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https://www.readbyqxmd.com/read/28329350/multicenter-evaluation-of-ceftolozane-tazobactam-for-serious-infections-caused-by-carbapenem-resistant-pseudomonas-aeruginosa
#1
Jose M Munita, Samuel L Aitken, William R Miller, Federico Perez, Rossana Rosa, Luis A Shimose, Paola N Lichtenberger, Lilian M Abbo, Rupali Jain, Masayuki Nigo, Audrey Wanger, Rafael Araos, Truc T Tran, Javier Adachi, Robert Rakita, Samuel Shelburne, Robert A Bonomo, Cesar A Arias
A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 μg/mL.
March 14, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28289035/wck-5107-zidebactam-wck-5153-novel-inhibitors-of-pbp2-showing-potent-%C3%AE-lactam-enhancer-activity-against-pseudomonas-aeruginosa-including-multidrug-resistant-metallo-%C3%AE-lactamase-producing-high-risk-clones
#2
Bartolome Moya, Isabel M Barcelo, Sachin Bhagwat, Mahesh Patel, German Bou, Krisztina M Papp-Wallace, Robert A Bonomo, Antonio Oliver
Zidebactam and WCK 5153 are novel β-lactam enhancers that are bicyclo-acyl hydrazides (BCH), derivatives of diazabicyclooctane (DBO) scaffold, targeted for the treatment of serious infections caused by highly drug-resistant Gram-negative pathogens. In this report, we determined the PBP inhibition profiles and the antimicrobial activity of zidebactam and WCK 5153 against P. aeruginosa, including multidrug-resistant (MDR) metallo-β-lactamase (MBL)-producing high-risk clones. MICs and time-kill assays were conducted for zidebactam, WCK 5153 and antipseudomonal β-lactams using wild-type PAO1 strain, MexAB-OprM-hyperproducing (mexR), porin deficient (oprD) and AmpC-hyperproducing (dacB) derivatives of PAO1 and MBL-expressing clinical strains, ST175 (blaVIM-2) and ST111 (blaVIM-1)...
March 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28270585/transcriptome-remodeling-of-acinetobacter-baumannii-during-infection-and-treatment
#3
Meredith S Wright, Michael R Jacobs, Robert A Bonomo, Mark D Adams
Acinetobacter baumannii is an increasingly common multidrug-resistant pathogen in health care settings. Although the genetic basis of antibiotic resistance mechanisms has been extensively studied, much less is known about how genetic variation contributes to other aspects of successful infections. Genetic changes that occur during host infection and treatment have the potential to remodel gene expression patterns related to resistance and pathogenesis. Longitudinal sets of multidrug-resistant A. baumannii isolates from eight patients were analyzed by RNA sequencing (RNA-seq) to identify differentially expressed genes and link them to genetic changes contributing to transcriptional variation at both within-patient and population levels...
March 7, 2017: MBio
https://www.readbyqxmd.com/read/28264560/overcoming-an-extreme-drug-resistant-xdr-pathogen-avibactam-restores-susceptibility-to-ceftazidime-for-burkholderia-cepacia-complex-isolates-from-cystic-fibrosis-patients
#4
Krisztina M Papp-Wallace, Scott A Becka, Elise T Zeiser, Nozumi Ohuchi, Maria F Mojica, Julian A Gatta, Monica Falleni, Delfina Tosi, Elisa Borghi, Marisa L Winkler, Brigid M Wilson, John J LiPuma, Michiyoshi Nukaga, Robert A Bonomo
Burkholderia multivorans is a significant health threat to persons with cystic fibrosis (CF). Infections are difficult to treat as this pathogen is inherently resistant to multiple antibiotics. Susceptibility testing of isolates obtained from CF respiratory cultures revealed that single agents selected from different antibiotic classes were unable to inhibit growth. However, all isolates were found to be susceptible to ceftazidime when combined with the novel non-β-lactam β-lactamase inhibitor, avibactam (all minimum inhibitor concentrations (MICs) were ≤ 8 mg/L of ceftazidime and 4 mg/L of avibactam)...
