scholarly journals Potentiation of antimicrobial activity of colistin with antibiotics of different groups against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa

2020 ◽  
Vol 22 (2) ◽  
pp. 128-136
Author(s):  
Dmitry V. Tapalskiy ◽  
T.A. Petrovskaya ◽  
A.I. Kozlova ◽  
Mikhail V. Edelstein
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Bactericidal Activity ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Potentiation Effect ◽  
Resistant Strains ◽  
Drug Resistant Strains

Objective. To reveal antibiotics being capable of potentiating the antimicrobial activity of colistin against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. Materials and Methods. The minimum inhibitory concentrations (MIC) of colistin alone and in combination with fixed concentrations of antibiotics of different groups were determined for 272 multidrug- and extensively drug-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa. Bactericidal activity of colistin, carbapenems, clarithromycin and their combinations were also determined at fixed PK/PD breakpoint concentrations of antibiotics. Results. Potentiation of colistin antibacterial activity in the presence of fixed concentration of rifampicin (0.5 mg/L) was observed as a 4–16-fold MIC decrease for K. pneumoniae and A. baumannii. In the presence of fixed concentrations of azithromycin (2 mg/L) or clarithromycin (1 mg/L), the colistin MICs decreased 64–512 times for K. pneumoniae, 4–32 times for A. baumannii, 16–64 times for P. aeruginosa. Two- or more-fold reduction of MIC of colistin in the presence of 1 mg/L clarithromycin was observed for 85.2% of K. pneumoniae, 86.3% of A. baumannii and 60.2% of P. aeruginosa strains. In the presence of 1 mg/L clarithromycin and 8 mg/L meropenem, the potentiation effect was enhanced and was observed for an even larger percent of isolates: 96.1% K. pneumoniae, 98.0% A. baumannii and 61.3% P. aeruginosa. Colistin-based combinations with clarithromycin-meropenem and clarithromycin-doripenem were bactericidal against most isolates of A. baumannii and P. aeruginosa (91.4–100%), and against colistin-sensitive K. pneumoniae (95.3%) and colistin-resistant K. pneumoniae (79.1%). Conclusions. The ability of macrolides to significantly potentiate the colistin antimicrobial activity against both colistin-sensitive and colistin-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa was shown. This potentiation effect was enhanced in the presence of carbapenems. The most potent bactericidal activity was revealed with dual and triple combinations of colistin-clarithromycin and colistinclarithromycin-carbapenems.

scholarly journals In vitro and in vivo efficacy of the combination of colistin and endolysins against clinical strains of Multi-Drug Resistant (MDR) pathogens

2019 ◽  
Author(s):  
L. Blasco ◽  
A. Ambroa ◽  
R. Trastoy ◽  
E. Perez-Nadales ◽  
F. Fernández-Cuenca ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Bactericidal Activity ◽  
Pathogenic Bacteria ◽  
Galleria Mellonella ◽  
Clinical Strain

ABSTRACTThe multidrug resistance (MDR) among pathogenic bacteria is jeopardizing the worth of antimicrobials, which had previously changed medical sciences. In this study, we used bioinformatic tools to identify the endolysins ElyA1 and ElyA2 (GH108-PG3 family) present in the genome of bacteriophages Ab1051Φ and Ab1052Φ, respectively. The muralytic activity of these endolysins over MDR clinical isolates (Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae) was tested using the turbidity reduction assay. The minimal inhibitory concentrations (MICs) of endolysin, colistin and their combination were determined using the microdilution checkerboard method. The antimicrobial activity of the combinations was confirmed by time kill curves and in vivo assays in larvae of Galleria mellonella. Our results showed that ElyA1 displayed activity against all 25 strains of A. baumannii and P. aeruginosa tested and against 13 out of 17 strains of K. pneumoniae. No activity was detected when assays were done with endolysin ElyA2. The combined antimicrobial activity of colistin and endolysin ElyA1 yielded a reduction in the colistin MIC for all strains studied, except K. pneumoniae. These results were confirmed in vivo in G. mellonella survival assays. In conclusion, the combination of colistin with new endolysins such as ElyA1 could increase the bactericidal activity and reduce the MIC of the antibiotic, thus also reducing the associated toxicity.IMPORTANCEThe development of multiresistance by pathogen bacteria increases the necessity of the development of new antimicrobial strategies. In this work, we combined the effect of the colistin with a new endolysin, ElyA1, from a bacteriophage present in the clinical strain of Acinetobacter baumannii Ab105. ElyA1 is a lysozyme-like family (GH108-GP3), whose antimicrobial activity was described for first time in this work. Also, another endolysin, ElyA2, with the same origin and family, was characterized but in this case no activity was detected. ElyA1 presented lytic activity over a broad spectrum of strains from A. baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. When colistin was combined with ElyA1 an increase of the antimicrobial activity was observed with a reduced concentration of colistin, and this observation was also confirmed in vivo in Galleria mellonella larvae. The combination of colistin with new endolysins as ElyA1 could increase the bactericidal activity and lowering the MIC of the antibiotic, thus also reducing the associated toxicity.

