Ramp Research Articles

Nano-scaled surfaces and sustainable-antibiotic-release from polymeric coating for application on intra-osseous implants and trans-mucosal abutments

Multifunctional surfaces may display the potential to accelerate and promote the healing process around dental implants. However, the initial cellular biocompatibility, molecular activity, and the release of functionalized molecules from these novel surfaces require extensive investigation for clinical use. Aiming to develop and compare innovative surfaces for application in dental implants, the present study utilized titanium disks, which were treated and divided into four groups: machined (Macro); acid-etched (Micro); anodized-hydrophilic surface (TNTs); and anodized surface coated with a rifampicin-loaded polymeric layer (poly(lactide-co-glycolide), PLGA) (TNTsRIMP). The samples were characterized regarding their physicochemical properties and the cumulative release of rifampicin (RIMP), investigated at different pH values. Additionally, differentiated osteoblasts from mesenchymal cells were used for cell viability and qRT-PCR analysis. Antibacterial properties of each surface treatment were investigated against Staphylococcus epidermidis. TNTsRIMP demonstrated controlled drug release for up to 7 days in neutral pH environments. Osteogenic cell cultures indicated that all the evaluated surfaces showed biocompatibility. The TNTs group revealed up-regulated values for bone-related gene quantification in 7 days, followed by the TNTsRIMP group. Furthermore, the antibiotic-functionalized surface revealed effectiveness to inhibit S. epidermidis and stimulate promising conditions for osteogenic cell behavior. Characteristics such as nanomorphology and hydrophilicity were determinants for the up-regulated quantification of osteogenic biomarkers related to early bone maturation, encouraging application in intra-osseous implant surfaces; in addition, antibiotic-functionalized surfaces demonstrated significant higher antibacterial properties compared to the other groups. Our findings suggest that polymeric-antibiotic-loaded coating might be applied for the prevention of early infections, favoring its application in multifunctional surfaces for intra- and/or trans-mucosal components of dental implants, while, hydrophilic nanotextured surfaces promoted optimistic properties to stimulate early bone-related cell responses, favoring its application in bone-anchored surfaces.

Impact of the Anti-Tuberculosis Drug Rifampicin on the Feeding, Growth and Embryonic Developmental Profile of the Mosquitofish <i>Gambusia affinis</i>

Although the accumulation of pharmaceutical drugs in aquatic bodies has increased rapidly in recent years, the effect of rifampicin (RIF), a first-line anti-tuberculosis drug, on fish feeding, growth, and embryonic development is unknown. This investigation aimed to determine the impact of RIF on growth and embryonic developmental profile in the mosquitofish Gambusia affinis. Experimental groups included controls, which were kept in normal water for 21 days, whereas those in the second, third, and fourth groups were exposed to 50, 200, and 500 mg RIF/L water, respectively. The food intake rate and Specific Growth Rate (SGR) showed a concentration-dependent significant decrease in RIF-treated fish compared with controls, and a strong positive correlation was found between food consumption and SGR. A significant decrease in the number of embryos at an early stage of development and the total number of embryos in RIF-treated fish was associated with several congenital anomalies such as lack of vitellogenin accumulation, yolk sac regression, decreased pigmentation, aggregations of blood vessels, and curvature of the spinal cord compared with controls. Together, these results reveal for the first time that RIF treatment not only impacts feeding and growth, but also exerts potential teratogenic effect on embryonic developmental stages in the mosquitofish G. affinis.

Amphiphilic tribasic galactosamines potentiate rifampicin in Gram-negative bacteria at low Mg++/Ca++concentrations

Many antibiotics specific to Gram-positive bacteria like rifampicin (RIF) are inactive in Gram-negative bacteria because of outer membrane (OM) impermeability. Enhancing the OM permeability of these antibiotics with the help of OM perturbants is a promising strategy to develop new agents against Gram-negative bacteria. Here we report the synthesis and biological properties of amphiphilic tribasic galactosamines as potential RIF potentiators. Our results demonstrate that tribasic galactose-based amphiphiles potentiate RIF in multidrug-resistant Acinetobacter baumannii and Escherichia coli but not Pseudomonas aeruginosa in low salt-containing media. Under these conditions, lead compounds 20, 22 and 35 lowered the minimum inhibitory concentration of RIF by 64- to 256-fold against Gram-negative bacteria. However, the RIF-potentiating effect was reduced when bivalent Mg++ or Ca++ ions were added in the media at physiological concentrations. Overall, our results indicate that amphiphilic tribasic galactosamine-based compounds show reduced RIF-potentiating effects when compared to amphiphilic tobramycin antibiotics at physiological salt concentrations.

