scholarly journals Efficacy of piperacillin in combination with novel β-lactamase inhibitor IID572 against β-lactamase-producing strains of Enterobacteriaceae and Staphylococcus aureus in murine neutropenic thigh infection models

2020 ◽  
Vol 75 (6) ◽  
pp. 1530-1536
Author(s):  
E J Growcott ◽  
L Gamboa ◽  
T Roth ◽  
S Lopez ◽  
C S Osborne
Keyword(s):  
Staphylococcus Aureus ◽  
Infection Model ◽  
Dependent Manner ◽  
Bacterial Strains ◽  
Bacterial Reduction ◽  
Class A ◽  
Infection Models ◽  
Dose Dependent ◽  
And Staphylococcus Aureus ◽  
Lactamase Inhibitor

Abstract Objectives The neutropenic murine thigh infection model was used to assess the effectiveness of IID572, a novel β-lactamase inhibitor, in rescuing piperacillin activity against bacterial strains expressing various β-lactamase enzymes. Methods Mice (n = 4/group) were inoculated with Enterobacteriaceae or Staphylococcus aureus bacterial strains expressing a range of β-lactamases via intramuscular injection. Two hours after bacterial inoculation, subcutaneous treatment with piperacillin/IID572 or piperacillin/tazobactam every 3 h was initiated. Animals were euthanized via CO2 24 h after the start of therapy and bacterial cfu (log10 cfu) per thigh was determined, and the static dose was calculated. Results In a dose-dependent manner, piperacillin/IID572 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing class A, C and D β-lactamases (e.g. ESBLs, KPC, CMY-2 and OXA-48). Piperacillin/IID572 was also efficacious against MSSA strains, including one producing β-lactamase. Static doses of piperacillin/IID572 were calculable from animals infected with all strains tested and the calculated static doses ranged from 195 to 4612 mg/kg/day piperacillin, the active component in the combination. Of the 13 strains investigated, a 1 log10 bacterial reduction was achieved for 9 isolates and a 2 log10 reduction was achieved for 3 isolates; piperacillin/tazobactam was not efficacious against 6 of the 13 isolates tested. Conclusions In contrast to tazobactam, IID572 was able to rescue piperacillin efficacy in murine thigh infection models established with β-lactamase-producing strains of Enterobacteriaceae and S. aureus, including those expressing ESBLs or serine carbapenemases.

scholarly journals Intracellular Accumulation of Linezolid and Florfenicol in OptrA-Producing Enterococcus faecalis and Staphylococcus aureus

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3195 ◽  
Author(s):  
Yingyu Wang ◽  
Xiaowei Li ◽  
Yang Wang ◽  
Stefan Schwarz ◽  
Jianzhong Shen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecalis ◽  
High Performance ◽  
Resistance Mechanism ◽  
Bacterial Strains ◽  
Quadrupole Mass ◽  
Active Efflux ◽  
Antibiotic Efflux ◽  
And Staphylococcus Aureus ◽  
Tandem Quadrupole

The optrA gene, which confers transferable resistance to oxazolidinones and phenicols, is defined as an ATP-binding cassette (ABC) transporter but lacks transmembrane domains. The resistance mechanism of optrA and whether it involves antibiotic efflux or ribosomal protection remain unclear. In this study, we determined the MIC values of all bacterial strains by broth microdilution, and used ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry to quantitatively determine the intracellular concentrations of linezolid and florfenicol in Enterococcus faecalis and Staphylococcus aureus. Linezolid and florfenicol both accumulated in susceptible strains and optrA-carrying strains of E. faecalis and S. aureus. No significant differences were observed in the patterns of drug accumulation among E. faecalis JH2-2, E. faecalis JH2-2/pAM401, and E. faecalis JH2-2/pAM401+optrA, but also among S. aureus RN4220, S. aureus RN4220/pAM401, and S. aureus RN4220/pAM401+optrA. ANOVA scores also suggested similar accumulation conditions of the two target compounds in susceptible strains and optrA-carrying strains. Based on our findings, the mechanism of optrA-mediated resistance to oxazolidinones and phenicols obviously does not involve active efflux and the OptrA protein does not confer resistance via efflux like other ABC transporters.

scholarly journals In Vitro Activity of LK-157, a Novel Tricyclic Carbapenem As Broad-Spectrum β-Lactamase Inhibitor

