Emergence of Colistin Resistance against Multi-Drug Resistance Microorganisms and its Clinical Outcomes

2021 ◽  
Vol 15 (10) ◽  
pp. 2838-2840
Author(s):  
Ahmed F. Mady ◽  
Basheer Abdulrahman ◽  
Mohammad Al Odat ◽  
Waqas Mahmood ◽  
Saima Akhtar ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clinical Outcomes ◽  
Length Of Hospital Stay ◽  
Multidrug Resistant ◽  
Multi Drug Resistance ◽  
Positive Finding ◽  
Colistin Resistance ◽  
The Past ◽  
Medical City ◽  
Evolution Of Resistance

Background: Over the past decade, excessive use of Colistin against multidrug-resistant, Gram-negative bacteria have resulted in the evolution of resistance to Colistin. Objective: To evaluate efficacy of Colistin against multidrug-resistant organisms (MDRO), the emergence of Colistin resistance and its effects on clinical outcomes. Study Design: Retrospective study Place and Duration of Study: King Saud Medical City (KSMC) from 1st October 2015 till 31st January 2016. Methodology: Forty-three patients, resistant to Colistin on blood culture and sensitivity were enrolled. Results: Colistin was not effective at breaking the MDRO. The results revealed no significant impact of Colistin on site of infection such as chest, urinary tract or skin (p=0.612), types of organisms (p=0.629), length of hospital stay and the IV Colistin days (p=0.097 and p=0.166 respectively) in the past 12 months. The positive finding was that more than two third (76.7%) of the ICU patients were alive. Conclusion: Emergence of Multi drug resistance organism is matter of global concern that caused the ineffectiveness of many potent antibiotics and led to the drastic clinical outcomes. Collaboration between medical, paramedical, and administrative staff, with strict implementation of preventive protocol can slow down the velocity of microbial multidrug resistance. Keywords: Multi-drug resistant, Colistin, Outbreak, Intensive care unit, critically ill patients

scholarly journals Baseline and Kinetic Circulating Tumor Cell Counts Are Prognostic Factors in a Prospective Study of Metastatic Colorectal Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 502
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Angelo Borsarelli Carvalho de Brito ◽  
Alexcia Camila Braun ◽  
Milena Shizue Tariki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Prospective Study ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Predictive Biomarkers ◽  
Multi Drug Resistance ◽  
Cell Counts ◽  
Potential Clinical Benefit ◽  
A Prospective Study

The discovery of predictive biomarkers in metastatic colorectal cancer (mCRC) is essential to improve clinical outcomes. Recent data suggest a potential role of circulating tumor cells (CTCs) as prognostic indicators. We conducted a follow-on analysis from a prospective study of consecutive patients with mCRC. CTC analysis was conducted at two timepoints: baseline (CTC1; before starting chemotherapy), and two months after starting treatment (CTC2). CTC isolation/quantification were completed by ISET® (Rarecells, France). CTC expressions of drug resistance-associated proteins were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method. Seventy-five patients were enrolled from May 2012 to May 2014. A CTC1 cut-off of >1.5 CTCs/mL was associated with an inferior median OS compared to lower values. A difference of CTC2−CTC1 > 5.5 CTCs/mL was associated with a reduced median PFS. By multivariate analysis, CTC1 > 1.5 CTCs/mL was an independent prognostic factor for worse OS. Multi-drug resistance protein-1 (MRP-1) expression was associated with poor median OS. CTC baseline counts, kinetics, and MRP-1 expression were predictive of clinical outcomes. Larger studies are warranted to explore the potential clinical benefit of treating mCRC patients with targeted therapeutic regimens guided by CTC findings.

scholarly journals Tackling resistance: emerging antimalarials and new parasite targets in the era of elimination

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1170 ◽  
Author(s):  
Emily S. Mathews ◽  
Audrey R. Odom John
Keyword(s):  
Drug Resistance ◽  
Malaria Elimination ◽  
Large Scale ◽  
Therapeutic Targets ◽  
Control Measures ◽  
Multi Drug Resistance ◽  
Development Projects ◽  
Combination Therapies ◽  
The Past ◽  
Antimalarial Compounds

Malaria remains a significant contributor to global human mortality, and roughly half the world’s population is at risk for infection with Plasmodium spp. parasites. Aggressive control measures have reduced the global prevalence of malaria significantly over the past decade. However, resistance to available antimalarials continues to spread, including resistance to the widely used artemisinin-based combination therapies. Novel antimalarial compounds and therapeutic targets are greatly needed. This review will briefly discuss several promising current antimalarial development projects, including artefenomel, ferroquine, cipargamin, SJ733, KAF156, MMV048, and tafenoquine. In addition, we describe recent large-scale genetic and resistance screens that have been instrumental in target discovery. Finally, we highlight new antimalarial targets, which include essential transporters and proteases. These emerging antimalarial compounds and therapeutic targets have the potential to overcome multi-drug resistance in ongoing efforts toward malaria elimination.

