scholarly journals Antimicrobial Activity of Solithromycin against Serotyped Macrolide-Resistant Streptococcus pneumoniae Isolates Collected from U.S. Medical Centers in 2012

2015 ◽  
Vol 59 (4) ◽  
pp. 2432-2434 ◽  
Author(s):  
D. J. Farrell ◽  
R. E. Mendes ◽  
R. N. Jones
Keyword(s):  
Antimicrobial Activity ◽  
Streptococcus Pneumoniae ◽  
Bacterial Pneumonia ◽  
Multidrug Resistant ◽  
Clinical Development ◽  
Next Generation ◽  
High Potency ◽  
Content Type ◽  
Medical Centers ◽  
Data Support

ABSTRACTSolithromycin, a next-generation macrolide and novel fluoroketolide, was tested against a 2012 collection of serotyped U.S. macrolide-resistantStreptococcus pneumoniaeisolates associated with community-acquired bacterial pneumonia (CABP). Against all 272 isolates, solithromycin demonstrated high potency (MIC50/90, 0.06/0.25 μg/ml), and it inhibited all strains at MICs of ≤0.5 μg/ml, including the two most prevalent macrolide-resistant serotypes (19A and 35B). These data support the continued clinical development of solithromycin for the treatment of multidrug-resistant CABP.

scholarly journals Antimicrobial Activity of Ceftaroline Tested against Drug-Resistant Subsets of Streptococcus pneumoniae from U.S. Medical Centers

2014 ◽  
Vol 58 (4) ◽  
pp. 2468-2471 ◽  
Author(s):  
Robert K. Flamm ◽  
Helio S. Sader ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
Antimicrobial Activity ◽  
Multidrug Resistance ◽  
Streptococcus Pneumoniae ◽  
Active Agent ◽  
Drug Resistant ◽  
Content Type ◽  
Medical Centers

ABSTRACTStreptococcus pneumoniaeisolates (6,958) were collected from patients at 163 U.S. medical centers during 2009 through 2012. Isolates were evaluated for multidrug resistance (MDR) to penicillin, ceftriaxone, erythromycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin. Ceftaroline was 16-fold more potent than ceftriaxone (MIC50/MIC90, ≤0.25/2 μg/ml) against all isolates. For MDR isolates (35.2% of tested strains), ceftaroline (MIC50/MIC90, 0.06/0.25 μg/ml; 100.0% susceptible) was the most active agent tested, being 8-fold more potent than ceftriaxone (MIC50/MIC90, 0.5/2 μg/ml) and 16-fold more potent than penicillin (MIC50/MIC90, 1/4 μg/ml).

scholarly journals In Vitro Activities of Ceftaroline and Comparators against Streptococcus pneumoniae Isolates from U.S. Hospitals: Results from Seven Years of the AWARE Surveillance Program (2010 to 2016)

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Michael A. Pfaller ◽  
Rodrigo E. Mendes ◽  
Leonard R. Duncan ◽  
Robert K. Flamm ◽  
Helio S. Sader
Keyword(s):  
Streptococcus Pneumoniae ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
Content Type ◽  
Medical Centers ◽  
Extensively Drug Resistant

ABSTRACT We evaluated trends in Streptococcus pneumoniae antimicrobial susceptibility in United States hospitals in the 2010 to 2016 period. A total of 8,768 clinical isolates from 47 medical centers were tested for susceptibility by broth microdilution methods. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) rates decreased from 25.7% and 12.4%, respectively, in 2010 to 17.7% and 3.6%, respectively, in 2016. The susceptibilities to most comparator antimicrobial agents increased, whereas the susceptibilities to ceftaroline, levofloxacin, linezolid, and tigecycline remained stable. Ceftaroline retained potent activity against S. pneumoniae (>99.9%) with no marked variations.

scholarly journals Antimicrobial Activity of Ceftaroline-Avibactam Tested against Clinical Isolates Collected from U.S. Medical Centers in 2010-2011

2013 ◽  
Vol 57 (4) ◽  
pp. 1982-1988 ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Streptococcus Pneumoniae ◽  
Enterobacter Cloacae ◽  
Broth Microdilution ◽  
Methicillin Resistant ◽  
Content Type ◽  
Microdilution Method ◽  
Medical Centers ◽  
Broth Microdilution Method

