Anästhesiol Intensivmed Notfallmed Schmerzther 2007; 42(2): 122-129
DOI: 10.1055/s-2007-971164
Fachwissen: Topthema: Antibiotikatherapie

© Georg Thieme Verlag Stuttgart · New York

Beatmungsassoziierte Pneumonie und multiresistente bakterielle Erreger

Ventilater-associated pneumonia and multiresistant bacteriaAlexandra Heininger, Klaus Unertl
Further Information

Publication History

Publication Date:
16 February 2007 (online)

Zusammenfassung

Die beatmungsassoziierte Pneumonie ist die bedeutendste nosokomiale Infektion in der Intensivmedizin. Eine frühzeitige adäquate Antibiotikatherapie hat höchste Priorität für das Outcome der Patienten; die Frage nach der optimalen diagnostischen Strategie steht dahinter zurück. Die initiale Antibiotikawahl richtet sich danach, ob multiresistente Erreger zu erwarten sind. Im Risikofall ist eine empirische Kombinationsbehandlung indiziert, die vorangegangene Antibiotikabehandlungen und lokale Resistenzmuster berücksichtigt. Die Reevaluation und Deeskalation der Therapie anhand der mikrobiologischen Befunde und die Begrenzung der Therapiedauer auf eine Woche sind entscheidend, um den Einsatz von Breit-spektrum-Antibiotika und die Selektion multiresistenter Erreger einzudämmen.

Summary

Ventilator-associated pneumonia remains the most serious nosocomial infection in critically ill patients. Providing appropriate antibiotic therapy promptly is crucial for successful treatment; whereas the diagnostic approach seems to play a minor role. The empirical antibiotic therapy should be guided by the risk for infections due to multiresistant bacteria. For patients at risk a combination therapy, considering local resistance data and formerly applied antibiotic substances, is recommended. Reevaluation and deescalation of antibiotic therapy based on microbiological culture results and discontinuation of antimicrobial treatment after one week is essential for the control of broadspectrum antibiotic use and antibiotic resistance.

Kernaussagen

  • Beatmete Patienten haben ein erheblich höheres Pneumonierisiko als spontan atmende Patienten; das Risiko steigt kumulativ mit der Beatmungsdauer.

  • Das Auftreten einer beatmungsassoziierten Pneumonie wird in erster Linie durch die Intubation begünstigt; entsprechend kann die Pneumoniehäufigkeit durch noninvasive Beatmung gesenkt werden.

  • Weitere sinnvolle Maßnahmen der Pneumonieprävention sind oropharyngeale Dekontamination, Oberkörperhochlagerung und subglottische Sekretabsaugung. Sedativa sollten restriktiv eingesetzt werden, um die Beatmungszeiten und das damit assoziierte Pneumonierisiko möglichst gering zu halten.

  • Ein allgemein anerkannter Goldstandard für die Diagnostik der VAP existiert nicht. Anhand klinischer und radiologischer Zeichen kann die Diagnose nicht eindeutig gestellt werden.

  • Durch bronchoskopische Gewinnung von Bronchialsekret in Kombination mit einer quantitativen mikrobiologischen Untersuchung kann die Diagnose mit hoher Spezifität gestellt werden; die Sensitivität ist allerdings - besonders bei bereits vorangegangener Antibiotikagabe - weit unter 100 %. Wichtig für den Erregernachweis ist, dass Blutkulturen und Proben von respiratorischen Sekreten vor Beginn der Antibiotikabehandlung gewonnen werden.

  • Die mikroskopische Untersuchung von Trachealsekret oder BAL kann Anhaltspunkte für die Wahl der empirischen Antibiotikatherapie geben.

  • Die häufigsten Erreger der VAP sind Pseudomonas aeruginosa, Staphylococcus aureus und Enterobacteriaceae. Wie weit mit multiresistenten Stämmen zu rechnen ist, hängt ab von der Dauer des Krankenhausaufenthalts, vorangegangenen Antibiotikabehandlungen sowie sog. Healthcare assoziierten Faktoren, wie z.B. Dialyse. Eine weitere wichtige Rolle spielt die lokale Prävalenz multiresistenter Isolate in der jeweiligen Intensivstation.