scholarly journals Drug Resistance Mechanism among Acinetobacter Species

2021 ◽  
Author(s):  
S. Jayashree ◽  
K.G. Rajeshwari ◽  
Mita D. Wadekar
Keyword(s):  
Drug Resistance ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Diffusion Method ◽  
Multi Drug Resistance ◽  
Intrinsic Resistance ◽  
Acinetobacter Species ◽  
Beta Lactamases ◽  
Resistant Strains

Acinetobacter species cause infections that are difficult to control due to multi-drug resistance and are noted for their intrinsic resistance to antibiotics and for their ability to acquire genes encoding resistance for the production of beta-lactamases and Aminoglycoside-modifying enzymes. MBLs are molecular class B and functional group 3 beta-lactamases which have the capability of hydrolyzing all β-lactams except the Monobactam, Aztreonam. Of several MBLs, only IMP, VIM and SIM types have been detected in these species. To analyze the antibiotic resistance patterns among Acinetobacter isolates and to detect Carbapenemase and MBL among MDR Acinetobacter isolates. The descriptive study of all phenotypically identified strains and multidrug-resistant strains of Acinetobacter species was conducted. A total of 303 isolates were isolated from various samples. They were processed and identified by standard Microbiological procedures. The antibiotics susceptibility testing was performed by Kirby- Bauer disc diffusion method using CLSI guidelines. Carbapenemase production was detected by employing 3 phenotypic test methods (MHT, CDM and DDST). Of 6355 samples processed, 303 were found to be Acinetobacter species, among those 50 were multidrug-resistant strains. The highest isolation of MDR Acinetobacter was from endotracheal tube tip (42%) and pus sample (32%). The majority of MDR Acinetobacter infection was found in male patients 36 (72%) compared to female patients 14 (28%). The majority of the strains were isolated from patients >/ 60 years of age group (%). A number of these isolates were more from ICU wards (30%) followed by Surgery wards (24%). Higher resistance for the Piperacillin/tazobactam ((82%), followed by Ceftazidime (80%), Imipenem (76%) etc. and the most susceptible drug was found to be the Tigecycline (82%) followed by Colistin (80%). Carbapenemase production was detected by MHT and 24 (48%) isolates were MHT positive. MBL production was detected by CDM and 34 (68%) isolates were CDM positive and by DDST 30 (60%) isolates were positive. Acinetobacter species are increasingly important nosocomial pathogens and are capable of rapid adaptation to the hospital environment. The variety of potential source of contamination or infection with these species in the hospital environment makes control of outbreaks caused by these difficult.

Multidrug-resistant P-glycoprotein assembly revealed by Tariquidar-probe’s super-resolution imaging

Nanoscale ◽  
2021 ◽  
Author(s):  
Hongda Wang ◽  
Junling Chen ◽  
Hongru Li ◽  
Qiang Wu ◽  
Tan Zhao ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Drug Resistance ◽  
Protein Expression ◽  
Efflux Pump ◽  
Super Resolution ◽  
Cell Types ◽  
Multidrug Resistant ◽  
Multi Drug Resistance ◽  
P Glycoprotein ◽  
Resolution Imaging

As an efflux pump, P-glycoproteins (P-gps) are over-expressed in many cancer cell types to confer them multi-drug resistance. Many studies have focused on elucidating its molecular structure or protein expression;...

scholarly journals Clinical and genomic epidemiology of mcr-9-carrying carbapenem-resistant Enterobacterales isolates in Metropolitan Atlanta, 2012-2017

2021 ◽  
Author(s):  
Ahmed Babiker ◽  
Chris Bower ◽  
Joseph Daniel Lutgring ◽  
Jessica Howard-Anderson ◽  
Uzma Ansari ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Heavy Metal Resistance ◽  
Multidrug Resistant ◽  
Metal Resistance ◽  
Phenotypic Characterization ◽  
Surveillance Program ◽  
Emerging Infections ◽  
Colistin Resistance ◽  
Convenience Sample ◽  
Carbapenem Resistant

