The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Jeronimo Pachon - One of the best experts on this subject based on the ideXlab platform.
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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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Sulbactam efficacy in experimental models caused by susceptible and intermediate acinetobacter baumannii strains
Journal of Antimicrobial Chemotherapy, 2001Co-Authors: Mariajesus Rodriguezhernandez, L Cuberos, C Pichardo, F J Caballero, Ignacio Moreno, Enrique M Jimenezmejias, A Garciacuriel, Jeronimo PachonAbstract:Sulbactam and imipenem were compared in an experimental pneumonia model in immunocompetent mice, using a susceptible strain of Acinetobacter baumannii, and in an experimental endocarditis model in rabbits, using an intermediately susceptible strain. In the former, Sulbactam was as efficacious as imipenem in terms of survival, sterility of lungs and in the bacterial clearance from lungs and blood, provided that the t > MIC for Sulbactam (1.84 h) was similar to that for imipenem (2.01 h). In the endocarditis model, imipenem (t > MIC, 2.12 h) was more efficacious than Sulbactam (t > MIC, 1.17 h) in bacterial clearance from vegetations. These results show the efficacy of Sulbactam in infections caused by susceptible strains of A. baumannii, with an MIC up to 4 mg/L, provided that doses reach a t > MIC similar to that of imipenem. The activity of Sulbactam was time dependent.
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treatment of multidrug resistant acinetobacter baumannii meningitis with ampicillin Sulbactam
Clinical Infectious Diseases, 1997Co-Authors: M E Jimenezmejias, Jeronimo Pachon, B Becerril, J Palominonicas, A Rodriguezcobacho, M P RevueltaAbstract:: The clinical features and the outcomes of eight cases of nosocomial Acinetobacter baumannii meningitis treated with ampicillin/Sulbactam are reported. All the patients had fever, neck stiffness or meningeal signs, and a low consciousness level, and in their cerebrospinal fluid (CSF), pleocytosis, a low glucose level, and an elevated protein level were noted. For all CSF isolates of A. baumannii, the MIC of ampicillin/Sulbactam was < or = 8/4 microg/mL. The MICs of Sulbactam by microdilution in two cases were 4 microg/mL. All isolates were resistant to cefotaxime, ceftriaxone, ceftazidime, ureidopenicillins, ciprofloxacin, and gentamicin. Seven isolates were resistant to imipenem. A. baumannii was isolated from other samples in seven episodes. All patients were treated with ampicillin/Sulbactam (seven with 2 g/l g every 6 hours and one with 2 g/l g every 8 hours). Six patients were cured and two patients died of meningitis. There were no side effects with the ampicillin/Sulbactam treatment. In conclusion, ampicillin/Sulbactam may be effective as therapy for meningitis caused by A. baumanii resistant to imipenem and other beta-lactam drugs.
Matthew E. Falagas - One of the best experts on this subject based on the ideXlab platform.
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Ampicillin/Sulbactam
Drugs, 2007Co-Authors: Petros I. Rafailidis, Eleni N. Ioannidou, Matthew E. FalagasAbstract:Ampicillin/Sulbactam is a β-lactam/β-lactamase inhibitor combination with a broad spectrum of antibacterial activity against Gram-positive, Gram-negative and anaerobic bacteria. Data from comparative studies justify the use of ampicillin/Sulbactam in a 2: 1 ratio in various severe bacterial infections. In comparative clinical trials, ampicillin/Sulbactam has proved to be a significant drug in the therapeutic armamentarium for lower respiratory tract infections and aspiration pneumonia, gynaecological/obstetrical infections, intra-abdominal infections, paediatric infections such as acute epiglottitis and periorbital cellulitis, diabetic foot infections, and skin and soft tissue infections. Of particular interest during this era of increasing antimicrobial resistance in various settings and populations is the effectiveness of Sulbactam against a considerable proportion of infections due to Acinetobacter baumannii.
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ampicillin Sulbactam current status in severe bacterial infections
Drugs, 2007Co-Authors: Petros I. Rafailidis, Eleni N. Ioannidou, Matthew E. FalagasAbstract:Abstract Ampicillin/Sulbactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against Gram-positive, Gram-negative and anaerobic bacteria. Data from comparative studies justify the use of ampicillin/Sulbactam in a 2 : 1 ratio in various severe bacterial infections. In comparative clinical trials, ampicillin/Sulbactam has proved to be a significant drug in the therapeutic armamentarium for lower respiratory tract infections and aspiration pneumonia, gynaecological/obstetrical infections, intra-abdominal infections, paediatric infections such as acute epiglottitis and periorbital cellulitis, diabetic foot infections, and skin and soft tissue infections. Of particular interest during this era of increasing antimicrobial resistance in various settings and populations is the effectiveness of Sulbactam against a considerable proportion of infections due to Acinetobacter baumannii.
Alita A Miller - One of the best experts on this subject based on the ideXlab platform.
