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2.
Int J Antimicrob Agents ; 56(4): 106128, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32758648

RESUMO

OBJECTIVES: Cefiderocol (CID), also known as S-649266, a novel siderophore cephalosporin, possesses potent activity against multidrug-resistant aerobic Gram-negative bacteria (GNB). This study aimed to determine the in vitro activity of CID against two different sets of GNB: i) a random sample of 213 clinical isolates, including 17 extended-spectrum beta-lactamase (ESBL) producers, obtained from intensive care unit patients with nosocomial infections collected during a multicentre surveillance study (set I); and ii) a group of 59 challenge GNB producing various types of carbapenemases (CP; set II). METHODS: Minimum inhibitory concentrations (MICs) were determined using the microdilution method according to the standard ISO 20776-1. Iron-depleted medium was used for testing CID. RESULTS: CID inhibited 97.2% of set I isolates at the EUCAST susceptibility breakpoint of ≤ 2 mg/L. The concentrations of CID inhibiting 50% and 90% (MIC50/90) of the Enterobacterales isolates (n = 146) were 0.12/1.0 mg/L, with ESBL-positive isolates tending to exhibit higher MICs than ESBL-negative isolates to CID. MIC50/90 values of CID for isolates of the Acinetobacter baumannii group (n = 13) and Pseudomonas aeruginosa (n = 54) were 0.06/0.12 mg/L and 0.12/0.5 mg/L, respectively. Further, CID inhibited 88.1% of set II CP-producing isolates at ≤ 2 mg/L. All seven class D CP-producing Acinetobacter baumannii were inhibited at ≤ 0.25 mg/L. MIC50/90 values for CP-producing Enterobacterales (n = 30) and Pseudomonas aeruginosa (n = 22) were 1/4 mg/L and 0.5/2 mg/L, respectively. CONCLUSION: CID showed potent activity against Acinetobacter baumannii, Enterobacterales and Pseudomonas aeruginosa, including CP-producing isolates. Overall, CID inhibited 259 of 272 (95.2%) GNB at ≤ 2 mg/L.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Farmacorresistência Bacteriana Múltipla/genética , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Alemanha , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Cefiderocol
3.
Int J Antimicrob Agents ; 55(6): 105959, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32325200

RESUMO

Pseudomonas aeruginosa (PA) is a major cause of healthcare-associated infections. Antipseudomonal carbapenems are among the antimicrobial agents used to treat PA infections, but several mechanisms of resistance, including the production of a carbapenemase (CP), may compromise their clinical efficacy. The objectives of this study were to determine: (i) the dissemination of carbapenem-resistant CP-negative and CP-positive PA isolates; and (ii) the in-vitro activity of ceftolozane-tazobactam (CTT) against carbapenem-susceptible and carbapenem-resistant isolates. Isolates were collected prospectively from January 2016 to April 2017 at 20 German medical laboratories. Each centre was asked to provide 50 consecutive isolates from hospitalized patients. Overall, 985 isolates were collected, of which 34% were obtained from intensive care patients. Seven hundred and thirty-eight (74.9%) isolates were susceptible to both imipenem and meropenem (Subgroup I), and 247 (25.1%) isolates were resistant to carbapenems (Subgroup II): 125 (12.7%) were imipenem-resistant but meropenem-susceptible, 12 (1.2%) were meropenem-resistant but imipenem-susceptible, and 110 (11.2%) were resistant to both carbapenems (Subgroup III). A CP was detected in 28 (2.8%) isolates (predominantly VIM-2). Nine hundred and fifty (96.4%) isolates were CTT-susceptible. Susceptibility to CTT was seen in 99.6% of Subgroup I isolates, 87% of Subgroup II isolates and 74.5% of Subgroup III isolates. Overall, 2.8% of PA produced a CP, while 22.2% were carbapenem-resistant, CP-non-producing isolates. Based on these findings, CTT may be considered for treatment of PA infections, particularly those caused by multi-drug-resistant CP-non-producing isolates.


Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Cefalosporinas/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Tazobactam/farmacologia , Idoso , Proteínas de Bactérias , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Alemanha/epidemiologia , Humanos , Imipenem/farmacologia , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , beta-Lactamases
4.
J Med Microbiol ; 68(8): 1189-1193, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31225790

RESUMO

PURPOSE: In an increasing number of cases the last therapeutic option for treatment of carbapenem-resistant Enterobacteriaceae is colistin. As the detection of colistin resistance is problematic and time-consuming, it is desirable to find a rapid and reliable test. The rapid polymyxin NP test developed by Nordmann et al. addresses this problem and has a sensitivity of 99.3  % and a specificity of 95.4  %, as described by the authors. METHODS: In this study, we aimed to evaluate the NP test and tested the effect of measuring the absorbance of the test with an enzyme-linked immunosorbent assay (ELISA) reader at 430 nm as an alternative objectified readout. We performed a study with 120 carbapenemase-producing Enterobacteriaceae isolates, including 40 colistin-resistant and 23 colistin-susceptible Klebsiella pneumoniae, 4 resistant and 23 susceptible Escherichia coli, and 20 susceptible and 10 resistant Enterobacter species, respectively. RESULTS: Our data showed lower values for sensitivity and specificity than previously, namely only 91  % and 70 %, respectively, due to visual inspection. Furthermore, the results revealed a weakness in the correct detection of colistin-susceptible Enterobacter species. With the measurement of the absorbance we optimized the results to prevent misinterpretations of weak or inconclusive colour changes and enhanced the accuracy and objectivity of the rapid polymyxin NP test results. CONCLUSION: We reinforced the rapid polymyxin NP test as a rapid and valuable tool for detecting colistin-resistant K. pneumoniae isolates, although false-positive results were obtained for several colistin-susceptible Enterobacter spp. By using the optimized method, we were able to increase the sensitivity and specificity values to 94  % and 95  %, respectively.


Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Polimixinas/farmacologia , Proteínas de Bactérias/metabolismo , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Sensibilidade e Especificidade , beta-Lactamases/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-29744043

RESUMO

Background: By using whole genome sequence data we aimed at describing a population snapshot of carbapenemase-producing K. pneumoniae isolated from hospitalized patients in Germany between 2008 and 2014. Methods: We selected a representative subset of 107 carbapenemase-producing K. pneumoniae clinical isolates possessing the four most prevalent carbapenemase types in Germany (KPC-2, KPC-3, OXA-48, NDM-1). Isolates were processed via illumina NGS. Data were analysed using different SNP-based mapping and de-novo assembly approaches. Relevant information was extracted from NGS data (antibiotic resistance determinants, wzi gene/cps type, virulence genes). NGS data from the present study were also compared with 238 genome data from two previous international studies on K. pneumoniae. Results: NGS-based analyses revealed a preferred prevalence of KPC-2-producing ST258 and KPC-3-producing ST512 isolates. OXA-48, being the most prevalent carbapenemase type in Germany, was associated with various K. pneumoniae strain types; most of them possessing IncL/M plasmid replicons suggesting a preferred dissemination of blaOXA-48 via this well-known plasmid type. Clusters ST15, ST147, ST258, and ST512 demonstrated an intermingled subset structure consisting of German and other European K. pneumoniae isolates. ST23 being the most frequent MLST type in Asia was found only once in Germany. This latter isolate contained an almost complete set of virulence genes and a K1 capsule suggesting occurrence of a hypervirulent ST23 strain producing OXA-48 in Germany. Conclusions: Our study results suggest prevalence of "classical" K. pneumonaie strain types associated with widely distributed carbapenemase genes such as ST258/KPC-2 or ST512/KPC-3 also in Germany. The finding of a supposed hypervirulent and OXA-48-producing ST23 K. pneumoniae isolates outside Asia is highly worrisome and requires intense molecular surveillance.


