Download PDF
Krankenhaushygiene up2date 2014; 09(04): 301-318
DOI: 10.1055/s-0034-1391290
Nosokomiale Infektionen
© Georg Thieme Verlag KG Stuttgart · New York

Therapieoptionen bei Infektion durch nosokomiale multiresistente Erreger

Christina Forstner
,
Stefan Hagel
,
Bettina Löffler
,
Florian Thalhammer
,
Mathias W. Pletz
Further Information

Publication History

Publication Date:
08 January 2015 (online)

Also available at
    Permissions and Reprints All articles of this category
Kernaussagen

  • Daptomycin ist zur Behandlung von pulmonalen Infektionen nicht geeignet.

  • Linezolid hat eine sehr gute orale Bioverfügbarkeit und kann daher frühzeitig oralisiert werden.

  • Tigecyclin ist zur Monotherapie von schweren nosokomialen Infektionen insbesondere bei Bakteriämie nicht geeignet.

  • Studien zur MRSA-Pneumonie mit Ceftarolin liegen nicht vor.

  • Die Resistenzentwicklung bei gramnegativen Bakterien ist bedrohlich und wird in den nächsten Jahren weiter zu nehmen.

  • Bei unkomplizierten Harnwegsinfektionen durch 3- und 4MRGN können in der Regel Alternativen (Nitrofurantoin, Fosfomycin) eingesetzt werden, wenn sie empfindlich getestet sind.

  • Bei schweren Infektionen durch 3MRGN ist eine Monotherapie der noch wirksamen Antibiotikagruppe, in der Regel eine Therapie mit einem Carbapenem – unter Umständen auch Piperacillin-Tazobactam, ausreichend.

  • Bei schweren Infektionen durch 4MRGN, insbesondere KPC scheint eine Kombinationstherapie (insbesondere eine Dreifachkombination mit Colistin und Carbapenem mit Tigecyclin oder Fosfomycin) vorteilhaft zu sein.

 

