Philip J. Turner

The MYSTIC (meropenem yearly susceptibility test information collection) programme.

The primary objective of the MYSTIC study is to monitor the performance of meropenem over a period of at least 3 years during which this carbapenem is prescribed in different hospital units thus allowing profiles to be established within individual hospitals. Monitoring is being carried out by assessing the antibiotic susceptibility of bacterial pathogens isolated from patients with a predominate problem of intraabdominal infections (IAI) and/or lower respiratory tract infections (LRTI), treated in specialist centres (haematology wards, the Intensive Care Unit [ICU], cystic fibrosis units) and non-specialised centres. Samples will be collected over each year and tested against meropenem and a set of comparators. The data obtained from the first year of the study (1997) come from 33 centres spread mainly throughout Europe but also in Israel and Mexico. The results shows that meropenem retains its broad spectrum and potency whilst there is evidence that the activity of comparator antibiotics is being eroded by a variety of resistance mechanisms. Data from subsequent years of the programme will determine whether these trends continue and will allow a series of individual centre profiles to be compiled and presented.

Extended-Spectrum β-Lactamases

The first beta-lactamase was identified in an isolate of Escherichia coli in 1940. To date, there are >130 TEM-type and >50 sulfhydryl variable (SHV)-type beta-lactamases, mainly in E. coli, Klebsiella pneumoniae, and Proteus mirabilis but also in other members of the Enterobacteriaceae family and in some nonenteric organisms, such as Acinetobacter species. The incidence of expanded-spectrum beta-lactamases (ESBLs) varies, depending on which area of the globe the isolates originate from. ESBLs render the oxyimino-cephalosporins ineffective, and ESBL-producing organisms frequently also possess resistance factors to other classes of antibiotics, such as aminoglycosides and fluoroquinolones, and possibly also piperacillin-tazobactam and cefepime. These results suggest that microbiology laboratories should routinely test for the presence of these strains among their isolates and that the antibiotics of choice for infections believed to be caused by these types of organisms are the carbapenems.

Integrating Escherichia coli Antimicrobial Susceptibility Data from Multiple Surveillance Programs

Collaboration between networks presents opportunities to increase analytical power and cross-validate findings. Multivariate analyses of 2 large, international datasets (MYSTIC and SENTRY) from the Global Advisory on Antibiotic Resistance Data program explored temporal, geographic, and demographic trends in Escherichia coli resistance from 1997 to 2001. Elevated rates of nonsusceptibility were seen in Latin America, southern Europe, and the western Pacific, and lower rates were seen in North America. For most antimicrobial drugs considered, nonsusceptibility was higher in isolates from men, older patients, and intensive care unit patients. Nonsusceptibility to ciprofloxacin was higher in younger patients, rose with time, and was not associated with intensive care unit status. In univariate analyses, estimates of nonsusceptibility from MYSTIC were consistently higher than those from SENTRY, but these differences disappeared in multivariate analyses, which supports the epidemiologic relevance of findings from the 2 programs, despite differences in surveillance strategies.

Antimicrobial susceptibility of Gram-negative bacteria in Brazilian hospitals: the MYSTIC Program Brazil 2003

Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2003. Gram-negative bacteria (n = 1,550) causing nosocomial infections were collected at 20 Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by Etest methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). Pseudomonas aeruginosa (30.3%) was the most frequent isolate, followed by E. coli (18.6%), Klebsiella pneumoniae (16.9%), Acitenobacter baumannii (8.8%), and Enterobacter cloacae (7.1%). Pseudomonas aeruginosa (n=470) isolates presented susceptibility rates of 64% to meropenem, 63.8% to piperacillin/tazobactam, 63.4% to amikacin, 58.7% to imipenem. Acitenobacter baumannii presented susceptibility rates to meropenem of 97.1%, and 73% to tobramycin. E. coli and K. pneumoniae were highly susceptible to both carbapenems. Carbapenem resistance among the Enterobacteriaceae is still rare in the region. Acitenobacter baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since they play an important role in nosocomial infections in this environment, the use of empirical combination therapy to treat these pathogens may be justified.

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.

