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Ali I, Hasan SZ, Garcia H, Bentalib A, Imanova G. Modeling of the Adsorption of Tigecycline from Water on CoFe 2O 4-Graphene Nanocomposites. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2024. [PMID: 39565711 DOI: 10.1021/acs.langmuir.4c03516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2024]
Abstract
A CoFe2O4(11.04%)-graphene (5.45%) nanocomposite was synthesized and characterized by spectroscopic techniques. This nanocomposite was used to eliminate tigecycline antibiotics from the water. The adsorbent showed 160.0 mg/g adsorption capacity of tigecycline antibiotic at 175 mg/L tigecycline, 0.75 g/L dose, 100 min of contact time, and a temperature of 25 °C. One-, two-, and three-parameter models were applied, i.e., Henry, Langmuir, Freundlich, D-R, Temkin, Flory-Huggins, Halsey, Jovanovich, Redlich-Peterson, and Sips models. According to statistical data, Langmuir and Sips models were the best fitted. The adsorption was spontaneous thermodynamically following pseudo-second-order kinetics. The adsorption occurred via a combination of intraparticle diffusion and external mass transfer mechanisms. The supramolecular mechanism showed the adsorption of the tigecycline antibiotic via coordination and π-π stacking bonds. The characterization results showed that the average nanoparticle size obtained was 91.45 nm. The removal efficiency of the adsorbent reduced up to the fifth cycle and later became constant at 50%. Hence, CoFe2O4-graphene nanocomposites propose a highly effective and recyclable solution for water treatment through adsorption, and hence, this method may be used to remove tigecycline antibiotics from water bodies.
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Affiliation(s)
- Imran Ali
- Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Sayed Zenab Hasan
- Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Hermenegildo Garcia
- Instituto Universitario de Tecnología Química CSIC-UPV, Universidad Politécnica de Valencia, Av. De los Naranjos s/n, 46022 Valencia, Spain
| | - Abdulaziz Bentalib
- Department of Chemical Engineering, College of Engineering, King Saud University, P.O. Box 800, Riyadh 11421, Saudi Arabia
| | - Gunel Imanova
- Institute of Radiation Problems, Ministry of Science and Education Republic of Azerbaijan, 9 B.Vahabzade Str., Baku AZ-1143, Azerbaijan
- Department of Physics and Electronics, Khazar University, 41 Mahsati Str., Baku AZ-1096, Azerbaijan
- Western Caspian University, Baku AZ-1001, Azerbaijan
- UNEC Research Center for Sustainable Development and Green Economy named after Nizami Ganjavi, Azerbaijan State University of Economics (UNEC), 6 Istiglaliyyat Str., Baku AZ-1001, Azerbaijan
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Zhong FL, He JJ, Bai KH, Shao RN, Wu GY, Tian XP, Wang DW, Dai YJ, Chen SL. Tigecycline-induced coagulation gene prognostic prediction model and intestinal flora signature in AML. Front Immunol 2024; 15:1486592. [PMID: 39611150 PMCID: PMC11602473 DOI: 10.3389/fimmu.2024.1486592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 10/21/2024] [Indexed: 11/30/2024] Open
Abstract
Infection is among the most common causes of death in patients with acute myeloid leukemia (AML) after chemotherapy. The anti-tumor effect of the intestinal microbiota in patients with AML is increasingly being recognized. Tigecycline, a broad-spectrum antibiotics, plays a vital role in the anti-infection treatment of AML patients with neutropenia and accompanying infections. Previously, this group reported that long-term use of tigecycline caused coagulation dysfunction in patients with hematological malignancies, increasing the risk of casualties. RNA sequencing was performed on CHO cells before and after tigecycline treatment. Further, the combined analysis of AML prognostic differentially expressed genes revealed 13 genes affected by tigecycline and closely related to AML prognosis. These genes were used for modeling analysis, and the results showed that the prepared model significantly improved the prognostic prediction efficiency for AML patients. The model also explored the correlation between prognosis score and immune cells infiltrating tumors and immune therapy targets. Moreover, 16S sequencing was performed on fecal samples from AML patients before and after tigecycline treatment. The results revealed that tigecycline significantly altered the distribution of intestinal microbiota in AML patients - These changes in microbiota are related to chemotherapy resistance. This study emphasizes the importance of intestinal microbiota in AML prognosis. Thus, the findings of this study show that the long-term use of antibiotics can not only cause dysbiosis of the intestinal microbiota but also indirectly affect the sensitivity of chemotherapy drugs, affecting the prognosis of AML patients.
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Affiliation(s)
- Feng-Luan Zhong
- Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Jia-Jun He
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Kun-Hao Bai
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ruo-Nan Shao
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Guo-Yan Wu
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiao-Peng Tian
- Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Da-Wei Wang
- National Research Center for Translational Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu-Jun Dai
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Si-Liang Chen
- Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
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Dettlaff K, Guzińska J, Klimaszewska M, Dominiak K, Jelińska A. Intravenous tigecycline with selected multichamber bag parenteral nutrition: A compatibility study. JPEN J Parenter Enteral Nutr 2024; 48:990-997. [PMID: 39257207 DOI: 10.1002/jpen.2683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/20/2024] [Accepted: 08/20/2024] [Indexed: 09/12/2024]
Abstract
BACKGROUND Tigecycline is widely used to treat infections in intensive care units. Drugs often need to be delivered to critically ill patients feeding by parenteral nutrition (PN). Before two preparations are administered in the same infusion line, the safety of this combination should be established. The objective of this study was to determine the compatibility of tigecycline with selected multichamber bag PN (MCB-PN). METHODS Tigecycline was diluted in 0.9% sodium chloride solution and 5% glucose solution to obtain two 0.5 mg/ml solutions. Then the solutions were combined with selected MCB-PN in appropriate proportions. The samples were visually assessed, and pH, osmolality, turbidity, particle size, and zeta potential were measured. These measurements were made immediately after combining the solutions and after 4 h of storage at 23°C ± 1°C. RESULTS It was determined that the pH values of the mixtures after combining with tigecycline changed by ≤0.1 unit. An increase in zeta potential was recorded, excluding one combination of tigecycline with the mixture. For all samples tested, the particle size distribution was within the acceptable range immediately after combination and after 4 h of storage. The difference in osmolality did not exceed ±3%, whereas the zeta potential decreased for only one combination. The turbidity of none of the samples exceeded a critical value. CONCLUSION The physical compatibility of the tigecycline with five MCB-PN was proved. They can therefore be administered to patients in one infusion line using the Y-site.
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Affiliation(s)
- Katarzyna Dettlaff
- Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical, Sciences, Poznań, Poland
| | - Julia Guzińska
- Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical, Sciences, Poznań, Poland
| | - Marta Klimaszewska
- Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical, Sciences, Poznań, Poland
| | - Katarzyna Dominiak
- Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical, Sciences, Poznań, Poland
| | - Anna Jelińska
- Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical, Sciences, Poznań, Poland
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Zhang Y, Guo D, Zhu Y, Liu L. Inhibition of mitochondrial function by approved drugs overcomes nasopharyngeal carcinoma chemoresistance. Anticancer Drugs 2024; 35:317-324. [PMID: 38215016 DOI: 10.1097/cad.0000000000001566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2024]
Abstract
The development of chemo-resistance in nasopharyngeal carcinoma (NPC) presents a significant therapeutic challenge, and its underlying mechanisms remain poorly understood. In our previous studies, we highlighted the association between isoprenylcysteine carboxylmethyltransferase (ICMT) and chemoresistance in NPC. In this current research, we revealed that both 5-FU and cisplatin-resistant NPC cells exhibited elevated mitochondrial function and increased expression of mitochondrial genes, independent of ICMT. Our investigations further showed that classic mitochondrial inhibitors, such as oligomycin, antimycin, and rotenone, were notably more effective in reducing viability in chemo-resistant NPC cells compared to parental cells. Moreover, we identified two antimicrobial drugs, tigecycline and atovaquone, recognized as mitochondrial inhibitors, as potent agents for decreasing chemo-resistant NPC cells by targeting mitochondrial respiration. Remarkably, tigecycline and atovaquone, administered at tolerable doses, inhibited chemo-resistant NPC growth in mouse models and extended overall survival rates. This work unveils the efficacy of mitochondrial inhibition as a promising strategy to overcome chemo-resistance in NPC. Additionally, our findings highlight the potential repurposing of clinically available drugs like tigecycline and atovaquone for treating NPC patients who develop chemoresistance.
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Affiliation(s)
- Yunlong Zhang
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Yangtze University
| | - Difeng Guo
- Department of Oncology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei Province, China
| | - Yongbo Zhu
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Yangtze University
| | - Lin Liu
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Yangtze University
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Firat O, Kara E, Malkan ÜY, Demirkan K, Inkaya AÇ. Tigecycline-associated hypofibrinogenemia: A single center, retrospective, controlled study. Thromb Res 2024; 236:155-160. [PMID: 38452447 DOI: 10.1016/j.thromres.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/27/2024] [Accepted: 03/04/2024] [Indexed: 03/09/2024]
Abstract
BACKGROUND Tigecycline-associated hypofibrinogenemia has been reported as an important adverse effect in recent years, but controlled studies minimizing confounding factors are needed. The objective of our study was to assess changes in fibrinogen levels in patients for hospitalization, comparing two antibiotic episodes (tigecycline and other) within the same patients. METHODS The retrospective, self-controlled case series study was conducted at our University Hospitals. The study compared the change in fibrinogen levels during the patient's hospitalization for tigecycline (TigePer) and another antibiotic period (OtherPer). In addition, bleeding events, bleeding risk (determined by the IMPROVE bleeding risk score), as well as 15- and 30-day mortality rates between TigePer and OtherPer were compared. RESULTS The study enrolled 50 patients with 100 episodes of antibiotic treatment. The median age (interquartile range) of the patients was 68.5 (21.5) years, and 38 % were female. As compared to OtherPer, TigePer had a statistically significant reduction in fibrinogen levels (p < 0.001), with a hypofibrinogenemia rate of 40 % in TigePer as compared to 2 % in OtherPer (p < 0.001). TigePer demonstrated a significantly higher 15-day mortality rate (p = 0.006). No significant differences were observed between the two periods in terms of bleeding risk, rate of bleeding events, and 30-day mortality rate (p > 0.05). CONCLUSION Hypofibrinogenemia and other coagulopathies, without associated bleeding events, are more frequently observed in patients receiving tigecycline. Therefore, it is crucial for clinicians to monitor fibrinogen levels during tigecycline use.
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Affiliation(s)
- Oğuzhan Firat
- Hacettepe University, Faculty of Pharmacy, Department of Clinical Pharmacy, Ankara, Turkiye.
| | - Emre Kara
- Hacettepe University, Faculty of Pharmacy, Department of Clinical Pharmacy, Ankara, Turkiye
| | - Ümit Yavuz Malkan
- Hacettepe University Faculty of Medicine, Department of Internal Diseases, Hematology Subdivision, Ankara, Turkiye
| | - Kutay Demirkan
- Hacettepe University, Faculty of Pharmacy, Department of Clinical Pharmacy, Ankara, Turkiye.
| | - Ahmet Çağkan Inkaya
- Hacettepe University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkiye
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Lan X, Qin S, Liu H, Guo M, Zhang Y, Jin X, Duan X, Sun M, Liu Z, Wang W, Zheng Q, Liao X, Chen J, Kang Y, Xie Y, Song X. Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii. J Nanobiotechnology 2024; 22:138. [PMID: 38555444 PMCID: PMC10981309 DOI: 10.1186/s12951-024-02373-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 02/26/2024] [Indexed: 04/02/2024] Open
Abstract
Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we prepared a novel core-shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aβ11 and Tween 80 (Aβ11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.
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Affiliation(s)
- Xing Lan
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
- State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, People's Republic of China
| | - Shugang Qin
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Huan Liu
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Mengran Guo
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Yupei Zhang
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Xinyang Jin
- School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau, China
- Shihezi University, Xinjiang, China
| | - Xing Duan
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Min Sun
- School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau, China
- Shihezi University, Xinjiang, China
| | - Zhenjun Liu
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Wenyan Wang
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Qian Zheng
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Xuelian Liao
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - Jinpeng Chen
- State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, People's Republic of China
| | - Yan Kang
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China.
| | - Yongmei Xie
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China.
| | - Xiangrong Song
- Department of Critical Care Medicine, Department of Clinical Pharmacy, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China.