March 6, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28170436/the-effect-of-empiric-antimicrobial-treatment-duration-on-detection-of-bacterial-dna-in-sterile-surgical-specimens
#5
John Joseph Farrell, Huaping Wang, Rangarajan Sampath, Kristin S Lowery, Robert A Bonomo
Initial antimicrobial treatment of patients with deep seated or invasive infections is typically empiric. Usually, cultures of specimens obtained from the suspected source of infection are performed to identify pathogens and guide continued antimicrobial treatment. When patients present with signs and symptoms of infection, but sterile body fluid or tissue specimens cannot be obtained in a timely fashion, growth of bacterial pathogens in culture may be inhibited following initiation of empiric antibiotic treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28167547/bacteremia-due-to-carbapenem-resistant-enterobacteriaceae-cre-a-multicenter-clinical-and-molecular-epidemiologic-analysis-in-the-nation-s-epicenter-for-cre
#6
Michael J Satlin, Liang Chen, Gopi Patel, Angela Gomez-Simmonds, Gregory Weston, Angela C Kim, Susan K Seo, Marnie E Rosenthal, Steven J Sperber, Stephen G Jenkins, Camille L Hamula, Anne-Catrin Uhlemann, Michael H Levi, Bettina C Fries, Yi-Wei Tang, Stefan Juretschko, Albert D Rojtman, Tao Hong, Barun Mathema, Michael R Jacobs, Thomas J Walsh, Robert A Bonomo, Barry N Kreiswirth
Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or transplantation...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167541/can-ceftazidime-avibactam-and-aztreonam-overcome-%C3%AE-lactam-resistance-conferred-by-metallo-%C3%AE-lactamases-in-enterobacteriaceae
#7
Steven Marshall, Andrea M Hujer, Laura J Rojas, Krisztina M Papp-Wallace, Romney M Humphries, Brad Spellberg, Kristine M Hujer, Emma K Marshall, Susan D Rudin, Federico Perez, Brigid M Wilson, Ronald B Wasserman, Linda Chikowski, David L Paterson, Alejandro J Vila, David van Duin, Barry N Kreiswirth, Henry F Chambers, Vance G Fowler, Michael R Jacobs, Mark E Pulse, William J Weiss, Robert A Bonomo
Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof...
April 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28062685/development-and-validation-of-the-increment-esbl-predictive-score-for-mortality-in-patients-with-bloodstream-infections-due-to-extended-spectrum-%C3%AE-lactamase-producing-enterobacteriaceae
#8
Zaira Raquel Palacios-Baena, Belén Gutiérrez-Gutiérrez, Marina De Cueto, Pierluigi Viale, Mario Venditti, Alicia Hernández-Torres, Antonio Oliver, Luis Martínez-Martínez, Esther Calbo, Vicente Pintado, Oriol Gasch, Benito Almirante, José Antonio Lepe, Johann Pitout, Murat Akova, Carmen Peña-Miralles, Mitchell J Schwaber, Mario Tumbarello, Evelina Tacconelli, Julia Origüen, Nuria Prim, German Bou, Helen Giamarellou, Joaquín Bermejo, Axel Hamprecht, Federico Pérez, Manuel Almela, Warren Lowman, Po-Ren Hsueh, Carolina Navarro-San Francisco, Julián Torre-Cisneros, Yehuda Carmeli, Robert A Bonomo, David L Paterson, Álvaro Pascual, Jesús Rodríguez-Baño
BACKGROUND: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. METHODS: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC)...
January 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27997706/exploring-the-potential-of-boronic-acids-as-inhibitors-of-oxa-24-40-%C3%AE-lactamase
#9
Josephine P Werner, Joshua M Mitchell, Magdalena A Taracila, Robert A Bonomo, Rachel A Powers
β-lactam antibiotics are crucial to the management of bacterial infections in the medical community. Due to overuse and misuse, clinically significant bacteria are now resistant to many commercially available antibiotics. The most widespread resistance mechanism to β-lactams is the expression of β-lactamase enzymes. To overcome β-lactamase mediated resistance, inhibitors were designed to inactivate these enzymes. However, current inhibitors (clavulanic acid, tazobactam, and sulbactam) for β-lactamases also contain the characteristic β-lactam ring, making them susceptible to resistance mechanisms employed by bacteria...
March 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27974412/clinical-and-pathophysiological-overview-of-acinetobacter-infections-a-century-of-challenges
#10
REVIEW
Darren Wong, Travis B Nielsen, Robert A Bonomo, Paul Pantapalangkoor, Brian Luna, Brad Spellberg
SUMMARYAcinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity...
