scholarly journals Multidrug-resistant bacteria as intestinal colonizers and evolution of intestinal colonization in healthy university students in Portugal

2020 ◽  
Author(s):  
Raquel Mota ◽  
Marisa Pinto ◽  
Josman Palmeira ◽  
Daniela Gonçalves ◽  
Helena Ferreira
Keyword(s):  
University Students ◽  
Type Species ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Intestinal Colonization ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Link Type

Multidrug-resistant bacteria have been increasingly described in healthcare institutions, however community resistance also seems to be emerging. Escherichia coli an intestinal commensal bacteria, is also a pathogen and represents an important intestinal reservoir of resistance. Our aim was the study of the intestinal colonization and of the persistence of antibiotic resistant intestinal bacteria in healthy university students of Porto, in the north of Portugal. Samples from 30 university students were collected and analysed. Two E. coli isolates were randomly obtained from each student and Gram-negative bacilli resistant to antibiotics were studied. In addition, we evaluated changes in the Gram-negative intestinal colonization of ten university students in a short period of time. Molecular characterization showed a high presence of bla TEM in commensal E. coli . Gram-negative bacteria with intrinsic and extrinsic resistance were isolated, namely Pseudomonas spp., Enterobacter spp. and Pantoea spp. We isolated three ESBL-producing E. coli from two students. These isolates showed bla CTX-M group 1 (n=1), bla CTX-M group 9 (n=2), bla TEM (n=2), bla SHV (n=1) and tetA (n=2) genes. Additionally, they showed specific virulence factors and conjugational transfer of antibiotic resistance and virulence genes. One Pseudomonas spp. isolate resistant to carbapenems was detected colonizing one student. Our results confirm that healthy young adults may be colonized with commensals showing clinically relevant antibiotic resistance mechanisms, creating a risk of silent spread of these bacteria in the community.

scholarly journals Species Diversity of Environmental GIM-1-Producing Bacteria Collected during a Long-Term Outbreak

2016 ◽  
Vol 82 (12) ◽  
pp. 3605-3610 ◽  
Author(s):  
Andreas F. Wendel ◽  
Sofija Ressina ◽  
Susanne Kolbe-Busch ◽  
Klaus Pfeffer ◽  
Colin R. MacKenzie
Keyword(s):  
Resistance Genes ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Resistant Bacteria ◽  
Environmental Sampling ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Content Type

ABSTRACTReports of outbreaks concerning carbapenemase-producing Gram-negative bacteria in which the main source of transmission is the hospital environment are increasing. This study describes the results of environmental sampling in a protracted polyspecies metallo-beta-lactamase GIM-1 outbreak driven by plasmids and bacterial clones ofEnterobacter cloacaeandPseudomonas aeruginosain a tertiary care center. Environmental sampling targeting wet locations (especially sinks) was carried out on a surgical intensive care unit and on a medical ward on several occasions in 2012 and 2013. We were able to demonstrate 43blaGIM-1-carrying bacteria (mainly nonfermenters but alsoEnterobacteriaceae) that were either related or unrelated to clinical strains in 30 sinks and one hair washbasin. GIM-1 was found in 12 different species, some of which are described here as carriers of GIM-1. Forty out of 43 bacteria displayed resistance to carbapenems and, in addition, to various non-beta-lactam antibiotics. Colistin resistance was observed in twoE. cloacaeisolates with MICs above 256 mg/liter. TheblaGIM-1gene was harbored in 12 different class 1 integrons, some without the typical 3′ end. TheblaGIM-1gene was localized on plasmids in five isolates.In vitroplasmid transfer by conjugation was successful in one isolate. The environment, with putatively multispecies biofilms, seems to be an important biological niche for multidrug-resistant bacteria and resistance genes. Biofilms may serve as a “melting pot” for horizontal gene transfer, for dissemination into new species, and as a reservoir to propagate future hospital outbreaks.IMPORTANCEIn Gram-negative bacteria, resistance to the clinically relevant broad-spectrum carbapenem antibiotics is a major public health concern. Major reservoirs for these resistant organisms are not only the gastrointestinal tracts of animals and humans but also the (hospital) environment. Due to the difficulty in eradicating biofilm formation in the latter, a sustained dissemination of multidrug-resistant bacteria from the environment can occur. In addition, horizontal transfer of resistance genes on mobile genetic elements within biofilms adds to the total “resistance gene pool” in the environment. To gain insight into the transmission pathways of a rare and locally restricted carbapenemases resistance gene (blaGIM-1), we analyzed the genetic background of theblaGIM-1gene in environmental bacteria during a long-term polyspecies outbreak in a German hospital.

