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PubMed2005

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.

Acinetobacter↗
PubMed2005

Trends in antimicrobial susceptibility in UK centres: the MYSTIC Programme (1997-2002).

Trends in antimicrobial susceptibilities in three UK centres participating in the MYSTIC Programme were examined from 1997 to 2002. Isolates were tested using standard methodology to determine the susceptibility breakpoints of meropenem and several other antimicrobial agents including imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. Data are grouped in 2-year blocks. The carbapenems were the most active agents tested against the Enterobacteriaceae (99-100% and 98-100% susceptibility to meropenem and imipenem, respectively) and non-fermenters, including Pseudomonas spp. and Acinetobacter spp. With the exception of susceptibility to ciprofloxacin, which decreased among Enterobacteriaceae at the end of the 6-year period, all antibiotics tested retained their levels of activity. The proportion of extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae increased during the study (4.8% and 11.3% in 1997-1998; 7.4% and 16.7% in 2001-2002, respectively). Both meropenem and imipenem retained their potency against these ESBL- and AmpC-producing isolates (100% for all time periods). All the other antimicrobial agents tested had much lower susceptibility against these resistant isolates and this decreased further over the 6-year period, with the exception of tazobactam, which maintained its low levels. Although all antibiotics tested retained acceptable activity, the carbapenems remained the most active antimicrobial agents against Gram-negative bacteria, including ESBL- and AmpC-producing isolates.

Anti-Infective Agents↗
PubMed2001

Carbapenem-resistant Serratia marcescens isolates producing Bush group 2f beta-lactamase (SME-1) in the United States: results from the MYSTIC Programme.

Two carbapenem (imipenem, meropenem)-resistant Serratia marcescens strains were isolated in the United States (Chicago, IL) through the 1999 MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Programme. The S. marcescens antimicrobial susceptible patterns were: susceptible to ceftriaxone, ceftazidime, and cefepime (MICs, < or = 0.25 microg/ml), and resistance to the carbapenems (imipenem and meropenem; MIC, > 32 microg/ml) and aztreonam (MIC, > = 16 microg/ml). Each S. marcescens isolate shared an identical epidemiologic type (ribotype and PFGE) and the outer membrane protein profile was also identical to those of the wild type susceptible strains from the same medical center. The PCR utilizing bla(sme-1) primers amplified a gene product that was identified as consistent with SME-1 after DNA sequencing. Imipenem and meropenem resistance due to production of carbapenem-hydrolyzing enzymes among clinical isolates is still very rare, but microbiology laboratories should be aware of these chromosomally encoded enzymes among class C beta-lactamases producing enteric bacilli such as S. marcescens and Enterobacter cloacae.

Drug Resistance, Microbial↗
PubMed2002

Ciprofloxacin as broad-spectrum empiric therapy--are fluoroquinolones still viable monotherapeutic agents compared with beta-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.

Anti-Bacterial Agents↗
PubMed1999

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.

Bacteria↗
PubMed2003

Susceptibility of multi-drug-resistant Pseudomonas aeruginosa in intensive care units: results from the European MYSTIC study group.

The MYSTIC program monitors worldwide in vitro susceptibilities of clinical bacterial isolates from centers that prescribe meropenem. This report focuses on 107 isolates of multi-drug resistant (MDR) Pseudomonas aeruginosa, which commonly causes infections that are difficult to treat in hospitalized patients. We chose samples from patients from 33 European intensive care units (ICUs). There was considerable inter-country variation in the proportion of P. aeruginosa that were MDR, ranging from 50% in Turkey to < or =3% in Spain, the UK, Germany, Bulgaria and Malta. Amongst the MDR isolates, the percentage resistance (MIC50/90 in mg/L) to the antibiotics tested were amikacin 18.7% (32/>128), meropenem 29.1% (8/64), imipenem 44.9% (16/64), cefepime 49.5% (32/64) and piperacillin/tazobactam 57.9% (128/>128).

Anti-Bacterial Agents↗
PubMed2004

Antimicrobial usage and resistance trend relationships from the MYSTIC Programme in North America (1999-2001).

