Optimizing
antibiotic therapy and antibiotic stewardship is a mantra often chanted,
yet together they seldom get the necessary recognition as a common
denominator that mutually impacts departments hospital-wide.
Unfortunately, laboratories are not always typically perceived as
central actors who take the leading role to drive the overall
success of a hospital enterprise by facilitating a key paradigm shift in
antibiotic management. As a result, the inappropriate use of
antimicrobial agents in the form of under- or over-treatment of
infections is a common problem; and optimizing antibiotic therapy for
patients continues to pose a major challenge.1
What is the problem, and how did we get here?
Unnecessary use or overuse of antibiotics is
associated with significant increases in healthcare costs, hospital length
of stay, and the development of pathogens that are resistant to many types
of antibiotic therapy.2-4 The failure to promptly deliver
or quickly administer antibiotic therapy to patients with potentially
life-threatening infections is associated with increased morbidity and
mortality.5-8
To exacerbate the problem, hospital physicians are
confronted with patients every day who potentially have life-threatening
bloodstream infections. As a result, clinicians are typically forced to
decide which antibiotic, if any, should be administered to the patient. In
order to appropriately cover a wide variety of increasingly resistant
pathogens, broad-spectrum antibiotic therapy is frequently administered when
blood-culture results are reported as positive and an infection is
suspected.
Moreover, bacteremia is also a leading cause of
infection among hospitalized patients. Staphylococci are the most frequent
bloodstream isolates, accounting for more than 50 of positive bloodstream
cultures.9-10
Although coagulase negative staphylococci (CoNS) are commonly isolated from
blood, only a minority of such cultures represent true infection.11
Conversely, blood cultures growing Staphylococcus aureus almost
invariably signify true bacteremia and may be associated with severe
complications, including foci of secondary infection at distant sites such
as bones, joints, endovascular structures, and the central nervous system.
Furthermore, a majority of nosocomial S aureus bloodstream infections
are now caused by MRSA strains.10
Delay in the institution of appropriate therapy in
patients with S aureus sepsis may lead to catastrophic complications,
including bacterial seeding of deep tissues; such delays are associated with
increased hospital costs, length of hospitalization, and death.8,12,13
As more clinical and microbiological data becomes available, antimicrobial
therapy is narrowed or discontinued, yet — in the interim — antibiotic
stewardship yields to the practical and immediate need to essentially treat
the patient and administer a broad-spectrum of drugs before a proper
diagnosis is secured.
New approaches to improve antibiotic stewardship
Antibiotic administration practices have become a
major focus of antibiotic-stewardship quality-improvement programs at many
hospitals. The pressures to provide prompt and effective antibiotic therapy
to patients most likely to benefit from it while minimizing the unnecessary
use of antibiotics have spurred alternative approaches to improve antibiotic
stewardship.
One target of antibiotic-reduction efforts has been
the over-utilization of broad anti-staphylococcal agents, particularly
vancomycin. These antibiotics are generally started when a Gram-positive
infection is suspected on clinical grounds or when bacterial stain and/or
cultures show Gram-positive cocci. An important diagnostic and therapeutic
branch point occurs when clinicians try to differentiate true staphylococcal
bacteremia from blood-culture contamination. Physicians often prescribe an
anti-staphylococcal antibiotic for patients with blood cultures growing
Gram-positive cocci in clusters.
When using traditional laboratory techniques,
identification of the organism as S aureus, or the more benign CoNS
may take up to 48 hours. Earlier differentiation between S aureus and
CoNS facilitates implementation of more targeted antibiotic therapy and
improved overall antibiotic-stewardship programs. To truly change and
improve these programs, however, faster and more rapid diagnostics must be
integrated into laboratories — and their results must be more expeditiously
delivered to attending physicians — to facilitate this paradigm shift.
Enabling the paradigm shift
To address this need, clinical laboratories and
microbiologists are frequently relying on more rapid diagnostic tests to
detect S aureus and improve antibiotic stewardship. Given the time
and resource constraints facing microbiologists, very rapid methods for the
detection of S aureus-specific nucleic-acid sequences, such as
peptide nucleic-acid fluorescence in situ hybridization (PNA FISH),
are used. PNA FISH tests enable microbiology labs to provide rapid and
accurate identification of bloodstream pathogens directly from positive
blood cultures in hours instead of days, providing the following benefits:
- rapidly differentiate S aureus from CoNS in bloodstream
isolates; - allow faster diagnoses and more accurate antibiotic-therapy
selection; and - guide dramatic improvements in antibiotic stewardship that results
in improved patient outcomes
and healthcare-resource
utilization.
Antibiotic stewardship also depends on improved communication between
labs, treating clinicians
The communication of
laboratory results to the treating clinician closes the loop initiated
at the time of blood-culture draw. In a study of 509 episodes of
clinically significant bloodstream infections, therapeutic interventions
typically occurred at the time of phlebotomy and after notification of
Gram-stain results by telephone.14 The clinical value of
rapid diagnostic tests depends on an expeditious reporting of the
results to the treating clinician.15 The rapid reporting of
results, coupled with education regarding the implications of S
aureus
vs. CoNS, can significantly affect resource utilization and clinical
outcomes.
Forrest, et al, reported that in the context of an
antimicrobial utilization team, the use of a rapid diagnostic technique (PNA
FISH) to identify S aureus was associated with a significant
reduction in median length of hospital stay from six to four days (P<0.05;
95 confidence interval [CI], 0.95-1.87), a trend toward less use of
vancomycin, and a decrease in associated hospital costs of approximately
$4,000 per patient.16 Ly, et al, demonstrated that the rapid
reporting of S aureus PNA FISH results was associated with a
reduction in overall mortality (8 vs. 17; P=0.05) and in duration of
antibiotic use in patients with CoNS (median, 2.5 days; P=0.01).17
These studies suggest that an approach whereby
accurate microbiology data is rapidly generated, disseminated, interpreted,
and acted upon by a highly integrated healthcare team can leverage the
combination of rapid diagnostics and antibiotic stewardship to guide
therapy, enhance appropriate use of antibiotics, and improve patient
outcomes.
The optimization of antibiotic therapy in
hospitalized patients coupled with the need for improved antibiotic
stewardship will continue to be a major challenge that new assays and
procedures are beginning to meet in the laboratory.18 The coming
years are expected to bring further advances in the rapid detection of
bloodstream microbes and the identification of resistant strains. Optimizing
the effects of these advances will require the delivery of results from the
diagnostic laboratory to clinicians in a more timely fashion. Coupling
advances in diagnostic techniques with current and emerging communication
technology will facilitate this process.
As data accumulate regarding the effect on clinical
outcomes of rapid diagnostics and clinician notification, these strategies
are expected to replace the slower, traditional methods. To truly change and
improve these programs, however, faster and more rapid diagnostics must be
integrated in laboratories, and test results must be more expeditiously
delivered to attending physicians.
Joe Romano
is a consultant for AdvanDx (www.AdvanDx.com),
located in Woburn, MA, a company that develops simple and easy-to-use
diagnostic tests based on molecular technology platforms that utilize
genomic information to identify specific gene or species-specific sequences
in bacteria and yeast.
References
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