Pneumologie 2018; 72(01): 15-63
DOI: 10.1055/s-0043-121734
Leitlinie
© Georg Thieme Verlag KG Stuttgart · New York

Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie – Update 2017[*]

S3-Leitlinie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V., der Deutschen Gesellschaft für Infektiologie e.V., der Deutschen Gesellschaft für Hygiene und Mikrobiologie e.V., der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V., der Paul-Ehrlich Gesellschaft für Chemotherapie e.V, der Deutschen Röntgengesellschaft und der Gesellschaft für VirologieEpidemiology, Diagnosis and Treatment of Adult Patients with Nosocomial Pneumonia – Update 2017S3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy, the German Radiological Society and the Society for Virology
K. Dalhoff
1   Medizinische Klinik III, Pneumologie, Universitätsklinikum Schleswig-Holstein, Lübeck
,
M. Abele-Horn
2   Institut für Hygiene und Mikrobiologie der Universität Würzburg, Würzburg
,
S. Andreas
3   Lungenfachklinik Immenhausen, Immenhausen
,
M. Deja
4   Charité, Universitätsmedizin Berlin, Klinik für Anästhesiologie m. S. operative Intensivmedizin, Campus Virchow Klinikum und Campus Mitte, Berlin
,
S. Ewig
5   Thoraxzentrum Ruhrgebiet, Kliniken für Pneumologie und Infektiologie, Evangelisches Krankenhaus Herne und Augusta-Kranken-Anstalt Bochum, Herne und Bochum
,
P. Gastmeier
6   Institut für Hygiene und Umweltmedizin, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin
,
S. Gatermann
7   Institut für Hygiene und Mikrobiologie, Abteilung für Medizinische Mikrobiologie, Ruhr-Universität Bochum, Bochum
,
H. Gerlach
 8   Klinik für Anästhesie, operative Intensivmedizin und Schmerztherapie, Vivantes Klinikum Neukölln, Berlin
,
B. Grabein
 9   Stabsstelle Klinische Mikrobiologie und Krankenhaushygiene am Klinikum der Universität München, München
,
C. P. Heußel
10   Thoraxklinik Heidelberg gGmbH, Abteilung für Diagnostische und Interventionelle Radiologie
,
G. Höffken
11   Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik 1, Fachabteilung für Pneumologie, Dresden
,
M. Kolditz
11   Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik 1, Fachabteilung für Pneumologie, Dresden
,
E. Kramme
1   Medizinische Klinik III, Pneumologie, Universitätsklinikum Schleswig-Holstein, Lübeck
,
H. Kühl
12   St. Bernhard-Hospital Kamp-Lintfort GmbH, Klinik für Radiologie, Kamp-Lintfort
,
C. Lange
13   Medizinische Klinik, Forschungszentrum Borstel, Borstel
,
K. Mayer
14   Zentrum für Innere Medizin, Medizinische Klinik II, Pneumologie und Intensivmedizin, Universitätsklinikum Gießen und Marburg, Standort Gießen
,
I. Nachtigall
15   Helios Klinikum Bad Saarow, Bad Saarow
,
M. Panning
16   Universitätsklinikum Freiburg, Institut für Medizinische Mikrobiologie und Hygiene, Freiburg
,
M. Pletz
17   Zentrum für Infektionsmedizin und Krankenhaushygiene, Universitätsklinikum Jena, Jena
,
P.-M. Rath
18   Institut für Medizinische Mikrobiologie, Universitätsklinikum Essen, Essen
,
G. Rohde
19   Klinikum der Johann Wolfgang Goethe-Universität, Pneumologie/Allergologie, Medizinische Klinik 1, Frankfurt am Main
,
S. Rosseau
20   Klinik Ernst von Bergmann Bad Belzig gGmbH, Pneumologisches Beatmungszentrum, Bad Belzig
,
B. Schaaf
21   Klinikum Dortmund gGmbH, Medizinischen Klinik, Pneumologie und Infektiologie, Dortmund
,
D. Schreiter
22   Helios Park-Klinikum Leipzig GmbH und Herzzentrum Leipzig GmbH, Universitätsklinik, Leipzig
,
H. Schütte
23   Klinikum Ernst von Bergmann gGmbH, Klinik für Pneumologie, Potsdam
,
H. Seifert
24   Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Klinikum der Universität zu Köln, Köln
,
C. Spies
25   Charitè, Universitätsmedizin Berlin, Klinik für Anästhesiologie m. S. operative Intensivmedizin, Campus Virchow Klinikum und Campus Mitte, Berlin
,
T. Welte
26   Klinik für Pneumologie, Medizinische Hochschule Hannover, Hannover
,
Unter Mitwirkung der folgenden Wissenschaftlichen Fachgesellschaften und Institutionen: Deutsche Gesellschaft für Chirurgie, Deutsche Gesellschaft für Innere Medizin e. V., Deutsche Gesellschaft für Internistische Intensivmedizin und Notfallmedizin, Deutsche Sepsis-Gesellschaft e. V., und Robert Koch-Institut › Author Affiliations
Further Information

Publication History

Publication Date:
16 January 2018 (online)

Zusammenfassung

Die nosokomiale Pneumonie bleibt eine häufige Komplikation von Krankenhausaufenthalten. Die meisten Daten liegen zur beatmungsassoziierten Pneumonie vor, aber auch auf Normalstationen ist vermehrt mit dieser Erkrankung zu rechnen. Problematisch ist die Zunahme von Infektionen mit multiresistenten Erregern (MRE). Diese erschwert die adäquate Initialtherapie und kann zu unkritischem Einsatz von Breitspektrumantibiotika führen.

Das vorliegende Update der S3-Leitlinie von 2012 wurde von einer interdisziplinären Arbeitsgruppe auf der Basis einer systematischen Literaturrecherche erarbeitet. Die Empfehlungen zu Diagnostik und Therapie wurden nach dem GRADE-System abgefasst. Graduierung und Empfehlungsstärke entsprechen der Methodik der Nationalen Versorgungsleitlinien.

Die Leitlinie besteht aus zwei Teilen. Der allgemeine Teil vermittelt einen aktuellen Überblick zu Epidemiologie, Erregerspektrum und Therapieoptionen der nosokomialen Pneumonie. Handlungsorientierte Empfehlungen zu Diagnostik und Therapie werden im zweiten Teil abgegeben. Neu in diesem Update sind detailliertere Empfehlungen zur bildgebenden Diagnostik, zur Diagnostik nosokomialer Virusinfektionen sowie zur prolongierten Applikation von Antiinfektiva. Die Angaben zur Bedeutung von Risikofaktoren für Infektionen mit MRE und die Empfehlungen zum Einsatz einer antibakteriellen Kombinationstherapie bei derartigen Infektionen wurden angepasst. Strukturierte Deeskalationskonzepte und eine konsequente Begrenzung der Therapiedauer zur Verminderung des Selektionsdrucks werden besonders betont.

Abstract

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.

This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.

This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized.

* Verabschiedet von den Vorständen der beteiligten Fachgesellschaften am 11.9. 2017.


