Resistance surveillance program report for selected European nations (2011)

Jones, Ronald N.; Flonta, Mirela; Gurler, Nazahat; Cepparulo, Mario; Mendes, Rodrigo E.; Castanheira, Mariana

doi:10.1016/j.diagmicrobio.2013.10.008

Cited by 80 publications

(48 citation statements)

References 18 publications

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“…The results of the present study clearly demonstrate that the cefepime-zidebactam combination possesses potent in vitro activity against Enterobacteriaceae, including isolates producing the ␤-lactamases most commonly found in hospitals worldwide, such as ESBLs, KPCs, and MBLs (3,4,(17)(18)(19)(20). Cefepime-zidebactam inhibited Ͼ99.9% of Enterobacteriaceae strains at MIC values of Յ8 g/ml, including 99.3% (152/153) of CRE strains.…”

Section: Discussionmentioning

confidence: 74%

WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015

Sader

Castanheira

Huband

et al. 2017

Antimicrob Agents Chemother

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WCK 5222 consists of cefepime combined with zidebactam, a bicyclo-acyl hydrazide ␤-lactam enhancer antibiotic with a dual action involving binding to Gram-negative bacterial PBP2 and ␤-lactamase inhibition. We evaluated the in vitro activity of cefepime-zidebactam against 7,876 contemporary (2015) clinical isolates of Enterobacteriaceae (n ϭ 5,946), Pseudomonas aeruginosa (n ϭ 1,291), and Acinetobacter spp. (n ϭ 639) from the United States (n ϭ 2,919), Europe (n ϭ 3,004), the Asia-Pacific (n ϭ 1,370), and Latin America (n ϭ 583). The isolates were tested by a reference broth microdilution method for susceptibility against cefepime-zidebactam (1:1 and 2:1 ratios) and comparator agents. Cefepimezidebactam was the most active compound tested against Enterobacteriaceae (MIC 50/ 90, Յ0.03/0.12 g/ml [1:1] and 0.06/0.25 g/ml [2:1]; 99.9% of isolates were inhibited at Յ4 [1:1] and Յ8 g/ml [2:1]). Cefepime-zidebactam was active against individual Enterobacteriaceae species (MIC 50/90 , Յ0.03 to 0.06/Յ0.03 to 0.5 g/ml [1:1]) and retained potent activity against carbapenem-resistant isolates (MIC 50/90 , 1/4 g/ml; 99.3% of isolates were inhibited at Յ8 g/ml [1:1]). Cefepime-zidebactam activity was consistent among geographic regions, and only one isolate showed MIC values of Ͼ8 g/ml (1:1). Cefepime-zidebactam was also very active against P. aeruginosa with MIC 50/90 values of 1/4 g/ml, and 99.5% of isolates were inhibited at Յ8 g/ml (1:1). The MIC values for cefepime-zidebactam at the 1:1 ratio were generally 2-fold lower than those for cefepime-zidebactam at the 2:1 ratio (MIC 50/90 , 2/8 g/ ml) and zidebactam alone (MIC 50/90 , 4/8 g/ml). Against Acinetobacter spp., cefepime-zidebactam at 1:1 and 2:1 ratios (MIC 50/90 , 16/32 g/ml for both) was 4-fold more active than cefepime or ceftazidime. Zidebactam exhibited potent in vitro antimicrobial activity against some organisms. These results support the clinical development of WCK 5222 for the treatment of Gram-negative bacterial infections, including those caused by multidrug-resistant isolates.KEYWORDS carbapenem-resistant Enterobacteriaceae, CRE, MDR, XDR, KPC, metallo-␤-lactamases T he trend of increasing antimicrobial resistance is most troublesome for Gramnegative bacteria because few antimicrobial agents targeting this group of organisms have been developed successfully (1). The occurrence of carbapenemaseproducing Enterobacteriaceae has increased rapidly in the last few years in some geographic regions (2-4). In particular, clonal Klebsiella pneumoniae strains with K. pneumoniae carbapenemases (KPC; class A carbapenemases) have disseminated widely in the United States, Israel, and some European countries (3-7). We are now facing infections caused by extensively drug-resistant (XDR) and pandrug-resistant (PDR) organisms that are resistant to all (PDR) or almost all (XDR) antimicrobial agents

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Section: Discussionmentioning

confidence: 74%

WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015

Sader

Castanheira

Huband

et al. 2017

Antimicrob Agents Chemother

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“…Preliminary in vitro experiments have demonstrated that sulbactam binds to penicillin-binding proteins (PBPs) of Acinetobacter spp., and it is presumed that this activity is responsible for the observed bacterial killing (18,19). Although historically ampicillin-sulbactam has been effective in treating VAP, bacteremia, and other nosocomial infections caused by A. baumannii (20)(21)(22)(23), clinical resistance is emerging (24). Several recent clinical studies evaluated the activity of sulbactam combined with other antibiotics, such as fosfomycin (25), cefoperazone (26), minocycline (26), aminoglycosides (27), and colistin (28), for improved efficacy against multidrug-resistant (MDR) A. baumannii.…”

mentioning

confidence: 99%

Molecular Mechanisms of Sulbactam Antibacterial Activity and Resistance Determinants in Acinetobacter baumannii

