Meropenem Yearly Susceptibility Test Information Collection Program Research Articles

Summary trends for the Meropenem Yearly Susceptibility Test Information Collection Program: a 10-year experience in the United States (1999–2008)

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program was a global, longitudinal antimicrobial resistance surveillance network of more than 100 medical centers worldwide monitoring the susceptibility of meropenem and selected other broad-spectrum comparator agents. In 1999, and from 2000 through 2008, a total of 10 or 15 United States (USA) medical centers each forwarded 200 nonduplicate clinical isolates from serious infections to a central processing laboratory. Over the 10-year period of this surveillance program, the activity of meropenem and an average of 11 other antimicrobial agents were assessed against a total of 27 289 bacterial isolates using Clinical and Laboratory Standards Institute reference methods. Meropenem consistently demonstrated low resistance rates against Enterobacteriaceae species isolates through 2008 and did not exhibit a widespread change in resistance rates over the monitored interval. In fact, the incidence of emerging carbapenemase-producing (KPC-type) Klebsiella spp. showed a decline in 2008 compared to the steeply increasing rates observed from 2004 to 2007. Moreover, the KPC serine carbapenemases have spread to other Enterobacteriaceae species monitored by the MYSTIC Program. Greatest increases in antimicrobial resistance rates were observed for the fluoroquinolones (ciprofloxacin, levofloxacin) among all species monitored by the MYSTIC Program. Current susceptibility rates for meropenem when tested against prevalent pathogens were Pseudomonas aeruginosa (439 strains, 85.4% susceptible), Enterobacteriaceae (1537 strains, 97.3% susceptible), methicillin-susceptible staphylococci (460 strains, 100.0% susceptible), Streptococcus pneumoniae (125 strains, 80.2% at meningitis susceptibility breakpoints), other streptococci (159 strains, 90.0–100.0% susceptible), and Acinetobacter spp. (127 strains, 45.7% susceptible), the widest spectrum among β-lactams tested in 2008 and throughout the last decade. Continued local surveillance of broad-spectrum agents following the completion of the MYSTIC Program (USA) appears critical to detect emerging resistances among pathogens causing the most serious infections requiring carbapenem agents.

Prevalence and molecular characterization of extended-spectrum β-lactamase-producing Klebsiella pneumoniae in Riyadh, Saudi Arabia

BACKGROUND AND OBJECTIVES:Reports on extended-spectrum β-lactamases (ESBL) production by Enterobacteriaceae, and especially in Klebsiella pneumoniae, are few in Saudi Arabia. Therefore, we determined the prevalence of ESBL in K pneumoniae from Riyadh and characterized the predominant β-lactamase gene in these isolates.METHODS:A total of 400 K pneumoniae samples were isolated from two hospitals in Riyadh during 2007 and screened for production of ESBL using ESBL-E-strips and combined disk methods. PCR assay was used to detect blaTEM, blaSHV, and blaCTX-M genes.RESULTS:Phenotypic characterization identified a high ESBL rate of 55% of K pneumoniae isolates. ESBL-producing K pneumoniae were PCR positive for SHV, TEM and CTX-M β-lactamase genes with prevalences 97.3%, 84.1% and 34.1%, respectively. Within the CTX-M family, two groups of enzymes, CTX-M-1 and CTX-M-9-like genes were found with prevalences of 60% and 40%, respectively.CONCLUSIONS:This study confirms the high rate of ESBL in K pneumoniae clinical isolates in hospitals in Riyadh. This study demonstrates the worldwide spread of blaCTX-M genes. This first report of the presence of the blaCTX-M gene in clincial isolates in Saudi Arabia is evidence of the continuing worldwide spread of this gene.

