Abstract
Nontypeable Haemophilus influenzae (NTHi) makes the clinical course of acute otitis media (AOM) intractable by forming a biofilm that may hamper the clearance of the bacteria from middle ear cavity. In this study, we evaluated the minimum biofilm eradication concentration (MBEC) of antimicrobial agents against biofilm-forming NTHi strains. Twelve NTHi strains isolated from middle ear fluids of Japanese children with intractable AOM before antimicrobial treatment were evaluated for MBEC of fluoroquinolones in comparison with those of β-lactams and macrolides. AMPC and CDTR required much higher concentration, i.e., high MBECs, to suppress the biofilm formation of NTHi. In contrast, fluoroquinolones followed by macrolides showed lower MBECs. MBEC would be a good parameter to infer the efficacies of antimicrobials against NTHi in biofilm.
Similar content being viewed by others
References
Teele DW, Klein JO, Rosner B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study. J Infect Dis. 1989;160:83–94.
Monasta L, Ronfani L, Marchetti F, Montico M, Vecchi Brumatti L, Bavcar A, et al. Burden of disease caused by otitis media: systematic review and global estimates. PLoS ONE. 2012;7:e36226.
Hotomi M, Yamanaka N, Shimada J, Ikeda Y, Faden H. Factors associated with clinical outcomes in acute otitis media. Ann Otol Rhinol Laryngol. 2004;113:846–52.
Murphy TF, Faden H, Bakaletz LO, Kyd JM, Forsgren A, Campos J, et al. Nontypeable Haemophilus influenzae as a pathogen in children. Pediatr Infect Dis J. 2009;28:43–8.
Hotomi M, Fujihara K, Billal DS, Suzuki K, Nishimura T, Baba S, et al. Genetic characteristics and clonal dissemination of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae strains isolated from the upper respiratory tract of patients in Japan. Antimicrob Agents Chemother. 2007;51:3969–76.
Moxon ER, Sweetman WA, Deadman ME, Ferguson DJ, Hood DW. Haemophilus influenzae biofilms: hypothesis or fact? Trends Microbiol. 2008;16:95–100.
Post JC. Direct evidence of bacterial biofilms in otitis media. Laryngoscope. 2001;111:2083–94.
Bakaletz LO. Bacterial biofilms in otitis media: evidence and relevance. Pediatr Infect Dis J. 2007;26:S17–9.
Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284:1318–22.
Stewart PS, Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet. 2001;358:135–8.
Anderson GG, O’Toole GA. Innate and induced resistance mechanisms of bacterial biofilms. Curr Top Microbiol Immunol. 2008;322:85–105.
American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics. 2004;113:1451–5.
Grubb MS, Spaugh DC. Treatment failure, recurrence, and antibiotic prescription rates for different acute otitis media treatment methods. Clin Pediatr (Phila). 2010;49:970–5.
Moriyama S, Hotomi M, Shimada J, Billal DS, Fujihara K, Yamanaka N. Formation of biofilm by Haemophilus influenzae isolated from pediatric intractable otitis media. Auris Nasus Larynx. 2009;36:525–31.
Subcommittee of Clinical Practice Guideline for Diagnosis and Management of Acute Otitis Media in Children (Japan Otological Society, Japan Society for Pediatric Otorhinolaryngology, Japan Society for Infectious Diseases in Otolaryngology). Clinical practice guidelines for the diagnosis and management of acute otitis media (AOM) in children in Japan. Auris Nasus Larynx 2012;39:1–8.
Murphy TF, Brauer AL, Sethi S, Kilian M, Cai X, Lesse AL. Haemophilus haemolyticus: a human respiratory tract commensal to be distinguished from Haemophilus influenzae. J Infect Dis. 2007;195:81–9.
Kaji C, Watanabe K, Apicella MA, Watanabe H. Antimicrobial effect of fluoroquinolones for the eradication of nontypeable Haemophilus influenzae isolates within biofilms. Tohoku J Exp Med. 2008;214:121–8.
National Committee for Clinical Laboratory Standards (2004) Performance standards for antimicrobial susceptibility testing. Fourteenth informational supplement. Approved standard M100-S14. Wayne, PA: NCCLS.
Billal DS, Fedorko DP, Yan SS, Hotomi M, Fujihara K, Nelson N, et al. In vitro induction and selection of fluoroquinolone-resistant mutants of Streptococcus pyogenes strains with multiple emm types. J Antimicrob Chemother. 2007;59:28–34.
Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol. 1999;37:1771–6.
Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26:1–10.
Anderl JN, Franklin MJ, Stewart PS. Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrob Agents Chemother. 2000;44:1818–24.
Fux CA, Costerton JW, Stewart PS, Stoodley P. Survival strategies of infectious biofilms. Trends Microbiol. 2005;13:34–40.
Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev. 2002;15:167–93.
Yamanaka N, Sugita R, Uno Y, Matsubara S, Hayashi Y, Sawada S. Clinical efficacy of tosufloxacin tosilate hydrate for the treatment of acute otitis media in children (in Japanese). Practica Oto-Rhino-Laryngologica 2012;105:381–392
Dagan R, Arguedas A, Schaad UB. Potential role of fluoroquinolone therapy in childhood otitis media. Pediatr Infect Dis J. 2004;23:390–8.
Reid G, Sharma S, Advikolanu K, Tieszer C, Martin RA, Bruce AW. Effects of ciprofloxacin, norfloxacin, and ofloxacin on in vitro adhesion and survival of Pseudomonas aeruginosa AK1 on urinary catheters. Antimicrob Agents Chemother. 1994;38:1490–5.
Acknowledgments
This work was supported by national grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology (grant 24791800).
Conflict of interest
We declare no conflict of interest for this study.
Author information
Authors and Affiliations
Corresponding author
Additional information
S. Takei and M. Hotomi contributed equally to this work.
About this article
Cite this article
Takei, S., Hotomi, M. & Yamanaka, N. Minimal biofilm eradication concentration of antimicrobial agents against nontypeable Haemophilus influenzae isolated from middle ear fluids of intractable acute otitis media. J Infect Chemother 19, 504–509 (2013). https://doi.org/10.1007/s10156-013-0592-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10156-013-0592-y