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2. Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

Author

Chai, Ming G., Tu, Quyen, Cotta, Menino O., Bauer, Michelle J., Balch, Ross, Okafor, Charles, Comans, Tracy, Kruger, Peter, Meyer, Jason, Shekar, Kiran, Brady, Kara, Fourie, Cheryl, Sharp, Natalie, Vlad, Luminita, Whiley, David, Ungerer, Jacobus P. J., Mcwhinney, Brett C., Farkas, Andras, Paterson, David L., Clark, Julia E., Hajkowicz, Krispin, Raman, Sainath, Bialasiewicz, Seweryn, Lipman, Jeffrey, Forde, Brian M., Harris, Patrick N. A., Schlapbach, Luregn J., Coin, Lachlan, Roberts, Jason A., and Irwin, Adam D.

Published
2024
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6. Statistical analysis plan for the BLING III study: A phase 3 multicentre randomised controlled trial of continuous versus intermittent beta-lactam antibiotic infusion in critically ill patients with sepsis

Author

Billot, Laurent, Lipman, Jeffrey, Brett, Stephen J, de Waele, Jan J, Cotta, Menino Osbert, Davis, Joshua S, Finfer, Simon, Hammond, Naomi, Knowles, Serena, McGuinness, Shay, Myburgh, John, Paterson, David L, Peake, Sandra, Rajbhandari, Dorrilyn, Rhodes, Andrew, Roberts, Jason A, Roger, Claire, Shirwadkar, Charudatt, Starr, Therese, Taylor, Colman, and Dulhunty, Joel M

Published
2021

7. Correction: Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

Author

Chai, Ming G., Tu, Quyen, Cotta, Menino O., Bauer, Michelle J., Balch, Ross, Okafor, Charles, Comans, Tracy, Kruger, Peter, Meyer, Jason, Shekar, Kiran, Brady, Kara, Fourie, Cheryl, Sharp, Natalie, Vlad, Luminita, Whiley, David, Ungerer, Jacobus P. J., Mcwhinney, Brett C., Farkas, Andras, Paterson, David L., Clark, Julia E., Hajkowicz, Krispin, Raman, Sainath, Bialasiewicz, Seweryn, Lipman, Jeffrey, Forde, Brian M., Harris, Patrick N. A., Schlapbach, Luregn J., Coin, Lachlan, Roberts, Jason A., and Irwin, Adam D.

Published
2024
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10. Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study

Author

Atamna, Alaa, Margalit, Ili, Ayada, Gida, Babich, Tanya, Naucler, Pontus, Valik, John Karlsson, Giske, Christian G., Benito, Natividad, Cardona, Ruben, Rivera, Alba, Pulcini, Celine, Fattah, Manal Abdel, Haquin, Justine, Macgowan, Alasdair, Chazan, Bibiana, Yanovskay, Anna, Ami, Ronen Ben, Landes, Michal, Nesher, Lior, Zaidman-Shimshovitz, Adi, McCarthy, Kate, Paterson, David L., Tacconelli, Evelina, Buhl, Michael, Mauer, Susanna, Rodríguez-Baño, Jesús, de Cueto, Marina, Oliver, Antonio, de Gopegui, Enrique Ruiz, Cano, Angela, Machuca, Isabel, Gozalo-Marguello, Monica, Martinez-Martinez, Luis, Gonzalez-Barbera, Eva M., Alfaro, Iris Gomez, Salavert, Miguel, Beovic, Bojana, Saje, Andreja, Mueller–Premru, Manica, Pagani, Leonardo, Vitrat, Virginie, Kofteridis, Diamantis, Zacharioudaki, Maria, Maraki, Sofia, Weissman, Yulia, Paul, Mical, Dickstei, Yaakov, and Yahav, Dafna

Published
2023
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13. Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria

Author

Mu, Andre, Klare, William P., Baines, Sarah L., Ignatius Pang, C. N., Guérillot, Romain, Harbison-Price, Nichaela, Keller, Nadia, Wilksch, Jonathan, Nhu, Nguyen Thi Khanh, Phan, Minh-Duy, Keller, Bernhard, Nijagal, Brunda, Tull, Dedreia, Dayalan, Saravanan, Chua, Hwa Huat Charlie, Skoneczny, Dominik, Koval, Jason, Hachani, Abderrahman, Shah, Anup D., Neha, Nitika, Jadhav, Snehal, Partridge, Sally R., Cork, Amanda J., Peters, Kate, Bertolla, Olivia, Brouwer, Stephan, Hancock, Steven J., Álvarez-Fraga, Laura, De Oliveira, David M. P., Forde, Brian, Dale, Ashleigh, Mujchariyakul, Warasinee, Walsh, Calum J., Monk, Ian, Fitzgerald, Anna, Lum, Mabel, Correa-Ospina, Carolina, Roy Chowdhury, Piklu, Parton, Robert G., De Voss, James, Beckett, James, Monty, Francois, McKinnon, Jessica, Song, Xiaomin, Stephen, John R., Everest, Marie, Bellgard, Matt I., Tinning, Matthew, Leeming, Michael, Hocking, Dianna, Jebeli, Leila, Wang, Nancy, Ben Zakour, Nouri, Yasar, Serhat A., Vecchiarelli, Stefano, Russell, Tonia, Zaw, Thiri, Chen, Tyrone, Teng, Don, Kassir, Zena, Lithgow, Trevor, Jenney, Adam, Cole, Jason N., Nizet, Victor, Sorrell, Tania C., Peleg, Anton Y., Paterson, David L., Beatson, Scott A., Wu, Jemma, Molloy, Mark P., Syme, Anna E., Goode, Robert J. A., Hunter, Adam A., Bowland, Grahame, West, Nicholas P., Wilkins, Marc R., Djordjevic, Steven P., Davies, Mark R., Seemann, Torsten, Howden, Benjamin P., Pascovici, Dana, Tyagi, Sonika, Schittenhelm, Ralf B., De Souza, David P., McConville, Malcolm J., Iredell, Jonathan R., Cordwell, Stuart J., Strugnell, Richard A., Stinear, Timothy P., Schembri, Mark A., and Walker, Mark J.

Published
2023
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14. 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

22. Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study

Author

van Duin, David, Arias, Cesar A, Komarow, Lauren, Chen, Liang, Hanson, Blake M, Weston, Gregory, Cober, Eric, Garner, Omai B, Jacob, Jesse T, Satlin, Michael J, Fries, Bettina C, Garcia-Diaz, Julia, Doi, Yohei, Dhar, Sorabh, Kaye, Keith S, Earley, Michelle, Hujer, Andrea M, Hujer, Kristine M, Domitrovic, T Nicholas, Shropshire, William C, Dinh, An, Manca, Claudia, Luterbach, Courtney L, Wang, Minggui, Paterson, David L, Banerjee, Ritu, Patel, Robin, Evans, Scott, Hill, Carol, Arias, Rebekka, Chambers, Henry F, Fowler, Vance G, Kreiswirth, Barry N, Bonomo, Robert A, and Investigators, Multi-Drug Resistant Organism Network

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Infectious Diseases, Clinical Research, Lung, Infection, Good Health and Well Being, Aged, Carbapenem-Resistant Enterobacteriaceae, Cohort Studies, Enterobacteriaceae Infections, Female, Humans, Male, Middle Aged, Phylogeny, Prospective Studies, United States, Multi-Drug Resistant Organism Network Investigators, Public Health and Health Services, Microbiology, Clinical sciences, Medical microbiology, Epidemiology
Abstract

BackgroundCarbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA.MethodsCRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Clinical data and bacteria were collected, and whole genome sequencing was done. This trial is registered with ClinicalTrials.gov, number NCT03646227.Findings1040 patients with unique isolates were included, 449 (43%) with infection and 591 (57%) with colonisation. The CDC-defined CRE admission rate was 57 per 100 000 admissions (95% CI 45-71). Three subsets of CDC-defined CRE were identified: carbapenemase-producing Enterobacterales (618 [59%] of 1040), non-carbapenemase-producing Enterobacterales (194 [19%]), and unconfirmed CRE (228 [22%]; initially reported as CRE, but susceptible to carbapenems in two central laboratories). Klebsiella pneumoniae carbapenemase-producing clonal group 258 K pneumoniae was the most common carbapenemase-producing Enterobacterales. In 449 patients with CDC-defined CRE infections, DOOR outcomes were not significantly different in patients with carbapenemase-producing Enterobacterales, non-carbapenemase-producing Enterobacterales, and unconfirmed CRE. At 30 days 107 (24%, 95% CI 20-28) of these patients had died.InterpretationAmong patients with CDC-defined CRE, similar outcomes were observed among three subgroups, including the novel unconfirmed CRE group. CDC-defined CRE represent diverse bacteria, whose spread might not respond to interventions directed to carbapenemase-producing Enterobacterales.FundingNational Institutes of Health.

Published
2020

23. Duration of Treatment for Pseudomonas aeruginosa Bacteremia: a Retrospective Study

Author

Babich, Tanya, Naucler, Pontus, Valik, John Karlsson, Giske, Christian G., Benito, Natividad, Cardona, Ruben, Rivera, Alba, Pulcini, Celine, Fattah, Manal Abdel, Haquin, Justine, Macgowan, Alasdair, Grier, Sally, Chazan, Bibiana, Yanovskay, Anna, Ami, Ronen Ben, Landes, Michal, Nesher, Lior, Zaidman-Shimshovitz, Adi, McCarthy, Kate, Paterson, David L., Tacconelli, Evelina, Buhl, Michael, Mauer, Susanna, Rodríguez-Baño, Jesús, de Cueto, Marina, Oliver, Antonio, de Gopegui, Enrique Ruiz, Cano, Angela, Machuca, Isabel, Gozalo-Marguello, Monica, Martinez-Martinez, Luis, Gonzalez-Barbera, Eva M., Alfaro, Iris Gomez, Salavert, Miguel, Beovic, Bojana, Saje, Andreja, Mueller–Premru, Manica, Pagani, Leonardo, Vitrat, Virginie, Kofteridis, Diamantis, Zacharioudaki, Maria, Maraki, Sofia, Weissman, Yulia, Paul, Mical, Dickstein, Yaakov, Leibovici, Leonard, and Yahav, Dafna

Published
2022
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24. Shewanella spp. Bloodstream Infections in Queensland, Australia

Author

Laupland, Kevin B., Stewart, Adam G., Edwards, Felicity, Paterson, David L., Coulter, Sonali, Heney, Claire, George, Narelle, and Harris, Patrick

Subjects
Queensland -- Health aspects, Bacteremia -- Statistics -- Risk factors -- Demographic aspects, Shewanella -- Statistics -- Health aspects, Health
Abstract

Shewanella spp., most commonly S. algae and S. putrefaciens, are infrequent but occasionally severe causes of human infection associated with exposure to warm marine environments (2,2). Cases of otogenic and [...]

