Abstract: Although, positive role of special bacteria in induction of Inflammatory Bowel Disease (IBD) including Ulcerative Colitis (UC) and Crohn’s Disease (CD) have been demonstrated in several studies but the consensus on etiology of IBD and beneficial effect of antibiotics has not been reached yet. And, also, no well-designed clinical trials in this regard have been done yet. This review focuses on various clinical trials which have been done in according to beneficial use of antibiotics in UC and CD from 1978 to date. For this purpose, all electronic databases such as PubMed, Scopus, Google Scholar and Cochrane library were searched. The results of clinical trials suggested that metronidazole, ciprofloxacin or the combinations of these antibiotics are effective in CD. However, ciprofloxacin is the first choice, because it has good coverage on gram negative and anaerobic bacterium which plays an important role in CD. However, there is a controversy on the use of antibiotics in UC and the efficacy of them in long-term treatment of UC is still in doubt. Various antibiotics such as anti-tuberculosis, macrolides (clarithromycin), fluoroquinolones, 5-nitroimidazoles, rifaximin, rifamycin derivatives (rifampin), aminoglycosides (tobramycin), rifabutin, clofazimine, tetracyclines (tetracycline and doxycycline) and vancomycin have been under attention of researchers in the recent years. Furthermore, other antibiotics with lower cost and adverse effects, effectiveness and availability are the third generation of cephalosporins and gentamicin and also penicillin or clindamycin that should be evaluated in future studies.
INTRODUCTION
Inflammatory bowel diseases: Inflammatory Bowel Diseases (IBD), including Crohn’s Disease (CD) and Ulcerative Colitis (UC) are characterized by gastrointestinal (GI) inflammation and some extra-intestinal indicators such as liver complications, arthritis, skin manifestations and eye problems (Williams et al., 2008). Site and nature of the inflammatory changes are the main differences between CD and UC (Table 1), in which CD can attack any portion of the GI tract from mouth to anus (skip lesions) and affect the whole bowel wall but a majority of the cases start in the terminal ileum, while, UC is restricted to the mucosa and epithelial lining of the gut, colon and the rectum (Walsh et al., 2011).
IBD considered in the past in the developed countries but their prevalence within developing countries has been increasing in the recent years. Also, if the prevalence of CD and UC is quite similar in developed countries such as North America, South America, Europe, Australia and New Zealand, however, there may be differences in developing countries such as Pakistan and India in which much less extra intestinal disease with both UC and CD has been reported. In Pakistan, few patients have perianal or fistulizing disease, however, the age of presentation of CD in India is a decade later than in the West, colonic involvement is also more common and fistulization appears less common in India (Bernstein et al., 2010). The incidence of IBD peaks in two age groups: mainly the third decade, with a smaller peak in the seventh decade.
| Table 1: | Summary of the main differences between ulcerative colitis (UD) and Crohn’s disease (CD) |
In adults, the prevalence of CD is higher among women but equal in both genders for UC (Kappelman et al., 2007). Furthermore, the incidence of CD varies from 0.7 to 14.6 individuals per 100,000 inhabitants, whereas the prevalence of UC varies from 1.5-24.5 individuals per 100,000 inhabitants. About 1.4 million people in the United States (US) suffer from IBD (Carbonnel et al., 2009; Lakatos, 2006). Therefore, different treating guideline should be considered in various around of the world that needs further studies.