BACKGROUND: The MYSTIC Programme is a global, longitudinal antimicrobial surveillance network of hospitals that frequently utilize carbapenems. One aspect of the programme is the ability to capture antimicrobial consumption data from participating institutions. The current report evaluates these relationships for Enterobacteriaceae and Pseudomonas aeruginosa over the initial 3 year period of the programme in the USA. METHODS: Between 10 and 15 medical centres participated during 1999-2001, each submitting up to 200 isolates/year (7003 strains overall). Evaluations of the relationship between drug usage and antimicrobial resistance in P. aeruginosa and Enterobacteriaceae for the carbapenems (imipenem and meropenem), cefepime, ceftazidime, ciprofloxacin, gentamicin and piperacillin-tazobactam were determined. Data were analysed based on: (1) aggregate usage results; (2) medical centre-specific usage compared with resistance rates; and (3) medical centre-specific usage results compared with yearly changes in resistance rates (DeltaR). The parameter of drug usage was the defined daily dose (DDD)/100 patient days calculated from total grams administered, using WHO definitions. RESULTS: Resistance (1999-2001) among Enterobacteriaceae did not change significantly for beta-lactams, but tended to increase slightly for gentamicin (+1.1%) and ciprofloxacin (+3.1%). P. aeruginosa resistance rates (1999-2001) for gentamicin (+9.0%) and ciprofloxacin (+10.2%) increased, in contrast to a significantly decreased resistance rate for meropenem (-7.7%). Formulary-use changes were noted: increased meropenem and ciprofloxacin use and decreased consumption for imipenem, aminoglycosides, ceftazidime and cefepime. Aggregate ciprofloxacin DDD/100 days rates were directly related (+3.3 DDD) to Enterobacteriaceae and P. aeruginosa resistance changes, whereas among P. aeruginosa, usage and resistance were inversely correlated for gentamicin (-3.8 DDD; +9.0% resistant). Medical centre-specific antimicrobial usage calculations did not demonstrate a correlation to rates of resistance (r = -0.38 to 0.61) or yearly changes in resistance rates (r = -0.56 to 0.43). CONCLUSIONS: The availability of aggregate USA medical centre antimicrobial usage data enabled us to identify several important trends in the incidence of resistance among P. aeruginosa and Enterobacteriaceae: (1) increased use of ciprofloxacin associated with a higher resistance among Enterobacteriaceae; and (2) a correlation between ciprofloxacin categories of resistance and levels of resistance to other antimicrobial classes in P. aeruginosa. Medical centre-specific antimicrobial usage and resistance did not demonstrate direct statistical relationships, and require a continued search for other monitoring methods that can better identify antimicrobial/environmental factors that lead to resistance.

Anti-Bacterial Agents↗
PubMed2004

Optimizing pharmacodynamic target attainment using the MYSTIC antibiogram: data collected in North America in 2002.

The OPTAMA Program is intended to examine typical antimicrobial regimens used in the treatment of common nosocomial pathogens and the likelihood of these regimens attaining appropriate pharmacodynamic exposure in different parts of the world. A 5,000-subject Monte Carlo simulation was used to estimate pharmacodynamic target attainment for meropenem, imipenem, ceftazidime, cefepime, piperacillin-tazobactam, and ciprofloxacin against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Standard dosing regimens from North America were used. Pharmacokinetic parameter variability was derived from existing healthy volunteer data, and MIC data came from the 2002 MYSTIC Program. Ciprofloxacin displayed the lowest target attainment against all bacterial species (41 to 46% for A. baumannii, 53 to 59% for P. aeruginosa, and 80 to 85% for the Enterobacteriaceae). Increasing the dose to 400 mg every 8 h did not significantly increase target attainment against nonfermenters. Piperacillin-tazobactam target attainments were similar to that of ceftazidime against all pathogens. Higher doses of both compounds were needed to achieve better target attainments against P. aeruginosa. Overall, meropenem, imipenem, and cefepime attained the highest probabilities of attainment against the Enterobacteriaceae (99 to 100%). The carbapenems appear to be the most useful agents against A. baumannii (88 to 92%), and these agents, along with higher doses of any of the beta-lactams, would be the most appropriate choices for empirical therapy for P. aeruginosa infection. Given the lack of agreement between percent susceptibility and probability of target attainment for certain antimicrobial regimens, a methodology employing stochastic pharmacodynamic analyses may be a more useful tool for differentiating the most-optimal compounds and dosing regimens in the clinical setting of initial empirical therapy.

