scholarly journals Synergistic Antibacterial Effects of Meropenem in Combination with Aminoglycosides against Carbapenem-Resistant Escherichia coli Harboring blaNDM-1 and blaNDM-5

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1023
Author(s):  
Pawarisa Terbtothakun ◽  
Ozioma Forstinus Nwabor ◽  
Thanyaluck Siriyong ◽  
Supayang P. Voravuthikunchai ◽  
Sarunyou Chusri
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
Treatment Options ◽  
Molecular Characteristics ◽  
Carbapenem Resistant ◽  
Aminoglycoside Therapy ◽  
Checkerboard Assay ◽  
Almost All ◽  
Time Kill

Infections due to carbapenem-resistant Escherichia coli (CREC) are problematic due to limitation in treatment options. Combination therapies of existing antimicrobial agents have become a reliable strategy to control these infections. In this study, the synergistic effects of meropenem in combination with aminoglycosides were assessed by checkerboard and time-kill assays. Of the 35 isolates, 19 isolates (54.3%) were resistant to carbapenems (imipenem and meropenem) with the MIC ranges from 16 to 128 µg/mL. These isolates were resistant to almost all antibiotic classes. Molecular characteristics revealed co-harboring of carbapenemase (blaNDM-1, blaNDM-5 and blaOXA-48) and extended-spectrum β-lactamases (ESBL) genes (blaCTX-M, blaSHV and blaTEM). The checkerboard assay displayed synergistic effects of meropenem and several aminoglycosides against most CREC isolates. Time-kill assays further demonstrated strong synergistic effects of meropenem in combination with either amikacin, gentamicin, kanamycin, streptomycin, and tobramycin. The results suggested that meropenem in combination with aminoglycoside therapy might be an efficient optional treatment for infections cause by CREC.

In vitro and in vivo synergistic effects of tigecycline combined with aminoglycosides on carbapenem-resistant Klebsiella pneumoniae

2021 ◽  
Author(s):  
Wentao Ni ◽  
Deqing Yang ◽  
Jie Guan ◽  
Wen Xi ◽  
Dexun Zhou ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Synergistic Effects ◽  
Molecular Characteristics ◽  
Synergistic Activity ◽  
Significant Activity ◽  
Clinical Pharmacokinetics ◽  
Carbapenem Resistant ◽  
Time Kill

Abstract Objectives Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections represent severe threats to public health worldwide. The aim of this study was to assess potential synergistic interaction between tigecycline and aminoglycosides via in vitro and in vivo studies. Methods Antibiotic resistance profiles and molecular characteristics of 168 CR-KP clinical isolates were investigated by susceptibility testing, PCR and MLST. Chequerboard tests and time–kill assays were performed for 20 CR-KP isolates to evaluate in vitro synergistic effects of tigecycline combined with aminoglycosides. A tissue-cage infection model of rats was established to evaluate in vivo synergistic effects. Different doses of tigecycline and aminoglycosides alone or in combination were administered for 7 days via tail vein injection. Antibiotic efficacy was evaluated in tissue-cage fluid and emergence of resistance was screened. Results The chequerboard tests showed that this combination displayed synergistic or partial synergistic activity against CR-KP. The time–kill assays further demonstrated that strong synergistic effects of such a combination existed against isolates that were susceptible to both drugs but for resistant isolates no synergy was observed if clinical pharmacokinetics were taken into consideration. The in vivo study showed that the therapeutic effectiveness of combination therapies was better than that of monotherapy for susceptible isolates, suggesting in vivo synergistic effects. Furthermore, combinations of tigecycline with an aminoglycoside showed significant activity in reducing the occurrence of tigecycline-resistant mutants. Conclusions Compared with single drugs, tigecycline combined with aminoglycosides could exert synergistic effects and reduce the emergence of tigecycline resistance. Such a combination might be an effective alternative when treating CR-KP infections in clinical practice.

scholarly journals Molecular Characterization of Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates from Egyptian Patients

2020 ◽  
Author(s):  
Reem M Hassan ◽  
Sherifa T Salem ◽  
Saly Ismail Mostafa Hassan ◽  
Asmaa Sayed Hegab ◽  
Yasmine S Elkholy
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Characterization ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
Common Mechanism ◽  
Carbapenem Resistant ◽  
Egyptian Patients ◽  
Global Threat

