New automated analysis to monitor neutrophil function point-of-care in the intensive care unit after trauma

BACKGROUND: Patients often develop infectious complications after severe trauma. No biomarkers exist that enable early identification of patients who are at risk. Neutrophils are important immune cells that combat these infections by phagocytosis and killing of pathogens. Analysis of neutrophil function used to be laborious and was therefore not applicable in routine diagnostics. Hence, we developed a quick and point-of-care method to assess a critical part of neutrophil function, neutrophil phagosomal acidification. The aim of this study was to investigate whether this method was able to analyze neutrophil functionality in severely injured patients and whether a relation with the development of infectious complications was present. RESULTS: Fifteen severely injured patients (median ISS of 33) were included, of whom 6 developed an infection between day 4 and day 9 after trauma. The injury severity score did not significantly differ between patients who developed an infection and patients who did not (p = 0.529). Patients who developed an infection showed increased acidification immediately after trauma (p = 0.006) and after 3 days (p = 0.026) and a decrease in the days thereafter to levels in the lower normal range. In contrast, patients who did not develop infectious complications showed high-normal acidification within the first days and increased tasset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients. CONCLUSION: Neutrophil function can be measured in the ICU setting by rapid point-of-care analysis of phagosomal acidification. This analysis differed between trauma patients who developed infectious complications and trauma patients who did not. Therefore, this assay might prove a valuable asset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients. TRIAL REGISTRATION: Central Committee on Research Involving Human Subjects, NL43279.041.13. Registered 14 February 2014. https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm

The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils

A malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16, and CD62L) in the absence or presence of a formyl peptide (fNLF). Forty-five SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (n = 20) or other viral (n = 10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSOM algorithm. Low blood eosinophil numbers (<100 cells/µL; p < 0.005) were found both in patients with COVID-19 and with other infectious diseases, albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11b bright population consisted of 5.4% (CI 95% = 3.8, 13.4) of total eosinophils. After activation, this population of CD11b bright cells comprised nearly half the population (42.21%, CI 95% = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11b bright cells before activation (7.6%, CI 95% = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11b bright fraction after activation (23.7%, CI 95% = 18.5, 27.6; p < 0.001). Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF. This might be caused by migration of fully functional cells to the tissue

An increase in CD62Ldim neutrophils precedes the development of pulmonary embolisms in COVID-19 patients

OBJECTIVES: A high incidence of pulmonary embolism (PE) is reported in patients with critical Corona Virus Disease 2019 (COVID-19). Neutrophils may contribute to this through a process referred to as immunothrombosis. The aim of this study was to investigate the occurrence of neutrophil subpopulations in blood preceding the development of COVID-19 associated PE. METHODS: We studied COVID-19 patients admitted to the ICU of our tertiary hospital between 19-03-2020 and 17-05-2020. Point-of-care fully automated flow cytometry was performed prior to ICU admission, measuring the neutrophil activation/maturation markers CD10, CD11b, CD16 and CD62L. Neutrophil receptor expression was compared between patients who did or did not develop PE (as diagnosed on CT angiography) during or after their ICU stay. RESULTS: Among 25 eligible ICU patients, 22 subjects were included for analysis, of whom nine developed PE. The median (IQR) time between neutrophil phenotyping and PE occurrence was 9 (7-12) days. A significant increase in the immune-suppressive neutrophil phenotype CD16bright /CD62Ldim was observed on the day of ICU admission (p=0.014) in patients developing PE compared to patients who did not. CONCLUSION: The increase in this neutrophil phenotype indicates that the increased number of CD16bright /CD62Ldim neutrophils might be used as prognostic marker to predict those patients that will develop PE in critical COVID19 patients