IBD can induce significant intestinal signs including diarrhea typically having blood and mucus, abdominal pain, vomiting and weight loss (Bernstein et al., 2010). Therefore, IBD patients are usually incapable to do their daily works, common relations and experiences (Al-Qabandi et al., 2011). Although, the etiology of IBD still remains unknown but the role of genetic, environment, immune response dysregulation, intestinal microbes and Oxidative Stress (OS) have been already demonstrated (Bernstein et al., 2010; Rezaie et al., 2007; Salari and Abdollahi, 2009). Some studies suggest that infection is the main etiology but distinctive microbes have not been isolated yet (Krisner, 1988). It has been suggested that CD parallels with Johne’s disease in cattle which is due to Mycobacterium avium subspecies Paratuberculosis (MAP). However, today this hypothesis is not acceptable because MAP is not the only bacterium that is associated with CD and other bacterial strains including Yersinia enterocolitica, Chlamydia trachomatis, Listeria and cell wall deficient pseudomonas are also important (Dalziel, 1913; Sartor, 2005). These organisms as a cause for IBD are still challenging and the evidences are poor but it is still believed that CD and UC are resulted from an irregular immunological reaction to gut microbiota in susceptible host (Abraham and Cho, 2009). It has been demonstrated that the concentration of intestinal microbes in IBD is higher than normal and increases progressively with the severity of the disease (Rahimi et al., 2007a). This is important that bowel inflammation does not occur without change in gut bacterial flora as proved in experimental models of colitis (Sellon et al., 1998). In the healthy gut, there is a cooperative connection between the host and the gut bacterial flora in which exposure leads to down-regulation of inflammatory genes and inhibiting the immune response of the gut to other pathogens (Hanauer, 2006). Metronidazole, ciprofloxacin or their combinations are commonly used by most clinicians as first-line treatment in patients with perianal disease, in combination with surgical drainage of abscesses (Baumgart, 2012). Therefore, the beneficial role of antibiotics in IBD has been discussed in this review. For this purpose, databases of PubMed, Google Scholar and Scopus were searched from 1978 to February 2012 for clinical trials conducted on UC and CD patients. The search terms were inflammatory bowel disease, IBD, ulcerative colitis, UC, Crohn’s disease, CD, antibiotic, antimicrobial agents, antiparasitic agents, antimycobacterials agents, β-lactams, penicillins, cephalosporins, ketolides, carbapenems, tetracyclines, macrolides, aminoglycosides, nitroimidazoles and fluroquinolones. The search strategy was limited to clinical trials and English language.
Pathophysiology of IBD: The pathology of CD is characterized by an intermittent inflammation and skips lesions of transmural bowel wall that can develop to fibrosis, strictures and fistulas. Though, these lesions can occur in any area of the GI tract, they usually take place within the ileum. UC is restricted to the colon and rectum and it involves inflammation of the bowel wall mucosa and submucosa and the lesions can range as far as the cecum (Walsh et al., 2011).
While the etiology of IBD is not well known, however, the role of genetic predisposition, environmental triggers, bacteria, Oxidative Stress (OS) and dysregulation of the immune response cannot be ignored (Rezaie et al., 2007; Hanauer, 2006; Danese et al., 2004). Studies have determined that genetic background can predispose a subset of IBD patients to the progress of disease (Mathew and Lewis, 2004). Studies on genome have discovered more than 40 susceptibility loci for IBD, some of them are distinct for UC or CD and some of them are linked with both (Hakonarson and Grant, 2009). The IBD1 gene encoding the protein NOD2 (also called CARD15) in CD, OCTN1/2 within the IBD5 locus in CD and UC, ATG16L in CD, IRGM1 in CD and IL23R in CD and UC can be noted (Mayer, 2010). Studies have indicated that defects in NOD2 or OCTN1/2 affect the ability of the host to restrict and eliminate microbes that gain access to gut tissue (Mathew and Lewis, 2004). Interestingly inflammation and lesions generally occur in intestinal regions with the highest bacterial concentration and the patients with IBD typically have greater numbers of adherent bacteria compared to normal subject (Rahimi et al., 2007a; Thompson-Chagoyan et al., 2005). Intestinal lamina propria contains intestinal epithelia and inflammatory cells which make available an innate immune protection for the GI tract that equilibrates the requirement for immune tolerance of microbiota with the defense against microbial pathogens. Dysfunction at the epithelial border (for example disturbed mucus layer, imperfect tight junctions) may cause failure of tolerance. This dysfunction can trigger innate immune cells, causing them to secrete several cytokines and chemokines to the host commensal microbiota (Abraham and Cho, 2009; Mayer, 2010). It is thought that other immunological factors downstream antigen recognition including over-activity of effector lymphocytes and pro-inflammatory cytokines, failure of regulatory lymphocytes and anti-inflammatory cytokines to control inflammation and resistance of T-cells to apoptosis (Bamias et al., 2005). Several studies have demonstrated that Toll-like Receptors (TLRs) represent key mediators of innate host defense in the intestine, involved in maintaining mucosal as well as commensal homeostasis. Recent studies in various experimental models of colitis have helped to reveal the mechanistic importance of TLR dysfunction in IBD pathogenesis. It has been demonstrated that environment, genetics and host immunity form a multidimensional and highly interactive regulatory triad controls TLR function in the intestinal mucosa. Imbalance between these factors may promote aberrant TLR signaling, significantly contributing to acute and chronic intestinal inflammatory processes in IBD (Cario, 2010).
