scholarly journals The characteristic and potential therapeutic effect of isolated multidrug-resistant Acinetobacter baumannii lytic phage

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Behnam Sisakhtpour ◽  
Arezoo Mirzaei ◽  
Vajihe Karbasizadeh ◽  
Nafiseh Hosseini ◽  
Mehdi Shabani ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Hela Cells ◽  
Bacterial Infections ◽  
Morphological Analysis ◽  
Bacterial Resistance ◽  
Host Cells ◽  
Lytic Phage ◽  
Lytic Bacteriophage ◽  
Drug Resistant ◽  
Bacteriophage Therapy

Abstract Background Widespread misuse of antibiotics caused bacterial resistance increasingly become a serious threat. Bacteriophage therapy promises alternative treatment strategies for combatting drug-resistant bacterial infections. In this study, we isolated and characterized a novel, potent lytic bacteriophage against multi-drug resistant (MDR) Acinetobacter baumannii and described the lytic capability and endolysin activity of the phage to evaluate the potential in phage therapy. Methods A novel phage, pIsf-AB02, was isolated from hospital sewage. The morphological analysis, its host range, growth characteristics, stability under various conditions, genomic restriction pattern were systematically investigated. The protein pattern of the phage was analyzed, and the endolysin activity of the phage was determined under the non-denaturing condition on SDS-PAGE. The optimal lytic titer of phage was assessed by co-culture of the phage with clinical MDR A. baumannii isolates. Finally, HeLa cells were used to examine the safety of the phage. Results The morphological analysis revealed that the pIsf-AB02 phage displays morphology resembling the Myoviridae family. It can quickly destroy 56.3% (27/48) of clinical MDR A. baumannii isolates. This virulent phage could decrease the bacterial host cells (from 108 CFU/ml to 103 CFU/ml) in 30 min. The optimum stability of the phage was observed at 37 °C. pH 7 is the most suitable condition to maintain phage stability. The 15 kDa protein encoded by pIsf-AB02 was detected to have endolysin activity. pIsf-AB02 did not show cytotoxicity to HeLa cells, and it can save HeLa cells from A. baumannii infection. Conclusion In this study, we isolated a novel lytic MDR A. baumannii bacteriophage, pIsf-AB02. This phage showed suitable stability at different temperatures and pHs, and demonstrated potent in vitro endolysin activity. pIsf-AB02 may be a good candidate as a therapeutic agent to control nosocomial infections caused by MDR A. baumannii.

Critically ill patient with multidrug-resistant Acinetobacter baumannii respiratory infection successfully treated with intravenous and nebulized bacteriophage therapy

2021 ◽  
Author(s):  
Sohail Rao ◽  
Monica Betancourt-Garcia ◽  
Yetunde O. Kare-Opaneye ◽  
Brett E. Swiercezewski ◽  
Jason W. Bennett ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acinetobacter Baumannii ◽  
Critically Ill ◽  
Respiratory Infection ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Critically Ill Patient ◽  
Drug Resistant ◽  
Bacteriophage Therapy ◽  
Chronic Comorbidities

Hospitalized patients are at risk of developing serious multi-drug resistant bacterial infections. This risk is heightened in patients who are on mechanical ventilation, are immunocompromised, and/or have chronic comorbidities. We report the case of a 52-year-old critically ill patient with a multidrug resistant Acinetobacter baumannii (MDR-A) respiratory infection who was successfully treated with antibiotics and intravenous and nebulized bacteriophage therapy.

scholarly journals Bacteriophage Therapy for Critical Infections Related to Cardiothoracic Surgery

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 232 ◽  
Author(s):  
Evgenii Rubalskii ◽  
Stefan Ruemke ◽  
Christina Salmoukas ◽  
Erin C. Boyle ◽  
Gregor Warnecke ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Phage Therapy ◽  
Cardiothoracic Surgery ◽  
Drug Resistant ◽  
Bacteriophage Therapy ◽  
Surgical Wounds ◽  
Implanted Medical Devices ◽  
Conventional Antibiotics