2008 ◽  
Vol 53 (2) ◽  
pp. 505-511 ◽  
Author(s):  
Susanne Paukner ◽  
Lars Hesse ◽  
Andrej Preželj ◽  
Tomaž Šolmajer ◽  
Uroš Urleb
Keyword(s):  
Clavulanic Acid ◽  
Broad Spectrum ◽  
Clinical Settings ◽  
In Vitro Activity ◽  
Bacterial Strains ◽  
Class A ◽  
Class C ◽  
Further Development ◽  
Lactamase Inhibitor

ABSTRACT LK-157 is a novel tricyclic carbapenem with potent activity against class A and class C β-lactamases. When tested against the purified TEM-1 and SHV-1 enzymes, LK-157 exhibited 50% inhibitory concentrations (IC50s) in the ranges of the clavulanic acid and tazobactam IC50s (55 nM and 151 nM, respectively). Moreover, LK-157 significantly inhibited AmpC β-lactamase (IC50, 62 nM), as LK-157 was >2,000-fold more potent than clavulanic acid and approximately 28-fold more active than tazobactam. The in vitro activities of LK-157 in combination with amoxicillin, piperacillin, ceftazidime, cefotaxime, ceftriaxone, cefepime, cefpirome, and aztreonam against an array of Ambler class A (TEM-, SHV-, CTX-M-, KPC-, PER-, BRO-, and PC-type)- and class C-producing bacterial strains derived from clinical settings were evaluated in synergism experiments and compared with those of clavulanic acid, tazobactam, and sulbactam. In vitro MICs against ESBL-producing strains (except CTX-M-containing strains) were reduced 2- to >256-fold, and those against AmpC-producing strains were reduced even up to >32-fold. The lowest MICs (≤0.025 to 1.6 μg/ml) were observed for the combination of cefepime and cefpirome with a constant LK-157 concentration of 4 μg/ml, thus raising an interest for further development. LK-157 proved to be a potent β-lactamase inhibitor, combining activity against class A and class C β-lactamases, which is an absolute necessity for use in the clinical setting due to the worldwide increasing prevalence of bacterial strains resistant to β-lactam antibiotics.

scholarly journals Anthill Inhibiting Bacteria, a Promising Source of Bio Efficacy

2020 ◽  
pp. 14-21
Author(s):  
A. A. Katun ◽  
A. R. Abdulmumin ◽  
M. U. Yahaya ◽  
N. K. Habeeb ◽  
A. Bala
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Salmonella Typhi ◽  
Biologically Active ◽  
Bacterial Strains ◽  
Active Metabolites ◽  
Bacillus Lentus ◽  
Total Prevalence ◽  
Promising Source ◽  
And Staphylococcus Aureus

The investigation into soil bacteria has been widely studied and becoming increasingly appreciated as an exceptional reservoir of unique naturally occurring biologically active metabolites with pharmaceutical applications. This article aimed to isolate, identify and biochemically characterize antibiotic-producing bacteria from anthill soils in the permanent site of Ibrahim Badamasi Babangida University, Lapai (IBBUL), Niger State, Nigeria. The sum of ten samples were collected from five sampling sites, the sampling was done in threefold (morning, noon and evening) and analyzed adopting standard microbiological protocols. The obtained result revealed that the total bacteria count in the morning ranges from 2.1×107 cfu/mL to 1.4×106 cfu/mL, noon count ranges from 3.1×107 to 2.6×106 cfu/mL while evening count was in the range of 2.1×107 cfu/mL to 1.7×106 cfu/mL. A total number of five (5) bacteria were isolated as Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Bacillus lentus and Micrococcus reseus. The total prevalence of the bacterial isolates in the morning, noon and evening were calculated as B. subtilis (109.08%), S. epidermidis (36.36%), M. reseus (36.36%), B. lentus (63.63%), and S. aureus (54.54%) respectively. These isolates were further assayed against Escherichia coli, Salmonella typhi, Klebsiella sp. and Staphylococcus aureus. The antibacterial outcome showed that two (2) (40%) anthill isolates exhibited antibacterial activity against three (3) tested bacteria (Escherichia coli, Salmonella typhi and Staphylococcus aureus). This research study has showcased that the production of inhibitory substances are common among some of the bacterial strains isolated from anthills.

