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ABSTRACT Bacterial keratitis caused by multidrug-resistant strains of Pseudomonas aeruginosa is a therapeutic challenge due to a limited number of active antimicrobials and rapid progression to corneal necrosis and perforation. To report the use of topical colistin and surgical tarsorrhaphy in a case of keratitis caused by extensively drug-resistant Pseudomonas aeruginosa in a patient with severe coronavirus disease-2019 (COVID-19) pneumonia. A 56-year-old male was admitted to the intensive care unit with clinical symptoms of severe COVID-19 pneumonia. During his stay in the unit, he developed rapidly progressive keratitis with Pseudomonas aeruginosa resistant to all drugs except for colistin on culture. Due to incomplete lid closure, a temporary tarsorrhaphy was performed, and a regimen of descending-dose topical colistin was initiated. After five weeks, keratitis resolved completely. Extensively drug-resistant Pseudomonas aeruginosa is an unusual cause of bacterial keratitis. We describe the safe and effective use of topical colistin in a case with severe corneal involvement.
RESUMO A ceratite bacteriana causada por cepas multirresistentes de Pseudomonas aeruginosa é um desafio terapêutico, devido à disponibilidade limitada de antimicrobianos e à rápida progressão para necrose e perfuração da córnea. O objetivo deste artigo é relatar o uso de colistina tópica e tarsorrafia cirúrgica em um caso de ceratite por Pseudomonas aeruginosa amplamente resistente a medicamentos em um paciente com pneumonia grave por COVID19. Um homem de 56 anos foi internado em uma unidade de terapia intensiva com sintomas clínicos de pneumonia grave por COVID19. Durante sua permanência na unidade de terapia intensiva, o paciente desenvolveu uma ceratite rapidamente progressiva, cuja cultura foi positiva para Pseudomonas aeruginosa resistente a todos os antimicrobianos, exceto colistina. Devido ao fechamento incompleto da pálpebra, foi realizada uma tarsorrafia temporária e foi instituído um esquema de colistina tópica em doses decrescentes. Após cinco semanas, a resolução completa da ceratite foi alcançada. Pseudomonas aeruginosa amplamente resistente a medicamentos é uma causa incomum de ceratite bacteriana. Este relato descreve o uso seguro e eficaz da colistina tópica em um caso com comprometimento corneano grave.
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Abstract Paclitaxel (PTX) is one of the most effective drugs used in the treatment of breast cancer. Nonetheless, the appearance of MDR1 (multidrug resistance 1) in tumor cells has become a significant hindrance for efficacious chemotherapy. In this study, we show that the expression level of Egr-1 (early growth response gene-1) in cancer tissues (from paclitaxel chemotherapy failure patients) and MCF-7/PTX cells (the breast cancer cell line that was resistant to paclitaxel) was increased. Cell proliferation assay and apoptosis assay revealed that Egr-1 could promote cell growth and inhibit apoptosis in MCF-7/PTX. Mechanistic studies indicated that Egr-1 could bind to the proximal MDR1 promoter and enhance MDR1 transcription. These findings indicate that paclitaxel induced Egr-1 accumulation and upregulated the expression of MDR1, thereby inducing the drug resistance in MCF-7/PTX. Our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance.
Subject(s)
Breast Neoplasms/pathology , Drug Resistance , ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis , Pharmaceutical Preparations/analysisABSTRACT
ABSTRACT Objective. Colistin is an antibiotic of last resort for treating serious Gram-negative bacterial infections. However, the misuse of colistin, especially as an animal growth promoter, has contributed to increasing antimicrobial resistance, mediated mainly through plasmid transfer of the mcr-1 gene. This study assessed the prevalence of phenotypic and molecular colistin resistance in Escherichia coli and Klebsiella pneumoniae in Ecuador in healthy humans and their chickens and pigs. Methods. Fecal samples were collected from humans and their chickens and pigs in two rural coastal and Amazon regions between April and August 2020. Gram-negative bacteria were isolated and identified using conventional techniques. Phenotypic resistance was determined using the broth microdilution technique, and the mcr-1 gene was detected using conventional polymerase chain reaction. Results. A total of 438 fecal samples were obtained from 137 humans, 147 pigs and 154 chickens. The prevalence of E. coli isolates was 86.3% (378/438) and K. pneumoniae, 37.4% (164/438). Overall, the mcr-1 gene was found in 90% (340/378) of E. coli isolates, with higher prevalences found in isolates from coastal regions (96.5%, 191/198), humans (95.6%, 111/116) and chickens (91.8%, 123/134); for K. pneumoniae, the gene was found in 19.5% (32/164) of isolates, with equal distribution between regions and hosts. Only four isolates, two E. coli and two K. pneumoniae, showed phenotypic resistance: mcr-1 was present in both E. coli strains but absent in the K. pneumoniae strains. Conclusions. Despite a low prevalence of phenotypic resistance to colistin, the high prevalence of the mcr-1 gene in E. coli is of concern. Ecuador's ban on using colistin in animal husbandry must be enforced, and continual monitoring of the situation should be implemented.