(1) Objective: Bacterial resistance to conventional antibiotic therapy is an increasingly significant worldwide challenge to human health. The objective is to evaluate whether bacteriophage therapy could complement or be a viable alternative to conventional antibiotic therapy in critical cases of bacterial infection related to cardiothoracic surgery. (2) Methods: Since September 2015, eight patients with multi-drug resistant or especially recalcitrant Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli infections were treated with bacteriophage preparations as a therapy of last resort according to Article 37 of the Declaration of Helsinki. Patients had infections associated with immunosuppression after organ transplantation or had infections of vascular grafts, implanted medical devices, and surgical wounds. Individualized phage preparations were administered locally, orally, or via inhalation for different durations depending on the case. All patients remained on conventional antibiotics during bacteriophage treatment. (3) Results: Patients ranged in age from 13 to 66 years old (average 48.5 ± 16.7) with seven males and one female. Eradication of target bacteria was reached in seven of eight patients. No severe adverse side effects were observed. (4) Conclusions: Phage therapy can effectively treat bacterial infections related to cardiothoracic surgery when conventional antibiotic therapy fails.

scholarly journals Mechanistic insights into synergy between nalidixic acid and tetracycline against clinical isolates of Acinetobacter baumannii and Escherichia coli

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Nalidixic Acid ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Infection Model ◽  
Drug Resistant ◽  
E Coli

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)

scholarly journals Lytic Myophage Abp53 Encodes Several Proteins Similar to Those Encoded by Host Acinetobacter baumannii and Phage phiKO2

2011 ◽  
Vol 77 (19) ◽  
pp. 6755-6762 ◽  
Author(s):  
Chia-Ni Lee ◽  
Tsai-Tien Tseng ◽  
Juey-Wen Lin ◽  
Yung-Chieh Fu ◽  
Shu-Fen Weng ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Burst Size ◽  
Sputum Sample ◽  
Polyacrylamide Gel Electrophoresis ◽  
Multiple Drug ◽  
Lytic Phage ◽  
Tail Fiber ◽  
Drug Resistant ◽  
Content Type ◽  
Multiple Drug Resistant

ABSTRACTAcinetobacter baumanniiis an important Gram-negative opportunistic pathogen causing nosocomial infections. The emergence of multiple-drug-resistantA. baumanniiisolates has increased in recent years. Directed toward phage therapy, a lytic phage ofA. baumannii, designated Abp53, was isolated from a sputum sample in this study. Abp53 has an isometric head and a contractile tail with tail fibers (belonging toMyoviridae), a latent period of about 10 min, and a burst size of approximately 150 PFU per infected cell. Abp53 could completely lyse 27% of theA. baumanniiisolates tested, which were all multiple drug resistant, but not other bacteria. Mg2+enhanced the adsorption and productivity of, and host lysis by, Abp53. Twenty Abp53 virion proteins were visualized in SDS-polyacrylamide gel electrophoresis, with a 47-kDa protein being the predicted major capsid protein. Abp53 has a double-stranded DNA genome of 95 kb. Sequence analyses of a 10-kb region revealed 8 open reading frames. Five of the encoded proteins, including 3 tail components and 2 hypothetical proteins, were similar to proteins encoded byA. baumanniistrain ACICU. ORF1176 (one of the tail components, 1,176 amino acids [aa]), which is also similar to tail protein gp21 ofKlebsiellaphage phiKO2, contained repeated domains similar to those within the ACICU_02717 protein ofA. baumanniiACICU and gp21. These findings suggest a common ancestry and horizontal gene transfer during evolution. As phages can expand the host range by domain duplication in tail fiber proteins, repeated domains in ORF1176 might have a similar significance in Abp53.

scholarly journals Enhanced Antibacterial Activity of Meropenem against Extensively Drug-Resistant Acinetobacter baumannii by Myrtaceae Plant Extracts

