These functions can be used to calculate the (co-)resistance or susceptibility of microbial isolates (i.e. percentage of S, SI, I, IR or R). All functions support quasiquotation with pipes, can be used in `summarise()`

from the `dplyr`

package and also support grouped variables, see *Examples*.

`resistance()`

should be used to calculate resistance, `susceptibility()`

should be used to calculate susceptibility.

## Usage

```
resistance(..., minimum = 30, as_percent = FALSE, only_all_tested = FALSE)
susceptibility(..., minimum = 30, as_percent = FALSE, only_all_tested = FALSE)
sir_confidence_interval(
...,
ab_result = "R",
minimum = 30,
as_percent = FALSE,
only_all_tested = FALSE,
confidence_level = 0.95,
side = "both",
collapse = FALSE
)
proportion_R(..., minimum = 30, as_percent = FALSE, only_all_tested = FALSE)
proportion_IR(..., minimum = 30, as_percent = FALSE, only_all_tested = FALSE)
proportion_I(..., minimum = 30, as_percent = FALSE, only_all_tested = FALSE)
proportion_SI(..., minimum = 30, as_percent = FALSE, only_all_tested = FALSE)
proportion_S(..., minimum = 30, as_percent = FALSE, only_all_tested = FALSE)
proportion_df(
data,
translate_ab = "name",
language = get_AMR_locale(),
minimum = 30,
as_percent = FALSE,
combine_SI = TRUE,
confidence_level = 0.95
)
sir_df(
data,
translate_ab = "name",
language = get_AMR_locale(),
minimum = 30,
as_percent = FALSE,
combine_SI = TRUE,
confidence_level = 0.95
)
```

## Source

**M39 Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data, 5th Edition**, 2022, *Clinical and Laboratory Standards Institute (CLSI)*. https://clsi.org/standards/products/microbiology/documents/m39/.

## Arguments

- ...
one or more vectors (or columns) with antibiotic interpretations. They will be transformed internally with

`as.sir()`

if needed. Use multiple columns to calculate (the lack of) co-resistance: the probability where one of two drugs have a resistant or susceptible result. See*Examples*.- minimum
the minimum allowed number of available (tested) isolates. Any isolate count lower than

`minimum`

will return`NA`

with a warning. The default number of`30`

isolates is advised by the Clinical and Laboratory Standards Institute (CLSI) as best practice, see*Source*.- as_percent
a logical to indicate whether the output must be returned as a hundred fold with % sign (a character). A value of

`0.123456`

will then be returned as`"12.3%"`

.- only_all_tested
(for combination therapies, i.e. using more than one variable for

`...`

): a logical to indicate that isolates must be tested for all antibiotics, see section*Combination Therapy*below- ab_result
antibiotic results to test against, must be one or more values of "S", "I", or "R"

- confidence_level
the confidence level for the returned confidence interval. For the calculation, the number of S or SI isolates, and R isolates are compared with the total number of available isolates with R, S, or I by using

`binom.test()`

, i.e., the Clopper-Pearson method.- side
the side of the confidence interval to return. The default is

`"both"`

for a length 2 vector, but can also be (abbreviated as)`"min"`

/`"left"`

/`"lower"`

/`"less"`

or`"max"`

/`"right"`

/`"higher"`

/`"greater"`

.- collapse
a logical to indicate whether the output values should be 'collapsed', i.e. be merged together into one value, or a character value to use for collapsing

- data
a data.frame containing columns with class

`sir`

(see`as.sir()`

)- translate_ab
a column name of the antibiotics data set to translate the antibiotic abbreviations to, using

`ab_property()`

- language
language of the returned text - the default is the current system language (see

`get_AMR_locale()`

) and can also be set with the package option`AMR_locale`

. Use`language = NULL`

or`language = ""`

to prevent translation.- combine_SI
a logical to indicate whether all values of S and I must be merged into one, so the output only consists of S+I vs. R (susceptible vs. resistant) - the default is

`TRUE`

## Details

The function `resistance()`

is equal to the function `proportion_R()`

. The function `susceptibility()`

is equal to the function `proportion_SI()`

.

