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Jeronimo Pachon - One of the best experts on this subject based on the ideXlab platform.
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efficacy of lysophosphatidylcholine in combination with antimicrobial agents against acinetobacter baumannii in experimental murine peritoneal sepsis and pneumonia models
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Parra R Millan, M Jimenez E Mejias, Sanchez V Encinales, Ayerbe R Algaba, Gutierrez A Valencia, M Pachon E Ibanez, Caridad Diaz, Perez J Del Palacio, L Lopez F Cortes, Jeronimo PachonAbstract:Immune response stimulation to prevent infection progression may be an adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC) is an immunomodulator involved in immune cell recruitment and activation. In this study, we aimed to evaluate the efficacy of LPC in combination with colistin, tigecycline, or Imipenem in experimental murine models of peritoneal sepsis and pneumonia. We used Acinetobacter baumannii strain Ab9, which is susceptible to colistin, tigecycline, and Imipenem, and multidrug-resistant strain Ab186, which is susceptible to colistin and resistant to tigecycline and Imipenem. Pharmacokinetic and pharmacodynamic parameters for colistin, tigecycline, and Imipenem and the 100% minimal lethal dose (MLD100) were determined for both strains. The therapeutic efficacies of LPC, colistin (60 mg/kg of body weight/day), tigecycline (10 mg/kg/day), and Imipenem (180 mg/kg/day), alone or in combination, were assessed against Ab9 and Ab186 at the MLD100 in murine peritoneal sepsis and pneumonia models. The levels of pro- and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA) for the same experimental models after inoculating mice with the MLD of both strains. LPC in combination with colistin, tigecycline, or Imipenem markedly enhanced the bacterial clearance of Ab9 and Ab186 from the spleen and lungs and reduced bacteremia and mouse mortality rates (P < 0.05) compared with those for colistin, tigecycline, and Imipenem monotherapies. Moreover, at 4 h post-bacterial infection, Ab9 induced higher TNF-α and lower IL-10 levels than those with Ab186 (4 μg/ml versus 3 μg/ml [P < 0.05] and 2 μg/ml versus 3.4 μg/ml [P < 0.05], respectively). LPC treatment combined with colistin, tigecycline, or Imipenem modestly reduced the severity of infection by A. baumannii strains with different resistance phenotypes compared to LPC monotherapy in both experimental models.
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efficacy of rifampin and its combinations with Imipenem sulbactam and colistin in experimental models of infection caused by Imipenem resistant acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Maria Eugenia Pachonibanez, C Pichardo, A Garciacuriel, Fernando Docoboperez, Rafael Lopezrojas, Juan Dominguezherrera, M E Jimenezmejias, Luis Jimenez, Jeronimo PachonAbstract:There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, Imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in experimental pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, Imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, Imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with Imipenem, sulbactam, or colistin, and of Imipenem plus sulbactam were assayed. In the pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with Imipenem, sulbactam, or colistin, (iii) colistin, or (iv) Imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 ± 0.27 [controls] versus 3.05 ± 1.91, 2.07 ± 1.82, 2.41 ± 1.37, 3.4 ± 3.07, 6.82 ± 3.4, and 4.22 ± 2.72 log 10 CFU/g, respectively [means ± standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (−2.6 and −4.4 log 10 CFU/ml). Rifampin in monotherapy or with Imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in experimental models of pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.
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risk factors for the acquisition of Imipenem resistant acinetobacter baumannii in spain a nationwide study
Clinical Microbiology and Infection, 2005Co-Authors: Jose Miguel Cisneros, German Bou, Jesus Rodriguezbano, Felipe Fernandezcuenca, Anna Ribera, Jordi Vila, Alvaro Pascual, Luis Martinezmartinez, Jeronimo PachonAbstract:ABSTRACT Potential risk-factors for the acquisition of Imipenem-resistant Acinetobacter baumannii were investigated in a cohort study in 25 Spanish hospitals. The clonal relationship among isolates was determined by pulsed-field gel electrophoresis (PFGE). In total, A. baumannii was isolated from 203 patients, with Imipenem-resistant (MIC90 128 mg/L) isolates being obtained from 88 patients (43%), and Imipenem-susceptible isolates from 115 patients (57%). A wide clonal distribution was observed among the Imipenem-resistant isolates, but spread of the same clone among centres was not demonstrated. The results indicated that Imipenem-resistant A. baumannii is a widely distributed nosocomial pathogen in Spain and reaches an alarming frequency in some centres. Independent risk-factors for the acquisition of Imipenem-resistant A. baumannii were a hospital size of > 500 beds (multivariate OR, 6.5; 95% CI, 1.8–23), previous antimicrobial treatment (multivariate OR, 4.3; 95% CI, 1.6–11), a urinary catheter (multivariate OR, 2.7; 95% CI, 1.1–6.7) and surgery (multivariate OR, 2; 95% CI, 1.07–3.8).
