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
++
Practical use in AMR +
+ +Basic WISCA antibiogram +
+
+antibiogram(data,
+ wisca = TRUE)
Amikacin | +Amoxicillin | +Amoxicillin/clavulanic acid | +Ampicillin | +Azithromycin | +Benzylpenicillin | +Cefazolin | +Cefepime | +Cefotaxime | +Cefoxitin | +Ceftazidime | +Ceftriaxone | +Cefuroxime | +Chloramphenicol | +Ciprofloxacin | +Clindamycin | +Colistin | +Doxycycline | +Erythromycin | +Flucloxacillin | +Fosfomycin | +Gentamicin | +Imipenem | +Kanamycin | +Linezolid | +Meropenem | +Metronidazole | +Moxifloxacin | +Mupirocin | +Nitrofurantoin | +Oxacillin | +Piperacillin/tazobactam | +Rifampicin | +Teicoplanin | +Tetracycline | +Tigecycline | +Tobramycin | +Trimethoprim | +Trimethoprim/sulfamethoxazole | +Vancomycin | +
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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 Group | +Amikacin | +Amoxicillin | +Amoxicillin/clavulanic acid | +Ampicillin | +Azithromycin | +Benzylpenicillin | +Cefazolin | +Cefepime | +Cefotaxime | +Cefoxitin | +Ceftazidime | +Ceftriaxone | +Cefuroxime | +Chloramphenicol | +Ciprofloxacin | +Clindamycin | +Colistin | +Doxycycline | +Erythromycin | +Flucloxacillin | +Fosfomycin | +Gentamicin | +Imipenem | +Kanamycin | +Linezolid | +Meropenem | +Metronidazole | +Moxifloxacin | +Mupirocin | +Nitrofurantoin | +Oxacillin | +Piperacillin/tazobactam | +Rifampicin | +Teicoplanin | +Tetracycline | +Tigecycline | +Tobramycin | +Trimethoprim | +Trimethoprim/sulfamethoxazole | +Vancomycin | +
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Other | +25% (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%) | +
UTI | +91.5% (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%) | +NA | +81.4% (78.3-84.3%) | +8.2% (6.3-10.4%) | +91.7% (89.6-93.8%) | +NA | +8.1% (6.3-10.4%) | +NA | +90.6% (86.5-93.3%) | +90.2% (87.9-92.2%) | +91.8% (89.7-93.8%) | +NA | +8.1% (6.1-10.2%) | +91.8% (89.6-93.8%) | +71.4% (31.8-91.6%) | +9.3% (6.7-13.3%) | +NA | +89.4% (86.9-91.7%) | +NA | +87.2% (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 acid | +Amoxicillin/clavulanic acid + Gentamicin | +Ciprofloxacin | +Gentamicin | +
---|---|---|---|
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:
+Regimen | +Coverage | +Lower_CI | +Upper_CI | +
---|---|---|---|
AMC | +0.72 | +0.65 | +0.78 | +
AMC + GEN | +0.88 | +0.83 | +0.93 | +
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.
+