diff --git a/404.html b/404.html index e649de219..9b9a9b1a8 100644 --- a/404.html +++ b/404.html @@ -31,7 +31,7 @@ AMR (for R) - 2.1.1.9263 + 2.1.1.9266 + + + + + +
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Introduction +

+

Clinical guidelines for empirical antimicrobial therapy require +probabilistic reasoning: what is the chance that a regimen will +cover the likely infecting organisms, before culture results are +available?

+

This is the purpose of WISCA, or:

+
+

Weighted-Incidence Syndromic Combination +Antibiogram

+
+

WISCA is a Bayesian approach that integrates: - Pathogen +prevalence (how often each species causes the syndrome), - +Regimen susceptibility (how often a regimen works +if the pathogen is known),

+

to estimate the overall empirical coverage of +antimicrobial regimens — with quantified uncertainty.

+

This vignette explains how WISCA works, why it is useful, and how to +apply it in AMR.

+
+
+
+

Why traditional antibiograms fall short +

+

A standard antibiogram gives you:

+

``` Species → Antibiotic → Susceptibility %

+

But clinicians don’t know the species a priori. They need to +choose a regimen that covers the likely pathogens — +without knowing which one is present.

+

Traditional antibiograms: - Fragment information by organism, - Do +not weight by real-world prevalence, - Do not account for combination +therapy or sample size, - Do not provide uncertainty.

+
+
+
+

The idea of WISCA +

+

WISCA asks:

+
+

“What is the probability that this regimen +will cover the pathogen, given the syndrome?”

+
+

This means combining two things: - Incidence of each +pathogen in the syndrome, - Susceptibility of each +pathogen to the regimen.

+

We can write this as:

+

``` coverage = ∑ (pathogen incidence × susceptibility)

+

For example, suppose: - E. coli causes 60% of cases, and 90% of +E. coli are susceptible to a drug. - Klebsiella causes 40% of +cases, and 70% of Klebsiella are susceptible.

+

Then:

+

``` coverage = (0.6 × 0.9) + (0.4 × 0.7) = 0.82

+

But in real data, incidence and susceptibility are estimated +from samples — so they carry uncertainty. WISCA models this +probabilistically, using conjugate Bayesian +distributions.

+
+
+
+

The Bayesian engine behind WISCA +

+
+

Pathogen incidence +

+

Let: - K be the number of pathogens, - +α = (1, 1, ..., 1) be a **Dirichlet** prior (uniform), - n += (n₁, …, nₖ) be the observed counts per species.

+

Then the posterior incidence follows:

+

``` incidence ∼ Dirichlet(α + n)

+

In simulations, we draw from this posterior using:

+

``` xᵢ ∼ Gamma(αᵢ + nᵢ, 1)

+

``` incidenceᵢ = xᵢ / ∑ xⱼ

+
+
+
+

Susceptibility +

+

Each pathogen–regimen pair has: - prior: Beta(1, 1) - +data: S susceptible out of N tested

+

Then:

+

``` susceptibility ∼ Beta(1 + S, 1 + (N - S))

+

In each simulation, we draw random susceptibility per species from +this Beta distribution.

+
+
+
+

Final coverage estimate +

+

Putting it together:

+

``` For each simulation: - Draw incidence ∼ Dirichlet - Draw +susceptibility ∼ Beta - Multiply → coverage estimate

+

We repeat this (e.g. 1000×) and summarise: - Mean: +expected coverage - Quantiles: credible interval +(default 95%)

+
+
+
+
+

Practical use in AMR +

+
+

Simulate a synthetic syndrome +

+
+library(AMR)
+data <- example_isolates
+
+# Add a fake syndrome column for stratification
+data$syndrome <- ifelse(data$mo %like% "coli", "UTI", "Other")
+
+
+

