Combination Of Rifampicin Research Articles

A high content screening assay for discovery of antimycobacterial compounds based on primary human macrophages infected with virulent Mycobacterium tuberculosis

Drug resistance in Mycobacterium tuberculosis is an emerging threat that makes the discovery of new candidate drugs a priority. In particular, drugs with high sterilizing activity within host cells are needed to improve efficacy and reduce treatment duration. We aimed to develope and validate a High Content Screening assay based on Mycobacterium tuberculosis-infected primary human monocyte-derived macrophages as its natural reservoir. Infected primary human monocyte-derived macrophages were exposed to control antibiotics or tested compounds on 384 well plates. Intracellular bacterial growth and macrophage numbers were evaluated using an ImageXpress High Content Screening system and Z′-factor was calculated to assess the reproducibility. The combination of isoniazid and rifampicin as a positive control rendered a Z′-factor above 0.4, demonstrating suitability of the assay for screening and compound profiling purposes. In a validation experiment, isoniazid, rifampicin, moxifloxacin and levofloxacin all effectively inhibited intracellular growth as expected. Finally, a pilot screening campaign including 5700 compounds from diverse libraries resulted in the identification of three compounds with confirmed antimycobacterial activity in the low micromolar range and low host cell toxicity. The assay represents an attractive screening platform for both academic research on host-pathogen mechanisms in tuberculosis and for the identification and characterization of novel antimycobacterial compounds.

Ofloxacin resistance in multibacillary new leprosy cases from Purulia, West Bengal: a threat to effective secondary line treatment for rifampicin-resistant leprosy cases

Purulia is one of the high-endemic districts for leprosy in West Bengal (the eastern part of India). The annual new case detection rate (ANCDR) of leprosy in West Bengal is 6.04/100000 (DGHS 2019-20). Our earlier report provided evidence of secondary drug resistance in relapse cases of leprosy. The aim of the current study was to observe primary drug resistance patterns for dapsone, rifampicin, and ofloxacin amongst new leprosy patients from Purulia, West Bengal in order to better understand the emergence of primary resistance to these drugs. In the present study, slit-skin smear samples were collected from 145 newly diagnosed leprosy cases from The Leprosy Mission (TLM) Purulia hospital between 2017 and 2018. DNA was extracted from these samples and the Mycobacterium leprae genome was analyzed for genes associated with drug resistance by polymerase chain reaction (PCR), followed by Sanger sequencing. Wild-type strain (Thai-53) and mouse footpad-derived drug-resistant strain (Z-4) were used as reference strains. Of 145 cases, 25 cases showed mutations in genes associated with resistance to rifampicin, dapsone, and ofloxacin (as described by the World Health Organization, rpoB, folP, and gyrA, respectively) through Sanger sequencing. Of these 25 cases, 16 cases showed mutations in ofloxacin, two cases showed mutations in combinations of ofloxacin and rifampicin, four cases showed a mutation only in rifampicin, one case showed mutations in combinations of rifampicin and dapsone, and two cases showed mutations only in dapsone. Results from this study indicated the emergence of resistance to antileprosy drugs in new cases of leprosy. As ofloxacin is the alternate drug for the treatment of rifampicin-resistant cases, the emergence of new cases with resistance to ofloxacin indicates that ofloxacin-resistant M. leprae strains are actively circulating in this endemic region (i.e., Purulia, West Bengal), posing challenges for the effective treatment of rifampicin-resistant cases.

