scholarly journals Cracking the Challenge of Antimicrobial Drug Resistance with CRISPR/Cas9, Nanotechnology and Other Strategies in ESKAPE Pathogens

2021 ◽  
Vol 9 (5) ◽  
pp. 954
Author(s):  
Tanzeel Zohra ◽  
Muhammad Numan ◽  
Aamer Ikram ◽  
Muhammad Salman ◽  
Tariq Khan ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Health Sector ◽  
Multidrug Resistant ◽  
Research Area ◽  
Resistance Mechanisms ◽  
Public Health Care ◽  
Antimicrobial Drug Resistance ◽  
Eskape Pathogens

Antimicrobial resistance is mushrooming as a silent pandemic. It is considered among the most common priority areas identified by both national and international agencies. The global development of multidrug-resistant strains now threatens public health care improvement by introducing antibiotics against infectious agents. These strains are the product of both continuous evolution and unchecked antimicrobial usage (AMU). The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are now multidrug-resistant, which pose significant challenges in clinical practice. Understanding these bacteria’s resistance mechanisms is crucial for developing novel antimicrobial agents or other alternative tools to fight against these pathogens. A mechanistic understanding of resistance in these pathogens would also help predict underlying or even unknown mechanisms of resistance of other emerging multidrug-resistant pathogens. Research and development to find better antibacterial drugs and research on tools like CRISPER-Cas9, vaccines, and nanoparticles for treatment of infections that can be further explored in the clinical practice health sector have recognized these alternatives as essential and highly effective tools to mitigate antimicrobial resistance. This review summarizes the known antimicrobial resistance mechanisms of ESKAPE pathogens and strategies for overcoming this resistance with an extensive overview of efforts made in this research area.

scholarly journals Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Sirijan Santajit ◽  
Nitaya Indrawattana
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Global Public Health ◽  
Drug Usage ◽  
Inappropriate Use ◽  
Public Health Challenges ◽  
Eskape Pathogens

The ESKAPE pathogens (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.

scholarly journals Bacterial Resistance to Antimicrobial Agents

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 593
Author(s):  
Manuel F. Varela ◽  
Jerusha Stephen ◽  
Manjusha Lekshmi ◽  
Manisha Ojha ◽  
Nicholas Wenzel ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Targets ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Health Sector ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Cellular Mechanisms ◽  
Causative Agents

Bacterial pathogens as causative agents of infection constitute an alarming concern in the public health sector. In particular, bacteria with resistance to multiple antimicrobial agents can confound chemotherapeutic efficacy towards infectious diseases. Multidrug-resistant bacteria harbor various molecular and cellular mechanisms for antimicrobial resistance. These antimicrobial resistance mechanisms include active antimicrobial efflux, reduced drug entry into cells of pathogens, enzymatic metabolism of antimicrobial agents to inactive products, biofilm formation, altered drug targets, and protection of antimicrobial targets. These microbial systems represent suitable focuses for investigation to establish the means for their circumvention and to reestablish therapeutic effectiveness. This review briefly summarizes the various antimicrobial resistance mechanisms that are harbored within infectious bacteria.

scholarly journals Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1502
Author(s):  
Abolfazl Dashtbani-Roozbehani ◽  
Melissa H. Brown
Keyword(s):  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Current Knowledge ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Multidrug Efflux Pump ◽  
New Antibiotics ◽  
Efflux Pump Inhibitors

The increasing emergence of antimicrobial resistance in staphylococcal bacteria is a major health threat worldwide due to significant morbidity and mortality resulting from their associated hospital- or community-acquired infections. Dramatic decrease in the discovery of new antibiotics from the pharmaceutical industry coupled with increased use of sanitisers and disinfectants due to the ongoing COVID-19 pandemic can further aggravate the problem of antimicrobial resistance. Staphylococci utilise multiple mechanisms to circumvent the effects of antimicrobials. One of these resistance mechanisms is the export of antimicrobial agents through the activity of membrane-embedded multidrug efflux pump proteins. The use of efflux pump inhibitors in combination with currently approved antimicrobials is a promising strategy to potentiate their clinical efficacy against resistant strains of staphylococci, and simultaneously reduce the selection of resistant mutants. This review presents an overview of the current knowledge of staphylococcal efflux pumps, discusses their clinical impact, and summarises compounds found in the last decade from plant and synthetic origin that have the potential to be used as adjuvants to antibiotic therapy against multidrug resistant staphylococci. Critically, future high-resolution structures of staphylococcal efflux pumps could aid in design and development of safer, more target-specific and highly potent efflux pump inhibitors to progress into clinical use.

scholarly journals Need for Annual Surveillance of Antimicrobial Resistance in Streptococcus pneumoniae in the United States: 2-Year Longitudinal Analysis

2001 ◽  
Vol 45 (4) ◽  
pp. 1037-1042 ◽  
Author(s):  
Daniel F. Sahm ◽  
James A. Karlowsky ◽  
Laurie J. Kelly ◽  
Ian A. Critchley ◽  
Mark E. Jones ◽  
...  
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
The United States ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Resistance Patterns ◽  
Changing Patterns ◽  
Resistance To Penicillin

