Risk Factors For Drug Resistance Research Articles

Trends in and Risk Factors for Drug Resistance in Mycobacterium tuberculosis in HIV-Infected Patients.

Trends in and risk factors for drug resistance in Mycobacterium tuberculosis (M. tuberculosis) in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of M. tuberculosis and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center between 2010 and 2022 were collected. The diagnosis of tuberculosis was confirmed by solid or liquid culture. The phenotypic drug susceptibility test was carried out via the proportional method, and the resistance to first-line and second-line drugs was analyzed. Logistic regression analysis was performed to identify associated risk factors for drug resistance in M. tuberculosis. Of the 304 patients with a M. tuberculosis-positive culture and first-line drug susceptibility test results, 114 (37.5%) were resistant to at least one first-line anti-tuberculosis drug. Of the 93 patients with first-line and second-line drug susceptibility test results, 40 (43%) were resistant to at least one anti-tuberculosis drug, and 20 (21.5%), 27 (29.0%), 19 (20.4%), 16 (17.2%), and 14 (15.1%) were resistant to rifampicin, streptomycin, ofloxacin, levofloxacin, and moxifloxacin, respectively; 17 patients (18.3%) had multidrug-resistant tuberculosis (MDR-TB). Between 2010 and 2021, the rate of resistance to streptomycin and rifampicin ranged from 14.3% to 40.0% and from 8.0% to 26.3%, respectively, showing an increasing trend year by year. From 2016 to 2021, the rate of resistance to quinolones fluctuated between 7.7% and 27.8%, exhibiting an overall upward trend. Logistic regression analysis showed that being aged <60 years old was a risk factor for streptomycin resistance, mono-drug resistance, and any-drug resistance (RR 4.139, p = 0.023; RR 7.734, p = 0.047; RR 3.733, p = 0.009). Retreatment tuberculosis was a risk factor for resistance to rifampicin, ofloxacin, of levofloxacin (RR 2.984, p = 0.047; RR 4.517, p = 0.038; RR 6.277, p = 0.014). The drug resistance rates of M. tuberculosis to rifampicin and to quinolones in HIV/AIDS patients were high and have been increasing year by year. Age and a history of previous anti-tuberculosis treatment were the main factors associated with the development of drug resistance in HIV/AIDS patients with tuberculosis.

Trends and risk factors for drug-resistant tuberculosis among children in Sichuan, China: A 10-year retrospective analysis, 2013-2022.

To investigate the status of the drug-resistant tuberculosis (DR-TB) among children in Sichuan, and to find out the risk factors and high-risk population related to drug resistance among children. The clinical data of tuberculosis patients ≤14 years old with culture-confirmed tuberculosis hospitalized in Chengdu Public Health Clinical Center from January 2013 through December 2022 were collected. Clinical data such as gender, age, ethnicity, history of anti-TB treatment, history of exposure to tuberculosis, nutritional status, and specific drug resistance of the children were collected and recorded. The drug resistance of children in different age groups (0-4 years old, 5-9 years old, 10-14 years old) and different periods (2013-2017 and 2018-2022) were grouped and compared. Logistic regression analysis was to analyze analysis of risk factors of drug resistance in children. A total of 438 children with culture-confirmed tuberculosis were screened. Among them, 26.19% (11/42) were 0 to 4 years old, 33.33% (22/66) were 5 to 9 years old, and 36.67% (121/330) were 10 to 14 years old among the resistant children. There was no statistically significant difference in the resistance rate among the 3 groups (P = .385). The proportions of DR-TB, monoresistant tuberculosis, polydrug-resistant tuberculosis were decreased during 2019 to 2022 compared with 2013 to 2017 (P < .0001). The resistance rates of drug resistant, monoresistant, polydrug-resistant, isoniazid-resistant, and rifampicin resistant during 2018 to 2022 were decreased compared with those from 2013 to 2017 (P < .05), but the multi-drug resistance rate was not decreased (P = .131, without statistical difference). The results of logistic regression analysis showed that male gender OR = 1.566 (95% CI 1.035-2.369), a history of antituberculosis therapy OR = 4.049 (95% CI 1.442-11.367), and pulmonary and extrapulmonary tuberculosis OR = 7.335 (95% CI 1.401-38.392) were risk factors for the development of drug resistance; but fever OR = 0.581 (95% CI 0.355-0.950) was Protective factor. The total drug resistance rate of children in Sichuan showed a downward trend, but the rate of multi-drug-resistant tuberculosis was still at a high level, and the form of drug resistance was still severe. Absence of fever, male, retreatment, and pulmonary concurrent with extrapulmonary tuberculosis are risk factors for DR-TB in children.

