Bacteriophage effectively kills multidrug resistant Staphylococcus aureus clinical isolates from chronic rhinosinusitis patients. 2018

Guimin Zhang, and Yin Zhao, and Sathish Paramasivan, and Katharina Richter, and Sandra Morales, and Peter-John Wormald, and Sarah Vreugde
Department of Otolaryngology-Head & Neck Surgery, Adelaide University, Adelaide, SA, Australia.

Bacteriophage (phage) therapy has been proposed as an alternative to antibiotics. Phages have been shown to kill antibiotic resistant Staphylococcus aureus strains; however, it is unknown whether stress-induced antibiotic tolerance affects S. aureus susceptibility to phages. Our objective was to determine the effectiveness of 2 phages currently in clinical development, against antibiotic-resistant and induced antibiotic-tolerant clinical S. aureus isolates. Antibiotic tolerant S. aureus strains were induced by incubation with increasing concentrations of gentamicin, mupirocin, and ciprofloxacin over time and their susceptibility to 2 clinically relevant phages (Sa83 and Sa87) was assessed. In addition, phage susceptibility was tested in relation to the antibiotic sensitivity of 65 clinical S. aureus isolates, harvested from the sinonasal cavities of chronic rhinosinusitis (CRS) patients. Phage sensitivity was assessed using a plaque spot assay and by measuring optical density values to observe planktonic S. aureus growth in the presence of the phage. Alamar Blue assays were used to assess biofilm viability after phage treatment. Frequency of antibiotic resistance amongst clinical S. aureus isolates was 90.7% (59/65) with 13 of 65 (20.0%) identified as multidrug-resistant. Tolerance to gentamicin, mupirocin, and ciprofloxacin was rapidly induced by incubation with increasing concentrations of respective antibiotics. There was no significant difference in phage sensitivity between antibiotic-sensitive and resistant/tolerant S. aureus clinical isolates in planktonic and biofilm form. Clinical S. aureus isolates from CRS patients have a high (20%) incidence of multidrug resistance. Antibiotic resistance or tolerance did not affect phage susceptibility of those isolates.

UI MeSH Term Description Entries
D002908 Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2). Chronic Condition,Chronic Illness,Chronically Ill,Chronic Conditions,Chronic Diseases,Chronic Illnesses,Condition, Chronic,Disease, Chronic,Illness, Chronic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071059 Phage Therapy Therapeutic use of BACTERIOPHAGES to treat diseases. Bacteriophage Therapy,Bacteriophage Therapies,Phage Therapies
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D012220 Rhinitis Inflammation of the NASAL MUCOSA, the mucous membrane lining the NASAL CAVITIES. Nasal Catarrh,Catarrh, Nasal,Catarrhs, Nasal,Nasal Catarrhs,Rhinitides
D012852 Sinusitis Inflammation of the NASAL MUCOSA in one or more of the PARANASAL SINUSES. Sinus Infections,Infection, Sinus,Infections, Sinus,Sinus Infection,Sinusitides
D013203 Staphylococcal Infections Infections with bacteria of the genus STAPHYLOCOCCUS. Infections, Staphylococcal,Staphylococcus aureus Infection,Staphylococcal Infection,Staphylococcus aureus Infections
D013204 Staphylococcus Phages Viruses whose host is Staphylococcus. Staphylococcal Phages,Staphylococcal Bacteriophage,Staphylococcal Bacteriophages,Staphylococcus Phage,Bacteriophage, Staphylococcal,Bacteriophages, Staphylococcal,Phage, Staphylococcal,Phage, Staphylococcus,Phages, Staphylococcal,Phages, Staphylococcus,Staphylococcal Phage
D013211 Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
D024901 Drug Resistance, Multiple, Bacterial The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Drug Resistance, Extensive, Bacterial,Drug Resistance, Extensively, Bacterial,Extensive Antibacterial Drug Resistance,Extensively Antibacterial Drug Resistance,Multidrug Resistance, Bacterial,Multiple Antibacterial Drug Resistance,Bacterial Multidrug Resistance,Bacterial Multidrug Resistances,Resistance, Bacterial Multidrug

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