January 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/27965456/comprehensive-genome-analysis-of-carbapenemase-producing-enterobacter-spp-new-insights-into-phylogeny-population-structure-and-resistance-mechanisms
#11
Kalyan D Chavda, Liang Chen, Derrick E Fouts, Granger Sutton, Lauren Brinkac, Stephen G Jenkins, Robert A Bonomo, Mark D Adams, Barry N Kreiswirth
Knowledge regarding the genomic structure of Enterobacter spp., the second most prevalent carbapenemase-producing Enterobacteriaceae, remains limited. Here we sequenced 97 clinical Enterobacter species isolates that were both carbapenem susceptible and resistant from various geographic regions to decipher the molecular origins of carbapenem resistance and to understand the changing phylogeny of these emerging and drug-resistant pathogens. Of the carbapenem-resistant isolates, 30 possessed blaKPC-2, 40 had blaKPC-3, 2 had blaKPC-4, and 2 had blaNDM-1 Twenty-three isolates were carbapenem susceptible...
December 13, 2016: MBio
https://www.readbyqxmd.com/read/27957505/bacterial-colonization-and-antibiotic-resistance-in-a-prospective-cohort-of-newborn-infants-during-the-first-year-of-life
#12
Sharon B Meropol, Kurt C Stange, Michael R Jacobs, Judith K Weiss, Saralee Bajaksouzian, Robert A Bonomo
BACKGROUND: Infants are virtually sterile at birth and frequently use antibiotics; our objective was to (1) characterize the longitudinal colonization with bacterial pathogens and associated antibiotic resistance in a cohort of community-dwelling infants in Northeast Ohio and (2) describe longitudinal concurrent antibiotic and daycare exposures. METHODS: For 35 newborns, nasopharyngeal swabs were cultured for Streptococcus pneumoniae, anterior nasal for Staphylococcus aureus, and perirectal for extended-spectrum beta-lactamase (ESBL)-producing Gram-negative enteric bacteria, at 3-month intervals for 12 months...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27940944/colistin-resistance-in-carbapenem-resistant-klebsiella-pneumoniae-laboratory-detection-and-impact-on-mortality
#13
Laura J Rojas, Madiha Salim, Eric Cober, Sandra S Richter, Federico Perez, Robert A Salata, Robert C Kalayjian, Richard R Watkins, Steve Marshall, Susan D Rudin, T Nicholas Domitrovic, Andrea M Hujer, Kristine M Hujer, Yohei Doi, Keith S Kaye, Scott Evans, Vance G Fowler, Robert A Bonomo, David van Duin
BACKGROUND: Polymyxins including colistin are an important "last-line" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide. METHODS: A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014...
December 10, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27872073/exploring-the-role-of-the-%C3%AE-loop-in-the-evolution-of-ceftazidime-resistance-in-the-pena-%C3%AE-lactamase-from-burkholderia-multivorans-an-important-cystic-fibrosis-pathogen
#14
Krisztina M Papp-Wallace, Scott A Becka, Magdalena A Taracila, Elise T Zeiser, Julian A Gatta, John J LiPuma, Robert A Bonomo
The unwelcome evolution of resistance to the advanced generation cephalosporin antibiotic, ceftazidime is hindering the effective therapy of Burkholderia cepacia complex (BCC) infections. Regrettably, BCC organisms are highly resistant to most antibiotics, including polymyxins; ceftazidime and trimethoprim-sulfamethoxazole are the most effective treatment options. Unfortunately, resistance to ceftazidime is increasing and posing a health threat to populations susceptible to BCC infection. We found that up to 36% of 146 tested BCC clinical isolates were nonsusceptible to ceftazidime (MICs ≥ 8 μg/ml)...