Algorithms↗
PubMed2005

New trends in the cyber and street market of recreational drugs? The case of 2C-T-7 ('Blue Mystic').

2C-T-7 ('Blue Mystic'), an illicit compound which shows similarities with MDMA and other designer drugs, has been only occasionally identified in the EU, but discussion on the Internet between experimenters has recently grown significantly. We aimed at collecting together in a review the available information on 2C-T-7, both at the cyber and at the street market level. 2C-T-7 was first synthesized in 1986; its desired effects include both a sense of empathy and of well-being. Hallucinations, nausea, anxiety, panic attacks and paranoid ideation are anecdotally reported. According to the different European sources here approached, the availability of 2C-T-7 at street level seems to be currently very low, although one death related to a mono-intoxication with 2C-T-7 has been documented in the USA. With respect to information on 2C-T-7 available online, due to both redundancy and relevance issues the initial identified sample of 360 was reduced to 118 websites. In 14 (11.9%) websites, the detailed description of the 2C-T-7 synthesis was given. Harm Reduction websites appeared significantly earlier in the search engines results' list than Anti drugs (p 0.006) websites. Five (4.2%) websites apparently offered 2C-T-7 for sale. The large body of knowledge available online seems to contrast with small numbers of seizures at street level; an exhaustive web mapping of drug-related issues may be of interest for the clinician. Projects aimed at designing more 'attractive' prevention websites should be planned and future studies should better assess the characteristics of those consumers who take advantage of the online information of hallucinogenic compounds.

Affect↗
PubMed2002

Resistance surveillance in Italy: four-year results from the MYSTIC program.

The MYSTIC program is an international, multicenter surveillance study that compares the activity of meropenem, in centers that are prescribers, with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. These Italian data are from 3 centers (neutropenia, cystic fibrosis and intensive care units). A total of 2,072 (238 Gram-positive and 1,834 Gram-negative) aerobic microorganisms were collected during the study. Pseudomonas aeruginosa (33.4%) was the most isolated species followed by Escherichia coli (14.4%). All except one Enterobacteriaceae strain isolated were fully susceptible to meropenem. Moreover, the activity of meropenem against Enterobacteriaceae was about eight-fold greater than that of imipenem and four- to eight-fold more active than that of ceftazidime. Meropenem was highly active against non-fermentative Gram-negative microorganisms, exceeding the activity of most of the other antimicrobial agents tested. Moreover, meropenem showed increasing activity during the 4 years of study (starting from 86.2% in 1997 to 94.0% in 2000). In conclusion, our results indicate that meropenem has excellent potency and spectrum of activity despite being prescribed for the treatment of seriously ill patients, and appears to be a reliable option for the initial empirical treatment of serious nosocomial infections.

Anti-Bacterial Agents↗
PubMed2005

Comparative antimicrobial potency of meropenem tested against Gram-negative bacilli: report from the MYSTIC surveillance program in the United States (2004).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal resistance surveillance network of more than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. In 2004 (year six), the antimicrobial activity of 12 broad-spectrum agents was assessed against 2,799 Gram-negative bacterial isolates submitted from 15 United States (USA) medical centers using Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS) recommended methods. Meropenem continued to demonstrate a high potency with MIC90 values 4- to 32-fold lower than imipenem against the Enterobacteriaceae. The wide spectrum of activity for meropenem against all Gram-negative isolates was demonstrated by the overall rank order of percentage susceptibility at CLSI breakpoints: amikacin (96.5%) > meropenem (96.0%) > imipenem (95.8%) > piperacillin/tazobactam (91.5%) > tobramycin (91.4%) > cefepime (91.2%) > ceftazidime (89.0%) > gentamicin (88.0%) > aztreonam (81.5%) > levofloxacin (80.5%) > ciprofloxacin (80.2%) > ceftriaxone (69.1%). Only the aminoglycosides (84.5%) and carbapenems (76.1-83.8%) exhibited acceptable levels of susceptibility against the Acinetobacter spp. isolates as this species group became more resistant to all antimicrobial classes. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin over the six years was observed, most alarming among Escherichia coli (20.2-20.7%) and indole-positive Proteus species (34.4-42.2%) isolates, some documented as clonal. Continued surveillance of these broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against Gram-negative pathogens causing serious infections and the emergence of new or novel resistance mechanisms that could compromise carbapenem therapy.

