Topical Therapy Failure in Chronic Suppurative Otitis Media is Due to Persister Cells in Biofilms.
Journal
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
ISSN: 1537-4505
Titre abrégé: Otol Neurotol
Pays: United States
ID NLM: 100961504
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
pubmed:
22
6
2021
medline:
8
10
2021
entrez:
21
6
2021
Statut:
ppublish
Résumé
Chronic suppurative otitis media (CSOM) is characterized by a chronically draining middle ear. CSOM is typically treated with multiple courses of antibiotics or antiseptics which are successful in achieving quiescence; however, the disease is prone to relapse. Understanding why these treatment failures occur is essential. The minimum inhibitory concentration (MIC), minimal biofilm eradication concentration, and the inhibitory zone were determined for ototopicals and ofloxacin for the laboratory strains and CSOM-derived isolates. The percentage of persister cells and bacterial biofilm formation were measured. Disease eradication was tested in a validated in-vivo model of CSOM after treatment with ofloxacin. Microbiology Laboratory. Basic science experiments were performed to measure the effectiveness of a number of compounds against CSOM bacteria in a number of distinct settings. The minimal biofilm eradication concentration is higher than is physiologically achievable with commercial preparations, except for povo-iodine. Clincial isolates of CSOM have equivalent biofilm-forming ability but increased proportions of persister cells. Ofloxacin can convert to inactive disease temporarily but fails to eradicate disease in an in-vivo model. Higher percentages of persister cells in clinical CSOM isolates are associated with resistance to ototopicals. Current ototopicals, except povo-iodine, have limited clinical effectiveness; however, it is unknown what the maximum achievable concentration is and there are ototoxicity concerns. Fluoroquinolones, while successful in producing inactive disease in the short term, have the potential to encourage antimicrobial resistance and disease recalcitrance and do not achieve a permanent remission. Given these limitations, clinicians should consider surgery earlier or use of clinically safe concentrations of povo-iodine earlier into the treatment algorithm.
Identifiants
pubmed: 34149028
doi: 10.1097/MAO.0000000000003222
pii: 00129492-202110000-00023
doi:
Substances chimiques
Anti-Bacterial Agents
0
Anti-Infective Agents, Local
0
Ofloxacin
A4P49JAZ9H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1263-e1272Informations de copyright
Copyright © 2021, Otology & Neurotology, Inc.
Déclaration de conflit d'intérêts
The authors disclose no conflicts of interest.
Références
Monasta L, Ronfani L, Marchetti F, et al. Burden of disease caused by otitis media: Systematic review and global estimates. PLoS One 2012; 7:e36226.
Acuin J. Chronic suppurative otitis media. Clin Evid 2004; 710–729.
Verhoeff M, van der Veen EL, Rovers MM, Sanders EAM, Schilder AGM. Chronic suppurative otitis media: A review. Int J Pediatr Otorhinolaryngol 2006; 70:1–12.
Jensen RG, Johansen HK, Bjarnsholt T, Eickhardt-Sørensen SR, Homøe P. Recurrent otorrhea in chronic suppurative otitis media: Is biofilm the missing link? Eur Arch Otorhinolaryngol 2017; 274:2741–2747.
Mittal R, Lisi CV, Gerring R, et al. Current concepts in the pathogenesis and treatment of chronic suppurative otitis media. J Med Microbiol 2015; 64:1103–1116.
Bakaletz LO. Bacterial biofilms in otitis media: Evidence and relevance. Pediatr Infect Dis J 2007; 26: (10 suppl): S17–S19.
Lewis K. Persister cells. Annu Rev Microbiol 2010; 64:357–372.
Conlon BP, Rowe SE, Gandt AB, et al. Persister formation in Staphylococcus aureus is associated with ATP depletion. Nat Microbiol 2016; 1:16051.
Ohyama M, Furuta S, Ueno K, et al. Ofloxacin otic solution in patients with otitis media: An analysis of drug concentrations. Arch Otolaryngol Head Neck Surg 1999; 125:337–340.
Panchasara A, Singh A, Mandavia D, Jha S, Tripathi C. Efficacy and safety of ofloxacin and its combination with dexamethasone in chronic suppurative otitis media. A randomised, double blind, parallel group, comparative study. Acta Otorhinolaryngol Ital 2015; 35:39–44.
Kiris M, Berktas M, Egeli E, Kutluhan A. The efficacy of topical ciprofloxacin in the treatment of chronic suppurative otitis media. Ear Nose Throat J 1998; 77: 904–5, 909.
