Antibiotika und der Gastrointestinaltrakt – Update 2019

Infektiöse Durchfallerkrankungen zählen zu den häufigsten Erkrankungen weltweit und sind laut der Weltgesundheitsorganisation eine der 5 häufigsten Todesursachen [1]. Dieser Beitrag beleuchtet den Einsatz von Antibiotika bei Infektionen des Gastrointestinaltrakts und die zunehmende Resistenzentwicklung der Erreger. Die antibiotischen Therapien der einzelnen Krankheitsbilder werden detailliert dargestellt und wichtige Hygienemaßnahmen erläutert.

Kernaussagen

• Die symptomatische Therapie steht bei der Behandlung von infektiös bedingten Durchfallerkrankungen im Vordergrund. Der Nutzen einer empirischen Antibiotikatherapie ist umstritten.

• Situationen, die eine gezielte Erregerdiagnostik und evtl. auch spezifische Therapie erfordern, sind: schweres Krankheitsbild, prolongierte Diarrhö, Zeichen einer Organinvasivität des Erregers, vermuteter Ausbruch, Immunsuppression und signifikante Komorbidität.

• Die gezielte antimikrobielle Therapie von schweren infektiös bedingten Durchfallerkrankungen setzt eine differenzierte mikrobiologische Stuhluntersuchung voraus.

• Antibiotikaresistenzen – gerade bei importierten Fällen (vor allem aus Indien) – sind in zunehmendem Maße zu berücksichtigen.

• Anders sieht es bei bakteriell bedingten Infektionen von Magen, Leber, Gallenwegen oder Peritonealraum aus. Hier stellt die in der Regel empirisch verabreichte Antibiotikatherapie eine wichtige Säule im Behandlungskonzept dar.

• Im Vordergrund stehen klare Entscheidungen für eine operative Therapie (Fokussanierung), bei der die Antibiotikatherapie nur adjuvanten Charakter besitzt. Darüber hinaus sind die Kenntnis und Wertung von Erregereigenschaften wie Resistenzen und wirtseigenen Faktoren wichtig für die optimale und sichere Auswahl geeigneter Therapeutika.

Schlüsselwörter

Antibiotika - Gastrointestinaltrakt - Infektion - Diarrhö - Clostridium difficile

