Antimicrobial Stewardship Program

Community-Acquired Meningitis

Background

• Meningitis refers to inflammation of the meninges.
• Bacterial meningitis is a medical emergency.
• Intravenous empiric antimicrobials should be initiated as soon as possible and should not be delayed while investigations are pending.
• Infectious Disease consult is recommended.

Empiric Therapy

• Ceftriaxone 2 g IV q12h PLUS
• Vancomycin 25 mg/kg IV once, followed by 15 mg/kg IV q12h PLUS
• Acyclovir 10 mg/kg IV q8h (until HSV encephalitis has been ruled out) PLUS
• Dexamethasone 10 mg IV q6h for 4 days* (start with or up to 4 h after the first dose of antibiotics)
• ADD Ampicillin 2 g IV q4h IF ≥ 50 years old, pregnant, or immunocompromised
  *Use of adjunctive dexamethasone has been associated with decreased mortality and neurologic sequelae for S. pneumoniae → continue dexamethasone for 4 days.
• Unclear benefit when other organisms are isolated → suggest discontinuing dexamethasone in these cases

Alternative for Severe Systemic/Cutaneous Adverse Reaction to Beta-lactams

• Moxifloxacin 400 mg IV q24h OR levofloxacin 750 mg IV q24h in place of ceftriaxone
• Sulfamethoxazole-trimethoprim 5 mg/kg (based on trimethoprim component) IV q6h in place of ampicillin

Targeted Therapy

Clinical Pearls

• Consider repeat lumbar puncture for patients failing to improve after 48 h of appropriate therapy.
• Chemoprophylaxis is recommended for close contacts, regardless of immunization status, in N. meningitidis and H. influenzae Type B meningitis. Both diseases are reportable to local public health in Ontario. Local public health will help coordinate recommendations for the chemoprophylaxis of community close contacts.

References:

1. 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;347(20):1549-1556. doi:10.1056/NEJMoa021334
2. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267-1284. doi:10.1086/425368
3. van de Beek D, Farrar JJ, de Gans J, et al. Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurol. 2010;9(3):254-263. doi:10.1016/S1474-4422(10)70023-5
4. van Ettekoven CN, van de Beek D, Brouwer MC. Update on community-acquired bacterial meningitis: guidance and challenges. Clin Microbiol Infect. 2017;23(9):601-606. doi:10.1016/j.cmi.2017.04.019

Last Revised: Jun/24/2025

Approvals:

• UHN Antimicrobial Subcommittee: Jul/02/2025
• UHN P&T: Jul/07/2025

Community-Acquired Pneumonia (CAP)

Background

• Pneumonia is a heterogeneous infection caused by viruses, bacteria, and occasionally fungi, although the pathogen is unknown in the majority of clinical cases.
• Mortality risk can be assessed using the CRB-65* score, which helps define management location and choice of antimicrobial.
• Consider an Infectious Disease consult in patients with no improvement or worsening symptoms after 3 days of therapy.

Empiric Therapy

*CRB-65 score: confusion (1 point), respiratory rate ≥ 30 breaths/min (1 point), systolic blood pressure < 90 mmHg (1 point), age ≥ 65 (1 point)

Targeted Therapy

• Preference is given to beta-lactam oral therapy whenever possible based on hemodynamic stability, enteral access, pathogen, and susceptibility.
• Choice of therapy for Legionella pneumonia is controversial, but should be monotherapy with either azithromycin or a fluoroquinolone.

Duration

Common Pathogens

• Respiratory viruses: influenza, parainfluenza, adenovirus, coronavirus, human metapneumovirus
• Streptococcus pneumoniae (most common bacterial cause)
• Haemophilus influenzae
• Staphylococcus aureus
• Mycoplasma pneumoniae
• Chlamydia pneumoniae

Clinical Pearls

• Reassess choice of duration daily using patient criteria above.
• In the absence of contraindications, treatment with PO/enteral therapy is appropriate.
• Consider duration of outpatient, emergency department and inpatient antimicrobial use when determining total treatment durations as the majority of patients receive more than necessary.
• Cough, fatigue and chest x-ray changes may take days to weeks to improve and do not require ongoing antimicrobial therapy.
• Chlamydia pneumoniae and Mycoplasma pneumoniae (non-Legionella "atypicals") are unlikely causes of CAP in adults requiring hospitalization.
• Early bronchoscopy should be considered in immunocompromised patients if patients fail to improve at 72 h.

This guidance differs from the 2019 IDSA CAP guideline:

Preference is given to management of common pathogens in patients hospitalized with CAP recognizing that Streptococcus pneumoniae is the core bacterial pathogen and that susceptibility with high-dose amoxicillin alone remains high (> 95%). In the otherwise healthy patient without structural lung disease, smoking history or immunocompromise, other pathogens are less likely and use of agents such as amoxicillin-clavulanic acid and cephalosporins may result in more adverse effects than clinical benefit.

References:

1. 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;200(7):e45-e67. doi:10.1164/rccm.201908-1581
2. Dinh A, Ropers J, Duran C, et al. Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial [published correction appears in Lancet. 2021 Jun 5;397(10290):2150. doi: 10.1016/S0140-6736(21)01157-0]. Lancet. 2021;397(10280):1195-1203. doi:10.1016/S0140-6736(21)00313-5
3. Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373(5):415–27
4. Shoar S, Musher DM. Etiology of community-acquired pneumonia in adults: a systematic review. Pneumonia (Nathan). 2020;12:11. Published 2020 Oct 5. doi:10.1186/s41479-020-00074-3
5. Gupta AB, Flanders SA, Petty LA, et al. Inappropriate Diagnosis of Pneumonia Among Hospitalized Adults. JAMA Intern Med. 2024;184(5):548-556. doi:10.1001/jamainternmed.2024.0077
6. Dyer AP, Dodds Ashley E, Anderson DJ, et al. Total duration of antimicrobial therapy resulting from inpatient hospitalization. Infect Control Hosp Epidemiol. 2019;40(8):847-854. doi:10.1017/ice.2019.118

Last Revised: Jun/24/2025

Approvals:

• UHN Antimicrobial Subcommittee: Jul/02/2025
• UHN P&T: Jul/07/2025

Hospital-Acquired Pneumonia (HAP)

Background

• HAP is commonly defined as pneumonia that develops ≥ 48 h after hospital admission and is NOT associated with mechanical ventilation.
• There is minimal literature exploring this syndrome, and as such, the causative pathogens are poorly understood.

Empiric Therapy

• For patients who are early in their admission, and who are deemed to be at low risk for drug-resistant pathogens, it is reasonable to select empiric therapy that will cover pathogens similar to those seen in community-acquired pneumonia (see section above). Though atypical coverage is generally not required.
• For patients who have had a prolonged hospital stay, particularly those who are bedbound and lying supine for extended periods of time, it is reasonable to select empiric therapy that will cover pathogens similar to those seen in ventilator-associated pneumonia (see section below).