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efficacy of cefepime and Imipenem in experimental murine pneumonia caused by porin deficient klebsiella pneumoniae producing cmy 2 β lactamase
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: C Pichardo, Jeronimo Pachon, Maria Eugenia Pachonibanez, Luis Martinezmartinez, Josemanuel Rodriguezmartinez, Carmen Conejo, Jose Ibanezmartinez, Alvaro PascualAbstract:Previous studies have shown decreased in vitro activity of zwitterionic cephalosporins and carbapenems against porin-deficient Klebsiella pneumoniae expressing a plasmid-mediated AmpC-type beta-lactamase (PACBL). The in vitro and in vivo activities of cefepime and Imipenem were evaluated against the porin-deficient strain K. pneumoniae C2 and its CMY-2-producing derivative [K. pneumoniae C2(pMG248)]. The MICs (in micrograms/milliliter) of cefepime and Imipenem against K. pneumoniae C2 were 0.125 and 0.25, respectively, while the corresponding values against K. pneumoniae C2(pMG248) were 8 and 16. Cefepime showed a greater inoculum effect than Imipenem against both strains. Imipenem showed a significant postantibiotic effect (>2 h) against K. pneumoniae C2(pMG248) at 1x, 2x, 4x, 6x, and 8x MIC. The maximum concentrations of drug in serum of cefepime and Imipenem in a pneumonia model using mice were 124.1 and 16.9 mug/ml, respectively. DeltaT/MIC for K. pneumoniae C2 and C2(pMG248) were 1.29 h and 0.34 h for Imipenem and 2.96 h and 1.27 h for cefepime. Both Imipenem (30 mg/kg of body weight every 3 h) and cefepime (60 mg/kg every 4 h), administered for 72 h, increased the survival rate (86.6% and 100%) compared with untreated control animals (26.6%, P < 0.003) infected with K. pneumoniae C2. For the CMY-2-producing strain, Imipenem, but not cefepime, increased the survival rate compared to the controls (86.6% and 40% versus 40%, P < 0.01). Bacterial concentration of the lungs was significantly decreased by both antimicrobials. In conclusion, Imipenem was more active in terms of survival than cefepime for the treatment of murine pneumonia caused by a porin-deficient K. pneumoniae expressing PACBL CMY-2.
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activity of tigecycline gar 936 against acinetobacter baumannii strains including those resistant to Imipenem
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Maria Eugenia Pachonibanez, C Pichardo, M E Jimenezmejias, Ana Cristina Llanos, Jeronimo PachonAbstract:We determined the in vitro activities of tigecycline and Imipenem against 49 isolates of Acinetobacter baumannii, including those resistant to Imipenem. The MIC at which 50% of the isolates were inhibited (MIC50) and the MIC90 for tigecycline and Imipenem were 2 and 2 mg/liter and 32 and 128 mg/liter, respectively, with 92 and 20%, respectively, of the strains being susceptible. Tigecycline did not show bactericidal activity in the time-kill studies (n = 9 strains). Imipenem showed bactericidal activity against seven out of nine strains. These in vitro results show that tigecycline has good in vitro bacteriostatic activity against A. baumannii, including strains resistant to Imipenem.
Daniel F Sahm - One of the best experts on this subject based on the ideXlab platform.
