scholarly journals Daptomycin in the treatment of infective endocarditis

2018 ◽  
Vol 20 (1) ◽  
pp. 35-40
Author(s):  
Dmitriy A. Popov
Keyword(s):  
Infective Endocarditis ◽  
Antimicrobial Therapy ◽  
Standard Treatment ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Treatment Regimens ◽  
Highly Effective ◽  
Resistant Strains ◽  
Lipopeptide Antibiotic ◽  
Clinical Cases

This review characterizes daptomycin as a highly effective lipopeptide antibiotic being active against Gram-positive microorganisms, including multidrug resistant strains. The data reflecting the up-to-date daptomycin-based approaches to antimicrobial therapy of infective endocarditis which utilize this drug advantages over standard treatment regimens are presented. The data presented are illustrated with clinical cases.

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 Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing

2019 ◽  
Vol 57 (8) ◽  
Author(s):  
Kingsley King-Gee Tam ◽  
Kenneth Siu-Sing Leung ◽  
Gilman Kit-Hang Siu ◽  
Kwok-Chiu Chang ◽  
Samson Sai-Yin Wong ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Direct Detection ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Activity Data ◽  
Content Type ◽  
Treatment Regimens ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Respiratory Specimens

ABSTRACT An in-house-developed pncA sequencing assay for analysis of pyrazinamide (PZA) resistance was evaluated using 162 archived Mycobacterium tuberculosis complex (MTBC) isolates with phenotypic PZA susceptibility profiles that were well defined by analysis of Bactec MGIT 960 PZA kit and PZase activity data. Preliminary results showed 100% concordance between pncA sequencing and phenotypic PZA drug susceptibility test (DST) results among archived isolates. Also, 637 respiratory specimens were prospectively collected, and 158 were reported as MTBC positive by the Abbott Realtime MTB assay (96.3% sensitivity [95% confidence interval {CI}: 92.2% to 98.7%]; 100% specificity [95% CI: 99.2% to 100.0%]). Genotypic and phenotypic PZA resistance profiles of these 158 MTBC-positive specimens were analyzed by pncA sequencing and Bactec MGIT 960 PZA kit, respectively. For analysis of PZA resistance, pncA sequencing detected pncA mutations in 5/5 (100%) phenotypic PZA-resistant respiratory specimens within 4 working days. No pncA mutations were detected among PZA-susceptible specimens. Combining archived isolates with prospective specimens, 27 were identified as phenotypic PZA resistant with pncA mutation. Among these 27 samples, 6/27 (22.2%) phenotypic PZA-resistant strains carried novel pncA mutations without rpsA and panD mutations. These included 5 with mutations (a deletion [Del] at 383T [Del383T], Del 380 to 390, insertion of A [A Ins] at position 127, A Ins at position 407, and G Ins at position 508) in pncA structural genes and 1 with a mutation (T-12C) at the pncA promoter region. All six of these strains had no or reduced PZase activities, indicating that the novel mutations might confer PZA resistance. Additionally, 25/27 phenotypic PZA-resistant strains were confirmed multidrug-resistant tuberculosis (MDR-TB) strains. As PZA is commonly used in MDR-TB treatment regimens, direct pncA sequencing will rapidly detect PZA resistance and facilitate judicious use of PZA in treating PZA-susceptible MDR-TB.

scholarly journals Identification, Typing, Antifungal Resistance Profile, and Biofilm Formation ofCandida albicansIsolates from Lebanese Hospital Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ibrahim Bitar ◽  
Roy A. Khalaf ◽  
Houda Harastani ◽  
Sima Tokajian
Keyword(s):  
Biofilm Formation ◽  
Fungal Pathogens ◽  
Recurrent Infection ◽  
Multidrug Resistant ◽  
Antifungal Resistance ◽  
Drug Resistant ◽  
Treatment Regimens ◽  
Evolutionary Relatedness ◽  
Resistant Strains ◽  
Drug Resistant Strains