Prevalence of Mycobacterium tuberculosis mutations associated with isoniazid and rifampicin resistance: A systematic review and meta-analysis

Tuberculosis (TB) is still one of the leading causes of worldwide death, especially following the emergence of strains resistant to isoniazid (INH) and rifampicin (RIF). This study aimed to systematically review published articles focusing on the prevalence of INH and/or RIF resistance-associated mutations of Mycobacterium tuberculosis isolates in recent years. Literature databases were searched using appropriate keywords. The data of the included studies were extracted and used for a random-effects model meta-analysis. Of the initial 1442 studies, 29 were finally eligible to be included in the review.The overall resistance to INH and RIF was about 17.2% and 7.3%, respectively. There was no difference between the frequency of INH and RIF resistance using different phenotypic or genotypic methods. The INH and/or RIF resistance was higher in Asia. The S315T mutation in KatG (23.7 %), C-15 T in InhA (10.7 %), and S531L in RpoB (13.5 %) were the most prevalent mutations. Altogether, the results showed that due to S531L in RpoB, S315T in KatG, and C-15 T in InhA mutations INH- and RIF-resistant M. tuberculosis isolates were widely distributed. Thus, it would be diagnostically and epidemiologically beneficial to track these gene mutations among resistant isolates.

Epidemiology-based wastewater monitoring for ecological risks of anti-tuberculosis drugs mixture effects

First-line anti-tuberculosis (TB) drugs are commonly used to treat TB worldwide, leading to more contaminated wastewater being widely discharged into aquatic environments. However, studies of mixture interactions of anti-TB drugs and their residues in aquatic environments are scarce. This study aimed to determine the toxic interactions of anti-TB drugs—isoniazid (INH), rifampicin (RMP), and ethambutol (EMB)—in binary and ternary mixtures on Daphnia magna and used the epidemiology of TB history to construct epidemiology-based wastewater monitoring for assessing the environmental release of residues and related ecological risks. The acute immobilization of median effect concentrations (EC50) was 25.6 mg L−1 for INH, 80.9 mg L−1 for RMP, and 188.8 mg L−1 for EMB, as toxic units (TUs) for assessing mixture toxicity. The ternary mixture exhibited the lowest TUs at 50 % effects with 1.12, followed by 1.28 for RMP + EMB, 1.54 for INH + RMP, and 1.93 for INH + EMB, indicating antagonistic interactions. Nevertheless, the combination index (CBI) was used to examine the mixture toxicity in response to immobilization, revealing that the ternary mixture of CBI ranged from 1.01 to 1.08, tending to have a nearly additive effect when suffering >50 % effect (at high concentration levels). The forecasted environmentally relevant concentrations of anti-TB drugs have been on downward trends with ng L−1 level from 2020 to 2030 in Kaohsiung, Taiwan. Although ecotoxicological risks from the wastewater treatment plant and receiving water in the field were slightly greater than the prediction from epidemiology-based wastewater monitoring, there were no risk concerns. Here, we achieved the establishment of evidence that anti-TB drug mixtures' interaction and epidemiological-based monitoring support a systematic approach, resolving the absence of the mixture toxicity information for anti-TB mixture risk assessment in aquatic environments.

Modifications of Ganoderma lucidum spores into digestive-tissue highly adherent porous carriers with selective affinity to hydrophilic or hydrophobic drugs