AbstractAcinetobacter baumannii (A. baumannii) represents a global threat owing to its ability to resist most of the currently available antimicrobial agents. Moreover, emergence of carbapenem resistant A. baumannii (CR-AB) isolates limits the available treatment options. Enzymatic degradation by variety of ß-lactamases, have been identified as the most common mechanism of carbapenem resistance in A. baumannii. The alarming increase in the prevalence of CR-AB necessitates continuous screening and molecular characterization to appreciate the problem. The present study was performed to assess the prevalence and characterize carbapenemases among 206 CR-AB isolated from various clinical specimens collected from different intensive care units at Kasr Al-Aini Hospital.All isolates were confirmed to be A. baumannii by detection of the blaOXA-51-like gene. Molecular screening of 13 common Ambler class bla carbapenemases genes in addition to insertion sequence (IS-1) upstream OXA-23 was performed by using four sets of multiplex PCR, followed by identification using gene sequencing technology. Among the investigated genes, the prevalence of blaOXA-23, and blaOXA-58 were 77.7%, and 1.9%, respectively. The ISAba1 was detected in 10% of the blaOXA-23 positive isolates. The prevalence of metallo-β-lactamases (MBLs) studied; blaNDM-1, blaSPM, blaVIM, blaSIM-1 were 11.7%, 6.3%, 0.5%, and 0.5% respectively. One of class A; bla KPC was detected in 10.7% of the investigated isolates. blaOXA-24/40, blaIMP, blaGES, blaVEB and blaGIM were not detected in any of the studied isolates. Moreover, 18.4% of the isolates have shown to harbor two or more of the screened bla genes. We concluded that the most prevalent type of ß-lactamases genes among CR-AB isolates collected from Egyptian patients were blaOXA-23 followed by blaNDM-1 and blaKPC.Author summaryCarbapenem-resistant A. baumannii has become a real global health threat. The aim of the present study was to characterize and to assess the prevalence of carbapenemases among 206 CR-AB clinical isolates from Egyptian patients. We concluded that the most prevalent type of ß-lactamases genes among CR-AB isolates collected from Egyptian patients were blaOXA-23 followed by blaNDM-1 and blaKPC. In this study, ISAba1 was detected upstream 10% of blaOXA-23 positive isolates only which indicates that the spread of resistance among Acinetobacter isolates could be either chromosomal or plamid-mediated.

scholarly journals Combination Effects of Cymbopogon sp. Essential Oil on Selected Bacteria

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Nur Aishah Abdul Wahab ◽  
Hairul Shahril Muhamad ◽  
Nabilah Ahmad Alhadi ◽  
Salina Mat Radzi ◽  
Maryam Mohamed Rehan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Bacillus Subtilis ◽  
Essential Oils ◽  
Staphylococcus Epidermidis ◽  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
Combination Effects ◽  
Cymbopogon Flexuosus ◽  
Combination Study

Combination effects between Cymbopogon flexuosus and Cymbopogon nardus essential oils were studied to determine whether the combination could emerge as better and more powerful antimicrobial agents against six selected bacteria includes Bacillus subtilis, Escherichia coli, Salmonella typhimurium, Serratia marcescens, Staphylococcus aureus, and Staphylococcus epidermidis. This combination study exhibited 40.67% additive, 28.67% antagonistic, 16.00% indifferent and 14.66% synergistic effects. C. flexuosus and C. nardus essential oils in combination showed a high inhibitory activity against S. aureus with 16% synergistic, 64% additive and 20% indifferent effects.

scholarly journals Semimechanistic Pharmacokinetic/Pharmacodynamic Modeling of Fosfomycin and Sulbactam Combination against Carbapenem-Resistant Acinetobacter baumannii

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Sazlyna Mohd Sazlly Lim ◽  
Aaron J. Heffernan ◽  
Jason A. Roberts ◽  
Fekade B. Sime
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Pharmacodynamic Modeling ◽  
Synergistic Activity ◽  
Bacterial Burden ◽  
Target Attainment ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Time Kill

ABSTRACT Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are now considered potential treatments for CR-AB. This study aimed to explore the utility of fosfomycin-sulbactam combination (FOS/SUL) therapy against CR-AB isolates. Synergism of FOS/SUL against 50 clinical CR-AB isolates was screened using the checkerboard method. Thereafter, time-kill studies against two CR-AB isolates were performed. The time-kill data were described using a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Monte Carlo simulations were then performed to estimate the probability of stasis, 1-log kill, and 2-log kill after 24 h of combination therapy. The FOS/SUL combination demonstrated a synergistic effect against 74% of isolates. No antagonism was observed. The MIC50 and MIC90 of FOS/SUL were decreased 4- to 8-fold, compared to the monotherapy MIC50 and MIC90. In the time-kill studies, the combination displayed bactericidal activity against both isolates and synergistic activity against one isolate at the highest clinically achievable concentrations. Our PK/PD model was able to describe the interaction between fosfomycin and sulbactam in vitro. Bacterial kill was mainly driven by sulbactam, with fosfomycin augmentation. FOS/SUL regimens that included sulbactam at 4 g every 8 h demonstrated a probability of target attainment of 1-log10 kill at 24 h of ∼69 to 76%, compared to ∼15 to 30% with monotherapy regimens at the highest doses. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that FOS/SUL may potentially be effective against some CR-AB infections.