Drugs used in the treatment of IBD: Medical treatment of IBD is rapidly developing with introduction of new biological agents that are likely to modify future therapeutic approaches (Walsh et al., 2011). Main objectives of current drug treatments are to maintain the patient in remission and ameliorate the disease’s secondary effects, rather than modifying or reversing the underlying pathogenic mechanism (Pithadia and Jain, 2011).
Many drugs and drug classes are available to manage both UC and CD, including 5-amino salicylate (5-ASA) (Nikfar et al., 2009; Rahimi et al., 2009a), corticosteroids (Rahimi et al., 2007b), immunosuppressive agents and anti tumor necrosis factor (TNF-α) (Rahimi et al., 2007c; Nikfar et al., 2010a; Amini-Shirazi et al., 2009), antioxidants (Ebrahimi et al., 2008; Khoshakhlagh et al., 2007), probiotics (Rahimi et al., 2008a; Elahi et al., 2008; Nikfar et al., 2010b), antibiotics (Loftus et al., 2008; Feagan et al., 2007) and some herbal medicines as supplemental therapy (Rahimi et al., 2009b; Rahimi et al., 2010; Abdolghaffari et al., 2010; Hasani-Ranjbar et al., 2009).
For management of mild to moderate IBD, salicylates are used although they are not without adverse effects. For management of moderate to severe IBD, glucocorticoides and immunosuppressive drugs are usually used (Rahimi et al., 2009b). New biological agents target TNF and adhesion proteins for inflammatory cell translocation. However, anti-TNF therapy may increase the risk of infection (Rutgeerts et al., 2009; Lakatos and Miheller, 2010; Nikfar et al., 2010b) and thus must be used with many caution and as the last options. Antibiotics are recommended in CD patients with perianal disease and fistulas and also in the treatment of C difficile infection (Prantera and Scribano, 2009). Although, antibiotics are often recommended to induce remission in mild to moderate CD, they are also effective for handling fistulas, bacterial overgrowth, abdominal abscesses and infections around the anus and genital areas (Pithadia and Jain, 2011).
Intestinal microflora can be changed by administering antibiotics and prebiotics that contain three species of Bifidobacterium, 4 species of Lactobacillus and Streptococcus salivarius (Prantera and Scribano, 2009; Travis et al., 2006) or probiotics (beneficial bacteria) or the combination of these methods (synbiotics). Studies support the protective role of probiotics and prebiotics in IBD or its complications (Salari et al., 2012; Ghasemi-Niri et al., 2011; Hedin et al., 2010; Nikfar et al., 2008; Rahimi et al., 2008b; Alivanis et al., 2010; Jamalifar et al., 2011) and even in irritable bowel syndrome (Hosseini et al., 2012) and therefore, they can be more effective in combination to antibiotics.
Generally, we can divide the treatment and management of IBD into five steps:
| • | Administration of oral aminosalicylate including sulfasalazine, mesalamine, balsalazide and olsalazine |
| • | Antibiotics including ciprofloxacin, metronidazole, antituberculosis therapy, macrolides, fluoroquinolones, 5-nitroimidazoles and rifaximin (alone or in combination) can be used. However, the adverse effects of antibiotics including nausea, anorexia, diarrhea and monilial (candidal) infections, peripheral neuropathy (mostly observed with metronidazole) should be concerned in each individual |
| • | Administration of corticosteroids such as intravenous (i.v.) methylprednisolone oral or rectal budesonide (Alivanis et al., 2010; Li et al., 2008) can be considered |
| • | Administration of immune modifiers including 6-mercaptopurine or azathioprine (1-2 mg kg-1 day-1), infliximab (5 mg kg-1 at 0, 2 and 6 weeks, followed by 5 mg kg-1 every 8 weeks thereafter), adalimumab and natalizumab should be considered (Ford et al., 2011; Lichtenstein et al., 2006) with adequate care |
| • | Administration of methotrexate (12.5-25 mg week-1, p.o. or IM), thalidomide (50-300 mg day-1, p.o.) and IL-11 (1 mg week-1, SC) in CD and cyclosporine A (i.v., 2-4 mg kg-1 day-1) butyrate enema (rectal, 200 mL day-1) and heparin (SC, 20,000 U day-1) in UC (Lichtenstein et al., 2006) should be considered |
The common bacteria in IBD: Several studies have shown differences in bacterial diversity between healthy individuals and IBD patients. Overall the result of these studies have shown evidence for a decline in bacterial diversity, an increase in fungal and a decrease in methanogen diversity in GI tract of IBD patients but they could not identify specific bacterial or fungal communities for this disease yet (Scanlan and Marchesi, 2008; Franke et al., 2008; Frank et al., 2007; Kuehbacher et al., 2006; Ott et al., 2008; Scanlan et al., 2008). Increase of Enterobacteria in patient with IBD has been previously shown (Kotlowski et al., 2007). Mycobacterium avium subsp. paratuberculosis, Chlamydia pneumoniae, Saccharomyces cerevisiae, Clostridium difficile, Campylobacter jejuni and adherent invasive Escherichia coli (E. coli) have all been shown to be potentially infectious organisms in the development of IBD (Reiff and Kelly, 2010; Berg et al., 2012; O’Hara et al., 2012). Other bacteria which have a positive role in induction of IBD in patients are indicated in Table 2. Some studies have shown that an increase in mucosal populations of adherent invasive E. coli which were found prevalent in CD is the strongest evidence of a specific pathogen in human IBD (Sasaki et al., 2007; Rhodes, 2007; Darfeuille-Michaud et al., 2004).
