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Treatment guidelines

These guidelines are intended as a resource for clinicians to help reduce resistance and complications associated with overuse and misuse of antibiotics.

Acute Exacerbations of COPD (AECOPD)

An acute exacerbation of COPD (AECOPD) is defined by an acute worsening of cough or dyspnea or increased sputum production. The role of antibiotics is best established for patients with purulent sputum (usually green) and those who will be admitted to hospital due to severity of their illness1-3. For patients with community-acquired pneumonia, please see this separate guideline. Antibiotics should not be administered to patients with mucoid sputum who will be managed as outpatients, or those admitted to hospital with an alternate etiology for dyspnea (eg. heart failure).

MOST COMMON ORGANISMS:

  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Moraxella catarrhalis

EMPIRIC ANTIMICROBIAL THERAPY:

  • Oralantibioticsarefirst-line*:
    • amoxicillin 500 mg/clavulanic acid 125 mg PO TID x 5 days
    • cefuroxime 500 mg PO BID x 5 days

  • In case of severe allergy to β-lactam*:
    • levofloxacin 750 mg PO daily x 5 days

* If a patient has had recent antimicrobial exposure (within the previous 3 months), consider using an antimicrobial agent from a different class

*If oral route not an option, consider ceftriaxone 1 g IV daily

Duration of therapy:

  • 5 days is recommended4,5

OTHER CONSIDERATIONS:

  • Systemic corticosteroid & Bronchodilator therapy
    • see COPD order set

  • Pneumonia:
    • AECOPD may be associated with pneumonia. The presence of pneumonia will alter the antibiotic recommendations.
    • refer to treatment guideline for Community-Acquired Pneumonia

REFERENCES:

  1. Quon et al. Contemporary management of acute exacerbations of COPD: A systematic review and metanalysis. Chest 2008; 133:756–766.
  2. Vollenweider DJ et al. Antibiotics for exacerbations of chronic obstructive pulmonary diseases (review). The Cochrane Collaboration 2012; JohnWiley and Sons, Ltd.
  3. Stockley RA et al. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest. 2000; 117:1638–1645.
  4. Falagas et al. Short- versus long-duration antimicrobial treatment for exacerbations of chronic bronchitis: a meta-analysis. Journal of Antimicrobial Chemotherapy. 2008; 62: 442–450.
  5. Moussaoui et al. Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies. Thorax. 2008; 63:415–422

Clostridium difficile infection

C. difficile-associated diarrhea may develop following disruption of the normal bacterial bowel flora, and this normally occurs during or following antimicrobial therapy (within 8 weeks). In addition to diarrhea, the organism can produce severe complications (systemic inflammatory response syndrome, shock, toxic megacolon, bowel perforation and death (mortality > 30%). About 25% of patients experience a relapse within 8 weeks.

ALL cases should be managed as follows:

  • Discontinue inciting antibiotics, when possible
  • Do not start new exacerbating antibiotics, when possible
  • Discontinue acid-suppressing agents (e.g. PPIs), when possible
  • Avoid antimotility agents and opioids

First-line therapy for all inpatients:

Vancomycin 125 mg PO QID x 10-14 days

Notes:

  • Vancomycin has been shown to be superior to metronidazole regardless of the severity of C. difficile infection
  • Vancomycin capsules are expensive and not currently covered by ODB (funding requires approval via the Telephone Request Service of the Exceptional Access Program).
  • Metronidazole can be considered for treatment of outpatients as the disease is less severe and there are access issues.
  • IV vancomycin is ineffective for treating C. difficile infection 

Severe & complicated infection (systemic inflammatory response (SIRS), sepsis, ileus or toxic megacolon):

  • Consider an ID consult & early consultation with General Surgery
  • Vancomycin 125 mg PO QID x 10-14 days*
  • Consider adding IV metronidazole 500 mg IV Q8H
  • Consider adding rectal vancomycin in patients with ileus: 
    Vancomycin retention enema 500 mg in 100 mL normal saline (250 mL preferred if bowel intact) instilled via rectal tube q6h (each dose to be retained for 60 min)

Recurrent C. difficile infection:

  • Consider an ID consult

Treatment options include:

  • Vancomycin usual regimen: 125 mg PO QID x 10-14 days

  • Vancomycin prolonged regimen with tapering (51 days):
    • 125 mg PO QID x 14 days
    • 125 mg PO BID x 7 days
    • 125 mg PO OD x 7 days
    • 125 mg PO Q2D x 8 days
    • 125 mg PO Q3D x 15 days

  • Fidaxomicin 200 mg PO BID x 10 days
    Note: Prescribing of fidaxomicin is restricted to Infectious Diseases due to the high cost of treatment (~ $2,500)

Febrile Neutropenia

Influenza

Intra-Abdominal Infection

» Community Acquired IAI: Uncomplicated

Type of IAI Examples Selection of Empiric Antibiotics
Community Acquired IAI: Uncomplicated Recommended Antibiotics Penicillin Allergyb Duration
Uncomplicated IAI

Non-perforated appendicitis

Cefazolin 2g IV Q8Ha + metronidazole 500mg PO/IV Q12H

Step-down to cephalexin 500mg PO QID + metronidazole PO Q12H

Ciprofloxacin 500mg PO/400mg IV Q12Ha + metronidazole 500mg PO/IV Q12H

Surgery performed: stop post-op

Medical management only: 7-10 days

Non-perforated diverticulitis

Cefazolin 2g IV Q8Ha + metronidazole 500mg PO/IV Q12H

Step-down to cephalexin 500mg PO QID + metronidazole PO Q12H

Non-severe prior reactionb: Cefazolin 2g IV Q8H + metronidazole 500mg PO/IV Q12H

Severe prior reactionc: Ciprofloxacin 500mg PO/400mg IV Q12H + metronidazole 500mg PO/IV Q12H