ABSTRACT Although changing patterns in antimicrobial resistance inStreptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniaeantimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997–1998 and 1998–1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997–1998 were encountered in 1998–1999. This longitudinal surveillance study of resistance inS. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

scholarly journals Characterization of Multidrug Resistance Patterns of Emerging Salmonella enterica Serovar Rissen along the Food Chain in China

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 660
Author(s):  
Xuebin Xu ◽  
Silpak Biswas ◽  
Guimin Gu ◽  
Mohammed Elbediwi ◽  
Yan Li ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Foodborne Pathogens ◽  
Food Chain ◽  
Salmonella Enterica ◽  
Antimicrobial Agents ◽  
Animal Husbandry ◽  
Multidrug Resistant ◽  
Salmonella Spp ◽  
Broth Microdilution Method ◽  
Resistance Patterns

Salmonella spp. are recognized as important foodborne pathogens globally. Salmonella enterica serovar Rissen is one of the important Salmonella serovars linked with swine products in numerous countries and can transmit to humans by food chain contamination. Worldwide emerging S. Rissen is considered as one of the most common pathogens to cause human salmonellosis. The objective of this study was to determine the antimicrobial resistance properties and patterns of Salmonella Rissen isolates obtained from humans, animals, animal-derived food products, and the environment in China. Between 2016 and 2019, a total of 311 S. Rissen isolates from different provinces or province-level cities in China were included here. Bacterial isolates were characterized by serotyping and antimicrobial susceptibility testing. Minimum inhibitory concentration (MIC) values of 14 clinically relevant antimicrobials were obtained by broth microdilution method. S. Rissen isolates from humans were found dominant (67%; 208/311). S. Rissen isolates obtained from human patients were mostly found with diarrhea. Other S. Rissen isolates were acquired from food (22%; 69/311), animals (8%; 25/311), and the environment (3%; 9/311). Most of the isolates were resistant to tetracycline, trimethoprim-sulfamethoxazole, chloramphenicol, streptomycin, sulfisoxazole, and ampicillin. The S. Rissen isolates showed susceptibility against ceftriaxone, ceftiofur, gentamicin, nalidixic acid, ciprofloxacin, and azithromycin. In total, 92% of the S. Rissen isolates were multidrug-resistant and ASSuT (27%), ACT (25%), ACSSuT (22%), ACSSuTAmc (11%), and ACSSuTFox (7%) patterns were among the most prevalent antibiotic resistance patterns found in this study. The widespread dissemination of antimicrobial resistance could have emerged from misuse of antimicrobial agents in animal husbandry in China. These findings could be useful for rational antimicrobial usage against Salmonella Rissen infections.

scholarly journals Antimicrobial resistance in bacteria isolated from pigs with respiratory clinical signs in Brazil

2020 ◽  
Vol 57 (1) ◽  
pp. e160956
Author(s):  
Maysa Serpa ◽  
Juliana Amália Fonte Bôa do Nascimento ◽  
Mirian Fátima Alves ◽  
Maria Isabel Maldonado Coelho Guedes ◽  
Adrienny Trindade Reis ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Clinical Signs ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Great Level ◽  
Respiratory Pathogens ◽  
Bacterial Strains ◽  
Disk Diffusion Method ◽  
Pig Farms

Antimicrobial resistance is a current and important issue to public health, and it is usually associated with the indiscriminate use of antimicrobials in animal production. This study aimed to evaluate the antimicrobial susceptibility profile in bacterial isolates from pigs with clinical respiratory signs in Brazil. One hundred sixty bacterial strains isolated from pigs from 51 pig farms in Brazil were studied. In vitro disk-diffusion method was employed using 14 antimicrobial agents: amoxicillin, penicillin, ceftiofur, ciprofloxacin, enrofloxacin, chlortetracycline, doxycycline, oxytetracycline, tetracycline, erythromycin, tilmicosin, florfenicol, lincomycin, and sulfadiazine/trimethoprim. The majority of isolates were resistant to at least one antimicrobial agent (98.75%; 158/160), while 31.25% (50/160) of the strains were multidrug resistant. Streptococcus suis and Bordetella bronchiseptica were the pathogens that showed higher resistance levels. Haemophilus parasuis showed high resistance levels to sulfadiazine/trimethoprim (9/18=50%). We observed that isolates from the midwestern and southern regions exhibited four times greater chance of being multidrug resistant than the isolates from the southeastern region studied. Overall, the results of the present study showed a great level of resistance to lincomycin, erythromycin, sulfadiazine/trimethoprim, and tetracycline among bacterial respiratory pathogens isolated from pigs in Brazil. The high levels of antimicrobial resistance in swine respiratory bacterial pathogens highlight the need for the proper use of antimicrobials in Brazilian pig farms.