Ganoderma lucidum spores (GLSs) have been suggested to provide optimal structures for transporting orally bioavailable drugs. However, the double-layer wall and cavities of GLSs are naturally closed. This study aimed to modify GLSs into porous carriers by opening the layers and internal cavity with iturin A (IA) followed by potassium hydroxide (KOH) or hydrochloric acid (HCl). The (IA + KOH)- and (IA + HCl)-treated GLS carriers exhibited a high loading rate of 301.50 ± 2.33 and 268.18 ± 7.72 mg/g for the hydrophilic methylene blue (MB) and hydrophobic rifampicin (RF), respectively. The mechanisms underlying the modification involved the enhancement of the specific surface area with IA and the exposure of hydrophilic groups or hydrophobic groups of the GLSs with KOH or HCl. The sustained 48-h molecule-release profiles of the MB- and RF-loaded GLS carriers were best fitted using a first-order kinetics model in simulated gastric (or intestinal) fluid compared with other models. In mice, the designed GLS carriers had high adhesion capacities onto the mucosa of the digestive tract and long retention times (120 h), and even promoted the secretion of mucus and expression of several key intestinal barrier proteins. This study provided a new method to modify GLSs into oral carriers with selective drug affinity, high loading capacity, sustained drug release, and high adhesion to the digestive tract.

Evaluation of Omadacycline Alone and in Combination with Rifampin against Staphylococcus aureus and Staphylococcus epidermidis in an In Vitro Pharmacokinetic/Pharmacodynamic Biofilm Model.

Biofilm-associated infections lead to substantial morbidity. Omadacycline (OMC) is a novel aminomethylcycline with potent in vitro activity against Staphylococcus aureus and Staphylococcus epidermidis, but data surrounding its use in biofilm-associated infections are lacking. We investigated the activity of OMC alone and in combination with rifampin (RIF) against 20 clinical strains of staphylococci in multiple in vitro biofilm analyses, including an in vitro pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor (CBR) model (simulating human exposures). The observed MICs for OMC demonstrated potent activity against the evaluated strains (0.125 to 1 mg/L), with an increase of MICs generally observed in the presence of biofilm (0.25 to >64 mg/L). Furthermore, RIF was shown to reduce OMC biofilm MICs (bMICs) in 90% of strains, and OMC plus RIF combination in biofilm time-kill analyses (TKAs) exhibited synergistic activity in most of the strains. Within the PK/PD CBR model, OMC monotherapy primarily displayed bacteriostatic activity, while RIF monotherapy generally exhibited initial bacterial eradication, followed by rapid regrowth likely due to the emergence of RIF resistance (RIF bMIC, >64 mg/L). However, the combination of OMC plus RIF produced rapid and sustained bactericidal activity in nearly all the strains (3.76 to 4.03 log10 CFU/cm2 reductions from starting inoculum in strains in which bactericidal activity was reached). Furthermore, OMC was shown to prevent the emergence of RIF resistance. Our data provide preliminary evidence that OMC in combination with RIF could be a viable option for biofilm-associated infections with S. aureus and S. epidermidis. Further research involving OMC in biofilm-associated infections is warranted.

Resistance Profiles to Second-Line Anti-Tuberculosis Drugs and Their Treatment Outcomes: A Three-Year Retrospective Analysis from South India.

Background: Patients with first-line drug resistance (DR) to rifampicin (RIF) or isoniazid (INH) as a first-line (FL) line probe assay (LPA) were subjected to genotypic DST using second-line (SL) LPA to identify SL-DR (including pre-XDR) under the National TB Elimination Program (NTEP), India. SL-DR patients were initiated on different DR-TB treatment regimens and monitored for their outcomes. The objective of this retrospective analysis was to understand the mutation profile and treatment outcomes of SL-DR patients. Materials and Methods: A retrospective analysis of mutation profile, treatment regimen, and treatment outcome was performed for SL-DR patients who were tested at ICMR-NIRT, Supra-National Reference Laboratory, Chennai between the years 2018 and 2020. All information, including patient demographics and treatment outcomes, was extracted from the NTEP Ni-kshay database. Results: Between 2018 and 2020, 217 patients out of 2557 samples tested were identified with SL-DR by SL-LPA. Among them, 158/217 were FQ-resistant, 34/217 were SLID-resistant, and 25/217 were resistant to both. D94G (Mut3C) of gyrA and a1401g of rrs were the most predominant mutations in the FQ and SLID resistance types, respectively. Favorable (cured and treatment complete) and unfavorable outcomes (died, lost to follow up, treatment failed, and treatment regimen changed) were recorded in a total of 82/217 and 68/217 patients in the NTEP Ni-kshay database. Conclusions: As per the testing algorithm, SL- LPA is used for genotypic DST following identification of first-line resistance, for early detection of SL-DR in India. The fluoroquinolone resistance pattern seen in this study population corelates with the global trend. Early detection of fluoroquinolone resistance and monitoring of treatment outcome can help achieve better patient management.