Management of tuberculosis during pregnancy: first line anti-tuberculosis drug

Tuberculosis is a widespread, infectious disease caused by various strains of mycobacteria, commonly Mycobacterium tuberculosis. Tuberculosis not only responsible for an important proportion of the global burden of disease, but it is also an important contributor to maternal mortality, with the disease being among the three leading causes of death among women aged fifteen to forty five years. The main goals of tuberculosis treatment are to cure the patients, to prevent maternal and perinatal complications and to minimize the possibility of transmission of the bacillus to healthy individuals. First-line anti-tuberculosis treatment for medicine-sensitive tuberculosis can be highly effective; however, in absence of well-controlled studies in pregnant women, first-line tuberculosis medications have been listed as United States Food and Drug Administration pregnancy category C (ie, no adequate well-controlled human studies have been performed, but benefits may be acceptable despite potential risks) except ethambutol categorized as pregnancy category B. Rifampicin can be highly used by pregnant women; due to it is believed to be safe for pregnancy and no teratogenic effects has been observed. Neonates who born from mothers who have been taken rifampicin combination therapy may be developed an increased risk of haemorrhagic disorders in the new-born (postpartum hemorrhage); to avoid this postpartum hemorrhage supplemental vitamin K (10mg/day) should be given for the last four to eight weeks of pregnancy.

Anti-plasmodial activity of rifampicin/ dihydro-artemisinin/piperaquine combination on Plasmodium berghei infected mice

Introduction: The huge cost of de-novo drug development and the problem of multidrug resistance by plasmodium parasites has made research on drugs with potential for repurposing attractive. The study evaluated the antiplasmodial properties of clinical doses of rifampicin in combination with dihydroartemisinic/piperaquine in Plasmodium berghei-infected mice. Materials/Methods: Curative, suppressive, and prophylactic tests were carried out on adult mice (26 – 30g) infected with P.berghei parasite. They were grouped and treated per oral (p.o) with RIF (15mg/kg), DP (2.5/20 mg/kg) and RIF/DP (15/2.5/20 mg/kg) daily. The negative control (NC) and the positive control (PC) were treated daily p.o with normal saline (0.2mL) and chloroquine (CQ) (10 mg/kg). Normal saline and chloroquine were administered to mice in the first and second groups, respectively, for 3 consecutive days. Similarly, the third group of mice were treated with dihydroartemisinin/piperaquine combination for 3 consecutive days, while rifampicin was given to the fourth group for 7 consecutive days. The last group of mice were administered the dihydroartemisinic/piperaquine dose for 3days and the rifampicin dose for 7 consecutive days. Results: There was significant reduction in parasitemia in the prophylactic, suppressive, and curative studies at RIF (15 mg/kg) (p<0.01), DP (2.5/20 mg/kg) (p<0.001) and RIF/DP (p<0.0001) when compared with to negative control. There was an approximately three-fold decrease in percentage parasitemia in the rifampicin/dihydroartemisinin/piperaquine treatment group when compared to the Chloroquine treatment group. Conclusion: The combination of rifampicin with dihydroartemisinin/piperaquine represent potentially viable additions to the antimalarial arsenal currently available. RIF may be repurposed in combination with DP for malaria treatment.

Aptamer-Targeted Drug Delivery for Staphylococcus aureus Biofilm.

Treatment of Staphylococcus aureus biofilm infections using conventional antibiotic therapy is challenging as only doses that are sublethal to the biofilm can be administered safely to patients. A potential solution to this challenge is targeted drug delivery. In this study, we tailored an aptamer-targeted liposomal drug delivery system for accumulation and delivery of antibiotics locally in S. aureus biofilm. In our search for a suitable targeting ligand, we identified six DNA aptamers that bound to S. aureus cells in biofilms, and we demonstrated that one of these aptamers could facilitate accumulation of liposomes around S. aureus cells inside the biofilm. Aptamer-targeted liposomes encapsulating a combination of vancomycin and rifampicin were able to eradicate S. aureus biofilm upon 24 h of treatment in vitro. Our results point to that aptamer-targeted drug delivery of antibiotics is a potential new strategy for treatment of S. aureus biofilm infections.

Use of colistin with rifampicin, trimethoprim-sulfamethoxazole and teicoplanin in Acinetobacter mouse infection model.

