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Erschienen in: Intensive Care Medicine 10/2017

21.07.2017 | Review

Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach

verfasst von: Matteo Bassetti, Garyphallia Poulakou, Etienne Ruppe, Emilio Bouza, Sebastian J. Van Hal, Adrian Brink

Erschienen in: Intensive Care Medicine | Ausgabe 10/2017

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Abstract

Purpose

To describe the current standards of care and major recent advances with regard to antimicrobial resistance (AMR) and to give a prospective overview for the next 30 years in this field.

Methods

Review of medical literature and expert opinion were used in the development of this review.

Results

There is undoubtedly a large clinical and public health burden associated with AMR in ICU, but it is challenging to quantify the associated excess morbidity and mortality. In the last decade, antibiotic stewardship and infection prevention and control have been unable to prevent the rapid spread of resistant Gram-negative bacteria (GNB), in particular carbapenem-resistant Pseudomonas aeruginosa (and other non-fermenting GNB), extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE). The situation appears more optimistic currently for Gram-positive, where Staphylococcus aureus, and particularly methicillin-resistant S. aureus (MRSA), remains a cardinal cause of healthcare-associated infections worldwide. Recent advancements in laboratory techniques allow for a rapid identification of the infecting pathogen and antibiotic susceptibility testing. Their impact can be particularly relevant in settings with prevalence of MDR, since they may guide fine-tuning of empirically selected regimen, facilitate de-escalation of unnecessary antimicrobials, and support infection control decisions.
Currently, antibiotics are the primary anti-infective solution for patients with known or suspected MDR bacteria in intensive care. Numerous incentives have been provided to encourage researchers to work on alternative strategies to reverse this trend and to provide a means to treat these pathogens. Although some promising antibiotics currently in phase 2 and 3 of development will soon be licensed and utilized in ICU, the continuous development of an alternative generation of compounds is extremely important. There are currently several promising avenues available to fight antibiotic resistance, such as faecal microbiota, and phage therapy.
Literatur
2.
4.
Zurück zum Zitat Karanika S, Karantanos T, Arvanitis M et al (2016) Fecal colonization with extended spectrum beta-lactamase-producing Enterobacteriaceae and risk factors among healthy individuals: a systematic review and meta analysis. Clin Infect Dis 63:310–318CrossRefPubMed Karanika S, Karantanos T, Arvanitis M et al (2016) Fecal colonization with extended spectrum beta-lactamase-producing Enterobacteriaceae and risk factors among healthy individuals: a systematic review and meta analysis. Clin Infect Dis 63:310–318CrossRefPubMed
5.
Zurück zum Zitat Lee BY, Bartsch SM, Wong KF et al (2016) The potential trajectory of carbapenem-resistant Enterobacteriaceae, an emerging threat to health-care facilities, and the impact of the centers for disease control and prevention toolkit. Am J Epidemiol 183(5):471–479CrossRefPubMedPubMedCentral Lee BY, Bartsch SM, Wong KF et al (2016) The potential trajectory of carbapenem-resistant Enterobacteriaceae, an emerging threat to health-care facilities, and the impact of the centers for disease control and prevention toolkit. Am J Epidemiol 183(5):471–479CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Teerawattanapong N, Kengkla K, Dilokthornsakul P et al (2017) Prevention and control of multidrug-resistant Gram-negative bacteria in adult intensive care units: a systematic review and network meta-analysis. Clin Infect Dis 64:51–60CrossRef Teerawattanapong N, Kengkla K, Dilokthornsakul P et al (2017) Prevention and control of multidrug-resistant Gram-negative bacteria in adult intensive care units: a systematic review and network meta-analysis. Clin Infect Dis 64:51–60CrossRef
7.
