Antimicrobial Stewardship (AMS)

Resources to help you ensure the safe and effective use of antimicrobials in NSHA patients.

About

Introduction

The Nova Scotia Health Authority Antimicrobial Handbook is a collaboration of the Antimicrobial Stewardship Program and the Antimicrobial Subcommittee. We would like to thank all of those who have contributed to this project. By combining local epidemiology and resistance patterns, this project tailors guidelines from expert societies for our patient population. We hope the Handbook will be a guide for prescribers and healthcare workers throughout NSHA.

Terms & Conditions

The recommendations on this page and in the 2012 Handbook are evidence-informed and incorporate local expert opinion. Formal literature reviews were not performed. Multidisciplinary stakeholder feedback was sought for each topic. The topics on this page and the 2012 Handbook cannot replace clinical judgment and unique patient situations. Physicians and other healthcare workers must use their own discretion in applying this information to individual patient care.

Adult Community Acquired Pneumonia

  • Community acquired pneumonia (CAP):  acute infection acquired outside of hospital or within 48 hours of admission

Last revised March 2020

  • Viruses are common causative pathogens and frequently implicated in co-infections with bacteria.
  • The most common bacterial pathogen is Streptococcus pneumoniae.
    • Less common bacteria: Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Legionella pneumophila, Enterobacterales (Enterobacteriaceae), Mycoplasma pneumoniae

Last updated March 2020

  • Differential diagnoses: acute exacerbation of COPD, acute bronchitis, heart failure, and pulmonary embolism
  • Infiltrate on chest radiograph with supportive clinical findings:
    • Symptoms include new onset fever, cough, sputum production, dyspnea, tachypnea, pleuritic chest pain 
    • Physical findings consistent with signs of air space disease (e.g. crackles, bronchial breath sounds)
    • If no infiltrate on initial x-ray, patients should be reassessed within 48 to 72 hours if a high clinical suspicion of pneumonia remains
  • Risk stratify using clinical judgement or the CRB-65 score:
CRB-65: Patient Criteria Points
Confusion (either based on specific mental test OR new disorientation to person, place or time) 1
Respiratory rate > 30 breaths per minute 1
Hypotension (systolic < 90 mm Hg OR diastolic < 60 mm Hg) 1
Age > 65 years old 1

CRB-65 Score 30 Day Mortality Management Setting
0 points AND O2 sat > 92% (on room air) 2.4 % (low risk) Outpatient treatment
1 – 2 points 13.3 % (moderate risk) Consider admission to inpatient ward
3 – 4 points 34.3 % (high risk) Often requires an ICU admission

Last reviewed March 2020

  • This guideline does not apply to patients with cystic fibrosis, febrile neutropenia, structural lung disease, and others colonized with multidrug-resistant microorganisms.
  • Macrolides are not first line because of poor S. pneumoniae coverage
  • Consider testing for Legionella urinary antigen in severe CAP (requiring ICU admission) or if patient is associated with a local Legionella outbreak
  • Influenza testing: recommended for CAP requiring hospital admission during periods of high influenza activity
  • Sputum cultures if any one of:
    • ICU admission requiring intubation, starting empiric treatment for or recent infection with MRSA or resistant Gram-negatives (e.g. Pseudomonas), hospitalization and receipt of parenteral antibiotics in the last 90 days, or copious sputum production
    • Low quality results may be misleading as cultured bacteria often represent colonization 
  • Blood cultures if any one of:
    • Fever, ICU admission requiring intubation, starting empiric treatment for or recent infection with MRSA or resistant Gram-negatives (e.g. Pseudomonas), or hospitalization and receipt of parenteral antibiotics in the last 90 days
  • Empiric coverage of atypical bacteria (e.g. Legionella, Mycoplasma):
    • Outpatient setting: not recommended
    • Non-ICU hospitalization: benefit is unclear and there is risk of adverse effects, especially in patients with a predisposition for QTc prolongation from macrolides (i.e. azithromycin) and multiple adverse effects from fluoroquinolones (i.e. levofloxacin)
    • ICU patients:  coverage for Legionella is routinely recommended (see below)
  • Aspiration pneumonia
    • Antimicrobial prophylaxis at the time of aspiration is not beneficial. Provide supportive care and reassess in 48 hours for signs and symptoms of pneumonia
    • Routine addition of anaerobic coverage, such as metronidazole, is not recommended unless treating an empyema or lung abscess.

Last reviewed March 2020

*May require renal dose adjustments.

Note: amoxicillin/clavulanate unnecessarily broad for most community acquired pneumonia in previously healthy individuals.

  • Oseltamivir 75 mg PO BID x 5 days (dose adjust in renal dysfunction) recommended as empiric treatment in hospitalized patients with suspicion of influenza, regardless of timing of symptom onset.
    • Higher doses of oseltamivir such as 150 mg BID are not recommended

 

Last reviewed March 2020

Usual duration is 5 days, exceptions include:

  • The patient is not yet clinically stable: ongoing vital sign abnormalities including tachycardic, tachypnea, hypotension, high oxygen requirements, or persistent fever
  • Associated bloodstream infections
  • Duration in cases of S. aureus or in known resistant Gram negative bacteria is at least 7 days; ID consultation should be considered
  • Longer durations required for empyema and lung abscess

Last reviewed March 2020

  • Review IV antibiotics within 48 hours of treatment initiation and consider switching to PO antibiotics once patient is clinically improving (e.g. afebrile, hemodynamically stable, adequate PO intake).
    • CAP is often inappropriately treated with prolonged IV therapy and prolonged antibiotic courses.

Last reviewed March 2020

1. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015; 373;5: pp 415-427.

2. Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. Am J Respir Crit Care Med. 2019; Vol 200 (Iss 7): pp 809-821.

3. National Institute for Health and Care Excellence. Pneumonia (community-acquired): antimicrobial prescribing. NICE Guideline. 2019. www.nice.org.uk/guidance/ng138. Accessed September 18, 2019

4. Antibiotics Why and Why Not 2018 Dalhousie CPD Academic Detailing Service, November 2018. http://www.medicine.dal.ca/departments/core-units/cpd/programs/academic-detailing-service.html. Accessed August 12, 2019

5. Management of Community Acquired Pneumonia in Adults. SHS + UHN Antimicrobial Stewardship Program, 2018. https://www.antimicrobialstewardship.com/community-acquired-pneumonia. Accessed August 19, 2019.

