scholarly journals A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Freya Harrison ◽  
Aled E. L. Roberts ◽  
Rebecca Gabrilska ◽  
Kendra P. Rumbaugh ◽  
Christina Lee ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Content Type ◽  
Natural Substances ◽  
Wound Model ◽  
Antistaphylococcal Activity ◽  
Microbial Infections ◽  
New Antibiotics ◽  
Combined Action ◽  
Materials Used

ABSTRACT Plant-derived compounds and other natural substances are a rich potential source of compounds that kill or attenuate pathogens that are resistant to current antibiotics. Medieval societies used a range of these natural substances to treat conditions clearly recognizable to the modern eye as microbial infections, and there has been much debate over the likely efficacy of these treatments. Our interdisciplinary team, comprising researchers from both sciences and humanities, identified and reconstructed a potential remedy for Staphylococcus aureus infection from a 10th century Anglo-Saxon leechbook. The remedy repeatedly killed established S. aureus biofilms in an in vitro model of soft tissue infection and killed methicillin-resistant S. aureus (MRSA) in a mouse chronic wound model. While the remedy contained several ingredients that are individually known to have some antibacterial activity, full efficacy required the combined action of several ingredients, highlighting the scholarship of premodern doctors and the potential of ancient texts as a source of new antimicrobial agents. IMPORTANCE While the antibiotic potential of some materials used in historical medicine has been demonstrated, empirical tests of entire remedies are scarce. This is an important omission, because the efficacy of “ancientbiotics” could rely on the combined activity of their various ingredients. This would lead us to underestimate their efficacy and, by extension, the scholarship of premodern doctors. It could also help us to understand why some natural compounds that show antibacterial promise in the laboratory fail to yield positive results in clinical trials. We have reconstructed a 1,000-year-old remedy which kills the bacteria it was designed to treat and have shown that this activity relies on the combined activity of several antimicrobial ingredients. Our results highlight (i) the scholarship and rational methodology of premodern medical professionals and (ii) the untapped potential of premodern remedies for yielding novel therapeutics at a time when new antibiotics are desperately needed.

scholarly journals Antistaphylococcal Activity of Oritavancin and Its Synergistic Effect in Combination with Other Antimicrobial Agents

2014 ◽  
Vol 58 (10) ◽  
pp. 6251-6254 ◽  
Author(s):  
Gengrong Lin ◽  
Glenn Pankuch ◽  
Peter C. Appelbaum ◽  
Klaudia Kosowska-Shick
Keyword(s):  
Staphylococcus Aureus ◽  
Synergistic Effect ◽  
Antimicrobial Agents ◽  
Methicillin Resistant ◽  
Content Type ◽  
Antistaphylococcal Activity ◽  
Vancomycin Resistant ◽  
Time Kill

ABSTRACTOritavancin exhibitedin vitroactivity against 169 strains of vancomycin-susceptible, methicillin-resistantStaphylococcus aureus(MRSA) with MICs ranging from 0.03 to 1 μg/ml and against vancomycin-intermediate MRSA (VISA;n= 29), heterogeneous vancomycin-intermediate MRSA (hVISA;n= 5), and vancomycin-resistant MRSA (n= 5) strains, with MICs ranging from 0.12 to 4 μg/ml. For 10 MRSA isolates comprising 5 VISA and 5 hVISA strains, synergy between oritavancin and gentamicin, linezolid, or rifampin was observed against most of the strains tested using a time-kill method.

scholarly journals Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: a Multicenter Study in Taiwan

2012 ◽  
Vol 56 (7) ◽  
pp. 3943-3949 ◽  
Author(s):  
Chun-Hsing Liao ◽  
Wen-Chien Ko ◽  
Jang-Jih Lu ◽  
Po-Ren Hsueh
Keyword(s):  
Clostridium Difficile ◽  
Care Setting ◽  
Antimicrobial Agents ◽  
Teaching Hospitals ◽  
Binary Toxin ◽  
Content Type ◽  
Vancomycin Mics ◽  
Major Teaching ◽  
Southern Taiwan