ABSTRACTCeftaroline-avibactam and comparator agents were tested by the broth microdilution method against 20,089 isolates consecutively collected in 2010 and 2011 from 75 U.S. medical centers. Ceftaroline-avibactam was active againstEnterobacteriaceae(4,908 strains; MIC90, 0.25 μg/ml; highest MIC, 4 μg/ml), including meropenem-nonsusceptibleKlebsiellaspp. and ceftazidime-nonsusceptibleEnterobacter cloacaestrains (MIC90, 1 μg/ml for both). Ceftaroline-avibactam was also active against ceftriaxone-nonsusceptibleStreptococcus pneumoniae(MIC90, 0.25 μg/ml) and methicillin-resistantStaphylococcus aureus(MIC90, 1 μg/ml).

scholarly journals Ceftaroline Activity against Bacterial Pathogens Frequently Isolated in U.S. Medical Centers: Results from Five Years of the AWARE Surveillance Program

2015 ◽  
Vol 59 (4) ◽  
pp. 2458-2461 ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Jennifer M. Streit ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Bacterial Pathogens ◽  
Surveillance Program ◽  
Broth Microdilution ◽  
Methicillin Resistant ◽  
Content Type ◽  
Medical Centers ◽  
Resistant Strains

ABSTRACTA total of 84,704 isolates were collected from 191 medical centers in 2009 to 2013 and tested for susceptibility to ceftaroline and comparator agents by broth microdilution methods. Ceftaroline inhibited allStaphylococcus aureusisolates at ≤2 μg/ml and was very active against methicillin-resistant strains (MIC at which 90% of the isolates tested are inhibited [MIC90], 1 μg/ml; 97.6% susceptible). AmongStreptococcus pneumoniaeisolates, the highest ceftaroline MIC was 0.5 μg/ml, and ceftaroline activity against the most commonEnterobacteriaceaespecies (MIC50, 0.12 μg/ml; 78.9% susceptible) was similar to that of ceftriaxone (MIC50, ≤0.25 μg/ml; 86.8% susceptible).

scholarly journals Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S. Medical Centers, 2013 to 2016

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Dee Shortridge ◽  
Rodrigo E. Mendes ◽  
Robert K. Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Large Collection ◽  
Content Type ◽  
Negative Results ◽  
Medical Centers ◽  
Extensively Drug Resistant ◽  
Genes Encoding

ABSTRACT The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa isolates. The isolates were consecutively collected from 94 U.S. hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥ 16 μg/ml) were evaluated for the presence of genes encoding extended-spectrum β-lactamases and carbapenemases. Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the susceptible breakpoint of ≤8 μg/ml and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/ml; 99.2% susceptible), extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/ml; 97.8% susceptible), and CRE (n = 513; MIC50/90, 0.5/2 μg/ml; 97.5% susceptible) isolates. Only 82.2% of MDR Enterobacteriaceae (n = 2,953) and 64.2% of ceftriaxone-nonsusceptible Klebsiella pneumoniae (n = 1,063) isolates were meropenem susceptible. Among Enterobacter cloacae (22.2% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.3% of the ceftazidime-nonsusceptible isolates, were ceftazidime-avibactam susceptible. Only 23 of 36,380 Enterobacteriaceae (0.06%) isolates were ceftazidime-avibactam nonsusceptible, including 9 metallo-β-lactamase producers and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. Ceftazidime-avibactam showed potent activity against P. aeruginosa (MIC50/90, 2/4 μg/ml; 97.1% susceptible), including MDR (MIC50/90, 4/16 μg/ml; 86.5% susceptible) isolates, and inhibited 71.8% of isolates nonsusceptible to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628). In summary, ceftazidime-avibactam demonstrated potent activity against a large collection (n = 44,248) of contemporary Gram-negative bacilli isolated from U.S. patients, including organisms resistant to most currently available agents, such as CRE and meropenem-nonsusceptible P. aeruginosa.

scholarly journals Macrolides and β-Lactam Antibiotics Enhance C3b Deposition on the Surface of Multidrug-Resistant Streptococcus pneumoniae Strains by a LytA Autolysin-Dependent Mechanism

