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
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
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
Xiangning Huang, Siquan Shen, Fan Chang, Xin Liu, Jinxi Yue, Ning Xie, Lin Yin, Fupin Hu, Daiwen Xiao
Summary: The emergence of new KPC variants leading to treatment failure with ceftazidime-avibactam presents a new challenge for clinical anti-infection treatment. In this study, a ceftazidime-avibactam-resistant K. pneumoniae strain carrying a novel KPC-134 variant was reported. The study highlights the importance of timely identification of KPC variants and effective anti-infective therapy for saving infected patients.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
J. Guzman-Puche, E. Perez-Nadales, M. Perez-Vazquez, M. Causse, I Gracia-Ahufinger, A. Mendez-Natera, Y. Allalou-Ruiz, C. Elias, J. Oteo-Iglesias, J. Torre-Cisneros, L. Martinez-Martinez
Summary: This study describes the emergence of CZA resistance in clinical isolates, which is related to mutations in the bla(KPC) gene. The study identifies new alleles, KPC-94 and KPC-95, that do not cause carbapenem resistance.
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
Francois Lebreton, Brendan W. Corey, Christi L. McElheny, Alina Iovleva, Lan Preston, Katie R. Margulieux, Robert J. Cybulski, Patrick Mc Gann, Yohei Doi, Jason W. Bennett
Summary: KPC-82 is a KPC-2 variant found in a carbapenem-nonsusceptible Citrobacter koseri, conferring high-level resistance to ceftazidime-avibactam. The bla(KPC-82) gene is carried on a chromosomally integrated Tn4401 transposon, resulting in a two-amino-acid insertion caused by a nucleotide tandem repeat. Despite decreased carbapenemase activity in a heterologous background, KPC-82 remains susceptible to carbapenem/beta-lactamase inhibitor combinations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Laura Campogiani, Pietro Vitale, Alessandra Lodi, Alessandra Imeneo, Carla Fontana, Cartesio D'Agostini, Mirko Compagno, Luigi Coppola, Ilaria Spalliera, Vincenzo Malagnino, Elisabetta Teti, Marco Iannetta, Massimo Andreoni, Loredana Sarmati
Summary: This study aimed to collect and describe real-life data on CAZ-AVI-resistant Klebsiella pneumoniae isolates in a University Hospital. The results showed that prior use of CAZ-AVI was associated with the emergence of drug resistance.
Article
Microbiology
Yanqin Huang, Tiffany Wu, Omar Perez, Amisha P. Rana, Liang Chen, Barry N. Kreiswirth, Michael J. Satlin, Zackery P. Bulman
Summary: Ceftazidime/avibactam is an important treatment option for infections caused by KPC-Kp, but resistance can emerge during treatment. The study aimed to define the concentrations required to suppress regrowth in ceftazidime/avibactam susceptible isolates and identify active therapies against ceftazidime/avibactam-resistant KPC-Kp.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Yingyi Guo, Ningjing Liu, Zhiwei Lin, Xiaoliang Ba, Chuyue Zhuo, Feifeng Li, Jiong Wang, Yitan Li, Likang Yao, Baomo Liu, Shunian Xiao, Ying Jiang, Chao Zhuo
Summary: This study identified a novel mechanism of CAZ-AVI resistance associated with mutations in the porin LamB in KPC-Kp strains.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Infectious Diseases
Li Ding, Siquan Shen, Renru Han, Dandan Yin, Yan Guo, Fupin Hu
Summary: This case provides a reference for treating infections caused by K. pneumoniae with a KPC variant in countries lacking new antimicrobial agents.
Article
Microbiology
Xiangning Huang, Siquan Shen, Fan Chang, Xin Liu, Jinxi Yue, Ning Xie, Lin Yin, Fupin Hu, Daiwen Xiao
Summary: This study reports a ceftazidime-avibactam-resistant Klebsiella pneumoniae strain carrying a novel KPC variant, KPC-134. The isolate showed resistance to multiple antibiotics but sensitivity to certain others. Further experiments revealed that the resistance was primarily mediated by a plasmid carrying the bla(KPC-134) gene, which also harbored other common resistance genes.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
Laurent Poirel, Mustafa Sadek, Ayda Kusaksizoglu, Patrice Nordmann
Summary: Resistance to ceftazidime-avibactam (CZA) has been increasingly reported in KPC variants, and this study shows that CZA-resistant KPC-3 variants, specifically KPC-41 and KPC-50, may also impact susceptibility to cefiderocol (FDC) leading to cross-resistance. Thus, susceptibility testing to FDC is mandatory prior to clinical use for treating infections caused by KPC producers.
