scholarly journals Bacterial Nosocomial Infections: Multidrug Resistance as a Trigger for the Development of Novel Antimicrobials

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 942
Author(s):  
Sílvia A. Sousa ◽  
Joana R. Feliciano ◽  
Tiago Pita ◽  
Catarina F. Soeiro ◽  
Beatriz L. Mendes ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Nosocomial Infections ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Healthcare Systems ◽  
High Morbidity ◽  
Therapeutic Approaches ◽  
New Compounds ◽  
Novel Therapeutic

Nosocomial bacterial infections are associated with high morbidity and mortality, posing a huge burden to healthcare systems worldwide. The ongoing COVID-19 pandemic, with the raised hospitalization of patients and the increased use of antimicrobial agents, boosted the emergence of difficult-to-treat multidrug-resistant (MDR) bacteria in hospital settings. Therefore, current available antibiotic treatments often have limited or no efficacy against nosocomial bacterial infections, and novel therapeutic approaches need to be considered. In this review, we analyze current antibacterial alternatives under investigation, focusing on metal-based complexes, antimicrobial peptides, and antisense antimicrobial therapeutics. The association of new compounds with older, commercially available antibiotics and the repurposing of existing drugs are also revised in this work.

An Overview on the Application of Bacteriophage Therapy in Combating Antibiotics Resistance: A Review

2021 ◽  
Vol 6 (1) ◽  
pp. 113-119
Author(s):  
A. F. Aishat ◽  
◽  
S. B. Manga ◽  
I. O. Obaroh ◽  
R. J. Bioku ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Antibiotics Resistance ◽  
Therapeutic Approaches ◽  
Bacteriophage Therapy ◽  
Advantages And Disadvantages ◽  
Naturally Occurring ◽  
Bacterial Viruses ◽  
Novel Therapeutic

The practice of phage therapy, which uses bacterial viruses (phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins, specifically against multidrug resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage- or antibioticbased, have relative advantages and disadvantages accordingly. Many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections. Although much is still unknown about the interactions between phage, bacteria, and human host, the time to take phage therapy seriously seems to be rapidly approaching Keywords: Antibiotic resistance; Antimicrobial; Bacteriophage; Biofilms; Multidrug resistance; Phage; Phage safety; Therapy.

scholarly journals Genomic Characterization of New Variant of Hydrogen Sulfide (H2S)-Producing Escherichia coli with Multidrug Resistance Properties Carrying the mcr-1 Gene in China

Antibiotics ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 80 ◽  
Author(s):  
Silpak Biswas ◽  
Mohammed Elbediwi ◽  
Guimin Gu ◽  
Min Yue
Keyword(s):  
Escherichia Coli ◽  
Hydrogen Sulfide ◽  
Multidrug Resistance ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Colistin Resistance ◽  
New Variant ◽  
Genomic Characterization ◽  
Human Infections

Colistin is considered to be a ‘last-resort’ antimicrobial for the treatment of multidrug-resistant Gram-negative bacterial infections. Identification of Enterobacteriaceae, carrying the transferable colistin resistance gene mcr-1, has recently provoked a global health concern. This report presents the first detection of a hydrogen sulfide (H2S)-producing Escherichia coli variant isolated from a human in China, with multidrug resistance (MDR) properties, including colistin resistance by the mcr-1 gene, which could have great implications for the treatment of human infections.

Nanomaterials combine multiple therapeutic approaches for cancer cell multidrug resistance, ferroptotic cell death is promising in various cancers

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Cell Death ◽  
Multidrug Resistance ◽  
Cancer Cell ◽  
High Efficiency ◽  
New Technologies ◽  
Multidrug Resistant ◽  
Therapeutic Approaches ◽  
Combination Strategies ◽  
New Strategy ◽  
Chemotherapy Patients