Published
2022
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25. Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting

Author

Isler, Burcu, Özer, Berna, Çınar, Güle, Aslan, Abdullah Tarık, Vatansever, Cansel, Falconer, Caitlin, Dolapçı, İştar, Şimşek, Funda, Tülek, Necla, Demirkaya, Hamiyet, Menekşe, Şirin, Akalin, Halis, Balkan, İlker İnanç, Aydın, Mehtap, Tigen, Elif Tükenmez, Demir, Safiye Koçulu, Kapmaz, Mahir, Keske, Şiran, Doğan, Özlem, Arabacı, Çiğdem, Yağcı, Serap, Hazırolan, Gülşen, Bakır, Veli Oğuzalp, Gönen, Mehmet, Chatfield, Mark D., Forde, Brian, Saltoğlu, Neşe, Azap, Alpay, Azap, Özlem, Akova, Murat, Paterson, David L., Can, Füsun, and Ergönül, Önder

Published
2022
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29. Sequential, Multiple-Assignment, Randomized Trials for COMparing Personalized Antibiotic StrategieS (SMART-COMPASS).

Author

Evans, Scott R, Follmann, Dean, Liu, Ying, Holland, Thomas, Doernberg, Sarah B, Rouphael, Nadine, Hamasaki, Toshimitsu, Jiang, Yunyun, Lok, Judith J, Tran, Thuy Tien T, Harris, Anthony D, Fowler, Vance G, Boucher, Helen, Kreiswirth, Barry N, Bonomo, Robert A, Van Duin, David, Paterson, David L, and Chambers, Henry

Subjects
Clinical Trials and Supportive Activities, Patient Safety, Antimicrobial Resistance, Clinical Research, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Evaluation of treatments and therapeutic interventions, 7.3 Management and decision making, Management of diseases and conditions, 5.1 Pharmaceuticals, Good Health and Well Being, Anti-Bacterial Agents, Clinical Decision-Making, Disease Management, Humans, Precision Medicine, Randomized Controlled Trials as Topic, Research Design, strategy, sequential randomization, pragmatic trial, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

Patient management is not based on a single decision. Rather, it is dynamic: based on a sequence of decisions, with therapeutic adjustments made over time. Adjustments are personalized: tailored to individual patients as new information becomes available. However, strategies allowing for such adjustments are infrequently studied. Traditional antibiotic trials are often nonpragmatic, comparing drugs for definitive therapy when drug susceptibilities are known. COMparing Personalized Antibiotic StrategieS (COMPASS) is a trial design that compares strategies consistent with clinical practice. Strategies are decision rules that guide empiric and definitive therapy decisions. Sequential, multiple-assignment, randomized (SMART) COMPASS allows evaluation when there are multiple, definitive therapy options. SMART COMPASS is pragmatic, mirroring clinical, antibiotic-treatment decision-making and addressing the most relevant issue for treating patients: identification of the patient-management strategy that optimizes the ultimate patient outcomes. SMART COMPASS is valuable in the setting of antibiotic resistance, when therapeutic adjustments may be necessary due to resistance.

Published
2019

30. Comparison of ceftazidime-avibactam susceptibility testing methods against OXA-48-like carrying Klebsiella blood stream isolates

Author

Isler, Burcu, Vatansever, Cansel, Özer, Berna, Çınar, Güle, Aslan, Abdullah Tarık, Stewart, Adam, Simos, Peter, Falconer, Caitlin, Bauer, Michelle J., Forde, Brian, Harris, Patrick, Şimşek, Funda, Tülek, Necla, Demirkaya, Hamiyet, Menekşe, Şirin, Akalin, Halis, Balkan, İlker İnanç, Aydın, Mehtap, Tigen, Elif Tükenmez, Demir, Safiye Koçulu, Kapmaz, Mahir, Keske, Şiran, Doğan, Özlem, Arabacı, Çiğdem, Yağcı, Serap, Hazırolan, Gülşen, Bakır, Veli Oğuzalp, Gönen, Mehmet, Saltoğlu, Neşe, Azap, Alpay, Azap, Özlem, Akova, Murat, Ergönül, Önder, Paterson, David L., and Can, Füsun

Published
2022
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35. Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial

Author

Lee, I. Russel, Tong, Steven Y. C., Davis, Joshua S., Paterson, David L., Syed-Omar, Sharifah F., Peck, Kwong Ran, Chung, Doo Ryeon, Cooke, Graham S., Libau, Eshele Anak, Rahman, Siti-Nabilah B. A., Gandhi, Mihir P., Shi, Luming, Zheng, Shuwei, Chaung, Jenna, Tan, Seow Yen, Kalimuddin, Shirin, Archuleta, Sophia, and Lye, David C.

