Antimicrobial resistance is leading to increased mortality, posing risk to those with chronic suppurative lung disease (CSLD). One therapeutic option may be to target treatment-resistant bacteria using viruses (bacteriophages [phages]). Currently, patients receiving phage therapy on compassionate grounds may not be receiving optimal treatment as there is no defined approach for phage use. This review aims to explore administration route, regimen, and need for supplementary antibiotics in phage therapy to treat bacterial infection in CSLD. Twelve articles totaling 18 participants included details of numerous phage administration routes with varying regimens. All articles reported an initial reduction of bacterial load or an improvement in patient symptoms, highlighting the potential of phage therapy in CSLD. Fifteen out of 18 used supplementary antibiotics. Standardized protocols informed by high-quality research are necessary to ensure safe and effective phage therapy. In the interim, systematic recording of information within case reports may be useful.
MurrayCJ, IkutaKS, ShararaF, et al.Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet, 2022; 399(10325):629–655; doi: 10.1016/S0140-6736(21)02724-0
3.
GoeminnePC, HernandezF, DielR, et al.The economic burden of bronchiectasis—Known and unknown: A systematic review. BMC Pulm Med, 2019; 19(1):54; doi: 10.1186/s12890-019-0818-6
4.
PlackettB. Why big pharma has abandoned antibiotics. Nature, 2020; 586(7830):S50–S52; doi: 10.1038/d41586-020-02884-3
5.
SharmaS, ChatterjeeS, DattaS, et al.Bacteriophages and its applications: An overview. Folia Microbiol (Praha), 2017; 62(1):17–55; doi: 10.1007/s12223-016-0471-x
6.
UyttebroekS, ChenB, OnseaJ, et al.Safety and efficacy of phage therapy in difficult-to-treat infections: A systematic review. Lancet Infect Dis, 2022; 22(8):e208–e220; doi: 10.1016/S1473-3099(21)00612-5
7.
StaceyHJ, De SoirS, JonesJD. The safety and efficacy of phage therapy: A systematic review of clinical and safety trials. Antibiotics, 2022; 11(10):1340; doi: 10.3390/antibiotics11101340
8.
GurneyJ, PradierL, GriffinJS, et al.Phage steering of antibiotic-resistance evolution in the bacterial pathogen, Pseudomonas aeruginosa. Evol Med Public Health, 2020; 2020(1):148–157; doi: 10.1093/emph/eoaa026
9.
BurmeisterAR, TurnerPE. Trading-off and trading-up in the world of bacteria–phage evolution. Curr Biol, 2020; 30(19):R1120–R1124; doi: 10.1016/j.cub.2020.07.036
10.
SuhGA, LodiseTP, TammaPD, et al.Considerations for the use of phage therapy in clinical practice. Antimicrob Agents Chemother, 2022; 66(3):e02071-21; doi: 10.1128/aac.02071-21
11.
WuN, DaiJ, GuoM, et al.Pre-optimized phage therapy on secondary Acinetobacter baumannii infection in four critical COVID-19 patients. Emerg Microbes Infect, 2021; 10(1):612–618; doi: 10.1080/22221751.2021.1902754
12.
ZaldastanishviliE, LeshkasheliL, DadianiM, et al.Phage therapy experience at the Eliava Phage Therapy Center: Three cases of bacterial persistence. Viruses, 2021; 13(10):1901; doi: 10.3390/v13101901
13.
HoyleN, ZhvaniyaP, BalarjishviliN, et al.Phage therapy against Achromobacter xylosoxidans lung infection in a patient with cystic fibrosis: A case report. Res Microbiol, 2018; 169(9):540–542; doi: 10.1016/j.resmic.2018.05.001
14.
LebeauxD, MerabishviliM, CaudronE, et al.A case of phage therapy against pandrug-resistant Achromobacter xylosoxidans in a 12-year-old lung-transplanted cystic fibrosis patient. Viruses, 2021; 13(1):60; doi: 10.3390/v13010060
15.
TanX, ChenH, ZhangM, et al.Clinical experience of personalized phage therapy against carbapenem-resistant Acinetobacter baumannii lung infection in a patient with chronic obstructive pulmonary disease. Front Cell Infect Microbiol, 2021; 11:631585; doi: 10.3389/fcimb.2021.631585
16.