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in vitro studies evaluating the activity of Imipenem in combination with relebactam against pseudomonas aeruginosa
BMC Microbiology, 2019Co-Authors: Katherine Young, Ronald E Painter, Susan L Raghoobar, Nichelle Hairston, Fred Racine, Douglas Wisniewski, Carl J Balibar, Artjohn Villafania, Rumin Zhang, Daniel F SahmAbstract:The prevalence of antibiotic resistance is increasing, and multidrug-resistant Pseudomonas aeruginosa has been identified as a serious threat to human health. The production of β-lactamase is a key mechanism contributing to Imipenem resistance in P. aeruginosa. Relebactam is a novel β-lactamase inhibitor, active against class A and C β-lactamases, that has been shown to restore Imipenem susceptibility. In a series of studies, we assessed the interaction of relebactam with key mechanisms involved in carbapenem resistance in P. aeruginosa and to what extent relebactam might overcome Imipenem non-susceptibility. Relebactam demonstrated no intrinsic antibacterial activity against P. aeruginosa, had no inoculum effect, and was not subject to efflux. Enzymology studies showed relebactam is a potent (overall inhibition constant: 27 nM), practically irreversible inhibitor of P. aeruginosa AmpC. Among P. aeruginosa clinical isolates from the SMART global surveillance program (2009, n = 993; 2011, n = 1702; 2015, n = 5953; 2016, n = 6165), Imipenem susceptibility rates were 68.4% in 2009, 67.4% in 2011, 70.4% in 2015, and 67.3% in 2016. With the addition of 4 μg/mL relebactam, Imipenem susceptibility rates increased to 87.6, 86.0, 91.7, and 89.8%, respectively. When all Imipenem–non-susceptible isolates were pooled, the addition of 4 μg/mL relebactam reduced the mode Imipenem minimum inhibitory concentration (MIC) 8-fold (from 16 μg/mL to 2 μg/mL) among all Imipenem–non-susceptible isolates. Of 3747 Imipenem–non-susceptible isolates that underwent molecular profiling, 1200 (32%) remained non-susceptible to the combination Imipenem/relebactam (IMI/REL); 42% of these encoded class B metallo-β-lactamases, 11% encoded a class A GES enzyme, and no class D enzymes were detected. No relationship was observed between alleles of the chromosomally-encoded P. aeruginosa AmpC and IMI/REL MIC. IMI/REL exhibited potential in the treatment of carbapenem-resistant P. aeruginosa infections, with the exception of isolates encoding class B, some GES alleles, and class D carbapenemases.
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activity of Imipenem relebactam against pseudomonas aeruginosa with antimicrobial resistant phenotypes from seven global regions smart 2015 2016
Journal of global antimicrobial resistance, 2018Co-Authors: Sibylle H Lob, James A Karlowsky, Katherine Young, Mary Motyl, Daniel F SahmAbstract:Abstract Objectives Relebactam inhibits Ambler class A and C β-lactamases. Imipenem/relebactam has completed one phase 3 clinical study of patients infected with Imipenem-non-susceptible Gram-negative bacilli. Two more phase 3 clinical studies are in progress for the treatment of patients with hospital-acquired and ventilator-associated bacterial pneumonia, complicated intra-abdominal infections and complicated urinary tract infections. In the current study, clinical Pseudomonas aeruginosa isolates cultured by medical centre laboratories in seven geographic regions (Africa, Asia, Europe, Latin America, Middle East, USA/Canada, South Pacific) were tested for susceptibility to Imipenem/relebactam and comparators. Methods A total of 12 170 isolates collected as part of the 2015–2016 Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program were tested using the Clinical and Laboratory Standards Institute (CLSI)-defined broth microdilution method. Relebactam was tested at a fixed concentration of 4 μg/mL in combination with doubling dilutions of Imipenem. Imipenem/relebactam MICs were interpreted using current CLSI breakpoints for Imipenem. Results At the Imipenem susceptible breakpoint (≤2 μg/mL), Imipenem/relebactam inhibited 90.8% of all P. aeruginosa isolates and 70.7% of multidrug-resistant (MDR) isolates (n = 3708). Relebactam restored Imipenem susceptibility to 70.3% (2656/3776) of Imipenem-non-susceptible isolates and increased percent susceptibility to Imipenem against isolates with ceftazidime-non-susceptible (by 35.2%), piperacillin/tazobactam-non-susceptible (by 36.6%), cefepime-non-susceptible (by 36.8%) and MDR (by 41.9%) phenotypes. Across the seven geographic regions studied, susceptibility to Imipenem/relebactam ranged from 84.0% (Latin America) to 96.0% (South Pacific). Conclusions Imipenem/relebactam could provide an important treatment option against infections with P. aeruginosa isolates that are non-susceptible to several currently available antipseudomonal β-lactams.