Antibiotic therapy in pediatric outpatient ENT infections

Inflammatory diseases of the ENT organs are currently the most common pathology in children. Diseases of the nasal cavity and paranasal sinuses occupy the leading place in the structure of primary morbidity, averaging 55.5%. In the paediatric population, ENT pathology develops more often as a secondary bacterial complication of a previous viral infection of the upper respiratory tract. Bacterial otorhinolaryngological complications often require the prescription of antibacterial drugs. In outpatient practice, the choice of rational and safe therapy is of utmost importance. The article presents clinical cases of ENT diseases in children and algorithms for the choice of initial antibacterial therapy. Recommended drugs for the treatment of ENT diseases and the main indications for their administration are presented. Most national and international guidelines recommend amoxicillin as a first-line drug for the treatment of major respiratory pathogens (S. pneumoniae, H. influenzae, S. pyogenes) and bacterial complications of ENT diseases in children, taking into account its low toxicity, cost and convenient form of administration. In case of ineffective therapy or in the presence of risk factors for drug resistance of pathogens, semi-synthetic penicillins in combination with β-lactamase inhibitors are recommended.

Transmission of Fluoroquinolones Resistance among Multidrug-Resistant Tuberculosis in Shanghai, China: A Retrospective population-based Genomic Epidemiology Study

ABSTRACT Fluoroquinolones (FQ) are essential for the treatment of multidrug-resistant tuberculosis (MDR-TB). The FQ resistance (FQ-R) rate in MDR-TB in China and its risk factors remain poorly understood. We conducted a retrospective, population-based genomic epidemiology study of MDR-TB patients in Shanghai, China, from 2009 to 2018. A genomic cluster was defined as strains with genetic distances ≤ 12 single nucleotide polymorphisms. The transmitted FQ-R was defined as the same FQ resistance-conferring mutations shared by ≥ 2 strains in a genomic cluster. We used multivariable logistic regression analysis to identify the risk factors for drug resistance. Among the total 850 MDR-TB patients included in the study, 72.8% (619/850) were male, the median age was 39 (interquartile range 28, 55) years, 52.7% (448/850) were migrants, and 34.5% (293/850) were previously treated patients. Most of the MDR-TB strains belong to the Beijing lineage (91.7%, 779/850). Overall, the genotypic resistance rate of FQ was 34.7% (295/850), and 47.1% (139/295) FQ-R patients were in genomic clusters, of which 98 (33.2%, 98/295) were presumed as transmitted FQ-R. Patients with treatment-naïve (aOR = 1.84; 95% CI: 1.09, 3.16), diagnosed in a district-level hospital (aOR = 2.69; 95% CI: 1.56, 4.75), and streptomycin resistance (aOR = 3.69; 95% CI: 1.65, 9.42) were significantly associated with the transmission of FQ-R. In summary, the prevalence of FQ-R among MDR-TB patients was high in Shanghai, and at least one-third were transmitted. Enforced interventions including surveillance of FQ drug susceptibility testing and screening among MDR-TB before initiation of treatment were urgently needed.

Distribution of multidrug-resistant bacterial infections in diabetic foot ulcers and risk factors for drug resistance: a retrospective analysis.

To investigate the distribution, drug resistance and risk factors of multi-drug resistant bacterias (MDROs) in patients with Type 2 diabetic foot ulcers (DFU). The clinical data, foot secretions, pathogenic microorganisms and drug sensitivity tests of 147 patients with type 2 diabetes admitted to our department from January 2018 to December 2021 were analyzed. Patients were divided into two groups according to whether they had been infected with MDROs or not. Seventy-one cases were infected with MDROs as the case group, and the remaining 76 cases were the control group. Chi-square test and t-test were used to analyze the results of MDROs infection and DFU, and logistic multivariate regression was used to evaluate the risk factors of MDROs infection. A total of 71 strains were isolated from the MDROs-positive group, with the top three being Staphylococcus aureus (46.48%), Escherichia coli (22.53%), and Pseudomonas aeruginosa (18.31%), respectively. Logistic multifactorial regression analysis showed that history of previous antimicrobial exposure, neuroischemic wound, Wagner grade 3-5, and combined osteomyelitis were associated with Type 2 diabetic foot infection MDROs (P<0.05). Previous history of antimicrobial exposure, neuroischemic wounds, Wagner grade 3-5, and combined osteomyelitis are independent risk factors for MDROs, which can identify the risk factors for MDROs at an early stage and help to identify people at high risk of MDROs infection and take relevant comprehensive treatment in time to slow down the development of the disease.