Clinical Pearls

• Antibiotics are not indicated for aspiration, unless a resulting pneumonia is suspected. It is expected to take 24-48 h for pneumonia to develop, thus early respiratory decompensation or imaging findings do not necessarily indicate pneumonia and may instead represent aspiration pneumonitis.
  • If an aspiration pneumonia is deemed likely, this can be treated similarly to other cases of HAP and does not require extended anaerobic coverage.
• Patients with suspected HAP should be screened for viral infections using a multiplex PCR.
• If a causative pathogen is identified, therapy should be tailored to target the pathogen.
• In the absence of contraindications, treatment with PO/enteral therapy is appropriate.
• Candida spp. are very rarely a cause of pneumonia. Isolation of Candida from sputum or BAL cultures is mostly consistent with colonization, rather than true infection.
  • This is distinct from empyema, where Candida isolated from pleural fluid cultures can be pathogenic.

References:

1. Kalil AC, Metersky ML, Klompas M, 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. Clinical Infectious Diseases. 2016; 63(5): e61-e111
2. Torres A, Niederman MS, Chastre J, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J. 2017;50(3):1700582. Published 2017 Sep 10. doi:10.1183/13993003.00582-2017
3. Dragan V, Wei Y, Elligsen M, Kiss A, Walker SAN, Leis JA. Prophylactic Antimicrobial Therapy for Acute Aspiration Pneumonitis. Clin Infect Dis. 2018;67(4):513-518. doi:10.1093/cid/ciy120

Last Revised: Jan/6/2025

Approvals:

• UHN Antimicrobial Subcommittee: Jul/02/2025
• UHN P&T: Jul/07/2025

Ventilator-Associated Pneumonia (VAP)

Background

• VAP is defined as pneumonia that develops > 48 h after endotracheal intubation.

Empiric Therapy

• Piperacillin-tazobactam 4.5 g IV q6h for 7 days*ⱡ
• Patients who meet any of the following criteria: Meropenem 1 g IV q8h for 7 days*ⱡ
• Septic shock
• Growth of ESBL OR ampC producing organism in the past year
• Growth of Pseudomonas aeruginosa resistant to piperacillin-tazobactam in the past year

Alternative for Non-Severe Penicillin Allergy

• Meropenem 1 g IV q8h for 7 days*ⱡ

Alternative for Severe Systemic/Cutaneous Adverse Reaction to Beta-lactams

• Levofloxacin 750 mg PO/IV q24h for 7 days*ⱡ

* In patients who are known to be colonized with MRSA or who have grown MRSA in a prior respiratory tract sample, the addition of vancomycin is recommended until culture and sensitivity results are known.

ⱡ In patients who are known to be colonized with MDR gram-negative organisms or who are in septic shock as a result of VAP, consider the addition of a second agent from a different class (i.e. ciprofloxacin OR levofloxacin) until culture and sensitivity results are known.

Common Pathogens

• Staphylococcus aureus
• Pseudomonas aeruginosa
• Enterobacterales (Klebsiella spp., Enterobacter spp., Serratia spp., etc)

Clinical Pearls

• The goal of antibiotic therapy in VAP should be clinical cure, rather than microbiological cure. Cultures may remain positive, despite clinical improvement, as a result of lung colonization.
• Antibiotic treatment is not routinely recommended in the absence of new radiographic infiltrates (sometimes referred to as 'ventilator-associated tracheobronchitis').
• Candida spp. are very rarely a cause of pneumonia. Isolation of Candida from the respiratory tract is most often consistent with colonization, rather than infection.
  • This is distinct from empyema, where Candida isolated from pleural fluid cultures can be pathogenic.
• Aminoglycosides are not recommended for the treatment of pneumonia when alternative agents are available, due to poor penetration into the epithelial lining fluid of the lung and risk of nephrotoxicity and ototoxicity.
• A negative MRSA respiratory swab within 7 days of diagnosis has a very high negative predictive value in respiratory infections.
• There is conflicting data to support the use of inhaled antibiotics for the treatment of VAP.
  • Monotherapy with inhaled antibiotics is not recommended.
  • Adjunctive therapy with inhaled antibiotics is not routinely recommended.

References:

1. Kalil AC, Metersky ML, Klompas M, 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. doi:10.1093/cid/ciw353
2. Torres A, Niederman MS, Chastre J, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J. 2017;50(3):1700582. Published 2017 Sep 10. doi:10.1183/13993003.00582-2017
3. Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588-2598. doi:10.1001/jama.290.19.2588

Last Revised: Jun/6/2025

Approvals:

• UHN Antimicrobial Subcommittee: Jul/02/2025
• UHN P&T: Jul/07/2025

• WPHC Guideline for Antimicrobial Use in HAP and VAP

C. difficile Infection (CDI)

Treatment

In addition to the severity criteria outlined below, severity should be based on clinical judgement.

For All Patients:

• Reassess and discontinue the following agents if possible:
  • Concurrent antibiotics
  • Proton pump inhibitors
  • Laxatives
  • Opioids
  • Antiperistaltic agents (i.e. loperamide)

Treatment of Initial Episode:

High Risk of Recurrence if:

• Age ≥ 65 AND ≥ 1 additional risk factor:
  • Immunosuppression (i.e. neutropenia, solid organ or stem cell transplantation, HIV with CD4 lymphocyte count less than 50x10⁶/L, systemic corticosteroids with equivalent of prednisone 20 mg daily)
  • Hospital-acquired CDI

^α Longer durations may be required for severe infection. This decision should be made in consultation with Infectious Disease

^β Solution is supplied by pharmacy as 5 g in 100 mL amber plastic or glass bottle (Final concentration of 500 mg per 10 mL). Each dose of 500 mg = 10 mL must be further diluted as instructed in the administration section. See UHN Nursing administration policy for intra colonic vancomycin

Treatment of Recurrent Episode:

• Recurrent episode at any time after resolution of treated initial episode
  • Epidemiological recurrence is defined as CDI within 8 weeks following the onset of a previous episode which resolved with treatment.
  • Clinically, if an episode recurs after more than 8 weeks, it should still be managed as recurrent.
• Consult Infectious Disease

^¥ Taper regimen i.e. 125 mg q6h for 10 to 14 days, q12h for 7 days, q24h for 7 days, and then every 2 to 3 days for 2 to 8 weeks

^α Longer durations may be required for severe infection. This decision should be made in consultation with Infectious Disease

^β Solution is supplied by pharmacy as 5 g in 100 mL amber plastic or glass bottle (Final concentration of 500 mg per 10 mL). Each dose of 500 mg = 10 mL must be further diluted as instructed in the administration section. See UHN Nursing administration policy for intra colonic vancomycin.