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RESUMO Objetivo. A colistina é um antibiótico de último recurso para o tratamento de infecções graves por bactérias Gram-negativas. Entretanto, o uso indevido da colistina, principalmente como promotor de crescimento animal, tem contribuído para o aumento da resistência a antimicrobianos, principalmente por transferência horizontal do gene mcr-1 mediada por plasmídeos. Este estudo avaliou a prevalência de resistência fenotípica e molecular à colistina em Escherichia coli e Klebsiella pneumoniae no Equador em humanos hígidos e em galinhas e porcos por eles criados. Métodos. Entre abril e agosto de 2020, foram coletadas amostras de fezes de habitantes de duas regiões litorâneas e amazônicas do Equador e de galinhas e porcos por eles criados. Bactérias Gram-negativas foram isoladas e identificadas por meio de técnicas convencionais. A resistência fenotípica foi determinada pela técnica de microdiluição em caldo, e o gene mcr-1 foi detectado por reação em cadeia da polimerase convencional. Resultados. Foram obtidas 438 amostras fecais de 137 humanos, 147 suínos e 154 galinhas. A prevalência de isolados de E. coli foi de 86,3% (378/438), e de K. pneumoniae, 37,4% (164/438). Em geral, o gene mcr-1 foi encontrado em 90% (340/378) dos isolados de E. coli, com maiores prevalências encontradas em isolados de regiões litorâneas (96,5%, 191/198), humanos (95,6%, 111/116) e galinhas (91,8%, 123/134); para K. pneumoniae, o gene foi encontrado em 19,5% (32/164) dos isolados, com igual distribuição entre regiões e hospedeiros. Somente quatro isolados, dois de E. coli e dois de K. pneumoniae, demonstraram resistência fenotípica: o gene mcr-1 estava presente em ambas as cepas de E. coli, mas ausente nas de K. pneumoniae. Conclusões. Apesar da baixa prevalência de resistência fenotípica à colistina, a alta prevalência do gene mcr-1 em E. coli é preocupante. É preciso fiscalizar a proibição ao uso agropecuário de colistina no Equador e implementar o monitoramento contínuo da situação.
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Objective To analyze the disease burden of multidrug-resistant tuberculosis (MDR-TB) in China and regions with different income levels in the world from 1990 to 2019. Methods Using the Global Burden of Disease Study 2019 (GBD2019) results, the changes of the disease burden of MDR-TB in China and regions with different income levels in the world were described and analyzed using the Joinpoint Regression Program 4.8.0.1 software. Results From 1990 to 2019, the age standardized incidence, mortality and DALY rates in China and other areas with different income levels in the world basically showed a trend of first rising and then decreasing at the turning point of the late 20th century and early 21st century, except for low-income areas where the age standardized incidence rate showed an overall upward trend. In 2019, the incidence rate, mortality and DALY rate of MDR-TB in China were 9 times, 6.67 times and 6.89 times higher than those in high-income areas, respectively. The incidence rate in China was 6 times lower than that in low and middle-income areas, while the mortality and DALY rate in China were 26 times and 32.53 times lower than those in low-income areas, respectively. The age standardized incidence, mortality rate and DALY rate of MDR-TB in men were higher than those in women. Risk factors for the burden of MDR-TB disease included alcohol consumption, smoking, and high fasting blood glucose. Conclusion From 1990 to 2019, there are significant regional and gender differences in the disease burden of multidrug-resistant tuberculosis in China and regions with different income levels in the world. Multidrug-resistant tuberculosis is still a major challenge for tuberculosis control in the world. It is necessary to develop more effective control strategies and health care systems to deal with multidrug-resistant tuberculosis.