Background: Infections with multidrug-resistant Gram-negative bacteria such as Acinetobacter baumannii are major cause of morbidity and mortality. Colistin is used commonly to treat these infections. In this study, we evaluated the efficacy of different colistin combinations in a A. baumannii infection mouse model. Materials & methods: An A. baumannii mouse infection model was developed in 150 experimental animals. Treatment groups were as follows: colistin, colistin+rifampicin, colistin+trimethoprim/sulfamethoxazole, colistin+teicoplanin and a control group. The outcome was bacterial burden in the lung and liver tissues. The treatment groups were subdivided into 24-, 48-and 72-h groups. Results: Colistin and combinations reduce the A. baumannii burden significantly in lung and liver tissues compared with the control group. Compared with colistin alone colistin+rifampicin and colistin+TMP-SMX provided significantly better reduction in the bacterial burden. Conclusion: These results may suggest that rifampicin and TMP-SMX combination with colistin may have a potential role in the treatment of A. baumannii infections.

Development and Validation of Stability Indicating RP-HPLC Method for Simultaneous Determination of Doxycycline and Rifampicin in Polymeric Nanoparticles

Background: The combination of doxycycline (DOXY) and rifampicin (RIF) is recom-mended as a treatment therapy for brucellosis by the World Health Organization. Objective: The aim of the current study was to develop and validate the stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method for the analysis of a combina-tion of doxycycline & rifampicin. Methods: The RP-HPLC method was developed and validated to estimate the doxycycline and ri-fampicin combination as per ICH guidelines. The drug combination solution was exposed to differ-ent stress conditions: acidic, basic, photo-oxidation, and oxidation. Results: The method was found linear in the range of 2 -10μg/mL for both the drugs with a reten-tion time of 3.5 min for doxycycline and 6.5 min for rifampicin at lambda maximum of 350 nm. The RP-HPLC method was precise and accurate with %RSD < 2%. The intra-day and inter-day precisions were calculated and found within the acceptable range of 5%. Both drugs demonstrated good stability in the mobile phase after 6 hours. The LOD and LOQ of doxycycline and rifampicin were 100 ng/mL & 200ng/mL and 150ng/mL & 500ng/mL, respectively. The forced degradation of the combination of drug solutions was performed. The degraded drug peaks were well-resolved from the peaks of drugs. The percentage encapsulation efficiency of doxycycline and rifampicin in the nanoparticle system was assessed by utilizing the validated RP-HPLC method and found >60% (DOXY) and >70% (RIF). Conclusion: The developed RP-HPLC method of DOXY-RIF combination was rapid, accurate, precise, and stability-indicating. The method can be appropriately applied todetecte drugs in the na-noparticulate system.

Real time monitoring of Staphylococcus aureus biofilm sensitivity towards antibiotics with isothermal microcalorimetry.

Biofilm-associated infections with Staphylococcus aureus are difficult to treat even after administration of antibiotics that according to the standard susceptibility assays are effective. Currently, the assays used in the clinical laboratories to determine the sensitivity of S. aureus towards antibiotics are not representing the behaviour of biofilm-associated S. aureus, since these assays are performed on planktonic bacteria. In research settings, microcalorimetry has been used for antibiotic susceptibility studies. Therefore, in this study we investigated if we can use isothermal microcalorimetry to monitor the response of biofilm towards antibiotic treatment in real-time. We developed a reproducible method to generate biofilm in an isothermal microcalorimeter setup. Using this system, the sensitivity of 5 methicillin-sensitive S. aureus (MSSA) and 5 methicillin-resistant S. aureus (MRSA) strains from different genetic lineages were determined towards: flucloxacillin, cefuroxime, cefotaxime, gentamicin, rifampicin, vancomycin, levofloxacin, clindamycin, erythromycin, linezolid, fusidic acid, co-trimoxazole, and doxycycline. In contrast to conventional assays, our calorimetry-based biofilm susceptibility assay showed that S. aureus biofilms, regardless MSSA or MRSA, can survive the exposure to the maximum serum concentration of all tested antibiotics. The only treatment with a single antibiotic showing a significant reduction in biofilm survival was rifampicin, yet in 20% of the strains, emerging antibiotic resistance was observed. Furthermore, the combination of rifampicin with flucloxacillin, vancomycin or levofloxacin was able to prevent S. aureus biofilm from becoming resistant to rifampicin. Isothermal microcalorimetry allows real-time monitoring of the sensitivity of S. aureus biofilms towards antibiotics in a fast and reliable way.

