minocycline and Colitis

Clostridium difficile colitis infection is on the rise and is considerably increasing the duration of hospital stay, as well as healthcare costs. The management of C. difficile colitis has become more challenging with the increasing failure of therapeutic response to metronidazole and oral vancomycin. Tigecycline is a new glycylcycline that has shown in vitro activity against C. difficile. We report herein a case of C. difficile colitis that failed to improve on a combination of metronidazole and oral vancomycin. The patient subsequently developed a surgical abdomen secondary to refractory C. difficile colitis, but was successfully treated with a combination of rifaximin and tigecycline after she refused to undergo surgical treatment.

Topics: Aged; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Colitis; Drug Therapy, Combination; Female; Humans; Metronidazole; Minocycline; Recurrence; Rifamycins; Rifaximin; Tigecycline; Treatment Outcome; Vancomycin

Abdominal pain is a common feature in inflammatory bowel disease (IBD) patients, and greatly compromises their quality of life. Therefore, the identification of new therapeutic tools to reduce visceral pain is one of the main goals for IBD therapy. Minocycline, a broad-spectrum tetracycline antibiotic, has gained attention in the scientific community because of its immunomodulatory and anti-inflammatory properties. The aim of this study was to evaluate the potential of this antibiotic as a therapy for the management of visceral pain in dextran sodium sulfate (DSS)-induced colitis in mice. Preemptive treatment with minocycline markedly reduced histological features of intestinal inflammation and the expression of inflammatory markers (Tlr4, Tnfα, Il1ß, Ptgs2, Inos, Cxcl2, and Icam1), and attenuated the decrease of markers of epithelial integrity (Tjp1, Ocln, Muc2, and Muc3). In fact, minocycline restored normal epithelial permeability in colitic mice. Treatment with the antibiotic also reversed the changes in the gut microbiota profile induced by colitis. All these ameliorative effects of minocycline on both inflammation and dysbiosis correlated with a decrease in ongoing pain and referred hyperalgesia, and with the improvement of physical activity induced by the antibiotic in colitic mice. Minocycline might constitute a new therapeutic approach for the treatment of IBD-induced pain. PERSPECTIVE: This study found that the intestinal anti-inflammatory effects of minocycline ameliorate DSS-associated pain in mice. Therefore, minocycline might constitute a novel therapeutic strategy for the treatment of IBD-induced pain.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Colitis; Colon; Disease Models, Animal; Inflammation; Inflammatory Bowel Diseases; Mice; Mice, Inbred C57BL; Minocycline; Quality of Life; Visceral Pain

Several reports demonstrated anti-inflammatory properties of minocycline in various inflammatory disorders including colitis. We have experimental evidence suggesting synergistic anti-inflammatory effect of minocycline with methyl prednisolone in reducing colitis severity in mice, but if this effect is in part related to modulating the composition of colonic microbiota is still unknown.. the effect of vehicle (V), minocycline (M), methyl prednisolone (MP), or combination (C) regimen on the composition of the microbiota of mice in a state of colon inflammation compared to untreated (UT) healthy mice was determined using 16s metagenomic sequencing, and the taxonomic and functional profiles were summarized.. Overall, the bacterial flora from the phylum Firmicutes followed by Bacteroidota were found to be predominant in all the samples. However, the composition of Firmicutes was decreased relatively in all the treatment groups compared to UT group. A relatively higher percentage of Actinobacteriota was observed in the samples from the C group. At the genus level, Muribaculaceae, Bacteroides, Bifidobacterium, and Lactobacillus were found to be predominant in the samples treated with both drugs (C). Whereas "Lachnospiraceae NK4A136 group" and Helicobacter in the M group, and Helicobacter in the MP group were found to be predominant. But, in the UT group, Weissella and Staphylococcus were found to be predominant. Eubacterium siraeum group, Clostridia vadinBB60 group, Erysipelatoclostridium and Anaeroplasma genera were identified to have a significant (FDR p < 0.05) differential abundance in V compared to C and UT groups. While at the species level, the abundance of Helicobacter mastomyrinus, Massiliomicrobiota timonensis and uncultured Anaeroplasma were identified as significantly low in UT, C, and M compared to V group. Functional categories related to amino acid, carbohydrate, and energy metabolism, cell motility and cell cycle control were dominated overall across all the samples. Methane metabolism was identified as an enriched pathway. For the C group, "Colitis (decrease)" was among the significant (p = 1.81E-6) associations based on the host-intrinsic taxon set.. Combination regimen of minocycline plus methyl prednisolone produces a synergistic anti-inflammatory effect which is part related to alternation in the colonic microbiota composition.

Topics: Animals; Anti-Inflammatory Agents; Bacteria; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Inflammation; Methylprednisolone; Mice; Mice, Inbred C57BL; Minocycline

Clostridium difficile infection (CDI) is the most frequent cause of nosocomial diarrhoea in adults. Cancer patients, in particular, are at a higher risk for CDI. Limited clinical data exist regarding the use of tigecycline for the treatment of CDI, especially in patients with oncologic and haematologic malignancies.. To characterize the use of tigecycline for treatment of CDI in oncology patients at an academic cancer centre.. This was a retrospective, single-centre, single-arm, chart review evaluating the use of tigecycline for the management of CDI in oncology patients at an academic cancer centre.. The median age of CDI diagnosis in this patient group (N=66) was 65 years (range: 16-84) and the majority of patients had solid tumour malignancies. Fifty-six percent of patients had severe CDI, 70.3% of which were classified as having severe complicated disease. The median time to initiation of tigecycline therapy was 2 days (mean: 3.83) and the median number of tigecycline doses was 13 (range: 1-50). Twelve non-CDI breakthrough infections were observed, and four patients developed CDI while receiving tigecycline for non-CDI indications. The rate of death was 18% and the recurrence rate was 15.2%.. Tigecycline did not lead to overt benefits in outcomes of oncology patients with CDI when compared to historical data. In addition, several breakthrough CDIs were observed in patients who received the drug for a non-CDI indication. Further prospective research is needed to validate the use of tigecycline for management of CDI.