Comparative activity of meropenem in US medical centers (2007): initiating the 2nd decade of MYSTIC program surveillance

Since 1997, the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program has monitored the antimicrobial activity of broad-spectrum agents against pathogens from hospitalized patients. In the United States, 2894 isolates were submitted in 2007 from 15 sites, including 1392 Enterobacteriaceae, 643 nonfermentative Gram-negative bacilli, and 829 Gram-positive cocci. All isolates were tested by broth microdilution methods. Meropenem (MIC 90 range, 0.12–2 μg/mL) exhibited the lowest resistance rates (1.9–2.4%) against Enterobacteriaceae, and fluoroquinolones had the highest rates of resistance (17.3–18.3%). KPC carbapenemases, usually found in Klebsiella pneumoniae, were also detected in Citrobacter freundii, Enterobacter spp., and Escherichia coli. Confirmed extended-spectrum β-lactamase–producing isolate rates for E. coli, Klebsiella spp., and Proteus mirabilis isolates were 6.0%, 12.0%, and 0.0%, respectively. Meropenem remained active against Gram-positive pathogens such as staphylococci (methicillin-susceptible; MIC 90, 0.12–0.25 μg/mL), Streptococcus pneumoniae (MIC 90, 0.5 μg/mL), and β-hemolytic and viridans group streptococci (MIC 90 range, 0.06–0.25 μg/mL). These US MYSTIC Program results demonstrate the continued emergence of novel β-lactamases and multidrug-resistant bacterial phenotypes necessitating monitoring of carbapenem activities against Enterobacteriaceae species as well as nonfermentative bacilli.

Trends in antimicrobial susceptibility of Gram-negative isolates from a paediatric intensive care unit in Warsaw: results from the MYSTIC programme (1997-2007)

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme is a longitudinal global surveillance study to monitor in vitro data on microbial susceptibility in centres that prescribe meropenem. This overview provides data on the susceptibility of Gram-negative bacteria (n = 1300) isolated from clinical specimens of children hospitalized in a paediatric intensive care unit (ICU) during 1997-2007. MICs of meropenem and eight other antibiotics were determined using the CLSI agar dilution method. Meropenem, imipenem and ciprofloxacin were most active (>90% susceptibility) against the tested isolates. A greater proportion of Pseudomonas aeruginosa isolates was susceptible to meropenem compared with imipenem. Antibiotic susceptibility of Enterobacteriaceae and Acinetobacter baumannii showed an increase in 2007. Only susceptibility of P. aeruginosa to ceftazidime and cefepime increased. The incidence of extended-spectrum beta-lactamase (ESBL) producers among Enterobacteriaceae isolates decreased from 37% in 1997 to 21.8% in 2007, and AmpC beta-lactamase producers decreased from 24.6% to 5.7%. Consumption of cephalosporins remained the same and piperacillin/tazobactam increased 3-fold. During 11 years, despite an increase in carbapenem consumption, meropenem and imipenem have retained excellent activity against the majority of isolates studied. The comparison of antibiotic susceptibility of Gram-negative isolates in 1997 and 2007 showed a trend of increase, and the number of beta-lactamase-producing isolates among Enterobacteriaceae showed a trend of decrease possibly related to changes in antibiotic policy.

Susceptibility of Bacterial Isolates From Turkey - A Report From the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program

The study monitored the susceptibility of nosocomial pathogens to meropenem and comparator antimicrobial agents isolated as part of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program from Turkish university hospitals. In terms of minimum inhibitory concentration 90% (MIC90) values, meropenem was two- and eight-fold more active than imipenem against Escherichia coli and Klebsiella pneumoniae, respectively. 40.5% of K. pneumoniae, 23.1% of Klebsiella oxytoca and 15.3% of E. coli isolates were extended-spectrum β-lactamase (ESBL) producers. Piperacillin/tazobactam was the most active agent against isolates of Pseudomonas aeruginosa, followed by meropenem and imipenem. Against Acinetobacter baumannii isolates, meropenem and imipenem were the most active agents. Continued surveillance by the MYSTIC Program appears to be prudent to help focus on effective empiric treatment regimens.

Meropenem activity against European isolates: report on the MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) 2006 results

The MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Program is a longitudinal antimicrobial surveillance study that has been in place since 1997 in centers that are actively prescribing meropenem. This report examines the activity of meropenem and other broad-spectrum antibacterial comparators against the 7124 isolates submitted by 40 European centers during 2006 and compares the results with those obtained in 2002. Cumulative susceptibility rates against all methicillin-susceptible staphylococci were amikacin (99.2%) > meropenem and imipenem (98.1%) > piperacillin + tazobactam (96.6%) > gentamicin (91.8%) > tobramycin (91.1%) > ciprofloxacin (83.1%) > ceftazidime (59.7%). Against all species of Enterobacteriaceae, the rates were meropenem (98.9%) > imipenem (97.9%) > amikacin (97.1%) > gentamicin (91.0%) > piperacillin + tazobactam (83.4%) > ceftazidime (82.3%) > ciprofloxacin (82.2%) > tobramycin (75.1%). The carbapenems were also the most effective class against nonfermenters, although there are increasing numbers of multidrug-resistant (MDR)- Acinetobacter spp. being reported. Overall meropenem is still retaining excellent activity against the majority of isolates studied. The continued need for surveillance studies such as MYSTIC in order that correct clinical decisions concerning antibiotic selection are made is once again demonstrated.

