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      Relationships between antimicrobial use and antimicrobial resistance in Gram-negative bacteria causing nosocomial infections from 1991–2003 at a university hospital in Taiwan


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          This study was conducted to evaluate the relationship between antimicrobial resistance and antimicrobial use in a university hospital in Taiwan. Disk susceptibility data of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus spp., Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia and other non-fermentative Gram-negative bacilli causing nosocomial infections were evaluated. Data on annual patient-days and annual consumption (defined daily dose (DDD) per 1000 patient-days) of extended-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftazidime, flumoxef, cefepime and cefpirome), β-lactam–β-lactamase inhibitor combinations (ticarcillin/clavulanic acid and piperacillin/tazobactam), carbapenems (imipenem and meropenem), aminoglycosides (amikacin, gentamicin and tobramycin), fluoroquinolones (ciprofloxacin (oral and injectable) and oral levofloxacin and moxifloxacin) from 1991 to 2003 were analysed. Increasing trends of incidences of several of these bacteria causing all nosocomial infections or nosocomial bloodstream infections were noted from 1991 to 2003. The annual patient-days of the hospital significantly increased, from 360 210 in 1991 to 672 676 in 2002 (linear regression analysis, P < 0.05), but slightly decreased in 2003 (629 168) owing to the severe acute respiratory syndrome epidemic in Taiwan. The rise in cefotaxime-resistant or ciprofloxacin-resistant E. coli and meropenem-resistant P. aeruginosa was significantly correlated with increased consumption of extended-spectrum cephalosporins, β-lactam–β-lactamase inhibitor combinations, carbapenems, fluoroquinolones and aminoglycosides (for ciprofloxacin-resistant E. coli and meropenem-resistant P. aeruginosa only) in the hospital (Pearson's correlation coefficient, r > 0.72 (or <−0.72) and P-value < 0.05). Increased ciprofloxacin-resistant K. pneumoniae and meropenem-resistant Acinetobacter spp. was significantly associated with the increased usage of extended-spectrum cephalosporins but not with the other four classes of antibiotics. This 13-year study in a hospital demonstrated significant changes in antimicrobial use, which may have affected antimicrobial resistance in certain Gram-negative bacteria at the hospital.

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          Most cited references32

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          Emerging carbapenemases in Gram-negative aerobes.

          Carbapenemases may be defined as beta-lactamases that significantly hydrolyze at least imipenem or/and meropenem. Carbapenemases involved in acquired resistance are of Ambler molecular classes A, B, and D. Class A, clavulanic acid-inhibited carbapenemases are rare. They are either chromosomally encoded (NMC-A, Sme-1 to Sme-3, IMI-1) in Enterobacter cloacae and Serratia marcescens, or plasmid encoded, such as KPC-1 in Klebsiella pneumoniae and GES-2 in Pseudomonas aeruginosa, the latter being a point-mutant of the clavulanic acid-inhibited extended-spectrum beta-lactamase GES-1. The class B enzymes are the most clinically significant carbapenemases. They are metalloenzymes of the IMP or VIM series. They have been reported worldwide but mostly from South East Asia and Europe. Metalloenzymes, whose genes are plasmid and integron located, hydrolyze virtually all beta-lactams except aztreonam. Finally, the class D carbapenemases are increasingly reported in Acinetobacter baumannii but compromise imipenem and meropenem susceptibility only marginally. The sources of the acquired carbapenemase genes remain unknown, as does the relative importance of the spread of epidemic strains as opposed to the spread of plasmid- or integron-borne genes. Because most of these carbapenemases confer only reduced susceptibility to carbapenems in Enterobacteriaceae, they may remain underestimated as a consequence of the lack of their detection.
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            Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use.

            Previous surveillance studies have documented increasing rates of antimicrobial resistance in US intensive care units (ICUs) in the early 1990s. To assess national rates of antimicrobial resistance among gram-negative aerobic isolates recovered from ICU patients and to compare these rates to antimicrobial use. Participating institutions, representing a total of 43 US states plus the District of Columbia, provided antibiotic susceptibility results for 35 790 nonduplicate gram-negative aerobic isolates recovered from ICU patients between 1994 and 2000. Each institution tested approximately 100 consecutive gram-negative aerobic isolates recovered from ICU patients. Organisms were identified to the species level. Susceptibility tests were performed, and national fluoroquinolone consumption data were obtained. The activity of most antimicrobial agents against gram-negative aerobic isolates showed an absolute decrease of 6% or less over the study period. The overall susceptibility to ciprofloxacin decreased steadily from 86% in 1994 to 76% in 2000 and was significantly associated with increased national use of fluoroquinolones. This study documents the increasing incidence of ciprofloxacin resistance among gram-negative bacilli that has occurred coincident with increased use of fluoroquinolones. More judicious use of fluoroquinolones will be necessary to limit this downward trend.
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              Surveillance of antimicrobial use and antimicrobial resistance in United States hospitals: project ICARE phase 2. Project Intensive Care Antimicrobial Resistance Epidemiology (ICARE) hospitals.

              The search for the means to understand and control the emergence and spread of antimicrobial resistance has become a public health priority. Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology) has established laboratory-based surveillance for antimicrobial resistance and antimicrobial use at a subset of hospitals participating in the National Nosocomial Infection Surveillance system. These data illustrate that for most antimicrobial-resistant organisms studied, rates of resistance were highest in the intensive care unit (ICU) areas and lowest in the outpatient areas. A notable exception was ciprofloxacin- or ofloxacin-resistant Pseudomonas aeruginosa, for which resistance rates were highest in the outpatient areas. For most of the antimicrobial agents associated with this resistance, the rate of use was highest in the ICU areas, in parallel to the pattern seen for resistance. These comparative data on use and resistance among similar areas (i.e., ICU or other inpatient areas) can be used as a benchmark by participating hospitals to focus their efforts at addressing antimicrobial resistance.

                Author and article information

                Int J Antimicrob Agents
                Int. J. Antimicrob. Agents
                International Journal of Antimicrobial Agents
                Elsevier B.V. and the International Society of Chemotherapy.
                8 November 2005
                December 2005
                8 November 2005
                : 26
                : 6
                : 463-472
                [a ]Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, 7, Chung-Shan South Road, Taipei, Taiwan
                [b ]Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, 7, Chung-Shan South Road, Taipei, Taiwan
                [c ]Department of Pharmacy, National Taiwan University Hospital, National Taiwan University College of Medicine, 7, Chung-Shan South Road, Taipei, Taiwan
                [d ]Infection Control Committee, National Taiwan University Hospital, National Taiwan University College of Medicine, 7, Chung-Shan South Road, Taipei, Taiwan
                Author notes
                [* ]Corresponding author. Tel.: +886 2 2312 3456x5363; fax: +886 2 2322 4263. hsporen@ 123456ha.mc.ntu.edu.tw
                Copyright © 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                : 10 February 2005
                : 19 August 2005

                Infectious disease & Microbiology
                antimicrobial use,antimicrobial resistance,nosocomial infection,gram-negative bacteria,taiwan


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