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Kazmierczak, Krystyna, Sibylle Lob, Gregory Stone, and Daniel F. Sahm. "1264. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa Collected < 48 Hours and ≥48 Hours Post-Admission from Pediatric Patients, ATLAS Surveillance Program 2016-2019." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S720—S721. http://dx.doi.org/10.1093/ofid/ofab466.1456.
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Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with in vitro activity against Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa) carrying Class A, C and some Class D β-lactamases. We examined the in vitro activity of CAZ-AVI and comparators against presumed community-acquired (CA; cultured < 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) isolates collected from pediatric patients as part of the ATLAS surveillance program. Methods 6654 non-duplicate isolates were collected in 52 countries in Europe (n=3423), Latin America (n=1323), Middle East/Africa (n=1177), and Asia/Pacific (excluding China; n=731) from patients (newborn to 17 y) with lower respiratory tract (LRTI; n=1687), urinary tract (UTI; n=1631), bloodstream (BSI; n=1149), skin and soft tissue (SSTI; n=1122), and intra-abdominal (IAI; n=981) infections. Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2021 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with CAZ or aztreonam MICs ≥2 µg/mL (Escherichia coli, Klebsiella spp., Proteus mirabilis) or meropenem MICs ≥2 µg/mL (all Ent species) or ≥4 µg/mL (Psa) were screened for β-lactamase genes. Results The in vitro activity of CAZ-AVI exceeded that of meropenem and other tested β-lactams against Ent (97.8% susceptible (S)) and Psa (92.1% S) collected globally from pediatric patients (Table). Percentages of susceptibility to CAZ-AVI ranged from 95.4-99.2% among CA Ent from different infection types and were reduced 0.6-1.3% among HA isolates from LRTI, UTI, SSTI, and IAI. Susceptibility to CAZ-AVI was also similar (92.6-95.8% S) among CA Psa from different infection types and was reduced 1.2-7.0% among HA isolates. Larger differences in susceptibility were typically seen for the tested comparator β-lactams. For Ent, the lowest percentages of susceptibility to the tested β-lactams were observed among isolates from BSI, while the pattern was less clear for Psa. Results Table Conclusion CAZ-AVI could provide a valuable therapeutic option for treatment of CA and HA infections caused by Ent and Psa in pediatric patients. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
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Kazmierczak, Krystyna, Greg Stone, and Daniel F. Sahm. "1568. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa Collected < 48 Hours and ≥48 Hours Post-Admission from Pediatric Patients, ATLAS Surveillance Program 2015-2018." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S783. http://dx.doi.org/10.1093/ofid/ofaa439.1748.
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Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with in vitro activity against Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa) carrying Class A, C and some Class D β-lactamases. We examined the in vitro activity of CAZ-AVI and comparators against presumed community-acquired (CA; cultured < 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) isolates collected from pediatric patients as part of the ATLAS surveillance program. Methods 6023 non-duplicate isolates were collected in 50 countries in Europe (n=3122), Latin America (n=1220), Middle East/Africa (n=1007), and Asia/Pacific (excluding China; n=674) from patients (newborn to 17 y) with lower respiratory tract (LRTI; n=1641), urinary tract (UTI; n=1595), skin and soft tissue (SSTI; n=1027), intra-abdominal (IAI; n=949), and bloodstream (BSI; n=811) infections. Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2020 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with CAZ or aztreonam MICs ≥2 µg/mL (Escherichia coli, Klebsiella spp., Proteus mirabilis) or meropenem MICs ≥2 µg/mL (all Ent species) or ≥4 µg/mL (Psa) were screened for β-lactamase genes. Results The in vitro activity of CAZ-AVI exceeded that of meropenem and other tested β-lactams against Ent (98.5% susceptible (S)) and Psa (93.1% S) collected globally from pediatric patients (Table). Percentages of susceptibility to CAZ-AVI ranged from 96.8-99.3% among CA Ent from different infection types and were reduced 0.4-1.0% among HA isolates from SSTI, IAI and BSI. Susceptibility to CAZ-AVI was also similar (92.7-95.4% S) among CA Psa from different infection types and was reduced 0.1-4.4% among HA isolates. For both Ent and Psa, the lowest percentages of susceptibility to the tested β-lactams were observed among isolates from BSI, which included a higher proportion of isolates carrying extended-spectrum β-lactamases and/or carbapenemases than isolates from other infection types. Table Conclusion CAZ-AVI could provide a valuable therapeutic option for treatment of CA and HA infections caused by Ent and Psa in pediatric patients. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
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Lei, Wen-Long, Kai-Wen Feng, Tao Wang, Li-Zhu Wu, and Qiang Liu. "Eosin Y- and Copper-Catalyzed Dark Reaction To Construct Ene-γ-Lactams." Organic Letters 20, no. 22 (November 7, 2018): 7220–24. http://dx.doi.org/10.1021/acs.orglett.8b03147.
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Tapia-Arreola, Ana K., Daniel A. Ruiz-Garcia, Hectorina Rodulfo, Ashutosh Sharma, and Marcos De Donato. "High Frequency of Antibiotic Resistance Genes (ARGs) in the Lerma River Basin, Mexico." International Journal of Environmental Research and Public Health 19, no. 21 (October 27, 2022): 13988. http://dx.doi.org/10.3390/ijerph192113988.
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The spread of beta-lactamase-producing bacteria is of great concern and the environment has been found to be a main source of contamination. Herein, it was proposed to determine the frequency of antimicrobial-resistant-Gram-negative bacteria throughout the Lerma River basin using phenotypic and molecular methods. Resistant bacteria were isolated with chromogenic media and antimicrobial susceptibility tests were used to characterize their resistance. ARGs for beta-lactams, aminoglycosides, and quinolones were detected by PCR. Species were identified by Sanger sequencing the 16S rRNA gene and the representative genomes of MDR strains were sequenced by NGS. A high variation in the number of isolates was observed in the 20 sampled sites, while observing a low diversity among the resistant bacteria. Of the 12 identified bacterial groups, C. freundii, E. coli, and S. marcescens were more predominant. A high frequency of resistance to beta-lactams, quinolones, and aminoglycosides was evidenced, where the blaCTX,qnrB, qnrS y, and aac(6′)lb-cr genes were the most prevalent. C. freundii showed the highest frequency of MDR strains. Whole genome sequencing revealed that S. marcescens and K. pneumoniae showed a high number of shared virulence and antimicrobial resistance genes, while E. coli showed the highest number of unique genes. The contamination of the Lerma River with MDR strains carrying various ARGs should raise awareness among environmental authorities to assess the risks and regulations regarding the optimal hygienic and sanitary conditions for this important river that supports economic activities in the different communities in Mexico.
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Luisa Maria Charco Roca, José María Jiménez Vizuete, and Antonio Ayelo Navarro. "Estrategias de optimización de uso de betalactámicos." Revista Electrónica AnestesiaR 11, no. 9 (October 2, 2019): 3. http://dx.doi.org/10.30445/rear.v11i9.786.
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Se han propuesto varias estrategias de mejora con la finalidad de optimizar el uso de antibióticos en los pacientes críticos. Entre ellas destacan la de-escalada, el ciclado, el tratamiento anticipado o el uso de parámetros farmacocinéticos/farmacodinámicos para ajustar la dosificación. Las alteraciones fisiopatológicas que ocurren en el paciente crítico condicionan la farmacocinética y la farmacodinamia de los antibióticos, especialmente de los betalactámicos. Por ello, la predicción del resultado antimicrobiano basado en sus concentraciones plasmáticas, puede ser muy difícil de establecer en el lugar de acción, debido a dichas alteraciones, pudiendo tener esto consecuencias clínicamente relevantes. Se puede mejorar el perfil farmacodinámico de los betalactámicos, mediante una exposición más prolongada con dosis más frecuentes o con infusiones continuas o extendidas, especialmente para tratar bacterias multirresistentes. ABSTRACT OPTIMIZATION STRATEGIES FOR THE USE OF BETA -LACTAMS. The importance of the pathophysiological peculiarities in the critically ill patient. There are several strategies aimed at improving the use of antibiotics in critical patients. These strategies include de-escalation, cycling, early treatment or the use of pharmacokinetic / pharmacodynamic parameters to adjust the dosage. The pathophysiological changes that occur in the critical patient can condition the pharmacokinetics and pharmacodynamics paramethers of antibiotics, especially in beta-lactams. Therefore, anticipating the antimicrobial result based on their plasma concentrations in the place of action can be very difficult to establish, which, in turn, may have clinically relevant consequences. The pharmacodynamic profile of beta-lactams can be improved, through longer exposure with more frequent doses or with continuous or extended infusions, especially to treat multiresistant bacteria.
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Bjergum, Matthew W., Erin F. Barreto, Marc H. Scheetz, Andrew D. Rule, and Paul J. Jannetto. "Stability and Validation of a High-Throughput LC-MS/MS Method for the Quantification of Cefepime, Meropenem, and Piperacillin and Tazobactam in Serum." Journal of Applied Laboratory Medicine 6, no. 5 (June 4, 2021): 1202–12. http://dx.doi.org/10.1093/jalm/jfab036.
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Abstract Background The class of antibiotics known as β-lactams are a commonly used due to their effectiveness and safety. Therapeutic drug monitoring has been proposed but requires an accurate assay along with well-characterized preanalytic stability, as β-lactams are known to be relatively unstable. Methods A high-throughput LC-MS/MS assay validation and stability study was performed for cefepime, meropenem, and piperacillin and tazobactam in serum. Patient samples, standards, and QCs were crashed with acetonitrile containing internal standard. Following centrifugation, an aliquot of the supernatant was diluted with clinical laboratory reagent water and analyzed by LC-MS/MS. Results The assay showed linearity between 0.5 and 60 µg/mL for each analyte. The intra- and interassay reproducibility at 3 different concentrations (approximately 2, 25, and 40 µg/mL) was <5% for each analyte. Accuracy studies for each analyte were compared using linear regression and demonstrated: slope = 1.0 ± 0.1; r2 ≥ 0.980; and y intercept 95% CI that included zero. Minimal ion suppression or enhancement was observed, and no significant carryover was observed up to 500 µg/mL of each analyte. Stability studies demonstrated significant loss in serum for each analyte at ambient and refrigerated temperatures (2–8 °C) and at −20 °C over days or weeks. In contrast, when stored at −80 °C, no significant loss was observed. Conclusions The LC-MS/MS assay showed acceptable performance characteristics for quantitation of β-lactams. With well-characterized stability, this assay can be used with residual specimens for pharmacokinetic modeling, which may lead to individualized dosing and improved patient care.
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Skagseth, Susann, Trine Josefine Carlsen, Gro Elin Kjæreng Bjerga, James Spencer, Ørjan Samuelsen, and Hanna-Kirsti S. Leiros. "Role of Residues W228 and Y233 in the Structure and Activity of Metallo-β-Lactamase GIM-1." Antimicrobial Agents and Chemotherapy 60, no. 2 (December 7, 2015): 990–1002. http://dx.doi.org/10.1128/aac.02017-15.