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in vitro activity of Imipenem relebactam against gram negative eskape pathogens isolated in 17 european countries 2015 smart surveillance programme
Journal of Antimicrobial Chemotherapy, 2018Co-Authors: James A Karlowsky, Sibylle H Lob, Krystyna M Kazmierczak, Katherine Young, Mary Motyl, Stephen Hawser, Sophie Magnet, Daniel F SahmAbstract:Objectives Relebactam is an inhibitor of class A β-lactamases, including KPC β-lactamases, and class C β-lactamases, and is currently under clinical development in combination with Imipenem. The objective of the current study was to evaluate the in vitro activity of Imipenem/relebactam against Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) submitted by clinical laboratories in 17 European countries to the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance programme in 2015. Methods MICs were determined using the CLSI standard broth microdilution method and interpreted using EUCAST clinical breakpoints. Relebactam was tested at a fixed concentration of 4 mg/L in combination with doubling dilutions of Imipenem. Imipenem/relebactam MICs were interpreted using breakpoints for Imipenem. Results Rates of susceptibility to Imipenem and Imipenem/relebactam for isolates of P. aeruginosa (n = 1705), K. pneumoniae (n = 1591) and Enterobacter spp. (n = 772) were 72.0/94.7%, 88.7/94.8% and 95.6/96.8%, respectively. Relebactam restored Imipenem susceptibility to 81.1%, 54.2% and 26.5% of Imipenem-non-susceptible isolates of P. aeruginosa (n = 477), K. pneumoniae (n = 179) and Enterobacter spp. (n = 34). Most Imipenem/relebactam-non-susceptible isolates carried MBLs, OXA-48 or GES carbapenemases. Relebactam did not increase the number of isolates of A. baumannii (n = 486) susceptible to Imipenem. Conclusions Relebactam restored susceptibility to Imipenem for the majority of Imipenem-non-susceptible isolates of P. aeruginosa and K. pneumoniae tested as well as some isolates of Imipenem-non-susceptible Enterobacter spp. Based on our results, Imipenem/relebactam appears to be a promising therapeutic option for treating patients with infections caused by antimicrobial-resistant Gram-negative bacilli.
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in vitro activity of Imipenem relebactam against gram negative eskape pathogens isolated by clinical laboratories in the united states in 2015 results from the smart global surveillance program
Antimicrobial Agents and Chemotherapy, 2017Co-Authors: Sibylle H Lob, James A Karlowsky, Meredith Hackel, Krystyna M Kazmierczak, Katherine Young, Mary Motyl, Daniel F SahmAbstract:Relebactam (formerly MK-7655) is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC), and is currently in clinical development in combination with Imipenem-cilastatin. Using Clinical and Laboratory Standards Institute (CLSI)-defined broth microdilution methodology, we evaluated the in vitro activities of Imipenem-relebactam, Imipenem, and seven routinely tested parenteral antimicrobial agents against Gram-negative ESKAPE pathogens (including Klebsiella pneumoniae, n = 689; Acinetobacter baumannii, n = 72; Pseudomonas aeruginosa, n = 845; and Enterobacter spp., n = 399) submitted by 21 clinical laboratories in the United States in 2015 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Relebactam was tested at a fixed concentration of 4 μg/ml in combination with doubling dilutions of Imipenem. Imipenem-relebactam MICs were interpreted using CLSI Imipenem breakpoints. The respective rates of susceptibility to Imipenem-relebactam and Imipenem were 94.2% (796/845) and 70.3% (594/845) for P. aeruginosa, 99.0% (682/689) and 96.1% (662/689) for K. pneumoniae, and 100% (399/399) and 98.0% (391/399) for Enterobacter spp. Relebactam restored Imipenem susceptibility to 80.5% (202/251), 74.1% (20/27), and 100% (8/8) of isolates of Imipenem-nonsusceptible P. aeruginosa, K. pneumoniae, and Enterobacter spp. Relebactam did not increase the number of isolates of Acinetobacter spp. susceptible to Imipenem, and the rates of resistance to all of the agents tested against this pathogen were >30%. Further development of Imipenem-relebactam is warranted given the demonstrated ability of relebactam to restore the activity of Imipenem against current clinical isolates of Enterobacteriaceae and P. aeruginosa that are nonsusceptible to carbapenems and its potential as a therapy for treating patients with antimicrobial-resistant Gram-negative infections.