  • Literatur

  • 1 D’Costa VM, King CE, Kalan L et al. Antibiotic resistance is ancient. Nature 2011; 477: 457-461
    CrossrefGoogle Scholar
  • 2 Carlet J, Jarlier V, Harbarth S et al. Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action. Antimicrob Resist Infect Control 2012; 1: 11
    CrossrefGoogle Scholar
  • 3 European Centre for Disease Prevention and Control/European Medicines Agency. ECDC/EMEA Joint Technical Report – The bacterial challenge: time to react. A call to narrow the gap between multidrug-resistant bacteria in the EU and the development of new antibacterial agents. EMEA doc. ref. EMEA/576176/2009 Stockholm: 2009 http://www.ecdc.europa.eu/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf
    Google Scholar
  • 4 European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2011. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm: ECDC; 2012
    Google Scholar
  • 5 Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States. 2013 http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf Last accessed on 24 February 2014
    Google Scholar
  • 6 Meyer E, Schröder C, Gastmeier P et al. The reduction of nosocomial MRSA infection in Germany—an Analysis of data from the Hospital Infection Surveillance System (KISS) between 2007 and 2012. Dtsch Arztebl 2014; 111: 331-336
    Google Scholar
  • 7 Whitby M, McLaws ML, Berry G. Risk of death from methicillin-resistant Staphylococcus aureus bacteraemia: a meta-analysis. Med J Aust 2001; 175: 264-267
    Google Scholar
  • 8 Cosgrove SE, Sakoulas G, Perencevich EN et al. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 2003; 36: 53-59
    CrossrefPubMedGoogle Scholar
  • 9 KRINKO. Empfehlungen zur Prävention und Kontrolle von Methicillin-resistenten Staphylococcus-aureus-Stämmen (MRSA) in medizinischen und pflegerischen Einrichtungen. Bundesgesundheitsbl 2014; 57: 696-732
    Google Scholar
  • 10 Wagener J, Seybold U. [MRSA - hygiene management, diagnostics and treatment]. Dtsch Med Wochenschr 2014; 139: 643-651
    Article in Thieme ConnectGoogle Scholar
  • 11 Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med 2004; 351: 1645-1654
    CrossrefPubMedGoogle Scholar
  • 12 Zimmerli W. Clinical practice. Vertebral osteomyelitis. N Engl J Med 2010; 362: 1022-1029
    CrossrefGoogle Scholar
  • 13 Moellering RC. Current treatment options for community-acquired methicillin-resistant Staphylococcus aureus infection. Clin Infect Dis 2008; 46: 1032-1037
    CrossrefGoogle Scholar
  • 14 Harbarth S, von Dach E, Pagani L et al. Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection. J Antimicrob Chemother 2014; pii:dku352
    Google Scholar
  • 15 Welte T, Pletz MW. Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options. Int J Antimicrob Agents 2010; 36: 391-400
    CrossrefPubMedGoogle Scholar
  • 16 Stevens DL, Bisno AL, Chambers HF et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014; 59: e10-52
    CrossrefGoogle Scholar
  • 17 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. Clin Infect Dis 2011; 52: e18-e55
    CrossrefPubMedGoogle Scholar
  • 18 Flandrois JP, Fardel G, Carret G. Early stages of in vitro killing curve of LY146032 and vancomycin for Staphylococcus aureus. Antimicrob Agents Chemother 1988; 32: 454-457
    CrossrefGoogle Scholar
  • 19 Knudsen JD, Fuursted K, Raber S et al. Pharmacodynamics of glycopeptides in the mouse peritonitis model of Streptococcus pneumoniae or Staphylococcus aureus infection. Antimicrob Agents Chemother 2000; 44: 1247-1254
    CrossrefGoogle Scholar
  • 20 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
    CrossrefGoogle Scholar
  • 21 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]. Pneumol Stuttg Ger 2012; 66: 707-765
    Google Scholar
  • 22 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
    CrossrefGoogle Scholar
  • 23 Poeppl W, Lingscheid T, Bernitzky D et al. Efficacy of fosfomycin compared to vancomycin in treatment of implant-associated chronic methicillin-resistant Staphylococcus aureus osteomyelitis in rats. Antimicrob Agents Chemother 2014; 58: 5111-5116
    CrossrefGoogle Scholar
  • 24 Xu-hong Y, Falagas ME, Dong W et al. In vitro activity of fosfomycin in combination with linezolid against clinical isolates of methicillin-resistant Staphylococcus aureus. J Antibiot 2014; 67: 369-371
    CrossrefGoogle Scholar
  • 25 Chan JD, Pham TN, Wong J et al. Clinical outcomes of linezolid vs vancomycin in methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia: retrospective analysis. J Intensive Care Med 2011; 26: 385-391
    CrossrefGoogle Scholar
  • 26 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
    CrossrefGoogle Scholar
  • 27 Muscedere JG, Day A, Heyland DK. Mortality, attributable mortality, and clinical events as end points for clinical trials of ventilator-associated pneumonia and hospital-acquired pneumonia. Clin Infect Dis 2010; 51: 120-S125
    CrossrefGoogle Scholar
