicrobial therapy

Improvement after 3-5 days Worsening or no improvement after 3-5 days

Improvement after 3-5 days


Broaden coverage or switch to different antimicrobial class

Worsening or no improvement after 3-5 days

Complete 7-10 days of antimicrobial therapyImprovement


Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging

Algorithm for the Management of Acute Bacterial Rhinosinusitis

Source: Clinical Infectious Diseases Advance http://cid.oxfordjournals.org/

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


Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in AdultsIndication First-line

(Daily dose)Second-line (Daily dose)

Initial empiric therapy

Amoxicillin-clavulanate 500 mg/125 mg PO TID

OrAmoxicillin-clavulanate 875 mg/125 mg PO BID

Amoxicillin-clavulanate 2000 mg/125 mg PO BID OrDoxycycline 100 mg PO BID or 200 mg PO daily


Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults (continued)• 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


Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults (continued)• Doxycycline- DRSP treatment failure risk, activity against gm negative organisms, stable in presence of beta-lactamase

–Pregnancy risk category D


Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults (continued)β-lactam allergy(Allergy to antimicrobials with beta-lactam ring such as penicillins, cephalosporins)

Doxycycline 100 mg PO BID Or

Doxycycline 200 mg PO dailyOr

Levofloxacin 500 mg PO dailyOr

Moxifloxacin 400 mg PO daily


Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults (continued)• Respiratory fluoroquinolones (FQ)-Activity against DRSP, gram-negative organisms, stable in presence of beta-lactamase


Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults (continued)Risk for antibiotic resistance or failed initial therapy

Amoxicillin-clavulanate 2000 mg/125 mg PO BIDOr

Levofloxacin 500 mg PO dailyOr

Moxifloxacin 400 mg PO daily


Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Adults (continued)• All options with activity against DRSP, gram-negative organisms, stable in presence of and/or active against beta-lactamase


Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in ChildrenIndication First-line

(Daily dose)Second-line (Daily dose)

Initial empirical therapy

Amoxicillin-clavulanate45 mg/kg/day PO BID

Amoxicillin-clavulanate 90 mg/kg/day PO BID



Antimicrobial Regimens for Acute Bacterial Rhinosinusitis in Children(continued)Risk for antibiotic resistance orfailed initial therapy

Amoxicillin-clavulanate 90 mg/kg/day PO BIDOrClindamycina 30–40 mg/kg/day PO TID plus cefixime 8 mg/kg/day PO BID or cefpodoxime 10 mg/kg/day PO BID OrLevofloxacin 10–20 mg/kg/day PO every 12–24 haResistance 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(continued)β-lactam allergy Type I

hypersensitivity Non–type I

hypersensitivity

Levofloxacin 10–20 mg/kg/day PO every 12–24 hOr

Clindamycina (30–40 mg/kg/day PO TID) pluscefixime (8 mg/kg/day PO BID) or cefpodoxime (10 mg/kg/day PO BID)aResistance 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


Where are the $4 drugs?• Amoxicillin

– Clinical limitations?• Ciprofloxacin

– Clinical limitations?

• TMP-SMX– Clinical limitations?

• Cephalexin– Clinical limitations?


Antimicrobials Not Recommended • Azithro-, clarithromycin

–DRSP treatment failure risk


General Rule with Peds Antibiotic Dosing• Safe products• Easily metabolized• Prescribe up to but do not exceed adult doses

– Source- Prescriber's Letter 2008; 15(4):240425.


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 http://fhea.com/main/content/Newsletter/fheanews_volume12_issue8.pdf


Type I Hypersensitivity Reaction • AKA immediate or anaphylactic hypersensitivity

–Reaction involves preferential production of IgE in response to certain antigens (allergens)


Type I Hypersensitivity Reaction (continued) • Usually involves skin (urticaria eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (wheeze, cough) and/or GI tract (gastroenteritis)


Type II Hypersensitivity• AKA cytotoxic hypersensitivity

–Antigens normally endogenous–Primarily mediated by IgM or IgG antibodies

• Reaction time–Minutes to hours


Type II Hypersensitivity (continued)• Clinical manifestations

–Drug-induced hemolytic anemia, granulocytopenia, thrombocytopenia


Conclusion


End of PresentationThank you for your time and attention.

Monica Tombasco, MS, MSNA, FNP-BC, CRNAwww.fhea.com [email protected]


All websites listed active at the time of publication.


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