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Objective:To analyze the antimicrobial resistance and genomic characteristics of Salmonella enterica serovar Derby strains isolated from human and food sources in Hangzhou. Methods:A total of 60 Salmonella enterica serovar Derby strains isolated in Hangzhou during the period from 2015 to 2020 were subjected to antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) typing and whole-genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and the identification of antimicrobial resistance genes were performed using the sequencing data. Phylogenetic tree based on the single nucleotide polymorphism (SNP) sites in the 60 genomes from Hangzhou and 379 genomes from public databases was constructed. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Hangzhou. The multidrug resistance (MDR) rate was 76.7% (46/60). All of the 60 Salmonella Derby strains were positive for the antimicrobial resistance genes aac(6′)- Iaa and fosA7. The 60 strains were subtyped into 46 molecular types by PFGE and 53 molecular types by cgMLST(HC2). Except for one strain belonging to ST3220, the other Salmonella Derby strains were ST40. The phylogenetic analysis showed that some strains isolated in Hangzhou were close to the strains in Southeast Asia, suggesting the possibility of cross-border transmission of ST40 strains, with the main food sources being pork and fish; other strains were close to those circulating in Beijing, Guangzhou, Hubei, Chongqing and other provinces, suggesting the possibility of cross-province transmission of the strains, with the main food sources being pork, beef and chicken. Conclusions:The epidemic of Salmonella Derby in Hangzhou was mainly caused by the spread of ST40 strains and MDR was common. Clinical infections might be closely related to the consumption of pork, beef, chicken and fish. There was the possibility of cross-border transmission of Salmonella Derby between Hangzhou and Southeast Asia and cross-province transmission in China.
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Objective:To explore the relationship and underlying mechanism between exosomes derived from doxorubicin-resistant osteosarcoma cells and MDR1 and miRNAs. Methods:MG63 and U2OS cell lines were selected to construct doxorubicin-resistant strains, and the 50% inhibitory concentration (half maximal inhibitory concentration, IC 50) of drug-resistant and sensitive strains was detected by MTT, and fluorescence staining was performed at intervals of 15 min between 15 and 120 min to detect the change of fluorescence intensity. RT-PCR and Western Blot were used to detect the expression levels of MDR1 P-gp to verify the drug resistance of osteosarcoma cells. Exosomes were identified by particle size analysis and Western Bolt detection. The endocytosis of PKH26-labeled exosomes from doxorubicin-resistant cells was observed, and the proliferation level and migration of exosomes from doxorubicin-resistant cells co-cultured with osteosarcoma cells were detected by MTT assay and cell scratch assay. The differential expression levels of miRNAs in osteosarcoma-sensitive and drug-resistant cells were verified by sequencing and bioinformatics analysis and RT-PCR assay. Tumor growth, serum exosome identification and mRNA expression level of miR-21-5p in tumor-bearing nude mice between normal osteosarcoma cell group and drug-resistant group, drug-resistant+normal exosome group, drug-resistant+drug-resistant+drug-resistant exosome group were observed. MDR1 expression level in tumor tissue was detected by RT-PCR, Western Blot and immunohistochemistry. Results:The IC 50 of two adriamycin resistant strains were 2.21 vs. 11.81 μg/ml and 0.93 vs. 11.81 μg/ml, respectively, and the fluorescence intensity decreased faster than that of normal strains. The relative mRNA expression levels of MDR1 in two cell lines were normal 1.12±0.16, 1.02±0.11 and drug-resistant 2.15±0.10, 2.127±0.12, respectively. The relative protein expression of P-gp was normal 0.92±0.11, 0.73±0.10 and drug-resistant 0.46±0.03, 0.30±0.04, the differences were statistically significant ( P<0.05). Drug-resistant exosomes can enter osteosarcoma cells through endocytosis and concentrate in the cytoplasm when co-cultured with normal strains. Osteosarcoma cells were co-cultured with drug-resistant exosomes at 2, 4, 6, and 8 μg/ml adriamycin, respectively. Compared with normal group, the proliferation level in drug-resistant group was significantly increased. Compared with the normal cell group 35.95±3.92, 6.72±3.55 and the normal exosome group 51.22±5.55, 19.31±1.93, the drug-resistant cell group 54.20±9.32, 19.24±2.88 and drug-resistant exosome group 76.40±5.41, 30.26±4.87, all had significantly higher cell mobility, the difference was statistically significant ( P<0.05). Exosome sequencing and biogenic analysis of 10 highly upregated miRNAs to validate mRNA expression differences between normal and drug-resistant strains by RT-PCR, showing a significant increase in miR-21-5p expression level of drug-resistant strains (5.89±0.26 vs. 0.99±0.06; 1.05±0.07 vs. 8.80±0.93, P<0.05), the difference was statistically significant ( P<0.05). In MG63 and U2OS, the normal cell group and drug-resistant cell group, and the normal exosome group and drug-resistant exosome group were compared, the tumor volume and the terminal tumor weight of nude mice were increased to varying degrees. MRNA relative expression levels of miR-21-5p in serum exosomes of nude mice after drug intervention were 0.86±0.07 and 0.86±0.05 in normal cell group, respectively. The values were 1.13±0.12, 1.14±0.12 in drug-resistant cell group, 0.71±0.05, 0.75±0.03 in normal exosome group, and 0.90±0.07, 0.93±0.04 in drug-resistant exosome group. Compared with normal and drug-resistant strains, the expression levels of normal and drug-resistant exosome groups were increased, with statistical significance ( P<0.05). Conclusion:The exosomes of drug-resistant cells in osteosarcoma could enhance the proliferation level and migration ability of cells through intercellular transfer of MDR1 and miRNAs. The expression of MDR1 and miR-21-5p in drug-resistant cells and tumor-forming nude mouse serum and tumor tissues were up-regulated which suggested that it might be involved in regulating the drug resistance process of osteosarcoma.