  • 28 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
    CrossrefGoogle Scholar
  • 29 Dalhoff K, Abele-Horn M, Andreas S et al. Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie. Pneumologie 2012; 66: 707-765
    Article in Thieme ConnectGoogle Scholar
  • 30 Arbeit RD, Maki D, Tally FP et al. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis 2004; 38: 1673-1681
    CrossrefGoogle Scholar
  • 31 Fowler VG Jr, Boucher HW, Corey GR et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 2006; 355: 653-665
    CrossrefGoogle Scholar
  • 32 Gould IM, Miró JM, Rybak MJ. Daptomycin: the role of high-dose and combination therapy for Gram-positive infections. Int J Antimicrob Agents 2013; 42: 202-210
    CrossrefGoogle Scholar
  • 33 Kullar R, Davis SL, Levine DP et al. High-dose daptomycin for treatment of complicated gram-positive infections: a large, multicenter, retrospective study. Pharmacotherapy 2011; 31: 527-536
    CrossrefGoogle Scholar
  • 34 Benvenuto M, Benzinger DP, Yankelev S et al. Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers. Antimicrob Agents Chemother 2006; 50: 3245-3249
    CrossrefGoogle Scholar
  • 35 Corey GR, Wilcox MH, Talbot GH et al. CANVAS 1: the first Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother 2010; 65 (Suppl. 04) iv41-iv51
    Google Scholar
  • 36 Wilcox MH, Corey GR, Talbot GH et al. CANVAS 2: the second Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother 2010; 65: iv53-iv65
    Google Scholar
  • 37 Friedland HD, O’Neal T, Biek D et al. CANVAS 1 and 2: analysis of clinical response at day 3 in two phase 3 trials of ceftaroline fosamil versus vancomycin plus aztreonam in treatment of acute bacterial skin and skin structure infections. Antimicrob Agents Chemother 2012; 56: 2231-2236
    CrossrefGoogle Scholar
  • 38 Casapao AM, Davis SL, Barr VO et al. Large retrospective evaluation of the effectiveness and safety of ceftaroline fosamil therapy. Antimicrob Agents Chemother 2014; 58: 2541-2546
    CrossrefGoogle Scholar
  • 39 Gastmeier P, Schröder C, Behnke M et al. Dramatic increase in vancomycin-resistant enterococci in Germany. J Antimicrob Chemother 2014; 69: 1660-1664
    CrossrefPubMedGoogle Scholar
  • 40 Robert-Koch-Institut. Vancomycin-resistente Enterokokken (VRE): Aktuelle Daten und Trends zur Resistenzentwicklung aus dem NRZ für Staphylokokken und Enterokokken, 2011 – 2012. Epidem Bull 2013; 33: 303-312
    Google Scholar
  • 41 Chatterjee I, Iredell JR, Woods M et al. The implications of enterococci for the intensive care unit. Crit Care Resusc J Australas Acad Crit Care Med 2007; 9: 69-75
    Google Scholar
  • 42 Holmes NE, Ballard SA, Lam MMC et al. Genomic analysis of teicoplanin resistance emerging during treatment of vanB vancomycin-resistant Enterococcus faecium infections in solid organ transplant recipients including donor-derived cases. J Antimicrob Chemother 2013; 68: 2134-2139
    CrossrefGoogle Scholar
  • 43 Whang DW, Miller LG, Partain NM et al. Systematic review and meta-analysis of linezolid and daptomycin for treatment of vancomycin-resistant enterococcal bloodstream infections. Antimicrob Agents Chemother 2013; 57: 5013-5018
    CrossrefGoogle Scholar
  • 44 Balli EP, Venetis CA, Miyakis S. Systematic review and meta-analysis of linezolid versus daptomycin for treatment of vancomycin-resistant enterococcal bacteremia. Antimicrob Agents Chemother 2014; 58: 734-739
    CrossrefGoogle Scholar
  • 45 Robert-Koch-Institut. Hygienemaßnahmen bei Infektionen oder Besiedlung mit multiresistenten gramnegativen Stäbchen. Empfehlungen der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) am Robert Koch-Institut (RKI). Bundesgesundheitsbl 2012; 55: 1311-1354 (DOI 10.1007/s00103-012-1549-5.)
    CrossrefGoogle Scholar
  • 46 Tenover FC. Mechanisms of antimicrobial resistance in bacteria. Am J Med 2006; 119: 3-S10
    Google Scholar
  • 47 Nikaido H, Pages JM. Broad specificity efflux pumps and their role in multidrug resistance of gram negative bacteria. FEMS Microbiol Rev 2012; 36: 340-363
    CrossrefGoogle Scholar
  • 48 De Waele JJ, Ravyts M, Depuydt P et al. De-escalation after empirical meropenem treatment in the intensive care: Fiction or reality?. J Crit Care 2010; 25: 641-646
    CrossrefGoogle Scholar
  • 49 Fournier D, Chirouze C, Leroy J et al. Alternatives to carbapenems in ESBL-producing Escherichia coli infections. Med Mal Infect 2013; 43: 62-66
    CrossrefGoogle Scholar
  • 50 Rodriguez-Bano J, Navarro MD, Retamar P et al. β-Lactam/β-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum β-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis 2012; 54: 167-174
    CrossrefGoogle Scholar
  • 51 Diaz MA, Hernandez-Bello JR, Rodriguez-Bano J et al. The diversity of Escherichia coli producing extended-spectrum beta-lactamases in Spain: second nationwide study. J Clin Microbiol 2010; 48: 2840-2845
    CrossrefGoogle Scholar