Surgery performed: stop post-op

Medical management only: 7-days

Perforation without established infection

Perforations of stomach, duodenum, and traumatic bowel perforations who are taken to the OR within 12-24 hours

Cefazolin 2g IV Q8Ha + metronidazole 500mg PO/IV Q12H

Ciprofloxacin 500mg PO/400mg IV Q12Ha + metronidazole 500mg PO/IV Q12H

Surgical source control without significant contamination: stop post-op

Surgical source control with significant contamination: 4 days post-op

Medical management: does not apply

» Community Acquired IAI: Complicated

Type of IAI Examples Selection of Empiric Antibiotics
Community Acquired IAI: Complicated Recommended Antibiotics Penicillin Allergyb Duration
Mild-to-Moderate Severity

Perforated appendicitis; perforated diverticulitis

Ceftriaxone 1g IV Q24H + metronidazole 500mg PO/IV Q12H

Step down to: Amoxicillin/clavulanic acid 875/125mg PO Q12H

Ciprofloxacin 500mg PO/400mg IV Q12Ha + metronidazole 500mg PO/IV Q12H

    Surgical source control: 4-days post-op

    Medical management: 10 days

    High Severity Shock; new organ failure; ICU patient

    Piperacillin/tazobactam 4.5g IV Q6Ha

    (consider meropenem 500mg IV Q6Ha if history of ESBL organisms)

    Meropenem 500mg IV Q6Ha

      Surgical source control: 4-days post-op

      Medical management: 10-days

      » Health-care associated IAI

      Type of IAI Examples Selection of Empiric Antibiotics

      Health-care Associated IAI

      (hospitalized >= 5 days)
      Recommended Antibiotics Penicillin Allergyb Duration
      Mild-to-Moderate

      Anastomotic leak; post-operative abscess

      Ceftriaxone 1g IV Q24H + metronidazole 500mg PO/IV Q12H

      Ertapenem 1g IV Q24Ha

      Surgical source control: 4-days post-op

      Medical management: 10-14 days but may require repeat imaging to guide

      High Severity Shock; new organ failure; ICU patient

      Piperacillin/tazobactam 4.5g IV Q6Ha

      (consider meropenem 500mg IV Q6Ha if history of ESBL organisms)

      Meropenem 500mg IV Q6Ha

      Surgical source control: 4-days post-op

      Medical management: does not apply

      » Biliary tract

      Type of IAI Examples Selection of Empiric Antibiotics
      Biliary Tract Recommended Antibiotics Penicillin Allergyb Duration
      Mild-to-Moderate Severity

      Acute calculous cholecysitits (without shock)

      Cefazolin 2g IV Q8Ha

      Ciprofloxacin 500mg PO/400mg IV Q12Ha

      Uncomplicated (no perforation) and surgical source control (eg. cholecystectomy): stop post-op

      Complicated (perforated) and surgical source control: 4 days post-op

      Medical management: 7-days

      Acute cholangitis (without shock)

      Ceftriaxone 1g IV Q24H

      Ciprofloxacin 500mg PO/400mg IV Q12Ha

      Source control (eg. decompression): 4-days

      Medical management: 7-days

      High Severity Shock; new organ failure; ICU patient

      Piperacillin/tazobactam 4.5g IV Q6Ha

      (consider meropenem 500mg IV Q6Ha if history of ESBL organisms)

      Meropenem 500mg IV Q6Ha

          Surgical source control: 4-days

          Medical management: 7-days

          Footnotes

          a View renal dosing here
          Ceftriaxone or cefazolin may be used in patients with history of Ig-E mediated reactions to penicillin including anaphylaxis (excluding near fatal reactions in the past 10 years), angioedema, wheezing, laryngeal edema, hives/urticaria. Severe non-IgE mediated reactions, where all beta-lactams should be avoided, include: Serum sickness, Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Acute Interstitial Nephritis (AIN), Drug Rash Eosinophilia Systemic Symptoms (DRESS) Syndrome, Hemolytic anemia.


          Updated August 2023

          Meningitis (community acquired bacterial)

          Background

          • The most common pathogens causing community-acquired bacterial meningitis in adults are Streptococcus pneumoniae and Neisseria meningitidis. Listeria monocytogenes should also be considered in the immunocompromised, pregnant or elderly patient.
          • Initiation of empiric therapy for meningitis should never be delayed while diagnostic procedures are pending (e.g., LP, CT).

          First-line Empiric Therapy

          Administer ceftriaxone first, ampicillin second (if indicated), then vancomycin last.