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Chemotherapy is one of the important methods to treat cancer, and the emergence of multidrug resistance (MDR) is one major cause for the failure of cancer chemotherapy. Almost all anti-tumor drugs develop drug resistance over a period of time of application in cancer patients, reducing their effects on killing cancer cells. Chemoresistance can lead to a rapid recurrence of cancers and ultimately patient death. MDR may be induced by multiple mechanisms, which are associated with a complex process of multiple genes, factors, pathways, and multiple steps, and today the MDR-associated mechanisms are largely unknown. In this paper, from the aspects of protein-protein interactions, alternative splicing (AS) in pre-mRNA, non-coding RNA (ncRNA) mediation, genome mutations, variance in cell functions, and influence from the tumor microenvironment, we summarize the molecular mechanisms associated with MDR in cancers. In the end, prospects for the exploration of antitumor drugs that can reverse MDR are briefly discussed from the angle of drug systems with improved targeting properties, biocompatibility, availability, and other advantages.
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La nueva norma técnica para el control y la eliminación de la tuberculosis es un gran avance para el diagnóstico de este microorganismo en Chile. Actualmente la principal técnica microbiológica para el diagnóstico de laboratorio es la biología molecular, que reduce el tiempo del resultado a tan solo un par de horas. La normativa actual indica que en el paciente caso presuntivo de tuberculosis (CPT) la técnica exclusiva a realizar es Biología molecular. La literatura indica que la detección a través de amplificación de material genético de la micobacteria tiene un límite de detección de 15,6 UFC/ ml, por tanto, todas las muestras bajo ese límite umbral potencialmente podrían no ser diagnosticadas bajo esta estructura emanada por el ministerio de Salud en Chile. Nuestra recomendación es continuar con el estudio de cultivo en medios líquidos o sólidos para todas las muestras hasta obtener literatura que avale lo contrario
The new technical standard for the control and elimination of tuberculosis in Chile is a great advance for the diagnosis of this microorganism. Currently the main microbiological technique for laboratory diagnosis is PCR, which reduces the time to result to just a couple of hours. The current regulations indicate that in the patient with a presumptive case of tuberculosis (CPT) t he exclusive technique to be performed is PCR. The literature indicates that the detection through amplification of genetic material of the mycobacterium has a detection limit of 15.6 CFU/ml, therefore, all samples under this threshold limit could potentially not be diagnosed under this structure emanated by the Ministry of Health in Chile. Our recommendation is to continue with the study of culture in liquid or solid media for all samples until literature confirms otherwise
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Tuberculosis/diagnosis , COVID-19 Nucleic Acid Testing , Mycobacterium tuberculosis/isolation & purification , Tuberculosis/microbiologyABSTRACT
Due to emerging drug resistance in pathogenic organisms, most of the second generation antibiotics are not effective in controlling the disease. As a consequence, the dosage and duration of drug intake has increased leading to drug induced toxicity and various side effects. A large number of natural products are being reported to ameliorate the toxicity and oxidative stress caused by antibiotics. Here, we explored the antioxidative potential of honey bee product propolis alone as well as in combination with antibiotics in Staphylococcus aureus infected BALB/c mice. For experimental design, mice were divided in to seven groups and decapitated after experimental period. Kidney was excised, homogenized and then used for different biochemical and histopathological estimations. Results observed after treatment with propolis and antibiotics were compared with those of S. aureus infected group. Results showed increase in lipid peroxidation, decrease in reduced glutathione levels and antioxidant enzymes such as; catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione reductase. On the contrary, treatment with propolis, led to reduction in levels of LPO and increase in activities of antioxidant enzymes. Also, histopathology of kidney and all kidney function enzymes were restored to near normal.
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Introduction: An estimated 9.9 million people fell ill with tuberculosis globally in 2020 with India and China contribu?ng a major percentage to the burden of TB. India is grouped under high TB, high HIV associated TB and MDR TB burden countries and 1.24 lakh fell ill with drug resistant TB out of which 56000 were started on second line treatment in 2020. Annually India accounts for 27% of missing TB cases. Diagnosis: The major forms of drug resistant TB that are of clinical importance are INH monoresistant TB, mul?drug resistant TB, pre- XDR TB and XDR TB.WHO approved newer molecular tests for MTB detec?on and drug suscep?bility tests. Treatment: Few newer drugs and few previously used drugs are showing promise when used in combina?on which have come up in recent years. Bedaquiline based regimens are showing improved cure rates. Conclusion: Guidelines based regimens should be strictly adhered to by both public and private TB case trea?ng physicians.
