High rifaximin out-of-pocket costs are associated with decreased treatment retention among patients with hepatic encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is associated with significant morbidity and mortality for those with cirrhosis. Despite the known benefits of rifaximin use for HE, treatment retention remains low. This study aimed to evaluate the impact of out-of-pocket (OOP) rifaximin cost on treatment retention among commercially insured patients in the United States. METHODS: Adult patients with cirrhosis and HE were identified from the IBM MarketScan claims database. Those who began rifaximin treatment between January 1, 2011, and December 1, 2021 were included. Regression models were used to analyze the relationship between patients' 30-day OOP rifaximin cost and rifaximin retention (≥80% eligible days with rifaximin supply) at 180, 360, and 540 days. Models were controlled for patient demographic and clinical characteristics including age, sex, comorbid conditions, Charlson comorbidity index (CCI), and lactulose use. RESULTS: A total of 6839 adult patients were included. Most patients were between 55 and 64 years (57.1%), male (60.4%), and living in urban settings (84.6%). Treatment retention was low for all time periods; retention rates for rifaximin were 42%, 25%, and 16% at 180, 360, and 540 days, respectively. In multivariable analysis, 30-day OOP costs of ≥ $150 were associated with a decreased likelihood of rifaximin retention at 180, 360, and 540 days [relative risk (RR) = 0.67, RR = 0.62, and R = 0.60, respectively]. Younger age was associated with reduced treatment retention for all time periods. Metastatic cancer and depression were associated with reduced treatment retention at 180 days (RR = 0.70 and RR = 0.87, respectively). CONCLUSIONS: Rates of rifaximin treatment retention are low despite the known benefits of rifaximin use for breakthrough HE. High 30-day OOP cost is associated with reduced rifaximin treatment retention.

Locally Used Antibiotics for Spinal Infection Prophylaxis and Their Effects on Epidural Fibrosis: an Experimental Laminectomy Study in Rats Using Rifamycin and Gentamycin.

The study aims to assess the effects of antibiotics (ABs), which are typically used in spinal infection prophylaxis, on the formation of epidural fibrosis (EF). Specifically, we investigated the effect of rifamycin and gentamycin on EF formation in laminectomized rats. Thirty-two rats were randomly and equally divided into four groups as follows: laminectomy and physiological saline (0.9% NaCl) solution (control); laminectomy and rifamycin; laminectomy and gentamicin; and laminectomy and a mixture of rifamycin and gentamicin. Laminectomy was performed on L1 and L2 vertebrae in all rats. One month after spinal surgery, spinal tissue samples surrounding the laminectomy were cut with a microtome and stained with hematoxylin-eosin and Masson's trichrome. The histopathological analysis included examining the extent of EF, fibroblast cell density, and cartilage and bone regeneration. Statistical analysis was performed using the IBM SPSS Statistics 22 program (SPSS IBM, Turkey). A value of p < 0.05 was considered statistically significant. EF value differences between the AB treatment groups and the control group were statistically significant (p = 0.030). Specifically, binary comparisons indicated that the EF value was significantly higher in the rifamycin group than that in the control group (p = 0.003; p < 0.05). Our study suggests that locally applied ABs, especially rifamycin, should be diluted before administration to the epidural space.

The intriguing role of Rifaximin in gut barrier chronic inflammation and in the treatment of Crohn's disease.

INTRODUCTION: The gastrointestinal tract acts as a functional unit organized as a semipermeable multilayer system, in which commensal gut microbiota represents the anatomical barrier. Recently, several studies have highlighted the involvement of gut microbiota in inflammatory bowel diseases (IBD) pathogenesis, in sustaining gut barrier chronic inflammation, and in conditioning disease course and therapeutical response. This evidence provides a rationale for treating patients with gut microbiota modifiers. Among these, Rifaximin represents a non-traditional antibiotic able to act as a 'eubiotic' on intestinal barrier. AREAS COVERED: The purpose of this narrative review is to explore the impact of Rifaximin on gut barrier and gut microbiota in IBD, in particular in Crohn's disease (CD), and to analyze its potential therapeutic applications. EXPERT OPINION: The possibility of a beneficial activity of Rifaximin in chronic intestinal inflammation and CD has been debated and evaluated with different studies having obtained promising but still preliminary data. Larger trials are therefore needed. This gut-specific antibiotic could represent an alternative to systemic antibiotics thanks to its favorable safety profile and promising efficacy data. Rifaximin could exert, when appropriate, a synergic effect with immunomodulators in IBD, acting on both the microbial and the immunological sides of gut barrier impairment.

