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# ==================================================================== #
# TITLE #
# Antimicrobial Resistance (AMR) Analysis #
# #
# SOURCE #
# https://gitlab.com/msberends/AMR #
# #
# LICENCE #
# (c) 2019 Berends MS (m.s.berends@umcg.nl), Luz CF (c.f.luz@umcg.nl) #
# #
# This R package is free software; you can freely use and distribute #
# it for both personal and commercial purposes under the terms of the #
# GNU General Public License version 2.0 (GNU GPL-2), as published by #
# the Free Software Foundation. #
# #
# This R package was created for academic research and was publicly #
# released in the hope that it will be useful, but it comes WITHOUT #
# ANY WARRANTY OR LIABILITY. #
# Visit our website for more info: https://msberends.gitlab.io/AMR. #
# ==================================================================== #
#' Determine multidrug-resistant organisms (MDRO)
#'
#' Determine which isolates are multidrug-resistant organisms (MDRO) according to (country-specific) guidelines.
#' @param x table with antibiotic columns, like e.g. \code{AMX} and \code{AMC}
#' @param guideline a specific guideline to mention, see Details. EUCAST guidelines will be used when left empty, see Details.
#' @param info print progress
#' @inheritParams eucast_rules
#' @param verbose print additional info: missing antibiotic columns per parameter
#' @inheritSection eucast_rules Antibiotics
#' @details Currently supported guidelines are:
#' \itemize{
#' \item{\code{guideline = "EUCAST"}: EUCAST Expert Rules Version 3.1 "Intrinsic Resistance and Exceptional Phenotypes Tables" (\href{http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Expert_Rules/Expert_rules_intrinsic_exceptional_V3.1.pdf}{link})}
#' \item{\code{guideline = "TB"}: World Health Organization "Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis" (\href{https://www.who.int/tb/publications/pmdt_companionhandbook/en/}{link})}
#' \item{\code{guideline = "MRGN"}: (work in progress)}
#' \item{\code{guideline = "BRMO"}: Rijksinstituut voor Volksgezondheid en Milieu "WIP-richtlijn BRMO (Bijzonder Resistente Micro-Organismen) [ZKH]" (\href{https://www.rivm.nl/Documenten_en_publicaties/Professioneel_Praktisch/Richtlijnen/Infectieziekten/WIP_Richtlijnen/WIP_Richtlijnen/Ziekenhuizen/WIP_richtlijn_BRMO_Bijzonder_Resistente_Micro_Organismen_ZKH}{link})}
#' }
#'
#' Please suggest your own (country-specific) guidelines by letting us know: \url{https://gitlab.com/msberends/AMR/issues/new}.
#' @return For TB (\code{mdr_tb()}): Ordered factor with levels \code{Negative < Mono-resistance < Poly-resistance < Multidrug resistance < Extensive drug resistance}.
#'
#' For everything else: Ordered factor with levels \code{Negative < Positive, unconfirmed < Positive}. The value \code{"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. molecular) tests.
#' @rdname mdro
#' @importFrom dplyr %>%
#' @importFrom crayon red blue bold
#' @export
#' @inheritSection AMR Read more on our website!
#' @source
#' EUCAST Expert Rules Version 3.1 "Intrinsic Resistance and Exceptional Phenotypes Tables" (\href{http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Expert_Rules/Expert_rules_intrinsic_exceptional_V3.1.pdf}{link})
#'
#' World Health Organization "Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis" (\href{https://www.who.int/tb/publications/pmdt_companionhandbook/en/}{link})
#'
#' Rijksinstituut voor Volksgezondheid en Milieu "WIP-richtlijn BRMO (Bijzonder Resistente Micro-Organismen) [ZKH]" (\href{https://www.rivm.nl/Documenten_en_publicaties/Professioneel_Praktisch/Richtlijnen/Infectieziekten/WIP_Richtlijnen/WIP_Richtlijnen/Ziekenhuizen/WIP_richtlijn_BRMO_Bijzonder_Resistente_Micro_Organismen_ZKH}{link})
#' @examples
#' library(dplyr)
#'
#' example_isolates %>%
#' mutate(EUCAST = mdro(.),
#' BRMO = brmo(.))