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Zhang S, Wen J, Wang Y, Zhong Z, Wang M, Jia R, Chen S, Liu M, Zhu D, Zhao X, Wu Y, Yang Q, Huang J, Ou X, Mao S, Gao Q, Sun D, Tian B, Cheng A. Decoding the enigma: unveiling the molecular transmission of avian-associated tet(X4)-positive E. coli in Sichuan Province, China. Poult Sci 2023; 102:103142. [PMID: 37879166 PMCID: PMC10618799 DOI: 10.1016/j.psj.2023.103142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 09/18/2023] [Accepted: 09/18/2023] [Indexed: 10/27/2023] Open
Abstract
Tigecycline is considered one of the "last resort antibiotics" for treating complex infections caused by multidrug-resistant (MDR) bacteria, especially for combating clinical resistant strains that produce carbapenemases. However, the tet(X4) gene, which carried by different plasmids can mediate high levels of bacterial resistance to tigecycline, was first reported in 2019. Here, we report the emergence of the plasmid-mediated tet(X4) in avian environment of Sichuan Province. A total of 21 tet(X4)-positive Escherichia coli (E. coli) strains were isolated and identified from avian samples in selected regions, with an isolation rate of 1.6% (21/1,286), and all of them were MDR strains. Multilocus Sequence Typing (MLST) method was used to classify the 21 tet(X4)-positive E. coli into the ST206, ST761, ST155, ST1638, ST542, and ST767 types, which also belong to the 3 phylogenetic subgroups A, B1, and C. Tet(X4) is located on mobile plasmids that can be efficiently and stably propagated. The results of fitness cost experiments showed that tet(X4)-positive plasmids may incur some fitness cost to host bacteria, but different tet(X4)-positive plasmids bring about differential fitness costs. Whole-genome sequencing further confirmed the tet(X4) gene can be located on IncX1-type plasmids and the core genetic structures are ISVsa3-rdmc-tet(X4) or rdmc-tet(X4)-ISVsa3, the former is a 7 copies tandem repeat structure. In this study, we isolated and identified tet(X4)-positive E. coli from the avian origin in Sichuan, analyzed the mobility of the tet(X4) by conjugational transfer and S1-PFGE, and evaluated the biological characteristics of the tet(X4)-positive plasmid using the results of conjugational frequency, plasmid stability, and fitness costs. Finally, combined with the third-generation whole-genome sequencing analysis, the molecular transmission characteristics of the tet(X4) were preliminarily clarified, providing a scientific basis for guiding veterinary clinical use in this area, as well as risk assessment and prevention of the transfer and spread of tigecycline resistant strains or genes.
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Affiliation(s)
- Shaqiu Zhang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Jinfeng Wen
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Yuwei Wang
- Mianyang Academy of Agricultural Sciences, Mianyang 621023, PR China
| | - Zhijun Zhong
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Mingshu Wang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Renyong Jia
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Shun Chen
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Mafeng Liu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Dekang Zhu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Xinxin Zhao
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Ying Wu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Qiao Yang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Juan Huang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Xumin Ou
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Sai Mao
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Qun Gao
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Di Sun
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Bin Tian
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China
| | - Anchun Cheng
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, PR China.
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Rakholiya B, Shah P, Patel Y, Patel G, Patel S, Patel A. A Review on Analytical Methods for Tigecycline Estimation From Its Bulk and Dosage Form. J AOAC Int 2023; 106:1689-1695. [PMID: 37676830 DOI: 10.1093/jaoacint/qsad099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 05/20/2023] [Accepted: 08/28/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Tigecycline (TIG) is a third-generation glycylcycline derivative used as an antimicrobial and anticancer agent for the past few years. Its intricate structure makes it more vulnerable toward degradation under the influence of various environmental factors and leads to the generation of impurities. Due to its stability issues, TIG is available as a lyophilized powder for injection. The analysis of TIG becomes a cumbersome task for analysts due to its instability in solution form. As TIG works as a life-saving drug, it is important to review its analytical methods for its quality control. OBJECTIVE The present review discusses various analytical methodologies for determining TIG from its bulk, lyophilized powder, pharmacopoeial methods and factors responsible for its instability. METHODS The present review represents the analysis of data reported in the literature from 1999-2022 for the analysis of TIG. RESULTS Numerous alternative analytical techniques such as UV-visible spectrophotometry, spectrofluorimetric methods, RP-HPLC (reversed-phase high-performance liquid chromatography) and FT-IR (Fourier transform infrared), and electrophoresis has been reported for quantification, identification, and characterization of TIG. CONCLUSIONS Several analytical techniques are available to be used as a quality control tool for tigecycline, including HPLC without derivatization, whereas the fluorescence technique requires derivatization using acidic dye. A few methods require tedious pre-sample preparation techniques, become time-consuming, and involve using one or more organic solvents; there is a need to develop eco-friendlier methods for analyzing tigecycline. HIGHLIGHTS Various analytical methods such as spectrometric, fluorimetric and chromatographic methods have been discussed for estimation of TIG from its bulk and different dosage form.
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Affiliation(s)
- Bansi Rakholiya
- Charotar University of Science and Technology, Department of Pharmaceutical Chemistry and Analysis, Ramanbhai Patel College of Pharmacy, CHARUSAT Campus, Changa, Petlad, Anand, Gujarat 388 421, India
| | - Priyangi Shah
- Charotar University of Science and Technology, Department of Pharmaceutical Chemistry and Analysis, Ramanbhai Patel College of Pharmacy, CHARUSAT Campus, Changa, Petlad, Anand, Gujarat 388 421, India
| | - Yash Patel
- Charotar University of Science and Technology, Department of Pharmaceutical Chemistry and Analysis, Ramanbhai Patel College of Pharmacy, CHARUSAT Campus, Changa, Petlad, Anand, Gujarat 388 421, India
| | - Gayatri Patel
- Charotar University of Science and Technology, Department of Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, CHARUSAT Campus, Changa, Petlad, Anand, Gujarat 388 421, India
| | - Samir Patel
- Charotar University of Science and Technology, Department of Pharmaceutical Chemistry and Analysis, Ramanbhai Patel College of Pharmacy, CHARUSAT Campus, Changa, Petlad, Anand, Gujarat 388 421, India
| | - Archita Patel
- Charotar University of Science and Technology, Department of Pharmaceutical Chemistry and Analysis, Ramanbhai Patel College of Pharmacy, CHARUSAT Campus, Changa, Petlad, Anand, Gujarat 388 421, India
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9
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Furlan JPR, Stehling EG. Predicting tigecycline susceptibility in multidrug-resistant Klebsiella species and Escherichia coli strains of environmental origin. Braz J Microbiol 2023; 54:1915-1921. [PMID: 37328679 PMCID: PMC10484842 DOI: 10.1007/s42770-023-01036-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 06/09/2023] [Indexed: 06/18/2023] Open
Abstract
Tigecycline (TGC) is an important antimicrobial agent used as a last resort for difficult-to-treat infections mainly caused by carbapenem-resistant Enterobacteriaceae, but TGC-resistant strains are emerging, raising concerns. In this study, 33 whole-genome characterized multidrug-resistant (MDR) strains (Klebsiella species and Escherichia coli) positive mainly to mcr-1, bla, and/or qnr from the environment were investigated for TGC susceptibility and mutations in TGC resistance determinants, predicting a genotype-phenotype relationship. TGC minimum inhibitory concentrations (MICs) of Klebsiella species and E. coli ranged from 0.25 to 8 and 0.125 to 0.5 mg/L, respectively. In this context, KPC-2-producing Klebsiella pneumoniae ST11 and Klebsiella quasipneumoniae subsp. quasipneumoniae ST4417 strains were resistant to TGC, while some E. coli strains of ST10 clonal complex positive for mcr-1 and/or blaCTX-M exhibited reduced susceptibility to this antimicrobial. Overall, neutral and deleterious mutations were shared among TGC-susceptible and TGC-resistant strains. A new frameshift mutation (Q16stop) in RamR was found in a K. quasipneumoniae strain and was associated with TGC resistance. Deleterious mutations in OqxR were identified in Klebsiella species and appear to be associated with decreased susceptibility to TGC. All E. coli strains were determined as susceptible, but multiple point mutations were identified, highlighting deleterious mutations in ErmY, WaaQ, EptB, and RfaE in strains exhibiting decreased susceptibility to TGC. These findings demonstrate that resistance to TGC is not widespread in environmental MDR strains and provide genomic insights about resistance and decreased susceptibility to TGC. From a One Health perspective, the monitoring of TGC susceptibility should be constant, improving the genotype-phenotype relationship and genetic basis.
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Affiliation(s)
- João Pedro Rueda Furlan
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Do Café, S/N, Ribeirão Preto, Monte Alegre, 14040-903, Brazil
| | - Eliana Guedes Stehling
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Do Café, S/N, Ribeirão Preto, Monte Alegre, 14040-903, Brazil.
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10
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Skinner AM, Petrella LA, Cheknis A, Johnson S. Antimicrobial susceptibility of Clostridioides difficile to omadacycline and comparator antimicrobials. J Antimicrob Chemother 2023; 78:1779-1784. [PMID: 37279600 DOI: 10.1093/jac/dkad170] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 05/11/2023] [Indexed: 06/08/2023] Open
Abstract
BACKGROUND Omadacycline is a novel aminomethylcycline tetracycline antimicrobial that was approved for the treatment of community-associated bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in 2018. Omadacycline has demonstrated a high degree of in vitro activity towards Clostridioides difficile and previous data have hypothesized that use of omadacycline for CABP or ABSSSI may decrease the risk of C. difficile infections. OBJECTIVES To compare the in vitro antimicrobial activity of omadacycline versus commonly used antimicrobials for the approved indications of use. METHODS We compared the antimicrobial activity of eight antimicrobials approved for CABP and ABSSSI against omadacycline by agar dilution on 200 clinically relevant contemporary C. difficile isolates representing local and national prevalent strain types. RESULTS The in vitro omadacycline geometric mean MIC was 0.07 mg/L. Ceftriaxone resistance was noted in >50% of all isolates tested. The epidemic strain group, identified as restriction endonuclease analysis (REA) group BI, was commonly resistant to azithromycin (92%), moxifloxacin (86%) and clindamycin (78%). REA group DH strains had an elevated trimethoprim/sulfamethoxazole geometric mean MIC of 17.30 mg/L compared with the geometric mean MIC of 8.14 mg/L noted in all other isolates. In the REA group BK isolates that had a doxycycline MIC of ≥2 mg/L, the omadacycline MIC was <0.5 mg/L. CONCLUSIONS Among 200 contemporary C. difficile isolates, there were no notable elevations in the in vitro omadacycline MIC, indicating a high level of activity towards C. difficile in comparison with commonly used antimicrobials for CABP and ABSSSI.
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Affiliation(s)
- Andrew M Skinner
- Department of Medicine, Loyola University Medical Center, Maywood, IL, USA
- Research Section, Infection Diseases Section, Edward Hines Jr. VA Hospital, Hines, IL, USA
| | - Laurica A Petrella
- Research Section, Infection Diseases Section, Edward Hines Jr. VA Hospital, Hines, IL, USA
| | - Adam Cheknis
- Research Section, Infection Diseases Section, Edward Hines Jr. VA Hospital, Hines, IL, USA
| | - Stuart Johnson
- Department of Medicine, Loyola University Medical Center, Maywood, IL, USA
- Research Section, Infection Diseases Section, Edward Hines Jr. VA Hospital, Hines, IL, USA
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11
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Zhuo J, Liang B, Zhang H, Chi Y, Cai Y. An overview of gram-negative bacteria with difficult-to-treat resistance: definition, prevalence, and treatment options. Expert Rev Anti Infect Ther 2023; 21:1203-1212. [PMID: 37811630 DOI: 10.1080/14787210.2023.2267765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 10/03/2023] [Indexed: 10/10/2023]
Abstract
INTRODUCTION Difficult-to-treat resistance (DTR) is a newly proposed resistance phenotype characterized by resistance to all first-line drugs. The emergence of DTR as a new resistance phenotype has significant implications for clinical practice. This new concept has the potential to be widely used instead of traditional phenotypes. AREAS COVERED This study carried out a detailed analysis about the definition, application, and evolution of various resistance phenotypes. We collected all the research articles on Gram-negative bacteria with difficult-to-treat resistance (GNB-DTR), analyzed the DTR in each region and each bacterial species. The advantages and doubts of DTR, the dilemma of GNB-DTR infections and the potential therapeutic strategies are summarized in the review. EXPERT OPINION Available studies show that the prevalence of GNB-DTR is not optimistic. Unlike traditional resistance phenotypes, DTR is more closely aligned with the clinical treatment perspective and can help with the prompt selection of an appropriate treatment plan. Currently, potential treatment options for GNB-DTR include a number of second-line drugs and novel antibiotics. However, the definition of first-line drugs is inherently dynamic. Therefore, the DTR concept based on first-line drugs needs to be continuously updated and refined, considering the emergence of new antibiotics, resistance characteristics, and pathogen prevalence in different regions.
