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19 results on '"Akova, Murat"'

1. Predictive modeling of mortality in carbapenem-resistant Acinetobacter baumannii bloodstream infections using machine learning.

Author

Özdede M, Zarakolu P, Metan G, Köseoğlu Eser Ö, Selimova C, Kızılkaya C, Elmalı F, and Akova M

Subjects
Humans, Male, Female, Middle Aged, Aged, Bacteremia mortality, Bacteremia drug therapy, Bacteremia microbiology, Drug Resistance, Bacterial, Acinetobacter baumannii drug effects, Carbapenems pharmacology, Carbapenems therapeutic use, Machine Learning, Acinetobacter Infections drug therapy, Acinetobacter Infections mortality, Acinetobacter Infections microbiology
Abstract

Acinetobacter baumannii , a notable drug-resistant bacterium, often induces severe infections in healthcare settings, prompting a deeper exploration of treatment alternatives due to escalating carbapenem resistance. This study meticulously examined clinical, microbiological, and molecular aspects related to in-hospital mortality in patients with carbapenem-resistant A . baumannii (CRAB) bloodstream infections (BSIs). From 292 isolates, 153 cases were scrutinized, reidentified through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and evaluated for antimicrobial susceptibility and carbapenemase genes via multiplex polymerase chain reaction (PCR). Utilizing supervised machine learning, the study constructed models to predict 14- and 30-day mortality rates, revealing the Naïve Bayes model's superior specificity (0.75) and area under the curve (0.822) for 14-day mortality, and the Random Forest model's impressive recall (0.85) for 30-day mortality. These models delineated eight and nine significant features for 14- and 30-day mortality predictions, respectively, with "septic shock" as a pivotal variable. Additional variables such as neutropenia with neutropenic days prior to sepsis, mechanical ventilator support, chronic kidney disease, and heart failure were also identified as ranking features. However, empirical antibiotic therapy appropriateness and specific microbiological data had minimal predictive efficacy. This research offers foundational data for assessing mortality risks associated with CRAB BSI and underscores the importance of stringent infection control practices in the wake of the scarcity of new effective antibiotics against resistant strains. The advanced models and insights generated in this study serve as significant resources for managing the repercussions of A . baumannii infections, contributing substantially to the clinical understanding and management of such infections in healthcare environments., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Gökhan Metan received honoraria for speaking at symposia and lectures organized by Gilead Merck, Sharp, and Dohme (MSD), and Pfizer, as well as a consultation fee from the United Nations Turkey Office. He has also received travel grants from MSD, Pfizer, and Gilead to participate in conferences. Other authors declare that they have no competing interests.

Published
2024
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2. Risk factors for bloodstream infections due to carbapenem-resistant Enterobacterales: a nested case-control-control study.

Author

Zhou H, Buetti N, Pérez-Galera S, Bravo-Ferrer J, Gutiérrez-Gutiérrez B, Paniagua-García M, Feifel J, Sauser J, Kostyanev T, Canton R, Tan LK, Basoulis D, Pintado V, Roilides E, Dragovac G, Torre-Cisneros J, Mediç D, Akova M, Goossens H, Bonten M, Harbarth S, Rodriguez-Baño J, and De Kraker MEA

Subjects
Humans, Case-Control Studies, Risk Factors, Male, Female, Aged, Middle Aged, Prospective Studies, Europe epidemiology, Aged, 80 and over, Enterobacteriaceae Infections epidemiology, Enterobacteriaceae Infections microbiology, Bacteremia microbiology, Bacteremia epidemiology, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Carbapenems pharmacology, Carbapenem-Resistant Enterobacteriaceae drug effects, Carbapenem-Resistant Enterobacteriaceae isolation & purification
Abstract

Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients)., Methods: A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied., Results: From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment., Conclusions: Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Published
2024
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3. Reducing the impact of carbapenem-resistant Enterobacteriaceae on vulnerable patient groups: what can be done?

Author

Metan G and Akova M

Subjects
Anti-Bacterial Agents therapeutic use, Azabicyclo Compounds therapeutic use, Ceftazidime therapeutic use, Colistin therapeutic use, Critical Illness, Drug Combinations, Drug Therapy, Combination, Enterobacteriaceae enzymology, Humans, Meropenem, Retrospective Studies, Thienamycins therapeutic use, beta-Lactamases biosynthesis, Carbapenems therapeutic use, Enterobacteriaceae drug effects, Enterobacteriaceae Infections diagnosis, Enterobacteriaceae Infections drug therapy, beta-Lactam Resistance
Abstract

Purpose of Review: Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide challenge and associated with a high mortality rate in critically ill patients. This review focused on rapid diagnosis, optimization of antimicrobial therapy, and implication of effective infection control precautions to reduce impact of CRE on vulnerable patients., Recent Findings: Several new diagnostic assays have recently been described for the early diagnosis of CRE. Retrospective studies are supportive for colistin plus meropenem combination for the treatment of CRE infections; however, solid evidence is still lacking. Ceftazidime-avibactam may be an effective therapeutic agent for infections caused by carbapenem-hydrolyzing oxacillinase-48 and Klebsiella pneumoniae carbapenamase-producing Enterobacteriaceae, but not for New Delhi metallo-β-lactamase producers. Gastrointestinal screening may permit early identification of patients with CRE infections. There is not enough evidence to recommend selective digestive decontamination for CRE carriers., Summary: The information for rapid diagnosis of CRE is accumulating. There are new agents with high in-vitro activity against CRE, but clinical experience is limited to case reports. Active surveillance with a high rate of compliance to basic infection control precautions seems to be the best approach to reduce the impact of CRE on vulnerable patients.

Published
2016
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4. Epidemiology of carbapenem-resistant Klebsiella pneumoniae colonization: a surveillance study at a Turkish university hospital from 2009 to 2013.

Author

Zarakolu P, Eser OK, Aladag E, Al-Zahrani IA, Day KM, Atmaca O, Boral B, Cakir B, Perry JD, and Akova M

Subjects
Adult, Aged, Carrier State microbiology, Epidemiological Monitoring, Female, Hospitals, University, Humans, Klebsiella Infections microbiology, Klebsiella pneumoniae isolation & purification, Male, Middle Aged, Tertiary Care Centers, Turkey, Young Adult, beta-Lactamases analysis, Anti-Bacterial Agents pharmacology, Carbapenems pharmacology, Carrier State epidemiology, Klebsiella Infections epidemiology, Klebsiella pneumoniae drug effects, beta-Lactam Resistance
Abstract

Between June 2009 and December 2013, 4105 patients were screened for carbapenem-resistant Klebsiella pneumoniae (CR-Kp) colonization in a tertiary care university hospital. The antimicrobial susceptibility and resistance determinants of 279 (6.8%) CR-Kp isolates from single patients were investigated. Additional analysis was performed to evaluate the characteristics and various risk factors for infection in patients with colonization. Of the 279 isolates, 270 harboured OXA-48-like enzymes, and a single isolate harboured IMP-type carbapenemase. A high proportion of isolates were susceptible to carbapenems - except ertapenem. All isolates were susceptible to amikacin and most (94%) were susceptible to colistin and fosfomycin. There was consistent high-level resistance for all isolates to temocillin, piperacillin-tazobactam, amoxicillin-clavulanate and ticarcillin-clavulanate. When colonized and infected patients were compared, only prior carbapenem administration (P = 0.003), was found to be significantly associated with patients with CR-Kp infection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Published
2016
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5. Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study.

Author

Gutiérrez-Gutiérrez B, Bonomo RA, Carmeli Y, Paterson DL, Almirante B, Martínez-Martínez L, Oliver A, Calbo E, Peña C, Akova M, Pitout J, Origüen J, Pintado V, García-Vázquez E, Gasch O, Hamprecht A, Prim N, Tumbarello M, Bou G, Viale P, Tacconelli E, Almela M, Pérez F, Giamarellou H, Cisneros JM, Schwaber MJ, Venditti M, Lowman W, Bermejo J, Hsueh PR, Mora-Rillo M, Gracia-Ahulfinger I, Pascual A, and Rodríguez-Baño J

Subjects
Aged, Enterobacteriaceae isolation & purification, Enterobacteriaceae Infections microbiology, Ertapenem, Female, Humans, Male, Middle Aged, Retrospective Studies, Sepsis microbiology, Survival Analysis, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Carbapenems therapeutic use, Enterobacteriaceae enzymology, Enterobacteriaceae Infections drug therapy, Sepsis drug therapy, beta-Lactamases metabolism, beta-Lactams therapeutic use
Abstract

Objectives: Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E., Methods: A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality., Results: The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; P = 0.58) and 1.04 (0.44-2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; P = 0.86) and for the propensity-matched cohorts it was 1.05 (0.46-2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems., Conclusions: Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Published
2016
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6. [Comparative evaluation of in vitro activities of carbapenems against gram-negative pathogens: Turkish data of COMPACT study].