mdro <- function(x,
guideline = NULL,
col_mo = NULL,
info = TRUE,
verbose = FALSE,
...) {
if (!is.data.frame(x)) {
stop("`x` must be a data frame.", call. = FALSE)
}
if (!is.null(list(...)$country)) {
warning("Using `country` is deprecated, use `guideline` instead. Please see ?mdro.", call. = FALSE)
guideline <- list(...)$country
}
if (length(guideline) > 1) {
stop("`guideline` must be a length one character string.", call. = FALSE)
}
if (is.null(guideline)) {
guideline <- "eucast"
}
if (tolower(guideline) == "nl") {
guideline <- "BRMO"
}
if (tolower(guideline) == "de") {
guideline <- "MRGN"
}
if (!tolower(guideline) %in% c("brmo", "mrgn", "eucast", "tb")) {
stop("invalid guideline: ", guideline, call. = FALSE)
}
guideline <- list(code = tolower(guideline))
# try to find columns based on type
# -- mo
if (is.null(col_mo)) {
col_mo <- search_type_in_df(x = x, type = "mo")
}
if (is.null(col_mo) & guideline$code == "tb") {
message(blue("NOTE: No column found as input for `col_mo`,",
bold("assuming all records contain", italic("Mycobacterium tuberculosis.\n"))))
x$mo <- AMR::as.mo("Mycobacterium tuberculosis")
col_mo <- "mo"
}
if (is.null(col_mo)) {
stop("`col_mo` must be set.", call. = FALSE)
}
if (guideline$code == "eucast") {
guideline$name <- "EUCAST Expert Rules, \"Intrinsic Resistance and Exceptional Phenotypes Tables\""
guideline$author <- "EUCAST (European Committee on Antimicrobial Susceptibility Testing)"
guideline$version <- "3.1"
guideline$source <- "http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Expert_Rules/Expert_rules_intrinsic_exceptional_V3.1.pdf"
} else if (guideline$code == "tb") {
guideline$name <- "Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis"
guideline$author <- "WHO (World Health Organization)"
guideline$version <- "WHO/HTM/TB/2014.11"
guideline$source <- "https://www.who.int/tb/publications/pmdt_companionhandbook/en/"
# support per country:
} else if (guideline$code == "mrgn") {
guideline$name <- "Germany"
guideline$name <- ""
guideline$version <- ""
guideline$source <- ""
} else if (guideline$code == "brmo") {
guideline$name <- "WIP-Richtlijn Bijzonder Resistente Micro-organismen (BRMO)"
guideline$author <- "RIVM (Rijksinstituut voor de Volksgezondheid)"
guideline$version <- "Revision as of December 2017"
guideline$source <- "https://www.rivm.nl/Documenten_en_publicaties/Professioneel_Praktisch/Richtlijnen/Infectieziekten/WIP_Richtlijnen/WIP_Richtlijnen/Ziekenhuizen/WIP_richtlijn_BRMO_Bijzonder_Resistente_Micro_Organismen_ZKH"
} else {
stop("This guideline is currently unsupported: ", guideline$code, call. = FALSE)
}
if (info == TRUE) {
cat("Determining multidrug-resistant organisms (MDRO), according to:\n",
"Guideline: ", red(guideline$name), "\n",
"Version: ", red(guideline$version), "\n",
"Author: ", red(guideline$author), "\n",
"Source: ", blue(guideline$source), "\n",
"\n", sep = "")
}
if (guideline$code == "tb") {
cols_ab <- get_column_abx(x = x,
soft_dependencies = c("CAP",
"ETH",
"GAT",
"INH",
"PZA",
"RIF",
"RIB",
"RFP"),
verbose = verbose, ...)
} else {
cols_ab <- get_column_abx(x = x, verbose = verbose, ...)
