Abstract
Background
The medical community has been witnessing a growing epidemic of infections due to Gram-negative bacteria resistant to many classes of antibiotics in most countries of the world (Sharma et al., 2005; Canton et al., 2003; Hsueh et al., 2002; Landman et al., 2002). Several investigators have studied the various aspects of these infections including mechanisms and risk factors of development of resistance as well as the effectiveness and toxicity of various therapeutic options (Harbarth & Samore, 2005; Epstein et al., 2004). In addition, the prevalence and epidemiology of bacteria resistant to antimicrobial agents have become the focus of numerous single-centre and multi-centre surveillance studies (Tambic et al., 2002; Jones, 2003).
We observed that different definitions regarding antimicrobial resistance are used in publications dealing with infections caused by Acinetobacter baumannii or Pseudomonas aeruginosa. In particular the terms multidrug-resistant (MDR) and pandrug-resistant (PDR) have been used to characterize isolates of A. baumannii or P. aeruginosa with a variety of genotypic and phenotypic characteristics. This is a noteworthy fact that causes considerable confusion among researchers and clinicians. Thus we sought to systematically examine the various definitions of MDR and PDR A. baumannii and P. aeruginosa used in the biomedical literature during recent years.
Literature search
We searched for relevant studies indexed in the PubMed database and published in the period 01/200009/2005. We searched for articles that had the words multidrug, multi-drug, MDR, multiresistance, multi-resistance, multiresistant, multi-resistant, pandrug, pan-drug or PDR and Acinetobacter baumannii or Pseudomonas aeruginosa in their title.
Our search was limited to studies that were performed in humans, were written in English, and had available abstracts in PubMed, by making use of the respective Limits' functions of the PubMed search engine. The title and the abstract of studies that were retrieved from the initial search were examined for relevance. Then, the full-published papers of the relevant studies were reviewed to extract the definitions of MDR or PDR A. baumannii or P. aeruginosa used in the papers. We excluded from further analysis studies that were written by the same first author when the same definition for MDR or PDR was used.
Reviewed publications
We reviewed the title and the abstract of 107 initially retrieved studies, out of which 53 studies reported results for A. baumannii and 54 for P. aeruginosa isolates. Based on our inclusion criteria we identified 50 (Abbo et al., 2005; Alarcon et al., 2001; Appleman et al., 2000; Blahova et al., 2001; Bou et al., 2000; Cawley et al., 2002; Corbella et al., 2000; El Shafie et al., 2004; Gales et al., 2001; Garnacho-Montero et al., 2003; Giacometti et al., 2000; Giamarellos-Bourboulis et al., 2001; Gorman et al., 2003; Higgins et al., 2004; Hsueh et al., 2002; Huys et al., 2005; Jain & Danziger, 2004; Jiménez-Mejías et al., 2002; Jones et al., 2004; Joshi et al., 2003; Kuo et al., 2003, 2004; Landman et al., 2002; Lee et al., 2005; Levin et al., 2001; Ling et al., 2001; Maniatis et al., 2003; Maragakis et al., 2004; Maslow et al., 2005; Michalopoulos et al., 2005a; Mussi et al., 2005; Oh et al., 2002; Paavilainen et al., 2001; Pimentel et al., 2005; Podnos et al., 2001; Roberts et al., 2001; Ruiz et al., 2003; Saugar et al., 2002; Simor et al., 2002; Smolyakov et al., 2003; Tognim et al., 2004; Turton et al., 2004; Urban et al., 2003; van Dessel et al., 2004; Wang et al., 2003; Wilson et al., 2004; Wood et al., 2003; Wu et al., 2004; Yoon et al., 2004; Zeana et al., 2003) and 42 (Ahmed et al., 2002; Belet et al., 2004; Bratu et al., 2005; Brito et al., 2003; Bukholm et al., 2002; Cao et al., 2004; Davies et al., 2003; Defez et al., 2004; Domenig et al., 2001; Douglas et al., 2001; Dubois et al., 2001; Erdem et al., 2003; Fraser et al., 2004; Giamarellos-Bourboulis et al., 2000, 2005; Goossens, 2003; Hamer, 2000; Hsueh et al., 2005; Jones et al., 2001; Jones et al., 2004; Jung et al., 2004; Kocazeybek et al., 2002; Landman et al., 2002; Lang et al., 2000; Lin et al., 2003; Luzzaro et al., 2001; Mirakhur et al., 2003; Miranda et al., 2001; Ohmagari et al., 2005; Oie et al., 2003; Ortega et al., 2004; Pagani et al., 2005; Paramythiotou et al., 2004; Pellegrino et al., 2002; Pirnay et al., 2003; Pitten et al., 2001; Rossolini & Mantengoli, 2005; Schelenz & French, 2000; Shahid et al., 2003; Takeyama et al., 2002; Tascini et al., 2004; Thong et al., 2004) studies that reported on MDR or PDR A. baumannii and P. aeruginosa isolates, respectively. Three studies that reported on MDR Acinetobacter were excluded because they referred to species other than A. baumannii (two studies) or had the same first author who used the same definition of MDR in another paper included in our systematic review (one study). Twelve studies that reported on MDR Pseudomonas were excluded because they described cellular mechanisms for multidrug resistance (five studies), had the same first author and used the same definition of MDR P. aeruginosa as another paper included in our review (four studies), referred to species other than P. aeruginosa (two studies), or reported on MDR cancer cells and not P. aeruginosa (one study).
MDR and PDR A. baumannii
In Table 1 we present the characteristics of the 50 studies that reported on MDR or PDR A. baumannii isolates. As shown, substantially different definitions were used in the identified studies. Four studies reported on PDR isolates (Kuo et al., 2003, 2004; Lee et al., 2005; Wang et al., 2003). The term PDR was used inappropriately in all of these studies. Specifically, the term PDR was used despite the fact that the isolates were not tested for in vitro susceptibility to sulbactam in two studies (Lee et al., 2005; Kuo et al., 2003) and to polymyxins in three studies (Kuo et al., 2003, 2004; Lee et al., 2005). In one study the isolates were defined as PDR although they were tested and found to be sensitive to colistin (Wang et al., 2003).