Cancer cell multidrug resistance (MDR) is one of the most significant barriers to chemotherapy patients' ability to treat malignant tumors.This review first discusses the basic processes of MDR and then details the newest usage of nanomaterials combining multiple therapeutic approaches (e.g. PDT, PTT, gas therapy, gene therapy, and CDT) with MDR chemotherapy. We also analyze the advantages and rationales of these combination systems and why they can reduce MDR cancer cells. Currently, together with various new treatment approaches, MDR-related chemotherapeutic research is gaining momentum in search of better therapeutic results. PDT, for example, has the ability to eliminate high-efficiency multidrug-resistant malignancies but has limited relevance to tumor treatment. In this perspective, SDT is a highly promising approach as it increases ROS production utilizing ultrasonic vibrations, allowing magnitude orders to reach deeper than light. PTT is also often criticized for NIR light's restricted penetration depth; thermomagnetic therapy, using magnetic fields to produce local tissue hyperthermia, can considerably alleviate this problem. However, current research on the possibilities of using these new technologies to fight MDR remains rather rare, and more combination strategies should be carefully investigated in the future. Moreover, ongoing discoveries of cell death pathways, highlighted by recent ferroptosis findings, present a new strategy for our battle against MDR and may revolutionize our knowledge of MDR formation. Ferroptotic cell death promises to treat MDR in various cancers. While most of this cutting-edge research is still in its infancy, we anticipate gaining a deeper understanding of the effectiveness of these revolutionary anti-MDR medicines in the near future.

scholarly journals Nosocomial Infections Due to Multidrug-Resistant Bacteria in Cancer Patients: A Six-Year Experience of an Oncology Center of Western China

2020 ◽  
Author(s):  
Ai-Min Jiang ◽  
Xin Shi ◽  
Na Liu ◽  
Huan Gao ◽  
Meng-Di Ren ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Cancer Patients ◽  
Nosocomial Infections ◽  
Bacterial Infections ◽  
Urinary Catheter ◽  
Multidrug Resistant ◽  
Western China ◽  
Smoking History ◽  
Resistant Bacteria ◽  
Indwelling Urinary Catheter

Abstract Background: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate characteristics, antibiotic-resistant patterns, and prognosis of nosocomial infections caused by multidrug-resistant (MDR) bacteria in cancer patients. Methods: This retrospective observational study analyzed cancer patients with MDR bacteria caused nosocomial infections from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the patient’s survival status after infection during hospitalization. Data were analyzed by using independent samples t-test, Chi-square test, and binary logistic regression. P -values < 0.05 were considered statistically significant. Results: Overall, 257 cancer patients developed nosocomial infections caused by MDR bacteria. Extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-PE) was the most frequently isolated multidrug-resistant Gram-negative bacteria (MDRGNB), followed by Acinetobacter baumannii , and Stenotrophomonas maltophilia . Smoking history, cancer patients who received intrapleural/abdominal infusion within 30 days, presence of indwelling urinary catheter, and haemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria were mainly sensitive to amikacin, meropenem, imipenem, tigecycline, and piperacillin/tazobactam. Conclusions: This study confirms that MDR bacteria caused nosocomial infections were widely prevalent in cancer patients. ESBL-PE was the most commonly MDR bacteria, and the isolated MDR strains were mainly sensitive to amikacin, meropenem, imipenem, tigecycline, and piperacillin/tazobactam. Former smokers, cancer patients who received intrapleural/abdominal infusion within 30 days, presence of indwelling urinary catheter, and anemia were associated with increased in-hospital mortality. Our findings suggest that clinicians should think highly of nosocomial infections caused by MDR in cancer patients and advise policymakers to develop a guideline.

scholarly journals Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae

2021 ◽  
Vol 11 ◽  
Author(s):  
Na Li ◽  
Yigang Zeng ◽  
Rong Bao ◽  
Tongyu Zhu ◽  
Demeng Tan ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
S1 Nuclease ◽  
Isolation And Characterization ◽  
Comprehensive Knowledge ◽  
Future Challenges ◽  
Lactamase Gene