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Background: India is having 27% of the world’s drug resistant TB burden. To address this emerging public health concern PMDT services were rolled out in the year 2007 and the nationwide coverage was achieved in the year 2013. In India, MDR RR TB patients started on se cond - line treatment in the years 2018 and 2020 under PMDT had favorable treatment outcomes of 56% and 57% respectively. Therefore, th is study was conducted to determine the treatment outcomes in patients of DR TB & MDR RR TB in Bengaluru city Karnataka, In dia. Methods: This was a descriptive cross - sectional study using programmatic data among the notified TB cases during the year 2017 - 2020 under NTEP of Bengaluru city. Socio - demographic data, clinical characteristics and diagnostic data were studied. Data analysis was conducted in Python (version 3.9.4) to ascertain the treatment outcomes and its trend in the study area. Results: A total of 689 patients were identified as DR TB cases having resistance to any first line anti TB drug during the year 2017 - 2020 . The mean age of the DR TB patients was observed as 36.7 years (95% CI: 22.3 - 51.1). Among them 434(63.0%) were male, 254(36.9%) were female and 01(0.1%) were transgender. The study revealed the favourable treatment outcomes of 56.6% among the overall DR T B patients and 42.2% among the MDR RR TB patients in Bengaluru city. Conclusion: The study depicted trends of improvements in the successful treatment outcomes among overall DR TB patients from the year 2017 to 2020, but on the other hand the same among th e MDR RR TB patients is a cause of concern. The study highlights adopting a multipronged scheme focusing on End TB strategy by improving diagnostic capability, assuring high - quality treatment and averting drug resistance propagation among
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La emergencia de cepas resistentes de Mycobacterium tuberculosis a múltiples drogas, las dificultades de su diagnóstico y tratamiento constituyen un desafío a la salud pública mundial. Para afrontar esta situación, se emplean nuevas drogas antituberculosis, como bedaquilina, pretomanid y delamanid, así como drogas repropuestas, como fluoroquinolonas, linezolid y clofazimina. Con base en la evidencia brindada por estudios multicéntricos, se han descubierto fármacos asociados a un mejor pronóstico de la tuberculosis drogorresistente y, recientemente, se ha propuesto una nueva clasificación, así como nuevos esquemas totalmente orales. En esta revisión, describimos los esquemas de tratamiento actuales y los aspectos farmacológicos prácticos necesarios a la hora de la prescripción de los nuevos regímenes de tratamiento de la tuberculosis drogorresistente.
The emergence of resistant strains of Mycobacterium tuberculosis to multiple drugs and the difficulties of their diagnosis and treatment constitute a challenge to global public health. To face this challenge, new anti-tuberculosis drugs, such as bedaquiline, pretomanid, and delamanid, as well as replacement drugs, such as fluoroquinolones, linezolid and clofazimine, are used. Based on the evidence provided by multicenter studies, drugs associated with a better prognosis of drug-resistant tuberculosis have been discovered and, recently, a new classification has been proposed, as well as new totally oral regimens. In this review, we describe current treatment regimens and practi cal pharmacological aspects required when prescribing new drug-resistant tuberculosis treatment regimens.
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ABSTRACT The emergence of resistant strains of Mycobacterium tuberculosis to multiple drugs and the difficulties of their diagnosis and treatment constitute a challenge to global public health. To face this challenge, new anti-tuberculosis drugs, such as bedaquiline, pretomanid, and delamanid, as well as replacement drugs, such as fluoroquinolones, linezolid and clofazimine, are used. Based on the evidence provided by multicenter studies, drugs associated with a better prognosis of drug-resistant tuberculosis have been discovered and, recently, a new classification has been proposed, as well as new totally oral regimens. In this review, we describe current treatment regimens and practical pharmacological aspects required when prescribing new drug-resistant tuberculosis treatment regimens.
RESUMEN La emergencia de cepas resistentes de Mycobacterium tuberculosis a múltiples drogas, las dificultades de su diagnóstico y tratamiento constituyen un desafío a la salud pública mundial. Para afrontar esta situación, se emplean nuevas drogas antituberculosis, como bedaquilina, pretomanid y delamanid, así como drogas repropuestas, como fluoroquinolonas, linezolid y clofazimina. Con base en la evidencia brindada por estudios multicéntricos, se han descubierto fármacos asociados a un mejor pronóstico de la tuberculosis drogorresistente y, recientemente, se ha propuesto una nueva clasificación, así como nuevos esquemas totalmente orales. En esta revisión, describimos los esquemas de tratamiento actuales y los aspectos farmacológicos prácticos necesarios a la hora de la prescripción de los nuevos regímenes de tratamiento de la tuberculosis drogorresistente.