Rifampicin Increases Expression of Plant Codon-Optimized Bacillus thuringiensis δ-Endotoxin Genes in Escherichia coli.

Transgenic crops expressing Cry δ-endotoxins of Bacillus thuringiensis for insect resistance have been commercialized worldwide with increased crop productivity and spectacular socioeconomic gains. To attain the enhanced level of protein expression, the cry genes have to be extensively modified for RNA stability and translation efficiency in the plant systems. However, such modifications in nucleotide sequences make it difficult to express the cry genes in Escherichia coli because of the presence of E. coli rare codons. Induction of gene expression through the T7 promoter/lac operator system results in high levels of transcription but limits the availability of activated tRNA corresponding to rare codons that leads to translation stalling at ribosomes. In the present study, an Isopropyl ß-D-1-thiogalactopyranoside (IPTG)/rifampicin combination-based approach was adopted to induce transcription of cry genes through T7 promoter/lac operator while simultaneously inhibiting the transcription of host genes through rifampicin. The results show that the IPTG/rifampicin combination leads to high-level expression of four plant codon-optimized cry genes (cry2Aa, cry1F, cry1Ac, and cry1AcF). Northern blot analysis of the cry gene expressing E. coli samples showed that the RNA expression level in the IPTG-induced samples was higher as compared to that in the IPTG/rifampicin-induced samples. Diet overlay insect bioassay of IPTG/rifampicin-induced Cry toxins with Helicoverpa armigera larvae showed bioactivity (measured as LC50) similar to the previous studies. The experiment has proved that recombinant synthetic gene (plant codon-optimized gene) with the combination of Rifampicin which inhibits DNA-dependent bacterial RNA polymerase and reduces the excessive baggage of translational machinery of the bacterial cell triggers the production of synthetic protein. Purification of protein using high pH buffer increases the solubility of the protein. Further, LC50 analysis shows no reduction of protein activity leads to protein stability. Further, purified cry toxin protein can be used for crop protection against pests and a purified form of the synthetic protein can be used for antibody production and perform the immunoassay for the identification of the transgenic plant. The crystallographic structure of synthetic protein could be used for interaction study with another insect to see insecticidal activity.

Quantification of within-patient Staphylococcus aureus phenotypic heterogeneity as a proxy for the presence of persisters across clinical presentations

ObjectivesDifficult-to-treat infections caused by antibiotic-susceptible strains have been linked to the occurrence of persisters, a subpopulation of dormant bacteria that tolerate antibiotic exposure despite lacking genetic resistance. These persisters can be identified phenotypically by plating on nutrient agar because of their altered growth dynamics, resulting in colony-size heterogeneity. The occurrence of within-patient bacterial phenotypic heterogeneity in various infections and clinical determinants of persister formation remains unknown. MethodsWe plated bacteria derived from 132 patient samples of difficult-to-treat infections directly on nutrient-rich agar and monitored colony growth by time-lapse imaging. We retained 36 Staphylococcus aureus monocultures for further analysis. We investigated clinical factors associated with increased colony growth-delay with regression analyses. We corroborated the clinical findings using in vitro grown static biofilms exposed to distinct antibiotics. ResultsThe extent of phenotypic heterogeneity of patient-derived S. aureus varied substantially between patients (from no delay to a maximum of 57.6 hours). Increased heterogeneity coincided with increased median colony growth-delay. Multivariable regression showed that rifampicin treatment was significantly associated with increased median growth-delay (13.3 hours; 95% CI 7.13–19.6 hours; p < 0.001). S. aureus grown in biofilms and exposed to high concentrations of rifampicin or a combination of rifampicin with clindamycin or levofloxacin exhibited prolonged growth-delay (p < 0.05 for 11 of 12 comparisons), correlating with a strain-dependent increase in antibiotic tolerance. DiscussionColony-size heterogeneity upon direct sampling of difficult-to-treat S. aureus infections was frequently observed. Hence, future studies are needed to assess the potential benefit of phenotypic heterogeneity quantification for staphylococcal infection prognosis and treatment guidelines.

