High Risk Of Drug Resistance Research Articles

Development of a Physiologically Based Pharmacokinetic Model for Nitrofurantoin in Rabbits, Rats, and Humans.

Nitrofurantoin (NFT) is a commonly used antibiotic for the treatment of urinary tract infections that can cause liver toxicity. Despite reports of hepatic adverse events associated with NFT exposure, there is still limited understanding of the interplay between NFT exposure, its disposition, and the risk of developing liver toxicity. In this study, we aim to develop a physiologically based pharmacokinetic (PBPK) model for NFT in three different species (rabbits, rats, and humans) that can be used as a standard tool for predicting drug-induced liver injury (DILI). We created several versions of the PBPK model using previously published kinetics data from rabbits, and integrated enterohepatic recirculation (EHR) using rat data. Our model showed that active tubular secretion and reabsorption in the kidney are critical in explaining the non-linear renal clearance and urine kinetics of NFT. We subsequently extrapolated the PBPK model to humans. Adapting the physiology to humans led to predictions consistent with human kinetics data, considering a low amount of NFT to be excreted into bile. Model simulations predicted that the liver of individuals with a moderate-to-severe glomerular filtration rate (GFR) is exposed to two-to-three-fold higher concentrations of NFT than individuals with a normal GFR, which coincided with a substantial reduction in the NFT urinary concentration. In conclusion, people with renal insufficiency may be at a higher risk of developing DILI due to NFT exposure, while at the same time having a suboptimal therapeutic effect with a high risk of drug resistance. Our PBPK model can in the future be used to predict NFT kinetics in individual patients on the basis of characteristics like age and GFR.

Treatment outcomes and its associated factors among pneumonia patients admitted to public hospitals in Harar, eastern Ethiopia: a retrospective follow-up study

ObjectiveAlthough there is a high risk of drug resistance, empiric treatment is a common approach for pneumonia management. In this respect, it is relevant to know treatment outcomes of patients...

Monoclonal Antibodies and Invasive Aspergillosis: Diagnostic and Therapeutic Perspectives.

Invasive aspergillosis (IA) is a life-threatening fungal disease that causes high morbidity and mortality in immunosuppressed patients. Early and accurate diagnosis and treatment of IA remain challenging. Given the broad range of non-specific clinical symptoms and the shortcomings of current diagnostic techniques, most patients are either diagnosed as “possible” or “probable” cases but not “proven”. Moreover, because of the lack of sensitive and specific tests, many high-risk patients receive an empirical therapy or a prolonged treatment of high-priced antifungal agents, leading to unnecessary adverse effects and a high risk of drug resistance. More precise diagnostic techniques alongside a targeted antifungal treatment are fundamental requirements for reducing the morbidity and mortality of IA. Monoclonal antibodies (mAbs) with high specificity in targeting the corresponding antigen(s) may have the potential to improve diagnostic tests and form the basis for novel IA treatments. This review summarizes the up-to-date application of mAb-based approaches in assisting IA diagnosis and therapy.

Depression in Tuberculosis Patient: A literature Review

Tuberculosis is one of the infectious diseases with the highest burden with the highest morbidity and mortality in the world. Tuberculosis is divided into two groups: latent tuberculosis and active tuberculosis. The diagnosis of tuberculosis can be established through anamnesis and investigations. Tuberculosis is often associated with levels of depression, the high incidence of depression in tuberculosis patients is caused by various factors including biological factors of the immune response system (IFN-g agents, TNF, IDO NALP3), social factors and behavioral factors. Management of anti-depressant therapy that is recommended as the first line is the SSRI group. Furthermore, patients with drug withdrawal or treatment failure, high risk of drug resistance, bad stigma about their disease will increase the risk of depression.

