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 microg/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 beta-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 microg/mL), Streptococcus pneumoniae (MIC(90), 0.5 microg/mL), and beta-hemolytic and viridans group streptococci (MIC(90) range, 0.06-0.25 microg/mL). These US MYSTIC Program results demonstrate the continued emergence of novel beta-lactamases and multidrug-resistant bacterial phenotypes necessitating monitoring of carbapenem activities against Enterobacteriaceae species as well as nonfermentative bacilli.     

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 beta-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-beta-lactamases that may further compromise their activity and that of other beta-lactam agents.     

Antimicrobial activity against strains of Escherichia coli and Klebsiella spp. with resistance phenotypes consistent with an extended-spectrum β-lactamase in Europe

Extended-spectrum β-lactamases (ESBLs) have continued to evolve after their initial detection in Europe nearly two decades ago. The summary results from the MYSTIC Program (31 medical centers) were utilized to assess the extent of ESBL occurrence in Europe from 1997 to 2000. ESBL phenotype rates in Klebsiella spp. (32.8%) and Escherichia coli (14.4%) were generally stable, but extensive hospital-to-hospital and unit-to-unit variations were noted. The highest ESBL rates were found in eastern Europe (including Turkey) and in intensive care unit patient populations. Carbapenems remained active against the ESBL-producing strains (meropenem MIC₉₀, 0.25–1 mg/L), while some other agents, such as aminoglycosides, fluoroquinolones, and piperacillin–tazobactam, were significantly less effective. International surveillance initiatives should be maintained to monitor future progression of this important resistance.     

The activity of meropenem and comparators against Acinetobacter strains isolated from European hospitals, 1997–2000

In vitro susceptibilities to meropenem and comparators of Acinetobacter strains isolated from serious infections in 37 European hospital centers participating in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program (1997–2000) were tested. There were 635 Acinetobacter strains collected: 490 A. baumannii ; 51 A. calcoaceticus var . lwoffii ; and 94 other Acinetobacter strains. Overall, meropenem and imipenem were the most effective agents tested. Resistance to the antimicrobials was: 14%, meropenem; 16%, imipenem; 39%, piperacillin–tazobactam; 41%, tobramycin; 45%, ceftazidime; and 53%, ciprofloxacin. Thus, the carbapenems have useful activity against Acinetobacter spp. and represent a viable choice for treating infections caused by these organisms.     

Contemporary activity of meropenem and comparator broad-spectrum agents: MYSTIC program report from the United States component (2005)

The Meropenem Yearly Susceptibility Test Information Collection Program is a 9-year-old antimicrobial resistance surveillance network of more than 100 medical centers worldwide, including 15 sites in the United States (US) that monitors the susceptibility of Gram-negative and Gram-positive bacterial pathogens especially to carbapenems. In 2005, the antimicrobial activity of 11 broad-spectrum agents was assessed against 2910 bacterial isolates (2493 Gram-negative and 417 staphylococci) submitted from the US medical centers to a reference laboratory using Clinical and Laboratory Standards Institute susceptibility testing methods and interpretative criteria. Meropenem continued to demonstrate 1) high potency with MIC(90) values 4- to 16-fold lower than imipenem against the Enterobacteriaceae, 2) equal activity against Pseudomonas aeruginosa, 3) 2-fold less activity compared with imipenem against Acinetobacter spp., and 4) 4- to 8-fold less activity compared with imipenem against the oxacillin-susceptible staphylococci. The wide spectrum of activity for carbapenems against Enterobacteriaceae (1657 strains) was confirmed by the overall rank order by percentage susceptibility at breakpoint criteria: imipenem (98.9%) > meropenem (98.7%) > cefepime (97.6%) > piperacillin/tazobactam (92.0%) > ceftriaxone (91.2%) > aztreonam (90.6%) > gentamicin = tobramycin (90.5%) > ceftazidime (90.4%) > levofloxacin (84.9%) > ciprofloxacin (83.9%). Against Acinetobacter spp. isolates, only tobramycin (92.0% susceptible) and carbapenems (92.0-85.6%) exhibited acceptable levels of activity. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin was observed with highest rates found among indole-positive Proteae species (36.5-33.3%) and Escherichia coli (21.6-20.4%) isolates, some documented by molecular typing methods as clonally related. Ongoing surveillance of meropenem and other broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against indicated Gram-negative and-positive pathogens causing serious infections in the hospital setting, and to detect the emergence of new or novel resistance mechanisms that could compromise clinical utility (serine and metallo-carbapenemases).     

Susceptibility of meropenem and comparators tested against 30,634 Enterobacteriaceae isolated in the MYSTIC Programme (1997-2003)

A total of 30,634 global Enterobacteriaceae isolates collected from the MYSTIC (Meropenem Yearly Surveillance Test Information Collection) Programme were tested using a reference methodology against meropenem and seven other broad-spectrum agents commonly used in the hospital setting (1997–2003). The most active compound was meropenem (99.6% susceptible), followed by imipenem (98.4%), cefepime (94.0%), gentamicin (86.8%), piperacillin/tazobactam (85.8%), ceftazidime (85.0%), ciprofloxacin (84.6%), and tobramycin (84.5%). Continued surveillance of antimicrobial compounds' in vitro activity is necessary to recommend regimens that are likely to be effective in clinical practice.     

Results of two worldwide surveys into physician awareness and perceptions of extended-spectrum β-lactamases

An omnibus survey of microbiologists (n = 400) and a survey of participants (n = 49) in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme were conducted to determine the awareness and prevalence of extended-spectrum beta-lactamases (ESBLs), and the regularity and method of screening. Of the omnibus survey participants, 69% screened regularly for ESBLs, compared with 83% of MYSTIC participants. In both surveys, ESBLs were more common in Klebsiella pneumoniae (73% and 79%, respectively) and Escherichia coli (63% and 81%, respectively) than in other bacteria. The surveys demonstrated that awareness of, and testing for, ESBLs is inconsistent.     

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.     

MYSTIC Europe 2007: activity of meropenem and other broad-spectrum agents against nosocomial isolates

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal antimicrobial surveillance study that has been in existence since 1997 in centers that are actively prescribing meropenem. This report examines the results from the study in Europe in 2007. A total of 5208 isolates were examined for activity (MIC) of meropenem and other broad-spectrum antibacterial comparators. Cumulative susceptibility rates using Clinical and Laboratory Standards Institute criteria against all methicillin-susceptible staphylococci were imipenem (97.7%) > meropenem (97.3%) > piperacillin/tazobactam (96.2%) > tobramycin (94.2%) > gentamicin (92.0%) > ciprofloxacin (84.0%) > ceftazidime (39.8%). Against all species of Enterobacteriaceae, the rates were meropenem (99.4%) > imipenem (98.3%) > tobramycin (92.0%) > gentamicin (89.5%) > ceftazidime (86.2%) > piperacillin/tazobactam (85.5%) > ciprofloxacin (84.2%). Meropenem was most effective against the nonfermenters, although multidrug-resistant Acinetobacter spp. and imipenem-resistant Pseudomonas aeruginosa strains were reported. The continued need for surveillance studies such as MYSTIC is exemplified, and results from these types of surveillance can, hopefully, help in the correct choice of empiric therapy.