Article
Microbiology
Yu-Shan Huang, Pao-Yu Chen, Pei-Chun Chou, Jann-Tay Wang
Summary: Cefiderocol and aztreonam-avibactam (ATM-AVI) both showed activity against carbapenem-resistant Gram-negative bacilli, including those that produce metallo-beta-lactamases (MBLs). However, Enterobacteriaceae isolates producing NDM carbapenemase displayed lower susceptibility to both antibiotics.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
Mariana Castanheira, Timothy B. Doyle, Lalitagauri M. Deshpande, Rodrigo E. Mendes, Helio S. Sader
Summary: Research on carbapenem-resistant Enterobacterales (CRE) without carbapenemase genes revealed complex resistance mechanisms, limited activity of most beta-lactam agents, and effective inhibition by ceftazidime/avibactam. Further studies are needed to understand the diverse resistance mechanisms and optimize treatment strategies for these isolates.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Microbiology
G. L. Drusano, Robert A. Bonomo, Steven M. Marshall, Laura J. Rojas, Mark D. Adams, Maria F. Mojica, Barry N. Kreiswirth, Liang Chen, Nino Mtchedlidze, Meredith Bacci, Michael Vicchiarelli, Jurgen B. Bulitta, Arnold Louie
Summary: The study investigated the impact of Ceftazidime-avibactam combination on Pseudomonas aeruginosa resistance and bacterial killing rate, finding a close relationship between AVI concentration and resistance emergence, and continuous infusion of AVI effectively suppressed resistance formation.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Krisztina M. Papp-Wallace, Melissa D. Barnes, Magdalena A. Taracila, Christopher R. Bethel, Joseph D. Rutter, Elise T. Zeiser, Katherine Young, Robert A. Bonomo
Summary: Ceftazidime-avibactam is ineffective against KPC-2 D179 variants, but imipenem-relebactam can overcome their resistance. The D179Y variant is unable to hydrolyze imipenem, while the D179N variant has a slower rate. Acyl complexes are less prevalent with the D179Y variant compared to the D179N variant. Imipenem-relebactam shows promise for treating clinical isolates harboring D179 variants of KPC-2.
Review
Engineering, Multidisciplinary
Tingting Xu, Yuqi Guo, Yang Ji, Baohong Wang, Kai Zhou
Summary: Carbapenem resistance is a major challenge for global public health, and understanding resistance mechanisms is crucial for guiding the development of new treatments. Optimizing current drug use and monitoring resistant pathogens are necessary.
Article
Chemistry, Physical
Vaishali Thakkur, Chandan Kumar Das, Nisanth N. Nair
Summary: The escalation of antibiotic resistance is a serious concern, particularly due to bacteria carrying class D beta-lactamases (DBLs). These enzymes can efficiently hydrolyze the last-reserved antibiotics for multidrug-resistant bacteria. This study investigates the inhibition mechanism of the OXA-48 DBL enzyme by the inhibitor avibactam through molecular dynamics simulations and free energy calculations. The findings provide insights into the reaction pathway and key intermediates, and reveal important chemical features for designing inhibitors, based on a comparison with the hydrolysis mechanism of meropenem.