2020 ◽  
Vol 17 (11) ◽  
pp. 1168-1176
Author(s):  
Dennapa SAELOH ◽  
Monton VISUTTHI ◽  
Marisa LEEHA ◽  
Surasak LIMSUWAN ◽  
Supayang Piyawan VORAVUTHIKUNCHAI
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Drug Resistant ◽  
Microdilution Method ◽  
Extensively Drug Resistant ◽  
Resistant Phenotype ◽  
Bacterial Growth Inhibition ◽  
Mic Value

Acinetobacter baumannii (A. baumannii) has been known as a major cause of nosocomial bacterial infections worldwide. The bacteria are increasingly associated with a broad spectrum of antibiotic resistance, and this has become a widespread concern in a variety of hospitals.Antibiotic development and alternative treatment have become priorities for the treatment of bacterial infections.This study investigated the efficacy of meropenem in combination with five ethanolic extracts of plants in Myrtaceae against extensively drug-resistant (XDR) A. baumannii. The resistant phenotype was previously determined by microdilution method. XDR-A. baumannii strains showed resistance to meropenem with the minimum inhibitory concentration (MIC) in a range of 16 - 128 µg/mL, whereas the MIC value of all extracts, including Calistemon lancealatus, Eucalyptus citridora, Rhodomytus tomentasa, Syzygium cumini, and Xanthortemon chrysanthus, was over 1,000 µg/mL. Interestingly, all extracts potentiated the activity of the antibiotic by reducing the MIC values of the antibiotic. Xanthortemon chrysanthus extract displayed excellent synergism against the bacteria by decreasing the MIC value of the drug greater than 8-fold. In addition, the extract, at concentrations of 31.25, 62.5, 125, 250, 500, and 1,000 µg/mL, obviously increased the inhibitory effect of meropenem (1/4´MIC) against A. baumannii. The percentage of bacterial growth inhibition by combination was 87.9, 88.8, 91.8, 93.6, 99.9, and 100, respectively. The results supported that the extract could improve the activity of ineffective antibiotics against drug-resistant pathogens.Therefore, the findings may serve as therapeutic options for XDR-A. baumannii infections in the future.

scholarly journals Characteristic and Potential Therapeutic Effect of Isolated MDR-Acinetobacter Baumannii Lytic Phage

2020 ◽  
Author(s):  
Behnam Sisakhtpour ◽  
Arezoo Mirzaei ◽  
Vajihe Karbasizadeh ◽  
Nafise Sadat Hosseini ◽  
Mehdi Shabani ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Resistance ◽  
Cross Sectional Study ◽  
Resistance Pattern ◽  
Lytic Phage ◽  
Klebsiella Pneumonia ◽  
Cross Sectional ◽  
Coomassie Blue ◽  
Phage Sensitivity ◽  
Multiple Drugs

Abstract Background: Acinetobacter baumannii is a major pathogen in the hospital, especially in Intensive Care Units (ICU) and the resistance to multiple drugs as a major contributor to hospital infection. Bacteriophages are viruses that attack bacteria and kill them that could be used for clinical treatment. The aim of the study is in evaluating the function of bacteriophage specificity of multi-drug resistant Acinetobacter baumannii, to be used as a useful method for treating of Acinetobacter Infections.Methods: Cross-sectional study during the year 2017, from patients admitted to the ICU, First, 48 isolates of Acinetobacter baumannii were identified by phenotypic method and amplified with blaOXA-51 gene. Then, the sensitivity of phages to pathogens namely ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp) evaluated. DNA of the phage was extracted using the Viral Nucleic Extraction Kit II (Geneaid, Taipei, Taiwan) according to the manufacturer's instructions. Then for protein analysis, PEG-precipitated purified phages were subjected directly to SDS-PAGE, and protein bands were visualized by coomassie Blue G-250 staining method. Finally for cell survival assay we investigated the toxicity of the isolated phage to Hela cells.Results: In the bacterial resistance pattern, the highest resistance belongs to ciprofloxacin. In optimal phage test, at dilution of 1 (MOI 1) it produced the best effect on bacteria in 30 minutes. Phage sensitivity to different hosts performed by double layer agar method, the phage was treated with ESKAPE bacteria and after 24 hours’ incubation at 37°C, only for Acinetobacter baumannii Plaque created. The genome analysis indicated that phage pIsf-AB2 has a double-stranded DNA genome. In bacterial control, all cells were killed by A. baumannii, and no live-cell was seen. The cells remained in control of the phage, and the phage did not affect the cells.Conclusion: Our findings support the potential application of the phage with potent endolysin activity against MDR A. baumannii and give useful information for its further study and use.