ABSTRACTA total of 403 nonduplicate isolates ofClostridium difficilewere collected at three major teaching hospitals representing northern, central, and southern Taiwan from January 2005 to December 2010. Of these 403 isolates, 170 (42.2%) were presumed to be nontoxigenic due to the absence of genes for toxins A or B or binary toxin. The remaining 233 (57.8%) isolates carried toxin A and B genes, and 39 (16.7%) of these also had binary toxin genes. The MIC90of all isolates for fidaxomicin and rifaximin was 0.5 μg/ml (range, ≤0.015 to 0.5 μg/ml) and >128 μg/ml (range, ≤0.015 to >128 μg/ml), respectively. All isolates were susceptible to metronidazole (MIC90of 0.5 μg/ml; range, ≤0.03 to 4 μg/ml). Two isolates had reduced susceptibility to vancomycin (MICs, 4 μg/ml). Only 13.6% of isolates were susceptible to clindamycin (MIC of ≤2 μg/ml). Nonsusceptibility to moxifloxacin (n= 81, 20.1%) was accompanied by single or multiple mutations ingyrAandgyrBgenes in all but eight moxifloxacin-nonsusceptible isolates. Two previously unreportedgyrBmutations might independently confer resistance (MIC, 16 μg/ml), Ser416 to Ala and Glu466 to Lys. Moxifloxacin-resistant isolates were cross-resistant to ciprofloxacin and levofloxacin, but some moxifloxacin-nonsusceptible isolates remained susceptible to gemifloxacin or nemonoxacin at 0.5 μg/ml. This study found the diversity of toxigenic and nontoxigenic strains ofC. difficilein the health care setting in Taiwan. All isolates tested were susceptible to metronidazole and vancomycin. Fidaxomicin exhibited potentin vitroactivity against all isolates tested, while the more than 10% of Taiwanese isolates with rifaximin MICs of ≥128 μg/ml raises concerns.

scholarly journals In VivoEfficacy of Anuran Trypsin Inhibitory Peptides against Staphylococcal Skin Infection and the Impact of Peptide Cyclization

2015 ◽  
Vol 59 (4) ◽  
pp. 2113-2121 ◽  
Author(s):  
U. Malik ◽  
O. N. Silva ◽  
I. C. M. Fensterseifer ◽  
L. Y. Chan ◽  
R. J. Clark ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Sequence Similarity ◽  
Infection Model ◽  
Content Type ◽  
Wide Range ◽  
Inhibitory Activities ◽  
The Impact

ABSTRACTStaphylococcus aureusis a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem, and the development of novel antimicrobial agents is crucial. Antimicrobial peptides from natural resources offer potential as new treatments against staphylococcal infections. In the current study, we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weakin vitroinhibitory activities againstS. aureus, but several had strong antibacterial activities againstS. aureusin anin vivomurine wound infection model. pYR, an immunomodulatory peptide fromRana sevosa, was the most potent, with complete bacterial clearance at 3 mg · kg−1. Cyclization of the peptides improved their stability but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.

scholarly journals Carbapenem-Nonsusceptible Pseudomonas aeruginosa Isolates from Intensive Care Units in the United States: a Potential Role for New β-Lactam Combination Agents

2019 ◽  
Vol 57 (8) ◽  
Author(s):  
Tomefa E. Asempa ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Intensive Care ◽  
Respiratory Tract ◽  
Potential Role ◽  
The United States ◽  
Content Type ◽  
New Antibiotics ◽  
Susceptibility Profiles ◽  
Lactamase Inhibitor

