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Objectives: To investigate the increase in the rates of OXA-48-like-producing isolates during 3 years of global surveillance.Methods: Among 55?>162 Enterobacterales isolates, 354 carbapenem-resistant isolates carried genes encoding OXA-48-like enzymes. Isolates were susceptibility tested for ceftazidime/avibactam and comparators by broth microdilution methods. Analysis of β-lactam resistance mechanisms and MLST was performed in silico using WGS data.Results: OXA-48-like-producing isolates increased from 0.5% (94/18 656) in 2016 to 0.9% (169/18?>808) in 2018. OXA-48 was the most common variant; isolates primarily were Klebsiella pneumoniae (318/354 isolates) from Europe and adjacent countries. MLST analysis revealed a diversity of STs, but K. pneumoniae belonging to ST395, ST23 and ST11 were observed most frequently. Thirty-nine isolates harboured MBLs and were resistant to most agents tested. The presence of blaCTX-M-15 (258 isolates), OmpK35 nonsense mutations (232) and OmpK36 alterations (316) was common among OXA-48 producers. Ceftazidime, cefepime and aztreonam susceptibility rates, when applying CLSI breakpoints, were 12%-15% lower for isolates carrying ESBLs alone and with either or both OmpK35 stop codons and OmpK36 alterations. Meropenem and, remarkably, meropenem/vaborbactam were affected by specific OmpK36 alterations when a deleterious mutation also was observed in OmpK35. These mechanisms caused a decrease of 12%-42% in the susceptibility rates for meropenem and meropenem/vaborbactam. Ceftazidime/avibactam susceptibility rates were >98.9%, regardless of the presence of additional β-lactam resistance mechanisms.Conclusions: Guidelines for the treatment of infections caused by OXA-48-producing isolates are scarce and, as the dissemination of these isolates continues, studies are needed to help physicians understand treatment options for these infections. [ABSTRACT FROM AUTHOR]

Background: While the resistance rates of commonly detected uropathogens are well described, those of less frequent Gram-negative uropathogenic bacteria have seldom been reported. The aim of this study was to examine the resistance rates of less frequent uropathogenic Gram-negatives in a population of patients treated in a Department of Urology of a tertiary referral centre in Central Europe over a period of 9 years.Methods: Data on all positive urine samples from urological in- and out-patients were extracted form the Department of Clinical Microbiology database from 2011 to 2019. Numbers of susceptible and resistant isolates per year were calculated for these uropathogens: Acinetobacter spp. (n = 74), Citrobacter spp. (n = 60), Enterobacter spp. (n = 250), Morganella morganii (n = 194), Providencia spp. (n = 53), Serratia spp. (n = 82) and Stenotrophomonas maltophilia (n = 27). Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin and colistin.Results: Penicillin derivatives have generally poor effect except piperacillin/tazobactam. Cefuroxime is not efficient unlike cefotaxime (except against Acinetobacter spp. and S. maltophilia). Susceptibility to fluoroquinolones is limited. Amikacin is somewhat more efficient than gentamicine but susceptibilities for both safely exceed 80%. Nitrofurantoin shows virtually no efficiency. Cotrimoxazole acts well against Citrobacter spp., Serratia spp. and it is the treatment of choice for S. maltophilia UTIs. Among carbapenems, ertapenem was less efficient than meropenem and imipenem except for S. maltophilia whose isolates were mostly not suceptible to any carbapenems.Conclusions: Uropathogenic microorganisms covered in this report are noteworthy for their frequently multi-drug resistant phenotypes. Knowledge of resistance patterns helps clinicians choose the right empirical antibiotic treatment when the taxonomical assignment of the isolate is known but sensitivity results are pending. [ABSTRACT FROM AUTHOR]