In vitro activity of antimicrobial agents with and without sulbactam, EDTA and sulbactam-EDTA on ESBLs-producing Escherichia coli isolated from healthy Tibetan yaks

2020 ◽  
Author(s):  
Baoguang Liu ◽  
Xiaoling Yuan ◽  
Yiheng Chen ◽  
Xiaoshen Li ◽  
Ming Bai ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Nasal Swab ◽  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
E Coli ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Third Generation Cephalosporins ◽  
Enhance Activity

Abstract Background The spread of ESBLs-producing bacteria has been strikingly rapid in many regions of the world and it causes therapeutic difficulties in everyday practice. The aims of this study were to investigate the prevalence and susceptibilities of ESBLs-producing Escherichia coli isolates from healthy Tibetan yaks in China, to evaluate the activity of drug combinations on ESBLs-producing E. coli isolates. Methods From July 2018 to August 2019, a total of 750 nasal swab samples were tested for the presence of E. coli and ESBLs-producing strains. The MICs of 11 antimicrobial agents alone and combinations with sulbactam, EDTA or sulbactam-EDTA against 240 ESBLs-producing E.coli strains were determined by the broth microdilution method. Results Overall, 59.87% (n = 449) of the samples were positive for E. coli, 240 (53.45%) of 449 E. coli isolates were confirmed to be ESBLs-producing. The addition of sulbactam to the third generation cephalosporins, amikacin and fosfomycin for all isolates resulted in low MICs, increasing the level of susceptibility from 0, 0 and 0% to 50 ~ 87.5, 4.2 and 100% respectively. The addition of EDTA to fluoroquinolones, doxycycline, florfenicol, amikacin and fosfomycin, showed improved activities and resulted in low MICs, increasing the level of susceptibility from 0, 0, 8.3, 0 and 0% to 4.2 ~ 29.2, 33.3, 33.3, 66.7 and 45.8%, respectively. All other antibacterials (except fluoroquinolones, doxycycline and florfenicol), when combined with sulbactam-EDTA, were found to be more active than combinations only with sulbactam or with EDTA against most of isolates, with lower MIC50s and MIC90s. Conclusion In conclusion, ESBLs-producing E. coli isolates were widespread in healthy Tibetan yaks in China. ESBLs-producing E. coli isolates exhibited varying degrees of multidrug resistance. This study these findings suggested that sulbactam can enhance activity of β-lactams and some non-β-lactams of antimicrobial agents and had a synergistic effects with EDTA in improving activities of some families of antimicrobials.

scholarly journals Nitrofurantoin Combined With Amikacin: A Promising Alternative Strategy for Combating MDR Uropathogenic Escherichia coli

2020 ◽  
Vol 10 ◽  
Author(s):  
Zi-Xing Zhong ◽  
Ze-Hua Cui ◽  
Xiao-Jie Li ◽  
Tian Tang ◽  
Zi-Jian Zheng ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Resistance ◽  
Galleria Mellonella ◽  
Synergistic Effects ◽  
Promising Alternative ◽  
Poor Patient Compliance ◽  
Life Threatening ◽  
Tract Infections ◽  
Time Kill

Urinary tract infections (UTI) are common infections that can be mild to life threatening. However, increased bacterial resistance and poor patient compliance rates have limited the effectiveness of conventional antibiotic therapies. Here, we investigated the relationship between nitrofurantoin and amikacin against 12 clinical MDR uropathogenic Escherichia coli (UPEC) strains both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in all 12 test strains by standard checkerboard and time-kill assays. Importantly, amikacin or nitrofurantoin at half of the clinical doses were not effective in the treatment of UPEC infections in the G. mellonella model but the combination therapy significantly increased G. mellonella survival from infections caused by all 12 study UPEC strains. Taken together, these results demonstrated synergy effects between nitrofurantoin and amikacin against MDR UPEC.

scholarly journals Synergistic Activity of Colistin-Containing Combinations against Colistin-ResistantEnterobacteriaceae

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Thea Brennan-Krohn ◽  
Alejandro Pironti ◽  
James E. Kirby
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Bacterial Outer Membrane ◽  
Time Kill ◽  
Synergistic Combinations

ABSTRACTResistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistantEnterobacteriaceae(CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistantEnterobacteriaceaeisolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.