Author

Korten V, Söyletir G, Yalçın AN, Oğünç D, Dokuzoğuz B, Esener H, Ulusoy S, Tünger A, Aygen B, Sümerkan B, Arman D, Dizbay M, Akova M, Hasçelik G, Eraksoy H, Başaran S, Köksal I, Bayramoğlu G, Akalın H, and Sınırtaş M

Subjects
Bacteremia microbiology, Doripenem, Drug Resistance, Bacterial, Humans, Imipenem pharmacology, Intensive Care Units, Meropenem, Microbial Sensitivity Tests, Pneumonia, Bacterial microbiology, Thienamycins pharmacology, Turkey, Anti-Bacterial Agents pharmacology, Carbapenems pharmacology, Cross Infection microbiology, Gram-Negative Bacteria drug effects, Gram-Negative Bacterial Infections microbiology
Abstract

The aim of this study was to determine the in vitro activities of doripenem, imipenem, and meropenem against clinical gram-negative isolates. A total of 596 clinical isolates were obtained from intensive care unit (ICU) and non-ICU patients in 10 centers over Turkey between September-December 2008. The origin of the isolates was patients with nosocomial pneumonia (42.4%), bloodstream infections (%40.4), and complicated intraabdominal infections (17.1%). Of the isolates, 51.8% were obtained from ICU patients. The study isolates consisted of Pseudomonas spp. in 49.8%, Enterobacteriaceae in 40.3%, and other gram-negative agents in 9.9%. The minimum inhibitory concentrations (MIC) for doripenem, imipenem and meropenem were determined for all isolates in each center using Etest® strips (AB Biodisk, Solna, Sweden). Of the isolates, 188 (31.5%) were resistant to at least one of the carbapenems. MIC50 of doripenem against Pseudomonas spp. Was 1 mg/L which was similar to that of meropenem and two-fold lower than imipenem. Susceptibility to carbapenems in P.aeruginosa was 64% for doripenem at an MIC level of 2 mg/L, 53.9% and 63% for imipenem and meropenem at an MIC level of 4 mg/L, respectively. Doripenem and meropenem showed similar activity with the MIC90 of 0.12 mg/L whereas imipenem was four-fold less active at 0.5 mg/L. Against other gramnegative pathogens, mostly Acinetobacter spp., MIC50 was 8 mg/L for doripenem and 32 mg/L for other two carbapenems. P.aeruginosa isolates were inhibited 84.2% with doripenem and 72.1% with meropenem at the MIC level of 8 mg/L. Doripenem generally showed similar or slightly better activity than meropenem and better activity than imipenem against pathogens collected in this study. Against Pseudomonas spp., doripenem was the most active of the three carbapenems. Doripenem and meropenem were equally active against Enterobacteriaceae and at least four-fold more active than imipenem. It was concluded that doripenem seemed to be a promising agent in the treatment of nosocomial pneumonia, blood stream infections and intraabdominal infections particularly in patients who were under risk of developing antimicrobial resistance.

Published
2011

7. Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study

Author

Tabah, Alexis, Buetti, Niccolò, Staiquly, Quentin, Ruckly, Stéphane, Akova, Murat, Aslan, Abdullah Tarik, Leone, Marc, Conway Morris, Andrew, Bassetti, Matteo, Arvaniti, Kostoula, Lipman, Jeffrey, Ferrer, Ricard, Qiu, Haibo, Paiva, José-Artur, Povoa, Pedro, De Bus, Liesbet, De Waele, Jan, Zand, Farid, Gurjar, Mohan, Alsisi, Adel, Abidi, Khalid, Bracht, Hendrik, Hayashi, Yoshiro, Jeon, Kyeongman, Elhadi, Muhammed, Barbier, François, Timsit, Jean-François, EUROBACT-2 Study Group, ESICM, Tabah, Alexis [0000-0003-3513-2778], Conway Morris, Andrew [0000-0002-3211-3216], De Bus, Liesbet [0000-0003-1456-5857], De Waele, Jan [0000-0003-1017-9748], Gurjar, Mohan [0000-0002-8489-0324], and Apollo - University of Cambridge Repository

Subjects
Adult, Cross Infection, antibiotic resistance, bloodstream infection, Bacteremia, Hospitals, Anti-Bacterial Agents, Cohort Studies, Intensive Care Units, Anti-Infective Agents, Carbapenems, Escherichia coli, Humans, hospital-acquired, Prospective Studies
Abstract

Funder: European Society of Clinical Microbiology and Infectious Diseases, Funder: Norva Dahlia foundation, Funder: Redcliffe Hospital Private Practice Trust Fund, Funder: European Society of Intensive Care Medicine, PURPOSE: In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. METHODS: We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. RESULTS: 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. CONCLUSIONS: HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.

Published
2023
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8. Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure : the DIANA study