Seizure outcome in medically treated patients with adult-onset epilepsy and cerebral cavernous malformation

PurposeWe evaluated long-term seizure outcomes of antiseizure medications (ASMs) and risk factors for drug resistance in patients with adult-onset epilepsy associated with cerebral cavernous malformation (CCM). Materials and methodsThis retrospective observational study included patients newly diagnosed with adult-onset focal epilepsy associated with CCM. Patients received individualized treatments with ASMs. All patients were followed-up for at least 2 years. The main outcome measure was terminal 2 year seizure freedom (2-YSF). ResultsForty eight subjects (28 men and 20 women) were included. Thirty-one (64.6%) subjects achieved a terminal 2-YSF (range 2.0–17.0 years). After treatment with the first drug regimen, 31 (64.6%) subjects achieved 2-YSF, with 23 remaining seizure-free until final follow-up visit. Of the 23 subjects treated with the second drug regimen and the six treated with the third drug regimen, ten (43.5%) and one (16.7%), respectively, achieved a terminal 2-YSF. Stepwise logistic regression analyses showed that terminal 2-YSF was negatively associated with epileptiform discharge on EEG at the time of diagnosis (odds ratio = 0.214, p = 0.047) and tended to be associated with age ≥ 45 years at seizure onset (odds ratio = 4.260, p = 0.056). ConclusionThe present study found that 64.6% of CCM patients with adult-onset epilepsy achieved terminal 2-YSF after ASM initiation. Interictal epileptiform discharge on EEG at the time of diagnosis was associated with poor prognosis. Failure to achieve sustained seizure freedom after two ASMs may indicate the need for surgical treatment.

Pathogen Distribution, Drug Resistance Risk Factors, and Construction of Risk Prediction Model for Drug-Resistant Bacterial Infection in Hospitalized Patients at the Respiratory Department During the COVID-19 Pandemic.

To investigate the distribution and drug resistance of pathogens among hospitalized patients in the respiratory unit during the COVID-19 pandemic, analyze the risk factors of drug resistance, construct a risk prediction model. This study isolated 791 strains from 489 patients admitted to the Affiliated Hospital of Chengdu University, who were retrospectively enrolled between December 2019 and June 2021. The patients were divided into training and validation sets based on a random number table method (8:2). The baseline information, clinical characteristics, and culture results were collected using an electronic database and WHONET 5.6 software and compared between the two groups. A risk prediction model for drug-resistant bacteria was constructed using multi-factor logistic regression. K. pneumoniae (24.78%), P. aeruginosa (17.19%), A. baumannii (10.37%), and E. coli (10.37%) were the most abundant bacterial isolates. 174 isolates of drug-resistant bacteria were collected, ie, Carbapenem-resistant organism-strains, ESBL-producing strains, methicillin-resistant S. aureus, multi-drug resistance constituting 38.51%, 50.57%, 6.32%, 4.60%, respectively. The nosocomial infection prediction model of drug-resistant bacteria was developed based on the combined use of antimicrobials, pharmacological immunosuppression, PCT>0.5 ng/mL, CKD stage 4-5, indwelling catheter, and age > 60 years. The AUC under the ROC curve of the training and validation sets were 0.768 (95% CI: 0.624-0.817) and 0.753 (95% CI: 0.657-0.785), respectively. Our model revealed an acceptable prediction demonstrated by a non-significant Hosmer-Lemeshow test (training set, p=0.54; validation set, p=0.88). K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli were the most abundant bacterial isolates. Antimicrobial resistance among the common isolates was high for most routinely used antimicrobials and carbapenems. COVID-19 did not increase the drug resistance pressure of the main strains. The risk prediction model of drug-resistant bacterial infection is expected to improve the prevention and control of antibacterial-resistant bacterial infection in hospital settings.

Doxycycline vs. macrolides in combination with a β-lactam antibiotic for the treatment of community-acquired pneumonia in inpatients.

