scholarly journals Characterization and Sequencing of a Novel Phage Abp95 Against Multi-genotypes of Carbapenem-resistant Acinetobacter Baumannii

2021 ◽  
Author(s):  
Li Huang ◽  
Siyi Huang ◽  
Lingli Jiang ◽  
Jingjie Tan ◽  
Xueping Yan ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Host Range ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Lytic Phage ◽  
Carbapenem Resistant ◽  
Wide Host Range ◽  
A Genome ◽  
Tract Infections

Abstract Acinetobacter baumannii has become a challenging conditional pathogen. A. baumannii can lead to different infections, such as wound or urinary tract infections and pneumonia. As an alternative strategy for antibiotic-resistant A. baumannii infections, phage therapy had been used and approved by several governments. Previously we had reported two potential phage therapy candidates named Abp1 and Abp9. In this study, a wide host range lytic phage Abp95 were isolated and sequenced. The biological characteristics of Abp95 are also stuied. Abp95 belongs to the myoviridae family, containing a G+C content of 38.07% with a genome of 43,176 bp. Abp95 genome encodes 77 hypothetical genes, without any known virulence genes. With a diabetic wound infection model, Abp95 could accelerate wound healing though clearing local infections of multidrug-resistant A. baumannii. In conclusion, wide host range lytic phage Abp95 shows the potential as phage therapy candidate against multi-genotypes of Carbapenem-Resistant Acinetobacter baumannii.

scholarly journals Preclinical Assessment of Bacteriophage Therapy against Experimental Acinetobacter baumannii Lung Infection

Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 33
Author(s):  
Sandra-Maria Wienhold ◽  
Markus C. Brack ◽  
Geraldine Nouailles ◽  
Gopinath Krishnamoorthy ◽  
Imke H. E. Korf ◽  
...  
Keyword(s):  
Single Dose ◽  
Acinetobacter Baumannii ◽  
Human Lung ◽  
Lung Infection ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Lytic Phage ◽  
Bacterial Burden ◽  
Bacteriophage Therapy ◽  
Cellular Recruitment

Respiratory infections caused by multidrug-resistant Acinetobacter baumannii are difficult to treat and associated with high mortality among critically ill hospitalized patients. Bacteriophages (phages) eliminate pathogens with high host specificity and efficacy. However, the lack of appropriate preclinical experimental models hampers the progress of clinical development of phages as therapeutic agents. Therefore, we tested the efficacy of a purified lytic phage, vB_AbaM_Acibel004, against multidrug-resistant A. baumannii clinical isolate RUH 2037 infection in immunocompetent mice and a human lung tissue model. Sham- and A. baumannii-infected mice received a single-dose of phage or buffer via intratracheal aerosolization. Group-specific differences in bacterial burden, immune and clinical responses were compared. Phage-treated mice not only recovered faster from infection-associated hypothermia but also had lower pulmonary bacterial burden, lower lung permeability, and cytokine release. Histopathological examination revealed less inflammation with unaffected inflammatory cellular recruitment. No phage-specific adverse events were noted. Additionally, the bactericidal effect of the purified phage on A. baumannii was confirmed after single-dose treatment in an ex vivo human lung infection model. Taken together, our data suggest that the investigated phage has significant potential to treat multidrug-resistant A. baumannii infections and further support the development of appropriate methods for preclinical evaluation of antibacterial efficacy of phages.

scholarly journals Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 627
Author(s):  
Sławomir Letkiewicz ◽  
Marzanna Łusiak-Szelachowska ◽  
Ryszard Międzybrodzki ◽  
Maciej Żaczek ◽  
Beata Weber-Dąbrowska ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Serum Antibody ◽  
Multidrug Resistant ◽  
Antibody Responses ◽  
Urogenital Infections ◽  
Reliable Model ◽  
Tract Infections ◽  
Antibody Levels

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.

scholarly journals Combating Carbapenem-ResistantAcinetobacter baumanniiby an Optimized Imipenem-plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Cornelia B. Landersdorfer ◽  
Rajbharan Yadav ◽  
Kate E. Rogers ◽  
Tae Hwan Kim ◽  
Beom Soo Shin ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Acinetobacter Baumannii ◽  
Hollow Fiber ◽  
Dosage Regimen ◽  
Infection Model ◽  
Bacterial Killing ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACTWe aimed to prospectively validate an optimized combination dosage regimen against a clinical carbapenem-resistantAcinetobacter baumannii(CRAB) isolate (imipenem MIC, 32 mg/liter; tobramycin MIC, 2 mg/liter). Imipenem at constant concentrations (7.6, 13.4, and 23.3 mg/liter, reflecting a range of clearances) was simulated in a 7-day hollow-fiber infection model (inoculum, ∼107.2CFU/ml) with and without tobramycin (7 mg/kg q24h, 0.5-h infusions). While monotherapies achieved no killing or failed by 24 h, this rationally optimized combination achieved >5 log10bacterial killing and suppressed resistance.