Zurück zum Zitat Kanamori H, Parobek CM, Juliano JJ et al (2017) A prolonged outbreak of KPC-3-producing Enterobacter cloacae and Klebsiella pneumoniae driven by multiple mechanisms of resistance transmission at a large academic burn center. Antimicrob Agents Chemother 61(2):e01516-16. doi:10.1128/AAC.01516-1 Kanamori H, Parobek CM, Juliano JJ et al (2017) A prolonged outbreak of KPC-3-producing Enterobacter cloacae and Klebsiella pneumoniae driven by multiple mechanisms of resistance transmission at a large academic burn center. Antimicrob Agents Chemother 61(2):e01516-16. doi:10.​1128/​AAC.​01516-1
9.
Zurück zum Zitat Newitt S, Myles PR, Birkin JA et al (2015) Impact of infection control interventions on rates of Staphylococcus aureus bacteraemia in National Health Service acute hospitals, East Midlands, UK, using interrupted time-series analysis. J Hosp Infect 90:28–37. doi:10.1016/j.jhin.2014.12.016 CrossRefPubMed Newitt S, Myles PR, Birkin JA et al (2015) Impact of infection control interventions on rates of Staphylococcus aureus bacteraemia in National Health Service acute hospitals, East Midlands, UK, using interrupted time-series analysis. J Hosp Infect 90:28–37. doi:10.​1016/​j.​jhin.​2014.​12.​016 CrossRefPubMed
10.
Zurück zum Zitat Grundmann H, Schouls LM, Aanensen DM et al (2014) The dynamic changes of dominant clones of Staphylococcus aureus causing bloodstream infections in the European region: results of a second structured survey. EuroSurveill 19:20987CrossRef Grundmann H, Schouls LM, Aanensen DM et al (2014) The dynamic changes of dominant clones of Staphylococcus aureus causing bloodstream infections in the European region: results of a second structured survey. EuroSurveill 19:20987CrossRef
11.
Zurück zum Zitat Andrey DO, François P, Manzano C et al (2017) Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013–2014 at the Geneva University Hospitals. Eur J Clin Microbiol Infect Dis 36:343–350. doi:10.1007/s10096-016-2807-5 CrossRefPubMed Andrey DO, François P, Manzano C et al (2017) Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013–2014 at the Geneva University Hospitals. Eur J Clin Microbiol Infect Dis 36:343–350. doi:10.​1007/​s10096-016-2807-5 CrossRefPubMed
14.
Zurück zum Zitat Murray E, Holmes A (2012) Addressing healthcare-associated infections and antimicrobial resistance from an organizational perspective: progress and challenges. J Antimicrob Chemother 67[Suppl 1]:i29–i36. doi:10.1093/jac/dks200 CrossRefPubMed Murray E, Holmes A (2012) Addressing healthcare-associated infections and antimicrobial resistance from an organizational perspective: progress and challenges. J Antimicrob Chemother 67[Suppl 1]:i29–i36. doi:10.​1093/​jac/​dks200 CrossRefPubMed
15.
Zurück zum Zitat Brink AJ, Messina AP, Feldman C et al (2017) From guidelines to practice: a pharmacist-driven prospective audit and feedback improvement model for peri-operative antibiotic prophylaxis in 34 South African hospitals. J Antimicrob Chemother 72:1227–1234. doi:10.1093/jac/dkw523 PubMed Brink AJ, Messina AP, Feldman C et al (2017) From guidelines to practice: a pharmacist-driven prospective audit and feedback improvement model for peri-operative antibiotic prophylaxis in 34 South African hospitals. J Antimicrob Chemother 72:1227–1234. doi:10.​1093/​jac/​dkw523 PubMed
17.
Zurück zum Zitat Bilinski J, Grzesiowski P, Muszynski J et al (2016) Fecal microbiota transplantation inhibits multidrug-resistant gut pathogens: preliminary report performed in an immunocompromised host. Arch Immunol Ther Exp 64:255–258CrossRef Bilinski J, Grzesiowski P, Muszynski J et al (2016) Fecal microbiota transplantation inhibits multidrug-resistant gut pathogens: preliminary report performed in an immunocompromised host. Arch Immunol Ther Exp 64:255–258CrossRef
18.
Zurück zum Zitat Dellinger RP, Levy MM, Rhodes A et al (2013) Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39:165–228CrossRefPubMed Dellinger RP, Levy MM, Rhodes A et al (2013) Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39:165–228CrossRefPubMed
19.
Zurück zum Zitat Cambray G, Sanchez-Alberola N et al (2014) Prevalence of SOS-mediated control of integron integrase expression as an adaptive trait of chromosomal and mobile integrons. Mob DNA 2011(2):6. doi:10.1186/1759-8753-2-6 Cambray G, Sanchez-Alberola N  et al (2014) Prevalence of SOS-mediated control of integron integrase expression as an adaptive trait of chromosomal and mobile integrons. Mob DNA 2011(2):6. doi:10.​1186/​1759-8753-2-6