Minimal Hepatic Encephalopathy in Cirrhosis- How Long to Treat?

Abstract: Introduction. Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE. Material and methods. In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months. Results. Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn’t. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse. Conclusion. Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

RiMINI - the influence of rifaximin on minimal hepatic encephalopathy (MHE) and on the intestinal microbiome in patients with liver cirrhosis: study protocol for a randomized controlled trial.

BACKGROUND: Hepatic encephalopathy (HE) is a clinically significant complication of liver cirrhosis impacting on the patients' quality of life. Minimal hepatic encephalopathy (MHE) is diagnosed by psychometric tests, found in up to 80 % of patients with liver cirrhosis and carries a high risk of progression to overt HE. Continuous therapy with rifaximin in combination with lactulose significantly reduces the risk of overt HE, recurrence of HE and HE-related hospitalizations in randomized, double-blind, placebo-controlled clinical trials. Rifaximin is approved for the therapy of overt HE in Germany. Treatment with lactulose has been shown to improve cognitive functions in patients with liver cirrhosis. Data from prospective clinical trials comparing the efficacy of rifaximin alone against a combination of rifaximin and lactulose in the treatment of MHE are scarce. Changes in the microbiome of the upper and lower gastrointestinal tract as a result of therapy with rifaximin have not yet been addressed in clinical studies. METHODS AND DESIGN: RiMINI is a monocentric exploratory pilot study on 60 patients with MHE as assessed by critical flicker frequency (CFF). Additionally, visual evoked potentials' (VEP) testing, electroencephalography (EEG) and psychometric testing (NCT-A) will be carried out. Patients will be randomized to treatment either with rifaximin alone (550 mg twice daily (bid) continuously for a period of 3 months) or with rifaximin (550 mg bid continuously) in combination with lactulose (30-60 ml daily) for 3 months. An esophagogastroduodenoscopy (EGD) will be performed at baseline, at the end of treatment and 6 and 12 weeks after the end of treatment to obtain gastric and duodenal biopsies and aspirates. The samples will be analyzed for their content of specific bacterial taxae by applying next generation sequencing (NGS) after rRNA isolation to identify the microbiome of the stomach and duodenum, and of the gut, in patients with liver cirrhosis and MHE before and after therapy. DISCUSSION: Differences of the effect of antibiotic therapy with rifaximin alone or in combination with lactulose on the clinical course of MHE are assessed. TRIAL REGISTRATION: The trial was registered as DRKS00006359 on March 17th 2015, with the universal trial number U1111-1163-9410 and with EudraCT2013-004414-18 .

An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.

Treatment optimization in patients co-infected with HIV and Mycobacterium tuberculosis infections: focus on drug-drug interactions with rifamycins.