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Affiliation(s)
- Jiaju Zhuo
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, China
| | - Beibei Liang
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, China
| | - Huan Zhang
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, China
| | - Yulong Chi
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, China
| | - Yun Cai
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, China
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12
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Zhang Y, Zhang J, Cai P, Lu Y, Sun RY, Cao MT, Xu XL, Webber MA, Jiang HX. IncHI1 plasmids are epidemic vectors that mediate transmission of tet(X4) in Escherichia coli isolated from China. Front Microbiol 2023; 14:1153139. [PMID: 37303808 PMCID: PMC10248516 DOI: 10.3389/fmicb.2023.1153139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 05/10/2023] [Indexed: 06/13/2023] Open
Abstract
Introduction This study aimed to investigate the genetic factors promoting widespread Q6 dissemination of tet(X4) between Escherichia coli and to characterize the genetic contexts of tet(X4). Methods We isolated E. coli from feces, water, soil and flies collected across a large-scale chicken farm in China in 2020. Antimicrobial susceptibility testing and PFGE typing were used to identify tigecycline resistance and assess clonal relationships among isolates. Plasmids present and genome sequences were analyzed by conjugation, S1 pulsed-field gel electrophoresis (PFGE), plasmid stability testing and whole-genome sequencing. Results A total of 204 tigecycline-resistant E. coli were isolated from 662 samples. Of these, we identified 165 tet(X4)-carrying E. coli and these strains exhibited a high degree of multidrug resistance. Based on the geographical location distribution of the sampled areas, number of samples in each area and isolation rate of tigecycline-resistant strains and tet(X4)-carrying isolates, 72 tet(X4)-positive isolates were selected for further investigation. Tigecycline resistance was shown to be mobile in 72 isolates and three types of tet(X4)-carrying plasmids were identified, they were IncHI1 (n = 67), IncX1 (n = 3) and pO111-like/IncFIA(HI1) (n = 2). The pO111-like/IncFIA(HI1) is a novel plasmid capable of transferring tet(X4). The transfer efficiency of IncHI1 plasmids was extremely high in most cases and IncHI1 plasmids were stable when transferred into common recipient strains. The genetic structures flanked by IS1, IS26 and ISCR2 containing tet(X4) were complex and varied in different plasmids. Discussion The widespread dissemination of tigecycline-resistant E. coli is a major threat to public health. This data suggests careful use of tetracycline on farms is important to limit spread of resistance to tigecycline. Multiple mobile elements carrying tet(X4) are in circulation with IncHI1 plasmids the dominant vector in this setting.
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Affiliation(s)
- Yan Zhang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Jie Zhang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Ping Cai
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Yang Lu
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Ruan-Yang Sun
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Meng-Tao Cao
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Xiao-Li Xu
- Instrumental Analysis and Research Center, South China Agricultural University, Guangzhou, China
| | | | - Hong-Xia Jiang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
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13
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Delroba K, Alaei M, Khalili H. Treatment options for infections caused by multidrug-resistant Gram-negative bacteria: a guide to good clinical practice. Future Microbiol 2023; 18:287-294. [PMID: 37140271 DOI: 10.2217/fmb-2022-0160] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2023] Open
Abstract
The rapid emergence of multidrug-resistant Gram-negative bacterial infections necessitates the development of new treatments or the repurposing of available antibiotics. Here, treatment options for treatment of these infections, recent guidelines and evidence are reviewed. Studies that included treatment options for infections caused by multidrug-resistant Gram-negative bacteria (Enterobacterales and nonfermenters), as well as extended-spectrum β-lactamase-producing and carbapenem-resistant bacteria, were considered. Potential agents for the treatment of these infections, considering type of microorganism, mechanism of resistant, source and severity of infection as well as pharmacotherapy considerations, are summarized.
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Affiliation(s)
- Khadijeh Delroba
- Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Maryam Alaei
- Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Hossein Khalili
- Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
- Research Center for Antibiotic Stewardship & Antimicrobial Resistance, Imam Khomeini Hospital, Tehran, 1417614411, Iran
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14
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Zhou H, Sun X, Lyu S, Yu X, Li R, Wang H, An Z. Evaluation of Tigecycline Utilization and Trends in Antibacterial Resistance from 2018 to 2021 in a Comprehensive Teaching Hospital in China. Infect Drug Resist 2023; 16:879-889. [PMID: 36820081 PMCID: PMC9938701 DOI: 10.2147/idr.s395158] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 02/03/2023] [Indexed: 02/16/2023] Open
Abstract
Purpose Tigecycline, the first glycylcycline antibiotic, which was widely used for off-label indications because of its broad-spectrum antibacterial activity. This study evaluated the indications for clinical use of tigecycline, clinical and microbiological effectiveness, factors associated with in hospital mortality, and bacterial resistance. Methods This retrospective study evaluated all inpatients who received tigecycline treatment for >72 hours between January 2018 and December 2021 in a comprehensive teaching hospital in China. The evaluation included indications, administration regimen, etiology, efficacy and so on. Univariate and multivariate analyses were used to evaluate the risk factors for all-cause mortality. Results There were 203 patients treated with tigecycline. Tigecycline was commonly prescribed for off-label indications (83.25%, 169/203), and hospital-acquired pneumonia ranked first (79.29%, 134/169). The most common pathogen was Acinetobacter baumannii. Clinical and microbiological success was 57.14% (116/203) and 32.28% (41/127), respectively. Fifty-four patients died and all-cause mortality was 26.60%. Univariate and multivariate analyses showed no significant difference in age, gender, off-label indication, duration of treatment, combination with other drugs, multidrug-resistant or extensively drug-resistant infections and tigecycline application scoring with respect to mortality. Conclusion Although detection of A. baumannii has decreased in the past 4 years in our hospital, resistance to tigecycline has increased. For clinical application, physicians attach importance to detection of pathogenic microorganisms, but there is still empirical medication without bacterial culture reports. Therefore, an antibiotic stewardship program oriented toward tigecycline should be strengthened to curb bacterial resistance.
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Affiliation(s)
- Hong Zhou
- Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Xiangyu Sun
- Drug and Equipment Department, Beijing Chaoyang Emergency Medical Rescuing Center, Beijing, People’s Republic of China
| | - Shaocheng Lyu
- Department of Hepatobiliary Surgery, Beijing Chao Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Xiaojia Yu
- Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Ran Li
- Department of Infectious Diseases and Clinical Microbiology, Capital Medical University, Beijing, People’s Republic of China
| | - Huaguang Wang
- Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China,Correspondence: Huaguang Wang; Zhuoling An, Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email ;
| | - Zhuoling An
- Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
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15
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Lin X, Liu X, Wu X, Xie X, Liu G, Wu J, Peng W, Wang R, Chen J, Huang H. Wide-spectrum antibiotic prophylaxis guarantees optimal outcomes in drowned donor kidney transplantation. Expert Rev Anti Infect Ther 2023; 21:203-211. [PMID: 36573685 DOI: 10.1080/14787210.2023.2163237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Drowned victims possibly obtain various pathogens from drowning sites. Using drowned renal donors to expand the donor pool still lacks consensus due to the potential risk of disease transmission. RESEARCH DESIGN AND METHODS This retrospective study enrolled 38 drowned donor renal recipients in a large clinical center from August 2012 to February 2021. A 1:2 matched cohort was generated with donor demographics, including age, gender, BMI, and ICU durations. Donor microbiological results, recipient perioperative infections, and early post-transplant and first-year clinical outcomes were analyzed. RESULTS Compared to the control group, drowned donors had significantly increased positive fungal cultures (36.84% vs.13.15%, p = 0.039). Recipients in the drowned group had significantly higher rates of gram-negative bacteria (GNB) and multidrug-resistant GNB infections (23.68% vs.5.26%, 18.42% vs. 3.95%, both p < 0.05). Other colonization and infections were also numerically more frequent in the drowned group. Drowned donor recipients receiving inadequate antibiotic prophylaxis had more perioperative bloodstream infections, higher DGF incidences, and more first-year respiratory tract infections and recipient loss than those receiving adequate prophylaxis (all p < 0.05). Clinical outcomes were similar between the adequate group and the control group. CONCLUSIONS Drowned donors could be suitable options under wide-spectrum and adequate antimicrobial prophylaxis.
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Affiliation(s)
- Xiaoli Lin
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
| | - Xinyu Liu
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
| | - Xiaoying Wu
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
| | - Xishao Xie
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
| | - Guangjun Liu
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
| | - Jianyong Wu
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
| | - Wenhan Peng
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
| | - Rending Wang
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
| | - Jianghua Chen
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
| | - Hongfeng Huang
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.,Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China.,Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.,Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Zhejiang, China
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16
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Current and Emerging Treatment Options for Multidrug Resistant Escherichia coli Urosepsis: A Review. Antibiotics (Basel) 2022; 11:antibiotics11121821. [PMID: 36551478 PMCID: PMC9774639 DOI: 10.3390/antibiotics11121821] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/13/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
Escherichia coli is a versatile commensal and pathogenic member of the human microflora. As the primary causative pathogen in urosepsis, E. coli places an immense burden on healthcare systems worldwide. To further exacerbate the issue, multi drug resistance (MDR) has spread rapidly through E. coli populations, making infections more troublesome and costlier to treat. This paper aimed to review the literature concerning the development of MDR in uropathogenic E. coli (UPEC) and explore the existing evidence of current and emerging treatment strategies. While some MDR strains maybe treated with β-lactam-β-lactamase inhibitor combinations as well as cephalosporins, cephamycin, temocillin and fosfomycin, current treatment strategies for many MDR UPEC strains are reliant on carbapenems. Carbapenem overreliance may contribute to the alarming dissemination of carbapenem-resistance amongst some UPEC communities, which has ushered in a new age of difficult to treat infections. Alternative treatment options for carbapenem resistant UPEC may include novel β-lactam-β-lactamase or carbapenemase inhibitor combinations, cefiderocol, polymyxins, tigecycline, aminoglycosides or fosfomycin. For metallo-β-lactamase producing strains (e.g., NDM, IMP-4), combinations of cefazidime-avibacam with aztreonam have been used. Additionally, the emergence of new antimicrobials brings new hope to the treatment of such infections. However, continued research is required to successfully bring these into the clinic for the treatment of MDR E. coli urosepsis.
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17
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Du N, Mao EQ, Yang ZT, Qu HP, Qian X, Shi Y, Bian XL, He J, Chen EZ. Intrathecal or Intraventricular Tigecycline Therapy for Central Nervous System Infection Associated with Carbapenem-Resistant Klebsiella pneumoniae. Infect Drug Resist 2022; 15:7219-7226. [PMID: 36533251 PMCID: PMC9747839 DOI: 10.2147/idr.s387346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 12/02/2022] [Indexed: 09/21/2023] Open
Abstract
PURPOSE Infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great challenge. Central nervous system (CNS) infection caused by CRKP is rarely reported, and effective treatment is limited. Thus, this study aimed to assess intrathecal (IT) or intraventricular (IVT) injection of tigecycline for clearing infection with CRKP in CNS. PATIENTS AND METHODS Two patients who had intracranial infection with CRKP after craniotomy were treated in our institution and analyzed retrospectively, summarizing their therapeutic schedules. RESULTS They all had a fever with the positive results of cerebrospinal fluid (CSF) test, and CSF culture showed positive for CPKP, which was sensitive only to tigecycline. In addition, the MIC of polymyxin B was not tested due to the limited laboratory conditions. After IT or IVT injection of tigecycline treatment, the temperature of the patients became normal in 3 days, with normal levels of white blood cells, protein, glucose and chlorine concentrations in the CSF. Crucially, twice CSF cultures also became negative with no clinical symptoms of intracranial infection after IT or IVT injection of tigecycline treatment. Moreover, there were no adverse drug reactions observed. CONCLUSION IT or IVT injection of tigecycline may be a bright choice to control intracranial infection with CRKP.