20.
Zurück zum Zitat Girmenia C, Viscoli C, Piciocchi A et al (2015) Management of carbapenem resistant Klebsiella pneumoniae infections in stem cell transplant recipients: an Italian multidisciplinary consensus statement. Haematologica 100:e373–e376CrossRefPubMedPubMedCentral Girmenia C, Viscoli C, Piciocchi A et al (2015) Management of carbapenem resistant Klebsiella pneumoniae infections in stem cell transplant recipients: an Italian multidisciplinary consensus statement. Haematologica 100:e373–e376CrossRefPubMedPubMedCentral
21.
22.
Zurück zum Zitat Bauer KA, Perez KK, Forrest GN et al (2014) Review of rapid diagnostic tests used by antimicrobial stewardship proGrams. Clin Infect Dis 59[Suppl 3]:S134–S145CrossRefPubMed Bauer KA, Perez KK, Forrest GN et al (2014) Review of rapid diagnostic tests used by antimicrobial stewardship proGrams. Clin Infect Dis 59[Suppl 3]:S134–S145CrossRefPubMed
23.
Zurück zum Zitat Arena F, Viaggi B, Galli L et al (2015) Antibiotic susceptibility testing: present and future. Pediatr Infect Dis J 34:1128–1130CrossRefPubMed Arena F, Viaggi B, Galli L et al (2015) Antibiotic susceptibility testing: present and future. Pediatr Infect Dis J 34:1128–1130CrossRefPubMed
24.
Zurück zum Zitat Banerjee R, Özenci V, Patel R (2016) Individualized approaches are needed for optimized blood cultures. Clin Infect Dis 63:1332–1339CrossRefPubMed Banerjee R, Özenci V, Patel R (2016) Individualized approaches are needed for optimized blood cultures. Clin Infect Dis 63:1332–1339CrossRefPubMed
25.
Zurück zum Zitat Kostrzewa M, Sparbier K, Maier T et al (2013) MALDI-TOF MS: an upcoming tool for rapid detection of antibiotic resistance in microorganisms. Proteomics Clin Appl 7:767–778CrossRefPubMed Kostrzewa M, Sparbier K, Maier T et al (2013) MALDI-TOF MS: an upcoming tool for rapid detection of antibiotic resistance in microorganisms. Proteomics Clin Appl 7:767–778CrossRefPubMed
26.
Zurück zum Zitat Gaibani P, Galea A, Fagioni M et al (2016) Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of KPC-producing Klebsiella pneumoniae. J Clin Microbiol 54:2609–2613CrossRefPubMedPubMedCentral Gaibani P, Galea A, Fagioni M et al (2016) Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of KPC-producing Klebsiella pneumoniae. J Clin Microbiol 54:2609–2613CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Salimnia H, Fairfax MR, Lephart PR et al (2016) Evaluation of the filmarray blood culture identification panel: results of a multicenter controlled trial. J Clin Microbiol 54:687–698CrossRefPubMedPubMedCentral Salimnia H, Fairfax MR, Lephart PR et al (2016) Evaluation of the filmarray blood culture identification panel: results of a multicenter controlled trial. J Clin Microbiol 54:687–698CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Leone M, Malavieille F, Papazian L et al (2013) Routine use of Staphylococcus aureus rapid diagnostic test in patients with suspected ventilator-associated pneumonia. Crit Care 17(4):R170CrossRefPubMedPubMedCentral Leone M, Malavieille F, Papazian L et al (2013) Routine use of Staphylococcus aureus rapid diagnostic test in patients with suspected ventilator-associated pneumonia. Crit Care 17(4):R170CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Dureau AF, Duclos G, Antonini F et al (2017) Rapid diagnostic test and use of antibiotic against methicillin-resistant Staphylococcus aureus in adult intensive care unit. Eur J Clin Microbiol Infect Dis 36(2):267–272CrossRefPubMed Dureau AF, Duclos G, Antonini F et al (2017) Rapid diagnostic test and use of antibiotic against methicillin-resistant Staphylococcus aureus in adult intensive care unit. Eur J Clin Microbiol Infect Dis 36(2):267–272CrossRefPubMed
30.
Zurück zum Zitat Cambau E, Durand-Zaleski I, Bretagne S et al (2017) Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial. Intensive Care Med. doi:10.1007/s00134-017-4766-4 PubMed Cambau E, Durand-Zaleski I, Bretagne S et al (2017) Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial. Intensive Care Med. doi:10.​1007/​s00134-017-4766-4 PubMed
31.
Zurück zum Zitat Schnabel RM, Boumans ML, Smolinska A et al (2015) Electronic nose analysis of exhaled breath to diagnose ventilator-associated pneumonia. Respir Med 109(11):1454–1459CrossRefPubMed Schnabel RM, Boumans ML, Smolinska A et al (2015) Electronic nose analysis of exhaled breath to diagnose ventilator-associated pneumonia. Respir Med 109(11):1454–1459CrossRefPubMed