Commensal microorganisms live with their hosts and are essential for development of a healthy gut. The role of commensal bacteria is to facilitate digestion, absorption and storage of nutrients as well as protection against pathogen colonization through competition for nutrients, secretion antimicrobial substances and micro-niche exclusion. In addition, commensal bacteria promote angiogenesis and development of the intestinal epithelium and have been shown necessary for normal development and function of the immune system (Artis, 2008). Overactive immune response towards commensal bacteria causes initiation and development of IBD. In fact, microbial balance is crucial to protect against bad gram negative pathogens, such as E. coli and Pseudomonas (Reiff and Kelly, 2010). Consequently, strong evidence from animal models recommends that the development of IBD is impossible in the presence of normal enteric flora (Triantafillidis et al., 2011).
Application of antibiotics in IBD: Most of studies that have indicated the role of special bacteria in induction of IBD, are not well designed. Most of existing clinical trials had small sample size (16 to 213 subjects), short duration (2 to 24 weeks) and methodological bias. In patients with IBD, the rate of Bacteroides, Escherichia coli and Enterococci increase in the bowel while Lactobacilli and Bifidobacteria decrease that necessitate use of antibiotics (Triantafillidis et al., 2011; Pithadia and Jain, 2011).
Some studies demonstrated that a decrease in mucosal peptide antibiotics (defensins) could be involved in the pathogenesis of IBD. Defensins are antimicrobial peptides made at a range of epithelial exteriors that their highest function is to retain equilibrium between protection from pathogens and tolerance to normal flora. It has been advised that diminished expression of defensins compromises host immunity resulting in inflammation. This deficiency may be due to change in the intracellular transcription of NF-κB and the intracellular peptidoglycan receptor NOD2. The beneficial effect of antibiotics in CD patients exhibits the theory of the presence of weakened mucosal antibacterial motion. Although recent studies suggest that defensin deficiency might be a result of mucosal surface damage in inflammatory course, it still needs to be clarified by further studies (Triantafillidis et al., 2011; Wehkamp et al., 2005; Ramasundara et al., 2009; Fellerman et al., 2003).
Generally, antibiotic can be used in IBD for numerous aims including as an assistant in the company of other medicines for handling of active IBD, as a management for a definite impediment of CD and as prophylaxis for disease relapse in postoperative CD (Triantafillidis et al., 2011). The conditions that use of antibiotics cannot be declined include (C. difficile and so forth) (Sartor, 2004):
| • | Phlegmon of intra-abdominal, hepatic or perianal abscesses and inflammation |
| • | Fistulae (perianal, enteroenteric, enterocolonic, enterocutaneous and enterovesical) |
| • | Anal fissures |
| • | Small intestinal bacterial overgrowth secondary to strictures, loss of ileocecal valve, enteroenteric and enterocolonic fistulae |
| • | Postoperative infections |
| • | Toxic megacolon |
| • | Secondary infections |
| Table 2: | Possible bacterium which has a positive role in IBD |
| AM: Amikacin, GM: Gentamicin, CTX: Cotrimoxazol, AMP: Ampicillin, MTZ: Metronidazole, VCM: Vancomycin, RFX: Rifaximin, FDX: Fidaxomicin, CDAD: Clostridium difficile associated diarrhea, ND: Not determined, ERM: Erythromycin, RFB: Rifabutin, MAP: Mycobacterium avium subspecies paratuberculosis, DOX: Doxycycline, CLR: Clarithromycin, TE: Tetracycline, AZ: Azathioprine, AMG: Aminoglycoside, AMC: Amoxicillin-clavulanic acid, FQ: Fluoroquinolones, CTX: Ceftriaxone, CAM: Chloramphenicol, CIP: Ciprofloxacin, CL: Clindamycin, PEN: Penicillin, NRF: Norfloxacin, CET: Cephalotin, AMX: Amoxicillin | |
Mechanisms of action of antibiotics in IBD include (Sartor, 2004):
| • | Reduction of luminal and adherent mucosal bacterial foci |
| • | Selective elimination of pathogenic luminal bacteria |
| • | Reduction of tissue invasion, microabscesses and secondary bacterial proliferation adjacent to mucosal ulcers and fistulae |
| • | Reduction of bacterial translocation and systemic dissemination of possible bacteria |
The use of antibiotics as principal or adjuvant treatment of UC and CD is still debated. Even though the systemic use of antibiotics against IBD can act against enteric commensal bacteria but controlled clinical trials support use of these agents (Sartor, 2004).