Last reviewed March 2020

Asymptomatic Bacteriuria

  • Bacteria present in a urine culture without signs or symptoms of a urinary tract infection (UTI)
  • Many people, especially the elderly and those with indwelling urethral or suprapubic catheters, will have asymptomatic carriage of bacteria in the urinary tract
  • Antimicrobial treatment is not recommended (exceptions: pregnancy and patients scheduled to undergo urological procedures in which mucosal trauma is expected)

Last reviewed February 2019

  • Gram-negative bacilli (E. coli, Klebsiella spp., Proteus spp.)
  • Enterococcus spp.

Last reviewed February 2019

  • Absence of typical UTI symptoms: dysuria, increased frequency, urgency, suprapubic tenderness, costovertebral tenderness
  • Cognitive changes, hematuria, or fever alone are not sufficient to diagnose UTI
  • Isolated leukocytosis (in blood), positive leukocyte esterase and/or nitrites do not confirm that there is a UTI
  • Screening with urine culture is recommended only for:
    • Pregnancy: at first prenatal visit
    • Prior to invasive urological procedures
  • DO NOT perform culture for:
    • Malodorous and/or cloudy urine without UTI symptoms
    • Change/insertion of catheter, blocked catheter, or as a test of cure (unless in pregnancy)

Last reviewed February 2019

  • Prescribing antibiotics for asymptomatic bacteriuria does not improve outcomes and increases the patient’s risk of adverse drug reactions, C. difficile infection, and promotes development of colonization and/or infection with multidrug resistant bacteria
  • Supportive treatment should be considered, including correcting dehydration
  • Remove urinary catheter if possible

Last reviewed February 2019

  • Pregnancy: see IWK spectrum app section Women’s Health- Genito-urinary PregnancyAsymptomatic Bacteriuria for treatment options, suggested duration and pregnancy consideration for antimicrobials
  • Invasive urological procedures in which mucosal trauma is likely:
    • Single antibiotic dose 1-2 hours pre-op.
    • Antimicrobial choice should be based on urine culture and sensitivity results.
  • Post renal transplant: limited evidence assessing routine treatment of ASB to prevent progression to symptomatic urinary tract infections or graft failure. More evidence is needed to make a definitive recommendation.

Last reviewed February 2019

If Staphylococcus aureus is isolated in the urine, bacteremia may be present. The patient must be assessed for other sources of infection.

Last reviewed February 2019

1. Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, et al. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clin Infect Dis; 2005;40:643-54.

2. AMMI Canada. Symptom-Free Pee: Let It Be. Accessed on-line 07/2018. https://www.ammi.ca.

3. Reproductive Care Program of Nova Scotia. http://rcp.nshealth.ca.

4. Coussement J, et al. Scemla A, Abramowicz D, Nagler EV, Webster AC. Antibiotics for asymptomatic bacteriuria in kidney transplant recipients. Cochrane Database Syst Rev. 2018 Feb 1;2:CD011357.

Last reviewed February 2019

Beta-lactam Allergy

​Beta-lactam Allergy Assessment and Management

  • Do not avoid all beta-lactams in patients reporting penicillin allergies.

    • Penicillin allergy is over reported and cross-allergy between penicillins and cephalosporins is overestimated

  • ​Beta-lactams include all penicillins (i.e. penicillin, ampicillin, amoxicillin, cloxacillin, piperacillin, etc.) including those combined with beta-lactamase inhibitors (amoxicillin/clavulanate, piperacillin/tazobactam), cephalosporins, and carbapenems.
  • The incidence of a true IgE mediated hypersensitivity reaction to a beta-lactam is
    • 1 to 5 per 10,000 treatment courses for penicillins
    • 0.1 to 100 per 100,000 for cephalosporins
    • Individuals with IgE mediated allergies are 3 times more likely to have de novo allergies to unrelated medications. 
  • Patients with a history suggestive of a serious or life-threatening non-IgE mediated reaction to ANY beta-lactam (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, hemolytic anemia, interstitial nephritis, hepatitis, serum sickness), should AVOID all beta-lactams. 
  • Penicillin, amoxicillin, and 1st generation cephalosporins are safe, effective, and inexpensive antibiotics.
    • Unnecessarily avoiding their use can result in therapy that is
      • less effective
      • more toxic
      • associated with greater risk of developing antibiotic resistant microorganisms
      • more costly
  • Since many people mistakenly attribute an adverse drug reaction to an allergy, it is important to clarify whether a reaction is
    • an IgE mediated hypersensitivity reaction
    • a non-IgE mediated hypersensitivity reaction
      • non-serious reaction
      • serious or life-threatening
        • e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms, erythema multiforme
    • a non-hypersensitivity drug-related adverse effect (e.g. GI complications, headache, yeast infections, isolated itch). 

Table 1: Onset, symptoms, and management options for various beta-lactam associated reactions

Reaction Onset Symptoms Management options

Hypersensitivity

  • IgE mediated

Usually <1 hour

(max 72 hours)

Anaphylaxis, urticaria, angioedema, laryngeal edema, wheeze, hypotension

Do not give the same drug again. Choose another cephalosporin with a different side chain.

Do not give another penicillin if culprit was a penicillin.

  • Non-IgE mediated1
>72 hours

Non-serious2

Contact dermatitis, pruritic maculopapular eruption

Not a contraindication to using a beta-lactam. Consider provocation challenge or an antibiotic with a different side chain.
    Serious or life-threatening3 AVOID all beta-lactams
Non-hypersensitivity Anytime Gastrointestinal symptoms, flushing during infusion, headache, yeast infection, isolated itch Not a contraindication to using a beta lactam

1Skin testing has no role in the diagnosis of non-IgE mediated reactions.

2>90% of rashes occurring after people take penicillin (amoxicillin) are mild non-IgE reactions. Rashes occur in up to 7% of people.

3Serious or life-threatening non-IgE mediated hypersensitivity reactions are rare with beta-lactams. They include Stevens-Johnson syndrome, topix epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, hemolytic anemia, interstitial nephritis, hepatitis, and serum sickness. 

Provocation Challenge

  • Give 10% of a therapeutic dose under observation
  • 30 minutes later, give remaining 90% of therapeutic dose
  • Observe for 1 hour after last dose.

  • Cross-reactivity risk between penicillin and cephalosporins is low.
    • For IgE-mediated allergies, the cross reaction between penicillin and cephalosporins is mediated by similarities of the specific chemical side chains of penicillin and cephalosporins, rather than the beta-lactam ring. See cross-reaction chart.
    • Beta-lactams with different side chains may be considered in those with a history of an IgE-mediated reaction.
    • This consideration is based on theoretical risk and studies using this approach are not yet available. 
  • If unable to rule in or rule out an IgE-mediated allergy, referral to an allergist is recommended. 

