Rifampin

The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansus...

Background: Multidrug-resistant strains of Acinetobacter baumannii have been reported increasingly around the world. The administration of an association of antibiotics has been proposed to create an active combination and to prevent the emergence of resistance. Methodology: The activity of colistin, rifampicin, gentamicin, imipenem and their associations was evaluated by means of killing curves in fourteen isolates belonging to three endemic PFGE types, in a university hospital of Buenos Aires city. The 14 isolates were selected on the basis of different mechanisms responsible for resistance to carbapenems and different susceptibility to colistin. Results: The mechanism responsible for the resistance to imipenem was the production of OXA-23 and OXA-58 carbapenemases. Heteroresistance to colistin was observed in six isolates. The associations colistin-rifampicin and colistin-imipenem were synergistic in heteroresistant isolates and prevented the development of colistin-resistant mut...

Antimicrobial Peripherally inserted central catheters (PICCs) might reduce the incidence of CLABSI. We tested biocompatibility of a novel gendine (combination of chlorhexidine-CHX and gentian violet-GV) PICC in a rabbit intravascular model and tested antimicrobial efficacy in comparison with commercially available minocycline/rifampin (M/R), and CHX PICCs in an in vitro biofilm colonization model.Gendine and uncoated control PICCs were inserted in the jugular veins of rabbits for 4 days. Histopathologic analysis was performed at the end of the four day period and circulating levels of CHX and GV in blood were measured at different time points using liquid chromatography/mass spectrometry. Antimicrobial efficacy of the PICCs were tested following simulated intravascular indwells of 24 hours and 1 week against clinical isolates of methicillin-resistant Staphylococcus aureus, Vancomycin-resistant enterococci Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Enterobacte...

Individuals in contact with patients who have leprosy have an increased risk of disease exposure, which reinforces the need for chemoprophylactic measures, such as the use of rifampicin. The objective of the review was to synthesize the best available evidence regarding the effectiveness of rifampicin chemoprophylaxis for contacts with patients with leprosy, and to synthesize the best available evidence on the experience and acceptability of rifampicin chemoprophylaxis as reported by the contacts and health professionals involved in the treatment of leprosy or Hansen's disease. In the quantitative component, individuals in contact with leprosy patients were included. In the qualitative component, in addition to contacts, health professionals who were in the practice of treating leprosy were included. The quantitative component considered as an intervention rifampicin at any dose, frequency and mode of administration, and rifampicin combination regimens.The qualitative component ...

Mathematical models for the population dynamics of de novo resistant Mycobacterium tuberculosis within individuals are studied. The models address the use of one or two antimicrobial drugs for treating latent tuberculosis (TB). They consider the effect of varying individual immune response strength on the dynamics for the appearance of resistant bacteria. From the analysis of the models, equilibria and local stabilities are determined. For assessing temporal dynamics and global stability for sensitive and drug-resistant bacteria, numerical simulations are used. Results indicate that for a low bacteria load that is characteristic of latent TB and for small reduction in an immune response, the use of a single drug is capable of curing the infection before the appearance of drug resistance. However, for severe immune deficiency, the use of two drugs will provide a larger time period before the emergence of resistance. Therefore, in this case, two-drugs treatment will be more efficient in controlling the infection.

The diagnosis of tuberculous lymphadenitis (TBL) remains challenging. The routinely used methods (cytology and smear microscopy) have sub-optimal sensitivity. Recently, WHO recommends GeneXpert to be used as the initial diagnostic test in patients suspected of having extra-pulmonary tuberculosis (EPTB). However, this was a conditional recommendation due to very low-quality evidence available and more studies are needed. In this study we evaluated the performance of Xpert for the diagnosis of TBL on concentrated fine needle aspirates (FNA) in Southwest Ethiopia. FNA was collected from presumptive TBL cases. Two smears were prepared from each aspirate and processed for cytology and conventional microscopy. The remaining aspirate was treated with N-acetyl-L-cysteine-NaOH and centrifuged for 15minutes at 3000g. The concentrated sediment was used for culture and Xpert test. Capilia TB-Neo test was used to differentiate M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM...

NON-PRESCRIPTION DEMENTIA MEDICINE DISCOVERY: The "golden touch" of Midas as far as medicine is concerned is to find a medicine from well-known drugs with little side effects which is also a non-description drug. More so, as this is more than just a faint promise of hope and the article is among those that may well become seminal papers in medical history due to vascular dementia, brain circulatory illnesses like haemorrhage and strokes affecting millions of people.

Universally Multivalent Coronavirus Vaccine (at Phase 1). Immune imprinting to the first exposure to a SARS-CoV-2 (SARS-CoV-2) virus shapes immunological outcomes of subsequent exposures to antigenically related new strains. SARS-CoV-2 Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by old Wuhan-Hu-1 spike mRNA vaccination rather than priming Omicron-specific naive B cells like XBB.1.5 current variant.

