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1. A blue fluorescent labeling technique utilizing micro- and nanoparticles for tracking in LIVE/DEAD® stained pathogenic biofilms of Staphylococcus aureus and Burkholderia cepacia

Author

Klinger-Strobel M, Ernst J, Lautenschläger C, Pletz MW, Fischer D, and Makarewicz O

Subjects
nanoparticles, 7-amino-4-methyl-3-coumarinylacetic acid, Staphylococcus aureus, Burkholderia cepacia, PLGA, PEG, confocal laser scanning microscopy, cystic fibrosis, Medicine (General), R5-920
Abstract

Mareike Klinger-Strobel,1,2,* Julia Ernst,3,* Christian Lautenschläger,4 Mathias W Pletz,1,2 Dagmar Fischer,3,5 Oliwia Makarewicz1,2 1Center for Infectious Diseases and Infection’s Control, 2Center for Sepsis Control and Care, Jena University Hospital, 3Department of Pharmaceutical Technology, Friedrich Schiller University Jena, 4Department of Internal Medicine IV, Jena University Hospital, 5Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Jena, Germany*These authors contributed equally to this work Abstract: Strategies that target and treat biofilms are widely applied to bacterial cultures using popular live/dead staining techniques with mostly red or green fluorescent markers (eg, with SYTO® 9, propidium iodide, fluorescein). Therefore, visualizing drugs or micro- and nanoparticulate delivery systems to analyze their distribution and effects in biofilms requires a third fluorescent dye that does not interfere with the properties of the live/dead markers. The present study establishes and evaluates a model for tracking polymeric particles in fluorescently stained biological material. To this end, poly(D,L-lactide-co-glycolide) (PLGA)-based micro- and nanoparticles were used as well-established model systems, which, because of their favorable safety profiles, are expected to play important future roles with regard to drug delivery via inhalation. PLGA was covalently and stably labeled with 7-amino-4-methyl-3-coumarinylacetic acid (AMCA), after which blue fluorescent poly(ethylene glycol)-block-PLGA (PEG-PLGA) particles were prepared using a mixture of fluorescent AMCA-PLGA and PEG-PLGA. Because chitosan is known to reduce negative surface charge, blue fluorescent PEG-PLGA-particles with chitosan were also prepared. These micro- and nanoparticles were physicochemically characterized and could be clearly distinguished from live/dead stained bacteria in biofilms using confocal laser scanning microscopy. Keywords: 7-amino-4-methyl-3-coumarinylacetic acid, PLGA, PEG, confocal laser scanning microscopy, cystic fibrosis, chitosan, hydrodynamic diameter

Published
2016

7. Infection control in the intensive care unit: expert consensus statements for SARS-CoV-2 using a Delphi method

Author

Nasa, P, Azoulay, E, Chakrabarti, A, Divatia, JV, Jain, R, Rodrigues, C, Rosenthal, VD, Alhazzani, W, Arabi, YM, Bakker, J, Bassetti, M, De Waele, J, Dimopoulos, G, Du, B, Einav, S, Evans, L, Finfer, S, Guerin, C, Hammond, NE, Jaber, S, Kleinpell, RM, Koh, Y, Kollef, M, Levy, MM, Machado, FR, Mancebo, J, Martin-Loeches, I, Mer, M, Niederman, MS, Pelosi, P, Perner, A, Peter, JV, Phua, J, Piquilloud, L, Pletz, MW, Rhodes, A, Schultz, MJ, Singer, M, Timsit, JF, Venkatesh, B, Vincent, JL, Welte, T, and Myatra, S

Abstract

During the current COVID-19 pandemic, health-care workers and uninfected patients in intensive care units (ICUs) are at risk of being infected with SARS-CoV-2 as a result of transmission from infected patients and health-care workers. In the absence of high-quality evidence on the transmission of SARS-CoV-2, clinical practice of infection control and prevention in ICUs varies widely. Using a Delphi process, international experts in intensive care, infectious diseases, and infection control developed consensus statements on infection control for SARS-CoV-2 in an ICU. Consensus was achieved for 31 (94%) of 33 statements, from which 25 clinical practice statements were issued. These statements include guidance on ICU design and engineering, health-care worker safety, visiting policy, personal protective equipment, patients and procedures, disinfection, and sterilisation. Consensus was not reached on optimal return to work criteria for health-care workers who were infected with SARS-CoV-2 or the acceptable disinfection strategy for heat-sensitive instruments used for airway management of patients with SARS-CoV-2 infection. Well designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.

Published
2022

10. Kalkulierte parenterale Initialtherapie bakterieller Infektionen: Respiratorische Infektionen

Author

Ott, SR, Bodmann, KF, Grabein, B, Höffken, G, Kolditz, M, Lode, H, Pletz, MW, and Thalhammer, F

Subjects
ddc: 610, lcsh:RC109-216, 610 Medical sciences, Medicine, lcsh:Infectious and parasitic diseases
Abstract

This is the fifth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. It provides recommendations for the empirical and targeted antimicrobial treatment of lower respiratory tract infections, with a special emphasis on the treatment of acute exacerbation of COPD, community-acquired pneumonia and hospital-acquired pneumonia., Dies ist das fünfte Kapitel der von der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) herausgegebenen S2k Leitlinie „Kalkulierte parenterale Initialtherapie bakterieller Erkrankungen bei Erwachsenen – Update 2018“ in der 2. aktualisierten Fassung. Es enthält Empfehlungen für die empirische und gezielte antimikrobielle Behandlung von Infektionen der unteren Atemwege mit besonderem Schwerpunkt auf der Behandlung bei akuter Exazerbation der COPD sowie ambulant und nosokomial erworbenen Pneumonien., GMS Infectious Diseases; 8:Doc15

Published
2020
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11. International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia