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
(2022)
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
Meng Yu, Qingzheng Wei, Weiqing Song, Jiangshui Yuan
Summary: This study aimed to investigate the development of resistance to ceftazidime-avibactam and carbapenems in a K. pneumonia strain expressing a novel KPC-2 variant. The results showed that the KPC-49 mutant strain was resistant to both ceftazidime-avibactam and carbapenems. Experimental whole genome sequencing combined with bioinformatics analysis was used to understand the drug resistance mechanisms of the mutant strains.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Microbiology
Cecilia G. Carvalhaes, Helio S. Sader, Jennifer M. Streit, Mariana Castanheira, Rodrigo E. Mendes
Summary: According to data from a 10-year study, oritavancin has shown strong activity against Gram-positive pathogens that cause bloodstream infections, and has demonstrated good efficacy against resistant strains of MRSA and Enterococcus.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Helio S. Sader, Cecilia G. Carvalhaes, Rodrigo E. Mendes, Mariana Castanheira
Summary: The in vitro study demonstrates that high-dose cefepime-tazobactam exhibits potent activity against Enterobacterales and P. aeruginosa, including multidrug-resistant isolates, supporting its clinical development as a carbapenem-sparing option.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Helio S. Sader, Rodrigo E. Mendes, Leonard R. Duncan, Cecilia G. Carvalhaes, Mariana Castanheria
Summary: The study evaluated the activity of cefepime/zidebactam against Gram-negative bacteria, showing good efficacy against Enterobacterales and carbapenem-resistant isolates. It demonstrated potential antibiotic effects on a global scale.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Immunology
Cecilia Godoy Carvalhaes, Helio Silva Sader, Paul Richard Rhomberg, Mariana Castanheira, Sean DeVries, Rodrigo Elisandro Mendes
Summary: This study assessed the activity of tedizolid and comparator agents against clinical surveillance isolates collected from pediatric patients with skin and skin structure infection in the United States. The results showed that tedizolid had high inhibitory activity against Staphylococcus aureus and MRSA isolates, and other antibiotics also displayed high susceptibility in different age groups and methicillin resistance profiles.
PEDIATRIC INFECTIOUS DISEASE JOURNAL
(2022)
Article
Infectious Diseases
Helio S. Sader, Mariana Castanheira, Leonard R. Duncan, Rodrigo E. Mendes
Summary: Ceftaroline showed high susceptibility against different types of infections, and it also exhibited good activity against methicillin-resistant strains.