Hospitalized patients with non-severe community-acquired pneumonia (CAP) are treated with a β-lactam plus either a macrolide or doxycycline. Limited data exist on the effectiveness of the latter combination. Therefore, we aimed to compare the combination of doxycycline vs. macrolide when either is combined with a β-lactam from effectiveness and safety perspectives. This was a retrospective cohort study in CAP inpatients between December 2013 and November 2020. Patients were divided into BL-D (β-lactam plus doxycycline) and BL-M (β-lactam plus a macrolide [azithromycin or clarithromycin]) groups. The primary endpoint was time to clinical stability. Secondary endpoints included length of stay (LOS) and in-hospital mortality. Of 197 patients included, 57 were in the BL-D arm and 140 were in the BL-M arm. Patients were similar at baseline, except for the presence of leukocytosis, risk factors for drug resistance, and duration of therapy (P < 0.05 for all comparisons). No difference in clinical cure rate was observed (94.7% vs. 91.4%; P = 0.43). Time to clinical stability and LOS were similar in both groups at 4 (P = 0.82) and 7days (P = 0.62), respectively. While only three patients died, only one (from the BL-M group) was due to sepsis. Liver enzymes elevation was more prominent in the BL-M group (21.4% vs. 5.3%; P = 0.01). A subgroup analysis showed shorter time to clinical stability with clarithromycin but higher cure rates with azithromycin. Data on doxycycline use with a β-lactam are scarce. Our study showed that such regimen was comparable in effectiveness to regimens involving macrolides with a better safety profile.

Analysis of Clinical Characteristics and Risk Factors for Drug Resistance in Newly-Treated Patients with Pulmonary Tuberculosis Complicated with Chronic Obstructive Pulmonary Disease.

ObjectiveTo analyze the clinical characteristics and risk factors of drug resistance of newly-treated chronic obstructive pulmonary disease (COPD) complicated pulmonary tuberculosis (PTB).MethodsA total of 489 newly-treated PTB patients admitted to Beijing Geriatric hospital were retrospectively enrolled in this study. Of these, 138 patients with COPD were allocated to the study group, and the remaining 351 patients without COPD were allocated to the control group. The baseline information, clinical characteristics of PTB and drug resistance of Mycobacterium tuberculosis were compared between the two groups. Logistic regression was used to explore the correlation between drug resistance and COPD complications.ResultsPatients complicated with COPD had a higher proportion of respiratory failure, cough, fever and night sweats, chest short breath, and emaciation between the study group and the control group (P<0.05). In terms of medical history, patients complicated with COPD also had a higher proportion of childhood TB history, cough, tuberculosis exposure rate, dust exposure rate, and malnutrition (P<0.05). There were significantly more patients with pulmonary cavities and a delayed diagnosis of TB in the study group than in the control group (P<0.05). The single drug resistance rates of isoniazid, ethambutol, rifampicin, pyrazinamide, and rifapentine, and drug resistance with any two or more drugs in the study group were significantly higher than those in the control group (P<0.05). Multivariate Logistic regression analysis showed that smoking, extrapulmonary tuberculosis, tuberculosis exposure history, malnutrition, pulmonary cavity, and delayed TB diagnosis were risk factors for drug resistance in newly-treated COPD complicated PTB patients.ConclusionThe symptoms of COPD complicated PTB were more serious. Smoking history, extrapulmonary tuberculosis, tuberculosis exposure history, malnutrition, pulmonary cavity, and delayed diagnosis of tuberculosis were risk factors for TB resistance in these patients.

Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy.

Cerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma-related epilepsy (CRE) and drug resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long-term seizure outcomes of medical and surgical treatment strategies. This was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007-2011 and followed up for 93.6months on average. The patients were divided into drug-resistant epilepsy (DRE; n= 29), non-DRE (n= 45), and no epilepsy (NE; n= 61). Temporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%, n= 33), and 50% had DRE, whereas only 14.7% (n= 5) with a nontemporal supratentorial CCM had DRE (p< .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p< .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio=11.1), particularly in those with DRE (odds ratio=15.4). The majority of patients who underwent resective surgery for DRE (76.5%, n= 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course. Temporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long-term seizure outcomes in patients with DRE.

Association between ABCB1 C3435T polymorphism and antiepileptic drug resistance in epilepsy: An updated meta-analysis based on 62 studies.