Kinetics of Neutrophil Subsets in Acute, Subacute, and Chronic Inflammation

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16dim banded neutrophils. These cells were probably released from the bone marrow (left shift). Acute inflammation induced by human experimental endotoxemia (LPS model) was additionally accompanied by an immediate increase in a CD62Llow neutrophil population, which was not as explicit after injury/trauma induced acute inflammation. The situation in sub-acute inflammation was more complex. CD62Llow neutrophils appeared in the peripheral blood several days (>3 days) after trauma with a peak after 10 days. A similar situation was found in the blood of COVID-19 patients returning from the ICU. Sorted CD16low and CD62Llow subsets from trauma and COVID-19 patients displayed the same nuclear characteristics as found after experimental endotoxemia. In diseases associated with chronic inflammation (stable COPD and treatment naive HIV) no increases in CD16low or CD62Llow neutrophils were found in the peripheral blood. All neutrophil subsets were present in the bone marrow during homeostasis. After LPS rechallenge, these subsets failed to appear in the circulation, but continued to be present in the bone marrow, suggesting the absence of recruitment signals. Because the subsets were reported to have different functionalities, these results on the kinetics of neutrophil subsets in a range of inflammatory conditions contribute to our understanding on the role of neutrophils in health and disease

Flow cytometric evaluation of the neutrophil compartment in COVID-19 at hospital presentation: A normal response to an abnormal situation

Coronavirus disease 2019 (COVID-19) is a rapidly emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Critical COVID-19 is thought to be associated with a hyper-inflammatory process that can develop into acute respiratory distress syndrome, a critical disease normally mediated by dysfunctional neutrophils. This study tested the hypothesis whether the neutrophil compartment displays characteristics of hyperinflammation in COVID-19 patients. Therefore, a prospective study was performed on all patients with suspected COVID-19 presenting at the emergency room of a large academic hospital. Blood drawn within 2 d after hospital presentation was analyzed by point-of-care automated flow cytometry and compared with blood samples collected at later time points. COVID-19 patients did not exhibit neutrophilia or eosinopenia. Unexpectedly neutrophil activation markers (CD11b, CD16, CD10, and CD62L) did not differ between COVID-19-positive patients and COVID-19-negative patients diagnosed with other bacterial/viral infections, or between COVID-19 severity groups. In all patients, a decrease was found in the neutrophil maturation markers indicating an inflammation-induced left shift of the neutrophil compartment. In COVID-19 this was associated with disease severity

Taking the pulse of Earth's tropical forests using networks of highly distributed plots