Assuntos
Proteínas de Bactérias/genética , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Genoma Bacteriano/genética , Alemanha/epidemiologia , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/metabolismo , Tipagem de Sequências Multilocus , Polimorfismo de Nucleotídeo Único/genética , Sequenciamento Completo do Genoma , beta-Lactamases/metabolismo
6.
FEMS Microbiol Lett ; 363(14)2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27252156

RESUMO

Among staphylococci Staphylococcus saprophyticus is the only species that is typically uropathogenic and an important cause of urinary tract infections in young women. The amino acid D-serine occurs in relatively high concentrations in human urine and has a bacteriostatic or toxic effect on many bacteria. In uropathogenic Escherichia coli and S. saprophyticus, the amino acid regulates the expression of virulence factors and can be used as a nutrient. The ability of uropathogens to respond to or to metabolize D-serine has been suggested as a factor that enables colonization of the urinary tract. Until now nothing is known about D-serine transport in S. saprophyticus We generated mutants of putative transporter genes in S. saprophyticus 7108 that show homology to the D-serine transporter cycA of E. coli and tested them in a D-serine depletion assay to analyze the D-serine uptake rate of the cells. The mutant of SPP1070 showed a strong decrease in D-serine uptake. Therefore, SSP1070 was identified as a major D-serine transporter in S. saprophyticus 7108 and was named D-serine transporter A (DstA). D-serine caused a prolonged lag phase of S. saprophyticus in a chemically defined medium. This negative effect was dependent on the presence of DstA.


Assuntos
Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Serina/metabolismo , Staphylococcus saprophyticus/genética , Staphylococcus saprophyticus/metabolismo , Alelos , Expressão Gênica , Mutação , Staphylococcus saprophyticus/crescimento & desenvolvimento
7.
Infect Immun ; 81(12): 4525-33, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24082071

RESUMO

Staphylococcus saprophyticus is the only species of Staphylococcus that is typically uropathogenic and possesses a gene coding for a D-serine-deaminase (DsdA). As D-serine is prevalent in urine and toxic or bacteriostatic to many bacteria, it is not surprising that the D-serine-deaminase gene is found in the genome of uropathogens. It has been suggested that D-serine-deaminase or the ability to respond to or to metabolize D-serine is important for virulence. For uropathogenic Escherichia coli (UPEC), a high intracellular D-serine concentration affects expression of virulence factors. S. saprophyticus is able to grow in the presence of high D-serine concentrations; however, its D-serine metabolism has not been described. The activity of the D-serine-deaminase was verified by analyzing the formation of pyruvate from D-serine in different strains with and without D-serine-deaminase. Cocultivation experiments were performed to show that D-serine-deaminase confers a growth advantage to S. saprophyticus in the presence of D-serine. Furthermore, in vivo coinfection experiments showed a disadvantage for the ΔdsdA mutant during urinary tract infection. Expression analysis of known virulence factors by reverse transcription-quantitative PCR (RT-qPCR) showed that the surface-associated lipase Ssp is upregulated in the presence of D-serine. In addition, we show that S. saprophyticus is able to use D-serine as the sole carbon source, but interestingly, D-serine had a negative effect on growth when glucose was also present. Taken together, D-serine metabolism is associated with virulence in S. saprophyticus, as at least one known virulence factor is upregulated in the presence of D-serine and a ΔdsdA mutant was attenuated in virulence murine model of urinary tract infection.


Assuntos
Hidroliases/metabolismo , Serina/metabolismo , Infecções Estafilocócicas/metabolismo , Staphylococcus saprophyticus/enzimologia , Infecções Urinárias/metabolismo , Amônia/metabolismo , Animais , Feminino , Camundongos , Camundongos Endogâmicos C3H , Ácido Pirúvico/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus saprophyticus/genética , Staphylococcus saprophyticus/patogenicidade , Infecções Urinárias/microbiologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
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