Author

Aliberti, S, Cook, GS, Babu, BL, Reyes, LF, Rodriguez, AH, Sanz, F, Soni, NJ, Anzueto, A, Faverio, P, Sadud, RF, Muhammad, I, Prat, C, Vendrell, E, Neves, J, Kaimakamis, E, Feneley, A, Swarnakar, R, Franzetti, F, Carugati, M, Morosi, M, Monge, E, Restrepo, MI, Aruj, PK, Attorri, S, Barimboim, E, Caeiro, JP, Garzon, MI, Cambursano, VH, Ceccato, A, Chertcoff, J, Lascar, F, Di Tulio, F, Diaz, AC, de Vedia, L, Ganaha, MC, Lambert, S, Lopardo, G, Lopez, V, Luna, CM, Malberti, AG, Morcillo, N, Tartara, S, Pensotti, C, Pereyra, B, Scapellato, PG, Stagnaro, JP, Shah, S, Lotsch, F, Thalhammer, F, Anseeuw, K, Francois, CA, Van Braeckel, E, Vincent, JL, Djimon, MZ, Bashi, J, Dodo, R, Nouer, SA, Chipev, P, Encheva, M, Miteva, D, Petkova, D, Balkissou, AD, Yone, EWP, Ngahane, BHM, Shen, N, Xu, JF, Rico, CAB, Buitrago, R, Paternina, FJP, Ntumba, JMK, Carevic, VV, Jakopovic, M, Jankovic, M, Matkovic, Z, Mitrecic, I, Jacobsson, MLB, Christensen, AB, Bodtger, UCH, Meyer, CN, Jensen, AV, Baunbaek-knudsen, G, Petersen, PT, Andersen, S, Abd El-Wahhab, IES, Morsy, NE, Shafiek, H, Sobh, E, Abdulsemed, KA, Bertrand, F, Brun-Buisson, C, de Montmollin, E, Fartoukh, M, Messika, J, Tattevin, P, Khoury, A, Ebruke, B, Dreher, M, Kolditz, M, Meisinger, M, Pletz, MW, Hagel, S, Rupp, J, Schaberg, T, Spielmanns, M, Creutz, P, Suttorp, N, Siaw-Lartey, B, Dimakou, K, Papapetrou, D, Tsigou, E, Ampazis, D, Bhatia, M, Dhar, R, D'Souza, G, Garg, R, Koul, PA, Mahesh, PA, Jayaraj, BS, Narayan, KV, Udnur, HB, Krishnamurthy, SB, Kant, S, Limaye, S, Salvi, S, Golshani, K, Keatings, VM, Martin-Loeches, I, Maor, Y, Strahilevitz, J, Battaglia, S, Carrabba, M, Ceriana, P, Confalonieri, M, Monforte, AD, Del Prato, B, De Rosa, M, Fantini, R, Fiorentino, G, Gammino, MA, Menzella, F, Milani, G, Nava, S, Palmiero, G, Petrino, R, Gabrielli, B, Rossi, P, Sorino, C, Steinhilber, G, Zanforlin, A, Carone, M, Patella, V, Scarlata, S, Comel, A, Kurahashi, K, Bacha, ZA, Ugalde, DB, Zuniga, OC, Villegas, JF, Medenica, M, van de Garde, EMW, Mihsra, DR, Shrestha, P, Ridgeon, E, Awokola, BI, Nwankwo, ONO, Olufunlola, AB, Olumide, S, Ukwaja, KN, Irfan, M, Minarowski, L, Szymon, S, Froes, F, Leuschner, P, Meireles, M, Ferrao, C, Ravara, SB, Brocovschii, V, Ion, C, Rusu, D, Toma, C, Chirita, D, Dorobat, CM, Birkun, A, Kaluzhenina, A, Almotairi, A, Bukhary, ZAA, Edathodu, J, Fathy, A, Enani, AMA, Mohamed, NE, Memon, JU, Bella, A, Bogdanovic, N, Milenkovic, B, Pesut, D, Borderias, L, Garcia, NMB, Alarcon, HC, Cilloniz, C, Torres, A, Diaz-Brito, V, Casas, X, Gonzalez, AE, Fernandez-Almira, ML, Gallego, M, Gaspar-Garcia, I, del Castillo, JG, Victoria, PJ, Martinez, EL, de Molina, RM, Marcos, PJ, Menendez, R, Pando-Sandoval, A, Aymerich, CP, de la Torre, AL, Garcia-Olive, I, Rello, J, Moyano, S, Sibila, O, Rodrigo-Troyano, A, Sole-Violan, J, Uranga, A, van Boven, JFM, Torra, EV, Pujol, JA, Feldman, C, Yum, HK, Fiogbe, AA, Yangui, F, Bilaceroglu, S, Dalar, L, Yilmaz, U, Bogomolov, A, Elahi, N, Dhasmana, DJ, Ions, R, Skeemer, J, Woltmann, G, Hancock, C, Hill, AT, Rudran, B, Ruiz-Buitrago, S, Campbell, M, Whitaker, P, Youzguin, A, Singanayagam, A, Allen, KS, Brito, V, Dietz, J, Dysart, CE, Kellie, SM, Franco-Sadud, RA, Meier, G, Gaga, M, Holland, TL, Bergin, SP, Kheir, F, Landmeier, M, Lois, M, Nair, GB, Patel, H, Reyes, K, Rodriguez-Cintron, W, Saito, S, Noda, J, Hinojosa, CI, Levine, SM, Angel, LF, Whitlow, KS, Hipskind, J, Sukhija, K, Totten, V, Wunderink, RG, Shah, RD, Mateyo, KJ, Noriega, L, Alvarado, E, Aman, M, Labra, L, Aliberti, S, Cook, G, Babu, B, Reyes, L, H. Rodriguez, A, Sanz, F, Soni, N, Anzueto, A, Faverio, P, Sadud, R, Muhammad, I, Prat, C, Vendrell, E, Neves, J, Kaimakamis, E, Feneley, A, Swarnakar, R, Franzetti, F, Carugati, M, Morosi, M, Monge, E, Restrepo, M, Aliberti, S., Cook, G. S., Babu, B. L., Reyes, L. F., Rodriguez, A. H., Sanz, F., Soni, N. J., Anzueto, A., Faverio, P., Sadud, R. F., Muhammad, I., Prat, C., Vendrell, E., Neves, J., Kaimakamis, E., Feneley, A., Swarnakar, R., Franzetti, F., Carugati, M., Morosi, M., Monge, E., Restrepo, M. I., Aruj, P. K., Attorri, S., Barimboim, E., Caeiro, J. P., Garzon, M. I., Cambursano, V. H., Ceccato, A., Chertcoff, J., Lascar, F., Di Tulio, F., Diaz, A. C., de Vedia, L., Ganaha, M. C., Lambert, S., Lopardo, G., Luna, C. M., Malberti, A. G., Morcillo, N., Tartara, S., Pensotti, C., Pereyra, B., Scapellato, P. G., Stagnaro, J. P., Shah, S., Lotsch, F., Thalhammer, F., Anseeuw, K., Francois, C. A., Van Braeckel, E., Vincent, J. L., Djimon, M. Z., Bashi, J., Dodo, R., Nouer, S. A., Chipev, P., Encheva, M., Miteva, D., Petkova, D., Balkissou, A. D., Yone, E. W. P., Ngahane, B. H. M., Shen, N., Xu, J. -F., Rico, C. A. B., Buitrago, R., Paternina, F. J. P., Ntumba, J. -M. K., Carevic, V. V., Jakopovic, M., Jankovic, M., Matkovic, Z., Mitrecic, I., Jacobsson, M. -L. B., Christensen, A. B., Bodtger, U. C. H., Meyer, C. N., Jensen, A. V., Baunbaek-Knudsen, G., Petersen, P. T., Andersen, S., El-Wahhab, I. E. -S. A., Morsy, N. E., Shafiek, H., Sobh, E., Abdulsemed, K. A., Bertrand, F., Brun-Buisson, C., de Montmollin, E., Fartoukh, M., Messika, J., Tattevin, P., Khoury, A., Ebruke, B., Dreher, M., Kolditz, M., Meisinger, M., Pletz, M. W., Hagel, S., Rupp, J., Schaberg, T., Spielmanns, M., Creutz, P., Suttorp, N., Siaw-Lartey, B., Dimakou, K., Papapetrou, D., Tsigou, E., Ampazis, D., Bhatia, M., Dhar, R., D'Souza, G., Garg, R., Koul, P. A., Mahesh, P. A., Jayaraj, B. S., Narayan, K. V., Udnur, H. B., Krishnamurthy, S. B., Kant, S., Limaye, S., Salvi, S., Golshani, K., Keatings, V. M., Martin-Loeches, I., Maor, Y., Strahilevitz, J., Battaglia, S., Carrabba, M., Ceriana, P., Confalonieri, M., D'Arminio Monforte, A., Del Prato, B., De Rosa, M., Fantini, R., Fiorentino, G., Gammino, M. A., Menzella, F., Milani, G., Nava, S., Palmiero, G., Petrino, R., Gabrielli, B., Rossi, P., Sorino, C., Steinhilber, G., Zanforlin, A., Carone, M., Patella, V., Scarlata, S., Comel, A., Kurahashi, K., Bacha, Z. A., Ugalde, D. B., Zuniga, O. C., Villegas, J. F., Medenica, M., van de Garde, E. M. W., Mihsra, D. R., Shrestha, P., Ridgeon, E., Awokola, B. I., Nwankwo, O. N. O., Olufunlola, A. B., Olumide, S., Ukwaja, K. N., Irfan, M., Minarowski, L., Szymon, S., Froes, F., Leuschner, P., Meireles, M., Ferrao, C., Ravara, S. B., Brocovschii, V., Ion, C., Rusu, D., Toma, C., Chirita, D., Dorobat, C. M., Birkun, A., Kaluzhenina, A., Almotairi, A., Bukhary, Z. A. A., Edathodu, J., Fathy, A., Enani, A. M. A., Mohamed, N. E., Memon, J. U., Bella, A., Bogdanovic, N., Milenkovic, B., Pesut, D., Borderias, L., Garcia, N. M. B., Alarcon, H. C., Cilloniz, C., Torres, A., Diaz-Brito, V., Casas, X., Gonzalez, A. E., Fernandez-Almira, M. L., Gallego, M., Gaspar-Garcia, I., Del Castillo, J. G., Victoria, P. J., Martinez, E. L., de Molina, R. M., Marcos, P. J., Menendez, R., Pando-Sandoval, A., Aymerich, C. P., de la Torre, A. L., Garcia-Olive, I., Rello, J., Moyano, S., Sibila, O., Rodrigo-Troyano, A., Sole-Violan, J., Uranga, A., van Boven, J. F. M., Torra, E. V., Pujol, J. A., Feldman, C., Yum, H. K., Fiogbe, A. A., Yangui, F., Bilaceroglu, S., Dalar, L., Yilmaz, U., Bogomolov, A., Elahi, N., Dhasmana, D. J., Ions, R., Skeemer, J., Woltmann, G., Hancock, C., Hill, A. T., Rudran, B., Ruiz-Buitrago, S., Campbell, M., Whitaker, P., Youzguin, A., Singanayagam, A., Allen, K. S., Brito, V., Dietz, J., Dysart, C. E., Kellie, S. M., Franco-Sadud, R. A., Meier, G., Gaga, M., Holland, T. L., Bergin, S. P., Kheir, F., Landmeier, M., Lois, M., Nair, G. B., Patel, H., Reyes, K., Rodriguez-Cintron, W., Saito, S., Noda, J., Hinojosa, C. I., Levine, S. M., Angel, L. F., Whitlow, K. S., Hipskind, J., Sukhija, K., Totten, V., Wunderink, R. G., Shah, R. D., Mateyo, K. J., Noriega, L., Alvarado, E., Aman, M., Labra, L., Aliberti S., Cook G.S., Babu B.L., Reyes L.F., Rodriguez A.H., Sanz F., Soni N.J., Anzueto A., Faverio P., Sadud R.F., Muhammad I., Prat C., Vendrell E., Neves J., Kaimakamis E., Feneley A., Swarnakar R., Franzetti F., Carugati M., Morosi M., Monge E., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano V.H., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Diaz A.C., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C.A., Van Braeckel E., Vincent J.L., Djimon M.Z., Bashi J., Dodo R., Nouer S.A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A.D., Yone E.W.P., Ngahane B.H.M., Shen N., Xu J.-F., Rico C.A.B., Buitrago R., Paternina F.J.P., Ntumba J.-M.K., Carevic V.V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Jacobsson M.-L.B., Christensen A.B., Bodtger U.C.H., Meyer C.N., Jensen A.V., Baunbaek-Knudsen G., Petersen P.T., Andersen S., El-Wahhab I.E.-S.A., Morsy N.E., Shafiek H., Sobh E., Abdulsemed K.A., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Bhatia M., Dhar R., D'souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Kant S., Limaye S., Salvi S., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., D'Arminio Monforte A., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Menzella F., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., van de Garde E.M.W., Mihsra D.R., Shrestha P., Ridgeon E., Awokola B.I., Nwankwo O.N.O., Olufunlola A.B., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Ravara S.B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C.M., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z.A.A., Edathodu J., Fathy A., Enani A.M.A., Mohamed N.E., Memon J.U., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Garcia N.M.B., Alarcon H.C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., Fernandez-Almira M.L., Gallego M., Gaspar-Garcia I., Del Castillo J.G., Victoria P.J., Martinez E.L., de Molina R.M., Marcos P.J., Menendez R., Pando-Sandoval A., Aymerich C.P., de la Torre A.L., Garcia-Olive I., Rello J., Moyano S., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F.M., Torra E.V., Pujol J.A., Feldman C., Yum H.K., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Ions R., Skeemer J., Woltmann G., Hancock C., Hill A.T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Franco-Sadud R.A., Meier G., Gaga M., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Whitlow K.S., Hipskind J., Sukhija K., Totten V., Wunderink R.G., Shah R.D., Mateyo K.J., Noriega L., Alvarado E., Aman M., and Labra L.