STUDY OF THE PREVENTIVE EFFECT OF ROYAL JELLY AGAINST THE HEPATOTOXICITY OF TWO ANTI-TUBERCULOSIS DRUGS

Aim: Hepatotoxicity is a well-known adverse effect during treatment with antituberculosis drugs, in particular the combination of rifampicin (RMP) and isoniazid (INH).&#x0D; Objective: The primary purpose of this study was to assess the contributory role of royal jelly decrease to in antituberculosis drug hepatotoxicity.&#x0D; Materials and Methods: This study is an experimental study in which the preventive effect of Royal jelly on isoniazid (INH), and rifampicin (RMP) hepatotoxicity is evaluated. In this study 21 male rabbit were randomly placed in three members groups including: control group, isoniazid and rifampicin and (isoniazid (INH), and rifampicin(RMP)) /royal jelly group. At the end of the study the laboratory criteria and histological features of liver toxicity were compared in different mentioned groups.&#x0D; Results: The treatment with isoniazid/ rifampicin led to Significant increase serum levels of liver enzymes, alkaline phosphate, alat and asat; and significant higher levels of albumin total proteins and Bilirubine, in compare to mixed isoniazid/ rifampicin / royal jelly also Group and the control.&#x0D; Whereas, the level of GSH concentration and enzymatic antioxidants SGSH-Px were decreased in the groups treatment by Isoniasid(INH), / rifampicin(RMP)comparative to the control grop but the MDA concentration is increased in this groups compared to addition of royal jelly are not present any significant change&#x0D; In addition, histological studies had not showed liver injury in isoniazid/rifampicin/ royal jelly group, while there was liver injury in isoniazid/ rifampicin alone group.&#x0D; Conclusion: The royal jelly, prevent the destructive effects of on the liver; probably because of its antioxidant properties.

Mechanism of anti-inflammatory effects of rifampicin in an ex vivo culture system of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the hair follicles leading to painful lesions, associated with increased levels of pro-inflammatory cytokines. Numerous guidelines recommend antibiotics like clindamycin and rifampicin in combination, as first-line systemic therapy in moderate-to-severe forms of inflammation. HS has been proposed to be mainly an auto-inflammatory disease associated with but not initially provoked by bacteria. Therefore, it has to be assumed that the pro-inflammatory milieu previously observed in HS skin is not solely dampened by the bacteriostatic inhibition of DNA-dependent RNA polymerase. To further clarify the mechanism of anti-inflammatory effects of rifampicin, ex vivo explants of lesional HS from 8 HS patients were treated with rifampicin, and its effect on cytokine production, immune cells as well as the expression of Toll-like receptor 2 (TLR2) were investigated. Analysis of cell culture medium of rifampicin-treated HS explants revealed an anti-inflammatory effect of rifampicin that significantly inhibiting interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α production. Immunohistochemistry of the rifampicin-treated explants suggested a tendency for it to reduce the expression of TLR2 while not affecting the number of immune cells.

Rifabutin versus rifampicin bactericidal and antibiofilm activities against clinical strains of Staphylococcus spp. isolated from bone and joint infections