Anti-Bacterial Agents↗
PubMed2000

MYSTIC (Meropenem Yearly Susceptibility Test Information Collection): a global overview.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) is a global, multicentre surveillance study that compares the activity of meropenem in centres that are prescribers with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. Of the 46 centres (intensive care units, cystic fibrosis units, neutropenia units and general wards) contributing to this study, 29 were in Europe, 14 in the Americas and three in the Middle East and Asia. The results for the most common isolates obtained in the first year of the study from these three regions show that meropenem has a broad spectrum of activity and potency in these centres, with 89% of the 6890 strains tested having an MIC 4 mg/L. The overall susceptibility was lower for the comparator antibiotics. There was evidence in all regions of strains producing beta-lactamases and other resistance mechanisms against the other beta-lactams tested, fluoroquinolones and aminoglycosides. Future years' results from this surveillance study will show whether meropenem will continue to exhibit such activity.

Journal Article↗
PubMed2000

MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from the Americas: resistance implications in the treatment of serious infections.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme aims to provide in vitro surveillance data for geographically diverse institutions where meropenem is available for use. The in vitro activity of meropenem and eight comparator antimicrobial agents against 2340 significant pathogens obtained in 1999 was assessed and compared in 14 study centres in Brazil, Mexico and the USA. Isolates were further characterized for production of extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases and carbapenemases. Carbapenems demonstrated their broad spectrum and potency, inhibiting >/=95% of all isolates irrespective of the geographical region or centre type. The overall order of activity of the nine agents tested against all pathogens in 1999 was meropenem (96%) > imipenem (95%) > cefepime (92%) > gentamicin (89%) > piperacillin/tazobactam (88%) > ceftazidime = tobramycin (86%) > cefotaxime (84%) > ciprofloxacin (83%). Thus far, the results from the Americas indicate that meropenem has excellent potency and spectrum of activity despite being prescribed for the treatment of seriously ill patients. In contrast, other ESBLs, fluoroquinolones and aminoglycosides have lost activity in many institutions as a result of the selection of strains producing ESBLs or having AmpC and other resistance determinants. Carbapenem resistance was observed rarely and at a prevalence similar to those reported in earlier studies. Carbapenems appear to be a continuing reliable option for the treatment of serious nosocomial infection.

Journal Article↗
PubMed2000

MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from Europe: comparison of antibiotic susceptibilities between countries and centre types.

The activity of meropenem and five comparators has been studied against 7886 isolates from 29 centres in 10 European countries from 1997 to 1999 as part of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance study. Gram-positive and Gram-negative isolates from intensive care units (ICUs), neutropenia centres, cystic fibrosis (CF) centres and general wards were investigated in Belgium (1 year), Czech Republic (2 years), Germany (3 years), Italy (3 years), Poland (2 years), Russia (2 years), Sweden (2 years), Switzerland (1 year), Turkey (1 year) and UK (3 years). Resistance to quinolones and aminoglycosides was observed, as was resistance to the cephalosporins and penicillins via extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases. Meropenem showed good activity against the pathogens tested, particularly in CF and neutropenia centres, over the 3 year period. The overall order of potency of the six antimicrobial agents tested was: meropenem > imipenem > piperacillin/tazobactam and ciprofloxacin > ceftazidime > gentamicin. No increase in resistance to the carbapenems, to date, has been detected in any of the European centres included in this study.

