scholarly journals Therapeutic potential of bacteriophage in treating Klebsiella pneumoniae B5055-mediated lobar pneumonia in mice

2008 ◽  
Vol 57 (12) ◽  
pp. 1508-1513 ◽  
Author(s):  
Sanjay Chhibber ◽  
Sandeep Kaur ◽  
Seema Kumari

Klebsiella pneumoniae causes infections in humans especially in immunocompromised patients. About 80 % of nosocomial infections caused by K. pneumoniae are due to multidrug-resistant strains. The emergence of antibiotic-resistant bacterial strains necessitates the exploration of alternative antibacterial therapies, which led our group to study the ability of bacterial viruses (known as bacteriophages or simply phages) to treat mice challenged with K. pneumoniae. Phage SS specific for K. pneumoniae B5055 was isolated and characterized, and its potential as a therapeutic agent was evaluated in an experimental model of K. pneumoniae-mediated lobar pneumonia in mice. Mice were challenged by intranasal (i.n.) inoculation with bacteria (108 c.f.u. ml−1). A single intraperitoneal injection of 1010 p.f.u. ml−1 phage administered immediately after i.n. challenge was sufficient to rescue 100 % of animals from K. pneumoniae-mediated respiratory infections. Administration of the phage preparation 3 h prior to i.n. bacterial challenge provided significant protection in infected mice, while even 6 h delay of phage administration after the induction of infection rendered the phage treatment ineffective. The results of this study therefore suggest that the timing of starting the phage therapy after initiation of infection significantly contributes towards the success of the treatment.

2019 ◽  
Vol 9 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Yousif Abdullah AlBany ◽  
Mohammad Ismail Al-Berfkani ◽  
Mahde Saleh Assaf

Klebsiella pneumoniae causes infection in human, especially in immunocompromised patients. About 80% of nosocomial infection caused by K. pneumoniae is due to multidrug-resistant strain. The emergence of antibiotic-resistant bacterial strains necessitates the exploration of alternative antibacterial therapies, which led to studying the ability of viruses that infect the bacteria (known as bacteriophage) to treat infection with K. pneumoniae. Bacterial biofilm which are crucial in the pathogenesis of much clinically important infection and are difficult to eradicate because they exist resistant to many antimicrobial treatment. Biofilm formation by K. pneumoniae is responsible for the catheter associated infection such as urinary tract infection and respiratory tract infection due to the colonization of the polymeric surface by forming multilayered cell cluster embedded in extracellular materials. In this study K. pneumoniae isolated from the hospital environment and characterized it and form the biofilm of that organism by microplate quantitative assay. Similarly bacteriophage specific for K. pneumoniae isolated from river water. The aim of work is the use of bacteriophage as a possible alternative for the treatment of bacterial infection of K. pneumoniae. We showed that biofilm is reduced by isolated phages by the comparative account of colony-forming unit versus plaque-forming unit. The result of this study, therefore, suggests that the timing of starting the phage therapy after initiation of infection significantly contributes toward the success of the treatment.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S782-S782
Author(s):  
Sailaja Puttagunta ◽  
Maya Kahan-Haanum ◽  
Sharon Kredo-Russo ◽  
Eyal Weinstock ◽  
Efrat Khabra ◽  
...  

Abstract Background The prevalence of extended-spectrum beta-lactamase (ESBL) producing and carbapenem resistant (CR) Klebsiella pneumoniae (KP) has significantly risen in all geographic regions. Infections due to these bacteria are associated with high mortality across different infection types. Even with newer options, there remains an unmet need for safe and effective therapeutic options to treat infections caused by ESBL and CR KP. Phage therapy offers a novel approach with an unprecedented and orthogonal mechanism of action for treatment of diseases caused by pathogenic bacterial strains that are insufficiently addressed by available antibiotics. Phage-based therapies confer a high strain-level specificity and have a strong intrinsic safety profile. Here we describe the identification of novel phages that can effectively target antibiotic resistant KP strains. Host range of the 21 phages on 33 strain KP panel via solid culture infectivity assays. Red marks resistance to infection while sensitivity to phage is marked in green Methods KP clinical strains were isolated from human stool specimens preserved in glycerol. Selective culturing was carried, followed by testing of individual colonies for motility, indole and urease production, sequenced and analyzed by Kleborate tool to determine antibiotic resistant genes. Natural phages were isolated from plaques that developed on susceptible bacterial targets, sequenced and characterized. Results Antibiotic-resistant KP strains encoding beta lactamase genes or a carbapenemase (n=33) were isolated from healthy individuals (n=3), and patients with inflammatory bowel disease (n=26) or primary sclerosing cholangitis (n=3). Isolates sequencing revealed bla CTX-M15 and/or bla SHV encoding strains and carbapenamase KPC-2. A panel of 21 phages targeting the beta-lactamase- and carbapenemase-producing KP strains were identified. Phage sequencing revealed that all phages belong to the Caudovirales order and include 6 Siphoviridae, 14 Myoviridae, and 1 Podoviridae. In vitro lytic activity of the phages was tested on the isolated bacteria and revealed a coverage of 70% of the 33 isolated antibiotic resistant strains, >50% of which were targeted by multiple phages. Conclusion Collectively, these results demonstrate the feasibility of identifying phage with potent activity against antibiotic resistant KP strains, and may provide a novel therapeutic approach for treatment of ESBL and CR KP infections. Disclosures All Authors: No reported disclosures


mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Roberto Adamo ◽  
Immaculada Margarit

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.


