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Top 5 Antimicrobial Stewardship Practices

J. Scott Weese, DVM, DVSc, DACVIM, FCAHS, Ontario Veterinary College, Ontario, Canada

Pharmacology & Medications

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November/December 2021
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Peer Reviewed
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Web-Exclusive

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Antimicrobial stewardship is a multifaceted approach to responsible antimicrobial use that optimizes clinical outcome, minimize adverse effects, and address the emerging threat of antimicrobial resistance while maintaining good patient care. There are many practical antimicrobial stewardship components that can be used in the clinic.

Following are the author’s top 5 suggested antimicrobial stewardship practices.

1

De-escalation

De-escalation is simple, cost-effective, and based on basic concepts of everyday decision-making that evaluate diagnostic testing and clinical response in order to decrease the number of antimicrobials used and/or the spectrum and duration of antimicrobial treatment. De-escalation depends on daily (or more frequent) reassessment of the patient to determine when to change or stop antimicrobial treatment. For example, broad-spectrum antimicrobials might be indicated when a patient is initially presented; however, based on additional testing and clinical evaluation, treatment could be narrowed by stopping one drug of a combination or by selecting a different drug. 

The decision to stop treatment is important, as excessively long treatment durations are common in veterinary patients. This may occur simply because the default is to continue treatment when there is no established stopping point. 

De-escalation has many benefits, including reduced cost, minimized risk for adverse effects, and lowered pressure for antimicrobial resistance selection, as well as allowing for easier transition from inpatient to at-home care. De-escalation may be underused because it is infrequently considered or because of lack of culture or other test results, lack of clinician confidence in narrowing the spectrum, and/or reluctance to change. 

Use of de-escalation can be encouraged via formal approaches (eg, mandatory review points), whereby inpatient antimicrobial regimens should be re-evaluated and treatment orders should be reissued after a specified period (eg, 48 hours). Making continuation of treatment an active decision can facilitate reassessment and transition to narrower spectrum treatment, as opposed to the active step of stopping treatment. Increased discussion and awareness are likely the most important components, prompting thought about the antimicrobial regimen and exercising confidence in making changes.

2

Clinical Guidelines

Clinical guidelines are increasingly available and provide guidance on the approaches recommended for most patients. Available guidelines include those on international disease-specific diagnoses and treatment.1-5 National prescribing guidelines are also available in many countries. Guidelines can assist with key decisions (eg, when to use an antimicrobial, which drug[s] to choose, treatment duration). Easy-to-access online versions are being developed for clinical use.

3

Antimicrobial Tiering

The tiering of antimicrobials raises awareness of the relative importance of different antimicrobials in veterinary and human medicine and the implications of resistance. The emphasis is mostly on the importance of the drug in human medicine and the potential impact of veterinary use on resistance in human pathogens. Antimicrobials can be classified using different systems (eg, those described by the World Health Organization [WHO]6 or the European Medicines Authority [EMA]7; Table). 

Third-generation cephalosporins and fluoroquinolones are the most commonly used higher-tier drugs in veterinary medicine. Use of higher-tier drugs may be appropriate in some patients, but tiering classifications should be considered when choosing an antimicrobial, with the goal of using the appropriate lowest tier drug.

TABLE

COMMONLY USED ANTIMICROBIAL EXAMPLES & CLASSIFICATIONS

Antimicrobial WHO Classification* EMA Classification
Third-generation cephalosporins (eg, cefovecin, cefpodoxime) Highest priority, critically important Restrict
Fluoroquinolones Highest priority, critically important Restrict
Potentiated penicillins (eg, amoxicillin/clavulanic acid) Critically important Caution
First-generation cephalosporins (eg, cephalexin, cefazolin) Highly important Caution
Tetracyclines (eg, doxycycline) Highly important Prudence
Penicillins (eg, amoxicillin) Highly important Prudence
Lincosamides (eg, clindamycin) Highly important Caution
Macrolides (eg, azithromycin) Highest priority, critically important Caution
Metronidazole Important Prudence
Trimethoprim-sulfonamides Highly important Prudence
Carbapenems (eg, meropenem) Critically important Avoid
Chloramphenicol Highly important Caution
*WHO categories include the following: highest priority, critically important; critically important; highly important; important
EMA categories include the following: avoid, restrict, caution, prudence
4

Use & Interpretation of Culture & Susceptibility Results

Culture results should be carefully interpreted, as they can be important for case management, but they can also be misleading, with false-positive or false-negative results (see Potential Explanations For False-Positive & False-Negative Culture Results). Detailed discussion is beyond the scope of this article, but relevance of results depends on whether the isolated organism makes sense for the disease process, the reported level of growth, other test results, and bacteria normally present at the site. 

Not all isolated bacteria need to be targeted. The focus should be on treatment, not test results. Resistant organisms are not more likely to cause disease or require a different treatment approach (apart from drug selection) as compared with their susceptible counterparts, so the susceptibility profile only dictates drug selection, not whether the organism is relevant or whether treatment is needed. Mixed cultures should be interpreted with caution, as they likely represent contamination. 

Prudent use of cultures should also be considered. Specimens should rarely be submitted for culture when there is no realistic need for treatment (eg, urine sample from a clinically normal patient) or when the sample may not be representative (eg, superficial swab of a draining tract).

POTENTIAL EXPLANATIONS FOR FALSE-POSITIVE & FALSE-NEGATIVE CULTURE RESULTS

False-Positive Results

  • Presence of resident microbiota at a normally polymicrobial site
  • Laboratory contamination
  • Contamination during sampling and handling
  • Use of overly sensitive methods (eg, broth enrichment)
  • Sampling incorrect site (eg, necrotic areas, external opening of draining tracts)

False-Negative Results

  • Nonbacterial cause
  • Inadequate or nonrepresentative sample
  • Fastidious organism that died during transportation
  • Poor sample handling, storage, or transportation
  • Organism is not readily grown under routine laboratory conditions
  • Ongoing or recent antimicrobial therapy
  • Poor sampling technique
  • Causative agent not identified because of overgrowth of contaminants
5

Delayed Prescribing

Delayed prescribing targets situations in which antimicrobials are not indicated at the time of examination but might be reasonable later based on the course of disease (determined by clinical signs and/or duration of disease) or pending test results. 

Delayed prescribing provides a specified treatment approach that goes beyond having the pet owner return if there is no improvement. The aim is to balance antimicrobial stewardship and owner satisfaction by indicating to the owner that antimicrobials are not yet recommended but will be made available in certain situations without a need for further examination or additional cost beyond that of the drug. This can consist of providing a postdated prescription or an indication (ideally written and provided to the owner) that if the stated criteria are met, the antimicrobial can be picked up from the clinic or a prescription provided. 

Delayed prescribing has been shown in human medicine to substantially reduce antimicrobial use without impacting patient outcome or complication rates,8 simultaneously leading to greater patient satisfaction as compared with not receiving a prescription at the time of the appointment.9 In veterinary medicine, this method can be considered in patients with acute diarrhea and upper respiratory tract infection. For example, the owner of a dog with acute diarrhea that is otherwise clinically normal can be instructed to manage the patient conservatively (eg, via diet) to provide time for the disease to self-resolve and be informed that an antimicrobial (eg, metronidazole) will be provided if the disease persists for a certain period (eg, >3 days). 

Delayed prescribing should be used with caution or avoided in patients in which the diagnosis is less certain, owner observation or follow-up may be poor, or the patient is likely at higher risk for complications.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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