Previous clinical studies and meta-analyses have shown controversial results on the association between C3435T polymorphism of the ABCB1 gene and anti-epileptic drug (AED) resistance. Based on the fact that sample size and confounding factors could contribute to the inconsistency, we performed an updated meta-analysis by including the most recent studies, and subgroup analysis was conducted to evaluate the effect of confounding factors on the association. We searched articles in 6 electronic databases including PubMed, Medline, Embase, Web of science, Cochrane Library, CNKI (China National Knowledge Infrastructure) for relevant articles up to June 2020. The current analysis showed that the C allele of C3435T variant was a risk factor for drug resistance in the overall populations (C allele vs. T allele, OR: 1.13; 95% CI: 1.02-1.25; p=0.02) and in the Caucasians (C allele vs. T allele, OR: 1.09; 95% CI: 1.09-1.43; p=0.002), while no association was observed in Asians and Indians. Particularly, our study reported for the first time that the 3435T allele was more common in epilepsy patients with drug resistance in the Tunisian population (C allele vs. T allele, OR: 0.31; 95% CI: 0.15-0.65; p=0.002). In addition, our present analysis suggested an association between C3435T and AED resistance in cryptogenic, symptomatic, but not in idiopathic patients. Subgroup studies based on age and gender showed no association. AED resistance in Caucasian and Tunisian populations may benefit from ABCB1 C3435T genotyping. We recommend that more details, such as gender and etiology of epilepsy, should be taken into account to draw a reliable conclusion in future studies.

Epidemiological Characteristics and Their Influencing Factors Among Pulmonary Tuberculosis Patients With and Without Diabetes Mellitus: A Survey Study From Drug Resistance Surveillance in East China.

BackgroundThe burden of pulmonary tuberculosis (TB) and diabetes mellitus (DM) have become serious global concerns, while the comprehensive evaluations of DM status and drug resistance in TB patients are still lacking.MethodsAll details of TB cases were collected from drug resistance monitoring sentinels in Zhejiang province. Fisher's exact test or Pearson chi-square test (χ2) was used to compare the baseline characteristics among TB with different DM statuses. The logistic regression model was used to estimate the relationship between DM and different drug resistance spectra. Univariate analysis and multivariate logistic model were used to explore the possible risk factors of drug resistance in TB patients with DM and no DM.Results936 TB cases with smear-positive in Zhejiang province were collected, in which 76 patients (8.12%) owned the co-morbidity of DM. TB-DM prevalence was higher in older, Han nationality, employed, accompanied by no health insurance and hepatitis B status. Among 860 cases of TB-no DM and 76 cases of TB-DM, drug resistance-TB accounted for 31.51% and 23.68% (P > 0.05), MR-TB accounted for 15.93% and 14.47% (P > 0.05), respectively. MDR-TB was 4.88% and 6.58% (P > 0.05). The incidence of poly-drug resistant tuberculosis (PDR-TB) in TB-no DM patients (10.70 vs. 2.63%, OR: 4.43; 95% CI, 1.07–18.36) was higher than that in the TB-DM group (P < 0.05). In univariate and multivariate analysis, none of the basic factors were statistically significant with drug resistance among TB-DM cases (all P > 0.05). Retreatment was the risk factor of drug resistance among TB-no DM cases.ConclusionsOur results showed that the drug resistance rate of the TB-DM group was not higher than that of the TB-no DM group. Patients with TB-no DM were at a higher risk for PDR-TB, but not for MDR-TB, MR-TB, and drug resistance-TB. Special attention should be paid to TB-no DM patients who have been previously treated. In the future, large-scale and well-designed prospective studies are needed to clarify the impact of DM on the drug-resistance among TB.

Assessment of Risk Factors for Drug Resistance of Dual Anti Platelet Therapy After PCI.

Since aspirin and clopidogrel are the widely and conventionally used drugs to treat acute myocardial infarction after percutaneous coronary intervention (PCI), it is important to explore potential risk factors of their resistance. The platelet aggregation rate with arachidonic acid (AA, PAg-AA%) and adenosine diphosphate (ADP, PAg-ADP%) of 219 PCI patients were measured after standard treatment for 24 h. The disease history and laboratory data (before PCI) were obtained. We found 101 (46.12%) patients to be aspirin-resistant, and PAg-ADP% was the most prominent risk factor of aspirin resistance. Clopidogrel resistance was present in 157 of 219 patients. Patients in the clopidogrel-resistant group carried more CYP2C19*3 or *2, which was associated with higher clopidogrel resistance in this group (69.11%, 47/68) than in the control group (64.29%, 36/56). Platelet count (109/L) and hemoglobin (g/L) were the prominent risk factors of clopidogrel resistance. Among the 219 patients, 98 showed dual antiplatelet drug resistance, for which platelet count (109/L) and monocyte count (g/L) were the risk factors. Aspirin resistance was found to usually accompany clopidogrel resistance.