2019 ◽  
Vol 8 (19) ◽  
Author(s):  
Katherine T. Nguyen ◽  
Rachele Bonasera ◽  
Garret Benson ◽  
Adriana C. Hernandez-Morales ◽  
Jason J. Gill ◽  
...  

May is a newly isolated myophage that infects multidrug-resistant strains of Klebsiella pneumoniae, a pathogen that is associated with antibiotic-resistant infections in humans. The genome of May has been shown to be similar to that of phage Vi01.


Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 175 ◽  
Author(s):  
Szaleniec ◽  
Gibała ◽  
Pobiega ◽  
Parasion ◽  
Składzień ◽  
...  

The chronically inflamed mucosa in patients with chronic rhinosinusitis (CRS) can additionally be infected by bacteria, which results in an acute exacerbation of the disease (AECRS). Currently, AECRS is universally treated with antibiotics following the guidelines for acute bacterial rhinosinusitis (ABRS), as our understanding of its microbiology is insufficient to establish specific treatment recommendations. Unfortunately, antibiotics frequently fail to control the symptoms of AECRS due to biofilm formation, disruption of the natural microbiota, and arising antibiotic resistance. These issues can potentially be addressed by phage therapy. In this study, the endoscopically-guided cultures were postoperatively obtained from 50 patients in order to explore the microbiology of AECRS, evaluate options for antibiotic treatment, and, most importantly, assess a possibility of efficient phage therapy. Staphylococcus aureus and coagulase-negative staphylococci were the most frequently isolated bacteria, followed by Haemophilus influenzae, Pseudomonas aeruginosa, and Enterobacteriaceae. Alarmingly, mechanisms of antibiotic resistance were detected in the isolates from 46% of the patients. Bacteria not sensitive to amoxicillin were carried by 28% of the patients. The lowest rates of resistance were noted for fluoroquinolones and aminoglycosides. Fortunately, 60% of the patients carried bacterial strains that were sensitive to bacteriophages from the Biophage Pharma collection and 81% of the antibiotic-resistant strains turned out to be sensitive to bacteriophages. The results showed that microbiology of AECRS is distinct from ABRS and amoxicillin should not be the antibiotic of first choice. Currently available bacteriophages could be used instead of antibiotics or as an adjunct to antibiotics in the majority of patients with AECRS.


Author(s):  
Logan Gildea ◽  
Joseph Ayariga ◽  
James Abugri ◽  
Robert Villafane

The emergence of multidrug-resistant bacterial strains, especially in the clinical setting, has renewed interest in alternative treatment methods. The utilization of prokaryotic viruses in phage therapy has demonstrated potential as a novel treatment method against multidrug-resistant bacterial infections. As the post-antibiotic era quickly approaches, the development and standardization of phage therapy is critically relevant to public health. This review serves to highlight the development of phage therapy against methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacterial strain responsible for severe clinical infections.


2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
B. Aditi Priyadarshini ◽  
Krishnan Mahalakshmi ◽  
Venkatesan Naveen Kumar

Background. Fluoroquinolone-resistant Klebsiella pneumoniae poses a therapeutic challenge when implicated in urinary tract infections, pyelonephritis, pneumonia, skin infections, osteomyelitis, and respiratory infections. The mutant prevention concentration (MPC) represents a concentration threshold above which increase of resistant mutants occurs rarely. The aim of the present study is to determine the MPC among ciprofloxacin-resistant K. pneumoniae clinical isolates. Materials and Methods. A total of 240 clinical isolates of K. pneumoniae were collected from a tertiary care hospital. The MPCs were determined for 24 selected strains using an inoculum of 1010 CFU/ml in Müller–Hinton agar plates with serial/various concentrations (0.003–100 μg) of ciprofloxacin. In addition to the MPC, phenotypic screening for ESBL, AmpC, and carbapenemase was performed. The detection of qnr genes for 24 isolates and DNA sequencing for six isolates were performed. Results. Ciprofloxacin resistance was observed in 19.6% of the K. pneumoniae clinical isolates. Among the ciprofloxacin-resistant isolates, 14 isolates showed an MPC value of more than 100 μg. The MPC ranged between 100 μg and 20 μg for ciprofloxacin-resistant isolates. ESBL producers and qnr gene-producing strains had a high MPC. 11 isolates showed the presence of either qnrB or qnrS genes. None of the samples showed the presence of the qnrA gene. Conclusion. From our study, we infer that ESBL producers and qnr gene-possessing strains are frequently resistant to ciprofloxacin. Estimation of the MPC in the case of multidrug-resistant isolates in the clinical setup may help in treating these drug-resistant strains.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Nagaveni Shivshetty ◽  
Rajeshwari Hosamani ◽  
Liyakat Ahmed ◽  
Ajay Kumar Oli ◽  
Syed Sannauallah ◽  
...  