  • Das Outcome der Patienten hängt von einer frühen und gleichzeitig adäquaten empirischen Antibiotikabehandlung ab.

  • Um für einen möglichst hohen Anteil der Patienten noch vor Erhalt der mikrobiologischen Befunde eine wirksame Therapie sicherzustellen, sollte in Fällen, die resistente Erreger erwarten lassen, empirisch mit einer Kombination von zwei pseudomonaswirksamen Substanzen sowie einem MRSA-wirksamen Präparat begonnen werden.

  • Nach Erhalt der mikrobiologischen Befunde sollte eine Reevaluation erfolgen, um die Behandlung entweder anhand des Antibiogramms nachgewiesener Erreger auf Antibiotika mit schmalerem Spektrum zu deeskalieren oder - falls sich der Verdacht auf eine Pneumonie nicht bestätigen lässt - die Therapie zu beenden.

  • Bei gesicherter Pneumonie kann die Dauer der Antibiotikabehandlung auf acht Tage mit einer einzelnen Substanz begrenzt werden; bei Pneumonien mit Pseudomonas aeruginosa ist dieses Vorgehen allerdings umstritten.

Literaturverzeichnis

  • 1 Vincent JL, Bihari DJ, Suter PM. et al. . The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infenction in Intensive Care (EPIC) Study.  JAMA. 1995;  274 639-644
  • 2 Kollef MH. What is ventilator-associated pneumonia and why is it important?.  Respir Care. 2005;  50 714-721
  • 3 Chastre J, Fagon JY. Ventilator-associated pneumonia.  Am J Respir Crit Care Med. 2002;  165 867
  • 4 Rello J, Ollendorf DA, Oster G. et al. . Epidemiology and outcomes of ventilator-associated pneumonia in a large US database.  Chest. 2002;  122 2115
  • 5 Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: A systematic review.  Crit Care Med. 2005;  33 2184-2193
  • 6 Hugonnet S, Eggiman P, Borst F, Maricot P, Chevrolet JC, Pittet D. Impact of ventilator-associated pneumonia on resource utilization and patient outcome.  Infect Control Hosp Epidemiol. 2004;  25 1090-1096
  • 7 Heyland DK, Cook DJ, Griffith L. et al. . The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient.  Am J Respir Crit Care Med. 1999;  159 1249-1256
  • 8 Bregeon F, Ciais V, Carret. et al. . Is ventilator-associated pneumonia an independent risk factor for death?.  Anesthesiology. 2001;  94 554-560
  • 9 Rello J. Bench-to-bedside review: therapeutic options and issues in the management of ventilator-associated bacterial pneumonia.  Crit Care. 200;  9 259-265
  • 10 Gastmeier P, Sohr D, Geffers C, Behnke M, Rüden H. Mortality risk factors for noso-comial infection in intensive care units: findings from the German nosocomial infection surveillance system (KISS). Infection Control Hosp Epidemiol in press
  • 11 American Thoracic Society/Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and health-care-associated pneumonia.  Am J Respir Crit Care Med. 2005;  171 388-416
  • 12 Safdar N, Crnich CJ, Maki DG. The pathogenesis of ventilator-associated pneumonia: its relevance to developing effective strategies for prevention.  Respir Care. 2005;  50 725-739
  • 13 Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A. et al. . Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease.  N Engl J Med. 1995;  333 817-821
  • 14 Hess DR. Noninvasive positive-pressure ventilation and ventilator-associated pneumonia.  Respir Care. 2005;  50 924-929
  • 15 Lightowler JV, Wedzicha JA, Elliott MW, Ram FS. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis.  BMJ. 2003;  326 185