Nanomotion technology in combination with machine learning: a new approach for a rapid antibiotic susceptibility test for Mycobacterium tuberculosis

Nanomotion technology is a growth-independent approach that can be used to detect and record the vibrations of bacteria attached to cantilevers. We have developed a nanomotion-based antibiotic susceptibility test (AST) protocol for Mycobacterium tuberculosis (MTB). The protocol was used to predict strain phenotype towards isoniazid (INH) and rifampicin (RIF) using a leave-one-out cross-validation (LOOCV) and machine learning techniques. This MTB-nanomotion protocol takes 21 h, including cell suspension preparation, optimized bacterial attachment to functionalized cantilever, and nanomotion recording before and after antibiotic exposure. We applied this protocol to MTB isolates (n = 40) and were able to discriminate between susceptible and resistant strains for INH and RIF with a maximum sensitivity of 97.4% and 100%, respectively, and a maximum specificity of 100% for both antibiotics when considering each nanomotion recording to be a distinct experiment. Grouping recordings as triplicates based on source isolate improved sensitivity and specificity to 100% for both antibiotics. Nanomotion technology can potentially reduce time-to-result significantly compared to the days and weeks currently needed for current phenotypic ASTs for MTB. It can further be extended to other anti-TB drugs to help guide more effective TB treatment.

Cartridge Based Nucleic Acid Amplification Test, an Important Diagnostic Tool for Tuberculosis both Pulmonary and Extra-Pulmonary Tuberculosis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), one of the top 10 causes of death worldwide (ranking above HIV/AIDS). About a quarter of the world's population is infected with TB and thus at risk of developing TB disease. The Global TB Report 2019 states that in 2018 a total of 1.5 million people died from TB, an estimated 10 million (range, 9.0–11.1 million) people fell ill worldwide.(1) Eight countries accounted for two-thirds of the total, with India leading the count, followed by China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh, and South Africa.(1) Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. The WHO estimates that there were 484 000 new cases with resistance to rifampicin (RIF) – the most effective first-line drug, which accounts for 78% MDR-TB cases. The MDR-TB burden largely falls on three countries – India, China, and the Russian Federation. About 6.2% of MDR-TB cases had extensively drug-resistant TB (XDR-TB) in 2018. Worldwide, only 56% of MDR-TB patients are currently successfully treated. Globally, TB incidence is falling at about 2% per year. This needs to accelerate to a 4%–5% annual decline to reach the 2020 milestones of the End TB Strategy.

Controlled Delivery of Amoxicillin and Rifampicin by Three‐Dimensional Polyvinyl alcohol/Bismuth Ferrite Scaffolds

AbstractSkin is a protective barrier that can protect against environmental influences and renew itself. However, in some cases, this regenerative property is lost, and this causes delays in wound healing. Wound healing is a complex and long‐lasting phase. Any bacterial infection during the wound healing process delays wound healing. The therapeutic efficacy can be increased by using nanocarrier drug delivery systems to the target tissue with modern wound dressings. Controlled nano drug delivery systems increase the therapeutic efficacy in the treatment of diseases and provide a faster recovery process. In this study, amoxicillin (AMX) and rifampicin (RIF) were loaded into the bismuth ferrite (BFO) particles which were synthesized with the co‐precipitation method. Then, these drug‐loaded BFO particles (0.075 %) were added separately to 13 % polyvinyl alcohol (PVA) solution and the solutions were printed three‐dimensionally to obtain three dimensional scaffolds. With these designed scaffolds, it is aimed to reduce the risk of inflammation in wound tissues and increase therapeutic efficacy with controlled release. The SEM images proved that homogeneous pore distributions could be achieved with these combinations. The tensile test results showed that drug‐loaded BFO addition increased the mechanical strength of the 13 % PVA scaffold. The biocompatibility test results demonstrated that the highest viability values of the human adipose tissue‐derived mesenchymal stem cells were obtained for AMX‐added 13 % PVA scaffolds.

Oral rifampicin interferes with urine dipstick tests for patients with pulmonary tuberculosis.