 
  • Literatur

  • 1 Dalhoff K, Abele-Horn M, Andreas S. et al. [Epidemiology, diagnosis and treatment of adult patients with nosocomial pneumonia. S-3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy]. Pneumologie 2012; 66: 707-765
  • 2 Kalil AC, Metersky ML, Klompas M. et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63: e61-e111
  • 3 The Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute. [Prevention of nosocomial ventilator-associated pneumonia]. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 2013; 56: 1578-1590
  • 4 National Clinical Guideline Centre (UK). Pneumonia: Diagnosis and Management of Community- and Hospital-Acquired Pneumonia in Adults. London: 2014
  • 5 Schaberg T, Bauer T, Dalhoff K. et al. [Management of a new influenza A/H1N1 virus pandemic within the hospital. Statement of the German Society of Pneumology]. Pneumologie 2010; 64: 124-129
  • 6 Reinhart K, Brunkhorst FM, Bone HG. et al. Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI)). Ger Med Sci 2010; 28: Doc14
  • 7 www.awmf.org
  • 8 Atkins D, Best D, Briss PA. et al. Grading quality of evidence and strength of recommendations. BMJ 2004; 328: 1490-1494
  • 9 Schünemann HJ, Jaeschke R, Cook DJ. et al. An official ATS statement: grading the quality of evidence and strength of recommendations in ATS guidelines and recommendations. Am J Respir Crit Care Med 2006; 174: 605-614
  • 10 American Thoracic Society. Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416
  • 11 Kollef MH, Shorr A, Tabak YP. et al. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005; 128: 3854-3862
  • 12 Kollef MH, Morrow LE, Baughman RP. et al. Health care-associated pneumonia (HCAP): a critical appraisal to improve identification, management, and outcomes-proceedings of the HCAP Summit. Clin Infect Dis 2008; 46: S296-S334
  • 13 Ewig S, Welte T, Chastre J. et al. Rethinking the concepts of community-acquired and health-care-associated pneumonia. Lancet Infect Dis 2010; 10: 279-287
  • 14 Dalhoff K, Ewig S, Höffken G. et al. Empfehlungen zur Diagnostik, Therapie und Prävention von Pneumonien bei erworbenem Immundefizit. [Recommendations for the diagnosis, therapy and prevention of pneumonia in the immunocompromised host]. Pneumologie 2002; 56: 807-831
  • 15 Maschmeyer G, Beinert T, Buchheidt D. et al. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients: Guidelines of the infectious diseases working party of the German Society of Haematology and Oncology. Eur J Cancer 2009; 45: 2462-2472
  • 16 CDC definitions. 2008 www cdcgov/hcidod/dhqp/nhsnhtml
  • 17 Wang Y, Eldridge N, Metersky ML. et al. National trends in patient safety for four common conditions, 2005-2011. N Engl J Med 2014; 370: 341-351
  • 18 Behnke M, Hansen S, Leistner R. et al. Nosocomial infection and antibiotic use: a second national prevalence study in Germany. Dtsch Arztebl Int 2013; 110: 627-633
  • 19 Deutsche Nationale Punkt-Prävalenzstudie zu nosokomialen Infektionen und Antibiotika-Anwendung. Abschlussbericht. 2011 http://wwwnrz-hygienede/nrz/praevalenzerhebung
  • 20 Gastmeier P, Geffers C. Nosokomiale Infektionen in Deutschland. Dtsch Med Wschr 2008; 133: 1111-1115
  • 21 European Centre for Disease prevention and Control. Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals. Stockholm: 2013
  • 22 Cassini A, Plachouras D, Eckmanns T. et al. Burden of Six Healthcare-Associated Infections on European Population Health: Estimating Incidence-Based Disability-Adjusted Life Years through a Population Prevalence-Based Modelling Study. PLoS medicine 2016; 13: e1002150
  • 23 Magill SS, Edwards JR, Bamberg W. et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014; 370: 1198-1208
  • 24 Melsen WG, Rovers MM, Bonten MJ. Ventilator-associated pneumonia and mortality: a systematic review of observational studies. Crit Care Med 2009; 37: 2709-2718
  • 25 Melsen WG, Rovers MM, Koeman M. et al. Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies. Crit Care Med 2011; 39: 2736-2742
  • 26 Melsen WG, Rovers MM, Groenwold RH. et al. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 2013; 13: 665-671
  • 27 Ibrahim EH, Tracy L, Hill C. et al. The occurrence of ventilator-associated pneumonia in a community hospital: risk factors and clinical outcomes. Chest 2001; 120: 555-561
  • 28 Cook DJ, Walter SD, Cook RJ. et al. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med 1998; 129: 433-444
  • 29 Schumacher M, Wangler M, Wolkewitz M. et al. Attributable mortality due to nosocomial infections. A simple and useful application of multistate models. Methods Inf Med 2007; 46: 595-600
  • 30 Wolkewitz M, Vonberg RP, Grundmann H. et al. Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models. Crit Care 2008; 12: R44
  • 31 Nguile-Makao M, Zahar JR, Français A. et al. Attributable mortality of ventilator-associated pneumonia: respective impact of main characteristics at ICU admission and VAP onset using conditional logistic regression and multi-state models. Intensive Care Med 2010; 36: 781-789
  • 32 Safdar N, Dezfulian C, Collard HR. et al. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 2005; 33: 2184-2193
  • 33 Beyersmann J, Gastmeier P, Grundmann H. et al. Use of multistate models to assess prolongation of intensive care unit stay due to nosocomial infection. Infect Control Hosp Epidemiol 2006; 27: 493-499
  • 34 Eber MR, Laxminarayan R, Perencevich EN. et al. Clinical and economic outcomes attributable to health care-associated sepsis and pneumonia. Arch Intern Med 2010; 170: 347-353
  • 35 Restrepo MI, Anzueto A, Arroliga AC. et al. Economic burden of ventilator-associated pneumonia based on total resource utilization. Infect Control Hosp Epidemiol 2010; 31: 509-515
  • 36 Meersseman W, Lagrou K, Spriet I. et al. Significance of the isolation of Candida species from airway samples in critically ill patients: a prospective, autopsy study. Intensive Care Med 2009; 35: 1526-1531
  • 37 Trouillet JL, Chastre J, Vuagnat A. et al. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med 1998; 157: 531-539
  • 38 Ewig S, Torres A, El-Ebiary M. et al. Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Incidence, risk factors, and association with ventilator-associated pneumonia. Am J Respir Crit Care Med 1999; 159: 188-198
  • 39 Depuydt PO, Vandijck DM, Bekaert MA. et al. Determinants and impact of multidrug antibiotic resistance in pathogens causing ventilator-associated-pneumonia. Crit Care 2008; 12: R142
  • 40 Giantsou E, Liratzopoulos N, Efraimidou E. et al. Both early-onset and late-onset ventilator-associated pneumonia are caused mainly by potentially multiresistant bacteria. Intensive Care Med 2005; 31: 1488-1494
  • 41 Martin-Loeches I, Deja M, Koulenti D. et al. Potentially resistant microorganisms in intubated patients with hospital-acquired pneumonia: the interaction of ecology, shock and risk factors. Intensive Care Med 2013; 39: 672-681
  • 42 Verhamme KM, De Coster W, De Roo L. et al. Pathogens in early-onset and late-onset intensive care unit-acquired pneumonia. Infect Control Hosp Epidemiol 2007; 28: 389-397
  • 43 Leroy O, Giradie P, Yazdanpanah Y. et al. Hospital-acquired pneumonia: microbiological data and potential adequacy of antimicrobial regimens. Eur Respir J 2002; 20: 432-439
  • 44 Leroy O, d'Escrivan T, Devos P. et al. Hospital-acquired pneumonia in critically ill patients: factors associated with episodes due to imipenem-resistant organisms. Infection 2005; 33: 129-135
  • 45 Seligman R, Ramos-Lima LF, Oliveira Vdo A. et al. Risk factors for infection with multidrug-resistant bacteria in non-ventilated patients with hospital-acquired pneumonia. J Bras Pneumol 2013; 39: 339-348
  • 46 Restrepo MI, Peterson J, Fernandez JF. et al. Comparison of the bacterial etiology of early-onset and late-onset ventilator-associated pneumonia in subjects enrolled in 2 large clinical studies. Respir Care 2013; 58: 1220-1225
