Article
Infectious Diseases
Tetsushu Onita, Kazuro Ikawa, Noriyuki Ishihara, Hiroki Tamaki, Takahisa Yano, Kohji Naora, Norifumi Morikawa
Summary: This study evaluated the dosing regimens of ampicillin/sulbactam for pneumonia by using pulmonary pharmacokinetic/pharmacodynamic (PK/PD) target attainment. The PK/PD targets in lung tissue were defined based on the time above the minimum inhibitory concentration (MIC) of antibiotics. The study found that the selection of ampicillin/sulbactam regimens for pneumonia should consider the specific bacteria causing the infection and evaluate the PK/PD in lung tissue rather than in the blood.
Article
Microbiology
Varsha Naidu, Bhumika Shah, Karthik S. Kamath, Arthur Chien, Stephanie Nagy, Alaska Pokhrel, Mark Molloy, Karl A. Hassan, Ian T. Paulsen
Summary: The study identified a new gene, aciT, in Acinetobacter baumannii strain AB5075-UW that confers tolerance to ciprofloxacin by promoting filamentation. The disruption of aciT gene increased susceptibility to ciprofloxacin, while complementation restored tolerance levels. Orthologs of aciT are widely conserved in Acinetobacter species, indicating its importance in antibiotic response.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Immunology
John P. O'Donnell, Sujata M. Bhavnani
Summary: Sulbactam-durlobactam is a combination of beta-lactam and beta-lactamase inhibitor that is being developed for the treatment of Acinetobacter infections, including multidrug-resistant strains. Sulbactam has intrinsic antibacterial activity against Acinetobacter, but its effectiveness has been reduced by increasing beta-lactamase-mediated resistance. Durlobactam, a rationally designed beta-lactamase inhibitor, effectively restores susceptibility to resistant isolates when combined with sulbactam. This review discusses the pharmacokinetic/pharmacodynamic relationship of the combination in nonclinical infection models and aids in determining effective dose regimens for humans.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Microbiology
Patricia Koenig, Alexander Wilhelm, Christoph Schaudinn, Anja Poehlein, Rolf Daniel, Marek Widera, Beate Averhoff, Volker Mueller
Summary: In this study, a new survival strategy of Acinetobacter baumannii, called viable but non-culturable (VBNC) state, was identified. This state allows the bacteria to survive under unfavorable conditions and evade classical detection methods, thereby impacting the detection and recurring infections of A. baumannii.
Review
Pharmacology & Pharmacy
J. Nicholas O'Donnell, Vibert Putra, Thomas P. Lodise
Summary: Treatment of patients with carbapenem-resistant Acinetobacter baumannii infections remains challenging, with limited viable treatment options and significant risk of nephrotoxicity associated with polymyxin therapy. New agents with clinically relevant activity against CRAB isolates and favorable toxicity profiles are urgently needed to address this urgent threat pathogen.
Review
Immunology
Chunli Sun, Yunsong Yu, Xiaoting Hua
Summary: Acinetobacter baumannii is a common pathogen causing various infectious diseases and has a high drug resistance rate, severely limiting antibiotic treatment options. Tigecycline and polymyxins are considered the last line of defense against multidrug resistant A. baumannii. This review focuses on the mechanisms of tigecycline resistance in A. baumannii and highlights the need for further investigation and development of new antibiotics.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Editorial Material
Microbiology
Santiago Castillo-Ramirez
Summary: A recent study published in mBio sequenced the genomes of 313 carbapenem-resistant A. baumannii isolates from over 100 hospitals in almost 50 countries, providing an updated view of the global distribution of major international clones and their carbapenemase genes. Future global genomic epidemiology studies can be enhanced by considering both human and non-human isolates and their antibiotic resistance profiles.
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.