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ABSTRACTMetallo-β-lactamases (MBLs) hydrolyze virtually all β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. The worldwide emergence of antibiotic-resistant bacteria harboring MBLs poses an increasing clinical threat. The MBL German imipenemase-1 (GIM-1) possesses an active site that is narrower and more hydrophobic than the active sites of other MBLs. The GIM-1 active-site groove is shaped by the presence of the aromatic side chains of tryptophan at residue 228 and tyrosine at residue 233, positions where other MBLs harbor hydrophilic residues. To investigate the importance of these two residues, eight site-directed mutants of GIM-1, W228R/A/Y/S and Y233N/A/I/S, were generated and characterized using enzyme kinetics, thermostability assays, and determination of the MICs of representative β-lactams. The structures of selected mutants were obtained by X-ray crystallography, and their interactions with β-lactam substrates were modeledin silico. Steady-state kinetics revealed that both positions are important to GIM-1 activity but that the effects of individual mutations vary depending on the β-lactam substrate. Activity against type 1 substrates bearing electron-donating C-3/C-4 substituents (cefoxitin, meropenem) could be enhanced by mutations at position 228, whereas hydrolysis of type 2 substrates (benzylpenicillin, ampicillin, ceftazidime, imipenem) with methyl or positively charged substituents was favored by mutations at position 233. The crystal structures showed that mutations at position 228 or the Y233A variant alters the conformation of GIM-1 loop L1 rather than that of loop L3, on which the mutations are located. Taken together, these data show that point mutations at both positions 228 and 233 can influence the catalytic properties and the structure of GIM-1.
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Fernández Balaguer, Gonzalo, Carmen del Águila, Carolina Hurtado Marcos, and Rubén Agudo Torres. "ANCESTRAL RECONSTRUCTION OF A β-LACTAMASE AND COMPARISON WITH ITS EXTANT PROTEINS." Anales de la Real Academia Nacional de Farmacia, no. 87(02) (2021): 155–70. http://dx.doi.org/10.53519/analesranf.2021.87.02.05.
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The β-lactamases are proteins of bacterial origin that are characterized by hydrolyzing antibiotics β-lactams, conferring microbial resistance against them. They are a heterogeneous family of proteins very relevant from a health point of view due to the ease they present to acquire resistance to new drugs due to their high capacity for evolution. The in vitro evolution of these proteins has served not only to develop their characterization and improve their knowledge, but as a new line of research that allows to predictively identify residues involved in the acquisition of antibiotic resistance. At the same time, the method of ancestral protein reconstruction has been revealed as a novel and useful tool to understand the evolution of β-lactamases and understand some of their characteristics such as their promiscuity. In this work, a study of ancestral β-lactamases reconstructed from the phylogeny of existing class A β-lactamases has been carried out. Of the four ancestral proteins studied, one has been obtained that is functional and has compared its hydrolytic activity with that of four of its current counterparts against eight β-lactam drugs. This ancestral protein has been shown to have a more generalistic antibiotic activity than any of the current proteins studied. In addition, the active ancestral protein showed more resistance to one of the drugs used than the rest of β-lactamases existing. Finally these results have been discussed and from them it is argued why reconstructed ancestral sequences can be a very attractive starting point when it comes to direct evolution of proteins for obtaining proteins of biotechnological interest.
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Ito, H., Y. Arakawa, S. Ohsuka, R. Wacharotayankun, N. Kato, and M. Ohta. "Plasmid-mediated dissemination of the metallo-beta-lactamase gene blaIMP among clinically isolated strains of Serratia marcescens." Antimicrobial Agents and Chemotherapy 39, no. 4 (April 1995): 824–29. http://dx.doi.org/10.1128/aac.39.4.824.
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The distribution of strains producing metallo-beta-lactamase among 105 strains of Serratia marcescens was investigated. All of these strains were isolated in seven general hospitals located in Aichi Prefecture, Japan, from April to May 1993. Southern hybridization analysis suggested that four S. marcescens strains, AK9373, AK9374, AK9385, and AK9391, had a metallo-beta-lactamase genes similar to the blaIMP gene found by our laboratory (E. Osano, Y. Arakawa, R. Wacharotayankun, M. Ohta, T. Horii, H. Ito, F. Yoshimura, and N. Kato, Antimicrob. Agents Chemother. 38:71-78, 1994), and these four strains showed resistance to carbapenems as well as to the other broad-spectrum beta-lactams. In particular, strains AK9373, AK9374, and AK9391 showed an extraordinarily high-level resistance to imipenem (MICs, > or = 64 micrograms/ml), whereas strain AK9385 demonstrated moderate imipenem resistance (MIC, 8 micrograms/ml). The imipenem resistance of AK9373 was transferred to Escherichia coli CSH2 by conjugation with a frequency of 10(-5). The DNA probe of the blaIMP gene hybridized to a large plasmid (approximately 120 kb) transferred into the E. coli transconjugant as well as to the large plasmids harbored by AK9373. On the other hand, although we failed in the conjugational transfer of imipenem resistance from strains AK9374, AK9385, and AK9391 to E. coli CSH2, imipenem resistance was transferred from these strains to E. coli HB101 by transformation. A plasmid (approximately 25 kb) was observed in each transformant which acquired imipenem resistance. The amino acid sequence at the N terminus of the enzyme purified from strain AK9373 was identical to that of the metallo-beta-lactamase IMP-1. In contrast, strains ES9348, AK9386, and AK93101, which were moderately resistant to imipenem (MICs, > or = 4 to < or = 8 micrograms/ml), had no detectable blaIMP gene. As a conclusion, 19% of clinically isolated S. marcescens strains in Aichi Prefecture, Japan, in 1993 were resistant to imipenem (MICs, > or = 2 micrograms/ml), and strains which showed high-level imipenem resistance because of acquisition of a plasmid-mediated blaIMP-like metallo-beta-lactamase gene had already proliferated as nosocomial infections, at least in a general hospital.
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Sebbane, Florent, and Nadine Lemaître. "Antibiotic Therapy of Plague: A Review." Biomolecules 11, no. 5 (May 12, 2021): 724. http://dx.doi.org/10.3390/biom11050724.
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Plague—a deadly disease caused by the bacterium Yersinia pestis—is still an international public health concern. There are three main clinical forms: bubonic plague, septicemic plague, and pulmonary plague. In all three forms, the symptoms appear suddenly and progress very rapidly. Early antibiotic therapy is essential for countering the disease. Several classes of antibiotics (e.g., tetracyclines, fluoroquinolones, aminoglycosides, sulfonamides, chloramphenicol, rifamycin, and β-lactams) are active in vitro against the majority of Y. pestis strains and have demonstrated efficacy in various animal models. However, some discrepancies have been reported. Hence, health authorities have approved and recommended several drugs for prophylactic or curative use. Only monotherapy is currently recommended; combination therapy has not shown any benefits in preclinical studies or case reports. Concerns about the emergence of multidrug-resistant strains of Y. pestis have led to the development of new classes of antibiotics and other therapeutics (e.g., LpxC inhibitors, cationic peptides, antivirulence drugs, predatory bacteria, phages, immunotherapy, host-directed therapy, and nutritional immunity). It is difficult to know which of the currently available treatments or therapeutics in development will be most effective for a given form of plague. This is due to the lack of standardization in preclinical studies, conflicting data from case reports, and the small number of clinical trials performed to date.
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Khademi, Farzad, and Amirhossein Sahebkar. "A Systematic Review and Meta-analysis on the Epidemiology of Antibiotic-resistant Yersinia Species in Food and Clinical Specimens in Iran." International Journal of Enteric Pathogens 7, no. 4 (December 21, 2019): 113–20. http://dx.doi.org/10.15171/ijep.2019.24.
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Objective: The aim of the present study was to investigate the antimicrobial susceptibility profiles of Yersinia species, especially Y. enterocolitica from non-clinical and clinical isolates in Iran. Materials and Methods: We systematically searched PubMed, Scopus, Google Scholar, and the Scientific Information Database (SID) using "antibiotic resistance", "Yersinia", and "Iran" as major keywords until June 10, 2019. According to the predefined article selection criteria, published studies addressing the epidemiology of antibiotic-resistant Yersinia species in Iran were included in the meta-analysis. Data were extracted and exported to the Comprehensive Meta-Analysis Software to evaluate antibiotic resistance rates, heterogeneity of studies and publication bias. Results: Twelve studies reported antimicrobial susceptibility testing using disk diffusion method. The pooled prevalence of antibiotic-resistant Yersinia species in food and clinical specimens in Iran was as follows: 22.4% to amoxicillin, 41.9% to ampicillin, 6% to gentamicin, 17% to trimethoprim/ sulfamethoxazole, 19% to tetracycline, 10.3% to ciprofloxacin, 10.5% to streptomycin, 3.8% to chloramphenicol, 79.3% to cephalothin, 18.4% to nalidixic acid, 6.6% to cefotaxime, and 12.2% to trimethoprim. Conclusion: This study revealed a high prevalence of resistant Y. enterocolitica strains isolated from food and clinical specimens in Iran to β-lactams, while the resistance rates to aminoglycosides, fluoroquinolone and chloramphenicol were low. Our findings recommended the necessity of a continuous surveillance of the resistance patterns and prudent use of trimethoprim/ sulfamethoxazole, tetracycline, and nalidixic acid to prevent the development of antibioticresistant Y. enterocolitica strains in Iran.
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Martínez-Martínez, Sonia, Elías-Fernando Rodríguez-Ferri, David Rodríguez-Lázaro, Marta Hernández, José-Ignacio Gómez-Campillo, María del Carmen Martínez-Nistal, María-Isabel Fernández-Natal, María-José García-Iglesias, Olga Mínguez-González, and César-Bernardo Gutiérrez-Martín. "In Vitro Antimicrobial Susceptibilities of Francisella tularensis subsp. holarctica Isolates from Tularemia Outbreaks That Occurred from the End of the 20th Century to the 2020s in Spain." Antibiotics 10, no. 8 (August 3, 2021): 938. http://dx.doi.org/10.3390/antibiotics10080938.
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A collection of 177 Francisella tularensis subsp. holarctica clinical isolates (29 from humans and 148 from animals, mainly hares and voles) was gathered from diverse tularemia outbreaks in the Castilla y León region (northwestern Spain) that occurred from the end of the 20th century to the 2020s. Along with four F. tularensis subsp. holarctica reference strains, all of these clinical isolates were tested using a broth microdilution method to determine their susceptibility to 22 antimicrobial agents, including β-lactams, aminoglycosides and one member each of the tetracycline, glycylcycline, quinolone and sulphonamide classes. Many multi-resistance profiles were found among the tested isolates, but especially among those of human origin (all but two isolates showed resistance to at least 13 of 18 antimicrobial agents). Even so, all human isolates were susceptible to gentamicin and tobramycin, while more than 96% of animal isolates were susceptible to these two aminoglycosides. Ciprofloxacin showed activity against more than 92% of animal and human isolates. However, almost 21% of human isolates were resistant to tetracycline, and more than 65% were resistant to tigecycline. Finally, a quite similar activity to other F. tularensis subsp. holarctica isolates collected 20 years earlier in Spain was observed.