Published
2022
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37. 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

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

Published
2022
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40. Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial.

Author

Dulhunty, Joel M., Brett, Stephen J., De Waele, Jan J., Rajbhandari, Dorrilyn, Billot, Laurent, Cotta, Menino O., Davis, Joshua S., Finfer, Simon, Hammond, Naomi E., Knowles, Serena, Liu, Xiaoqiu, McGuinness, Shay, Mysore, Jayanthi, Paterson, David L., Peake, Sandra, Rhodes, Andrew, Roberts, Jason A., Roger, Claire, Shirwadkar, Charudatt, and Starr, Therese

Subjects
CLOSTRIDIOIDES difficile, INTENSIVE care units, HOSPITAL mortality, CLINICAL trials, CONTINUOUS groups
Abstract

Key Points: Question: Is there a difference in mortality between continuous and intermittent infusions of β-lactam antibiotics in critically ill patients with sepsis? Findings: In this randomized clinical trial that included 7031 adult patients with sepsis, there was not a statistically significant difference in the proportion of patients who died within 90 days who received continuous (24.9%) compared with intermittent (26.8%) β-lactam antibiotic infusions (odds ratio, 0.91). Meaning: In critically ill patients with sepsis, continuous vs intermittent β-lactam antibiotic infusions did not significantly reduce 90-day mortality in the primary analysis. Importance: Whether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. Objective: To evaluate whether continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis. Design, Setting, and Participants: An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis. Intervention: Eligible patients were randomized to receive an equivalent 24-hour dose of a β-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality. Results: Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, −1.9% [95% CI, −4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P =.08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different. Conclusions and Relevance: The observed difference in 90-day mortality between continuous vs intermittent infusions of β-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03213990 This clinical trial compares the efficacy of continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) in decreasing all-cause mortality at 90 days in critically ill patients with sepsis. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Rapid Diagnostic Tests and Antimicrobial Stewardship Programs for the Management of Bloodstream Infection: What Is Their Relative Contribution to Improving Clinical Outcomes? A Systematic Review and Network Meta-analysis.

Author

Peri, Anna Maria, Chatfield, Mark D, Ling, Weiping, Furuya-Kanamori, Luis, Harris, Patrick N A, and Paterson, David L

Subjects
BLOOD, RESEARCH funding, ANTIMICROBIAL stewardship, RAPID diagnostic tests, META-analysis, DESCRIPTIVE statistics, EVALUATION of medical care, CELL culture, SYSTEMATIC reviews, ODDS ratio, SEPSIS, MASS spectrometry, LENGTH of stay in hospitals, CONFIDENCE intervals
Abstract

Background Evidence about the clinical impact of rapid diagnostic tests (RDTs) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (B Cs) embedded within antimicrobial stewardship programs (ASPs) is unknown. Methods We performed network meta-analyses using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS), and time to optimal therapy. Results Eighty-eight papers were selected, including 25 682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The network meta-analyses showed a significant reduction in mortality associated with the use of RDT + ASP versus BC alone (odds ratio [OR], 0.72; 95% confidence interval [CI],.59–.87) and with the use of RDT + ASP versus BC + ASP (OR, 0.78; 95% CI,.63–.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP versus BC alone (OR, 0.91; 95% CI,.84–.98) whereas no difference in LOS was shown between any other groups. A reduced time to optimal therapy was shown when RDT + ASP was compared to BC alone (−29 hours; 95% CI, −35 to −23), BC + ASP (−18 hours; 95% CI, −27 to −10), and to RDT alone (−12 hours; 95% CI, −20 to −3). Conclusions The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Pseudomonas stutzeri bloodstream infection is a prevailing community-onset disease with important mortality rates: results from a retrospective observational study in Australia.