Basic WISCA antibiogram +

+
+antibiogram(data,
+            wisca = TRUE)
+ ++++++++++++++++++++++++++++++++++++++++++ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
AmikacinAmoxicillinAmoxicillin/clavulanic acidAmpicillinAzithromycinBenzylpenicillinCefazolinCefepimeCefotaximeCefoxitinCeftazidimeCeftriaxoneCefuroximeChloramphenicolCiprofloxacinClindamycinColistinDoxycyclineErythromycinFlucloxacillinFosfomycinGentamicinImipenemKanamycinLinezolidMeropenemMetronidazoleMoxifloxacinMupirocinNitrofurantoinOxacillinPiperacillin/tazobactamRifampicinTeicoplaninTetracyclineTigecyclineTobramycinTrimethoprimTrimethoprim/sulfamethoxazoleVancomycin
41.7% (37.2-47.5%)35.7% (33.3-38.2%)73.7% (71.7-75.8%)35.8% (33.6-38.1%)43.8% (41.5-46%)28.2% (25.8-30.8%)69.3% (64.9-73.8%)74.8% (70.5-78.8%)73.3% (69.2-77.3%)69.6% (65.5-73.7%)35.9% (33.6-38.2%)73.3% (68.9-77.2%)71.9% (69.8-74%)64.9% (51.7-78.5%)77% (74.5-79.6%)47.3% (44.7-49.6%)33% (30.8-35.1%)63.6% (52.1-74.9%)43.7% (41.6-46%)59.3% (47-71%)60.5% (55.5-65.8%)72.7% (70.7-74.8%)78.2% (74-82.2%)25.6% (13.5-37.7%)54.9% (50.4-59%)77.1% (72.8-81.2%)56.1% (39.5-70.7%)49.6% (43.6-55.6%)65.2% (52.7-78.1%)76.5% (69.4-82.3%)57.8% (45.4-69.6%)69.4% (64.2-74.2%)52.4% (47.6-56.8%)48.1% (43.4-52.9%)61.4% (53.6-70.5%)81.9% (78.1-85.5%)60.7% (57.8-63.5%)61% (58.8-63.5%)76.5% (74.5-78.5%)61.9% (59.8-64.2%)
+
+
+

Stratify by syndrome +

+
+antibiogram(data,
+            syndromic_group = "syndrome",
+            wisca = TRUE)
+ +++++++++++++++++++++++++++++++++++++++++++ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Syndromic GroupAmikacinAmoxicillinAmoxicillin/clavulanic acidAmpicillinAzithromycinBenzylpenicillinCefazolinCefepimeCefotaximeCefoxitinCeftazidimeCeftriaxoneCefuroximeChloramphenicolCiprofloxacinClindamycinColistinDoxycyclineErythromycinFlucloxacillinFosfomycinGentamicinImipenemKanamycinLinezolidMeropenemMetronidazoleMoxifloxacinMupirocinNitrofurantoinOxacillinPiperacillin/tazobactamRifampicinTeicoplaninTetracyclineTigecyclineTobramycinTrimethoprimTrimethoprim/sulfamethoxazoleVancomycin
Other25% (20.2-31.7%)31.6% (28.7-34%)70.1% (67.7-72.4%)31.6% (29.1-34.1%)56.4% (53.8-58.8%)36.3% (33.1-39.4%)61.5% (55.7-66.5%)68.5% (63.4-73.8%)66.7% (61.4-71.9%)63% (57.7-68.6%)18.3% (15.9-20.8%)66.6% (61.4-71.5%)65.5% (62.7-68%)69.6% (60-77.2%)74% (70.8-77.2%)60.9% (58.1-63.6%)13.9% (11.8-15.8%)67.4% (63.7-70.9%)56.4% (54-58.9%)61.4% (56-67.6%)49.6% (43.2-56.3%)65.6% (62.8-68.1%)71.8% (66.7-77%)18.6% (13.1-25.9%)70.8% (65.1-75.8%)70.6% (65.1-75.7%)49.8% (34.2-66.6%)63.3% (56.2-70.3%)69.8% (62.6-76.4%)70.5% (61.2-77.5%)60% (54.4-65.4%)62.4% (56.4-68.6%)67.6% (61.9-73.2%)61.9% (55.4-67.6%)67.8% (64.8-70.6%)77% (72.3-81.8%)50.1% (46.7-53.6%)61.1% (58.4-64%)78.8% (76.4-80.9%)79.6% (77.4-81.8%)
UTI91.5% (88.8-93.5%)50% (45.5-54.6%)80.9% (77.8-84%)49.9% (45.6-54.3%)8.2% (6.4-10.5%)8.2% (6.3-10.3%)88.9% (84.2-92.3%)89.4% (86.5-91.8%)89.9% (87.4-92.1%)86.1% (82.9-88.9%)89.8% (87.2-91.9%)89.8% (87.1-92.1%)87.4% (84.5-89.8%)NA81.4% (78.3-84.3%)8.2% (6.3-10.4%)91.7% (89.6-93.8%)NA8.1% (6.3-10.4%)NA90.6% (86.5-93.3%)90.2% (87.9-92.2%)91.8% (89.7-93.8%)NA8.1% (6.1-10.2%)91.8% (89.6-93.8%)71.4% (31.8-91.6%)9.3% (6.7-13.3%)NA89.4% (86.9-91.7%)NA87.2% (84.4-89.6%)8.2% (6.3-10.4%)8.2% (6.3-10.3%)41.2% (14.3-74.4%)90.9% (87.7-93.3%)89.6% (87.1-91.8%)59.1% (54.7-63.4%)65.3% (61.3-69.2%)8.2% (6.2-10.3%)
+
+
+