Antibiotic resistance surveillance over a 4-year period (2000–2003) in Turkey: results of the MYSTIC Program

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global study that provides antimicrobial susceptibility data in centers prescribing meropenem. The activity of meropenem and 7 broad-spectrum antimicrobials have been examined against 5208 bacterial isolates from 9 Turkish centers between 2000 and 2003. Cumulative susceptibility rates against all species of Enterobacteriaceae combined were ranked as follows: meropenem (99.3%), imipenem (97.6%), cefepime (80.0%), piperacillin–tazobactam (73.6%), ceftazidime (70.3%), ciprofloxacin (70.1%), cefotaxime (66.9%), and tobramycin (67.2%). The production of extended-spectrum β-lactamases (ESBLs) was detected in 48.7% of Klebsiella pneumoniae and in 19.5% of Escherichia coli isolates. Of ESBL producing K. pneumoniae isolates, 75.7% were resistant to tobramycin, 40.3% to ciprofloxacin, and 48.3% to piperacillin–tazobactam. Only piperacillin/tazobactam and carbapenems were active against more than 50% of Pseudomonas aeruginosa at the National Committee for Clinical Laboratory Standards-susceptible breakpoint, and the carbapenems were the most active compounds against Acinetobacter spp. These data confirm the continued potency of meropenem against Enterobacteriaceae in units where it is actively being prescribed.

Activity of meropenem as serine carbapenemases evolve in US Medical Centers: monitoring report from the MYSTIC Program (2006)

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Surveillance Program was designed to monitor the antimicrobial potency and spectrum of meropenem, and selected broad-spectrum comparison agents against pathogens from hospitalized patients. In the 2006 (year 8 of the study) United States sample, a total of 2841 isolates (94.7% compliance) including 641 Escherichia coli, 619 Klebsiella spp., 606 Pseudomonas aeruginosa, 456 oxacillin-susceptible Staphylococcus aureus, 300 streptococci, 149 Enterococcus faecalis, and 70 Gram-positive anaerobic organisms were tested by reference broth microdilution or agar dilution susceptibility methods. The carbapenems, especially meropenem, consistently demonstrated the lowest resistance rates against Enterobacteriaceae strains, and the fluoroquinolones had the highest and increasing resistance rates. The presence of qnr-mediated fluoroquinolone resistance was investigated using polymerase chain reaction methods but was only observed at very low levels (2.1%) and was not clonally associated. Confirmed extended-spectrum β-lactamase rates for E. coli and Klebsiella spp. were only 4.8% and 5.0%, respectively, with mobile AmpC (CMY-2 and FOX-5) enzymes shown in 13 additional Enterobacteriaceae isolates. Clonally related KPC-type serine carbapenemase production (57 strains, 9.5%) was observed at a rate 2-fold greater than the prior year among Klebsiella spp. isolates, primarily from 1 geographic region (Middle Atlantic States). These MYSTIC Program (2006) results demonstrate the continued need to monitor the carbapenem class potency and spectrum of activity against Enterobacteriaceae as well as P. aeruginosa because of the documented presence of serine carbapenemases and rare incidence of metallo-β-lactamases that may further compromise their activity and that of other β-lactam agents.