Colistin is a last-resort antibiotic for multidrug-resistant gram-negative infections. Recently, the ninth allele of the mobile colistin resistance (mcr) gene family, designated mcr-9, was reported. However, its clinical and public health significance remains unclear. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 from a convenience sample of clinical isolates collected between 2012-2017 through the Georgia Emerging Infections Program, a population- and laboratory-based surveillance program. Isolates underwent phenotypic characterization and whole genome sequencing. Phenotypic characteristics, genomic features, and clinical outcomes of mcr-9 positive and negative CRE cases were then compared. Among 235 sequenced CRE genomes, thirteen (6%) were found to harbor mcr-9, all of which were Enterobacter cloacae complex. The median MIC, rates of heteroresistance and inducible resistance to colistin were similar between mcr-9 positive and negative isolates. However, rates of resistance were higher among mcr-9 positive isolates across most antibiotic classes. All cases had significant healthcare exposures. The 90-day mortality was similarly high in both mcr-9 positive (31%) and negative (7%) CRE cases. Nucleotide identity and phylogenetic analysis did not reveal geo-temporal clustering.  mcr-9 positive isolates had a significantly higher number of median [range] AMR genes (16 [4-22] vs. 6 [2-15]; p <0.001) compared to mcr-9 negative isolates. Pan genome tests confirmed a significant association of mcr-9 detection with mobile genetic element and heavy metal resistance genes. Overall, the presence of mcr-9 was not associated with significant changes in colistin resistance or clinical outcomes but continued genomic surveillance to monitor for emergence of AMR genes is warranted

Expression Levels of Glutathione Peroxidase 1 (GPx1) and Multi-Drug Resistance 1 (MDR1; ABCB1) Identify Patients with Diffuse Large B-Cell Lymphoma (DLBCL) That Have Superior Clinical Outcomes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 839-839
Author(s):  
Charalambos Andreadis ◽  
Phyllis Gimotty ◽  
Rachel Hammond ◽  
Peter Wahl ◽  
Jane Houldsworth ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clinical Outcomes ◽  
Classification Tree ◽  
Recursive Partitioning ◽  
B Cell Lymphoma ◽  
Validation Dataset ◽  
Multi Drug Resistance ◽  
High Dose ◽  
Progression Rate ◽  
Univariable Analysis

Abstract Background: Standard chemotherapy fails in 40–50% of patients with DLBCL. Some patients can be salvaged with high-dose regimens, suggesting a role for drug resistance in this disease. While genes in the glutathione (GSH) pathway and ATP-dependent transporter (ABC) family have been implicated in drug resistance in other malignancies, their role in lymphoma, and DLBCL in particular, remains unclear. Methods: We examined expression of 21 key members of these families in two tissue-based expression-microarray datasets of DLBCL patients, prior to CHOP chemotherapy. Expression signals derived from Affymetrix MAS 5.0 software (SF/NF=1) were publicly available for the primary dataset (Monti et al, Blood2005; 105: 1851; http://www.broad.mit.edu/cgi-bin/cancer/datasets.cgi) and were independently generated for the validation dataset (Houldsworth et al, Blood, 2004; 103: 1862). Univariable analysis was performed for freedom from progression (FFP) using a linear-effects Cox proportional-hazards model. Recursive partitioning with CART (Salford Systems, San Diego, CA) was used to develop a classification tree for the 2-year freedom-from-progression rate (FFP2) based on median-adjusted gene expression. Results: In univariable analysis, expression of GPx1 had the most significant adverse association with FFP in the primary dataset (n=130), hazard ratio (HR) 1.68 (95% CI: 1.26 – 2.22, p&lt;0.001). This effect remained highly statistically significant after controlling for the Monti biological signature, the LLMPP cell of origin signature, and the IPI score, and was confirmed in the validation dataset (n=39) (HR 1.5, 95% CI: 1.01 – 2.3, p=0.048). None of the ABC transporters examined were associated with FFP in the univariable analysis. Recursive partitioning identified a group of patients (n=34) with low-level expression of GPx1 and ABCB1 that had no early failures (FFP2: 100%, 95% CI: 90% – 100%). Notably, this group was comprised of patients in all IPI and LLMPP signature subgroups and achieved superior long-term FFP compared to the entire cohort (p&lt;0.001). Conclusions: Overall, our findings suggest an important role for redox-stress defense and drug elimination in the treatment failure of DLBCL and identify GPx1 and ABCB1 as potentially powerful biomarkers of early response and response duration. Coordinate expression of these genes delineates a subgroup of patients with superior clinical outcomes regardless of other clinical and biological risk stratification in current use. Prospective, treatment-based studies with uniform inclusion and response criteria are needed to validate these markers in clinical practice.