}
AMC <- cols_ab["AMC"]
AMK <- cols_ab["AMK"]
AMP <- cols_ab["AMP"]
AMX <- cols_ab["AMX"]
ATM <- cols_ab["ATM"]
AZL <- cols_ab["AZL"]
AZM <- cols_ab["AZM"]
CAZ <- cols_ab["CAZ"]
CED <- cols_ab["CED"]
CHL <- cols_ab["CHL"]
CIP <- cols_ab["CIP"]
CLI <- cols_ab["CLI"]
CLR <- cols_ab["CLR"]
COL <- cols_ab["COL"]
CRO <- cols_ab["CRO"]
CTX <- cols_ab["CTX"]
CXM <- cols_ab["CXM"]
CZO <- cols_ab["CZO"]
DAP <- cols_ab["DAP"]
DOX <- cols_ab["DOX"]
ERY <- cols_ab["ERY"]
ETP <- cols_ab["ETP"]
FEP <- cols_ab["FEP"]
FLC <- cols_ab["FLC"]
FOS <- cols_ab["FOS"]
FOX <- cols_ab["FOX"]
FUS <- cols_ab["FUS"]
GEN <- cols_ab["GEN"]
IPM <- cols_ab["IPM"]
KAN <- cols_ab["KAN"]
LIN <- cols_ab["LIN"]
LNZ <- cols_ab["LNZ"]
LVX <- cols_ab["LVX"]
MEM <- cols_ab["MEM"]
MEZ <- cols_ab["MEZ"]
MTR <- cols_ab["MTR"]
MFX <- cols_ab["MFX"]
MNO <- cols_ab["MNO"]
NAL <- cols_ab["NAL"]
NEO <- cols_ab["NEO"]
NET <- cols_ab["NET"]
NIT <- cols_ab["NIT"]
NOR <- cols_ab["NOR"]
NOV <- cols_ab["NOV"]
OFX <- cols_ab["OFX"]
PEN <- cols_ab["PEN"]
PIP <- cols_ab["PIP"]
PLB <- cols_ab["PLB"]
PRI <- cols_ab["PRI"]
QDA <- cols_ab["QDA"]
RID <- cols_ab["RID"]
RIF <- cols_ab["RIF"]
RXT <- cols_ab["RXT"]
SIS <- cols_ab["SIS"]
SXT <- cols_ab["SXT"]
TCY <- cols_ab["TCY"]
TEC <- cols_ab["TEC"]
TGC <- cols_ab["TGC"]
TIC <- cols_ab["TIC"]
TMP <- cols_ab["TMP"]
TOB <- cols_ab["TOB"]
TZP <- cols_ab["TZP"]
VAN <- cols_ab["VAN"]
# additional for TB
CAP <- cols_ab["CAP"]
ETH <- cols_ab["ETH"]
GAT <- cols_ab["GAT"]
INH <- cols_ab["INH"]
PZA <- cols_ab["PZA"]
RIF <- cols_ab["RIF"]
RIB <- cols_ab["RIB"]
RFP <- cols_ab["RFP"]
abx_tb <- c(CAP, ETH, GAT, INH, PZA, RIF, RIB, RFP)
abx_tb <- abx_tb[!is.na(abx_tb)]
if (guideline$code == "tb" & length(abx_tb) == 0) {
stop("No antimycobacterials found in data set.", call. = FALSE)
}
ab_missing <- function(ab) {
isTRUE(ab %in% c(NULL, NA)) | length(ab) == 0
}
# antibiotic classes
aminoglycosides <- c(TOB, GEN)
cephalosporins <- c(FEP, CTX, FOX, CED, CAZ, CRO, CXM, CZO)
cephalosporins_3rd <- c(CTX, CRO, CAZ)
carbapenems <- c(ETP, IPM, MEM)
fluoroquinolones <- c(OFX, CIP, LVX, MFX)
# helper function for editing the table
trans_tbl <- function(to, rows, cols, any_all) {
cols <- cols[!ab_missing(cols)]
cols <- cols[!is.na(cols)]
if (length(rows) > 0 & length(cols) > 0) {
if (any_all == "any") {
row_filter <- which(x[, cols] == "R")
} else if (any_all == "all") {
row_filter <- x %>%
mutate(index = 1:nrow(.)) %>%
filter_at(vars(cols), all_vars(. == "R")) %>%
pull((index))
}
rows <- rows[rows %in% row_filter]
x[rows, "MDRO"] <<- to
}
}
x <- x %>%
mutate_at(vars(col_mo), as.mo) %>%
# join to microorganisms data set
left_join_microorganisms(by = col_mo) %>%
# add unconfirmed to where genus is available
mutate(MDRO = ifelse(!is.na(genus), 1, NA_integer_))
if (guideline$code == "eucast") {
# EUCAST ------------------------------------------------------------------
# Table 5
trans_tbl(3,
which(x$family == "Enterobacteriaceae"
| x$fullname %like% "^Pseudomonas aeruginosa"
| x$genus == "Acinetobacter"),
COL,
"all")
trans_tbl(3,
