Rhinosinusitis%20-%20acute,%20bacterial Treatment

General Antibiotic Therapy Principles

• Empiric therapy should be started as soon as acute bacterial rhinosinusitis (ABRS) is diagnosed
  • Therapy should be based on cost, safety, likely pathogen, local resistance patterns and recent antibiotic use
• Antibiotic therapy should be started in patients with the following presentations:
  • Severe ABRS: Patient with >3 consecutive days of fever (≥39°C) with purulent nasal discharge or facial pain
  • Worsening ABRS: Presence of increased nasal discharge, headache or new fever after a typical viral URTI of 5-6 days that was initially improving
  • Persistent ABRS: ≥10 days symptoms (nasal discharge of any quality, cough) without signs of improvement
  • Severe, worsening or persistent ABRS with accompanying acute otitis media, pharyngitis, adenitis or pneumonia, or if suspected to have orbital or intracranial involvement
  • Uncomplicated severe, worsening or persistent ABRS without concomitant disease
• Initial antibiotic prescribed should be the most narrow-spectrum agent that is active against the likely pathogens: S pneumoniae, H influenzae, M catarrhalis
  
  • Consider the local prevalence of resistance among each of the likely bacterial species
• Initial empiric therapy coverage for S aureus or methicillin-resistant S aureus is not recommended
• Factors that predispose patients to antibiotic-resistant bacteria need to be considered (eg antibiotic usage within the past month, hospitalization in the past 5 days, age <2 or >65 years, exposure to daycare, comorbid conditions, impaired immune response, severe infection, living in areas with high rates of resistance)

Goals of Antibiotic Therapy

• Eradicate bacterial infection from the sinuses
• Hasten resolution of symptoms
• Prevent complications
• Decrease the development of chronic disease

Mild Disease and No Antibiotics Within the Last 4-6 Weeks

• In patients who have not responded to symptomatic therapy alone or those whose symptoms have worsened

Amoxicillin (Usual or High Dose)

• Amoxicillin continues to be the agent of choice for ABRS due to its safety, efficacy, low cost and narrow microbiologic spectrum when still effective in the locality
  • Should be taken for 5-10 days
• In areas with high incidence of resistant S pneumoniae, high-dose Amoxicillin should be considered
• Generally considered the most active of all oral beta-lactams against streptococci and only S pneumoniae that is highly resistant to Penicillin will not respond to conventional doses of Amoxicillin
  • Activity against beta-lactamase-negative strains of H influenzae is fair to good but it is ineffective against beta-lactamase-producing strains

Amoxicillin/Clavulanic Acid with or without High-Dose Amoxicillin

• Recommended as initial empiric therapy for ABRS rather than Amoxicillin alone
• Recommended in patients with moderate to severe disease who have failed high-dose Amoxicillin or if beta-lactamase-producing strains of H influenzae, M catarrhalis or oral anaerobes are suspected
• Amoxicillin may be added to Amoxicillin/clavulanic acid to overcome drug resistance of S pneumoniae and should be considered in areas with high incidence of resistant S pneumoniae

Cephalosporins (Second and Third Generation)

• Eg Cefaclor, Cefdinir, Cefixime, Cefuroxime, Cefpodoxime, Ceftriaxone
• Alternative agents that may be considered for patients with ABRS who have non-type 1 allergy to Penicillin
  • Because of variable resistance to S pneumoniae, it is not recommended for single-agent empiric therapy
  • Local resistance patterns and antimicrobial spectrum of the cephalosporins to S pneumoniae, H influenzae and M catarrhalis will need to be considered prior to choosing an agent
• Cefaclor has poor overall efficacy against bacterial respiratory tract pathogens
• Cefixime has potent activity against H influenzae
• Cefpodoxime is the preferred agent for patients with treatment failure on high-dose Amoxicillin or Amoxicillin/clavulanic acid
  • Has similar activity with Cefuroxime and Cefdinir against S pneumoniae but greater efficacy against H influenzae
• Cefuroxime has good efficacy against S pneumoniae but less active than Cefpodoxime against H influenzae
• Intravenous/intramuscular Ceftriaxone (50 mg/kg single-dose) may be considered for patients intolerant to oral medications and highly unlikely to adhere to prescribed medications