James J Rahal - One of the best experts on this subject based on the ideXlab platform.
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in vitro double and triple synergistic activities of polymyxin b Imipenem and rifampin against multidrug resistant acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Jimmy Yoon, Noriel Mariano, James J Rahal, Carl Urban, Christian TerzianAbstract:Eight unrelated clinical Acinetobacter baumannii isolates resistant to all commonly used antibiotics were subjected to three-dimensional checkerboard microtiter plate dilution and time-kill studies at one-fourth of their MICs of polymyxin B, Imipenem, and rifampin. Synergy was demonstrated with combinations of polymyxin B and Imipenem, polymyxin B and rifampin, and polymyxin B, Imipenem, and rifampin. Double combinations of polymyxin B and Imipenem and of polymyxin B and rifampin were bactericidal for seven of eight isolates, and triple combinations were bactericidal for all isolates within 24 h. Future clinical studies using double and triple therapy with these antibacterials may provide an effective option against potentially lethal infection due to multiresistant Acinetobacter baumannii.
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clinical characteristics and molecular epidemiology associated with Imipenem resistant klebsiella pneumoniae
Clinical Infectious Diseases, 1999Co-Authors: Muhammad Ahmad, Noriel Mariano, Carl Urban, Patricia A Bradford, Ellen Calcagni, Steven J Projan, Karen Bush, James J RahalAbstract:Eight patients were infected or colonized with Imipenem-resistant Klebsiella pneumoniae (IRKP) from December 1994 to November 1995. Initial Klebsiella isolates were susceptible to Imipenem but resistant to all cephalosporins, aminoglycosides, and β-lactam inhibitor combinations. All patients had been in the surgical intensive care unit and had undergone abdominal surgery or tracheostomy during hospitalization. The average age of the patients was 71 years (range, 41-81 years). All patients were treated with Imipenem for 5 to 36 days, and IRKP was recovered from each during or after therapy. Pulsed-field gel electrophoresis (PFGE) of the IRKP isolates revealed three distinct clonal patterns. Paired sequential isolates of Imipenem-susceptible K. pneumoniae and IRKP from two patients had identical PFGE patterns, suggesting the development of clonal stepwise resistance to Imipenem during therapy. Thus, Imipenem resistance in Klebsiella may occur when this agent is used for treatment of infection due to ceftazidime- and aminoglycoside-resistant strains.
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interaction of sulbactam clavulanic acid and tazobactam with penicillin binding proteins of Imipenem resistant and susceptible acinetobacter baumannii
Fems Microbiology Letters, 1995Co-Authors: Eddie Go, Noriel Mariano, James J Rahal, Carl UrbanAbstract:We have encountered clinical isolates of Acinetobacter baumannii which are resistant to all available antibiotics used in hospitals except for polymyxin B and the beta-lactamase inhibitor, sulbactam. To investigate the mechanisms of this unique activity, affinities of sulbactam and other beta-lactamase inhibitors for penicillin binding proteins were compared using Imipenem-resistant and Imipenem-sensitive isolates. The results of competition binding experiments indicate that all three beta-lactamase inhibitors bound to Imipenem-susceptible Acinetobacter. Binding of sulbactam was greater than that of tazobactam and not detected with clavulanic acid to penicillin binding proteins of the Imipenem-resistant strain of Acinetobacter.