which(x$fullname %like% "^Salmonella Typhi"),
c(carbapenems, fluoroquinolones),
"any")
trans_tbl(3,
which(x$fullname %like% "^Haemophilus influenzae"),
c(cephalosporins_3rd, carbapenems, fluoroquinolones),
"any")
trans_tbl(3,
which(x$fullname %like% "^Moraxella catarrhalis"),
c(cephalosporins_3rd, fluoroquinolones),
"any")
trans_tbl(3,
which(x$fullname %like% "^Neisseria meningitidis"),
c(cephalosporins_3rd, fluoroquinolones),
"any")
trans_tbl(3,
which(x$fullname %like% "^Neisseria gonorrhoeae"),
AZM,
"any")
# Table 6
trans_tbl(3,
which(x$fullname %like% "^Staphylococcus (aureus|epidermidis|coagulase negatief|hominis|haemolyticus|intermedius|pseudointermedius)"),
c(VAN, TEC, DAP, LNZ, QDA, TGC),
"any")
trans_tbl(3,
which(x$genus == "Corynebacterium"),
c(VAN, TEC, DAP, LNZ, QDA, TGC),
"any")
trans_tbl(3,
which(x$fullname %like% "^Streptococcus pneumoniae"),
c(carbapenems, VAN, TEC, DAP, LNZ, QDA, TGC, RIF),
"any")
trans_tbl(3, # Sr. groups A/B/C/G
which(x$fullname %like% "^Streptococcus (pyogenes|agalactiae|equisimilis|equi|zooepidemicus|dysgalactiae|anginosus)"),
c(PEN, cephalosporins, VAN, TEC, DAP, LNZ, QDA, TGC),
"any")
trans_tbl(3,
which(x$genus == "Enterococcus"),
c(DAP, LNZ, TGC, TEC),
"any")
trans_tbl(3,
which(x$fullname %like% "^Enterococcus faecalis"),
c(AMP, AMX),
"any")
# Table 7
trans_tbl(3,
which(x$genus == "Bacteroides"),
MTR,
"any")
trans_tbl(3,
which(x$fullname %like% "^Clostridium difficile"),
c(MTR, VAN),
"any")
}
if (guideline$code == "mrgn") {
# Germany -----------------------------------------------------------------
stop("We are still working on German guidelines in this beta version.", call. = FALSE)
}
if (guideline$code == "brmo") {
# Netherlands -------------------------------------------------------------
aminoglycosides <- aminoglycosides[!is.na(aminoglycosides)]
fluoroquinolones <- fluoroquinolones[!is.na(fluoroquinolones)]
carbapenems <- carbapenems[!is.na(carbapenems)]
amino <- AMX %or% AMP
third <- CAZ %or% CTX
ESBLs <- c(amino, third)
ESBLs <- ESBLs[!is.na(ESBLs)]
if (length(ESBLs) != 2) {
ESBLs <- character(0)
}
# Table 1
trans_tbl(3,
which(x$family == "Enterobacteriaceae"),
c(aminoglycosides, fluoroquinolones),
"all")
trans_tbl(2,
which(x$family == "Enterobacteriaceae"),
carbapenems,
"any")
trans_tbl(2,
which(x$family == "Enterobacteriaceae"),
ESBLs,
"all")
# Table 2
trans_tbl(2,
which(x$genus == "Acinetobacter"),
c(carbapenems),
"any")
trans_tbl(3,
which(x$genus == "Acinetobacter"),
c(aminoglycosides, fluoroquinolones),
"all")
trans_tbl(3,
which(x$fullname %like% "^Stenotrophomonas maltophilia"),
SXT,
"all")
if (!ab_missing(MEM) & !ab_missing(IPM)
& !ab_missing(GEN) & !ab_missing(TOB)
& !ab_missing(CIP)
& !ab_missing(CAZ)
& !ab_missing(TZP) ) {
x$psae <- 0
x[which(x[, MEM] == "R" | x[, IPM] == "R"), "psae"] <- 1 + x[which(x[, MEM] == "R" | x[, IPM] == "R"), "psae"]
x[which(x[, GEN] == "R" & x[, TOB] == "R"), "psae"] <- 1 + x[which(x[, GEN] == "R" & x[, TOB] == "R"), "psae"]
x[which(x[, CIP] == "R"), "psae"] <- 1 + x[which(x[, CIP] == "R"), "psae"]