  • 47 Ibrahim EH, Ward S, Sherman G. et al. A comparative analysis of patients with early-onset vs late-onset nosocomial pneumonia in the ICU setting. Chest 2000; 117: 1434-1442
  • 48 Parker CM, Kutsogiannis J, Muscedere J. et al. Ventilator-associated pneumonia caused by multidrug-resistant organisms or Pseudomonas aeruginosa: prevalence, incidence, risk factors, and outcomes. J Crit Care 2008; 23: 18-26
  • 49 Rangel EL, Butler KL, Johannigman JA. et al. Risk factors for relapse of ventilator-associated pneumonia in trauma patients. J Trauma 2009; 67: 91-95
  • 50 Gastmeier P, Sohr D, Geffers C. et al. Early- and late-onset pneumonia: is this still a useful classification?. Antimicrob Agents Chemother 2009; 53: 2714-2718
  • 51 Tilahun B, Faust AC, McCorstin P. et al. Nasal colonization and lower respiratory tract infections with methicillin-resistant Staphylococcus aureus. Am J Crit Care 2015; 24: 8-12
  • 52 Dangerfield B, Chung A, Webb B. et al. Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother 2014; 58: 859-864
  • 53 Sarikonda KV, Micek ST, Doherty JA. et al. Methicillin-resistant Staphylococcus aureus nasal colonization is a poor predictor of intensive care unit-acquired methicillin-resistant Staphylococcus aureus infections requiring antibiotic treatment. Crit Care Med 2010; 38: 1991-1995
  • 54 Ziakas PD, Anagnostou T, Mylonakis E. The prevalence and significance of methicillin-resistant Staphylococcus aureus colonization at admission in the general ICU Setting: a meta-analysis of published studies. Crit Care Med 2014; 42: 433-444
  • 55 Biehl LM, Schmidt-Hieber M, Liss B. et al. Colonization and infection with extended spectrum beta-lactamase producing Enterobacteriaceae in high-risk patients - Review of the literature from a clinical perspective. Crit Rev Microbiol 2016; 42: 1-16
  • 56 Commission recommendation for hospital hygiene and infection prevention (KRINKO) at the Robert Koch Institute (RKI). [Hygiene measures for infection or colonization with multidrug-resistant gram-negative bacilli. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 2012; 55: 1311-1354
  • 57 Lübbert C, Straube L, Stein C. et al. Colonization with extended-spectrum beta-lactamase-producing and carbapenemase-producing Enterobacteriaceae in international travelers returning to Germany. Int J Med Microbiol 2015; 305: 148-156
  • 58 Heudorf U, Albert-Braun S, Hunfeld KP. et al. Multidrug-resistant organisms in refugees: prevalences and impact on infection control in hospitals. GMS Hyg Infect Control 2016; 11: Doc16
  • 59 Kollef MH, Chastre J, Fagon JY. et al. Global prospective epidemiologic and surveillance study of ventilator-associated pneumonia due to Pseudomonas aeruginosa. Crit Care Med 2014; 42: 2178-2187
  • 60 Montero M, Sala M, Riu M. et al. Risk factors for multidrug-resistant Pseudomonas aeruginosa acquisition. Impact of antibiotic use in a double case-control study. Eur J Clin Microbiol Infect Dis 2010; 29: 335-339
  • 61 Koulenti D, Blot S, Dulhunty JM. et al. COPD patients with ventilator-associated pneumonia: implications for management. Eur J Clin Microbiol Infect Dis 2015; 34: 2403-2411
  • 62 http://www.p-e-g.org/ag_resistenz/main.htm
  • 63 Hoban DJ, Biedenbach DJ, Mutnick AH. et al. Pathogen of occurrence and susceptibility patterns associated with pneumonia in hospitalized patients in North America: results of the SENTRY Antimicrobial Surveillance Study (2000). Diagn Microbiol Infect Dis 2003; 45: 279-285
  • 64 Kohlenberg A, Schwab F, Behnke M. et al. Pneumonia associated with invasive and noninvasive ventilation: an analysis of the German nosocomial infection surveillance system database. Intensive Care Med 2010; 36: 971-978
  • 65 Jones RN. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clin Infect Dis 2010; 51: S81-S87
  • 66 Sopena N, Sabrià M. Multicenter study of hospital-acquired pneumonia in non-ICU patients. Chest 2005; 127: 213-219
  • 67 Koulenti D, Lisboa T, Brun-Buisson C. et al. Spectrum of practice in the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation in European intensive care units. Crit Care Med 2009; 37: 2360-2368
  • 68 Pirracchio R, Mateo J, Raskine L. et al. Can bacteriological upper airway samples obtained at intensive care unit admission guide empiric antibiotherapy for ventilator-associated pneumonia?. Crit Care Med 2009; 37: 2559-2563
  • 69 Gacouin A, Barbarot N, Camus C. et al. Late-onset ventilator-associated pneumonia in nontrauma intensive care unit patients. Anesth Analg 2009; 109: 1584-1590
  • 70 Leone M, Garcin F, Bouvenot J. et al. Ventilator-associated pneumonia: breaking the vicious circle of antibiotic overuse. Crit Care Med 2007; 35: 379-385
  • 71 Awad SS, Rodriguez AH, Chuang YC. et al. A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia. Clin Infect Dis 2014; 59: 51-61
  • 72 Chastre J, Wunderink R, Prokocimer P. et al. Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Crit Care Med 2008; 36: 1089-1096
  • 73 Kollef MH, Morrow LE, Niederman MS. et al. Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Chest 2006; 129: 1210-1218
  • 74 Chastre J, Wolff M, Fagon JY. et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290: 2588-2598
  • 75 Combes A, Figliolini C, Trouillet JL. et al. Incidence and outcome of polymicrobial ventilator-associated pneumonia. Chest 2002; 121: 1618-1623
  • 76 Hayon J, Figliolini C, Combes A. et al. Role of serial routine microbiologic culture results in the initial management of ventilator-associated pneumonia. Am J Respir Crit Care Med 2002; 165: 41-46
  • 77 Fowler RA, Flavin KE, Barr J. et al. Variability in antibiotic prescribing patterns and outcomes in patients with clinically suspected ventilator-associated pneumonia. Chest 2003; 123: 835-844
  • 78 Epidemiologisches Bulletin. https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2016/Ausgaben/02_16.pdf?__blob=publicationFile
  • 79 Lübbert C, Lippmann N, Busch T. et al. Long-term carriage of Klebsiella pneumoniae carbapenemase-2-producing K pneumoniae after a large single-center outbreak in Germany. Am J Infect Control 2014; 42: 376-380
  • 80 Heyland DK, Dodek P, Muscedere J. et al. Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med 2008; 36: 737-744
  • 81 Garnacho-Montero J, Amaya-Villar R, Ortiz-Leyba C. et al. Isolation of Aspergillus spp. from the respiratory tract in critically ill patients: risk factors, clinical presentation and outcome. Crit Care 2005; 9: R191-199
  • 82 Alshabani K, Haq A, Miyakawa R. et al. Invasive pulmonary aspergillosis in patients with influenza infection: report of two cases and systematic review of the literature. Expert Rev Respir Med 2015; 9: 89-96
  • 83 Luyt CE, Combes A, Deback C. et al. Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation. Am J Respir Crit Care Med 2007; 175: 935-942
  • 84 Gooskens J, Jonges M, Claas EC. et al. Morbidity and mortality associated with nosocomial transmission of oseltamivir-resistant influenza A(H1N1) virus. JAMA 2009; 301: 1042-1046
  • 85 Chiche L, Forel JM, Roch A. et al. Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients. Crit Care Med 2009; 37: 1850-1857
  • 86 Antimicrobial resistance surveillance in Europe. 2015 http://ecdc.europa.eu/en/publications/Publications/antimicrobial-resistance-europe-2015.pdf
  • 87 Yahav D, Paul M, Fraser A. et al. Efficacy and safety of cefepime: a systematic review and meta-analysis. Lancet Infect Dis 2007; 7: 338-348
  • 88 Kim PW, Wu YT, Cooper C. et al. Meta-analysis of a possible signal of increased mortality associated with cefepime use. Clin Infect Dis 2010; 51: 381-389
  • 89 Badia JR, Soy D, Adrover M. et al. Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive care unit (ICU) patients. J Antimicrob Chemother 2004; 54: 508-514
  • 90 Giamarellos-Bourboulis EJ, Pechère JC, Routsi C. et al. Effect of clarithromycin in patients with sepsis and ventilator-associated pneumonia. Clin Infect Dis 2008; 46: 1157-1164