*Fidaxomicin Accessibility

• Inpatient access
  • Fidaxomicin is a high-cost, non-formulary drug. Please follow the drug approval process for high-cost, non-formulary drugs.
  • Consider an Infectious Disease consult (not required).
• Outpatient access
  • Infectious Disease consult not required for fidaxomicin if the patient meets Ontario Drug Benefit (ODB) criteria.
  • Patients who do not meet ODB criteria for fidaxomicin coverage or do not have private coverage may benefit from an Infectious Disease consult.

Therapeutic Considerations:

• Alternatives for Allergies
  • IgE-mediated hypersensitivity reactions to vancomycin are rare.
  • Cross-reactivity amongst macrolides and fidaxomicin has been reported.¹¹
  • Consider consulting Infectious Disease in setting of hypersensitivity reactions.
• Immunocompromised Host Considerations
  • Except for instances of febrile neutropenia, treatment of CDI in immunocompromised hosts is not automatically considered "severe."
  • Patients should be assessed on a case-by-case basis considering risk factors and disease severity. Consult Transplant or Oncology Infectious Disease.
• Additional Considerations
  • When a patient requires antimicrobials for a concurrent infection that extends beyond the treatment duration of C. difficile infection, there is limited evidence to guide the duration of C. difficile therapy. Variability in practice exists.
  • There is insufficient evidence to support routine antimicrobial prophylaxis for CDI for patients requiring systemic antibiotic treatment.⁴
  • Higher doses of oral vancomycin may result in systemic absorption. Associated toxicities should be considered in patients at higher risk of nephrotoxicity.

Monitoring Parameters

• Complete daily assessment (including assessment of response to treatment and abdominal exam), including input and outputs and stool frequency and consistency.
• Patient is failing to respond to therapy by the end of day 4* if any of the following:
  *for immunocompromised patients reassessment for response to treatment should be completed at the end of day 2
  • Frequency and volume of loose bowel movements unchanged
  • Fever greater than 38°C (by the end of day 2 for all patients)
  • White blood cell (WBC) count greater than 15x10⁹/L
  • Worsening symptoms/deteriorating at any point
• Reconsider diagnosis if rapid improvement of symptoms occurs within 24 h

Diagnostic Considerations

• Only patients with symptoms suggestive of active CDI should be tested
  • 3 or more unformed stools in 24 h, without another reasonable explanation (i.e. new laxative use)
• Nucleic Acid Amplification Test (PCR) detects the presence of gene encoding Clostridioides difficile toxin. It has high sensitivity and specificity but cannot distinguish between asymptomatic carriage and active toxin production.¹
  • It has a high negative predictive value (~99%), with positive predictive value performing more variably depending on prevalence¹
• There is no evidence to support test for cure by repeating C. difficile testing. Spores may remain for some time and consequently C. difficile test may remain positive 6-8 weeks or longer in some cases.

Frequently Asked Questions

• Clostridioides difficile infection (CDI) remains a major cause of healthcare-associated diarrhea in Canada, associated with significant morbidity and mortality^5,11
• 3–14% of people admitted to hospital are asymptomatically colonized in their gut; length of stay impacts this likelihood⁵
  • Patients colonized with toxigenic strains are at variable risk of progression to clinical CDI, and host factors may modulate the severity of presentation⁵
• Approximately 20–25% of patients with CDI experience a recurrent episode, which increases with subsequent episodes.^5,11

What is the basis for the recommendations in this guidance?

The majority of evidence evaluating CDI treatment exists in patients with initial episode of CDI. For patients with recurrence, the best available evidence is derived from subgroup meta-analysis of RCTs.^2,3,5,10 It should be noted that there is variability in severity definitions amongst trials. There are no data that demonstrate superiority of fidaxomicin or vancomycin over one another in fulminant CDI.⁴

In meta-analyses by the Infectious Diseases Society of America (IDSA) of RCTs evaluating vancomycin and fidaxomicin, no difference in all-cause mortality was found for any subset of patients.² Sustained cure at four weeks was significantly increased for patients with first episode based on four RCTs. Recurrent episodes were evaluated through subgroup analysis of a much smaller subset of patients within three RCTs, and sustained cure at four weeks was significantly increased. IDSA acknowledged the overall low certainty of evidence for patients with recurrent episodes, given the small number of events and small sample size of these subgroups, as well as risk of bias due to the unblinded design in the EXTEND trial.⁴ Availability of moderate quality evidence for fidaxomicin benefit decreases with each subsequent recurrence.⁸

Decreased recurrence rates were confirmed in a systematic review and meta-analysis of 3944 patients across 14 studies (including observational and RCTs).¹⁰ This systematic review included one additional RCT from 2020 evaluating the impact of combined therapy with bezlotoxumab and standard of care. This additional RCT individually did not demonstrate a significant risk reduction of recurrence events amongst the 46 patients included. A significant risk reduction for recurrence was found notably for initial episodes and first recurrences, but not for second and subsequent recurrences (small numbers included). A significant reduction was also noted for both non-severe and severe CDI subsets.¹⁰

Given that the fidaxomicin vs vancomycin trials have not demonstrated all-cause mortality difference, and the findings from a recent cost-effectiveness analysis demonstrating that the current Canadian cost for fidaxomicin use will not be offset through recurrence prevention^{10,11, 12,13}, in addition to limited data with ≥ 2 recurrences, a risk stratified approach for maximizing utility of a high cost resource is reasonable.

Why is metronidazole no longer suggested for all UHN patients with mild illness?

Given that the IDSA and European Society of Clinical Microbiology and Infectious Diseases are no longer recommending metronidazole as a first line option for treatment of any subset of CDI, the severity differentiation has become less relevant for their recommendations and as such, are stratified by episode frequency/recurrence as it relates to fidaxomicin and vancomycin literature.

A 2017 Cochrane review analyzing metronidazole vs. vancomycin demonstrated a small benefit of sustained clinical cure with vancomycin in patients with non-severe CDI, however acknowledge that there remains uncertainty if mildly ill patients require treatment given the inability to conduct placebo arm studies.⁸ We have therefore suggested metronidazole only in patients with mild infection who have known allergy to vancomycin.

How were the risk stratification criteria determined?

It has been found that 10–30% of patients with initial C. difficile infection will experience a recurrence, and prognostic risk factors for recurrence have been established.^2,3,5,7 This is in keeping with a recent meta-analysis of recent fidaxomicin and vancomycin RCTs, finding a recurrence rate of 22%.¹⁰ The 2021 ESCMID guideline acknowledges that when availability of fidaxomicin is limited, a risk stratified approach is reasonable if the clinician deems the patient at high risk of recurrence (proposing increased age and at least one additional risk factor as criteria).