          Antibiotic

          Notes

          Ceftriaxone 2 g IV q12h PLUS

          Vancomycin 2g IV load, then 1 g IV q8h*

          Continuous infusion of vancomycin is recommended – please see Vancomycin dosing guidelines for details

          Ampicillin 2 g IV q4h*

          (in patients at risk for Listeria infection)

          Addition of ampicillin for coverage of Listeria is recommended in patients with the following risk factors:

          · age > 50 years

          · pregnancy

          · immunocompromise

          *dose adjustment required in renal impairment – see vancomycin and/or ampicillin dosing guidelines

          Beta-Lactam Allergy

          • Individuals with prior immediate hypersensitivity reactions to penicillins may still receive non-cross reactive cephalosporins, including ceftriaxone.
          • Individuals with ceftriaxone allergy should receive alternate first-line empiric therapy with:
            • Meropenem 2 g IV q8h PLUS
            • Vancomycin 2 g IV loading dose followed by 1 g IV q8H – continuous infusion of vancomycin is recommended – please see Vancomycin dosing guidelines for details
          • Individuals with history of delayed reactions with systemic involvement to beta-lactam antibiotics including SCARs (SJS/TEN, DRESS, AGEP), serum-sickness like reaction, cytopenia, and nephritis should avoid all beta-lactam antibiotics. Contact the Infectious Diseases Consult service for antibiotic recommendations.

          Adjunctive Therapy

          • Dexamethasone (10 mg q6h x 4 days) is indicated in patients with suspected community-acquired bacterial meningitis. Use of dexamethasone has been associated with a reduction in rates of hearing loss and other neurologic sequelae, as well as mortality in cases of meningitis caused by S. pneumoniae. Therapy must be given shortly before or concurrently with initial antimicrobials. Dexamethasone should be discontinued if an alternate causative pathogen is established.

          Targeted Therapy

          Organism

          First-Line Therapy

          Duration

          S. pneumoniae

          10 days

          · Penicillin-susceptible
          (MIC ≤ 0.06 µg/mL)

          Penicillin G 4 MU IV q4h

          · Penicillin-resistant

          (MIC ≥ 0.12 µg/mL)

          AND

          Ceftriaxone-susceptible

          (MIC < 0.5 µg/mL)

          Ceftriaxone 2 g IV q12h

          · Penicillin-resistant

          (MIC ≥ 0.12 µg/mL)

          AND

          Ceftriaxone-resistant

          (MIC ≥ 1.0 µg/mL)

          Vancomycin 1 g IV q8h

          PLUS

          Ceftriaxone 2 g IV q12h

          Neisseria meningitidis

          7 days

          · Penicillin-susceptible (MIC < 0.12 µg/mL)

          Penicillin G 4 MU IV q4h

          · Penicillin-resistant (MIC ≥ 0.12 µg/mL)

          Ceftriaxone 2 g IV q12h

          Listeria monocytogenes

          21 days

          · Cephalosporins are not effective

          Ampicillin 2 g IV q4h

          ±

          Gentamicin 1 – 1.5 mg/kg IV q8h

          References

          • Beckham JD, Tyler KL; IDSA. Initial management of acute bacterial meningitis in adults: summary of IDSA guidelines. Rev Neurol Dis. 2006 Spring;3(2):57-60.
          • Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2015 Sep 12;2015(9).
          • de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002 Nov 14;347(20):1549-56.
          • Amoah J, Klein EY, Chiotos K, Cosgrove SE, Tamma PD; CDC Prevention Epicenters Program. Administration of a β-lactam Prior to Vancomycin as the First Dose of Antibiotic Therapy Improves Survival in Patients with Bloodstream Infections. Clin Infect Dis. 2021 Oct 4:ciab865. doi: 10.1093/cid/ciab865. Epub ahead of print. PMID: 34606585.

            Last updated: December 16, 2021

            Meningitis (community acquired bacterial)

            Infectious Diseases should be consulted in cases of suspected neurosurgical meningitis.

            Background

            • Post-neurosurgical meningitis can be subtle in presentation and challenging to diagnose.
            • Findings of acute onset fever, nuchal rigidity and severe headache may not be present.
            • Patients may present with a subacute history of lethargy, headache, or nausea/vomiting.
            • CSF parameters may be confounded by non-infectious diagnoses (e.g. hemorrhage, trauma or seizure).
              • Low glucose can support diagnosis but does not rule out meningitis.
              • CSF lactate is not sensitive or specific.
            • Unlike community-acquired meningitis, the most common pathogens causing post-neurosurgical meningitis include Staphylococcus aureus and aerobic Gram-negative bacilli (e.g., Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, etc).
            • If foreign material is present (e.g. VP shunt or mesh), pathogens may also include Coagulase-negative staphylococci and Cutibacterium acnes.
            • If there was preceding basal skull fracture, pathogens may also include Streptococcus pneumoniae and Haemophilus influenzae.

            Empiric Therapy

            • Initiation of empiric therapy for meningitis should never be delayed for additional diagnostic investigations (e.g., LP, CT, MRI).

            First-line Empiric Therapy: Administer meropenem first, then vancomycin.



            Antibiotic

            Notes

            Meropenem 2g IV q8h PLUS

            Vancomycin 2g IV load, then 1g IV q8-12h

            Continuous infusion of vancomycin is recommended. Vancomycin should be dosed according to renal function.

            Based on local susceptibility patterns of CSF isolates, ceftazidime should not be used as empiric therapy. Ceftazidime can be used as definitive therapy if susceptibility is confirmed.

            Beta-Lactam Allergy

            Individuals with prior immediate hypersensitivity reactions to penicillin may still receive non-cross reactive cephalosporins. Due to a structurally different side chain, meropenem can be safely given in those with a history of reported penicillin or cephalosporin allergy.

            Individuals with a history of delayed reactions with systemic involvement to beta-lactam antibiotics including severe cutaneous adverse reactions (SJS/TEN, DRESS, AGEP), serum sickness like reaction, cytopenia and nephritis should avoid all beta lactam antibiotics. Contact the Infectious Diseases Consult service for antibiotic recommendations.