  • 91 González C, Rubio M, Romero-Vivas J. et al. Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms. Clin Infect Dis 1999; 29: 1171-1177
  • 92 The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 7.1 2017. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_7.1_Breakpoint_Tables.xls
  • 93 Plachouras D, Karvanen M, Friberg LE. et al. Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrob Agents Chemother 2009; 53: 3430-3436
  • 94 Garonzik SM, Li J, Thamlikitkul V. et al. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother 2011; 55: 3284-3294
  • 95 Reina R, Estenssoro E, Sáenz G. et al. Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a prospective cohort study. Intensive Care Med 2005; 31: 1058-1065
  • 96 Falagas ME, Kasiakou SK, Kofteridis DP. et al. Effectiveness and nephrotoxicity of intravenous colistin for treatment of patients with infections due to polymyxin-only-susceptible (POS) gram-negative bacteria. Eur J Clin Microbiol Infect Dis 2006; 25: 596-599
  • 97 Furtado GH, d'Azevedo PA, Santos AF. et al. Intravenous polymyxin B for the treatment of nosocomial pneumonia caused by multidrug-resistant Pseudomonas aeruginosa. Int J Antimicrob Agents 2007; 30: 315-319
  • 98 Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 2006; 10: R27
  • 99 Dickstein Y, Leibovici L, Yahav D. et al. Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol. BMJ open 2016; 6: e009956
  • 100 Lenhard JR, Nation RL, Tsuji BT. Synergistic combinations of polymyxins. Int J Antimicrob Agents 2016; 48: 607-613
  • 101 Linden PK, Paterson DL. Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clin Infect Dis 2006; 43: S89-S94
  • 102 Michalopoulos A, Fotakis D, Virtzili S. et al. Aerosolized colistin as adjunctive treatment of ventilator-associated pneumonia due to multidrug-resistant Gram-negative bacteria: a prospective study. Respir Med 2008; 102: 407-412
  • 103 Lu Q, Luo R, Bodin L. et al. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology 2012; 117: 1335-1347
  • 104 Falagas ME, Kastoris AC, Kapaskelis AM. et al. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis 2010; 10: 43-50
  • 105 Pfausler B, Spiss H, Dittrich P. et al. Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis. J Antimicrob Chemother 2004; 53: 848-852
  • 106 Matzi V, Lindenmann J, Porubsky C. et al. Extracellular concentrations of fosfomycin in lung tissue of septic patients. J Antimicrob Chemother 2010; 65: 995-998
  • 107 del Río A, Gasch O, Moreno A. et al. Efficacy and safety of fosfomycin plus imipenem as rescue therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial. Clin Infect Dis 2014; 59: 1105-1112
  • 108 Freire AT, Melnyk V, Kim MJ. et al. Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis 2010; 68: 140-151
  • 109 de With K, Allerberger F, Amann S. et al. Strategies to enhance rational use of antibiotics in hospital: a guideline by the German Society for Infectious Diseases. Infection 2016; 44: 395-439
  • 110 Davey P, Marwick CA, Scott CL. et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2017; 2: CD003543
  • 111 Ego A, Preiser JC, Vincent JL. Impact of diagnostic criteria on the incidence of ventilator-associated pneumonia. Chest 2015; 147: 347-355
  • 112 Johanson Jr. WG, Pierce AK, Sanford JP. et al. Nosocomial respiratory infections with gram-negative bacilli. The significance of colonization of the respiratory tract. Ann Intern Med 1972; 77: 701-706
  • 113 Fábregas N, Ewig S, Torres A. et al. Clinical diagnosis of ventilator associated pneumonia revised: comparative validation using immediate post-mortem lung biopsies. Thorax 1999; 54: 867-873
  • 114 Fagon JY, Chastre J, Hance AJ. et al. Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients. Chest 1993; 103: 547-553
  • 115 Wunderink RG, Woldenberg LS, Zeiss J. et al. The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia. Chest 1992; 101: 458-463
  • 116 Russell CD, Koch O, Laurenson IF. et al. Diagnosis and features of hospital-acquired pneumonia: a retrospective cohort study. J Hosp Infect 2016; 92: 273-279
  • 117 Burton LA, Price R, Barr KE. et al. Hospital-acquired pneumonia incidence and diagnosis in older patients. Age Ageing 2016; 45: 171-174
  • 118 Helling TS, Van Way C, Krantz S. et al. The value of clinical judgment in the diagnosis of nosocomial pneumonia. Am J Surg 1996; 171: 570-575
  • 119 Graat ME, Choi G, Wolthuis EK. et al. The clinical value of daily routine chest radiographs in a mixed medical-surgical intensive care unit is low. Crit Care 2006; 10: R11
  • 120 Winer-Muram HT, Rubin SA, Ellis JV. et al. Pneumonia and ARDS in patients receiving mechanical ventilation: diagnostic accuracy of chest radiography. Radiology 1993; 188: 479-485
  • 121 Butler KL, Sinclair KE, Henderson VJ. et al. The chest radiograph in critically ill surgical patients is inaccurate in predicting ventilator-associated pneumonia. Am Surg 1999; 65: 805-809
  • 122 Esayag Y, Nikitin I, Bar-Ziv J. et al. Diagnostic value of chest radiographs in bedridden patients suspected of having pneumonia. Am J Med 2010; 123: 88 .e1-5
  • 123 Miyashita N, Kawai Y, Tanaka T. et al. Detection failure rate of chest radiography for the identification of nursing and healthcare-associated pneumonia. J Infect Chemother 2015; 21: 492-496
  • 124 Beydon L, Saada M, Liu N. et al. Can portable chest x-ray examination accurately diagnose lung consolidation after major abdominal surgery? A comparison with computed tomography scan. Chest 1992; 102: 1697-1703
  • 125 Schäfer-Prokop C. Aufnahmetechnik der Bettlungenaufnahme. In: Radiologische Diagnostik in der Intensivmedizin. Stuttgart: Thieme; 2009: 15-19
  • 126 Agarwal P, Wielandner A. [Nosocomial pneumonia from a radiological perspective]. Radiologe 2017; 57: 13-21
  • 127 Berlet T, Etter R, Fehr T. et al. Sonographic patterns of lung consolidation in mechanically ventilated patients with and without ventilator-associated pneumonia: a prospective cohort study. J Crit Care 2015; 30: 327-333
  • 128 Mongodi S, Via G, Girard M. et al. Lung Ultrasound for Early Diagnosis of Ventilator-Associated Pneumonia. Chest 2016; 149: 969-980
  • 129 Bourcier JE, Paquet J, Seinger M. et al. Performance comparison of lung ultrasound and chest x-ray for the diagnosis of pneumonia in the ED. Am J Emerg Med 2014; 32: 115-118
  • 130 Sartori S, Tombesi P. Emerging roles for transthoracic ultrasonography in pulmonary diseases. World J Radiol 2010; 2: 203-214
  • 131 Claessens YE, Debray MP, Tubach F. et al. Early Chest Computed Tomography Scan to Assist Diagnosis and Guide Treatment Decision for Suspected Community-acquired Pneumonia. Am J Respir Crit Care Med 2015; 192: 974-982
  • 132 Fartoukh M, Maitre B, Honoré S. et al. Diagnosing pneumonia during mechanical ventilation: the clinical pulmonary infection score revisited. Am J Respir Crit Care Med 2003; 168: 173-179
  • 133 Jung B, Embriaco N, Roux F. et al. Microbiogical data, but not procalcitonin improve the accuracy of the clinical pulmonary infection score. Intensive Care Med 2010; 36: 790-798
  • 134 Shan J, Chen HL, Zhu JH. Diagnostic accuracy of clinical pulmonary infection score for ventilator-associated pneumonia: a meta-analysis. Respir Care 2011; 56: 1087-1094
  • 135 Singer M, Deutschman CS, Seymour CW. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 801-810
  • 136 Seymour CW, Liu VX, Iwashyna TJ. et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 762-774
  • 137 Combes A, Luyt CE, Fagon JY. et al. Early predictors for infection recurrence and death in patients with ventilator-associated pneumonia. Crit Care Med 2007; 35: 146-154
  • 138 Zhou XY, Ben SQ, Chen HL. et al. A comparison of APACHE II and CPIS scores for the prediction of 30-day mortality in patients with ventilator-associated pneumonia. IJID 2015; 30: 144-147
  • 139 Larsson J, Itenov TS, Bestle MH. Risk prediction models for mortality in patients with ventilator-associated pneumonia: A systematic review and meta-analysis. J Crit Care 2016; 37: 112-118
