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# Determine Multidrug-Resistant Organisms (MDRO)

Source: `R/mdro.R`
`mdro.Rd`

Determine which isolates are multidrug-resistant organisms (MDRO) according to international, national, or custom guidelines.

## Usage

    mdro(
      x = NULL,
      guideline = "CMI 2012",
      col_mo = NULL,
      esbl = NA,
      carbapenemase = NA,
      mecA = NA,
      mecC = NA,
      vanA = NA,
      vanB = NA,
      info = interactive(),
      pct_required_classes = 0.5,
      combine_SI = TRUE,
      verbose = FALSE,
      only_sir_columns = any(is.sir(x)),
      infer_from_combinations = TRUE,
      ...
    )

    brmo(x = NULL, only_sir_columns = any(is.sir(x)), ...)

    mrgn(x = NULL, only_sir_columns = any(is.sir(x)), verbose = FALSE, ...)

    mdr_tb(x = NULL, only_sir_columns = any(is.sir(x)), verbose = FALSE, ...)

    mdr_cmi2012(x = NULL, only_sir_columns = any(is.sir(x)), verbose = FALSE, ...)

    eucast_exceptional_phenotypes(
      x = NULL,
      only_sir_columns = any(is.sir(x)),
      verbose = FALSE,
      ...
    )

## Arguments

x

  A data.frame with antimicrobials columns, like `AMX` or `amox`. Can be left blank for automatic determination.

guideline

  A specific guideline to follow, see sections Supported International / National Guidelines and Using Custom Guidelines below. When left empty, the publication by Magiorakos et al. (see below) will be followed.

col_mo

  Column name of the names or codes of the microorganisms (see `as.mo()`) - the default is the first column of class `mo`. Values will be coerced using `as.mo()`.

esbl

  logical values, or a column name containing logical values, indicating the presence of an ESBL gene (or production of its proteins).

carbapenemase

  logical values, or a column name containing logical values, indicating the presence of a carbapenemase gene (or production of its proteins).

mecA

  logical values, or a column name containing logical values, indicating the presence of a mecA gene (or production of its proteins).

mecC

  logical values, or a column name containing logical values, indicating the presence of a mecC gene (or production of its proteins).

vanA

  logical values, or a column name containing logical values, indicating the presence of a vanA gene (or production of its proteins).

vanB

  logical values, or a column name containing logical values, indicating the presence of a vanB gene (or production of its proteins).

info

  A logical to indicate whether progress should be printed to the console - the default is only print while in interactive sessions.

pct_required_classes

  Minimal required percentage of antimicrobial classes that must be available per isolate, rounded down. For example, with the default guideline, 17 antimicrobial classes must be available for S. aureus. Setting this `pct_required_classes` argument to `0.5` (default) means that for every S. aureus isolate at least 8 different classes must be available. Any lower number of available classes will return `NA` for that isolate.

combine_SI

  A logical to indicate whether all values of S and I must be merged into one, so resistance is only considered when isolates are R, not I. As this is the default behaviour of the `mdro()` function, it follows the redefinition by EUCAST about the interpretation of I (increased exposure) in 2019, see section 'Interpretation of S, I and R' below. When using `combine_SI = FALSE`, resistance is considered when isolates are R or I.

verbose

  A logical to turn Verbose mode on and off (default is off). In Verbose mode, the function returns a data set with the MDRO results in logbook form with extensive info about which isolates would be MDRO-positive, or why they are not.

only_sir_columns

  A logical to indicate whether only antimicrobial columns must be included that were transformed to class sir on beforehand. Defaults to `FALSE` if no columns of `x` have a class sir.

infer_from_combinations

  A logical to indicate whether resistance for a missing base beta-lactam drug should be inferred from an available drug+inhibitor combination (e.g., piperacillin from piperacillin/tazobactam). The clinical basis is that resistance in a combination always implies resistance in the base drug, since the enzyme inhibitor provides no benefit when the organism is truly resistant. Only resistance is inferred; susceptibility in a combination does not imply susceptibility in the base drug (the inhibitor may be responsible). Defaults to `TRUE`.

...

  Column names of antimicrobials. To automatically detect antimicrobial column names, do not provide any named arguments; `guess_ab_col()` will then be used for detection. To manually specify a column, provide its name (case-insensitive) as an argument, e.g. `AMX = "amoxicillin"`. To skip a specific antimicrobial, set it to `NULL`, e.g. `TIC = NULL` to exclude ticarcillin. If a manually defined column does not exist in the data, it will be skipped with a warning.

## Value

- If `verbose` is set to `TRUE`:
  A data.frame containing columns `row_number`, `microorganism`, `MDRO`, `reason`, `all_nonsusceptible_columns`, `guideline`

- CMI 2012 paper - function `mdr_cmi2012()` or `mdro()`:
  Ordered factor with levels `Negative` < `Multi-drug-resistant (MDR)` < `Extensively drug-resistant (XDR)` < `Pandrug-resistant (PDR)`

- TB guideline - function `mdr_tb()` or `mdro(..., guideline = "TB")`:
  Ordered factor with levels `Negative` < `Mono-resistant` < `Poly-resistant` < `Multi-drug-resistant` < `Extensively drug-resistant`

- German guideline - function `mrgn()` or `mdro(..., guideline = "MRGN")`:
  Ordered factor with levels `Negative` < `3MRGN` < `4MRGN`

- Everything else, except for custom guidelines:
  Ordered factor with levels `Negative` < `Positive, unconfirmed` < `Positive`. The value `"Positive, unconfirmed"` means that, according to the guideline, it is not entirely sure if the isolate is multi-drug resistant and this should be confirmed with additional (e.g. genotypic) tests

## Details

These functions are context-aware. This means that the `x` argument can be left blank if used inside a data.frame call, see Examples.