ABSTRACT Pseudomonas aeruginosa, a frequent pathogen in the intensive care unit (ICU), has the propensity to develop antibiotic resistance. In particular, carbapenem-nonsusceptible (NS) P. aeruginosa poses tremendous challenges, and new antibiotics will be needed to treat this phenotype. Here we determine carbapenem nonsusceptibility rates for contemporary P. aeruginosa isolates from U.S. ICUs and in vitro activities of new β-lactam combination agents. Between July 2017 and June 2018, consecutive nonduplicate P. aeruginosa isolates from blood and respiratory tract sources were recovered from patients admitted to the ICUs of 36 geographically diverse U.S. hospitals. Antimicrobial susceptibility to the following antipseudomonal agents was tested: ceftazidime, imipenem, meropenem, ceftazidime-avibactam, and imipenem-relebactam (an investigational β-lactam/β-lactamase inhibitor). MICs and susceptibility rates were measured using Clinical and Laboratory Standards Institute reference broth microdilution methodology. Among the 538 consecutive ICU P. aeruginosa isolates collected, carbapenem nonsusceptibility was observed for 35% of the isolates and was more common among respiratory tract versus bloodstream specimens. Susceptibility rates, MIC50 values, and MIC90 values were as follows: ceftazidime-avibactam, 92.8%, 2 μg/ml, and 8 μg/ml; imipenem-relebactam, 91.5%, 0.25 μg/ml, and 2 μg/ml; ceftazidime, 77.1%, 4 μg/ml, and 64 μg/ml; meropenem, 72.7%, 1 μg/ml, and 16 μg/ml; imipenem, 67.1%, 2 μg/ml, and 16 μg/ml. Most (>75%) of the carbapenem-NS isolates were susceptible to ceftazidime-avibactam and imipenem-relebactam. In these U.S. hospital ICUs, carbapenem-NS P. aeruginosa isolates from respiratory sources were frequently observed. Novel β-lactam combination agents appear to retain active in vitro susceptibility profiles against these isolates and may play a role in the treatment of infections caused by carbapenem-NS P. aeruginosa strains.

scholarly journals In Vitro Activity of Eravacycline against Gram-Positive Bacteria Isolated in Clinical Laboratories Worldwide from 2013 to 2017

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Ian Morrissey ◽  
Stephen Hawser ◽  
Sibylle H. Lob ◽  
James A. Karlowsky ◽  
Matteo Bassetti ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Clinical Isolates ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Microdilution Method ◽  
Clinical Laboratories ◽  
Broth Microdilution Method ◽  
Doubling Dilution

ABSTRACT Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, including those caused by resistant Gram-positive pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a recent global collection of frequently encountered clinical isolates of Gram-positive bacteria. The CLSI broth microdilution method was used to determine in vitro MIC data for isolates of Enterococcus spp. (n = 2,807), Staphylococcus spp. (n = 4,331), and Streptococcus spp. (n = 3,373) isolated primarily from respiratory, intra-abdominal, urinary, and skin specimens by clinical laboratories in 37 countries on three continents from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. There were no substantive differences (a >1-doubling-dilution increase or decrease) in eravacycline MIC90 values for different species/organism groups over time or by region. Eravacycline showed MIC50 and MIC90 results of 0.06 and 0.12 μg/ml, respectively, when tested against Staphylococcus aureus, regardless of methicillin susceptibility. The MIC90 values of eravacycline for Staphylococcus epidermidis and Staphylococcus haemolyticus were equal (0.5 μg/ml). The eravacycline MIC90s for Enterococcus faecalis and Enterococcus faecium were 0.06 μg/ml and were within 1 doubling dilution regardless of the vancomycin susceptibility profile. Eravacycline exhibited MIC90 results of ≤0.06 μg/ml when tested against Streptococcus pneumoniae and beta-hemolytic and viridans group streptococcal isolates. In this surveillance study, eravacycline demonstrated potent in vitro activity against frequently isolated clinical isolates of Gram-positive bacteria (Enterococcus, Staphylococcus, and Streptococcus spp.), including isolates collected over a 5-year period (2013 to 2017), underscoring its potential benefit in the treatment of infections caused by common Gram-positive pathogens.

scholarly journals In Vitro Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Suzannah M. Schmidt-Malan ◽  
Avisya J. Mishra ◽  
Ammara Mushtaq ◽  
Cassandra L. Brinkman ◽  
Robin Patel
Keyword(s):  
Antimicrobial Agents ◽  
Empirical Therapy ◽  
Drug Resistant ◽  
Rapid Diagnostics ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Content Type ◽  
Inhibitor Combination ◽  
Selection Of