  • 140 Lisboa T, Diaz E, Sa-Borges M. et al. The ventilator-associated pneumonia PIRO score: a tool for predicting ICU mortality and health-care resources use in ventilator-associated pneumonia. Chest 2008; 134: 1208-1216
  • 141 Furtado GH, Wiskirchen DE, Kuti JL. et al. Performance of the PIRO score for predicting mortality in patients with ventilator-associated pneumonia. Anaesth Intensive Care 2012; 40: 285-291
  • 142 Duflo F, Debon R, Monneret G. et al. Alveolar and serum procalcitonin: diagnostic and prognostic value in ventilator-associated pneumonia. Anesthesiology 2002; 96: 74-79
  • 143 Ramirez P, Garcia MA, Ferrer M. et al. Sequential measurements of procalcitonin levels in diagnosing ventilator-associated pneumonia. Eur Respir J 2008; 31: 356-362
  • 144 Luyt CE, Combes A, Reynaud C. et al. Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia. Intensive Care Med 2008; 34: 1434-1440
  • 145 Linssen CF, Bekers O, Drent M. et al. C-reactive protein and procalcitonin concentrations in bronchoalveolar lavage fluid as a predictor of ventilator-associated pneumonia. Ann Clin Biochem 2008; 45: 293-298
  • 146 Oppert M, Reinicke A, Müller C. et al. Elevations in procalcitonin but not C-reactive protein are associated with pneumonia after cardiopulmonary resuscitation. Resuscitation 2002; 53: 167-170
  • 147 Gibot S, Cravoisy A, Levy B. et al. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med 2004; 350: 451-458
  • 148 Determann RM, Millo JL, Gibot S. et al. Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia. Intensive Care Med 2005; 31: 1495-1500
  • 149 Horonenko G, Hoyt JC, Robbins RA. et al. Soluble triggering receptor expressed on myeloid cell-1 is increased in patients with ventilator-associated pneumonia: a preliminary report. Chest 2007; 132: 58-63
  • 150 Huh JW, Lim CM, Koh Y. et al. Diagnostic utility of the soluble triggering receptor expressed on myeloid cells-1 in bronchoalveolar lavage fluid from patients with bilateral lung infiltrates. Crit Care 2008; 12: R6
  • 151 Anand NJ, Zuick S, Klesney-Tait J. et al. Diagnostic implications of soluble triggering receptor expressed on myeloid cells-1 in BAL fluid of patients with pulmonary infiltrates in the ICU. Chest 2009; 135: 641-647
  • 152 Oudhuis GJ, Beuving J, Bergmans D. et al. Soluble Triggering Receptor Expressed on Myeloid cells-1 in bronchoalveolar lavage fluid is not predictive for ventilator-associated pneumonia. Intensive Care Med 2009; 35: 1265-1270
  • 153 Morris CA, Kefala K, Wilkinson TS. et al. Diagnostic importance of pulmonary interleukin-1beta and interleukin-8 in ventilator-associated pneumonia. Thorax 2010; 65: 201-207
  • 154 Uzzan B, Cohen R, Nicolas P. et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med 2006; 34: 1996-2003
  • 155 Nakamura A, Wada H, Ikejiri M. et al. Efficacy of procalcitonin in the early diagnosis of bacterial infections in a critical care unit. Shock 2009; 31: 586-591
  • 156 Casserly B, Phillips GS, Schorr C. et al. Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med 2015; 43: 567-573
  • 157 Shankar-Hari M, Phillips GS, Levy ML. et al. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 775-787
  • 158 Gu WJ, Zhang Z, Bakker J. Early lactate clearance-guided therapy in patients with sepsis: a meta-analysis with trial sequential analysis of randomized controlled trials. Intensive Care Med 2015; 41: 1862-1863
  • 159 Luna CM, Videla A, Mattera J. et al. Blood cultures have limited value in predicting severity of illness and as a diagnostic tool in ventilator-associated pneumonia. Chest 1999; 116: 1075-1084
  • 160 Park DR. The microbiology of ventilator-associated pneumonia. Respir Care 2005; 50: 742-763
  • 161 Shimada T, Noguchi Y, Jackson JL. et al. Systematic review and metaanalysis: urinary antigen tests for Legionellosis. Chest 2009; 136: 1576-1585
  • 162 Olsen CW, Elverdal P, Jørgensen CS. et al. Comparison of the sensitivity of the Legionella urinary antigen EIA kits from Binax and Biotest with urine from patients with infections caused by less common serogroups and subgroups of Legionella. Eur J Clin Microbiol Infect Dis 2009; 28: 817-820
  • 163 Gottesman T, Yossepowitch O, Lerner E. et al. The accuracy of Gram stain of respiratory specimens in excluding Staphylococcus aureus in ventilator-associated pneumonia. J Crit Care 2014; 29: 739-742
  • 164 OʼHoro JC, Thompson D, Safdar N. Is the gram stain useful in the microbiologic diagnosis of VAP? A meta-analysis. Clin Infect Dis 2012; 55: 551-561
  • 165 Liu C, Du Z, Zhou Q. et al. Microscopic examination of intracellular organisms in bronchoalveolar lavage fluid for the diagnosis of ventilator-associated pneumonia: a prospective multi-center study. Chin Med J 2014; 127: 1808-1813
  • 166 Baselski VS, el-Torky M, Coalson JJ. et al. The standardization of criteria for processing and interpreting laboratory specimens in patients with suspected ventilator-associated pneumonia. Chest 1992; 102: 571S-579S
  • 167 Souweine B, Veber B, Bedos JP. et al. Diagnostic accuracy of protected specimen brush and bronchoalveolar lavage in nosocomial pneumonia: impact of previous antimicrobial treatments. Crit Care Med 1998; 26: 236-244
  • 168 The Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630
  • 169 Berton DC, Kalil AC, Teixeira PJ. Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated pneumonia. Cochrane Database Syst Rev 2012; 1: CD006482
  • 170 Berton DC, Kalil AC, Teixeira PJ. Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated pneumonia. Cochrane Database Syst Rev 2014; 10: CD006482
  • 171 Huttner A, Emonet S, Harbarth S. et al. Polymerase-chain reaction/electrospray ionization-mass spectrometry for the detection of bacteria and fungi in bronchoalveolar lavage fluids: a prospective observational study. Clin Microbiol Infect 2014; 20: O1059-1066
  • 172 Vincent JL, Brealey D, Libert N. et al. Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections. Crit Care Med 2015; 43: 2283-2291
  • 173 Kunze N, Moerer O, Steinmetz N. et al. Point-of-care multiplex PCR promises short turnaround times for microbial testing in hospital-acquired pneumonia--an observational pilot study in critical ill patients. Ann Clin Microbiol Antimicrob 2015; 14: 33
  • 174 Douglas IS, Price CS, Overdier KH. et al. Rapid automated microscopy for microbiological surveillance of ventilator-associated pneumonia. Am J Respir Crit Care Med 2015; 191: 566-573
  • 175 Ruiz M, Torres A, Ewig S. et al. Noninvasive versus invasive microbial investigation in ventilator-associated pneumonia: evaluation of outcome. Am J Respir Crit Care Med 2000; 162: 119-125
  • 176 Sanchez-Nieto JM, Torres A, Garcia-Cordoba F. et al. Impact of invasive and noninvasive quantitative culture sampling on outcome of ventilator-associated pneumonia: a pilot study. Am J Respir Crit Care Med 1998; 157: 371-376
  • 177 Solé-Violán J, Rodríguez de Castro F, Rey A. et al. Usefulness of microscopic examination of intracellular organisms in lavage fluid in ventilator-associated pneumonia. Chest 1994; 106: 889-894
  • 178 Papazian L, Thomas P, Garbe L. et al. Bronchoscopic or blind sampling techniques for the diagnosis of ventilator-associated pneumonia. Am J Respir Crit Care Med 1995; 152: 1982-1991
  • 179 Marquette CH, Copin MC, Wallet F. et al. Diagnostic tests for pneumonia in ventilated patients: prospective evaluation of diagnostic accuracy using histology as a diagnostic gold standard. Am J Respir Crit Care Med 1995; 151: 1878-1888
  • 180 Fagon JY, Chastre J, Wolff M. et al. Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. A randomized trial. Ann Intern Med 2000; 132: 621-630
  • 181 Fàbregas N, Torres A, El-Ebiary M. et al. Histopathologic and microbiologic aspects of ventilator-associated pneumonia. Anesthesiology 1996; 84: 760-771
  • 182 Kirtland SH, Corley DE, Winterbauer RH. et al. The diagnosis of ventilator-associated pneumonia: a comparison of histologic, microbiologic, and clinical criteria. Chest 1997; 112: 445-457