            Adjunctive Therapy

            • There is NO role for the use of dexamethasone in post-neurosurgical meningitis
              • Existing evidence only supports use of dexamethasone for community acquired, pneumococcal meningitis

            Targeted Therapy and Duration of Treatment

            • Choice of antibiotic depends on causative organism and antimicrobial susceptibilities
            • Infectious Diseases should be consulted in cases of suspected neurosurgical meningitis.
            • Duration of therapy depends on multiple factors, such as:
              • Causative organism
              • Presence of CSF shunt or prosthetic device
              • Skull bone involvement (e.g., osteomyelitis)
              • Brain abscess
              • Clinical response to therapy
            Meningitis

            Organism

            First-Line Therapy

            General Duration

            S. aureus

            MSSA: Cloxacillin 2g IV q4h

            MRSA: Vancomycin 1g IV q8-12h

            14 days

            C. acnes

            Penicillin G 4 million units IV q4h

            10-14 days

            Coagulase-negative staphylococci

            Vancomycin 1 g IV q8-12h

            10-14 days

            Gram negative bacilli

            Antimicrobial therapy based on susceptibilities

            • Avoid piperacillin-tazobactam due to limited CNS penetration

            21 days

            References

            Amoah J, Klein EY, Chiotos K, Cosgrove SE, Tamma PD; CDC Prevention Epicenters Program. Administration of a β-lactam Prior to Vancomycin as the First Dose of Antibiotic Therapy Improves Survival in Patients with Bloodstream Infections. Clin Infect Dis. 2021 Oct 4:ciab865. doi: 10.1093/cid/ciab865. Epub ahead of print. PMID: 34606585.

            Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2015 Sep 12;2015(9).

            de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002 Nov 14;347(20):1549-56.

            Tunkel AR, Hasbun R, Bhimrag A, Byers K, Kaplan SL, Scheld M, van de Beek D, Pleck TP, Garton HJL, & Zunt JR. Practice Guidelines for Healthcare-associated Ventriculitis and Meningitis. Clinical Infectious Diseases. 2017 March 15;64;6:e34-e65.

            Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, & Whitley RJ. Practice Guidelines for the Management of Bacterial Meningitis. Clinical Infectious Diseases. 2004;39:1267-1284.


              Last updated: March 10, 2023

              Pneumonia (community acquired)

              Guidelines for Empiric Treatment

              • The approach to the management of community-acquired pneumonia (CAP) is dependent on the severity of presentation and individual patient factors (i.e., presence of structural lung disease).
              • The following guidelines are for the empiric management of CAP in adults who require hospitalization and are not significantly immunocompromised.

              Organisms

              • Streptococcus pneumoniae
              • Haemophilus influenzae
              • Chlamydia pneumoniae
              • Mycoplasma pneumoniae
              • Legionella pneumophila (for select populations, see below)

              Treatment: Choose one of the two options below

              Regimen Dosing Notes
              β-lactam Monotherapy

              Ceftriaxone 1g IV q24h OR Amoxicillin-clavulanate 875/125 mg PO q12h

              Consider for patients with CRB-65 score* of 1-2 on admission without risk factors or clinical syndrome compatible with Legionnaire’s disease

              β-lactam + Macrolide

              Ceftriaxone 1g IV q24h AND Azithromycin 500mg IV/PO day q24h

              Consider for select populations:
              1. Patients with CRB-65 score* of ≥ 3
              2. With risk factors or clinical presentation compatible with Legionnaire’s disease
              3. Admitted to ICU or step-up/step-down
              4. Worsening despite β-lactam monotherapy

              Respiratory Fluoroquinolone Levofloxacin 750mg IV/PO q24h (levofloxacin is the preferred respiratory fluoroquinolone for CAP at SHSC)

              Consider for patients unable to receive ceftriaxone and/or azithromycin (e.g. allergy or intolerance)

              Reduce dose in renal insufficiency
              • If patient colonized with MRSA, can consider addition of empirical IV vancomycin
              • If patient colonized with Pseudomonas in the lungs in the past year, can consider broadening of therapy to include anti-pseudomonal coverage (e.g. piperacillin-tazobactam)

              *CRB-65 score: 1 point each for: Respiratory rate ≥ 30 breaths/minute, age ≥ 65 years, systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg, OR confusion (MMSE < 9 or new disorientation to person, place, or time)

              Legionella pneumophila risk factors (aside from immunocompromise) include: significant contact with stagnant or aerosolized water, air conditioning systems, water heating systems, or residence in an institution with known Legionella outbreak. Incidence is highest during June to October based on Public Health Ontario data. Clinical presentation may include: confusion, myalgias, diarrhea, abdominal pain, headache, hyponatremia, transaminitis, and hypophosphatemia – absence of these features does not rule out Legionella infection.


              Suspected Macroaspiration:

              • Most cases are chemical pneumonitis. If rapid clinical improvement after suspected aspiration event, consider discontinuation of antibiotics and close monitoring.
              • Ceftriaxone has adequate oral anaerobic coverage and may be used alone.
              • In the setting of severe anaerobic pulmonary infection (e.g., lung abscess, empyema), additional anaerobic coverage (clindamycin or metronidazole) may be added.

              Beta-Lactam Allergy

              • Individuals with prior immediate hypersensitivity reactions to penicillins may still receive non-cross reactive cephalosporins, including ceftriaxone and cefuroxime.