32.
Zurück zum Zitat Montuschi P, Mores N, Trove A et al (2013) The electronic nose in respiratory medicine. Respir Int Rev Thorac Dis 85(1):72e84 Montuschi P, Mores N, Trove A et al (2013) The electronic nose in respiratory medicine. Respir Int Rev Thorac Dis 85(1):72e84
33.
Zurück zum Zitat Hanson CW 3rd, Thaler ER (2005) Electronic nose prediction of a clinical pneumonia score: biosensors and microbes. Anesthesiology 102(1):63–68CrossRefPubMed Hanson CW 3rd, Thaler ER (2005) Electronic nose prediction of a clinical pneumonia score: biosensors and microbes. Anesthesiology 102(1):63–68CrossRefPubMed
34.
Zurück zum Zitat Hockstein NG, Thaler ER, Torigian D et al (2004) Diagnosis of pneumonia with an electronic nose: correlation of vapor signature with chest computed tomography scan findings. Laryngoscope 114(10):1701–1705CrossRefPubMed Hockstein NG, Thaler ER, Torigian D et al (2004) Diagnosis of pneumonia with an electronic nose: correlation of vapor signature with chest computed tomography scan findings. Laryngoscope 114(10):1701–1705CrossRefPubMed
36.
39.
Zurück zum Zitat Gosalbes MJ, Vázquez-Castellanos JF, Angebault C et al (2016) Carriage of Enterobacteria producing extended-spectrum β-lactamases and composition of the gut microbiota in an Amerindian Community. Antimicrob Agents Chemother 60:507–514. doi:10.1128/AAC.01528-15 CrossRef Gosalbes MJ, Vázquez-Castellanos JF, Angebault C et al (2016) Carriage of Enterobacteria producing extended-spectrum β-lactamases and composition of the gut microbiota in an Amerindian Community. Antimicrob Agents Chemother 60:507–514. doi:10.​1128/​AAC.​01528-15 CrossRef
41.
Zurück zum Zitat Bhalla A, Pultz NJ, Ray AJ et al (2003) Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-resistant, Gram-negative bacilli and vancomycin-resistant enterococci in the stool of colonized patients. Infect Control Hosp Epidemiol 24:644–649. doi:10.1086/502267 CrossRefPubMed Bhalla A, Pultz NJ, Ray AJ et al (2003) Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-resistant, Gram-negative bacilli and vancomycin-resistant enterococci in the stool of colonized patients. Infect Control Hosp Epidemiol 24:644–649. doi:10.​1086/​502267 CrossRefPubMed
42.
Zurück zum Zitat Bernard J, Armand-Lefèvre L, Luce E et al (2016) Impact of a short exposure to levofloxacin on faecal densities and relative abundance of total and quinolone-resistant Enterobacteriaceae. Clin Microbiol Infect 22(7):646.e1–4. doi:10.1016/j.cmi.2016.04.015 Bernard J, Armand-Lefèvre L, Luce E et al (2016) Impact of a short exposure to levofloxacin on faecal densities and relative abundance of total and quinolone-resistant Enterobacteriaceae. Clin Microbiol Infect 22(7):646.e1–4. doi:10.​1016/​j.​cmi.​2016.​04.​015
43.
Zurück zum Zitat Ruppé E, Lixandru B, Cojocaru R et al (2013) Relative fecal abundance of extended-spectrum-β-lactamase-producing Escherichia coli strains and their occurrence in urinary tract infections in women. Antimicrob Agents Chemother 57:4512–4517. doi:10.1128/AAC.00238-13 CrossRefPubMedPubMedCentral Ruppé E, Lixandru B, Cojocaru R et al (2013) Relative fecal abundance of extended-spectrum-β-lactamase-producing Escherichia coli strains and their occurrence in urinary tract infections in women. Antimicrob Agents Chemother 57:4512–4517. doi:10.​1128/​AAC.​00238-13 CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Woerther P-L, Micol J-B, Angebault C et al (2015) Monitoring antibiotic-resistant enterobacteria faecal levels is helpful in predicting antibiotic susceptibility of bacteraemia isolates in patients with haematological malignancies. J Med Microbiol 64:676–681. doi:10.1099/jmm.0.000078 CrossRefPubMed Woerther P-L, Micol J-B, Angebault C et al (2015) Monitoring antibiotic-resistant enterobacteria faecal levels is helpful in predicting antibiotic susceptibility of bacteraemia isolates in patients with haematological malignancies. J Med Microbiol 64:676–681. doi:10.​1099/​jmm.​0.​000078 CrossRefPubMed
45.