We have therefore adopted this approach as a suggestion in the management algorithm to best utilize a high-cost resource for patients most likely to benefit from reduced recurrence rates based on evidence. Criteria to determine patients at high risk of recurrence were identified per a recent systematic review.⁷

References:

1. Deshpande et al., Diagnostic Accuracy of Real-time Polymerase Chain Reaction in Detection of Clostridium difficile in the Stool Samples of Patients With Suspected Clostridium difficile Infection: A Meta-Analysis, Clinical Infectious Diseases, Volume 53, Issue 7, 1 October 2011, Pages e81–e90.
2. McDonald C et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA), Clinical Infectious Diseases, Volume 66, Issue 7, 1 April 2018, Pages e1–e48,https://doi.org/10.1093/cid/cix1085.
3. Johnson S et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults, Clinical Infectious Diseases, Volume 73, Issue 5, 1 September 2021, Pages e1029–e1044,https://doi.org/10.1093/cid/ciab549
4. Kelly, C et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. The American Journal of Gastroenterology: June 2021.116:6;1124-114
5. Loo V et al. Association of Medical Microbiology and Infectious Disease Canada treatment practice guidelines for Clostridium difficile infection. Can J Infect Dis Med Microbiol. 2018.3(2);71-92.
6. Prehn J. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021; 27:1-21.
7. Van Rossen T et al. Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review. Clin Microbiol Infect. 2022; 28(3):321-331.
8. Nelson RL, SudaKJ, Evans CT. Antibiotic treatment for Clostridium difficile‐associated diarrhoea in adults. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD004610. DOI: 10.1002/14651858.CD004610.pub5. Accessed 21 November 2022.
9. Mikamo H et al. Toyoshima J, Kato K. Efficacy and safety of fidaxomicin for the treatment of Clostridioides(Clostridium) difficile infection in a randomized, double-blind, comparative Phase III study in Japan. J Infect Chemother. 2018 Sep;24(9):744-752. doi: 10.1016/j.jiac.2018.05.010. Epub2018 Jun 19. PMID: 29934056.
10. Guery B, et al. EXTEND Clinical Study Group. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis. 2018 Mar;18(3):296-307. doi: 10.1016/S1473-3099(17)30751-X. Epub2017 Dec 19. PMID: 29273269
11. Patel D, et al. Fidaxomicin to prevent recurrent Clostridioides difficile: what will it cost in the USA and Canada? JAC Antimicrob Resist. 2023 Jan 7;5(1):dlac138. doi: 10.1093/jacamr/dlac138. PMID: 36632358; PMCID: PMC9825808.
12. Peterson R, Nicolle L, Bayoumi A, et al. Fidaxomicin. Dificid—Optimer Pharmaceuticals Canada Inc Indication: Clostridium difficile infections in Adults [Internet] Ottawa: Canadian Agency for Drugs and Technologies in Health; 2012 (Common Drug Report) [cited 2017–05–27]. Available from: https:// www.cadth.ca/sites/default/files/cdr/complete/cdr_complete_Dificid_December_21_12.pdf

Intra-Abdominal Infection (IAI)

Background

• IAI encompasses several infectious processes including appendicitis, diverticulitis, peritonitis, cholecystitis, and cholangitis.
• Source control is a vital component of managing IAI. The efficacy of antimicrobial management alone, although often done in practice, is uncertain.

Definitions

Community-Acquired Infection: Not meeting criteria for healthcare-associated infection.

Healthcare-Associated Infection:

• Hospitalized for ≥ 48h before onset of infection
• Post-operative infections
• Received IV therapy, wound care, renal replacement therapy, chemotherapy or radiotherapy within the previous 30 days
• Residence in nursing home or long-term care facility within the previous 30 days

Uncomplicated infection: Contamination or inflammation that does not extend beyond the source organ. Does not include evidence of perforation or abscess.

Complicated infection: Infectious process extends beyond the source organ causing peritonitis. Can include evidence of perforation or abscess.

Mild-moderate severity: Not meeting criteria for high severity. Non-critically ill patients.

High severity: Critically ill patients, new organ failure, diffuse peritonitis, delay or inability to achieve adequate source control. May also include infections occurring in the following: elderly, extensive comorbidity, immunosuppressed.

Empiric Therapy

Community-Acquired IAI, Uncomplicated

*absence of hematological malignancy, solid organ transplant, HIV, immunosuppressant therapy

Community-Acquired IAI, Complicated

(i.e. perforated appendicitis, perforated diverticulitis)

Healthcare-Associated IAI

Biliary Tract Infections - Cholecystitis and Cholangitis

Common Pathogens

• Enterobacterales (i.e. Escherichia coli, Klebsiella pneumoniae)
• Anaerobes (i.e. Bacteroides fragilis)
  • Anaerobic pathogens are less common in biliary tract infections, unless biliary-enteric anastomosis is present
• Streptococcus spp.
• Additional organisms to consider in healthcare-associated infections:
  • Pseudomonas spp.
  • Enterococcus spp.
  • Multidrug-resistant Enterobacterales (i.e. ESBL, ampC-producing, CRE)
  • Candida spp.

Clinical Pearls

• In the absence of contraindications, treatment with PO/enteral therapy is appropriate.
• Where Enterococcus spp coverage is indicated, if the patient has known colonization or prior infection with vancomycin-resistant Enterococcus (VRE), consider empiric VRE coverage with daptomycin or linezolid.
• Patients with healthcare-associated infections may benefit from empiric antifungal coverage in the presence of risk factors (i.e. upper gastrointestinal source, recurrent bowel perforations) AND/OR if there is no clinical improvement on broad-spectrum antibiotics and incomplete source control.
  • Patients who have yeast identified on gram stain or culture should have antifungal therapy initiated.
• Cultures taken from chronic drains may indicate colonization of organisms rather than pathogenic organisms. Thoroughly evaluate the clinical significance of these cultures before adjusting antimicrobial therapy.

References:

