Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae

Wang, Zijing; Cai, Ruopeng; Wang, Gang; Guo, Zhimin; Liu, Xiao; Yuan, Guohui; Ji, Yalu; Zhang, Hao; Xi, Hengyu; Zhao, Rihong; Bi, Lanting; Liu, Shanshan; Yang, Li; Feng, Xin; Sun, Changjiang; Lei, Liancheng; Wang, Han; Gu, Jingmin

doi:10.3389/fmicb.2021.674068

Cited by 31 publications

(21 citation statements)

References 45 publications

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“…Some of these phages have better therapeutic effects than antibiotics ( Sunagar et al, 2010 ). Recent studies have demonstrated that the combination of phage and antibiotics is more effective than monotherapy in the treatment of bacterial infections ( Oechslin et al, 2017 ; Wang et al, 2021 ). In the synergistic therapy of phages and antibiotics, phage selection pressure can make bacteria sensitive to antibiotics ( Segall et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Characteristics of a Bacteriophage, vB_Kox_ZX8, Isolated From Clinical Klebsiella oxytoca and Its Therapeutic Effect on Mice Bacteremia

Zhang

Yan

et al. 2021

Front. Microbiol.

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Klebsiella oxytoca is an important nosocomial and community-acquired opportunistic pathogenic Klebsiella and has become the second most prevalent strain in the clinic after K. pneumoniae. However, there have been few reports of bacteriophages used for treating K. oxytoca. In this study, a novel bacteriophage, vB_Kox_ZX8, which specifically infects K. oxytoca AD3, was isolated for the first time from human fecal samples. The biological characteristics of vB_Kox_ZX8 showed an incubation period of 10 min, a burst size of 74 PFU/cell, and a stable pH range of 3–11. Genomic bioinformatics studies of vB_Kox_ZX8 showed that it belongs to the genus Przondovirus, subfamily Studiervirinae, family Autographiviridae. The genome of vB_Kox_ZX8 is 39,398 bp in length and contains 46 putative open reading frames encoding functional proteins, such as DNA degradation, packaging, structural, lysin-holin, and hypothetical proteins. We further investigated the efficacy of vB_Kox_ZX8 phage in the treatment of mice with bacteremia caused by K. oxytoca infection. The results showed that vB_Kox_ZX8 (5 × 109 PFU/mouse) injected intraperitoneally alone was metabolized rapidly in BALB/c mice, and no significant side effects were observed in the control and treatment groups. Importantly, intraperitoneal injection with a single dose of phage vB_Kox_ZX8 (5 × 107 PFU/mouse) for 1 h post-infection saved 100% of BALB/c mice from bacteremia induced by intraperitoneal challenge with a minimum lethal dose of K. oxytoca AD3. However, all negative control mice injected with PBS alone died. Owing to its good safety, narrow host infectivity, high lysis efficiency in vitro, and good in vivo therapeutic effect, phage vB_Kox_ZX8 has the potential to be an excellent antibacterial agent for clinical K. oxytoca-caused infections.

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Section: Discussionmentioning

confidence: 99%

Characteristics of a Bacteriophage, vB_Kox_ZX8, Isolated From Clinical Klebsiella oxytoca and Its Therapeutic Effect on Mice Bacteremia

Zhang

Yan

et al. 2021

Front. Microbiol.

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“…However, some concerns regarding phage therapy, such as the emergence of phage-resistant bacteria, have been reported [ 48 ]. This limitation can be overcome by combination treatments [ 49 , 50 ]. Based on our results, the re-growth of MDR A. baumannii after phage vWUPSU treatment was also observed.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Novel Lytic Myoviridae Phage Infecting Multidrug-Resistant Acinetobacter baumannii and Synergistic Antimicrobial Efficacy between Phage and Sacha Inchi Oil

