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3. Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions.

Author

Wang, Minggui, Ge, Lizhao, Chen, Liang, Komarow, Lauren, Hanson, Blake, Reyes, Jinnethe, Cober, Eric, Alenazi, Thamer, Zong, Zhiyong, Xie, Qing, Liu, Zhengyin, Li, Lanjuan, Yu, Yunsong, Gao, Hainv, Kanj, Souha, Figueroa, Jairo, Herc, Erica, Cordova, Ezequiel, Weston, Gregory, Ananth Tambyah, Paul, Garcia-Diaz, Julia, Kaye, Keith, Dhar, Sorabh, Munita, Jose, Salata, Robert, Vilchez, Samuel, Stryjewski, Martin, Villegas Botero, Maria, Iovleva, Alina, Evans, Scott, Baum, Keri, Hill, Carol, Kreiswirth, Barry, Patel, Robin, Paterson, David, Arias, Cesar, Bonomo, Robert, Chambers, Henry, Fowler, Vance, Satlin, Michael, van Duin, David, and Doi, Yohei

Subjects
carbapenem-resistant Acinetobacter baumannii, clinical impact, international epidemiology, Humans, Acinetobacter baumannii, Carbapenems, Prospective Studies, Microbial Sensitivity Tests, Acinetobacter Infections, beta-Lactamases, Bacterial Proteins, Anti-Bacterial Agents
Abstract