• Literatur

• 1 World Health Organization (WHO). Diarrhoeal disease. Im Internet: http://www.who.int/en/news-room/fact-sheets/detail/diarrhoeal-disease Stand: 15.11.2018
• 2 Lübbert C, Mutters R. Gastrointestinale Infektionen. Internist 2017; 58: 149-169
• 3 Lübbert C. Antibiotika und der Gastrointestinaltrakt. Gastroenterologie up2date 2015; 11: 161-180
• 4 Theuretzbacher U. Accelerating resistance, inadequate antibacterial drug pipelines and international responses. Int J Antimicrob Agents 2012; 39: 295-299
• 5 Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis 2001; 1: 101-114
• 6 Thielman NM. Guerrant Rl. Clinical practice. Acute infectious diarrhea. N Engl J Med 2004; 350: 38-47
• 7 Wistrom J, Jertborn M, Ekwall E. et al. Empiric treatment of acute diarrheal disease with norfloxacin: A randomized, placebo-controlled study. Swedish Study Group. Ann Intern Med 1992; 117: 202-208
• 8 Lübbert C. Antimicrobial therapy of acute diarrhoea – a clinical review. Expert Rev Anti Infect Ther 2016; 14: 193-206
• 9 Adachi JA, Ericsson CD, Jiang ZD. et al. Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico. Clin Infect Dis 2003; 37: 1165-1171
• 10 Hong KS, Kim JS. Rifaximin for the treatment of acute infectious diarrhea. Therap Adv Gastroenterol 2011; 4: 227-235
• 11 Taneja N. Changing epidemiology of shigellosis and emergence of ciprofloxacin-resistant Shigellae in India. J Clin Microbiol 2007; 45: 678-679
• 12 Vogelmann R, Ebert M. Multiresistente Erreger in der Gastroenterologie: Folgen für die Wahl des Antibiotikums. Gastroenterologe 2014; 9: 565-578
• 13 Lübbert C, Rodloff AC, Laudi S. et al. Lessons learned from excess mortality associated with Klebsiella pneumoniae carbapenemase-2-producing K. pneumoniae in liver transplant recipients. Liver Transpl 2014; 20: 736-738
• 14 Holmes AH, Moore LS, Sundsfjord A. et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 2016; 387: 176-187
• 15 European Centre for Disease Prevention and Control (ECDC). Annual Epidemiological Report for 2016: Antimicrobial consumption. Im Internet: http://ecdc.europa.eu/en/publications-data/antimicrobial-consumption-annual-epidemiological-report-2016 Stand: 15.11.2018
• 16 Robert Koch-Institut (RKI). Antibiotika Resistenz Surveillance (ARS). Im Internet: http://ars.rki.de/ Stand: 15.06.2018
• 17 Onwuezobe IA, Oshun PO, Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev 2012; (11) CD001167
• 18 Robert Koch-Institut (RKI). Salmonellose. Ratgeber für Ärzte. Im Internet: http://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Salmonellose.html Stand: 15.11.2018
• 19 Connor BA, Schwartz E. Typhoid and paratyphoid fever in travellers. Lancet Infect Dis 2005; 5: 623-628
• 20 Wain J, Hendriksen RS, Mikoleit ML. et al. Typhoid fever. Lancet 2015; 385: 1136-1145
• 21 Robert Koch-Institut (RKI). Shigellose. Ratgeber für Ärzte. Im Internet: http://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Shigellose.html Stand: 15.11.2018
• 22 Christopher PR, David KV, John SM. et al. Antibiotic therapy for Shigella dysentery. Cochrane Database Syst Rev 2010; (08) CD006784
• 23 Robert Koch-Institut (RKI). Campylobacter-Enteritis. Ratgeber für Ärzte. Im Internet: http://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Campylobacter.html Stand: 15.11.2018
• 24 Kirkpatrick BD, Tribble DR. Update on human Campylobacter jejuni infections. Curr Opin Gastroenterol 2010; 27: 1-7
• 25 Lehtopolku M, Kotilainen P, Haanpera-Heikkinen M. et al. Ribosomal mutations as the main cause of macrolide resistance in Campylobacter jejuni and Campylobacter coli. Antimicrob Agents Chemother 2011; 55: 5939-5941
• 26 Buchholz U, Bernard H, Werber D. et al. German outbreak of Escherichia coli O104:H4 associated with sprouts. N Engl J Med 2011; 365: 1763-1770
• 27 Nitschke M, Sayk F, Hartel C. et al. Association between azithromycin therapy and duration of bacterial shedding among patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4. JAMA 2012; 307: 1046-1052
• 28 Harris JB, Larocque RC, Qadri F. et al. Cholera. Lancet 2012; 379: 2466-2476
• 29 Lübbert C, John E, von Müller L. Clostridium difficile infection: guideline-based diagnosis and treatment. Dtsch Arztebl Int 2014; 111: 723-731
• 30 Lübbert C, Zimmermann L, Borchert J. et al. Epidemiology and recurrence rates of Clostridium difficile infections in Germany: a secondary data analysis. Infect Dis Ther 2016; 5: 545-554
