Author(s): Giannoula S Tansarli 1 , Drosos E Karageorgopoulos 1 2 , Anastasios Kapaskelis 1 , Matthew E Falagas [*] 3 4
carbapenem-resistant; costs; economic impact; extended-spectrum b-lactamase; hospital charges; methicillin-resistant Staphylococcus aureus; multidrug resistance
The alarmingly increasing antimicrobial resistance raises global concerns regarding the impact on patients with multidrug-resistant (MDR) infections. Important efforts have been made to study the clinical outcomes among patients infected with such pathogens, showing higher mortality and more frequent treatment failure among them compared with those infected with the susceptible isolates [1,2] . Apart from the worse clinical outcomes, MDR infections are expected to be more costly for healthcare systems than the susceptible ones, due to the higher length of stay (LOS) in the hospital associated with the infection [3,4] . A previous study has focused on the impact of common MDR Gram-negative (Gram[-]) bacilli, including the associated costs  . However, many new studies have been published since then and a cumulative collection and presentation of this important data has not yet been performed.
In this context, the authors aimed to systematically review and evaluate the available evidence in order to determine the impact of antimicrobial multidrug resistance on the inpatient care costs.
The authors performed a systematic search in the PubMed and Scopus (Health Sciences and Life Sciences subject areas) databases in May 2012. The following search pattern was applied to all published articles: '(MDR or multidrug-resistant or extended-spectrum b-lactamase (ESBL) or carbapenem-resistant or imipenem-resistant or meropenem-resistant or MRSA) and (cost or economic or 'charges')'. In addition, the bibliographies of relevant studies were hand-searched in order to identify further studies potentially eligible for inclusion. Articles published in languages other than English, French, German, Spanish, Italian or Greek were not evaluated.
Any article comparing the inpatient care costs of infection with MDR organisms (MDROs) with the costs of the non-MDRO of the same species was considered eligible for inclusion in this review. Studies evaluating only patients with colonization with MDROs were excluded. Multidrug resistance in Gram(-) bacteria was defined as resistance to three or more classes of antibiotics  . ESBL production in Enterobacteriaceae and carbapenem resistance (i.e., resistance to imipenem or meropenem) in Gram(-) nonfermentative bacilli or Enterobacteriaceae were types of antimicrobial resistance eligible for inclusion, as such pathogens are typically resistant to many classes of antibiotics. Finally, methicillin-resistant Staphylococcus aureus (MRSA) is, by definition, an MDR pathogen  ; thus, relevant studies on MRSA were also eligible for this review.
To clearly record the costs attributed to antimicrobial resistance, only studies providing the costs after the isolation of the pathogens of interest for this review were considered eligible. Therefore, when studies reported on the costs of the total hospital LOS, including the period before the onset of infection, they were not included in the review. In addition, when the control group of a study comprised uninfected patients or patients with infections caused by pathogens with an indeterminate or ineligible antimicrobial resistance profile, this particular study was excluded. Finally, studies with a definition for MDR...