Tropical forests are the most diverse and productive ecosystems on Earth. While better understanding of these forests is critical for our collective future, until quite recently efforts to measure and monitor them have been largely disconnected. Networking is essential to discover the answers to questions that transcend borders and the horizons of funding agencies. Here we show how a global community is responding to the challenges of tropical ecosystem research with diverse teams measuring forests tree-by-tree in thousands of long-term plots. We review the major scientific discoveries of this work and show how this process is changing tropical forest science. Our core approach involves linking long-term grassroots initiatives with standardized protocols and data management to generate robust scaled-up results. By connecting tropical researchers and elevating their status, our Social Research Network model recognises the key role of the data originator in scientific discovery. Conceived in 1999 with RAINFOR (South America), our permanent plot networks have been adapted to Africa (AfriTRON) and Southeast Asia (T-FORCES) and widely emulated worldwide. Now these multiple initiatives are integrated via ForestPlots.net cyber-infrastructure, linking colleagues from 54 countries across 24 plot networks. Collectively these are transforming understanding of tropical forests and their biospheric role. Together we have discovered how, where and why forest carbon and biodiversity are responding to climate change, and how they feedback on it. This long-term pan-tropical collaboration has revealed a large long-term carbon sink and its trends, as well as making clear which drivers are most important, which forest processes are affected, where they are changing, what the lags are, and the likely future responses of tropical forests as the climate continues to change. By leveraging a remarkably old technology, plot networks are sparking a very modern revolution in tropical forest science. In the future, humanity can benefit greatly by nurturing the grassroots communities now collectively capable of generating unique, long-term understanding of Earth's most precious forests.Additional co-authors: Susan Laurance, William Laurance, Francoise Yoko Ishida, Andrew Marshall, Catherine Waite, Hannsjoerg Woell, Jean-Francois Bastin, Marijn Bauters, Hans Beeckman, Pfascal Boeckx, Jan Bogaert, Charles De Canniere, Thales de Haulleville, Jean-Louis Doucet, Olivier Hardy, Wannes Hubau, Elizabeth Kearsley, Hans Verbeeck, Jason Vleminckx, Steven W. Brewer, Alfredo Alarcón, Alejandro Araujo-Murakami, Eric Arets, Luzmila Arroyo, Ezequiel Chavez, Todd Fredericksen, René Guillén Villaroel, Gloria Gutierrez Sibauty, Timothy Killeen, Juan Carlos Licona, John Lleigue, Casimiro Mendoza, Samaria Murakami, Alexander Parada Gutierrez, Guido Pardo, Marielos Peña-Claros, Lourens Poorter, Marisol Toledo, Jeanneth Villalobos Cayo, Laura Jessica Viscarra, Vincent Vos, Jorge Ahumada, Everton Almeida, Jarcilene Almeida, Edmar Almeida de Oliveira, Wesley Alves da Cruz, Atila Alves de Oliveira, Fabrício Alvim Carvalho, Flávio Amorim Obermuller, Ana Andrade, Fernanda Antunes Carvalho, Simone Aparecida Vieira, Ana Carla Aquino, Luiz Aragão, Ana Claudia Araújo, Marco Antonio Assis, Jose Ataliba Mantelli Aboin Gomes, Fabrício Baccaro, Plínio Barbosa de Camargo, Paulo Barni, Jorcely Barroso, Luis Carlos Bernacci, Kauane Bordin, Marcelo Brilhante de Medeiros, Igor Broggio, José Luís Camargo, Domingos Cardoso, Maria Antonia Carniello, Andre Luis Casarin Rochelle, Carolina Castilho, Antonio Alberto Jorge Farias Castro, Wendeson Castro, Sabina Cerruto Ribeiro, Flávia Costa, Rodrigo Costa de Oliveira, Italo Coutinho, John Cunha, Lola da Costa, Lucia da Costa Ferreira, Richarlly da Costa Silva, Marta da Graça Zacarias Simbine, Vitor de Andrade Kamimura, Haroldo Cavalcante de Lima, Lia de Oliveira Melo, Luciano de Queiroz, José Romualdo de Sousa Lima, Mário do Espírito Santo, Tomas Domingues, Nayane Cristina dos Santos Prestes, Steffan Eduardo Silva Carneiro, Fernando Elias, Gabriel Eliseu, Thaise Emilio, Camila Laís Farrapo, Letícia Fernandes, Gustavo Ferreira, Joice Ferreira, Leandro Ferreira, Socorro Ferreira, Marcelo Fragomeni Simon, Maria Aparecida Freitas, Queila S. García, Angelo Gilberto Manzatto, Paulo Graça, Frederico Guilherme, Eduardo Hase, Niro Higuchi, Mariana Iguatemy, Reinaldo Imbrozio Barbosa, Margarita Jaramillo, Carlos Joly, Joice Klipel, Iêda Leão do Amaral, Carolina Levis, Antonio S. Lima, Maurício Lima Dan, Aline Lopes, Herison Madeiros, William E. Magnusson, Rubens Manoel dos Santos, Beatriz Marimon, Ben Hur Marimon Junior, Roberta Marotti Martelletti Grillo, Luiz Martinelli, Simone Matias Reis, Salomão Medeiros, Milton Meira-Junior, Thiago Metzker, Paulo Morandi, Natanael Moreira do Nascimento, Magna Moura, Sandra Cristina Müller, Laszlo Nagy, Henrique Nascimento, Marcelo Nascimento, Adriano Nogueira Lima, Raimunda Oliveira de Araújo, Jhonathan Oliveira Silva, Marcelo Pansonato, Gabriel Pavan Sabino, Karla Maria Pedra de Abreu, Pablo José Francisco Pena Rodrigues, Maria Piedade, Domingos Rodrigues, José Roberto Rodrigues Pinto, Carlos Quesada, Eliana Ramos, Rafael Ramos, Priscyla Rodrigues, Thaiane Rodrigues de Sousa, Rafael Salomão, Flávia Santana, Marcos Scaranello, Rodrigo Scarton Bergamin, Juliana Schietti, Jochen Schöngart, Gustavo Schwartz, Natalino Silva, Marcos Silveira, Cristiana Simão Seixas, Marta Simbine, Ana Claudia Souza, Priscila Souza, Rodolfo Souza, Tereza Sposito, Edson Stefani Junior, Julio Daniel do Vale, Ima Célia Guimarães Vieira, Dora Villela, Marcos Vital, Haron Xaud, Katia Zanini, Charles Eugene Zartman, Nur Khalish Hafizhah Ideris, Faizah binti Hj Metali, Kamariah Abu Salim, Muhd Shahruney Saparudin, Rafizah Mat Serudin, Rahayu Sukmaria Sukri, Serge Begne, George Chuyong, Marie Noel Djuikouo, Christelle Gonmadje, Murielle Simo-Droissart, Bonaventure Sonké, Hermann Taedoumg, Lise Zemagho, Sean Thomas, Fidèle Baya, Gustavo Saiz, Javier Silva Espejo, Dexiang