The emergence of antibiotic-resistant bacterial strains has become a global crisis and is vulnerable for the exploration of alternative antibacterial therapies. The present study emphasizes the use of bacteriophage for the treatment of multidrug resistantP. aeruginosa.P. aeruginosawas used to induce septicemia in streptozotocin (STZ) induced diabetic and nondiabetic mice by intraperitoneal (i.p.) injection of 3 × 108 CFU, resulting in a fatal bacteremia within 48 hrs. A single i.p. injection of 3 × 109 PFU phage GNCP showed efficient protection in both diabetic (90%) and nondiabetic (100%) bacteremic mice. It was further noted that the protection rate was reduced in diabetic mice when phage GNCP was administered after 4 h and 6 h of lethal bacterial challenge. In contrast, nondiabetic bacteremic mice were rescued even when treatment was delayed up to 20 h after lethal bacterial challenge. Evaluation of results confirmed that a single intraperitoneal injection of the phage dose (3 × 109 PFU/mL) was more effective than the multiple doses of imipenem. These results uphold the efficacy of phage therapy against perniciousP. aeruginosainfections, especially in cases of immunocompromised host.


2021 ◽  
Vol 1 (30) ◽  
pp. 57-60
Author(s):  
I. N. Protasova ◽  
N. V. Bakhareva ◽  
N. A. Ilyenkova ◽  
E. S. Sokolovskaya ◽  
T. A. Elistratova ◽  
...  

Purpose. To investigate the serotype distribution, clonal structure and antimicrobial resistance of pneumococci isolated from schoolchildren.Materials and methods. During the period from 2012 to 2018 we examined 498 healthy school children aged 6 to 17 years. Oropharyngeal swab was taken from each child for culture, after that all S. pneumoniae strains were genotyped for serotype and ST-type deduction (PCR and sequencing, respectively). Antimicrobial resistance was also determined.Results. Pneumococcal culture was positive in 10.6 % of children. S. pneumoniae isolates belonged to seven serogroups and seven serotypes. Serogroup 6 and serotype 19F strains (15.1% each), and serogroup 9 strains (13.2%) were the most prevalent. S. pneumoniae33FA/37 and 3 (9.4 and 5.7%), serogroups 15 and 18 (7.6 and 5.7%), and 10A serotype (3.8%) were determined at a lower frequency. 20 detected ST-types belonged to 14 clonal complexes (CCs); CC156, CC447, and CC320 were predominant. 1.9% of isolates were penicillin-resistant; 13.2% – macrolide-, clindamycin-, and tetracycline-resistant. S. pneumoniae antibiotic resistant strains belonged to multidrug-resistant CCs 320, 315, and 156.Conclusion. S. pneumoniae prevalence in school children is not high. Pneumococcal population is characterized by serotype and clonal diversity including ‘invasive’ serotypes and genotypes. Most of strains are susceptible to antimicrobials.


2021 ◽  
Vol 13 ◽  
Author(s):  
Meron Moges Tsegaye ◽  
Garima Chouhan ◽  
Molla Fentie ◽  
Priya Tyagi ◽  
Parma Nand

Background: The recent treatment challenges posed by the widespread emergence of pathogenic Multidrug‐Resistant (MDR) bacterial strains are a cause of huge health troubles worldwide. Infections caused by MDR organisms are associated with longer period of hospitalization, increased mortality, and inflated healthcare costs. Staphylococcus aureus is one of these MDR organisms identified as an urgent threat to human health by the World Health Organization. Infections caused by S. aureus may range from simple cutaneous infestations to life threatening bacteremia. S. aureus infections get easily escalated in severely ill, hospitalized and or immunocompromised patients with incapacitated immune system. Also, in HIV-positive patients S. aureus ranks amongst one of the most common comorbidities where it can further worsen a patient’s health condition. At present anti-staphylococcal therapy is reliant typically on chemotherapeutics that are gathering resistance and pose unfavorable side-effects. Thus, newer drugs are required that can bridge these shortcomings and aid effective control against S. aureus. Objective: In this review, we summarize drug resistance exhibited by S. aureus and lacunae in current anti-staphylococcal therapy, nanoparticles as an alternative therapeutic modality. The focus lays on various green synthesized nanoparticles, their mode of action and application as potent antibacterial compounds against S. aureus. Conclusion: Use of nanoparticles as anti-bacterial drugs has gained momentum in recent past and green synthesized nanoparticles, which involves microorganisms and plants or their byproducts for synthesis of nanoparticles offer a potent, as well as environment friendly solution in warfare against MDR bacte.


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