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clinical and molecular epidemiology of acinetobacter infections sensitive only to polymyxin b and sulbactam
The Lancet, 1994Co-Authors: Carl Urban, Noriel Mariano, James J Rahal, Barry N Kreiswirth, Janice Burns, K Mosinkasnipas, W EisnerAbstract:A nosocomial outbreak of infections due to Imipenem-resistant Acinetobacter baumannii occurred in a New York hospital after increased use of Imipenem for cephalosporin-resistant klebsiella infections. We identified all A baumannii isolates over 12 months, reviewed corresponding patient records, and compared strains with different antibiotic susceptibility patterns by restriction endonuclease analysis. Environmental surveillance cultures were done before and after institution of control measures. 59 patients harboured Imipenem-resistant A baumannii, and 18 were infected. Isolates from patients were resistant to all routinely tested antibiotics, including Imipenem. Further studies showed susceptibility to polymyxin B and sulbactam. These isolates were identical by restriction endonuclease analysis to A baumannii isolates susceptible to Imipenem alone, or to Imipenem and amikacin, but differed from broadly susceptible isolates. Surveillance cultures showed hand and environmental colonisation by Imipenem-resistant strains. Infection and colonisation were eliminated by intensive infection control measures, and irrigation of wounds with polymyxin B. Increased use of Imipenem against cephalosporin-resistant klebsiella may lead to Imipenem resistance among other species, particularly acinetobacter. Such resistance appears to derive from a prior multi-resistant clone, in contrast to one which retains susceptibility to several antibiotics.
Changphone Fung - One of the best experts on this subject based on the ideXlab platform.
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differences in phenotypic and genotypic characteristics among Imipenem non susceptible acinetobacter isolates belonging to different genomic species in taiwan
International Journal of Antimicrobial Agents, 2009Co-Authors: Yitzu Lee, Fu Der Wang, Liyueh Huang, Dunghung Chiang, Chienpei Chen, Teli Chen, Changphone Fung, L K SiuAbstract:Abstract In this study, we investigated the distribution of genes encoding various carbapenemases as well as their association with carbapenem resistance in clinical isolates of Acinetobacter genomic species from Taiwan. A total of 129 Imipenem-non-susceptible and 79 Imipenem-susceptible isolates were examined, of which 185 (88.9%) were Acinetobacter baumannii. Among the 185 A. baumannii isolates, Imipenem non-susceptibility was more common in isolates with IS Aba1–bla OXA-51-like (72/75; 96%), bla OXA-58-like (33/33; 100%) or bla OXA-24-like (7/7; 100%) than in isolates with only bla OXA-51-like (4/72; 5.6%). A metallo-β-lactamase (MBL) gene was present in two isolates of Imipenem-resistant A. baumannii , and bla OXA-58-like was also present in these isolates. A total of 18% and 1% of Imipenem-non-susceptible isolates of A. baumannii were resistant to tigecycline and colistin, respectively. Among the 23 isolates of non- baumannii Acinetobacter spp., bla OXA-58-like and MBL genes were widely disseminated in the Imipenem-resistant isolates, and isolates with bla OXA-58-like and MBL genes had higher Imipenem minimum inhibitory concentrations than those with bla OXA-58-like alone. Although the rate of non-susceptibility to colistin was 26.7% among the Imipenem-non-susceptible isolates of non- baumannii Acinetobacter , 93.3% and 100% were susceptible to ciprofloxacin and tigecycline, respectively. In conclusion, different isolates of Imipenem-non-susceptible A. baumannii and non- baumannii Acinetobacter contained different carbapenemases and had different antimicrobial susceptibilities.