Subjects
0301 basic medicine, Male, Streptococcus pneumonia, antibiotic resistance, Internationality, sputum examination, bronchiectasis, very elderly, Antibiotics, Prevalence, Drug resistance, medicine.disease_cause, Logistic regression, Global Health, Community-Acquired Infections/epidemiology, lung lavage, 0302 clinical medicine, Community-acquired pneumonia, Cost of Illness, Risk Factors, drug resistant Streptococcus pneumoniae pneumonia, 030212 general & internal medicine, Microbial drug resistant, Aged, 80 and over, adult, international cooperation, drug effect, Middle Aged, influenza vaccination, Anti-Bacterial Agents, antiinfective agent, Europe, Community-Acquired Infections, Hospitalization, Global burden of disease, Streptococcus pneumoniae, Infectious Diseases, risk factor, bacterium identification, Female, community acquired infection, influenza, liver disease, pneumococcal vaccination, Pneumococcal infection, hospitalization, medicine.drug, Microbiology (medical), medicine.medical_specialty, Asia, medicine.drug_class, 030106 microbiology, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Article, Anti-Bacterial Agents/pharmacology, 03 medical and health sciences, Internal medicine, Drug Resistance, Bacterial, Pneumonia, Pneumococcal/epidemiology, medicine, Humans, controlled study, human, tetracycline, Hospitalization/statistics & numerical data, Aged, levofloxacin, nonhuman, business.industry, disease association, microbiology, community acquired pneumonia, macrolide, Pneumonia, asthma, South America, Pneumonia, Pneumococcal, vaccination, medicine.disease, major clinical study, antibiotic sensitivity, penicillin derivative, Penicillin, Streptococcus pneumoniae/drug effects, blood examination, Africa, North America, microbiological examination, business
Abstract

Objective: Streptococcus pneumoniae is the most frequent bacterial pathogen isolated in subjects with Community-acquired pneumonia (CAP) worldwide. Limited data are available regarding the current global burden and risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP) in CAP subjects. We assessed the multinational prevalence and risk factors for DRSP-CAP in a multinational point-prevalence study. Design: The prevalence of DRSP-CAP was assessed by identification of DRSP in blood or respiratory samples among adults hospitalized with CAP in 54 countries. Prevalence and risk factors were compared among subjects that had microbiological testing and antibiotic susceptibility data. Multivariate logistic regressions were used to identify risk factors independently associated with DRSP-CAP. Results: 3,193 subjects were included in the study. The global prevalence of DRSP-CAP was 1.3% and continental prevalence rates were 7.0% in Africa, 1.2% in Asia, and 1.0% in South America, Europe, and North America, respectively. Macrolide resistance was most frequently identified in subjects with DRSP-CAP (0.6%) followed by penicillin resistance (0.5%). Subjects in Africa were more likely to have DRSP-CAP (OR: 7.6; 95% CI: 3.34-15.35, p < 0.001) when compared to centres representing other continents. Conclusions: This multinational point-prevalence study found a low global prevalence of DRSP-CAP that may impact guideline development and antimicrobial policies. Published by Elsevier Ltd on behalf of The British Infection Association.

Published
2019

24. Umsetzung von ABS Strategien in einem Universitätsklinikum – Auswirkungen auf den Antibiotikaverbrauch sowie die Erreger- bzw. Resistenzepidemiologie

Author

Hagel, S, Brandt, C, Leichenberg, K, Hartmann, M, Roedel, J, Löffler, B, and Pletz, MW

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

ABS-Programme im Krankenhaus haben das Ziel die Qualität der Verordnung von Anti-infektiva kontinuierlich zu verbessern, um beste klinische Behandlungsergebnisse unter Beachtung einer Minimierung von Toxizität für den Patienten sowie von Resistenz-entwicklung und Kosten zu erreichen. [zum vollständigen Text gelangen Sie über die oben angegebene URL], Infektiologie Update 2016; 25. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

Published
2016
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25. Schnellverfahren zum Nachweis von Betalaktam-Resistenzen direkt aus Vollblutproben

Author

Stein, C, Makarewicz, O, and Pletz, MW

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Die globale Verbreitung von bakteriellen Betalaktam-Resistenzen ist eine große Bedrohung für die öffentliche Gesundheit. Der schnelle und sensitive Nachweis von Resistenzen ist vor allem bei Sepsispatienten überlebenswichtig. Betalaktam-Resistenzen mit erweitertem Wirkungsspektrum[for full text, please go to the a.m. URL], Infektiologie Update 2014; 24. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

Published
2014
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26. Die Chronik von Antibiotika und -Resistenzen dargestellt durch scientometrische Daten

Author

Brandt, C, Makarewicz, O, Fischer, T, Stein, C, Pfeifer, Y, Werner, G, and Pletz, MW

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Um die schnelle und globale Verbreitung von Antibiotikaresistenzen zu überwachen sind überregionale Surveillance Programme zwingend nötig. Diese Daten sind von Natur aus Zeit und Ort limitiert, basieren nur auf aggregierten Informationen der teilnehmenden Laboratorien und stehen selten[for full text, please go to the a.m. URL], Infektiologie Update 2014; 24. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