Cefazolin for Surgical Prophylaxis in Patients with a Beta-lactam Allergy

Cefazolin is the drug of choice for surgical prophylaxis

  • Cefazolin is more effective than alternatives like clindamycin and vancomycin for reducing surgical site infections.
  • Cefazolin is a safe medication with less toxicities than clindamycin and vancomycin.
  • Cefazolin can be administered quickly prior to incision.

Can patients with a beta-lactam allergy receive cefazolin safely?

  • Cefazolin has a unique side chain. Since side chain similarities are responsible for IgE-mediated (anaphylaxis) cross-reactions, cefazolin does not cross-react with other beta-lactams.
  • Cefazolin for surgical prophylaxis is given in a monitored preoperative setting. 
  • Cefazolin should be avoided if
    • History suggestive of a serious or life-threatening non-IgE-mediated reation to beta-lactams (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, hemolytic anemia, interstitial nephritis, hepatitis, serum sickness)
    • Anaphylaxis to cefazolin specifically

Surgical Prophylaxis Algorithm for Patients with Beta-lactam Allergy

Candidemia

  • Candida albicans
  • C. glabrata
  • C. parapsilosis
  • C. tropicalis
  • C. krusei

Last reviewed November 2018

  • C. glabrata is usually resistant to fluconazole and should be treated with an echinocandin
  • C. krusei is resistant to fluconazole and should be treated with an echinocandin

Last reviewed November 2018

  • If yeast suspected, draw a set of blood cultures from two different sites
  • Candida in blood should generally NOT be considered a contaminant

Last reviewed November 2018

  • Infectious Diseases (ID) consultation is recommended; particularly if an endovascular or device-related infection suspected
  • Replace all central lines as soon as possible
  • Ophthalmology assessment is recommended to rule out ophthalmic disease within 1 week of therapy (or after neutrophil count recovery in neutrophenic patient)
  • Collect 2 aerobic blood culture bottles every 48 hours until negative to demonstrate sterilization

 

Last reviewed November 2018

  • Fluconazole if patient is NOT critically ill (i.e. hemodynamically stable) and unlikely to have a fluconazole-resistant Candida (no azole exposure within three months):
    • Fluconazole 800 mg IV/PO x 1, then 400 mg IV/PO once daily (adjust for renal function)
  • An echinocandin:
    • Caspofungin 70 mg IV x initial dose on day 1; subsequent dosing 50 mg IV daily 
  • Amphotericin B:
    • Amphotericin B lipisomal (AmBisome) 5 mg/kg IV daily 

Last reviewed November 2018

  • Minimum 2 weeks after first negative blood culture in absence of metastatic complications

Last reviewed November 2018

  • Febrile patients with hematologic malignancy recovering from neutropenia are at risk of chronic disseminated (hepatosplenic) candidiasis
  • Echinocandins do not achieve high urinary concentrations
  • Candida in respiratory secretions and catheter urine in asymptomatic patients is usually colonization and rarely requires therapy
  • Consider endocarditis if blood cultures consistently positive, persistent fever despite therapy, new heart murmur or embolic phenomena
  • Microbiology report S-DD (susceptible-dose dependent):
    • Susceptibility depends on maximum blood levels. This requires a higher fluconazole dose than the standard dosing in adults with normal renal function. ID should be consulted if fluconazole is used in this situation. 

Last reviewed November 2018

1. Pappas, PG, Kauffman, CA, Andes, DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 62(4): e1-50.

2. Local Antibiograms.

3. CLSI M60-ED1:2017 Performance Standards for Antifungal Susceptibility Testing of Yeasts.

Last reviewed November 2018

Cellulitis (non-purulent)

  • Group A streptococcus (Streptococcus pyogenes)
  • Non group A beta-hemolytic streptococci (groups B/C/G)
  • Staphylococcus aureus

Last reviewed June 2019

  • Acute, unilateral, spreading area of erythema
  • Characterized by heat, pain/tenderness, and swelling
  • Superficial skin swabs are not recommended for diagnosis
  • Important to exclude conditions with similar signs and symptoms:
    • Charcot foot (neuropathic arthropathy)
    • Deep vein thrombosis
    • Erythema migrans (Lyme disease)
    • Gout
    • Lymphedema
    • Venous stasis dermatitis
  • Early assessment for red flag symptoms is recommended to rapidly identify complicated skin and soft tissue infection:
    • Animal or human bites
    • Immunosuppression, including  asplenia
    • Loss of sensation in the affected area
    • Necrosis, hemorrhagic bullae, crepitus
    • Rapid onset of severe pain, especially if out of proportion to clinical findings
    • Rapid progression despite antibiotic use
    • Significant periorbital involvement
  • Blood cultures are recommended if systemic symptoms are present

Last reviewed June 2019

  • Elevation of the affected area (above level of heart) for majority of the day is essential
  • Skin should be hydrated to avoid dryness and cracking, avoiding  interdigital maceration
  • Treat underlying predisposing conditions (e.g. tinea pedis)
  • Assess vascular supply if suspicion of arterial insufficiency (e.g. Ankle Brachial Index)
  • Long-term management of chronic venous insufficiency and lymphedema with compression

Last reviewed June 2019

  • Various severity classification schemes have been developed to assist in management
  • None of these schemes have been validated and they are meant for guidance only. For example, not every immunocompromised patient has a severe cellulitis.

*2 or more of: Temp >38 °C or <36 °C; respiratory rate >24 breaths/min; heart rate >90 bpm; WBC >12 or <4 x 109 /L

Last reviewed June 2019

 

Place in therapy

Antibiotic regimen


1st line

Cephalexin 500 mg PO QID3

 

2nd line

Cefuroxime500 mg PO BID3
Alternative if unable to use any beta lactam Clarithromycin 500 mg PO BID3
1st line

Cefazolin1,2 

Outpatients: 2 g IV q12-24h & 1 g probenecid PO 30min before each cefazolin dose*

Inpatients: 2 g IV q8h3

1st line Cloxacillin2 g IV q4h 
2nd line Ceftriaxone1 g IV q24h
Alternative if unable to use any beta lactam Vancomycin15 mg/kg IV q12h3
 

Immediate expert consultation

Broad spectrum antimicrobials

  • Antimicrobial choice and route of administration should be guided by severity of illness

*Probenecid not required if:

  • CrCl less than 50 ml/min AND using cefazolin q12h OR
  • CrCl less than 30 mL/min AND using cefazolin q24h

1. 1st line in patients with IgE mediated penicillin allergy
2.  Can transition to oral therapy when systemic symptoms resolved for at least 24 hours
3.  Dose adjustment required for renal dysfunction

Last reviewed June 2019

  • Usually 5-7 days

Last reviewed June 2019

  • Erythema and extension often progress in first 24 hours of treatment. This is not considered a treatment failure.
  • Systemic symptoms usually improve in 24-48 hours if on appropriate treatment
  • Residual skin discoloration  or edema may be present at end of antibiotic course and is not a reason to prolong antibiotics. Full skin healing may take weeks while limb edema can persist for months after signs of infection resolve.