Risk Factors of Drug Resistance and the Potential Risk of HIV-1 Transmission of Patients with ART Virological Failure: A Population-Based Study in Sichuan, China.

BackgroundSichuan Province, in the interior of Southwest China, is the most severe HIV-affected area in China. Few data are currently available for people living with HIV/AIDS (PLWH) with virological failure of antiretroviral therapy (ART). Estimating the HIV-1 drug-resistant spread influencing factors and transmission patterns of the HIV-1 epidemic of PLWH with ART virological failure are critical in Sichuan.MethodsWe evaluated the drug-resistant transmission patterns on 5790 PLWH in 2018 with identified pol sequences of the five main HIV-1 subtypes (ie, subtype B, CRF08_BC, CRF85_BC, CRF07_BC, and CRF01_AE) in Sichuan Province, China. The multivariate logistic regression model was used to explore potential influencing factors of the spread of drug resistance (DR) clustering in the genetic transmission network. Spatial analyses were applied to demonstrate drug-resistant spatial clustering patterns of spatial connections of HIV-1 intercity transmission. Genetic transmission networks were performed by comparing sequences, calculating the pairwise distance, and visualizing the network.ResultsThere were identified 452 transmission clusters containing 2159 of 5790 patients (37.29%) in the HIV-1 genetic transmission networks. Some clinical and demographic factors (eg, route of transmission, subtype) determined the DR clustering in the genetic transmission networks. The high drug-resistant clustering rates were mainly distributed in the Southern and Northeast of Sichuan Province (eg, Deyang, Neijiang), especially for CRF85_BC, which showed the highest clustering rate. Some cities had with strong intracity links (eg, Yibin, Neijiang), some cities had with strong transmission links with another city (eg, Ziyang and Guangyuan), 12 of 37 drug resistance mutation sites had a significant difference in the five subtypes (P < 0.001).ConclusionOur findings revealed the HIV-1 drug-resistant spread influencing factors and transmission patterns of PLWH with ART virological failure, which showed regions with high drug-resistant transmission of PLWH may not be a match for regions with severe epidemics in Sichuan, and it provided evidence-based to drug-resistant transmission targeting interventions.

Risk Factors for Drug Resistance in Epileptic Children with Age of Onset above Five Years: A Case-Control Study.

Background Children with epilepsy with onset above five years encompass distinct epidemiological and clinical characteristics that may have specific risk factors for resistance to antiseizure medications (ASMs). Studies on this age group are limited. Purpose To identify risk factors for drug resistance in children with epilepsy with the age of onset above five years. Methods A case-control study was conducted on children with epilepsy with the age of onset above five years visiting the Pediatric Neurology Clinic of Cipto Mangunkusumo and Mohammad Hoesin Hospital between September 2015 and August 2016. Cases consisted of drug-resistant children while control consisted of drug-responsive children according to 2010 ILAE classification. Risk factors studied include onset, number of seizures, illness duration before treatment, cause, seizure type, status epilepticus, initial and evolution of EEG, brain imaging, and initial treatment response. Results Thirty-two pairs of children were included in the study. After logistic regression analysis, symptomatic etiology and failure to achieve early response to treatment were found to be associated with drug resistance with adjusted OR of 84.71 (95% CI: 5.18-1359.15) and 72.55 (95% CI: 7.08-743.85), respectively. Conclusion Poor initial response to ASM and symptomatic etiology are independent risk factors for drug resistance in children with epilepsy with the age of onset above five years.

Analysis of the Reactivity of Aspirin and Clopidogrel and Its Influencing Factors in Patients with Coronary Heart Disease at High Altitude.