LawN, LoganC, YungG, et al.Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient. Infection, 2019; 47(4):665–668; doi: 10.1007/s15010-019-01319-0
17.
AslamS, CourtwrightAM, KovalC, et al.Early clinical experience of bacteriophage therapy in three lung transplant recipients. Am J Transplant, 2019; 19(9):2631–2639; doi: 10.1111/ajt.15503
18.
KvachadzeL, BalarjishviliN, MeskhiT, et al.Evaluation of lytic activity of staphylococcal bacteriophage Sb-1 against freshly isolated clinical pathogens. Microb Biotechnol, 2011; 4(5):643–650; doi: 10.1111/j.1751-7915.2011.00259.x
19.
MaddocksS, FabijanAP, HoJ, et al.Bacteriophage therapy of ventilator-associated pneumonia and empyema caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med, 2019; 200(9):1179–1181; doi: 10.1164/rccm.201904-0839LE
20.
DedrickRM, Guerrero-BustamanteCA, GarlenaRA, et al.Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat Med, 2019; 25(5):730–733; doi: 10.1038/s41591-019-0437-z
21.
DedrickRM, FreemanKG, NguyenJA, et al.Potent antibody-mediated neutralization limits bacteriophage treatment of a pulmonary Mycobacterium abscessus infection. Nat Med, 2021; 27(8):1357–1361; doi: 10.1038/s41591-021-01403-9
22.
GaineyAB, BurchA-K, BrownsteinMJ, et al.Combining bacteriophages with cefiderocol and meropenem/vaborbactam to treat a pan-drug resistant Achromobacter species infection in a pediatric cystic fibrosis patient. Pediatr Pulmonol, 2020; 55(11):2990–2994; doi: 10.1002/ppul.24945
23.
CronlyJA, DuffAJ, RiekertKA, et al.Health-related quality of life in adolescents and adults with cystic fibrosis: Physical and mental health predictors. Respir Care, 2019; 64(4):406–415; doi: 10.4187/respcare.06356
24.
KeoghRH, TannerK, SimmondsNJ, et al.The changing demography of the cystic fibrosis population: Forecasting future numbers of adults in the UK. Sci Rep, 2020; 10:10660; doi: 10.1038/s41598-020-67353-3
25.
SnellN, GibsonJ, JarroldI, et al.Epidemiology of bronchiectasis in the UK: Findings from the British lung foundation's ‘Respiratory health of the nation’ project. Respir Med, 2019; 158:21–23; doi: 10.1016/j.rmed.2019.09.012
26.
PolverinoE, GoeminnePC, McDonnellMJ, et al.European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J, 2017; 50(3); doi: 10.1183/13993003.00629-2017
27.
BushA, FlotoRA. Pathophysiology, causes and genetics of paediatric and adult bronchiectasis. Respirology, 2019; 24(11):1053–1062; doi: 10.1111/resp.13509
28.
ReddingGJ, CarterER. Chronic suppurative lung disease in children: Definition and spectrum of disease. Front Pediatr, 2017; 5:30; doi: 10.3389/fped.2017.00030
29.
OliveiraMJ, CoutinhoD, VazD, et al.Bacterial colonization in patients with bronchiectasis. Eur Respir J, 2014; 44(Suppl 58):2529.
IkutaKS, SwetschinskiLR, AguilarGR, et al.Global mortality associated with 33 bacterial pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 2022; 400(10369):2221–2248; doi: 10.1016/S0140-6736(22)02185-7
32.
StepmanG, DabbK, KhanIA, et al.Bilateral pneumonia in a patient with chronic bronchiectasis caused by Achromobacter xylosoxidans subspecies denitrificans. Cureus n.d.;12(3):e7381; doi: 10.7759/cureus.7381
33.
LeeM-R, ShengW-H, HungC-C, et al.Mycobacterium abscessus complex infections in humans. Emerg Infect Dis, 2015; 21(9):1638–1646; doi: 10.3201/2109.141634
StrathdeeSA, HatfullGF, MutalikVK, et al.Phage therapy: From biological mechanisms to future directions. Cell, 2023; 186(1):17–31; doi: 10.1016/j.cell.2022.11.017
36.