Last reviewed June 2019

1. Antibiotics Why and Why Not 2018 Dalhousie CPD Academic Detailing Service, November 2018.

2. 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. Clinical Infectious Diseases 2014;59(2): e10–52.

3. Raff AB, Kroshinsky D. Clinical Review and Education: Cellulitis. JAMA. 2016;316(3):325-337.

Last reviewed June 2019

Clostridioides (Clostridium) difficile Infection in Adults 

Clostridioides difficile infection (CDI) is defined by the presence of:

  • Unexplained and new-onset ≥3 unformed stools in 24 hours* AND
    • Stool test positive for C. difficile toxins OR
    • Colonoscopic or histopathologic findings revealing pseudomembranous colitis

* Patients with severe disease may not have loose stools if they have toxic megacolon or ileus.

Last reviewed May 2019

  • If CDI is suspected,  send a stool sample for testing and initiate contact precautions.
  • Empiric therapy for CDI should be started while awaiting diagnosis if:
    • Substantial delay in laboratory confirmation is expected
    • Patient symptoms are consistent with severe CDI
  • Assess patient for medications or interventions that are known to cause diarrhea, such as laxative therapy and enteral feeds, etc.
  • Do not test stool of asymptomatic patients (3% - 14% carriage in  adults admitted to hospital).
  • Test of cure is not recommended since testing can remain positive even after successful treatment.

Last reviewed May 2019

  • Discontinue antimicrobials if possible. Consider switching to an antimicrobial associated with a lower risk for CDI if antimicrobials are required.
  • Consider discontinuing proton pump inhibitor therapy if appropriate.
  • Avoid opioids and antimotility agents (e.g. loperamide).
  • No antimicrobial treatment for CDI is required if diarrhea has resolved.*

*Exception - cases where ileus may be possible (e.g. severe and complicated disease)

  • Infectious Diseases & Surgery consultation is recommended for severe and complicated CDI.
  • Probiotics are not currently recommended for the treatment or prevention of CDI.

Last reviewed May 2019

  • Consider consultation with Infectious Diseases if severe allergy to vancomycin.
  • Fidaxomicin may be used in the setting of vancomycin allergy. There is increased risk of fidoxomicin hypersensitivity with macrolide allergy history.

 

 

INITIAL EPISODE

Category Severity criteria Treatment recommendation

Mild to moderate

  • WBC ≤15 x 109 / L., and 
  • Creatinine ≤1.5 x baseline, and
  • Age ≤ 65 years 
  • Metronidazole 500 mg PO TID for 10 days or 
  • Vancomycin 125 mg PO QID for 10 days

Severe, uncomplicated

  • WBC > 15 x 109 / L or
  • Creatinine > 1.5 x baseline or
  • Age > 65 years or
  • Hypoalbuminemia

 

  • Vancomycin 125 mg PO QID for 10 days

Severe, complicated 

  • Hypotension
  • Shock
  • Ileus
  • Megacolon
  • Vancomycin 250-500 mg PO/NG QID for 14 days AND 
  • Metronidazole 500 mg IV Q8h until no longer critically ill AND
  • If paralytic ileus, consider adding vancomycin rectally: 500 mg in 100 mL normal saline per rectum Q6h as a retention enema
  • Consider surgical consultation 

RECURRENT EPISODES

Category Severity criteria Treatment recommendation

First recurrence, mild to moderate

  • WBC ≤15 x 109 / L., and 
  • Creatinine ≤1.5 x baseline, and
  • Age ≤ 65 years 
  • Preferred: Vancomycin 125 mg PO QID for 14 days or 
  • Alternative: Metronidazole 500 mg PO TID for 14 days


First recurrence, severe, uncomplicated

  • WBC > 15 x 109 / L or
  • Creatinine > 1.5 x baseline or
  • Age > 65 years or
  • Hypoalbuminemia

 

  • Vancomycin 125 mg PO QID for 14 days 

Second or subsequent recurrence

 
  • Consider consulting Infectious Diseases following one failed Vancomycin taper
     

Last reviewed May 2019

1. Loo VG, Davis I, Embil J, Evans GA, et al. Association of Medical Microbiology and Infectious Disease Canada treatment practice guidelines for Clostridium difficile infection. Journal of the Association of Medical Microbiology and Infectious Disease Canada. 2018; 3(2): 71-92.

2. McDonald LC, Gerding DN, Johnson S, Bakken JS, 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). Clin Infect Dis. 2018; 66(7):e1-e48.

3. Van Hise NW, Bryant AM, Hennessey EK, Crannage AJ, et al. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents. Clin Infect Dis. 2016 Sep 1;63(5):651-3.

4. Appaneal HJ, Caffrey AR, LaPlante KL. What is the role for metronidazole in the treatment of Clostridium difficile infection? Results from a national cohort study of Veterans with initial mild disease. Clin Infect Dis. 2018; Dec 18 [Epub ahead of print].

5. Fabre V, Dzintars K, Avdic E, Cosgrove SE. Role of Metronidazole in Mild Clostridium difficile Infections. Clin Infect Dis. 2018;67(12):1956-1958.

Last reviewed May 2019

Cystitis (uncomplicated)

  • Infection of the lower urinary tract
  • No signs or symptoms that suggest an infection extending beyond the bladder (such as fever, chills, back pain, nausea, vomiting)
  • No risk factors for complicated infection 

Last reviewed February 2019

  • Escherichia coli
  • Other Enterobacteriaceae (Klebsiella sp., Proteus sp.)