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Lepak, Alexander J., Miao Zhao, Qingmei Liu, Ping Wang, Yanli Wang, Justin C. Bader, Paul G. Ambrose, and David R. Andes. "1389. Pharmacokinetic/Pharmacodynamic (PK/PD) Evaluation of a Novel Aminomethylcycline Antibiotic, KBP-7072, in the Neutropenic Murine Pneumonia Model Against S. aureus (SA) and S. pneumoniae (SPN)." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S426. http://dx.doi.org/10.1093/ofid/ofy210.1220.
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Abstract Background KBP-7072 is a novel aminomethylcycline antibiotic with broad-spectrum activity that includes organisms with drug-resistance to β-lactams and tetracyclines. We examined the PK/PD relationship between KBP-7072 drug exposures and treatment effect using a neutropenic murine pneumonia model against a diverse group of SA and SPN. Methods Five SAs (three MRSAs) and six SPNs (three PCNs NS, two TetR) strains were used. MICs were determined by CLSI Methods. Plasma and ELF PK was determined after SC dosing (range 1–256 mg/kg). Lung burden was assessed by CFU counts at the beginning and end of therapy (24 hours). Infected mice were treated with KBP-7072 by SC route: SA dose range 0.25–64 mg/kg/6 hours, SPN dose range 0.06–16 mg/kg/6 hours. The Emax Hill equation was used to model the dose–response data to the PK/PD index AUC/MIC. The magnitude of the PK/PD index (plasma free and ELF total concentrations) associated with net stasis, 1- and 2-log kill were determined in the pneumonia model for all strains. Results SA MICs were 0.25 mg/L for all isolates and SPN MICs were 0.008–0.016 mg/L. Plasma PK of KBP-7072 included: Cmax 0.12–25.2 mg/L, AUC0-∞ 1.1–234 mg hour/L, T1/2 3.2–4.6 h. ELF PK by urea correction methods included: Cmax 0.06–13.3 mg/L, AUC0-∞ 0.4–95 mg hour/L, T1/2 3.1–4 hours. ELF penetration based on free plasma drug concentrations (77.5% bound) ranged from 82 to 238%. AUC was linear over the dose range (R2 = 0.99). Potent dose-dependent cidal activity (3–5 log kill) was observed against all strains. AUC/MIC was a robust predictor of efficacy (SA R2 = 0.89, SPN R2 0.80). Median static, 1- and 2-log kill AUC/MIC values are shown in the table. Conclusion KBP-7072 demonstrated potent in vivo efficacy against SA and SPN, including strains with elevated minocycline MIC and β-lactam resistance, in the neutropenic murine pneumonia model. A 3–5 log kill was observed and AUC/MIC was strongly associated with efficacy. The AUC/MIC target for net stasis was comparable between SA and SPN at a plasma fAUC/MIC target of ~1 and ELF AUC/MIC target ~2. Cidal targets were similarly very low. All targets were numerically lower than comparative tetracyclines. These results should prove useful for clinical dosing regimen optimization. Disclosures A. J. Lepak, KBP Biosciences: Research Contractor, Research support. Q. Liu, KBP Biosciences: Employee, Salary. P. Wang, KBP Biosciences: Employee, Salary. Y. Wang, KBP Biosciences: Employee, Salary. J. C. Bader, KBP Biosciences: Research Contractor, Research support. P. G. Ambrose, KBP Biosciences: Research Contractor, Research support. D. R. Andes, KBP Biosciences: Research Contractor, Research support.
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Thonda, O. A., A. O. Oluduro, O. O. Adewole, and P. O. Obiajunwa. "Phenotypic and genotypic characterization of plasmid-mediated AmpC beta-lactamases in enteric Gram-negative bacteria from patients with lower respiratory tract infections in a tertiary hospital, southwest Nigeria." African Journal of Clinical and Experimental Microbiology 22, no. 4 (September 27, 2021): 465–72. http://dx.doi.org/10.4314/ajcem.v22i4.6.
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Background: AmpC or class C or group 1 beta lactamases are class C cephalosporinases that hydrolyse a wide variety of beta-lactam antibiotics including alpha methoxy beta-lactams (cefoxitin), narrow and broad spectrum cephalosporins. This study was conducted to characterize plasmid-mediated AmpC producing enteric Gram- negative bacteria from patients with lower respiratory tract infections in Obafemi Awolowo University Teaching Hospital Complex (OAUTHC) Ile Ife, Osun State, NigeriaMethodology: A total of 149 patients with clinical features of lower respiratory tract infections (LRTI) were selected by simple random sampling for the study. All Gram-negative isolates recovered from standard microbiological cultures of respiratory specimens of these patients were tested against cefoxitin, third generation cephalosporins (3GCs), and other antibiotics using the disc diffusion AST method, and also screened for production of AmpC beta-lactamases phenotypically by the CLSI method. Plasmid DNA extraction was carried out on twenty-nine cefoxitin-resistant selected isolates using the Kado and Lin method, while genotypic detection of plasmid-mediated AmpC gene was carried out by the polymerase chain reaction (PCR) assay.Results: The results showed that 204 (43.3%) of 471 isolates recovered from the 149 selected patients were resistant to 3GC in the AST assay, among which 121 (59.3%) were resistant to cefoxitin, and 189 of the 471 isolates (40.1%) were AmpC producers. The AmpC producers concurrently showed multiple resistance pattern to other antibiotics tested in this study. Ninety six percent of the 29 selected isolates for plasmid analysis contained plasmids, 45% of which amplified positive on PCR for CMY, 38% for FOX, and 31% for ACC types of AmpC genes.Conclusion: This study showed a high degree of antibiotic resistance among enteric Gram-negative bacteria recovered from patients with LRTIs, as well as high degree of plasmid-encoded AmpC genes responsible for this high antibiotic resistance among the isolates. Proper antibiotic policy and regulation are required to limit the spread of plasmid mediated AmpC β-lactamase producing organisms because they can lead to therapeutic failure in infected patients in the nearest future.
French title: Caractérisation phénotypique et génotypique des bêta-lactamases AmpC à médiation plasmidique dans les bactéries entériques Gram-négatives de patients atteints d'infections des voies respiratoires inférieures dans un hôpital tertiaire, sud-ouest du Nigéria
Contexte: Les bêta-lactamases AmpC ou de classe C ou de groupe 1 sont des céphalosporinases de classe C qui hydrolysent une grande variété d'antibiotiques bêta-lactamines, y compris les alpha-méthoxy bêta-lactamines (céfoxitine), les céphalosporines à spectre étroit et large. Cette étude a été menée pour caractériser les bactéries à Gram négatif entériques produisant de l'AmpC à médiation plasmidique chez des patients atteints d'infections des voies respiratoires inférieures du complexe hospitalier universitaire d'Obafemi Awolowo (OAUTHC) Ile Ife, État d'Osun, NigériaMéthodologie: Un total de 149 patients présentant des caractéristiques cliniques d'infections des voies respiratoires inférieures (LRTI) ont été sélectionnés par échantillonnage aléatoire simple pour l'étude. Tous les isolats à Gram négatif récupérés à partir de cultures microbiologique standard d'échantillons respiratoires de ces patients ont été testés contre la céfoxitine, les céphalosporines de troisième génération (3GC) et d'autres antibiotiques en utilisant la méthode AST de diffusion sur disque, et également criblés pour la production de bêtalactamases AmpC phénotypiquement par le Méthode CLSI. L'extraction de l'ADN plasmidique a été réalisée sur 29 isolats sélectionnés résistants à la céfoxitine en utilisant la méthode Kado et Lin, tandis que la détection génotypique du gène AmpC à médiation plasmidique a été réalisée par le test de réaction en chaîne par polymérase (PCR).Résultats: Les résultats ont montré que 204 (43,3%) des 471 isolats récupérés des 149 patients sélectionnés étaient résistants à la 3GC dans le test AST, parmi lesquels 121 (59,3%) étaient résistants à la céfoxitine et 189 des 471 isolats (40,1%) étaient des producteurs d'AmpC. Les producteurs d'AmpC ont montré simultanément plusieurs profils de résistance à d'autres antibiotiques testés dans cette étude. Quatre-vingt-seize pour cent des 29 isolats sélectionnés pour l'analyse des plasmides contenaient des plasmides, dont 45% amplifiés positifs par PCR pour CMY, 38% pour FOX et 31% pour les types ACC des gènes AmpC.Conclusion: Cette étude a montré un degré élevé de résistance aux antibiotiques parmi les bactéries entériques Gram-négatives récupérées chez des patients atteints de LRTI, ainsi qu'un degré élevé de gènes AmpC codés par plasmide responsable de cette résistance élevée aux antibiotiques parmi les isolats. Une politique et une réglementation appropriées en matière d'antibiotiques sont nécessaires pour limiter la propagation des organismes producteurs β-lactamase d'AmpC à médiation plasmidique car ils peuvent conduire à un échec thérapeutique chez les patients infectés dans un avenir proche.
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Ströher, Jeferson Aloísio, Raquel Carvalho Machado Kamphorst, and Rosiele Lappe Padilha. "Detecção de resíduos de antibiótico de produtores do norte do Rio Grande do Sul." Revista Eletrônica Científica da UERGS 8, no. 3 (December 23, 2022): 247–57. http://dx.doi.org/10.21674/2448-0479.83.247-257.
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A legislação brasileira estabelece para o leite cru refrigerado, segundo a Instrução Normativa nº 77 (BRASIL, 2018), que em todos os tanques isotérmicos de leite, recebidos pela indústria, devem ser realizados testes de detecção de antibióticos (resíduos de produtos de uso veterinário). Estas análises são obrigatórias e devem ser analisados pelo menos dois grupos destes resíduos em cada recebimento de leite. Um leite com a presença destes contaminantes é prejudicial à saúde humana, podendo levar à resistência bacteriana a estas substâncias. O leite cru refrigerado, coletado pela indústria nas propriedades rurais, deve ser enviado mensalmente para análises físico-químicas e microbiológicas, com periodicidade mínima de pelo menos uma amostra mensal em laboratório credenciado da Rede Brasileira de Qualidade do Leite (RBQL). Tendo em vista que, presença de antibióticos no leite é de grande preocupação sanitária, o objetivo deste trabalho foi avaliar a presença de resíduos de antibióticos dos grupos das sulfonamidas, fluoroquinolonas, beta-lactâmicos, cefalexina, tetraciclinas e quinolonas de sete transportadores de leite, totalizando 651 amostras de leite durante o mês de agosto de 2021, de uma indústria de beneficiamento de leite e derivados do norte do Rio Grande do Sul. Como resultado, foi observada a existência de um compartimento de uma rota de leite com a presença de fluoroquinolonas positiva, cujo leite foi condenado e descartado pela empresa. Palavras-chave: Resíduos de antibióticos; leite cru refrigerado; qualidade do leite; saúde pública.