PiresDP, CostaAR, PintoG, et al.Current challenges and future opportunities of phage therapy. FEMS Microbiol Rev, 2020; 44(6):684–700; doi: 10.1093/femsre/fuaa017
37.
KutateladzeM, AdamiaR. Bacteriophages as potential new therapeutics to replace or supplement antibiotics. Trends Biotechnol, 2010; 28(12):591–595; doi: 10.1016/j.tibtech.2010.08.001
ScalesK. Intravenous therapy: A guide to good practice. Br J Nurs Mark Allen Publ, 2008; 17(19):S4–S12; doi: 10.12968/bjon.2008.17.Sup8.31469
40.
FinneganMJ, HughesDV, HodsonME. Comparison of nebulized and intravenous terbutaline during exacerbations of pulmonary infection in patients with cystic fibrosis. Eur Respir J, 1992; 5(9):1089–1091.
41.
HamedK, ContiV, TianH, et al.Adherence to tobramycin inhaled powder vs inhaled solution in patients with cystic fibrosis: Analysis of US insurance claims data. Patient Prefer Adherence, 2017; 11:831–838; doi: 10.2147/PPA.S134759
42.
MontazersahebS, Hosseiniyan KhatibiSM, HejaziMS, et al.COVID-19 infection: An overview on cytokine storm and related interventions. Virol J, 2022; 19(1):92; doi: 10.1186/s12985-022-01814-1
43.
LittleJS, DedrickRM, FreemanKG, et al.Bacteriophage treatment of disseminated cutaneous Mycobacterium chelonae infection. Nat Commun, 2022; 13(1):2313; doi: 10.1038/s41467-022-29689-4
44.
LaVergneS, HamiltonT, BiswasB, et al.Phage therapy for a multidrug-resistant Acinetobacter baumannii craniectomy site infection. Open Forum Infect Dis, 2018; 5(4):ofy064; doi: 10.1093/ofid/ofy064
45.
DoubJB, NgVY, JohnsonAJ, et al.Salvage bacteriophage Therapy for a chronic MRSA prosthetic joint infection. Antibiotics, 2020; 9(5):241; doi: 10.3390/antibiotics9050241
46.
LiuD, Van BelleghemJD, de VriesCR, et al.The safety and toxicity of phage therapy: A review of animal and clinical studies. Viruses, 2021; 13(7):1268; doi: 10.3390/v13071268
47.
HietalaV, Horsma-HeikkinenJ, CarronA, et al.The removal of endo- and enterotoxins from bacteriophage preparations. Front Microbiol, 2019; 10:1674; doi: 10.3389/fmicb.2019.01674
StahlDL, RichardKM, PapadimosTJ. Complications of bronchoscopy: A concise synopsis. Int J Crit Illn Inj Sci, 2015; 5(3):189–195; doi: 10.4103/2229-5151.164995
50.
PirnayJ-P, De VosD, VerbekenG, et al.The phage therapy paradigm: Prêt-à-Porter or Sur-mesure?. Pharm Res, 2011; 28(4):934–937; doi: 10.1007/s11095-010-0313-5
51.
Ramirez-SanchezC, GonzalesF, BuckleyM, et al.Successful treatment of Staphylococcus aureus prosthetic joint infection with bacteriophage therapy. Viruses, 2021; 13(6):1182; doi: 10.3390/v13061182
52.
KhanA, RaoTS, JoshiHM. Phage therapy in the Covid-19 era: Advantages over antibiotics. Curr Res Microb Sci, 2022; 3:100115; doi: 10.1016/j.crmicr.2022.100115
53.
Van BelleghemJD, DąbrowskaK, VaneechoutteM, et al.Interactions between bacteriophage, bacteria, and the mammalian immune system. Viruses, 2018; 11(1):10; doi: 10.3390/v11010010
54.
MaselliDJ, KeytH, RestrepoMI. Inhaled antibiotic therapy in chronic respiratory diseases. Int J Mol Sci, 2017; 18(5):1062; doi: 10.3390/ijms18051062
55.
JonesJD, FergusonPR, SulemanM. The practical, ethical and legal reasons why patients should not be transferred between NHS trusts for phage therapy. J Patient Saf Risk Manag, 2022; 27(6):263–267; doi: 10.1177/25160435221120300
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