2012 ◽  
Vol 56 (11) ◽  
pp. 5534-5540 ◽  
Author(s):  
Elisa Ramos-Sevillano ◽  
Cinthya Rodríguez-Sosa ◽  
Roberto Díez-Martínez ◽  
María-José Giménez ◽  
Eduardo Olmedillas ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Multidrug Resistant ◽  
Therapeutic Strategies ◽  
Host Immune System ◽  
Content Type ◽  
Main Cell ◽  
Resistant Strains ◽  
Novel Therapeutic Strategies ◽  
Study Offer ◽  
Dependent Mechanism

ABSTRACTThe emergence ofStreptococcus pneumoniaestrains displaying high levels of multidrug resistance is of great concern worldwide and a serious threat for the outcome of the infection. Modifications of the bacterial envelope by antibiotics may assist the recognition and clearance of the pathogen by the host immune system. Recognition ofS. pneumoniaeresistant strains by the complement component C3b was increased in the presence of specific anti-pneumococcal antibodies and subinhibitory concentrations of different macrolides and β-lactam antibiotics for all the strains investigated. However, C3b levels were unchanged in the presence of serum containing specific antibodies and sub-MICs of levofloxacin. To investigate whether LytA, the main cell wall hydrolase ofS. pneumoniae, might be involved in this process,lytA-deficient mutants were constructed. In the presence of antibiotics, loss of LytA was not associated with enhanced C3b deposition on the pneumococcal surface, which confirms the importance of LytA in this interaction. The results of this study offer new insights into the development of novel therapeutic strategies using certain antibiotics by increasing the efficacy of the host immune response to efficiently recognize pneumococcal resistant strains.

scholarly journals The Microbiology of Bloodstream Infection: 20-Year Trends from the SENTRY Antimicrobial Surveillance Program

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Daniel J. Diekema ◽  
Po-Ren Hsueh ◽  
Rodrigo E. Mendes ◽  
Michael A. Pfaller ◽  
Kenneth V. Rolston ◽  
...  
Keyword(s):  
Bloodstream Infection ◽  
Acinetobacter Calcoaceticus ◽  
Multidrug Resistant ◽  
Geographic Region ◽  
Surveillance Program ◽  
Surveillance Period ◽  
Content Type ◽  
E Coli ◽  
Medical Centers ◽  
Antimicrobial Surveillance

ABSTRACT Bloodstream infection (BSI) organisms were consecutively collected from >200 medical centers in 45 nations between 1997 and 2016. Species identification and susceptibility testing followed Clinical and Laboratory Standards Institute broth microdilution methods at a central laboratory. Clinical data and isolates from 264,901 BSI episodes were collected. The most common pathogen overall was Staphylococcus aureus (20.7%), followed by Escherichia coli (20.5%), Klebsiella pneumoniae (7.7%), Pseudomonas aeruginosa (5.3%), and Enterococcus faecalis (5.2%). S. aureus was the most frequently isolated pathogen overall in the 1997-to-2004 period, but E. coli was the most common after 2005. Pathogen frequency varied by geographic region, hospital-onset or community-onset status, and patient age. The prevalence of S. aureus isolates resistant to oxacillin (ORSA) increased until 2005 to 2008 and then declined among hospital-onset and community-acquired BSI in all regions. The prevalence of vancomycin-resistant enterococci (VRE) was stable after 2012 (16.4% overall). Daptomycin resistance among S. aureus and enterococci (DRE) remained rare (<0.1%). In contrast, the prevalence of multidrug-resistant (MDR) Enterobacteriaceae increased from 6.2% in 1997 to 2000 to 15.8% in 2013 to 2016. MDR rates were highest among nonfermentative Gram-negative bacilli (GNB), and colistin was the only agent with predictable activity against Acinetobacter baumannii-Acinetobacter calcoaceticus complex (97% susceptible). In conclusion, S. aureus and E. coli were the predominant causes of BSI worldwide during this 20-year surveillance period. Important resistant phenotypes among Gram-positive pathogens (MRSA, VRE, or DRE) were stable or declining, whereas the prevalence of MDR-GNB increased continuously during the monitored period. MDR-GNB represent the greatest therapeutic challenge among common bacterial BSI pathogens.

scholarly journals The Ancestral N-Terminal Domain of Big Defensins Drives Bacterially Triggered Assembly into Antimicrobial Nanonets