For the `pct_required_classes` argument, values above 1 will be divided by 100. This is to support both fractions (`0.75` or `3/4`) and percentages (`75`).

Note: Every test that involves the Enterobacteriaceae family, will internally be performed using its newly named order Enterobacterales, since the Enterobacteriaceae family has been taxonomically reclassified by Adeolu et al. in 2016. Before that, Enterobacteriaceae was the only family under the Enterobacteriales (with an i) order. All species under the old Enterobacteriaceae family are still under the new Enterobacterales (without an i) order, but divided into multiple families. The way tests are performed now by this `mdro()` function makes sure that results from before 2016 and after 2016 are identical.

### Supported International / National Guidelines

Please suggest to implement guidelines by letting us know.

Currently supported guidelines are (case-insensitive):

- `guideline = "CMI 2012"` (default)

  Magiorakos AP, Srinivasan A et al. "Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance." Clinical Microbiology and Infection (2012) (doi:10.1111/j.1469-0691.2011.03570.x )

- `guideline = "EUCAST 3.3"` (or simply `guideline = "EUCAST"`)

  The European international guideline - EUCAST Expert Rules Version 3.3 "Intrinsic Resistance and Unusual Phenotypes" (link)

  Also:

  - `guideline = "EUCAST 3.2"`

    The former European international guideline - EUCAST Expert Rules Version 3.2 "Intrinsic Resistance and Unusual Phenotypes" (link)

  - `guideline = "EUCAST 3.1"`

    The former European international guideline - EUCAST Expert Rules Version 3.1 "Intrinsic Resistance and Exceptional Phenotypes Tables" (link)

- `guideline = "TB"`

  The international guideline for multi-drug resistant tuberculosis - World Health Organization "Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis" (link)

- `guideline = "MRGN"`

  The German national guideline - Mueller et al. (2015) Antimicrobial Resistance and Infection Control 4:7; doi:10.1186/s13756-015-0047-6

- `guideline = "BRMO 2024"` (or simply `guideline = "BRMO"`)

  The Dutch national guideline - Samenwerkingverband Richtlijnen Infectiepreventie (SRI) (2024) "Bijzonder Resistente Micro-Organismen (BRMO)" (link)

  Also:

  - `guideline = "BRMO 2017"`

    The former Dutch national guideline - Werkgroep Infectiepreventie (WIP), RIVM, last revision as of 2017: "Bijzonder Resistente Micro-Organismen (BRMO)"

### Using Custom Guidelines

Using a custom MDRO guideline is of importance if you have custom rules to determine MDROs in your hospital, e.g., rules that are dependent on ward, state of contact isolation or other variables in your data.

Custom guidelines can be set with the `custom_mdro_guideline()` function.

## 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 (https://www.eucast.org/bacteria/clinical-breakpoints-and-interpretation/definition-of-s-i-and-r/).

This AMR package follows insight; use `susceptibility()` (equal to `proportion_SI()`) to determine antimicrobial susceptibility and `count_susceptible()` (equal to `count_SI()`) to count susceptible isolates.

## See also

`custom_mdro_guideline()`

## Examples

    out <- mdro(example_isolates)
    #> Warning: in `mdro()`: NA introduced for isolates where the available percentage of
    #> antimicrobial classes was below 50% (set with `pct_required_classes`)
    str(out)
    #>  Ord.factor w/ 4 levels "Negative"<"Multi-drug-resistant (MDR)"<..: NA NA 1 1 1 1 NA NA 1 1 ...
    table(out)
    #> out
    #>                         Negative       Multi-drug-resistant (MDR)
    #>                             1617                              128
    #> Extensively drug-resistant (XDR)          Pandrug-resistant (PDR)
    #>                                0                                0

    out <- mdro(example_isolates, guideline = "EUCAST 3.3")
    table(out)
    #> out
    #>              Negative Positive, unconfirmed              Positive
    #>                  1994                     0                     6

    # \donttest{
    if (require("dplyr")) {
      # no need to define `x` when used inside dplyr verbs:
      example_isolates %>%
        mutate(MDRO = mdro()) %>%
        count(MDRO)
    }
    #> Warning: There was 1 warning in `mutate()`.
    #> ℹ In argument: `MDRO = mdro()`.
    #> Caused by warning:
    #> ! in `mdro()`: NA introduced for isolates where the available percentage of
    #> antimicrobial classes was below 50% (set with `pct_required_classes`)
    #> # A tibble: 3 × 2
    #>   MDRO                           n
    #>   <ord>                      <int>
    #> 1 Negative                    1617
    #> 2 Multi-drug-resistant (MDR)   128
    #> 3 NA                           255
    # }