scholarly journals Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
W. Mouton ◽  
J. Josse ◽  
C. Jacqueline ◽  
L. Abad ◽  
S. Trouillet-Assant ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Post Infection ◽  
Infection Model ◽  
Dependent Manner ◽  
Differentiation Process ◽  
Osteoblastic Activity ◽  
Bone Parameters ◽  
Early Differentiation

AbstractStaphylococcus aureus is the most frequent aetiology of bone and joint infections (BJI) and can cause relapsing and chronic infections. One of the main factors involved in the chronicization of staphylococcal BJIs is the internalization of S. aureus into osteoblasts, the bone-forming cells. Previous studies have shown that S. aureus triggers an impairment of osteoblasts function that could contribute to bone loss. However, these studies focused mainly on the extracellular effects of S. aureus. Our study aimed at understanding the intracellular effects of S. aureus on the early osteoblast differentiation process. In our in vitro model of osteoblast lineage infection, we first observed that internalized S. aureus 8325-4 (a reference lab strain) significantly impacted RUNX2 and COL1A1 expression compared to its non-internalized counterpart 8325-4∆fnbAB (with deletion of fnbA and fnbB). Then, in a murine model of osteomyelitis, we reported no significant effect for S. aureus 8325-4 and 8325-4∆fnbAB on bone parameters at 7 days post-infection whereas S. aureus 8325-4 significantly decreased trabecular bone thickness at 14 days post-infection compared to 8325-4∆fnbAB. When challenged with two clinical isogenic strains isolated from initial and relapse phase of the same BJI, significant impairments of bone parameters were observed for both initial and relapse strain, without differences between the two strains. Finally, in our in vitro osteoblast infection model, both clinical strains impacted alkaline phosphatase activity whereas the expression of bone differentiation genes was significantly decreased only after infection with the relapse strain. Globally, we highlighted that S. aureus internalization into osteoblasts is responsible for an impairment of the early differentiation in vitro and that S. aureus impaired bone parameters in vivo in a strain-dependent manner.

Exposure to Plant Extract Causes the Variation of Antibiotic Susceptibility of Two Bacterial Strains (Salmonella Serotype Typhi and Staphylococcus aureus)

2018 ◽  
Vol 12 (2) ◽  
pp. 1-14
Author(s):  
Fabrice Ezo’o Mengo ◽  
Stéphanie Claire Tchonang ◽  
Hermann Ludovic Kemaleu ◽  
Sylvain Leroy Sado Kamdem ◽  
Jean Justin Essia Ngang
Keyword(s):  
Staphylococcus Aureus ◽  
Plant Extract ◽  
Antibiotic Susceptibility ◽  
Bacterial Strains ◽  
Salmonella Serotype ◽  
And Staphylococcus Aureus

scholarly journals Subinhibitory Concentrations of Linezolid Reduce Staphylococcus aureus Virulence Factor Expression

2004 ◽  
Vol 48 (2) ◽  
pp. 546-555 ◽  
Author(s):  
Katussevani Bernardo ◽  
Norbert Pakulat ◽  
Silke Fleer ◽  
Annabelle Schnaith ◽  
Olaf Utermöhlen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Polyacrylamide Gel Electrophoresis ◽  
Protein A ◽  
Sodium Dodecyl ◽  
Elongation Factor ◽  
Dependent Manner ◽  
Triacylglycerol Lipase ◽  
Subinhibitory Concentrations ◽  
Dose Dependent

ABSTRACT The influence of the antibiotic linezolid on the secretion of exotoxins by Staphylococcus aureus was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry and Western blot analysis. S. aureus suspensions were treated with grading subinhibitory concentrations of linezolid (12.5, 25, 50, and 90% of MIC) at different stages of bacterial growth (i.e., an optical density at 540 nm [OD540] of 0.05 or 0.8). When added to S. aureus cultures at an OD540 of 0.05, linezolid reduced in a dose-dependent manner the secretion of specific virulence factors, including staphylococcal enterotoxin A (SEA) and SEB, bifunctional autolysin, autolysin, protein A, and alpha- and beta-hemolysins. In contrast, other presumably nontoxic exoproteins remained unchanged or even accumulated in supernatants in the presence of linezolid at a 90% MIC. Similarily, when added at OD540 of 0.8, that is, after quorum sensing, linezolid reduced the release of virulence factors, whereas the relative abundance of nontoxic exoproteins such as triacylglycerol lipase, glycerol ester hydrolase, DnaK, or translation elongation factor EF-Tu was found to be increased. Consistently, linezolid reduced in a dose-dependent manner the tumor necrosis factor-inducing activity secreted by S. aureus into the culture supernatants. The results of our study suggest that the expression of virulence factors in S. aureus is especially sensitive to the inhibition of protein synthesis by linezolid, which should be an advantage in the treatment of infections with toxin-producing S. aureus.