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Karine Loth ◽  
Agnès Vergnes ◽  
Cairé Barreto ◽  
Sébastien N. Voisin ◽  
Hervé Meudal ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Bactericidal Activity ◽  
Multidrug Resistant ◽  
High Salt ◽  
Clinical Isolates ◽  
Host Defense Peptides ◽  
Hydrophobic Domain ◽  
Content Type ◽  
Terminal Domain

ABSTRACT Big defensins, ancestors of β-defensins, are composed of a β-defensin-like C-terminal domain and a globular hydrophobic ancestral N-terminal domain. This unique structure is found in a limited number of phylogenetically distant species, including mollusks, ancestral chelicerates, and early-branching cephalochordates, mostly living in marine environments. One puzzling evolutionary issue concerns the advantage for these species of having maintained a hydrophobic domain lost during evolution toward β-defensins. Using native ligation chemistry, we produced the oyster Crassostrea gigas BigDef1 (Cg-BigDef1) and its separate domains. Cg-BigDef1 showed salt-stable and broad-range bactericidal activity, including against multidrug-resistant human clinical isolates of Staphylococcus aureus. We found that the ancestral N-terminal domain confers salt-stable antimicrobial activity to the β-defensin-like domain, which is otherwise inactive. Moreover, upon contact with bacteria, the N-terminal domain drives Cg-BigDef1 assembly into nanonets that entrap and kill bacteria. We speculate that the hydrophobic N-terminal domain of big defensins has been retained in marine phyla to confer salt-stable interactions with bacterial membranes in environments where electrostatic interactions are impaired. Those remarkable properties open the way to future drug developments when physiological salt concentrations inhibit the antimicrobial activity of vertebrate β-defensins. IMPORTANCE β-Defensins are host defense peptides controlling infections in species ranging from humans to invertebrates. However, the antimicrobial activity of most human β-defensins is impaired at physiological salt concentrations. We explored the properties of big defensins, the β-defensin ancestors, which have been conserved in a number of marine organisms, mainly mollusks. By focusing on a big defensin from oyster (Cg-BigDef1), we showed that the N-terminal domain lost during evolution toward β-defensins confers bactericidal activity to Cg-BigDef1, even at high salt concentrations. Cg-BigDef1 killed multidrug-resistant human clinical isolates of Staphylococcus aureus. Moreover, the ancestral N-terminal domain drove the assembly of the big defensin into nanonets in which bacteria are entrapped and killed. This discovery may explain why the ancestral N-terminal domain has been maintained in diverse marine phyla and creates a new path of discovery to design β-defensin derivatives active at physiological and high salt concentrations.

scholarly journals Membrane Perturbation Action Mode and Structure-Activity Relationships of Protonectin, a Novel Antimicrobial Peptide from the Venom of the Neotropical Social Wasp Agelaia pallipes pallipes

2013 ◽  
Vol 57 (10) ◽  
pp. 4632-4639 ◽  
Author(s):  
Kairong Wang ◽  
Wen Dang ◽  
Jiexi Yan ◽  
Ru Chen ◽  
Xin Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Social Wasp ◽  
Multidrug Resistant ◽  
Structural Features ◽  
Helical Conformation ◽  
Resistant Bacteria ◽  
Content Type ◽  
Natural Analog ◽  
Action Mode

ABSTRACTWith the extensive use of antibiotics, multidrug-resistant bacteria emerge frequently. New antimicrobial agents with novel modes of action are urgently needed. It is now widely accepted that antimicrobial peptides (AMPs) could be promising alternatives to conventional antibiotics. In this study, we aimed to study the antimicrobial activity and mechanism of action of protonectin, a cationic peptide from the venom of the neotropical social waspAgelaia pallipes pallipes. We demonstrated that protonectin exhibits potent antimicrobial activity against a spectrum of bacteria, including multidrug-resistant strains. To further understand this mechanism, the structural features of protonectin and its analogs were studied by circular dichroism (CD). The CD spectra demonstrated that protonectin and its natural analog polybia-CP formed a typical α-helical conformation in the membrane-mimicking environment, while its proline-substituted analog had much lower or even no α-helix conformation. Molecular dynamics simulations indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity. In conclusion, protonectin exhibits potent antimicrobial activity by disruption of the integrity of the bacterial membrane, and its α-helical confirmation in the membrane is essential for this action.

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