  • 183 Torres A, Fàbregas N, Ewig S. et al. Sampling methods for ventilator-associated pneumonia: validation using different histologic and microbiological references. Crit Care Med 2000; 28: 2799-2804
  • 184 Wermert D, Marquette CH, Copin MC. et al. Influence of pulmonary bacteriology and histology on the yield of diagnostic procedures in ventilator-acquired pneumonia. Am J Respir Crit Care Med 1998; 158: 139-147
  • 185 Timsit JF, Misset B, Azoulay E. et al. Usefulness of airway visualization in the diagnosis of nosocomial pneumonia in ventilated patients. Chest 1996; 110: 172-179
  • 186 Bauer TT, Torres A, Ewig S. et al. Effects of bronchoalveolar lavage volume on arterial oxygenation in mechanically ventilated patients with pneumonia. Intensive Care Med 2001; 27: 384-393
  • 187 Kumar A, Roberts D, Wood KE. et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34: 1589-1596
  • 188 Levy H. Comparison of Ballard catheter bronchoalveolar lavage with bronchoscopic bronchoalveolar lavage. Chest 1994; 106: 1753-1756
  • 189 Kollef MH, Bock KR, Richards RD. et al. The safety and diagnostic accuracy of minibronchoalveolar lavage in patients with suspected ventilator-associated pneumonia. Ann Intern Med 1995; 122: 743-748
  • 190 de Lassence A, Joly-Guillou ML, Martin-Lefevre L. et al. Accuracy of delayed cultures of plugged telescoping catheter samples for diagnosing bacterial pneumonia. Crit Care Med 2001; 29: 1311-1317
  • 191 de Lassence A, Joly-Guillou ML, Salah A. et al. Accuracy of delayed (24 hours) processing of bronchoalveolar lavage for diagnosing bacterial pneumonia. Crit Care Med 2004; 32: 680-685
  • 192 Kneidinger N, Warszawska J, Schenk P. et al. Storage of bronchoalveolar lavage fluid and accuracy of microbiologic diagnostics in the ICU: a prospective observational study. Crit Care 2013; 17: R135
  • 193 Meersseman W, Lagrou K, Maertens J. et al. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med 2008; 177: 27-34
  • 194 Sulahian A, Touratier S, Ribaud P. False positive test for aspergillus antigenemia related to concomitant administration of piperacillin and tazobactam. N Engl J Med 2003; 349: 2366-2367
  • 195 Mattei D, Rapezzi D, Mordini N. et al. False-positive Aspergillus galactomannan enzyme-linked immunosorbent assay results in vivo during amoxicillin-clavulanic acid treatment. J Clin Microbiol 2004; 42: 5362-5363
  • 196 Girmenia C, Santilli S, Ballarò D. et al. Enteral nutrition may cause false-positive results of Aspergillus galactomannan assay in absence of gastrointestinal diseases. Mycoses 2011; 54: e883-884
  • 197 Racil Z, Kocmanova I, Lengerova M. et al. Intravenous PLASMA-LYTE as a major cause of false-positive results of platelia Aspergillus test for galactomannan detection in serum. J Clin Microbiol 2007; 45: 3141-3142
  • 198 Senn L, Robinson JO, Schmidt S. et al. 1,3-Beta-D-glucan antigenemia for early diagnosis of invasive fungal infections in neutropenic patients with acute leukemia. Clin Infect Dis 2008; 46: 878-885
  • 199 Denning DW, Cadranel J, Beigelman-Aubry C. et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J 2016; 47: 45-68
  • 200 Springer J, Lackner M, Nachbaur D. et al. Prospective multicentre PCR-based Aspergillus DNA screening in high-risk patients with and without primary antifungal mould prophylaxis. Clin Microbiol Infect 2016; 22: 80-86
  • 201 Aguado JM, Vázquez L, Fernández-Ruiz M. et al. Serum galactomannan versus a combination of galactomannan and polymerase chain reaction-based Aspergillus DNA detection for early therapy of invasive aspergillosis in high-risk hematological patients: a randomized controlled trial. Clin Infect Dis 2015; 60: 405-414
  • 202 Hong HL, Hong SB, Ko GB. et al. Viral infection is not uncommon in adult patients with severe hospital-acquired pneumonia. PloS one 2014; 9: e95865
  • 203 van Someren Gréve F, Ong DS, Cremer OL. et al. Clinical practice of respiratory virus diagnostics in critically ill patients with a suspected pneumonia: A prospective observational study. J Clin Virol 2016; 83: 37-42
  • 204 Liao RS, Appelgate DM, Pelz RK. An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility for the elderly in Oregon. J Clin Virol 2012; 53: 171-173
  • 205 Giannella M, Rodríguez-Sánchez B, Roa PL. et al. Should lower respiratory tract secretions from intensive care patients be systematically screened for influenza virus during the influenza season?. Crit Care 2012; 16: R104
  • 206 Hagel S, Ludewig K, Moeser A. et al. Characteristics and management of patients with influenza in a German hospital during the 2014/2015 influenza season. Infection 2016; 44: 667-672
  • 207 Huzly D, Kurz S, Ebner W. et al. Characterisation of nosocomial and community-acquired influenza in a large university hospital during two consecutive influenza seasons. J Clin Virol 2015; 73: 47-51
  • 208 Templeton KE, Scheltinga SA, van den Eeden WC. et al. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin Infect Dis 2005; 41: 345-351
  • 209 Chartrand C, Tremblay N, Renaud C. et al. Diagnostic Accuracy of Rapid Antigen Detection Tests for Respiratory Syncytial Virus Infection: Systematic Review and Meta-analysis. J Clin Microbiol 2015; 53: 3738-3749
  • 210 Drexler JF, Helmer A, Kirberg H. et al. Poor clinical sensitivity of rapid antigen test for influenza A pandemic (H1N1) 2009 virus. Emerg Infect Dis 2009; 15: 1662-1664
  • 211 Chen JH, Lam HY, Yip CC. et al. Clinical Evaluation of the New High-Throughput Luminex NxTAG Respiratory Pathogen Panel Assay for Multiplex Respiratory Pathogen Detection. J Clin Microbiol 2016; 54: 1820-1825
  • 212 Kang CI, Kim SH, Kim HB. et al. Pseudomonas aeruginosa bacteremia: risk factors for mortality and influence of delayed receipt of effective antimicrobial therapy on clinical outcome. Clin Infect Dis 2003; 37: 745-751
  • 213 Iregui M, Ward S, Sherman G. et al. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 2002; 122: 262-268
  • 214 Yakovlev SV, Stratchounski LS, Woods GL. et al. Ertapenem versus cefepime for initial empirical treatment of pneumonia acquired in skilled-care facilities or in hospitals outside the intensive care unit. Eur J Clin Microbiol Infect Dis 2006; 25: 633-641
  • 215 Höffken G, Barth J, Rubinstein E. et al. A randomized study of sequential intravenous/oral moxifloxacin in comparison to sequential intravenous ceftriaxone/oral cefuroxime axetil in patients with hospital-acquired pneumonia. Infection 2007; 35: 414-420
  • 216 Aarts MA, Hancock JN, Heyland D. et al. Empiric antibiotic therapy for suspected ventilator-associated pneumonia: a systematic review and meta-analysis of randomized trials. Crit Care Med 2008; 36: 108-117
  • 217 Sieger B, Berman SJ, Geckler RW. et al. Empiric treatment of hospital-acquired lower respiratory tract infections with meropenem or ceftazidime with tobramycin: a randomized study. Meropenem Lower Respiratory Infection Group. Crit Care Med 1997; 25: 1663-1670
  • 218 Kollef MH, Chastre J, Clavel M. et al. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care 2012; 16: R218
  • 219 Fink MP, Snydman DR, Niederman MS. et al. Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group. Antimicrob Agents Chemother 1994; 38: 547-557
  • 220 Croce MA, Fabian TC, Stewart RM. et al. Empiric monotherapy versus combination therapy of nosocomial pneumonia in trauma patients. J Trauma 1993; 35: 303-309
  • 221 Brun-Buisson C, Sollet JP, Schweich H. et al. Treatment of ventilator-associated pneumonia with piperacillin-tazobactam/amikacin versus ceftazidime/amikacin: a multicenter, randomized controlled trial. VAP Study Group. Clin Infect Dis 1998; 26: 346-354
  • 222 Florescu DF, Qiu F, McCartan MA. et al. What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression. Clin Infect Dis 2012; 54: 670-680