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

Published
2024

7. WHO global research priorities for antimicrobial resistance in human health

Author

Aanensen, David, Alanio, Alexandre, Alastruey-Izquierdo, Ana, Alemayehu, Tinsae, Al-Hasan, Majdi, Allegaert, Karel, Al-Maani, Amal Saif, Al-Salman, Jameela, Alshukairi, Abeer Nizar, Amir, Afreenish, Applegate, Tanya, Araj, George F, Villalobos, Marlen Arce, Årdal, Christine, Ashiru-Oredope, Diane, Ashley, Elizabeth A, Babin, François-Xavier, Bachmann, Laura H, Bachmann, Till, Baker, Kate Susan, Balasegaram, Manica, Bamford, Colleen, Baquero, Fernando, Barcelona, Laura Isabel, Bassat, Quique, Bassetti, Matteo, Basu, Sulagna, Beardsley, Justin, Vásquez, Grey Benoit, Berkley, James A, Bhatnagar, Anuj K, Bielicki, Julia, Bines, Julie, Bongomin, Felix, Bonomo, Robert A, Bradley, John S, Bradshaw, Catriona, Brett, Ana, Brink, Adrian, Brown, Colin, Brown, Jeremy, Buising, Kirsty, Carson, Carolee, Carvalho, Anna Cristina, Castagnola, Elio, Cavaleri, Marco, Cecchini, Michele, Chabala, Chishala, Chaisson, Richard E, Chakrabarti, Arunaloke, Chandler, Clare, Chandy, Sujith John, Charani, Esmita, Chen, Lisa, Chiara, Francesca, Chowdhary, Anuradha, Chua, Arlene, Chuki, Pem, Chun, Doo Ryeon, Churchyard, Gavin, Cirillo, Daniela, Clack, Lauren, Coffin, Susan E, Cohn, Jennifer, Cole, Michelle, Conly, John, Cooper, Ben, Corso, Alejandra, Cosgrove, Sara E, Cox, Helen, Daley, Charles L, Darboe, Saffiatou, Darton, Tom, Davies, Gerry, de Egea, Viviana, Dedeić-Ljubović, Amela, Deeves, Miranda, Denkinger, Claudia, Dillon, Jo-Anne R, Dramowski, Angela, Eley, Brian, Roberta Esposito, Susanna Maria, Essack, Sabiha Y, Farida, Helmia, Farooqi, Joveria, Feasey, Nicholas, Ferreyra, Cecilia, Fifer, Helen, Finlayson, Heather, Frick, Mike, Gales, Ana Cristina, Galli, Luisa, Gandra, Sumanth, Gerber, Jeffrey S, Giske, Christian, Gordon, Bruce, Govender, Nelesh, Guessennd, Nathalie, Guindo, Ibrehima, Gurbanova, Elmira, Gwee, Amanda, Hagen, Ferry, Harbarth, Stephan, Haze, John, Heim, Jutta, Hendriksen, Rene, Heyderman, Robert Simon, Holt, Kathryn Elizabeth, Hönigl, Martin, Hook, Edward W, Hope, William, Hopkins, Heidi, Hughes, Gwenda, Ismail, Ghada, Issack, Mohammad Iqbal, Jacobs, Jan, Jasovský, Dušan, Jehan, Fyeza, Pearson, Antonieta Jimenez, Jones, Makoto, Joshi, Mohan P, Kapil, Arti, Kariuki, Samuel, Karkey, Abhilasha, Kearns, Gregory L, Keddy, Karen Helena, Khanna, Nina, Kitamura, Akiko, Kolho, Kaija-Leena, Kontoyiannis, Dimitrios P, Kotwani, Anita, Kozlov, Roman S, Kranzer, Katharina, Kularatne, Ranmini, Lahra, Monica M, Langford, Bradley J, Laniado-Laborin, Rafael, Larsson, Joakim, Lass-Flörl, Cornelia, Le Doare, Kirsty, Lee, Hyukmin, Lessa, Fernanda, Levin, Anna S, Limmathurotsakul, Direk, Lincopan, Nilton, Lo Vecchio, Andrea, Lodha, Rakesh, Loeb, Mark, Longtin, Yves, Lye, David Chien, Mahmud, Asif Mujtaba, Manaia, Célia, Manderson, Lenore, Mareković, Ivana, Marimuthu, Kalisvar, Martin, Irene, Mashe, Tapfumanei, Mei, Zeng, Meis, Jacques F, Lyra Tavares De Melo, Flávio Augusto, Mendelson, Marc, Miranda, Angelica Espinosa, Moore, David, Morel, Chantal, Moremi, Nyambura, Moro, Maria Luisa, Moussy, Francis, Mshana, Stephen, Mueller, Arno, Ndow, Francis J, Nicol, Mark, Nunn, Andrew, Obaro, Stephen, Obiero, Christina W, Okeke, Iruka N, Okomo, Uduak, Okwor, Tochi J, Oladele, Rita, Omulo, Sylvia, Ondoa, Pascale, Ortellado de Canese, Juana Medarda, Ostrosky-Zeichner, Luis, Padoveze, Maria Clara, Pai, Madhukar, Park, Benjamin, Parkhill, Julian, Parry, Christopher M, Peeling, Rosanna, Sobreira Vieira Peixe, Luísa Maria, Perovic, Olga, Pettigrew, Melinda M, Principi, Nicola, Pulcini, Céline, Puspandari, Nelly, Rawson, Timothy, Reddy, Denasha Lavanya, Reddy, Kessendri, Redner, Paulo, Rodríguez Tudela, Juan Luis, Rodríguez-Baño, Jesús, Van Katwyk, Susan Rogers, Roilides, Emmanuel, Rollier, Christine, Rollock, Leslie, Ronat, Jean-Baptiste, Ruppe, Etienne, Sadarangani, Manish, Salisbury, David, Salou, Mounerou, Samison, Luc Hervé, Sanguinetti, Maurizio, Sartelli, Massimo, Schellack, Natalie, Schouten, Jeroen, Schwaber, Mitchell J, Seni, Jeremiah, Senok, Abiola, Shafer, William M, Shakoor, Sadia, Sheppard, Donald, Shin, Jong-Hee, Sia, Sonia, Sievert, Dawn, Singh, Ishwar, Singla, Rupak, Skov, Robert Leo, Soge, Olusegun O, Sprute, Rosanne, Srinivasan, Arjun, Srinivasan, Subasree, Sundsfjord, Arnfinn, Tacconelli, Evelina, Tahseen, Sabira, Tangcharoensathien, Viroj, Tängdén, Thomas, Thursky, Karin, Thwaites, Guy, Tigulini de Souza Peral, Renata, Tong, Deborah, Tootla, Hafsah Deepa, Tsioutis, Constantinos, Turner, Katy M, Turner, Paul, Omar, Shaheed Vally, van de Sande, Wendy WJ, van den Hof, Susan, van Doorn, Rogier, Veeraraghavan, Balaji, Verweij, Paul, Wahyuningsih, Retno, Wang, Hui, Warris, Adilia, Weinstock, Hillard, Wesangula, Evelyn, Whiley, David, White, Peter J, Williams, Phoebe, Xiao, Yonghong, Moscoso, Martin Yagui, Yang, Hsu Li, Yoshida, Sachiyo, Yu, Yunsong, Żabicka, Dorota, Zignol, Matteo, Rudan, Igor, Bertagnolio, Silvia, Dobreva, Zlatina, Centner, Chad M, Olaru, Ioana Diana, Donà, Daniele, Burzo, Stefano, Huttner, Benedikt D, Chaillon, Antoine, Gebreselassie, Nebiat, Wi, Teodora, Hasso-Agopsowicz, Mateusz, Allegranzi, Benedetta, Sati, Hatim, Ivanovska, Verica, Kothari, Kavita U, Balkhy, Hanan H, Cassini, Alessandro, Hamers, Raph L, and Weezenbeek, Kitty Van