Use `sir_confidence_interval()`

to calculate the confidence interval, which relies on `binom.test()`

, i.e., the Clopper-Pearson method. This function returns a vector of length 2 at default for antimicrobial *resistance*. Change the `side`

argument to "left"/"min" or "right"/"max" to return a single value, and change the `ab_result`

argument to e.g. `c("S", "I")`

to test for antimicrobial *susceptibility*, see Examples.

**Remember that you should filter your data to let it contain only first isolates!** This is needed to exclude duplicates and to reduce selection bias. Use `first_isolate()`

to determine them in your data set with one of the four available algorithms.

These functions are not meant to count isolates, but to calculate the proportion of resistance/susceptibility. Use the `count()`

functions to count isolates. The function `susceptibility()`

is essentially equal to `count_susceptible() / count_all()`

. *Low counts can influence the outcome - the proportion functions may camouflage this, since they only return the proportion (albeit being dependent on the minimum argument).*

The function `proportion_df()`

takes any variable from `data`

that has an `sir`

class (created with `as.sir()`

) and calculates the proportions S, I, and R. It also supports grouped variables. The function `sir_df()`

works exactly like `proportion_df()`

, but adds the number of isolates.

## Combination Therapy

When using more than one variable for `...`

(= combination therapy), use `only_all_tested`

to only count isolates that are tested for all antibiotics/variables that you test them for. See this example for two antibiotics, Drug A and Drug B, about how `susceptibility()`

works to calculate the %SI:

```
--------------------------------------------------------------------
= FALSE only_all_tested = TRUE
only_all_tested ----------------------- -----------------------
Drug A Drug B include as include as include as include as
numerator denominator numerator denominator-------- -------- ---------- ----------- ---------- -----------
S or I S or I X X X X
R S or I X X X X<NA> S or I X X - -
S or I R X X X X- X - X
R R <NA> R - - - -
<NA> X X - -
S or I <NA> - - - -
R <NA> <NA> - - - -
--------------------------------------------------------------------
```

Please note that, in combination therapies, for `only_all_tested = TRUE`

applies that:

```
count_S() + count_I() + count_R() = count_all()
proportion_S() + proportion_I() + proportion_R() = 1
```

and that, in combination therapies, for `only_all_tested = FALSE`

applies that:

```
count_S() + count_I() + count_R() >= count_all()
proportion_S() + proportion_I() + proportion_R() >= 1
```

Using `only_all_tested`

has no impact when only using one antibiotic as input.

## Interpretation of SIR

In 2019, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) has decided to change the definitions of susceptibility testing categories S, I, and R as shown below (https://www.eucast.org/newsiandr/):

**S - Susceptible, standard dosing regimen**

A microorganism is categorised as "Susceptible, standard dosing regimen", when there is a high likelihood of therapeutic success using a standard dosing regimen of the agent.**I - Susceptible, increased exposure**" when there is a high likelihood of therapeutic success because exposure to the agent is increased by adjusting the dosing regimen or by its concentration at the site of infection.

A microorganism is categorised as "Susceptible, Increased exposure**R = Resistant**

A microorganism is categorised as "Resistant" when there is a high likelihood of therapeutic failure even when there is increased exposure.*Exposure*is a function of how the mode of administration, dose, dosing interval, infusion time, as well as distribution and excretion of the antimicrobial agent will influence the infecting organism at the site of infection.

This AMR package honours this insight. Use `susceptibility()`

(equal to `proportion_SI()`

) to determine antimicrobial susceptibility and `count_susceptible()`

(equal to `count_SI()`

) to count susceptible isolates.

## See also

`count()`

to count resistant and susceptible isolates.