Review
Biochemistry & Molecular Biology
Meysam Sarshar, Daniela Scribano, Anna Teresa Palamara, Cecilia Ambrosi, Andrea Masotti
Summary: Research on bacterial small RNAs (sRNAs) has been accelerated due to advances in RNA-seq technologies. These regulatory sRNAs play important roles in controlling physiological processes and surviving antimicrobial challenges. Secreted RNAs from bacterial pathogens have gained attention, especially in the context of infection. This review discusses how secreted sRNAs interact with targets in infected cells, providing a novel perspective on host cell manipulation during bacterial infection. Recent findings on sRNA regulation in A. baumannii are also summarized, highlighting the role of sRNAs in its adaptation and pathogenicity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Infectious Diseases
A. R. Noel, M. Attwood, K. E. Bowker, A. P. MacGowan
Summary: Pre-clinical pharmacodynamics of omadacycline against Escherichia coli and Acinetobacter baumannii were studied in vitro, showing varying effects on the two pathogens at different fAUC/MIC ratios.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Jinxin Zhao, Yan Zhu, Mei-Ling Han, Jing Lu, Heidi H. Yu, Hasini Wickremasinghe, Qi Tony Zhou, Phillip Bergen, Gauri Rao, Tony Velkov, Yu-Wei Lin, Jian Li
Summary: This study investigated the antimicrobial synergy of polymyxin/rifampicin combination against multidrug-resistant Acinetobacter baumannii. Results showed that the combination of polymyxin B and rifampicin effectively inhibited the growth of A. baumannii and prevented bacterial regrowth within 48 hours. This finding suggests that this combination therapy may be a promising option for treating bloodstream and tissue infections caused by multidrug-resistant A. baumannii.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Microbiology
Greater Kayode Oyejobi, Sunday Olabode Olaniyan, Nana-Aishat Yusuf, Deborah Adepeju Ojewande, Mobolaji Johnson Awopetu, Goodness Opeyemi Oyeniran, Fazal Mehmood Khan, Peter Alabi Dare, Maryam Kikelomo Adegbite-Badmus
Summary: Acinetobacter baumannii is an important nosocomial and opportunistic pathogen with high antibiotic resistance. New treatment approaches like the use of bacteriophage, phage-antibiotic combinations, and resistance-driven fitness losses are crucial for controlling its infections.
MICROBIOLOGICAL RESEARCH
(2022)
Article
Chemistry, Medicinal
Keith D. Green, Nishad Thamban Chandrika, Loan Y. Vu, Allan H. Pang, Oleg V. Tsodikov, Sylvie Garneau-Tsodikova
Summary: The emergence of multidrug-resistant bacteria and the poor efficacy of available antibiotics have led to the urgent need for novel antibiotics. In this study, we synthesized a series of 46 aromatic hydrazides as potential treatments for A. baumannii infections. 34 compounds showed low-to sub-mu M inhibitory effects on A. baumannii growth and demonstrated high potency against multidrug-resistant clinical isolates, while being non-toxic to mammalian cells. These compounds have the potential to be developed into a selective anti-A. baumannii antibiotic.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Aminul Islam, Luis A. Actis, Timothy J. Wilson
Summary: This study reveals that natural antibodies (NAbs) enhance the host's immune response against A. baumannii infection, potentially leading to the development of effective therapies for human infections caused by antibiotic-resistant A. baumannii.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Alan R. Noel, Marie Attwood, Karen E. Bowker, Alasdair P. MacGowan, Maha Albur
Summary: Study reveals that different sub-classes of beta-lactams have varying antibacterial effects against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Iain J. Abbott, Elke van Gorp, Kelly L. Wyres, Steven C. Wallis, Jason A. Roberts, Joseph Meletiadis, Anton Y. Peleg
Summary: The effectiveness of oral fosfomycin in treating urinary tract infections caused by non-Escherichia coli uropathogens, including Klebsiella pneumoniae, is uncertain.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Cardiac & Cardiovascular Systems
Bradley J. Gardiner, Sue J. Lee, Allisa N. Robertson, Yvonne Cristiano, Gregory I. Snell, C. Orla Morrissey, Anton Y. Peleg, Glen P. Westall
Summary: This study reviewed the application of Quantiferon-Cytomegalovirus (QF-CMV) testing in lung transplant recipients and found a strong correlation between QF-CMV results and serostatus. D+/R- patients were unlikely to test positive while receiving prophylaxis. Extended prophylaxis was associated with delayed, reduced, and milder CMV infection. However, the incremental predictive value of QF-CMV was limited after accounting for serostatus.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Genetics & Heredity
Mohammad Hamidian, Ram P. Maharjan, Daniel N. Farrugia, Natasha N. Delgado, Hue Dinh, Francesca L. Short, Xenia Kostoulias, Anton Y. Peleg, Ian T. Paulsen, Amy K. Cain
Summary: This study reports the complete genome sequences of six diverse environmental strains of A. baumannii and reveals their similar virulence potential to nosocomial strains but greater sensitivity to antibiotics.