1. Chabok A, Påhlman L, Hjern F, Haapaniemi S, Smedh K; AVOD Study Group. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012;99(4):532-539. doi:10.1002/bjs.8688
2. CODA Collaborative, Flum DR, Davidson GH, et al. A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis. N Engl J Med. 2020;383(20):1907-1919. doi:10.1056/NEJMoa2014320
3. Colling KP, Besshoff KE, Forrester JD, Kendrick D, Mercier P, Huston JM. Surgical Infection Society Guidelines for Antibiotic Use in Patients Undergoing Cholecystectomy for Gallbladder Disease. Surg Infect (Larchmt). 2022;23(4):339-350. doi:10.1089/sur.2021.207
4. de Wijkerslooth EML, Boerma EG, van Rossem CC, et al. 2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial. Lancet. 2023;401(10374):366-376. doi:10.1016/S0140-6736(22)02588-0
5. Gomi H, Solomkin JS, Schlossberg D, et al. Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci. 2018;25(1):3-16. doi:10.1002/jhbp.518
6. Huston JM, Barie PS, Dellinger EP, et al. The Surgical Infection Society Guidelines on the Management of Intra-Abdominal Infection: 2024 Update. Surg Infect (Larchmt). 2024;25(6):419-435. doi:10.1089/sur.2024.137
7. Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection. Surg Infect (Larchmt). 2017;18(1):1-76. doi:10.1089/sur.2016.261
8. Mora-López L, Ruiz-Edo N, Estrada-Ferrer O, et al. Efficacy and Safety of Nonantibiotic Outpatient Treatment in Mild Acute Diverticulitis (DINAMO-study): A Multicentre, Randomised, Open-label, Noninferiority Trial. Ann Surg. 2021;274(5):e435-e442. doi:10.1097/SLA.0000000000005031
9. Pisano M, Allievi N, Gurusamy K, et al. 2020 World Society of Emergency Surgery updated guidelines for the diagnosis and treatment of acute calculus cholecystitis. World J Emerg Surg. 2020;15(1):61. Published 2020 Nov 5. doi:10.1186/s13017-020-00336-x
10. Salminen P, Paajanen H, Rautio T, et al. Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial. JAMA. 2015;313(23):2340-2348. doi:10.1001/jama.2015.6154
11. Sartelli M, Barie P, Agnoletti V, et al. Intra-abdominal infections survival guide: a position statement by the Global Alliance For Infections In Surgery. World J Emerg Surg. 2024;19(1):22. Published 2024 Jun 8. doi:10.1186/s13017-024-00552-9
12. Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection [published correction appears in N Engl J Med. 2018 Feb 15;378(7):686. doi: 10.1056/NEJMx180006]. N Engl J Med. 2015;372(21):1996-2005. doi:10.1056/NEJMoa1411162
13. Simeonova M, Daneman N, Lam PW, Elligsen M. Addition of anaerobic coverage for treatment of biliary tract infections: a propensity score-matched cohort study. JAC Antimicrob Resist. 2023;5(1):dlac141. Published 2023 Jan 21. doi:10.1093/jacamr/dlac141
14. Sippola S, Haijanen J, Grönroos J, et al. Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis: The APPAC II Randomized Clinical Trial. JAMA. 2021;325(4):353-362. doi:10.1001/jama.2020.23525
15. Unlü C, de Korte N, Daniels L, et al. A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial). BMC Surg. 2010;10:23. Published 2010 Jul 20. doi:10.1186/1471-2482-10-23

Last revised: Jun/27/2025

Approvals:

• UHN Antimicrobial Subcommittee: Jul/02/2025
• UHN P&T: Jul/07/2025

Urinary Tract Infection (UTI)

Background

• The diagnosis of UTI should be primarily based on clinical signs and symptoms. While clinical symptoms may be integrated with microbiology findings, microbiology should not be the sole basis for diagnosis.
• Some signs and symptoms of UTI include:
  • Dysuria
  • Urinary urgency
  • Urinary frequency
  • Suprapubic pain or tenderness
  • Flank pain or tenderness
  • Perineal pain or painful prostate exam
  • Macroscopic haematuria
  • Urinary incontinence

Empiric Therapy

With rising rates of gram-negative resistance, consider patients' prior microbiology when selecting empiric therapy.

* Avoid using Nitrofurantoin when CrCl < 30 mL/min or in patients on renal replacement therapy due to concerns of decreased efficacy and increased risk of toxicity

UTI in Pregnancy

* Avoid during 1st and 3rd trimester; reasonable to use if no appropriate alternatives are available

Common Pathogens

• Enterobacterales: Escherichia coli (most likely), Klebsiella pneumoniae, Proteus mirabilis
• Enterococcus spp.
• Staphylococcus saprophyticus
• Less common: Staphylococcus aureus, Pseudomonas aeruginosa, Candida spp.

Clinical Pearls

• Routine urine culture is NOT recommended in the following scenarios in the absence of symptoms: cloudy/foul-smelling urine or isolated mental status change.
• De-escalate antibiotic to narrowest spectrum option based on urine culture result.
• In the absence of contraindications, treatment with PO/enteral therapy is appropriate.
• Therapy with appropriate empiric antibiotics should produce improvement within 48-72 h. If the patient does not improve, complications of acute pyelonephritis or an alternative diagnosis should be considered, and evaluation by imaging of urinary tract may be warranted.
• Source control is required in case of nephrolithiasis, perirenal, renal, or prostate abscess, and emphysematous UTI.
• In males with recurrent UTI, consider evaluating for prostatitis and the ability to empty bladder.
• For catheter-associated UTI:
  • Treat similarly to patients with systemic symptoms.
  • Replace or discontinue existing catheters prior to the collection of cultures and initiation of antimicrobial treatment.

Frequently Asked Questions

My patient has delirium and their urine culture came back positive. Can I safely withhold antibiotics?

Urinalysis and urine culture results can be misleading as both may be positive in non-infectious etiologies. Asymptomatic bacteriuria is common in older adults, particularly those residing in long-term care facilities. Virtually all patients with indwelling catheters will develop bacteriuria after one month of use due to biofilm formation on the surface of the catheter.

Current evidence does not support immediately administering antibiotics in non-catheterized patients with delirium and a positive urine culture who are afebrile, hemodynamically stable and have no urinary symptoms. Rather, a trial of rehydration over 24 hours and careful observation while assessing for alternative diagnoses are recommended (1, 2). Non-UTI causes of acute changes in mental status include, but are not limited to: medication side effects, metabolic disorders, electrolyte imbalance, untreated pain, and constipation.

However, systemic inflammatory response syndrome (SIRS) criteria have been shown to be sensitive in identifying bacteremia in all patients including elderly patients in particular when there are no localizing symptoms of infection (3). Bacteremic UTI should be suspected in patients presenting with sepsis by SIRS criteria and a positive urine culture with a known uropathogen.

What is the preferred treatment duration for catheter-associated UTI? When do I have to remove the catheter?

For catheter-associated UTI, 5-7 days of antibiotic treatment is likely sufficient for patients with rapid symptom resolution. For patients with a delayed response, regardless of whether they remain catheterized, 10-14 days can be considered (4, 5).

Most catheter-associated UTIs are preventable by reducing inappropriate insertion of catheters and shortening the duration of catheterization. In catheter-associated UTI, the catheter should be removed or replaced when feasible, before collecting urine culture and starting antibiotic therapy (6). If an indwelling catheter has been in place for more than two weeks at the onset of catheter-associated UTI and is still indicated, the catheter should be replaced to hasten resolution of symptoms and to reduce the risk of reinfection (4)

When should I consider empiric coverage of ESBL-producing organisms?

Patients with risk factors for infections caused by ESBL-producing organisms include:

• Prior infection or colonization with an ESBL-producing organism within the past 3 months
• Previous and/or prolonged hospital stay
• Previous and/or prolonged use of broad-spectrum beta-lactam antibiotics
• Travel to areas with high rates of resistance eg. southern Asia

The time interval between these exposures and UTI symptom onset is not well defined. The threshold for empiric coverage of ESBL-producing organisms depends on the severity of infection, with a lower threshold warranted for more severe disease. Resistance to third-generation cephalosporins among E. coli and K. pneumoniae isolates has remained relatively stable in Ontario between 2016-2021, with resistance rates hovering at 10% and 5-7%, respectively (12). At UHN and Sinai Health, that number varies between ~15-25% depending on the location and patient population (2020-2021 data for urine isolates).