  • 223 Alvarez-Lerma F, Insausti-Ordeñana J, Jordá-Marcos R. et al. Efficacy and tolerability of piperacillin/tazobactam versus ceftazidime in association with amikacin for treating nosocomial pneumonia in intensive care patients: a prospective randomized multicenter trial. Intensive Care Med 2001; 27: 493-502
  • 224 Cometta A, Baumgartner JD, Lew D. et al. Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients. Antimicrob Agents Chemother 1994; 38: 1309-1313
  • 225 Rubinstein E, Lode H, Grassi C. Ceftazidime monotherapy vs. ceftriaxone/tobramycin for serious hospital-acquired gram-negative infections. Antibiotic Study Group. Clin Infect Dis 1995; 20: 1217-1228
  • 226 Chaudhary M, Shrivastava SM, Varughese L. et al. Efficacy and safety evaluation of fixed dose combination of cefepime and amikacin in comparison with cefepime alone in treatment of nosocomial pneumonia patients. Curr Clin Pharmacol 2008; 3: 118-122
  • 227 Garnacho-Montero J, Sa-Borges M, Sole-Violan J. et al. Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: an observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med 2007; 35: 1888-1895
  • 228 Peña C, Suarez C, Ocampo-Sosa A. et al. Effect of adequate single-drug vs combination antimicrobial therapy on mortality in Pseudomonas aeruginosa bloodstream infections: a post Hoc analysis of a prospective cohort. Clin Infect Dis 2013; 57: 208-216
  • 229 Rubinstein E, Lalani T, Corey GR. et al. Telavancin versus vancomycin for hospital-acquired pneumonia due to gram-positive pathogens. Clin Infect Dis 2011; 52: 31-40
  • 230 Corey GR, Kollef MH, Shorr AF. et al. Telavancin for hospital-acquired pneumonia: clinical response and 28-day survival. Antimicrob Agents Chemother 2014; 58: 2030-2037
  • 231 Singh N, Rogers P, Atwood CW. et al. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000; 162: 505-511
  • 232 Dennesen PJ, van der Ven AJ, Kessels AG. et al. Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia. Am J Respir Crit Care Med 2001; 163: 1371-1375
  • 233 Seligman R, Meisner M, Lisboa TC. et al. Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia. Crit Care 2006; 10: R125
  • 234 Hillas G, Vassilakopoulos T, Plantza P. et al. C-reactive protein and procalcitonin as predictors of survival and septic shock in ventilator-associated pneumonia. Eur Respir J 2010; 35: 805-811
  • 235 Luyt CE, Guérin V, Combes A. et al. Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 48-53
  • 236 Nobre V, Harbarth S, Graf JD. et al. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 2008; 177: 498-505
  • 237 Stolz D, Smyrnios N, Eggimann P. et al. Procalcitonin for reduced antibiotic exposure in Ventilator Associated Pneumonia - a randomized study. Eur Respir J 2009; 34: 1364-1375
  • 238 Lisboa T, Seligman R, Diaz E. et al. C-reactive protein correlates with bacterial load and appropriate antibiotic therapy in suspected ventilator-associated pneumonia. Crit Care Med 2008; 36: 166-171
  • 239 Giantsou E, Liratzopoulos N, Efraimidou E. et al. De-escalation therapy rates are significantly higher by bronchoalveolar lavage than by tracheal aspirate. Intensive Care Med 2007; 33: 1533-1540
  • 240 Eachempati SR, Hydo LJ, Shou J. et al. Does de-escalation of antibiotic therapy for ventilator-associated pneumonia affect the likelihood of recurrent pneumonia or mortality in critically ill surgical patients?. J Trauma 2009; 66: 1343-1348
  • 241 Pugh R, Grant C, Cooke RP. et al. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev 2015; 8: CD007577
  • 242 Hedrick TL, McElearney ST, Smith RL. et al. Duration of antibiotic therapy for ventilator-associated pneumonia caused by non-fermentative gram-negative bacilli. Surg Infect 2007; 8: 589-597
  • 243 Cosgrove SE, Fowler Jr. VG. Management of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 2008; 46: S386-393
  • 244 Liu C, Bayer A, Cosgrove SE. et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis 2011; 52: 285-292
  • 245 Walsh TJ, Anaissie EJ, Denning DW. et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46: 327-360
  • 246 Micek ST, Ward S, Fraser VJ. et al. A randomized controlled trial of an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia. Chest 2004; 125: 1791-1799
  • 247 de Jong E, van Oers JA, Beishuizen A. et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016; 16: 819-827
  • 248 Bouadma L, Luyt CE, Tubach F. et al. Use of procalcitonin to reduce patientsʼ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375: 463-474
  • 249 Shorr AF, Cook D, Jiang X. et al. Correlates of clinical failure in ventilator-associated pneumonia: insights from a large, randomized trial. J Crit Care 2008; 23: 64-73
  • 250 El-Solh AA, Aquilina AT, Dhillon RS. et al. Impact of invasive strategy on management of antimicrobial treatment failure in institutionalized older people with severe pneumonia. Am J Respir Crit Care Med 2002; 166: 1038-1043
  • 251 el-Ebiary M, Torres A, González J. et al. Quantitative cultures of endotracheal aspirates for the diagnosis of ventilator-associated pneumonia. Am Rev Respir Dis 1993; 148: 1552-1557
  • 252 Wu CL, Yang D, Wang NY. et al. Quantitative culture of endotracheal aspirates in the diagnosis of ventilator-associated pneumonia in patients with treatment failure. Chest 2002; 122: 662-668
  • 253 Nseir S, Favory R, Jozefowicz E. et al. Antimicrobial treatment for ventilator-associated tracheobronchitis: a randomized, controlled, multicenter study. Crit Care 2008; 12: R62
  • 254 Nseir S, Martin-Loeches I, Makris D. et al. Impact of appropriate antimicrobial treatment on transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia. Crit Care 2014; 18: R129
  • 255 Palmer LB, Smaldone GC, Chen JJ. et al. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Crit Care Med 2008; 36: 2008-2013
  • 256 Palmer LB, Smaldone GC. Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med 2014; 189: 1225-1233
  • 257 Korbila IP, Michalopoulos A, Rafailidis PI. et al. Inhaled colistin as adjunctive to intravenous colistin for the treatment of microbiologically documented VAP: a comparative cohort study. Clin Microbiol Infect 2009; 16: 1230-1236
  • 258 Tumbarello M, De Pascale G, Trecarichi EM. et al. Effect of aerosolized colistin as adjunctive treatment on the outcomes of microbiologically documented ventilator-associated pneumonia caused by colistin-only susceptible gram-negative bacteria. Chest 2013; 144: 1768-1775
  • 259 Ghannam DE, Rodriguez GH, Raad II. et al. Inhaled aminoglycosides in cancer patients with ventilator-associated Gram-negative bacterial pneumonia: safety and feasibility in the era of escalating drug resistance. Eur J Clin Microbiol Infect Dis 2009; 28: 253-259
  • 260 Abdellatif S, Trifi A, Daly F. et al. Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: a prospective, randomised trial. Ann Intensive Care 2016; 6: 26
  • 261 Arnold HM, Sawyer AM, Kollef MH. Use of adjunctive aerosolized antimicrobial therapy in the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii ventilator-associated pneumonia. Respir Care 2012; 57: 1226-1233
  • 262 Czosnowski QA, Wood GC, Magnotti LJ. et al. Adjunctive aerosolized antibiotics for treatment of ventilator-associated pneumonia. Pharmacotherapy 2009; 29: 1054-1060
  • 263 Valachis A, Samonis G, Kofteridis DP. The role of aerosolized colistin in the treatment of ventilator-associated pneumonia: a systematic review and metaanalysis. Crit Care Med 2015; 43: 527-533
  • 264 Zampieri FG, Nassar AP, Gusmao-Flores D. et al. Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis. Crit Care 2015; 19: 150
  • 265 Rello J, Torres A, Ricart M. et al. Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes. Am J Respir Crit Care Med 1994; 150: 1545-1549
  • 266 West M, Boulanger BR, Fogarty C. et al. Levofloxacin compared with imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia: a multicenter, prospective, randomized, open-label study. Clin Ther 2003; 25: 485-506
  • 267 Combes A, Luyt CE, Fagon JY. et al. Impact of methicillin resistance on outcome of Staphylococcus aureus ventilator-associated pneumonia. Am J Respir Crit Care Med 2004; 170: 786-792