As leading opportunistic fungal pathogens identification and subtyping ofCandidaspecies are crucial in recognizing outbreaks of infection, recognizing particularly virulent strains, and detecting the emergence of drug resistant strains. In this study our objective was to compare identification ofCandida albicansby the hospitals through the use of conventional versus identification based on the ITS (Internal Transcribed Spacer) and to assess biofilm forming capabilities, drug resistance patterns and correlate these with MLST typing. ITS typing revealed a 21.2% hospital misidentification rate. Multidrug resistance to three drugs out of four tested was detected within 25% of the isolates raising concerns about the followed treatment regimens. Drug resistant strains as well as biofilm formers were phylogenetically related, with some isolates with significant biofilm forming capabilities being correlated to those that were multidrug resistant. Such isolates were grouped closely together in a neighbor-joining tree generated by MLST typing indicating phylogenetic relatedness, microevolution, or recurrent infection. In conclusion, this pilot study gives much needed insight concerningC. albicansisolates circulating in Lebanese hospitals and is the first study of its kind correlating biofilm formation, antifungal resistance, and evolutionary relatedness.

scholarly journals In Vitro Activities of RWJ-54428 (MC-02,479) against Multiresistant Gram-Positive Bacteria

2001 ◽  
Vol 45 (5) ◽  
pp. 1422-1430 ◽  
Author(s):  
Suzanne Chamberland ◽  
Johanne Blais ◽  
Monica Hoang ◽  
Cynthia Dinh ◽  
Dylan Cotter ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Penicillin G ◽  
Significant Activity ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Level Of Activity ◽  
Resistant Strains ◽  
High Level

ABSTRACT RWJ-54428 (MC-02,479) is a new cephalosporin with a high level of activity against gram-positive bacteria. In a broth microdilution susceptibility test against methicillin-resistant Staphylococcus aureus (MRSA), RWJ-54428 was as active as vancomycin, with an MIC at which 90% of isolates are inhibited (MIC90) of 2 μg/ml. For coagulase-negative staphylococci, RWJ-54428 was 32 times more active than imipenem, with an MIC90 of 2 μg/ml. RWJ-54428 was active against S. aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC range, ≤0.0625 to 1 μg/ml). RWJ-54428 was eight times more potent than methicillin and cefotaxime against methicillin-susceptible S. aureus (MIC90, 0.5 μg/ml). For ampicillin-susceptible Enterococcus faecalis (including vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428 had an MIC90 of 0.125 μg/ml. RWJ-54428 was also active against Enterococcus faecium, including vancomycin-, gentamicin-, and ciprofloxacin-resistant strains. The potency against enterococci correlated with ampicillin susceptibility; RWJ-54428 MICs ranged between ≤0.0625 and 1 μg/ml for ampicillin-susceptible strains and 0.125 and 8 μg/ml for ampicillin-resistant strains. RWJ-54428 was more active than penicillin G and cefotaxime against penicillin-resistant, -intermediate, and -susceptible strains ofStreptococcus pneumoniae (MIC90s, 0.25, 0.125, and ≤0.0625 μg/ml, respectively). RWJ-54428 was only marginally active against most gram-negative bacteria; however, significant activity was observed against Haemophilus influenzae andMoraxella catarrhalis (MIC90s, 0.25 and 0.5 μg/ml, respectively). This survey of the susceptibilities of more than 1,000 multidrug-resistant gram-positive isolates to RWJ-54428 indicates that this new cephalosporin has the potential to be useful in the treatment of infections due to gram-positive bacteria, including strains resistant to currently available antimicrobials.

scholarly journals Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms

2019 ◽  
Vol 7 (8) ◽  
pp. 270 ◽  
Author(s):  
Koulenti ◽  
Xu ◽  
Mok ◽  
Song ◽  
Karageorgopoulos ◽  
...  
Keyword(s):  
Healthcare Costs ◽  
Multidrug Resistant ◽  
Current Evidence ◽  
Efficacy And Safety ◽  
Antibiotic Agent ◽  
Gram Positive ◽  
Resistance Development ◽  
Gram Positive Bacteria ◽  
Highly Effective ◽  
Novel Antibiotics