Rifampicin (RMP) and its major metabolite, desacetyl rifampicin (dRMP), can interfere with urine dipstick tests (UDTs) in patients with tuberculosis (TB) who receive oral RMP. This study sought to examine the effects of RMP and dRMP on UDTs using 2 different urine dipsticks (i.e., Arkray's Aution Sticks 10EA and GIMA's Combi-Screen 11SYS Plus sticks). Urine colorimetry was applied to measure RMP concentrations and determine the range of total RMP concentration in the urine within 2-6 and 12-24 h of oral administration of RMP. In vitro interference assays and confirmatory tests were performed to evaluate the effects of RMP and dRMP on the analytes. The total RMP concentration in the urine of the 40 TB patients analyzed as urine sample was 88-376 µg/mL within 2-6 h and 22-112 µg/mL within 12-24 h of oral administration of RMP. Interference was observed for different analytes at consistent or varied RMP concentrations between the in vitro interference assays and the confirmatory tests, including 75 patients [Aution Sticks 10EA: 250, 250 µg/mL for protein (PRO); 400, 300 µg/mL for leukocyte esterase (LEU); Combi-Screen 11SYS Plus: 125, 150 µg/mL for ketones (KET); 500, 350 µg/mL for nitrite (NIT); 200, 300 µg/mL for PRO; 125, 150 µg/mL for LEU]. RMP and dRMP interfered with the analytes of the UDTs using the 2 urine dipsticks in different levels. The in vitro interference assay is not an ideal substitute for the confirmatory test. The collection of urine samples within 12-24 h of administration of RMP can prevent the interference caused by RMP and dRMP.

Profile and Frequency of Mutations Conferring Drug-Resistant Tuberculosis in the Central, Southeastern and Eastern Ethiopia.

Advances in molecular tools that assess genes harboring drug resistance mutations have greatly improved the detection and treatment of drug-resistant tuberculosis (DR-TB). This study was conducted to determine the frequency and type of mutations that are responsible for resistance to rifampicin (RIF), isoniazid (INH), fluoroquinolones (FLQs) and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis (MTB) isolates obtained from culture-positive pulmonary tuberculosis (TB) patients in the central, southeastern and eastern Ethiopia. In total, 224 stored culture-positive MTB isolates from pulmonary TB patients referred to Adama and Harar regional TB laboratories between August 2018 and January 2019 were assessed for mutations conferring RIF, INH, FLQs and SLIDs resistance using GenoType®MTBDRplus (MTBDRplus) and GenoType®MTBDRsl (MTBDRsl). RIF, INH, FLQs and SLIDs resistance-conferring mutations were identified in 88/224 (39.3%), 85/224 (38.0%), 7/77 (9.1%), and 3/77% (3.9%) of MTB isolates, respectively. Mutation codons rpoB S531L (59.1%) for RIF, katG S315T (96.5%) for INH, gyrA A90V (42.1%) for FLQs and WT1 rrs (100%) for SLIDs were observed in the majority of the isolates tested. Over a 10th of rpoB mutations detected in the current study were unknown. In this study, the most common mutations conferring drug resistance to RIF, INH, FLQs were identified. However, a significant proportion of RIF-resistant isolates manifested unknown rpoB mutations. Similarly, although few in number, all SLID-resistant isolates had unknown rrs mutations. To further elucidate the entire spectrum of mutations, tool such as whole-genome sequencing is imperative. Furthermore, the expansion of molecular drug susceptibility testing services is critical for tailoring patient treatment and preventing disease transmission.

Adequacy of WHO weight-band dosing and fixed-dose combinations for the treatment of TB in children.

BACKGROUND: We examined whether the updated WHO weight-band dosing recommendations and fixed-dose combination tablets for the treatment of TB in children achieves recommended calculated dosages and adequate drug plasma exposure.DESIGN/METHODS: Children on first-line TB treatment per WHO guidelines were enrolled. Blood sampling at pre-dose, 1, 2, 4, 8, and 12 h post-dose after at least 4 weeks of treatment was performed. Drugs concentrations were measured using validated liquid chromatography tandem with mass spectrometry and pharmacokinetic parameters calculated using noncompartmental analysis. Plasma drug exposure below the lower limit of the 95% confidence interval of the mean for children was considered low and above the upper limit was high.RESULTS: Of 71 participants, 34 (47.9%) had HIV coinfection. The median calculated dose for isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) was 10.0 (range 4.3-13.3), 15.0 (range 8.6-20.0), 30.0 (range 21.0-40.0), and 20.4 (range 14.3-26.7) mg/kg, respectively. Overall, most patients had under-exposure for RIF and PZA and over-exposure for INH and EMB. Drug dose and weight-for-age Z-score were associated with area under the curve from time 0-24 h for all drugs.CONCLUSIONS: Despite adherence to WHO dosing guidelines, low PZA and RIF plasma exposures were frequent in our study population. Higher than currently recommended dosages of RIF and PZA may be needed in children.