Background: Aztreonam-avibactam is under clinical development for treatment of infections caused by carbapenem-resistant Enterobacterales (CRE), especially those resistant to recently approved β-lactamase inhibitor combinations (BLICs)., Objectives: To evaluate a large collection of CRE isolates, including those non-susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam., Methods: Overall, 24 580 Enterobacterales isolates were consecutively collected (1/patient) in 2020-2022 from 64 medical centres located in Western Europe (W-EU), Eastern Europe (E-EU), Latin America (LATAM), and the Asia-Pacific region (APAC). Of those, 1016 (4.1%) were CRE. Isolates were susceptibility tested by broth microdilution. CRE isolates were screened for carbapenemase genes by whole genome sequencing., Results: Aztreonam-avibactam inhibited 99.6% of CREs at ≤8 mg/L. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam were active against 64.6%, 57.4%, and 50.7% of CRE isolates, respectively; most of the non-susceptible isolates carried metallo-beta-lactamases. Aztreonam-avibactam was active against ≥98.9% of isolates non-susceptible to these BLICs. The activity of these BLICs varied by region, with highest susceptibility rates observed in W-EU (76.9% for ceftazidime-avibactam, 72.5% for meropenem-vaborbactam, 63.8% for imipenem-relebactam) and the lowest susceptibility rates identified in the APAC region (39.9% for ceftazidime-avibactam, 37.8% for meropenem-vaborbactam, and 27.5% for imipenem-relebactam). The most common carbapenemase types overall were KPC (44.6% of CREs), NDM (29.9%), and OXA-48-like (16.0%). KPC predominated in LATAM (64.1% of CREs in the region) and W-EU (61.1%). MBL occurrence was highest in APAC (59.5% of CREs in the region), followed by LATAM (34.0%), E-EU (28.9%), and W-EU (23.6%)., Conclusions: Aztreonam-avibactam demonstrated potent activity against CRE isolates resistant to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam independent of the carbapenemase produced., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To determine the spread of ESBLs and carbapenemases in Enterobacterales and Pseudomonas aeruginosa in Europe.Methods: 45 335 Gram-negative bacilli were collected in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme from 2013 to 2017. Antimicrobial susceptibility was determined using broth microdilution, and 9546 isolates were screened for β-lactamase genes by PCR and sequencing.Results: ESBLs were identified in 35.5% of Klebsiella pneumoniae and 18.5% of Escherichia coli. ESBL carriage was lowest among isolates in Northern/Western Europe and highest in Eastern Europe. CTX-M-15 was the dominant ESBL in all countries except Greece, where SHV-type ESBLs were more common. Carbapenemases (KPC, OXA-48-like, GES, NDM and VIM) were found in 3.4% of Enterobacterales and were most common among K. pneumoniae (10.5% of those collected). Carbapenemase carriage was lowest in Northern/Western and highest in Southern Europe. KPC-positive Enterobacterales were most abundant but the percentages of OXA-48-like-, NDM- and VIM-positive isolates increased over time and were correlated with an increase in meropenem non-susceptibility. Carbapenemases (VIM, IMP, NDM and GES) were also identified in 5.1% of P. aeruginosa and were commonly found in Eastern Europe. Carbapenemase carriage and meropenem non-susceptibility among P. aeruginosa fluctuated over the 5 years studied and were not well correlated.Conclusions: ESBL and carbapenemase carriage varied by species and European subregion. Meropenem non-susceptibility in European isolates of Enterobacterales can be attributed to carbapenemase carriage and is increasingly caused by MBLs and OXA-48-like carbapenemases. Carbapenemases or other β-lactamases are not a common cause of meropenem non-susceptibility in P. aeruginosa in Europe. [ABSTRACT FROM AUTHOR]

Objectives: The activity of ceftazidime/avibactam was assessed against 24 750 isolates of Enterobacteriaceae collected from 96 medical centres in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme from 2012 to 2015. Activity was analysed against subsets of isolates based on resistant phenotypes and β-lactamase content.Methods: Antimicrobial susceptibility testing was performed using broth microdilution and the presence of β-lactamase genes in isolates of interest was determined using PCR and sequencing.Results: Ceftazidime/avibactam was the most active agent, compared with all other tested comparator agents, against the overall collection of Enterobacteriaceae isolates (99.4% susceptible) and against subsets of ceftazidime-non-susceptible (97.7% susceptible), colistin-resistant (98.2% susceptible), MDR (96.7% susceptible) and meropenem-non-susceptible, MBL-negative (98.5% susceptible) isolates. At the country level, susceptibility to ceftazidime/avibactam ranged from 96.3% to 100% among Enterobacteriaceae isolates, with decreased susceptibilities only observed in countries where MBLs were more frequently encountered (e.g. Greece and Romania). Ceftazidime/avibactam was active against 99.7% of Enterobacteriaceae isolates that carried serine β-lactamases, including ESBLs, AmpC cephalosporinases and carbapenemases (KPC, GES and OXA-48-like) in all combinations. As expected, ceftazidime/avibactam was not active against isolates carrying MBLs.Conclusions: The data show that ceftazidime/avibactam is highly potent in vitro against clinical isolates of Enterobacteriaceae collected in European countries, including isolates that exhibit resistance to ceftazidime, meropenem and colistin and combined resistance to agents from multiple drug classes. [ABSTRACT FROM AUTHOR]