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Affiliation(s)
- Ning Du
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of China
| | - En-Qiang Mao
- Emergency Intensive Care Unit, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Zhi-Tao Yang
- Emergency Intensive Care Unit, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Hong-Ping Qu
- Department of Critical Care Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Xian Qian
- Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China
| | - Ying Shi
- Department of Clinical Pharmacy, Shaoxing Hospital of Traditional Chinese Medicine, Zhejiang, People’s Republic of China
| | - Xiao-Lan Bian
- Department of Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Juan He
- Department of Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Er-Zhen Chen
- Emergency Intensive Care Unit, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
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Zhu L, Lian Y, Lin D, Lin G, Wang M. The profile and persistence of clinically critical antibiotic resistance genes and human pathogenic bacteria in manure-amended farmland soils. Front Cell Infect Microbiol 2022; 12:1073118. [PMID: 36506020 PMCID: PMC9729351 DOI: 10.3389/fcimb.2022.1073118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 11/01/2022] [Indexed: 11/25/2022] Open
Abstract
Introduction Microbial contamination in farmlands is usually underestimated and understudied. Different fertilization times and manure origins might introduce and change the microorganism diversity in farmland soils and thus might influence the abundance and persistence of microbial contamination including antibiotic resistance genes (ARGs), human bacterial pathogens (HBPs), and virulence factor genes (VFGs). Methods A 0.5-/1.5-year fertilization experiment was performed, and metagenomic sequencing was conducted to quantify microbial contamination. The resistomes of soil samples revealed that ARGs against antibiotics which were extensively used in veterinary medicine as well as clinically critical ARGs (CCARGs) persisted in manure-amended soils. Here the extended-spectrum beta-lactamase and carbapenemase bla genes, the high-level mobilized colistin resistance gene mcr, the tigecycline resistance gene tet(X), and the vancomycin resistance gene van, all of which can circumvent the defense line of these "last-resort" antibiotics were selected to investigate CCARG pollution in farm environments. Results A total of 254 potential HBPs and 2106 VFGs were detected in soil samples. Overall, our results revealed that (1) farmland soils could serve as a reservoir of some important bla, mcr, tet(X), and van gene variants, (2) the diversity and relative abundance of HBPs and VFGs increased significantly with incremental fertilization times and were discrepant among different manureamended soils, and (3) most CCARGs and VFGs coexisted in HBPs. Disscusion The results of this study suggested a biological risk of manure in spreading antimicrobial resistance and pathogenicity.
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Affiliation(s)
- Lin Zhu
- School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou, China
| | - Yulu Lian
- School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou, China
| | - Da Lin
- School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou, China
| | - Guoping Lin
- School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou, China
| | - Meizhen Wang
- School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou, China,Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, Hangzhou, China,*Correspondence: Meizhen Wang,
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Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro. Curr Issues Mol Biol 2022; 44:4639-4657. [PMID: 36286032 PMCID: PMC9600611 DOI: 10.3390/cimb44100317] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 09/17/2022] [Accepted: 09/22/2022] [Indexed: 11/22/2022] Open
Abstract
(1) Antibiotics are an important weapon in the fight against serious bacterial infections and are considered a common cause of drug-induced liver injury (DILI). The hepatotoxicity of many drugs, including antibiotics, is poorly analyzed in human in vitro models. (2) A standardized assay with a human hepatoma cell line was used to test the hepatotoxicity of various concentrations (Cmax, 5× Cmax, and 10× Cmax) of antibiotics. In an ICU, the most frequently prescribed antibiotics, ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, meropenem, rifampicin, tigecycline, and vancomycin, were incubated with HepG2/C3A cells for 6 days. Cell viability (XTT assay, LDH release, and vitality), albumin synthesis, and cytochrome 1A2 activity were determined in cells. (3) In vitro, vancomycin, rifampicin, and tigecycline showed moderate hepatotoxic potential. The antibiotics ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, and meropenem were associated with mild hepatotoxic reactions in test cells incubated with the testes Cmax concentration. Rifampicin and cefuroxime showed significantly negative effects on the viability of test cells. (4) Further in vitro studies and global pharmacovigilance reports should be conducted to reveal underlying mechanism of the hepatotoxic action of vancomycin, rifampicin, tigecycline, and cefuroxime, as well as the clinical relevance of these findings.
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Zhang S, Wen J, Wang Y, Wang M, Jia R, Chen S, Liu M, Zhu D, Zhao X, Wu Y, Yang Q, Huang J, Ou X, Mao S, Gao Q, Sun D, Tian B, Cheng A. Dissemination and prevalence of plasmid-mediated high-level tigecycline resistance gene tet (X4). Front Microbiol 2022; 13:969769. [PMID: 36246244 PMCID: PMC9557194 DOI: 10.3389/fmicb.2022.969769] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 09/05/2022] [Indexed: 11/20/2022] Open
Abstract
With the large-scale use of antibiotics, antibiotic resistant bacteria (ARB) continue to rise, and antibiotic resistance genes (ARGs) are regarded as emerging environmental pollutants. The new tetracycline-class antibiotic, tigecycline is the last resort for treating multidrug-resistant (MDR) bacteria. Plasmid-mediated horizontal transfer enables the sharing of genetic information among different bacteria. The tigecycline resistance gene tet(X) threatens the efficacy of tigecycline, and the adjacent ISCR2 or IS26 are often detected upstream and downstream of the tet(X) gene, which may play a crucial driving role in the transmission of the tet(X) gene. Since the first discovery of the plasmid-mediated high-level tigecycline resistance gene tet(X4) in China in 2019, the tet(X) genes, especially tet(X4), have been reported within various reservoirs worldwide, such as ducks, geese, migratory birds, chickens, pigs, cattle, aquatic animals, agricultural field, meat, and humans. Further, our current researches also mentioned viruses as novel environmental reservoirs of antibiotic resistance, which will probably become a focus of studying the transmission of ARGs. Overall, this article mainly aims to discuss the current status of plasmid-mediated transmission of different tet(X) genes, in particular tet(X4), as environmental pollutants, which will risk to public health for the "One Health" concept.
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Affiliation(s)
- Shaqiu Zhang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Jinfeng Wen
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Yuwei Wang
- Mianyang Academy of Agricultural Sciences, Mianyang, China
| | - Mingshu Wang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Renyong Jia
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Shun Chen
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Mafeng Liu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Dekang Zhu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Xinxin Zhao
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Ying Wu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Qiao Yang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Juan Huang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Xumin Ou
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Sai Mao
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Qun Gao
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Di Sun
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Bin Tian
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Anchun Cheng
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
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Serum concentration as a predictor of tigecycline-induced hypofibrinogenemia in critically ill patients: a retrospective cohort study. Int J Infect Dis 2022; 123:136-142. [PMID: 36028209 DOI: 10.1016/j.ijid.2022.08.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/15/2022] [Accepted: 08/16/2022] [Indexed: 01/14/2023] Open
Abstract
OBJECTIVES The objective of this study was to determine the thresholds of serum concentration as a predictor of tigecycline-induced hypofibrinogenemia in critically ill patients. METHODS A retrospective cohort study was conducted in ICU patients treated with tigecycline. The clinical data and serum concentration were extracted from the patients' electronic medical records. Patients were divided into hypofibrinogenemia (HF) group and normal group according to fibrinogen (FIB) value. The receiver operating characteristic (ROC) curves and logistic regression was used to derive serum concentration thresholds and quantify the association between exposure thresholds and hypofibrinogenemia while adjusting for confounders. RESULTS In total, 100 patients were included. ROC curves analyse showed that tigecycline concentration parameters were strongly predictive of hypofibrinogenemia. Adjusting for duration of tigecycline, C1/2 ≥ 0.645 mg/L, AUC0-24 ≥ 20.76 mg∙h/L and Cmin ≥ 0.455mg/L were associated with a 3- to 5-fold increased risk of tigecycline-induced hypofibrinogenemia in logistic regression. CONCLUSION The findings from this study provide evidence that tigecycline exposure is highly predictive of hypofibrinogenemia, with approximately 3- to 5-fold increased risk. C1/2 ≥ 0.645 mg/L with best area under ROC curve and NPV appears to be the most appropriate toxicity threshold.
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22
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Lei H, Liu X, Li Z, Wang C. Analysis of the clinical characteristics of tigecycline-induced hypofibrinogenemia. J Chemother 2022:1-6. [PMID: 35904191 DOI: 10.1080/1120009x.2022.2105488] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
Knowledge regarding the association between hypofibrinogenemia and tigecycline is based mainly on case reports. However, the clinical features of tigecycline-induced hypofibrinogenemia are unclear. We collected 20 patients (16 males and 4 females) with tigecycline-induced hypofibrinogenemia by searching the Chinese and English databases from June 2005 to May 2021, with a median age of 63.5 years (range 39∼90 years). Hypofibrinogenemia developed at a median of 9 days (range 2∼35 days). Most patients had no typical clinical manifestations, and only a few patients had bleeding and ecchymosis. Fibrinogen levels gradually decreased from 3.98 ± 2.05 g/L to 0.87 ± 0.45 g/L (P = 0.000), and the activated partial thromboplastin time (APTT) increased from 38.26 ± 8.80 s to 83.43 ± 47.23 s (P = 0.002). Fibrinogen levels in all patients recovered to the normal range within a median of 4 days (range 1∼12 days) after tigecycline cessation. Our results suggest that fibrinogen levels should be closely monitored in patients treated with tigecycline, specifically patients who may have renal insufficiency or patients with long-term use.