Published
2014
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27. Aktuelle Aspekte zu Nebenwirkungen und Interaktionen von Antibiotika

Author

Forstner, C and Pletz, MW

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Antibiotika sind die Eckpfeiler in der Prävention und Therapie schwerer bakterieller Infektionskrankheiten. Allerdings können unerwünschte Antibiotika-induzierte Reaktionen und Interaktionen mit der Komedikation häufig die antimikrobielle Therapie komplizieren bzw. unter Umständen[for full text, please go to the a.m. URL], Infektiologie Update 2014; 24. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

Published
2014
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28. Neue Influenza A (H1N1) – Impferfolg bei Lungentransplantierten

Author

Pletz, MW, Duesberg, CB, Schweiger, B, Müller, D, Schreder, T, Knuth, C, Welte, T, and Gottlieb, J

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund: Virusinfektionen kommen bei immunsupprimierten Patienten häufiger vor als in der Normalbevölkerung, dabei sind Lungentransplantierte aufgrund verschiedener Faktoren (fehlender Hustenreiz wegen Denervierung, gestörte mukoziliäre Clearance) besonders vulnerabel. Die jährliche[for full text, please go to the a.m. URL], 10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Published
2010
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29. Prevalence of first-step parC mutants with amino acid alterations at resistance hot spots S79 and D83 among Streptococcus pneumoniae isolates in Germany

Author

Körber-Irrgang, B, Röhrig, A, Pletz, MW, and Kresken, M

Subjects
ddc: 610, bacteria, heterocyclic compounds, biochemical phenomena, metabolism, and nutrition, 610 Medical sciences, Medicine, bacterial infections and mycoses
Abstract

Objectives: Resistance (R) of S. pneumoniae (SPN) to fluoroquinolones (FQ) is mainly associated with mutations in the genes parC and gyrA encoding for the ParC subunit of topoisomerase IV and the GyrA subunit of DNA gyrase, respectively. Complete R to anti-pneumococcal FQs such as levofloxacin (LVX)[for full text, please go to the a.m. URL], 10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Published
2010
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30. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis

Author

Migliori, G. B., Eker, B., Richardson, M. D., Sotgiu, G., Zellweger, J. P., Skrahina, A., Ortmann, J., Girardi, E., Hoffmann, H., Besozzi, G., Bevilacqua, N., Kirsten, D., Centis, R., Lange, C., Hurevich, H, Skrahin, A, Muetterlein, R, Schaberg, T, Eberhardt, R, Flick, H, de Roux, A, Hamm, M, Hang, H, Hannemann, P, Hillemann, D, Kretz, B, Laumanns, C, Paulick, A, Pletz, Mw, Rau, M, Schaudt, C, Matteelli, A, Spanevello, Antonio, Toungoussova, O, D'Ambrosio, L, De Lorenzo, S, Troupioti, P, De Iaco, G, Gualano, A, De Mori, P, Lauria, Fn, Ferrara, G, Cirillo, D, and Janssens, J. P.

Subjects
Pulmonary and Respiratory Medicine, Male, safety, medicine.medical_specialty, Efficacy, Antitubercular Agents, Drug resistance, linezolid, Cohort Studies, chemistry.chemical_compound, Anti-Infective Agents, Internal medicine, Acetamides, Drug Resistance, Bacterial, Tuberculosis, Multidrug-Resistant, Odds Ratio, Medicine, Humans, extensively drug-resistant tuberculosis, Efficacy, extensively drug-resistant tuberculosis, linezolid, multidrug-resistant tuberculosis, safety, tolerability, Dosing, tolerability, Oxazolidinones, Antibacterial agent, Retrospective Studies, business.industry, Extensively drug-resistant tuberculosis, medicine.disease, multidrug-resistant tuberculosis, Surgery, Discontinuation, Europe, Regimen, Treatment Outcome, Tolerability, chemistry, Linezolid, Regression Analysis, Female, business
Abstract

Linezolid is used to treat patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-tuberculosis (TB) cases, although clinical data on its safety, tolerability and efficacy are lacking. We performed a retrospective, nonrandomised, unblinded observational study evaluating the safety and tolerability of linezolid at 600 mg q.d. or b.i.d. in MDR/XDR-TB treatment in four European countries. Efficacy evaluation compared end-points of 45 linezolid-treated against 110 linezolid-nontreated cases. Out of 195 MDR/XDR-TB patients, 85 were treated with linezolid for a mean of 221 days. Of these, 35 (41.2%) out of 85 experienced major side-effects attributed to linezolid (anaemia, thrombocytopenia and/or polyneuropathy), requiring discontinuation in 27 (77%) cases. Most side-effects occurred after 60 days of treatment. Twice-daily administration produced more major side-effects than once-daily dosing (p = 0.0004), with no difference in efficacy found. Outcomes were similar in patients treated with/without linezolid (p = 0.8), although linezolid-treated cases had more first-line (p = 0.002) and second-line (p = 0.02) drug resistance and a higher number of previous treatment regimens (4.5 versus 2.3; p = 0.07). Linezolid 600 mg q.d. added to an individualised multidrug regimen may improve the chance of bacteriological conversion, providing a better chance of treatment success in only the most complicated MDR/XDR-TB cases. Its safety profile does not warrant use in cases for which there are other, safer, alternatives.

Published
2009

31. Prävention durch Impfungen – Pneumokokken und Influenza

Author

Pletz Mw

Subjects
Gynecology, medicine.medical_specialty, business.industry, Drug Discovery, medicine, General Medicine, business, Virology
Abstract