AbstractDetection of antibiotic residues in refrigerated raw milk from producers in northern Rio Grande do SulBrazilian legislation establishes for raw refrigerated milk, according to Normative Instruction number 77 (BRASIL, 2018), that in all isothermal milk tanks, received by the industry, antibiotic detection tests (residues of products for veterinary use) must be performed. These analyses are mandatory and at least two groups of these residues must be analyzed in each milk receipt. Milk with the presence of these contaminants is harmful to human health, and can lead to bacterial resistance to these substances. The raw refrigerated milk, collected by the industry from rural properties, must be sent monthly for physical-chemical and microbiological analysis, with a minimum frequency of at least one monthly sample in an accredited laboratory of the Brazilian Milk Quality Network (RBQL). Considering that the presence of antibiotics in milk is a major health concern, the objective of this study was to evaluate the presence of antibiotic residues from sulfonamides, fluoroquinolones, beta-lactams, cephalexin, tetracyclines and quinolones groups in seven milk carriers, totaling 651 milk samples during the month of August 2021, from a milk processing industry in the north of Rio Grande do Sul. As a result, it was observed the existence of a compartment of a milk route with the presence of fluoroquinolones positive, whose milk was condemned and discarded by the company.Keywords: Antibiotic residues; raw chilled milk; milk quality; public health.
Resumen Detección de residuos de antibióticos en leche cruda refrigerada de productores del norte de Rio Grande do SulLa legislación brasileña establece para la leche cruda refrigerada, según la Instrucción Normativa nº 77 (BRASIL, 2018), que, en todos los tanques de leche isotérmica recibidos por la industria, se deben realizar pruebas de detección de antibióticos (residuos de productos de uso veterinario). Estos análisis son obligatorios y deben examinarse al menos dos grupos de estos residuos en cada recepción de leche. La leche que contiene estos contaminantes es perjudicial para la salud humana y puede provocar una resistencia bacteriana a estas sustancias. La leche cruda refrigerada recolectada por la industria en las propiedades rurales debe ser enviada mensualmente para análisis físico-químicos y microbiológicos, con una frecuencia mínima de una muestra mensual en un laboratorio acreditado de la Rede Brasileira de Qualidade do Leite (RBQL). Considerando que la presencia de antibióticos en la leche es de gran preocupación sanitaria, el objetivo de este trabajo fue evaluar la presencia de residuos de antibióticos de los grupos de las sulfonamidas, fluoroquinolonas, betalactámicos, cefalexina, tetraciclinas y quinolonas de siete transportadores de leche, totalizando 651 muestras durante el mes de agosto de 2021, provenientes de una industria procesadora de leche y derivados en el norte de Rio Grande do Sul. Como resultado, se observó la existencia de un compartimento de una ruta láctea con presencia de fluoroquinolonas positivas, cuya leche fue condenada y descartada por la empresa.Palabras clave: Residuos de antibióticos; leche cruda refrigerada; calidad de la leche; salud pública.
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Meyer, Kevin, Maressa Santarossa, Larry H. Danziger, and Eric Wenzler. "Compatibility of Ceftazidime-Avibactam, Ceftolozane-Tazobactam, and Piperacillin-Tazobactam with Vancomycin in Dextrose 5% in Water." Hospital Pharmacy 52, no. 3 (March 2017): 221–28. http://dx.doi.org/10.1310/hpj5203-221.
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Objectives The compatibility of vancomycin with existing and novel β-lactam/β-lactamase inhibitors at clinically relevant concentrations in 5% dextrose in water has not been fully explored to date. Methods Vancomycin concentrations tested ranged from 5 to 20 mg/mL. Ceftazidime-avibactam was tested at 8, 20, and 40 mg/mL, ceftolozane-tazobactam at 15 mg/mL, and piperacillin-tazobactam at 28 mg/mL. Compatibility of drug admixtures were tested via both simulated and actual y-site infusion. For the simulated y-site compatibility assessment, 1:1 mixtures of each respective drug were analyzed over 24 hours. Actual y-site infusion followed a 4-hour extended-infusion protocol, with aliquots tested hourly for 4 hours. At all time points, the compatibility of each admixture was determined using 6 different methods: visual, microscopic, Tyndall beam, nephelometric, pH, and microbiologic bioassay assessment. If any admixture failed any one of these 6 assays, it was considered incompatible. Any combination deemed incompatible was filtered through a 0.22 μm filter and reanalyzed to assess impact of particle size. Results There were no differences in compatibility categorizations between simulated and actual y-site infusion. There were no changes in compatibility over the time course of any experiment. Ceftazidime-avibactam at 8 mg/mL was incompatible with vancomycin at 5 mg/mL. The maximum compatible vancomycin concentrations were 5 mg/mL and 10 mg/mL with 20 and 40 mg/mL of ceftazidime-avibactam, respectively. Ceftolozane-tazobactam 15 mg/mL was compatible with vancomycin concentrations up to 10 mg/mL. The maximum compatible vancomycin concentration with piperacillin-tazobactam 28 mg/mL was 5 mg/mL. None of the β-lactam/β-lactamase inhibitors tested were compatible with 15 or 20 mg/mL of vancomycin. None of the admixtures considered incompatible by other methods displayed any decrease in antimicrobial activity as assessed by bioassay. After filtration, all admixtures originally deemed incompatible maintained their visual turbidity and microscopic particulate matter. Conclusions Ceftazidime-avibactam prepared at the lowest concentration recommended in the package insert is incompatible with vancomycin. Ceftolozane-tazobactam did not display incompatibility until vancomycin concentrations above 10 mg/mL were tested. Piperacillin-tazobac-tam at a typical extended-infusion concentration is compatible with vancomycin in D5W. To our knowledge, this is the first study to assess compatibility of antibiotic admixtures via direct measurement of antimicrobial activity. The lack of any decrement in antibacterial activity of any apparently incompatible admixture and maintenance of incompatibility after passage through a 0.22 μm filter may suggest a lack of clinically relevant adverse effects when co-administered. Future compatibility studies should incorporate appropriate methods to accurately assess both efficacy and safety of co-administered drug products.
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Berkecz, R., I. Ilisz, E. Forró, F. Fülöp, D. W. Armstrong, and A. Péter. "LC Enantioseparation of Aryl-Substituted β-Lactams Using Variable-Temperature Conditions." Chromatographia 63, S13 (January 23, 2006): S29—S35. http://dx.doi.org/10.1365/s10337-005-0700-y.
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Cinar, Seda, Canan Unaleroglu, Ayşe Ak, and Bora Garipcan. "Design, synthesis and cytotoxic evaluation of β-aryl-α-dimethoxyphosphoryl-γ-lactams." Medicinal Chemistry Research 26, no. 5 (March 3, 2017): 1022–28. http://dx.doi.org/10.1007/s00044-017-1816-y.
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Gondal, Humaira Yasmeen, and Didier Buisson. "A facile approach to α,β-unsaturated lactams by ring-closing metathesis." Chemistry of Heterocyclic Compounds 52, no. 3 (March 2016): 183–91. http://dx.doi.org/10.1007/s10593-016-1858-y.
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Seoane, Asunción, Emilia Sánchez, and Juan M. García-Lobo. "Tandem Amplification of a 28-Kilobase Region from the Yersinia enterocolitica Chromosome Containing the blaA Gene." Antimicrobial Agents and Chemotherapy 47, no. 2 (February 2003): 682–88. http://dx.doi.org/10.1128/aac.47.2.682-688.2003.
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ABSTRACT Most Yersinia enterocolitica strains are resistant to β-lactam antibiotics due to the production of one or two chromosomally encoded β-lactamases. Strain Y56 is a Y. enterocolitica O:3 serotype natural isolate that is resistant to moderate amounts of penicillins and that produces a single class A β-lactamase. To select mutants with increased levels of resistance to β-lactam antibiotics, strain Y56 was grown on plates containing increasing amounts of ampicillin, and variants resistant to up to 500 μg of ampicillin per ml were obtained. Chromosomal DNA from hyperresistant isolates was analyzed by Southern hybridization with a blaA-specific probe to detect gene rearrangements. The use of pulsed-field gel electrophoresis revealed that the increase in the resistance level correlated with the amplification in tandem of a DNA fragment of about 28 kb containing the blaA gene. The phenotype of these isolates was not stable, and they recovered the basal low resistance level when the ampicillin used for selection was withdrawn from the growth medium. This loss of resistance was followed by the recovery of the original chromosomal structure. To understand this amplification process, the 28-kb amplification unit was cloned, and the ends were sequenced. The analysis of these sequences did not reveal the presence of either repeats or transposable elements to explain this process. However, we found short sequences similar to some DNA gyrase target sequences that have been described. In addition, we observed that the frequency of appearance of ampicillin-hyperresistant isolates by amplification of the blaA locus was lowered in the presence of the gyrase inhibitor novobiocin. These findings suggest that the DNA gyrase could be involved in this amplification event.
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Armijos Nieves, Bryan, Leandro Herrera Silva, Jovanny Santos Luna, Andrés Medina Preciado, and Marisela Segura Osorio. "Resistencia de la bacteria Escherichiacoli por la beta-lactamasas.// Resistence of the bacterium Escherichia coli by beta-lactamases." Ciencia Unemi 10, no. 24 (December 15, 2017): 65. http://dx.doi.org/10.29076/issn.2528-7737vol10iss24.2017pp65-73p.