scholarly journals Investigation of urban birds as source of β-lactamase-producing Gram-negative bacteria in Marseille city, France

2019 ◽  
Vol 61 (1) ◽  
Author(s):  
Edgarthe Priscilla Ngaiganam ◽  
Isabelle Pagnier ◽  
Wafaa Chaalal ◽  
Thongpan Leangapichart ◽  
Selma Chabou ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Urban Birds ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Stool Samples

Abstract Background We investigate here the presence of multidrug-resistant bacteria isolated from stool samples of yellow-legged gulls and chickens (n = 136) in urban parks and beaches of Marseille, France. Bacterial isolation was performed on selective media, including MacConkey agar with ceftriaxone and LBJMR medium. Antibiotic resistance genes, including extended-spectrum β-lactamases (ESBL) (i.e. blaCTX-M, blaTEM and blaSHV), carbapenemases (blaKPC, blaVIM, blaNDM, blaOXA-23, blaOXA-24, blaOXA-48 and blaOXA-58) and colistin resistance genes (mcr-1 to mcr-5) were screened by real-time PCR and standard PCR and sequenced when found. Results Of the 136 stools samples collected, seven ESBL-producing Gram-negative bacteria (BGN) and 12 colistin-resistant Enterobacteriaceae were isolated. Among them, five ESBL-producing Escherichia coli and eight colistin-resistant Hafnia alvei strains were identified. Four blaTEM-1 genes were detected in yellow-legged gulls and chickens. Three CTX-M-15 genes were detected in yellow-legged gulls and pigeons, and one CTX-M-1 in a yellow-legged gull. No mcr-1 to mcr-5 gene were detected in colistin-resistant isolates. Genotyping of E. coli strains revealed four different sequence types already described in humans and animals and one new sequence type. Conclusions Urban birds, which are believed to have no contact with antibiotics appear as potential source of ESBL genes. Our findings highlight the important role of urban birds in the proliferation of multidrug-resistant bacteria and also the possible zoonotic transmission of such bacteria from wild birds to humans.

Evaluation of the rapid ResaPolymyxin Acinetobacter/Pseudomonas NP test for rapid colistin resistance detection in lactose non-fermenting Gram-negative bacteria

2021 ◽  
Vol 70 (6) ◽  
Author(s):  
Hyunsul Jung ◽  
Johann D. D. Pitout ◽  
Barend C. Mitton ◽  
Kathy-Anne Strydom ◽  
Chanel Kingsburgh ◽  
...  
Keyword(s):  
Type Species ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Major Error ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
Link Type ◽  
Extensively Drug Resistant

Introduction. Colistin is one of the last-resort antibiotics for treating multidrug-resistant (MDR) or extensively drug-resistant (XDR) lactose non-fermenting Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii . Gap Statement. As the rate of colistin resistance is steadily rising, there is a need for rapid and accurate antimicrobial susceptibility testing methods for colistin. The Rapid ResaPolymyxin Acinetobacter / Pseudomonas NP test has recently been developed for rapid detection of colistin resistance in P. aeruginosa and A. baumannii . Aim. The present study aimed to evaluate the performance of the Rapid ResaPolymyxin Acinetobacter / Pseudomonas NP test in comparison with the reference broth microdilution (BMD) method. Methodology. The Rapid ResaPolymyxin Acinetobacter / Pseudomonas NP test was performed using a total of 135 P . aeruginosa (17 colistin-resistant and 118 colistin-susceptible) and 66 A. baumannii isolates (32 colistin-resistant and 34 colistin-susceptible), in comparison with the reference BMD method. Results. The categorical agreement of the Rapid ResaPolymyxin Acinetobacter / Pseudomonas NP test with the reference BMD method was 97.5 % with a major error rate of 0 % (0/152) and a very major error (VME) rate of 10.2 %. The VME rate was higher (23.5 %) when calculated separately for P. aeruginosa isolates. The overall sensitivity and specificity were 89.8 and 100 %, respectively. Conclusion. The Rapid ResaPolymyxin Acinetobacter / Pseudomonas NP test performed better for A. baumannii than for P. aeruginosa .

