Antimicrobial Choice

Introduction

Till today, I still find there is so many bugs and so many empirical treatments (that we should remember) in infectious disease.

Often, to find a quick answer for the antibiotic for a certain infectious disease, I will look up National Antimicrobial Guideline (2024), Guide to Antimicrobial Therapy in the Adult ICU (2023) or Sanford Guide to Antimicrobial Therapy.

Guide to Antimicrobial Therapy in the Adult ICU

Importantly, the 4th edition of the National Antimicrobial Guideline (2024) represents a revolutionary update over the previous PDF version.

Unlike the PDF, this edition will be reviewed and updated periodically to reflect the latest changes.

Appropriate Antimicrobial Prescribing

An appropriate antimicrobial prescribing includes the following steps:

Decide whether antimicrobial therapy is indicated

The cause of patient's symptoms is a direct result of an infection or another non-infectious etiology such as malignancy, emboli, autoimmune disease or drug-related?

When microbiological testing is indicated, collect samples for testing before the first dose of antimicrobial
Select an antimicrobial for the indication that is consistent with appropriate clinical guideline recommendations, or based on advice from an infectious disease physician or clinical microbiologist.

Consider the required spectrum of activity (use the narrowest spectrum therapy required), potential adverse effects, drug interactions and cost, as well as patient factors such as history of antimicrobial hypersensitivity, recent antimicrobial use, and pregnancy and breastfeeding.

Select an appropriate dose, frequency and route; use oral therapy when clinically appropriate.

Take into account patient factors, the pharmacokinetic and pharmacodynamic properties of the drug, and potential drug interactions.
Example of patients with altered pharmacokinetics (e.g. altered drug clearance or volume of distribution) include

patient with septic shock
patient with severe burns
patient with cystic fibrosis
pregnant women
obese patients

Prescribe the shortest possible duration therapy, consistent with the condition being treated and the patient's clinical response.
Document the antimicrobial therapy in the patient's medical record or medication chart, including the indication and the intended duration of therapy before further review or cessation.

Empirical and Directed Antimicrobial Therapy

Empirical antimicrobial therapy is used to treat an established infection when the pathogen has not been identified (i.e. before the availability of culture or susceptibility testing result).

In other words, empirical therapy is therapy based on experience, and more specifically, therapy begun on the basis of a clinical "educated guess" in the absence of complete or perfect information.
The antimicrobial choice will be based on the clinical presentation and the expected antimicrobial susceptibility of the most likely or important pathogen(s).

Once a pathogen is identified, a directed antimicrobial therapy will then be employed.

Consider deescalating a broad-spectrum to a narrower spectrum antimicrobial
Consider changing parenteral therapy to oral therapy if appropriate

Antibiogram

What is an Antibiogram?

A record usually produced semi-annually or annually of antimicrobial susceptibility for bacterial isolates collected at a hospital or outpatient facility.
Presents a spectrum of susceptibility to antimicrobials that exists among common microorganisms detected by the laboratory.
Must have at least 30 isolates of a specific pathogen to report susceptibilities.

The antibiogram is used to

Assess local susceptibility rates
Monitor resistance trends over time
Guide selection of empiric antimicrobial treatment
Guide decisions about which antimicrobials are included on formularies.

Limitations

Do not provide syndrome or disease specific advice.
No distribution of organisms for a given infection.
Not helpful in polymicrobial infections or infections empirically treated with more than one agent.
Current hospital antibiograms do not take into account risk factors that influence susceptibility (such as presenting living situation).
They lack external validity and are only applicable to single site.

PK/PD Indices for Optimal Antimicrobial Activity

Based on their kill or inhibition characteristics, antimicrobials are broadly described as concentration- or time-dependent or a combination (concentration- and time-dependent antimicrobial).

Concentration-dependent antimicrobials, for which increasing concentrations progressively enhance antimicrobial killing and the ratio of Cmax/MIC best describes their activity (e.g. aminoglycosides).
Time-dependent antimicrobials, for which prolonging the duration of effective drug exposure leads to greater antimicrobial killing and fT_>MIC) best describes their activity (e.g. β-lactam antibiotics).
Both concentration- and time-dependent kill characteristics, for which the ratio of AUC_0-24/MIC best describes their antimicrobial activity (e.g. fluoroquinolones and glycopeptides.

(Source: IDSAP PK/PD in Special Populations and Antimicrobial Prophylaxis, 2020)

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