Emergence of rifampin-resistant staphylococci after rifaximin administration in cirrhotic patients

Objectives Rifaximin, a poorly absorbed antibiotics, has gut-specific therapeutic effects. Although frequently prescribed to manipulate intestinal luminal bacterial population in various diseases, the possible induction of antibacterial cross-resistance to a target pathogen is a major concern in long-term rifaximin administration. We aimed to evaluate whether rifampin-resistant staphylococci could evolve after rifaximin treatment in cirrhotic patients. Method A total of 25 cirrhotic patients who were administered rifaximin for the prevention of hepatic encephalopathy were enrolled. Swabs from both hands and the perianal skin were acquired on day 0 (before rifaximin treatment), period 1 (1–7 weeks after treatment), and period 2 (8–16 weeks after treatment) the staphylococcal strain identification and rifampin-resistance testing. Results A total of 198 staphylococcal isolates from 15 species were identified. Staphylococcus epidermidis was isolated most frequently, and Staphylococcus haemolyticus was the most common resistant species both from hands and perianal skin. Eleven patients (44.0%) developed rifampin-resistant staphylococcal isolates in period 1. Among these patients, only six (54.5%) were found to have rifampin-resistant isolates in period 2, with no significant infectious events. Rifampin-resistant staphylococcal isolates were more frequently found in perianal skin than from the hands. No patients acquired a newly resistant strain in period 2. Conclusions About one-half of cirrhotic patients in this study developed rifampin-resistant staphylococcal isolates after rifaximin treatment. Although the resistant strains were no longer detected in about half of the patients in the short-term, the long-term influence of this drug treatment should be determined.

[1]  E. Padilla,et al.  Rifampin Resistance in Staphylococci after Rifaximin Intake for Surgical Prophylaxis in Elective Colorectal Surgery , 2018, Antimicrobial Agents and Chemotherapy.

[2]  P. Schoenfeld,et al.  Repeat Treatment With Rifaximin Is Safe and Effective in Patients With Diarrhea-Predominant Irritable Bowel Syndrome. , 2016, Gastroenterology.

[3]  J. Henricson,et al.  Staphylococcus aureus colonization related to severity of hand eczema , 2016, European Journal of Clinical Microbiology & Infectious Diseases.

[4]  A. Ford,et al.  Rifaximin for the treatment of diarrhea-predominant irritable bowel syndrome , 2016, Expert review of gastroenterology & hepatology.

[5]  P. G. Choe,et al.  Clinical and Epidemiological Factors Associated with Methicillin Resistance in Community-Onset Invasive Staphylococcus aureus Infections: Prospective Multicenter Cross-Sectional Study in Korea , 2014, PloS one.

[6]  M. Hoenigl,et al.  Bacteraemia with rifampin-resistant Staphylococcus aureus and the potential role of cross-resistance between rifampin and rifaximin. , 2014, The Journal of infection.

[7]  A. Sanyal,et al.  Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy. , 2014, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[8]  A. Trampuz,et al.  High Activity of Fosfomycin and Rifampin against Methicillin-Resistant Staphylococcus aureus Biofilm In Vitro and in an Experimental Foreign-Body Infection Model , 2014, Antimicrobial Agents and Chemotherapy.

[9]  Mi-Sung Kim,et al.  The Effect of Rifaximin on Gut Flora and Staphylococcus Resistance , 2013, Digestive Diseases and Sciences.

[10]  D. Farrell Rifaximin in the Treatment of Irritable Bowel Syndrome: Is There a High Risk for Development of Antimicrobial Resistance? , 2013, Journal of clinical gastroenterology.

[11]  H. Dupont,et al.  Rifaximin Resistance in Escherichia coli Associated with Inflammatory Bowel Disease Correlates with Prior Rifaximin Use, Mutations in rpoB, and Activity of Phe-Arg-β-Naphthylamide-Inhibitable Efflux Pumps , 2012, Antimicrobial Agents and Chemotherapy.

[12]  Xin Zhou,et al.  Molecular characterization of rifampicin-resistant Staphylococcus aureus isolates in a Chinese teaching hospital from Anhui, China , 2012, BMC Microbiology.