  • 52 Payne DJ, Cramp R, Winstanley DJ et al. Comparative activities of clavulanic acid, sulbactam, and tazobactam against clinically important beta-lactamases. Antimicrob Agents Chemother 1994; 38: 767-772
    CrossrefGoogle Scholar
  • 53 Balakrishnan I, Awad-El-Kariem M, Aali A et al. Temocillin use in England: clinical and microbiological efficacies in infections caused by extended-spectrum and/or derepressed AmpC β-lactamase-producing Enterobacteriaceae. J Antimicrob Chemother 2011; 66: 2628-2631
    CrossrefGoogle Scholar
  • 54 Livermore DM, Warner M, Mushtaq S et al. What remains against carbapenem-resistant Enterobacteriaceae? Evalulation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents 2011; 37: 415-419
    CrossrefGoogle Scholar
  • 55 Plachouras D, Karvanem M, Friberg LE. 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
    CrossrefGoogle Scholar
  • 56 Honore PM, Jacobs R, Joannes-Boyau O et al. Continuous renal replacement therapy-related strategies to avoid colistin toxicity: a clinically orientated review. Blood Purif 2014; 37: 291-295
    CrossrefGoogle Scholar
  • 57 Michalopoulos AS, Livaditis IG, Gougoutas V. The revival of fosfomycin. Int J Infect Dis 2011; 15: e732-e739
    CrossrefGoogle Scholar
  • 58 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
    CrossrefGoogle Scholar
  • 59 Neuner EA, Sekeres J, Gerri SH et al. Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother 2012; 56: 5744-5748
    CrossrefGoogle Scholar
  • 60 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
    CrossrefPubMedGoogle Scholar
  • 61 Ramirez J, Dartois N, Gandjini H et al. A randomized phase 2 trial to evaluate the clinical efficacy of two high tigecycline dosage regimens versus imipenem/cilastatin in hospital-acquired pneumonia. Antimicrob Agents Chemother 2013; 57: 1756-1762
    CrossrefGoogle Scholar
  • 62 Zavascki AP, Bulitta JB, Landersdorfer CB. Combination therapy for carbapenem-resistant gram-negative bacteria. Expert Rev Anti Infect Ther 2013; 11: 1333-1353
    CrossrefPubMedGoogle Scholar
  • 63 Tumbarello M, Viale P, Viscoli C et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis 2012; 55: 943-950
    CrossrefGoogle Scholar
  • 64 Daikos GL, Tsaousi S, Tzouvelekis LS et al. Carbapenmase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotics combination schemes and the role of carbapenems. Antimicrob Agents Chemother 2014; 58: 2322-2328
    CrossrefGoogle Scholar
  • 65 Michalopoulos A, Virtzili S, Rafailidis P et al. Intravenous fosfomycin for the treatment of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae in critically ill patients: a prospective evaluation. Clin Microbiol Infect 2010; 16: 184-186
    CrossrefGoogle Scholar
  • 66 Karageorgopoulos DE, Miriagou V, Tzouvelekis LS et al. Emergence of resistance to fosfomycin used as adjunct therapy in KPC Klebsiella pneumonia bacteraemia: report of three cases. J Antimicrob Chemother 2012; 67: 2777-2779
    CrossrefGoogle Scholar
  • 67 Giamarellou H, Galani L, Baziaka F et al. Effectiveness of a double-carbapenem regimen for infections in humans due to carbapenemase-producing pandrug-resistant Klebsiella pneumoniae. Antimicrob Agents Chemother 2013; 57: 2388-2390
    CrossrefGoogle Scholar
  • 68 Batirel A, Balkan II, Karabay O et al. Comparison of colistin-carbapenem, colistin-sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections. Eur J Clin Microbiol Infect Dis 2014; 33: 1311-1322
    CrossrefGoogle Scholar
  • 69 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
    CrossrefGoogle Scholar
  • 70 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
    CrossrefGoogle Scholar
  • 71 Kofteridis DP, Alexopoulou C, Valachis A et al. Aerosolized plus intravenous colistin versus intravenous colistin alone for the treatment of ventilator-associated pneumonia: a matched case-control study. Clin Infect Dis 2010; 51: 1245-1247
    CrossrefGoogle Scholar
  • 72 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
    CrossrefGoogle Scholar
  • 73 Phee L, Hornsey M, Wareham DW. In vitro activity of daptomycin in combination with low-dose colistin against a diverse collection of Gram-negative bacterial pathogens. Eur J Clin Microbiol Infect Dis 2013; 32: 1291-1294
    CrossrefGoogle Scholar
  • 74 Galani I, Orlandou K, Moraitou H. Colistin/daptomycin: an unconventional antimicrobial combination synergistic in vitro against multidrug-resistant Acinetobacter baumannii. Int J Antimicrob Agents 2014; 43: 370-374
    CrossrefGoogle Scholar
  • 75 Mushtaq S, Warner M, Livermore DM. In vitro activity of ceftazidime+NXL104 against Pseudomonas aeruginosa and other non-fermenters. J Antimicrob Chemother 2010; 65: 2376-2381
    CrossrefGoogle Scholar
  • 76 Livermore DM, Mushtaq S, Warner M et al. Activities of NXL104 combinations with ceftazidime and aztreonam against carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother 2011; 55: 390-394
    CrossrefGoogle Scholar