Author

De Bus, Liesbet, Depuydt, Pieter, Steen, Johan, Dhaese, Sofie, De Smet, Ken, Tabah, Alexis, Akova, Murat, Cotta, Menino Osbert, De Pascale, Gennaro, Dimopoulos, George, Fujitani, Shigeki, Garnacho-Montero, Jose, Leone, Marc, Lipman, Jeffrey, Ostermann, Marlies, Paiva, José-Artur, Schouten, Jeroen, Sjövall, Fredrik, Timsit, Jean-François, Roberts, Jason A., Zahar, Jean-Ralph, Zand, Farid, Zirpe, Kapil, De Waele, Jan J., Fernando Rios, Alejandro Risso Vazquez, Maria Gabriela Vidal, Graciela Zakalik, Antony George Attokaran, Iouri Banakh, Smita Dey-Chatterjee, Julie Ewan, Janet Ferrier, Loretta Forbes, Cheryl Fourie, Anne Leditschke, Lauren Murray, Philipp Eller, Patrick Biston, Stephanie Bracke, Luc De Crop, Nicolas De Schryver, Eric Frans, Herbert Spapen, Claire Van Malderen, Stijn Vansteelandt, Daisy Vermeiren, Elias Pablo Arévalo, Mónica Crespo, Roberto Zelaya Flores, Petr Píza, Diego Morocho Tutillo, Andreas Elme, Anne Kallaste, Joel Starkopf, Jeremy Bourenne, Mathieu Calypso, Yves Cohen, Claire Dahyot-Fizelier, François Depret, Max Guillot, Nadia Imzi, Sebastien Jochmans, Achille Kouatchet, Alain Lepape, Olivier Martin, Markus Heim, Stefan J Schaller, Kostoula Arvaniti, Anestis Bekridelis, Panagiotis Ioannidis, Cornelia Mitrakos, Metaxia N Papanikolaou, Sofia Pouriki, Anna Vemvetsou, Babu Abraham, Pradip Kumar Bhattacharya, Anusha Budugu, Subhal Dixit, Sushma Gurav, Padmaja Kandanuri, Dattatray Arun Prabhu, Darshana Rathod, Kavitha Savaru, Ashwin Neelavar Udupa, Sunitha Binu Varghese, Hossein Haddad Bakhodaei, Gholamreza Dabiri, Mohammad Javad Fallahi, Farnia Feiz, Mohammad Firoozifar, Vahid Khaloo, Behzad Maghsudi, Mansoor Masjedi, Reza Nikandish, Golnar Sabetian, Brian Marsh, Ignacio Martin-Loeches, Jan Steiner, Maria Barbagallo, Anselmo Caricato, Andrea Cortegiani, Rocco D'Andrea, Cristian Deana, Abele Donati, Massimo Girardis, Giuliana Mandalà, Giovanna Panarello, Daniela Pasero, Lorella Pelagalli, Paolo Maurizio Soave, Savino Spadaro, Yoshihito Fujita, Shinsuke Fujiwara, Yuya Hara, Hideki Hashi, Satoru Hashimoto, Hideki Hashimoto, Katsura Hayakawa, Masash Inoue, Shutaro Isokawa, Shinya Kameda, Hidenobu Kamohara, Masafumi Kanamoto, Shinshu Katayama, Toshiomi Kawagishi, Yasumasa Kawano, Yoshiko Kida, Mami Kita, Atsuko Kobayashi, Akira Kuriyama, Takaki Naito, Hiroshi Nashiki, Kei Nishiyama, Shunsuke Shindo, Taketo Suzuki, Akihiro Takaba, Chie Tanaka, Komuro Tetsuya, Yoshihiro Tomioka, Youichi Yanagawa, Hideki Yoshida, Syamhanin Adnan, Mohd Shahnaz Hasan, Helmi Sulaiman, Gilberto A Gasca Lopez, Carmen M Hernández-Cárdenas, Silvio A Ñamendys-Silva, Carina Bethlehem, Dylan de Lange, Nicole Hunfeld, Sandra Numan, Henk van Leeuwen, Daniel Owens, Mónica Almeida, Elsa Fragoso, Tiago Leonor, José-Manuel Pereira, Daniela Filipescu, Ioana Grigoras, Mihai Popescu, Dana Tomescu, Mohammed S Alshahrani, Manuel Alvarez-Gonzalez, Irene Barrero-García, Miguel Angel Blasco-Navalpotro, Laura Claverias, Ángel Estella, Lorena Forcelledo Espina, Jose Luis Garcia Garmendia, Emilio García Prieto, Gracia Gómez-Prieto, Carlos Jiménez Conde, Fernando Martinez Sagasti, Alicia Muñoz Cantero, Alberto Orejas-Gallego, Elisabeth Papiol, Demetrio Pérez-Civantos, Juan Carlos Pozo Laderas, Josep Trenado Álvarez, Paula Vera-Artázcoz, Pablo Vidal Cortés, Anders Oldner, Martin Spångfors, Emine Alp, Iftihar Köksal, Volkan Korten, Arife Özveren, Anna Hall, Kevin W Hatton, Krzysztof Laudanski, Experimental and Applied Psychology, Clinique de réanimation médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], University of Queensland [Brisbane], Centro Hospitalar Universitário São João - Faculty of Medicine - University of Porto - Grupo de Infecção e Sepsis, Porto, Radboud University Medical Center [Nijmegen], Skane University Hospital [Malmo], Lund University [Lund], Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ghent University Hospital, Ghent, Belgium, De Bus, Liesbet, Depuydt, Pieter, Steen, Johan, Dhaese, Sofie, De Smet, Ken, Tabah, Alexi, Akova, Murat, Cotta, Menino Osbert, De Pascale, Gennaro, Dimopoulos, George, Fujitani, Shigeki, Garnacho-Montero, Jose, Leone, Marc, Lipman, Jeffrey, Ostermann, Marlie, Paiva, José-Artur, Schouten, Jeroen, Sjövall, Fredrik, Timsit, Jean-Françoi, Roberts, Jason A., Zahar, Jean-Ralph, Zand, Farid, Zirpe, Kapil, De Waele, Jan J., and Fernando Rios, Alejandro Risso Vazquez, Maria Gabriela Vidal, Graciela Zakalik, Antony George Attokaran, Iouri Banakh, Smita Dey-Chatterjee, Julie Ewan, Janet Ferrier, Loretta Forbes, Cheryl Fourie, Anne Leditschke, Lauren Murray, Philipp Eller, Patrick Biston, Stephanie Bracke, Luc De Crop, Nicolas De Schryver, Eric Frans, Herbert Spapen, Claire Van Malderen, Stijn Vansteelandt, Daisy Vermeiren, Elias Pablo Arévalo, Mónica Crespo, Roberto Zelaya Flores, Petr Píza, Diego Morocho Tutillo, Andreas Elme, Anne Kallaste, Joel Starkopf, Jeremy Bourenne, Mathieu Calypso, Yves Cohen, Claire Dahyot-Fizelier, François Depret, Max Guillot, Nadia Imzi, Sebastien Jochmans, Achille Kouatchet, Alain Lepape, Olivier Martin, Markus Heim, Stefan J Schaller, Kostoula Arvaniti, Anestis Bekridelis, Panagiotis Ioannidis, Cornelia Mitrakos, Metaxia N Papanikolaou, Sofia Pouriki, Anna Vemvetsou, Babu Abraham, Pradip Kumar Bhattacharya, Anusha Budugu, Subhal Dixit, Sushma Gurav, Padmaja Kandanuri, Dattatray Arun Prabhu, Darshana Rathod, Kavitha Savaru, Ashwin Neelavar Udupa, Sunitha Binu Varghese, Hossein Haddad Bakhodaei, Gholamreza Dabiri, Mohammad Javad Fallahi, Farnia Feiz, Mohammad Firoozifar, Vahid Khaloo, Behzad Maghsudi, Mansoor Masjedi, Reza Nikandish, Golnar Sabetian, Brian Marsh, Ignacio Martin-Loeches, Jan Steiner, Maria Barbagallo, Anselmo Caricato, Andrea Cortegiani, Rocco D'Andrea, Cristian Deana, Abele Donati, Massimo Girardis, Giuliana Mandalà, Giovanna Panarello, Daniela Pasero, Lorella Pelagalli, Paolo Maurizio Soave, Savino Spadaro, Yoshihito Fujita, Shinsuke Fujiwara, Yuya Hara, Hideki Hashi, Satoru Hashimoto, Hideki Hashimoto, Katsura Hayakawa, Masash Inoue, Shutaro Isokawa, Shinya Kameda, Hidenobu Kamohara, Masafumi Kanamoto, Shinshu Katayama, Toshiomi Kawagishi, Yasumasa Kawano, Yoshiko Kida, Mami Kita, Atsuko Kobayashi, Akira Kuriyama, Takaki Naito, Hiroshi Nashiki, Kei Nishiyama, Shunsuke Shindo, Taketo Suzuki, Akihiro Takaba, Chie Tanaka, Komuro Tetsuya, Yoshihiro Tomioka, Youichi Yanagawa, Hideki Yoshida, Syamhanin Adnan, Mohd Shahnaz Hasan, Helmi Sulaiman, Gilberto A Gasca Lopez, Carmen M Hernández-Cárdenas, Silvio A Ñamendys-Silva, Carina Bethlehem, Dylan de Lange, Nicole Hunfeld, Sandra Numan, Henk van Leeuwen, Daniel Owens, Mónica Almeida, Elsa Fragoso, Tiago Leonor, José-Manuel Pereira, Daniela Filipescu, Ioana Grigoras, Mihai Popescu, Dana Tomescu, Mohammed S Alshahrani, Manuel Alvarez-Gonzalez, Irene Barrero-García, Miguel Angel Blasco-Navalpotro, Laura Claverias, Ángel Estella, Lorena Forcelledo Espina, Jose Luis Garcia Garmendia, Emilio García Prieto, Gracia Gómez-Prieto, Carlos Jiménez Conde, Fernando Martinez Sagasti, Alicia Muñoz Cantero, Alberto Orejas-Gallego, Elisabeth Papiol, Demetrio Pérez-Civantos, Juan Carlos Pozo Laderas, Josep Trenado Álvarez, Paula Vera-Artázcoz, Pablo Vidal Cortés, Anders Oldner, Martin Spångfors, Emine Alp, Iftihar Köksal, Volkan Korten, Arife Özveren, Anna Hall, Kevin W Hatton, Krzysztof Laudanski

Subjects
Original, DELPHI METHOD, Critical Care and Intensive Care Medicine, GUIDELINES, law.invention, 0302 clinical medicine, Anti-Infective Agents, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Epidemiology, Medicine and Health Sciences, Antimicrobial de-escalation, EPIDEMIOLOGY, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Ventilator-associated pneumonia, Intensive care unit, Anti-Bacterial Agents, 3. Good health, Intensive Care Units, STEWARDSHIP PROGRAM, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cohort, Bacterial infection, Clinical cure, Empirical therapy, Adult, medicine.medical_specialty, Combination therapy, Critical Illness, ANTIBIOTIC-THERAPY, NO, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, BETA-LACTAM, Internal medicine, Settore MED/41 - ANESTESIOLOGIA, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, VENTILATOR-ASSOCIATED PNEUMONIA, business.industry, SEPTIC SHOCK, R-PACKAGE, bacterial infection, 030208 emergency & critical care medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Discontinuation, SEVERE SEPSIS, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Carbapenems, 030228 respiratory system, Relative risk, business, De-escalation
Abstract

© 2020 The Author(s)., [Purpose]: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation., [Methods]: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure., [Results]: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60–1.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14–1.64)., [Conclusion]: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely.

Published
2020
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9. Extended spectrum β-lactamase producing enterobacteriaceae: carbapenem sparing options.