IXCHIQ is a single-doze vaccine for the prevention of disease by chikungunya virus (CHIKV) for adults over 18 years of age; CHIKV death rate is about 1/1,000 cases. 2023 has seen over 440,000 chikungunya cases resulting over 350 deaths.

One of the biggest prizes in disease eradication achieved: One of the greatest coups in medicine on infections diseases is happening right now with malaria. Matrix-M Plasmodium falciparum malaria vaccine costs between US$2-4 US a dose. WHO announced 2nd October 2023 the vaccine WHO stamp of approval, "prequalification," that allows i.e. UNICEF and the global vaccine alliance Gavi to buy the vaccines for distribution. RTS,S vaccine 15 million therapies is rolled out in some African countries early 2024, and the R21/Matrix-M vaccine 200 million therapies becomes available by the middle of 2024.

Other recent highlights. Immunization Schedule. Influenza A (H5N1) update: "Bird flu spillover to mammals needs to be monitored closely, risk to humans currently low but we must prepare". (WHO). Respiratory Syncytial Virus (RSV) Bivalent Subgroups A and B Vaccine for Infants and Adults ABRYSVO™ (Pfizer) and RSVpreF3 for adults AREXVY (GlaxoSmithKline). False Listing of RB51 as Approved Medicine for Brucellosis or Malta Fever.  Streptococcus pneumoniae PCV20. R21/Matrix-M™ Malaria (Plasmodium falciparum) vaccine 77% efficacy (approved and in mass production). Bivalent SARS-Cov-2.

[I am very thankful to receive links, additions and corrections to update, and to remove any obsolete material herein if spotted. Anti-Covid-19, anti-MMR, anti-Gardasil, anti-poliovirus anti-vaxxer depopulating messages are both unwelcome and repulsive to me.]

BREAKING NEWS: Vaccine Catastrophe - Veterinary Vaccine (Live-Attenuated Brucella abortus strain RB51) has incorrectly been indicated as an 'approved' prophylactic therapy for human vaccination against Brucellosis or Malta Fever (also variously known as ‘Mediterranean Fever’ and ‘Undulant Fever’). This error is totally inexcusable as this strain is extremely harmful when given to humans. Immunisation Schedule for Zaire Ebola virus for work where large bull (bovine) and buffalo herds are present (put together for the rescue and care insurers). Zaire Ebola contamination management in large herds of aforesaid large ruminants proves problematic with the biohazard suit that protect from the disease vectors as the animals respond aggressively to the human protective gear leading to panicking animals attacks, attempts of human butchery and animal rummage where people and properties can suddenly become threatened, as a health protection gives rise to animal threat by the rummaging animals trampling and horn attacking people in biohazard gear. The ring fencing experimental Zaire Ebola vaccines were not available at the time of this original plan instigated where the China-based organisation prepared an emergency quantitative easing (QE) cash programme, ‘helicopter drops of money’ as a mitigation strategy to persuade the food producers and food vendors to continue serving the general public against an infection risk during a major ebola epidemic - to prevent food industry's distribution and production collapses as the personnel might otherwise decide to stop working and to stay home so as to avoid infecting themselves by the dangerous pathogen (in this case a Zaire Ebola Virus). The above can lead to severe food shortages and ultimately potential starvation occurrence unless that epidemic had not subsided soon enough to prevent this secondary consequence from emerging. Because of similarity of early Zaire Ebola symptoms to other infectious illnesses at the early stages, the work undertaken in remote areas, the lead time in medical evacuations in case of illnesses, and the immense cost of privately-funded flying hospital dispatch to carry out a rescue operation, an exhaustive mutual exclusion prophylactic scheme was initiated to minimise unnecessary calls for such a flying hospital facility (remote medical service) from overseas.

Reported BEXSERO to GlaxoSmithKline on an unlisted side effect of stealthy temperature rise (see 19/03/2020 version, page 7) to +42.3C / +108.1F with weakening of normal body temperature control like sweating and relative lack of sense of highly elevated body temperature able to cause heat stroke and other related damage to body.