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an oxa 66 oxa 51 like carbapenemase and possibly an efflux pump are associated with resistance to Imipenem in acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2007Co-Authors: Wensi S Hu, Changphone Fung, Yiping HsiehAbstract:We investigated the mechanisms involved in Imipenem resistance in 23 clinical strains of Acinetobacter baumannii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of a 30-kDa protein in Imipenem-intermediate A. baumannii (IIAB) and Imipenem-resistant A. baumannii (IRAB) strains; this protein was almost undetectable in Imipenem-susceptible A. baumannii (ISAB) strains. The 30-kDa protein was identified as an OXA-51-like carbapenemase using two-dimensional gel electrophoresis and mass spectrometry. Similar to other recent findings, blaOXA-51-like genes were found to exist in all 23 clinical strains; however, the transcript levels of blaOXA-51-like in the IIAB and IRAB were higher than in the ISAB strains using reverse transcriptase PCR (RT-PCR) and real-time RT-PCR assays. This change was due to the presence of an insertion sequence, ISAba1, upstream of blaOXA-51-like in the IIAB and IRAB strains that was not present in the ISAB strains. The introduction of blaOXA-66 (a blaOXA-51-like gene), identified in ISAB ab1254 and IRAB ab1266, into Escherichia coli TOP10 cells resulted in 3.95-fold and 7.90-fold elevations in resistance to Imipenem, respectively. Furthermore, when ISAB ab8 and ISAB ab1254 and their in vitro-selected Imipenem-resistant mutants ISAB ab8(r) and ISAB ab1254(r) were compared, the results showed no change in the blaOXA-66/blaOXA-51-like gene sequences, in expression of the gene, and in the outer membrane protein profiles. However, there was a four- to eightfold reduction in Imipenem resistance upon adding carbonyl cyanide m-chlorophenylhydrazone. Taken together, these results suggest that the OXA-66/OXA-51-like carbapenemase contributes to intrinsic resistance to Imipenem; however, drug export by an efflux pump may be more important and/or occur more frequently in Imipenem-resistant A. baumannii. Furthermore, this is the first report of a Taiwanese strain of an OXA-66/OXA-51-like carbapenemase that confers Imipenem resistance in A. baumannii.
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an oxa 66 oxa 51 like carbapenemase and possibly an efflux pump are associated with resistance to Imipenem in acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2007Co-Authors: Shuman Yao, Changphone Fung, Yiping Hsieh, Changpan Liu, Jingfang LinAbstract:We investigated the mechanisms involved in Imipenem resistance in 23 clinical strains of Acinetobacter baumannii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of a 30-kDa protein in Imipenem-intermediate A. baumannii (IIAB) and Imipenem-resistant A. baumannii (IRAB) strains; this protein was almost undetectable in Imipenem-susceptible A. baumannii (ISAB) strains. The 30-kDa protein was identified as an OXA-51-like carbapenemase using two-dimensional gel electrophoresis and mass spectrometry. Similar to other recent findings, blaOXA-51-like genes were found to exist in all 23 clinical strains; however, the transcript levels of blaOXA-51-like in the IIAB and IRAB were higher than in the ISAB strains using reverse transcriptase PCR (RT-PCR) and real-time RT-PCR assays. This change was due to the presence of an insertion sequence, ISAba1, upstream of blaOXA-51-like in the IIAB and IRAB strains that was not present in the ISAB strains. The introduction of blaOXA-66 (a blaOXA-51-like gene), identified in ISAB ab1254 and IRAB ab1266, into Escherichia coli TOP10 cells resulted in 3.95-fold and 7.90-fold elevations in resistance to Imipenem, respectively. Furthermore, when ISAB ab8 and ISAB ab1254 and their in vitro-selected Imipenem-resistant mutants ISAB ab8(r) and ISAB ab1254(r) were compared, the results showed no change in the blaOXA-66/blaOXA-51-like gene sequences, in expression of the gene, and in the outer membrane protein profiles. However, there was a four- to eightfold reduction in Imipenem resistance upon adding carbonyl cyanide m-chlorophenylhydrazone. Taken together, these results suggest that the OXA-66/OXA-51-like carbapenemase contributes to intrinsic resistance to Imipenem; however, drug export by an efflux pump may be more important and/or occur more frequently in Imipenem-resistant A. baumannii. Furthermore, this is the first report of a Taiwanese strain of an OXA-66/OXA-51-like carbapenemase that confers Imipenem resistance in A. baumannii.
Yiping Hsieh - One of the best experts on this subject based on the ideXlab platform.