February 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27844027/prosthetic-valve-endocarditis-caused-by-bartonella-henselae-a-case-report-of-molecular-diagnostics-informing-nonsurgical-management
#15
Patricia Bartley, Emmanouil Angelakis, Didier Raoult, Rangarajan Sampath, Robert A Bonomo, Robin L P Jump
Identifying the pathogen responsible for culture-negative valve endocarditis often depends on molecular studies performed on surgical specimens. A patient with Ehlers-Danlos syndrome who had an aortic graft, a mechanical aortic valve, and a mitral anulloplasty ring presented with culture-negative prosthetic valve endocarditis and aortic graft infection. Research-based polymerase chain reaction (PCR)/electrospray ionization mass spectrometry on peripheral blood samples identified Bartonella henselae. Quantitative PCR targeting the16S-23S ribonucleic acid intergenic region and Western immunoblotting confirmed this result...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27795336/informing-antibiotic-treatment-decisions-evaluating-rapid-molecular-diagnostics-to-identify-susceptibility-and-resistance-to-carbapenems-against-acinetobacter-spp-in-primers-iii
#16
Scott R Evans, Andrea M Hujer, Hongyu Jiang, Carol B Hill, Kristine M Hujer, Jose R Mediavilla, Claudia Manca, Thuy Tien T Tran, T Nicholas Domitrovic, Paul G Higgins, Harald Seifert, Barry N Kreiswirth, Robin Patel, Michael R Jacobs, Liang Chen, Rangarajan Sampath, Thomas Hall, Christine Marzan, Vance G Fowler, Henry F Chambers, Robert A Bonomo
The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter sp...
January 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27742735/%C3%AE-lactamases-a-focus-on-current-challenges
#17
REVIEW
Robert A Bonomo
β-Lactamases, the enzymes that hydrolyze β-lactam antibiotics, remain the greatest threat to the usage of these agents. In this review, the mechanism of hydrolysis is discussed for both those enzymes that use serine at the active site and those that require divalent zinc ions for hydrolysis. The β-lactamases now include >2000 unique, naturally occurring amino acid sequences. Some of the clinically most important of these are the class A penicillinases, the extended-spectrum β-lactamases (ESBLs), the AmpC cephalosporinases, and the carbapenem-hydrolyzing enzymes in both the serine and metalloenzyme groups...
January 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27741230/treatment-selection-choices-should-not-be-based-on-benefits-or-costs-alone-a-head-to-head-randomized-controlled-trial-of-antiviral-drugs-for-hepatitis-c
#18
Perica Davitkov, Apoorva Krishna Chandar, Amy Hirsch, Anita Compan, Marina G Silveira, Donald D Anthony, Suzanne Smith, Clare Gideon, Robert A Bonomo, Yngve Falck-Ytter
BACKGROUND: Clinicians often face dilemmas with decisions related to formulary choices when two similar drugs are simultaneously available in the market. We studied the comparative safety, effectiveness, and treatment costs of the two first generation direct-acting antiviral agents (DAA), boceprevir and telaprevir as uncertainty existed regarding the drug of choice between these two seemingly equally Hepatitis-C treatment options. METHODS: We randomly assigned 50 patients in an open-label, pragmatic randomized controlled trial (RCT) at a VA Medical Center to either boceprevir or telaprevir in combination with peginterferon and ribavirin, stratified by the presence of cirrhosis and prior treatment experience...
2016: PloS One
https://www.readbyqxmd.com/read/27712635/a-predictive-model-of-mortality-in-patients-with-bloodstream-infections-due-to-carbapenemase-producing-enterobacteriaceae
#19
Belén Gutiérrez-Gutiérrez, Elena Salamanca, Marina de Cueto, Po-Ren Hsueh, Pierluigi Viale, José Ramón Paño-Pardo, Mario Venditti, Mario Tumbarello, George Daikos, Vicente Pintado, Yohei Doi, Felipe Francisco Tuon, Ilias Karaiskos, Isabel Machuca, Mitchell J Schwaber, Özlem Kurt Azap, Maria Souli, Emmanuel Roilides, Spyros Pournaras, Murat Akova, Federico Pérez, Joaquín Bermejo, Antonio Oliver, Manel Almela, Warren Lowman, Benito Almirante, Robert A Bonomo, Yehuda Carmeli, David L Paterson, Alvaro Pascual, Jesús Rodríguez-Baño
OBJECTIVE: To develop a score to predict mortality in patients with bloodstream infections (BSIs) due to carbapenemase-producing Enterobacteriaceae (CPE). PATIENTS AND METHODS: A multinational retrospective cohort study (INCREMENT project) was performed from January 1, 2004, through December 31, 2013. Patients with clinically relevant monomicrobial BSIs due to CPE were included and randomly assigned to either a derivation cohort (DC) or a validation cohort (VC)...
October 2016: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/27624957/editorial-commentary-ceftazidime-avibactam-and-carbapenem-resistant-enterobacteriaceae-we-re-gonna-need-a-bigger-boat
#20
EDITORIAL
Brad Spellberg, Robert A Bonomo
No abstract text is available yet for this article.
December 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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