scholarly journals Discovery of the Antibiotic Polyketide Tatiomicin via a Genomics Guided Analysis of Amycolatopsis sp. DEM30355

Author(s):  
Bernhard Kepplinger ◽  
Joseph Cowell ◽  
Stephanie Morton-Laing ◽  
Corinne Wills ◽  
Emma Marrs ◽  
...  

The application of genomic techniques to the investigation of understudied species of actinobacteria provides an expedited route to the discovery of new bioactive natural products. We report the isolation of the antibiotic polyketide tatiomicin, through a genomics and bioactivity informed analysis of the metabolome of the extremophile <i>Amycolatopsis</i> sp. DEM30355. Structural elucidation including absolute stereochemical assignment was performed using complementary crystallographic, spectroscopic and computational methods. Tatiomicin shows antibiotic activity against Gram-positive bacteria, including Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).

2020 ◽  
Author(s):  
Bernhard Kepplinger ◽  
Joseph Cowell ◽  
Stephanie Morton-Laing ◽  
Corinne Wills ◽  
Emma Marrs ◽  
...  

The application of genomic techniques to the investigation of understudied species of actinobacteria provides an expedited route to the discovery of new bioactive natural products. We report the isolation of the antibiotic polyketide tatiomicin, through a genomics and bioactivity informed analysis of the metabolome of the extremophile <i>Amycolatopsis</i> sp. DEM30355. Structural elucidation including absolute stereochemical assignment was performed using complementary crystallographic, spectroscopic and computational methods. Tatiomicin shows antibiotic activity against Gram-positive bacteria, including Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).


2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.


2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Derong Ding ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  

ABSTRACT The activities of four oxadiazoles were investigated with 210 methicillin-resistant Staphylococcus aureus (MRSA) strains. MIC50 and MIC90 values of 1 to 2 and 4 μg/ml, respectively, were observed. We also evaluated the activity of oxadiazole ND-421 against other staphylococci and enterococci and in the presence of oxacillin for selected MRSA strains. The MIC for ND-421 is lowered severalfold in combination with oxacillin, as they synergize. The MIC90 of ND-421 against vancomycin-resistant enterococci is ≤1 μg/ml.


2009 ◽  
Vol 53 (12) ◽  
pp. 5141-5144 ◽  
Author(s):  
N. Patel ◽  
P. Lubanski ◽  
S. Ferro ◽  
M. Bonafede ◽  
S. Harrington ◽  
...  

ABSTRACT An increase in the distribution of vancomycin MIC values among methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates has been noted. It is postulated that the shift in vancomycin MIC values may be associated with a concurrent rise in the MIC values of other anti-MRSA agents. Scant data are available on the correlation between vancomycin MIC values and the MIC values of other anti-MRSA agents. This study examined the correlation between vancomycin MIC values and the MIC values of daptomycin, linezolid, tigecycline, and teicoplanin among 120 patients with bloodstream infections caused by MRSA at a tertiary care hospital between January 2005 and May 2007. For each included patient, the MIC values of the antibiotics under study were determined by the Etest method and were separated into the following two categories: day 1 (index) and post-day 1 (subsequent). For subsequent isolates, the MIC values for each antibiotic from the post-day 1 terminal isolate were used. Among the index isolates, there was a significant correlation (P value, <0.01) between the MIC values for vancomycin and daptomycin and between the MIC values for vancomycin and teicoplanin. The MIC values for daptomycin were significantly correlated with linezolid, tigecycline, and teicoplanin MIC values. Among the 48 patients with subsequent isolates, vancomycin MIC values were significantly correlated with MIC values for daptomycin, linezolid, and teicoplanin (ρ value of ≥0.38 for all comparisons). This study documented an association between vancomycin MIC values and the MIC values of other anti-MRSA antibiotics among patients with bloodstream infections caused by MRSA primarily treated with vancomycin.


2012 ◽  
Vol 56 (5) ◽  
pp. 2485-2492 ◽  
Author(s):  
Sophie Lefèvre ◽  
Maher Saleh ◽  
Luc Marcellin ◽  
Audrey Subilia ◽  
Tristan Bourcier ◽  
...  

ABSTRACTStaphylococcus aureusis a frequent cause of acute endophthalmitis, and infection with this virulent bacterium is often associated with a poor visual outcome. In this study, we investigated the bactericidal efficacy and the safety of intravitreal daptomycin (DAP), a lipopeptide antibiotic with broad-spectrum activity against Gram-positive bacteria, compared with those of intravitreal vancomycin (VAN) in a methicillin-resistantS. aureusendophthalmitis rabbit model. The pharmacokinetics and pharmacodynamics of daptomycin in the infected eyes were also studied. Rabbits were randomly divided into three treatment groups (n= 8) and one untreated group (n= 4), to compare the effect of single intravitreal injections of 0.2 mg and 1 mg of daptomycin (DAP 0.2 and DAP 1 groups, respectively) with that of 1 mg of intravitreal vancomycin (VAN 1 group). Vitreal aspirates were regularly collected and grading of ocular inflammation was regularly performed until euthanasia on day 7. In the DAP 0.2 group, 62.5% of the eyes were sterilized and the mean bacterial count presented a reduction of 1 log unit. In the DAP 1 and VAN 1 groups, the infection was eradicated (100% and 87.5% of eyes sterilized, respectively), with a 4-log-unit reduction of the mean bacterial count. The bactericidal efficacy in the DAP 1 group was not inferior to that in the VAN 1 group and was superior to that of the other regimens in limiting the ocular inflammation and preserving the architecture of the ocular structures (P< 0.05). The elimination half-life (t1/2β) of daptomycin was independent of the administered dose (38.8 ± 16.5 h and 40.9 ± 6.7 h, respectively, for the DAP 0.2 and DAP 1 groups) and was significantly longer than thet1/2βof vancomycin (20.5 ± 2.0 h for the VAN 1 group) (P< 0.05). This antibiotic could therefore be considered for the treatment of intraocular infections caused by Gram-positive bacteria.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4755-4755
Author(s):  
André Domingues Pereira ◽  
Jessica Fernandes Ramos ◽  
Mariana Guarana ◽  
Simone A Nouér ◽  
Marcio Nucci ◽  
...  