Author

Aslan, Abdullah Tarık and Akova, Murat

Abstract

Introduction: Carbapenems have an important place in our antibiotic armamentarium and have been trusted to effectively treat infections caused by ESBL-producing Enterobacteriaceae for many years. However, the utility of carbapenems has been compromised by the emergence of resistance especially in Enterobacteriaceae. Therefore, carbapenem-sparing alternative antibiotics are of extreme importance in clinical practice.Areas covered: We reviewed studies addressing currently available antibiotic options used as both empiric and definitive therapy for the treatment of infections due to ESBL-producing Enterobacteriaceae published in the PubMed/MEDLINE, Web of Science and Scopus databases without any date restriction. Current treatment alternatives included beta-lactam/beta-lactamase inhibitor combinations, cefepime, cephamycins, fluoroquinolones, aminoglycosides, fosfomycin, pivmecillinam, temocillin and, various oral alternative agents. We also summarized the clinical and molecular epidemiology, early prediction methods and impact of initial empirical therapy and de-escalation approach for ESBL-producing Enterobacteriaceae infections.Expert opinion: The current literature would endorse the carbapenem utilization for patients with severe and high inoculum-high risk infections. However, for milder infections particularly for urinary tract infections, various carbapenem-sparing antibiotics can be considered in selected cases. For infections including easily drainable intra-abdominal infections and catheter-related infections in which catheter removal is readily available more reliable data are needed to recommend non-carbapenem antibiotics confidently. [ABSTRACT FROM AUTHOR]

Published
2019
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10. A Predictive Model of Mortality in Patients With Bloodstream Infections due to Carbapenemase-Producing Enterobacteriaceae

Author

Gutiérrez Gutiérrez, Belén, Salamanca, Elena, de Cueto, Marina, Pascual, Alvaro, Rodríguez Baño, Jesús, Hsueh, Po Ren, Viale, Pierluigi, Paño Pardo, José Ramón, Venditti, Mario, Tumbarello, Mario, Daikos, George, Pintado, Vicente, Doi, Yohei, Tuon, Felipe Francisco, Karaiskos, Ilias, Machuca, Isabel, Schwaber, Mitchell J., Azap, Özlem Kurt, Souli, Maria, Roilides, Emmanuel, Pournaras, Spyros, Akova, Murat, Pérez, Federico, Bonomo, Robert A., Bermejo, Joaquín, Oliver, Antonio, Almela, Manel, Lowman, Warren, Almirante, Benito, Carmeli, Yehuda, Paterson, David L., Falcone, M., Russo, A., Giamarellou, H., Trecarichi, Enrico Maria, Losito, Angela Raffaella, García Vázquez, E., Hernández, A., Gómez, J., Iosifidis, E., Prim, N., Navarro, F., Mirelis, B., Origüen, J., San Juan, R., Fernández Ruiz, M., Larrosa, N., Puig Asensio, M., Cisneros, J. M., Molina, J., González, V., Rucci, V., Ruiz de Gopegui, E., Marinescu, C. I., Martínez Martínez, L., Fariñas, M. C., Cano, M. E., Gozalo, M., Mora Rillo, M., Navarro San Francisco, C., Peña, C., Gómez Zorrilla, S., Tubau, F., Tsakris, A., Zarkotou, O., Azap, Ö. K., Pitout, J., Virmani, D., Torre Cisneros, J., Natera, C., Helvaci, Ö., Sahin, A. O., Cantón, R., Ruiz, P., Bartoletti, M., Giannella, M., Taconelli, E., Riemenschneider, F., Calbo, E., Badia, C., Xercavins, M., Gasch, E., Fontanals, D., and Jové, E.

Subjects
0301 basic medicine, Male, medicine.medical_specialty, carbapenems, klebsiella pneumoniae, pneumoniae carbapenemase, 030106 microbiology, Bacteremia, Comorbidity, Logistic regression, Settore MED/17 - MALATTIE INFETTIVE, Sensitivity and Specificity, beta-Lactamases, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, Enterobacteriaceae, Predictive Value of Tests, Internal medicine, medicine, Humans, In patient, 030212 general & internal medicine, Aged, Anti-Bacterial Agents, Enterobacteriaceae Infections, Female, Logistic Models, Middle Aged, Retrospective Studies, Receiver operating characteristic, business.industry, Medicine (all), Retrospective cohort study, General Medicine, medicine.disease, Surgery, Predictive value of tests, Observational study, business
Abstract

Objective To develop a score to predict mortality in patients with bloodstream infections (BSIs) due to carbapenemase-producing Enterobacteriaceae (CPE). Patients and Methods A multinational retrospective cohort study (INCREMENT project) was performed from January 1, 2004, through December 31, 2013. Patients with clinically relevant monomicrobial BSIs due to CPE were included and randomly assigned to either a derivation cohort (DC) or a validation cohort (VC). The variables were assessed on the day the susceptibility results were available, and the predictive score was developed using hierarchical logistic regression. The main outcome variable was 14-day all-cause mortality. The predictive ability of the model and scores were measured by calculating the area under the receiver operating characteristic curve. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for different cutoffs of the score. Results The DC and VC included 314 and 154 patients, respectively. The final logistic regression model of the DC included the following variables: severe sepsis or shock at presentation (5 points); Pitt score of 6 or more (4 points); Charlson comorbidity index of 2 or more (3 points); source of BSI other than urinary or biliary tract (3 points); inappropriate empirical therapy and inappropriate early targeted therapy (2 points). The score exhibited an area under the receiver operating characteristic curve of 0.80 (95% CI, 0.74-0.85) in the DC and 0.80 (95% CI, 0.73-0.88) in the VC. The results for 30-day all-cause mortality were similar. Conclusion A validated score predictive of early mortality in patients with BSIs due to CPE was developed. Trial Registration clinicaltrials.gov Identifier: NCT01 764490.

Published
2016

11. Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: A multinational pre-registered cohort study

Author

Gutiérrez-Gutiérrez, Belén, Bonomo Robert, A., Carmeli, Yehuda, Paterson David, L., Almirante, Benito, Martínez-Martínez, Luis, Oliver, Antonio, Calbo, Esther, Peña, Carmen, Akova, Murat, Pitout, Johann, Origüen, Julia, Pintado, Vicente, García-Vázquez, Elisa, Gasch, Oriol, Hamprecht, Axel, Prim, Nuria, Tumbarello, Mario, Bou, German, Viale, Pierluigi, Tacconelli, Evelina, Almela, Manel, Pérez, Federico, Giamarellou, Helen, Cisneros José Miguel, Schwaber Mitchell, J., Venditti, Mario, Lowman, Warren, Bermejo, Joaquín, Hsueh, Po-Ren, Mora-Rillo, Marta, Gracia-Ahulfinger, Irene, Pascual, Alvaro, Rodríguez-Baño, Jesús, Karaiskos, I., Trecarichi, E. M., Losito, A. R., Hernández, A., Gómez, J., Navarro, F., Mirelis, B., Larrosa, N., Puig, M., Rucci, V., Bartoletti, M., Giannella, M., Riemenschneider, F., Badia, C., Xercavins, M., Gálvez, J., de Cueto, M., Salamanca, E., Falcone, M., Russo, A., Daikos, G., Paterson, D. L., Roilides, E., Iosifidis, E., Doi, Y., Tuon, F. F., San Juan, R., Fernández-Ruiz, M., Molina, J., González, V., Ruiz de Gopegui, E., Marinescu, C. I., Fariñas, M. C., Cano, M. E., Gozalo, M., Paño-Pardo, J. R., Navarro-San Francisco, C., Gómez-Zorrilla, S., Tubau, F., Pournaras, S., Tsakris, A., Zarkotou, O., Azap, Ö. K., Souli, M., Antoniadou, A., Poulakou, G., Virmani, D., Machuca, I., Pérez-Nadales, E., Torre-Cisneros, J., Helvaci, Ö., Sahin, A. O., Cantón, R., Ruiz, P., Fontanals, D., Jové, E., Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Red Española de Investigación en Patología Infecciosa, US Department of Veterans Affairs, Geriatric Research Education and Clinical Center (US), National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), and İç Hastalıkları

Subjects
0301 basic medicine, Male, Carbapenem, Pediatrics, chemistry.chemical_compound, Septic shock, polycyclic compounds, Molecular targeted therapy, Pharmacology (medical), Pharmacology & Pharmacy, Original Research, Enterobacteriaceae Infections, Middle Aged, Anti-Bacterial Agents, Treatment Outcome, Infectious Diseases, Cohort, Female, Sensitivity analysis, Ertapenem, medicine.drug, Cohort study, Microbiology (medical), medicine.medical_specialty, Aged, Carbapenems, Enterobacteriaceae, Humans, Retrospective Studies, Sepsis, Survival Analysis, beta-Lactamases, beta-Lactams, 030106 microbiology, Settore MED/17 - MALATTIE INFETTIVE, Microbiology, 03 medical and health sciences, Severe extended-spectrum beta lactamases, Internal medicine, medicine, Mortality, Pharmacology, business.industry, Retrospective cohort study, biochemical phenomena, metabolism, and nutrition, medicine.disease, bacterial infections and mycoses, chemistry, Propensity score matching, bacteria, Bloodstream infections, business, human activities
Abstract