Increasing multidrug-resistance to Gram-positive pathogens, particularly to staphylococci, enterococci and streptococci, is a major problem, resulting in significant morbidity, mortality and healthcare costs. In recent years, only a small number of novel antibiotics effective against Gram-positive bacteria has been approved. This review will discuss the current evidence for novel branded antibiotics that are highly effective in the treatment of multidrug-resistant infections by Gram-positive pathogens, namely ceftobiprole, ceftaroline, telavancin, oritavancin, dalbavancin, tedizolid, besifloxacin, delafloxacin, ozenoxacin, and omadacycline. The mechanism of action, pharmacokinetics, microbiological spectrum, efficacy and safety profile will be concisely presented. As for any emerging antibiotic agent, resistance is likely to develop against these highly effective antibiotics. Only through appropriate dosing, utilization and careful resistance development monitoring will these novel antibiotics continue to treat Gram-positive pathogens in the future.

scholarly journals Genetic Basis for Daptomycin Resistance in Enterococci

2011 ◽  
Vol 55 (7) ◽  
pp. 3345-3356 ◽  
Author(s):  
Kelli L. Palmer ◽  
Anu Daniel ◽  
Crystal Hardy ◽  
Jared Silverman ◽  
Michael S. Gilmore
Keyword(s):  
Bacterial Infections ◽  
Serial Passage ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Health Concern ◽  
Susceptible Host ◽  
Content Type ◽  
Resistant Strains ◽  
Whole Genome Resequencing ◽  
Lipopeptide Antibiotic

ABSTRACTThe emergence of multidrug-resistant enterococci as a leading cause of hospital-acquired infection is an important public health concern. Little is known about the genetic mechanisms by which enterococci adapt to strong selective pressures, including the use of antibiotics. The lipopeptide antibiotic daptomycin is approved to treat Gram-positive bacterial infections, including those caused by enterococci. Since its introduction, resistance to daptomycin by strains ofEnterococcus faecalisandEnterococcus faeciumhas been reported but is still rare. We evolved daptomycin-resistant strains of the multidrug-resistantE. faecalisstrain V583. Based on the availability of a fully closed genome sequence for V583, we used whole-genome resequencing to identify the mutations that became fixed over short time scales (∼2 weeks) upon serial passage in the presence of daptomycin. By comparison of the genome sequences of the three adapted strains to that of parental V583, we identified seven candidate daptomycin resistance genes and three different mutational paths to daptomycin resistance inE. faecalis. Mutations in one of the seven candidate genes (EF0631), encoding a putative cardiolipin synthase, were found in each of the adaptedE. faecalisV583 strains as well as in daptomycin-resistantE. faecalisandE. faeciumclinical isolates. Alleles of EF0631 from daptomycin-resistant strains are dominant intransand confer daptomycin resistance upon a susceptible host. These results demonstrate a mechanism of enterococcal daptomycin resistance that is genetically distinct from that occurring in staphylococci and indicate that enterococci possessing alternate EF0631 alleles are selected for during daptomycin therapy. However, our analysis ofE. faecalisclinical isolates indicates that resistance pathways independent from mutant forms of EF0631 also exist.

scholarly journals Antimicrobial Diterpenes from Azorella Species against Gram-Positive Bacteria

2015 ◽  
Vol 10 (11) ◽  
pp. 1934578X1501001 ◽  
Author(s):  
Viviana Donoso ◽  
Mitchell Bacho ◽  
Solange Núñez ◽  
Juana Rovirosa ◽  
Aurelio San-Martín ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Mycobacterium Smegmatis ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Resistant Strains ◽  
Andean Plants

The present study was aimed at evaluating the antibacterial activity of mulinane and azorellane diterpenes isolated from the Andean plants Azorella compacta and A. trifoliolata and semisynthetic derivatives against reference and multidrug-resistant strains. The results revealed that the semisynthetic compound 7-acetoxy-mulin-9,12-diene (5) exhibited antibacterial activity against reference and multidrug-resistant strains of Staphylococcus aureus and moderate antimycobacterial activity against Mycobacterium smegmatis ATCC 14468.

scholarly journals The Lipopeptide Antibiotic Friulimicin B Inhibits Cell Wall Biosynthesis through Complex Formation with Bactoprenol Phosphate

2009 ◽  
Vol 53 (4) ◽  
pp. 1610-1618 ◽  
Author(s):  
T. Schneider ◽  
K. Gries ◽  
M. Josten ◽  
I. Wiedemann ◽  
S. Pelzer ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Envelope ◽  
Teichoic Acid ◽  
Multidrug Resistant ◽  
Water Soluble ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Cyclic Lipopeptide ◽  
Excellent Activity ◽  
Lipopeptide Antibiotic