Introduction: The prompt initiation of a betalactam antibiotic in febrile neutropenia (FN) is standard of care in patients with hematologic malignancies and hematopoietic cell transplant (HCT) recipients. The use of a glycopeptide is recommended by guidelines in situations such as suspected catheter-related, skin and soft tissue infection, pneumonia or hemodynamic instability, but the level of these recommendations is weak. The aim of this study was to evaluate the use of vancomycin in febrile neutropenia (FN) in four Brazilian centers in which more restrictive criteria for using vancomycin have been applied. Methods: We retrospectively reviewed all episodes of FN from 2013-2019 in four hospitals: 2 teaching public, 1 public and 1 private hospital, and looked at reasons for giving vancomycin and outcomes. Criteria for using vancomycin was infection by methicillin-resistant Gram-positive bacteria, skin or soft tissue infection and shock. Results: We recorded 461 episodes of FN in 312 patients. Median age was 50 years (17 - 86) and 61% were male. FN occurred after chemotherapy in 70% of cases and after HCT in 30% (allogeneic in 11.5%). The most frequent underlying diseases were acute myeloid leukemia (28%), non-Hodgkin's lymphoma (25%), acute lymphoid leukemia (16%) and multiple myeloma (13.4%). Colonization by methicillin-resistant Staphylococcus aureus (MRSA) was present in only 3%, and quinolone prophylaxis was given in 32% of episodes. According to international guidelines, vancomycin should have been started at first fever in 120 episodes (26%) but it was given in only 28 (6%). Reasons for use at first fever were skin or soft tissue infection (n=10), hypotension or shock (n=8), catheter-related infection (n=3), mucositis (n=1), and no apparent reason (n=6). Vancomycin was added after day 1 in 69 episodes (15%), for the following reasons: Gram-positive bacteremia (n=36), skin or soft tissue infection (n=7), mucositis (n=7), hypotension or shock (n=6), pneumonia (n=3) and no apparent reason (n=10). Bacteremia was documented in 143 episodes (31%): 81 by Gram-negative and 62 by Gram-positive bacteria. Bacteremia due to Staphylococcus aureus occurred in only 4 episodes (1 MRSA). The 15- and 30-day mortality was 5.4% and 9.8%, respectively, with no significant differences among private (7.6%) and public (11.3%) hospitals. Conclusions: Despite the lack of benefit of empiric vancomycin in FN either in terms of fever duration or mortality, vancomycin is still widely used in to manage FN in hematologic patients and HCT recipients, potentially increasing toxicity. In our hospitals vancomycin was given in a very low proportion of episodes, despite having classic indications for its use as per guidelines. Our findings highlight the importance of caution in adopting recommendations from guidelines without looking at local epidemiology especially if the level recommendation is weak. These measures have the potential to decrease coast and toxicity. Disclosures No relevant conflicts of interest to declare.


1998 ◽  
Vol 42 (3) ◽  
pp. 700-702 ◽  
Author(s):  
Kumiko Nagata ◽  
Kei-Ichi Hirai ◽  
Junko Koyama ◽  
Yasunao Wada ◽  
Toshihide Tamura

ABSTRACT Analogs of furanonaphthoquinone (FNQ) from Tecoma ipeMart had MICs ranging from 1.56 to 25 μg/ml against gram-positive bacteria. FNQ showed significantly lower MICs against methicillin-resistant Staphylococcus aureus than against methicillin-sensitive S. aureus. FNQ inhibitedHelicobacter pylori with an MIC of 0.1 μg/ml. Fungi, including pathogenic species, were sensitive to FNQ with MICs similar to those of amphotericin B.


2001 ◽  
Vol 45 (12) ◽  
pp. 3640-3643 ◽  
Author(s):  
Kavindra V. Singh ◽  
Kumthorn Malathum ◽  
Barbara E. Murray

ABSTRACT The in vitro activities of ABT-773 were evaluated against 324 strains of gram-positive bacteria, including multidrug-resistantStaphylococcus spp. and Enterococcus spp. ABT-773 had lower MIC ranges, MICs at which 50% of isolates are inhibited (MIC50s), and MIC90s than erythromycin or clindamycin for almost all isolates tested. The MICs of ABT-773 were also lower than those of quinupristin-dalfopristin (Q-D) for methicillin-susceptible Staphylococcus aureus,Rhodococcus spp., and Streptococcus spp., while the MICs of Q-D were lower than those of ABT-773 for methicillin-resistant S. aureus and Enterococcus faecium, including vancomycin-resistant isolates.


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