|
This online tutorial series "Quality Improvement: Tool Time" reinforces practical
application of tools and competencies acquired during the live activity. Each Tool
is a combination of faculty commentary on essentials in clinical practice, links
to relevant scientific publications, and a printable handout that will serve as
a reminder. Please select the topic:
- Ensuring Quality of Care
- Optimizing Vancomycin for MRSA Infections
- Selecting Appropriate Therapy for ESBL- and KPC-Producers
- Dosing Strategies for MDR P. aeruginosa/A. baumannii Infections
- Adjusting Antimicrobial Regimens for Efficacy and Safety
|
|
Adjusting Antimicrobial Regimens for Efficacy and Safety
|
|
Applying Culture Results to Adjust Treatment: De-escalation of Therapy
|
|
De-escalation of therapy reduces the unnecessary use of
antimicrobials and has the potential to decrease the risk
of development of resistance without affecting clinical
outcomes. More research is needed to arrive at the optimal
approach for de-escalation of therapy.
The Table on the right can serve as a useful guide in
adopting a strategy for de-escalation.[1] Adjustments
should be made based on the individual patient
characteristics and specific conditions at
each institution.
|
|
Strategy for de-escalation: A guide
[1]
|
- Obtain microbiologic samples as soon as an infection is suspected
- Begin empiric therapy based on patient risk factors for multidrug-resistant pathogens and local susceptibility patterns
- Evaluate and de-escalate once culture results and susceptibility profiles are obtained
|
|
Individualizing Antimicrobial Dosing According to Patient Factors
Pharmacokinetics of antimicrobials can vary significantly
based on patient factors—age, weight, and severity of
illness, among others. Dose adjustment for patients with
renal impairment is an established practice. However,
pharmacists must also consider other patient factors
when deciding on an optimal dose to ensure effectiveness
while minimizing the risk for adverse events.
|
Weight
|
Severity of Illness
|
|
Research has demonstrated that doses of some antimicrobial
agents may need to be increased in obese patients to achieve
effective concentrations at the site of infection. A
study of obese patients treated with 600 mg of linezolid
for cellulitis found that drug concentrations were
diminished in obese patients compared to healthy
volunteers.[2]
Though some antimicrobials use weight-based dosing, such
as vancomycin and the aminoglycosides, the question
that follows is—are there limits on the maximum dose
when treating obese or morbidly obese patients?
Studies are needed to gain a better understanding of
the pharmacokinetics of other antimicrobials in obese
patients to ensure effective and safe doses are
administered.
|
In addition to weight, the severity of illness can
impact antimicrobial pharmacokinetics. One study
compared the pharmacokinetics of intravenous levofloxacin
in critically ill patients versus healthy volunteers
(Table).[3]
The results revealed significantly higher
drug exposure in critically ill patients, potentially
increasing the risk of adverse events, and supporting
the need for dose adjustment in these patients.
|
Variable
|
Critically
III
Patients
(N=26)
|
Healthy
Volunteers
(N=10)
|
P
Values
|
|
Cmax (mg/L)
|
7.5
|
6.4
|
.0008
|
|
Cmin (mg/L)
|
1.0
|
0.6
|
.0006
|
AUC0-24
(mg.h/L)
|
66.1
|
54.6
|
.042
|
|
Half-life (h)
|
8.0
|
7.0
|
.021
|
|
In the absence of clinical data that clearly demonstrate
how patient factors can impact pharmacokinetics of
certain antimicrobials, pharmacists must work together
with other team members to ensure that appropriate
and safe dosing of drugs is administered to their
patients.
|
|
References
- Kollef MH, Micek ST. Strategies to prevent antimicrobial resistance
in the intensive care unit. Crit Care Med. 2005;33:1845-1853.
Click here for abstract
- Stein GE, Schooley SL, Peloquin CA, et al. Pharmacokinetics and
pharmacodynamics of linezolid in obese patients with cellulitis. Ann
Pharmacother. 2005;39:427-432.
Click here for abstract
- Rebuck JA, Fish DN, Abraham E. Pharmacokinetics of intravenous
and oral levofloxacin in critically ill adults in a medical intensive
care unit. Pharmacotherapy. 2002;22:1216-1225.
Click here for abstract
|
|
Suggested Reading
Faulkner CM, Cox HL, Williamson JC. Unique aspects of antimicrobial
use in older adults. Clin Infect Dis. 2005;40:997-1004. Click here
for complete article
This article reviews complications of prescribing antimicrobials
for elderly patients. Polypharmacy, a common issue due to the
presence of comorbidities, increases the risk of drug–drug
interactions. Adverse events are more common. The physiological
changes associated with advanced age can alter drug pharmacokinetics.
Accurate estimates of renal function cannot be made with standard
methods.
Herring AR, Williamson JC. Principles of antimicrobial use in older
adults. Clin Geriatr Med. 2007;23:481-497.
Click here for abstract
This review describes how some of the fundamental principles of
antimicrobial therapy can change when treating elderly patients—selection
of empiric therapy, risk stratification for severe or atypical
infections, potential drug–drug interactions related to polypharmacy,
and age-related impact on pharmacokinetic parameters. The authors
emphasize a greater need to include elderly patients in clinical
trials to assess differences in efficacy and safety of antimicrobials.
Hibbard ML, Kopelman TR, O’Neill PJ, et al. Empiric, broad-spectrum
antibiotic therapy with an aggressive de-escalation strategy does not
induce gram-negative pathogen resistance in ventilator-associated
pneumonia. Surg Infect (Larchmt). 2010;11:427-432.
Click here for abstract
This retrospective study evaluated changes in susceptibilities of
gram-negative bacteria at one institution that implemented an
aggressive policy of de-escalation of therapy following empiric
broad-spectrum coverage for VAP. There was no evidence for increased
resistance following this strategy and the authors concluded that
de-escalation of therapy is a valid practice.
Pai MP, Bearden DT. Antimicrobial dosing considerations in obese
adult patients. Pharmacotherapy. 2007;27:1081-1091.
Click here for abstract
This article explores the effects of obesity on antimicrobial
disposition and pharmacokinetics. The authors review the available
clinical data, which historically have focused on antimicrobials
requiring therapeutic drug monitoring, such as vancomycin and
aminoglycosides. The authors conclude that additional studies
are needed to establish dosing recommendations in obese patients.
|
