Amino Acid Modified Xanthone Derivatives: Novel, Highly Promising Membrane-Active Antimicrobials for Multidrug-Resistant Gram-Positive Bacterial Infections

2014 ◽  
Vol 58 (2) ◽  
pp. 739-752 ◽  
Author(s):  
Jun-Jie Koh ◽  
Shuimu Lin ◽  
Thet Tun Aung ◽  
Fanghui Lim ◽  
Hanxun Zou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Xanthone Derivatives

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 Identification of novel mobilized colistin resistance gene mcr-9 in a multidrug-resistant, colistin-susceptible Salmonella enterica serotype Typhimurium isolate using a combination of high-throughput, in silico screening and functional analysis

2019 ◽  
Author(s):  
Laura M Carroll ◽  
Ahmed Gaballa ◽  
Claudia Guldimann ◽  
Genevieve Sullivan ◽  
Lory O Henderson ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Amino Acid ◽  
In Silico ◽  
Salmonella Enterica ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Human Medicine ◽  
Colistin Resistance ◽  
Phenotypic Resistance ◽  
Typhimurium Strain

Mobilized colistin resistance (mcr) genes are plasmid-borne genes that confer resistance to colistin, an antibiotic used to treat severe bacterial infections. To date, eight known mcr homologues have been described (mcr-1 to -8). Here, we describe mcr-9, a novel mcr homologue, detected in a Salmonella enterica serotype Typhimurium (S. Typhimurium) genome using an in silico approach, followed by experimental functional analysis. The amino acid sequence of mcr-9, detected in a multidrug resistant (MDR) S. Typhimurium strain isolated from a human patient in Washington State in 2010, most closely resembled mcr-3, aligning with 64.5% amino acid identity and 99.5% coverage using translated nucleotide blast. The S. Typhimurium strain was tested for phenotypic resistance to colistin and was found to be sensitive at the 2 mg/L European Committee on Antimicrobial Susceptibility Testing breakpoint under the tested conditions. To determine whether it was capable of conferring resistance to colistin when expressed in a heterologous host, mcr-9 was cloned in colistin-susceptible Escherichia coli NEB5α under an IPTG-induced promoter. Expression of mcr-9 conferred resistance to colistin in E. coli NEB5α at 1, 2, and 2.5 mg/L colistin, albeit at a lower level when compared to mcr-3. Pairwise comparisons of the predicted protein structures associated with all nine mcr homologues (Mcr-1 to -9) revealed that Mcr-9, Mcr-3, and Mcr-7 share a high degree of similarity at the structural level. The results of our approach indicate that mcr-9 is capable of conferring phenotypic resistance to colistin in Enterobacteriaceae and should be immediately considered when monitoring plasmid-mediated colistin resistance. Importance: Colistin is a last-resort antibiotic that is used to treat severe infections caused by MDR and extensively drug resistant (XDR) bacteria. The World Health Organization (WHO) has designated colistin as a Highest Priority Critically Important Antimicrobial for human medicine (WHO, Critically Important Antimicrobials for Human Medicine, 5th Revision, 2017), as it is often one of the only therapies available for treating serious bacterial infections in critically ill patients. Plasmid-borne mcr genes that confer resistance to colistin pose a threat to public health at an international scale, as they can be transmitted via horizontal gene transfer and have the potential to spread globally. Therefore, the establishment of a complete reference of mcr genes that can be used to screen for plasmid-mediated colistin resistance is essential for developing effective control strategies.

scholarly journals Antibacterial Activity and Membrane-Targeting Mechanism of Aloe-Emodin Against Staphylococcus epidermidis

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Li ◽  
Yan Lu ◽  
Hua Zhang ◽  
Lei Wang ◽  
Ross C. Beier ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Bacterial Infections ◽  
Sulfur Metabolism ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Antibiotic Development ◽  
Peptidoglycan Biosynthesis ◽  
Selective Permeability ◽  
Aloe Emodin ◽  
Bacterial Outer Membrane

The emergence of multidrug-resistant Staphylococcus epidermidis (S. epidermidis) dwarfs the current antibiotic development and calls for the discovery of new antibacterial agents. Aloe-emodin is a plant-derived compound that holds promise to battle against these strains. This work reports the antimicrobial activity of aloe-emodin against S. epidermidis and other Gram-positive pathogenic species, manifesting minimum inhibitory concentrations (MICs) and minimum bactericidal concentration (MBCs) around 4–32 and 32–128 μg/mL, respectively. For Gram-negative bacteria tested, the MICs and MBCs of aloe-emodin were 128–256 and above 1024 μg/mL, respectively. Aloe-emodin at the MBC for 4 h eradicated 96.9% of S. epidermidis cells. Aloe-emodin treatment led to deformities in the morphology of S. epidermidis cells and the destroy of the selective permeability of the cell membranes. Analysis of the transcriptional profiles of aloe-emodin-treated cells revealed changes of genes involved in sulfur metabolism, L-lysine and peptidoglycan biosynthesis, and biofilm formation. Aloe-emodin therefore can safely control Gram-positive bacterial infections and proves to target the bacterial outer membrane.