Published
2024
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26. Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study

Author

Wang, Minggui, Earley, Michelle, Chen, Liang, Hanson, Blake M, Yu, Yunsong, Liu, Zhengyin, Salcedo, Soraya, Cober, Eric, Li, Lanjuan, Kanj, Souha S, Gao, Hainv, Munita, Jose M, Ordoñez, Karen, Weston, Greg, Satlin, Michael J, Valderrama-Beltrán, Sandra L, Marimuthu, Kalisvar, Stryjewski, Martin E, Komarow, Lauren, Luterbach, Courtney, Marshall, Steve H, Rudin, Susan D, Manca, Claudia, Paterson, David L, Reyes, Jinnethe, Villegas, Maria V, Evans, Scott, Hill, Carol, Arias, Rebekka, Baum, Keri, Fries, Bettina C, Doi, Yohei, Patel, Robin, Kreiswirth, Barry N, Bonomo, Robert A, Chambers, Henry F, Fowler, Vance G, Arias, Cesar A, van Duin, David, Investigators, Multi-Drug Resistant Organism Network, Abbo, Lilian M, Anderson, Deverick J, Chew, Kean Lee, Cross, Heather R, De, Partha Pratim, Desai, Samit, Dhar, Sorabh, Di Castelnuovo, Valentina, Diaz, Lorena, Dinh, AN Q, Eilertson, Brandon, Evans, Beth, Garcia-Diaz, Julia, Garner, Omai B, Greenwood-Quaintance, Kerryl, Hanson, Blake, Herc, Erica, Jacob, Jesse T, Jiang, Jianping, Kalayjian, Robert C, Kaye, Keith S, Kim, Angela, Lauterbach, Courtney, Marshall, Steven H, McCarty, Todd, Munita, Jose, Ng, Oon Tek, Gutierrez, Jose Millan Oñate, Peleg, Anton, Salata, Robert A, Schmidt-Malan, Suzannah, and Smitasin, Nares

Subjects
Pneumonia & Influenza, Lung, Clinical Research, Pneumonia, Infectious Diseases, Infection, Good Health and Well Being, Anti-Bacterial Agents, Bacteremia, Carbapenem-Resistant Enterobacteriaceae, Carbapenems, Cohort Studies, Humans, Klebsiella Infections, Klebsiella pneumoniae, Prospective Studies, Respiratory Sounds, Multi-Drug Resistant Organism Network Investigators, Clinical Sciences, Medical Microbiology, Public Health and Health Services, Microbiology
Abstract

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.MethodsIn this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov, NCT03646227, and is complete.FindingsBetween June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2-6] vs 2 [0-4] vs 2 [0-4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2-5] vs 1 [0-3] vs 1 [0-2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42-65) for China versus South America, 50% (41-61) for the USA versus China, and 53% (41-66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8-16; 29 of 246) than in the USA (23%, 16-30; 30 of 130) and South America (28%, 20-37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22-10·50) and the USA (aOR 3·34, 1·50-7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70-2·96).InterpretationGlobal CRKP epidemics have important regional differences in patients' baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions.FundingThe National Institutes of Health.