Staphylococci account for approximately 60% of periprosthetic joint infections (PJIs). Rifampicin (RMP) combination therapy is generally considered to be the treatment of choice for staphylococcal PJIs but carries an important risk of adverse events and drug-drug interactions. Rifabutin (RFB) shares many of the properties of rifampicin but causes fewer adverse events. To compare the minimal inhibitory concentration (MIC), the minimum bactericidal concentrations (MBC), and the minimum biofilm eradication concentrations (MBEC) of rifabutin and rifampicin for staphylococcal clinical strains isolated from PJIs. 132 clinical strains of rifampicin-susceptible staphylococci [51 Staphylococcus aureus (SA), 48 Staphylococcus epidermidis (SE) and 33 other coagulase-negative staphylococci (CoNS)] were studied. The MBC and the MBEC were determined using the MBEC® Assay for rifabutin and rifampicin and were compared. When compared with the rifampicin MIC median value, the rifabutin MIC median value was significantly higher for SA (P < 0.05), but there was no statistically significant difference for SE (P = 0.25) and CoNS (P = 0.29). The rifabutin MBC median value was significantly higher than that of rifampicin for SA (P = 0.003) and was lower for SE (P = 0.003) and CoNS (P = 0.03). Rifabutin MBEC median value was statistically lower than that of rifampicin for all strains tested. Using the determination of MBEC values, our study suggests that rifabutin is more effective than rifampicin against clinical strains of Staphylococcus spp. obtained from PJIs. Using MBECs instead of MICs seems to be of interest when considering biofilms. In vivo higher efficacy of rifabutin when compared with rifampicin needs to be confirmed.

Analytical Method Development and Validation for the Simultaneous Estimation of Rifampicin and Isoniazid in its Bulk and Pharmaceutical Dosage Forms by RP-HPLC

Background A combination of Rifampicin and Isoniazid is the drug of choice to treat tuberculosis patients in sustenance or those travelling to a region where there is a probability of being infected with tuberculosis.Objective The main objective of the simultaneous estimation of combined drug was to establish identity purity physical characteristics and potency of the drugs.Methodology The chromatographic environment was fortunately evolved for the partition of Rifampicin and Isoniazid by using column thermosil RPC18 4.5times100 nm 5.0 microm flow rate was 1 mLmin mobile phase ratio was 7030 vv methanolsodium acetate buffer. A pH of 3 was adjusted with Ortho phosphoric acid wavelength was detected at 240 nm. Column dimensions were Thermosil C184.6times100mm 5.0 microm.Results The results were in good agreement with those obtained with official HPLC with absorption maximum at 240 nm by preparing mobile phase 7030 methanolsodium acetate buffer with a flow rate 1 mLmin and it ran for 5 minutes by selecting thermosil RPC18 4.5times100 nm of ambient temperature. All the results obtained were precise accurate and robust as per international conference on Harmonization ICH guidelines.Conclusion It can be concluded that the proposed Reverse Phase High Performance Liquid Chromatographic RPHPLC method is accurate precise sensitive specific robust and reproducible for the simultaneous analysis of Rifampicin and Isoniazid with less tailing factor and is also economical. Thermosil RPC18 4.5times100 nm 5.0 microm flow rate was 1 mLmin. Both the samples were in the range of 200 to 400 nm and maximum wavelength was identified at 240 nm.

Enhanced Antibacterial Activity of Doxycycline and Rifampicin Combination Loaded in Nanoparticles against Intracellular Brucella abortus

Brucellosis is a zoonotic disease that is prevalent in livestock animals. The bacteria reside inside the macrophage cells of the host. The WHO has endorseda combination treatment therapy for brucellosis against the conventional monotherapy to avoid relapse and resistance. Therefore, we developed nanoparticles incorporating doxycycline and rifampicin in combination. The aim of the study is to develop polymeric nanoparticles incorporating doxycycline as well as rifampicin and investigate the antibacterial activity of nanoparticles in U937 human macrophage cells infected with B. abortus. Polymeric nanoparticles were developed by the emulsion-solvent diffusion method, and characterization was performed. The nanoparticles with high entrapment efficiency of both the drugs were developed successfully. Scanning electron microscopy revealed a spherical morphology with a size ranging ~450nm, which can be easily engulfed by the macrophages. Zeta potential confirmed the colloidal stability. Differential scanning calorimetry and X-ray diffraction suggested amorphization of doxycycline and rifampicin in nanoparticles. Fourier transfer infrared spectroscopy could not confirm the interaction of drugs with AOT. In vitro haemolysis study confirmed the safety of nanoparticles (<10%) for IV administration. Further, nanoparticles revealed the sustained release of both drugs, which followed diffusion kinetics. Nanoparticles were found stable for 6 months as per WHO guidelines. The internalization study revealed nanoparticles could be easily uptaken by U-937 human macrophage cells. The efficacy study demonstrated significantly high antibacterial activity of nanoparticles as compared to free drug solution in U937 human macrophages cells infected with Brucella abortus. It can be concluded that the developed nanoparticles entrapping doxycycline and rifampicin combination can be considered as a promising delivery system for enhancing the antibacterial activity against Brucella abortus.