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Affiliation(s)
- Haibo Lei
- Department of Clinical Pharmacy, Xiangtan Central Hospital, Xiangtan, China
| | - Xiang Liu
- Department of Clinical Pharmacy, Xiangtan Central Hospital, Xiangtan, China
| | - Zuojun Li
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Chunjiang Wang
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China
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Jiang T, Huang X, Liu Q, Feng H, Huang Y, Lin J, Huang L, Chen S, Zhuang Y, Weng C. Risk Factors for Tigecycline-Associated Hepatotoxicity in Patients in the Intensive Care Units of Two Tertiary Hospitals: A Retrospective Study. J Clin Pharmacol 2022; 62:1426-1434. [PMID: 35670488 DOI: 10.1002/jcph.2099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 06/02/2022] [Indexed: 11/09/2022]
Abstract
Tigecycline is a broad-spectrum antibacterial agent. As the incidence of multidrug-resistant bacterial infections has increased in intensive care units (ICUs) over the past decades, tigecycline is often used in ICUs. Information about tigecycline-associated hepatotoxicity in ICU patients is limited. To investigate the potential risk factors for tigecycline-associated hepatotoxicity in ICU patients, 148 patients from two centers who had received tigecycline for at least 4 days were retrospectively analyzed. Hepatotoxicity was classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE 5.0) grading system. As a result, 33.8% of patients experienced hepatotoxicity events in the ICU. The multivariate analysis showed that an albumin concentration <25 g/L at baseline [odds ratio (OR) 3.714, 95% confidence interval (CI), 1.082-12.744, P = 0.037) and treatment duration (OR 1.094, 95% CI, 1.032-1.160, P = 0.003) were significantly correlated with tigecycline-associated hepatotoxicity. The median time to onset of hepatotoxicity was 8.0 days. The median duration ICU stay and the in-hospital mortality rate were not different between the hepatotoxicity group and the nonhepatotoxicity group [33.5 days (interquartile range (IQR) 21.0-72.0) vs. 31.0 days (IQR 21-62.5), P = 0.850; 38.0% vs. 43.8%, P = 0.504]. Therefore, close monitoring of liver function is recommended for patients with baseline albumin concentrations < 25 g/L or for patients who receive tigecycline therapy for more than 8 days. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Tingting Jiang
- Department of Pharmacy, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Xuhui Huang
- Department of Pharmacy, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Qinghua Liu
- Department of Otorhinolaryngology, Fujian Provincial Hospital, the Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Hangwei Feng
- Department of Critical Care Medicine, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Yiting Huang
- Department of Pharmacy, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jian Lin
- Department of Critical Care Medicine, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Long Huang
- Department of Critical Care Medicine, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Shufang Chen
- Department of Pharmacy, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Yingfeng Zhuang
- Department of Critical Care Medicine, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Cuilian Weng
- Department of Critical Care Medicine, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian Province, China
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Abstract
Relebactam is a novel β-lactamase inhibitor of Ambler class A and C β-lactamases that has been developed in combination with imipenem/cilastatin for the treatment of carbapenem-resistant bacterial infections. In this study, we evaluated the in vitro antibacterial activity of imipenem/relebactam (IMR) against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. Two sets of antibacterial susceptibility tests were conducted according to the susceptibility testing standard of the Clinical and Laboratory Standards Institute. In the first set, antibacterial susceptibility as measured by the MIC50/90 (MIC range) of IMR was assessed for the following 61 imipenem-nonsusceptible strains: 2 Enterobacter cloacae complex (not determined [0.25 μg/mL]), 33 Klebsiella aerogenes (0.5/1 μg/mL [0.5 to 1 μg/mL]), 2 Serratia marcescens (not determined [1 to 2 μg/mL]), and 24 P. aeruginosa (2/128 μg/mL [0.25 to >128 μg/mL]). In the second set, antibacterial susceptibility was assessed for the following 8 imipenem-nonsusceptible strains: 4 Escherichia coli, 1 E. cloacae complex and 3 Klebsiella pneumoniae. The MIC ranges of IMR for these strains were 0.25 to 0.5 μg/mL, 0.5 μg/mL, and 0.5 to 16 μg/mL, respectively. The antibacterial activity of IMR was similar to or lower than that of amikacin and comparable to or greater than those of other reference drugs. In conclusion, IMR has shown antibacterial activity against clinical isolates from Japan and, therefore, is expected to become a new therapeutic option for carbapenem-resistant infections in Japan. IMPORTANCE Carbapenem-resistant Enterobacterales and carbapenem-resistant Pseudomonas aeruginosa strains pose a global threat. Antibacterial activity of imipenem/relebactam (IMR) against clinical isolates of these bacteria from several global regions has been shown; however, as yet there are no reports on Japanese isolates. In this study, we evaluated the in vitro antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. The antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales was generally comparable to that of amikacin (AMK) and comparable to or higher than those of other reference drugs tested. The antibacterial activity of IMR against imipenem-nonsusceptible P. aeruginosa isolates was lower than that of AMK but comparable to or higher than those of other drugs. These results support the use of IMR as a new treatment option for infections due to Enterobacterales and P. aeruginosa strains that are resistant to existing β-lactams and other antibacterial agents.
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Daya T, Jeje O, Maake R, Aloke C, Khoza T, Achilonu I. Expression, Purification, and Biophysical Characterization of Klebsiella Pneumoniae Nicotinate Nucleotide Adenylyltransferase. Protein J 2022; 41:141-156. [DOI: 10.1007/s10930-021-10037-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2021] [Indexed: 10/19/2022]
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Lin IH, Tsai CH. Tigecycline sclerotherapy for recurrent pseudotumor in aseptic lymphocyte-dominant vasculitis-associated lesion after metal-on-metal total hip arthroplasty: A case report. World J Clin Cases 2021; 9:10696-10701. [PMID: 35005003 PMCID: PMC8686126 DOI: 10.12998/wjcc.v9.i34.10696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/06/2021] [Accepted: 10/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Metal-on-metal (MoM) total hip arthroplasty (THA) has been associated with adverse reactions to metal debris, presenting clinically as pseudotumors.
CASE SUMMARY This case report presents a female aged 73 year-old with MoM THA-related pseudotumor. After arthrotomy and bursectomy surgeries, histologic examinations of surgical specimens revealed a specific lymphocyte-dominant immunologic response, now known as aseptic lymphocyte-dominant vasculitis-associated lesion (ALVAL). Due to soft tissue persisting effusion after arthrotomy and bursectomy, revision surgery was then performed with ceramic-on-polyethylene THA. However, revision did not resolve the patient’s symptoms. Here we describe our application of tigecycline sclerotherapy to treat recurrent pseudotumor after revision THA and no recurrence after 24-mo follow-up.
CONCLUSION Tigecycline sclerotherapy is safe and effective in the management of recurrent pseudotumor after revision non-MoM THA in ALVAL cases.
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Affiliation(s)
- I-Hao Lin
- Department of Orthopedics, China Medical University Hospital, China Medical University, Taichung 406040, Taiwan
| | - Chun-Hao Tsai
- Department of Orthopedics, China Medical University Hospital, China Medical University, Taichung 406040, Taiwan
- School of Medicine, China Medical University, Taichung 406040, Taiwan
- Department of Sports Medicine, China Medical University, Taichung 406040, Taiwan
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The Development of Third-Generation Tetracycline Antibiotics and New Perspectives. Pharmaceutics 2021; 13:pharmaceutics13122085. [PMID: 34959366 PMCID: PMC8707899 DOI: 10.3390/pharmaceutics13122085] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/01/2021] [Accepted: 12/03/2021] [Indexed: 01/04/2023] Open
Abstract
The tetracycline antibiotic class has acquired new valuable members due to the optimisation of the chemical structure. The first modern tetracycline introduced into therapy was tigecycline, followed by omadacycline, eravacycline, and sarecycline (the third generation). Structural and physicochemical key elements which led to the discovery of modern tetracyclines are approached. Thus, several chemical subgroups are distinguished, such as glycylcyclines, aminomethylcyclines, and fluorocyclines, which have excellent development potential. The antibacterial spectrum comprises several resistant bacteria, including those resistant to old tetracyclines. Sarecycline, a narrow-spectrum tetracycline, is notable for being very effective against Cutinebacterium acnes. The mechanism of antibacterial action from the perspective of the new compound is approached. Several severe bacterial infections are treated with tigecycline, omadacycline, and eravacycline (with parenteral or oral formulations). In addition, sarecycline is very useful in treating acne vulgaris. Tetracyclines also have other non-antibiotic properties that require in-depth studies, such as the anti-inflammatory effect effect of sarecycline. The main side effects of modern tetracyclines are described in accordance with published clinical studies. Undoubtedly, this class of antibiotics continues to arouse the interest of researchers. As a result, new derivatives are developed and studied primarily for the antibiotic effect and other biological effects.
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Bassetti M, Falletta A, Cenderello G, Giacobbe DR, Vena A. Safety evaluation of current therapies for high-risk severely ill patients with carbapenem-resistant infections. Expert Opin Drug Saf 2021; 21:487-498. [PMID: 34632905 DOI: 10.1080/14740338.2022.1990262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Infections due to carbapenem-resistant Gram-negative bacteria (CR-GNB) are increasingly frequent events, which are associated with a high mortality rate. Traditionally, combination regimens including high doses of "old antibiotics" such as polymyxins, tigecycline, and aminoglycosides have been used to treat these infections, but they were often associated with low efficacy and high excess of side effects and toxicity, especially nephrotoxicity. Along with the development of new compounds, the last decade has seen substantial improvements in the management of CR infections. AREAS COVERED In this review, we aimed to discuss the safety characteristics and tolerability of different new options for treatment of CR infections. EXPERT OPINION The availability of new drugs showing a potent in vitro activity against CR-GNB represents a unique opportunity to face the threat of resistance, while potentially reducing toxicity. A thorough understanding of the safety profile from clinical trials may guide the use of these new drugs in critically ill patients at high risk for the development of adverse events. Future data coming from real-life studies for drugs targeting CR infections are crucial to confirm the safety profile observed in pivotal trials.
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Affiliation(s)
- Matteo Bassetti
- Clinica Malattie Infettive, San Martino Policlinico Hospital - IRCCS for Oncology and Neurosciences, Genoa, Italy.,Department of Health Sciences, University of Genoa, Genoa, Italy
| | - Antonio Falletta
- Clinica Malattie Infettive, San Martino Policlinico Hospital - IRCCS for Oncology and Neurosciences, Genoa, Italy.,Department of Health Sciences, University of Genoa, Genoa, Italy
| | | | - Daniele R Giacobbe
- Clinica Malattie Infettive, San Martino Policlinico Hospital - IRCCS for Oncology and Neurosciences, Genoa, Italy.,Department of Health Sciences, University of Genoa, Genoa, Italy
| | - Antonio Vena
- Clinica Malattie Infettive, San Martino Policlinico Hospital - IRCCS for Oncology and Neurosciences, Genoa, Italy
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Perletti G, Trinchieri A, Stamatiou K, Magri V. Safety considerations with new antibacterial approaches for chronic bacterial prostatitis. Expert Opin Drug Saf 2021; 21:171-182. [PMID: 34260337 DOI: 10.1080/14740338.2021.1956459] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Introduction: Chronic bacterial prostatitis (CBP) is a difficult-to-eradicate infection. Antibacterial therapy with currently licensed agents is hindered due to the increasing emergence of pathogen resistance worldwide and to frequent infection relapse. With limited treatment options, physicians are investigating new agents, which, however, may raise safety concerns.Areas covered: Antibacterial agents currently licensed for CBP were not considered. Available reports about the safety and efficacy of antibacterial agents that have been clinically tested or tentatively used to treat CBP in single cases were evaluated. This review also focused on agents targeting Gram-positive pathogens, whose prevalence as causative agents of CBP is increasing.Expert opinion: (i) Most antibacterial agents considered in this review have been administered off-label in the interest of patients, and their use requires particular caution. (ii) Reports describing the usage of many of the drugs reviewed here are still scant, and readers should be warned of the limited published evidence supporting therapy for CBP with these agents. (iii) As treatment must extend over several weeks, medium-term adverse events may occur and therapy should be individualized, taking into account the dosage and the potential toxicity of each specific antibiotic. Regarding dangerous drug-drug interactions, particular attention should be paid to the risk of ECG-QT-interval elongation.
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Affiliation(s)
- Gianpaolo Perletti
- Department of Biotechnology and Life Sciences, Section of Medical and Surgical Sciences, University of Insubria, Varese, Italy.,Department of Human Function and Repair, Faculty of Medicine and Medical Sciences, Ghent University, Ghent, Belgium
| | - Alberto Trinchieri
- Department of Urology, IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Milan, Italy
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30
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Li X, Li L, Liu T, Hai X, Sun B. Leukocytosis induced by tigecycline in two patients with severe acute pancreatitis. Br J Biomed Sci 2021; 78:225-228. [PMID: 33599194 DOI: 10.1080/09674845.2021.1885865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- X Li
- Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - L Li
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - T Liu
- Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, China
| | - X Hai
- Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - B Sun
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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31
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Duane TM, Huston JM, Collom M, Beyer A, Parli S, Buckman S, Shapiro M, McDonald A, Diaz J, Tessier JM, Sanders J. Surgical Infection Society 2020 Updated Guidelines on the Management of Complicated Skin and Soft Tissue Infections. Surg Infect (Larchmt) 2021; 22:383-399. [PMID: 33646051 DOI: 10.1089/sur.2020.436] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background: The Surgical Infection Society (SIS) Guidelines for the treatment of complicated skin and soft tissue infections (SSTIs) were published in October 2009 in Surgical Infections. The purpose of this project was to provide a succinct update on the earlier guidelines based on an additional decade of data. Methods: We reviewed the previous guidelines eliminating bite wounds and diabetic foot infections including their associated references. Relevant articles on the topic of complicated SSTIs from 2008-2020 were reviewed and graded individually. Comparisons were then made between the old and the new graded recommendations with review of the older references by two authors when there was disparity between the grades. Results: The majority of new studies addressed antimicrobial options and duration of therapy particularly in complicated abscesses. There were fewer updated studies on diagnosis and specific operative interventions. Many of the topics addressed in the original guidelines had no new literature to evaluate. Conclusions: Most recommendations remain unchanged from the original guidelines with the exception of increased support for adjuvant antimicrobial therapy after drainage of complex abscess and increased data for the use of alternative antimicrobial agents.