  • 16 Niederman MS. Gram-negative colonization of the respiratory tract: pathogenesis and clinical consequences.  Semin Respir Infect. 1990;  5 173-184
  • 17 Torre FJ De la, Pont T, Ferrer A, Rossello J, Palmar M, Planas M. Pattern of tracheal colonization during mechanical ventilation.  Am J Respir Crit Care Med. 1995;  152 1028-1033
  • 18 Ewig S, Torres A, El-Ebiary M, Fabregas N, Hernandez C, Gonzalez J. et al. . Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Incidence, risk factors, and association with ventilator-associated pneu-monia.  Am J Respir Crit Care Med. 1999;  159 188-198
  • 19 Johanson WG, Pierce AK, Sanford JP, Thomas GD. Nosocomial respiratory infections with Gram-negative bacilli: the significance of colonization of the respiratory tract.  Ann Intern Med. 1972;  77 701-706
  • 20 George DL, Falk PS, Wunderink RG, Leeper KV, Meduri Gu, Steere EL. et al. . Epidemiology of ventilator-associated pneumonia based on protected bronchoscopic sampling.  Am J Respir Crit Care Med. 1998;  158 1839-1847
  • 21 Bergmans DCJJ, Bonten MJM, Gaillard CA. et al. . Prevention of ventilator-associated pneumonia by oral decontamination.  Am J Respir Crit Care Med. 2001;  164 382-388
  • 22 Abele-Horn M, Dauber A, Bauernfeind A. et al. . Decrease in nosocomial pneumonia in ventilated pateints by selective oropharyngeal decontamination (SOD).  Intensive Care Med. 2007;  23 187
  • 23 Riso AJ De, Ladowski JS, Dillon TA, Justice JW, Peterson AC. Chlorhexidine gluconate 0,12 % oral rinse reduces the incidence of total nosocomial espiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery. Chest 1996
  • 24 Houston S, Hougland P, Anderson JJ, LaRocco M, Kennedy V, Gentry LO. Effectiveness of 0,12 % chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery.  Am J Crit Care. 2002;  11 567-570
  • 25 Fourrier F, Dubois D, Pronnier P. PIRAD Study Group . Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled multicenter study.  Crit Care Med. 2005;  33 1728-1735
  • 26 Kollef M, Pittet D, Sanchez M Garcia. Prevention of Pneumonia Study (POPS-1) Trial Group. A randomised double-blind trial of iseganan prevention of ventilator-associated pneumonia.  Am J Respir Crit Care Med. 2006;  173 91-9
  • 27 Bonten MJ, Bergmann DC, Ambergen AW, Leeuw PW De, Geest S Van der, Stobberingh EE, Gaillard CA. Risk factors for pneumonia and colonization of respiratory tract and stomach in mechanically ventilated ICU patients.  Am J Respir Crit Care Med. 1996;  154 1339-1346
  • 28 Krueger WA, Lenhart FP, Neeser G, Et al.. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections. Organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomised, double-blind, placebo-controlled clinical trial.  Am J Respir Crit Care Med. 2002;  166 1029
  • 29 Jonge E De, Schultz MJ, Spanjaard L. et al. . Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.  Lancet. 2003;  362 1011
  • 30 Cal MA De La, Cerda E, Garcia P Hierro, Saene HK van, Gomez-Santos D, Negro E, Lorente JA. Survival benefit in critically ill burned patients receiving selective decontamination of the digestive tract: a randomized, placebo-controlled, double-blind trial.  Ann Surg. 2005;  241 424-430
  • 31 Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften. Diagnose und Therapie der Sepsis. AWMF-Reg.-Nr. 079/001 Entwicklungsstufe 2, Stand 12/05, gültig bis 12/07 leitlinien.net