• 31 Hensgens MP, Goorhuis A, Dekkers OM. et al. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother 2011; 67: 742-748
• 32 Von Braun A, Lübbert C. Therapie akuter und rekurrenter Clostridium-difficile-Infektionen: Was gibt es Neues?. Internist 2018; 59: 505-513
• 33 McDonald LC, Gerding DN, Johnson S. et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66: 987-994
• 34 Louie TJ, Miller MA, Mullane KM. et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011; 364: 422-431
• 35 Debast SB, Bauer MP, Kuijper EJ. et al. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 2014; 20: 21-26
• 36 Ooijevaar RE, van Beurden YH, Terveer EM. et al. Update of treatment algorithms for Clostridium difficile infection. Clin Microbiol Infect 2018; 24: 452-462
• 37 Goldenberg JZ, Yap C, Lytvyn L. et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 2017; (12) CD006095
• 38 Johnston BC, Ma SS, Goldenberg JZ. et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med 2013; 157: 878-888
• 39 Figueroa I, Johnson S, Sambol SP. et al. Relapse versus reinfection: recurrent Clostridium difficile infection following treatment with fidaxomicin or vancomycin. Clin Infect Dis 2012; 55 (Suppl. 02) S104-S109
• 40 Boero M, Berti E, Morgando A. et al. Treatment for colitis caused by Clostridium difficile: results of a randomized open study of rifaximin vs. vancomycin. Microbiol Med 1990; 5: 74-77
• 41 Gawronska A, Banasiuk M, Lachowicz D. et al. Metronidazole or rifaximin for treatment of clostridium difficile in pediatric patients with inflammatory bowel disease: a randomized clinical trial. Inflamm Bowel Dis 2017; 23: 2209-2214
• 42 Huang JS, Jiang ZD, Garey KW. et al. Use of rifamycin drugs and development of infection by rifamycin-resistant strains of Clostridium difficile. Antimicrob Agents Chemother 2013; 57: 2690-2693
• 43 Wilcox MH, Gerding DN, Poxton IR. et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med 2017; 376: 305-317
• 44 Lübbert C, Salzberger B, Mössner J. Fäkaler Mikrobiomtransfer. Internist 2017; 58: 456-468
• 45 Kao D, Roach B, Silva M. et al. Effect of oral capsule- vs. colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: a randomized clinical trial. JAMA 2017; 318: 1985-1993
• 46 Cammarota G, Ianiro G, Tilg H. et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut 2017; 66: 569-580
• 47 Lalle M. Giardiasis in the post genomic era: treatment, drug resistance and novel therapeutic perspectives. Infect Disord Drug Targets 2010; 10: 283-294
• 48 Granados CE, Reveiz L, Uribe LG. et al. Drugs for treating giardiasis. Cochrane Database Syst Rev 2012; (12) CD007787
• 49 Stanley jr. SL. Amoebiasis. Lancet 2003; 361: 1025-1034
• 50 Haque R, Huston CD, Hughes M. et al. Amebiasis. N Engl J Med 2003; 348: 1565-1573
• 51 Marth T, Raoult D. Whippleʼs disease. Lancet 2003; 361: 239-246
• 52 Feasey NA, Healey P, Gordon MA. Review article: the aetiology, investigation and management of diarrhoea in the HIV positive patient. Aliment Pharmacol Ther 2011; 34: 587-603
• 53 Allers K, Schneider T. Gastrointestinale Manifestationen der HIV-Infektion. Gastroenterologie up2date 2012; 8: 219-234
• 54 Nissapatorn V, Sawangjaroen N. Parasitic infections in HIV infected individuals: diagnostic & therapeutic challenges. Indian J Med Res 2011; 134: 878-897
• 55 Abubakar I, Aliyu SH, Arumugam C. et al. Prevention and treatment of cryptosporidiosis in immunocompromised patients. Cochrane Database Syst Rev 2007; (01) CD004932
• 56 Wright SG. Protozoan infections of the gastrointestinal tract. Infect Dis Clin North Am 2012; 26: 323-339
• 57 Lutz P, Nischalke HD, Strassburg CP. et al. Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver. World J Hepatol 2015; 7: 304-314
• 58 Jalan R, Fernandez J, Wiest R. et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol 2014; 60: 1310-1324
• 59 Navasa M, Follo A, Llovet JM. et al. Randomized, comparative study of oral ofloxacin versus intravenous cefotaxime in spontaneous bacterial peritonitis. Gastroenterology 1996; 111: 1011-1017
• 60 Chavez-Tapia NC, Soares-Weiser K, Brezis M. et al. Antibiotics for spontaneous bacterial peritonitis in cirrhotic patients. Cochrane Database Syst Rev 2009; (01) CD002232