Leafy greens as a potential source of multidrug-resistant diarrhoeagenic Escherichia coli and Salmonella

Microbiology ◽  
2021 ◽  
Vol 167 (6) ◽  
Author(s):  
Priyanka ◽  
Prem Raj Meena ◽  
Keshav Kumar Meghwanshi ◽  
Anuj Rana ◽  
Arvind Pratap Singh
Keyword(s):  
Escherichia Coli ◽  
Urban Areas ◽  
Type Species ◽  
Multidrug Resistant ◽  
Content Type ◽  
E Coli ◽  
Rural And Urban Areas ◽  
Leafy Greens ◽  
Link Type ◽  
Rural And Urban

A continued rise in leafy green-linked outbreaks of disease caused by pathogenic Escherichia coli or Salmonella , particularly strains exhibiting multidrug resistance (MDR), has emerged as a major threat to human health and food safety worldwide. Thus, the present study was conducted to examine antimicrobial resistance, including MDR, in diarrhoeagenic E. coli (DEC) and Salmonella isolates obtained from leafy greens from rural and urban areas of India. Of the collected samples (830), 14.1 and 6.5% yielded 117 E. coli (40 DEC and 77 non-DEC) and 54 Salmonella isolates, respectively. Among the DEC pathotypes, enteroaggregative E. coli was the most prevalent (10.2 %), followed by enteropathogenic E. coli (9.4 %), enteroinvasive E. coli (7.6 %) and enterohemorrhagic E. coli (6.8 %). Antimicrobial susceptibility testing of all bacterial isolates with respect to drugs categorized as critically or highly important in both human and veterinary medicine revealed moderate to high (30–90%) resistance for amoxicillin/clavulanic acid, ampicillin, gentamycin and colistin, but relatively low resistance (>30 %) for ciprofloxacin, trimethoprim/sulfamethoxazole and fosfomycin. Notably, all DEC and more than 90% non-DEC or Salmonella isolates were found to be multidrug-resistant to drugs of both human and animal importance. Overall, the results of the present study suggest that leafy greens are potential reservoirs or sources of multidrug-resistant DEC and Salmonella strains in the rural or urban areas of India.

scholarly journals A Whole-Cell Screen Identifies Small Bioactives That Synergize with Polymyxin and Exhibit Antimicrobial Activities against Multidrug-Resistant Bacteria

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Shawn M. Zimmerman ◽  
Audrey-Ann J. Lafontaine ◽  
Carmen M. Herrera ◽  
Amanda B. Mclean ◽  
M. Stephen Trent
Keyword(s):  
Bacterial Infections ◽  
Large Scale ◽  
The United States ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Synergistic Activity ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Eskape Pathogens