Moderne Impfstrategien fokussieren nicht mehr ausschlieslich auf die Pravention von Kinderkrankheiten. Die Impfung von Alteren ruckt zunehmend in den Fokus der Forschung. Die meisten der bislang fur Erwachsene verfugbaren und auch empfohlenen Impfungen richten sich gegen die haufigsten Erreger der ambulant erworbenen Pneumonie: Pneumokokken und Influenza. Dabei wird zunehmend klar, dass das gealterte Immunsystem (Immunseneszenz) nicht nur mit einer erhohten Vulnerabilitat gegenuber Infektionen einhergeht, sondern auch eine im Vergleich zu Kindern verminderte Impfantwort generiert. Aus epidemiologischer Sicht kann die Entwicklung der Pneumokokkenkonjugatvakzine als Durchbruch bezeichnet werden. Mit der Konjugatvakzine steht erstmals eine Impfung gegen den wichtigsten bakteriellen Erreger von Atemwegsinfektionen zur Verfugung, die so wirksam ist, dass sie in verschiedenen Regionen der Welt zu einer Eradikation der enthaltenen Pneumokokkenserotypen gefuhrt hat. Allerdings resultierte die Eradikation in einer „okologischen Nische“ im Nasopharynx der Kleinkinder, die das Hauptreservoir von Pneumokokken darstellen. Diese Nische wurde von nicht-Vakzin-Serotypen okkupiert. Der Anstieg von Besiedelungen und auch Infektionen durch nicht-Vakzin-Serotypen wird als „Replacement“ bezeichnet. Die derzeitige Strategie gegen „Replacement“ besteht in einer Erweiterung der in der Konjugatvakzine enthaltenen Serotypen. Die erste zugelassene Konjugatvakzine war 7-valent und wurde in 2010 durch eine 10und eine 13-valente Vakzine ersetzt. Derzeit ist eine 15-valente Vakzine in Entwicklung. Seit 2011 ist die primar fur Kleinkinder entwickelte 13-valente Konjugatvakzine auch fur den Einsatz bei Erwachsenen zugelassen. Damit stehen fur die Impfung beim Erwachsenen zwei Impfstoffe zu Verfugung: die altere, wenig immunogene Polysaccharidvakzine mit einem breiten Serotypenspektrum (23 Serotypen) und die besser wirksame Konjugatvakzine mit einem schmaleren Spektrum. Meta-Analysen zeigen, dass die Polysaccharidvakzine das Risiko einer Pneumokokkenbakteriamie reduziert, aber nicht vor nicht-bakteriamischer Pneumonie schutzt und dass die Schutzwirkung bei Personen mit hohem Risiko fur Pneumokokkeninfektionen (Altere und Immunsupprimierten) eingeschrankt ist. Die bislang nur auf Kongressen vorgestellten Ergebnisse einer randomisierten, kontrollierten Studie mit 85000 Erwachsenen uber 65 Jahre (CAPITA) belegen fur die Konjugatvakzine hingegen eine Schutzwirkung vor nichtbakteriamischer Pneumokokkenpneumonie. Derzeit divergieren die Empfehlungen, welcher Impfstoff bei Erwachsenen angewendet werden sollte. Sinnvoll scheint die sequenzielle Impfung (Konjugatgefolgt von Polysaccharidvakzine), die zunehmend von verschiedenen Kommissionen fur Patienten mit einem besonders hohen Risiko fur schwere Pneumokokkeninfektionen (z.B. bei Asplenie) empfohlen wird. Wichtig ist hierbei die Einhaltung der Reihenfolge, da eine vorhergehende Impfung mit der Polysacchardivakzine die Impfantwort einer nachfolgenden Vakzinierung vermindert (Hyporesponsiveness). Gegen den bedeutendsten viralen Erreger respiratorischer Infektionen, Influenzaviren, wurden in den letzten Jahren mehrere innovative Impfstoffe entwickelt. Das Spektrum reicht von huhnereiweisfreien Impfstoffen fur Allergiker uber adjuvantierte oder intradermal injizierte Impfstoffe, die bei Alteren eine bessere Impfantwort induzieren sollen, bis hin zur injektionsfreien, intranasal applizierten Lebendvakzine fur Kinder. Die neueste Entwicklung ist ein tetravalenter Impfstoff mit einer breiteren Wirksamkeit, der in den nachsten Jahren wahrscheinlich die trivalenten Vakzine ablosen wird. Dieser Impfstoff enthalt im Gegensatz zu trivalenten Vakzinen (2× A plus 1× B) zwei Influenza B Stamme. Je nach Zusammensetzung der saisonal zirkulierenden Influenzastamme kann damit eine durchschnittlich um 16% breitere Schutzwirkung erreicht werden. Die Vertraglichkeit der verschiedenen Vakzine ist gut und ernsthafte Nebenwirkungen sind ausgesprochen selten. Zum Teil ergeben sich fur einzelne Indikationsgruppen Hinweise darauf, dass ein bestimmter Impfstofftyp besonders geeignet ist bzw. Vorteile gegenuber der klassischen trivalenten Spaltvakzine hat. Die Schutzwirkung gegenuber einer Labor-bestatigten Influenza-Infektion ist fur eine grose Zahl von Indikationsgruppen ausreichend gut belegt.Weitere Studien zu der Frage, ob auch klinische Ereignisse (Pneumonie, Hospitalisierung, Tod) durch die Impfung verhindert werden konnen, sind jedoch nach wie vor wunschenswert. Daten des Kompetenznetzes zur ambulant erworbenen Pneumonie, CAPNETZ, belegen, dass die sekundar bakterielle Pneumonie (meist durch Pneumokokken) nach einer primaren Influenzainfektion besonders schwer verlauft und daraus folgend, dass die kombinierte Impfung gegen Pneumokokken und Influenza, die simultan erfolgen kann, eine besonders effektive Schutzwirkung vermittelt. Interessenkonflikte: Vortragshonorare von und Berater fur GSK, MSD, Novartis und Pfizer.

Published
2014

35. Early outcomes in CAP: clinical stability, clinical failure and nonresolving pneumonia

Author

Stefano Aliberti, Paola Faverio, Chalmers, JD, Pletz, MW, Aliberti, S, Welte, T, and Faverio, P

Subjects
medicine.medical_specialty, Pneumonia, business.industry, medicine, community acquired pneumonia, Clinical failure, Intensive care medicine, business, medicine.disease
Abstract

Clinical stability is the first step of clinical improvement in patients with pneumonia. Clinical stability has been proven to be useful in guiding the switch of antibiotic therapy from intravenous to oral formulations. Given its importance in patient management, several sets of criteria have been created to standardise its definition. However, a single set of criteria cannot fit everybody; therefore, a personalised approach based on the resolution of the patient's most prominent clinical features should be considered. Moreover, it is important to choose the set of criteria that best fits the standard of care at each site of practice. Clinical failure is considered a predictive factor of adverse clinical outcomes. The identification of the aetiology of clinical failure is important to determine the subsequent patient management. The term 'nonresolving pneumonia' is used to indicate a failure to improve without clinical deterioration. Few epidemiological data have been published on this condition. Therefore, future studies should specifically address this topic. © 2014.

Published
2014

36. Effect of acyclovir therapy on the outcome of mechanically ventilated patients with lower respiratory tract infection and detection of herpes simplex virus in bronchoalveolar lavage: protocol for a multicentre, randomised controlled trial (HerpMV).

Author

Hagel S, Brillinger N, Decker S, Deja M, Ertmer C, Fiedler S, Franken P, Heim M, Weigand MA, Zarbock A, and Pletz MW

Subjects
Humans, Prospective Studies, Herpes Simplex drug therapy, Bronchoalveolar Lavage methods, Randomized Controlled Trials as Topic, Intensive Care Units, Multicenter Studies as Topic, Respiratory Tract Infections drug therapy, Respiratory Tract Infections virology, Bronchoalveolar Lavage Fluid virology, Male, Adult, Treatment Outcome, Female, Herpesvirus 1, Human isolation & purification, Simplexvirus isolation & purification, Acyclovir therapeutic use, Acyclovir administration & dosage, Antiviral Agents therapeutic use, Respiration, Artificial
Abstract

Introduction: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome., Methods and Analysis: Prospective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥10 5 copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial., Ethics and Dissemination: The trial was approved by the responsible ethics committee and by Germany's Federal Institute for Drugs and Medical Devices. The clinical trial application was submitted under the new Clinical Trials Regulation through CTIS (The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany's Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers., Trial Registration Number: NCT06134492., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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37. Beyond muscles: Investigating immunoregulatory myokines in acute resistance exercise - A systematic review and meta-analysis.

Author

Ringleb M, Javelle F, Haunhorst S, Bloch W, Fennen L, Baumgart S, Drube S, Reuken PA, Pletz MW, Wagner H, Gabriel HHW, and Puta C

Subjects
Humans, Interleukin-10 metabolism, Interleukin-6 metabolism, Myokines, Interleukin 1 Receptor Antagonist Protein, Tumor Necrosis Factor-alpha metabolism, Muscle, Skeletal metabolism, Interleukin-7 metabolism, Exercise physiology, Interleukin-15 metabolism, Resistance Training
Abstract

Myokines, released from the muscle, enable communication between the working muscles and other tissues. Their release during physical exercise is assumed to depend on immune-hormonal-metabolic interactions concerning mode (endurance or resistance exercise), duration, and intensity. This meta-analysis aims to examine the acute changes of circulating myokines inducing immunoregulatory effects caused by a bout of resistance exercise and to consider potential moderators of the results. Based on this selection strategy, a systematic literature search was conducted for resistance exercise intervention studies measuring interleukin (IL-) 6, IL-10, IL-1ra, tumor necrosis factor (TNF-) α, IL-15, IL-7, transforming growth factor (TGF-) β1, and fractalkines (FKN) before and immediately after resistance exercise in healthy individuals. Random-effects meta-analysis was performed for each myokine. We identified a moderate positive effect of resistance exercise for IL-6 and IL-1ra. Regarding IL-15 and TNF-α, small to moderate effects were found. For IL-10, no significant effect was observed. Due to no data, meta-analyses for IL-7, TGF-β1, and FKN could not be performed. No moderators (training status, type of exercise, risk of bias, age, sex, time of day, exercise volume, exercise intensity, exercise dose) of the results were detected for all tested myokines. Taken together, this systematic review and meta-analysis showed immediate positive effects of an acute resistance exercise session on IL-6, IL-1ra, TNF-α, and IL-15 levels., (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Published
2024
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38. Ultraviolet C inactivation of Coxiella burnetii for production of a structurally preserved whole cell vaccine antigen.