Miliary Tuberculosis Following an Appendectomy, a Case Report

Background Miliary tuberculosis (MTB) is a type of disseminated and active tuberculosis that presents with radiopathologic signs of tuberculous micronodules, as well as microbiologic evidence from detection of Mycobacterium tuberculosis or other Mycobacterium strains in PCR or culture [1]. Case Presentation A 21 year-old student presented with weight loss, fever, cough productive of yellow sputum without hemoptysis, and anorexia of 5 weeks duration. 7 weeks prior to presentation, she had an appendectomy on account of acute appendicitis. Following surgery, there was resolution of symptoms of acute appendicitis. Histopathologic report of the resected appendix showed foci of caseating granulomas. She was immediately commenced on a fixed drug combination of rifampicin, isoniazid, pyrazinamide, and ethambutol for treatment of military tuberculosis and showed clinical and radiologic improvement. Conclusion Miliary tuberculosis following an appendectomy can be due to dissemination of tuberculous foci from the appendix during surgery and surgical stress.

Latent Tuberculosis Cascade of Care Among Healthcare Workers: A Nationwide Cohort Analysis in Korea Between 2017 and 2018.

BackgroundIn 2017, Korea implemented nationwide latent tuberculosis infection (LTBI) project targeting healthcare workers (HCWs). We aimed to assess its performance using the cascade of care model.MethodsWe included 45,503 employees of medical institutions with positive interferon-gamma release assay result who participated between March 2017 and December 2018. We described percentages of LTBI participants completing each step in the cascade of care. Poisson regression model was conducted to assess individual characteristics and factors associated with not-visiting clinics for further care, not-initiating LTBI treatment, and not-completing treatment.ResultsProportions of visiting clinics and initiating and completing treatment in HCWs were 54.9%, 38.5%, and 32.0%, respectively. Despite of less likelihood of visiting clinics and initiating LTBI treatment, older age ≥ 65 years were more likely to complete treatment (adjusted relative risk [aRR], 0.80; 95% confidence interval [CI], 0.64–0.99), compared to young age < 35 years. Compared to nurses, doctors were less likely to visit clinic; however, were more likely to initiate treatment (aRR, 0.88; 95% CI, 0.81–0.96). Those who visited public health centers were associated with not-initiating treatment (aRR, 1.34; 95% CI, 1.29–1.40). When treated at private hospitals, 9-month isoniazid monotherapy was less likely to complete treatment, compared to 3-month isoniazid and rifampicin combination therapy (aRR, 1.33; 95% CI, 1.16–1.53).ConclusionAmong employees of medical institutions with LTBI, only one third completed treatment. Age, occupation, treatment center, and initial regimen were significantly related to LTBI treatment performance indicators. Rifampicin-based short treatment regimens were effective under standard of care.

The Inhibitory Effect of the Combination Treatment of Rifampicin and D-limonene on the Growth and Biofilm Formation of Staphylococcus epidermidis RP62A