Objectives: The activity of ceftazidime/avibactam was assessed against 5716 Pseudomonas aeruginosa isolates collected from 96 medical centres in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme from 2012 to 2015. Activity was analysed against subsets of isolates based on resistance phenotypes and β-lactamase content.Methods: Antimicrobial susceptibility testing was performed by broth microdilution and β-lactamase genes were detected by PCR screening and sequencing.Results: Ceftazidime/avibactam was highly active in vitro against the overall collection of P. aeruginosa isolates and colistin-resistant isolates (92.4% and 92.9% susceptible, respectively). Although activity was slightly reduced against MBL-negative subsets of ceftazidime-non-susceptible (79.6% susceptible), meropenem-non-susceptible (85.1% susceptible) and MDR (81.6% susceptible) P. aeruginosa, ceftazidime/avibactam remained the second most active entity, after colistin, compared with all other comparator agents tested. At the country level, susceptibility to ceftazidime/avibactam ranged from 74.6% to 99.6%, with decreased susceptibilities only observed in countries where MBLs are more frequently encountered, such as the Czech Republic, Greece, Romania and Russia. Ceftazidime/avibactam was also active in vitro against 87.6% of meropenem-non-susceptible isolates in which no acquired β-lactamases were detected by molecular methods; these isolates were assumed to hyperproduce the chromosomally encoded AmpC in combination with alterations in OprD or drug efflux. As expected, ceftazidime/avibactam was not active against isolates carrying MBLs.Conclusions: The data show that ceftazidime/avibactam is highly potent in vitro against clinical isolates of P. aeruginosa collected in European countries, including isolates that exhibit resistance to ceftazidime, meropenem and colistin and combined resistance to agents from multiple drug classes. [ABSTRACT FROM AUTHOR]

Background: Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking.Objectives: To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS).Methods: Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed.Results: A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome.Conclusions: Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered. [ABSTRACT FROM AUTHOR]

Objectives: Previously, web-based tools for cross-sectional antimicrobial point prevalence surveys (PPSs) have been used in adults to develop indicators of quality improvement. We aimed to determine the feasibility of developing similar quality indicators of improved antimicrobial prescribing focusing specifically on hospitalized neonates and children worldwide.Methods: A standardized antimicrobial PPS method was employed. Included were all inpatient children and neonates receiving an antimicrobial at 8:00 am on the day of the PPS. Denominators included the total number of inpatients. A web-based application was used for data entry, validation and reporting. We analysed 2012 data from 226 hospitals (H) in 41 countries (C) from Europe (174H; 24C), Africa (6H; 4C), Asia (25H; 8C), Australia (6H), Latin America (11H; 3C) and North America (4H).Results: Of 17,693 admissions, 6499 (36.7%) inpatients received at least one antimicrobial, but this varied considerably between wards and regions. Potential indicators included very high broad-spectrum antibiotic prescribing in children of mainly ceftriaxone (ranked first in Eastern Europe, 31.3%; Asia, 13.0%; Southern Europe, 9.8%), cefepime (ranked third in North America, 7.8%) and meropenem (ranked first in Latin America, 13.1%). The survey identified worryingly high use of critically important antibiotics for hospital-acquired infections in neonates (34.9%; range from 14.2% in Africa to 68.0% in Latin America) compared with children (28.3%; range from 14.5% in Africa to 48.9% in Latin America). Parenteral administration was very common among children in Asia (88%), Latin America (81%) and Europe (67%). Documentation of the reasons for antibiotic prescribing was lowest in Latin America (52%). Prolonged surgical prophylaxis rates ranged from 78% (Europe) to 84% (Latin America).Conclusions: Simple web-based PPS tools provide a feasible method to identify areas for improvement of antibiotic use, to set benchmarks and to monitor future interventions in hospitalized neonates and children. To our knowledge, this study has derived the first global quality indicators for antibiotic use in hospitalized neonates and children. [ABSTRACT FROM AUTHOR]