Author

Horcajada, Juan P., Edwards, Felicity, Fonio, Silvia, Montero, Milagro, Harris, Patrick, Paterson, David L., and Laupland, Kevin B.

Subjects
PSEUDOMONAS stutzeri, DEATH rate, NUMERIC databases, OLDER men, DRUG resistance in microorganisms
Abstract

The recognition of Pseudomonas stutzeri as a cause of infections in humans has been increasing. However, only case reports and small series of P. stutzeri bloodstream infections have been published. Epidemiological data on these infections are extremely scarce. Our objective was to describe the incidence, epidemiology, antimicrobial resistance rates, and outcomes of P. stutzeri bloodstream infections in a large population-based cohort in Australia. Retrospective, laboratory-based surveillance study conducted in Queensland, Australia (population ≈ 5 million) during 2000–2019. Clinical information was obtained from public hospital admissions and vital statistics databases. In total, 228 episodes of P. stutzeri bloodstream infections were identified. Increased incidence was observed in the later years, especially in older men, and was higher during the rainy months of the year and in the warmest and more humid regions of the state. The majority of bloodstream infections were community-onset with 120 (52.6%) community-associated and 59 (25.9%) ambulatory healthcare-associated episodes. Only 49 cases (21.5%) were nosocomial. The most common foci of infection were skin and soft tissue, lower respiratory tract, and intra-abdominal. No isolate showed antimicrobial resistance. Thirty-one patients (13.6%) died. The mortality rate in patients with a respiratory infectious source was higher (21%). P. stutzeri bloodstream infection was predominantly a community-onset condition including ambulatory healthcare related cases, with increasing incidence, especially in older males. No antimicrobial resistance was observed. Mortality was high in patients with respiratory infectious source. This new observational data have implications when considering the epidemiology of these infections and for patient management. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Comparison of nasopharyngeal swab vs. lower respiratory tract specimen PCR for the diagnosis of Pneumocystis jirovecii pneumonia

Author

Chew, Rusheng, primary, Tozer, Sarah, additional, Ulett, Kimberly, additional, Paterson, David L, additional, Whiley, David, additional, Sloots, Theo, additional, Fielding, David, additional, Zappala, Christopher, additional, Bashirzadeh, Farzad, additional, Hundloe, Justin, additional, Bletchley, Cheryl, additional, and Woods, Marion L, additional

Published
2024
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48. Rapid nanopore sequencing and predictive susceptibility testing of positive blood cultures from intensive care patients with sepsis

Author

Harris, Patrick N. A., primary, Bauer, Michelle J., additional, Lüftinger, Lukas, additional, Beisken, Stephan, additional, Forde, Brian M., additional, Balch, Ross, additional, Cotta, Menino, additional, Schlapbach, Luregn, additional, Raman, Sainath, additional, Shekar, Kiran, additional, Kruger, Peter, additional, Lipman, Jeff, additional, Bialasiewicz, Seweryn, additional, Coin, Lachlan, additional, Roberts, Jason A., additional, Paterson, David L., additional, and Irwin, Adam D., additional

Published
2024
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50. Statistical analysis plan for the BLING III study: a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis

Author

Billot, Laurent, Lipman, Jeffrey, Brett, Stephen J., De Waele, Jan J., Cotta, Menino Osbert, Davis, Joshua S., Finfer, Simon, Hammond, Naomi E., Knowles, Serena, McGuinness, Shay, Myburgh, John, Paterson, David L., Peake, Sandra, Rajbhandari, Dorrilyn, Rhodes, Andrew, Roberts, Jason A., Roger, Claire, Shirwadkar, Charudatt, Starr, Therese, Taylor, Colman, and Dulhunty, Joel M.

Published
2021
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