Aims: To discover an alternative chemical that could potentially be used in combination with antibiotics to inhibit the growth of Staphylococcus epidermidis RP62A.&#x0D; Study Design: The studies of the growth inhibition in both the biofilm forming strain of S. epidermidis RP62A and the wild-type strain ATCC 12228, were conducted with different concentrations of rifampicin and D-limonene using the measurement of the optical density.&#x0D; Place and Duration of Study: All experiments were conducted in the Department of Biology at Manhattanville College between September 2015 and December 2019.&#x0D; Methodology: Different concentrations of rifampicin (0.0025 µg/mL, 0.005 µg/mL, 0.01 µg/mL and 0.02 µg/mL) and D-limonene (152.8 µg/mL, 305.6 µg/mL, 611.2 µg/mL and 1222.4 µg/mL) were used in the study. The minimal inhibitory concentrations (MIC) of rifampicin and D-limonene on RP62A and ATCC 12228 were obtained. The combination of rifampicin and D-limonene on the inhibition of the growth of RP62A and ATCC 12228 was conducted using a microtiter plate by measuring optical density. The alamarBlue® assay was further used to evaluate the viability of RP62A and ATCC 12228 with the combination treatment. The biofilm assay was then conducted on RP62A with the combination treatment of rifampicin and D-limonene.&#x0D; Results: The MIC of the combination treatment of rifampicin and D-limonene on RP62A was found to be 0.01 µg/mL and 1222.4 µg/mL respectively. A combination treatment of 0.005 µg/mL of rifampicin with 611.2 µg/mL of D-limonene significantly inhibited the growth and biofilm formation of RP62A than the same concentration of rifampicin.&#x0D; Conclusion: The addition of the D-limonene to the rifampicin was found to be effective in inhibiting the growth and biofilm formation of RP62A. This indicates that the combination of alternative mineral oil may have the potential to lower the antibiotic concentration in the inhibition of the growth of the bacteria S. epidermidis.

Oligomer-Targeting Prevention of Neurodegenerative Dementia by Intranasal Rifampicin and Resveratrol Combination - A Preclinical Study in Model Mice.

Amyloidogenic protein oligomers are thought to play an important role in the pathogenesis of neurodegenerative dementia, including Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies. Previously we demonstrated that oral or intranasal rifampicin improved the cognition of APP-, tau-, and α-synuclein-transgenic mice by reducing the amount of Aβ, tau, and α-synuclein oligomers in the brain. In the present study, to explore more effective and safer medications for dementia, we tested the drug combination of rifampicin and resveratrol, which is a multifunctional natural polyphenol with the potential to antagonize the adverse effects of rifampicin. The mixture was intranasally administered to APP-, tau-, and α-synuclein-transgenic mice, and their memory and oligomer-related pathologies were evaluated. Compared with rifampicin and resveratrol alone, the combinatorial medicine significantly improved mouse cognition, reduced amyloid oligomer accumulation, and recovered synaptophysin levels in the hippocampus. The plasma levels of liver enzymes, which reflect hepatic injury and normally increase by rifampicin treatment, remained normal by the combination treatment. Notably, resveratrol alone and the combinatorial medicine, but not rifampicin alone, enhanced the levels of brain-derived neurotrophic factor (BDNF) and its precursor, pro-BDNF, in the hippocampus. Furthermore, the combination showed a synergistic effect in ameliorating mouse cognition. These results show the advantages of this combinatorial medicine with regards to safety and effectiveness over single-drug rifampicin. Our findings may provide a feasible means for the prevention of neurodegenerative dementia that targets toxic oligomers.

Not a wild goose chase: long-lasting MRSA negative status following eradication therapy for chronic MRSA infection in patients with cystic fibrosis

ABSTRACT Objectives Prevalence of MRSA in patients with CF has risen over the past decades, and chronic infection with MRSA is associated with worse outcome in this patient group. Methods This retrospective observational study investigated long-term eradication rate in pediatric and adult CF patients with chronic MRSA infection, using a 6-month eradication regimen containing 2 oral antibiotics, combined with topical decolonisation measures. Respiratory tract cultures were performed at least every three months, from the first MRSA-positive culture onwards. Results A total of 24 patients with chronic MRSA infection were identified from our CF patient registry, of which 13 patients underwent an eradication attempt. The regimen consisted of 2 oral antibiotics: a combination of rifampicin, fusidic acid, clindamycin and co-trimoxazol, based on the sensitivity pattern of the MRSA strain. At the end of the study period (median 8.2 years), 12 out of 13 patients (92%) were MRSA negative. None of the patients interrupted treatment due to side-effects. Conclusions Eradication of chronic MRSA infection is feasible, well-tolerated and highly successful, and can offer a long-lasting MRSA-negative status, obviating the need for patient segregation.