Emergence of serine carbapenemases (KPC and SME) among clinical strains of Enterobacteriaceae isolated in the United States Medical Centers: Report from the MYSTIC Program (1999–2005)

Among 8885 Enterobacteriaceae tested in the 1999 to 2005 period as part of the USA Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program, 51 strains with increased imipenem and meropenem MIC values (≥2 μg/mL) were detected. bla KPC was identified from 28 Klebsiella pneumoniae from 3 medical centers in the New York City area (8 ribotypes), 2 Klebsiella oxytoca from Arkansas (same ribotype), 7 Citrobacter freundii (6 from New York [5 ribotypes] and 1 from Delaware), 4 Enterobacter spp. from New York (2 species, different ribotypes), 3 Escherichia coli (2 from New York and 1 from Ohio, same ribotype), and 1 Serratia marcescens (New York). Sequencing confirmed KPC-2 or -3 in all of the strains. S. marcescens strains harboring SME-1 (2 isolates, same ribotype) and SME-2 (1 isolate) were identified from medical centers in Illinois and Washington state, respectively. Our results indicate that bla KPC-2/3 has emerged widely (New York City area, Arkansas, Delaware, and Ohio) among Enterobacteriaceae isolated in the MYSTIC Program participant sites (2000–2005) and continues to be isolated from multiple species, as a result of clonal expansion and horizontal gene transfer. The escalating occurrence (0.35%) of serine carbapenemases could compromise the role of carbapenems and other β-lactams in USA clinical practice although observed in only a few locations to date.

An overview of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program: 1997–2004

This overview provides a summary of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program over an 8-year period from 1997 to 2004. The evolution of the MYSTIC Program is described, as well as its design compared with other surveillance programs. In addition, the global MYSTIC Program data, published to date, are summarized, and the empiric use of carbapenems, their current indications, and meropenem usage versus resistance was discussed. From 1997 to 2004, 120 medical centers that were actively prescribing meropenem in 32 countries worldwide participated in the program. The MYSTIC Program results demonstrate the sustained potency and continued effectiveness of meropenem globally against clinically relevant Gram-negative and Gram-positive pathogens including extended spectrum β-lactamase– and AmpC β-lactamase–producing organisms, which may also display resistance to the fluoroquinolones and/or aminoglycosides. Furthermore, in centers actively prescribing meropenem, resistance to meropenem is not increasing despite greater resistance among the comparator antimicrobial agents. Thus, antipseudomonal carbapenems such as meropenem and imipenem remain an effective treatment option.

Overview of the Meropenem Yearly Susceptibility Test Information Collection (1997–2004)

Global overuse of commonly prescribed antimicrobial agents has led to the development of high levels of resistance (Rybak, 2004). To try to control the spread of specific antimicrobial resistance mechanisms, long-term surveillance studies are required to monitor trends in antimicrobial susceptibility (Masterton et al., 2003; Masterton, 2000; Morris and Masterton, 2002). The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is one such study and was set up in 1997 to monitor the in vitro activity of meropenem and comparator broad-spectrum antimicrobials against Grampositive and Gram-negative aerobic clinical isolates from hospital centers where meropenem is prescribed (Turner et al., 1999; Turner, 2000). This collection of articles will provide an overview of the MYSTIC Program and will discuss changes in worldwide resistance patterns. In addition, it will describe computer programs that have been established to aid analysis of the extensive data sets collected. In the first article, Jones et al. (2005) describe the evolution of the MYSTIC Program and how it compares with other surveillance projects, as well as providing an overview of current key geographical and susceptibility observations. The 2 articles that follow present data from the MYSTIC Program. Goossens and Grabien (2005) present prevalence and susceptibility data from the MYSTIC Program in Europe (1997–2004) and the United States (1999–2004) for Enterobacteriaceae that produce ESBLand/or AmpC h-lactamases with regard to changes in resistance patterns over time as well as regional and global differences. Unal and Garcia-Rodriguez (2005) examine the susceptibility of Pseudomonas aeruginosa and Acinetobacter spp. isolated from MYSTIC centers

Activity of meropenem and comparators against Pseudomonas aeruginosa and Acinetobacter spp. isolated in the MYSTIC Program, 2002–2004