Objectives Doripenem is a new carbapenem recently introduced into Europe. The COMParative Activity of Carbapenem Testing (COMPACT) study compared the susceptibility of common Gram-negative bacilli causing serious infections in hospitalized patients with doripenem, imipenem and meropenem. Methods Gram-negative isolates (4498 total: 2171 Pseudomonas species; 1910 Enterobacteriaceae; and 417 other Gram-negative bacilli) were collected from 80 centres in 16 countries in Europe, the Middle East and Africa during 2008–09. The MICs of doripenem, imipenem and meropenem were determined using Etest methodology and broth microdilution. Susceptibility was interpreted according to CLSI, EUCAST and FDA breakpoints. Results The MIC90s of doripenem, imipenem and meropenem for all isolates were 8, ≥64 and 32 mg/L, respectively. Doripenem had the lowest MIC90 for Pseudomonas species at 16 mg/L, with imipenem and meropenem values of ≥64 mg/L. Enterobacteriaceae were highly susceptible to all three carbapenems, with MIC90s of doripenem, imipenem and meropenem of 0.06, 0.5 and 0.12 mg/L, respectively. Other Gram-negative isolates, predominantly Acinetobacter baumannii, were resistant to all three carbapenems (MIC90 ≥64 mg/L). Susceptibility to doripenem was observed in 14.9% of isolates resistant to imipenem and/or meropenem. Conclusions Doripenem showed excellent activity against Gram-negative isolates; generally it was more active than imipenem and at least as good as meropenem. Against Pseudomonas species, doripenem was more active than both imipenem and meropenem, with doripenem susceptibility observed for some imipenem- and/or meropenem-resistant isolates. [ABSTRACT FROM PUBLISHER]

Abstract: 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. [Copyright &y& Elsevier]

The in vitro antimicrobial susceptibility of organisms isolated from bacteraemic versus non-bacteraemic patients was evaluated using data (1997–2001) from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme. Minimum inhibitory concentration values and susceptibility breakpoints of meropenem and other broad-spectrum antimicrobials were determined using standard methodology. Three thousand one hundred and thirty-six blood culture (BC) isolates and 17,261 non-BC isolates were obtained from 51 European MYSTIC centres. Gram-positive bacteria appeared to be more prevalent in BC isolates compared with other sources. Escherichia coli, methicillin-susceptible Staphylococcus aureus and Pseudomonas aeruginosa were isolated most frequently. Antimicrobial susceptibility of isolates from bacteraemic versus non-bacteraemic patients was similar. Meropenem and imipenem were the most active agents against the majority of the Gram-positive and Gram-negative organisms. Ceftazidime, gentamicin and ciprofloxacin generally exhibited the lowest activities against the most commonly isolated organisms. Meropenem was most active against P. aeruginosa and showed the highest potency and activity against all extended-spectrum and AmpC β-lactamase producers. These results are relevant to the choice of initial, empirical therapy for patients with suspected bacteraemia. [Copyright &y& Elsevier]