Perbandingan Kadar HB Sebelum dan Sesudah Pengobatan Oat Fase Intensif pada Penderita Tuberkulosis Paru di Puskesmas Petanahan Kebumen Tahun 2021

Treatment of tuberculosis with main anti-tuberculosis drugs (OAT) includes isoniazid (INH), rifampin (RIF), ethambutanol (EMB), streptomycin (SM), and pyrazinamide (PZA). Although most Anti-Tuberculosis Drugs (OAT) are acceptable in therapy, they have potential side effects, including the side effects of hematological reactions such as anemia. This study's purpose was to compare HB levels before and after the intensive phase of Anti-Tuberculosis Drugs treatment in TB patients at Petanahan Public Health Care Center, Kebumen Regency. This was an analytic observational study with a cross-sectional design. The sample in this study was 28 people. The result showed that the average Hb level of pulmonary TB patients at Petanahan Public Health Care Center before and after the treatment were 11.05 g/dl and 11.6 g/dl, respectively. Therefore there was an effect of comparing Hb levels before and after the intensive phase of Anti-Tuberculosis Drugs treatment in pulmonary TB patients at the Petanahan Public Health Center in 2021. The increase in the average Hb levels of patients with pulmonary TB before and after the treatment was 0.55. The sig values obtained from the analysis of Hb levels before and after the treatment were a = 0.200 (p0.005) and 0.023, respectively. Due to the P value (0.023 < 0.05), Ho was rejected. It meant that there was a difference in Hb levels before and after the Intensive Phase of Anti-Tuberculosis Drugs treatment in patients with pulmonary TB at Petanahan Public Health Care Center, Kebumen Regency.

A comprehensive electrochemical study on anti-tuberculosis drug rifampicin. Investigating reactions of rifampicin-quinone with other anti-tuberculosis drugs, isoniazid, pyrazinamide and ethambutol

Electrochemical behavior of rifampicin (RIF) as an anti-tuberculosis drug was studied in detail in water/ethanol mixture using different voltammetric techniques. The results indicate that rifampicin is oxidized in two steps, the first step is related to the reversible oxidation of hydroquinone moiety to benzoquinone and the second one is related to the irreversible oxidation of phenolic ring of RIF. In this work, the adsorption activity and diffusion coefficient of RIF was also determined and shows that the first oxidation step is diffusion control while second one is a diffusion/adsorption control process. Furthermore, our results show that the oxidation of RIF (especially in the first step) is complex and highly pH-dependent. The Pourbaix diagram was drawn for this drug and useful information was obtained regarding the oxidized and reduced forms of RIF and the acid/base properties of the species obtained from RIF and its oxidized form (RIF-Q). The first line of tuberculosis drug treatment currently includes the simultaneous use of rifampicin, isoniazid, pyrazinamide and ethambutol (Fixed Dose Combinations, FDCs). Understanding the mechanism of drug-drug interactions is not only useful in preventing drug toxicity or side effects, but also in devising safer treatments for diseases. In this study, based on the obtained electrochemical data, we suggest plausible mechanisms for the reaction of RIF-Q with the medicines prescribed in FDC. The obtained results show that the mentioned drugs through their free amino group can react with RIF-Q. Our findings also show that the rate of these reactions is low in acidic environments such as the stomach and high in neutral or alkaline environments such as the small intestine. In these reactions, ethambutol has the highest rate and pyrazinamide has the lowest rate for the reaction with RIF.