Last reviewed February 2019

  • Increasing E.coli resistance to fluoroquinolones. These agents are not recommended for empiric or first-line treatment of uncomplicated cystitis. 
  • Local uropathogens' susceptibilities should be considered when choosing empiric treatment: 
    • Trimethoprim/sulfamethoxazole should not be used if resistance exceeds 20 %
    • Ciprofloxacin should not be used if local resistance exceeds 10%

 

Last reviewed February 2019

  • Signs and symptoms: dysuria, urgency, frequency, suprapubic pain/tenderness
  • No symptoms of upper urinary tract infection: fever, chills, flank pain, costovertebral angle tenderness
  • No risk factors for complicated infection: 
    • Pregnancy
    • Immunosuppression
    • Diabetes (especially if long term complications) 
    • Indwelling catheter
    • Anatomical abnormality 
    • Voiding dysfunction
    • Obstruction
    • Recent urogenital procedure 
  • Cystitis in men is often, but not always, considered complicated. Investigation for anatomical abnormalities or prostatitis should be considered. 
  • Urine culture is not generally recommended unless:
    • Antibiotic use or UTI in last 3-6 months
    • Suspected UTI in a male
    • Travel outside North America in last 6 months
    • Recent hospitalization 
    • History of a UTI caused by a multidrug resistant microorganism 
    • Complicated UTI 
    • Failure to respond to empiric therapy after 48hrs 
  • The reliability of the urine dipstick as a diagnostic tool for UTI is low due to an inability to differentiate between an infection and asymptomatic bacteriuria, and is not recommended as a test for diagnosing UTI. 

 

Last reviewed February 2019

  • Post treatment urine cultures are not recommended if adequate response to therapy

Last reviewed February 2019

  • First line: 
    • Nitrofurantoin macrocrystals 100 mg twice daily x 5 days*
  • Second line:
    • Fosfomycin 3 g x 1 dose
    • Trimethoprim-sulfamethoxazole (TMP-SMX) 1 DS tablet twice daily x 3 days*
    • Cephalexin 500 mg qid x 5-7 days*
    • Amoxicillin-clavulanate 875/125 mg twice daily x 5-7 days*

* Treatment duration of 7 days is recommended in males with uncomplicated cystitis 

Last reviewed February 2019

  • Ciprofloxacin is no longer recommended as fist line treatment due to high risk of adverse effects including tendinopathy, aortic dissection, peripheral neuropathy, central nervous system effects and C. difficile infection.
  • Moxifloxacin should not be used as it does not attain sufficient concentration in the urine 
  • TMP-SMX 
    • Associated with higher risk of renal injury, hyperkalemia, and sudden death if
      • Patients aged 65 years and older
      • Patients on medications that can increase potassium: angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), or K+ sparing diuretic (e.g. spironolactone)
    • Regular monitoring of kidney function and electrolytes are recommended for patients with risk factors for hyperkalemia or prolonged duration of therapy.
  • Nitrofurantoin should not be used in patients with: 
    • CrCl less than than 30 ml/min
    • Infections outside lower urinary tract due to poor distribution into serum and tissue
  • If Staphylococcus aureus is isolated in the urine, bacteremia may be present. The patient must be assessed for other sources of infection. 

 

Last reviewed February 2019

1. Toronto Central Local Health Integration Network. Guidelines for Empiric Treatment of Urinary Tract Infections in Adults. January 2015. Accessed online 09/2017. www.antimicrobialstewardship.com.

2. Gupta K, Hooton TM, Naber KG, Wullt B, et al. International Practice Guidelines for the Treatment of Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.

3. Fralick M, Macdonald EM, Gomes T, Antoniou T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of reninangiotensin system: population based study. BMJ. 2014 Oct 30;349:g6196

4. Crellin E, Mansfield KE, Leyrat C, Nitsch D, et al. Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study.BMJ. 2018 Feb 9;360:k341.

Last reviewed February 2019

Hospital Acquired Pneumonia

Hospital acquired pneumonia (HAP): pneumonia not present at the time of hospital admission and occurring ≥ 48 hours after admission

Last reviewed April 2020

  • Streptococcus pneumoniae
  • Staphylococcus aureus
  • Haemophilus influenzae
  • Gram-negative bacilli
    • Escherichia coli, Klebsiella spp., Enterobacter spp., Serratia spp., Pseudomonas aeruginosa

Last reviewed April 2020

  • Sputum culture
  • Blood cultures (aerobic and anaerobic) x 2 sets using two sites
  • Suspect HAP if
    • Chest imaging shows new pulmonary infiltrate, PLUS one of:
      • Fever
      • Purulent respiratory secretions
      • Leukocytosis
      • Dyspnea or increase in oxygen requirements

Last reviewed April 2020

  • Usual duration of therapy is 7 days
  • Longer duration indicated for abscess, empyema, or severely immunocompromised

Last reviewed April 2020

  • Therapy should be tailored once culture and sensitivity results or other diagnostic information becomes available.
  • Aspiration pneumonitis: antimicrobial therapy is not indicated for acute macroaspiration events. Pneumonia may develop, reassess after 48 hours.            
  • Aspiration pneumonia: routine addition of anaerobic coverage, such as metronidazole, is not recommended unless treating an empyema or lung abscess.

Last reviewed April 2020

  • Review patient’s prior culture results and prior antibiotic use to inform empiric choices

 

Risk Factors Regimen
  • No rapid clinical deterioration
  • Not admitted to ICU
  • No IV antibiotic use within preceding 90 days

Ceftriaxone 1 g IV q24h

OR

Amoxicillin-clavulanate* 875 mg PO BID

OR

Levofloxacin* 750 mg PO/IV q24h

Any ONE of the following:

  • HAP requiring ICU management: septic shock and/or intubation
  • Colonization or prior infection with Pseudomonas or other resistant Gram-negative bacilli (e.g. extended spectrum beta-lactamase producing E. coli, Klebsiella)
  • Prolonged hospitalization (>2 weeks)
  • IV antibiotic use within 90 days

Piperacillin-tazobactam* 3.375g IV q6h†

OR

Meropenem* 500 mg IV q6h

Preferred if: colonized/infected with piperacillin-tazobactam resistant microorganism OR IgE mediated penicillin allergy

If double antipseudomonal coverage is indicated:

  • HAP requiring ICU management: septic shock and/or intubation AND
    • Colonization or prior infection with Pseudomonas or other resistant Gram-negative bacilli (e.g. extended spectrum beta-lactamase producing E. coliKlebsiella) OR
    • Broad spectrum IV antibiotic use within 90 days

Consider adding:

Ciprofloxacin* 400 mg IV q8h

OR

Tobramycin* 5-7 mg/kg IV q24h‡

Discontinue if multidrug-resistant Gram-negative bacilli does not grow from high-quality sputum specimen within 48 to 72 hours

If MRSA suspected:

  • Known MRSA colonization
  • Previous MRSA infection

ADD:

Vancomycin* IV

(See NSHA Antimicrobial Handbook or Spectrum App)

*May require renal dose adjustments, see NSHA Spectrum app or dosing table

†Critical care may have a prolonged infusion protocol

‡Dosing should be reviewed with clinical pharmacist

 

Last reviewed April 2020

1. Kalil AC, Metersky ML, Klompas M, Musced-ere J, Sweeney DA, Palmer LB, 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: pp e61-e111.