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Affiliation(s)
| | - Jared M Huston
- Departments of Surgery and Science Education, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | | | - Adam Beyer
- Department of Surgery, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Sara Parli
- Department of Pharmacy Services, University of Kentucky, Lexington, Kentucky, USA
| | - Sara Buckman
- Department of Surgery, Washington University, St. Louis, Missouri, USA
| | - Mark Shapiro
- Acute Care Surgery, Portsmouth, New Hampshire, USA
| | - Amy McDonald
- Department of Veterans Affairs, Cleveland, Ohio, USA
| | - Jose Diaz
- Department of Surgery, University of Maryland, Baltimore, Maryland, USA
| | - Jeffrey M Tessier
- Division of Infectious Diseases, University of Texas Southwestern, Dallas Texas, USA
| | - James Sanders
- Department of Pharmacy and Division of Infectious Diseases, University of Texas Southwestern, Dallas, Texas, USA
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32
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Qu J, Feng C, Li H, Lv X. Antibiotic strategies and clinical outcomes for patients with carbapenem-resistant Gram-negative bacterial bloodstream infection. Int J Antimicrob Agents 2021; 57:106284. [PMID: 33484833 DOI: 10.1016/j.ijantimicag.2021.106284] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 07/09/2020] [Accepted: 12/19/2020] [Indexed: 02/08/2023]
Abstract
Carbapenem-resistant Gram-negative bacterial bloodstream infection (CRGNB-BSI) has become a rapidly growing global threat with limited antibiotic options and significant mortality. The aim of this study was to explore the antibiotic strategies and clinical outcomes of patients with CRGNB-BSI in Western China. We retrospectively investigated the demographic, microbiological and clinical characteristics of 355 patients with CRGNB-BSI from 2012-2017. Treatment failure and 28-day in-hospital mortality rates were 49.3% (175/355) and 23.7% (84/355), respectively. The most frequently isolated micro-organism was Acinetobacter baumannii (58.6%; 208/355). Patients with treatment failure had higher procalcitonin and interleukin-6 levels (P < 0.05). High-dosage tigecycline therapy (200 mg loading dose followed by 100 mg every 12 h) was not superior to standard tigecycline dosing (P > 0.05). Multivariable analysis revealed that multiple organ dysfunction syndrome (MODS) (OR = 2.226, 95% CI 1.376-3.602; P = 0.001) and intensive care unit (ICU) admission (OR = 3.116, 95% CI 1.905-5.097; P = 0.000) were independent risk factors for treatment failure, whereas monotherapy (OR = 0.386, 95% CI 0.203-0.735; P = 0.004) had a protective effect. Survival analysis revealed that inappropriate therapy, MODS and ICU admission were associated with a higher 28-day in-hospital mortality rate (P < 0.001). Combination antimicrobial therapy was not superior to monotherapy (P = 0.387). This study demonstrates that appropriate therapy is significantly associated with lower treatment failure and 28-day in-hospital mortality rates. Tigecycline might not be a suitable option for CRGBN-BSI. Patients with MODS and admitted to the ICU had poor clinical outcomes.
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Affiliation(s)
- Junyan Qu
- Center of Infectious Disease, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu 610041, China
| | - Chunlu Feng
- Center of Infectious Disease, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu 610041, China
| | - Huan Li
- Center of Infectious Disease, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu 610041, China
| | - Xiaoju Lv
- Center of Infectious Disease, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu 610041, China.
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Abstract
Introduction: Nosocomial pneumonia unfortunately remains a frequent event for which appropriate antibiotic treatment is central to improving outcomes. Physicians must choose an early and appropriate empirical treatment, basing their decision on the safety profile and possible side effects. Areas covered: In this review, we analyzed the safety profiles of the most common antimicrobials for treating nosocomial pneumonia. Beta-lactams are used most often for these infections, with a high percentage (6% to 25%) of patients reporting allergy or hypersensitivity reactions; however, exhaustive evaluation is key because it seems possible to de-label as many as 90% by proper assessment. Combinations including a beta-lactam are recommended in patients with risk factors for drug-resistant microorganisms and septic shock. Although aminoglycosides are safe for 3-5 days of therapy, renal function should be monitored. Fluoroquinolones must also be used with care given the risk of collagen degradation and cardiovascular events, mainly aneurysm or aortic dissection. Linezolid or vancomycin are both viable for the treatment of methicillin-resistant Staphylococcus aureus, but linezolid seems to be the superior option. Antibiotic stewardships programs must be developed for each center. Expert opinion: Choosing the most appropriate antimicrobial based on information from national and international guidelines, local microbiology data, and stewardship programs may reduce the use of broad-spectrum antibiotics. Daily assessment for the emergence of adverse events related to antimicrobial use is essential.
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Yaghoubi S, Zekiy AO, Krutova M, Gholami M, Kouhsari E, Sholeh M, Ghafouri Z, Maleki F. Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review. Eur J Clin Microbiol Infect Dis 2021; 41:1003-1022. [PMID: 33403565 PMCID: PMC7785128 DOI: 10.1007/s10096-020-04121-1] [Citation(s) in RCA: 152] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 12/02/2020] [Indexed: 12/14/2022]
Abstract
Tigecycline is unique glycylcycline class of semisynthetic antimicrobial agents developed for the treatment of polymicrobial infections caused by multidrug-resistant Gram-positive and Gram-negative pathogens. Tigecycline evades the main tetracycline resistance genetic mechanisms, such as tetracycline-specific efflux pump acquisition and ribosomal protection, via the addition of a glycyclamide moiety to the 9-position of minocycline. The use of the parenteral form of tigecycline is approved for complicated skin and skin structure infections (excluding diabetes foot infection), complicated intra-abdominal infections, and community-acquired bacterial pneumonia in adults. New evidence also suggests the effectiveness of tigecycline for the treatment of severe Clostridioides difficile infections. Tigecycline showed in vitro susceptibility to Coxiella spp., Rickettsia spp., and multidrug-resistant Neisseria gonnorrhoeae strains which indicate the possible use of tigecycline in the treatment of infections caused by these pathogens. Except for intrinsic, or often reported resistance in some Gram-negatives, tigecycline is effective against a wide range of multidrug-resistant nosocomial pathogens. Herein, we summarize the currently available data on tigecycline pharmacokinetics and pharmacodynamics, its mechanism of action, the epidemiology of tigecycline resistance, and its clinical effectiveness.
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Affiliation(s)
- Sajad Yaghoubi
- Department of Clinical Microbiology, Iranshahr University of Medical Sciences, Iranshahr, Iran
| | - Angelina Olegovna Zekiy
- Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Russian Federation, Trubetskaya st., 8-2, 119991, Moscow, Russia
| | - Marcela Krutova
- Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
| | - Mehrdad Gholami
- Department of Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Ebrahim Kouhsari
- Laboratory Sciences Research Center, Golestan University of Medical Sciences, P.O. Box 6939177143, Gorgan- Sari Road, Golestan Province, Gorgan, Iran. .,Department of Laboratory Sciences, Faculty of Paramedicine, Golestan University of Medical Sciences, P.O. Box 6939177143, Gorgan- Sari Road, Golestan Province, Gorgan, Iran.
| | - Mohammad Sholeh
- Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Ghafouri
- Department of Biochemistry, Biophysics and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Farajolah Maleki
- Department of Laboratory Sciences, School of Allied Medical Sciences, Ilam University of Medical sciences, Ilam, Iran.
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35
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Fan Q, Huang W, Weng Y, Xie X, Shi Z. Hypofibrinogenemia induced by high-dose tigecycline-case report and review of literature. Medicine (Baltimore) 2020; 99:e22638. [PMID: 33120753 PMCID: PMC7581097 DOI: 10.1097/md.0000000000022638] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
RATIONALE Extensive off-label use may affect the safety profile of tigecycline. Tigecycline-associated hypofibrinogenemia is potentially life threatening, although the frequency of life-threatening reactions is unknown and their incidence is easily overlooked. We report a case of 2 instances of treatment with high-dose tigecycline, each of which presented with hypofibrinogenemia. PATIENT CONCERNS An 86-year-old male patient was treated twice with high-dose tigecycline and presented with hypofibrinogenemia both times. The decrease in fibrinogen occurred within 3 to 7 days of tigecycline treatment. Other coagulation parameters had slightly prolonged values. DIAGNOSES Coagulopathy and hypofibrinogenemia. INTERVENTIONS We discontinued the tigecycline. OUTCOMES The fibrinogen level normalized within 5 days after the withdrawal of tigecycline. Following 80 days of hospitalization, the patient was transferred to the rehabilitation hospital for further treatment. LESSONS We suggest routine strict monitoring of coagulation parameters, particularly fibrinogen. Attention should be paid to below-normal fibrinogen levels due to increased bleeding risk and severity of reaction at fibrinogen levels below 1 g/L.
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36
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Ruiz J, Ramirez P, Villarreal E, Gordon M, Sánchez MÁ, Martín M, Castellanos-Ortega Á. Effect of pharmacokinetic/pharmacodynamic ratio on tigecycline clinical response and toxicity in critically ill patients with multidrug-resistant Gram-negative infections. SAGE Open Med 2020; 8:2050312120958897. [PMID: 32999720 PMCID: PMC7506777 DOI: 10.1177/2050312120958897] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 08/25/2020] [Indexed: 11/29/2022] Open
Abstract
Introduction: The information about the pharmacokinetics and optimal dose of tigecycline in
critically ill patients with severe underlying diseases is limited and
controversial. In this study, we evaluate the pharmacokinetic parameters of
tigecycline in critically ill patients with multidrug-resistant
Gram-negative infection and explore the association between the
pharmacokinetic/pharmacodynamic ratio and treatment response. Methods: A prospective study was designed including critically ill patients treated
with tigecycline for multidrug-resistant Gram-negative infections. Blood
samples were collected at day 3–5 of treatment, and pharmacokinetics
parameters were evaluated using NONMEM® software. Relationship
between area under the free concentration–time curve and minimum inhibitory
concentration ratio (fAUC/MIC) and treatment failure was evaluated.
Association between tigecycline fAUC and hepatobiliary toxicity was also
investigated. Results: Twenty-five critically ill patients were included in the study. In the
pharmacokinetic model, weight and total bilirubin level were found to be
significant predictors of tigecycline clearance. Fifteen (60.0%) patients
achieved an fAUC/MIC ratio >4.5, seven (28.0%) an fAUC/MIC > 6.96 and
only three (12.0%) an fAUC/MIC > 17.9. No differences in fAUC/MIC ratio
were obtained between those patients with and without clinical failure (5.28
(IC95%: 2.57–7.94) vs 8.71 (3.57–13.84)). fAUC values were higher in those
patients who suffered hepatobiliary disorders (7.63 (3.93–11.34) vs 17.63
(7.85–26.28) mg/L/h). Conclusion: An important percentage of critically ill patients with multidrug-resistant
Gram-negative infection treated with tigecycline do not achieve an
appropriate pharmacokinetic/pharmacodynamic value. Tigecycline fAUC seems to
be associated with hepatobiliary disorders in this study population. The
effect of fAUC/MIC ratio on clinical response remains unclear.
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Affiliation(s)
- Jesus Ruiz
- Intensive Care Unit, IIS La Fe, Hospital Universitario y Politecnico de La Fe, Valencia, Spain
| | - Paula Ramirez
- Intensive Care Unit, Hospital Universitario y Politecnico de La Fe, Valencia, Spain
| | - Esther Villarreal
- Intensive Care Unit, Hospital Universitario y Politecnico de La Fe, Valencia, Spain
| | - Mónica Gordon
- Intensive Care Unit, Hospital Universitario y Politecnico de La Fe, Valencia, Spain
| | | | - María Martín
- Pharmacy Department, IIS La Fe, Hospital Universitario y Politecnico de La Fe, Valencia, Spain
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Zhang R, Dong N, Shen Z, Zeng Y, Lu J, Liu C, Zhou H, Hu Y, Sun Q, Cheng Q, Shu L, Cai J, Chan EWC, Chen G, Chen S. Epidemiological and phylogenetic analysis reveals Flavobacteriaceae as potential ancestral source of tigecycline resistance gene tet(X). Nat Commun 2020; 11:4648. [PMID: 32938927 PMCID: PMC7494873 DOI: 10.1038/s41467-020-18475-9] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 08/25/2020] [Indexed: 11/25/2022] Open
Abstract
Emergence of tigecycline-resistance tet(X) gene orthologues rendered tigecycline ineffective as last-resort antibiotic. To understand the potential origin and transmission mechanisms of these genes, we survey the prevalence of tet(X) and its orthologues in 2997 clinical E. coli and K. pneumoniae isolates collected nationwide in China with results showing very low prevalence on these two types of strains, 0.32% and 0%, respectively. Further surveillance of tet(X) orthologues in 3692 different clinical Gram-negative bacterial strains collected during 1994–2019 in hospitals in Zhejiang province, China reveals 106 (2.7%) tet(X)-bearing strains with Flavobacteriaceae being the dominant (97/376, 25.8%) bacteria. In addition, tet(X)s are found to be predominantly located on the chromosomes of Flavobacteriaceae and share similar GC-content as Flavobacteriaceae. It also further evolves into different orthologues and transmits among different species. Data from this work suggest that Flavobacteriaceae could be the potential ancestral source of the tigecycline resistance gene tet(X). Emergence of tigecycline-resistance tet(X) genes is of concern. Here, the authors determine tet(X) prevalence in more than 6,000 clinical Gram-negative bacterial isolates collected between 1994 to 2019 in hospitals in China and suggest that Flavobacteriaceae could be the potential ancestral source of the tigecycline resistance genes.