[13]  Suzanna Gim,et al.  Rifaximin: new therapeutic indication and future directions. , 2011, Clinical therapeutics.

[14]  J. Marimón,et al.  Epidemiological and molecular aspects of rifampicin-resistant Staphylococcus aureus isolated from wounds, blood and respiratory samples. , 2011, The Journal of antimicrobial chemotherapy.

[15]  M. Otto Staphylococcus colonization of the skin and antimicrobial peptides. , 2010, Expert review of dermatology.

[16]  Jane W. Marsh,et al.  High frequency of rifampin resistance identified in an epidemic Clostridium difficile clone from a large teaching hospital. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  D. Gerding,et al.  Rifampin and Rifaximin Resistance in Clinical Isolates of Clostridium difficile , 2008, Antimicrobial Agents and Chemotherapy.

[18]  A. Gasbarrini,et al.  High dosage rifaximin for the treatment of small intestinal bacterial overgrowth , 2007, Alimentary pharmacology & therapeutics.

[19]  C. Scarpignato,et al.  Rifaximin, a Poorly Absorbed Antibiotic: Pharmacology and Clinical Potential , 2005, Chemotherapy.

[20]  H. Dupont,et al.  Rifaximin: a novel antimicrobial for enteric infections , 2005 .

[21]  B. Lowe,et al.  Therapy of travelers’ diarrhea with rifaximin on various continents , 2003, American Journal of Gastroenterology.

[22]  A. Marchese,et al.  In vitro Activity of Rifaximin, Metronidazole and Vancomycin against Clostridium difficile and the Rate of Selection of Spontaneously Resistant Mutants against Representative Anaerobic and Aerobic Bacteria, Including Ammonia-Producing Species , 2000, Chemotherapy.

[23]  T. Wichelhaus,et al.  Molecular Characterization of rpoBMutations Conferring Cross-Resistance to Rifamycins on Methicillin-Resistant Staphylococcus aureus , 1999, Antimicrobial Agents and Chemotherapy.

[24]  S. Kohno,et al.  Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis. , 1998, The Journal of antimicrobial chemotherapy.

[25]  P. Gangadharam,et al.  Contribution of rpoB Mutations to Development of Rifamycin Cross-Resistance in Mycobacterium tuberculosis , 1998, Antimicrobial Agents and Chemotherapy.

[26]  P. Gionchetti,et al.  Rifaximin systemic absorption in patients with ulcerative colitis , 1998, European Journal of Clinical Pharmacology.

[27]  E. Debbia,et al.  Selection of rifampicin-resistant Mycobacterium tuberculosis does not occur in the presence of low concentrations of rifaximin. , 1997, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[28]  P. M. Terry,et al.  Rapid development of ciprofloxacin resistance in methicillin-susceptible and -resistant Staphylococcus aureus. , 1991, The Journal of infectious diseases.

[29]  E. Marchi,et al.  Antimycobacterial activity of rifaximin (L/105) in experimental tuberculosis in the guinea pig. , 1984, Chemioterapia : international journal of the Mediterranean Society of Chemotherapy.

[30]  P. Sensi History of the development of rifampin. , 1983, Reviews of infectious diseases.

[31]  L. Frontali,et al.  Effect of Rifamycin on Protein Synthesis , 1965, Nature.

[32]  Firdaus Rana RIFAMPICIN- AN OVERVIEW , 2013 .

[33]  K. Wellington,et al.  Rifaximin , 2012, Drugs.

[34]  E. Leitner,et al.  Rifaximin intake leads to emergence of rifampin-resistant staphylococci. , 2011, The Journal of infection.

[35]  Herbert L. DuPont,et al.  Reviews Of Anti‐infective Agents: Rifaximin: A Novel Nonabsorbed Rifamycin for Gastrointestinal Disorders , 2006 .

[36]  D. Dubourg,et al.  Pharmacokinetic study of rifaximin after oral administration in healthy volunteers. , 1994, International journal of clinical pharmacology research.