scholarly journals Piperine Plays an Anti-Inflammatory Role inStaphylococcus aureusEndometritis by Inhibiting Activation of NF-κB and MAPK Pathways in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Wen-jun Zhai ◽  
Zhen-biao Zhang ◽  
Nian-nian Xu ◽  
Ying-fang Guo ◽  
Changwei Qiu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Biological Activities ◽  
Dependent Manner ◽  
Pathogenic Microorganisms ◽  
Histopathological Changes ◽  
Natural Medicine ◽  
Anti Inflammatory ◽  
Dose Dependent

Endometritis is commonly caused by pathogenic microorganisms, includingStaphylococcus aureus(S. aureus). Piperine, which is a natural medicine, has shown a variety of biological activities. To explore the effect and mechanism of piperine onS. aureusendometritis, a mouse model ofS. aureusendometritis was successfully established in the present study. Histopathological changes were observed with H&E staining, cytokines were analyzed by ELISA, mRNA was analyzed by qPCR, and proteins were detected by western blot. The results showed that piperine could significantly alleviate inflammatory injury inS. aureusendometritis. The qPCR and ELISA results showed that piperine effectively reduced theS. aureus-induced overexpression of TNF-α, IL-1β, and IL-6 but increased the expression of IL-10. TheS. aureus-induced inflammation was related to TLR-2 and TLR-4 because the results showed that their expression was increased inS. aureusinfection but then decreased with piperine treatment. To further confirm that piperine caused an anti-inflammatory response by targeting NF-κB and MAPKs, the expression of I-κB, p65, p38, ERK, and JNK was measured. The phosphorylation of I-κB, p65, p38, ERK, and JNK was inhibited by piperine in a dose-dependent manner. All of the results indicated that piperine may be a potential anti-inflammatory drug both in endometritis and in otherS. aureus-induced diseases.

scholarly journals Effect of Different Saudi Honey Types Mixed with Natural Substances on Some Bacterial Strains

2017 ◽  
Vol 24 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Fatimah A. Nashawi ◽  
Hani Y. Abdullah ◽  
Nahlaa A. Khalifa ◽  
Ibrahim A. Alzahrani ◽  
Ahmed A. Al-Ghamdi
Keyword(s):  
Staphylococcus Aureus ◽  
Klebsiella Pneumoniae ◽  
Antibacterial Effect ◽  
Synergistic Effects ◽  
Bacterial Species ◽  
Bacterial Strains ◽  
Natural Substances ◽  
Different Types ◽  
And Staphylococcus Aureus ◽  
Natural Honey

To evaluate the antibacterial eff ects of three types of Saudi honey (Feghra, Sider and Natural honey) alone and mixed with ginger or lemon in comparison to Manuka honey as a potential natural antibacterial agent. Saudi honeys were evaluated against five types of bacterial strains; Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae. Chocolate agars were prepared first with different concentrations of each type of honey, and then with specific concentrations either of ginger or lemon added to honey. Bacterial species were inoculated on each agar and incubated at 37oC in a CO2 incubator overnight. Significant differences were found between diff erent types of honey and different concentrations of the same honey on bacterial growth. There are no significant differences and synergistic effects when adding ginger to diff erent honey types. Addition of lemon show significant differences and good synergistic effects against all tested bacterial species except Klebsiella pneumoniae and Staphylococcus aureus at 15 and 20% honey concentration. In conclusion, antibacterial effects of different types of honey are type and concentration dependent. Adding lemon to the different types of honey changes the pH and acidity and increases the honey’s antibacterial effect.