  • 32 Heininger A, Meyer E, Schwab F, Marschal M, Unertl K, Krueger A. Effects of long-term routine use of selective digestive decontamination on antimicrobial resistance.  Intensive Care Medicine. 2006;  32 1569-1576
  • 33 Chastre J. Conference Summary: Ventilator-associated pneumonia.  Respir Care. 2005;  50 975-983
  • 34 Dezfulian C, Shojania K, Collard HR. et al. . Subglottic secretion drainage for preventing ventilator-associated pneumonia: a meta-analysis.  Am J Med. 2005;  118 11
  • 35 Cobben NA, Drent M, Jonkers M, Wouters EF, Vaneechoutte M, Stobberingh EE. Outbreak of severe Pseudomonas aeruginosa respiratory infections due to contaminated nebulizers.  J Hosp Infect. 1996;  33 63-70
  • 36 Srinivasan A, Wolfenden LL, Song X, Mackie K, Hartsell TL, Jones HD. et al. . An outbreak of Pseudomonas aeruginosa infections associated with flexible bronchoscopes.  N Engl J Med. 2003;  348 221-227
  • 37 Struelens MJ, Carlier E, Maes N, Serays E, Quint WG, Belkum A van. Nosocomial colonization and infection with multirsistant Acinetobacter baumanii: outbreak delineation using DNA macrorestriction analysis and PCR-fingerprinting.  J Hosp Infect. 1993;  25 15-32
  • 38 Unertl K, Heininger A, Unger G. Kommission für Krankenhaushygiene und Infektionsprävention am Robert-Koch-Institut. . Prävention der nosokomialen Pneumonie.  Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz. 2000;  43 302-309
  • 39 Tablan OC, Anderson LJ, Besser R. et al. . Healthcare Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Guidelines for preventing health-care-associated pneumonia, 2003: recommendations of the CDC and the Healthcare Infection Control Practices Advisory Committee.  MMWR Recomm Rep. 2004;  53 1
  • 40 Needleman J, Buerhaus P, Mattke S, Stewart M, Zelevinsky K. Nurse-staffing levels and the quality of care n hospitals.  N Engl J Med. 2002;  346 1715-1722
  • 41 Zack JE, Garrison T, Trovillion E, Clinkscale D, Coopersmith CM, Fraser VJ, Kollef MH. Effect of an education program aimed at reducing the occurrence of ventilator-associated pneumonia.  Crti Care Med. 2002;  30 2407-2412
  • 42 Torres A, Ewig S. Diagnosing ventilator-associated pneumonia.  N Engl J Med. 2004;  350 433-435
  • 43 Heininger A, Krueger WA, Doring G, Unertl K. Ventilator-associated pneumonia.  Curr Opin Anaesthesiol. 2002;  15 153-159
  • 44 Porzecanski I, Bowton DL. Diagnosis and treatment of ventilator-associated pneumonia.  Chest. 2006;  130 597-604
  • 45 Ostendorf U, Ewig S, Torres A. Nosocomial pneumonia.  Curr Opin Infet Dis. 2006;  19 327-338
  • 46 Fabregas N, Ewig S, Torres A. et al. . Clinical diagnosis of ventilator-associated pneumonia revisisted: comparative validation using immediate postmortem lung biopsies.  Thorax. 1999;  54 867
  • 47 Niederman MS. The clinical diagnosis of ventilator-associated pneumonia.  Respir Care. 2005;  50 788-796
  • 48 Chastre J, Combes A, Luyt C-E. The invasive (quantitative) diagnosis of ventilator-associated pneumonia.  Respir Care. 2005;  50 797-807
  • 49 Torres A, El-Ebiary M. Bronchoscopic BAL in the diagnosis of ventilator-associated pneumonia.  Chest. 2000;  117 S198-S202
  • 50 Timsit JF, cheval C, Gachot B. et al. . Usefulness of a strategy based on bronchoscopy with direct examination of bronchoalveolar lavage fluid in the initial antibiotic therapy of suspected ventilator-associated pneumonia.  Intensive Care Med. 2001;  27 640-647