ABSTRACT Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empirical therapy as mechanistic rapid diagnostics are adopted. In this study, we determined the MICs of a novel β-lactam–β-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 282 drug-resistant isolates of Gram-negative bacilli. For isolates harboring blaKPC (n = 110), the addition of relebactam to imipenem lowered the MIC50/MIC90 from 16/>128 μg/ml for imipenem alone to 0.25/1 μg/ml. For isolates harboring blaCTX-M (n = 48), the MIC50/MIC90 of ceftolozane-tazobactam were 0.5/16 μg/ml (83% susceptible). For isolates harboring blaCMY-2 (n = 17), the MIC50/MIC90 of ceftolozane-tazobactam were 4/8 μg/ml (47% susceptible). Imipenem-relebactam was active against most KPC-producing (but not NDM- or IMP-producing) Enterobacteriaceae and is an encouraging addition to the present antibiotic repertoire.

scholarly journals In Vitro Activities of Eravacycline and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Ken B. Waites ◽  
Donna M. Crabb ◽  
Li Xiao ◽  
Lynn B. Duffy ◽  
Sixto M. Leal
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Ureaplasma Urealyticum ◽  
Mycoplasma Hominis ◽  
Mycoplasma Genitalium ◽  
Content Type ◽  
Ureaplasma Parvum

ABSTRACT We performed in vitro susceptibility testing for eravacycline in comparison to 4 other antimicrobials against 10 Mycoplasma genitalium, 40 Mycoplasma hominis, 44 Mycoplasma pneumoniae, 20 Ureaplasma parvum, and 20 Ureaplasma urealyticum isolates. All eravacycline MICs were ≤0.25 μg/ml, except that for one isolate of M. genitalium, for which the MIC was 2 μg/ml. Eravacycline was markedly more potent than tetracycline, azithromycin, moxifloxacin, and clindamycin against all isolates tested, which included 37 macrolide, tetracycline, and/or fluoroquinolone-resistant organisms.

scholarly journals In Vitro Activity of Tedizolid Compared to Linezolid and Five Other Antimicrobial Agents against 332 Anaerobic Isolates, Including Bacteroides fragilis Group, Prevotella, Porphyromonas, and Veillonella Species

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Ellie J. C. Goldstein ◽  
C. Vreni Merriam ◽  
Diane M. Citron
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Bacteroides Fragilis ◽  
Vitro Activity ◽  
Mixed Infections ◽  
In Vitro Activity ◽  
Content Type ◽  
Bacteroides Fragilis Group ◽  
Group Species

ABSTRACT Tedizolid’s anaerobic activity is unappreciated. In this study, it was active against all 332 anaerobic isolates tested at ≤2 μg/ml except Bilophila wadsworthia and was more active than linezolid against Bacteroides fragilis group species (MIC90, 1 μg/ml versus 2 to 4 μg/ml). Tedizolid was active against Gram-positive anaerobes (MIC90 for clostridia, 0.25 to 1 μg/ml; MIC90 for anaerobic cocci, ≤0.06 to 0.25 μg/ml). Our data coupled with clinical reports indicate that clinicians should consider its use in mixed infections where Staphylococcus aureus and anaerobes are involved.

scholarly journals Apotransferrin in Combination with Ciprofloxacin Slows Bacterial Replication, Prevents Resistance Amplification, and Increases Antimicrobial Regimen Effect

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Paul G. Ambrose ◽  
Brian D. VanScoy ◽  
Brian M. Luna ◽  
Jun Yan ◽  
Amber Ulhaq ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Bactericidal Effect ◽  
Bacterial Density ◽  
Infection Model ◽  
Time Curve ◽  
Content Type ◽  
Wide Range ◽  
Bacterial Replication ◽  
The Impact