Article
Pharmacology & Pharmacy
Shashikant Srivastava, Tawanda Gumbo, Tania Thomas
Summary: Cefazolin-avibactam combination has shown efficacy against MDR-TB and drug susceptible TB strains in children through PK/PD principles. The optimal dosing strategy was determined based on age-specific CFR and Mtb susceptibility breakpoint, highlighting the potential of repurposing cefazolin for pediatric TB treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Infectious Diseases
Mariana Castanheira, Jill Lindley, Timothy B. Doyle, Andrew P. Davis, Helio S. Sader
Summary: Five Enterobacter cloacae isolates were exposed to cefepime, meropenem, or ceftazidime-avibactam through serial passage in broth microdilution. The study evaluated the increase in minimum inhibitory concentration (MIC) and resistance mechanisms in post-exposure isolates. The results showed diverse mechanisms of resistance and higher MIC values for cefepime and meropenem compared to ceftazidime-avibactam.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Microbiology
Dereje A. Negatu, Ruben Gonzalez del Rio, Monica Cacho-Izquierdo, David Barros-Aguirre, Joel Lelievre, Joaquin Rullas, Patricia Casado, Uday S. Ganapathy, Matthew D. Zimmerman, Martin Gengenbacher, Veronique Dartois, Thomas Dick
Summary: The combination of tebipenem and avibactam, both belonging to the beta-lactam class, exhibits strong bactericidal activity against Mycobacterium abscessus in vitro. In a mouse model of M. abscessus lung infection, the combination of their respective oral prodrugs, tebipenem-pivoxil and avibactam ARX-1796, showed efficacy. These findings suggest that tebipenem-avibactam is a promising oral drug candidate for the treatment of M. abscessus pulmonary disease and could guide the design of clinical trials.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Moonsuk Bae, Taeeun Kim, Joung Ha Park, Seongman Bae, Heungsup Sung, Mi-Na Kim, Jiwon Jung, Min Jae Kim, Sung-Han Kim, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Yong Pil Chong
Summary: Beta-lactam-avibactam combinations such as ceftazidime-avibactam and aztreonam-avibactam showed good in vitro activities against extended-spectrum beta-lactam-resistant Enterobacterales blood isolates, with lower inoculum effect frequencies compared to meropenem. Aztreonam-avibactam demonstrated better in vitro activity but was more susceptible to the inoculum effect than ceftazidime-avibactam, suggesting potential use as carbapenem-sparing strategies for treating infections.
Article
Infectious Diseases
Helio S. Sader, Rodrigo E. Mendes, S. J. Ryan Arends, Cecilia G. Carvalhaes, Mariana Castanheira
Summary: The study evaluated the activity of aztreonam-avibactam against Enterobacterales isolates from European medical centers and the occurrence of carbapenemases. The results showed that aztreonam-avibactam had high inhibitory activity against Enterobacterales isolates and retained potent activity against resistant strains. The study also found that isolates from the Eastern European and Mediterranean region had lower susceptibility to comparator agents compared to isolates from Western Europe.
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
(2022)
Review
Infectious Diseases
Huan Zhang, Beibei Liang, Jin Wang, Yun Cai
Summary: This study compared the efficacy of non-carbapenem beta-lactam/beta-lactamase inhibitors (BLBLIs) with carbapenems for the treatment of UTIs caused by ESBL-PE. The results showed no significant difference in clinical success and mortality between the two treatment groups, but a slightly higher rate of microbiological success was observed in the BLBLIs group.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Chemistry, Medicinal
Rahul Kumar, Vikas Pathania, Shashi Kumar, Mahender Kumar, Hemraj Nandanwar, Sushil K. Maurya
Summary: In order to combat antibiotic resistance, a novel class of conjugates based on ciprofloxacin and avibactam were synthesized and found to have improved antibacterial efficacy against certain pathogens. Combination studies with ceftazidime showed less synergistic effect compared to avibactam-ceftazidime co-dosing. Furthermore, two conjugates exhibited higher inhibition profile against β-lactamase-II compared to avibactam, suggesting the integration of avibactam with ciprofloxacin is a promising approach for next-generation non-β-lactam-β-lactamase inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Worapong Nasomsong, Parnrada Nulsopapon, Dhitiwat Changpradub, Manat Pongchaidecha, Supanun Pungcharoenkijkul, Piraporn Juntanawiwat, Waristha Simsiriporn, Wichai Santimaleeworagun
Summary: This study in Thailand found that CZA exhibited a fairly susceptible rate among CRKP isolates carrying the OXA-48 gene, with the recommended dose of 2.5 g infused every 8 hours for 2-3 hours.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Sangita Sarma, Banani Deka, Pankaj Pradeep Panyang, Anil Kumar Singh