2. National Institute for Health and Care Excellence. Pneumonia (hosptial-acquired): antimicrobial prescribing. NICE Guideline. 2019. www.nice.org.uk/guidance/ng138. Accessed March 13, 2020.

3. Management of Hospital-Acquired Pneumonia in Adults. SHS + UHN Antimicrobial Stewardship Program, 2018. https://www.antimicrobialstewardship.com/community-acquired-pneumonia. Accessed March 13, 2020.

4. Treatment Guidelines. Sunnybrook Health Sciences Centre. https://sunnybrook.ca/content/?page=antimicrobial-stewardship-treatment-guidelines. Accessed April 5, 2020.

Last reviewed April 2020

Meningitis (adult community acquired)

  • Streptococcus pneumoniae
  • Neisseria meningitidis
  • Listeria monocytogenes (age >50 years, excessive alcohol consumption, pregnant, immunocompromised)
  • Haemophilus influenzae (now very rare)
  • Viruses: Enteroviruses most common  

 

Last reviewed November 2018

  • Local ceftriaxone resistance in S. pneumoniae is estimated to be less than or equal to 3%

Last reviewed November 2018

  • Collect 2 sets of blood cultures
  • Head CT prior to lumbar puncture if focal neurological signs, papilledema, altered mentation, new onset seizures, impaired cellular immunity
  • Lumbar puncture
    • Defer if high bleeding risk (INR >1.4, platelets < 50 x 109/L ) 
    • Cell count, glucose, protein, Gram stain, culture, opening pressure
    • Negative Gram stain does not exclude bacterial meningitis: sensitivity 60-90%, lower for Listeria (<50%)
    • Typical CSF findings: elevated WBC (predominately neutrophils; may be predominantly lymphocytes and/or monocytes with Listeria), elevated protein, low glucose
      • Predictors of bacterial infection: WBC ≥ 500 x 106/L, CSF-blood glucose ratio ≤ 0.4
    • CSF PCR if suspect viral causes (e.g. Enteroviruses)

Last reviewed November 2018

  • Delay of antibiotics increases mortality. Do not delay antibiotics if neuroimaging and/or LP is delayed.
  • Initiate droplet and contact precautions and notify Infection Prevention and Control
  • Contact Public Health
  • Repeat LP if poor clinical response after 48 hours OR resistant S. pneumoniae confirmed 

Last reviewed November 2018

  • Dexamethasone 10 mg IV q6h should be started with or immediately before the FIRST dose of antibiotic and continued for 4 days if the causative agent is found to be S. pneumoniae. 
  • Ceftriaxone 2 g IV q12h + vancomycin 25 mg/kg total body weight (TBW) IV loading dose followed by 15 mg/kg IV q8-12h (adjust for renal function)
    • Vancomycin should be discontinued for S. pneumoniae if susceptibility to ceftriaxone is confirmed (using CNS minimum inhibitory concentration (MIC) breakpoints). 
  • Add ampicillin 2 g IV q4h (adjust for renal function) for Listeria coverage if age > 50 or risk factors (excessive alcohol consumption, immunocompromised, pregnant)

Last reviewed November 2018

  • For allergies to any first line agents consult Infectious Diseases 

Last reviewed November 2018

  • Neisseria meningitidis 7 days
  • Haemophilus influenzae 7 days
  • Streptococcus pneumoniae 10–14 days
  • Listeria monocytogenes ≥ 21 days  
     

Last reviewed November 2018

  • Immunocompromised (steroids, transplant patients, those with HIV) may may be at risk for fungal meningitis (e.g. Cryptococcus)
  • For S. pneumoniae CNS infections, the minimum inhibitory concentration (MIC) breakpoints for penicillin and ceftriaxone differ from non-CNS infections. Consult microbiology for interpretation of susceptibility results if necessary.
     

Last reviewed November 2018

1. Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267-84.

2. Tunkel AR, van de Beek D, Scheld WM. Acute meningitis. [edited by] John E. Bennett, Raphael Dolin, Martin J. Blaser. Mandell, Douglas, And Bennett's Principles and Practice of Infectious Diseases. Philadelphia, PA :Elsevier/Saunders, 2015. Print.

3. Straus SE, Thorpe KE, Holroyd-Leduc J.How do I perform a lumbar puncture and analyze the results to diagnose bacterial meningitis? JAMA. 2006 Oct 25;296(16):2012-22.

4. Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2015 Sep 12;(9):CD004405.

Last reviewed November 2018

Seasonal Influenza in Adults

  • Influenza A and B cause seasonal outbreaks, weekly surveillance reports are available at Weekly FluWatch report
  • Co-infection with bacterial microorganisms (e.g. Streptococcus pneumoniae, Staphylococcus aureus) may be present

Last reviewed March 2020

  • Clinical manifestations vary widely and may include
    • Systemic symptoms: fever, myalgia, arthralgia, headache, nausea, vomiting, diarrhea
    • Upper respiratory tract symptoms: sore throat, rhinorrhea
    • Lower respiratory tract symptoms: cough, shortness of breath
  • High suspicion for influenza warranted in immunocompromised patients as symptom severity may be attenuated
  • Nasopharyngeal (NP) swab detects presence of influenza A and B and respiratory syncytial virus (RSV)
    • Influenza testing will detect live and dead virus, so test of cure unnecessary in most patients

 

Last reviewed March 2020

  • All patients requiring hospitalization with suspected influenza should be:
    • Initiated on droplet and contact precautions
    • Treated empirically with oseltamivir until NP swab result returns negative infection (regardless of vaccination status or onset of symptoms)
  • Healthy patients with mild influenza in the community are not likely to benefit from oseltamivir
  • If severe illness at onset or if deterioration after initial improvement, consider treatment of bacterial co-infection (see CAP chapter)

 

Last reviewed March 202

  • Oseltamivir (Tamiflu®) 75 mg PO BID x 5 days, renal adjustment if necessary
    • For administration via NG or OG: suspension available or capsules may be opened and contents administered
    • High-dose oseltamivir (150 mg BID) is not recommended

 

Last reviewed March 2020

  • 5 days is the standard duration (except in CrCl < 10 mL/min and PD)
    • In critically ill and immunocompromised patients, longer courses of up to 10 days may be appropriate. Consider ID consult.

