Antibiotic-Resistant Pathogens in Ear, Nose, and Throat Infections

  • Itzhak Brook


The management of ear, nose, and throat infections requires an accurate clinical and bacteriological diagnosis, followed by an initial empiric antimicrobial therapy that may be adjusted once the identification of the causative organisms is available. The increasing antimicrobial resistance of many bacterial pathogens has made the treatment of these infections more challenging. This chapter presents the microbiology, antimicrobial resistance, and antimicrobial therapy of resistant acute and chronic head and neck infections pathogens.


Antibiotic resistance Multidrug-resistant organisms Head and neck infections 


  1. 1.
    Niederman MS. Principles of appropriate antibiotic use. Int J Antimicrob Agents. 2005;26:S170–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Brook I. Antibiotic resistance of oral anaerobic bacteria and their effect on the management of upper respiratory tract and head and neck infections. Semin Respir Infect. 2002;17:195–203.PubMedCrossRefGoogle Scholar
  3. 3.
    Hentges DJ. The anaerobic microflora of the human body. Clin Infect Dis. 1993;16:S175–80.PubMedCrossRefGoogle Scholar
  4. 4.
    Gibbons RJ. Aspects of the pathogenicity and ecology of the indigenous oral flora of man. In: Ballow A, Dehaan RM, Dowell VR, Guze LB, editors. Anaerobic bacteria: role in disease. Springfield, IL: Charles C. Thomas Publisher; 1974. p. 267–85.Google Scholar
  5. 5.
    Brook I. Anaerobic infections diagnosis and management. New York, NY: Informa Healthcare USA, Inc; 2007.CrossRefGoogle Scholar
  6. 6.
    Finegold SM. Anaerobic bacteria in human disease. New York, NY: Academic Press; 1977.Google Scholar
  7. 7.
    Brook I. β-Lactamase-producing bacteria in upper respiratory tract infections. Curr Infect Dis Rep. 2010;12:110–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Brook I. The role of beta-lactamase-producing bacteria in the persistence of streptococcal tonsillar infection. Rev Infect Dis. 1984;6:601–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Brook I, Yocum P. In vitro protection of group A beta-hemolytic streptococci from penicillin and cephalothin by Bacteroides fragilis. Chemotherapy. 1983;29:18–23.PubMedCrossRefGoogle Scholar
  10. 10.
    Hackman AS, Wilkins TD. In vivo protection of Fusobacterium necrophorum from penicillin by Bacteroides fragilis. Antimicrob Agents Chemother. 1975;7:698–703.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Brook I, Pazzaglia G, Coolbaugh JC, Walker RI. In vivo protection of penicillin susceptible Bacteroides melaninogenicus from penicillin by facultative bacteria which produce beta-lactamase. Can J Microbiol. 1984;30:98–104.PubMedCrossRefGoogle Scholar
  12. 12.
    Brook I. Beta-lactamase-producing bacteria recovered after clinical failures with various penicillin therapy. Arch Otolaryngol. 1984;110:228–31.PubMedCrossRefGoogle Scholar
  13. 13.
    Van Eldere J, Slack MP, Ladhani S, Cripps AW. Non-typeable Haemophilus influenzae, an under-recognised pathogen. Lancet Infect Dis. 2014;14:1281–92.PubMedCrossRefGoogle Scholar
  14. 14.
    San Millan A, Santos-Lopez A, Ortega-Huedo R, Bernabe-Balas C, Kennedy SP, Gonzalez-Zorn B. Small-plasmid-mediated antibiotic resistance is enhanced by increases in plasmid copy number and bacterial fitness. Antimicrob Agents Chemother. 2015;59:3335–41.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Resman F, Ristovski M, Forsgren A, et al. Increase of β-lactam-resistant invasive Haemophilus influenzae in Sweden, 1997 to 2010. Antimicrob Agents Chemother. 2012;56:4408–15.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Hasegawa K, Kobayashi R, Takada E, et al. High prevalence of type b beta-lactamase-non-producing ampicillin-resistant Haemophilus influenzae in meningitis: the situation in Japan where Hib vaccine has not been introduced. J Antimicrob Chemother. 2006;57:1077.PubMedCrossRefGoogle Scholar
  17. 17.
