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.
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
Jacqueline Findlay, Laurent Poirel, Mario Juhas, Patrice Nordmann
Summary: This study evaluated the impact of KPC variants on CZA resistance, finding increased susceptibility to cephalosporins and carbapenems but increased resistance to ceftazidime and piperacillin-tazobactam. The KPC variants exhibited increased affinity towards ceftazidime and slightly decreased sensitivity to avibactam, impacting CZA resistance while concurrently negatively impacting carbapenemase activities.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Vincenzo Di Pilato, Noemi Aiezza, Valentina Viaggi, Alberto Antonelli, Luigi Principe, Tommaso Giani, Francesco Luzzaro, Gian Maria Rossolini
Summary: This study characterized a Klebsiella pneumoniae isolate with high-level resistance to ceftazidime-avibactam due to the presence of KPC-53, a variant of KPC-3 with unique genetic features. Whole-genome sequencing revealed the presence of two copies of blaKPC-53 on different plasmids, shedding light on the mechanisms of resistance to ceftazidime-avibactam.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Remy A. Bonnin, Sandrine Bernabeu, Cecile Emeraud, Elodie Creton, Oceane Vanparis, Thierry Naas, Agnes B. Jousset, Laurent Dortet
Summary: This study demonstrates that the addition of relebactam and vaborbactam did not significantly modify the susceptibility of OXA-48-like-producing Enterobacterales to imipenem and meropenem. However, the addition of avibactam strongly restored ceftazidime susceptibility.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Microbiology
Yanqin Huang, Karol Sokolowski, Amisha Rana, Nidhi Singh, Jiping Wang, Ke Chen, Yinzhi Lang, Jieqiang Zhou, Neera Kadiyala, Fiorella Krapp, Egon A. Ozer, Alan R. Hauser, Jian Li, Jurgen B. Bulitta, Zackery P. Bulman
Summary: Combining aminoglycosides with ceftazidime/avibactam shows promising synergy against KPC-producing Klebsiella pneumoniae infections, leading to reduced bacterial counts. Selecting aminoglycosides based on genes or susceptibilities can enhance the pharmacodynamic activity of the combination therapy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Lin Wang, Weiyi Shen, Rong Zhang, Jiachang Cai
Summary: This study identified a novel ceftazidime-avibactam-resistant KPC-2 variant, KPC-123, in a Citrobacter koseri isolated from a patient in a Chinese hospital. The KPC-123 variant showed high-level resistance to ceftazidime and ceftazidime/avibactam, but remained susceptible to carbapenems. Whole-genome sequencing and genomic analysis revealed the transfer and in vivo evolution of the bla(KPC)-carrying plasmid. Active surveillance is needed to prevent and control the dissemination of ceftazidime/avibactam resistance.
FRONTIERS IN MICROBIOLOGY
(2022)
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
Vincenzo Di Pilato, Luigi Principe, Lilia Andriani, Noemi Aiezza, Marco Coppi, Silvia Ricci, Tommaso Giani, Francesco Luzzaro, Gian Maria Rossolini
Summary: This article reports an outbreak caused by carbapenemase-producing Klebsiella pneumoniae that is resistant to ceftazidime/avibactam and variably resistant to carbapenem-based beta-lactam/beta-lactamase inhibitor combinations. The overproduction of KPC-3 was identified as the main mechanism of cross-resistance to ceftazidime/avibactam and meropenem/vaborbactam, while resistance to imipenem/relebactam was less affected.