Tuberculosis (TB) and HIV continue to be two of the major causes of morbidity and mortality in the world, and together are responsible for the death of millions of people every year. There is overwhelming evidence to recommend that patients with TB and HIV co-infection should receive concomitant therapy of both conditions regardless of the CD4 cell count level. The principles for treatment of active TB disease in HIV-infected patients are the same as in HIV-uninfected patients. However, concomitant treatment of both conditions is complex, mainly due to significant drug-drug interactions between TB and HIV drugs. Rifamycins are potent inducers of the cytochrome P450 (CYP) pathway, leading to reduced (frequently sub-therapeutic) plasma concentrations of some classes of antiretrovirals. Rifampicin is also an inducer of the uridine diphosphate glucuronosyltransferase (UGT) 1A1 enzymes and interferes with drugs, such as integrase inhibitors, that are metabolized by this metabolic pathway. Rifampicin is also an inducer of the adenosine triphosphate (ATP) binding cassette transporter P-glycoprotein, which may also lead to decreased bioavailability of concomitantly administered antiretrovirals. On the other side, rifabutin concentrations are affected by the antiretrovirals that induce or inhibit CYP enzymes. In this review, the pharmacokinetic interactions, and the relevant clinical consequences, of the rifamycins-rifampicin, rifabutin, and rifapentine-with antiretroviral drugs are reviewed and discussed. A rifampicin-based antitubercular regimen and an efavirenz-based antiretroviral regimen is the first choice for treatment of TB/HIV co-infected patients. Rifabutin is the preferred rifamycin to use in HIV-infected patients on a protease inhibitor-based regimen; however, the dose of rifabutin needs to be reduced to 150 mg daily. More information is required to select optimal treatment regimens for TB/HIV co-infected patients whenever efavirenz cannot be used and rifabutin is not available. Despite significant pharmacokinetic interactions between antiretrovirals and antitubercular drugs, adequate clinical response of both infections can be achieved with an acceptable safety profile when the pharmacological characteristics of drugs are known, and appropriate combination regimens, dosing, and timing of initiation are used. However, more clinical research is needed for newer drugs, such as rifapentine and the recently introduced integrase inhibitor antiretrovirals, and for specific population groups, such as children, pregnant women, and patients affected by multidrug-resistant TB.

Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn's disease.

BACKGROUND & AIMS: Bacteria might be involved in the development and persistence of inflammation in patients with Crohn's disease (CD), and antibiotics could be used in therapy. We performed a clinical phase 2 trial to determine whether a gastroresistant formulation of rifaximin (extended intestinal release [EIR]) induced remission in patients with moderately active CD. METHODS: We performed a multicenter, randomized, double-blind trial of the efficacy and safety of 400, 800, and 1200 mg rifaximin-EIR, given twice daily to 402 patients with moderately active CD for 12 weeks. Data from patients given rifaximin-EIR were compared with those from individuals given placebo, and collected during a 12-week follow-up period. The primary end point was remission (Crohn's Disease Activity Index <150) at the end of the treatment period. RESULTS: At the end of the 12-week treatment period, 62% of patients who received the 800-mg dosage of rifaximin-EIR (61 of 98) were in remission, compared with 43% of patients who received placebo (43 of 101) (P = .005). A difference was maintained throughout the 12-week follow-up period (45% [40 of 89] vs 29% [28 of 98]; P = .02). Remission was achieved by 54% (56 of 104) and 47% (47 of 99) of the patients given the 400-mg and 1200-mg dosages of rifaximin-EIR, respectively; these rates did not differ from those of placebo. Patients given the 400-mg and 800-mg dosages of rifaximin-EIR had low rates of withdrawal from the study because of adverse events; rates were significantly higher among patients given the 1200-mg dosage (16% [16 of 99]). CONCLUSIONS: Administration of 800 mg rifaximin-EIR twice daily for 12 weeks induced remission with few adverse events in patients with moderately active CD.

Efficacy of rifaximin in prevention of travelers' diarrhea: a meta-analysis of randomized, double-blind, placebo-controlled trials.

BACKGROUND: Rifaximin has been used successfully for the prevention of travelers' diarrhea (TD), the most general cause of disability among international travelers to developing tropical and semitropical regions. METHODS: We sought to better evaluate the efficacy of rifaximin in the prevention of TD. Randomized controlled trials (RCTs) of rifaximin for the prevention of TD published in Pubmed, the Cochrane Central Register of Controlled Trials, Embase, and the Science Citation Index were searched. [Correction added on 3 October 2012, after first online publication: the phrase "protection of TD" was replaced with "prevention of TD".] The primary efficacy outcome was occurrence of TD over a 2-week treatment period. Secondary outcomes were requirement for antibiotic treatment, occurrence of mild diarrhea (MD), occurrence of TD in the third week after drug withdrawal, incidence of TD associated with isolation of diarrheagenic Escherichia coli (ie, ETEC, EAEC), and adverse events. RESULTS: Four RCTs with 502 participants were included in the systematic review. Rifaximin treatment showed a significant protection against TD (risk ratios, RR: 0.41, 95% CI: 0.30-0.56, p < 0.00001) and needed antibiotic-treated TD (relative risk [RR]: 0.30, 95% confidence interval [CI]: 0.18-0.49, p < 0.00001). There was no significant difference between rifaximin and placebo in the occurrence of MD (RR: 1.11, 95% CI: 0.78-1.59, p = 0.55) and the occurrence of TD in the third week after drug withdrawal (RR: 0.73, 95% CI: 0.30-1.73, p = 0.47). Enterotoxigenic E. coli was the major cause of TD, and all trials reported no differences in adverse events between rifaximin and placebo. CONCLUSIONS: Rifaximin can prevent TD caused by non-invasive enteric pathogens. Further research is needed for the treatment of invasive enteric pathogens. [Correction added on 3 October 2012, after first online publication: the phrase "Rifaximin can protect TD" was replaced with "Rifaximin can prevent TD".].