REIPI/ESGBIS/INCREMENT Group: J. Gálvez, M. de Cueto, E. Salamanca, M. Falcone, A. Russo, G. Daikos, I. Karaiskos, E. M. Trecarichi, A. R. Losito, D. L. Paterson, A. Hernández, J. Gómez, E. Roilides, E. Iosifidis, Y. Doi, F. F. Tuon, F. Navarro, B. Mirelis, R. San Juan, M. Fernández-Ruiz, N. Larrosa, M. Puig, J. Molina, V. González, V. Rucci, E. Ruiz de Gopegui, C. I. Marinescu, M. C. Fariñas, M. E. Cano, M. Gozalo, J. R. Paño-Pardo, C. Navarro-San Francisco, S. Gómez-Zorrilla, F. Tubau, S. Pournaras, A. Tsakris, O. Zarkotou, Ö. K. Azap, M. Souli, A. Antoniadou, G. Poulakou, D. Virmani, I. Machuca, E. Pérez-Nadales, J. Torre-Cisneros, Ö. Helvaci, A. O. Sahin, R. Cantón, P. Ruiz, M. Bartoletti, M. Giannella, F. Riemenschneider, C. Badia, M. Xercavins, D. Fontanals, E. Jové., [Objectives] Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E., [Methods] A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality., [Results] The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24–20.08; P = 0.58) and 1.04 (0.44–2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43–3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43–2.03; P = 0.86) and for the propensity-matched cohorts it was 1.05 (0.46–2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems., [Conclusions] Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock., This study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015) and FIS (PI10/02021). The study was also supported in part by funds and/or facilities provided by the Cleveland Department of Veterans Affairs, the Veterans Affairs Merit Review Program and the Geriatric Research Education and Clinical Center VISN 10 (VISN 10 GRECC) to R. A. B. The NIAID of the NIH under Award Numbers R01AI072219 and R01AI063517 also supported R. A. B.

Published
2016

12. Comparative evaluation of in vitro activities of carbapenemes against gram-negative pathogens: Turkish data of COMPACT study

Author

Korten, Volkan, Söyletir, Güner, Yalçın, Ata Nevzat, Oğünç, Dilara, Dokuzoğuz, Başak, Esener, Harika, Ulusoy, Sercan, Tünger, Alper, Aygen, Bilgehan, Sümerkan, Bülent, Arman, Dilek, Dizbay, Murat, Akova, Murat, Hasçelik, Gülşen, Eraksoy, Haluk, Başaran, Seniha, Köksal, İftihar, Bayramoğlu, Gülçin, Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı., Akalın, Halis, and Sinirtaş, Melda

Subjects
Ertapenem, Tebipenem, Anti-Bacterial Agents, Declining sensitivities, Turkey, Antibiotic resistance, Gram-negative bacterial infections, Bacteremia, Gram negative bacterium, Microbial sensitivity tests, Infections, Bacilli, Microbiology, Article, Turkey (republic), Gram-negative pathogen, Cross infection, Anti-bacterial agents, In vitro activity, Humans, Karbapenem, Intensive care unit, Carbapenem, Antiinfective agent, Drug resistance, bacterial, Intensive care units, Doripenem, Mutants, Meropenem, Carbapenem derivative, Dire consequences, Daunting challenges, Multicenter study, Bacterial pneumonia, Clinical trial, Drug effect, Imipenem, Carbapenems, Gram-negative bacteria, Gram negative infection, Gram-negatif patojen, Pneumonia, bacterial, Thienamycins, Microbiological examination, In vitro aktivite, Comparative study, Thienamycin derivative, Antibiotic-resistance, Human
Abstract

Bu çalışmada, doripenem, imipenem ve meropenemin gram-negatif klinik izolatlara karşı in vitro aktivitesinin değerlendirilmesi amaçlanmıştır. Türkiye genelinde toplam 10 merkezden Eylül-Aralık 2008 tarihleri arasında, yoğun bakım ünitesi (YBÜ) ve YBÜ dışı hastalardan, toplam 596 adet klinik izolat toplanmıştır. Bunlardan %42.4’ü nozokomiyal pnömoni, %40.4’ü kan dolaşımı enfeksiyonu ve %17.1’i komplike intraabdominal enfeksiyon kaynaklı olup; %51.8’i YBÜ hastalarından alınmıştır. İzolatların %49.8’i Pseudomonas spp., %40.3’ü Enterobacteriaceae ve %9.9’u diğer gram-negatif etkenlerden oluşmaktadır. Her merkezde Etest® (AB Biodisk, Solna, İsveç) kullanılarak tüm izolatlar için doripenem, imipenem ve meropenemin minimum inhibitör konsantrasyonu (MİK) belirlenmiştir. İzolatlardan 188 (%31.5)’i en az bir karbapeneme dirençli bulunmuştur. Pseudomonas türlerine karşı doripenem için MİK50 değerleri meropeneme benzer olarak 1 mg/L bulunurken, imipenemden iki kat daha düşük olduğu izlenmiştir. Pseudomonas aeruginosa izolatlarının duyarlılıkları, doripenem için MİK 2 mg/L düzeyinde %64, imipenem ve meropenem için MİK 4 mg/L düzeyinde sırasıyla %53.9 ve %63 olarak tespit edilmiştir. Doripenem ve meropenem, Enterobacteriaceae türlerine karşı benzer aktivite gösterirken (MİK90 0.12 mg/L), imipenem dört kat daha az aktif (0.5 mg/L) bulunmuştur. Büyük çoğunluğunu Acinetobacter türlerinin oluşturduğu diğer gram-negatif basiller için doripenem MİK50 değeri 8 mg/L, diğer iki ilaç için ise 32 mg/L’dir. P.aeruginosa izolatları 8 mg/L MİK düzeyinde doripenem ile %84.2, meropenem ile %72.1 oranında inhibe olmuştur. Sonuç olarak doripenem, bu çalışmada toplanan patojenlere karşı genel olarak meropenem ile benzer ya da daha iyi; imipenemden ise belirgin olarak daha iyi in vitro aktiviteye sahiptir. Üç karbapenem arasında Pseudomonas türlerine karşı en aktif olan ilacın doripenem olduğu görülmüştür. Doripenem ve meropenem Enterobacteriaceae türlerine karşı benzer aktiviteye sahip olup, imipenemden en az dört kat daha aktiftir. Bu bulgular ışığında, hastanede YBÜ’de ya da YBÜ dışında tedavi gören nozokomiyal pnömoni, kan dolaşımı enfeksiyonu ve intraabdominal enfeksiyonu olan hastalar ile antibiyotik direnci gelişim riski olan hastaların antimikrobiyal tedavisinde doripenemin öne çıkan yeni bir antibiyotik olduğu kanısına varılmıştır. The aim of this study was to determine the in vitro activities of doripenem, imipenem, and meropenem against clinical gram-negative isolates. A total of 596 clinical isolates were obtained from intensive care unit (ICU) and non-ICU patients in 10 centers over Turkey between September-December 2008. The origin of the isolates was patients with nosocomial pneumonia (42.4%), bloodstream infections (%40.4), and complicated intraabdominal infections (17.1%). Of the isolates, 51.8% were obtained from ICU patients. The study isolates consisted of Pseudomonas spp. in 49.8%, Enterobacteriaceae in 40.3%, and other gram-negative agents in 9.9%. The minimum inhibitory concentrations (MIC) for doripenem, imipenem and meropenem were determined for all isolates in each center using Etest (R) strips (AB Biodisk, Solna, Sweden). Of the isolates, 188 (31.5%) were resistant to at least one of the carbapenems. MIC(50) of doripenem against Pseudomonas spp. was 1 mg/L which was similar to that of meropenem and two-fold lower than imipenem. Susceptibility to carbapenems in P.aeruginosa was 64% for doripenem at an MIC level of 2 mg/L, 53.9% and 63% for imipenem and meropenem at an MIC level of 4 mg/L, respectively. Doripenem and meropenem showed similar activity with the MIC(90) of 0.12 mg/L whereas imipenem was four-fold less active at 0.5 mg/L. Against other gram-negative pathogens, mostly Acinetobacter spp., MIC(50) was 8 mg/L for doripenem and 32 mg/L for other two carbapenems. P.aeruginosa isolates were inhibited 84.2% with doripenem and 72.1% with meropenem at the MIC level of 8 mg/L. Doripenem generally showed similar or slightly better activity than meropenem and better activity than imipenem against pathogens collected in this study. Against Pseudomonas spp., doripenem was the most active of the three carbapenems. Doripenem and meropenem were equally active against Enterobacteriaceae and at least four-fold more active than imipenem. It was concluded that doripenem seemed to be a promising agent in the treatment of nosocomial pneumonia, blood stream infections and intraabdominal infections particularly in patients who were under risk of developing antimicrobial resistance.