The immunisation schedule incorporates emergency authorisation Covid-19 immunisations and coronavirus vaccines that shortly complete their approval. Some of the Covid-19 immunisations likely vanish from marketplace as soon as the pandemic is over whereas some other vaccine designs may seek themselves second life as generic coronavirus immunisations. (The research field of coronaviruses is rapidly changing with these overlooked viruses also causing many common colds is brought into spotlight.) Almost all Covid-19 products have not been tested for concomitant use with many other immunisation products and therefore a reasonable space should be allowed between immunisations to avoid adverse effect risks. Because of this one ought to consider whether at current pandemic situation some immunisation products of lesser importance should be taken and whether it is better to defer them until situation clears (considering the ongoing infections with Covid-19 variants and especially in some remote regions where sequencing of the variants is very sparse as the protection to Covid-19 is very important).  Because of above reason, this schedule is not currently geared for rapid deployment in tropics as too many uncertainties lie within which good protection against Covid-19 must prevail. Section on Covid-19 products is continually expiring due to evolving situation.

Updates on Streptococcus pneumoniae PCV20.

The latest version of the document supersedes all earlier versions that ought to be discarded and not used.

Brucellosis is rare in pregnancy. Recently, an increase in the incidence of this disease has been observed in our area. We present 7 cases of brucellosis in pregnancy and review the literature on the effects of brucellosis on the outcome of pregnancy. Brucellosis is rare in the Middle East and Africa and the most common source of infection is unpasteurized milk products. Brucella is a coccobacillus, gram-negative bacterium, whose hosts are mostly animals. There is controversy about the relationship between brucellosis and the outcome of pregnancy. There is some evidence that there is a higher rate of complications such as abortion, premature rupture of membranes and preterm delivery in infected animals. Reasons for this difference in the impact of brucella in animals and man include the absence of the carbohydrate erythritol in the human placenta, which appears to be a preferential medium and growth factor for brucella in the placentas of animals. There is uncertainty regarding effe...

The aim of this study was to investigate the frequency, location and type of rpoB mutations in Mycobacterium tuberculosis isolated from patients in Iran. 91 sputum were collected from suspected tuberculosis patients, 34 Rif-r isolates (87%) were identified as M. tuberculosis. Polymerase chain reaction (PCR) amplification and DNA sequencing methods were performed. 411 bp fragments of rpoB gene were sequenced and mutations in 81 bp regions were analyzed. 60 mutations and 13 micro deletions were identified in 29 RIF-r MBT (85%). Among 60 mutations, 6 silent and 54 missense were identified. Missense mutations produced 23 types of amino acid substitutions. In 5 RIF-r MBT isolates (15%) no mutations were found in the core region of the rpoB gene. All silent mutations were localized in codon 507. Most frequent mutations detected from Iranian strains were in codons 523 and 526. Five alleles in codon 526 and 3 alleles in triplets in each codons 507, 508, 513 were found. 6 (19%) strains harbo...

Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were m...

Present methods of antimicrobial susceptibility testing of Bordetella pertussis are time consuming and require specialized media that are not commercially available. We tested 52 isolates of B. pertussis for resistance to erythromycin, trimethoprim-sulfamethoxazole, chloramphenicol, and rifampin by agar dilution with Bordet-Gengou agar (BGA) containing 20% horse blood (reference method), Etest using BGA and Regan-Lowe agar without cephalexin (RL−C), and disk diffusion using BGA and RL−C. The organisms tested included four erythromycin-resistant isolates of B. pertussis from a single patient, a second erythromycin-resistant strain of B. pertussis from an unrelated patient in another state, and 47 nasopharyngeal surveillance isolates of B. pertussis from children in the western United States. The results of agar dilution testing using direct inoculation of the organisms suspended in Mueller-Hinton broth were within ±1 dilution of those obtained after overnight passage of the inoculum ...

Curable disease tuberculosis is becoming incurable or difficult to treat due to drug resistance. Multi drug resistance tuberculosis is a major health problem for less developed countries. Development of drug resistance is mainly as result of man related factors and poor lifestyle. Identifying predictors of drug resistance and working on them is the important way of reducing the expansion in high burden countries. Ethiopia is one of TB, TB/HIV, and multi-drug resistant tuberculosis (MDR-TB) high burden country globally. This study was aimed to assess predictor of MDR-TB in southwest part of Ethiopia. Unmatched case control study was conducted in case to control ratio of 1:1.2 in southwest part of Ethiopia. The cases were recruited from confirmed MDR-TB patient enrolled on second line treatment in Shenen Gibe Hospital (MDR-TB treatment center of the prefecture) and the controls were recruited from previously TB patients who cured or patient with smear negative at the end of treatment ...

ABSTRACTThe objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (Cmax) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower medianCmaxand lower exposure (area under the time-concentration curve from 0 to 8 h [AUC0–8]) of INH (Cmax, 2.5 versus 5.1 μg...