Zurück zum Zitat Ruppé E, Armand-Lefèvre L, Estellat C et al (2015) High rate of acquisition but short duration of carriage of multidrug-resistant Enterobacteriaceae after travel to the tropics. Clin Infect Dis 61:593–600. doi:10.1093/cid/civ333 CrossRefPubMed Ruppé E, Armand-Lefèvre L, Estellat C et al (2015) High rate of acquisition but short duration of carriage of multidrug-resistant Enterobacteriaceae after travel to the tropics. Clin Infect Dis 61:593–600. doi:10.​1093/​cid/​civ333 CrossRefPubMed
48.
Zurück zum Zitat de Gunzburg J, Ducher A, Modess C et al (2015) Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: a proof of concept study in healthy subjects. J Clin Pharmacol 55:10–16. doi:10.1002/jcph.359 CrossRefPubMed de Gunzburg J, Ducher A, Modess C et al (2015) Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: a proof of concept study in healthy subjects. J Clin Pharmacol 55:10–16. doi:10.​1002/​jcph.​359 CrossRefPubMed
49.
50.
Zurück zum Zitat Manges AR, Steiner TS, Wright AJ (2016) Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobial-resistant opportunistic pathogens: a review. Infect Dis Lond Engl 48:587–592. doi:10.1080/23744235.2016.1177199 CrossRef Manges AR, Steiner TS, Wright AJ (2016) Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobial-resistant opportunistic pathogens: a review. Infect Dis Lond Engl 48:587–592. doi:10.​1080/​23744235.​2016.​1177199 CrossRef
56.
Zurück zum Zitat Khanna S, Pardi DS, Kelly CR et al (2016) A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection. J Infect Dis 214:173–181. doi:10.1093/infdis/jiv766 CrossRefPubMed Khanna S, Pardi DS, Kelly CR et al (2016) A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection. J Infect Dis 214:173–181. doi:10.​1093/​infdis/​jiv766 CrossRefPubMed
57.
Zurück zum Zitat Bar-Yoseph H, Hussein K, Braun E (2016) Natural history and decolonization strategies for ESBL/carbapenem-resistant Enterobacteriaceae carriage: systematic review and meta-analysis. J Antimicrob Chemother 71:2729–2739CrossRefPubMed Bar-Yoseph H, Hussein K, Braun E (2016) Natural history and decolonization strategies for ESBL/carbapenem-resistant Enterobacteriaceae carriage: systematic review and meta-analysis. J Antimicrob Chemother 71:2729–2739CrossRefPubMed
58.
Zurück zum Zitat Buffie CG, Bucci V, Stein RR et al (2015) Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517:205–208. doi:10.1038/nature13828 Buffie CG, Bucci V, Stein RR et al (2015) Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517:205–208. doi:10.​1038/​nature13828
59.
Zurück zum Zitat d’Herelle F (1931) Bacteriophage as a treatment in acute medical and surgical infections. Bull N Y Acad Med 7:329–348PubMedPubMedCentral d’Herelle F (1931) Bacteriophage as a treatment in acute medical and surgical infections. Bull N Y Acad Med 7:329–348PubMedPubMedCentral
61.
Zurück zum Zitat Wright A, Hawkins CH, Anggård EE et al (2009) A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin Otolaryngol 34:349–357. doi:10.1111/j.1749-4486.2009.01973.x CrossRefPubMed Wright A, Hawkins CH, Anggård EE et al (2009) A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin Otolaryngol 34:349–357. doi:10.​1111/​j.​1749-4486.​2009.​01973.​x CrossRefPubMed
67.
81.
Zurück zum Zitat van Delden C, Köhler T, Brunner-Ferber F et al (2012) Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial. Intensive Care Med 38:1118–1125. doi:10.1007/s00134-012-2559-3 CrossRefPubMed van Delden C, Köhler T, Brunner-Ferber F et al (2012) Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial. Intensive Care Med 38:1118–1125. doi:10.​1007/​s00134-012-2559-3 CrossRefPubMed
82.
Zurück zum Zitat Crowther GS, Baines SD, Todhunter SL et al (2013) Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection. J Antimicrob Chemother 68:168–176. doi:10.1093/jac/dks359 CrossRefPubMed Crowther GS, Baines SD, Todhunter SL et al (2013) Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection. J Antimicrob Chemother 68:168–176. doi:10.​1093/​jac/​dks359 CrossRefPubMed
Metadaten
Titel
Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach
verfasst von
Matteo Bassetti
Garyphallia Poulakou
Etienne Ruppe
Emilio Bouza
Sebastian J. Van Hal
Adrian Brink
Publikationsdatum
21.07.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Intensive Care Medicine / Ausgabe 10/2017
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-017-4878-x

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