Published
2022

29. Clinical Impact of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage in the Diagnosis and Management of Pneumonia A Multicenter Prospective Observational Study

Author

Zhou, Hua, Larkin, Paige MK, Zhao, Dongdong, Ma, Qiang, Yao, Yake, Wu, Xiaohong, Wang, Jiaoli, Zhou, XiaoHu, Li, Yaqing, Wang, Gang, Feng, Malong, Wu, Lei, Chen, Jinyin, Zhou, Changsheng, Hua, Xiaoting, Zhou, Jianying, Yang, Shangxin, and Yu, Yunsong

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pneumonia, Lung, Infectious Diseases, Pneumonia & Influenza, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Infection, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Bronchoalveolar Lavage Fluid, Child, Child, Preschool, DNA, Bacterial, DNA, Fungal, DNA, Viral, Diagnostic Tests, Routine, Female, High-Throughput Nucleotide Sequencing, Humans, Infant, Male, Metagenomics, Middle Aged, Prospective Studies, Sensitivity and Specificity, Young Adult, Medical Microbiology, Pathology, Clinical sciences, Oncology and carcinogenesis
Abstract

Rapid and accurate pathogen identification is necessary for appropriate treatment of pneumonia. Here, we describe the use of shotgun metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage for pathogen identification in pneumonia in a large-scale multicenter prospective study with 159 patients enrolled. The results of mNGS were compared with standard methods including culture, staining, and targeted PCR, and the clinical impact of mNGS was evaluated. A positive impact was defined by a definitive diagnosis made using the mNGS results, or change of management because of the mNGS results, leading to a favorable clinical outcome. Overall, mNGS identified more organisms than standard methods (117 versus 72), detected 17 pathogens that consistently were missed in all cases by standard methods, and had an overall positive clinical impact in 40.3% (64 of 159) of cases. mNGS was especially useful in identification of fastidious and atypical organisms causing pneumonia, contributing to detection of definitive pathogens in 45 (28.3%) cases in which standard results were either negative or insufficient. mNGS also helped reassure antibiotic de-escalation in 19 (11.9%) cases. Overall, mNGS led to a change of treatment in 59 (37.1%) cases, including antibiotic de-escalation in 40 (25.2%) cases. This study showed the significant value of mNGS of bronchoalveolar lavage for improving the diagnosis of pneumonia and contributing to better patient care.

Published
2021

31. Efficacy and safety of ZX-7101A, an inhibitor of influenza cap-dependent endonuclease, in adults with uncomplicated influenza: a randomized, double-blind, placebo-controlled phase 2/3 trial

Author

Wang, Hongyu, Wang, Gang, Gao, Yan, Qu, Lihong, Wang, Hong, Deng, Min, Gao, Hainv, Li, Yilin, Yang, Nan, Wang, Baogui, Liu, Rongge, Ma, Xuzhu, Tao, Zhen, Zhang, Guoqiang, Wang, Qian, Zhao, Weifeng, Yu, Yunsong, Chen, Lin, Liang, Lianchun, Wang, Shengyu, Shao, Lei, Yang, Tao, Cao, JingLei, Cao, Yuan, Qin, Xiaoli, Ai, Jingwen, Zhu, Huadong, and Zhang, Wenhong

Published
2024
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38. Seawater-Associated Highly Pathogenic Francisella hispaniensis Infections Causing Multiple Organ Failure - Volume 26, Number 10—October 2020 - Emerging Infectious Diseases journal - CDC

Author

Zhou, Hua, Yang, Qing, Shen, Lisha, Yao, Yake, Xu, Jun, Ye, Junhui, Wu, Xiaomai, Yu, Yunsong, Li, Ziqin, Zhou, Jianying, and Yang, Shangxin

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Biodefense, Rare Diseases, Vaccine Related, Prevention, Emerging Infectious Diseases, Infection, Good Health and Well Being, China, Francisella, Humans, Male, Multiple Organ Failure, Seawater, Francisella hispaniensis, bacteremia, bacteria, moxifloxacin, multiorgan failure, seawater, wound, Public Health and Health Services, Microbiology, Clinical sciences, Epidemiology, Health services and systems
Abstract

A rare case of Francisella hispaniensis infection associated with seawater exposure occurred in a deep-sea diving fisherman in Zhejiang, China. He had skin and soft tissue infection that progressed to bacteremia and multiple organ failure. Moxifloxacin treatment cleared the infections, but the patient suffered a sequela of heart damage.