MICROBIAL GENOMICS
(2022)
Review
Infectious Diseases
Kelly A. Cairns, Iain J. Abbott, Michael J. Dooley, Anton Y. Peleg, Trisha N. Peel, Andrew A. Udy
Summary: This study aimed to determine whether daptomycin therapeutic drug monitoring (TDM), including dose adjustment, improves the clinical outcomes of adult patients with Gram-positive infections. A systematic review found no studies exploring the efficacy of routine daptomycin TDM in comparison with fixed dosing regimens. Further well-designed, comparative studies are needed to determine the role of daptomycin TDM in patients with Gram-positive infections.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Infectious Diseases
Iain J. Abbott, Elke van Gorp, Hugh Cottingham, Nenad Macesic, Steven C. Wallis, Jason A. Roberts, Joseph Meletiadis, Anton Y. Peleg
Summary: The study found that high-dose oral ciprofloxacin therapy (750 mg 12 hourly) has good antibacterial activity against ceftriaxone-resistant Escherichia coli, especially with ciprofloxacin MIC <= 1 mg/L.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Review
Microbiology
Kelly A. Cairns, Andrew A. Udy, Trisha N. Peel, Iain J. Abbott, Michael J. Dooley, Anton Y. Peleg
Summary: Vancomycin-resistant enterococci (VRE) are a common cause of bloodstream infections (BSIs) with high morbidity and mortality rates. The management of VRE BSI presents significant challenges, including drug dosing, resistance emergence, and optimal treatment strategies. Therapeutic drug monitoring (TDM) shows promise in predicting drug toxicity for VRE-active agents, but there is limited evidence for predicting antimicrobial efficacy for VRE BSIs. This article provides an overview of treatment options, the role of TDM in clinical infection management, and future challenges and perspectives.
CLINICAL MICROBIOLOGY REVIEWS
(2023)
Article
Microbiology
Micaela Mossop, Luca Robinson, Jhih-Hang Jiang, Anton Y. Peleg, Luke Blakeway, Nenad Macesic, Audrey Perry, Stephen Bourke, Fatima R. Ulhuq, Tracy Palmer
Summary: One third of CF patients in the UK are co-infected with both Staphylococcus aureus and Pseudomonas aeruginosa, which contribute to lung tissue destruction and respiratory failure. This study aims to characterize twenty-five clinical S. aureus isolates from CF patients, including those with mono- and coinfection with P. aeruginosa, using molecular and phenotypic tools.
JOURNAL OF MEDICAL MICROBIOLOGY
(2023)
Article
Pathology
Xenia Kostoulias, Christina C. Chang, Jessica Wisniewski, Iain J. Abbott, Helen Zisis, Amanda Dennison, Denis W. Spelman, Anton Y. Peleg
Summary: We investigated the effectiveness of ceftolozane-tazobactam (C/T) in a high-risk population for antimicrobial resistance, specifically patients with cystic fibrosis (CF) and lung transplantation (LTx). Out of 163 clinical Pseudomonas aeruginosa isolates collected from a tertiary hospital in Melbourne, Australia, 81.6% were susceptible to C/T. Among the multidrug resistant (MDR) and extensively drug resistant (XDR) isolates, C/T showed susceptibility in 88.3% and 28.1% of cases, respectively. In conclusion, C/T maintained its activity against a significant portion of MDR and XDR P. aeruginosa isolates from CF and post-LTx patients.
Article
Computer Science, Interdisciplinary Applications
Yashpal Ramakrishnaiah, Nenad Macesic, Geoffrey I. Webb, Anton Y. Peleg, Sonika Tyagi
Summary: The adoption of electronic health records (EHRs) has created opportunities for predicting clinical outcomes and improving patient care. However, non-standardized data representations and anomalies present major challenges in digital health research. To address these challenges, we have developed EHR-QC, a tool with two modules: data standardization and preprocessing. We believe that the development and adoption of tools like EHR-QC are critical for advancing digital health.
JOURNAL OF BIOMEDICAL INFORMATICS
(2023)
Article
Microbiology
Yue Qu, David McGiffin, Lina Duque Sanchez, Thomas Gengenbach, Chris Easton, Helmut Thissen, Anton Y. Peleg
Summary: This study comprehensively assessed the anti-biofilm capability of the Carbothane driveline against leading microorganisms causing VAD driveline infections and explored its physicochemical characteristics. The Carbothane driveline demonstrated anti-biofilm activity, and the surface characteristics may explain its ability to inhibit biofilm formation.
Review
Microbiology
Jhih-Hang Jiang, David R. Cameron, Cara Nethercott, Marta Aires-de-Sousa, Anton Y. Peleg
Summary: This review focuses on the mechanisms that trigger the establishment and maintenance of current, dominant MRSA lineages across the globe. Factors that influence MRSA's ability to colonize and cause disease within a host are discussed, with an emphasis on colonization and niche adaptation. Understanding these mechanisms may lead to the development of targeted therapies.
CLINICAL MICROBIOLOGY REVIEWS
(2023)