• 61 Fernández J, Navasa M, Planas R. et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology 2007; 133: 818-824
• 62 Ginés P, Rimola A, Planas R. et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology 1990; 12: 716-724
• 63 Fernández J, Acevedo J, Castro M. et al. Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology 2012; 55: 1551-1561
• 64 Bodmann KF. Expertenkommission der Infektliga. Komplizierte intraabdominelle Infektionen: Erreger, Resistenzen. Chirurg 2010; 81: 38-49
• 65 Doklestić SK, Bajec DD, Djukić RV. et al. Secondary peritonitis – evaluation of 204 cases and literature review. J Med Life 2014; 7: 132-138
• 66 Solomkin JS, Ristagno RL, Das AF. et al. Source control review in clinical trials of anti-infective agents in complicated intraabdominal infections. Clin Infect Dis 2013; 56: 1765-1773
• 67 Peery AF, Dellon ES, Lund J. et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 2012; 143: 1179-1187
• 68 Chabok A, Pahlmann L, Hjern F. et al. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg 2012; 99: 532-539
• 69 Fuks D, Cossé C, Régimbeau JM. Antibiotic therapy in acute calculous cholecystitis. J Visc Surg 2013; 150: 3-8
• 70 Ambe P, Weber SA, Christ H. et al. Cholecystectomy for acute cholecystitis. How time-critical are the so called “golden 72 hours”? Or better “golden 24 hours” and “silver 25–72 hour”? A case control study. World J Emerg Surg 2014; 9: 60
• 71 Mayumi T, Okamoto K, Takada T. et al. Tokyo Guidelines 2018: management bundles for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci 2018; 25: 96-100
• 72 Regimbeau JM, Fuks D, Pautrat K. et al. Effect of postoperative antibiotic administration on postoperative infection following cholecystectomy for acute calculous cholecystitis: a randomized clinical trial. JAMA 2014; 312: 145-154
• 73 Mazeh H, Mizrahi I, Dior U. et al. Role of antibiotic therapy in mild acute calculous cholecystitis: a prospective randomized controlled trial. World J Surg 2012; 36: 1750-1759
• 74 Mosler P. Management of acute cholangitis. Gastroenterol Hepatol (NY) 2011; 7: 121-123
• 75 Gravito-Soares E, Gravito-Soares M, Gomes D. et al. Clinical applicability of Tokyo guidelines 2018/2013 in diagnosis and severity evaluation of acute cholangitis and determination of a new severity model. Scand J Gastroenterol 2018; 53: 329-334
• 76 Lübbert C, Wiegand J, Karlas T. Therapy of liver abscesses. Viszeralmedizin 2014; 30: 334-341
• 77 Malfertheiner P, Chan FK, McColl KE. Peptic ulcer disease. Lancet 2009; 374: 1449-1461
• 78 Fischbach W, Malfertheiner P, Lynen Jansen P. et al. S2k-Leitlinie Helicobacter pylori und gastroduodenale Ulkuskrankheit. Z Gastroenterol 2016; 54: 327-363
• 79 Banks PA, Freeman ML. Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006; 101: 2379-2400
• 80 Villatoro E, Mulla M, Larvin M. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev 2010; (05) CD002941
• 81 Hoffmeister A, Mayerle J, Beglinger C. et al. [S3-Consensus guidelines on definition, etiology, diagnosis and medical, endoscopic and surgical management of chronic pancreatitis German Society of Digestive and Metabolic Diseases (DGVS)]. Z Gastroenterol 2012; 50: 1176-1224
• 82 Behnke M, Aghdassi SJ, Hansen S. et al. The prevalence of nosocomial infection and antibiotic use in German hospitals. Dtsch Arztebl Int 2017; 114: 851-857
• 83 Ott E, Saathoff S, Graf K. et al. The prevalence of nosocomial and community acquired infections in a university hospital: an observational study. Dtsch Arztebl Int 2013; 110: 533-540
• 84 Maechler F, Peña Diaz LA, Schröder C. et al. Prevalence of carbapenem-resistant organisms and other Gram-negative MDRO in German ICUs: first results from the national nosocomial infection surveillance system (KISS). Infection 2015; 43: 163-168
• 85 Remschmidt C, Schröder C, Behnke M. et al. Continuous increase of vancomycin resistance in enterococci causing nosocomial infections in Germany – 10 years of surveillance. Antimicrob Resist Infect Control 2018; 7: 54
• 86 Pittet D, Hugonnet S, Harbarth S. et al. Effectiveness of a hospital-wide programme to improve compliance with hand hygiene. Infection Control Programme. Lancet 2000; 356: 1307-1312
• 87 Allegranzi B, Gayet-Ageron A, Damani N. et al. Global implementation of WHOʼs multimodal strategy for improvement of hand hygiene: a quasi-experimental study. Lancet Infect Dis 2013; 13: 843-851