Author

Mertens-Scholz K, Moawad AA, Liebler-Tenorio EM, Helming A, Andrack J, Miethe P, Neubauer H, Pletz MW, and Richter IG

Subjects
Animals, Rabbits, Coxiella burnetii, Q Fever microbiology, Vaccines
Abstract

Q fever, a worldwide-occurring zoonotic disease, can cause economic losses for public and veterinary health systems. Vaccines are not yet available worldwide and currently under development. In this regard, it is important to produce a whole cell antigen, with preserved structural and antigenic properties and free of chemical modifications. Thus, inactivation of Coxiella burnetii with ultraviolet light C (UVC) was evaluated. C. burnetii Nine Mile phase I (NMI) and phase II (NMII) were exposed to decreasing intensities in a time-dependent manner and viability was tested by rescue cultivation in axenic medium or cell culture. Effects on the cell structure were visualized by transmission electron microscopy and antigenicity of UVC-treated NMI was studied by immunization of rabbits. NMI and NMII were inactivated at UVC intensities of 250 µW/cm 2 for 5 min or 100 µW/cm 2 for 20 min. Reactivation by DNA repair was considered to be unlikely. No morphological changes were observed directly after UVC inactivation by transmission electron microscopy, but severe swelling and membrane degradation of bacteria with increasing severity occurred after 24 and 48 h. Immunization of rabbits resulted in a pronounced antibody response. UVC inactivation of C. burnetii resulted in a structural preserved, safe whole cell antigen and might be useful as antigen for diagnostic purposes or as vaccine candidate., (© 2024. The Author(s).)

Published
2024
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40. In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations.

Author

Santerre Henriksen A, Jeannot K, Oliver A, Perry JD, Pletz MW, Stefani S, Morrissey I, and Longshaw C

Subjects
Humans, Meropenem pharmacology, Cefiderocol, beta-Lactamase Inhibitors pharmacology, Pseudomonas aeruginosa, Lactams pharmacology, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Cephalosporins pharmacology, Gram-Negative Bacteria, Microbial Sensitivity Tests, beta-Lactamases genetics, Pseudomonas Infections drug therapy, Acinetobacter
Abstract

Carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. represent major threats and have few approved therapeutic options. Non-‍fermenting Gram-negative isolates were collected from hospitalized inpatients from 49 sites in 6 European countries between 01 January 2020 and 31 December 2020 and underwent susceptibility testing against cefiderocol and β-lactam/β-lactamase inhibitor combinations. Meropenem-resistant (MIC >8 mg/L), cefiderocol-susceptible isolates were analyzed by PCR, and cefiderocol-resistant isolates were analyzed by whole-genome sequencing to identify resistance mechanisms. Overall, 1,451 (950 P . aeruginosa ; 501 Acinetobacter spp.) isolates were collected, commonly from the respiratory tract (42.0% and 39.3%, respectively). Cefiderocol susceptibility was higher than ‍β‍-‍l‍a‍c‍t‍a‍m‍/‍β‍-‍l‍a‍c‍t‍a‍mase‍ inhibitor combinations against P. aeruginosa (98.9% vs 83.3%-91.4%), and P. ‍aeruginosa resistant to meropenem ( n = 139; 97.8% vs 12.2%-59.7%), β-lactam/β-lactamase inhibitor combinations (93.6%-98.1% vs 10.7%-71.8%), and both meropenem and ceftazidime-avibactam (96.7% vs 5.0%-‍‍45.0%) or ‍ceftolozane-tazobactam (98.4% vs 8.1%-54.8%), respectively. Cefiderocol and sulbactam-durlobactam susceptibilities were high against Acinetobacter spp. (92.4% and 97.0%) and meropenem-resistant Acineto‍bacter ‍spp. ( n = 227; 85.0% and 93.8%) but lower against sulbactam-durlobactam- ( n ‍= 15; 13.3%) and cefiderocol- ( n = 38; 65.8%) resistant isolates, respectively. Among meropenem-resistant P. aeruginosa and Acinetobacter spp., the most common β-‍‍lactamase genes were metallo-β-lactamases [30/139; bla VIM-2 (15/139)] and oxacillinases [215/227; bla OXA-23 (194/227)], respectively. Acquired β-lactamase genes were identified in 1/10 and 32/38 of cefiderocol-resistant P. aeruginosa and Acinetobacter spp., and pirA -like or piuA mutations in 10/10 and 37/38, respectively. Conclusion: cefiderocol susceptibility was high against P. aeruginosa and Acinetobacter spp., including meropenem-resistant isolates and those resistant to recent β-lactam/β-lactamase inhibitor combinations common in first-line treatment of European non-fermenters., Importance: This was the first study in which the in vitro activity of cefiderocol and non-licensed β-lactam/β-lactamase inhibitor combinations were directly compared against Pseudomonas aeruginosa and Acinetobacter spp., including meropenem- and β-lactam/β-lactamase inhibitor combination-resistant isolates. A notably large number of European isolates were collected. Meropenem resistance was defined according to the MIC breakpoint for high-dose meropenem, ensuring that data reflect antibiotic activity against isolates that would remain meropenem resistant in the clinic. Cefiderocol susceptibility was high against non-fermenters, and there was no apparent cross resistance between cefiderocol and β-lactam/β-lactamase inhibitor combinations, with the exception of sulbactam-durlobactam. These results provide insights into therapeutic options for infections due to resistant P. aeruginosa and Acinetobacter spp. and indicate how early susceptibility testing of cefiderocol in parallel with β-lactam/β-lactamase inhibitor combinations will allow clinicians to choose the effective treatment(s) from all available options. This is particularly important as current treatment options against non-fermenters are limited., Competing Interests: A.S.H. is an employee of Maxel Consulting ApS, Jyllinge, Denmark and is a contract employee of Shionogi B.V. Both K.J. and A.O. declare honoraria and grants from Shionogi, Pfizer, and MSD. I.M. is an employee of Antimicrobial Focus Ltd and was involved with the reporting of the study data by IHMA. C.L. is an employee of Shionogi B.V. J.D.P., M.W.P., and S.S. have no relevant conflicts of interest to disclose.

Published
2024
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41. Fatal pulmonary hemorrhage, pneumothorax and skin necrosis caused by IRIS to an Aspergillus flavus infection in a young patient with metamizole associated agranulocytosis.

Author

Banz M, Stallmach A, Gaßler N, Schulze PC, Fritzenwanger M, Cornely O, Kurzai O, and Pletz MW

Subjects
Humans, Female, Aspergillus flavus, Dipyrone, Hemorrhage, Necrosis, Pneumothorax, Aspergillosis complications, Aspergillosis drug therapy, Lung Diseases, Sepsis, Agranulocytosis, Lymphohistiocytosis, Hemophagocytic microbiology
Abstract

We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients., (© 2023. The Author(s).)

Published
2024
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42. Exploring secretory proteome and cytokine kinetic of human peripheral blood mononuclear cells exposed to methicillin-resistant Staphylococcus aureus biofilms and planktonic bacteria.

Author

Gheitasi R, Röll D, Müller MM, Naseri M, König R, Slevogt H, Pletz MW, and Makarewicz O

Subjects
Humans, Cytokines, Staphylococcus aureus, Interleukin-18, Proteome, Plankton, Leukocytes, Mononuclear, Biofilms, Methicillin-Resistant Staphylococcus aureus physiology
Abstract

Staphylococcus aureus is a highly successful pathogen infecting various body parts and forming biofilms on natural and artificial surfaces resulting in difficult-to-treat and chronic infections. We investigated the secreted cytokines and proteomes of isolated peripheral blood mononuclear cells (PBMCs) from healthy volunteers exposed to methicillin-resistant S. aureus (MRSA) biofilms or planktonic bacteria. Additionally, the cytokine profiles in sera from patients with community-acquired pneumonia (CAP) caused by S. aureus were investigated. The aim was to gain insights into the immune response involved and differentiate between the planktonic and sessile MRSA forms. We identified 321 and 298 targets that were significantly differently expressed in PBMCs when exposed to planktonic or biofilm-embedded bacteria, respectively. PBMCs exposed to planktonic MRSA cells secreted increased levels of TNF-α, while IL-18 was elevated when exposed to the biofilm. The machine-learning analyses of the cytokine profiles obtained for the in vitro PBMCs and CAP sera distinguished between the two types of bacteria forms based on cytokines IL-18, IL12, and IL-17, and with a lower importance IL-6. Particularly, IL-18 which has not been correlated with S. aureus biofilms so far might represent a suitable marker for monitoring chronification during MRSA infection to individualize the therapy, but this hypothesis must be proved in clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gheitasi, Röll, Müller, Naseri, König, Slevogt, Pletz and Makarewicz.)