Background Clinical guidelines have recommended oral antibiotics such as the cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of urinary tract infections (UTI's) caused by Escherichia coli (EC). The utility of these agents continues to be eroded by increased prevalence of expanded spectrum β-lactamase (ESBL) genes and concomitant resistance determinants to other antimicrobial classes. This study assessed the prevalence of ESBL phenotypes among EC from UTIs in the United States and 11 countries in Europe (EU) in 2017 and the impact of co-resistance to oral agents used to treat UTIs. Methods 2422 unique EC from UTIs in the United States and EU in the SENTRY Surveillance program were evaluated for susceptibility to various agents. All isolates were consecutively collected and centrally tested by CLSI methods and interpretive criteria. Isolates that met ESBL MIC screening criteria were characterized for the presence of β-lactamase genes. Results Among the 2422 isolates of EC from UTI's in the United States and EU the resistance (R) rates for cefuroxime (CEF), levofloxacin (LEV) and TMP-SMX were 17.9%, 25.6% and 33.2%, respectively. The overall prevalence of ESBL phenotypes was 18.2% (18.7% in the United States and 21.0% in EU). Among the 411 ESBL phenotypes, R to CEF, LEV and TMP-SMX were: 94.3%, 70.6%, and 61.6%, respectively. In contrast, <0.1% of all EC or 0.2% of ESBL EC were meropenem (MER)-R. Only two carbapenemase-producing organisms were identified, an NDM-5- and a KPC-2-producing EC from Turkey and Greece, respectively. The CTX-M-15 was the most prevalent ESBL and identified among 167 isolates; with co-resistance to CEF, LEV and TMP-SMX noted in 100%, 82.6% and 70.7%, respectively. All CTX-M-15 isolates were susceptible to MER. Conclusion Oral agents such as CEF, LEV, and TMP-SMX exhibit R rates ≥17.9%. Co-resistance to CEF, LEV, and TMP-SMX were considerably higher among ESBL phenotypes (>61.1%) and confirmed bla CTX-M-15 genotypes (70.7%). In contrast, the carbapenems remained active against ESBL phenotypes and genotypes, such as bla CTX-M-15. New oral agents with the spectrum and potency of the carbapenems would address an unmet need for new options to treat multi-drug-resistant EC UTIs. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

• Meropenem generics were tested for antimicrobial activity (P. aeruginosa), stability and degradation, and dissolution rate. • While showing essentially similar MICs, some generics were less stable in concentrated solutions. • The generics released more coloured degradation products and dissolved more slowly. • Suitability of each generic needs to be assessed in the specific environment(s) where it will be used. Meropenem generics are often imposed on prescribers, however scarce information is available on key properties such as antimicrobial potency, stability and colouration in solution, and dissolution time. This study aimed to generate comparative information for products available in Europe. The originator (ASTRA) and four generics (HOSPIRA, SANDOZ, FRESENIUS and AUROVIT) were compared for: (i) MICs against Pseudomonas aeruginosa clinical isolates (range, 0.125–191 mg/L); (ii) colouration (visual and photometry) and stability of concentrated solutions for prolonged or continuous infusion and maintained at 25–37 °C for up to 8 h (acceptable limit, ≥90% of original concentration); and (iii) dissolution time of concentrated solutions (50 mg/mL [for bolus administration]: turbidimetry and nursing personnel assessment). No significant difference was observed for MICs (except 2/80 isolates). For concentrated solutions storage: (i) SANDOZ produced about two times more yellow-coloured degradation products than the other preparations; (ii) meropenem loss was time-, concentration- and temperature-dependent; (iii) FRESENIUS was the least stable (limit for 1 g/48 mL, ~8 h at 25 °C and 4.5 h at 37 °C); (iv) at 2 g/48 mL, the storage time limit was 5–6 h at 25 °C and ~3 h at 37 °C for all preparations. Complete dissolution (turbidimetry) required 240 s for generics (120 s for ASTRA), and nurses reported longer but highly variable times for generics. Substantial differences between innovator and generics have been identified that could impact on their clinical use and/or make multicentric studies difficult to interpret, requiring suitability studies in the environments of their intended use. [ABSTRACT FROM AUTHOR]