References

1. Blondel-Hill E, Patrick D, Nott C, Abbass K, TY Lau T, German G. AMMI Canada position statement on asymptomatic bacteriuria. Official Journal of the Association of Medical Microbiology and Infectious Disease Canada. 2018;3(1):4.
2. Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, et al. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2019;68(10):1611-5.
3. Bai AD, Bonares MJ, Thrall S, Bell CM, Morris AM. Presence of urinary symptoms in bacteremic urinary tract infection: a retrospective cohort study of Escherichia coli bacteremia. BMC Infect Dis. 2020;20(1):781.
4. Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(5):625-63.
5. Darouiche RO, Al Mohajer M, Siddiq DM, Minard CG. Short versus long course of antibiotics for catheter-associated urinary tract infections in patients with spinal cord injury: a randomized controlled noninferiority trial. Arch Phys Med Rehabil. 2014;95(2):290-6.
6. Raz R, Schiller D, Nicolle LE. Chronic indwelling catheter replacement before antimicrobial therapy for symptomatic urinary tract infection. The Journal of urology. 2000;164(4):5.
7. Talan DA, Stamm WE, Hooton TM, et al. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial. JAMA : the journal of the American Medical Association 2000; 283(12): 1583-90.
8. 10.1136/bmj.38602.586343.55. Epub 2005 Sep 8. PMID: 16150741; PMCID: PMC1226247.
9. Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology 2008; 71(1): 17-22.
10. Klausner HA, Brown P, Peterson J, et al. A trial of levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400 mg and/or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis. Current medical research and opinion 2007; 23(11): 2637-45.
11. Stone ND, Ashraf MS, Calder J, Crnich CJ, Crossley K, Drinka PJ, et al. Surveillance Definitions of Infections in Long-Term Care Facilities: Revisiting the McGeer Criteria. Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America. 2012;33(10):965-77. Epub
12. van Nieuwkoop C, van der Starre WE, Stalenhoef JE, et al. Treatment duration of febrile urinary tract infection: a pragmatic randomized, double-blind, placebo-controlled non-inferiority trial in men and women. BMC Medicine. 2017; 15:70-8.
13. Drekonja DM, Trautner B, Amundson C, et al. Effect of 7 vs 14 Days of Antibiotic Therapy on Resolution of Symptoms Among Afebrile Men With Urinary Tract Infection: A Randomized Clinical Trial. JAMA 2021; 326(4):324-331.
14. Lee RA, Centor RM, Humphrey LL, Jokela JA, Andrews R, Qaseem A, Scientific Medical Policy Committee of the American College of Physicians. Akl EA, Bledsoe TA, Forciea MA, Haeme R, Kansagara DL, Marcucci M, Miller MC, Obley AJ. Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice From the American College of Physicians. Ann Intern Med. 2021 Jun;174(6):822-827
15. Lafaurie M, Chevret S, Fontaine JP, Mongiat-Artus P, de Lastours V, Escaut L, Jaureguiberry S, Bernard L, Bruyere F; PROSTASHORT Study Group. Antimicrobial for 7 or 14 Days for Febrile Urinary Tract Infection in Men: A Multicenter Noninferiority Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Clin Infect Dis. 2023 Jun 16;76(12):2154-2162. doi: 10.1093/cid/ciad070. PMID: 36785526.
16. Urinary Tract Infections in Pregnant Individuals | ACOG
17. Bilsen MP, Conroy SP, Schneeberger C, et al. A reference standard for urinary tract infection research: a multidisciplinary Delphi consensus study. Lancet Infect Dis. 2024;24(8):e513-e521. doi:10.1016/S1473-3099(23)00778-8
18. Nelson Z, Tarik Aslan A, Beahm NP, et al. Guidelines for the Prevention, Diagnosis, and Management of Urinary Tract Infections in Pediatrics and Adults: A WikiGuidelines Group Consensus Statement. JAMA Netw Open. 2024;7(11):e2444495. Published 2024 Nov 4. doi:10.1001/jamanetworkopen.2024.44495

Last Revised: Jun/30/2025

Approvals:

• UHN Antimicrobial Subcommittee: Jul/02/2025
• UHN P&T: Jul/07/2025

• WPHC Guideline for Antimicrobial Use in UTI

Syphilis

Treatment

• The recommended treatments are the same for pregnant patients and people with HIV
• An acute febrile reaction accompanied by headache, myalgia, rash and mild hypotension may occur within 24 h of starting therapy (Jarisch-Herxheimer reaction); this is a non-allergic inflammatory reaction
  • Usually resolves in 12-24 h; manage with NSAIDs or acetaminophen if needed
  • Pregnant patients should be told to contact their provider if symptoms occur since the reaction may precipitate uterine contractions, preterm labor or fetal distress in the 2^nd half of pregnancy
• All patients with syphilis should be tested for HIV

Penicillin Allergy

• Many people who report a penicillin allergy can safely receive penicillin
• If true penicillin allergy, consult Infectious Diseases

Testing and Treatment of Sexual Contacts

• The public health authority where the patient resides should be notified (Toronto Public Health STI Program at 416 338 2373)
• All partners who have had sexual contact with an index case of primary, secondary or early latent syphilis within 90 days should be presumptively treated for infectious syphilis (even if serology is negative)
• Partners who have had sexual contact with an index case of primary, secondary or early latent syphilis after 90 days should be treated based on clinical assessment and serology; if test results are not available, they should be presumptively treated for infectious syphilis

Follow-Up Recommendations

• Outpatients should be evaluated 2-3 days after treatment initiation; if there is no symptom improvement, further work-up is indicated and hospital admission for parenteral therapy may be required
• Patients should abstain from sexual intercourse until treatment is completed, symptoms have resolved and partners have been treated (see below)
• All patients diagnosed with PID should be tested for Neisseria gonorrhoeae, Chlamydia trachomatis, HIV and syphilis

Terminology

• Primary syphilis: New infection with Treponema pallidum; most commonly manifested as painless chancre and regional adenopathy
• Secondary syphilis: May follow untreated primary infection; manifests as systemic illness with spirochetemia (disseminated rash, condylomata lata, lymphadenopathy, alopecia, hepatitis, glomerulonephritis)
• Latent syphilis: Patient has no clinical signs or symptoms of syphilis but has serologic evidence of infection
  • Early latent syphilis: infection was acquired within 12 months
  • Late latent syphilis: infection was acquired greater than 12 months ago
  • Latent syphlis of unknown duration: latent syphilis infection without clear timing of acquisition
• Tertiary syphilis: Late syphilis (acquired > 12 months before diagnosis) with manifestations involving the cardiovascular system or gummatous syphilis
• Neurosyphilis: neurological manifestations that can occur at any stage of infection

References

1. Government of Canada. Section 5-10: Canadian Guidelines on Sexually Transmitted Infections – Management and treatment of specific infections: Syphilis. Updated Dec 2016. https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/syphilis.html
2. Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187.
3. Clement ME, Okeke NL, Hicks CB. Treatment of syphilis: a systematic review. JAMA. 2014;312(18):1905-17.