Enhanced adsorptive removal of rifampicin and tigecycline from single system using nano-ceria decorated biochar of mango seed kernel

Pharmaceutically active compounds (PhACs) represent an emerging class of contaminants. With a potential to negatively impact human health and the ecosystem, existence of pharmaceuticals in the aquatic systems is becoming a worrying concern. Antibiotics is a major class of PhACs and their existence in wastewater signifies a health risk on the long run. With the purpose of competently removing antibiotics from wastewater, cost-effective, and copiously available waste-derived adsorbents were structured. In this study, mango seeds kernel (MSK), both as a pristine biochar (Py–MSK) and as a nano-ceria-laden (Ce–Py–MSK) were applied for the remediation of rifampicin (RIFM) and tigecycline (TIGC). To save time and resources, adsorption experiments were managed using a multivariate-based scheme executing the fractional factorial design (FrFD). Percentage removal (%R) of both antibiotics was exploited in terms of four variables: pH, adsorbent dosage, initial drug concentration, and contact time. Preliminary experiments showed that Ce–Py–MSK has higher adsorption efficiency for both RIFM and TIGC compared to Py–MSK. The %R was 92.36% for RIFM compared to 90.13% for TIGC. With the purpose of comprehending the adsorption process, structural elucidation of both sorbents was performed using FT-IR, SEM, TEM, EDX, and XRD analyses which confirmed the decoration of the adsorbent surface with the nano-ceria. BET analysis revealed that Ce–Py–MSK has a higher surface area (33.83 m2/g) contrasted to the Py–MSK (24.72 m2/g). Isotherm parameters revealed that Freundlich model best fit Ce–Py–MSK–drug interactions. A maximum adsorption capacity (qm) of 102.25 and 49.28 mg/g was attained for RIFM and TIGC, respectively. Adsorption kinetics for both drugs conformed well with both pseudo-second order (PSO) and Elovich models. This study, therefore, has established the suitability of Ce–Py–MSK as a green, sustainable, cost-effective, selective, and efficient adsorbent for the treatment of pharmaceutical wastewater.

Diagnostic performance of the GenoType MTBDRplus VER 2.0 line probe assay for the detection of isoniazid resistant Mycobacterium tuberculosis in Ethiopia.

Isoniazid (INH) resistant Mycobacterium tuberculosis (Hr-TB) is the most common type of drug resistant TB, and is defined as M tuberculosis complex (MTBC) strains resistant to INH but susceptible to rifampicin (RIF). Resistance to INH precedes RIF resistance in almost all multidrug resistant TB (MDR-TB) cases, across all MTBC lineages and in all settings. Therefore, early detection of Hr-TB is critical to ensure rapid initiation of appropriate treatment, and to prevent progression to MDR-TB. We assessed the performance of the GenoType MTBDRplus VER 2.0 line probe assay (LPA) in detecting isoniazid resistance among MTBC clinical isolates. A retrospective study was conducted among M. tuberculosis complex (MTBC) clinical isolates obtained from the third-round Ethiopian national drug resistance survey (DRS) conducted between August 2017 and December 2019. The sensitivity, specificity, positive predictive value, and negative predictive value of the GenoType MTBDRplus VER 2.0 LPA in detecting INH resistance were assessed and compared to phenotypic drug susceptibility testing (DST) using the Mycobacteria Growth Indicator Tube (MGIT) system. Fisher's exact test was performed to compare the performance of LPA between Hr-TB and MDR-TB isolates. A total of 137 MTBC isolates were included, of those 62 were Hr-TB, 35 were MDR-TB and 40 were INH susceptible. The sensitivity of the GenoType MTBDRplus VER 2.0 for detecting INH resistance was 77.4% (95% CI: 65.5-86.2) among Hr-TB isolates and 94.3% (95% CI: 80.4-99.4) among MDR-TB isolates (P = 0.04). The specificity of the GenoType MTBDRplus VER 2.0 for detecting INH resistance was 100% (95% CI: 89.6-100). The katG 315 mutation was observed in 71% (n = 44) of Hr-TB phenotypes and 94.3% (n = 33) of MDR-TB phenotypes. Mutation at position-15 of the inhA promoter region alone was detected in four (6.5%) Hr-TB isolates, and concomitantly with katG 315 mutation in one (2.9%) MDR-TB isolate. GenoType MTBDRplus VER 2.0 LPA demonstrated improved performance in detecting INH resistance among MDR-TB cases compared to Hr-TB cases. The katG315 mutation is the most common INH resistance conferring gene among Hr-TB and MDR-TB isolates. Additional INH resistance conferring mutations should be evaluated to improve the sensitivity of the GenoType MTBDRplus VER 2.0 for the detection of INH resistance among Hr-TB cases.