Use combination regimens +

+

The antibiogram() function supports combination +regimens:

+
+antibiogram(data,
+            antimicrobials = c("AMC", "GEN", "AMC + GEN", "CIP"),
+            wisca = TRUE)
+ ++++++ + + + + + + + + + + + + +
Amoxicillin/clavulanic acidAmoxicillin/clavulanic acid + GentamicinCiprofloxacinGentamicin
73.8% (71.7-75.8%)89.7% (88.2-91.2%)77% (74.3-79.6%)72.8% (70.6-74.9%)
+
+
+
+
+

Interpretation +

+

Suppose you get this output:

+ + + + + + + + + + + + + + + + + + + + + +
RegimenCoverageLower_CIUpper_CI
AMC0.720.650.78
AMC + GEN0.880.830.93
+

Interpretation:

+
+

“AMC + GEN covers 88% of expected pathogens for this syndrome, +with 95% certainty that the true coverage lies between 83% and +93%.”

+
+

Regimens with few tested isolates will show wider +intervals.

+
+
+
+

Sensible defaults, but you can customise +

+
    +
  • +minimum = 30: exclude regimens with <30 isolates +tested.
  • +
  • +simulations = 1000: number of Monte Carlo samples.
  • +
  • +conf_interval = 0.95: coverage interval width.
  • +
  • +combine_SI = TRUE: count “I”/“SDD” as susceptible.
  • +
+
+
+
+

Limitations +

+
    +
  • WISCA does not model time trends or temporal resistance shifts.
  • +
  • It assumes data are representative of current clinical +practice.
  • +
  • It does not account for patient-level covariates (yet).
  • +
  • Species-specific data are abstracted into syndrome-level +estimates.
  • +
+
+
+
+

Reference +

+

Bielicki JA et al. (2016).
Weighted-incidence syndromic combination antibiograms to guide +empiric treatment in pediatric bloodstream infections.
J Antimicrob Chemother, 71(2):529–536. doi:10.1093/jac/dkv397

+
+
+
+

Conclusion +

+

WISCA shifts empirical therapy from simple percent susceptible toward +probabilistic, syndrome-based decision support. It is a +statistically principled, clinically intuitive method to guide regimen +selection — and easy to use via the antibiogram() function +in the AMR package.

+

For antimicrobial stewardship teams, it enables +disease-specific, reproducible, and data-driven +guidance — even in the face of sparse data.

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+ + + + +
+ + + + + + + diff --git a/articles/datasets.html b/articles/datasets.html index 1cf630113..d5b72d8b4 100644 --- a/articles/datasets.html +++ b/articles/datasets.html @@ -30,7 +30,7 @@ AMR (for R) - 2.1.1.9263 + 2.1.1.9266 - - - - - -
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Note: to keep the package size as small as possible, we only include -this vignette on CRAN. You can read more vignettes on our website about -how to conduct AMR data analysis, determine MDROs, find explanation of -EUCAST and CLSI breakpoints, and much more: https://amr-for-r.org.

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-

The AMR package is a peer-reviewed, free and open-source R -package with zero -dependencies to simplify the analysis and prediction of -Antimicrobial Resistance (AMR) and to work with microbial and -antimicrobial data and properties, by using evidence-based methods. -Our aim is to provide a standard for clean and -reproducible AMR data analysis, that can therefore empower -epidemiological analyses to continuously enable surveillance and -treatment evaluation in any setting. We are a team of many different researchers -from around the globe to make this a successful and durable project!