Published
2011

13. Empiric Therapy With Carbapenem-Sparing Regimens for Bloodstream Infections due to Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Results From the INCREMENT Cohort.

Author

Palacios-Baena, Zaira Raquel, Gutiérrez-Gutiérrez, Belén, Calbo, Esther, Almirante, Benito, Viale, Pierluigi, Oliver, Antonio, Pintado, Vicente, Gasch, Oriol, Martínez-Martínez, Luis, Pitout, Johann, Akova, Murat, Peña, Carmen, Molina Gil-Bermejo, José, Hernández, Alicia, Venditti, Mario, Prim, Nuria, Bou, German, Tacconelli, Evelina, Tumbarello, Mario, and Hamprecht, Axel

Subjects
ANTIBIOTICS, BACTEREMIA, CONFIDENCE intervals, DRUG resistance in microorganisms, ENTEROBACTERIACEAE, LENGTH of stay in hospitals, PROPORTIONAL hazards models, RETROSPECTIVE studies, CARBAPENEMS, ENTEROBACTERIACEAE diseases, ODDS ratio
Abstract

Background. There is little information about the efficacy of active alternative drugs to carbapenems except β-lactam/β-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems. Methods. A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with OADs or carbapenems was performed. Cox regression including a propensity score for receiving OADs was performed to analyze 30-day all-cause mortality as main outcome. Clinical failure and length of stay were also analyzed. Results. Overall, 335 patients were included; 249 received empiric carbapenems and 86 OADs. The most frequent OADs were aminoglycosides (43 patients) and fluoroquinolones (20 patients). Empiric therapy with OADs was not associated with mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI], .38-1.48) in the Cox regression analysis. Propensity score-matched pairs, subgroups, and sensitivity analyses did not show different trends; specifically, the adjusted HR for aminoglycosides was 1.05 (95% CI, .51-2.16). OADs were neither associated with 14-day clinical failure (adjusted odds ratio, 0.62; 95% CI, .29-1.36) nor length of hospital stay. Conclusions. We were unable to show that empiric treatment with OAD was associated with a worse outcome compared with carbapenems. This information allows more options to be considered for empiric therapy, at least for some patients, depending on local susceptibility patterns of ESBL-E. [ABSTRACT FROM AUTHOR]

Published
2017
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14. Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort.

Author

Abdul-Aziz, Mohd H., Lipman, Jeffrey, Akova, Murat, Bassetti, Matteo, De Waele, Jan J., Dimopoulos, George, Dulhunty, Joel, Kaukonen, Kirsi-Maija, Koulenti, Despoina, Martin, Claude, Montravers, Philippe, Rello, Jordi, Rhodes, Andrew, Starr, Therese, Wallis, Steven C., Roberts, Jason A., and DALI Study Group

Subjects
PHARMACOKINETICS, CRITICALLY ill, PIPERACILLIN, TAZOBACTAM, MEROPENEM, HEALTH outcome assessment, PHARMACODYNAMICS, INTENSIVE care patients, ANTIBIOTICS, BLOOD testing, CATASTROPHIC illness, COMPARATIVE studies, INTENSIVE care units, INTRAVENOUS therapy, LONGITUDINAL method, PENICILLIN, RESEARCH methodology, MEDICAL cooperation, MICROBIAL sensitivity tests, RESEARCH, EVALUATION research, TREATMENT effectiveness, CARBAPENEMS, AMPICILLIN
Abstract

Objectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT>MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P = 0.012]. Additionally, in patients with a SOFA score of ≥9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P = 0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P = 0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections. [ABSTRACT FROM AUTHOR]

Published
2016
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15. Molecular characterization of NDM-1-producing Acinetobacter pittii isolated from Turkey in 2006.

Author

Roca, Ignasi, Mosqueda, Noraida, Altun, Belgin, Espinal, Paula, Akova, Murat, and Vila, Jordi

Subjects
BETA lactamases, ACINETOBACTER, METASTASIS, CHEMOTHERAPY complications, RADIOTHERAPY complications, DRUG resistance in microorganisms, PATIENTS
Abstract

The article discusses research on the occurrence of New Delhi Metallo-beta-lactamase-1 (NDM-1) in Acinetobacter pittii, with the isolate recovered from a female patient in eastern Turkey, who underwent surgery for metastatic carcinoma. Topics covered include the complications experienced by the patient from chemo- and radiotherapy, the results of the antibiotic susceptibility testing conducted on the patient, and the features of the genetic platform harbouring NDM-1 in the isolate.

Published
2014
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16. Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study.

Author

Harris, Patrick N.A., Pezzani, M. Diletta, Gutiérrez-Gutiérrez, Belén, Viale, Pierluigi, Hsueh, Po-Ren, Ruiz-Garbajosa, Patricia, Venditti, Mario, Tumbarello, Mario, Navarro-Francisco, Carolina, Calbo, Esther, Akova, Murat, Giamarellou, Helen, Oliver, Antonio, Almirante, Benito, Gasch, Oriol, Martínez-Martínez, Luis, Schwaber, Mitchell J., Daikos, George, Pitout, Johann, and Peña, Carmen

Subjects
*BLOOD disease treatment, *BETA lactamases, *ENTEROBACTERIACEAE, *DRUG resistance in bacteria, *REGIONAL differences, *BIOGEOGRAPHY
Abstract

We describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Patients ( n  = 1482) in 12 countries from an observational study of BSI caused by ESBL-E or CPE were included. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of β-lactam/β-lactamase inhibitors (BLBLIs) or carbapenems, targeted use of BLBLIs for ESBL-E and use of targeted combination therapy for CPE. Compared with Spain, BLBLI use for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14–0.81), Greece (aOR 0.49, 95% CI 0.26–0.94) and Canada (aOR 0.31, 95% CI 0.11–0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11–2.25) and Turkey (aOR 2.09, 95% CI 1.14–3.81). Empirical carbapenem use was more likely in sites from Taiwan (aOR 1.73, 95% CI 1.03–2.92) and USA (aOR 1.89, 95% CI 1.05–3.39) and less likely in Italy (aOR 0.44, 95% CI 0.28–0.69) and Canada (aOR 0.10, 95% CI 0.01–0.74). Targeted BLBLIs for ESBL-E was more likely in Italian sites. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. Better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts. [ABSTRACT FROM AUTHOR]

Published
2017
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17. Efficacy of β-Lactam/β-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia

Author

F. Herrera, Jordi Carratalà, Guillermo Maestro de la Calle, Cristina Royo-Cebrecos, Carlos Cervera, Murat Akova, Maddalena Peghin, Georg Maschmeyer, Pilar Martín-Dávila, Mercè Gurguí, Jesús Rodríguez-Baño, Isabel Ruiz-Camps, Angela Cano, Yolanda Meije, Adriana Manzur, Teresa C. Sukiennik, Edson Abdala, Wanessa Trindade Clemente, Alison G. Freifeld, Cristian Tebe, Miguel Montejo, Thomas Gottlieb, Lucía Gómez, Carlota Gudiol, R. Alvarez, European Society of Clinical Microbiology and Infectious Diseases, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Red Española de Investigación en Patología Infecciosa, [Gudiol, Carlota] Univ Barcelona, Bellvitge Univ Hosp, IDIBELL, Infect Dis Dept, Barcelona, Spain, [Royo-Cebrecos, Cristina] Univ Barcelona, Bellvitge Univ Hosp, IDIBELL, Infect Dis Dept, Barcelona, Spain, [Carratala, Jordi] Univ Barcelona, Bellvitge Univ Hosp, IDIBELL, Infect Dis Dept, Barcelona, Spain, [Gudiol, Carlota] Duran & Reynals Hosp, ICO, Barcelona, Spain, [Abdala, Edson] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Sao Paulo, Brazil, [Akova, Murat] Hacettepe Univ, Sch Med, Ankara, Turkey, [Alvarez, Rocio] Univ Seville, CSIC, Univ Hosp Virgen Rocio & Virgen Macarena, Inst Biomed Seville IBiS,Infect Dis Res Grp,Clin, Seville, Spain, [Maestro-de la Calle, Guillermo] Univ Complutense, Sch Med, Octubre Univ Hosp 12, Inst Invest Hosp Octubre 12 i 12,Infect Dis Unit, Madrid, Spain, [Cano, Angela] UCO, Reina Sofia Univ Hosp, IMIBIC, Cordoba, Spain, [Cervera, Carlos] Univ Alberta Hosp, Edmonton, AB, Canada, [Clemente, Wanessa T.] Univ Fed Minas Gerais, Hosp Clin, Digest Transplant Serv, Belo Horizonte, MG, Brazil, [Martin-Davila, Pilar] Hosp Ramon & Cajal, Infect Dis Dept, Madrid, Spain, [Freifeld, Alison] Univ Nebraska, Med Ctr, Internal Med Infect Dis Sect, Omaha, NE 68182 USA, [Gomez, Lucia] Univ Hosp Mutua Terrassa, Internal Med, Barcelona, Spain, [Gottlieb, Thomas] Concord Hosp, Dept Microbiol & Infect Dis, Concord, NSW, Australia, [Gurgui, Merce] Univ Autonoma Barcelona, Hosp Santa Creu & Sant Pau, Infect Dis Unit, Barcelona, Spain, [Gurgui, Merce] Univ Autonoma Barcelona, Inst Invest Biomed Sant Pau, Barcelona, Spain, [Herrera, Fabian] CEMIC, Dept Med, Infect Dis Sect, Buenos Aires, DF, Argentina, [Manzur, Adriana] Hosp Rawson, Infect Dis, San Juan, Argentina, [Maschmeyer, Georg] Charite, Med Sch, Acad Teaching Hosp, Dept Hematol Oncol & Palliat Care,Klinikum Ernst, Berlin, Germany, [Meije, Yolanda] Barcelona Hosp, SCIAS, Internal Med Dept, Infect Dis Unit, Barcelona, Spain, [Montejo, Miguel] Cruces Univ Hosp, Infect Dis Unit, Bilbao, Spain, [Peghin, Maddalena] Santa Maria Misericordia Univ Hosp, Infect Dis Div, Udine, Italy, [Rodriguez-Bano, Jesus] Univ Seville, Univ Hosp Virgen Macarena & Virgen Rocio IBiS, Dept Med, Clin Unit Infect Dis Microbiol & Prevent Med, Seville, Spain, [Ruiz-Camps, Isabel] Vall Hebron Univ Hosp, Infect Dis Dept, Barcelona, Spain, [Sukiennik, Teresa C.] Hosp Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, Brazil, [Tebe, Cristian] Rovira & Virgili Univ, Inst Biomed Res Bellvitge, Stat Advisory Serv, Tarragona, Spain, [Gudiol, Carlota] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Royo-Cebrecos, Cristina] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Meije, Yolanda] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Montejo, Miguel] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Rodriguez-Bano, Jesus] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Ruiz-Camps, Isabel] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, [Carratala, Jordi] Inst Salud Carlos III, REIPI Spanish Network Res Infect Dis, Madrid, Spain, ESGBIS, ESGICH, Ministerio de Economia y Competitividad, Instituto de Salud Carlos III - European Development Regional Fund 'A way to achieve Europe' EDRF, Spanish Network for the Research in Infectious Diseases, COMBACTE-NET, COMBACTE-CARE, COMBACTE-MAGNET, Innovative Medicines Initiative (European Union), Innovative Medicines Initiative (EFPIA), Merck, Astellas, Novartis, Pfizer, MSD, Janssen, Astra-Zeneca, and İç Hastalıkları

Subjects
0301 basic medicine, Male, Definitive Therapy, Bacteremia, Escherichia-coli, Cohort Studies, chemistry.chemical_compound, Bloodstream infection, Case fatality rate, polycyclic compounds, beta-lactam/beta-lactamase inhibitors, Pharmacology (medical), Pharmacology & Pharmacy, Cancer, biology, Klebsiella-pneumoniae, Enterobacteriaceae Infections, Middle Aged, Enterobacteriaceae, Anti-Bacterial Agents, Risk-factors, Infectious Diseases, Beta-lactam/beta-lactamase inhibitors, Cohort, Lactam, Female, beta-Lactamase Inhibitors, Adult, medicine.medical_specialty, Neutropenia, 030106 microbiology, bloodstream infection, Outcomes, Clinical Therapeutics, beta-Lactams, Microbiology, beta-Lactamases, 03 medical and health sciences, β lactamase inhibitor, Piperacillin-tazobactam, Internal medicine, medicine, Humans, Mortality, Intensive care medicine, Pharmacology, business.industry, biochemical phenomena, metabolism, and nutrition, medicine.disease, biology.organism_classification, bacterial infections and mycoses, mortality, chemistry, ESBLs, Carbapenems, bacteria, Therapy, Bloodstream infections, business
Abstract

β-Lactam/β-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-β-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients., We thank the ESGBIS and the ESGICH study groups for supporting the study. This study was supported by Ministerio de Economía y Competitividad, Instituto de Salud Carlos III—cofinanced by European Development Regional Fund “A way to achieve Europe” EDRF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015).

Published
2017

18. Geographical variation in therapy for bloodstream infections due to multidrug-resistant enterobacteriaceae: a post hoc analysis of the INCREMENT study

Author

Patrick N.A. Harris, M. Diletta Pezzani, Belén Gutiérrez-Gutiérrez, Pierluigi Viale, Po-Ren Hsueh, Patricia Ruiz-Garbajosa, Mario Venditti, Mario Tumbarello, Carolina Navarro-Francisco, Esther Calbo, Murat Akova, Helen Giamarellou, Antonio Oliver, Benito Almirante, Oriol Gasch, Luis Martínez-Martínez, Mitchell J. Schwaber, George Daikos, Johann Pitout, Carmen Peña, Alicia Hernández-Torres, Yohei Doi, Federico Pérez, Felipe Francisco Tuon, Evelina Tacconelli, Yehuda Carmeli, Robert A. Bonomo, Álvaro Pascual, David L. Paterson, Jesús Rodríguez-Baño, M.D. del Toro, J. Gálvez, M. Falcone, A. Russob, I. Karaiskos, E.M. Trecarichi, A.R. Losito, E. García-Vázquez, J. Gómez, E. Roilides, E. Iosifidis, S. Pournaras, N. Prim, F. Navarro, B. Mirelis, J. Origüen, R. San Juan, M. Fernández-Ruiz, M. Almela, C. de la Calle, J.A. Martínez, L. Morata, N. Larrosa, M. Puig-Asensio, G. Bou, J. Molina, V. González, J. Bermejo, V. Rucci, E. Ruiz de Gopegui, C.I. Marinescu, M.C. Fariñas, M.E. Cano, M. Gozalo, J.R. Paño-Pardo, Marta Mora-Rillo, S. Gómez-Zorrilla, F. Tubau, A. Tsakris, O. Zarkotou, A. Antoniadou, G. Poulakou, M. Souli, W. Lowman, D. Virmani, Julian Torre-Cisneros, I. Machuca, Irene Gracia-Ahufinger, Ö.K. Azap, Ö. Helvaci, A.O. Sahin, R. Cantón, V. Pintado, M. Bartoletti, M. Giannella, S. Peter, A. Hamprecht, C. Badia, M. Xercavins, D. Fontanals, E. Jové, Universidad de Cantabria, Harris, Patrick N.A., Pezzani, M. Diletta, Gutiérrez-Gutiérrez, Belén, Viale, Pierluigi, Hsueh, Po-Ren, Ruiz-Garbajosa, Patricia, Venditti, Mario, Tumbarello, Mario, Navarro-Francisco, Carolina, Calbo, Esther, Akova, Murat, Giamarellou, Helen, Oliver, Antonio, Almirante, Benito, Gasch, Oriol, Martínez-Martínez, Lui, Schwaber, Mitchell J., Daikos, George, Pitout, Johann, Peña, Carmen, Hernández-Torres, Alicia, Doi, Yohei, Pérez, Federico, Tuon, Felipe Francisco, Tacconelli, Evelina, Carmeli, Yehuda, Bonomo, Robert A., Pascual, Álvaro, Paterson, David L., Rodríguez-Baño, Jesú, del Toro, M.D., Gálvez, J., Falcone, M., Russo, A., Karaiskos, I., Trecarichi, E.M., Losito, A.R., García-Vázquez, E., Gómez, J., Roilides, E., Iosifidis, E., Pournaras, S., Prim, N., Navarro, F., Mirelis, B., Origüen, J., Juan, R. San, Fernández-Ruiz, M., Almela, M., de la Calle, C., Martínez, J.A., Morata, L., Larrosa, N., Puig-Asensio, M., Bou, G., Molina, J., González, V., Bermejo, J., Rucci, V., de Gopegui, E. Ruiz, Marinescu, C.I., Fariñas, M.C., Cano, M.E., Gozalo, M., Paño-Pardo, J.R., Mora-Rillo, Marta, Gómez-Zorrilla, S., Tubau, F., Tsakris, A., Zarkotou, O., Antoniadou, A., Poulakou, G., Souli, M., Lowman, W., Virmani, D., Torre-Cisneros, Julian, Machuca, I., Gracia-Ahufinger, Irene, Azap, Ã .K., Helvaci, Ã ., Sahin, A.O., Cantón, R., Pintado, V., Bartoletti, M., Giannella, M., Peter, S., Hamprecht, A., Badia, C., Xercavins, M., Fontanals, D., and Jové, E.