scholarly journals Successful Treatment of Postneurosurgical Ventriculitis Caused by Extensively Drug-resistant Acinetobacter baumannii in a Child: Case Report

2022 ◽  
Vol 14 (2) ◽  
Author(s):  
Rui Yang ◽  
Fang Li ◽  
Wei Wei Mao ◽  
Xin Wei ◽  
Xinzhu Liu ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Intraventricular Hemorrhage ◽  
Therapeutic Option ◽  
Polymyxin B ◽  
External Ventricular Drainage ◽  
Drug Resistant ◽  
Ventricular Drainage ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

Introduction: The incidence of postneurosurgical Acinetobacter baumannii ventriculitis/meningitis, primarily due to drug-resistant strains, has increased considerably in recent years. However, limited therapeutic options are available because most antibiotics poorly penetrate the blood-brain barrier, especially in pediatric patients. Case Presentation: A five-year-old boy developed ventriculitis due to extensively drug-resistant A. baumannii (XDRAB) after bilateral frontal external ventricular drainage for spontaneous intraventricular hemorrhage. The boy was safely and successfully treated with intraventricular (IVT)/intrathecal (ITH) polymyxin B together with intravenous tigecycline plus cefoperazone/sulbactam. Conclusions: In the present case, postneurosurgical XDRAB ventriculitis was closely associated with intraventricular hemorrhage and the placement of external ventricular drainage. IVT/ITH polymyxin B combined with intravenous tigecycline and cefoperazone sulbactam could be a therapeutic option against XDRAB ventriculitis in children.

scholarly journals The Biology and Role of Interleukin-32 in Tuberculosis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wu Li ◽  
Wanyan Deng ◽  
Jianping Xie
Keyword(s):  
Multidrug Resistant ◽  
Drug Resistant ◽  
Host Molecule ◽  
Tuberculosis Control ◽  
Promising Alternative ◽  
Extensively Drug Resistant ◽  
Important Host ◽  
Resistant Strains ◽  
Drug Resistant Strains

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of morbidity and mortality globally, with nearly 10.4 million new cases of incidence and over 1.7 million deaths annually. Drug-resistant M. tuberculosis strains, especially multidrug-resistant or extensively drug-resistant strains, have further intensified the problem associated with tuberculosis control. Host-directed therapy is a promising alternative for tuberculosis control. IL-32 is increasingly recognized as an important host molecule against tuberculosis. In this review, we highlight the proinflammatory properties of IL-32 and the mode of action of IL-32 in mycobacterial infections to inspire the development of novel immunity-based countermeasures and host-directed therapies against tuberculosis.

scholarly journals Clinical characteristics of patients with pneumonia caused by Klebsiella pneumoniae in Taiwan and prevalence of antimicrobial-resistant and hypervirulent strains: a retrospective study

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Chih-Han Juan ◽  
Shih-Yu Fang ◽  
Chia-Hsin Chou ◽  
Tsung-Ying Tsai ◽  
Yi-Tsung Lin
Keyword(s):  
Retrospective Study ◽  
Klebsiella Pneumoniae ◽  
Clinical Characteristics ◽  
Community Acquired Pneumonia ◽  
Drug Resistant ◽  
Hospital Acquired Pneumonia ◽  
Resistant Strains ◽  
Healthcare Associated ◽  
Drug Resistant Strains ◽  
Hospital Acquired