-

This work was published in the Journal of Statistical Software -(Volume 104(3); ) and formed the basis of two PhD theses ( and ).

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After installing this package, R knows ~79 -000 distinct microbial species (updated June 2024) and all -~620 -antimicrobial and antiviral drugs by name and code -(including ATC, EARS-Net, ASIARS-Net, PubChem, LOINC and SNOMED CT), and -knows all about valid SIR and MIC values. The integral clinical -breakpoint guidelines from CLSI 2011-2025 and EUCAST 2011-2025 are -included, even with epidemiological cut-off (ECOFF) values. It supports -and can read any data format, including WHONET data. This package works -on Windows, macOS and Linux with all versions of R since R-3.0 (April -2013). It was designed to work in any setting, including those -with very limited resources. It was created for both routine -data analysis and academic research at the Faculty of Medical Sciences -of the University of Groningen and the -University Medical Center -Groningen.

-

The AMR package is available in English, Chinese, Czech, -Danish, Dutch, Finnish, French, German, Greek, Italian, Japanese, -Norwegian, Polish, Portuguese, Romanian, Russian, Spanish, Swedish, -Turkish, and Ukrainian. Antimicrobial drug (group) names and colloquial -microorganism names are provided in these languages.

-

This package was intended as a comprehensive toolbox for integrated -AMR data analysis. This package can be used for:

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    -
  • Reference for the taxonomy of microorganisms, since the package -contains all microbial (sub)species from the List of Prokaryotic names -with Standing in Nomenclature (LPSN) and the Global Biodiversity -Information Facility (GBIF) (manual)
  • -
  • Interpreting raw MIC and disk diffusion values, based on any CLSI or -EUCAST guideline (manual)
  • -
  • Retrieving antimicrobial drug names, doses and forms of -administration from clinical health care records (manual)
  • -
  • Determining first isolates to be used for AMR data analysis (manual)
  • -
  • Calculating antimicrobial resistance (tutorial)
  • -
  • Determining multi-drug resistance (MDR) / multi-drug resistant -organisms (MDRO) (tutorial)
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  • Calculating (empirical) susceptibility of both mono therapy and -combination therapies (tutorial)
  • -
  • Apply AMR function in predictive modelling (tutorial)
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  • Getting properties for any microorganism (like Gram stain, species, -genus or family) (manual)
  • -
  • Getting properties for any antimicrobial (like name, code of -EARS-Net/ATC/LOINC/PubChem, defined daily dose or trade name) (manual)
  • -
  • Plotting antimicrobial resistance (tutorial)
  • -
  • Applying EUCAST expert rules (manual)
  • -
  • Getting SNOMED codes of a microorganism, or getting properties of a -microorganism based on a SNOMED code (manual)
  • -
  • Getting LOINC codes of an antibiotic, or getting properties of an -antibiotic based on a LOINC code (manual)
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  • Machine reading the EUCAST and CLSI guidelines from 2011-2021 to -translate MIC values and disk diffusion diameters to SIR (link)
  • -
  • Principal component analysis for AMR (tutorial)
  • -
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All reference data sets in the AMR package - including information on -microorganisms, antimicrobials, and clinical breakpoints - are freely -available for download in multiple formats: R, MS Excel, Apache Feather, -Apache Parquet, SPSS, and Stata.

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For maximum compatibility, we also provide machine-readable, -tab-separated plain text files suitable for use in any software, -including laboratory information systems.

-

Visit our -website for direct download links, or explore the actual files in our -GitHub repository.

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-

This AMR package for R is free, open-source software and -licensed under the GNU -General Public License v2.0 (GPL-2). These requirements are -consequently legally binding: modifications must be released under the -same license when distributing the package, changes made to the code -must be documented, source code must be made available when the package -is distributed, and a copy of the license and copyright notice must be -included with the package.

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- - - - - - - diff --git a/authors.html b/authors.html index 487d4b7b4..ddba195cf 100644 --- a/authors.html +++ b/authors.html @@ -7,7 +7,7 @@ AMR (for R) - 2.1.1.9263 + 2.1.1.9266