              Duration of Treatment

              • Options for oral step-down therapy from ceftriaxone include:
                • Cefuroxime axetil 500mg PO BID
                • Amoxicillin-clavulanic acid 875/125 mg PO BID
              • Duration of therapy:
                • 5 days, however 7 days may be considered if not yet reaching clinical stability
                • A dose of 1500 mg azithromycin is sufficient for treatment of Mycoplasma pneumoniae or Chlamydia pneumoniae
                • If Legionella infection confirmed, the duration of dedicated Legionella therapy is often extended to minimum of 7 days

              References

              Jain S, Self WH, Wunderink RG, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015 Jul 30;373(5):415-27. doi: 10.1056/NEJMoa1500245.

              Postma DF, van Werkhoven CH, van Elden LJ, et al. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015 Apr 2;372(14):1312-23.

              Garin N, Genné D, Carballo S, et al. β-Lactam monotherapy vs β-lactam-macrolide combination treatment in moderately severe community-acquired pneumonia: a randomized noninferiority trial. JAMA Intern Med. 2014 Dec;174(12):1894-901.

              Socan M. Treatment of atypical pneumonia with azithromycin: comparison of a 5-day and a 3-day course. J Chemother. 1998 Feb;10(1):64-8.

              Schönwald S, Kuzman I, Oresković K, et al. Azithromycin: single 1.5 g dose in the treatment of patients with atypical pneumonia syndrome--a randomized study. Infection. 1999;27(3):198-202.

              Gershengorn HB, Keene A, Dzierba AL, et al. The association of antibiotic treatment regimen and hospital mortality in patients hospitalized with Legionella pneumonia. Clin Infect Dis. 2015 Jun 1;60(11):e66-79.

              Nie W, Li B, Xiu Q. β-Lactam/macrolide dual therapy versus β-lactam monotherapy for the treatment of community-acquired pneumonia in adults: a systematic review and meta-analysis. J Antimicrob Chemother. 2014 Jun;69(6):1441-6.

              Eliakim-Raz N, Robenshtok E, Shefet D, et al. Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults. Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD004418.

              Shefet D, Robenshtok E, Paul M, et al. Empirical atypical coverage for inpatients with community-acquired pneumonia: systematic review of randomized controlled trials. Arch Intern Med. 2005 Sep 26;165(17):1992-2000.

              Eljaaly K, Alshehri S, Aljabri A, et al. Clinical failure with and without empiric atypical bacteria coverage in hospitalized adults with community-acquired pneumonia: a systematic review and meta-analysis. BMC Infect Dis. 2017 Jun 2;17(1):385.

              Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.

              Toronto Central Local Health Integration Network. Management of Community Acquired Pneumonia in Adults. Retrieved on March 24, 2023 from https://www.hqontario.ca/Portals/0/Documents/evidence/clinical-handbooks/community-acquired-pneumonia-140227-en.pdf

              Ebell MH, Walsh ME, Fahey T, et al. Meta-analysis of Calibration, Discrimination, and Stratum-Specific Likelihood Ratios for the CRB-65 Score. J Gen Intern Med. 2019 Jul;34(7):1304-1313.

              Dragan V, Wei Y, Elligsen M, et al. Prophylactic Antimicrobial Therapy for Acute Aspiration Pneumonitis. Clin Infect Dis. 2018 Aug 1;67(4):513-518.

              Last updated: July 13, 2023

              Pneumonia (hospital acquired)

              Hospital-acquired pneumonia (HAP) is defined as pneumonia occurring 48 hours or greater after admission and excludes any infection that may be incubating at the time of admission.

              The following guidelines are intended for the empiric management of HAP in immunocompetent adults without ventilator-associated pneumonia. Therapy should be tailored once culture and sensitivity results or other diagnostic information becomes available.

              Usual organisms:

              • Staphylococcus aureus
              • Aerobic gram-negative bacilli (e.g., Pseudomonas aeruginosa, Klebsiella, Enterobacter, Serratia, E. coli, Haemophilus influenzae)

              GUIDELINES FOR EMPIRIC TREATMENT

              A. Patients Without Risk Factors for Pseudomonas aeruginosa (see below)*

              • First-line empiric therapy:
                • Ceftriaxone 1 g IV q24h
              • Second-line empiric therapy (if severe beta-lactam allergy):
                • Levofloxacin 750 mg po/IV q24h *note: while IV levofloxacin is on backorder, IV moxifloxacin (400 mg IV q24h) may be used if a patient with a severe beta-lactam allergy is unable to take oral therapy.
              • Stepdown to oral therapy when improving:
                • Amoxicillin-clavulanic acid 875 mg po BID
                  OR
                  Levofloxacin 750 mg po q24h (if severe beta-lactam allergy)

              B. Patients With Risk Factors for Pseudomonas aeruginosa*

              • Risk factors include the following:
                • Severe illness (hypotension, hypoxia requiring intubation, HAP requiring transfer to ICU)
                • Known colonization or recent infection with Pseudomonas aeruginosa
                • Recent (within past 2 weeks) or current ICU exposure
                • Previous antibiotic exposure during current hospitalization
                • Prolonged hospitalization ( ≥ 2 weeks)
              • First-line empiric therapy:
                • Piperacillin-tazobactam 4.5 g IV q6h
              • Second-line empiric therapy: meropenem 500 mg IV q6h (instead of piperacillin-tazobactam) in the following circumstances:
                • Severe beta-lactam allergy
                • Known ESBL colonization
                • Prior isolation of a piperacillin-tazobactam resistant Pseudomonas aeruginosa

              *Add coverage for MRSA with vancomycin only if the patient is known to be colonized with MRSA

              Usual Duration of Therapy: 7 days

              References

              1. Kalil et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis.2016; 63(5):e61-e111
              2. Rotstein et al. Clinical practice guidelines for hospital-acquired pneumonia and ventilator-associated pneumonia in adults Can J Infect Dis Med Microbiol. 2008;1 9(1): 19–53.
              3. Daneman et al. Duration of hospital admission and the need for empirical antipseudomonal therapy. J Clin Microbiol. 2012; 50(8):2695-701.
              4. Ewig et al. Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Incidence, risk factors, and association with ventilator-associated pneumonia. Am J Respir Crit Care Med 1999;159:188–98.