scholarly journals Dynamic Changes of G-CSF etc. Nine Cytokines in Mouse Bloodstream Infection Models of Staphylococcus aureus and Klebsiella pneumoniae and their Clinical Performances

2019 ◽  
Author(s):  
Shang He ◽  
Ming Yang ◽  
Xinjun Li ◽  
Chen Chen ◽  
Ma Yating ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Klebsiella Pneumoniae ◽  
Bacterial Infection ◽  
Bloodstream Infection ◽  
Roc Curve ◽  
Control Group ◽  
Infection Model ◽  
Roc Curve Analysis ◽  
Dynamic Changes ◽  
Infection Models

AbstractBlood culture has been considered as the gold standard to diagnose the bacterial bloodstream infection, but its long turnaround time gravely obstructed the clinical medication by physicians. Cytokines play an important role in bacterial infection. The purpose of this study was to monitor the kinetic changes of nine cytokines in mouse infection models and to infer their diagnostic value in early infection.MethodsThe mouse bloodstream infection model of Staphylococcus aureus and the other model of Staphylococcus aureus and Klebsiella pneumoniae were constructed respectively, and the dynamic changes of nine cytokines were monitored within 48 hours after infected with 1/2 LD50 bacterial concentration. Cytokines with significant differences between the two groups and PBS control group from 0 to 6 hours after infection were selected for theoretical proof in patient sera that were clearly diagnosed as bloodstream infection. Receiver operating characteristic (ROC) curve analysis was conducted to determine the clinical differentiation of different cytokines.ResultsTwo models of S.aureus and K. pneumoniae bloodstream infection in mice were constructed successfully. In the two mouse models, six of the nine cytokines monitored were different (P<0.05) in each experimental group. In the 121 patient sera samples, three cytokines, IL-6, IL-12p70 and G-CSF in the infection groups and control group had showed differences. In particular, AUC of G-CSF was 0.9051, the accuracy is better than IL-6 for diagnosing the infection. In addition, only G-CSF was significantly different between the two infection groups and in the analysis of ROC curve, AUC is equal to 0.735.ConclusionsG-CSF can not only judge the bacterial infection and non-infection, but also distinguish the infection of S.aureus from K. pneumoniae.

scholarly journals Therapeutic efficacy of BO-3482, a novel dithiocarbamate carbapenem, in mice infected with methicillin-resistant Staphylococcus aureus.

1997 ◽  
Vol 41 (10) ◽  
pp. 2278-2281 ◽  
Author(s):  
R Nagano ◽  
K Shibata ◽  
T Naito ◽  
A Fuse ◽  
K Asano ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Therapeutic Efficacy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Infection Model ◽  
Dependent Manner ◽  
Methicillin Resistant ◽  
Mrsa Strains ◽  
Systemic Infections

The in vivo activity of BO-3482, which has a dithiocarbamate chain at the C-2 position of 1beta-methyl-carbapenem, was compared with those of vancomycin and imipenem in murine models of septicemia and thigh infection with methicillin-resistant Staphylococcus aureus (MRSA). Because BO-3482 was more susceptible than imipenem to renal dehydropeptidase I in a kinetic study of hydrolysis by this renal enzyme, the therapeutic efficacy of BO-3482 was determined during coadministration with cilastatin. In the septicemia models, which involved two homogeneous MRSA strains and one heterogeneous MRSA strain, the 50% effective doses were, respectively, 4.80, 6.06, and 0.46 mg/kg of body weight for BO-3482; 5.56, 2.15, and 1.79 mg/kg for vancomycin; and >200, >200, and 15.9 mg/kg for imipenem. BO-3482 was also as effective as vancomycin in an MRSA septicemia model with mice with cyclophosphamide-induced immunosuppression. In the thigh infection model with a homogeneous MRSA strain, the bacterial counts in tissues treated with BO-3482-cilastatin were significantly reduced in a dose-dependent manner compared with the counts in those treated with vancomycin and imipenem-cilastatin (P < 0.001). These results indicate that BO-3482-cilastatin is as effective as vancomycin in murine systemic infections and is more bactericidal than vancomycin in local-tissue infections. The potent in vivo activity of BO-3482-cilastatin against such MRSA infections can be ascribed to the good in vitro anti-MRSA activity and improved pharmacokinetics in mice when BO-3482 is combined with cilastatin and to the bactericidal nature of the carbapenem.

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