Last reviewed March 2020

  • Drug resistance is rare; if suspected consult ID

Last reviewed March 2020

1. Government of Canada. Flu (influenza) for Health Professionals. Accessed online 02/2020. https://www.canada.ca/en/public-health/services/diseases/flu-influenza/health-professionals.html

2. Communicable disease Prevention and Control -Respiratory Watch Report. Accessed online 2/2020. https://novascotia.ca/dhw/cdpc/respiratory-watch.asp

3. Aoki FY, Allen UD, Mubareka S, Papenburg J, Stiver HG, Evans GA. Use of antiviral drugs for seasonal influenza: Foundation document for practitioners—Update 2019. Journal of the Association of Medical Microbiology and Infectious Disease Canada. 2019;4(2):60–82.

4. Association of Medical Microbiology and Infectious Disease Canada: Guidance on Use of Antiviral Agents for the 2019-20 Influenza season. Accessed online 2/20. https://www.ammi.ca/Content/AC-%20Guidance%20of%20Antiviral%20Agents%2019-20.pdf

5. SHS-UHN Antimicrobial Stewardship Program: https://www.antimicrobialstewardship.com/influenza-treatment

Last reviewed March 2020

Staphylococcus aureus Bacteremia

  • Methicillin-sensitive Staphylococcus aureus (MSSA)
  • Methicillin-resistant Staphylococcus aureus (MRSA) 
     

Last reviewed April 2018

  • All patients should have an echocardiogram to rule out endocarditis, transesophageal echocardiogram (TEE) is preferred
  • Identify any indwelling prosthetic devices (e.g. orthopedic hardware, cardiac device) and inspect for infection
  • Source and extent of infection should be determined through careful history, physical exam and imaging as needed 
     

Last reviewed April 2018

  • Infectious Diseases consultation recommended
  • Mortality rate: 10-30%
  • Remove focus of infection if possible e.g. catheter-associated infection
  • Repeat blood cultures q48hours until negative to demonstrate sterilization 
  • MRSA bacteremia cases with high vancomycin minimum inhibitory concentrations (MIC) ≥2 mcg/mL should be referred to Infectious Diseases

Last reviewed April 2018

  • Cloxacillin 2 g IV q4h
  • Cefazolin 2 g IV q8h (adjust for renal function) 
  • Vancomycin is recommended if known or at risk of MRSA: injection drug use, abscesses, known MRSA colonization, previous MRSA infection
    • Loading dose: 25 mg/kg total body weight (TBW) IV x 1 followed by
    • Maintenance dose: 15 mg/kg TBW IV q8-12hours (adjust for renal function)
    • Maintain trough level of 15-20 mg/L 
       

Last reviewed April 2018

  • Cefazolin 2g IV q8h (adjust for renal function) may be appropriate in patients with history of penicillin allergy as it does not share similar side chain with any penicillin
  • Vancomycin IV
  • Daptomycin IV – if cannot use beta-lactam or vancomycin 
     

Last reviewed April 2018

  • Dependent on presence or absence of complications
  • 14 days IV therapy minimum counting from first negative blood culture can be considered if ALL of the following criteria for uncomplicated S. aureus bacteremia are met:
    • Infective endocarditis has been excluded, no implanted prostheses are present, follow-up cultures drawn 2-4 days after initial set are sterile, patient is afebrile within 72 hrs of antibiotic therapy, no evidence of metastatic infection present
  • 4-6 weeks IV therapy recommended for all complicated cases  
     

Last reviewed April 2018

  • For patients with febrile neutropenia, please see Febrile Neutropenia guidelines for management considerations. 

Last reviewed April 2018

1. Holland TL, Arnold C, Fowler VG Jr. Clinical management of Staphylococcus aureus bacteremia: a review. JAMA. 2014 Oct; 312(13):1330-41.

2. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011; 52(3):e18.

3. Van Hal SJ, Lodise TP, Paterson DL. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis. 2012 Mar;54(6):755-71.

4. Van Hal SJ, et al. Predictors of Mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev. 2012; 25 (2): 362-86.

5. Local Antibiograms:https://library.nshealth.ca/AMS/Antibiograms

Last reviewed April 2018

Vancomycin

  • Serious infections due to beta-lactam resistant, Gram-positive microorganisms such as:
    • Methicillin resistant Staphylococcus aureus (MRSA)
    • Ampicillin resistant Enterococcus spp.
    • Methicillin resistant coagulase-negative staphylococci
    • Ceftriaxone resistant S. pneumoniae (meningitis)
  • Infections due to Gram-positive microorganisms in patients with a history of severe delayed skin reactions/organ dysfunction to beta-lactam antimicrobials [e.g. Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia & systemic symptoms (DRESS)] 
  • Surgical prophylaxis
    • Vancomycin should be reserved for patients with a history of severe delayed skin reaction/organ dysfunction (ex: SJS, TEN, drug reaction with eosinophilia and systemic symptoms) to any beta-lactam antimicrobial OR a history of anaphylaxis to cefazolin (refer to NSHA beta-lactam allergy document).
    • MRSA colonized patients  
       

Last reviewed February 2019

  • Nephrotoxicity
  • Cytopenias (esp. neutropenia, thrombocytopenia)
  • Ototoxicity
  • Histamine-release (red person syndrome) or flushing can result from rapid infusion rates and is not a true allergy. Refer to the IV manual for recommended minimum administration time.  
     

Last reviewed February 2019

  • Oral vancomycin administration is suitable only for C. difficile infection as it is not absorbed beyond the GI tract. Do not use oral vancomycin as stepdown therapy for IV vancomycin.
  • Vancomycin is a less effective choice than a beta-lactam antimicrobial for methicillin susceptible staphylococcal infections. 
  • Staphylococcus aureus with an MIC of greater than or equal to 2 mg/L have a high failure rate; consider an ID consult. 
     