Diverse factors may be measured in IBD clinical trials include CD activity index (CDAI) and Serum Orosomucoid (SO) which can be measured to estimate the improvement of disease activity (mean CDAI; 217; range, 160-305) (Colombel et al., 1999). Other factors include median pre-treatment Harvey Bradshaw index (HBI) (9; range 5-16) and median serum C-reactive protein (CRP) (21.5 mg L-1; range <5-117) and production of provocative cytokines (Leiper et al., 2000).
Antibiotics in CD; current clinical trials: In recent times, several clinical trials have been published on the use of broad-spectrum antibiotics in CD patients. The antibiotic used so far in patients with CD include metronidazole, rifaximin, clarithromycin, ciprofloxacin, clofazimine and anti-tuberculosis drugs. Ciprofloxacin and metronidazole or their combination are considered as standard for prompting remission in CD while ciprofloxacin is the first choice because it has good coverage on gram negative and anaerobic bacteria such as E. coli (Sreedhar et al., 2008). A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) by Khan et al. (2011) showed the benefit of antibiotics in treatment of IBD. They were effective in both remission of active CD (Relative Risk (RR) of active disease not in remission was 0.85) and conservation of CD (RR of relapse was 0.62) (Khan et al., 2011). Anti-tuberculosis, macrolides, fluroquinolones, 5-nitroimidazoles, rifaximin and rifamycin derivatives were tested in this study (Khan et al., 2011). Cotrimoxazole and tetracycline are other antibiotics were also used for CD (Triantafillidis et al., 2011).
As we mentioned in Table 3, rifaximin as a rifamycin analog with a broad spectrum of activity in form of rifaximin-extended intestinal release has been used in CD and the results showed improvement in remission as CDAI reduced. Also metronidazole was used in CD as monotherapy or in combination with ciprofloxacin and cotrimoxazole in several clinical trials successfully and led to remission and decrease of CDAI. Results of the clinical trials demonstrated that ciprofloxacin is an effective drug in a proportion of patients with active CD mainly located in the colon. Clarithromycin as a broad-spectrum antibiotic has been used in CD but it was found ineffective in active CD. It is notable that use of clarithromycin in combination with rifabutin has been good in decreasing CDAI. Although, it has been shown that antituberculosis compounds are ineffective in CD but rifabutin in combination with clofazimine and clarithromycin reduced inflammation in CD.
Further clinical trial studies about antibiotic therapy in CD are summarized in Table 3.
Antibiotics in UC; current clinical trials: In comparison to CD, there are a few studies about the advantageous of antibiotics in UC where they seem ineffective for long-term treatment (Table 1) in spite of implicating of bacteria such as Enterococci, Peptostreptococci and Enterobacteria which live on the lining of the bowel being involved in UC. The failure of antibiotics may possibly return to poor identification of involved bacteria in UC and unsuitable pick of antibiotics. Nevertheless, most of studies have reported the benefit of ciprofloxacin, metronidazole and tobramycin in UC (Mantzaris et al., 1994, 2004; Madden et al., 1994; Chiba et al., 2011).