              Leroy et al. Hospital-acquired pneumonia: microbiological data and potential adequacy of antimicrobial regimens. Eur Respir J 2002; 20:432–9.


              Last updated: April 24, 2017

              Ventilator-associated pneumonia (VAP)

              Ventilator-associated pneumonia (VAP) is defined as pneumonia arising 48 hours or greater after mechanical ventilation. For patients with pneumonia who are ventilated <48 hours of their diagnosis, see the HAP guidelines if transferred from the ward or the CAP guidelines if admitted from community.

              The following guidelines are intended for the empiric management of VAP in immunocompetent adults. Empiric therapy should be based on the patient’s recent microbiologic history and should be tailored once culture and sensitivity results or other diagnostic information becomes available.

              Usual organisms:

              • Staphylococcus aureus
              • Streptococcus pneumoniae
              • Aerobic Gram negative bacilli (e.g. Pseudomonas aeruginosa, Klebsiella, Enterobacter, Serratia, E. coli, Haemophilus influenzae)

              Empiric Treatment:

              Without septic shock
              • piperacillin-tazobactam 4.5 g IV q6h (Piperacillin-tazobactam alone will cover >80% of ICU respiratory pathogens) *

              Alternative if severe beta-lactam allergy:

              • meropenem 500mg IV Q6h
              With septic shock

              Select one of following options to optimize empiric coverage:

              • piperacillin-tazobactam 4.5 g IV q6h +
                ciprofloxacin 400 mg IV Q8h*
              • ceftazidime 2 g IV Q8h +
                cloxacillin 2 g IV Q4h +
                ciprofloxacin 400 mg IV Q8h*

              * add vancomycin if the patient is known to be colonized with MRSA (NOTE: substitute for cloxacillin if this empiric therapy is being used).

              Usual duration of therapy

              Rapid improvement or minimal change in ventilator settings (e.g. daily minimum positive end-expiratory pressure (PEEP) of ≤5 cm H2O and daily minimum fraction of inspired oxygen (FiO2) of ≤40% on the day antibiotics were started and the following 2 calendar days):

              • Stop within 1-3 days

              VAP confirmed:

              • Target therapy based on Endotracheal Tube Aspirate or Bronchoalveolar Lavage (when available)
              • Complete 7 days of total therapy

              References

              1. Kalil et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis.2016; 63(5):e61-e111
              2. Rotstein et al. Clinical practice guidelines for hospital-acquired pneumonia and ventilator-associated pneumonia in adults Can J Infect Dis Med Microbiol 2008;1 9(1): 19–53.
              3. Daneman et al. Duration of hospital admission and the need for empirical antipseudomonal therapy. J Clin Microbiol 2012; 50(8):2695-701.
              4. Ewig et al. Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Incidence, risk factors, and association with ventilator-associated pneumonia. Am J Respir Crit Care Med 1999;159:188–98.
              5. Klompas M et al. Ultra-Short-Course Antibiotics for Patients With Suspected Ventilator-Associated Pneumonia but Minimal and Stable Ventilator Settings. Clin Infect Dis 2017; 64: 870-76.
              6. Singh N et al. Short-course Empiric Antibiotic Therapy for Patients with Pulmonary Infiltrates in the Intensive Care Unit: A Proposed Solution for Indiscriminate Antibiotic Prescription. Am J Respir Crit Care Med 2000; 162: 511-15.

              Last updated: April 18, 2018

              Skin and soft tissue infection

              Guidelines for Empiric Treatment

              A. Non-suppurative cellulitis or erysipelas

              • Usually caused by β-hemolytic streptococci (Groups A & B) or by S. aureus

              • First-line empiric therapy:
                • Cefazolin 1-2 g IV q8H

              • Second-line empiric therapy (if allergic or intolerant to above):
                • Vancomycin 1 g IV Q12H

              • Stepdown to oral therapy when improving:
                • Cephalexin 500 mg PO QID
                  OR
                  Clindamycin 300-450 mg PO QID (in the presence of significant penicillin allergy)
              • Usual duration of therapy is 7 days

              B. Suppurative Cellulitis

              • Usually caused by S. aureus, including MRSA
              • Consider an Infectious Diseases consult for cases of suppurative cellulitis
              • If abscess is present, consider large bore (16-18G) needle aspiration for both drainage and microbiologic diagnosis (send for culture)
              • When abscess is present, incision and drainage is more important than antimicrobial treatment
              • First line empiric therapy: (to be modified according to culture results)
                • Co-trimoxazole (TMP/SMX) 10 mg/kg/day TMP component PO in divided doses (see weight-based dosing table below)
                Body weight (KG) Dosage
                40-49 2 SS (single-strength) tabs Q8H
                50-64 2 ss tabs Q6H
                65-74 3 ss tabs Q8H
                75-99 3 ss tabs Q6H
                100-129 4 ss tabs Q6H