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Affiliation(s)
- Rong Zhang
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China
| | - Ning Dong
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, China
| | - Zhangqi Shen
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Yu Zeng
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China
| | - Jiauyue Lu
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China
| | - Congcong Liu
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China
| | - Hongwei Zhou
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China
| | - Yanyan Hu
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China
| | - Qiaoling Sun
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China
| | - Qipeng Cheng
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, China.,State Key Lab of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, China
| | - Lingbing Shu
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China
| | - Jiachang Cai
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China
| | - Edward Wai-Chi Chan
- State Key Lab of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, China
| | - Gongxiang Chen
- Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, Hangzhou, China.
| | - Sheng Chen
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, China.
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38
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Riccardi N, Monticelli J, Antonello RM, Di Lallo G, Frezza D, Luzzati R, Di Bella S. Therapeutic Options for Infections due to vanB Genotype Vancomycin-Resistant Enterococci. Microb Drug Resist 2020; 27:536-545. [PMID: 32799629 DOI: 10.1089/mdr.2020.0171] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Enterococci are ubiquitous, facultative, anaerobic Gram-positive bacteria that mainly reside, as part of the normal microbiota, in the gastrointestinal tracts of several animal species, including humans. These bacteria have the capability to turn from a normal gut commensal organism to an invasive pathogen in patients debilitated by prolonged hospitalization, concurrent illnesses, and/or exposed to broad-spectrum antibiotics. The majority of vancomycin-resistant enterococcus (VRE) infections are linked to the vanA genotype; however, outbreaks caused by vanB-type VREs have been increasingly reported, representing a new challenge for effective antimicrobial treatment. Teicoplanin, daptomycin, fosfomycin, and linezolid are useful antimicrobials for infections due to vanB enterococci. In addition, new drugs have been developed (e.g., dalbavancin, telavancin, and tedizolid), new molecules will soon be available (e.g., eravacycline, omadacycline, and oritavancin), and new treatment strategies are progressively being used in clinical practice (e.g., combination therapies and bacteriophages). The aim of this article is to discuss the pathogenesis of infections due to enterococci harboring the vanB operon (vanBVRE) and their therapeutic, state-of-the-art, and future treatment options and provide a comprehensive and easy to use review for clinical purposes.
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Affiliation(s)
- Niccolò Riccardi
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
| | - Jacopo Monticelli
- Hospital Direction, AULSS6 Euganea Ospedali Riuniti Padova Sud, Monselice, Italy
| | | | - Gustavo Di Lallo
- Department of Biology, University of Rome "Tor Vergata," Rome, Italy
| | - Domenico Frezza
- Department of Biology, University of Rome "Tor Vergata," Rome, Italy
| | - Roberto Luzzati
- Infectious Diseases Department, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy
| | - Stefano Di Bella
- Infectious Diseases Department, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy
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39
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Sharavanan SPN, Venkatesan CS, Sathiyanarayanan S, Kabilan S. Potential Impurities of Tigecycline: Synthesis, Isolation, Characterization and In Vitro Pharmacological Evaluation. CURR PHARM ANAL 2020. [DOI: 10.2174/1573412915666190225160030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Tigecycline is a known antibiotic in the tetracycline family and a chemical
analog of minocycline. It may be used for the treatment against drug-resistant bacteria.
Methods:
HPLC method was used for related substance analysis. The degraded impurities during the
process were isolated and characterized by IR, HRMS (High Resolution Mass Spectrometry) and NMR
spectral analysis.
Results:
Four impurities of tigecycline, a broad spectrum antibacterial agent, were identified, synthesized
and characterized. The in vitro biological evaluation of the isolated compounds showed significant
antimicrobial and antioxidant properties to that of tigecycline. Apart from these, the tigecycline drug
substance showed significant degradation under oxidation conditions.
Conclusion:
The extensive investigational data confirm the structure of the four impurities. The specification
limit for these impurities is applied based on the toxicological data. The antimicrobial activity
revealed that the impurity 4 shows excellent activity towards both Gram-positive and Gram-negative
bacteria when compared with tigecycline. The results obtained for DPPH (2,2-diphenyl-1-
picrylhydrazyl) antioxidant activity concluded that the impurity 2 and the impurity 3 showed good antioxidant
properties when compared with tigecycline. There was no activity observed on fungi for both
isolated degradants as well as tigecycline.
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Affiliation(s)
| | | | | | - Senthamaraikannan Kabilan
- Department of Chemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu 608002, India
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40
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De Oliveira DMP, Forde BM, Kidd TJ, Harris PNA, Schembri MA, Beatson SA, Paterson DL, Walker MJ. Antimicrobial Resistance in ESKAPE Pathogens. Clin Microbiol Rev 2020; 23:788-99. [PMID: 32404435 DOI: 10.1111/imb.12124] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/23/2023] Open
Abstract
Antimicrobial-resistant ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. The acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced the treatment options for serious infections, increased the burden of disease, and increased death rates due to treatment failure and requires a coordinated global response for antimicrobial resistance surveillance. This looming health threat has restimulated interest in the development of new antimicrobial therapies, has demanded the need for better patient care, and has facilitated heightened governance over stewardship practices.
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Affiliation(s)
- David M P De Oliveira
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - Brian M Forde
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - Timothy J Kidd
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - Patrick N A Harris
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
- UQ Centre for Clinical Research, The University of Queensland, QLD, Australia
| | - Mark A Schembri
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - Scott A Beatson
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - David L Paterson
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
- UQ Centre for Clinical Research, The University of Queensland, QLD, Australia
| | - Mark J Walker
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
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De Oliveira DMP, Forde BM, Kidd TJ, Harris PNA, Schembri MA, Beatson SA, Paterson DL, Walker MJ. Antimicrobial Resistance in ESKAPE Pathogens. Clin Microbiol Rev 2020; 33:e00181-19. [PMID: 32404435 PMCID: PMC7227449 DOI: 10.1128/cmr.00181-19] [Citation(s) in RCA: 1102] [Impact Index Per Article: 220.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Antimicrobial-resistant ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. The acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced the treatment options for serious infections, increased the burden of disease, and increased death rates due to treatment failure and requires a coordinated global response for antimicrobial resistance surveillance. This looming health threat has restimulated interest in the development of new antimicrobial therapies, has demanded the need for better patient care, and has facilitated heightened governance over stewardship practices.
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Affiliation(s)
- David M P De Oliveira
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - Brian M Forde
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - Timothy J Kidd
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - Patrick N A Harris
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
- UQ Centre for Clinical Research, The University of Queensland, QLD, Australia
| | - Mark A Schembri
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - Scott A Beatson
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
| | - David L Paterson
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
- UQ Centre for Clinical Research, The University of Queensland, QLD, Australia
| | - Mark J Walker
- School of Chemistry and Molecular Biosciences, The University of Queensland, QLD, Australia
- Australian Infectious Diseases Research Centre, The University of Queensland, QLD, Australia
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Clinical characteristics and risk factors of tigecycline-associated hypofibrinogenaemia in critically ill patients. Eur J Clin Pharmacol 2020; 76:913-922. [PMID: 32355990 PMCID: PMC7224009 DOI: 10.1007/s00228-020-02860-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 03/26/2020] [Indexed: 12/18/2022]
Abstract
Purpose To analyze the clinical features and risk factors of tigecycline-associated hypofibrinogenaemia and study whether cefoperazone/sulbactam combined with tigecycline aggravates coagulopathy or hypofibrinogenaemia. Methods A retrospective case–control study of patients with severe infection who were treated with tigecycline was conducted. Patients were assigned to the hypofibrinogenaemia group (< 2.0 g/L) and normal fibrinogen (normal) group (≥ 2.0 g/L) to assess the clinical features of patients with tigecycline-associated hypofibrinogenaemia. The traits of patients treated with cefoperazone/sulbactam in the hypofibrinogenaemia group were also analyzed. Results In total, 127 patients were enrolled in the study, including 71 patients with hypofibrinogenaemia and 56 patients with normal fibrinogen levels. Hypofibrinogenaemia developed at a median of 6 (4–8) days after tigecycline treatment, and the fibrinogen level returned to normal at a median of 3 (3–5) days after tigecycline discontinuation. In the multivariate analysis, intra-abdominal infection (p = 0.005), fibrinogen level at tigecycline initiation (p < 0.001), maintenance dose (p = 0.039), and treatment duration (p = 0.002) were found to be related to hypofibrinogenaemia. Treatment with cefoperazone/sulbactam was not associated with hypofibrinogenaemia (p = 0.681), but patients treated with cefoperazone/sulbactam had a higher incidence of coagulopathy (p = 0.009) and needed more blood products (p = 0.003) than those treated without cefoperazone/sulbactam. Conclusion Tigecycline-associated hypofibrinogenaemia often developed on the 6th (4th–8th) day of tigecycline use and was associated with intra-abdominal infection, fibrinogen level at tigecycline initiation, maintenance dose, and treatment duration of tigecycline but not cefoperazone/sulbactam.
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Zha L, Pan L, Guo J, French N, Villanueva EV, Tefsen B. Effectiveness and Safety of High Dose Tigecycline for the Treatment of Severe Infections: A Systematic Review and Meta-Analysis. Adv Ther 2020; 37:1049-1064. [PMID: 32006240 PMCID: PMC7223407 DOI: 10.1007/s12325-020-01235-y] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Studies assessing the effect of high dose tigecycline on severe infections are limited and remain controversial. OBJECTIVES To assess systematically the effectiveness and safety of high dose tigecycline in the treatment of severe infections. METHODS Pubmed, Web of Science, Embase, MEDLINE, Cochrane Library and ClinicalTrials were searched up to February 20, 2019 for studies that compared the effectiveness and safety of high dose tigecycline with standard dose tigecycline or other non-tigecycline-containing regimens in the treatment of severe infections. Rates for all-cause mortality, clinical cure, microbiological eradication and adverse events were analysed. RESULTS Ten studies with 593 patients were included. The results indicated that using high dose tigecycline resulted in better outcomes compared with controls with lower all-cause mortality (OR 0.44, 95% CI 0.30-0.66, p < 0.0001), higher clinical cure (OR 3.43, 95% CI 2.09-5.63, p < 0.00001), higher microbiological eradication (OR 2.25, 95% CI 1.44-3.50, p = 0.0003), and without increasing adverse events rates. Subgroup analysis showed that high dose tigecycline reduced all-cause mortality in nosocomial acquired pneumonia (OR 0.39, 95% CI 0.22-0.70, p = 0.002), bloodstream infections (OR 0.19, 95% CI 0.06-0.58, p = 0.004) and mixed infections (OR 0.20, 95% CI 0.07-0.59, p = 0.003), with no statistical differences in complicated intra-abdominal infections (OR 2.04, 95% CI 0.80-5.23, p = 0.14). In carbapenem-resistant pathogens, the microbiological eradication rate in those given high dose tigecycline did not differ from controls (OR 1.07, 95% CI 0.44-2.60, p = 0.87), although mortality was reduced (OR 0.20, 95% CI 0.09-0.45, p = 0.0001). The main limitation of the review is that most of the included studies are observational studies with small sample sizes and high risks of bias. CONCLUSIONS High dose tigecycline treatment is effective and safe for severe infections owing to its lower all-cause mortality, higher clinical cure, microbiological eradication and comparable adverse events. However, as a result of the high risks of bias of the included studies, well-designed randomised clinical trials are warranted to establish the effectiveness and safety of high dose tigecycline compared with standard dose tigecycline and other commonly used antibiotics.