Miliary Pulmonary Tuberculosis After Intravesical BCG Instillation in a Patient with High-Grade Bladder Cancer

Intravesical administration of Bacillus Calmette-Guerin (BCG) vaccine is used in the treatment of superficial bladder cancer. In clinical practice, intravesical BCG immunotherapy after transurethral tumor resection is a highly effective treatment option in preventing tumor recurrence and progression in medium and high risk superficial bladder tumors. Since patients are given live tuberculosis (TB) bacillus, serious side effects such as pneumonia, sepsis and even death can be seen. Lung involvement occurs in less than 1% of patients and most commonly presents as interstitial pneumonia or miliary TB. Miliary TB is difficult to diagnose and is usually based on high clinical suspicion, as Mycobacterium bovis is not isolated in most cases. Treatment is not completely standardized. However, in severe cases, a combination of antituberculosis drugs and corticosteroids is recommended. In this report, a case of miliary tuberculosis, a very rare complication after instillation of BCG into the bladder in a patient with a diagnosis of superficial bladder cancer, was presented. A 73-year-old male patient diagnosed with bladder tumor underwent transurethral resection of bladder tumor, and then weekly intravesical injection of BCG-MEDAC for six weeks had no adverse effects. Three weeks of intravesical BCG supplementation was planned for the patient who had no signs of recurrence when checked three months later by cystoscopy. Two hours after the first dose, the patient, who applied to the emergency department with the complaint of chills and shivering, was hospitalized for further follow-up and treatment. Afterwards, repeat cultures were taken from the patient whose fever continued on the seventh day of treatment with broad-spectrum antibiotics (meropenem and teicoplanin). In addition, when abdominal and thorax computed tomography (CT) were performed, multiple miliary nodular lesions were detected in both lungs and were evaluated in favor of miliary TB. With these findings, the patient was started on miliary TB therapy [isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (STM)] targeting Mycobacterium bovis, since it was an infection that developed after BCG injection. In the third week of the treatment, the patient's fever was under control, and he was discharged on the 25th day of his hospitalization because of significant improvement in infection markers [C-reactive protein(CRP)-procalcitonin]. At the end of two months, there was clear regression of pulmonary abnormalities on control thorax CT. In conclusion, miliary TB developing after intravesical BCG instillation is a very rare condition, the cause of which is not fully understood, the etiology of fever can be easily missed, and the diagnosis is difficult. In addition, this case is presented to draw attention to a critical disease that requires long treatment and follow-up and requires attention.

A pro-oxidant property of vitamin C to overcome the burden of latent Mycobacterium tuberculosis infection: A cross-talk review with Fenton reaction.

Tuberculosis (TB), caused by the bacillus M. tuberculosis, is one of the deadliest infectious illnesses of our day, along with HIV and malaria.Chemotherapy, the cornerstone of TB control efforts, is jeopardized by the advent of M. tuberculosis strains resistant to many, if not all, of the existing medications.Isoniazid (INH), rifampicin (RIF), pyrazinamide, and ethambutol are used to treat drug-susceptible TB for two months, followed by four months of INH and RIF, but chemotherapy with potentially harmful side effects is sometimes needed to treat multidrug-resistant (MDR) TB for up to two years. Chemotherapy might be greatly shortened by drugs that kill M. tuberculosis more quickly while simultaneously limiting the emergence of drug resistance.Regardless of their intended target, bactericidal medicines commonly kill pathogenic bacteria (gram-negative and gram-positive) by producing hydroxyl radicals via the Fenton reaction.Researchers have concentrated on vitamins with bactericidal properties to address the rising cases globally and have discovered that these vitamins are effective when given along with first-line drugs. The presence of elevated iron content, reactive oxygen species (ROS) generation, and DNA damage all contributed to VC's sterilizing action on M. tb in vitro. Moreover, it has a pleiotropic effect on a variety of biological processes such as detoxification, protein folding - chaperons, cell wall processes, information pathways, regulatory, virulence, metabolism etc.In this review report, the authors extensively discussed the effects of VC on M. tb., such as the generation of free radicals and bactericidal mechanisms with existing treatments, and their further drug development based on ROS production.