Objective To evaluate the efficacy of dual-antiplatelet treatment (DAPT) in patients with coronary heart disease (CHD) at high altitude by using thrombelastogram (TEG) and to analyze the related biochemical factors affecting drug reactivity. Methods Totally 118 CHD patients who admitted to the Qinghai People's Hospital from September 2019 to September 2020 were enrolled in the group. Those people have lived in Qinghai for a long time. Seven days after DAPT, venous blood was collected on an empty stomach in the early morning of the next day; blood routine, coagulation function, and biochemical items were tested. Thrombelastogram (TEG) was used to draw curves to calculate platelet, coagulation and fibrinolysis functions, and drug inhibition rate. Patients were divided into the aspirin resistance (AR) group, clopidogrel resistance (CR) group, dual-antiplatelet drug resistance (DAR) group, and drug-sensitive group according to different inhibition rates. The drug efficacy was analyzed, and the clinical data, biochemical indexes, and TEG parameters of each group were compared to identify the risk factors of drug resistance. Results Those 118 CHD patients at high altitude were incorporated into the study, ranging from 38 to 84 years of age, including 81 males (68.64%) and 37 females (31.36%). The platelet function and coagulation-fibrinolysis function were detected by TEG, and MATHROMBI, MAADP, and MAAA were higher than the reference range. There were 82 cases (69.49%) of drug resistance, 36 cases (32.53%) of drug sensitivity, 17 cases (14.41%) of AR alone, and 16 cases (12.71%) of CR alone. There was no significant difference in age, gender, BMI, oxygen saturation, TG, GFR, and history of diabetes and hypertension between ACS and CCS groups (P > 0.05). PLT and FIB in the ACS group were higher than those in the CCS group, and the difference was statistically significant (P < 0.05). In addition, MATHROMBIN, MAFIBRIN, E, A, A30, and coagulation composite index were also higher than those in the CCS group, with a statistically significant difference (P < 0.05). Univariate analysis and logistic regression analysis suggested that age, HbA1c, FBG, and diabetes were the main factors of drug resistance. Conclusion Antiplatelet drugs aspirin and clopidogrel resistance are associated with increased age, elevated HbA1c and FBG, and diabetes. Therefore, it is necessary to take reasonable treatment measures based on the actual situation of patients.

Detection of isoniazid, fluoroquinolone, ethionamide, amikacin, kanamycin, and capreomycin resistance by the Xpert MTB/XDR assay: a cross-sectional multicentre diagnostic accuracy study

The WHO End TB Strategy requires drug susceptibility testing and treatment of all people with tuberculosis, but second-line diagnostic testing with line-probe assays needs to be done in experienced laboratories with advanced infrastructure. Fewer than half of people with drug-resistant tuberculosis receive appropriate treatment. We assessed the diagnostic accuracy of the rapid Xpert MTB/XDR automated molecular assay (Cepheid, Sunnyvale, CA, USA) to overcome these limitations. We did a prospective study involving individuals presenting with pulmonary tuberculosis symptoms and at least one risk factor for drug resistance in four sites in India (New Delhi and Mumbai), Moldova, and South Africa between July 31, 2019, and March 21, 2020. The Xpert MTB/XDR assay was used as a reflex test to detect resistance to isoniazid, fluoroquinolones, ethionamide, amikacin, kanamycin, and capreomycin in adults with positive results for Mycobacterium tuberculosis complex on Xpert MTB/RIF or Ultra (Cepheid). Diagnostic performance was assessed against a composite reference standard of phenotypic drug-susceptibility testing and whole-genome sequencing. This study is registered with ClinicalTrials.gov, number NCT03728725. Of 710 participants, 611 (86%) had results from both Xpert MTB/XDR and the reference standard for any drug and were included in analysis. Sensitivity for Xpert MTB/XDR detection of resistance was 94% (460 of 488, 95% CI 92-96) for isoniazid, 94% (222 of 235, 90-96%) for fluoroquinolones, 54% (178 of 328, 50-61) for ethionamide, 73% (60 of 82, 62-81) for amikacin, 86% (181 of 210, 81-91) for kanamycin, and 61% (53 of 87, 49-70) for capreomycin. Specificity was 98-100% for all drugs. Performance was equivalent to that of line-probe assays. The non-determinate rate of Xpert MTB/XDR (ie, invalid M tuberculosis complex detection) was 2·96%. The Xpert MTB/XDR assay showed high diagnostic accuracy and met WHO's minimum target product profile criteria for a next-generation drug susceptibility test. The assay has the potential to diagnose drug-resistant tuberculosis rapidly and accurately and enable optimum treatment. German Federal Ministry of Education and Research through KfW, Dutch Ministry of Foreign Affairs, and Australian Department of Foreign Affairs and Trade.

Incidence of Hepatotoxicity and Factors Associated During Highly Active Antiretroviral Therapy in People Living with HIV in Ethiopia: A Prospective Cohort Study.