Penwell

Shapiro

Giacobbe

et al. 2015

Antimicrob Agents Chemother

156

136

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Sulbactam is a class A ␤-lactamase inhibitor with intrinsic whole-cell activity against certain bacterial species, including Acinetobacter baumannii. The clinical use of sulbactam for A. baumannii infections is of interest due to increasing multidrug resistance in this pathogen. However, the molecular drivers of its antibacterial activity and resistance determinants have yet to be precisely defined. Here we show that the antibacterial activities of sulbactam vary widely across contemporary A. baumannii clinical isolates and are mediated through inhibition of the penicillin-binding proteins (PBPs) PBP1 and PBP3, with very low frequency of resistance; the rare pbp3 mutants with high levels of resistance to sulbactam are attenuated in fitness. These results support further investigation of the potential clinical utility of sulbactam.

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“…Além de apresentar resistência intrínseca a vários antimicrobianos, o gênero Enterococcus possui grande habilidade em adquirir resistência a múltiplos agentes comumente utilizados no tratamento de infecções como penicilinas, aminoglicosídeos, glicopeptídeos e mais recentemente a linezolide (ALMEIDA et al, 2014;JONES et al 2014;SANTAYANA et al, 2012).…”

Section: Introductionunclassified

“…como o segundo colocado (14%) entre os microrganismos causadores de infecções relacionadas à assistência em saúde, sendo que, em infecções da corrente sanguínea, 83% de E. faecium e 9,4% de E. faecalis eram resistentes à vancomicina (SIEVERT et al, 2013). Na Europa a frequência de ERV E é bem menor, variando de 2% na Holanda e Finlândia a 20% na Grécia e Portugal (EUROPEAN CENTER FOR DISEASE PREVENTION AND CONTROL, 2013;JONES et al, 2014). Já na América do Sul a frequência de VRE é baixa, embora tenham sido descritos alguns surtos hospitalares em diferentes países (ARIAS, MURRAY, 2012;JONES et al, 2013).…”

Section: Introductionunclassified

“…Na Europa a frequência de ERV E é bem menor, variando de 2% na Holanda e Finlândia a 20% na Grécia e Portugal (EUROPEAN CENTER FOR DISEASE PREVENTION AND CONTROL, 2013;JONES et al, 2014). Já na América do Sul a frequência de VRE é baixa, embora tenham sido descritos alguns surtos hospitalares em diferentes países (ARIAS, MURRAY, 2012;JONES et al, 2013).…”

Section: Introductionunclassified

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Enterococcus spp. resistentes à vancomicina: características clínicas e fatores de risco

Perugini

Sugahara

Dias

et al. 2015

Semin. Cienc. Biol. Saude

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Enterococcus spp. resistentes à vancomicina (ERV) têm emergido como um patógeno multirresistente relevante e de etiologia potencialmente letal nas infecções associadas à assistência em saúde ao redor do mundo. Este estudo pretende mostrar epidemiologia e características clínicas de pacientes com ERV em um hospital do sul do Brasil. Um estudo retrospectivo foi conduzido no período de janeiro de 2005 a novembro de 2007 no Hospital Universitário de Londrina. Todos os pacientes com cultura clínica com ERV foram identificados e seu prontuário médico revisado. A presença de colonização foi avaliada através de culturas de swab retal e a identificação das amostras clínicas foi realizada pelo método automatizado MicroScan®. A média de idade dos pacientes foi de 54 anos. Trato urinário (68,0%) e corrente sanguínea (23,8%) foram os sítios mais frequentes, e a UTI apresentouse como setor de maior ocorrência (49,2%) das culturas positivas. E. faecium foi a espécie predominante, em 82,8% dos casos. Os fatores de risco observados foram a duração da internação (média de 58,2 dias), uso de antimicrobianos prévios e realização de procedimento invasivos, como o uso de cateter venoso central, sonda vesical e ventilação mecânica. Medidas de controle e culturas de vigilância são imprescindíveis no controle da disseminação do ERV. Os resultados obtidos no presente trabalho contribuem para uma melhor compreensão da dinâmica epidemiológica das infecções e da disseminação do ERV no Hospital Universitário de Londrina.

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Resistance surveillance program report for selected European nations (2011)

Cited by 80 publications

References 18 publications

WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015

WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015

Molecular Mechanisms of Sulbactam Antibacterial Activity and Resistance Determinants in Acinetobacter baumannii

Enterococcus spp. resistentes à vancomicina: características clínicas e fatores de risco

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