Published
2024
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43. COVID-19 outbreak among employees of a German hospital: risk factor analysis based on a follow-up questionnaire and seroprevalence.

Author

Kosenkow J, Ankert J, Baier M, Kesselmeier M, and Pletz MW

Abstract

Background: The Co-FriSero study describes a COVID-19 outbreak at the Friedrichroda hospital in Thuringia, Germany, with 185 beds and 404 employees, at the onset of the pandemic between March 30th, 2020, and April 13th, 2020. This study aimed to analyze potential sources of SARS-CoV-2 transmission amongst hospital employees., Methods: After the outbreak, a comprehensive follow-up was conducted through a questionnaire and a seroprevalence study using two different immunoassays for IgG detection and a third for discordant results., Results: PCR screenings confirmed SARS-CoV-2 infection in 25 of 229 employees, with an additional 7 detected through serology. Statistical analysis indicated that direct patient contact, exposure to high flow ventilation in non-isolated rooms, direct contact with colleagues, shared use of recreational rooms, and carpooling were associated with an increased infection risk. Conversely, contact with family and friends, public transportation, public events, and use of locker rooms were not associated with infection. Male gender showed a lower infection likelihood, independent of age and other risk factors., Conclusion: This study highlights the role of direct patient care and internal staff interactions in the spread of SARS-CoV-2 in the hospital setting. It suggests that non-traditional transmission routes like carpooling require consideration in pandemic preparedness., (© 2024. The Author(s).)

Published
2024
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44. Costs and resource utilization patterns in surgical site infections: a pre-COVID-19 perspective from France, Germany, Spain, and the UK.

Author

Salmanton-García J, Bruns C, Rutz J, Albertsmeier M, Ankert J, Bernard L, Bataille C, Couvé-Deacon E, Fernández-Ferrer M, Fortún J, Galar A, Grill E, Guimard T, Classen AY, Vehreschild JJ, Stemler J, Naendrup JH, Hampl J, Tallon B, Sprute R, Horcajada JP, Mollar-Maseres J, Muñoz P, Pletz MW, Serracino-Inglott F, Soriano A, Vilz TO, Seifert H, Cornely OA, Mellinghoff SC, Liss BJ, and Wingen-Heimann SM

Abstract

Background: Surgical site infections (SSIs), mainly caused by Staphylococcus aureus, pose a significant economic burden in Europe, leading to increased hospitalization duration, mortality, and treatment costs, particularly with drug-resistant strains such as meticillin-resistant S. aureus., Aim: To conduct a case-control study on the economic impact of S. aureus SSI in adult surgical patients across high-volume centres in France, Germany, Spain, and the UK, aiming to assess the overall and procedure-specific burden across Europe., Methods: The SALT study is a multinational, retrospective cohort study with a nested case-control analysis focused on S. aureus SSI in Europe. The study included participants from France, Germany, Italy, Spain, and the UK who underwent invasive surgery in 2016 and employed a micro-costing approach to evaluate health economic factors, matching S. aureus SSI cases with controls., Findings: In 2016, among 178,904 surgical patients in five European countries, 764 developed S. aureus SSI. Matching 744 cases to controls, the study revealed that S. aureus SSI cases incurred higher immediate hospitalization costs (€8,810), compared to controls (€6,032). Additionally, S. aureus SSI cases exhibited increased costs for readmissions within the first year post surgery (€7,961.6 versus €5,298.6), with significant differences observed. Factors associated with increased surgery-related costs included the cost of hospitalization immediately after surgery, first intensive care unit (ICU) admission within 12 months, and hospital readmission within 12 months, as identified through multivariable analysis., Conclusion: The higher rates of hospitalization, ICU admissions, and readmissions among S. aureus SSI cases highlight the severity of these infections and their impact on healthcare costs, emphasizing the potential benefits of evidence-based infection control measures and improved patient care to mitigate the economic burden., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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45. The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population-A comparison of two German registries.

Author

Hasseli R, Hanses F, Stecher M, Specker C, Weise T, Borgmann S, Hasselberger M, Hertenstein B, Hower M, Hoyer BF, Koll C, Krause A, von Lilienfeld-Toal M, Lorenz HM, Merle U, Nunes de Miranda SM, Pletz MW, Regierer AC, Richter JG, Rieg S, Roemmele C, Ruethrich MM, Schmeiser T, Schulze-Koops H, Strangfeld A, Vehreschild MJGT, Voit F, Voll RE, Vehreschild JJ, Müller-Ladner U, and Pfeil A

Abstract

Objectives: To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared., Methods: 4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total., Results: Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19., Conclusion: Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease., Competing Interests: TW was employed by company Biocontrol Jena. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hasseli, Hanses, Stecher, Specker, Weise, Borgmann, Hasselberger, Hertenstein, Hower, Hoyer, Koll, Krause, von Lilienfeld-Toal, Lorenz, Merle, Nunes de Miranda, Pletz, Regierer, Richter, Rieg, Roemmele, Ruethrich, Schmeiser, Schulze-Koops, Strangfeld, Vehreschild, Voit, Voll, Vehreschild, Müller-Ladner and Pfeil.)

Published
2024
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46. Pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH) in the German CAPNETZ-Cohort.

Author

Schleenvoigt BT, Ankert J, Barten-Neiner G, Voit F, Suttorp N, Boesecke C, Hoffmann C, Stolz D, Pletz MW, Rohde G, Witzenrath M, Panning M, Essig A, Rupp J, Degen O, and Stephan C

Subjects
Humans, Prospective Studies, Streptococcus pneumoniae, Anti-Bacterial Agents therapeutic use, Haemophilus influenzae, Pneumonia, Bacterial epidemiology, Haemophilus Infections drug therapy, HIV Infections complications, HIV Infections epidemiology, HIV Infections drug therapy, Community-Acquired Infections epidemiology, Community-Acquired Infections drug therapy
Abstract

Objectives: The objective of this study was to identify the pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH), and to compare it with a matched HIV negative group in order to reassess therapeutic strategies for PLWH., Methods: Seventy-three (n = 73) PLWH (median CD4 3-6 months before CAP: 515/µl; SD 309) with community acquired pneumonia (CAP) were matched with 218 HIV-negative CAP controls in a prospective study design. Pathogen identifications used blood culture, samples from the upper and lower respiratory tract (culture and multiplex PCR) and urinary pneumococcal and legionella antigen test., Results: Although the vaccination rate among PLWH with CAP was significantly higher (pneumococcal vaccination: 27.4 vs. 8.3%, p < 0.001; influenza vaccination: 34.2 vs. 17.4%, p = 0.009), pneumococci were found most frequently as pathogen among both PLWH (n = 19/21.3%) and controls (n = 34/17.2%; p = 0.410), followed by Haemophilus influenzae (PLWH, n = 12/13.5%, vs. controls, n = 25 / 12.6%; p = 0.850). Staphylococcus aureus was found equally in 20.2 and 19.2% in PLWH and controls, but infection or colonization could not be distinguished. Mortality during 6-month follow-up was significantly higher for PLWH (5/73, or 6.8%) versus controls (3/218, or 1.4%), however with lower case numbers than previously reported. Typical HIV-associated pathogens such as Pneumocystis jirovecii were found only exceptionally., Conclusions: Our study underscores the persistent clinical burden of CAP for PLWH. From pathogen perspective, empirical antibiotic treatment for CAP in PLWH on antiretroviral therapy should cover pneumococci and Haemophilus influenzae and may be adopted from valid common recommendations., (© 2023. The Author(s).)

Published
2024
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47. Bacteriophage-mediated decolonization of Klebsiella pneumoniae in a novel Galleria mellonella gut colonization model with Enterobacteriaceae.