Summary: The study identified novel mutations of beta-lactamase and their clinical importance in Enterobacteriaceae family, highlighting the resistance pattern and molecular mechanisms in bacteria isolated from acute diarrheal patients. The identified mutations in BlaSHV protein and their interactions with antibiotics provide insight into antibiotic resistance in Klebsiella pneumoniae isolates.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Microbiology
Krisztina M. Papp-Wallace, Adam B. Shapiro, Scott A. Becka, Elise T. Zeiser, John J. LiPuma, Douglas J. Lane, Rekha G. Panchal, John P. Mueller, John P. O'Donnell, Alita A. Miller
Summary: Burkholderia genus, including pathogens causing Melioidosis and Glanders, are hard to treat, but the combination of sulbactam-durlobactam (SUL-DUR) shows potential for treating these infections by inhibiting bacterial growth and reducing beta-lactamase activity.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Barbara Ghiglione, Maria Margarita Rodriguez, Florencia Brunetti, Krisztina M. Papp-Wallace, Ayumi Yoshizumi, Yoshikazu Ishii, Robert A. Bonomo, Gabriel Gutkind, Sebastian Klinke, Pablo Power
Summary: The CTX-M-151 variant, isolated from a Salmonella strain in Japan, shows a unique hydrolytic preference towards ceftriaxone and is well inhibited by clavulanic acid. Its structure reveals new features and suggests it may represent a new subgroup within the CTX-M family.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Malligarjunan Rajavel, Vijay Kumar, Ha Nguyen, Jacob Wyatt, Steven H. Marshall, Krisztina M. Papp-Wallace, Prasad Deshpande, Satish Bhavsar, Ravindra Yeole, Sachin Bhagwat, Mahesh Patel, Robert A. Bonomo, Focco van den Akker
Summary: The study on the inhibition of multidrug-resistant pathogens by a new compound and the resistance mechanisms of antibiotics may offer insights into designing novel antibiotics to combat resistant strains.
Article
Multidisciplinary Sciences
Jasmine Martinez, Chelsea Razo-Gutierrez, Casin Le, Robert Courville, Camila Pimentel, Christine Liu, Sammie E. Fung, Marisel R. Tuttobene, Kimberly Phan, Alejandro J. Vila, Parvin Shahrestani, Veronica Jimenez, Marcelo E. Tolmasky, Scott A. Becka, Krisztina M. Papp-Wallace, Robert A. Bonomo, Alfonso Soler-Bistue, Rodrigo Sieira, Maria Soledad Ramirez
Summary: This study investigates the genetic changes and virulence factor expression of Acinetobacter baumannii in the cerebrospinal fluid (CSF) environment, showing its adaptability and survival capabilities. While a highly virulent strain showed no transcriptome changes in the presence of CSF, a low-virulence isolate exhibited significant differences in gene expression. Exposure to CSF induced increased expression of virulence factors without promoting bacterial growth, but rather increasing the expression of genes associated with transcription, translation, and ATP synthesis.
SCIENTIFIC REPORTS
(2021)
Article
Microbiology
Alessandro Moriano, Diego O. Serra, Amparo Hoard, Sabrina Montana, Jose Degrossi, Robert A. Bonomo, Krisztina M. Papp-Wallace, Maria Soledad Ramirez
Summary: Polymicrobial lung infections in individuals with Cystic Fibrosis are complex and can be caused by opportunistic pathogens like S. aureus, P. aeruginosa and Burkholderia cepacia complex. Interaction studies between S. aureus and Bcc reveal potential impact on the severity and outcomes of infections in CF patients.
CURRENT MICROBIOLOGY
(2021)
Article
Microbiology
Scott A. Becka, Elise T. Zeiser, John J. LiPuma, Krisztina M. Papp-Wallace
Summary: The study demonstrates that the combination of imipenem-relebactam shows promising antimicrobial activity against MDR Bcc and B. gladioli strains, especially those resistant to ceftazidime-avibactam.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Casin Le, Camila Pimentel, Marisel R. Tuttobene, Tomas Subils, Brent Nishimura, German M. Traglia, Federico Perez, Krisztina M. Papp-Wallace, Robert A. Bonomo, Marcelo E. Tolmasky, Maria Soledad Ramirez
Summary: HSA enhances natural transformation and modifies the expression levels of competence genes and antibiotic resistance in Acinetobacter baumannii. When combined with carbapenems, HSA increases the expression of genes involved in natural competence, potentially accelerating the acquisition of foreign DNA and evolution in A. baumannii.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Casin Le, Camila Pimentel, Marisel R. Tuttobene, Tomas Subils, Krisztina M. Papp-Wallace, Robert A. Bonomo, Luis A. Actis, Marcelo E. Tolmasky, Maria Soledad Ramirez
Summary: Acinetobacter baumannii, a multidrug-resistant pathogen, is affected by exposure to human body fluids, leading to changes in gene expression and pathogenic behavior, with different strains showing varying degrees of susceptibility. Human serum albumin plays a crucial role in HPF, modulating gene expression and behavior in A. baumannii.