As we mentioned in Table 4, use of amoxicillin in combination with tetracycline and metronidazole in UC improved clinical symptoms, reduced Clinical Activity Index (CAI) and retained disease in remission. Furthermore, use of amoxicillin with clavulanic reduced production of inflammatory cytokines. Ciprofloxacin has been investigated in patients with UC with diverse results and needs further studies but in overall it seems effective. Rifaximin was also studied in patients with UC and showed no significant differences in clinical efficacy however it improved stool frequency, rectal bleeding and sigmoidoscopic score.
| Table 3: | Summary of clinical trials of antibiotic therapy in CD |
| RFX-EIR: Rifaximin-extended intestinal release, PO: Per oral, IV: Intravenous, N: Number of patients, AMX: Amoxicillin, TE: Tetracycline, MTZ: Metronidazole, CIP: Ciprofloxacin, MTX: Methotrexate, 5-ASA: Aminosalicylates, CS: Cyclosporin, IFX: Infliximab, AZ: Azathioprine, 6-MP: 6-mercaptopurine, ND: Not determined, MMF: Mycophenolate mofetil, PDN: Prednisolone, BUD: Budesonide, RFX: Rifaximin, CLR: Clarithromycin, OLZ: Olsalazine, NAG: N-acetyl glucosamine, BS: Bismuth subcitrate, RFB: Rifabutin, CFZ: Clofazimine, MP: Methylprednisolone, MO: microorganism, ETB: Ethambutol, HBI: Harvey Bradshaw index, CDAI: Crohn’s disease activity index, RFP: Rifampicin, CLO: Clofazimine, INH: Isoniazid, DDS: Dapsone, FA: Fusidic acid (an antibiotic with T-cell specific immunosuppressive effects similar to those of cylosporin): VN: Vivonex, FM: Framycetin, COL: Colistin, NYS: Nystatin, SSZ: Sulfasalazine, CTX: Cotrimoxazol | |
| Table 4: | Summary of clinical trials of antibiotic therapy in UC |
| PO: Per oral, IV: Intravenous, N: Number of patients, SD: Study design, AMX: Amoxicillin, TE: Tetracycline, MTZ: Metronidazole, CAI: Clinical activity index, CIP: Ciprofloxacin, PDN: Prednisolone, HCT: Hydrocortisone, SSZ: Sulfasalazine, RFX: Rifaximin, AMC: Amoxicillin-clavulanic acid, MP: Methylprednisolone, BMZ: betamethasone, OLZ: Olsalazine, TOB: Tobramycin, VCM: Vancomycin, MIP-1: Macrophage inflammatory protein-1, CRP: C-reactive protein, IL: interleukin, HBT: HBT (hydrogen breath test) is a simple and non-invasive test for clinical diagnosis of IBD patients which is performed after a short period of fasting (typically 8–12 hours), EC: enteric-coated | |
Investigations demonstrated that use of metronidazole in UC in conjunction with corticosteroids produced no better results when compared with placebo plus corticosteroids in inducing remission. It was reported that use of metronidazole in combination with tobramycin showed no significant improvement in remission rate.
Further clinical trials about antibiotic therapy in UC are summarized in Table 4.
CONCLUSIONS
Taking collectively, undesirable effects of aerobic and anaerobic bacteria in etiology of IBD cannot be neglected (Artis, 2008) and thus it is not surprising to see usefulness of antibiotics in active UC or CD and also in relapsing quiescent CD (Pineton de Chambrun et al., 2008). Antibiotics when used with 5-ASAs or corticosteroids or probiotics or immunosuppressive showed better effects than monotherapy. Metronidazole, ciprofloxacin, anti tuberculosis or the combinations of these antibiotics seem effective in CD. In UC, concurrent use of amoxicillin, tetracycline and metronidazole keeps patients in remission much better than monotherapy. New antibiotics such as anti-tuberculosis, macrolides clarithromycin, fluroquinolones, 5-nitroimidazoles, rifaximin, rifamycin derivatives (rifampin), aminoglycosides (tobramycin), rifabutin, clofazimine, tetracyclines (tetracycline and doxycycline) and vancomycin have shown some benefits in UC and CD. Up to now, most of supports go to use of ciprofloxacin and metronidazole. Rifaximin has also received good supports in management of CD. Regarding pharmacoeconomics essentials, low cost and toxicity antibiotics such as first to third generation of cephalosporin and gentamicin (effective against E. coli) or penicillin and clindamycin (effective against C. difficile) should be trailed in future trials. The final point is that the debate on the use of antibiotics in IBD still remains and need further well-designed studies to help identify which patients need antibiotic or antibiotic combination and if yes, what is the preferred compound with what dosage and duration of treatment.
ACKNOWLEDGMENT
This paper is the outcome of an in-house financially non-supported study.