x[which(x[, CAZ] == "R"), "psae"] <- 1 + x[which(x[, CAZ] == "R"), "psae"]
x[which(x[, TZP] == "R"), "psae"] <- 1 + x[which(x[, TZP] == "R"), "psae"]
} else {
x$psae <- 0
}
x[which(
x$fullname %like% "Pseudomonas aeruginosa"
& x$psae >= 3
), "MDRO"] <- 3
# Table 3
trans_tbl(3,
which(x$fullname %like% "Streptococcus pneumoniae"),
PEN,
"all")
trans_tbl(3,
which(x$fullname %like% "Streptococcus pneumoniae"),
VAN,
"all")
trans_tbl(3,
which(x$fullname %like% "Enterococcus faecium"),
c(PEN, VAN),
"all")
}
prepare_drug <- function(ab) {
# returns vector values of drug
# if `ab` is a column name, looks up the values in `x`
if (length(ab) == 1 & is.character(ab)) {
if (ab %in% colnames(x)) {
ab <- as.data.frame(x)[, ab]
}
}
ab <- as.character(as.rsi(ab))
ab[is.na(ab)] <- ""
ab
}
drug_is_R <- function(ab) {
# returns logical vector
ab <- prepare_drug(ab)
if (length(ab) == 1) {
rep(ab, NROW(x)) == "R"
} else {
ab == "R"
}
}
drug_is_not_R <- function(ab) {
# returns logical vector
ab <- prepare_drug(ab)
if (length(ab) == 1) {
rep(ab, NROW(x)) != "R"
} else {
ab != "R"
}
}
if (guideline$code == "tb") {
# Tuberculosis ------------------------------------------------------------
x <- x %>%
mutate(mono_count = 0,
mono_count = ifelse(drug_is_R(INH), mono_count + 1, mono_count),
mono_count = ifelse(drug_is_R(RIF), mono_count + 1, mono_count),
mono_count = ifelse(drug_is_R(ETH), mono_count + 1, mono_count),
mono_count = ifelse(drug_is_R(PZA), mono_count + 1, mono_count),
mono_count = ifelse(drug_is_R(RIB), mono_count + 1, mono_count),
mono_count = ifelse(drug_is_R(RFP), mono_count + 1, mono_count),
# from here on logicals
mono = mono_count > 0,
poly = ifelse(mono_count > 1 & drug_is_not_R(RIF) & drug_is_not_R(INH),
TRUE, FALSE),
mdr = ifelse(drug_is_R(RIF) & drug_is_R(INH),
TRUE, FALSE),
xdr = ifelse(drug_is_R(LVX) | drug_is_R(MFX) | drug_is_R(GAT),
TRUE, FALSE),
second = ifelse(drug_is_R(CAP) | drug_is_R(KAN) | drug_is_R(AMK),
TRUE, FALSE),
xdr = ifelse(mdr & xdr & second, TRUE, FALSE)) %>%
mutate(mdr_tb = case_when(xdr ~ 5,
mdr ~ 4,
poly ~ 3,
mono ~ 2,
TRUE ~ 1),
# keep all real TB, make other species NA
mdr_tb = ifelse(x$fullname == "Mycobacterium tuberculosis", mdr_tb, NA_real_))
}
# return results
if (guideline$code == "tb") {
factor(x = x$mdr_tb,
levels = 1:5,
labels = c("Negative", "Mono-resistance", "Poly-resistance", "Multidrug resistance", "Extensive drug resistance"),
ordered = TRUE)
} else {
factor(x = x$MDRO,
levels = 1:3,
labels = c("Negative", "Positive, unconfirmed", "Positive"),
ordered = TRUE)
}
}
#' @rdname mdro
#' @export
brmo <- function(x, guideline = "BRMO", ...) {
mdro(x, guideline = "BRMO", ...)
}
#' @rdname mdro
#' @export
mrgn <- function(x, guideline = "MRGN", ...) {
mdro(x = x, guideline = "MRGN", ...)
}
#' @rdname mdro
#' @export
mdr_tb <- function(x, guideline = "TB", ...) {
mdro(x = x, guideline = "TB", ...)
}
#' @rdname mdro
#' @export
eucast_exceptional_phenotypes <- function(x, guideline = "EUCAST", ...) {
mdro(x = x, guideline = "EUCAST", ...)
}
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