CURRENT MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Joel A. Goldberg, Vijay Kumar, Elizabeth J. Spencer, Denton Hoyer, Steven H. Marshall, Andrea M. Hujer, Kristine M. Hujer, Christopher R. Bethel, Krisztina M. Papp-Wallace, Federico Perez, Michael R. Jacobs, David van Duin, Barry N. Kreiswirth, Focco van den Akker, Mark S. Plummer, Robert A. Bonomo
Summary: This study demonstrates the preclinical evaluation of a novel γ-lactam siderophore antibiotic, YU253911, showing potent antimicrobial activity against multidrug-resistant Gram-negative pathogens. The compound targets penicillin-binding protein 3 in Pseudomonas aeruginosa and has dose-dependent efficacy in a mouse infection model. Additionally, a combination with a novel beta-lactamase inhibitor was shown to enhance the effectiveness of the antibiotic against carbapenem-resistant Acinetobacter spp.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Infectious Diseases
Camila Pimentel, Casin Le, Marisel R. Tuttobene, Tomas Subils, Krisztina M. Papp-Wallace, Robert A. Bonomo, Marcelo E. Tolmasky, Maria Soledad Ramirez
Summary: The study exposed different Acinetobacter baumannii strains to human serum albumin (HSA) and human serum (HS) to evaluate their response in terms of antimicrobial resistance, biofilm formation, and quorum sensing. The results showed varying gene expression levels and responses among different strains when exposed to HSA and HS, indicating different adaptative responses in infecting A. baumannii strains.
Editorial Material
Microbiology
Krisztina M. Papp-Wallace, Jean-Denis Docquier, Frederic Kerff, Pablo Power
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
T. A. Alsenani, S. L. Viviani, V Kumar, M. A. Taracila, C. R. Bethel, M. D. Barnes, K. M. Papp-Wallace, R. K. Shields, M. H. Nguyen, C. J. Clancy, R. A. Bonomo, F. van den Akker
Summary: The structural study of KPC-2 D179 variants revealed destabilization of the Omega loop, contributing to ceftazidime-avibactam resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Magdalena A. Taracila, Christopher R. Bethel, Andrea M. Hujer, Krisztina M. Papp-Wallace, Melissa D. Barnes, Joseph D. Rutter, Jamie VanPelt, Ben A. Shurina, Focco van den Akker, Cornelius J. Clancy, M. Hong Nguyen, Shaoji Cheng, Ryan K. Shields, Richard C. Page, Robert A. Bonomo
Summary: This study investigates the susceptibility and resistance mechanism of D179Y variant of KPC-2 and -3 to carbapenems and ceftazidime and ceftazidime-avibactam, and it reveals that conformational changes and overall disorder caused by D179Y substitution contribute to the unexpected phenotype.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Philip Hinchliffe, Catherine L. Tooke, Christopher R. Bethel, Benlian Wang, Christopher Arthur, Kate J. Heesom, Stuart Shapiro, Daniela M. Schlatzer, Krisztina M. Papp-Wallace, Robert A. Bonomo, James Spencer
Summary: This study reveals the mechanism of action of two β-lactamase inhibitors, enmetazobactam and tazobactam, on CTX-M-15 β-lactamase in Escherichia coli, including the formation of protein cross-link and epimerization of amino acids.
Article
Infectious Diseases
Scott A. Becka, Elise T. Zeiser, John J. LiPuma, Krisztina M. Papp-Wallace
Summary: This study evaluated the antimicrobial activity of Tebipenem against multiple strains of Enterobacterales pathogens. The results showed that all strains of Burkholderia cepacia complex (Bcc) and Burkholderia gladioli tested were resistant to Tebipenem. Further experiments revealed that the resistance may be related to the inducible beta-lactamases PenA and AmpC produced by these strains.