Efficacy of Phage-Antibiotic Combinations Against Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates

Qurat-ul-Ain, Hafiza; Ijaz, Muhammad; Siddique, Abu Baker; Muzammil, Saima; Shafique, Muhammad; Rasool, Muhammad Hidayat; Almatroudi, Ahmad; Khurshid, Mohsin; Chaudhry, Tamoor Hamid; Aslam, Bilal

doi:10.5812/jjm.111926

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…This is supported by previous evidence where a study evaluated the therapeutic effect of a newly isolated phage (φNK5) against K. pneumoniae infection in an intragastric mice model and showed the characteristics of potent lytic activity (within 60 min), with a quick absorption rate (5 min) and a short latent period (10 min). Similarly, Qurat-ul-Ain et al (2021) documented phage-cefepime and tetracycline combinations with promising therapeutic effect against MDR K. pneumoniae .…”

Section: Discussionmentioning

confidence: 96%

Re-sensitising XDR biofilms using a combination of bacteriophage cocktails and colistin: a natural approach

Ragupathi

Sethuvel

Gopikrishnan

et al. 2022

Preprint

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Persistent antibiotic use results in the rise of antimicrobial resistance with limited or no choice for multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria. This necessitates a need for alternative therapy to effectively combat clinical pathogens that are resistant to last resort antibiotics. The study investigates hospital sewage as a potential source of bacteriophages to control MDR/XDR bacterial pathogens. 81 samples were screened for phages against selected clinical pathogens. 10 phages were isolated against A. baumannii, 5 phages against K. pneumoniae and 16 phages obtained against P. aeruginosa. The novel phages were observed to be strain-specific with a complete growth inhibition of up to 6 hrs. Phage plus colistin combinations further reduced the MBEC of colistin up to 16 folds. Notably, cocktail of phages exhibited supreme efficacy with complete killing at 0.5-1 μg/ml colistin concentrations. Thus, phages specific to clinical strains has a higher edge in treating nosocomial pathogens with their proven anti-biofilm efficacy. In addition, analysis of phage genomes revealed close phylogenetic relations with phages reported from Europe, China and other neighbouring countries. This study serves as a reference and can be extended to other antibiotics and phage types to assess optimum synergistic combinations to combat various drug resistant pathogens in the ongoing AMR crisis.

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Section: Discussionmentioning

confidence: 96%

Re-sensitising XDR biofilms using a combination of bacteriophage cocktails and colistin: a natural approach

Ragupathi

Sethuvel

Gopikrishnan

et al. 2022

Preprint

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“…Phage therapy has been proven to be the most efficient method to overcome antibiotic resistance. Previously, we have reported the efficacy of phage-antibiotic combination therapy against MDR K. pneumoniae (23). However, this study reports the occurrence of hvKp and the lytic potential of bacteriophage against the isolates that alone demonstrated very promising results and significant lytic and stability patterns.…”

Section: Objectivesmentioning

confidence: 88%

Occurrence of Hypervirulent Klebsiella pneumoniae in Clinical Settings and Lytic Potential of Bacteriophages Against the Isolates

Ahmad

Siddique

Muzammil

et al. 2022

Jundishapur J Microbiol

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Background: Antibiotic resistance is a major health hazard around the globe. Hypervirulent Klebsiella Pneumoniae (hvKp) is associated with hospital-acquired and community-acquired infections. Since there is a lack of new antibiotics against multidrug-resistant (MDR) pathogens, phage therapy might provide an alternative approach to confer antibiotic resistance. Objectives: This study aimed to estimate the occurrence of hvKp and characterize the bacteriophage against the hvKp prevalence in clinical settings, which might be used as an alternative to antibiotics. Methods: Different clinical samples (n = 50) were collected to isolate K. pneumoniae, and the assessment of multidrug resistance was carried out based on the Clinical and Laboratory Standards Institute guidelines (2020). The bacteriophage was isolated from hospital waste, and the double agar overlay method was used for phage purification and propagation. Spot test and one-step curve were performed to determine host-phage interactions. For the evaluation of phage stability in environmental conditions, the phage was incubated at various ranges of temperature, pH, and chloroform. Results: Out of the collected samples, 22 (44%) isolates were confirmed as K. pneumoniae. Among confirmed K. pneumoniae isolates, a total of 11 (50%) isolates were detected as hvKp. Moreover, 14 (64%) isolates were detected as MDR, out of which 5 (35%) isolates were among hvKp phenotypes. Maximum resistance was observed against ampicillin (86%) followed by ceftriaxone (81%) which was the highest among cephalosporins. The isolated bacteriophage showed a broad host range, short latent period, and stability. Overall, 16 isolates (85%) of K. pneumoniae were susceptible to phage infection, among which 12 isolates were MDR (75%); however, all 5 (100%) hvKp isolates were susceptible to phage infection. One-step growth analysis revealed a burst size of 190 phages/host bacterial cells with a short latent period of 24 minutes. Conclusions: Altogether, the significant prevalence of hvKp was estimated in clinical settings, and the isolated bacteriophage showed significant lytic activity as it killed all the hvKp strains. Phage therapy might be exploited and used as a potential alternative therapeutic approach against infections caused by this resistant pathogen.

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“…Additionally, the impact of PhC as an adjunct to antibiotic treatment is an important consideration for future phage therapy studies. Phage-antibiotic synergy has previously been reported and has shown promise in treating bacterial infections, including those caused by K. pneumoniae [42–44].…”

Section: Discussionmentioning

confidence: 99%

Bacteriophage cocktail shows no toxicity and improves the survival ofGalleria mellonellainfected withKlebsiellaspp.

Kelly,

Jameson

2023

Preprint

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Klebsiellaspp. are causative agents of healthcare associated infections in patients who are immunocompromised and use medical devices. The antibiotic resistance crisis has led to an increase in infections caused by these bacteria, which can develop into potentially life-threatening illness if not treated swiftly and effectively. Thus, new treatment options forKlebsiellaare urgently required. Phage therapy can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria infections. The aim of the present study was to produce a safe and effective phage cocktail treatment againstK. pneumoniaeandK. oxytoca, both in liquidin vitroculture and anin vivo Galleria mellonellainfection model. The phage cocktail was significantly more effective at killingK. pneumoniaeandK. oxytocastrains compared with monophage treatments. Preliminary phage cocktail safety was demonstrated through application in thein vivo G. mellonellamodel: where the phage cocktail induced no toxic side effects inG. mellonella. In addition, the phage cocktail significantly improved the survival ofG. mellonellawhen administered as a prophylactic treatment, compared with controls. In conclusion, our phage cocktail was demonstrated to be safe and effective againstKlebsiellaspp. in theG. mellonellainfection model. This provides a strong case for future treatment forKlebsiellainfections, either as an alternative, or adjunct to, antibiotics.

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Efficacy of Phage-Antibiotic Combinations Against Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates

Cited by 7 publications

References 27 publications

Re-sensitising XDR biofilms using a combination of bacteriophage cocktails and colistin: a natural approach

Re-sensitising XDR biofilms using a combination of bacteriophage cocktails and colistin: a natural approach

Occurrence of Hypervirulent Klebsiella pneumoniae in Clinical Settings and Lytic Potential of Bacteriophages Against the Isolates

Bacteriophage cocktail shows no toxicity and improves the survival ofGalleria mellonellainfected withKlebsiellaspp.

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