Use and safety of rifaximin in children with inflammatory bowel disease.

BACKGROUND: Rifaximin, Food and Drug Administration approved for traveler's diarrhea, has been used in adult patients with active inflammatory bowel disease (IBD). This retrospective review was undertaken to determine its role in the treatment of pediatric IBD. METHODS: A review of children with IBD, who were treated with rifaximin from 2005 to 2007 at our institution, was performed. Collected data included diagnosis, age, medication history, recent therapy, symptom, and interval to improvement. Response was rated as none, moderate, or optimum relief for each symptom. RESULTS: Twenty-three patients were identified, 12 with Crohn disease and 11 with ulcerative colitis (UC) with a median age of 13 years. The most common complaints were diarrhea in 20 patients (87%), abdominal pain in 17 (74%), and bloody stools in 15 (65%). Rifaximin was given at doses ranging between 10 and 30 mg/kg (Table 1). Of the 20 patients who presented with diarrhea 5 (25%) had relief of diarrhea within 1 week of starting rifaximin and total of 12 patients (60%) experienced relief within 4 weeks. Abdominal pain resolved in 3 of 17 patients (17.6%) within 1 week and in 12 of 17 (70.6%) within 4 weeks. Visible bleeding resolved in 10 of 15 patients (66.7%) within 4 weeks of therapy (Table 2). Analysis of concurrent medications showed 61% experienced relief of symptoms when addition of rifaximin was the only meaningful treatment change. CONCLUSIONS: Rifaximin was well-tolerated and showed favorable results. Larger doses of rifaximin were statistically better for abdominal pain. Further studies are needed to evaluate efficacy and optimal dosing of rifaximin in this population.

Germs, gas and the gut; the evolving role of the enteric flora in IBS.

Gas-related symptoms are common in irritable bowel syndrome (IBS), though their pathophysiology remains poorly understood, various studies invoking increased gas production, impaired gas transit, and increased sensitivity to gas. Recent evidence suggests a potential role for bacterial overgrowth in some patients with IBS; the study discussed herein provides further support for this concept by describing an amelioration of bloating and flatulence following a short course of the poorly absorbed antibiotic, rifaximin.

Long-term treatment with mesalazine and rifaximin versus rifaximin alone for patients with recurrent attacks of acute diverticulitis of colon.

BACKGROUND/AIMS: To compare efficacy of combined therapy with rifaximin and mesalazine versus rifaximin alone in treatment of patients with recurrent diverticulitis in order to evaluate: 1) rapidity in improvement of symptoms, 2) regulation of bowel attacks, 3) prevention of recurrence of diverticulitis. METHODS: A total of 218 consecutive eligible patients (131 males, 87 females age 64.3 years, range 51-79), affected by diverticulitis were monitored. Of these, 109 patients were treated with rifaximin 400 mg bid plus mesalazine 800 mg tid for 7 days, followed by rifaximin 400 mg bid plus mesalazine 800 mg bid for 7 days/month (group A); 109 patients were treated with rifaximin 400 mg bid for 7 days, followed by rifaximin 400 mg bid for 7 days/month (group B). Colonoscopy was performed after 3, 6 and 12 months of therapy. RESULTS: At end of follow-up, 193 patients were fully compliant to therapy Two patients died during study (1 in group A, 1 in group B), while four patients were lost to follow-up [1 in group A (0.91%) and 3 in group B (2.75%)]. The only side-effects recorded were transient urticaria (1 in group B, 0.91%) and epigastric pain (9 in group A, 8.25%). Severity of symptoms improved significantly in group A vs group B within 3 months (p < 0.005, p < 0.001 and p < 0.0001 and p < 0.0005 at 3, 6, 9 and 12 months, respectively). Bowel habits inproved significantly in group A vs group B within 3 months (p < 0.005, p < 0.0005, p < 0.001 and p < 0.0001 at 3,6,9 and 12 months respectively). Symptomatic recurrence of diverticulitis occurred in 3 patients in group A, while 13 patients showed recurrence of diverticulitis in group B (p < 0.005) during follow-up. CONCLUSIONS: This study clearly shows that rifaximin plus mesalazine are more effective than rifaximin alone in resolution of symptoms and prevention of recurrence of diverticulitis.