Wintachai

Voravuthikunchai

2022

Pharmaceuticals

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Multidrug-resistant (MDR) strains of Acinetobacter baumannii have become a major cause of hospital-acquired infections, resulting in an increase in morbidity and mortality worldwide. Many alternative treatments, including phage therapy, are attractive approaches for overcoming problems posed by antibiotic resistance. A newly isolated phage, vWUPSU-specific MDR A. baumannii, showed a narrow host range against MDR A. baumannii. This research was conducted to isolate, characterize, and apply the phage with sacha inchi oil as an alternative antimicrobial agent. Genome analysis suggested that phage vWUPSU is a novel phage belonging to the family Myoviridae, order Caudoviridae. This phage prevented biofilm formation and eradicated preformed biofilms in a dose-dependent manner. In addition, a synergistic antimicrobial effect of the interaction between phage vWUPSU and sacha inchi oil on planktonic cells was observed. The combination of phage and sacha inchi oil significantly inhibited and removed biofilms, compared with the effects of either single treatment. The results of this work indicate that phage vWUPSU could potentially be applied to control MDR A. baumannii. The antibacterial and antibiofilm activities of the combination of phage vWUPSU and sacha inchi oil have attracted significant interests in the development of antibacterial phage products as beneficial treatment options.

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“…The research concluded that the best result on the course of infection was in the combined therapy group, where birds were completely protected from the infection [ 83 ]. The other study of synergy of a combined treatment with the K. pneumoniae phage P-KP2 and gentamicin in mice vs. mono-treatments with acute pneumonia caused by K. pneumoniae W-KP2 (K47 serotype) was demonstrated by Wang et al [ 84 ]. Mice were infected intranasally with bacteria and 1 h post-infection were treated intranasally with the phage 1 × 10 9 PFU and 30 min after phage administration gentamicin at dose 1.5 mg/kg was administered.…”

Section: Phages and Antibiotics In Animal Modelsmentioning

confidence: 99%

“…Pneumonia symptoms in mono-treatments were significantly alleviated and the survival rate increased to 70%. That the combined treatment of phages and gentamicin completely rescued infected mice suggests the existence of synergy between the phage and the antibiotic [ 84 ]. The synergisitic effect was also investigated in a neutropenic mouse model of acute lung infection when using ciprofloxacin 0.33 mg/mg and the Pseudomonas phage PEV20 (10 6 PFU/mg) in powder [ 85 ].…”

Section: Phages and Antibiotics In Animal Modelsmentioning

confidence: 99%

Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far

et al. 2022

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Bacteriophages (phages) may be used as an alternative to antibiotic therapy for combating infections caused by multidrug-resistant bacteria. In the last decades, there have been studies concerning the use of phages and antibiotics separately or in combination both in animal models as well as in humans. The phenomenon of phage–antibiotic synergy, in which antibiotics may induce the production of phages by bacterial hosts has been observed. The potential mechanisms of phage and antibiotic synergy was presented in this paper. Studies of a biofilm model showed that a combination of phages with antibiotics may increase removal of bacteria and sequential treatment, consisting of phage administration followed by an antibiotic, was most effective in eliminating biofilms. In vivo studies predominantly show the phenomenon of phage and antibiotic synergy. A few studies also describe antagonism or indifference between phages and antibiotics. Recent papers regarding the application of phages and antibiotics in patients with severe bacterial infections show the effectiveness of simultaneous treatment with both antimicrobials on the clinical outcome.

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Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype Klebsiella pneumoniae

Cited by 31 publications

References 45 publications

Characteristics of a Bacteriophage, vB_Kox_ZX8, Isolated From Clinical Klebsiella oxytoca and Its Therapeutic Effect on Mice Bacteremia

Characteristics of a Bacteriophage, vB_Kox_ZX8, Isolated From Clinical Klebsiella oxytoca and Its Therapeutic Effect on Mice Bacteremia

Characterization of Novel Lytic Myoviridae Phage Infecting Multidrug-Resistant Acinetobacter baumannii and Synergistic Antimicrobial Efficacy between Phage and Sacha Inchi Oil

Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far

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