This study examines the susceptibilities of meropenem and other broad-spectrum antimicrobials tested against bacterial isolates collected from hospitalized patients during 2002–2004 from worldwide medical centers participating in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program. The in vitro activity of meropenem and 5 comparator antimicrobial agents was assessed against Pseudomonas aeruginosa and Acinetobacter spp. Generally, the susceptibility of Australasian and North American isolates was higher than that of the European and South American isolates. The rank order of activity of the antimicrobial agents tested against a worldwide collection of P. aeruginosa was piperacillin/tazobactam (77.7% susceptible) > meropenem (75.4%) > ceftazidime (70.0%) > imipenem (69.7%) > gentamicin (66.1%) > ciprofloxacin (62.0%). Against a worldwide collection of Acinetobacter spp. meropenem (76.1% susceptible) was the most active compound followed by imipenem (74.7%) > gentamicin (51.9%) > ciprofloxacin (40.5%) > piperacillin/tazobactam (39.8%) > ceftazidime (38.1%). The carbapenems appear to be a valuable option for the treatment of serious nosocomial infections caused by P. aeruginosa or Acinetobacter spp. over a broad geographical region.

Use of a program-specific website to disseminate surveillance data obtained from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Study

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a multicenter, longitudinal surveillance study initiated in 1997 that compares the activity of meropenem and comparator antimicrobials in centers that are actively prescribing meropenem. Antimicrobial surveillance programs, such as MYSTIC, provide important information on the emergence of bacterial resistance and the nature of the underlying mechanisms in different geographical regions. Data concerning these mechanisms and patterns of antimicrobial resistance allow the implementation of changes in antimicrobial prescribing practices and infection control interventions. Therefore, it is important that data from surveillance programs be analyzed and accessible to clinicians within reasonable, clinically useful, intervals. In this article, the use of a website designed to disseminate data collected from the MYSTIC program is described. This web-based program allows specific surveillance data to be examined in a timely manner and can assist the clinician when choosing the most appropriate antibiotic for the situation encountered and hopefully maximize successful clinical outcomes.

The OPTAMA programme: utilizing MYSTIC (2002) to predict critical pharmacodynamic target attainment against nosocomial pathogens in Europe

The Optimising Pharmacodynamic Target Attainment using the MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Antibiogram (OPTAMA) programme identifies antibiotic regimens with the highest probability of attaining critical pharmacodynamic targets, accounting for the inherent variability in pharmacokinetics, dosages and MIC distributions. European MIC data were obtained from the MYSTIC programme. Pharmacodynamic target attainment was calculated by Monte Carlo simulation for meropenem, imipenem, ceftazidime, cefepime, piperacillin/tazobactam and ciprofloxacin against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. Significant differences in probability of target attainment were found, with Northern Europe demonstrating the highest probabilities of target attainment and Eastern Europe the lowest. The carbapenems had the highest target attainments and susceptibility levels across all regions and pathogens. The cephalosporins demonstrated high target attainments and susceptibility results against E. coli and K. pneumoniae in Northern and Southern Europe. Piperacillin/tazobactam and ciprofloxacin had the lowest levels for both parameters in all regions. Desirable target attainment was not achieved (except for carbapenems in Northern Europe) for A. baumannii and P. aeruginosa; thus, combination therapy may be appropriate empirical therapy for these pathogens in Southern and Eastern Europe. The closest correlations between target attainment and susceptibility were for meropenem 1 g every 8 h, imipenem 0.5 g every 6 h and ceftazidime 1 g every 8 h. The study highlighted significant overestimations between the probability of target attainment and the reported percentage susceptibility, particularly for piperacillin/tazobactam and ciprofloxacin. The approach of the OPTAMA programme provides a novel tool which complements susceptibility data to help in the selection of appropriate empirical antibiotic therapy.

Determination of epidemic clonality among multidrug-resistant strains of Acinetobacter spp. and Pseudomonas aeruginosa in the MYSTIC Programme (USA, 1999–2003)