    García-Cobos S, Campos J, Lázaro E, et al. Ampicillin-resistant non-beta-lactamase-producing Haemophilus influenzae in Spain: recent emergence of clonal isolates with increased resistance to cefotaxime and cefixime. Antimicrob Agents Chemother. 2007;51:2564–73.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Ladhani S, Slack MP, Heath PT, et al. Invasive Haemophilus influenzae Disease, Europe, 1996-2006. Emerg Infect Dis. 2010;16:455–63.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Nakamura S, Yanagihara K, Seki M, et al. Clinical characteristics of pneumonia caused by beta-lactamase negative ampicillin resistant Haemophilus influenzae (BLNAR). Scand J Infect Dis. 2007;39:521–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Ohno A, Ishii Y, Kobayashi I, Yamaguchi K. Antibacterial activity and PK/PD of ceftriaxone against penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae isolates from patients with community-acquired pneumonia. J Infect Chemother. 2007;13:296–301.PubMedCrossRefGoogle Scholar
  21. 21.
    Khan MA, Northwood JB, Levy F, Verhaegh SJ, Farrell DJ, Van Belkum A, Hays JP. bro {beta}-lactamase and antibiotic resistances in a global cross-sectional study of Moraxella catarrhalis from children and adults. J Antimicrob Chemother. 2010;65:91–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Liu Y, Xu H, Xu Z, Kudinha T, Fan X, Xiao M, Kong F, Sun H, Xu Y. High-level macrolide-resistant moraxella catarrhalis and development of an allele-specific PCR assay for detection of 23S rRNA gene A2330T mutation: a three-year study at a chinese tertiary hospital. Microb Drug Resist. 2015;21:507–11.PubMedCrossRefGoogle Scholar
  23. 23.
    Sahm DF, Brown NP, Thornsberry C, Jones ME. Antimicrobial susceptibility profiles among common respiratory tract pathogens: a GLOBAL perspective. Postgrad Med. 2008;120(3 Suppl 1):16–24.PubMedCrossRefGoogle Scholar
  24. 24.
    Andam CP, Hanage WP. Mechanisms of genome evolution of Streptococcus. Infect Genet Evol. 2015;33:334–42.PubMedCrossRefGoogle Scholar
  25. 25.
    Sujatha S, Praharaj I. Glycopeptide resistance in gram-positive cocci: a review. Interdiscip Perspect Infect Dis. 2012;2012:781679.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Moreno F, Crisp C, Jorgensen JH, Patterson JE. The clinical and molecular epidemiology of bacteremias at a university hospital caused by pneumococci not susceptible to penicillin. J Infect Dis. 1995;172:427–32.PubMedCrossRefGoogle Scholar
  27. 27.
    Ruhe JJ, Myers L, Mushatt D, Hasbun R. High-level penicillin-nonsusceptible Streptococcus pneumoniae bacteremia: identification of a low-risk subgroup. Clin Infect Dis. 2004;38:508–14.PubMedCrossRefGoogle Scholar
  28. 28.
    Vanderkooi OG, Low DE, Green K, et al. Predicting antimicrobial resistance in invasive pneumococcal infections. Clin Infect Dis. 2005;40:1288–97.PubMedCrossRefGoogle Scholar
  29. 29.
    Hakenbeck R, Brückner R, Denapaite D, Maurer P. Molecular mechanisms of β-lactam resistance in Streptococcus pneumoniae. Future Microbiol. 2012;7:395–410.PubMedCrossRefGoogle Scholar
  30. 30.
    Hotomi M, Billal DS, Shimada J, Suzumoto M, Yamauchi K, Fujihara K, Yamanaka N. Increase of macrolide-resistant Streptococcus pneumoniae-expressing mefE or ermB gene in the nasopharynx among children with otitis media. Laryngoscope. 2005;115:317–20.PubMedCrossRefGoogle Scholar
  31. 31.