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an oxa 66 oxa 51 like carbapenemase and possibly an efflux pump are associated with resistance to Imipenem in acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2007Co-Authors: Wensi S Hu, Changphone Fung, Yiping HsiehAbstract:We investigated the mechanisms involved in Imipenem resistance in 23 clinical strains of Acinetobacter baumannii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of a 30-kDa protein in Imipenem-intermediate A. baumannii (IIAB) and Imipenem-resistant A. baumannii (IRAB) strains; this protein was almost undetectable in Imipenem-susceptible A. baumannii (ISAB) strains. The 30-kDa protein was identified as an OXA-51-like carbapenemase using two-dimensional gel electrophoresis and mass spectrometry. Similar to other recent findings, blaOXA-51-like genes were found to exist in all 23 clinical strains; however, the transcript levels of blaOXA-51-like in the IIAB and IRAB were higher than in the ISAB strains using reverse transcriptase PCR (RT-PCR) and real-time RT-PCR assays. This change was due to the presence of an insertion sequence, ISAba1, upstream of blaOXA-51-like in the IIAB and IRAB strains that was not present in the ISAB strains. The introduction of blaOXA-66 (a blaOXA-51-like gene), identified in ISAB ab1254 and IRAB ab1266, into Escherichia coli TOP10 cells resulted in 3.95-fold and 7.90-fold elevations in resistance to Imipenem, respectively. Furthermore, when ISAB ab8 and ISAB ab1254 and their in vitro-selected Imipenem-resistant mutants ISAB ab8(r) and ISAB ab1254(r) were compared, the results showed no change in the blaOXA-66/blaOXA-51-like gene sequences, in expression of the gene, and in the outer membrane protein profiles. However, there was a four- to eightfold reduction in Imipenem resistance upon adding carbonyl cyanide m-chlorophenylhydrazone. Taken together, these results suggest that the OXA-66/OXA-51-like carbapenemase contributes to intrinsic resistance to Imipenem; however, drug export by an efflux pump may be more important and/or occur more frequently in Imipenem-resistant A. baumannii. Furthermore, this is the first report of a Taiwanese strain of an OXA-66/OXA-51-like carbapenemase that confers Imipenem resistance in A. baumannii.
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an oxa 66 oxa 51 like carbapenemase and possibly an efflux pump are associated with resistance to Imipenem in acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2007Co-Authors: Shuman Yao, Changphone Fung, Yiping Hsieh, Changpan Liu, Jingfang LinAbstract:We investigated the mechanisms involved in Imipenem resistance in 23 clinical strains of Acinetobacter baumannii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of a 30-kDa protein in Imipenem-intermediate A. baumannii (IIAB) and Imipenem-resistant A. baumannii (IRAB) strains; this protein was almost undetectable in Imipenem-susceptible A. baumannii (ISAB) strains. The 30-kDa protein was identified as an OXA-51-like carbapenemase using two-dimensional gel electrophoresis and mass spectrometry. Similar to other recent findings, blaOXA-51-like genes were found to exist in all 23 clinical strains; however, the transcript levels of blaOXA-51-like in the IIAB and IRAB were higher than in the ISAB strains using reverse transcriptase PCR (RT-PCR) and real-time RT-PCR assays. This change was due to the presence of an insertion sequence, ISAba1, upstream of blaOXA-51-like in the IIAB and IRAB strains that was not present in the ISAB strains. The introduction of blaOXA-66 (a blaOXA-51-like gene), identified in ISAB ab1254 and IRAB ab1266, into Escherichia coli TOP10 cells resulted in 3.95-fold and 7.90-fold elevations in resistance to Imipenem, respectively. Furthermore, when ISAB ab8 and ISAB ab1254 and their in vitro-selected Imipenem-resistant mutants ISAB ab8(r) and ISAB ab1254(r) were compared, the results showed no change in the blaOXA-66/blaOXA-51-like gene sequences, in expression of the gene, and in the outer membrane protein profiles. However, there was a four- to eightfold reduction in Imipenem resistance upon adding carbonyl cyanide m-chlorophenylhydrazone. Taken together, these results suggest that the OXA-66/OXA-51-like carbapenemase contributes to intrinsic resistance to Imipenem; however, drug export by an efflux pump may be more important and/or occur more frequently in Imipenem-resistant A. baumannii. Furthermore, this is the first report of a Taiwanese strain of an OXA-66/OXA-51-like carbapenemase that confers Imipenem resistance in A. baumannii.