scholarly journals 694. In vitro Antibacterial Activity of Sulbactam–Durlobactam (ETX2514SUL) Against 121 Recent Acinetobacter baumannii Isolated from Patients in India

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S314-S314
Author(s):  
Alita Miller ◽  
Sarah McLeod ◽  
Tarun Mathur ◽  
Ian Morrissey
Keyword(s):  
Antibacterial Activity ◽  
Acinetobacter Baumannii ◽  
Package Insert ◽  
Multidrug Resistant ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
In Vitro Antibacterial Activity ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

Abstract Background The incidence of infections caused by multidrug-resistant Acinetobacter baumannii is increasing at an alarming rate in Southeast Asia and other parts of the world. Sulbactam (SUL) has intrinsic antibacterial activity against A. baumannii; however, the prevalence of β-lactamases in this species has limited its therapeutic use. Durlobactam (ETX2514, DUR) is a novel β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C and D β-lactamases. DUR restores SUL in vitro activity against multidrug-resistant A. baumannii. Against >3,600 globally diverse, clinical isolates from 2012–2017, addition of 4 mg/L DUR reduced the SUL MIC90 from >32 to 2 mg/L. SUL-DUR is currently in Phase 3 clinical development for the treatment of infections caused by carbapenem-resistant Acinetobacter spp.The goal of this study was to determine the activity of SUL-DUR and comparator antibiotics (amikacin (AMK), ampicillin-sulbactam (AMP-SUL), cefoperazone-sulbactam (CFP-SUL) and meropenem (MEM)) against A. baumannii isolated from hospitalized patients in India. Methods A total of 121 clinical A. baumannii isolates from multiple hospital settings and infection sources were collected between 2016–2019 from six geographically diverse hospitals in India. Species identification was performed by MALDI-TOF. Susceptibility of these isolates to SUL-DUR (10µg/10µg) and comparator antibiotics was determined by disk diffusion using CLSI methodology and interpretive criteria, except for CFP-SUL, for which resistance was defined using breakpoints from the CFP-SUL package insert. Results As shown in Table 1, resistance of this collection of isolates to marketed agents was extremely high. In contrast, based on preliminary breakpoint criteria, only 11.5% of isolates were resistant to SUL-DUR. Conclusion The in vitro antibacterial activity of SUL-DUR was significantly more potent than comparator agents against multidrug-resistant A. baumannii isolates collected from diverse sites in India. These data support the continued development of SUL-DUR for the treatment of antibiotic-resistant infections caused by A. baumannii. Disclosures All authors: No reported disclosures.

scholarly journals Pilot Ex Vivo and In Vitro Evaluation of a Novel Foley Catheter with Antimicrobial Periurethral Irrigation for Prevention of Extraluminal Biofilm Colonization Leading to Catheter-Associated Urinary Tract Infections (CAUTIs)

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Nylev Vargas-Cruz ◽  
Joel Rosenblatt ◽  
Ruth A Reitzel ◽  
Anne-Marie Chaftari ◽  
Ray Hachem ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Foley Catheter ◽  
Irrigation Treatment ◽  
Multidrug Resistant ◽  
Indwelling Catheter ◽  
Carbapenem Resistant ◽  
Colonization Model ◽  
Tract Infections

CAUTI remains a serious healthcare issue for incontinent patients whose urine drainage is managed by catheters. A novel double-balloon Foley catheter was developed which was capable of irrigating the extraluminal catheter surfaces within the periurethral space between the urethral-bladder junction and meatus. The catheter has a retention cuff that is inflated to secure the catheter in the bladder and a novel irrigation cuff proximal to the urethral-bladder junction capable of providing periurethral irrigation from the urethral-bladder junction to the meatus. Uniform periurethral irrigation was demonstrated in an ex vivo porcine model by adding a dye to the antimicrobial urethral irrigation solution. An in vitro biofilm colonization model was adapted to study the ability of periurethral irrigation with a newly developed antimicrobial combination consisting of polygalacturonic acid + caprylic acid (PG + CAP) to prevent axial colonization of the extraluminal urethral indwelling catheter shaft by common uropathogens. The extraluminal surface of control catheters that were not irrigated formed biofilms along the entire axial urethral tract after 24 hours. Significant (p<0.001) inhibition of colonization was seen against multidrug-resistant Pseudomonas aeruginosa (PA), carbapenem-resistant Escherichia coli (EC), and carbapenem-resistant Klebsiella pneumoniae (KB). For other common uropathogens including Candida albicans (CA), Proteus mirabilis (PR), and Enterococcus faecalis (EF), a first irrigation treatment completely inhibited colonization of half of the indwelling catheter closest to the bladder and a second treatment largely disinfected the remaining intraurethral portion of the catheter towards the meatus. The novel Foley catheter and PG + CAP antimicrobial irrigant prevented biofilm colonization in an in vitro CAUTI model and merits further testing in an in vivo CAUTI prevention model.

scholarly journals Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the Murine Neutropenic Thigh Model