Objectives: This study reports on the activity of aztreonam/avibactam (ATM-AVI) against a collection of Klebsiella pneumoniae collected in 2016 and 2017., Methods: Non-duplicate K. pneumoniae isolates were collected from four regions (Africa/Middle East, n = 785; Asia-Pacific, n = 1433; Europe, n = 4236; Latin America, n = 1499) and five culture sources (blood, n = 902; intra-abdominal, n = 992; urinary tract, n = 2148; skin and skin structure, n = 1409; lower respiratory tract, n = 2502). MICs were determined at a central laboratory using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methodology. Susceptibility was determined using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints., Results: For all culture sources, against all K. pneumoniae, the highest rates of susceptibility were seen for amikacin (>84%), ceftazidime/avibactam (>94%), colistin (>92%) and meropenem (>83%), and >99.9% of isolates were inhibited at an ATM-AVI MIC of ≤4 mg/L. Among meropenem-resistant (MEM-R, n = 583) and meropenem-resistant metallo-β-lactamase-negative (MEM-R-MBLN; n = 469) isolates, susceptibility was highest to ceftazidime/avibactam (79.9% and 99.4%, respectively) and colistin (67.2% and 62.7%, respectively). All MEM-R-MBLN isolates from blood, intra-abdominal, urinary tract and skin and skin structure sources, and all but one isolate from respiratory sources, were inhibited at an ATM-AVI MIC of ≤2 mg/L. Against the meropenem-resistant metallo-β-lactamase positive (MEM-R-MBLP; n = 114) isolates, susceptibility to colistin was between 75.0% (urinary tract isolates) and 93.3% (lower respiratory tract isolates). All MEM-R-MBLP isolates were inhibited at an ATM-AVI MIC of ≤0.5 mg/L., Conclusions: ATM-AVI is active against K. pneumoniae isolates from a range of culture sources across Africa/Middle East, Asia-Pacific, Europe and Latin America. ATM-AVI also has activity against MEM-R-MBLN and MEM-R-MBLP isolates., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: European centers (n = 226) involved in the Tigecycline Evaluation and Surveillance Trial (TEST, 2004-2014) submitted data and bacterial isolates., Methods: Minimal inhibitory concentrations and susceptibility were determined using Clinical and Laboratory Standards Institute methods and European Committee on Antimicrobial Susceptibility Testing breakpoints., Results: The rates of the following resistant pathogens increased from 2004 to 2014: extended-spectrum β-lactamase (ESBL)-positive Escherichia coli (from 8.9 to 16.9%), multidrug-resistant Acinetobacter baumannii complex (from 15.4 to 48.5%), and ESBL-positive Klebsiella pneumoniae (from 17.2 to 23.7%). The rate of methicillin-resistant Staphylococcus aureus was 27.5% in 2004 and 28.9% in 2014. Resistance to the carbapenems (imipenem and meropenem) was 37.4 and 14.5% for A. baumannii complex and Pseudomonas aeruginosa, respectively. Carbapenem resistance was ≤4.3% among the Enterobacteriaceae and 0.2% against Streptococcus pneumoniae. The resistance to tigecycline ranged between 7.4% against ESBL-producing K. pneumoniae and 0.0% against S. aureus., Conclusions: The carbapenems and tigecycline were active against Enterobacteriaceae. Agents with activity against A. baumannii complex and P. aeruginosa are limited. The carbapenems, tigecycline, linezolid, and vancomycin were active against Gram-positive organisms., (© 2016 S. Karger AG, Basel.)