## Examples

```
# example_isolates is a data set available in the AMR package.
# run ?example_isolates for more info.
example_isolates
#> # A tibble: 2,000 × 46
#> date patient age gender ward mo PEN OXA FLC AMX
#> <date> <chr> <dbl> <chr> <chr> <mo> <sir> <sir> <sir> <sir>
#> 1 2002-01-02 A77334 65 F Clinical B_ESCHR_COLI R NA NA NA
#> 2 2002-01-03 A77334 65 F Clinical B_ESCHR_COLI R NA NA NA
#> 3 2002-01-07 067927 45 F ICU B_STPHY_EPDR R NA R NA
#> 4 2002-01-07 067927 45 F ICU B_STPHY_EPDR R NA R NA
#> 5 2002-01-13 067927 45 F ICU B_STPHY_EPDR R NA R NA
#> 6 2002-01-13 067927 45 F ICU B_STPHY_EPDR R NA R NA
#> 7 2002-01-14 462729 78 M Clinical B_STPHY_AURS R NA S R
#> 8 2002-01-14 462729 78 M Clinical B_STPHY_AURS R NA S R
#> 9 2002-01-16 067927 45 F ICU B_STPHY_EPDR R NA R NA
#> 10 2002-01-17 858515 79 F ICU B_STPHY_EPDR R NA S NA
#> # ℹ 1,990 more rows
#> # ℹ 36 more variables: AMC <sir>, AMP <sir>, TZP <sir>, CZO <sir>, FEP <sir>,
#> # CXM <sir>, FOX <sir>, CTX <sir>, CAZ <sir>, CRO <sir>, GEN <sir>,
#> # TOB <sir>, AMK <sir>, KAN <sir>, TMP <sir>, SXT <sir>, NIT <sir>,
#> # FOS <sir>, LNZ <sir>, CIP <sir>, MFX <sir>, VAN <sir>, TEC <sir>,
#> # TCY <sir>, TGC <sir>, DOX <sir>, ERY <sir>, CLI <sir>, AZM <sir>,
#> # IPM <sir>, MEM <sir>, MTR <sir>, CHL <sir>, COL <sir>, MUP <sir>, …
# base R ------------------------------------------------------------
# determines %R
resistance(example_isolates$AMX)
#> [1] 0.5955556
sir_confidence_interval(example_isolates$AMX)
#> [1] 0.5688204 0.6218738
sir_confidence_interval(example_isolates$AMX,
confidence_level = 0.975
)
#> [1] 0.5650148 0.6255670
sir_confidence_interval(example_isolates$AMX,
confidence_level = 0.975,
collapse = ", "
)
#> [1] "0.565, 0.626"
# determines %S+I:
susceptibility(example_isolates$AMX)
#> [1] 0.4044444
sir_confidence_interval(example_isolates$AMX,
ab_result = c("S", "I")
)
#> [1] 0.3781262 0.4311796
# be more specific
proportion_S(example_isolates$AMX)
#> [1] 0.4022222
proportion_SI(example_isolates$AMX)
#> [1] 0.4044444
proportion_I(example_isolates$AMX)
#> [1] 0.002222222
proportion_IR(example_isolates$AMX)
#> [1] 0.5977778
proportion_R(example_isolates$AMX)
#> [1] 0.5955556
# dplyr -------------------------------------------------------------
# \donttest{
if (require("dplyr")) {
example_isolates %>%
group_by(ward) %>%
summarise(
r = resistance(CIP),
n = n_sir(CIP)
) # n_sir works like n_distinct in dplyr, see ?n_sir
}
#> # A tibble: 3 × 3
#> ward r n
#> <chr> <dbl> <int>
#> 1 Clinical 0.147 869
#> 2 ICU 0.190 447
#> 3 Outpatient 0.161 93
if (require("dplyr")) {
example_isolates %>%
group_by(ward) %>%
summarise(
cipro_R = resistance(CIP),
ci_min = sir_confidence_interval(CIP, side = "min"),
ci_max = sir_confidence_interval(CIP, side = "max"),
)
}
#> # A tibble: 3 × 4
#> ward cipro_R ci_min ci_max
#> <chr> <dbl> <dbl> <dbl>
#> 1 Clinical 0.147 0.124 0.173
#> 2 ICU 0.190 0.155 0.230
#> 3 Outpatient 0.161 0.0932 0.252
if (require("dplyr")) {
# scoped dplyr verbs with antibiotic selectors
# (you could also use across() of course)
example_isolates %>%
group_by(ward) %>%
summarise_at(
c(aminoglycosides(), carbapenems()),
resistance
)
}
#> ℹ For aminoglycosides() using columns 'GEN' (gentamicin), 'TOB'