  • 51 Brun-Buisson C, Fartoukh M, Lechapt E. et al. . Contribution of blinded protected quantitative specimens to the diagnostic and therapeutic management of ventilator-associated pneumonia.  Chest. 2005;  128 2706-2713
  • 52 Fagon J-Y, Chastre J, Wolff M. et al. . Invasive and non-invasive strategies for management of suspected ventilator-associated pneumonia.  Ann Intern Med. 2000;  132 621-630
  • 53 Sanchez M Nieto, Torres A, Garcia-Cordoba F. et al. . Impact of invasive and noninvasive quantiative culture sampling on outcome of ventilator-associated pneumonia.  Am J Respir Crit Care med. 1998;  157 371-376
  • 54 Ruiz M, Torres A, Ewig S. et al. . Noninvasive versus invasive microbial investigation in ventilator-associated pneumonia.  Am J Respir Crit Care Med. 2000;  162 199-125
  • 55 Violan JS, Fernande JA, Benitez AB. et al. . Impact of quantitative diagnostic techniques in the management and outcome of mechanically ventilated patients with suspected pneumonia.  Crit Care med. 2000;  28 2737-2741
  • 56 Shorr A, Sherner JH, Jackson WL, Kollef MH. Invasive approaches to the diagnosis of ventilator-associated pneumonia: a meta-analysis.  Crit Care Med. 2005;  33 46
  • 57 Blot F, Baynard B, Chachaty E, Tancrede C, Antoun S, Nitenberg G. Value of Gram stain examination of lower respiratory tract secretions for early diagnosis of nosocomial pneumonia.  Am J Respir Crit Care Med. 2000;  162 1731-1737
  • 58 Veinstein A, Brun-Buisson C, Derrode N, Alvarez A, Pinsard M, Robert R, Blot F. Validation of an algorithm based on direct examination of specimens in suspected ventilator-associated pneumonia.  Intensive Care Med. 2006;  32 676-683
  • 59 Vidaur L, Sirgo G, Rodriguez AH, Rello J. Clinical approach to the patient with suspected ventilator-associated pneumonia.  Respir Care. 2005;  50 965-974
  • 60 Lynch J. Hospital-acquired pneumonia: risk factors, microbiology and treatment. Chest 2001: S373-S384
  • 61 Park DR. The microbiology of ventilator-associated pneumonia.  Respir Care. 2005;  50 742-763
  • 62 Gastmeier P. Surveillance nosokomialer Infektionen: Schwerpunkt Intensivmedizin.  www.p-e-g.org/arhicv_tmp/bad_honnef_symposiuim2006/ga
  • 63 Combes A, Figliolini C, Trouillet JL, Kassis N, Wolff M, Gibert C. et al. . Incidence and outcome of polymicrobial ventilator-associated pneumonia.  Chest. 2002;  121 1618-1623
  • 64 Craven DE. Epidemiology of ventilator-associated pneumonia.  Chest. 2000;  117 S186-S187
  • 65 Langer M, Cigada M, Mandelli M, Mosconi P, Tognoni G. Ealrly onset-pneumonia: a multicenter study in intensive care units.  Intensive Care Med. 1987;  13 342-346
  • 66 Ibrahim EH, Ward S, Sherman G, Kollef MH. A comparative analysis of patients with early-onset versus late-onset nosocomial pneumonia (NP) in the ICU setting.  Chest. 2000;  117 1434-1442
  • 67 Giantsou E, Liratzopoulos N, Efraimidou E, Panopoulou M, Alepopoulou E, Kartali-Ktenidou S, Minopoulos GI, Zakynthinos S, Manolas KI. Both early-onset and late-onset ventilator-associated pneumonia are caused mainly by potentially multiresistant bacteria.  Intensive Care Med. 2005;  31 1488-1494
  • 68 Jacoby GA. Epidemiology of extended-spectrum beta-lactamases.  Clin Infect Dis. 1998;  27 81
  • 69 Pena C, Pujol M, Ardanuy C. et al. . Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended-spectrum beta-lactamases.  Antimicrob Agents Chemother. 1998;  42 53
  • 70 Champs C De, Rouby D, Guelon D. et al. . A case-control study of an outbreak of infections caused by Klebsiella pneumoniae strains producing CTX-1(TEM-3) beta-lactamase.  J Hosp Infect. 1991;  18 5