Author

Mirza KA, Nietzsche S, Makarewicz O, Pletz MW, and Thieme L

Subjects
Animals, Anti-Bacterial Agents pharmacology, Bacteria, Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, Larva microbiology, Mammals, Bacteriophages, Moths microbiology
Abstract

Galleria mellonella larvae have emerged as an invertebrate model for investigating bacterial pathogenesis and potential therapies, addressing ethical concerns related to mammalian models. This model has the advantage of having a simple gut microbiome, which is suitable for gut colonization studies. Intestinal colonization by Enterobacteriaceae significantly contributes to the spread of antibiotic resistance. This study aimed to establish a novel Enterobacteriaceae gut colonization larval model and assess its suitability for evaluating distinct antimicrobial efficacies. Larvae were force-fed sequentially with bacterial doses of K. pneumoniae and E. coli at 0, 24, and 48 h, with survival monitoring at 24 h intervals. Bacterial counts were assessed after 48 h and 120 h of force-feeding. Successfully colonized larvae were subjected to one-time force feeding of a bacteriophage cocktail (10 7 PFU/larvae) or MIC-based meropenem and ciprofloxacin. The colonized bacterial load was quantified by CFU count. Three doses of 10 6  CFU/larvae resulted in stable gut colonization, independent of the K. pneumoniae or E. coli strain. Compared with the control, force-feeding of the bacteriophage reduced the colonization of the strain Kp 419614 by 5 log 10 CFU/larvae, while antibiotic treatment led to a 3 log 10 CFU/larval reduction. This novel G. mellonella model provides a valuable alternative for gut colonization studies, facilitating proof-of-concept investigations and potentially reducing or replacing follow-up experiments in vertebrate models., (© 2024. The Author(s).)

Published
2024
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48. Multidrug-resistant isolates from Ukrainian patients in a German health facility: a genomic surveillance study focusing on antimicrobial resistance and bacterial relatedness.

Author

Stein C, Zechel M, Spott R, Pletz MW, and Kipp F

Subjects
Humans, Escherichia coli, Drug Resistance, Bacterial genetics, Microbial Sensitivity Tests, beta-Lactamases genetics, Bacterial Proteins genetics, Klebsiella pneumoniae, Genomics, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Cross Infection microbiology
Abstract

Purpose: Antimicrobial resistance is a pressing issue in Ukraine, with healthcare-associated infections caused by multidrug-resistant organisms being a major concern. A recent prospective multicenter study revealed a staggering rate of 48.4% antimicrobial resistance to carbapenems among Enterobacterales causing a healthcare-associated infection. We conducted a systematic survey to investigate the incidence rate and incidence density of carbapenemase-producing Gram-negative bacteria (CPGN) among refugees and war-wounded Ukrainians in connection with the German health system., Methods: From the onset of the war until November 2022, seven Ukrainian patients were admitted to our hospital. Upon admission, screening samples and samples from the focus of suspected infection were taken from all seven patients. The incidence rate and the incidence density of CPGN were calculated as a result of the microbiological findings. We sequenced all CPGN using Illumina technology., Results: The incidence rate of CPGN at our hospital was 0.06 for 2021 and 0.18 for 2022. All seven Ukrainian patients were infected or colonized with at least one CPGN, including K. pneumoniae (14/25), P. aeruginosa (6/25), A. baumannii (1/25), Providencia stutartii (1/25), C. freundii (1/25), and E. coli (2/25). Genomic surveillance revealed that (i) most frequently detected carbapenemases among all sequenced isolates were bla NDM (17/25) and bla OXA-48 (6/25), (ii) most commonly observed plasmid replicons among the K. pneumoniae isolates recovered from Ukrainian patients were Col(pHAD28) (12/14), IncHI1B(pNDM-MAR) (9/14), IncFIB(pNDM-Mar) (12/14), and (iii) clonal relation between the pathogens of the Ukrainian isolates, but not for the isolates from our hospital surveillance system., Conclusion: The rising prevalence of community-acquired colonization and infection with CPGN is having a direct effect on the infection prevention measures, such as higher number of isolations, reprocessing of patient rooms, additional microbiological testing and overall organization within hospitals., (© 2023. The Author(s).)

Published
2023
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49. [Measures and Recommendations for Ensuring Adequate Inpatient Care Capacities for Pandemic Management within a Region: Results of a Hybrid Delphi Method].

Author

Panchyrz I, Hoffmann J, Harst L, Pohl S, Bauer M, Blaschke S, Bodenstein M, Engelhart S, Gärtner B, Graf J, Hanses F, Held HC, Hinzmann D, Khan N, Kleber C, Kolibay F, Kubulus D, Liske S, Oberfeld J, Pletz MW, Prückner S, Rohde G, Spinner CD, Stehr S, Willam C, and Schmitt J

Subjects
Humans, Delphi Technique, Germany epidemiology, Surveys and Questionnaires, Inpatients, Pandemics
Abstract

Introduction: Since the beginning of the pandemic in spring 2020, inpatient healthcare has been under enormous burden, which is reflected especially in overworked staff, imprecise bed planning and/or data transfer. According to the recommendation of the Science Council, university clinics should play a controlling role in regional healthcare and act in conjunction with surrounding hospitals and practices., Methods: In September 2021, 31 representatives from 18 university hospitals were invited to a hybrid Delphi study with a total of 4 survey rounds to discuss criteria for effective inpatient care in a pandemic situation, which were extracted from previous expert interviews. Criteria that were classified as very important/relevant by≥75% of the participants in the first round of the survey (consensus definition) were then further summarized in 4 different small groups. In a third Delphi round, all participants came together again to discuss the results of the small group discussions. Subsequently, these were prioritized as Optional ("can"), Desirable ("should") or Necessary ("must") recommendations., Results: Of the invited clinical experts, 21 (67.7%) participated in at least one Delphi round. In an online survey (1st Delphi round), 233 criteria were agreed upon and reduced to 84 criteria for future pandemic management in four thematic small group discussions (2nd Delphi round) and divided into the small groups as follows: "Crisis Management and Crisis Plans" (n=20), "Human Resources Management and Internal Communication" (n=16), "Regional Integration and External Communication" (n=24) and "Capacity Management and Case & Care" (n=24). In the following group discussion (3rd Delphi round), the criteria were further modified and agreed upon by the experts, so that in the end result, there were 23 essential requirements and recommendations for effective inpatient care in a pandemic situation., Conclusion: The results draw attention to key demands of clinical representatives, for example, comprehensive digitization, standardization of processes and better (supra) regional networking in order to be able to guarantee needs-based care even under pandemic conditions. The present consensus recommendations can serve as guidelines for future pandemic management in the inpatient care sector., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Published
2023
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50. Incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infection in European hospitals: the COMBACTE-NET ARTHR-IS multi-centre study.

Author

Espíndola R, Vella V, Benito N, Mur I, Tedeschi S, Zamparini E, Hendriks JGE, Sorlí L, Murillo O, Soldevila L, Scarborough M, Scarborough C, Kluytmans J, Ferrari MC, Pletz MW, McNamara I, Escudero-Sanchez R, Arvieux C, Batailler C, Dauchy FA, Liu WY, Lora-Tamayo J, Praena J, Ustianowski A, Cinconze E, Pellegrini M, Bagnoli F, Rodríguez-Baño J, and Del-Toro-López MD

Subjects
Humans, Staphylococcus aureus, Incidence, Retrospective Studies, Hospitals, Patient Acceptance of Health Care, Cost of Illness, Prosthesis-Related Infections epidemiology, Prosthesis-Related Infections etiology, Arthroplasty, Replacement, Hip adverse effects, Staphylococcal Infections epidemiology
Abstract

Background: The aim of this study was to estimate the incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infections (SA-PJI) after primary hip and knee arthroplasty in European centres., Methods: This study was conducted in patients who underwent primary hip and knee arthroplasty in 19 European hospitals between 2014 and 2016. The global incidence of PJI and SA-PJI was calculated. The associated disease burden was measured indirectly as infection-related mortality plus loss of function. For healthcare utilization, number and duration of hospitalizations, number and type of surgical procedures, duration of antibiotic treatments, and number of outpatient visits were collected. Subgroup and regression analyses were used to evaluate the impact of SA-PJI on healthcare utilization, controlling for confounding variables., Results: The incidence of PJI caused by any micro-organism was 1.41%, and 0.40% for SA-PJI. Among SA-PJI, 20.7% were due to MRSA with substantial regional differences, and were more frequent in partial hip arthroplasty (PHA). Related deaths and loss of function occurred in 7.0% and 10.2% of SA-PJI cases, respectively, and were higher in patients with PHA. Compared with patients without PJI, patients with SA-PJI had a mean of 1.4 more readmissions, 25.1 more days of hospitalization, underwent 1.8 more surgical procedures, and had 5.4 more outpatient visits, controlling for confounding variables. Healthcare utilization was higher in patients who failed surgical treatment of SA-PJI., Conclusions: This study confirmed that the SA-PJI burden is high, especially in PHA, and provided a solid basis for planning interventions to prevent SA-PJI., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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