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae strains co-producing klebsiella pneumoniae carbapenemase (KPC) and verona integron-encoded metallo-beta-lactamase (VIM) are frequently isolated in Greece and have also occurred in other European countries. Conventional combined disc tests exhibit low sensitivity against these emerging pathogens. We have evaluated modifications of the KPC/Metallo-β-Lactamase Confirmation kit (ROSCO) exhibiting high diagnostic value against KPC, VIM and KPC + VIM producers. The key changes were the inclusion of additional combined tablets containing meropenem plus two inhibitors (dipicolinic acid (1000 μg per tablet) for metallo-β-lactamases and a boronic acid derivative for KPCs) and the replacement of aminophenylboronic acid by phenylboronic acid (400 μg per tablet)., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Tigecycline was approved by the United States Food and Drug Administration in 2005 and has generally retained activity against resistant Gram-positive and Gram-negative organisms. We monitored the in vitro activity of this glycylcycline in 2011 for continued potency worldwide. A total of 22,005 unique clinical isolates were consecutively collected in North America (NA; 9232 isolates), Europe (EU; 6776), Latin America (LA; 2016), and Asia-Pacific region (APAC, 3981) and tested for susceptibility according to the reference broth microdilution method recommendations against tigecycline and numerous comparators. Oxacillin (methicillin) resistance rates in methicillin-resistant Staphylococcus aureus (MRSA) were 49.3%, 30.2%, 42.9%, and 37.8%, and vancomycin resistance rates in enterococci (VRE) were 27.0%, 11.3%, 6.3%, and 4.0% in NA, EU, LA, and APAC, respectively. All MRSA (2839) and >99% of VRE were susceptible to tigecycline. Among Escherichia coli, extended-spectrum β-lactamase (ESBL) rates varied from 12.6% in the NA to 57.4% in APAC, and only one strain was nonsusceptible to tigecycline. Tigecycline was active against ESBL phenotype (96.5-98.4% susceptible) and meropenem-nonsusceptible Klebsiella spp. (94.3-100.0% susceptible). Only 4 of 213 (1.9%) meropenem-nonsusceptible Klebsiella spp. were tigecycline-nonsusceptible, all with tigecycline minimum inhibitory concentration (MIC) of 4 μg/mL (intermediate). Among ceftazidime-nonsusceptible Enterobacter spp., 94.7-98.2% were susceptible to tigecycline. Meropenem-nonsusceptible Acinetobacter spp. varied from 51.2% in NA to 80.9% in APAC; and 83.8% (LA) to 93.9% (APAC) of strains were inhibited at a tigecycline MIC of ≤2 μg/mL. Tigecycline showed potent activity against Stenotrophomonas maltophilia (89.3-98.3% inhibited at ≤2 μg/mL). In summary, tigecycline has sustained potent activity and a broad-spectrum against clinically important bacteria causing infections worldwide, including multidrug-resistant organism subsets., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Acinetobacter baumannii and Pseudomonas aeruginosa pathogens are the most common causes of fatal pneumonia among patients treated in Intensive Care Units (ICU). Carbapenems remain a group of antibiotics characterized by the highest effectiveness in treatment of heavy infections of the lower respiratory tract. This study compared in vitro sensitivity of A. baumannii and P. aeruginosa to three carbapenems: imipenem, meropenem and doripenem. The material was collected from 71 patients treated in the ICU from April 2009 to January 2010. Bronchial tree was the predominant source of samples. Fifty-four strains of A. baumannii and 17 strains of P. aeruginosa were analyzed. Sensitivity to carbapenems was interpreted in line with Clinical and Laboratory Standard Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria (imipenem and meropenem) or in compliance with the Food and Drug Administration (FDA) and CLSI guidelines (doripenem). We found that A. baumannii was significantly more often sensitive to imipenem than to doripenem and meropenem, but only according to the CLSI and FDA and not EUCAST criteria. The sensitivity of P. aeruginosa was higher to imipenem than to doripenem and meropenem, according to both CLSI and EUCAST criteria (64.7 %). We conclude that the EUCAST criteria demonstrate a higher rigor than those of CLSI and FDA in the determination of carbapenems sensitivity. Imipenem appears more effective than doripenem and meropenem in treatment of A. baumannii and P. aeruginosa infections.

The first case in Europe of Klebsiella pneumoniae carbapenemase (KPC) 2 transfer from K. pneumoniae to Escherichia coli in the same patient is described. KPC-positive plasmids from the two species were identical, indicating horizontal plasmid transfer. Selection of the KPC-producing E. coli strain was triggered by therapy with meropenem.

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.

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).

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 beta-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 microg/ml; 86% susceptible). Unexpectedly, 3.6% of P. mirabilis were imipenem-resistant (MIC, > or = 16 microg/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.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global study providing in-vitro surveillance data on microbial susceptibility in centers that prescribe meropenem. This paper summarizes data on the activity of meropenem and five comparator agents against 13,793 clinical isolates from 31 centers in 10 European countries, 1997-2000. Meropenem and imipenem demonstrated broad-spectrum activity against the tested organisms, including beta-lactamase-producing strains that were co-resistant to quinolones and aminoglycosides. The carbapenems were active against the most frequently isolated pathogens including staphylococci (98-100% susceptible), Pseudomonas aeruginosa (65-82% susceptible) and Klebsiella pneumoniae (98-100% susceptible). Resistance to penicillins and cephalosporins was observed, particularly among Enterobacter species in Southern and Eastern Europe. Eastern Europe showed a high prevalence of AmpC beta-lactamase and extended-spectrum beta-lactamase-producing strains in Russia (2000); 47% and 28% of Enterobacteriaceae isolates were AmpC or ESBL-producers, respectively. There was no significant decrease in susceptibility to the carbapenems throughout the four-year period. Meropenem and imipenem appear to remain reliable options for the treatment of serious nosocomial infections.

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.