Wigger C, Leach AJ, Beissbarth J, et al. Povidone-iodine ear wash and oral cotrimoxazole for chronic suppurative otitis media in Australian aboriginal children: Study protocol for factorial design randomised controlled trial. BMC Pharmacol Toxicol 2019; 20:46.
Bigger J. Treatment of staphylococcal infections with penicillin by intermittent sterilisation. Lancet 1944; 244:497–500.
Peterson E, Kaur P. Antibiotic resistance mechanisms in bacteria: Relationships between resistance determinants of antibiotic producers, environmental bacteria, and clinical pathogens. Front Microbiol 2018; 9:2928.
Kaldalu N, Hauryliuk V, Tenson T. Persisters—as elusive as ever. Appl Microbiol Biotechnol 2016; 100:6545–6553.
Spoering AL, Lewis K. Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials. J Bacteriol 2001; 183:6746–6751.
Khlebodarova TM, Likhoshvai VA. Persister cells—a plausible outcome of neutral coevolutionary drift. Sci Rep 2018; 8:14309.
Gilbert P, Das J, Foley I. Biofilm susceptibility to antimicrobials. Adv Dent Res 1997; 11:160–167.
Joers A, Kaldalu N, Tenson T. The frequency of persisters in Escherichia coli reflects the kinetics of awakening from dormancy. J Bacteriol 2010; 192:3379–3384.
Keren I, Kaldalu N, Spoering A, Wang Y, Lewis K. Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett 2004; 230:13–18.
Mok WWK, Brynildsen MP. Timing of DNA damage responses impacts persistence to fluoroquinolones. Proc Natl Acad Sci U S A 2018; 115:E6301–E6309.
Singh R, Ray P, Das A, Sharma M. Penetration of antibiotics through Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Antimicrob Chemother 2010; 65:1955–1958.
Barret TC, Mok WWK, Murawski AM, Brynildsen MP. Enhanced antibiotic resistance development from fluoroquinolone persisters after a single exposure to antibiotic. Nat Commun 2019; 10:1177.
Goodman SD, Obergfell KP, Jurcisek JA, et al. Biofilms can be dispersed by focusing the immune system on a common family of bacterial nucleoid-associated proteins. Mucosal Immunol 2011; 4:625–637.
Walters MC 3rd, Roe F, Bugnicourt A, Franklin M, Stewart PS. Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrob Agents Chemother 2003; 47:317–323.
Bahamondez-Canas TF, Zhang H, Tewes F, Leal J, Smyth HDC. PEGylation of tobramycin improves mucus penetration and antimicrobial activity against pseudomonas aeruginosa biofilms in vitro. Mol Pharm 2018; 15:1643–1652.
Guilhen C, Charbonnel N, Parisot N, et al. Transcriptional profiling of Klebsiella pneumoniae defines signatures for planktonic, sessile and biofilm-dispersed cells. BMC Genomics 2016; 17:237.
Marks LR, Davidson BA, Knight PR, Hakansson AP. Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease. mBio 2013; 4:e00438–13.
Uppuluri P, Lopez-Ribot JL. Go Forth and Colonize: Dispersal from clinically important microbial biofilms. PLoS Pathog 2016; 12:e1005397.
Cogan NG, Harro JM, Stoodley P, Shirtliff ME. Predictive computer models for biofilm detachment properties in Pseudomonas aeruginosa. mBio 2016; 7:
Verderosa AD, Totsika M, Fairfull-Smith KE. Bacterial biofilm eradication agents: A current review. Front Chem 2019; 7:824.
Jaya C, Job A, Mathai E, Antonisamy B. Evaluation of topical povidone-iodine in chronic suppurative otitis media. Arch Otolaryngol Head Neck Surg 2003; 129:1098–1100.
Minja BM, Moshi NH, Ingvarsson L, Bastos I, Grenner J. Chronic suppurative otitis media in Tanzanian school children and its effects on hearing. East Afr Med J 2006; 83:322–325.
Loock JW. A randomised controlled trial of active chronic otitis media comparing courses of eardrops versus one-off topical treatments suitable for primary, secondary and tertiary healthcare settings. Clin Otolaryngol 2012; 37:261–270.
Vishwakarma K, Khan FA, Nizamuddin S, Singh P, Yadav L. Role of topical acetic acid in comparison to gentamicin for the management of chronic suppurative otitis media. Int Arch BioMedical Clin Res 2015; 1:13–16.
McDonnell G, Russell AD. Antiseptics and disinfectants: Activity, action, and resistance. Clin Microbiol Rev 1999; 12:147–179.
Bigliardi PL, Alsagoff SAL, El-Kafrawi HY, Pyon J-K, Wa CTC, Villa MA. Povidone iodine in wound healing: A review of current concepts and practices. Int J Surg 2017; 44:260–268.