Topics: Academic Medical Centers; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Colitis; Female; Humans; Male; Middle Aged; Minocycline; Neoplasms; Retrospective Studies; Tigecycline; Treatment Outcome; Young Adult

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5min of administration, systemic injection of the drug produced a delayed effect (60min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia.

Topics: Analgesics; Animals; Behavior, Animal; Colitis; Colon; Disease Models, Animal; Ganglia, Spinal; Hyperalgesia; Injections, Intraperitoneal; Injections, Spinal; Male; Mechanotransduction, Cellular; Microglia; Minocycline; Pain Perception; Pressure; Rats, Sprague-Dawley; Spinal Cord; Time Factors; Trinitrobenzenesulfonic Acid; Visceral Pain

Some antibiotics, including minocycline, have recently been reported to display immunomodulatory properties in addition to their antimicrobial activity. The use of a compound with both immunomodulatory and antibacterial properties could be very interesting in the treatment of inflammatory bowel disease (IBD), so the aim of our study was to evaluate the anti-inflammatory effect of minocycline in several experimental models of IBD. Firstly, the immunomodulatory activity of the antibiotic was tested in vitro using Caco-2 intestinal epithelial cells and RAW 264.7 macrophages; minocycline was able to inhibit IL-8 and nitrite production, respectively. In vivo studies were performed in trinitrobenzenesulfonic acid (TNBS)-induced rat colitis and dextran sodium sulfate (DSS)-induced mouse colitis. The results revealed that minocycline exerted an intestinal anti-inflammatory effect when administered as a curative treatment in the TNBS model, modulating both immune and microbiological parameters, being confirmed in the DSS model; whereas none of the other antibiotics tested (tetracycline and metronidazole) showed anti-inflammatory effect. However, minocycline administration before the colitis induction was not able to prevent the development of the intestinal inflammation, thus showing that only its antimicrobial activity is not enough for the anti-inflammatory effect. In conclusion, minocycline displays an anti-inflammatory effect on different models of rodent colitis which could be attributed to the association of its antibacterial and immunomodulatory properties.

Topics: Animals; Anti-Inflammatory Agents; Caco-2 Cells; Cell Line; Colitis; Dextran Sulfate; Female; Humans; Immunologic Factors; Inflammatory Bowel Diseases; Macrophages; Mice; Mice, Inbred C57BL; Minocycline; Rats; Rats, Wistar; Trinitrobenzenesulfonic Acid

Antibiotics have been empirically used for human inflammatory bowel disease, being limited to short periods. Probiotics are able to attenuate intestinal inflammation due to its immunomodulatory properties, being considered as safe when chronically administered. The aim was to test the association of minocycline, a tetracycline with immunomodulatory properties, and the probiotic Escherichia coli Nissle 1917 (EcN) in a mouse model of reactivated colitis. For this purpose, female C57BL/6J mice were assigned to different groups: non-colitic and dextran sodium sulfate (DSS)-control groups (without treatment), minocycline (50 mg/kg/day; p.o.), EcN (5×10(8) CFU/day; p.o.), and minocycline plus EcN treated groups. Colitis was induced by adding DSS in the drinking water (3%) for 5 days; 2 weeks later, colitis was reactivated by subsequent exposure to DSS. The inflammatory status was evaluated daily by a disease activity index (DAI); colonic damage was assessed histologically and biochemically by evaluating mRNA relative expression of different mediators by qPCR. Finally, a microbiological analysis of the colonic contents was performed. Minocycline and EcN exerted intestinal anti-inflammatory effect and attenuated the reactivation of the colitis, as shown by the reduced DAI values, being these effects greater when combining both treatments. This was evidenced histologically and biochemically, by reduced expression of TNFα, IL-1β, IL-2, MIP-2, MCP-1, ICAM-1, iNOS and MMP-9, together with increased MUC-3 and ZO-1 expression. Finally, the altered microbiota composition of colitic mice was partially restored after the different treatments. In conclusion, EcN supplementation to minocycline treatment improves the recovery of the intestinal damage and prevents the reactivation of experimental colitis.

Topics: Animals; Anti-Bacterial Agents; Colitis; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli; Female; Gene Expression Regulation; Inflammation; Matrix Metalloproteinase 9; Membrane Proteins; Mice; Mice, Inbred C57BL; Minocycline; Mucin-3; Nitric Oxide Synthase Type II; Phosphoproteins; Probiotics; Zonula Occludens-1 Protein

In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitric oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Colitis; Cytokines; Dextran Sulfate; Disease Models, Animal; Enzyme Inhibitors; Inflammation; Male; Matrix Metalloproteinases; Metronidazole; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Minocycline; Nitric Oxide Synthase Type II; RNA, Messenger; Species Specificity; Survival Analysis; Trinitrobenzenesulfonic Acid

Topics: Acne Vulgaris; Administration, Oral; Candidiasis, Vulvovaginal; Clindamycin; Colitis; Demeclocycline; Drug Evaluation; Erythromycin; Female; Humans; Minocycline; Photosensitivity Disorders; Tetracycline; Time Factors

Topics: Anti-Bacterial Agents; Carrier State; Colitis; Diarrhea; Humans; Lincomycin; Minocycline