scholarly journals Synergy of Linezolid with Several Antimicrobial Agents against Linezolid-Methicillin-Resistant Staphylococcal Strains

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 496
Author(s):  
María-José Valderrama ◽  
María Alfaro ◽  
Icíar Rodríguez-Avial ◽  
Elvira Baos ◽  
Carmen Rodríguez-Avial ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
Ribosomal Subunit ◽  
Antagonistic Effect ◽  
Prolonged Treatment ◽  
Synergistic Activity ◽  
Methicillin Resistant ◽  
Resistant Strains ◽  
Time Kill ◽  
Selection Of

Linezolid is a synthetic oxazolydinone active against multi-resistant Gram-positive cocci that inhibits proteins synthesis by interacting with the 50S ribosomal subunit. Although linezolid-resistant strains are infrequent, several outbreaks have been recently described, associated with prolonged treatment with the antibiotic. As an alternative to monotherapy, the combination of different antibiotics is a commonly used option to prevent the selection of resistant strains. In this work, we evaluated combinations of linezolid with classic and new aminoglycosides (amikacin, gentamicin and plazomicin), carbapenems (doripenem, imipenem and meropenem) and fosfomycin on several linezolid- and methicillin-resistant strains of Staphylococcus aureus and S. epidermidis, isolated in a hospital intensive care unit in Madrid, Spain. Using checkerboard and time-kill assays, interesting synergistic effects were encountered for the combination of linezolid with imipenem in all the staphylococcal strains, and for linezolid–doripenem in S.epidermidis isolates. The combination of plazomicin seemed to also have a good synergistic or partially synergistic activity against most of the isolates. None of the combinations assayed showed an antagonistic effect.

scholarly journals Structure-activity relationships of 3-substituted-5,5- diphenylhydantoins as potential antiproliferative and antimicrobial agents

2011 ◽  
Vol 76 (12) ◽  
pp. 1597-1606 ◽  
Author(s):  
Nemanja Trisovic ◽  
Bojan Bozic ◽  
Ana Obradovic ◽  
Olgica Stefanovic ◽  
Snezana Markovic ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Human Colon ◽  
Antibacterial Activities ◽  
E Coli ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Almost All

A series of twelve 3-substituted-5,5-diphenylhydantoins was synthesized, including some whose anticonvulsant activities have already been reported in the literature. Their antiproliferative activities against HCT-116 human colon carcinoma cells were evaluated to determine structure-activity relationships. Almost all of the compounds exhibited statistically significant antiproliferative effects at a concentration of 100 ?M, while the derivative bearing a benzyl group was active even at lower concentrations. Moreover, their in vitro antibacterial activities against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and clinical isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus aureus were evaluated. Only the 3-iso-propyl and 3-benzyl derivatives showed weak antibacterial activities against the Gram-positive bacterium E. faecalis and the Gram-negative bacteria E. coli ATCC 25922 and E. coli.

scholarly journals A novel antimicrobial peptide significantly enhances acid-induced killing of Shiga toxin-producing Escherichia coli O157 and non-O157 serotypes

Microbiology ◽  
2011 ◽  
Vol 157 (6) ◽  
pp. 1768-1775 ◽  
Author(s):  
M. Lino ◽  
J. V. Kus ◽  
S. L. Tran ◽  
Z. Naqvi ◽  
B. Binnington ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Antimicrobial Peptide ◽  
Shiga Toxin ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Survival Rates ◽  
Acid Stress ◽  
Toxin Production ◽  
Risk Of Progression

Shiga toxin-producing Escherichia coli (STEC) colonizes the human intestine, causing haemorrhagic colitis and haemolytic uraemic syndrome (HUS). Treatment options are limited to intravenous fluids in part because sublethal doses of some antibiotics have been shown to stimulate increased toxin release and enhance the risk of progression to HUS. Preventative antimicrobial agents, especially those that build on the natural antimicrobial action of the host defence, may provide a better option. In order to survive the acid stress of gastric passage, STEC is equipped with numerous acid resistance and DNA repair mechanisms. Inhibition of acid-induced DNA repair may offer a strategy to target survival of ingested STEC. We report here that brief pretreatment with a novel antimicrobial peptide, which was previously shown to inhibit bacterial DNA repair, significantly and profoundly reduces survival of acid-stressed O157 : H7 and non-O157 : H7 STEC seropathotypes that are highly associated with HUS. Reduction in survival rates of STEC range from 3 to 5 log. We also show that peptide/acid treatment results in little or no increase in toxin production, thereby reducing the risk of progression to HUS. This study identifies the peptide wrwycr as a potential new candidate for a preventative antimicrobial for STEC infection.

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