Chen, Alan Hamilton, Yide Li, Tushou Luo, Shukui Niu, Han Xu, Zhang Zhou, Esteban Álvarez-Dávila, Juan Carlos Andrés Escobar, Henry Arellano-Peña, Jaime Cabezas Duarte, Jhon Calderón, Lina Maria Corrales Bravo, Borish Cuadrado, Hermes Cuadros, Alvaro Duque, Luisa Fernanda Duque, Sandra Milena Espinosa, Rebeca Franke-Ante, Hernando García, Alejandro Gómez, Roy González-M., Álvaro Idárraga-Piedrahíta, Eliana Jimenez, Rubén Jurado, Wilmar López Oviedo, René López-Camacho, Omar Aurelio Melo Cruz, Irina Mendoza Polo, Edwin Paky, Karen Pérez, Angel Pijachi, Camila Pizano, Adriana Prieto, Laura Ramos, Zorayda Restrepo Correa, James Richardson, Elkin Rodríguez, Gina M. Rodriguez M., Agustín Rudas, Pablo Stevenson, Markéta Chudomelová, Martin Dancak, Radim Hédl, Stanislav Lhota, Martin Svatek, Jacques Mukinzi, Corneille Ewango, Terese Hart, Emmanuel Kasongo Yakusu, Janvier Lisingo, Jean-Remy Makana, Faustin Mbayu, Benjamin Toirambe, John Tshibamba Mukendi, Lars Kvist, Gustav Nebel, Selene Báez, Carlos Céron, Daniel M. Griffith, Juan Ernesto Guevara Andino, David Neill, Walter Palacios, Maria Cristina Peñuela-Mora, Gonzalo Rivas-Torres, Gorky Villa, Sheleme Demissie, Tadesse Gole, Techane Gonfa, Kalle Ruokolainen, Michel Baisie, Fabrice Bénédet, Wemo Betian, Vincent Bezard, Damien Bonal, Jerôme Chave, Vincent Droissart, Sylvie Gourlet-Fleury, Annette Hladik, Nicolas Labrière, Pétrus Naisso, Maxime Réjou-Méchain, Plinio Sist, Lilian Blanc, Benoit Burban, Géraldine Derroire, Aurélie Dourdain, Clement Stahl, Natacha Nssi Bengone, Eric Chezeaux, Fidèle Evouna Ondo, Vincent Medjibe, Vianet Mihindou, Lee White, Heike Culmsee, Cristabel Durán Rangel, Viviana Horna, Florian Wittmann, Stephen Adu-Bredu, Kofi Affum-Baffoe, Ernest Foli, Michael Balinga, Anand Roopsind, James Singh, Raquel Thomas, Roderick Zagt, Indu K. Murthy, Kuswata Kartawinata, Edi Mirmanto, Hari Priyadi, Ismayadi Samsoedin, Terry Sunderland, Ishak Yassir, Francesco Rovero, Barbara Vinceti, Bruno Hérault, Shin-Ichiro Aiba, Kanehiro Kitayama, Armandu Daniels, Darlington Tuagben, John T. Woods, Muhammad Fitriadi, Alexander Karolus, Kho Lip Khoon, Noreen Majalap, Colin Maycock, Reuben Nilus, Sylvester Tan, Almeida Sitoe, Indiana Coronado G., Lucas Ojo, Rafael de Assis, Axel Dalberg Poulsen, Douglas Sheil, Karen Arévalo Pezo, Hans Buttgenbach Verde, Victor Chama Moscoso, Jimmy Cesar Cordova Oroche, Fernando Cornejo Valverde, Massiel Corrales Medina, Nallaret Davila Cardozo, Jano de Rutte Corzo, Jhon del Aguila Pasquel, Gerardo Flores Llampazo, Luis Freitas, Darcy Galiano Cabrera, Roosevelt García Villacorta, Karina Garcia Cabrera, Diego García Soria, Leticia Gatica Saboya, Julio Miguel Grandez Rios, Gabriel Hidalgo Pizango, Eurídice Honorio Coronado, Isau Huamantupa-Chuquimaco, Walter Huaraca Huasco, Yuri Tomas Huillca Aedo, Jose Luis Marcelo Peña, Abel Monteagudo Mendoza, Vanesa Moreano Rodriguez, Percy Núñez Vargas, Sonia Cesarina Palacios Ramos, Nadir Pallqui Camacho, Antonio Peña Cruz, Freddy Ramirez Arevalo, José Reyna Huaymacari, Carlos Reynel Rodriguez, Marcos Antonio Ríos Paredes, Lily Rodriguez Bayona, Rocio del Pilar Rojas Gonzales, Maria Elena Rojas Peña, Norma Salinas Revilla, Yahn Carlos Soto Shareva, Raul Tupayachi Trujillo, Luis Valenzuela Gamarra, Rodolfo Vasquez Martinez, Jim Vega Arenas, Christian Amani, Suspense Averti Ifo, Yannick Bocko, Patrick Boundja, Romeo Ekoungoulou, Mireille Hockemba, Donatien Nzala, Alusine Fofanah, David Taylor, Guillermo Bañares-de Dios, Luis Cayuela, Íñigo Granzow-de la Cerda, Manuel Macía, Juliana Stropp, Maureen Playfair, Verginia Wortel, Toby Gardner, Robert Muscarella, Hari Priyadi, Ervan Rutishauser, Kuo-Jung Chao, Pantaleo Munishi, Olaf Bánki, Frans Bongers, Rene Boot, Gabriella Fredriksson, Jan Reitsma, Hans ter Steege, Tinde van Andel, Peter van de Meer, Peter van der Hout, Mark van Nieuwstadt, Bert van Ulft, Elmar Veenendaal, Ronald Vernimmen, Pieter Zuidema, Joeri Zwerts, Perpetra Akite, Robert Bitariho, Colin Chapman, Eilu Gerald, Miguel Leal, Patrick Mucunguzi, Miguel Alexiades, Timothy R. Baker, Karina Banda, Lindsay Banin, Jos Barlow, Amy Bennett, Erika Berenguer, Nicholas Berry, Neil M. Bird, George A. Blackburn, Francis Brearley, Roel Brienen, David Burslem, Lidiany Carvalho, Percival Cho, Fernanda Coelho, Murray Collins, David Coomes, Aida Cuni-Sanchez, Greta Dargie, Kyle Dexter, Mat Disney, Freddie Draper, Muying Duan, Adriane Esquivel-Muelbert, Robert Ewers, Belen Fadrique, Sophie Fauset, Ted R. Feldpausch, Filipe França, David Galbraith, Martin Gilpin, Emanuel Gloor, John Grace, Keith Hamer, David Harris, Tommaso Jucker, Michelle Kalamandeen, Bente Klitgaard, Aurora Levesley, Simon L. Lewis, Jeremy Lindsell, Gabriela Lopez-Gonzalez, Jon Lovett, Yadvinder Malhi, Toby Marthews, Emma McIntosh, Karina Melgaço, William Milliken, Edward Mitchard, Peter Moonlight, Sam Moore, Alexandra Morel, Julie Peacock, Kelvin Peh, Colin Pendry, R. Toby Pennington, Luciana de Oliveira Pereira, Carlos Peres, Oliver L. Phillips, Georgia Pickavance, Thomas Pugh, Lan Qie, Terhi Riutta, Katherine Roucoux, Casey Ryan, Tiina Sarkinen, Camila Silva Valeria, Dominick Spracklen, Suzanne Stas, Martin Sullivan, Michael Swaine, Joey Talbot, James Taplin, Geertje van der Heijden, Laura Vedovato, Simon Willcock, Mathew Williams, Luciana Alves, Patricia Alvarez Loayza, Gabriel Arellano, Cheryl Asa, Peter Ashton, Gregory Asner, Terry Brncic, Foster Brown, Robyn Burnham, Connie Clark, James Comiskey, Gabriel Damasco, Stuart Davies, Tony Di Fiore, Terry Erwin, William Farfan-Rios, Jefferson Hall, David Kenfack, Thomas Lovejoy, Roberta Martin, Olga Martha Montiel, John Pipoly, Nigel Pitman, John Poulsen, Richard Primack, Miles Silman, Marc Steininger, Varun Swamy, John Terborgh, Duncan Thomas, Peter Umunay, Maria Uriarte, Emilio Vilanova Torre, Ophelia Wang, Kenneth Young, Gerardo A. Aymard C., Lionel Hernández, Rafael Herrera Fernández, Hirma Ramírez-Angulo, Pedro Salcedo, Elio Sanoja, Julio Serrano, Armando Torres-Lezama, Tinh Cong Le, Trai Trong Le, Hieu Dang Tra