Subjects
Male, 0301 basic medicine, Carbapenem, Global Health, Logistic regression, 0302 clinical medicine, Drug Resistance, Multiple, Bacterial, Antimicrobial stewardship, Pharmacology (medical), 030212 general & internal medicine, Aged, 80 and over, Enterobacteriaceae Infections, General Medicine, Middle Aged, Extended-spectrum beta-lactamase, Klebsiella pneumoniae, Infectious Diseases, Beta-lactam/beta-lactamase inhibitors, Female, beta-Lactamase Inhibitors, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, Combination therapy, β-Lactam/β-lactamase inhibitor, 030106 microbiology, Infectious Disease, Biology, beta-Lactams, Carbapenemase, 03 medical and health sciences, Extended-spectrum β-lactamase, Enterobacteriaceae, Sepsis, Post-hoc analysis, medicine, Escherichia coli, Humans, Aged, Retrospective Studies, Carbapenems, β-Lactam/β-lactamase inhibitor, Odds ratio, biochemical phenomena, metabolism, and nutrition, Extended-spectrum β-lactamase, Surgery, Multiple drug resistance, Observational study, Demography
Abstract

We aimed to describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). 1,482 patients in 12 countries were included from an observational study of BSI caused by ESBL-E or CPE. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ?-lactam/?-lactamase inhibitors (BLBLI) or carbapenems, targeted use of BLBLI for ESBL-E and use of targeted combination therapy for CPE. The use of BLBLI for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.2) and Turkey (aOR 2.09, 95% CI 1.14-3.81), compared to Spain as a reference. Empirical carbapenems were more likely to be used in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89; 95% CI 1.05-3.39), and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLI for ESBL-E was more likely in sites from Italy. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. A better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts. PH is supported by an Australian Postgraduate Award from the University of Queensland. The study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund "A way to achieve Europe" ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). BGG, JRB, APH and YC also received funds from the COMBACTE-CARE project (grant agreement 115620), Innovative Medicines Initiative (IMI), the European Union's Seventh Framework Programme (FP7/2007-2013) and in-kind contributions from EFPIA companies.

Published
2017

19. Hacettepe Üniversitesi erişkin hastanesinde 2004-2012 yılları arasında kan kültürlerinde üreyen enterobacteriaceae üyelerinin genişletilmiş spektrumlu betalaktamaz ve karbapenemaz pozitifliklerinin değerlendirilmesi

Author

Helvaci, Özant, Akova, Murat, and İç Hastalıkları Anabilim Dalı

Subjects
Blood, Beta lactamases, Enterobacteriaceae, Carbapenems, Cross infection, Mikrobiyoloji, Hacettepe University, Clinical Microbiology and Infectious Diseases, Klinik Bakteriyoloji ve Enfeksiyon Hastalıkları, Microbiology, Hospitals-university
Abstract

Helvacı Özant, Hacettepe Üniversitesi Erişkin Hastanesinde 2004-2012 yılları arasında kan kültürlerinde üreyen Enterobacteriaceae üyelerinin genişletilmiş spektrumlu betalaktamaz ve karbapenemaz pozitifliklerinin değerlendirilmesi, Hacettepe Üniversitesi Tıp Fakültesi İç Hastalıkları Uzmanlık Tezi, Ankara 2014. Amaç: Bu çalışmada, 2004-2012 yılları arasında kan kültürlerinde üremiş Enterobacteriaceae üyelerinin genişletilmiş spektrumlu betalaktamaz ve karbapenemaz pozitifliklerinin saptanması ve karbapenemaz pozitif üreme saptanan hastaların klinik özelliklerinin saptanması planlanmıştır.Gereç ve Yöntem: Hacettepe Üniversitesi Erişkin Hastanesinde 2004-2012 yılları arasında kan kültürlerinde üreyen E.coli, K. pneumoniae, Enterobacter spp. ve diğer Enterobacteriaceae üyelerinde GSBL pozitifliği oranları incelendi. Bir hastanın aynı infeksiyon epizodundan alınan çok sayıdaki kan kültürleri bir üreme olarak sayılarak `düzeltilmiş üreme sayısı` hesaplandı. CLSI 2010 kılavuzuna göre karbapenemaz pozitifliği için belirgin risk taşıyan 50 hastanın suşları karbapenemaz için PCR yöntemi ile `VIM, IMP, KPC, NDM, OXA` karbapenemazları araştırıldı.Bulgular: 1138 E. coli üremesinin 382'isi (%31.8), 703 Klebsiella spp. üremesinin 175 (%24.8) ve 237 Enterobacter spp. üremesinin 46'sı (%24.8) GSBL pozitifti. PCR yapılan 11 E. coli suşundan 7'sinde (%63.6) ve 36 Klebsiella spp. Suşundan 28'inde (%77) karbapenemaz saptandı. Karbapenemaz alt tipleri incelendiğinde Klebsiella spp.'lerin 22'sinde OXA, 3'ünde VIM, 2'sinde IMP ve bir suşta OXA ve VIM eş zamanlı pozitif olduğu saptandı. E.coli suşlarından ise 5'i OXA, 2'si ise OXA ve VIM eş zamanlı pozitifti. NDM ve KPC alt tipleri saptanmadı.Sonuç: Hastanemizdeki GSBL ve/veya karbapenemaz üreten Enterobacteriaceae sıklığı Türkiye ve Avrupa ile benzer değerlerdedir. Bazı yıllarda muhtemelen lokal veya ülke geneli salgınlara bağlı olarak bu değerlerde ani yükselişler olmaktadır. Artmış antibiyotik direnci tedaviyi zorlaştırmakta ve mortaliteyi arttırmaktadır. Bu bakteriler ile bulaşın engellenmesi için uluslarası infeksiyon kontrol merkezlerinin önerilerine uyulmalıdır. Anahtar Kelimeler: Betalaktamaz, GSBL, karbapenemaz, Enterobacteriaceae, Hastane kaynaklı infeksiyon Helvacı Özant, Evaluation of extended spectrum beta lactamase and carbapenemase positivity rates of Enterobacteriaceae causing bacteremia between years 2004-2012 in Hacettepe University Faculty of Medicine, Ankara 2014. Aim: The aim of this study was to determine ESBL and carbapenemase positivity of Enterobacteriaceae that grew in blood cultures and define the clinical properties of patients infected with carbapenemase positive strains. .Material and method: E.coli, K. pneumoniae, Enterobacter spp. and other Enterobacteriaceae in blood cultures between years 2004-2012 in Hacettepe Üniversity Faculty of Medicine were evaluated for ESBL and carbapenemase positivity. ESBL was defined with standart phenotypic method and carbapenemase with PCR for `VIM, IMP, KPC, NDM, OXA` carbapenemases..Findings: 382 of 1138 E. coli bacteremias (%31.8), 175 of 703 Klebsiella spp. bacteremias (%24.8) and 46 of 237 Enterobacter spp. bacteremias (%24.8) were ESBL positive. PCR was performed on 11 E. coli strains and 36 Klebsiella spp. strains. 7 of E. coli strains (%63.6) and 28 of Klebsiella spp.strains (%77) were carbapenemase positive. Klebsiella spp. subgroup analysis showed that 22 strains were OXA, 3 were VIM, 2 were IMP and one strain was OXA+VIM pozitive. For E.coli strains; 5 were OXA, 2 were OXA+VIM pozitive. NDM and KPC subtypes were detected.Results: Our hospitals ESBL and/or carbapenemase positive Enterobacteriaceae frequency is similar with Europe and Turkey. In some years, there were sharp rises in ESBL producing bacteria rates , probably due to local epidemias Resistance to antibiotics, increased mortality can be caused by these species. Since treatment options are limited, every precaution necessary should be taken to avoid spreading of resistant Enterobacteriaceae. 43

Published
2014

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