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A escala Nacional en el ámbito sanitariocomúnmentese presentan infecciones bacterianas E.colicon múltiples factores que encarecen su tratamiento, siendoel objetivoen este trabajodeterminar la influencia de la enzima beta-lactamasa en la resistencia de la bacteria E. coli frente a los antibióticos,reconociendo los antibacterianos de las familias de las penicilinas y cefalosporinas ineficientes en su tratamiento. Basándose en un estudio documental de artículos científicos sobre la temática en estudio se concluye que la presencia de la enzima beta-lactamasas influye en gran medida en laresistencia desarrollada por la bacteria E. coli hacia los antibióticos como las penicilinas y cefalosporinas de primera, segunda, tercera y cuarta generación. Además se determinó que los antibióticos derivados de la penicilina como la ampicilina y los antibióticos de la familia de las cefalosporinas: cefazolina, cefalotina, cefotaxima, cefepime y cefoptaximepor hidrolisis de estas drogas que no ejercen ningún efecto antibacteriano de la E.coli resistente,representando un gran problema que puede aumentar el riesgo de mortalidad del paciente.Recomendando que ante la sospecha de infecciónE. coli,se realice un antibiograma para detectar el tratamiento indicado.ABSTRACTE. coli bacterial infections are frequently present with multiple factors that make their treatment more expensive, in the health field at the national level. The objective of this work is to determine the influence of the beta-lactamase enzyme on E. coli resistance against antibiotics, recognizing the antibacterials from the families of penicillins and cephalosporins inefficient in their treatment. Based on a documentary study of scientific articles on the subject under study, it is conclude that the presence of the enzyme beta-lactamase greatly influences the resistance developed by the bacterium E. coli towards antibiotics such as penicillins and cephalosporins first, second, third and fourth generation. In addition, it was determined that the antibiotics derived from penicillin, such as ampicillin and antibiotics of the cephalosporin family cefazolin, cephalothin, cefotaxime, cefepime and cefoptaxime by hydrolysis of these drugs, do not exert any antibacterial effect of resistant E. coli, representing a big problem that may increase the risk of patient mortality. It is recommended that, in case of suspected E. coli infection, an antibiogram be performed to detect the indicated treatment.
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Hanessian, Stephen, Michael J. Rozema, G. Bhaskar Reddy, and John F. Braganza. "Tricyclic β-lactams: total synthesis and antibacterial activity of 5α- and 5β-methoxy-tribactams." Bioorganic & Medicinal Chemistry Letters 5, no. 21 (November 1995): 2535–40. http://dx.doi.org/10.1016/0960-894x(95)00445-y.
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Murayama, Toshiyuki, Toyohiko Kobayashi, and Takashi Miura. "A convenient preparative method for β-lactams from β-amino acids using sulfenamide/triphenylphosphine." Tetrahedron Letters 36, no. 21 (May 1995): 3703–6. http://dx.doi.org/10.1016/0040-4039(95)00658-y.
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Bylikin, S. Yu, A. G. Shipov, E. P. Kramarova, O. B. Artamkina, Vad V. Negrebetskii, and Yu I. Baukov. "Reactivity of N-(chlorodimethylgermyl)methyl and N-(chlorodimethylsilyl)methyl derivatives of lactams and amides toward Grignard reagents." Russian Journal of General Chemistry 74, no. 9 (September 2004): 1356–58. http://dx.doi.org/10.1007/s11176-005-0010-y.
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Périchon, Bruno, Sylvie Goussard, Violaine Walewski, Lenka Krizova, Gustavo Cerqueira, Cheryl Murphy, Michael Feldgarden, et al. "Identification of 50 Class D β-Lactamases and 65 Acinetobacter-Derived Cephalosporinases in Acinetobacter spp." Antimicrobial Agents and Chemotherapy 58, no. 2 (November 25, 2013): 936–49. http://dx.doi.org/10.1128/aac.01261-13.
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ABSTRACTWhole-genome sequencing of a collection of 103Acinetobacterstrains belonging to 22 validly named species and another 16 putative species allowed detection of genes for 50 new class D β-lactamases and 65 newAcinetobacter-derived cephalosporinases (ADC). All oxacillinases (OXA) contained the three typical motifs of class D β-lactamases, STFK, (F/Y)GN, and K(S/T)G. The phylogenetic tree drawn from the OXA sequences led to an increase in the number of OXA groups from 7 to 18. The topologies of the OXA and RpoB phylogenetic trees were similar, supporting the ancient acquisition ofblaOXAgenes byAcinetobacterspecies. The class D β-lactamase genes appeared to be intrinsic to several species, such asAcinetobacter baumannii,Acinetobacter pittii,Acinetobacter calcoaceticus, andAcinetobacter lwoffii. NeitherblaOXA-40/143- norblaOXA-58-like genes were detected, and their origin remains therefore unknown. The phylogenetic tree analysis based on the alignment of the sequences deduced fromblaADCrevealed five main clusters, one containing ADC belonging to species closely related toA. baumanniiand the others composed of cephalosporinases from the remaining species. No indication ofblaOXAorblaADCtransfer was observed between distantly related species, except forblaOXA-279, possibly transferred fromAcinetobactergenomic species 6 toAcinetobacter parvus. Analysis of β-lactam susceptibility of seven strains harboring new oxacillinases and cloning of the corresponding genes inEscherichia coliand in a susceptibleA. baumanniistrain indicated very weak hydrolysis of carbapenems. Overall, this study reveals a large pool of β-lactamases in differentAcinetobacterspp., potentially transferable to pathogenic strains of the genus.
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Fournier, B., P. H. Roy, P. H. Lagrange, and A. Philippon. "Chromosomal beta-lactamase genes of Klebsiella oxytoca are divided into two main groups, blaOXY-1 and blaOXY-2." Antimicrobial Agents and Chemotherapy 40, no. 2 (February 1996): 454–59. http://dx.doi.org/10.1128/aac.40.2.454.
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The chromosomally encoded beta-lactamase gene (blaOXY-2) of the wild-type Klebsiella oxytoca SL911 was cloned and sequenced. Its nucleotide sequence similarity with the previously sequenced K. oxytoca beta-lactamase gene (blaOXY-1) (Y. Arakawa, M. Ohta, N. Kido, M. Mori, H. Ito, T. Komatsu, Y. Fujii, and N. Kato, Antimicrob. Agents Chemother. 33:63-70, 1989) is 87.3%, and its amino acid similarity is 89.7%. This group of K. oxytoca beta-lactamases is related to chromosomal beta-lactamases of Citrobacter diversus, Proteus vulgaris, and Yersinia enterocolitica and to the plasmid-mediated extended-spectrum beta-lactamases MEN-1 and Toho-1. By colony hybridization with 86 strains susceptible and resistant to aztreonam, isolated in six countries, K. oxytoca beta-lactamase genes hybridized with either a specific blaOXY-1 DNA probe (668 bp) or a blaOXY-2 DNA probe (723 bp). Thus, beta-lactamase genes could be divided into two groups: blaOXY-1 (47% of the strains) and blaOXY-2 (53% of the strains). A study of isoelectric points confirmed the great variability reported in the literature. However, the two beta-lactamase groups were each represented by four different pIs: for OXY-2, 5.2, 5.7, 6.4, and 6.8, with the 5.2 form representing 59% of all OXY-2 enzymes, and for OXY-1, 7.1, 7.5, 8.2, and 8.8, with the 7.5 form representing 88% of all OXY-1 enzymes.
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Muller, Cécile, Yoann Le Breton, Thierry Morin, Abdellah Benachour, Yanick Auffray, and Alain Rincé. "The Response Regulator CroR Modulates Expression of the Secreted Stress-Induced SalB Protein in Enterococcus faecalis." Journal of Bacteriology 188, no. 7 (April 1, 2006): 2636–45. http://dx.doi.org/10.1128/jb.188.7.2636-2645.2006.
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ABSTRACT The Enterococcus faecalis two-component signal transduction system CroRS, also referred as the RR-HK05 pair, is required for intrinsic β-lactam resistance (Y. R. Comenge, R. Quintiliani, Jr., L. Li, L. Dubost, J. P. Brouard, J. E. Hugonnet, and M. Arthur, J. Bacteriol. 185:7184-7192, 2003) and is also suspected to be involved in the expression of salB (previously referred to as sagA), a gene important for resistance to environmental stress and cell morphology (Y. Le Breton, G. Boël, A. Benachour, H. Prévost, Y. Auffray, and A. Rincé, Environ. Microbiol. 5:329-337, 2003). In this report, we provide genetic and biochemical evidence that salB encodes a secreted protein that is expressed from a monocistronic stress-inducible operon. Consistent with CroR being a direct transcriptional activator of the salB expression, CroR was found to bind to the salB promoter region in electrophoretic mobility shift assays. Interestingly, we provide evidence that SalB does not play a role in the intrinsic β-lactam resistance associated with CroRS. We also show that the CroRS system is able to regulate its own expression. The sequence of the CroRS binding site in the salB and croR promoter regions was determined using DNase I footprinting assays.
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Dunne, Michael, Steven I. Aronin, Stephanie A. Halasohoris, Lisa M. Pysz, Sanae Lembirik, and James M. Meinig. "1072. In Vitro Antibacterial Susceptibility Testing of Sulopenem Against Category A and B Bio-threat Bacterial Pathogens." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S628. http://dx.doi.org/10.1093/ofid/ofab466.1266.
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Abstract Background Sulopenem is a thiopenem β-lactam antibiotic being developed for the treatment of infections caused by multi-drug resistant bacteria. Sulopenem possesses potent activity against species of the Enterobacterales that encode ESBLs or AmpC-type β-lactamases that confer resistance to third generation cephalosporins. It has also demonstrated good in vitro microbiological activity against a range of bacterial pathogens including penicillin resistant S. pneumoniae, β-lactamase-producing H. influenzae and M. catarrhalis. Sulopenem is available as intravenous and oral pro-drug formulations, and its activity aligns with the most urgent drug-resistant antimicrobial threats defined by the CDC. Methods Bacterial inoculums were prepared by suspending colonies into cation adjusted Mueller Hinton broth (CAMHB) from 18-24 h (B. anthracis, B. pseudomallei and B. mallei plates incubated at 35ºC); or 36-48 h (F. tularensis and Y. pestis plates incubated at 35ºC and 28ºC, respectively). Sheep blood agar plates were used for B. anthracis and Y. pestis. Chocolate agar plates were used for F. tularensis, B. pseudomallei and B. mallei. Suspended cultures were diluted with CAMHB to achieve a turbidity equivalent to a 0.5 McFarland standard. MICs were determined by the microdilution method in 96-well microplates according to CLSI guidelines (Clinical and Laboratory Standards Institute, 2020). Antibiotic ranges used for sulopenem were 0.03 - 64 μg/mL and 0.004 - 8 μg/mL for the diversity strains of B. anthracis, F. tularensis, Y. pesis, B. mallei, and B. pseudomallei, based on a final well volume of 100 μl after inoculation. Results A summary of sulopenem MIC90 results versus bio-threat bacterial pathogens in presented in the table. Criteria for down selection into mice was met for all pathogens except F. tularensis. Sulopenem MIC90 Summary for Down Selection Criteria Conclusion Sulopenem is active in vitro against a number of bio-threat pathogens at concentrations likely to be achieved after oral dosing in humans and meets criteria to be tested in the murine model of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei. Disclosures Michael Dunne, MD, Iterum Therapeutics (Board Member, Consultant, Shareholder) Steven I. Aronin, MD, Iterum Therapeutics (Employee, Shareholder)
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Chen, Melanie, Valerie Buurma, Monica Shah, and Germin Fahim. "Evaluation of studies on extended versus standard infusion of beta-lactam antibiotics." American Journal of Health-System Pharmacy 76, no. 18 (September 3, 2019): 1383–94. http://dx.doi.org/10.1093/ajhp/zxz154.