Gonorrhea

Treatment of Uncomplicated Anogenital & Pharyngeal Disease

Preferred Treatment

• Ceftriaxone 500 mg IM/IV once (1 g if weight ≥ 150 kg)
  • Ceftriaxone can be given IV in patients with established IV access
  • For IM injection only: dilute with 1.1 mL of 1% lidocaine to reduce pain

Alternative Treatment

All alternatives are less effective than ceftriaxone. In addition, cefixime use has been associated with accelerating population resistance to ceftriaxone.

There is reduced susceptibility among Neisseria gonorrhoeae isolates to azithromycin in Ontario (3.6-15% from 2016-2020).

• If cephalosporin allergy: Gentamicin 240 mg IM/IV (in 2 separate 3 mL injections of 40 mg/mL if given IM) PLUS azithromycin 2 g PO once
• If IM/IV administration contra-indicated (least preferred): Cefixime 800 mg PO once

Prefferred Treatment in Pregnancy

• Ceftriaxone 500 mg IM/IV once
  • Consult specialist if preferred treatment cannot be used

Follow-Up Recommendations

• A test of cure is recommended if:
  • First-line therapy is not used
  • Known or suspected pharyngeal infection
  • Pregnancy
  • Suspected treatment failure
• Culture a minimum of 3 days post-treatment is recommended; NAAT 2 weeks post-treatment is an alternative
• Re-screen all cases 3 months post-treatment

Testing and Treatment of Sexual Contacts

• All partners who have had sexual contact with the index case within 60 days should be notified, tested and empirically treated. In addition to patient counselling, your local health authority should be notified (Toronto Public Health STI Program at 416-338-2373). Expedited partner therapy may be considered for difficult to reach contacts.
• Testing at rectal and/or pharyngeal sites is recommended in MSM, people engaged in sex work, sexual contacts of a person with gonorrhea, or upon clinical assessment of risk and symptoms; NAAT is the preferred specimen type.

References

1. Government of Canada. Section 5-6: Canadian Guidelines on Sexually Transmitted Infections – Management and treatment of specific infections: Gonococcal Infections. 2010, updated 2016. https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/sexually-transmitted-infections/canadian-guidelines-sexually-transmitted-infections-34.html
2. Canada PHAC. National Surveillance of Antimicrobial Susceptibilities of Neisseria gonorrhoeae Annual Summary 2019. Ottawa; 2019.
3. Ontario Agency for Health Protection and Promotion (Public Health Ontario). Ontario Gonorrhea Testing and Treatment Guide. 2nd ed. Toronto, ON: Queen's Printer for Ontario; 2018.
4. Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187.
5. Barbee LA, St. Cyr SB. Management of Neisseria gonorrhoeae in the United States: Summary of Evidence From the Development of the 2020 Gonorrhea Treatment Recommendations and the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Treatment Guidelines. Clinical Infectious Diseases. 2022;74(Supplement_2):S95-S111.

Chlamydia

Treatment of Uncomplicated Anogenital & Pharyngeal Disease

Preferred Treatment

• Doxycycline 100 mg PO q12h for 7 days
• If lymphogranuloma venereum (LGV): Doxycycline 100 mg PO q12h for 21 days

Alternative Treatment

• Azithromycin 1 g PO once

Doxycycline is the preferred treatment due to higher microbiological cure rates in both males and females for rectal chlamydia. Concurrent rectal Chlamydia trachomatis infection is common and often asymptomatic, even without direct rectal contact and can spread to urogenital sites.

Treatment in Pregnancy

• Preferred: Azithromycin 1 g PO once
• Alternative: Amoxicillin 500 mg PO q8h for 7 days

Follow-Up Recommendations

• A test of cure is recommended if the patient is pregnant, there is suspected treatment failure or the course of antibiotics was incomplete
• NAAT at least 4 weeks post-treatment if test of cure indicated
  • Testing earlier than 4 weeks may lead to false-positive results due to remaining genetic material but no active infection
• Re-screen all cases 3 months post-treatment

Testing and Treatment of Sexual Contacts

• All partners who have had sexual contact with the index case within 60 days should be notified, tested and empirically treated. In addition to patient counselling, your local public health authority should be notified (Toronto Public Health STI Program at 416-338-2373). Expedited partner therapy may be considered for difficult to reach contacts.
• Testing at rectal and/or pharyngeal sites is recommended in MSM, people engaged in sex work, sexual contacts of a person with chlamydia, or upon clinical assessment of risk and symptoms; NAAT is the preferred specimen type.

References

1. Government of Canada. Section 5-2: Canadian Guidelines on Sexually Transmitted Infections – Management and treatment of specific infections: Chlamydia Infections. 2010, updated 2016. https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/chlamydia-lgv.html
2. Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187.
3. Páez-Canro C, Alzate JP, González LM, Rubio-Romero JA, Lethaby A, Gaitán HG. Antibiotics for treating urogenital Chlamydia trachomatis infection in men and non-pregnant women. The Cochrane database of systematic reviews. 2019;1(1):Cd010871.
4. Cluver C, Novikova N, Eriksson DO, Bengtsson K, Lingman GK. Interventions for treating genital Chlamydia trachomatis infection in pregnancy. The Cochrane database of systematic reviews. 2017;9(9):Cd010485.
5. Chen L-F, Wang T-C, Chen F-L, Hsu S-C, Hsu C-W, Bai C-H, et al. Efficacy of doxycycline versus azithromycin for the treatment of rectal chlamydia: a systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy. 2021;76(12):3103-10.