ABSTRACT Friulimicin B is a naturally occurring cyclic lipopeptide, produced by the actinomycete Actinoplanes friuliensis, with excellent activity against gram-positive pathogens, including multidrug-resistant strains. It consists of a macrocyclic decapeptide core and a lipid tail, interlinked by an exocyclic amino acid. Friulimicin is water soluble and amphiphilic, with an overall negative charge. Amphiphilicity is enhanced in the presence of Ca2+, which is also indispensable for antimicrobial activity. Friulimicin shares these physicochemical properties with daptomycin, which is suggested to kill gram-positive bacteria through the formation of pores in the cytoplasmic membrane. In spite of the fact that friulimicin shares features of structure and potency with daptomycin, we found that friulimicin has a unique mode of action and severely affects the cell envelope of gram-positive bacteria, acting via a defined target. We found friulimicin to interrupt the cell wall precursor cycle through the formation of a Ca2+-dependent complex with the bactoprenol phosphate carrier C55-P, which is not targeted by any other antibiotic in use. Since C55-P also serves as a carrier in teichoic acid biosynthesis and capsule formation, it is likely that friulimicin blocks multiple pathways that are essential for a functional gram-positive cell envelope.

scholarly journals Chromone Derivatives and Other Constituents from Cultures of the Marine Sponge-Associated Fungus Penicillium erubescens KUFA0220 and Their Antibacterial Activity

Marine Drugs ◽  
2018 ◽  
Vol 16 (8) ◽  
pp. 289 ◽  
Author(s):  
Decha Kumla ◽  
José Pereira ◽  
Tida Dethoup ◽  
Luis Gales ◽  
Joana Freitas-Silva ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Growth Inhibition ◽  
Marine Sponge ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Negative ◽  
Chromone Derivatives ◽  
Gram Positive Bacteria ◽  
Resistant Strains

A previously unreported chromene derivative, 1-hydroxy-12-methoxycitromycin (1c), and four previously undescribed chromone derivatives, including pyanochromone (3b), spirofuranochromone (4), 7-hydroxy-6-methoxy-4-oxo-3-[(1E)-3-oxobut-1-en-1-yl]-4H-chromene-5-carboxylic acid (5), a pyranochromone dimer (6) were isolated, together with thirteen known compounds: β-sitostenone, ergosterol 5,8-endoperoxide, citromycin (1a), 12-methoxycitromycin (1b), myxotrichin D (1d), 12-methoxycitromycetin (1e), anhydrofulvic acid (2a), myxotrichin C (2b), penialidin D (2c), penialidin F (3a), SPF-3059-30 (7), GKK1032B (8) and secalonic acid A (9), from cultures of the marine sponge- associated fungus Penicillium erubescens KUFA0220. Compounds 1a–e, 2a, 3a, 4, 7–9, were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. Only 8 exhibited an in vitro growth inhibition of all Gram-positive bacteria whereas 9 showed growth inhibition of methicillin-resistant Staphyllococus aureus (MRSA). None of the compounds were active against Gram-negative bacteria tested.

scholarly journals The choice of antimicrobial therapy for infective endocarditis in the conditions of gram-positive microorganism dominance in the etiological structure in the russian federation

2021 ◽  
Vol 66 (5-6) ◽  
pp. 30-34
Author(s):  
A. I. Danilov ◽  
R. S. Kozlov ◽  
A. V. Evseev ◽  
L. L. Lyamets
Keyword(s):  
Heart Failure ◽  
Infective Endocarditis ◽  
Russian Federation ◽  
Multicenter Study ◽  
Antimicrobial Therapy ◽  
Infectious Endocarditis ◽  
Gram Positive ◽  
Target Organs ◽  
The Russian Federation

The problem of infectious endocarditis currently deserves special attention. According to the data, intrahospital mortality caused by this pathology reaches 20%, which is largely due to the development of potential complications, the most common among which are the development and progression of heart failure, as well as thromboembolic manifestations with the damage to target organs of various localization. The article presents the results of a multicenter study establishing the features of antimicrobial therapy in patients with infectious endocarditis under the conditions of the dominance of gram-positive microorganisms in the etiological structure in the Russian Federation. 440 cases of definite and probable infectious endocarditis in the period from September 2006 to December 2020 were analyzed.

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