  • 71 Schippa DA, Hayden MK, Mathushek MG. et al. . Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation.  J Infect Dis. 1996;  174 529
  • 72 Lucet JC, Chevret S, Decre D. et al. . Outbreak of multiply resistant enterobacteriaceae in an intensive care unit: epidemiology and risk factors for acquisition.  Clind Infect Dis. 1996;  22 430
  • 73 Jacoby GA, Munoz-Price LS. The new beata-lactamases.  N Engl J Med. 2005;  352 380
  • 74 Rello J, Allegri C, Rodriguez A, Vidaur L, Sirgo G, Gomez F, Agbaht K, Pobo A, Diaz E. Risk factors for ventilator-associated pneumonia by Pseudomonas aeruginosa in presence of recent antibiotic exposure.  Anaesthesiology. 2006;  105 709-714
  • 75 Babcock HM, Zack JE, Garrison T, Trovillion E, Kollef MH, Fraser VJ. Ventilator-associated pneumonia in a multi-hospital system: differences in microbiology by location.  Infect Control Hosp Epidemiology. 2003;  24 853-858
  • 76 Park DR. Antimicrobial treatment of ventilator-associated pneumonia.  Resp Care. 2005;  50 932-952
  • 77 Dellinger RP, Carlet J, Masur H. et al. . Surviving sepsis campaign for management of severe sepsis and septic shock.  Crit Care Med. 2004;  32 858-872
  • 78 Kollef MH, Ward S. The influence of mini-BAL cultutes on patients outcomes: implications for the antibiotic management of ventilator-associated pneumonia.  Chest. 1998;  113 412-420
  • 79 Kollef MH. Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients.  Clin Infect Dis. 2000;  31 S131-S138
  • 80 Dupont H, Mentec H, Sollet JP. et al. . Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia.  Intensive Care Med. 2001;  27 355-362
  • 81 Luna CM, Vujacich P, Niederman MS. et al. . Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia.  Chest. 2007;  111 676-685
  • 82 Eggimann P, Revelly J-P. Should antibiotic combinations be used to treat ventilator-associated pneumonia?.  Semin Respir Crit Care Med. 2006;  27 68-81
  • 83 Micek ST, Lloyd AE, Ritchie DJ. et al. . Pseudomonas aeruginosa bloodstream infection: importance of appropriate initial antimicrobial treatment.  Antimicrob agents chemother. 2005;  49 1306-1311
  • 84 Michel F, Franceschini B, Berger P. et al. . Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: a role for routine endotracheal aspirate cultures.  Chest. 2005;  127 589-597
  • 85 Depuydt PO, Blot SI, Benoit DD, Claeys GW, Verschraegen GL, Vandewoude KH, Vogelaers DP, Decruyenaere JM, Colardyn FA. Antimicrobial resistance in nosocomial bloodstream infection associated with pneumonia and the value of systematic surveillance cultures in an adult intensive care unit.  Crit Care Med. 2006;  34 653-659
  • 86 Singh N, Rogers P, Watwood 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
  • 87 Chastre J, Wolff M, Fagon JY. et al. . Comparison of 8 vs. 14 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial.  JAMA. 2003;  290 2588
  • 88 Paul M, Silbiger I, Grozinsky S. et al. . Beta lactam antibiotic monotherapy vs. beta lactamaminoglycoside antibiotic combination therapy for sepsis.  Cochrane Database Syst Rev. 2006;  25
  • 89 Bliziotis IA, Samonis G, Vardakas KZ. et al. . Effect of aminoglycoside and beta-lactam combination therapy vs. beta-lacltam monotherapy on the emrgence of antimicrobial resistance: A meta-analysis of randomized controlled trials.  Clin Infect Dis. 2005;  41 149-158