Antimicrobial Resistance and Association with Class 1 Integrons in Escherichia coli Isolated from Turkey Meat Products

2008 ◽  
Vol 71 (8) ◽  
pp. 1679-1684 ◽  
Author(s):  
M. L. KHAITSA ◽  
J. OLOYA ◽  
D. DOETKOTT ◽  
R. KEGODE
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Population Attributable Fraction ◽  
Meat Products ◽  
Resistance Mechanisms ◽  
E Coli ◽  
Class 1 Integrons ◽  
Turkey Meat ◽  
Class 1

The objective of this study was to quantify the role of class 1 integrons in antimicrobial resistance in Escherichia coli isolated from turkey meat products purchased from retail outlets in the Midwestern United States. Of 242 E. coli isolates, 41.3% (102 of 242) tested positive for class 1 integrons. A significant association was shown between presence of class 1 integrons in E. coli isolates and the resistance to tetracycline, ampicillin, streptomycin, gentamicin, sulfisoxazole, and trimethoprim-sulfamethoxazole. Attributable risk analysis revealed that for every 100 E. coli isolates carrying class 1 integrons, resistance was demonstrated for ampicillin (22%), gentamycin (48%), streptomycin (29%), sulfisoxazole (40%), trimethoprimsulfamethoxazole (7%), and tetracycline (26%). Non–integron-related antimicrobial resistance was demonstrated for ampicillin (65%), gentamycin (16.9%), streptomycin (42.1%), sulfisoxazole (35.8%), and tetracycline (49.7%). Population-attributable fraction analysis showed that class 1 integrons accounted for the following resistances: gentamycin, 71% (50 of 71), amoxicillin–clavulanic acid, 19.6% (6 of 33), nalidixic acid, 34% (7 of 21), streptomycin, 28% (30 of 107), sulfisoxazole, 38% (40 of 106), and tetracycline, 14%, (26 of 185). In conclusion, although class 1 integrons have been implicated in resistance to antimicrobial agents, other non–integron resistance mechanisms seem to play an important part.

scholarly journals Antimicrobial Susceptibility and Clonality of Vaginally Derived Multidrug-Resistant Mobiluncus Isolates in China

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Xueying Zhang ◽  
Yongying Bai ◽  
Long Zhang ◽  
Mohamed S. Draz ◽  
Zhi Ruan ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Antimicrobial Resistance ◽  
Transposable Element ◽  
Genome Sequencing ◽  
Antimicrobial Susceptibility ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Whole Genome ◽  
Content Type ◽  
High Diversity

ABSTRACT Here, the antimicrobial susceptibility, resistance mechanisms, and clonality of Mobiluncus sp. isolates recovered from gynecological outpatients in China were investigated. Compared to M. mulieris, M. curtisii exhibited higher antimicrobial resistance to metronidazole, clindamycin, and tetracycline. Whole-genome sequencing indicated that the clindamycin resistance gene erm(X) was located on a transposable element, Tn5432, which was composed of two IS1249 sequences. Phylogenetic analysis indicated that Mobiluncus spp. had high diversity, with isolates being grouped into several sporadic clades.

Surveillance and Antimicrobial Resistance of Salmonella Strains Isolated from Slaughtered Pigs in Spain

2007 ◽  
Vol 70 (6) ◽  
pp. 1502-1506 ◽  
Author(s):  
RAFAEL JESÚS ASTORGA MÁRQUEZ ◽  
AURORA ECHEITA SALABERRIA ◽  
ALFONSO MALDONADO GARCÍA ◽  
SILVIA VALDEZATE JIMENEZ ◽  
ALFONSO CARBONERO MARTINEZ ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistance ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Phage Type ◽  
Multidrug Resistant ◽  
Gold Coast ◽  
Resistance Patterns ◽  
Salmonella Serotypes ◽  
Slaughtered Pigs

The prevalence of and the antibiotic resistance shown by Salmonella isolated from pigs in Andalusia (southern Spain) is reported. Salmonella enterica was recovered from 40 (33%) of 121 sampled herds, and a total of 65 isolates were serotyped. The most common Salmonella serotypes were Typhimurium and Rissen (30.7% each); others included Derby (9.2%), Brandenburg (9.2%), Newport (7.7%), Bredeney (4.6%), Anatum (3.0%), Hadar (1.5%), and Goldcoast (1.5%). One strain (1.5%) belonging to the monophasic variant of the Typhimurium serotype (Salmonella 4,5,12:i:−) was also detected. Definitive phage type (DT) 104b was the most common Typhimurium phage type isolated. These Salmonella strains were resistant to various antimicrobial agents, including tetracycline (84.6%), streptomycin (69.2%), neomycin (63.0%), sulfonamides (61.5%), ampicillin (53.8%), and amoxicillin (53.8%). All isolates were fully susceptible to ceftriaxone, ciprofloxacin, and colistin. Thirty-nine strains (64%) resistant to four or more antimicrobial agents were defined as multidrug resistant. Multidrug resistance profiles were observed in Salmonella serotypes Typhimurium, Rissen, Brandenburg, Bredeney, a monophasic variant, Gold-coast, Hadar, and Anatum, with serotypes Typhimurium and Brandenburg showing the most complicated resistance patterns (resistant to ≥11 drugs).

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