Antimicrobial susceptibility in intensive care units: MYSTIC Program Brazil 2002

OBJECTIVE Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2002. MATERIAL AND METHODS Gram-negative bacteria (n = 503) causing nosocomial infections were collected at seven Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by E-test methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). RESULTS Pseudomonas aeruginosa (33%) was the most frequently isolated, followed by A. baumannii (17.1%), K. pneumoniae (12.1%), E. coli (10.5%), and E. cloacae (7.9%). Pseudomonas aeruginosa isolates had susceptibility rates of 67.5% to piperacillin/tazobactam, 59.8% to meropenem, 57.3% to imipenem. A. baumannii presented susceptibility rates to meropenem of 89.5%, 88.4% to imipenem, and 74.4% to tobramycin. E. coli and K. pneumoniae were fully susceptible to both carbapenems. CONCLUSIONS Carbapenem resistance among Enterobacteriaceae is still rare in this region. A. baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since these two bacterial species play an important role in nosocomial infections, the use of empirical combination therapy to treat these pathogens may be justified.

Unit differences in pathogen occurrence arising from the MYSTIC program European database (1997–2000)

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal global antimicrobial surveillance study that compares the activity of meropenem and comparator antimicrobial agents against pathogens isolated from intensive care, neutropenic or cystic fibrosis patients, and general wards. Data from the different European MYSTIC Program units (1997-2000) showed that the most prevalent isolates tested overall were methicillin-susceptible Staphylococcus aureus (MSSA; in accordance with study design methicillin-resistant S. aureus was not tested), Pseudomonas aeruginosa and Escherichia coli. In all the unit types, E. coli (approximately 20% having an extended spectrum beta-lactamase phenotype) and MSSA were highly susceptible to meropenem (97-99% susceptibility). Isolates of MSSA showed lower levels of susceptibility to ciprofloxacin (61-77% susceptibility) in both cystic fibrosis and neutropenia patients, and particularly high levels of resistance to ceftazidime (38% susceptibility) in cystic fibrosis units. Ciprofloxacin (54% susceptibility) and gentamicin (46% susceptibility) demonstrated low levels of activity against P. aeruginosa (frequently encountered in cystic fibrosis units). Meropenem and piperacillin/tazobactam were the most active agents against P. aeruginosa in all the unit types. Carbapenems and piperacillin/tazobactam have sustained > 90% susceptibility rates overall against the most frequently isolated pathogens. The analysis of specific units that house patients with a high-risk of contracting antimicrobial-resistant pathogens remains very important for the optimal selection of empiric regimens.

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

OBJECTIVES 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. METHODS MICs of meropenem and eight other antibiotics were determined using the CLSI agar dilution method. RESULTS 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. CONCLUSIONS 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 patterns of Gram-negative bacteria from a Polish intensive care unit, 1997-2000

The susceptibility of Gram-negative bacterial strains (n=400) isolated from clinical specimens of children hospitalized in a Polish intensive care unit (ICU) between 1997 and 2000 was tested. Meropenem, imipenem and ciprofloxacin were most active (>90% susceptibility) against the tested isolates, with no observed reduction in activity over 4 years. Extended-spectrum beta-lactamases and AmpC beta-lactamase producers among Enterobacteriaceae isolates from this ICU continued to be a serious therapeutic problem, although the carbapenems were highly active against these resistance phenotypes. Resistance to aminoglycosides (gentamicin, tobramycin) and ceftazidime was a characteristic of >40% of tested isolates.

Klebsiella pneumoniae with multiple antimicrobial resistance

A Klebsiella pneumoniae strain was isolated from the urine of a patient at one of the centers participating in the 2001 edition of the MYSTIC program in Brazil. The initial phenotypic findings of the isolated K. pneumoniae presented an unusual MIC of 8 microg/mL to meropenem, 2 microg/mL to imipenem, elevated MICs to broad spectrum cephalosporins (ceftazidime/cefotaxime/cefepime MIC > 256 microg/mL), aminoglycosides (gentamycin > 256 microg/mL and tobramycin = 48 microg/mL), piperacillin/tazobactam (MIC > 256 microg/mL) and susceptibility to ciprofloxacin (MIC = 0.25 microg/mL). The strain also tested positive for ESBL production with double-disk and E-test methodologies. More detailed investigation revealed that the strain produced a SHV-4 type enzyme and also lacked a 36 kDa outer membrane porin.