Klebsiella pneumoniae is a dominant cause of community-acquired and nosocomial infections, specifically among immunocompromised individuals. The increasing occurrence of multidrug-resistant (MDR) isolates has significantly impacted the effectiveness of antimicrobial agents. As antibiotic resistance is becoming increasingly prevalent worldwide, the use of bacteriophages to treat pathogenic bacterial infections has recently gained attention. Elucidating the details of phage-bacteria interactions will provide insights into phage biology and the better development of phage therapy. In this study, a total of 22 K. pneumoniae isolates were assessed for their genetic and phenotypic relatedness by multi-locus sequence typing (MLST), endonuclease S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and in vitro antibiotic susceptibility testing. In addition, the beta-lactamase gene (blaKPC) was characterized to determine the spread and outbreak of K. pneumoniae carbapenemase (KPC)-producing enterobacterial pathogens. Using these ST11 carbapenem-resistant K. pneumoniae isolates, three phages (NL_ZS_1, NL_ZS_2, and NL_ZS_3) from the family of Podoviridae were isolated and characterized to evaluate the application of lytic phages against the MDR K. pneumoniae isolates. In vitro inhibition assays with three phages and K. pneumoniae strain ZS15 demonstrated the strong lytic potential of the phages, however, followed by the rapid growth of phage-resistant and phage-sensitive mutants, suggesting several anti-phage mechanisms had developed in the host populations. Together, this data adds more comprehensive knowledge to known phage biology and further emphasizes their complexity and future challenges to overcome prior to using phages for controlling this important MDR bacterium.

scholarly journals Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

2020 ◽  
Vol 8 (2) ◽  
pp. 191 ◽  
Author(s):  
Despoina Koulenti ◽  
Elena Xu ◽  
Andrew Song ◽  
Isaac Yin Sum Mok ◽  
Drosos E. Karageorgopoulos ◽  
...  
Keyword(s):  
Safety Profile ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Multi Drug Resistance ◽  
Gram Positive ◽  
Treatment Regimens ◽  
Gram Positive Bacteria

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

scholarly journals Antibiotic Use and Resistance Pattern in Ethiopia: Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Oumer Abdu Muhie
Keyword(s):  
Multidrug Resistance ◽  
Bacterial Infections ◽  
Detection Rate ◽  
Public Health Problem ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Resistance Pattern ◽  
Global Public Health ◽  
Bacterial Strains ◽  
Bacterial Detection

Background. In the last decades, medicines have had an unprecedented positive effect on health, leading to reduced mortality and disease burden and consequently to an improved quality of life. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. In the absence of the development of new generations of antibiotic drugs, appropriate use of existing antibiotics is needed to ensure the long-term availability of effective treatment for bacterial infections. Irrational use of antibiotics is an ongoing global public health problem that deserves more attention. This review is conducted to evaluate the prevalence of inappropriate antibiotic utilization and resistance to antibiotics in Ethiopia. Methods. Electronic search in PubMed/MEDLINE and Google was used to find published literature with reference lists of relevant articles searched manually. Titles and abstracts were initially screened for eligibility. The full texts of articles judged to be eligible were reviewed if they meet the inclusion criteria. Data were extracted on important variables like the sample size, region of the study, the inappropriate antibiotic use, bacterial detection rate, multidrug resistance pattern, and more other variables. Microsoft Excel was used for data extraction. Quantitative analysis was performed using STATA version 11. Results. The electronic searches identified 193 articles of which 33 were found eligible. The random-effects model was used to provide point estimates (with 95% confidence interval (CI)) of bacterial detection rate, inappropriate antibiotic use, and multidrug resistance rate to account for heterogeneity. The pooled bacteria detection rate was 29.1 with 95% CI (16.6–41.7). The pooled prevalence of multidrug resistant strains identified was 59.7% (95% CI: 43.5–75.9). The pooled estimate of inappropriate antibiotic use was 49.2% (95% CI: 32.2–66.2). The pooled proportion of self-antibiotic prescription was 43.3% (95% CI: 15.7–70.9). Other reasons for inappropriate antibiotic use included a wrong indication, wrong duration, improper route of administration, use of leftover antibiotics from a family member, and immature discontinuation of antibiotics. Conclusion and Recommendations. Inappropriate antibiotic use is a huge problem in Ethiopia, and many bacteria were resistant to commonly used antibiotics and similarly, multidrug-resistant bacterial strains are numerous. Appropriate antibiotic use should be ensured by prohibiting over-the-counter sale of antibiotics and strengthening antimicrobial stewardship.