scholarly journals Treatment of Multi-Drug Resistant Gram-Negative Bacterial Pathogenic Infections

2020 ◽  
Vol 14 (3) ◽  
pp. 1639-1647
Author(s):  
Wardah Mohammad Akram ◽  
Godfred Antony Menezes ◽  
Nida Abbas ◽  
Wasim Ahmad ◽  
Ahmed Mohamed Ahmed
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Empirical Therapy ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Review Management ◽  
Emergence Of Resistance ◽  
Novel Therapeutic

The multidrug-resistant Gram-negative bacteria (MDR-GNB) infections in severely infected patients present numerous difficulties in terms of treatment failure where antibiotics cannot arrest such drug resistant bacteria. Based on the patient’s medical history and updated microbiological epidemiology data, an effective empirical treatment remains critical for optimal results to safeguard human health. The aim of this manuscript is to review management of MDR-Gram negative pathogenic bacterial infections. Quick diagnosis and narrow antimicrobial spectrum require rapid and timely diagnosis and effective laboratories in accordance with antimicrobial stewardship (AS) principles. Worldwide, there is an increased emergence of Carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii. Recently, novel therapeutic options, such as meropenem/vaborbactam, ceftazidime/avibactam, ceftolozane/tazobactam, eravacycline and plazomicin became accessible to effectively counteract severe infections. Optimally using these delays the emergence of resistance to novel therapeutic agents. Further study is required, however, due to uncertainties in pharmacokinetic/pharmacodynamics optimization of dosages and therapeutic duration in severely ill patients. The novel agents should be verified for (i) action on carbapenem resistant Acinetobacter baumannii; (ii) action on CRE of β-lactam/β-lactamase inhibitors dependence on type of carbapenemase; (iii) emergence of resistance to novel antibacterials and dismiss selective pressure promoting development of resistance. Alternative treatments should be approached alike phage therapy or antibacterial peptides. The choice of empirical therapy is complicated by antibiotic resistance and can be combated by accurate antibiotic and their combinations usage, which is critical to patient survival. Noteworthy are local epidemiology, effective teamwork and antibiotic stewardship to guarantee that medications are utilized properly to counter the resistance.

scholarly journals Multidrug-Resistant Acinetobacter baumannii Genetic Characterization and Spread in Lithuania in 2014, 2016, and 2018

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 151
Author(s):  
Tatjana Kirtikliene ◽  
Aistė Mierauskaitė ◽  
Ilona Razmienė ◽  
Nomeda Kuisiene
Keyword(s):  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Essential Information ◽  
Acinetobacter Spp