                OR

                • Doxycycline 100 mg PO BID

                OR

                • Vancomycin 1g IV Q12H (recommended as empiric therapy in patients with suppurative cellulitis who are systemically unwell)

                C. Skin and Soft Tissue Infections in Patients with Diabetes

                • Empiric therapy depends on clinical syndrome and severity (see Table 1 below)
                • Patients with severe infections should be referred to Infectious Diseases

                Table 1: Skin and Soft Tissue Infections in Patients with Diabetes

                Clinical Syndrome Usual Etiology Empiric First-line Therapy

                Alternatives
                (for significant beta-lactam allergy)

                Typical Duration of Therapy
                Cellulitis +/- non-suppurative ulcer

                β-hemolytic streptococci,
                S. aureus

                Cefazolin 1-2 g IV Q8H

                OR

                Cephalexin 500mg PO QID

                Vancomycin 1 g IV Q12H 7 days

                Suppurative ulcer without contiguous osteomyelitis

                S. aureus* +/- β-hemolytic streptococci

                *currently, 20-25% are MRSA

                Incision and drainage* of abscess

                AND

                Cefazolin 1-2 g IV Q8H

                OR

                Co-trimoxazole (TMP/SMX) 10 mg/kg/day TMP component PO in divided doses (see dosing table)

                OR

                Doxycycline 100 mg PO BID

                *may be sufficient in the absence of systemic symptoms

                Vancomycin 1 g IV Q12H

                OR

                Co-trimoxazole (TMP/SMX) 10 mg/kg/day TMP component PO in divided doses (see dosing table)

                OR

                Doxycycline 100 mg PO BID

                7 -14 days
                Ulcer with evidence of necrosis, tissue liquefaction, extension to bone and/or sepsis

                Mixed aerobic Gram-positive cocci, including enterococci, Enterobacteriaceae,
                non-fermentative Gram-negative rods (e.g. Pseudomonas), and obligate anaerobes

                Debridement +/- bone biopsy for bacterial culture for ulcers that probe to bone

                AND

                Ceftriaxone 2g IV Q12-24H plus Metronidazole 500mg PO BID

                OR

                Piperacillin-tazobactam 4.5 g IV Q6H

                Vancomycin 1 g IV Q12H plus Ciprofloxacin 750 mg PO BID plus Metronidazole 500 mg PO BID

                OR

                Moxifloxacin 400mg PO Q24H

                6 weeks

                In patients with known colonization with ESBL-producing Gram negative rods or MRSA, alternate antimicrobial therapy should be considered in consultation with the Infectious Diseases service.

                D. Necrotizing Skin and Soft Tissue Infection

                • May be caused by Group A streptococci or mixed aerobes/anaerobes or other rare etiologies

                • Urgent Infectious Diseases and Surgical consultation is strongly suggested in all suspected cases
                • First-line empiric therapy:
                  • Piperacillin-tazobactam 4.5 g IV Q6H plus Clindamycin 900 mg IV Q8H

                • Consider intravenous immune globulin (IVIg) for patients with necrotizing fasciitis and streptococcal toxic shock syndrome in consultation with Infectious Diseases (administered at a dose of 1 g/kg/day on day 1, then 0.5 g/kg/day on days 2 & 3)
                  • Detailed information on IVIg is available on Sunnynet (search using keyword “IVIg”)
                  • IVIg is prepared and issued by the Blood Bank (requisition required)

                References

                1. Lipsky BA et al, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012;54:e132-73.

                Last updated: June 6, 2022

                Spontaneous bacterial peritonitis (SBP)

                Spontaneous bacterial peritonitis (SBP) is an acute bacterial infection of ascitic fluid1.

                The following guidelines are intended for the empiric management of SBP. Therapy should be tailored once culture and sensitivity results or other diagnostic information becomes available.

                USUAL ORGANISMS

                • Almost all SBP is monomicrobial; if polymicrobial consider intra-abdominal source (secondary peritonitis)
                • Gram negative organisms, particularly Enterobacteriaceae, make up the vast majority of SBP infections in community acquired infections (E. coli is most common)
                • May also be Streptococcus, Enterococcus spp., or S. aureus

                DIAGNOSING SBP

                • All patients presenting with ascites should receive a diagnostic paracentesis
                • SBP is defined as 250 polymorphonuclear (PMN) leukocyte cells/mm3 with or without a positive culture
                • Variants of SBP1,2:
                  • Culture-positive SBP: PMNs ≥ 250 cells/mm3 with positive culture
                  • Culture-negative SBP: PMNs ≥ 250 cells/mm3 with negative culture
                  • Monomicrobial bacterascites: PMNs ≤ 250 cells/mm3 with positive culture

                GUIDELINES FOR EMPIRIC TREATMENT

                • Preferred treatment: Ceftriaxone 1g IV q24h (This dose is extrapolated from treatment guidelines for intra-abdominal infection and secondary peritonitis).
                • Alternative if severe non-IgE mediated reaction (e.g., Steven-Johnson Syndrome) or anaphylaxis/urticaria to ceftriaxone: Ciprofloxacin 500 mg PO BID or 400 mg IV BID
                • Duration of Therapy: 5 days3
                • Options for Oral Stepdown4,5,6:
                  • Based on culture susceptibilities, or
                  • If culture negative, ciprofloxacin 500 mg PO BID or amoxicillin-clavulanic acid 875-125 mg PO BID