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme was initiated in 1997 (1999 for the United States). This program monitors resistance in participant medical centers where carbapenems are prescribed and drug use data can be obtained. An earlier report found antimicrobial use was not a clear cause of local or aggregate changes in resistance rates. This study addresses the role of dissemination of resistant clones on susceptibility rates for nonfermentors, Acinetobacter spp. (ACB) and Pseudomonas aeruginosa (PSA). Carbapenem (CARB)-multidrug-resistant strains (MDR) from among 236 ACB and 1,111 PSA were tested by reference broth microdilution methods, automated ribotyping, and pulsed field gel electrophoresis to determine possible clonal dissemination. Each strain was also tested for metallo-β-lactamases (MβL) (phenotypic and polymerase chain reaction); and then analyzed by CARB-R rate and defined daily dose (DDD)/100 days use groupings (high, moderate, and low). For the aggregate 15 sites in the MYSTIC Programme each year, the CARB-resistant rate decreased over 5 years; but other drug-resistance rates generally escalated. Changes were not related to antimicrobial use calculations. The discovered clonally spread MDR-PSA strains were more frequent in high- (1.8 clones/site) and moderate-resistance (0.6 clones/site) rate centers (21.7% to 29.5% were clonal), compared with unique strains in low-resistance hospitals. ACB clonality was extreme in one geographic area, with dissemination of 5 different clones (931.7/B, C, or D; 1090.2/A; 167.5/A) in 4 centers (02, 04, 06, and 18). Resistance rates in ACB and PSA were clearly related to clonal occurrence and spread, and one MβL (VIM-7) was detected. Decreased CARB resistance rates from 1999 through 2002 were directly attributed to the disappearance of resistance clones in some locations. In conclusion, ACB and PSA CARB and MDR resistance rates in MYSTIC Programme institutions have been greatly influenced by clonal dissemination and less by antimicrobial use patterns. The most serious examples of resistance were the clonality observed among ACB in New York City and the documented endemic nature of VIM-7-producing PSA (0.09% of all PSA isolates). Meropenem remained the most active antimicrobial agent tested in the program, and surveillance networks must implement epidemiologic typing to accurately assess the role of clonal spread on the study results.

Results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme: report of the 2001 data from 15 United States medical centres

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme is an international surveillance network of more than 100 medical centres where meropenem is the primary therapeutic carbapenem. Institutions have been monitored since 1997 (1999 in United States (US)) using National Committee for Clinical Laboratory Standards (NCCLS) reference susceptibility methods to monitor in vitro activity of meropenem and selected other broad-spectrum antimicrobial agents. In 2001, a total of 2874 strains were processed from the 15 US medical centres. Molecular methods were associated with MIC methods as needed for defining epidemic spread of resistant strains. The meropenem MIC 90 values were 0.03 mg/l for Citrobacter spp., Escherichia coli and Klebsiella spp.; 0.06 mg/l for Proteus mirabilis and Serratia spp. and 0.12 mg/l for Enterobacter spp. This potency was 8–16-fold greater than that of imipenem and the meropenem spectrum of activity versus the Enterobacteriaceae was the broadest of all tested antimicrobial agents. Only piperacillin/tazobactam (MIC 9, 64 mg/l) and tobramycin (MIC 90, 4 mg/l) were active against more than 90.0% of Pseudomonas aeruginosa at the NCCLS susceptible breakpoint, and the carbapenems were the most active compounds against Acinetobacter spp. However, Acinetobacter spp. isolates were resistant to all of the antimicrobial agents tested and the molecular typing results suggested that they were epidemiologically related. Only ciprofloxacin and ceftazidime had significantly reduced activity against oxacillin-susceptible staphylococci (87.9–92.6% susceptible. These 2001 US MYSTIC Programme results demonstrated no significant decline in carbapenem activity or susceptibility rates compared with the previously monitored years (1999–2000). Most apparent were the decreasing susceptibility rates for ciprofloxacin and ceftazidime against staphylococci. Continued surveillance in these institutions appears warranted as sites of high potential emerging resistance risk.

Antimicrobial spectrum of activity for meropenem and nine broad spectrum antimicrobials: report from the MYSTIC Program (2002) in North America

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program provides susceptibility data for participating medical centers where carbapenems are utilized. The activity of meropenem and nine broad-spectrum antimicrobial agents were assessed against 3,047 bacterial isolates collected during 2002 from 16 North American sites. The overall rank order of susceptibility of the 10 antimicrobial agents tested against Gram-negative isolates was: meropenem (98%) > imipenem (97%) > cefepime (95%) > tobramycin (93%) > piperacillin/tazobactam = gentamicin (92%) > ceftazidime (91%) > ciprofloxacin (87%) > aztreonam (86%) > ceftriaxone (74%). These results and those from previous years, demonstrate the continued excellent potency and spectrum of activity for meropenem. The utility of meropenem against Pseudomonas aeruginosa isolates has increased steadily with a rise in percent susceptibility each year from 78.2% in 1999 to a present rate of 93.1% susceptible. Conversely, we showed the susceptibility for ciprofloxacin against these same P. aeruginosa isolates has decreased from 82.9 to 72.3% susceptible over four years. Many medical centers have observed a decreased activity of some aminoglycosides, cephalosporins and fluoroquinolones due to increases in rates of extended-spectrum β-lactamases, Amp C and other resistance mechanisms. Carbapenem resistance remains rarely documented and these β-lactamase-stable agents appear to be an alternative treatment option for serious community-acquired or nosocomial infections in high risk patient populations.