  • 90 Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L. Beta-lactam monotherapy versus beta-lacta-aminoglycoside combination theapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomized trials.  BMJ. 2004;  328 668-672
  • 91 Cornetta 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
  • 92 Safdar N, Handelsman J, Maki DG. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis.  Lancet Infect Dis. 2004;  4 519-527
  • 93 Meyer E, Jonas D, Schwab F, Gastmeier P, Rüden H, Daschner FD. SARI: Surveillance der Antibiotikaanwendung und bakteriellen Resistenzentwicklung auf deutschen Intensivstationen.  Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz. 2004;  47 345-351
  • 94 Kollef MH. Gram-negative bacterial resistance: evolving patterns and treatment paradigms.  Clin Infect Dis. 2005;  40 S85-S88
  • 95 Nordmann P, Poirel L. Emerging carabapenemases in Gram-negative anaerobes.  Clin Microbiol Infect. 2002;  8 321-331
  • 96 Borgmann S, Wolz C, Grobner S, Autenrieth IB, Heeg P, Goerke C, Muller K, Kyme P, Marschal M. Metallo-beta-lactamase expressing multi-resistant Acinetobacter baumanii transmitted in the operation area.  J Hosp Infect. 2004;  57 308-315
  • 97 Wood GC, Hanes SD, Croce MA, Fabian TC, Boucher BA. Comparison of ampicillin-sulbactam and impenem-cilastatin for the treatment of Acinetobacter ventilator-associated pneumonia.  Clin Infect Dis. 2002;  34 1425-1430
  • 98 Pachon-Ibanez ME, Jimenez-Mejias ME, Pichardo C, Llanos AC, Pachon J. Activity of tigecycline against Acinetobacter baumanii strains, including those resistant to imipenem.  Antimicrob Agents Chemother. 2004;  48 4479-4481
  • 99 Bonomo R, Szabo D. Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa.  Clin Infect Dis. 2006;  43 S49-S56
  • 100 Levin AS, Barone AA, Penco J, Santos MV, Marinho IS, Aruda EA. et al. . Intravenous colistin as therapy for nosocomial infetions caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumanii.  Clin Infect Dis. 1999;  28 1008-1011
  • 101 Michalopoulos AS, Tsiodras S, Rellos K, Mentzelopulos S, Falagas ME. 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
  • 102 Rahal JJ. Novel antibiotic combinations against infections with almost completely resistant Pseudomonas aeruginosa and Acinetobacter species.  Clin Infect Dis. 2006;  43 S95-S99
  • 103 Murray CK, Hospenthal DR. Treatment of multidrug resistant Acinetobacter.  Curr Opin Infect Dis. 2005;  18 502-506
  • 104 Döring G, Conway SP, Heijerman HGM. et al. . Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus.  Eur Respir J. 2000;  16 749-767
  • 105 Adair CG, Gorman SP, Byers LM, Jones DS, Feron B, Crowe M. et al. . Eradication of endotracheal tube biofilm by nebulised gentamicin.  Intensive Care Med. 2002;  28 426-431
  • 106 Hamer DH. Treatment of nosocomial pneumonia and tracheobrochitis caused by mul-tidrug-resistant Pseudomonas aeruginosa with aerosolised colistin.  Am J Respir Crit Care Med. 2000;  162 328-330
  • 107 Michalopoulos A, Kasiakou SK, Mastora Z, Rellos K, Kapaskelis AM, Falagas ME. Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant gram-negative bacteria in patients without cystic fibrosis.  Crit Care. 2005;  9 53-59
  • 108 Kwa ALH, Loh CS, Low JGH, Kurup A, Tam VH. Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumanii and Pseudomonas aeruginosa.  Clin Infect Dis. 2005;  41 754-757