Abstract Background We aimed to compare the clinical characteristics of patients with community-acquired pneumonia (CAP), healthcare-associated pneumonia (HCAP), and hospital-acquired pneumonia (HAP) caused by Klebsiella pneumoniae and analyze the antimicrobial resistance and proportion of hypervirluent strains of the microbial isolates. Methods We conducted a retrospective study on patients with pneumonia caused by K. pneumoniae at the Taipei Veterans General Hospital in Taiwan between January 2014 and December 2016. To analyze the clinical characteristics of these patients, data was extracted from their medical records. K. pneumoniae strains were subjected to antimicrobial susceptibility testing, capsular genotyping and detection of the rmpA and rmpA2 genes to identify hypervirulent strains. Results We identified 276 patients with pneumonia caused by K. pneumoniae, of which 68 (24.6%), 74 (26.8%), and 134 (48.6%) presented with CAP, HCAP, and HAP, respectively. The 28-day mortality was highest in the HAP group (39.6%), followed by the HCAP (29.7%) and CAP (27.9%) groups. The HAP group also featured the highest proportion of multi-drug resistant strains (49.3%), followed by the HCAP (36.5%) and CAP groups (10.3%), while the CAP group had the highest proportion of hypervirulent strains (79.4%), followed by the HCAP (55.4%) and HAP groups (41.0%). Conclusion Pneumonia caused by K. pneumoniae was associated with a high mortality. Importantly, multi-drug resistant strains were also detected in patients with CAP. Hypervirulent strains were prevalent in all 3 groups of pneumonia patients, even in those with HAP.

scholarly journals Draft Genome Sequences of Two Extensively Drug-Resistant Strains ofMycobacterium tuberculosisBelonging to the Euro-American S Lineage

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Lesibana A. Malinga ◽  
Thomas Abeel ◽  
Christopher A. Desjardins ◽  
Talent C. Dlamini ◽  
Gail Cassell ◽  
...  
Keyword(s):  
Draft Genome ◽  
Drug Efflux ◽  
Drug Resistant ◽  
Nucleotide Polymorphisms ◽  
Genome Sequences ◽  
Single Nucleotide ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

We report the whole-genome sequencing of two extensively drug-resistant tuberculosis strains belonging to the Euro-American S lineage. The RSA 114 strain showed single-nucleotide polymorphisms predicted to have drug efflux activity.

scholarly journals In Vitro Activity and MIC of Sitafloxacin against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis Isolated in Thailand

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Manoon Leechawengwongs ◽  
Therdsak Prammananan ◽  
Sarinya Jaitrong ◽  
Pamaree Billamas ◽  
Nampueng Makhao ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Concentration ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT New fluoroquinolones (FQs) have been shown to be more active against drug-resistant Mycobacterium tuberculosis strains than early FQs, such as ofloxacin. Sitafloxacin (STFX) is a new fluoroquinolone with in vitro activity against a broad range of bacteria, including M. tuberculosis. This study aimed to determine the in vitro activity of STFX against all groups of drug-resistant strains, including multidrug-resistant M. tuberculosis (MDR M. tuberculosis), MDR M. tuberculosis with quinolone resistance (pre-XDR), and extensively drug-resistant (XDR) strains. A total of 374 drug-resistant M. tuberculosis strains were tested for drug susceptibility by the conventional proportion method, and 95 strains were randomly submitted for MIC determination using the microplate alamarBlue assay (MABA). The results revealed that all the drug-resistant strains were susceptible to STFX at a critical concentration of 2 μg/ml. Determination of the MIC90s of the strains showed different MIC levels; MDR M. tuberculosis strains had a MIC90 of 0.0625 μg/ml, whereas pre-XDR and XDR M. tuberculosis strains had identical MIC90s of 0.5 μg/ml. Common mutations within the quinolone resistance-determining region (QRDR) of gyrA and/or gyrB did not confer resistance to STFX, except that double mutations of GyrA at Ala90Val and Asp94Ala were found in strains with a MIC of 1.0 μg/ml. The results indicated that STFX had potent in vitro activity against all the groups of drug-resistant M. tuberculosis strains and should be considered a new repurposed drug for treatment of multidrug-resistant and extensively drug-resistant TB.

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