  • 268 Zahar JR, Clec'h C, Tafflet M. et al. Is methicillin resistance associated with a worse prognosis in Staphylococcus aureus ventilator-associated pneumonia?. Clin Infect Dis 2005; 41: 1224-1231
  • 269 Kalil AC, Murthy MH, Hermsen ED. et al. Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: a systematic review and meta-analysis. Crit Care Med 2010; 38: 1802-1808
  • 270 Wunderink RG, Rello J, Cammarata SK. et al. Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest 2003; 124: 1789-1797
  • 271 Peyrani P, Wiemken TL, Kelley R. et al. Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: results from the IMPACT-HAP study. Crit Care 2014; 18: R118
  • 272 Wunderink RG, Niederman MS, Kollef MH. et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis 2012; 54: 621-629
  • 273 Kalil AC, Klompas M, Haynatzki G. et al. Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis. BMJ open 2013; 3: e003912
  • 274 Wysocki M, Delatour F, Faurisson F. et al. Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother 2001; 45: 2460-2467
  • 275 Jung YJ, Koh Y, Hong SB. et al. Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia.. Crit Care Med 2010; 38: 175-180
  • 276 Torres A, Rubinstein E, Corey GR. et al. Analysis of Phase 3 telavancin nosocomial pneumonia data excluding patients with severe renal impairment and acute renal failure. J Antimicrob Chemother 2014; 69: 1119-1126
  • 277 Jaccard C, Troillet N, Harbarth S. et al. Prospective randomized comparison of imipenem-cilastatin and piperacillin-tazobactam in nosocomial pneumonia or peritonitis. Antimicrob Agents Chemother 1998; 42: 2966-2972
  • 278 Hartenauer U, Weilemann LS, Bodmann KF. et al. Comparative clinical trial of ceftazidime and imipenem/cilastatin in patients with severe nosocomial pneumonias and septicaemias. J Hosp Infect 1990; 15: 61-64
  • 279 Norrby SR, Finch RG, Glauser M. Monotherapy in serious hospital-acquired infections: a clinical trial of ceftazidime versus imipenem/cilastatin. European Study Group. J Antimicrob Chemother 1993; 31: 927-937
  • 280 Luyt CE, Aubry A, Lu Q. et al. Imipenem, meropenem, or doripenem to treat patients with Pseudomonas aeruginosa ventilator-associated pneumonia. Antimicrob Agents Chemother 2014; 58: 1372-1380
  • 281 Michalopoulos AS, Tsiodras S, Rellos K. et al. Colistin treatment in patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria: the renaissance of an old antibiotic. Clin Microbiol Infect 2005; 11: 115-121
  • 282 MacGowan AP, Rynn C, Wootton M. et al. In vitro assessment of colistinʼs antipseudomonal antimicrobial interactions with other antibiotics. Clin Microbiol Infect 1999; 5: 32-36
  • 283 Hamer DH. Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin. Am J Respir Crit Care Med 2000; 162: 328-330
  • 284 Bassetti M, Righi E, Fasce R. et al. Efficacy of ertapenem in the treatment of early ventilator-associated pneumonia caused by extended-spectrum beta-lactamase-producing organisms in an intensive care unit. J Antimicrob Chemother 2007; 60: 433-435
  • 285 Paterson DL, Ko WC, Von Gottberg A. et al. Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol 2001; 39: 2206-2212
  • 286 Hirsch EB, Tam VH. Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection. J Antimicrob Chemother 2010; 65: 1119-1125
  • 287 Looney WJ, Narita M, Mühlemann K. Stenotrophomonas maltophilia: an emerging opportunist human pathogen. Lancet Infect Dis 2009; 9: 312-323
  • 288 Blanquer D, De Otero J, Padilla E. et al. Tigecycline for treatment of nosocomial-acquired pneumonia possibly caused by multi-drug resistant strains of Stenotrophomonas maltophilia. J Chemother 2008; 20: 761-763
  • 289 Wadl M, Heckenbach K, Noll I. et al. Increasing occurrence of multidrug-resistance in Acinetobacter baumannii isolates from four German University Hospitals, 2002-2006. Infection 2010; 38: 47-51
  • 290 Wood GC, Hanes SD, Boucher BA. et al. Tetracyclines for treating multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia. Intensive Care Med 2003; 29: 2072-2076
  • 291 Curcio D, Fernández F, Vergara J. et al. Late onset ventilator-associated pneumonia due to multidrug-resistant Acinetobacter spp.: experience with tigecycline. J Chemother 2009; 21: 58-62
  • 292 Schafer JJ, Goff DA, Stevenson KB. et al. Early experience with tigecycline for ventilator-associated pneumonia and bacteremia caused by multidrug-resistant Acinetobacter baumannii. Pharmacotherapy 2007; 27: 980-987
  • 293 Levin AS, Levy CE, Manrique AE. et al. Severe nosocomial infections with imipenem-resistant Acinetobacter baumannii treated with ampicillin/sulbactam. Int J Antimicrob Agents 2003; 21: 58-62
  • 294 Betrosian AP, Frantzeskaki F, Xanthaki A. et al. Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia. J Infect 2008; 56: 432-436
  • 295 Wood GC, Hanes SD, Croce MA. et al. Comparison of ampicillin-sulbactam and imipenem-cilastatin for the treatment of acinetobacter ventilator-associated pneumonia. Clin Infect Dis 2002; 34: 1425-1430
  • 296 Wang D. Experience with extended-infusion meropenem in the management of ventilator-associated pneumonia due to multidrug-resistant Acinetobacter baumannii. Int J Antimicrob Agents 2009; 33: 290-291
  • 297 Levin AS, Barone AA, Penço J. et al. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin Infect Dis 1999; 28: 1008-1011
  • 298 Bassetti M, Repetto E, Righi E. et al. Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections. J Antimicrob Chemother 2008; 61: 417-420
  • 299 Chuang YC, Cheng CY, Sheng WH. et al. Effectiveness of tigecycline-based versus colistin- based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting: a matched cohort analysis. BMC Infect Dis 2014; 14: 102
  • 300 Durante-Mangoni E, Signoriello G, Andini R. et al. Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin Infect Dis 2013; 57: 349-358
  • 301 Aydemir H, Akduman D, Piskin N. et al. Colistin vs. the combination of colistin and rifampicin for the treatment of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia. Epidemiol Infect 2013; 141: 1214-1222
  • 302 Kalin G, Alp E, Akin A. et al. Comparison of colistin and colistin/sulbactam for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia. Infection 2014; 42: 37-42
  • 303 López-Cortés LE, Cisneros JM, Fernández-Cuenca F. et al. Monotherapy versus combination therapy for sepsis due to multidrug-resistant Acinetobacter baumannii: analysis of a multicentre prospective cohort. J Antimicrob Chemother 2014; 69: 3119-3126
  • 304 Craig WA. Basic pharmacodynamics of antibacterials with clinical applications to the use of beta-lactams, glycopeptides, and linezolid. Infect Dis Clin North Am 2003; 17: 479-501
  • 305 Mohd Hafiz AA, Staatz CE, Kirkpatrick CM. et al. Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics. Minerva Anestesiol 2012; 78: 94-104
  • 306 Rybak M, Lomaestro B, Rotschafer JC. et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2009; 66: 82-98
  • 307 Taccone FS, Laterre PF, Dugernier T. et al. Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care 2010; 14: R126
  • 308 Pletz MW, Bloos F, Burkhardt O. et al. Pharmacokinetics of moxifloxacin in patients with severe sepsis or septic shock. Intensive Care Med 2010; 36: 979-983
  • 309 Scaglione F, Esposito S, Leone S. et al. Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia. Eur Respir J 2009; 34: 394-400
  • 310 Dulhunty JM, Roberts JA, Davis JS. et al. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin Infect Dis 2013; 56: 236-244
  • 311 Dulhunty JM, Roberts JA, Davis JS. et al. A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. Am J Respir Crit Care Med 2015; 192: 1298-1305
  • 312 Roberts JA, Abdul-Aziz MH, Davis JS. et al. Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials. Am J Respir Crit Care Med 2016; 194: 681-691
  • 313 Abdul-Aziz MH, Sulaiman H, Mat-Nor MB. et al. Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis. Intensive Care Med 2016; 42: 1535-1545