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Drug Resistance Index (DRI): A Tool for
Managing Antibiotic Resistance
Aditi A.
1,2
Sharma ,
1
Braykov ,
1,2
Pitchik ,
Nikolay
Helen
1,2,3
Ramanan Laxminarayan
Suraj
1,2
Pant ,
1.  Center for Disease Dynamics, Economics and Policy, 2. Public Health Foundation of India,
3. Princeton University
New Delhi, India
Background
With the rise of ‘superbugs,’ it has become clear, not just to
the medical profession, but also to those following media
stories, that antibiotics are losing effectiveness around the
world. Despite increased attention to the resistance
problem, there has been little progress in allocating
financial resources either to conserve the effectiveness of
existing drugs, or to incentivize the development of new
antibiotics. There are hundreds of bacteria-antibiotic
combinations, resistance patterns are in constant flux, and
some antibiotics are more important to preserve than
others. These factors make it difficult for a non-expert to
track the evolution of the antibiotic resistance problem.
The Drug Resistance Index (DRI) was developed as a
composite measure that combines the ability of antibiotics
to treat infections with the extent of their use in clinical
practice. The DRI helps quantify and communicate overall
changes in the effectiveness of the antibiotic arsenal within
a given setting (hospital, region, country) in a more intuitive
way.
Methodology
Assessing an intervention with the DRI
1.  The DRI should be comparable across time and location so
that it can be used to measure changes in drug
effectiveness over time across hospitals, regions, states or
countries.
2.  The DRI should be calculated with minimal data
requirements that include the maximum level of detail
(disaggregated by month or date, and by patient location).
Calculation involves two major components: proportion of
non-susceptible isolates and weighted antibiotic use.
Fixed-used
Adaptive
Two forms of the DRI are calculated: the fixed use (static) and
the adaptive (dynamic). Comparison of the two allows for the
assessment of the effectiveness of antimicrobial stewardship
interventions. ρtik is the proportion of resistance among
organism i to drug k at time t and q0ik is the weighted
antibiotic use of drug k used to treat organism i in the base
year of the analysis, while qtik tracks antibiotic use over time.
•  Antibiotic Resistance- measured by the susceptibility
information on clinical isolates tested at a facility’s lab.
What is the Drug Resistance Index
(DRI)?
The Drug Resistance Index (DRI) aggregates information
about antibiotic resistance and antibiotic use into a single
composite measure that quantifies the decay of antibiotic
effectiveness over time.
It is an epidemiological and communications tool to
convey trends in drug resistance to non-experts:
healthcare managers, policymakers, and media about
the overall extent and evolution of antibiotic resistance of
acute and non acute patient settings.
The DRI expresses the resistance*drug use relationship in a
scale from 0-1,
•  A value of 1 means that infections are untreatable
with any of the antibiotics used in the given setting.
•  A value of 0 means all isolates included in the
.
calculation were susceptible.
. •  Values in between express overall susceptibility of
infections, adjusted for local prescribing practices.
Figure 2: Antibiotic Resistance is calculated as the proportion of non-susceptible isolates over
the total number of isolates. The figure above demonstrates the proportion of non-susceptible
isolates in five different classes of antibiotic drugs. Categorical susceptibility results should be
aggregated by bacterial species and drug class of antibiotics. For the purposes of this study,
“Resistant” and “Non-susceptible” (Resistant +Intermediates) may be used interchangeably.
Data can be exported from WHONET or the laboratory information systems.
•  Weighted antibiotic use- Volume of antibiotics dispensed.
Figure 3: Antibiotic Use. The resistance of a pathogen to a specific drug should be weighted
by the extent to which that drug is used for treating the pathogen, in much the same way
that an inflation index weights the price of different commodities by the average share of
income devoted to them. This is calculated by looking at the proportion of use of a particular
drug as compared to all the drugs used. Defined Daily Dose (DDD) is the preferred unit of
measurement.
Figure 1: Sample DRI summarizes annual resistance of 3 species of
uropathogens to 5 antibiotic drug classes. DRI values are represented on a
scale from 0 to 1.
3.  The DRI should be simple for policymakers, the lay public
and non-infectious disease medical practitioners to
comprehend.
4.  The resistance index should be sensitive to changes in the
types of drugs being used.
Figure 4: The comparison of adaptive and fixed DRI reflects how effective antibiotics would have
been after new interventions and treatment options were introduced. Both fixed and adaptive DRIs
show resistance stopped increasing after 2004, when the introduction of MRSA universal screening
stabilized the proportion of drug-resistant Gram-positive organisms.
Introduction of linezolid in 2003 brings the adaptive DRI (blue line) down, as the powerful drug gives
physicians more treatment options. As its share of overall use is increasing, it contributes to lower DRI.
The fixed DRI (red line) does not reflect this decrease, as it is based on antibiotic usage in the baseline
year (1999), when there was no linezolid.
The Utility of the DRI
Clinicians and antimicrobial stewards:
•  Summarize trends for epidemiological reporting.
•  Measure overall effect of prescribing interventions on
resistance.
•  Utilize routinely generated data more efficiently.
Administrators and policymakers:
•  Benchmark performance against other DRI adopters to
guide resource allocation for stewardship or
improvements in infection control.
•  Aggregate at national/regional level to illustrate dearth of
new drugs and call for policy action.
Conclusions
•  Antibiotic resistance imposes a substantial public health
burden. Quantifying overall changes in resistance over
time and across locations is difficult because resistance
of pathogens to individual drugs must be aggregated to
assess overall burden. Here, we take a first step towards
the development of resistance indices, summarizing
resistance at the level of the infectious agent.
•  A DRI can be a valuable part of an antimicrobial
stewardship toolkit, helping clinicians tailor antibiotic
purchasing and prescribing policies to an individual
hospital’s resistance profile, and informing hospital
administrators about the relative success of different
interventions.
References
Laxminarayan
R, Klugman
KP. Communicating Trends(A) in
Figure 2. Dynamic imaging
of in vivo cell motility
by multiphoton intravital microscopy.
In
conventional one-photon microscopy, single high energy photons excite fluorophores from a ground state to
resistance
a drugreturns
resistance
index.
BMJ
2011.
an excited state.using
As the fluorophore
to its unexcited
ground state
dueOpen.
to vibrational
relaxation, it
emits fluorescence. During two-photon microscopy, two infrared photons, typically identical photons each
possessing half the energy required of one-photon microscopy, are absorbed simultaneously to excite the
fluorophore. Vibrational relaxation and fluorescent emission occur as in one-photon microscopy. (B) In twophoton microscopy, a titanium:sapphire laser releases short (~100 femtosecond), high-intensity pulses of
infrared light onto a thick specimen. Stacks of optical sections are generated, and serially reacquired.
These optical sections form z stacks, which can be then compiled into 3D images or movies. Cells may
then be tracked over time and motility parameters can be calculated.
Acknowledgements
We would like to thank the members of the Center for
Disease Dynamics, Economics and Policy and the Public
Health Foundation of India for their guidance and support.
This project was supported by the Global Antibiotic Resistance Partnership under a grant from the Bill & Melinda Gates Foundation and by the Extending the Cure project under a grant from the Robert Wood Johnson Foundation’s Pioneer Portfolio.