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AbstractPurposeTo summarize the current literature on the use and clinical efficacy of extended-infusion (EI) beta-lactam antibiotics, including piperacillin–tazobactam, meropenem, and cefepime.SummaryGram-negative infections are a serious concern among hospitalized patients and require innovative pharmacokinetic dosing strategies to achieve clinical success, especially as the emergence of resistant gram-negative pathogens has outpaced the development of new antibiotics. Beta-lactam antibiotics exhibit time-dependent activity, which means that optimal efficacy is achieved when free drug concentrations stay above the minimum inhibitory concentration for an extended duration of the recommended dosage interval. EI piperacillin–tazobactam therapy has demonstrated improved clinical outcomes and decrease mortality in critically ill patients with gram-negative infections, particularly Pseudomonas aeruginosa infections. EI meropenem has shown higher therapeutic success rates for patients with febrile neutropenia and shorter intensive care unit (ICU) length of stay (LOS) with a reduction in ventilator days in patients with multidrug-resistant ventilator-associated pneumonia. However, a larger study showed no difference in clinical outcomes between standard-infusion and EI meropenem. EI cefepime has been associated with decreased mortality and shorter ICU LOS in patients with Pseudomonas aeruginosa infections. Common challenges associated with EI beta-lactam antibiotics include Y-site incompatibilities, lack of intravenous access, and tubing residuals. It is important to note that factors such as diverse patient populations and study methodology, along with various antibiotic dose regimens, may have contributed to conflicting data on EI beta-lactam therapy.ConclusionBased on most published literature, there appears to be a favorable trend toward use of EI beta-lactam therapy in clinical practice, particularly in critically ill patients with gram-negative infections.
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Del Pozo, Liliana, Nazario Silva, Augusto Valencia, Javier Soto, Juan C. Riveros, Rosa Sacsaquispe, Róger Calderón, and Víctor Suarez. "Estudio de un brote intrahospitalario por Salmonella typhimurium productora de beta-lactamasa de espectro extendido SHV-5." Anales de la Facultad de Medicina 67, no. 4 (March 5, 2013): 318. http://dx.doi.org/10.15381/anales.v67i4.1313.
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Antecedentes: Presencia de un brote intrahospitalario de Salmonella typhimurium productora de beta-lactamasas de espectro extendido ocurrido en el Hospital San Bartolome, entre el 17 de febrero y el 6 de marzo del año 2001. Objetivo: Identificar los mecanismos implicados en la transmisión de Salmonella typhimurium y caracterización de los genes asociados a la resistencia en beta-lactámicos. Diseño: Estudio clínico-bacteriológico retrospectivo. Lugar: Hospital Nacional Docente Madre Niño (Honadomani) San Bartolomé. Materiales biológicos: Aislamientos bacterianos provenientes de pacientes lactantes. Intervenciones: Se determinó la diversidad genética de cinco aislamientos bacterianos provenientes de pacientes lactantes hospitalizados en la Unidad pediátrica del hospital, utilizando REP-PCR y fingerprint plasmídico. Previamente, se caracterizó la resistencia antimicrobiana, determinando la presencia de beta-lactamasa de espectro extendido mediante la prueba de sinergia de doble disco; la variante fue identificada por PCR-secuenciamiento del gen blashv. Principales medidas de resultados: Presencia de genotipos, plásmidos y beta-lactamasa de Salmonella typhimurium. Resultados: Se determinó la presencia de dos genotipos en los aislamientos de Salmonella typhimurium; el caso índice (sensible) presentó un genotipo diferente al de otros aislamientos resistentes pertenecientes a pacientes hospitalizados. Se determinó la presencia en S. typhimurium de un plásmido de peso molecular elevado de tamaño distinto a los de K. pneumoniae, pero probablemente relacionado con una cepa de E. coli intrahospitalaria. Se encontró la beta-lactamasa de espectro extendido SHV- 5 en los aislamientos de S. typhimurium y E. coli. Conclusiones: El estudio sugiere que la diseminación de estas bacterias en los lactantes puede haber sido favorecida por varios factores que habrían intervenido en la transferencia de elementos genéticos responsables de la resistencia antimicrobiana.
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Xu, Jingli, Jianquan Yang, Rene Gonzalez, Darrell R. Fisher, and Yubin Miao. "Melanoma-Targeting Property of Y-90-Labeled Lactam-Cyclized α-Melanocyte-Stimulating Hormone Peptide." Cancer Biotherapy and Radiopharmaceuticals 34, no. 9 (November 1, 2019): 597–603. http://dx.doi.org/10.1089/cbr.2019.3049.
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Younis, Gamal, Mona Mady, and Amal Awad. "Yersinia enterocolitica: Prevalence, virulence, and antimicrobial resistance from retail and processed meat in Egypt." July-2019 12, no. 7 (July 2019): 1078–84. http://dx.doi.org/10.14202/vetworld.2019.1078-1084.
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Aim: The objectives of this study were to investigate the prevalence of Yersinia enterocolitica in retail chicken meat, ground and processed beef meat, determine their virulence-associated genes, antimicrobial susceptibility pattern, molecular detection of extended-spectrum β-lactamases, and their capability of biofilm formation in vitro. Materials and Methods: A total of 210 samples (120 retail chicken meat, 30 ground beef, 30 beef burger, and 30 sausage samples) were collected from different retail chicken outlets and markets located at Mansoura city between December 2016 and April 2017. Meat samples were examined bacteriologically for the existence of Y. enterocolitica; bacterial colonies that displayed positive biochemical properties were subjected to polymerase chain reaction targeting 16 rRNA gene. Y. enterocolitica isolates were tested for their susceptibility to six antimicrobial agents using disk diffusion method. Uniplex PCR was used for screening Y. enterocolitica isolates for the presence of two virulence chromosome-associated genes (ail and yst), and β-lactamases (blaTEM and blaSHV). The capability of Y. enterocolitica to form biofilms was detected by tube method. Results: Thirty Y. enterocolitica isolates (14.29%) were recovered including 19 (15.83%) isolates from chicken meat, 3 (10%) from ground beef, 5 (16.67%) from beef burger, and 3 (10%) from sausage samples. Regarding ail gene, it was detected in 6.67% (2/30), while yst gene detected in 20% (6/30) Y. enterocolitica isolates. About 80%, 70%, 63.33%, and 50% of Y. enterocolitica isolates were sensitive to ciprofloxacin, gentamicin, cefotaxime, and streptomycin, respectively, while 83.33% of Y. enterocolitica isolates were resistant to both ampicillin and cephalothin. Interestingly, 21 (70%) isolates had the capability of biofilms formation in vitro. Among the multidrug-resistant (MDR) strains, a significant difference (p<0.05) was found between MDR and biofilm formation. However, biofilm formation was correlated with the resistance of the isolates to β-lactam antimicrobials and the presence of β-lactam-resistant genes. Conclusion: The presence of Y. enterocolitica in chicken meat, ground and processed beef meat represents a significant health risk for meat consumers, which reflects the contamination of slaughterhouses and processing operations, therefore, strict hygienic measures should be applied to minimize carcasses contamination.
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Yao, Shenggen, Margaret A. Smith-White, Erica K. Potter, and Raymond S. Norton. "Stabilization of the Helical Structure of Y2-Selective Analogues of Neuropeptide Y by Lactam Bridges." Journal of Medicinal Chemistry 45, no. 11 (May 2002): 2310–18. http://dx.doi.org/10.1021/jm010543z.
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Gillies, Glenn, Daniel Dönnecke, and Wolfgang Imhof. "How to Control the Chemoselectivity of the Catalytic Formation of Chiral γ-Lactams or 2,3-Disubstituted Pyrroles by the Choice of Solvent." Monatshefte für Chemie - Chemical Monthly 138, no. 7 (May 11, 2007): 683–86. http://dx.doi.org/10.1007/s00706-007-0653-y.
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Castro Gutierrez, Lisbeth Teresa, Maria Ines Torres Caycedo, Luz M. Aribel Castañeda Orduz, Diana Paola López, and Carlos Fernando Prada Quiroga. "Caracterización fenotípica de bacilos Gram negativos con betalactamasas de espectro extendido y carbapenemasas." Revista Investigación en Salud Universidad de Boyacá 2, no. 2 (December 15, 2015): 116. http://dx.doi.org/10.24267/23897325.132.
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Introducción: La resistencia bacteriana de los bacilos Gram negativos tiene un importante impacto económico y social en salud pública. Ha incrementado la morbilidad y la mortalidad en los últimos años, conllevando incremento de costos en salud; es un hecho significativo que orienta la implementación de acciones de prevención y estudio, mediante la identificación de los perfiles regionales como estrategia de vigilancia y contención de la resistencia. Objetivo: Caracterizar fenotípicamente la resistencia en cepas de bacilos Gram negativos aislados de infecciones, en un centro hospitalario de segundo nivel en el departamento de Boyacá, Colombia. Métodos: Se hizo un estudio descriptivo de corte transversal. La identificación bacteriana y las pruebas de sensibilidad se determinaron mediante el método automatizado VITEK®. Los fenotipos de resistencia a β-lactamasas de espectro extendido y carbapenemasas, se confirmaron siguiendo la metodología del Clinical and Laboratory Standards Institute (CLSI). Resultados: Se procesaron 458 cultivos durante cuatro meses, de los cuales 298 fueron negativos y 160 mostraron aislamientos bacterianos positivos; 127 eran procedentes de urocultivo. El patógeno prevalente fue Escherichia coli. De las cepas de estudio, se confirmó el fenotipo β-lactamasa en 11 aislamientos y uno para el fenotipo β-lactamasa/carbapenemasa. Conclusiones: Los hallazgos del presente estudio evidencian que E. coli es el microorganismo predominante a partir de los aislamientos que presentan un fenotipo multirresistente. La identificación de este tipo de cepas bacterianas, que son una amenaza en el ambiente hospitalario y el comunitario, amerita un cambio en las estrategias de contención de la multirresistencia; igualmente, los resultados identifican el panorama epidemiológico regional. Palabras clave: farmacorresistencia bacteriana, infecciones bacterianas, betalactamasas, salud pública.
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Vallejo Agudelo, Marta Elena, Diana Paola Cuesta Castro, Andrés Eduardo Marín Castro, Natalia Castaño Villegas, Andrés Acevedo, and Luz Elena Flórez. "Descripción del uso de ertapenem en un hospital público de alta complejidad en Medellín, Colombia." Archivos de Medicina (Manizales) 18, no. 2 (November 19, 2018): 394–403. http://dx.doi.org/10.30554/archmed.18.2.2655.2018.