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BACKGROUND: Multi-drug resistant tuberculosis has become major public health problem and obstacle to effective control of tuberculosis. Over a period of time, there are several landmark achievements including policy and system preparedness for universal access to TB care including mandatory noti?cation of TB cases, development of standard for TB care in India, comprehensive real time TB information management system-NIKSHAY, use of rapid molecular diagnostics, successful innovations in private sector engagement for TB care-Universal access to TB care. Objective was to ?nd out the challenges in initiation of treatment of Multi Drug Resistant-TB patients get admitted in ITKI Sanatorium Ranchi Jharkhand. METHODS: It was a hospital based cross sectional study carried out from August 2016 to Nov.2018 on Multi drug resistant tuberculosis patients admitted in MDR-TB centre Itki Sanatorium Ranchi after approved from institutional ethics committee. Total study subjects included in study was 64. RESULTS: Most of the study subjects 58 (90.6%) did not know about the MDR-TB. Most of the study subjects 40 (62.5%) had been given reports of CB-NAAT test on same day followed by study subjects 24 (37.5%) on alternate day. No one study subjects 64 (100%) had been given any type of incentive for travelling to pretreatment evaluation centre. In above table, most of the patients 51 (79.7%) had made payment for investigations at district hospital/ SDH level followed by 13 (20.3%) who were free of any expenditure for investigations. Most of the study subjects 60 (93.7%) were not visited by any health staff between ?nal diagnosis of MDR-TB and initiation of treatment for MDR-TB followed by subjects 4 (6.3%) who were being visited by health staff. Most of the study subjects 48 (75%) were unaware about the NIKSHAY POSHAN SCHEME for MDR-TB patients followed by subjects 16 (25%) who knew about the NIKSHAY POSHAN SCHEME for MDR-TB patients by means of various medium.
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Urinary tract infections (UTIs) are one of the most common bacterial infections encountered in clinical practice both in community and hospital settings in all age groups. It is the second most frequently occurring infection in general population after upper respiratory tract infection .Urinary tract infections (UTIs) are the leading cause of Gram negative sepsis in hospitalized patients and are the origin for about half of all hospital acquired infections caused by urinary catheters and are associated with considerable cost in terms of morbidity and economic and research expenditure. Material And Methods: This prospective cross sectional study was carried out in the Department of Microbiology of Government Medical College, Srinagar. A total of 800 patients were taken up for the study. The sample falling under the set inclusion criteria were selected from the urine specimen received in the laboratory for urine culture and sensitivity from Hospitalized patients (IPD). Culture and sensitivity reports and patient data obtained from hospital records was analyzed for this study. Out of 800 samples taken up for the study 208 (26%) were culture positive and 592Results: (74%) were negative. 208 positive samples 125(60.10%) were females and 83(39.90%) were males. female predominance was observed with 71% whereas 29% males were affected by UTI. UTI was predominantly in females of age group (21-40 yrs). most common organism isolated on culture was Escherichia coli(43.26%) both in short stay patients (<48hrs hospital stay) /OPD 22.59% as well as in IPD (>48hrs hospital stay) 20.67%.E.coli was isolated from patients of both uncomplicated and complicated UTI. The second most common organism isolated in our study was Enterococcus faecalis(22.59%), the rate of isolation was much higher 18.75% in inpatients (>48hrs hospital stay) and only 3.84% in OPD/short stay patients (<48hrs hospital stay). In our study Enterococcus spp ranked second amongst uropathogens, in IPD patients isolation rate was almost 5 times higher. Pseudomonas spp was 1 isolate in OPD (0.48%) and 6 (2.88%) in IPD, Acinetobacter 3 (1.44%), Proteus 1 (0.48%) found only in hospitalized patients (stay >48hrs). E.coli showed following sensitivity pattern 96.7% to nitrofurantoin, 93.3% to imipenem, 90.0% to amikacin, 75.6% to gentamycin, 73.3% to cefoperazone-salbactam and meropenem both, 68.9% to pipercillin tazobactam.The sensitivity to TMP-SMX was 45.6%, and to ceftriaxone and cefipime was only 22.2% and 21.1% respectively. The organism also showed resistance to drugs like levofloxacin 82.2% and ciprofloxacin 76.7%.Enterococcus faecalis isolated in our study was sensitive to Vancomycin 95.74% followed by Linezolid (93.6%), Nitrofurantoin (78.7%), HL-Amikacin (74.5%),HL- Gentamycin (70.2%). Enterococcus faecalis showed resistance to drugs commonly used to treat UTI i.e. 91.5% resistant to Ciprofloxacin and 89.4% resistant to Levofloxacin. Gram negative bacteria were most predominantConclusion: microorganisms resulting in more than 50% infections causing urinary tract infection. In our study we have seen that Gram positive cocci especially Enterococcus result in UTI in a significant proportion of patients. In our study Enterococcus spp ranked second amongst uropathogens, in IPD patients isolation rate was almost 5 times higher. The implementation of antibiotic stewardship programs is crucial to minimize resistance. Appropriate antibiotics need to be prescribed based on the antibiotic susceptibility testing which will be narrow spectrum, effective and less expensive with least side effects.