Intracellular Penetration and Effects of Antibiotics on <i>Staphylococcus aureus</i> Inside Human Neutrophils: A Comprehensive Review

Neutrophils are important assets in defense against invading bacteria like staphylococci. However, (dysfunctioning) neutrophils can also serve as reservoir for pathogens that are able to survive inside the cellular environment. Staphylococcus aureus is a notorious facultative intracellular pathogen. Most vulnerable for neutrophil dysfunction and intracellular infection are immune-deficient patients or, as has recently been described, severely injured patients. These dysfunctional neutrophils can become hide-out spots or &#8220;Trojan horses&#8221; for S. aureus. This location offers protection to bacteria from most antibiotics and allows transportation of bacteria throughout the body inside moving neutrophils. When neutrophils die, these bacteria are released at different locations. In this review, we therefore focus on the capacity of several groups of antibiotics to enter human neutrophils, kill intracellular S. aureus and affect neutrophil function. We provide an overview of intracellular capacity of available antibiotics to aid in clinical decision making. In conclusion, quinolones, rifamycins and sulfamethoxazole-trimethoprim seem very effective against intracellular S. aureus in human neutrophils. Oxazolidinones, macrolides and lincosamides also exert intracellular antibiotic activity. Despite that the reviewed data are predominantly of in vitro origin, these findings should be taken into account when intracellular infection is suspected, as can be the case in severely injured patients