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Anthony D. Kang ◽  
Kenneth P. Smith ◽  
Anders H. Berg ◽  
Katherine A. Truelson ◽  
George M. Eliopoulos ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Maximum Concentration ◽  
Area Under The Curve ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Gram Negative ◽  
Content Type ◽  
Model Treatment

ABSTRACT Apramycin, an aminocyclitol aminoglycoside, was rapidly bactericidal against Acinetobacter baumannii . In a neutropenic murine thigh infection model, treatment-associated A. baumannii CFU reductions of >4 log 10 per thigh were observed for all exposures for which area under the curve (AUC)/MIC ratio was >50 and maximum concentration of drug in serum ( C max )/MIC was ≈10 or higher. Based on these findings, we suggest that apramycin deserves further preclinical exploration as a repurposed therapeutic for multidrug-resistant Gram-negative pathogens, including A. baumannii .

scholarly journals Phenotypic and genotypic characterization of multidrug-resistant isolates from patients with catheter-associated urinary tract infection in a tertiary care hospital

2019 ◽  
Vol 11 (03) ◽  
pp. 206-211
Author(s):  
Jaison Jayakaran ◽  
Nirupa Soundararajan ◽  
Priyadarshini Shanmugam
Keyword(s):  
Urinary Tract ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Care Hospital ◽  
Disk Diffusion Method ◽  
Carbapenem Resistant ◽  
Tract Infections

Abstract INTRODUCTION: Urinary tract infections (UTIs) remain as the most common infection. Catheter-associated (CA) UTI can lead to bacteremia and thereby is the leading cause of morbidity and mortality in hospitalized patients in our country. AIMS AND OBJECTIVES: This study aims to check the prevalence of CAUTI and study the phenotypic and genotypic characters of the multidrug-resistant organisms in a tertiary care hospital, with special reference to NDM-1 and OXA-23. MATERIALS AND METHODS: A total of 231 urine samples from patients with CA-UTI in different wards in a tertiary care hospital over a period of 3 months between June and August 2018 were collected and processed following the standard protocol. Antibiotic susceptibility tests were performed by disk-diffusion method. Modified Hodge test (MHT) was done to isolate carbapenem-resistant isolates, and polymerase chain reaction was done to detect NDM-1 and OXA-23. RESULTS: Out of 231 samples, 101 samples yielded significant growth. These 38 samples were Gram-negative bacilli which were resistant to carbapenems. Out of the 38 which showed carbapenem resistance, 23 were MHT positive. Out of the 23 MHT-positive isolates, 8 (21.05%) were positive for NDM-1 gene and only 1 (2.6%) was positive for the OXA-23 gene. CONCLUSION: This study has shown that carbapenem-resistant isolates from all the CA urinary tract-infected patients were 52.77% and most of them were Klebsiella. About 21% of them harbored the NDM-1 gene whereas only 2% had the OXA-23 gene. There has been an alarming increase in the spread of carbapenem resistance.

scholarly journals Tigecycline susceptibility of multidrug-resistant Acinetobacter baumannii from intensive care units in the western Balkans

2020 ◽  
Vol 67 (3) ◽  
pp. 176-181
Author(s):  
Ina Gajic ◽  
Lazar Ranin ◽  
Dusan Kekic ◽  
Natasa Opavski ◽  
Aleksandra Smitran ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Inappropriate Therapy ◽  
Antibiotic Susceptibility Testing ◽  
Broth Microdilution ◽  
Western Balkans ◽  
Colistin Resistance ◽  
European Committee ◽  
Carbapenem Resistant

AbstractTigecycline can be effective to treat infections of carbapenem-resistant Acinetobacter baumannii (CRAB) however, no interpretive criteria have been approved so far. The objectives of this study were to evaluate the proportion of CRAB isolates and to compare gradient test with a broth microdilution (BMD) method for tigecycline susceptibility testing of A. baumannii.This study included 349 multidrug-resistant (MDR) Acinetobacter spp. collected from Serbia, Montenegro, Bosnia and Herzegovina in 2016 and 2017. Antibiotic susceptibility testing was performed by disk diffusion, VITEK2, gradient, ComASP Colistin. Tigecycline susceptibilities were interpreted according to breakpoints of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA).Majority of the tested isolates were CRAB (92.8%). Tigecycline MIC50/MIC90 values were 4/8 μg/mL by BMD and 0.5/4 μg/mL by gradient test. Essential agreement for BMD and gradient test amounted to 65.1%. With EUCAST breakpoints, categorical agreement (CA) was achieved in 38% isolates. Major discordance (MD-false susceptibility/resistance) and minor discordance (mD-false categorization involving intermediate results) were observed in 10% and 57% A. baumannii, respectively. With FDA breakpoints, CA, MD and mD were observed in 44%, 16% and 47% isolates, respectively. Colistin resistance was 2.1%.The study highlights a high proportion of CRAB and several discordances between BMD and gradient test which may lead to inappropriate therapy.

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