Halstead FD, Rauf M, Moiemen NS, et al. The antibacterial activity of acetic acid against biofilm-producing pathogens of relevance to burns patients. PLoS One 2015; 10:e0136190.
Tsang STJ, Gwynne PJ, Gallagher MP, Simpson AHRW. The biofilm eradication activity of acetic acid in the management of periprosthetic joint infection. Bone Joint Res 2018; 7:517–523.
Yamano T, Higuchi H, Nakagawa T, Morizono T. Ototoxicity of acetic acid on the guinea pig cochlea. J Otolaryngol Head Neck Surg 2015; 44:54.
Kim H, Bae HY, Choo O-S, Choung Y-H. Efficacy of tympanoplasty without mastoidectomy for treating chronic otitis media in patients with mastoid cavity opacification in temporal bone computed tomography findings. Clin Exp Otorhinolaryngol 2018; 11:30–34.
Youn CK, Jun Y, Jo E-R, Jang S-J, Song H, Cho SI. Comparative efficacies of topical antiseptic eardrops against biofilms from methicillin-resistant Staphylococcus aureus and quinolone-resistant Pseudomonas aeruginosa. J Laryngol Otol 2018; 132:519–522.
Gronseth T, Vestby LK, Nesse LL, et al. Lugol's solution eradicates Staphylococcus aureus biofilm in vitro. Int J Pediatr Otorhinolaryngol 2017; 103:58–64.
Ozturkcan S, Dündar R, Katilmis H, Ilknur AE, Aktaş S, Haciömeroğlu S. The ototoxic effect of boric acid solutions applied into the middle ear of guinea pigs. Eur Arch Otorhinolaryngol 2009; 266:663–667.
Salihoglu M, Dogru S, Cesmeci E, et al. Ototoxicity of boric acid powder in a rat animal model. Braz J Otorhinolaryngol 2018; 84:332–337.
Oduwole KO, Glynn AA, Molony DC, et al. Anti-biofilm activity of sub-inhibitory povidone-iodine concentrations against Staphylococcus epidermidis and Staphylococcus aureus. J Orthop Res 2010; 28:1252–1256.
Hoekstra MJ, Westgate SJ, Mueller S. Povidone-iodine ointment demonstrates in vitro efficacy against biofilm formation. Int Wound J 2017; 14:172–179.
Piromchai P. Ototoxicity of povidone-iodine: A case report. J Otol 2019; 14:30–32.
Ozkiris M, Kapusuz Z, Saydam L. Ototoxicity of different concentrations povidone-iodine solution applied to the middle ear cavity of rats. Indian J Otolaryngol Head Neck Surg 2013; 65:168–172.
Singh S, Blakley B. Systematic review of ototoxic pre-surgical antiseptic preparations—what is the evidence? J Otolaryngol Head Neck Surg 2018; 47:18.
da Costa SS, Rosito LP, Dornelles C. Sensorineural hearing loss in patients with chronic otitis media. Eur Arch Otorhinolaryngol 2009; 266:221–224.
Mittal R, Grati M, Gerring R, et al. In vitro interaction of Pseudomonas aeruginosa with human middle ear epithelial cells. PLoS One 2014; 9:e91885.
Garai P, Berry L, Moussouni M, Bleves S, Blanc-Potard A-B. Killing from the inside: Intracellular role of T3SS in the fate of Pseudomonas aeruginosa within macrophages revealed by mgtC and oprF mutants. PLoS Pathog 2019; 15:e1007812.
Aggarwal R, Saeed SR, Green KJ. Myringoplasty. J Laryngol Otol 2006; 120:429–432.
Karela M, Berry S, Watkins A, Phillipps JJ. Myringoplasty: Surgical outcomes and hearing improvement: Is it worth performing to improve hearing? Eur Arch Otorhinolaryngol 2008; 265:1039–1042.
Trinidade A, Page JC, Dornhoffer JL. Therapeutic mastoidectomy in the management of noncholesteatomatous chronic otitis media: Literature review and cost analysis. Otolaryngol Head Neck Surg 2016; 155:914–922.
Bhat KV, Naseeruddin K, Nagalotimath US, Kumar PR, Hegde JS. Cortical mastoidectomy in quiescent, tubotympanic, chronic otitis media: Is it routinely necessary? J Laryngol Otol 2009; 123:383–390.
Neeff M, Biswas K, Hoggard M, Taylor MW, Douglas R. Molecular microbiological profile of chronic suppurative otitis media. J Clin Microbiol 2016; 54:2538–2546.