ABSTRACT
High resistance to antimicrobials is associated with biofilm formation responsible for infectious microbes to withstand severe conditions. Therefore, new alternatives are necessary as biofilm inhibitors to control infections. In this study, the antimicrobial and antibiofilm activities of Fagonia indica extracts were evaluated against MDR clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica has antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against multidrug resistant (MDR) clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica had antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against MDR isolates. The maximum inhibitory effects of Fagonia indica chloroform extract on biofilm formation was observed on Staphylococcus aureus (71.84%) followed by Klebsiella pneumoniae (70.83%) after 48 hrs showing that inhibition is also time dependent. Our results about bacterial cell protein leakage indicated that MDR isolates treated with chloroform extract of Fagonia indica showed maximum protein leakage of K. pneumoniae (59.14 µg mL-1) followed by S. aureus (56.7 µg mL-1). Cell attachment assays indicated that chloroform extract resulted in a 43.5-53.5% inhibition of cell adherence to a polystyrene surface. Our results revealed that extracts of Fagonia indica significantly inhibited biofilm formation among MDR clinical isolates, therefore, could be applied as antimicrobial agents and cost effective biofilm inhibitor against these MDR isolates.
A alta resistência aos antimicrobianos está associada à formação de biofilme responsável por micróbios infecciosos para suportar condições severas. Portanto, novas alternativas são necessárias como inibidores de biofilme para controlar infecções. Neste estudo, as atividades antimicrobiana e antibiofilme dos extratos de Fagonia indica foram avaliadas contra isolados clínicos MDR. O extrato exibiu seu efeito antibiofilme ao alterar a aderência e a desintegração da parede celular bacteriana. Fagonia indica tem efeito antibacteriano com valores de concentração inibitória mínima (CIM) variando de 125 a 500 µg mL-1, e valor de concentração bactericida mínima (MBC) de 500-3000 µg mL-1 contra isolados clínicos multirresistentes (MDR). O extrato exibiu seu efeito antibiofilme ao alterar a aderência e a desintegração da parede celular bacteriana. Fagonia indica teve efeito antibacteriano com valores de concentração inibitória mínima (CIM) variando de 125 a 500 µg mL-1, e concentração bactericida mínima (MBC) de 500-3000 µg mL-1 contra isolados MDR. Os efeitos inibitórios máximos do extrato de clorofórmio Fagonia indica na formação de biofilme foi observada em Staphylococcus aureus (71,84%), seguido por Klebsiella pneumoniae (70,83%) após 48 horas, mostrando que a inibição também é dependente do tempo. Nossos resultados sobre extravasamento de proteínas de células bacterianas indicaram que isolados MDR tratados com extrato clorofórmico de Fagonia indica apresentaram vazamento máximo de proteínas de K. pneumoniae (59,14 µg mL-1), seguido por S. aureus (56,7 µg mL-1). Ensaios de fixação de células indicaram que o extrato de clorofórmio resultou em uma inibição de 43,5-53,5% da aderência das células a uma superfície de poliestireno. Nossos resultados revelaram que extratos de Fagonia indica inibiram significativamente a formação de biofilme entre isolados clínicos MDR, portanto, poderiam ser aplicados como agentes antimicrobianos e inibidores de biofilme de baixo custo contra esses isolados MDR.
Subject(s)
Staphylococcus aureus , Plant Extracts/pharmacology , Bacteria , Microbial Sensitivity Tests , Biofilms , Drug Resistance, Multiple, BacterialABSTRACT
Objective: To investigate anti-multidrug resistance (MDR) activity and safety of the bioactive fraction (CL11) from Codiaeum luzonicum crude leaf extract. Methods: Cytotoxic activity of CL11 against MDR and non- resistant colon cancer cells was assessed using MTT assay. Mode of cell death was investigated by annexin V-propidium iodide staining, TUNEL, and JC-1 assays. To examine mechanism of action, the effect on the expression and function of the MDR-implicated protein P-glycoprotein was tested using Western blotting and calcein assay, respectively. Results: CL11 had an EC 50 of 0.18, 1.03 and 38.52 μg/mL against HCT-15, HCT-15/Dox and HCT116, respectively. Cytotoxicity was mediated by inhibition of P-glycoprotein function and expression. The mode of cell death involved mitochondrial membrane depolarization and was mostly non-apoptotic at EC 50 concentrations against HCT-15 and HCT-15/Dox. Conclusions: Fraction CL11 of Codiaeum luzonicum induces non- apoptotic cell death in MDR cancer cells by overcoming MDR through inhibition of P-glycoprotein expression and function.