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
(2023)
Article
Infectious Diseases
Helio S. Sader, Rodrigo E. Mendes, S. J. Ryan Arends, Cecilia G. Carvalhaes, Dee Shortridge, Mariana Castanheira
Summary: This study evaluated the in-vitro activity of several antibiotics against contemporary Pseudomonas aeruginosa isolates and found that ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam showed excellent activity against multi-drug resistant strains.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Immunology
Helio S. Sader, Rodrigo E. Mendes, John H. Kimbrough, Valerie Kantro, Mariana Castanheira
Summary: The CLSI lowered the breakpoints for amikacin, gentamicin, and tobramycin, which are commonly used to treat multidrug-resistant Enterobacterales infections. These changes resulted in a reduction in the susceptibility rates of Enterobacterales, particularly against resistant subsets. Plazomicin demonstrated potent activity against antimicrobial-resistant Enterobacterales, including CRE and MDR strains.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Immunology
Helio S. Sader, Rodrigo E. Mendes, Cecilia G. Carvalhaes, John H. Kimbrough, Mariana Castanheira
Summary: As the prevalence of metallo-beta-lactamase (MBL)-producing Enterobacterales is increasing, there is an urgent need for effective antimicrobials. This study evaluated the activity of aztreonam-avibactam against 27,834 Enterobacterales isolates collected from US medical centers. The results showed that aztreonam-avibactam was highly effective, inhibiting over 99.9% of isolates at a concentration of <= 8 mg/L.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Microbiology
A. J. Lepak, M. Trang, J. P. Hammel, H. S. Sader, S. M. Bhavnani, B. D. VanScoy, J. M. Pogue, P. G. Ambrose, D. R. Andes
Summary: STIC using only epidemiological data may not accurately reflect the therapeutic effect of antimicrobial agents against A. baumannii. In this study, a comprehensive evaluation was conducted using in vitro surveillance data, preclinical murine models, and population pharmacokinetics to establish appropriate STIC for commonly recommended antimicrobials.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Helio S. Sader, Rodrigo E. Mendes, Leonard Duncan, John H. Kimbrough, Cecilia G. Carvalhaes, Mariana Castanheira
Summary: A total of 35,360 Enterobacterales isolates were collected from US medical centers from 2018 to 2022. Among them, 7.4% were identified as multidrug-resistant (MDR). Susceptibility testing and whole genome sequencing were conducted to determine the resistance profiles and carbapenemase genes. The most active β-lactamase inhibitor combination against carbapenem-resistant Enterobacterales (CRE) isolates was ceftazidime-avibactam, followed by meropenem-vaborbactam and imipenem-relebactam. Ceftazidime-avibactam exhibited greater activity against OXA-48-type producers.
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
(2023)
Article
Infectious Diseases
Helio S. Sader, Cecilia G. Carvalhaes, Michael D. Huband, Rodrigo E. Mendes, Mariana Castanheira
Summary: We evaluated the in vitro activity of ceftibuten-avibactam against Enterobacterales causing urinary tract infection (UTI). The results showed that ceftibuten-avibactam exhibited high activity against a large collection of multidrug-resistant Enterobacterales isolated from patients with UTI, making it a valuable option for oral treatment of UTI caused by multidrug-resistant Enterobacterales.
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Helio S. Sader, Mariana Castanheira, John H. Kimbrough, Valerie Kantro, Rodrigo E. Mendes
Summary: This study evaluated the in vitro activity of aztreonam/avibactam and comparators against carbapenem-resistant Enterobacterales. The results showed that aztreonam/avibactam exhibited high inhibitory activity against most isolates, including those resistant to ceftazidime/avibactam. Additionally, aztreonam/avibactam retained activity against isolates producing MBL and/or OXA-48-like enzymes, supporting its development as a treatment for infections caused by carbapenem-resistant Enterobacterales, including MBL producers.
JAC-ANTIMICROBIAL RESISTANCE
(2023)
Article
Oncology
M. A. Pfaller, R. E. Mendes, H. S. Sader, M. Castanheira, C. G. Carvalhaes
Summary: Oritavancin demonstrated potent activity against clinically relevant Gram-positive pathogens in European hospitals, with minimal differences in minimum inhibitory concentration (MIC) values and varying resistance phenotypes between Eastern and Western Europe.
JOURNAL OF CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Cecilia G. Carvalhaes, Helio S. Sader, Jennifer M. Streit, Rodrigo E. Mendes
Summary: The study evaluated the activity and resistance of tedizolid against different bacteria. The results showed that tedizolid exhibited good antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus group, without any resistance trends.
JAC-ANTIMICROBIAL RESISTANCE
(2022)
Article
Infectious Diseases
Mariana Castanheira, Lalitagauri M. Deshpande, Rodrigo E. Mendes, Timothy B. Doyle, Helio S. Sader
Summary: The study found that Klebsiella pneumoniae serine carbapenemase (KPC) production was the most common resistance mechanism among carbapenem-nonsusceptible Enterobacterales (CNSE) clinical isolates collected in US hospitals during a 5-year period. Ceftazidime/avibactam showed high activity against all carbapenemase groups except for metallo-beta-lactamase (MBL)-producing isolates.
JAC-ANTIMICROBIAL RESISTANCE
(2022)