Assessment of effects of multi drug resistance on dielectric properties of K562 leukemic cells using electrorotation

RSC Advances ◽  
2014 ◽  
Vol 4 (85) ◽  
pp. 44879-44887 ◽  
Author(s):  
Garsha Bahrieh ◽  
Murat Erdem ◽  
Ebru Özgür ◽  
Ufuk Gündüz ◽  
Haluk Külah
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistant ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Multi Drug Resistance ◽  
Human Leukemia ◽  
Dielectric Characterization ◽  
Human Leukemia Cells ◽  
3D Electrodes

In this study, dielectric characterization of multidrug resistant (MDR) K562 human leukemia cells was carried out using a MEMS based electrorotation (ER) device with 3D electrodes.

scholarly journals The Combination of Sulfamethoxazole, Trimethoprim, and Isoniazid or Rifampin Is Bactericidal and Prevents the Emergence of Drug Resistance in Mycobacterium tuberculosis

2012 ◽  
Vol 56 (10) ◽  
pp. 5142-5148 ◽  
Author(s):  
Catherine Vilchèze ◽  
William R. Jacobs
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Drug Resistant ◽  
Content Type ◽  
The Past ◽  
Tb Treatment

ABSTRACTThe challenges of developing new drugs to treat tuberculosis (TB) are indicated by the relatively small number of candidates entering clinical trials in the past decade. To overcome these issues, we reexamined two FDA-approved antibacterial drugs, sulfamethoxazole (SMX) and trimethoprim (TMP), for use in TB treatment. SMX and TMP inhibit folic acid biosynthesis and are used in combination to treat infections of the respiratory, urinary, and gastrointestinal tracts. The MICs of SMX and TMP, alone and in combination, were determined for drug-susceptible, multidrug-resistant (MDR), and extensively drug-resistantMycobacterium tuberculosisstrains. While TMP alone was not effective againstM. tuberculosis, the combination of TMP and SMX was bacteriostatic againstM. tuberculosis. Surprisingly, the combination of SMX and TMP was also active against a subset of MDRM. tuberculosisstrains. Treatment ofM. tuberculosiswith TMP-SMX and a first-line anti-TB drug, either isoniazid or rifampin, was bactericidal, demonstrating that the combination of TMP and SMX with isoniazid or rifampin was not antagonistic. Moreover, the addition of SMX-TMP in combination with either isoniazid or rifampin also prevented the emergence of drug resistancein vitro. In conclusion, this study further illustrates the opportunity to reevaluate the activity of TMP-SMXin vivoto prevent the emergence of drug-resistantM. tuberculosis.

scholarly journals Detection of enterotoxin gene (sea) and biofilm formation ability among multidrug resistant Staphylococcus aureus isolated from shawarma sandwich sold at selected kiosks in Klang Valley, Malaysia

Food Research ◽  
2020 ◽  
Vol 4 (4) ◽  
pp. 1234-1244
Author(s):  
Salahaldin Fathalla M. ◽  
N.A. Mahyudin ◽  
F. Mohamad Ghazali ◽  
Y. Rukayadi
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Resistance ◽  
Biofilm Formation ◽  
Resistance Index ◽  
Multidrug Resistant ◽  
Animal Origin ◽  
Multi Drug Resistance ◽  
Potential Hazard ◽  
Drug Resistant ◽  
Microtitre Plate Assay

The occurrence of multi-drug resistant Staphylococcus aureus in food product of animal origin has increased the concern about their spread into the food supply chain. Presence of multidrug-resistant S. aureus in food products, including ready-to-eat foods imposes potential hazard for consumers. The objective of this research was to investigate the presence of multi-drug resistance of S. aureus in sixty ready-to-eat shawarma sandwiches. Agar-disc diffusion assay determined their resistance to 11 antibiotics. The sea and sed enterotoxin genes were detected by polymerase chain reaction method. Biofilm formation potential (BFP) was quantified by microtitre plate assay. The result revealed that thirty-six samples (60%) were positive for S. aureus. Majority of the isolates (n = 29; 80.6%) were resistant to at least one antibiotic. The isolates demonstrated highest resistance against ampicillin (69.4%) and penicillin (69.4%), while resistance to ciprofloxacin, tetracycline and kanamycin were 47.2%, 33.3% and 22.2%, respectively. Several isolates were resistant to trimethoprim (5.6%), trimethoprim-sulfamethoxazole- (2.8%), gentamicin (2.8%) and cephalothin (2.8%), while none exhibited resistance to chloramphenicol and nitrofurantoin. Out of the thirty-six isolates, twelve isolates (33.3%) were resistant to three or more classes of antibiotic (multidrug-resistant) and 50% had a Multiple Antibiotic Resistance index value more than 0.25. Of the multi-drug resistant isolates, four were positive for sea genes but no sed genes were present. All multi-drug resistance isolates were biofilm formers with five and six isolates were strong and moderate formers, respectively. Additionally, all the sea gene carrying multi-drug resistance isolates were strong biofilm formers. These findings revealed shawarma as a potential vehicle for the spread of multidrug-resistant S. aureus, suggesting more control measures for ready-to-eat food.

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