Last reviewed February 2019

1. CHOOSE SERUM TROUGH CONCENTRATION TARGET based on suspected or known cause of infection 

 

10-15 mg/L 15-20 mg/L

Non-severe infection

  • Cellulitis / skin and soft tissue infections
  • Urinary tract infections
  • S. aureus infection
  • Central nervous system infection
  • Endocarditis*
  • Osteomyelitis
  • Joint infection
  • Pneumonia
  • Bloodstream infection

*IDSA recommends a target of 10-20 mg/L for endocarditis caused by enterococci or coagulase negative staphylococci. IDSA recommends a target of 10-15 mg/L for streptococcal endocarditis 

 

2. CHOOSE ONE TIME LOADING DOSE 

Target trough 10-15 mg/L Target trough 15-20 mg/L

No load required

  • Loading Dose: 25 – 30 mg/kg
  • Round to the nearest 250mg. Use actual body weight, maximum dose 3000mg

CALCULATE MAINTENANCE DOSE 

15 mg/kg
  • Round to the nearest 250mg
  • Use actual body weight, maximum dose 2500mg
  • Consider ID consult if more than 4000mg/day

 

3. SELECT INTERVAL 

CrCl (mL/min) Target trough 10-15mg/L Target trough 15-20 mg/L

≥80

q12h

q8h (if <60 years old)

q12h (if ≥60 years old)

40-79

q24h

q12h

20-39

q36h

q24h

10-19

q48h

q48h

<10

Give first dose , then consult pharmacist

Give first dose , then consult pharmacist

Hemodialysis

Usually dosed after each dialysis, consult pharmacist and dialysis order sets

Usually dosed after each dialysis, consult pharmacist and dialysis order sets

 

4. THERAPEUTIC DRUG MONITORING

  • Pre-vancomycin (trough) level (within 30 min prior to dose) before 4th dose if patient is expected to be on vancomycin for longer than 48 hours
    • In patients with variable kidney function, altered volume of distribution (burns, cystic fibrosis, sepsis, critical care), and/or requiring larger doses, monitor levels more frequently
    • If level outside desired range, contact clinical pharmacist for assistance with dosing and interpretation of levels as required
    • Do not hold further scheduled vancomycin doses while trough level is pending, unless there has been an acute deterioration in the patient's creatinine clearance
  • Repeat pre-vancomycin level at least weekly to ensure it is within desired range once target trough is achieved and serum creatinine is stable 
  • Random vancomycin levels may be ordered to assist clinical pharmacists and infectious diseases physicians with pharmacokinetic monitoring but are not routinely required  

 

5. OTHER MONITORING 

  • Serum creatinine- baseline and weekly while on therapy, provided creatinine is stable
  • Complete blood count with differential (for cytopenias)- baseline and weekly while on therapy
  • May monitor laboratory values more frequently if warranted by clinical scenario 
     

Last reviewed February 2019

1. Rybak et al. American Journal of Health-System Pharmacy January 2009, 66 (1) 82-98.

2. Rybak et al. J Antimicrob Chemother. 1990; 25:679-87.

3. Rybak et al. Antimicrob Agents Chemother.1999; 43:1549-55.

4. Lodise et al. Antimicrob Agents Chemother. 2008; 52:1330-6.

5. Burgess LD, Drew RH. Pharmacotherapy. 2014; 34:670-6.

6. Hammond et al. Clin Infect Dis. 2017; 64: 666-74.

7. Luther et al. Crit Care Med. 2018; 46: 12-20.

8. Baddour LM, et al. Circulation. 2015;132:1435-1486.

9. Crass RL et al. J Antimicrob Chemother. 2018 Nov 1;73(11):3081-3086.

Last reviewed February 2019

Ventilator Associated Pneumonia in Adults

Ventilator associated pneumonia (VAP): pneumonia occurring ≥ 48 hours after mechanical ventilation

Last reviewed April 2020

  • Staphylococcus aureus
  • Haemophilus influenzae
  • Gram-negative bacilli
    • Escherichia coli, Klebsiella spp., Enterobacter spp., Serratia spp., Pseudomonas aeruginosa

Last reviewed April 2020

  • Sputum culture
    • Endotracheal aspiration is generally preferred over invasive sampling (e.g. bronchoalveolar lavage)
  • Blood cultures (aerobic and anaerobic) x 2 sets using two sites
  • Suspect VAP if
    • Chest imaging shows new pulmonary infiltrate, PLUS one of:
      • Fever
      • Purulent respiratory secretions
      • Leukocytosis
      • Increase in oxygen requirements or ventilatory settings

Last reviewed April 2020

  • Usual duration of therapy is 7 days
  • Longer duration indicated for abscess, empyema, or severely immunocompromised

Last reviewed April 2020

  • Antimicrobial therapy should be narrowed based on microbiology of respiratory samples.
  • Stenotrophomonas maltophilia can cause VAP and should be suspected if patients is not improving despite broad-spectrum antimicrobial therapy. Trimethoprim/sulfamethoxazole is the antibiotic of choice.
  • Candida is a very rare cause of pneumonia and does not require treatment unless evidence of systemic infection such as bloodstream infection.
  • Respiratory cultures can continue to be positive despite successful treatment; avoid repeating cultures if patient is clinically improving.

Last reviewed April 2020

  • Review patient’s prior culture results and prior antibiotic use to inform empiric choices

 

Considerations Regimen
First line

Piperacillin-tazobactam* 3.375g IV q6h†

OR

 Meropenem* 500 mg IV q6h

Preferred if: colonized/infected with piperacillin-tazobactam resistant microorganism OR IgE-mediated penicillin allergy

If double antipseudomonal coverage is indicated:

  • Septic shock AND
    • Colonization or prior infection with Pseudomonas or other resistant Gram-negative bacilli (e.g. extended spectrum beta-lactamase producing E. coli, Klebsiella) OR
    • Broad spectrum IV antibiotic use within 90 days

Consider adding:

Ciprofloxacin* 400 mg IV q8h

OR

Tobramycin* 5-7 mg/kg IV q24h‡

Discontinue if multidrug-resistant Gram-negative bacilli does not grow from high-quality sputum specimen within 48 to 72 hours

If MRSA suspected:

  • Known MRSA colonization
  • Previous MRSA infection

ADD:

Vancomycin* IV

(See NSHA Antimicrobial Handbook or Spectrum App)

*May require renal dose adjustments, see NSHA Spectrum app or dosing table.

†Critical care may have a prolonged infusion protocol.

‡Dosing should be reviewed with clinical pharmacist.

 

Last reviewed April 2020

1. Kalil AC, Metersky ML, Klompas M, Musced-ere J, Sweeney DA, Palmer LB, 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: pp e61-e111.

2. National Institute for Health and Care Excellence. Pneumonia (hosptial-acquired): antimicrobial prescribing. NICE Guideline. 2019. www.nice.org.uk/guidance/ng138. Accessed March 13, 2020.

3. Ventilator-Associated Pneumonia. SHS + UHN Antimicrobial Stewardship Program, 2020. https://www.antimicrobialstewardship.com/community-acquired-pneumonia. Accessed March 13, 2020.

Last reviewed April 2020