Q- What are Pan resistant gram negative rods (GNR)? Ans: Panresistant gram-negative bacilli are not susceptible to all of the following antibiotics: Antipseudomonal cephalosporins (e.g., ceftazidime and cefepime) Antipseudomonal carbapenems (e.g., imipenem and meropenem) Piperacillin/tazobactam Ciprofloxacin and levofloxacin Q- What are Extreme drug resistant (XDR) GNR? Ans: XDR gram-negative bacilli are not susceptible to all of the following antibiotics: Antipseudomonal cephalosporins (e.g., ceftazidime and cefepime) Antipseudomonal carbapenems (e.g., imipenem and meropenem) Piperacillin/tazobactam, ticarcillin-clavulanate, and ampicillinsulbactam Ciprofloxacin and levofloxacin Aminoglycosides (i.e., gentamicin, tobramycin, and amikacin) Tigecycline Polymyxins (e.g., polymyxin B and colistin) Q- Why is Panresistant and XDR GNR a problem? Ans: These are of concern because treatment options for these infections are very limited. Clinical infections with such organisms pose serious therapeutic challenges, with increasing reports of poor patient outcomes and death. Moreover accurate detection of resistance is also a problem. Q- How do bacteria acquire resistance to carbapenems (e.g., imipenem and meropenem)? Ans: This is mainly due to acquisition of genes responsible for expression of metallo-beta-lactamases (MBLs) producing enzymes. MBLs production renders the bacteria resistant to carbapenems. Such enzymes have emerged in many geographical locations and confer high-level resistance to all β-lactams except aztreonam. Five enzyme types have been identified (IMP, VIM, SPM, GIM, and SIM types), involving various host organisms, most commonly Pseudomonas spp., Acinetobacter spp., and Enterobacteriaceae. Q- Why are MBL enzymes capable of transmission to other bacteria? Ans: MBL genes are located on integron structures that reside on mobile genetic elements such as plasmids or transposons thus enabling widespread dissemination. Copyright @ Antimicrobial Resistance Network 2008, All right reserved Q- Why MBLs production is necessary to detect in a routine clinical laboratory? Ans: Globally occurrence, types, and rate of dissemination of MBLs is increasing, therefore early detection is critical. The benefits of such include timely implementation of strict infection control practices as well as clinical guidance regarding the potential risks for therapeutic failure. Moreover, given the poor outcomes, such as death, persistent fevers, and infection relapse, laboratory detection of carbapenem-susceptible MBL-carrying organisms should be considered to be of paramount clinical importance. Q- Is MBLs production easy to detect in laboratory? Ans: No, because as seen with extended-spectrum β-lactamases (ESBL) and AmpC-type β-lactamases, MBL-carrying organisms can appear susceptible to carbapenems using current Clinical and Laboratory Standards Institute (CLSI) or British Society for Antimicrobial Chemotherapy (BSAC) breakpoints. As a result of being difficult to detect, such organisms pose significant risks, particularly due to their role in unnoticed spread within institutions and their ability to participate in horizontal MBL gene transfer with other pathogenic hospital-related organisms. Q- How MBLs producing strains are detected in the laboratory? Ans: The gold standard is the detection of MBL producing gene by molecular techniques. However this is not practical and cost effective for most of the laboratories in Pakistan. Therefore phenotypic methods have been developed including Double-disc synergy tests (DDSTs) Using a ceftazidime disc and a 2-mercaptopropionic acid (MPA) disc Imipenem disc and an EDTA disc Double Etest (Imipenem on one side and Imipenem+EDTA on other side Although different phenotypic methods have been described, the CLSI (along with other international committees) currently does not include standardized recommendations for MBL screening. However organisms that appear to be carbapenem susceptible on antimicrobial susceptibility testing but that have phenotypic or genotypic evidence of production of carbapenemases should be regarded as nonsusceptible to all carbapenems. Copyright @ Antimicrobial Resistance Network 2008, All right reserved Q- What should be done to prevent spread of these strains in the hospitals? Identify high-risk colonized patients (especially international medical transfers or those sharing a room with persons who are known to be colonized or infected) by use of rectal swabs plated onto selective media Perform molecular epidemiologic analysis of strains recovered from infected or colonized patients Institute contact isolation precautions for all patients infected or colonized with carbapenem-resistant or carbapenemase-producing organisms Enhance hand hygiene Enhance environmental cleaning Copyright @ Antimicrobial Resistance Network 2008, All right reserved Copyright @ Antimicrobial Resistance Network 2008, All right reserved