Bacterial resistance to antimicrobial agents plays an important role in the treatment of bacterial infections in healthcare institutions. The spread of multidrug-resistant bacteria can occur during inter- and intra-hospital transmissions among patients and hospital personnel. For this reason, more studies must be conducted to understand how resistance occurs in bacteria and how it moves between hospitals by comparing data from different years and looking out for any patterns that might emerge. Multidrug-resistant (MDR) Acinetobacter spp. was studied at 14 healthcare institutions in Lithuania during 2014, 2016, and 2018 using samples from human bloodstream infections. In total, 194 isolates were collected and identified using MALDI-TOF and VITEK2 analyzers as Acinetobacter baumannii group bacteria. After that, the isolates were analyzed for the presence of different resistance genes (20 genes were analyzed) and characterized by using the Rep-PCR and MLVA (multiple-locus variable-number tandem repeat analysis) genotyping methods. The results of the study showed the relatedness of the different Acinetobacter spp. isolates and a possible circulation of resistance genes or profiles during the different years of the study. This study provides essential information, such as variability and diversity of resistance genes, genetic profiling, and clustering of isolates, to better understand the antimicrobial resistance patterns of Acinetobacter spp. These results can be used to strengthen the control of multidrug-resistant infections in healthcare institutions and to prevent potential outbreaks of this pathogen in the future.

scholarly journals Antibacterial and Antibiofilm Activity and Mode of Action of Magainin 2 against Drug-Resistant Acinetobacter baumannii

2018 ◽  
Vol 19 (10) ◽  
pp. 3041 ◽  
Author(s):  
Min Kim ◽  
Na Kang ◽  
Su Ko ◽  
Jonggwan Park ◽  
Eunji Park ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
High Stability ◽  
Therapeutic Agents ◽  
Antibiofilm Activity ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Biofilm Inhibition ◽  
Antibiotic Resistant

Antimicrobial peptides (AMPs) are promising therapeutic agents for treating antibiotic-resistant bacterial infections. Previous studies showed that magainin 2 (isolated from African clawed fogs Xenopus laevis) has antimicrobial activity against gram-positive and gram-negative bacteria. The present study was conducted to investigate the antibacterial activity of magainin 2 against Acinetobacter baumannii. Magainin 2 showed excellent antibacterial activity against A. baumannii strains and high stability at physiological salt concentrations. This peptide was not cytotoxic towards HaCaT cells and showed no hemolytic activity. Biofilm inhibition and elimination were significantly induced in all A. baumannii strains exposed to magainin 2. We confirmed the mechanism of magainin 2 on the bacterial outer and inner membranes. Collectively, these results suggest that magainin 2 is an effective antimicrobial and antibiofilm agent against A. baumannii strains.

scholarly journals Effectiveness of a Lytic Phage SRG1 against Vancomycin-ResistantEnterococcus faecalisin Compost and Soil

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sidra Rahmat Ullah ◽  
Saadia Andleeb ◽  
Taskeen Raza ◽  
Muhsin Jamal ◽  
Khalid Mehmood
Keyword(s):  
Soil Sample ◽  
Burst Size ◽  
Alternative Therapy ◽  
Maximum Growth ◽  
Sewage Water ◽  
Infection Process ◽  
Lytic Phage ◽  
Lytic Bacteriophage ◽  
Bacteriophage Therapy ◽  
Tract Infections

Nosocomial infections caused by vancomycin-resistantEnterococcushave become a major problem. Bacteriophage therapy is proposed as a potential alternative therapy. Bacteriophages are viruses that infect bacteria and are ubiquitous in nature. Lytic bacteriophage was isolated from sewage water that infects VREF, the causative agent of endocarditis, bacteraemia, and urinary tract infections (UTIs). The phage produced clear plaques with unique clear morphology and well-defined boundaries. TEM results of phage revealed it to be108±0.2 nm long and90±0.5 nm wide. The characterization of bacteriophage revealed that infection process of phage was calcium and magnesium dependent and phage titers were highest under optimum conditions for VREF, with an optimal temperature range of 37–50°C. The maximum growth was observed at 37°C, hence having 100% viability. The latent period for phage was small with a burst size of 512 viral particles per bacterial cell. The phage was tested against various clinical strains and results proved it to be host specific. It can be used as a potential therapeutic agent for VREF infections. The phage efficiently eradicated VREF inoculated in cattle compost, poultry compost, and a soil sample which makes it a potential agent for clearing compost and soil sample.

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