ABSTRACT The threat of diminished antibiotic discovery has global health care in crisis. In the United States, it is estimated each year that over 2 million bacterial infections are resistant to first-line antibiotic treatments and cost in excess of 20 billion dollars. Many of these cases result from infection with the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which are multidrug-resistant bacteria that often cause community- and hospital-acquired infections in both healthy and immunocompromised patients. Physicians have turned to last-resort antibiotics like polymyxins to tackle these pathogens, and as a consequence, polymyxin resistance has emerged and is spreading. Barring the discovery of new antibiotics, another route to successfully mitigate polymyxin resistance is to identify compounds that can complement the existing arsenal of antibiotics. We recently designed and performed a large-scale robotic screen to identify 43 bioactive compounds that act synergistically with polymyxin B to inhibit the growth of polymyxin-resistant Escherichia coli. Of these 43 compounds, 5 lead compounds were identified and characterized using various Gram-negative bacterial organisms to better assess their synergistic activity with polymyxin. Several of these compounds reduce polymyxin to an MIC of <2 μg/ml against polymyxin-resistant and polymyxin-heteroresistant Gram-negative pathogens. Likewise, four of these compounds exhibit antimicrobial activity against Gram-positive bacteria, one of which rapidly eradicated methicillin-resistant Staphylococcus aureus. We present multiple first-generation (i.e., not yet optimized) compounds that warrant further investigation and optimization, since they can act both synergistically with polymyxin and also as lone antimicrobials for combating ESKAPE pathogens.

scholarly journals Inhibition of Multidrug-Resistant Gram-Positive and Gram-Negative Bacteria by a Photoactivated Porphyrin

2017 ◽  
Vol 66 (4) ◽  
pp. 533-536 ◽  
Author(s):  
Moreno Bondi ◽  
Anna Mazzini ◽  
Simona de Niederhäusern ◽  
Ramona Iseppi ◽  
Patrizia Messi
Keyword(s):  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
In Vitro Antibacterial Activity

The authors studied the in vitro antibacterial activity of the photo-activated porphyrin meso-tri(N-methyl-pyridyl), mono(N-tetradecyl-pyridyl)porphine (C14) against four multidrug-resistant bacteria: Staphylococcus aureus, Enterococcus faecalis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative). Using 10 μg/ml of porphyrin and 60 sec irradiation we observed the remarkable susceptibility of S. aureus and E. faecalis to treatment while, under the same conditions, E. coli and P. aeruginosa showed very low susceptibility. In a later stage, suspensions of Gram-negative bacteria were processed with EDTA before photo-activation, obtaining a significant decrease in viable counts. In view of the results, if the combination of low porphyrin concentrations and short irradiation times will be effective in vivo also, this approach could be a possible alternative to antibiotics, in particular against localized infections due to multidrug-resistant microorganisms.

scholarly journals Exploration of the Pharmacokinetic-Pharmacodynamic Relationships for Fosfomycin Efficacy Using anIn VitroInfection Model

2015 ◽  
Vol 59 (12) ◽  
pp. 7170-7177 ◽  
Author(s):  
Brian D. VanScoy ◽  
Jennifer McCauley ◽  
Evelyn J. Ellis-Grosse ◽  
Olanrewaju O. Okusanya ◽  
Sujata M. Bhavnani ◽  
...  
Keyword(s):  
United States ◽  
The United States ◽  
Multidrug Resistant ◽  
Dose Fractionation ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Content Type ◽  
E Coli ◽  
Drug Concentrations ◽  
Tract Infections

ABSTRACTFosfomycin, a phosphonic class antibiotic with a broad spectrum of antibacterial activity, has been used outside the United States since the early 1970s for the treatment of a variety of infections. In the United States, an oral (tromethamine salt) formulation is used for uncomplicated urinary tract infections. Recently, there has been interest in the use of an intravenous solution (ZTI-01) for the treatment of a broad range of infections associated with multidrug-resistant bacteria. In this era of multidrug-resistant bacteria with few treatment options, it is critical to understand the pharmacokinetic-pharmacodynamic (PK-PD) determinants for fosfomycin efficacy. Since such data are limited, a one-compartmentin vitroinfection model was used to determine the PK-PD index associated with efficacy and the magnitude of this measure necessary for various levels of effect. One challenge isolate (Escherichia coliATCC 25922, for which the fosfomycin agar MIC is 0.5 mg/liter and the broth microdilution MIC is 1 mg/liter) was evaluated in the dose fractionation studies, and two additional clinicalE. coliisolates were evaluated in the dose-ranging studies. Mutation frequency studies indicated the presence of an inherently fosfomycin resistantE. colisubpopulation (agar MIC = 32 to 64 mg/liter) within the standard starting inoculum of a susceptibility test. Due to the presence of this resistant subpopulation, we identified the percentage of the dosing interval that drug concentrations were above the inherent resistance inhibitory concentration found at baseline to be the PK-PD index associated with efficacy (r2= 0.777). The magnitudes of this PK-PD index associated with net bacterial stasis and 1- and 2-log10CFU/ml reductions from baseline at 24 h were 11.9, 20.9, and 32.8, respectively. These data provide useful information for modernizing and optimizing ZTI-01 dosing regimens for further study.