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Objetivo: Describir el uso de ertapenem y las características clínico-microbiológicas de los pacientes durante la admisión en centro de cuarto nivel de complejidad en Medellín, Colombia entre 2009 y 2012. Materiales y métodos: estudio descriptivo retrospectivo en pacientes que recibieron ertapenem como terapia antibiótica. Resultados: 1390 historias clínicas revisadas, 835 cumplieron criterios de selección. Ertapenem se usó un 36,9% para manejo de infecciones urinarias y 28,1% en infección intraabdominal principalmente; En 84% se realizó cultivo microbiológico y en 80% se aisló algún germen, entre ellos 42,5% E. coli, 24,3% K. pneumoniae y 5,8% P. mirabilis. Las cepas Beta Lactamasa de Espectro Extendido de E. coli y K. pneumoniae fueron 39,8% y 57% respectivamente. La susceptibilidad a ertapenem en E. coli fue de 96,6% y K. pneumoniae 94,4%. Conclusiones: Ertapenem ofrece resultados clínicos favorables en el manejo de infecciones urinarias e intraabdominales. Es una alternativa para el manejo empírico de infecciones de origen comunitario y como terapia dirigida en infecciones hospitalarias.
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Bou, Germán, Antonio Oliver, Mar Ojeda, Carmelo Monzón, and Jesús Martínez-Beltrán. "Molecular Characterization of FOX-4, a New AmpC-Type Plasmid-Mediated β-Lactamase from an Escherichia coli Strain Isolated in Spain." Antimicrobial Agents and Chemotherapy 44, no. 9 (September 1, 2000): 2549–53. http://dx.doi.org/10.1128/aac.44.9.2549-2553.2000.
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ABSTRACT A clinical strain of Escherichia coli (Ec GCE) displayed resistance to cefoxitin, cefotetan, cefotaxime, and ceftazidime. Susceptibility was not restored by the addition of clavulanic acid. Two β-lactamases with apparent pIs of 5.4 and 6.4 were identified; the β-lactamase with a pI of 6.4 was transferred by conjugation and associated with a 40-kb plasmid. Analysis of the nucleotide sequence showed a new ampC β-lactamase gene that is closely related to those encoding the FOX-3, FOX-2, and FOX-1 β-lactamases but whose product has four novel amino acid mutations, at positions 11 (M→T), 43 (A→E), 233 (V→A), and 280 (Y→H). This first cephamycinase from Spain was named FOX-4.
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Trần, Thị Bảo An, Kim Khánh Lê, Thanh Truyền Nguyễn, and Huỳnh Như Mai. "NGHIÊN CỨU TÌNH HÌNH SỬ DỤNG KHÁNG SINH NHÓM BETA – LACTAM TRONG ĐIỀU TRỊ BỆNH GIÃN PHẾ QUẢN TẠI BỆNH VIỆN LAO VÀ BỆNH PHỔI VĨNH LONG NĂM 2019 – 2020." Tạp chí Y Dược học Cần Thơ, no. 52 (October 18, 2022): 99–106. http://dx.doi.org/10.58490/ctump.2022i52.283.
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Đặt vấn đề: Giãn phế quản (GPQ) là bệnh lý mạn tính, phổ biến, tỷ lệ mắc ngày càng tăng, dẫn đến nhiều biến chứng và nguy cơ tử vong cao. Theo nghiên cứu của Nguyễn Văn Kính (2013) cho thấy chi phí sử dụng kháng sinh chiếm 36% chi phí điều trị trung bình tại bệnh viện, chủ yếu nhóm beta – lactam. Hiện nay, việc sử dụng kháng sinh (KS) không hợp lý là nguyên nhân gia tăng đề kháng KS và tăng đáng kể chi phí khám chữa bệnh. Mục tiêu nghiên cứu: Nghiên cứu đặc điểm sử dụng và đánh giá sử dụng hợp lý kháng sinh nhóm β – lactam trong điều trị bệnh GPQ tại Bệnh viện Lao và Bệnh phổi Vĩnh Long năm 2019 – 2020. Đối tượng và phương pháp nghiên cứu: Nghiên cứu mô tả cắt ngang trên 385 bệnh nhân GPQ có chỉ định sử dụng kháng sinh nhóm β – lactam điều trị tại Bệnh viện Lao và Bệnh phổi Vĩnh Long từ 1/1/2019 - 31/12/2020. Kết quả: Tỷ lệ chỉ định dùng nhóm penicillin cao nhất là 52,2%, (ampicilin/sulbactam 51,6%), nhóm cephem 42,3% (ceftazidim 50,5%), nhóm carbapenem có tỷ lệ dùng thấp nhất 5,5% (imipenem/cilastatin 95,2%). Tỷ lệ sử dụng phù hợp về liều dùng, khoảng cách, thời gian dùng kháng sinh chiếm tỷ lệ là 77,1%, 60,3%, 21,8%. Kết luận: Để đem lại hiệu quả điều trị cao và giảm đề kháng kháng sinh, cần đặc biệt chú ý tuân thủ hướng dẫn của Bộ Y tế về thời gian sử dụng kháng sinh.
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Contreras, Valeria, Sebastián Sepúlveda, and Ana Heredia. "Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?" Medwave 16, no. 01 (February 2, 2016): e6379-e6379. http://dx.doi.org/10.5867/medwave.2016.6379.
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Saris, Nina, Heidi Holkeri, Rachel A. Craven, Colin J. Stirling, and Marja Makarow. "The Hsp70 Homologue Lhs1p Is Involved in a Novel Function of the Yeast Endoplasmic Reticulum, Refolding and Stabilization of Heat-denatured Protein Aggregates." Journal of Cell Biology 137, no. 4 (May 19, 1997): 813–24. http://dx.doi.org/10.1083/jcb.137.4.813.
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Heat stress is an obvious hazard, and mechanisms to recover from thermal damage, largely unknown as of yet, have evolved in all organisms. We have recently shown that a marker protein in the ER of Saccharomyces cerevisiae, denatured by exposure of cells to 50°C after preconditioning at 37°C, was reactivated by an ATP-dependent machinery, when the cells were returned to physiological temperature 24°C. Here we show that refolding of the marker enzyme Hsp150Δ–β-lactamase, inactivated and aggregated by the 50°C treatment, required a novel ER-located homologue of the Hsp70 family, Lhs1p. In the absence of Lhs1p, Hsp150Δ–β-lactamase failed to be solubilized and reactivated and was slowly degraded. Coimmunoprecipitation experiments suggested that Lhs1p was somehow associated with heat-denatured Hsp150Δ– β-lactamase, whereas no association with native marker protein molecules could be detected. Similar findings were obtained for a natural glycoprotein of S. cerevisiae, pro-carboxypeptidase Y (pro-CPY). Lhs1p had no significant role in folding or secretion of newly synthesized Hsp150Δ–β-lactamase or pro-CPY, suggesting that the machinery repairing heat-damaged proteins may have specific features as compared to chaperones assisting de novo folding. After preconditioning and 50°C treatment, cells lacking Lhs1p remained capable of protein synthesis and secretion for several hours at 24°C, but only 10% were able to form colonies, as compared to wild-type cells. We suggest that Lhs1p is involved in a novel function operating in the yeast ER, refolding and stabilization against proteolysis of heatdenatured protein. Lhs1p may be part of a fundamental heat-resistant survival machinery needed for recovery of yeast cells from severe heat stress.
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McNamara, Lucy A., Caelin Potts, Amy E. Blain, Adam C. Retchless, Natashia Reese, Stephanie Swint, David Lonsway, et al. "Detection of Ciprofloxacin-Resistant, β-Lactamase–Producing Neisseria meningitidis Serogroup Y Isolates — United States, 2019–2020." MMWR. Morbidity and Mortality Weekly Report 69, no. 24 (June 19, 2020): 735–39. http://dx.doi.org/10.15585/mmwr.mm6924a2.
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Jeong, Young Sook, Je Chul Lee, Hee Young Kang, Hak Sun Yu, Eun Young Lee, Chul Hee Choi, Seong Ho Tae, Yoo Chul Lee, Dong Taek Cho, and Sung Yong Seol. "Epidemiology of Nalidixic Acid Resistance and TEM-1- and TEM-52-Mediated Ampicillin Resistance of Shigella sonnei Isolates Obtained in Korea between 1980 and 2000." Antimicrobial Agents and Chemotherapy 47, no. 12 (December 2003): 3719–23. http://dx.doi.org/10.1128/aac.47.12.3719-3723.2003.
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ABSTRACT The resistance to ampicillin and nalidixic acid in Shigella sonnei isolates obtained in Korea during the period 1998 to 2000 was characterized. Recently (J. Y. Oh, H. S. Yu, S. K. Kim, S. Y. Seol, D. T. Cho, and J. C. Lee, J. Clin. Microbiol. 41:421-423, 2003) ampicillin and nalidixic acid resistance was found in 49 and 70%, respectively, of the 67 S. sonnei isolates obtained during this period. We analyzed 138 S. sonnei isolates collected during the same period. Ampicillin and nalidixic acid resistance was found in 30 and 86% of the isolates, respectively. The ampicillin resistance was mediated by a TEM-1β -lactamase, and TEM-52 extended-spectrum β-lactamase was identified in one sporadic S. sonnei isolate from 1999. bla TEM-1 and bla TEM-52 were located in conjugative R-plasmids. Tn3 was detected in 41% of the ampicillin-resistant isolates. The R-plasmids from the transconjugants that transferred resistance to ampicillin exhibited different restriction fragment length polymorphism patterns, and a bla TEM-1 probe was hybridized with the different fragments. The nalidixic acid resistance was exclusively associated with an amino acid substitution, Ser83→Leu (TCG→TTG), in gyrA. These findings indicate that the genetically related S. sonnei strains readily acquire resistance to ampicillin, streptomycin, trimethoprim, and sulfamethoxazole but not nalidixic acid through conjugative R-plasmids from difference sources when confronted by antibiotic selective pressures.
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Ríos Deidán, Carlos, Luis Pacheco-Ojeda, Mercedes Narváez Black, and Karla Quisiguiña Sánchez. "Angina de Ludwig. Experiencia en 29 pacientes Ludwig’s angina." ACTA DE OTORRINOLARINGOLOGÍA & CIRUGÍA DE CABEZA Y CUELLO 41, no. 1 (August 31, 2018): 19–24. http://dx.doi.org/10.37076/acorl.v41i1.162.
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Introducción: La angina de Ludwig es una celulitis severa del cuello, con afectación rápida del espacio submandibular. Tiene suma importancia por el potencial riesgo de muerte. Objetivo: del presente estudio fue conocer las características clínicas y terapéuticas de esta patología.Diseño: estudio analítico, retrospectivo Materiales y métodos: se incluyeron 29 pacientes atendidos en el Hospital Carlos Andrade Marín, de Quito, Ecuador, entre enero del 2005 y enero del 2013. Se analizarondatos demográficos, clínicos, bacteriológicos, de manejo de la vía aérea, de abordaje quirúrgico y de morbi-mortalidad. Resultados: El sexo masculino fue predominante. En el 79% el foco etiológico fue odontogénico. La tomografía axial computarizada (TAC) se realizó en el 85% de los casos, y mostró áreas abscedadas en un 68%. Se practicó cervicotomía en 24 pacientes, en 12 de los cuales fue unilateral, sin que se aumentara la morbilidad, y se disminuyó la estancia hospitalaria. La bacteria aislada más frecuente fue el estreptococo milleri, y en el 58% se encontró gas en la cavidad quirúrgica. En el 24% de los casos se efectuó traqueotomía. El antibiótico más usado fue un betalactámico +inhibidor de β-lactamasa. La estancia hospitalaria media fue de diez días. Un 66% de pacientes presentaron complicaciones, pero no mortalidad.Conclusión: La antibioticoterapia de amplio espectro y la descompresión quirúrgica fueron eficaces en el manejo de la angina de Ludwig de nuestros pacientes.