Co-trimoxazole

• Depending on the sensitivity pattern of local isolates, Co-trimoxazole may be considered an alternative for patients with type 1 allergy to Penicillin
  • Not advised for empiric therapy due to increased rates of resistance to both S pneumoniae and H influenzae

Doxycycline

• Alternative agent to Amoxicillin or Amoxicillin/clavulanic acid in initial empiric therapy or to those who have type 1 allergy to Penicillin
• Doxycycline has activity against Penicillin-susceptible pneumococci and M catarrhalis, but limited coverage for H influenzae
  • The probability of non-susceptibility to Doxycycline tends to rise in pneumococcal strains that have any level of Penicillin resistance

Macrolides

• These agents may be considered alternatives in patients who have type 1 allergy to Penicillin
• All macrolides have good activity against macrolide-susceptible pneumococci but are not recommended for empiric therapy because of increasing prevalence of macrolide-resistant S pneumoniae
• Azithromycin and Clarithromycin are relatively weak against penicillin-resistant H influenzae and S pneumoniae

Moderate-Severe Disease or Antibiotics Received Within the Last 4-6 Weeks

• Patients who failed first-line therapy may be considered with this group of patients

Amoxicillin/Clavulanic Acid with High-Dose Amoxicillin

• Considered first-line agent by many authorities for patients who have failed Amoxicillin or in those with risk for resistant organisms
• Therapy should be initiated using higher doses of Amoxicillin (add Amoxicillin therapy to Amoxicillin/clavulanic acid); this will increase the coverage of S pneumoniae

Ceftriaxone

• Five-day therapy may be considered in those at risk for resistant organisms or in those who have failed first-line therapy

Respiratory Quinolones

• Eg Levofloxacin, Moxifloxacin
• Provide excellent coverage for all the likely pathogens, especially S pneumoniae and H influenzae
• Because of the potential for increased resistance and toxicity, these agents should be reserved for adults with type 1 allergy to Penicillin and risk factors for resistant organisms, moderate disease, or in those who have failed recent antibiotic coverage

Combination Therapy

• Eg Cefixime + high-dose Amoxicillin or Clindamycin or Rifampicin + high-dose Amoxicillin or Clindamycin
• Combination therapy that has adequate Gram-positive and negative coverage may be considered in patients with risk of resistant organisms, moderate disease or have failed first-line therapy
• At this time, there is no clinical evidence supporting the use or safety of combination therapy but it is recommended based on in vitro spectrum activity
• Rifampicin + Clindamycin
  • Rifampicin should not be used as monotherapy or for longer than 10-14 days because resistance develops rapidly to this agent
• Clindamycin/Linezolid + Cefixime
  • Recommended for patients with severe type 1 Penicillin hypersensitivity with moderate-severe sinusitis

Duration of Antibiotic Therapy

• The appropriate duration of antibiotic therapy is not well defined
• Most patients with ABRS that have been treated with the appropriate antibiotic agent will show clinical improvement within 48-72 hours
• If ABRS is worse within 72 hours after initiating treatment:
  • If initially advised further observation, may start Amoxicillin with or without Clavulanate therapy
  • If initially prescribed with Amoxicillin, may increase dose and may add Clavulanate
  • If initially prescribed with high-dose Amoxicillin-Clavulanate, may shift to Clindamycin + Cefixime OR Linezolid + Cefixime OR Levofloxacin

• No clinical improvement seen after 72 hours:
  • If initially advised further observation, may start antibiotic therapy
  • If initially prescribed with Amoxicillin, may initiate high-dose Amoxicillin/clavulanate therapy
  • If initially prescribed with high-dose Amoxicillin-Clavulanate, may continue giving high-dose Amoxicillin-Clavulanate OR may shift to Clindamycin + Cefixime OR Linezolid + Cefixime OR Levofloxacin

• In patients without severe ABRS and comorbidities, they may benefit from short-course treatment which leads to better compliance, fewer adverse effects, lower resistance rates and lower costs of medications
• Short-course treatment with appropriate oral antibiotic treatment is given in 7 days
  • May be extended to 14 days if symptoms fail to resolve
• The duration of antibiotic therapy in patients with moderate to severe ABRS is 7 to 14 days