scholarly journals CTX-M-type ESBL-mediated resistance to third-generation cephalosporins and conjugative transfer of resistance in Gram-negative bacteria isolated from hospitals in Tamil Nadu, India

2020 ◽  
Author(s):  
Ramesh Nachimuthu ◽  
Velu Rajesh Kannan ◽  
Bulent Bozdogan ◽  
Vaithilingam Krishnakumar ◽  
Karutha Pandian S ◽  
...  
Keyword(s):  
Type Species ◽  
Tamil Nadu ◽  
Gram Negative Bacteria ◽  
Third Generation ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Link Type ◽  
Third Generation Cephalosporins ◽  
Group 1

Clinical pathogens, especially Gram-negative bacteria developing resistance to third-generation cephalosporins, are making clinical outcomes more complicated and serious. This study was undertaken to evaluate the distribution of CTX-M-type extended-spectrum β-lactamases (ESBLs) in Tamil Nadu, India. For this study, clinical samples were collected from five different hospitals located in Tamil Nadu and the ESBL-producing Gram-negative isolates were characterized. MIC was performed using cefotaxime and ceftazidime. The bla ESBL-producing genes were screened using multiplex PCR for the genes, CTX-M group-1, -2, -8, -9, -26. The conjugation studies were performed using Escherichia coli AB1157 as a recipient for the isolates harbouring plasmid-borne resistance following broth-mating experiment. In total, 1500 samples were collected and 599 Gram-negative bacteria were isolated that included E. coli (n=233), Klebsiella pneumoniae (n=182), Pseudomonas aeruginosa (n=79), Citrobacter spp. (n=30), Proteus mirabilis (n=28), Salmonella spp. (n=21), Acinetobacter baumannii (n=12), Serratia spp. (n=6), Shigella spp. (n=4), Morganella morganii (n=3) and Providencia spp. (n=1). MIC results showed that 358 isolates were resistant to cefotaxime and ceftazidime. Further, ESBL gene-amplification results showed that 19 isolates had CTX-M group-1 gene including E. coli (n=16), K. pneumoniae (n=2) and P. aeruginosa (n=1) whereas one M. morganii isolate had CTX-M group-9, which was plasmid-borne. Through conjugation studies, 12/20 isolates were found to be involved in the transformation of its plasmid-borne resistance gene. Our study highlighted the importance of horizontal gene transfer in the dissemination of plasmid-borne bla CTX-M-type resistance genes among the clinical isolates.

Antimicrobial resistance genes and genetic characteristics of multidrug-resistant Escherichia coli in a veterinary hospital in Taiwan

2021 ◽  
Vol 70 (11) ◽  
Author(s):  
Lii-Tzu Wu ◽  
Xin-Xia Wu ◽  
Se-Chin Ke ◽  
Yi-Pei Lin ◽  
Ying-Chen Wu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Type Species ◽  
Multidrug Resistant ◽  
Content Type ◽  
E Coli ◽  
Link Type ◽  
Antimicrobial Resistance Genes ◽  
Veterinary Hospital