Intracellular Penetration and Effects of Antibiotics on Staphylococcus aureus Inside Human Neutrophils : A Comprehensive Review

Neutrophils are important assets in defense against invading bacteria like staphylococci. However, (dysfunctioning) neutrophils can also serve as reservoir for pathogens that are able to survive inside the cellular environment. Staphylococcus aureus is a notorious facultative intracellular pathogen. Most vulnerable for neutrophil dysfunction and intracellular infection are immune-deficient patients or, as has recently been described, severely injured patients. These dysfunctional neutrophils can become hide-out spots or "Trojan horses" for S. aureus. This location offers protection to bacteria from most antibiotics and allows transportation of bacteria throughout the body inside moving neutrophils. When neutrophils die, these bacteria are released at different locations. In this review, we therefore focus on the capacity of several groups of antibiotics to enter human neutrophils, kill intracellular S. aureus and affect neutrophil function. We provide an overview of intracellular capacity of available antibiotics to aid in clinical decision making. In conclusion, quinolones, rifamycins and sulfamethoxazole-trimethoprim seem very effective against intracellular S. aureus in human neutrophils. Oxazolidinones, macrolides and lincosamides also exert intracellular antibiotic activity. Despite that the reviewed data are predominantly of in vitro origin, these findings should be taken into account when intracellular infection is suspected, as can be the case in severely injured patients