#> (tobramycin), 'AMK' (amikacin), and 'KAN' (kanamycin)
#> ℹ For carbapenems() using columns 'IPM' (imipenem) and 'MEM' (meropenem)
#> Warning: There was 1 warning in `summarise()`.
#> ℹ In argument: `KAN = (function (..., minimum = 30, as_percent = FALSE,
#> only_all_tested = FALSE) ...`.
#> ℹ In group 3: `ward = "Outpatient"`.
#> Caused by warning:
#> ! Introducing NA: only 23 results available for KAN in group: ward =
#> "Outpatient" (minimum = 30).
#> # A tibble: 3 × 7
#> ward GEN TOB AMK KAN IPM MEM
#> <chr> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl>
#> 1 Clinical 0.229 0.315 0.626 1 0.0498 0.0458
#> 2 ICU 0.290 0.400 0.662 1 0.0862 0.0894
#> 3 Outpatient 0.2 0.368 0.605 NA 0.0541 0.0541
if (require("dplyr")) {
example_isolates %>%
group_by(ward) %>%
summarise(
R = resistance(CIP, as_percent = TRUE),
SI = susceptibility(CIP, as_percent = TRUE),
n1 = count_all(CIP), # the actual total; sum of all three
n2 = n_sir(CIP), # same - analogous to n_distinct
total = n()
) # NOT the number of tested isolates!
# Calculate co-resistance between amoxicillin/clav acid and gentamicin,
# so we can see that combination therapy does a lot more than mono therapy:
example_isolates %>% susceptibility(AMC) # %SI = 76.3%
example_isolates %>% count_all(AMC) # n = 1879
example_isolates %>% susceptibility(GEN) # %SI = 75.4%
example_isolates %>% count_all(GEN) # n = 1855
example_isolates %>% susceptibility(AMC, GEN) # %SI = 94.1%
example_isolates %>% count_all(AMC, GEN) # n = 1939
# See Details on how `only_all_tested` works. Example:
example_isolates %>%
summarise(
numerator = count_susceptible(AMC, GEN),
denominator = count_all(AMC, GEN),
proportion = susceptibility(AMC, GEN)
)
example_isolates %>%
summarise(
numerator = count_susceptible(AMC, GEN, only_all_tested = TRUE),
denominator = count_all(AMC, GEN, only_all_tested = TRUE),
proportion = susceptibility(AMC, GEN, only_all_tested = TRUE)
)
example_isolates %>%
group_by(ward) %>%
summarise(
cipro_p = susceptibility(CIP, as_percent = TRUE),
cipro_n = count_all(CIP),
genta_p = susceptibility(GEN, as_percent = TRUE),
genta_n = count_all(GEN),
combination_p = susceptibility(CIP, GEN, as_percent = TRUE),
combination_n = count_all(CIP, GEN)
)
# Get proportions S/I/R immediately of all sir columns
example_isolates %>%
select(AMX, CIP) %>%
proportion_df(translate = FALSE)
# It also supports grouping variables
# (use sir_df to also include the count)
example_isolates %>%
select(ward, AMX, CIP) %>%
group_by(ward) %>%
sir_df(translate = FALSE)
}
#> # A tibble: 12 × 7
#> ward antibiotic interpretation value ci_min ci_max isolates
#> * <chr> <chr> <ord> <dbl> <dbl> <dbl> <int>
#> 1 Clinical AMX SI 0.423 0.389 0.457 357
#> 2 Clinical AMX R 0.577 0.543 0.611 487
#> 3 Clinical CIP SI 0.853 0.827 0.876 741
#> 4 Clinical CIP R 0.147 0.124 0.173 128
#> 5 ICU AMX SI 0.369 0.323 0.417 158
#> 6 ICU AMX R 0.631 0.583 0.677 270
#> 7 ICU CIP SI 0.810 0.770 0.845 362
#> 8 ICU CIP R 0.190 0.155 0.230 85
#> 9 Outpatient AMX SI 0.397 0.288 0.515 31
#> 10 Outpatient AMX R 0.603 0.485 0.712 47
#> 11 Outpatient CIP SI 0.839 0.748 0.907 78
#> 12 Outpatient CIP R 0.161 0.0932 0.252 15
# }
```