IntroductionHepatotoxicity is one of the risk factors associated with treatment non-adherence, which is the main risk factor for drug resistance. Therefore, this study aimed to determine the incidence and risk factors of hepatotoxicity during highly active antiretroviral therapy (HAART) among people living with HIV in Ethiopia.MethodsA prospective cohort study was conducted between April 2007 and January 2011 at Saint Peter Specialized Hospital, Akaki and Kality Health Centers, Addis Ababa, Ethiopia. A total of 316 HIV-infected adult individuals (70 participants were HIV and TB co-infected and 246 were infected with HIV alone) were included in this study. The study participants were followed for a total of 18 months with or without HAART. Socio-demographic data were collected using a structured questionnaire, and venous blood samples were collected for laboratory tests. Logistic regression and Poisson regression were used to determine the independent effect of each variable on hepatotoxicity at baseline and end of follow-up.ResultsOf 316 HIV-infected people, 72 (22.8%) participants had an elevated ALT/AST which was 100% mild-to moderate hepatotoxicity at baseline. Baseline CD4 T-cell count (p = 0.027) and HIV co-infection with TB (p < 0.001) were independently associated with hepatotoxicity at baseline. The overall incidence rate of hepatotoxicity in participants on HAART (21.8 per 100 person-years) was lower than participants who were HAART naïve (33.3 per 100 person-years) (p = 0.009).ConclusionHigh incidence of mild-to-moderate hepatotoxicity and low severe hepatotoxicity were observed in HIV-infected individuals who were on HAART or were HAART naïve. HAART may minimize the occurrence of hepatotoxicity. Although HAART could minimize hepatotoxicity among HIV-infected people, to manage mild and moderate hepatotoxicity liver function test monitoring is required.

Prevalence and Possible Predictors of Drug-Resistant Pseudomonas aeruginosa in External Ocular Infections: A Single-Center, Retrospective, Cross-Sectional Study.

ObjectiveOcular infections due to multi-drug-resistant Pseudomonas aeruginosa (MDRP) have been reported in recent years. This study was undertaken to determine the culture-positivity rate of P. aeruginosa and drug resistance among patients with suspected external ocular infections and to predict systemic risk factors for drug resistance in P. aeruginosa.MethodsThis retrospective, single-center, cross-sectional study involved 781 consecutive patients who provided samples for aerobic culture to test for a suspected external ocular infection. DRP was defined as a strain resistant to one or two of three antibiotics, levofloxacin, gentamicin, and imipenem; MDRP was defined as that which was resistant to all three.ResultsAmong 108 patients in whom gram-negative bacilli were observed, P. aeruginosa was isolated from nine patients, including three DRP-positive cases; no MDRP was isolated. P. aeruginosa was not isolated from those <69 years of age. Among patients in whom gram-negative bacilli were detected, the isolation rate of P. aeruginosa was 0 for patients aged ≤64 and 0.1 for those aged ≥65, indicating a significant difference. For patients with gram-negative bacilli, the DRP-positivity rate was significantly higher for hospitalized patients than outpatients. Thus, in addition to being geriatric, being hospitalized was a risk factor for DRP infection among patients with gram-negative bacilli. All the P. aeruginosa strains isolated were susceptible to colistin.ConclusionsOur findings may suggest that once gram-negative bacilli are isolated in an elderly hospitalized patient, possible DRP infection and the topical use of colistin should be taken into consideration even before the results of culture and susceptibility testing are obtained.

Sea lice exposure to non-lethal levels of emamectin benzoate after treatments: a potential risk factor for drug resistance

The avermectin derivative emamectin benzoate (EMB) has been widely used by salmon industries around the world to control sea lice infestations. Resistance to this anti-parasitic drug is also commonly reported in these industries. The objective of this study was to quantify the number of sea lice potentially exposed to sub-lethal concentrations of EMB while fish clear the drug after treatments. We assessed juvenile sea lice abundance after 38 EMB treatments on six Atlantic salmon farms, in a small archipelago in British Colombia, Canada, between 2007 and 2018. We fitted a standard EMB pharmacokinetic curve to determine the time when fish treated with this product would have EMB tissue concentrations below the recommended target therapeutic level. During the study, we estimated that for each sea lice treatment there was, on average, an abundance of 0.12 juvenile sea lice per fish during the time period when the concentrations of EMB would have been lower than 60ppb, the recommended therapeutic treatment level for sea lice. The findings from this study on metaphylactic anti-parasitic treatments identify a potential driver for drug resistance in sea lice that should be further explored.