Pelvic Inflammatory Disease

Preferred Treatment

• Outpatient/emergency department:
  • Ceftriaxone 500 mg IM/IV once PLUS
  • Doxycycline 100 mg PO q12h for 14 days PLUS
  • Metronidazole 500 mg PO q12h for 14 days
• Inpatient:
  • Ceftriaxone 1 g IV q24h PLUS
  • Doxycycline 100 mg PO q12h PLUS
  • Metronidazole 500 mg IV/PO q12h
  • When clinically improved, transition to doxycycline 100 mg PO q12h PLUS metronidazole 500 mg PO q12h to complete 14 days

Alternative Treatment

• Consult Infectious Diseases if first-line outpatient regimen cannot be used
• Inpatient, if cephalosporin allergy: Clindamycin 900 mg IV q8h PLUS gentamicin 3-5 mg/kg IV q24h
  • When clinically improved, transition to clindamycin 450 mg PO q6h OR doxycycline 100 mg PO q12h PLUS metronidazole 500 mg PO q12h to complete 14 days

Pregnancy

• Consult Obstetrics: PID is uncommon during pregnancy and there is a large differential diagnosis for acute abdominal pain in pregnancy

Follow-Up Recommendations

• Outpatients should be evaluated 2-3 days after treatment initiation; if there is no symptom improvement, further work-up is indicated and hospital admission for parenteral therapy may be required
• Patients should abstain from sexual intercourse until treatment is completed, symptoms have resolved and partners have been treated (see below)
• All patients diagnosed with PID should be tested for Neisseria gonorrhoeae, Chlamydia trachomatis, HIV and syphilis

Testing and Treatment of Sexual Contacts

• All partners who have had sexual contact with an index case of PID within 60 days should be evaluated, tested and presumptively treated for chlamydia and gonorrhea
• If the last sexual contact was greater than 60 days from PID diagnosis/symptom onset, the most recent sexual partner should be evaluated, tested and presumptively treated for chlamydia and gonorrhea

References

1. Government of Canada. Section 4-4: Canadian Guidelines on Sexually Transmitted Infections – Management and treatment of specific syndromes – Pelvic Inflammatory Disease (PID). Updated 2016.
2. https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/sexually-transmitted-infections/canadian-guidelines-sexually-transmitted-infections-22.html
3. Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187.
4. Savaris RF, et al. Antibiotic therapy for pelvic inflammatory disease. Cochrane Database of Systematic Reviews 2020, Issue 8, Art . No. CD010285.
5. Wiesenfeld HC, Meyn LA, Darville T, Macio IS, Hillier SL. A Randomized Controlled Trial of Ceftriaxone and Doxycycline, With or Without Metronidazole, for the Treatment of Acute Pelvic Inflammatory Disease. Clinical Infectious Diseases. 2020;72(7):1181-9.

Skin and Soft Tissue Infection (SSTI)

This document covers cellulitis, erysipelas, skin abscess, furuncle, carbuncle and necrotizing fasciitis.

Background

Non-purulent – erysipelas, cellulitis

• Antibiotics indicated
  
• Surgical debridement indicated if: necrotizing infection, gangrene

Purulent – skin abscess, furuncle, carbuncle

• Incision and drainage required for treatment and usually antibiotics are not needed
• Antibiotics indicated if: systemic symptoms, immunocompromised, extensive surrounding cellulitis, multiple lesions, recurrent abscess

Non-Necrotizing SSTI

Empiric Therapy

^ⱡ See ODB formulary for criteria for use and coverage.

Duration

• 5 days
• It is reasonable to expect that patients receiving appropriate therapy may not show signs of improvement for up to 72 hours, and some may initially experience localized worsening.

Common Pathogens

• Non-purulent infection - Usually Streptococcus pyogenes (Group A Strep) or other Streptococcus spp.
• Purulent infection - Usually Staphylococcus aureus

Necrotizing Fasciitis

Necrotizing fasciitis is a subset of aggressive SSTI that causes muscle fascia and subcutaneous tissue necrosis. It is a medical emergency.

Empiric Therapy

Clinical Pearls

• Superficial skin swabs are generally not recommended, send purulent fluid for culture.
• Abscess without surrounding cellulitis may be cured with lancing (I&D: send C&S) alone and no antibiotics.
• S. pyogenes (GAS) resistance to clindamycin is rising. GAS remains 100% susceptible to penicillin.
• MRSA accounts for approximately 20% of S. aureus isolates in Canada (CARSS Surveillance data).
• Consider other pathogens if wound has these features:
  • Enterobacterales (chronic wounds, perineum/perirectal wounds)
  • Pseudomonas aeruginosa (chronic wounds, wet wounds, ecthyma gangrenosum)
  • Anaerobes (gangrene, necrotic wounds, bites, head & neck)
• If not improving or if immunocompromised consider Infectious Disease consult.
• Can change to PO therapy when clinically stable.
• Bilateral cellulitis is extremely rare, consider alternative diagnosis.
  • Non-infectious mimickers include: DVT, contact dermatitis, drug reaction, hematoma, insect bites, lymphedema, IV infiltration, vasculitis, and gout.

References:

1. Staphylococcus Aureus. Antimicrobial Resistance: Canadian Antimicrobial Resistance Surveillance System (CARSS). Published: Novemeber 24, 2023. Accessed: Aug 4, 2024. https://health-infobase.canada.ca/carss/amr/results.html?ind=14
2. Burnham, J.P., Kirby, J.P. & Kollef, M.H. Diagnosis and management of skin and soft tissue infections in the intensive care unit: a review. Intensive Care Med.2016;42:1899–1911.
3. Stevens DL, Bisno AL, Chambers HF, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10–e52.
4. Moran GJ, Krishnadasan A, Mower WR, et al. Effect of cephalexin plus trimethoprim-sulfamethoxazole vs cephalexin alone on clinical cure of uncomplicated cellulitis. JAMA 2017;317(20):2088.
5. Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med 2015; 372:1093–103.
6. Hepburn MJ, Dooley DP, Skidmore PJ, Ellis MW, Starnes WF, Hasewinkle WC. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med. 2004;164(15):1669-1674.
7. Morris AD. Cellulitis and erysipelas. BMJ Clin Evid. 2008;1708. Published 2008 Jan 2.
8. Sartelli M, Guirao X, Hardcastle TC, et al. 2018 WSES/SIS-E consensus conference: recommendations for the management of skin and soft-tissue infections. World J Emerg Surg. 2018;13:58.
9. Sartelli, M., Coccolini, F., Kluger, Y. et al. WSES/GAIS/WSIS/SIS-E/AAST global clinical pathways for patients with skin and soft tissue infections. World J Emerg Surg. 2022;17:3.
10. Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection [published correction appears in Ann Emerg Med. 2010 Nov;56(5):588]. Ann Emerg Med. 2010;56(3):283-287.
11. Karakonstantis S. Is coverage of S. aureus necessary in cellulitis/erysipelas? A literature review. Infection. 2020;48(2):183-191.
12. Clebak KT, Reedy-Cooper A, Partin MT, Davis CR. A guide to the Tx of cellulitis and other soft-tissue infections. J Fam Pract. 2021;70(5):214-219.
13. Rrapi R, Chand S, Kroshinsky D. Cellulitis: A Review of Pathogenesis, Diagnosis, and Management. Med Clin North Am. 2021;105(4):723-735.
14. Wallace HA, Perera TB. Necrotizing Fasciitis. [Updated 2023 Feb 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. https://www.ncbi.nlm.nih.gov/books/NBK430756/

Last Revised: Jun/27/2025

Approvals:

• UHN Antimicrobial Subcommittee: Jul/02/2025
• UHN P&T: Jul/07/2025