Estudo morfológico de aderências peritoneais induzidas pela rifamicina em ratos / Morphological study of peritoneal adhesions induced by rifamycin in rats

O uso da rifamicina sv intraperitoneal e a sua influência na formação de aderências peritoneais pós-operatórias (APs), foram analisados num estudo experimental em 90 ratos, machos, da linhagem Wistar-UNIG, distribuídos em dois grupos iguais. O grupo A (n = 45) foi submetido à laparotomia e instilação de 2 mL de solução salina de cloreto de sódio a 0,9 por cento, realizando-se movimento digital rítmico, nos quatro quadrantes da cavidade peritoneal, totalizando um tempo de manuseio de dois minutos. Após este procedimento, a solução remanescente foi aspirada com seringa, seguida de laparorrafia imediata. O grupo B (n = 45), foi submetido a procedimento semelhante com a instilação de uma solução de rifamicina sv 500mg diluída em 500mL de solução salina de cloreto de sódio a 0,9 por cento, utilizando manobra idêntica àquela utilizada no grupo A. Os animais do grupo A e os do grupo B foram separados em três subgrupos com igual número (n = 15) de acordo com o período de eutanásia, que foi de 7, 14 e 21 dias pós-operatório. As aderências peritoneais foram quantificadas nos seus respectivos períodos de eutanásia, utilizando um método descrito por MORENO-EGEA, AGUAYO, ZAMBUDIO e PARRILLA (1993). O grupo B apresentou aderências significantemente mais intensas que o grupo A em todos os subgrupos. Esta diferença foi mais marcante nos animais submetidos à eutanásia após 21 dias.

Severe anaphylaxis from rifamycin SV.

BACKGROUND: Anaphylaxis to topical application of rifamycin SV, which is used topically in the fields of surgery and dermatology, is rare. METHODS: We report two cases of systemic reactions occurring after local administration of rifamycin (Rifocine, Gruppo Lepetit, Italy). Both of them needed repeated intermittent topical applications. Skin prick tests with Rifocine constituents were performed on our patients, and also on ten atopic and ten nonatopic subjects. Although an old investigative tool, Prausnitz-Küstner (P-K) test was also performed on one of the patient's spouses to show passive transfer and the IgE-mediated mechanism. RESULTS: Allergy assessment with skin tests on the patients were negative for aeroallergens, latex, and Rifocine constituents (except rifamycin SV). The patients' prick tests with rifamycin SV were positive, and the control subjects were negative. P-K testing was positive. CONCLUSION: Two case reports support the existence of IgE-mediated reactions to rifamycin SV. IgE-mediated anaphylactic reactions from rifamycin SV appear to be extremely rare.

TB drugs interact adversely with protease inhibitors.

AIDS: Levels of HIV in the bloodstream increase 5- to 160-fold in HIV-positive people with active tuberculosis (TB). This explains why HIV-positive people with active TB have a poorer prognosis than those without TB. The findings from a National Institute of Allergy and Infectious Disease (NIAID) study emphasize the importance of early diagnosis and treatment of TB in HIV-infected patients. There is a potentially negative interaction between protease inhibitors and TB drugs such as rifampin or rifabutin. For AIDS patients whose antiretroviral regimens have been unsuccessful, delaying protease inhibitor treatment while they receive TB treatment could be unacceptable. The CDC is issuing an alert to help TB and AIDS clinicians sort through the drug interactions and offer possible treatment options. Researchers have concluded that rifabutin, rifampin, and clarithromycin have drug interactions with protease inhibitors.^ieng

[Anaphylactic shock after tourniquet removal in orthopedic surgery]. / Chocs anaphylactiques après levée de garrot en chirurgie orthopédique.