                GUIDELINES FOR PRE-EMPTIVE TREATMENT OF SBP IN CIRRHOTIC PATIENTS WITH UPPER GASTROINTESTINAL BLEED (UGIB)7

                • Peritoneal fluid analysis is not required. These patients should receive pre-emptive treatment for SBP.
                • In the case of UGIB in patients with known ascites, preferred pre-emptive treatment: ceftriaxone 1 g IV q24h for 5 days

                REFERENCES

                1. Runyon BA. Management of Adult Patients with Ascites Due to Cirrhosis: Update 2012. AASLD 2012.
                2. Dever JB, Sheikh MY. Review article: spontaneous bacterial peritonitis – bacteriology, diagnosis, treatment, risk factors and prevention. Aliment Pharmacol Ther 2015; 41: 1116 – 1131.
                3. Runyon BA. Short-course versus long-course antibiotic treatment of spontaneous bacterial peritonitis. A randomized controlled study of 100 patients. Gastroenterology 1991; 100(6): 1737-42.
                4. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. European Association for the Study of the Liver. Journal of Hepatology 2010; 53: 397 – 417.
                5. Ricart E et al. Amoxicillin-clavulanic acid versus cefotaxime in the therapy of bacterial infections in cirrhotic patients. Journal of Hepatology 2000; 32(4): 596 - 602.
                6. Angeli P. Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost. Aliment Pharmacol Ther 2006; 23: 75 – 84.
                7. Moon AM et al. Use of Antibiotics Among Patients With Cirrhosis and Upper Gastrointestinal Bleeding Is Associated With Reduced Mortality. Clinical Gastroenterology and Hepatology 2016; 14(11). doi:10.1016/j.cgh.2016.05.040.

                Last updated: May 25, 2021

                Urinary tract infection

                • Usual organisms: E.coli (>80%); others include K. pneumoniae, P. mirabilis, Enterococcus spp, and S. saprophyticus in women of child-bearing age

                • The presence of a positive urine culture in a patient lacking acute localizing urinary symptoms (e.g. dysuria, urgency, frequency, suprapubic pain) represents asymptomatic bacteriuria, a condition that does NOT require antimicrobial therapy except in the following two patient populations:
                  • during pregnancy
                  • prior to urologicsurgery in which mucosal bleeding is expected

                • Delirium without fever or lower urinary tract symptoms is NOT considered a symptom of UTI among non-catheterized patients

                A. Empiric Therapy for Outpatients

                1. Acute Uncomplicated Cystitis (in the presence of a structurally normal genitourinary tract):

                • Non-pregnant women:
                  • Macrobid 100 mg PO BID or Nitrofurantoin 50 mg PO QID (for enteral feeding or crushing) when CrCl > 40 mL/min x 5 days
                    OR
                  • Co-trimoxazole (TMP/SMX) 1 DS tab PO BID x 3 day

                • Pregnant women:
                  • Amoxicillin-clavulanic acid 500 mg PO TID or 875 mg PO BID x 7 days (should be avoided in women at risk of preterm delivery due to increased risk of neonatal necrotising enterocolitis)
                    OR
                  • Macrobid 100 mg PO BID or Nitrofurantoin 50 mg PO QID (for enteral feeding or crushing) x 7 days (avoid beyond 36 weeks gestation and women at risk of preterm delivery)
                    OR
                  • Co-trimoxazole (TMP/SMX) 1 DS tab PO BID x 7 days (avoid in 1st trimester, at term and women at risk of preterm delivery)

                2. Acute Cystitis in Men*

                • Co-trimoxazole (TMP/SMX) 1 DS tab PO BID x 7 days
                  OR
                • Ciprofloxacin 500 mg PO BID x 7 days
                  OR
                • Macrobid 100 mg PO BID or Nitrofurantoin 50 mg PO QID (for enteral feeding or crushing) when CrCl > 40 mL/min x 7 days

                *If prostatic involvement, nitrofurantoin should NOT be used and a longer course of therapy is required

                3. Acute Uncomplicated Pyelonephritis

                • Obtain urine culture to confirm susceptibility
                • First-line empiric therapy:
                  • Ciprofloxacin 500 mg PO BID x 7 days
                  • Co-trimoxazole (TMP/SMX) 1 DS tab PO BID x 7 days

                B. Empiric Therapy for Patients who require Inpatient Management

                • Obtain urine culture to confirm susceptibility

                • First-line empiric therapy*:
                  • Ceftriaxone 1g IV Q24H +/- Ampicillin 2 g IV Q6H (enterococcal coverage should be considered for pyelonephritis in men, presence of catheter or in hemodyamic instability)

                • Second-line empiric therapy* (if allergic or intolerant to the above):
                  • Gentamicin 7 mg/kg IV Q24H
                    OR
                  • Ciprofloxacin 500 mg PO BID
                • Step down to appropriate oral antibiotics when patient is afebrile and hemodynamically stable, based on culture and susceptibility results

                • Usual duration of therapy is 7 days for uncomplicated pyelonephritis; complicated infections (e.g. abnormal genitourinary tract) require 10-14 days of therapy and occasionally longer, in consultation with Urology and Infectious Diseases

                *Suggest coverage for extended-spectrum beta-lactamase (ESBL) producing organisms in the following circumstances:

                • Known ESBL colonization
                • Previous urine culture of ESBL-producing organism within previous 6 months
                • Septic shock

                • First-line empiric therapy for suspected ESBL:
                  • Ertapenem 1 g IV Q24H
                Last updated: March 10, 2023

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