Published
2020

39. Discovery of a Novel Hypervirulent Acinetobacter baumannii Strain in a Case of Community-Acquired Pneumonia

Author

Zhou, Hua, Larkin, Paige MK, Huang, Jinwei, Yao, Yake, Zhu, Bingquan, Yang, Qing, Hua, Xiaoting, Zhou, Jianying, Yang, Shangxin, and Yu, Yunsong

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Microbiology, Clinical Sciences, Medical Microbiology, Infectious Diseases, Pneumonia, Emerging Infectious Diseases, Pneumonia & Influenza, Lung, Biotechnology, Genetics, 2.2 Factors relating to the physical environment, Aetiology, Infection, Acinetobacter baumannii, hypervirulent, community-acquired pneumonia, novel strain, emerging pathogen, Pharmacology and Pharmaceutical Sciences, Clinical sciences
Abstract

PurposeAcinetobacter baumannii is associated with both hospital-acquired infections and community-acquired pneumonia (CAP). Here, we describe a novel strain of A. baumannii in a case of CAP in a previously healthy rural villager from Central Eastern China.Materials and methodsA. baumannii isolated from the patient (LS01) was compared to well-characterized pathogenic strain (AB5075), nosocomial circulating strain in China (ZJ06), and wild-type strain (ATCC17978). Growth rate studies were conducted under different environmental stressors, and virulence studies were performed using Galleria mellonella larvae. Whole genome sequencing (WGS) was performed using MinIon and MiSeq. Center for Genomic Epidemiology, CLCbio, Geneious, and Virulence Factors of Pathogenic Bacteria database were used for genomic analysis.ResultsLS01 grew significantly faster at 37°C and 42°C and in the presence of zinc compared to other strains. LS01 was more virulent in G. mellonella, killing all larvae within 8 h. Although WGS revealed 44 virulence genes, these genes were also present in the other strains. While two chromosomally encoded β-lactamases were identified, there were no plasmids identified and LS01 was pan-susceptible to all antibiotics tested. Phylogenetic analysis revealed that the closest related strains were only 72.552% identical, supporting a novel strain.ConclusionLS01 is a novel strain of hypervirulent yet pan-drug susceptible A. baumannii isolated from a patient with no prior hospitalizations, sick contacts, or any of the typical risk factors. This raises concerns for an emerging pathogen, and more epidemiological studies should be conducted to assess the prevalence of this A. baumannii strain.

Published
2020

45. Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli

Author

Zeng, Mei, Xia, Jun, Zong, Zhiyong, Shi, Yi, Ni, Yuxing, Hu, Fupin, Chen, Yijian, Zhuo, Chao, Hu, Bijie, Lv, Xiaoju, Li, Jiabin, Liu, Zhengyin, Zhang, Jing, Yang, Wenjie, Yang, Fan, Yang, Qiwen, Zhou, Hua, Li, Xin, Wang, Jianhua, Li, Yimin, Ren, Jian'an, Chen, Baiyi, Chen, Dechang, Wu, Anhua, Guan, Xiangdong, Qu, Jieming, Wu, Depei, Huang, Xiaojun, Qiu, Haibo, Xu, Yingchun, Yu, Yunsong, and Wang, Minggui

Published
2023
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47. Risk factors and molecular epidemiology of intestinal colonization by carbapenem-resistant Gram-negative bacteria in patients with hematological diseases: a multicenter case‒control study

Author

Hu, Huangdu, primary, Wang, Yinping, additional, Sun, Jian, additional, Wang, Yuting, additional, Zhou, Junxin, additional, Shi, Qiucheng, additional, Han, Xinhong, additional, Jiang, Yan, additional, Wu, Depei, additional, Huang, Xiaojun, additional, and Yu, Yunsong, additional

Published
2024
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