  • 109 Kollef MH. Antibiotic management of ventilator-associated pneumonia due to antibiotic-resistant gram-positive bacterial infection.  Eur J Clin Microbiol Infect Dis. 2005;  24 794-803
  • 110 Fagon J, Patrick H, Haas DW. et al. . Treatment of Gram-positive nosocomial pneumonia: prospective randomized comparison of quinupristin/dalfopristin versus vancomycin.  Am J Respir Crit Care Med. 2000;  161 753
  • 111 Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef MH. Linezolid vs. vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia.  Chest. 2003;  124 1789-1797
  • 112 Byl B, Jacobs F, Wallemacq P. et al. . Vancomycin penetration of uninfected pleural fluid exudate after continuous or intermittent infusion.  Antimicrob Agents Chemother. 2003;  47 2015-2017
  • 113 Lamer C, Beco V de, Soler P. et al. . Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients.  Antimicrob Agents Chemother. 1993;  37 281-286
  • 114 Shorr AF, Duh MS, Kelly KM, Kollef MH. Red blood cell transfusion and ventilator-associated pneumonia: a potential link?.  Crit Care Med. 2004;  32 666-674
  • 115 Bornstain C, Azoulay E, Lassence A De. et al. . Sedation, sucralfate, and antibiotic use are potneital means for protection against early-onset ventilator-associated pneumonia.  Clin Infect Dis. 2004;  38 1401-1408
  • 116 Pawar M, Mehta Y, Khurana P. et al. . Ventilator-associated pneumonia: incidence, risk factors, outcome, and microbiology.  J Cardiothorac Vasc Anesth. 2003;  31 1312-1317
  • 117 Kobashi Y, Matshushima T. Clinical analysis of patients requring long-term mechanical ventilaton over three months: ventilator-associated pneumonia as a primary complication.  Intern Med. 2003;  43 25-32
  • 118 Alp E, Guven M, Yildiz O. et al. . Incidence, risk factors and mortality of nosocomial pneumonia in intensive care units: a prospective study.  Ann Clin Microbiol Antimicrob. 2004;  3 17
  • 119 Bullock TK, Waltrip TJ, Price SA, Galndiuk S. A retrospective study of nosocomial pneumonia in postoperative patients shows a higher mortality rate in patients receiving nasogastgric tube feeding.  Am Surg. 2004;  70 822-826
  • 120 Erbay RH, Yalcin AN, Zencir M. et al. . Costs and risk factors for ventilator-associated pneumonia in a Turkish University Hospital`s Intensive Care Unit: a case-control study.  BMC Pulm Med. 2004;  4 3
  • 121 Warren DK, Shukla SJ, Olsen MA. et al. . Outcome and attributable cost of ventilator-associated pneumonia among intensive care unit patients in asuburban medical center.  Crit Care Med. 2003;  31 1312-1317
  • 122 ElSolh AA, Bhat A, Gunen H, Berbary E. Extubation failure in the elderly.  Respir Med. 2004;  98 661-668
  • 123 Almuneef M, Memish ZA, Balkhy HH. et al. . Ventilator-associated pneumonia in a pediatric intensive care unit in Saudi Arabia: in a 30-month prospective surveillance.  Infect Control Hosp Epidemiol. 2004;  25 753-758
  • 124 Mukhopadhyay C, Bhargava A, Ayyagari A. Role of mechanical ventilation and development of multidrug resistant organisms in hospital acquired pneumonia.  Indian J Med Res. 2003;  118 229-235
  • 125 Sirvent JM, Torres A, Vidaur L. et al. . Tracheal colonisation within 24 h of intubation in patients with head trauma: risk factor for developing early-onset ventilator-associated pneumonia.  Intensive Care Med. 2000;  26 1369-1372

Dr. med. Alexandra Heininger
Prof. Dr. med. Klaus Unertl

Email: alexandra.heininger@med.uni-tuebingen.de

Email: klaus.unertl@med.uni-tuebingen.de

    >