Multidrug resistance (MDR) involves resistance to both isoniazid and rifampicin, which makes the treatment of tuberculosis very difficult. Extensive drug resistance (XDR) occurs when, in addition to isoniazid and rifampicin resistance, the microorganisms are resistant to a fluoroquinolone and an injectable agent (e.g., kanamycin, amikacin, or capreomycin). Generally, drug susceptibility testing takes more than 3-4 weeks after the initial cultivation. There is an urgent need to identify methods that can rapidly detect both the presence of Mycobacterium tuberculosis and the status of drug resistance. This study was aimed at evaluating the line probe assay (LiPA; Nipro Co.), for the identification of Mycobacterium species and detection of mutations associated with antituberculous drugs. We found that LiPA enabled the rapid identification of M. tuberculosis, M. avium, M. intracellulare, and M. kansasii. When the results of the LiPA and conventional drug susceptibility tests were compare...

The current strategy for leprosy control depends mainly on early case detection and providing the recommended multidrug therapy (MDT) dosage. Understanding the molecular mechanisms of drug resistance to each of these drugs is essential in providing effective treatment and preventing the spread of resistant strains in the community. The progress of molecular biology research provides a very efficient opportunity for the diagnosis of drug resistance by in vitro method. We aimed to investigate the point mutations within the rpoB gene region of the Mycobacterium leprae genome, which are responsible for resistance to rifampicin, in order to determine the emergence of drug resistance in leprosy in the Kolkata region of West Bengal. A total of 50 patients with a relapse of leprosy were enrolled in the study. Skin smears were obtained for estimation of bacillary index and biopsies were obtained in 70% alcohol for extraction of DNA. The extracted DNA was amplified by M. leprae-polymerase cha...

In this report we describe an animal experiment which showed delayed clearance of preformed 125I-HSA-anti-HSA immune complexes (with five times excess HSA) from the circulation of mice treated with antileprosy drugs (dapsone, clofazimine, and rifampin--multidrug therapy for 7 days) in comparison with normal (untreated) mice. The results also showed delayed retention of the preformed immune complexes in the spleen and kidneys of the antileprosy-drug-treated animals. The exact mechanism of the delayed handling of preformed immune complexes in mice fed antileprosy drugs could not be ascertained. However, in light of the anticomplementary effects of clofazimine and dapsone, as reported earlier, and in light of the large accumulation of clofazimine and rifampin in macrophages, it has been postulated that in the drug-fed animals either the immune complexes could not be phagocytosed by macrophages, through the avenue of their C3b receptors, or the immune complexes could not be downgraded e...

The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansus...

BACKGROUND: Implementation of the World Health Organization's DOTS strategy (Directly Observed Treatment Short-course therapy) can result in significant reduction in tuberculosis incidence. We estimated potential costs and benefits of DOTS expansion in Haiti from the government, and societal perspectives. METHODS: Using decision analysis incorporating multiple Markov processes (Markov modelling), we compared expected tuberculosis morbidity, mortality and costs in Haiti with

Rapid and correct diagnosis is crucial for the management of multidrug resistance (MDR) in Mycobacterium tuberculosis (MTB). The present study aims at rapid diagnosis for identification of multidrug resistance tuberculosis (MDR-TB) using real-time PCR. FRET hybridization probes targeting most prominent four selected codons for rpoB526 and 531 and for katG314 and 315 genes were designed and evaluated on 143 clinical MTB isolates and paired sputa for rapid detection of MDR-TB. The results of real-time PCR were compared with gold standard L-J proportion method and further validated by DNA sequencing. Of the 143 MTB positive cultures, 85 and 58 isolates were found to be 'MDR' and 'pan susceptible', respectively by proportion L-J method. The sensitivity of real-time PCR for the detection of rifampicin (RIF) and isoniazid (INH) were 85.88 and 94.11%, respectively, and the specificity of method was found to be 98.27%. DNA sequencing of 31 MTB isolates having distinct meltin...

H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amoxicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard thi...

Understanding the circulating Mycobacterium tuberculosis resistance mutations is vital for better TB control strategies, especially to inform a new MDR-TB treatment programme. We complemented the phenotypic drug susceptibility testing (DST) based drug resistance surveys (DRSs) conducted in Uganda between 2008 and 2011 with Whole Genome Sequencing (WGS) of 90 Mycobacterium tuberculosis isolates phenotypically resistant to rifampicin and/or isoniazid to better understand the extent of drug resistance. A total of 31(34.4 %) patients had MDR-TB, 5 (5.6 %) mono-rifampicin resistance and 54 (60.0 %) mono-isoniazid resistance by phenotypic DST. Pyrazinamide resistance mutations were identified in 32.3% of the MDR-TB patients. Resistance to injectable agents was detected in 4/90 (4.4%), and none to fluoroquinolones or novel drugs. Compensatory mutations in rpoC were identified in two patients. The sensitivity and specificity of drug resistance mutations compared to phenotypic DST were for r...