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Lugo Saldaña, Rodolfo, and Enedina Escamilla Ramírez. "Prevalencia del síndrome de apnea obstructiva del sueño en adultos que acuden a la consulta externa de medicina familiar, en Monterrey, México (El saos sigue siendo una entidad subdiagnosticada en latinoamérica)." ACTA DE OTORRINOLARINGOLOGÍA & CIRUGÍA DE CABEZA Y CUELLO 41, no. 1 (August 31, 2018): 25–31. http://dx.doi.org/10.37076/acorl.v41i1.163.
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Introducción: La angina de Ludwig es una celulitis severa del cuello, con afectación rápida del espacio submandibular. Tiene suma importancia por el potencial riesgo de muerte. Objetivo: del presente estudio fue conocer las características clínicas y terapéuticas de esta patología. Diseño: estudio analítico, retrospectivo Materiales y métodos: se incluyeron 29 pacientes atendidos en el Hospital Carlos Andrade Marín, de Quito, Ecuador, entre enero del 2005 y enero del 2013. Se analizaron datos demográficos, clínicos, bacteriológicos, de manejo de la vía aérea, de abordaje quirúrgico y de morbi-mortalidad. Resultados: El sexo masculino fue predominante. En el 79% el foco etiológico fue odontogénico. La tomografía axial computarizada (TAC) se realizó en el 85% de los casos, y mostró áreas abscedadas en un 68%. Se practicó cervicotomía en 24 pacientes, en 12 de los cuales fue unilateral, sin que se aumentara la morbilidad, y se disminuyó la estancia hospitalaria. La bacteria aislada más frecuente fue el estreptococo milleri, y en el 58% se encontró gas en la cavidad quirúrgica. En el 24% de los casos se efectuó traqueotomía. El antibiótico más usado fue un betalactámico + inhibidor de β-lactamasa. La estancia hospitalaria media fue de diez días. Un 66% de pacientes presentaron complicaciones, pero no mortalidad. Conclusión: La antibioticoterapia de amplio espectro y la descompresión quirúrgica fueron eficaces en el manejo de la angina de Ludwig de nuestros pacientes
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Lin, Lynn-Yao, McClain Vail, Dmitri Debabov, and Ian Critchley. "Comparative in vitro Activities of Ceftazidime–Avibactam and Ceftolozane-tazobactam Against Characterized β-Lactamase-producing Pseudomonas aeruginosa." Open Forum Infectious Diseases 4, suppl_1 (2017): S367. http://dx.doi.org/10.1093/ofid/ofx163.897.
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Abstract Background Ceftazidime-avibactam (CAZ-AVI) and ceftolozane-tazobactam (TOL-TAZ) are cephalosporin/β-lactamase inhibitor combinations recently approved for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). Both agents are reported to have antibacterial activity against P. aeruginosa including multi-drug-resistant strains, but few studies have directly compared the activities of both agents against the same strains in a single study. This study evaluated the activities of both agents against characterized β-lactamase-producing P. aeruginosa using broth microdilution (BMD) and disk diffusion (DD) methods. Methods A total of 98 clinical isolates of P. aeruginosa, including characterized β-lactamase-producing strains were tested for susceptibility to CAZ-AVI and TOL-TAZ using BMD and DD and results were interpreted using FDA/CLSI breakpoints. The isolates tested included CTX-M (ESBL), AmpC, KPC, OXA and metallo-β-lactamase (MBL) producing organisms. The results from both BMD and DD were analyzed to assess the correlation between the testing methods and ability to differentiate isolates susceptible and resistant to both agents. Results CAZ-AVI and TOL-TAZ exhibited similar MIC values against all isolates with MIC50/90 values of 2 and 16 µg/mL, respectively. When results were interpreted using FDA/CLSI breakpoints, the susceptibility rates for CAZ-AVI and TOL-TAZ were 82.7% and 62.2%, respectively. Isolates resistant to CAZ-AVI were predominantly MBL-producers whereas isolates resistant to TOL-TAZ included both MBL and KPC-producing P. aeruginosa. Both agents were active against AmpC-producing P. aeruginosa and both agents showed good correlation between BMD and DD methods. Conclusion CAZ-AVI and TOL-TAZ were active against β-lactamase-producing subsets of P. aeruginosa isolates in this challenge set. Both AmpC and KPC-producing P. aeruginosa were susceptible to CAZ-AVI whereas TOL-TAZ activity was limited to AmpC-producing organisms. Neither agent was active against MBL-producing organisms. Disclosures L. Y. Lin, Allergan plc: Employee, Salary; M. Vail, Allergan plc: Employee and Intern during study conduct and analysis, Educational support; D. Debabov, Allergan plc: Employee, Salary; I. Critchley, Allergan plc: Employee, Salary
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Oliver, Antonio, Teresa M. Coque, Diana Alonso, Aránzazu Valverde, Fernando Baquero, and Rafael Cantón. "CTX-M-10 Linked to a Phage-Related Element Is Widely Disseminated among Enterobacteriaceae in a Spanish Hospital." Antimicrobial Agents and Chemotherapy 49, no. 4 (April 2005): 1567–71. http://dx.doi.org/10.1128/aac.49.4.1567-1571.2005.
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ABSTRACT CTX-M-10 has been widely disseminated among multiple clones of several species of Enterobacteriaceae, harboring seemingly different plasmids, for over a decade in Ramón y Cajal University Hospital, Madrid, Spain. Cloning and sequencing of a 12.2-kb DNA fragment from plasmid pRYCE21 from Klebsiella pneumoniae strain KP4aC revealed a novel phage-related element immediately upstream of bla CTX-M-10 conserved among different CTX-M-10-producing strains. This is the first report showing an extended-spectrum-β-lactamase gene linked to a phage-related element.
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Santi, M. N., E. Lorenzón, F. Costabel, and G. G. Tonarelli. "Ciclación de Péptidos Sintéticos a Través de la Formación de Lactamas y Puentes Disulfuro. Aplicación a Diferentes Modelos de Interés Biológico." FABICIB 12 (December 13, 2008): 33–45. http://dx.doi.org/10.14409/fabicib.v12i1.816.
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Dahyot, Sandrine, and Hedi Mammeri. "Hydrolysis Spectrum Extension of CMY-2-Like β-Lactamases Resulting from Structural Alteration in the Y-X-N Loop." Antimicrobial Agents and Chemotherapy 56, no. 3 (January 9, 2012): 1151–56. http://dx.doi.org/10.1128/aac.05630-11.
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ABSTRACTTheCitrobacter freundiiisolate CHA, which was responsible for postoperative peritonitis after 10 days of cefepime therapy, displayed a phenotype of resistance consistent with extended-spectrum AmpC (ESAC) β-lactamase. The chromosome-borneblaAmpC-CHAgene was amplified and sequenced, revealing five amino acid substitutions, I125V, R148H, Q196H, V305A, and V348A, in the product compared to the sequence of native AmpC. A cloning experiment yielded theEscherichia coliTOP10(pAmpC-CHA) strain, which was resistant to all extended-spectrum cephalosporins (ESCs), including cefepime. To ascertain whether the R148H substitution accounted for the hydrolysis spectrum extension, it was reverted by site-directed mutagenesis. The resultingE. coliTOP10(pAmpC-CHA-H148R) strain was fully susceptible to cefepime, thus confirming that the Arg-148 replacement was mandatory for substrate profile enlargement. To further characterize the phenotypical and biochemical effects induced by the R148H change, it was introduced by site-directed mutagenesis into the CMY-2 β-lactamase, which is structurally related to the chromosome-borne cephalosporinase ofC. freundii. The CMY-2-R148H variant conferred increased MICs of ESCs, whereas those of carbapenems were unchanged even in a porin-deficientE. colistrain. Moreover, it exhibited increased catalytic efficiency (kcat/Km) toward ceftazidime (100-fold) due to an enhanced hydrolysis rate (kcat), whereas the enzymatic parameters toward imipenem were unchanged. The structural analysis of the AmpC variant showed that the R148H replacement occurred in the loop containing the Y-X-N motif, which is the counterpart of the SDN loop in class A β-lactamases. This study shows that the Y-X-N loop is a novel hot spot for mutations accounting for hydrolysis spectrum extension in CMY-2-type enzymes.
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Rivera-Jacinto, Marco, Claudia Rodríguez-Ulloa, and Gladys Huayán-Dávila. "Frecuencia de aislamientos ambientales de Staphylococcus aureus y su actividad beta-lactamasa en un hospital de Cajamarca, Perú." Infectio 13, no. 3 (September 2009): 192–95. http://dx.doi.org/10.1016/s0123-9392(09)70149-3.
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Guevara Duncan, José, Jorge Navach, Rosaluz Aróstegui, Winni Agurto, Alfredo Goytendía, Mario Chong, Hernán Sánchez, et al. "Moraxella Catarrhalis en las Infecciones Respiratorias Altas." Anales de la Facultad de Medicina 58, no. 3 (April 7, 2014): 192. http://dx.doi.org/10.15381/anales.v58i3.4680.
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Durante 12 meses se estudian las infecciones otorrinolaringológicas en dos hospitales de Lima, tanto en niños como en adultos, con especial énfasis en Moraxella catarrhalis. Se tomaron 318 muestras de igual número de pacientes, de los cuales el 40% resultó negativo a bacterias patógenas. Del 60% restante se identificó staphylococcus aureus como el causante del 31% de las infecciones, seguido de Streptococcus pneumoniae colt el 19%, hieto Moraxella catarrhalis colt 16% y en cuarto lugar Haemophilus influenzae colt 10%. Rinorrea purulenta fue el principal síntoma en todos los casos. Streptococcus pneumoniae, Moraxella catarrhalis y Haemophilus influenza se aislaron mayoritariamente en niños menores de 14 años. El 15% de los S. aureus fueron oxacilino-ressistentes, el 11% de S. pneumoniae fueron resistentes a la penicilina, el 70% de M. catarrhalis eran productoras de B-1actailiasay cl 5% de H. influenzae también producían lactamasa. Nuestros resultados permiten oriental-mayor el tratamiento antibiótico de las infecciones respiratorias altas.