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).

scholarly journals Expression of the multidrug resistance operon mexA-mexB-oprM in Pseudomonas aeruginosa: mexR encodes a regulator of operon expression.

1996 ◽  
Vol 40 (9) ◽  
pp. 2021-2028 ◽  
Author(s):  
K Poole ◽  
K Tetro ◽  
Q Zhao ◽  
S Neshat ◽  
D E Heinrichs ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Gene Product ◽  
Antimicrobial Agents ◽  
Resistant Mutant ◽  
Multidrug Resistant ◽  
Lacz Fusion ◽  
Base Substitution ◽  
Knockout Mutant

The region upstream of the multiple antibiotic resistance efflux operon mexA-mexB-oprM in Pseudomonas aeruginosa was sequenced, and a gene, mexR, was identified. The predicted MexR product contains 147 amino acids with a molecular mass of 16,964 Da, which is consistent with the observed size of the overexpressed mexR gene product. MexR was homologous to MarR, the repressor of MarA-dependent multidrug resistance in Escherichia coli, and other repressors of the MarR family. A mexR knockout mutant showed a twofold increase in expression of both plasmid-borne and chromosomal mexA-reporter gene fusions compared with the MexR+ parent strain, indicating that the mexR gene product negatively regulates expression of the mexA-mexB-oprM operon. Furthermore, the cloned mexR gene product reduced expression of a plasmid-borne mexA-lacZ fusion in E. coli, indicating that MexR represses mexA-mexB-oprM expression directly. Consistent with the increased expression of the efflux operon in the mexR mutant, the mutant showed an increase (relative to its MexR+ parent) in resistance to several antimicrobial agents. Expression of a mexR-lacZ fusion increased threefold in a mexR knockout mutant, indicating that mexR is negatively autoregulated. OCR1, a nalB multidrug-resistant mutant which overproduces OprM, exhibited a greater than sevenfold increase in expression of a chromosomal mexA-phoA fusion compared with its parent. Introduction of a mexR knockout mutation in strain OCR1 eliminated this increase in efflux gene expression and, as expected, increased the susceptibility of the strain to a variety of antibiotics. The nucleotide sequences of the mexR genes of OCR1 and its parental strain revealed a single base substitution in the former which would cause a predicted substitution of Trp for Arg at position 69 of its mexR product. These data suggest that MexR possesses both repressor and activator function in vivo, the activator form being favored in nalB multidrug-resistant strains.

scholarly journals Multidrug Resistant Enteric Bacterial Pathogens in a Psychiatric Hospital in Ghana: Implications for Control of Nosocomial Infections

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Kwabena O. Duedu ◽  
George Offei ◽  
Francis S. Codjoe ◽  
Eric S. Donkor
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistance ◽  
Psychiatric Hospital ◽  
Nosocomial Infections ◽  
Public Health Problem ◽  
Enteric Bacteria ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Important Public Health Problem ◽  
Microbiological Methods

Enteric bacteria are commonly implicated in hospital-acquired or nosocomial infections. In Ghana, these infections constitute an important public health problem but little is known about their contribution to antibiotic resistance. The aim of the study was to determine the extent and pattern of antibiotic resistance of enteric bacteria isolated from patients and environmental sources at the Accra Psychiatric Hospital. A total of 265 samples were collected from the study site including 142 stool and 82 urine samples from patients, 7 swab samples of door handle, and 3 samples of drinking water. Enteric bacteria were isolated using standard microbiological methods. Antibiograms of the isolates were determined using the disc diffusion method. Overall, 232 enteric bacteria were isolated. Escherichia coli was the most common (38.3%), followed by Proteus (19.8%), Klebsiella (17.7%), Citrobacter (14.7%), Morganella (8.2%), and Pseudomonas (1.3%). All isolates were resistant to ampicillin but sensitive to cefotaxime. The resistance ranged from 15.5% to 84.5%. Multidrug resistance was most prevalent (100%) among isolates of Proteus and Morganella and least prevalent among isolates of Pseudomonas (33.3%). Multidrug resistance among enteric bacteria at the study hospital is high and hence there is a need for screening before therapy to ensure prudent use of antibiotics.

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