Case report of six patients who experienced symptoms of severe anaphylactic shock, after tourniquet release at the end of minor orthopaedic surgery of the limbs under regional anaesthesia. The immunological mechanism of the shock was confirmed by prick tests. The causative agent was rifamycin SV used for cleaning the surgical wound prior to its closure. In case of repetitive surgery and/or in allergic patients the use of another antibiotic or the simple cleaning of the wound with normal saline should be considered. In case of surgery using a tourniquet, an iv access should be maintained for 1 hour after tourniquet release and the patient closely monitored in the recovery room. The allergologic assessment should take place 3 to 6 weeks later and include all drugs administered during the 10 minutes preceding the occurrence of shock.

Anaphylactic reaction to local administration of rifamycin SV.

BACKGROUND AND OBJECTIVE: Systemic reactions during anesthesia are commonly attributed to muscle relaxants, hypnotics, macromolecular solutions, latex, or parenteral antibiotics. After exclusion of these different components as causes, we were interested in the potential implication of rifamycin in the systemic reaction, which occurred during anesthesia, and in the immunologic mechanism by which it can trigger this reaction. METHODS: We report four cases of systemic reactions occurring after local administration of rifamycin. Three patients needed orthopedic surgery, and the fourth needed a urethrotomy. Severe systemic reactions occurred in all four patients when the surgeon washed the incision area with a rifamycin solution. All patients correctly responded to appropriate treatment and recovered. Skin tests were performed 2 months after the incident with the drugs used during anesthesia, latex, and rifamycin. To assess the relationship with a possible IgE-mediated mechanism, two in vitro tests were concomitantly performed to evaluate the cell reactivity to rifamycin: (1) determination of histamine release from peripheral basophils and (2) platelet cytotoxicity test, which explored the presence on platelets of specific IgE antibodies bound to the low-affinity receptor for IgE. RESULTS: Skin tests were performed with different drugs used during surgery, and results were only positive for rifamycin in the four cases, accompanied in two cases by a systemic reaction. Histamine release from basophils was positive in three of four patients. The platelet cytotoxicity test results were positive in all four cases. CONCLUSION: It appears that rifamycin, used locally during surgery, is apt to trigger severe systemic anaphylactic reactions, which are linked to an IgE-related process. This situation is worth pointing out, especially in patients who undergo repeated orthopedic operations during which, at least in Europe, rifamycin is commonly used for the prevention of local sepsis.

Reprimun--an antibiotic with large spectrum and immunomodulatory properties.

Reprimun contains an oxyminomethyl rifamycin-SV derivative as the active substance and has a large spectrum antibiotic activity, on Mycobacterium tuberculosis too. Reprimun also shows an inhibitory activity on viral and human lymphocyte reverse transcriptases, an antiproliferative effect on retrovirus, as well as a selective immunomodulator action at the level of TCD4+ lymphocyte. In animal, the toxicity tests demonstrated a good tolerance. In human subject, the drug is quite well tolerated: no severe adverse reactions were noted during and after its administration for 10-12 months. In man, Reprimun administration demonstrated a therapeutical effect in bacterial infections (tuberculosis included), sarcoidosis, immune thrombocytopenia, as well as in Kaposi's sarcoma. The drug is only for oral administration. It is well absorbed at the level of duodenum, achieving a repeated entero-hepatic circuit that provides a prolonged efficient concentration of Reprimun in blood serum. Like many other ansamycin derivatives, Reprimun can be given intermittently (e.g. twice or three times weekly). In case of antisarcoidosis therapy, Reprimun was applied with good results in 112 supervised cases, including 37 failures of a prior cortisone treatment its administration could be of a high benefit in HIV serum positive persons in which it can prevent both tuberculosis and HIV infection developments.