scholarly journals Bacteriology of diabetic foot infections and their antibacterial susceptibility

2018 ◽  
Vol 6 (10) ◽  
pp. 3276
Author(s):  
Alex Aiswariya ◽  
Kalagara Pavani ◽  
Bhanudas Surpam Rajendra
Keyword(s):  
Diabetic Foot ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Negative ◽  
Clinical Specimens ◽  
Antimicrobial Susceptibility Pattern ◽  
Diabetic Foot Infections ◽  
Microbiological Techniques ◽  
Gram Positive Cocci

Background: Diabetic foot infections are the most common bacterial infections encountered in patients with diabetes mellitus and remain the leading complication requiring frequent hospitalization.  Hence, this study was carried out to determine the prevalence of bacteria in diabetic foot infections and their antibiogram which can help to inform therapeutic choices.Methods: A prospective study conducted on clinical specimens taken from patients with diabetic foot infections, over 3 years duration. The clinical specimens were processed by using the standard microbiological techniques. The antimicrobial susceptibility pattern was studied by the Kirby-Bauer disc diffusion method.Results: Among 103 cases studied, 97 were culture positive. Out of these specimens, 25 (25.77%) had monomicrobial flora and 72 (74.23%) had polymicrobial flora. A total of 176 bacteria were obtained which include 62 gram positive cocci and 114 gram negative bacilli. All gram negative bacilli showed good sensitivity to imipenem (97.30%), followed by cefaperazone sulbactam (81.98%), piperacillin-tazobactam (75.68%) and amikacin (72.97%). All gram positive cocci remained 100% sensitive to Vancomycin and Linezolid followed by clindamycin (not tested for Enterococci Spp.) and gentamicin  in a range of  91.43 % to 72.88%. The prevalence of multidrug resistant organisms among aerobic isolates were 59.66%.Conclusions: Diabetic foot infections are polymicrobial. Pseudomonas aeruginosa and Staphylococus aureus were the most common isolates. The most sensitive antibiotics are imipenem for gram negative bacilli while vancomycin and linezolid were effective for gram positive cocci. The antibiogram of isolates will be helpful in determining the drugs for the empirical treatment of diabetic foot infection.

scholarly journals Multidrug-Resistant Gram-Positive Bacterial Infections

2015 ◽  
Vol 88 (5) ◽  
pp. 487 ◽  
Author(s):  
Younghee Jung ◽  
Hong Bin Kim
Keyword(s):  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Gram Positive

scholarly journals Antimicrobial resistance in patients with decompensated liver cirrhosis and bacterial infections in a tertiary center in Northern Germany

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Annika Hillert ◽  
Marie Schultalbers ◽  
Tammo L. Tergast ◽  
Ralf-Peter Vonberg ◽  
Jessica Rademacher ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Antimicrobial Resistance ◽  
Nosocomial Infections ◽  
Bacterial Infections ◽  
Empiric Therapy ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Decompensated Liver Cirrhosis ◽  
Tertiary Center ◽  
Culture Positive

Abstract Background and aims Bacterial infections are common in patients with decompensated liver cirrhosis and a leading cause of death. Reliable data on antibiotic resistance are required to initiate effective empiric therapy. We here aim to assess the antimicrobial resistance profile of bacteria among patients with liver cirrhosis and infection. Methods Overall, 666 cirrhotic patients admitted to Hannover Medical School between January 2012 and April 2018 with ascites were assessed for bacterial infection. In case of infection, bacteria cultured from microbiological specimens of ascites, blood or urine were identified and analyzed for resistances against common antibiotic agents. Furthermore, analyses compared two periods of time and community-acquired vs. nosocomial infections. Results In 281 patients with infection, microbiological sampling was performed and culture-positive results were obtained in 56.9%. Multidrug-resistant (MDR)-bacteria were found in 54 patients (19.2%). Gram-positive organisms were more common (n = 141/261, 54.0%) and detected in 116/192 culture-positive infections (60.4%). Comparing infections before and after 2015, a numerical decline for MDR-bacteria (23.8% vs. 15.6%, p = 0.08) was observed with a significant decline in meropenem resistance (34.9% vs. 19.5%, p = 0.03). MDR-bacteria were more frequent in the case of nosocomial infections. Of note, in ascites the majority of the tested bacteria were resistant against ceftriaxone (73.8%) whereas significantly less were resistant against meropenem (27.0%) and vancomycin (25.9%). Conclusions In our tertiary center, distinct ratios of gram-positive infection with overall low ratios of MDR-bacteria were found. Adequate gram-positive coverage in the empiric therapy should be considered. Carbapenem treatment may be omitted even in nosocomial infection. In contrast, 3rd generation cephalosporins cannot be recommended even in community-acquired infection in our cirrhotic population.

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