Introduction. Antimicrobial resistance associated with animal hosts is easily transmitted to humans either by direct contact with resistant organisms or by transferring resistance genes into human pathogens. Gap statement. There are limited studies on antimicrobial resistance genes and genetic elements of multidrug-resistant (MDR) Escherichia coli in veterinary hospitals in Taiwan. Aim. The aim of this study was to investigate antimicrobial resistance genes in multidrug-resistant Escherichia coli from animals. Methodology. Between January 2014 and August 2015, 95 multidrug-resistant Escherichia coli isolates were obtained from pigs (n=66), avians (n=18), and other animals (n=11) in a veterinary hospital in Taiwan. Susceptibility testing to 24 antimicrobial agents of 14 antimicrobial classes was performed. Antimicrobial resistance genes, integrons, and insertion sequences were analysed by polymerase chain reaction and nucleotide sequencing. Pulsed-field gel electrophoresis (PFGE), and multi-locus sequence typing were used to explore the clonal relatedness of the study isolates. Results. Different antimicrobial resistance genes found in these isolates were associated with resistance to β-lactams, tetracycline, phenicols, sulfonamides, and aminoglycosides. Fifty-five of 95 E. coli isolates (55/95, 57.9 %) were not susceptible to extended-spectrum cephalosporins, and bla CTX-M-55 (11/55, 20.0 %) and bla CMY-2 (40/55, 72.7 %) were the most common extended-spectrum β-lactamase (ESBL) and AmpC genes, respectively. Both bla CTX-M and bla CMY-2 were present on conjugative plasmids that contained the insertion sequence ISEcp1 upstream of the bla genes. Plasmid-mediated FOX-3 β-lactamase-producing E. coli was first identified in Taiwan. Forty isolates (40/95, 42 %) with class 1 integrons showed seven resistance phenotypes. Genotyping of 95 E. coli isolates revealed 91 different XbaI pulsotypes and 52 different sequence types. PFGE analysis revealed no clonal outbreaks in our study isolates. Conclusion. This study showed a high diversity of antimicrobial resistance genes and genotypes among MDR E. coli isolated from diseased livestock in Taiwan. To our knowledge, this is the first report of plasmid-mediated ESBL in FOX-3 β-lactamase-producing E. coli isolates in Taiwan. MDR E. coli isolates from animal origins may contaminate the environment, resulting in public health concerns, indicating that MDR isolates from animals need to be continuously investigated.

scholarly journals In vitro activity of antimicrobial peptide CDP-B11 alone and in combination with colistin against colistin-resistant and multidrug-resistant Escherichia coli

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaitlin S. Witherell ◽  
Jason Price ◽  
Ashok D. Bandaranayake ◽  
James Olson ◽  
Douglas R. Call
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Membrane Integrity ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
E Coli ◽  
Minimal Media

AbstractMultidrug-resistant bacteria are a growing global concern, and with increasingly prevalent resistance to last line antibiotics such as colistin, it is imperative that alternative treatment options are identified. Herein we investigated the mechanism of action of a novel antimicrobial peptide (CDP-B11) and its effectiveness against multidrug-resistant bacteria including Escherichia coli #0346, which harbors multiple antibiotic-resistance genes, including mobilized colistin resistance gene (mcr-1). Bacterial membrane potential and membrane integrity assays, measured by flow cytometry, were used to test membrane disruption. Bacterial growth inhibition assays and time to kill assays measured the effectiveness of CDP-B11 alone and in combination with colistin against E. coli #0346 and other bacteria. Hemolysis assays were used to quantify the hemolytic effects of CDP-B11 alone and in combination with colistin. Findings show CDP-B11 disrupts the outer membrane of E. coli #0346. CDP-B11 with colistin inhibits the growth of E. coli #0346 at ≥ 10× lower colistin concentrations compared to colistin alone in Mueller–Hinton media and M9 media. Growth is significantly inhibited in other clinically relevant strains, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In rich media and minimal media, the drug combination kills bacteria at a lower colistin concentration (1.25 μg/mL) compared to colistin alone (2.5 μg/mL). In minimal media, the combination is bactericidal with killing accelerated by up to 2 h compared to colistin alone. Importantly, no significant red blood hemolysis is evident for CDP-B11 alone or in combination with colistin. The characteristics of CDP-B11 presented here indicate that it can be used as a potential monotherapy or as combination therapy with colistin for the treatment of multidrug-resistant infections, including colistin-resistant infections.

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