ABSTRACT
Abstract Introduction Spinal Tuberculosis (STB) represents between 1% and 2% of total tuberculosis cases. STB management remains challenging; the first-line approach consists of medical treatment, while surgery is reserved for patients with complications. No data regarding STB treatment with bedaquiline-containing regimens are available in the literature. Case description Herein, we report the case of a 21-year-old man from Côte d'Ivoire with a multidrug resistance STB with subcutaneous abscess. After approval of the hospital off-label drug committee, we started bedaquiline 400 mg daily for two weeks, followed by 200 mg three times per week, for 22 weeks, associated with linezolid 600 mg daily, rifabutin 450 mg daily, and amikacin 750 mg daily (interrupted after eight weeks). During treatment, we performed a weekly EKG. No QT prolongation was shown, but inverted T waves appeared, requiring several cardiological consultations and cardiac MRI, but no cardiac dysfunction was found. After 24 weeks, bedaquiline was replaced with moxifloxacin 400 mg daily. The patient continued treatment for another year. We performed another computer tomography at the end of treatment, confirming the cure. Discussion A salvage regimen containing bedaquiline proved effective in treating multidrug-resistance tuberculosis spinal infection without causing severe adverse effects. However, further studies are needed to evaluate better bedaquiline bone penetration and the correct duration of treatment with bedaquiline in MDR spinal tuberculosis.
ABSTRACT
Abstract This study investigated the synergy testing of penicillin, cephalosporin, amphenicols, and aminoglycoside in the camel milk (n=768 samples), subsequently used for isolation of MDR S. aureus targeting mecA gene. Antibiotic susceptibility of S. aureus showed >90% isolates were sensitive to ciprofloxacin and trimethoprim and resistant against oxacillin, ampicillin, and cefoxitin. Further, 50-85% of the S. aureus were sensitive to gentamicin, oxytetracycline, and chloramphenicol and resistant against cefotaxime, vancomycin, and cefixime. Minimum inhibitory concentration (MIC) of cefotaxime, (C) and ampicillin (A) in combination with gentamicin (G) was reduced by 99.34% and 70.46%, respectively, while with chloramphenicol (Ch), reduction was 57.49% and 60%, respectively. In addition, the Fractional Inhibitory Concentration Index (FICI) of G+A, Ch+C and Ch+G combinations showed synergy against 80%, 60%, and 30% of MDR S. aureus, respectively. Similarly, C+A and Ch+G displayed indifferent interaction against 70 % and 30% of isolates, respectively, while the later showed additive interaction against 10% of MDR S. aureus. Altogether, our results described effective combination of gentamicin and chloramphenicol with ampicillin and cefotaxime to combat MDR S. aureus
Subject(s)
Penicillins/agonists , Staphylococcus aureus/pathogenicity , Chloramphenicol/agonists , Drug Synergism , Aminoglycosides/agonists , Camelus/classification , Microbial Sensitivity Tests/instrumentation , Genes, MDR , Milk/classificationABSTRACT
ABSTRACT Background: Rapid molecular methods such as the line probe assay (LPA) and Xpert® MTB/RIF assay (Xpert) have been recommended by the World Health Organization for drug-resistant tuberculosis (DR-TB) diagnosis. We conducted an interventional trial in DR-TB reference centers in Brazil to evaluate the impact of the use of LPA and Xpert. Methods: Patients with DR-TB were eligible if their drug susceptibility testing results were available to the treating physician at the time of consultation. The standard reference MGITTM 960 was compared with Xpert (arm 1) and LPA (arm 2). Effectiveness was considered as the start of the appropriate TB regimen that matched drug susceptibility testing (DST) and the proportions of culture conversion and favorable treatment outcomes after 6 months. Results: A higher rate of empirical treatment was observed with MGIT alone than with the Xpert assay (97.0% vs. 45.0%) and LPA (98.2% vs. 67.5%). Patients started appropriate TB treatment more quickly than those in the MGIT group (median 15.0 vs. 40.5 days; p<0.01) in arm 1. Compared to the MGIT group, culture conversion after 6 months was higher for Xpert in arm 1 (90.9% vs. 79.3%, p=0.39) and LPA in arm 2 (80.0% vs. 83.0%, p=0.81). Conclusions: In the Xpert arm, there was a significant reduction in days to the start of appropriate anti-TB treatment and a trend towards greater culture conversion in the sixth month.