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frequency and mechanism of spontaneous resistance to Sulbactam combined with the novel β lactamase inhibitor etx2514 in clinical isolates of acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2017Co-Authors: Sarah M Mcleod, Adam B Shapiro, Samir H Moussa, Michele Johnstone, Robert E Mclaughlin, Boudewijn L M De Jonge, Alita A MillerAbstract:: The novel diazabicyclooctenone ETX2514 is a potent, broad-spectrum serine β-lactamase inhibitor that restores Sulbactam activity against resistant Acinetobacter baumannii The frequency of spontaneous resistance to Sulbactam-ETX2514 in clinical isolates was found to be 7.6 × 10-10 to <9.0 × 10-10 at 4× MIC and mapped to residues near the active site of penicillin binding protein 3 (PBP3). Purified mutant PBP3 proteins demonstrated reduced affinity for Sulbactam. In a Sulbactam-sensitive isolate, resistance also mapped to stringent response genes associated with resistance to PBP2 inhibitors, suggesting that in addition to β-lactamase inhibition, ETX2514 may enhance Sulbactam activity in A. baumannii via inhibition of PBP2.
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molecular mechanisms of Sulbactam antibacterial activity and resistance determinants in acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2015Co-Authors: William F Penwell, Adam B Shapiro, Robert E Mclaughlin, Robert A Giacobbe, Rongfang Gu, Jason Thresher, Michael D Huband, Boudewijn Lodewijk Maria Dejonge, David E Ehmann, Alita A MillerAbstract:ABSTRACT Sulbactam is a class A β-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.
Teli Chen - One of the best experts on this subject based on the ideXlab platform.
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contribution of acinetobacter derived cephalosporinase 30 to Sulbactam resistance in acinetobacter baumannii
Frontiers in Microbiology, 2015Co-Authors: Tsailing Lauderdale, Weicheng Huang, Mingfen Chuang, Chienpei Chen, Sheychiang Su, Teli ChenAbstract:The Sulbactam resistance rate in Acinetobacter baumannii has increased worldwide. Previous reports have shown that the β-lactamase blaTEM-1 confers resistance to Sulbactam in A. baumannii. The purpose of this study was to examine whether other β-lactamases including, the Acinetobacter-derived cephalosporinase (ADC), OXA-23, OXA-24/72, and OXA-58 families, also contribute to Sulbactam resistance in A. baumannii. The correlation between these β-lactamases and the Sulbactam minimal inhibitory concentration (MIC) was determined using A. baumannii clinical isolates from diverse clonality, which were collected in a nationwide surveillance program from 2002 to 2010 in Taiwan. A possible association between the genetic structure of ISAba1-blaADC-30 and Sulbactam resistance was observed because this genetic structure was detected in 97% of Sulbactam-resistant strains compared with 10% of Sulbactam-susceptible strains. Transformation of ISAba1-blaADC-30 into susceptible strains increased the Sulbactam MIC from 2 to 32 μg/ml, which required blaADC-30 overexpression using an upstream promoter in ISAba1. Flow cytometry showed that ADC-30 production increased in response to Sulbactam, ticarcillin, and ceftazidime treatment. This effect was regulated at the RNA level but not by an increase in the blaADC-30 gene copy number as indicated by quantitative PCR. Purified ADC-30 decreased the inhibitory zone created by Sulbactam or ceftazidime, similarly to TEM-1. In conclusion, ADC-30 overexpression conferred resistance to Sulbactam in diverse clinical A. baumannii isolates.
Yehuda Carmeli - One of the best experts on this subject based on the ideXlab platform.
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risk factors for recovery of ampicillin Sulbactam resistant escherichia coli in hospitalized patients
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: Keith S Kaye, Anthony D Harris, Howard S Gold, Yehuda CarmeliAbstract:Ampicillin-Sulbactam resistance in Escherichia coli is an emerging problem. This study determined risk factors for the recovery of ampicillin-Sulbactam-resistant E. coli in hospitalized patients. A case-control design was used to compare two groups of case patients with control patients. The first group of case patients consisted of patients from whom nosocomially acquired ampicillin-Sulbactam-resistant E. coli strains were isolated, and the second group of case patients consisted of patients from whom ampicillin-Sulbactam-susceptible E. coli strains were isolated. Control patients were a random selection among 5% of all patients admitted during the same time period. Risk factors analyzed included antimicrobial drug exposure, comorbid conditions, and demographics. Univariate and multivariate analyses were performed. Ampicillin-Sulbactam-resistant E. coli strains were isolated from 175 patients, and ampicillin-Sulbactam-susceptible E. coli strains were isolated from 577 patients. Nine hundred thirty-four control patients were selected. Exposure to penicillin antibiotics as a class and to ampicillin and ampicillin-Sulbactam individually were the only significant, independent risk factors associated with the isolation of ampicillin-Sulbactam-resistant E. coli (odds ratio [OR] = 2.32 [P < 0.001], OR = 3.04 [P = 0.02], and OR = 1.72 [P = 0.04], respectively), but they were not associated with the isolation of ampicillin-Sulbactam-susceptible E. coli. Interestingly, exposure to piperacillin-tazobactam tended to protect against the isolation of E. coli strains resistant to ampicillin-Sulbactam, but this did not reach statistical significance (OR = 0.13; P = 0.11).