ABSTRACT There has been renewed interest in combining traditional small-molecule antimicrobial agents with nontraditional therapies to potentiate antimicrobial effects. Apotransferrin, which decreases iron availability to microbes, is one such approach. We conducted a 48-h one-compartment in vitro infection model to explore the impact of apotransferrin on the bactericidal activity of ciprofloxacin. The challenge panel included four Klebsiella pneumoniae isolates with ciprofloxacin MIC values ranging from 0.08 to 32 mg/liter. Each challenge isolate was subjected to an ineffective ciprofloxacin monotherapy exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC/MIC ratio] ranging from 0.19 to 96.6) with and without apotransferrin. As expected, the no-treatment and apotransferrin control arms showed unaltered prototypical logarithmic bacterial growth. We identified relationships between exposure and change in bacterial density for ciprofloxacin alone (R2 = 0.64) and ciprofloxacin in combination with apotransferrin (R2 = 0.84). Addition of apotransferrin to ciprofloxacin enabled a remarkable reduction in bacterial density across a wide range of ciprofloxacin exposures. For instance, at a ciprofloxacin AUC/MIC ratio of 20, ciprofloxacin monotherapy resulted in nearly 2 log10 CFU increase in bacterial density, while the combination of apotransferrin and ciprofloxacin resulted in 2 log10 CFU reduction in bacterial density. Furthermore, addition of apotransferrin significantly reduced the emergence of ciprofloxacin-resistant subpopulations compared to monotherapy. These data demonstrate that decreasing the rate of bacterial replication with apotransferrin in combination with antimicrobial therapy represents an opportunity to increase the magnitude of the bactericidal effect and to suppress the growth rate of drug-resistant subpopulations.

scholarly journals In VitroActivity of Ceftaroline against Staphylococcus aureus Isolated in 2012 from Asia-Pacific Countries as Part of the AWARE Surveillance Program

2015 ◽  
Vol 60 (1) ◽  
pp. 343-347 ◽  
Author(s):  
Douglas J. Biedenbach ◽  
Richard A. Alm ◽  
Sushmita D. Lahiri ◽  
Edina Reiszner ◽  
Daryl J. Hoban ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Generation Cephalosporin ◽  
Sequence Type ◽  
Asia Pacific ◽  
Surveillance Program ◽  
Ceftaroline Fosamil ◽  
Content Type ◽  
Susceptibility Data

ABSTRACTCeftaroline, the active metabolite of the prodrug ceftaroline-fosamil, is an advanced-generation cephalosporin with activity against methicillin-resistantStaphylococcus aureus(MRSA). This investigation providesin vitrosusceptibility data for ceftaroline against 1,971S. aureusisolates collected in 2012 from seven countries (26 centers) in the Asia-Pacific region as part of the Assessing Worldwide Antimicrobial Resistance and Evaluation (AWARE) program. Broth microdilution as recommended by the CLSI was used to determine susceptibility. In all, 62% of the isolates studied were MRSA, and the ceftaroline MIC90for allS. aureusisolates was 2 μg/ml (interpretive criteria: susceptible, ≤1 μg/ml). The overall ceftaroline susceptibility rate forS. aureuswas 86.9%, with 100% of methicillin-sensitiveS. aureusisolates and 78.8% of MRSA isolates susceptible to this agent. The highest percentages of ceftaroline-nonsusceptible MRSA isolates came from China (47.6%), all of which showed intermediate susceptibility, and Thailand (37.1%), where over half (52.8%) of isolates were resistant to ceftaroline (MIC, 4 μg/ml). Thirty-eight ceftaroline-nonsusceptible isolates (MIC values of 2 to 4 μg/ml) were selected for molecular characterization. Among the isolates analyzed, sequence type 5 (ST-5) was the most common sequence type encountered; however, all isolates analyzed from Thailand were ST-228. Penicillin-binding protein 2a (PBP2a) substitution patterns varied by country, but all isolates from Thailand had the Glu239Lys substitution, and 12 of these also carried an additional Glu447Lys substitution. Ceftaroline-fosamil is a useful addition to the antimicrobial agents that can be used to treatS. aureusinfections. However, with the capability of this species to develop resistance to new agents, it is important to recognize and monitor regional differences in trends as they emerge.

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