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Article
Microbiology
Ping Zhang, Huangdu Hu, Qiucheng Shi, Long Sun, Xueqing Wu, Xiaoting Hua, Alan McNally, Yan Jiang, Yunsong Yu, Xiaoxing Du
Summary: This study aimed to clarify the evolutionary trajectory of a KPC-producing K. pneumoniae population during beta-lactam antibiotic therapy. Five highly homologous KPC-Kp isolates were collected from a single patient, and whole-genome sequencing and comparative genomics analysis were performed. Experimental evolution assays revealed that multi-copy bla(KPC-2) cells increased under antibiotic selection, generating low-level and high-level resistance to ceftazidime-avibactam. Both gene amplification and mutation played important roles in KPC-Kp evolution under antibiotic selection.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
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
Infectious Diseases
Ke Ma, Yu Feng, Zhiyong Zong
Summary: Aztreonam/avibactam has additional coverage for metallo-beta-lactamases compared with ceftazidime/avibactam, but some strains may develop resistance to aztreonam/avibactam while remaining susceptible to ceftazidime/avibactam.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Infectious Diseases
Charalampos Zarras, Elias Iosifidis, Maria Simitsopoulou, Styliani Pappa, Angeliki Kontou, Emmanuel Roilides, Anna Papa
Summary: This article reports a case of neonatal sepsis caused by CAZ/AVI-resistant bla(KPC-2)-harboring Klebsiella pneumoniae carrying bla(VEB-25), and describes the use of a customized active surveillance program and enhanced infection control measures. The emergence of bla(VEB-25) signals horizontal plasmid transfer in hospital facilities and highlights the importance of monitoring for novel resistance mechanisms. Molecular diagnostics can guide appropriate antimicrobial therapy and the early implementation of infection control measures against antimicrobial resistance.
Article
Microbiology
Carla Fontana, Marco Favaro, Laura Campogiani, Vincenzo Malagnino, Silvia Minelli, Maria Cristina Bossa, Anna Altieri, Massimo Andreoni, Loredana Sarmati
Summary: This study described four clinical isolates of CAZ-AVI resistant KPC-3 Klebsiella pneumoniae subsp. pneumoniae, which exhibited multiple KPC gene mutations, including a novel variant. These isolates escaped common tests used for prompt detection of KPC-positive strains.
Article
Infectious Diseases
Claire Amaris Hobson, Aurelie Cointe, Herve Jacquier, Alaksh Choudhury, Melanie Magnan, Celine Courroux, Olivier Tenaillon, Stephane Bonacorsi, Andre Birgy
Summary: This study reveals that CZA-resistant KPC variants may lead to cross-resistance to cefiderocol by increasing the MICs. Additionally, cefiderocol is greatly impacted by the inoculum effect, indicating precautions should be taken when treating infections with suspected high inoculum levels.
CLINICAL MICROBIOLOGY AND INFECTION
(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
Chemistry, Medicinal
Michiyoshi Nukaga, Michael J. Yoon, Magdalena A. Taracilia, Tyuji Hoshino, Scott A. Becka, Elise T. Zeiser, Joseph R. Johnson, Krisztina M. Papp-Wallace
Summary: The Burkholderia cepacia complex (Bcc) poses a serious health threat to individuals with cystic fibrosis or compromised immune systems due to its high level of antibiotic resistance, notably through the PenA-like beta-lactamases. This study evaluated different beta-lactamase inhibitors against PenA1 to restore susceptibility to antibiotics in whole cell based assays, revealing avibactam as the most effective inhibitor. Specific amino acids, such as S130, R220, and K234, were found to play important roles in inactivation by avibactam, indicating potential targets for future drug development.
ACS INFECTIOUS DISEASES
(2021)
Article
Microbiology
Camila Pimentel, Casin Le, Marisel R. Tuttobene, Tomas Subils, Jasmine Martinez, Rodrigo Sieira, Krisztina M. Papp-Wallace, Niroshika Keppetipola, Robert A. Bonomo, Luis A. Actis, Marcelo E. Tolmasky, Maria Soledad Ramirez
Summary: Acinetobacter baumannii, a nosocomial pathogen with high antibiotic resistance, has been shown to adapt to different host environments, providing insights into potential novel antimicrobial strategies. Research on the gene expression profile of A. baumannii when exposed to human fluids revealed key pathways involved in the pathogen's response.
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.