Antimicrobial susceptibility of inducible AmpC β-lactamase-producing Enterobacteriaceae from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme, Europe 1997–2000

Among 11 345 clinical isolates from 31 European centres in the MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Programme (1997–2000), the potential AmpC-producing pathogens were Enterobacter spp. (904 cases), Citrobacter spp. (144) and Serratia marcescens (288). Resistance to ceftazidime or cefotaxime (11–34%) and piperacillin/tazobactam (12%) was observed, indicating stably derepressed expression of AmpC cephalosporinases. Meropenem (MIC 90, 0.25 mg/l; >99% susceptible) and imipenem (MIC 90, 2 mg/l; 98% susceptible) were active, even against these stably derepressed AmpC-producers: Enterobacter spp. (305 strains), Citrobacter spp. (29) and S. marcescens (35). The overall rank order of spectrum (% susceptible) versus the stably derepressed subset of isolates was: meropenem=imipenem (98%)>cefepime (89%)>gentamicin (73%)>ciprofloxacin (62%)>tobramycin (60%) >piperacillin/tazobactam (21%). We suggest increased attention in Europe to: (1) the recognition of these resistant phenotypes, (2) infection control practices, and (3) limiting the overuse of certain selecting extended-spectrum β-lactam agents (e.g. ceftazidime).

Ciprofloxacin as broad-spectrum empiric therapy—are fluoroquinolones still viable monotherapeutic agents compared with β-lactams: Data from the MYSTIC Program (US)?

Antimicrobial susceptibility data from United States medical centers participating in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance program were analyzed. These results indicate that ciprofloxacin resistance in commonly encountered nosocomial pathogens has reached a level where fluoroquinolones may no longer provide assured empiric monotherapy for serious infections nor provide a spectrum as a co-drug equivalent to aminoglycosides. Local susceptibility testing data must be assessed before fluoroquinolone empiric therapy can be used with confidence.

Emerging Antimicrobial Resistances Among Proteus mirabilis in Europe: Report from the MYSTIC Program (1997-2001)

Resistance patterns that are currently problematic in Europe can vary greatly within the same species over time, among various patient populations and among geographic regions on the same continent. The results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program, which monitors carbapenem resistance rates in institutions using meropenem, were used to determine resistance differences among Proteus mirabilis. MIC results from 688 P. mirabilis strains were classified into 4 patient care groups: ICU (n=426), neutropenia patients (NP; n=145), general wards (n=97) and cystic fibrosis patients (CF; n=20). A total of 40 centers from 12 European countries have participated since 1997, divided into 3 geographic regions (East, North, South). All testing was performed by NCCLS reference methods and interpretive criteria, including screening of extended-spectrum β-lactamase (ESBL) phenotypes. Over the monitored interval the resistance rates varied for each agent without a clear trend toward a greater rate. Rank order of susceptibility was: meropenem (99%) > piperacillin/tazobactam (TAZ; 96%) > cefepime (95%) > ceftazidime (CAZ; 94%) > imipenem (IPM; 92%). Ciprofloxacin (CIP) was the least active agent tested (MIC90, 4 μg/ml; 86% susceptible). Unexpectedly, 3.6% of P. mirabilis were imipenem-resistant (MIC, >16 μg/ml). Greater rates of resistance were found for strains from NP and CF patients, and from eastern or southern European sites, usually associated with epidemic clusters. Generally susceptible species such as P. mirabilis have recently emerged as therapeutic problems in European medical centers following mutations that compromise CIP, CAZ and aminoglycoside use. Imipenem also showed decreased susceptibility of greater than 7% compared to less than 1% for meropenem. Continued surveillance by the MYSTIC Program appears to be a prudent practice to focus effective empiric treatment regimens.