Multi drugs resistance to Diabetes Mellitus patients with tuberculosis in Manado City

Diabetes mellitus (DM) with pulmonary tuberculosis (TB) is an infectious disease if not educated regularly, there will be a high risk of drug resistance and even some anti-tuberculosis drugs. This study aims to identify anti-tuberculosis drug resistance in DM patients with TB in Manado City. The population in the study types 2 DM patients as amount 80 patients. Based on TCM/GenExpert examination from 47 respondents, there were 17 respondents positive multi drugs resistance rifampicin (RR). Sampling taking based on inclusion criteria, i.e., have had type DM for five years, had suffered TB MDR RR based on GenXpert examination as much as 17 respondents followed in the resistance test with Sputum TB culture and MGIT method. The result of the study showed that MDR DM-TB with MGIT method as followed is obtained from 17 samples, six samples (35.30%) resistance INH 0.4 mg and 1 sample (5.88%) MDR canamycin, and still sensitive INH 0.4 mg and camaycin is ten samples (58.82%). This study results could be used to program planning of prevention and controlling efforts TB-DM in this treatment obedience and regimen anti-tuberculosis medicine for MDR-TB patients.

Bisphosphonates in common pediatric and adult bone sarcomas

The therapeutic strategies proposed currently for bone sarcomas are based on neo-adjuvant chemotherapy, delayed en-bloc wide resection, and adjuvant chemotherapy. Unfortunately, bone sarcomas are characterized by high rates of poor drug response, with a high risk of drug resistance, local recurrence and/or a high propensity for induced metastases. The pathogenesis of bone sarcomas is strongly associated with dysregulation of local bone remodeling and increased osteolysis that plays a part in tumor development. In this context, bisphosphonates (BPs) have been proposed as a single agent or in combination with conventional drugs to block bone resorption and the vicious cycle established between bone and sarcoma cells. Pre-clinical in vitro studies revealed the potential "anti-tumor" activities of nitrogen-bisphosphonates (N-BPs). In pre-clinical models, N-BPs reduced significantly primary tumor growth in osteosarcoma and Ewing sarcoma, and the installation of lung metastases. In chondrosarcoma, N-BPs reduced the recurrence of local tumors after intralesional curettage, and increased overall survival. In pediatric and adult osteosarcoma patients, N-BPs have been assessed in combination with conventional chemotherapy and surgery in randomized phase 3 studies with no improvement in clinical outcome. The lack of benefit may potentially be explained by the biological impact of N-BPs on macrophage differentiation/recruitment which may alter CD8+-T lymphocyte infiltration. Thanks to their considerable affinity for the mineralized extracellular matrix, BPs are an excellent platform for drug delivery in malignant bone sites with reduced systemic toxicity, which opens up new opportunities for their future use.

In vivo targeted therapy of gastric tumors via the mechanical rotation of a flower-like Fe3O4@Au nanoprobe under an alternating magnetic field

Owing to their hypotoxicity, great spatial resolution and tomographic properties, Fe3O4 nanoparticles (NPs) are becoming one of the most promising materials for noninvasive biological imaging and shape-dependent therapeutic agents for malignant tumor therapy. Conventional spherical NPs are unable to effectively destroy cellular structure in therapy and thus result in tumors with a high risk of drug resistance. Herein we developed a novel flower-like targeting Fe3O4@Au-HPG-Glc nanoprobe (thiol-containing hyperbranched polyglycerol (HPG); 4-aminophenyl β-D-glucopyranoside (Glc)) that can enhance magnetic resonance imaging (MRI) for cancer therapy. With the guidance of a targeting molecule, Fe3O4@Au-HPG-Glc nanoprobes can precisely target tumor cells. Under an alternating magnetic field (AMF), the flower-like Fe3O4@Au-HPG-Glc nanoprobes can rotate along the central axis of the core to substantially destroy tumor cells by damaging the nucleus or cell membrane. Our results showed that this shape-dependent therapeutic agent-based strategy had remarkable efficacy for MRI-guided tumor therapy. Furthermore, the inhibition of tumor growth in tumor-bearing mice was up to approximately 47.3% on the twelfth day of treatment compared with the level of inhibition in a blank group. Different from other reported methods for cancer therapy, our proposed AMF-dependent targeted cancer therapy is a novel strategy that can potentially reduce drug resistance in gastric tumors.