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Affiliation(s)
- Lei Zha
- Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu, China.
- Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
- Emergency and Critical Care Unit, Conch Hospital, Wuhu, Anhui, China.
| | - Lingling Pan
- Cardiology Department, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Jun Guo
- Critical Care Unit, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Neil French
- Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
| | - Elmer V Villanueva
- Department of Health and Environmental Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu, China
| | - Boris Tefsen
- Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu, China
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Carbapenem-Resistant Gram-Negative Bacterial Infections in Children. Antimicrob Agents Chemother 2020; 64:AAC.02183-19. [PMID: 31844014 DOI: 10.1128/aac.02183-19] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Carbapenem-resistant organisms (CRO) are a major global public health threat. Enterobacterales hydrolyze almost all β-lactams through carbapenemase production. Infections caused by CRO are challenging to treat due to the limited number of antimicrobial options. This leads to significant morbidity and mortality. Over the last few years, several new antibiotics effective against CRO have been approved. Some of them (e.g., plazomicin or imipenem-cilastatin-relebactam) are currently approved for use only by adults; others (e.g., ceftazidime-avibactam) have recently been approved for use by children. Recommendations for antibiotic therapy of CRO infections in pediatric patients are based on evidence mainly from adult studies. The availability of pediatric pharmacokinetic and safety data is the cornerstone to broaden the use of proposed agents in adults to the pediatric population. This article provides a comprehensive review of the current knowledge regarding infections caused by CRO with a focus on children, which includes epidemiology, risk factors, outcomes, and antimicrobial therapy management, with particular attention being given to new antibiotics.
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Mao Y, Shi Q, Zhang P, Jiang Y, Yu Y. Effect of ramR loss-of-function insertion on tigecycline resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae. J Glob Antimicrob Resist 2020; 21:410-413. [PMID: 32006749 DOI: 10.1016/j.jgar.2020.01.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 01/10/2020] [Accepted: 01/13/2020] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVES Tigecycline is an antibacterial agent restricted for use against carbapenem-resistant Klebsiella pneumoniae (CRKP). This study aimed to identify the tigecycline resistance mechanism in clinical CRKP isolates obtained from a 60-year-old femalepatient during tigecycline treatment. METHODS Three K. pneumoniae isolates obtained during tigecycline treatment were subjected to antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing, and whole-genome sequencing and analysis. The function of ramR was confirmed by gene complementation. RESULTS Three K. pneumoniae isolates (W814, W112 and W113) were collected from the patient on Days 0, 10 and 13, respectively, of ongoing tigecycline treatment. Antimicrobial susceptibility testing showed resistance to all antibiotics except tigecycline and ceftazidime/avibactam. The tigecycline minimum inhibitory concentration (MIC) for strains W814 and W112 was 4 mg/L compared with 16 mg/L for strain W113. The three strains belonged to sequence type 11 (ST11) and had a similar PGFE pattern. Insertion sequence (IS) element ISKpn18 in ramR was identified in strain W113. A parent strain transformed with plasmid pCR2.1-Hyg carrying ramR enhanced tigecycline susceptibility, thus confirming that a loss-of-function insertion in ramR contributes to tigecycline resistance. CONCLUSION ISKpn18 insertion in the ramR gene contributes to the tigecycline resistance mechanism in the isolated K. pneumoniae strains.
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Affiliation(s)
- Yihan Mao
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Qiucheng Shi
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Ping Zhang
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Yan Jiang
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Yunsong Yu
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China.
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Kwon YS, Levin A, Kasperbauer SH, Huitt GA, Daley CL. Efficacy and safety of tigecycline for Mycobacterium abscessus disease. Respir Med 2019; 158:89-91. [PMID: 31622813 DOI: 10.1016/j.rmed.2019.10.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 09/23/2019] [Accepted: 10/07/2019] [Indexed: 11/19/2022]
Abstract
PURPOSE Mycobacterium abscessus disease is one of the most difficult mycobacterial infections to cure, as the bacterium is highly resistant to conventional antibiotics. The purpose of this study was to evaluate the efficacy and safety of tigecycline treatment of M. abscessus disease. PROCEDURE We performed retrospective chart reviews of patients with M. abscessus disease receiving tigecycline-containing regimens at National Jewish Health from January 2009 to December 2017. MAIN FINDINGS Among the 35 patients, pulmonary disease was the most common presentation of M. abscessus disease (n = 29, 82.9%). Of those receiving tigecycline treatment, 17.4% (4/23) showed microbiological improvement (≥2 consecutive negative sputum cultures), while 86.2% (25/29) and 59.3% (16/27) showed symptomatic and radiological improvements, respectively. The rate of dose reduction or discontinuation of tigecycline owing to adverse drug reactions was 57.1% (20/35) at a median of 56.5 days (IQR 10.8-122.3). The most common adverse drug reactions were gastrointestinal side effects, including nausea, vomiting, and diarrhea. CONCLUSIONS Tigecycline-containing regimens for M. abscessus disease have a high rate of symptomatic and radiological improvement. However, considering the poor microbiological response and the common adverse effects, selection of patients for tigecycline treatment and monitoring for adverse drug reactions should be performed carefully.
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Affiliation(s)
- Yong-Soo Kwon
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, South Korea; Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO, USA.
| | - Adrah Levin
- Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO, USA
| | - Shannon H Kasperbauer
- Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO, USA; Department of Medicine, University of Colorado, Denver, CO, USA
| | - Gwen A Huitt
- Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO, USA; Department of Medicine, University of Colorado, Denver, CO, USA
| | - Charles L Daley
- Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO, USA; Department of Medicine, University of Colorado, Denver, CO, USA.
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Wang Y, Xie F, Chen D, Wang L. Inhibition of mitochondrial respiration by tigecycline selectively targets thyroid carcinoma and increases chemosensitivity. Clin Exp Pharmacol Physiol 2019; 46:890-897. [PMID: 31209921 DOI: 10.1111/1440-1681.13126] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 05/15/2019] [Accepted: 06/12/2019] [Indexed: 01/07/2023]
Abstract
The role of mitochondria in cancer and mitochondria-targeted therapy has been gaining attention for its effectiveness and selectivity between cancer and normal cells. In line with this notion, our work demonstrates that inducing mitochondrial dysfunction by tigecycline, a FDA-approved antibiotic, selectively targets thyroid cancer and enhances chemosensitivity. We found that tigecycline inhibited proliferation and induced apoptosis in a panel of thyroid cancer cell lines. Consistently, tigecycline inhibited thyroid cancer growth in mice without causing significant toxicity. The combination of tigecycline with paclitaxel achieved greater efficacy than paclitaxel alone in vitro and in vivo. Mechanistically, tigecycline inhibited mitochondrial respiration and ATP reduction through decreasing mitochondrial membrane potential and inhibiting mitochondrial translation, leading to oxidative stress and damage. In contrast, tigecycline was ineffective in mitochondrial respiration-deficient cells, confirming that tigecycline acts on thyroid cancer via inhibiting mitochondrial respiration. Interestingly, although tigecycline inhibited mitochondrial respiration in both thyroid cancer and normal thyroid cells in a similar manner, tigecycline was more effective in thyroid cancer than normal thyroid cells, suggesting that thyroid cancer cells are more dependent on mitochondrial functions than normal thyroid cells. This was supported by our observations that thyroid cancer cells had higher level of mitochondrial biogenesis compared to normal thyroid cells. Our work is the first to demonstrate that the combination of chemotherapy with tigecycline is a potential sensitizing strategy for thyroid cancer treatment. Our findings also highlight the higher dependence of thyroid cancer cells on mitochondrial functions than normal thyroid cells.
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Affiliation(s)
- Yuehua Wang
- Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, China
| | - Fei Xie
- Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, China
| | - Dejie Chen
- Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, China
| | - Ling Wang
- Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, China
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Chow KM, Pang WF, Chan GCK, Leung CB, Szeto CC, Li PKT. Beware of drug interaction between tigecycline and tacrolimus. Nephrology (Carlton) 2019; 25:99-100. [PMID: 31099103 DOI: 10.1111/nep.13594] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2019] [Indexed: 11/30/2022]
Affiliation(s)
- Kai Ming Chow
- Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Wing Fai Pang
- Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Gordon Chun Kau Chan
- Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Chi Bon Leung
- Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Cheuk Chun Szeto
- Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
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Zheng X, Jiang H, Xue L, Qiu F, Zhu S, Li X. Delirium induced by tigecycline treatment for Acinetobacter baumannii infection: A case report. Medicine (Baltimore) 2019; 98:e15399. [PMID: 31083168 PMCID: PMC6531112 DOI: 10.1097/md.0000000000015399] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 03/23/2019] [Accepted: 04/02/2019] [Indexed: 12/02/2022] Open
Abstract
RATIONALE Tigecycline is a broad-spectrum antimicrobial agent structurally belong to tetracyclines and covers against many multidrug-resistant organisms. Arising clinical cases reporting its adverse drug reactions have emerged alongside with the increasing off label use globally. By literature review, delirium caused by tigecycline has not been reported yet. We present what we believe to be the first case of tigecycline-induced delirium. PATIENT CONCERNS A 77-year-old male patient with end-stage renal disease was hospitalized due to acute exacerbation of chronic obstructive pulmonary disease. DIAGNOSIS The patient developed delirium after infused with a loading dose of tigecycline for pulmonary infection. INTERVENTIONS All potential causes inducing delirium were evaluated and the symptoms improved soon after discontinuation of tigecycline. He experienced delirium once again after reusing tigecycline for the exacerbation of the pulmonary infection even without a loading dose. Tigecycline was discontinued and the symptoms quickly relieved. OUTCOMES According to the Naranjo adverse drug reaction probability scale, tigecycline was the probable cause of his delirium. LESSONS Clinicians should be aware of this potential adverse effect of tigecycline. We recommend that clinicians monitor patients for signs and symptoms of delirium during treatment with tigecycline.
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Ritsema JA, der Weide HV, Te Welscher YM, Goessens WH, van Nostrum CF, Storm G, Bakker-Woudenberg IA, Hays JP. Antibiotic-nanomedicines: facing the challenge of effective treatment of antibiotic-resistant respiratory tract infections. Future Microbiol 2018; 13:1683-1692. [PMID: 30499686 DOI: 10.2217/fmb-2018-0194] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Respiratory tract infections are one of the most frequent infections worldwide, with an increasing number being associated with (multiple) antibiotic-resistant pathogens. Improved treatment requires the development of new therapeutic strategies, including the possible development of antibiotic-nanomedicines. Antibiotic-nanomedicines comprise antibiotic molecules coupled to nanocarriers via surface adsorption, surface attachment, entrapment or conjugation and can be administered via aerosolization. The efficacy and tolerability of this approach has been shown in clinical studies, with amikacin liposome inhalation suspension being the first inhalatory antibiotic-nanomedicine approved by the US FDA. In this special report, we summarize and discuss the potential value and the clinical status of antibiotic-nanomedicines for the treatment of (antibiotic-resistant) respiratory tract infections.
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Affiliation(s)
- Jeffrey As Ritsema
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Hessel van der Weide
- Department of Medical Microbiology & Infectious Diseases, Erasmus University Medical Center Rotterdam (Erasmus MC), Rotterdam, The Netherlands
| | - Yvonne M Te Welscher
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Wil Hf Goessens
- Department of Medical Microbiology & Infectious Diseases, Erasmus University Medical Center Rotterdam (Erasmus MC), Rotterdam, The Netherlands
| | - Cornelus F van Nostrum
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Gert Storm
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Irma Ajm Bakker-Woudenberg
- Department of Medical Microbiology & Infectious Diseases, Erasmus University Medical Center Rotterdam (Erasmus MC), Rotterdam, The Netherlands
| | - John P Hays
- Department of Medical Microbiology & Infectious Diseases, Erasmus University Medical Center Rotterdam (Erasmus MC), Rotterdam, The Netherlands
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