Journal Article↗
PubMed2000

MYSTIC (Meropenem Yearly Susceptibility Test Information Collection): a global overview.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) is a global, multicentre surveillance study that compares the activity of meropenem in centres that are prescribers with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. Of the 46 centres (intensive care units, cystic fibrosis units, neutropenia units and general wards) contributing to this study, 29 were in Europe, 14 in the Americas and three in the Middle East and Asia. The results for the most common isolates obtained in the first year of the study from these three regions show that meropenem has a broad spectrum of activity and potency in these centres, with 89% of the 6890 strains tested having an MIC < or = 4 mg/L. The overall susceptibility was lower for the comparator antibiotics. There was evidence in all regions of strains producing beta-lactamases and other resistance mechanisms against the other beta-lactams tested, fluoroquinolones and aminoglycosides. Future years' results from this surveillance study will show whether meropenem will continue to exhibit such activity.

Anti-Bacterial Agents↗
PubMed1994

[Samuel Hahnemann: a mystical empiricist. A study of the origin and development of the homeopathic medical system].

Homeopathy is the product of the time of its birth and systematization and its founder's cultural background. From the beginning, homeopathy looked in two directions at the same time. On the one hand, it looked towards scientific enquiry and empirical proof and, on the other, towards religion, metaphysics and mysticism. The origin of this lies in the double orientation of Hahnemann's work: while affirming a rational system of therapeutics based on observation, he also developed a metaphysical theory of illness as well as of the action of medicines.

Germany↗
PubMed2006

[Antimicrobial susceptibility pattern of nosocomial gram negative pathogens: results from MYSTIC study in Hacettepe University Adult Hospital (2000-2004)].

Antimicrobial susceptibility patterns of Gram negative pathogens (n: 699) isolated from nosocomial infections in Hacettepe University Adult Hospital included in MYSTIC programme between 2000-2004 were determined by Etest (AB BIODISK, Solna, Sweden) using CLSI criteria. Of the total Escherichia coli (n: 179), Klebsiella pneumoniae (n: 168), Pseudomonas aeruginosa (n: 179) and Acinetobacter baumannii (n: 173) isolates, 55% were from patients in inpatient clinics and 45% were from patients in intensive care units. The extended-spectrum beta-lactamase (ESBL) production rate of E. coli and K. pneumoniae isolates were 28% and 47%, respectively. All E. coli and K. pneumoniae isolates were found susceptible to carbapenems. The susceptibility of ESBL positive E. coli isolates to piperacillin+tazobactam was 76% and 65% to cefepime, 63% to ceftazidime, 56% to tobramycin, 24% to ciprofloxacin. For ESBL negative E. coli isolates, the susceptibility rates were found 95%, 92%, 84% and 58% for ceftazidime and tobramycin, cefepime, piperacillin+tazobactam and ciprofloxacin, respectively. The susceptibility rates of ESBL positive K. pneumoniae isolates to piperacillin+tazobactam was 55% and 51% to cefepime, 49% to ciprofloxacin, 45% to tobramycin, 42% to ceftazidime. For ESBL negative K. pneumoniae isolates, the susceptibility rates were determined as follows; 92% for cefepime, 87% for tobramycin, 70% for piperacillin+tazobactam, 62% for ceftazidime and 60% for ciprofloxacin. Of the P. aeruginosa isolates, 77% were multi-drug resistant with susceptibility rates to piperacillin+tazobactam, ciprofloxacin, meropenem and imipenem as 55%, 53%, 51% and 49%, respectively. The susceptibilities of P. aeruginosa isolates were 48% to ceftazidime, 41% to cefepime and 35% to tobramycin. Of the A.baumannii isolates, 67% were multi-drug resistant with higher susceptibility rates to meropenem (53%), imipenem (48%) and tobramycin (44%) compared to other antimicrobials cefepime (37%), ciprofloxacin (29%), piperacillin+tazobactam (26%) and ceftazidime (22%).

Acinetobacter baumannii↗