Risk factors for resistance in urinary tract infections in women in general practice: A cross-sectional survey

In 2012 and 2013, a cross-sectional survey was conducted in women visiting a general practitioner for a urinary tract infection (UTI) to i) describe the patterns of antibiotic resistance of Enterobacteriaceae involved in community-acquired UTIs and ii) identify the factors associated with UTIs due to a multi-drug-resistant Enterobacteriaceae (MDREB). Urine analyses were performed systematically for all adult women presenting with signs of UTI. Characteristics of women with UTI due to MDREB were compared to those with UTI due to non-MDREB. Weighted logistic regressions were performed to adjust for the sampling design of the survey. Significant factors associated with MDREB included the use of penicillin by the patient in the last three months (OR = 3.1; [1.2-8.0]); having provided accommodation in the previous 12 months to a resident from a country at high risk for drug resistance (OR = 4.0; [1.2-15.1]); and the consumption of raw meat within the previous three months (OR = 0.3; [0.1-0.9]). In the community, antibiotic use and exposure to a person returning from an area with a high risk of drug resistance are associated with UTIs due to MDREB. The potentially protective role of raw meat consumption warrants further study.

Systematic review of the performance of rapid rifampicin resistance testing for drug-resistant tuberculosis.

IntroductionRapid tests for rifampicin resistance may be useful for identifying isolates at high risk of drug resistance, including multidrug-resistant TB (MDR-TB). However, choice of diagnostic test and prevalence of rifampicin resistance may both impact a diagnostic strategy for identifying drug resistant-TB. We performed a systematic review to evaluate the performance of WHO-endorsed rapid tests for rifampicin resistance detection.MethodsWe searched MEDLINE, Embase and the Cochrane Library through January 1, 2012. For each rapid test, we determined pooled sensitivity and specificity estimates using a hierarchical random effects model. Predictive values of the tests were determined at different prevalence rates of rifampicin resistance and MDR-TB.ResultsWe identified 60 publications involving six different tests (INNO-LiPA Rif. TB assay, Genotype MTBDR assay, Genotype MTBDRplus assay, Colorimetric Redox Indicator (CRI) assay, Nitrate Reductase Assay (NRA) and MODS tests): for all tests, negative predictive values were high when rifampicin resistance prevalence was ≤ 30%. However, positive predictive values were considerably reduced for the INNO-LiPA Rif. TB assay, the MTBDRplus assay and MODS when rifampicin resistance prevalence was < 5%.LimitationsIn many studies, it was unclear whether patient selection or index test performance could have introduced bias. In addition, we were unable to evaluate critical concentration thresholds for the colorimetric tests.DiscussionRapid tests for rifampicin resistance alone cannot accurately predict rifampicin resistance or MDR-TB in areas with a low prevalence of rifampicin resistance. However, in areas with a high prevalence of rifampicin resistance and MDR-TB, these tests may be a valuable component of an MDR-TB management strategy.

Efficacy and tolerability of anti-tuberculotic chemotherapy in patients with newly diagnosed cavitary infiltrative pulmonary tuberculosis and a high risk of drug resistance in prisons

Summary. In penitentiary hospitals, patients with infiltrative pulmonary tuberculosis and cavitation not having HIV infection were treated with combined antituberculosis therapy including Lomekomb. After 3 months of treatment, sputum culture conversion was observed in 73.5 % of patients and cavity closure in 32.4 %. Adverse events were seen in 97.1 % of cases, all of them were reversible. The most frequent adverse events were combined toxic and allergic reactions (67.6 % of patients) followed by toxic reactions (20.6 %) and allergic reactions (8.8 %) alone. Urticaria was observed in 17.6 % of patients, blood eosinophilia in 73.5 %, and elevated transaminases in 82.4 %.

EFFICACY OF PARENTERAL VS ORAL ADMINISTRATION OF ANTITUBERCULOSIS DRUGS IN PATIENTS WITH CAVITATING PULMONARY TUBERCULOSIS

Summary . The article contains results of a randomized clinical trial involved 120 patients with cavitating pulmonary tuberculosis. The patients were administered anti-tuberculosis drugs by different routes with the focus on parenteral (lymphotropic and intravenous) administration. The benefit of parenteral administration has been validated as sputum conversion was achieved and lung cavities disappeared much more often including patients with primary drug resistance in comparison to those treated with oral single or combined anti-tuberculosis drugs. The rates of adverse events did not differ significantly in parenteral and oral route of the drug administration. Recommendations have been made on parenteral (lymphotropic and intravenous) administration of anti-tuberculosis drugs in first-diagnosed cavitating pulmonary tuberculosis with high risk of drug resistance of the pathogen.