    Jorgensen JH, Weigel LM, Swenson JM, Whitney CG, Ferraro MJ, Tenover FC. Activities of clinafloxacin, gatifloxacin, gemifloxacin, and trovafloxacin against recent clinical isolates of levofloxacin-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother. 2000;44:2962–8.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Jacobs MR, Good CE, Windau AR, Bajaksouzian S, Biek D, Critchley IA, Sader HS, Jones RN. Activity of ceftaroline against recent emerging serotypes of Streptococcus pneumoniae in the United States. Antimicrob Agents Chemother. 2010;54:2716–9.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Weinstein MP, Klugman KP, Jones RN. Rationale for revised penicillin susceptibility breakpoints versus Streptococcus pneumoniae: coping with antimicrobial susceptibility in an era of resistance. Clin Infect Dis. 2009;48:1596–600.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Centers for Disease Control and Prevention. Streptococcus pneumoniae. Active bacterial core surveillance report, emerging infections program Network 2013. Available at: Google Scholar
  35. 35.
    Brook I. Role of methicillin-resistant Staphylococcus aureus in head and neck infections. J Laryngol Otol. 2009;123:1301–7.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Naseri I, Jerris RC, Sobol SE. Nationwide trends in pediatric staphylococcus aureus head and neck infections. Arch Otolaryngol Head Neck Surg. 2009;135:14–6.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Fong SM, Watson M. Lemierre syndrome due to non-multiresistant methicillin- aureus. J Paediatr Child Health. 2002;38:305–7.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Boga C, Ozdogu H, Diri B, Oguzkurt L, Asma S, Yeral M. Lemierre syndrome variant: Staphylococcus aureus associated with thrombosis of both the right internal jugular vein and the splenic vein after the exploration of a river cave. J Thromb Thrombolysis. 2007;23:151–4.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Brook I, Foote PA, Hausfeld JN. Increase in the frequency of recovery of methicillin-resistant Staphylococcus aureus in acute and chronic maxillary sinusitis. J Med Microbiol. 2008;57:1015–7.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Gerencer RZ. Successful outpatient treatment of sinusitis exacerbations caused by community-acquired methicillin-resistant Staphylococcus aureus. Otolaryngol Head Neck Surg. 2005;132:828–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Enright MC, Robinson DA, Randle G, et al. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc Natl Acad Sci U S A. 2002;99:7687–92.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Panzer JD, Brown DC, Epstein WL, Lipson RL, Mahaffey HW, Atkinson WH. Clindamycin levels in various body tissues and fluids. J Clin Pharmacol New Drugs. 1972;12:259–62.PubMedCrossRefGoogle Scholar
  43. 43.
    Daum RS. Clinical practice. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med. 2007;357:380–90.PubMedCrossRefGoogle Scholar
  44. 44.
    Siberry GK, Tekle T, Carroll K, Dick J. Failure of clindamycin treatment of methicillin-resistant Staphylococcus aureus expressing inducible clindamycin resistance in vitro. Clin Infect Dis. 2003;37:1257–60.PubMedCrossRefGoogle Scholar
  45. 45.
    Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH. Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol. 2003;41:4740–4.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, Talan DA, Methicillin-resistant S. aureus infections among patients in the emergency department. EMERGEncy ID Net Study Group. N Engl J Med. 2006;355:666–74.PubMedCrossRefGoogle Scholar
  47. 47.
    Stevens DL, Herr D, Lampiris H, Hunt JL, Batts DH, Hafkin B. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis. 2002;34:1481–90.PubMedCrossRefGoogle Scholar
  48. 48.
    Silverman JA, Mortin LI, Vanpraagh AD, Li T, Alder J. Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. J Infect Dis. 2005;191:2149–52.PubMedCrossRefGoogle Scholar
  49. 49.
    Sakoulas G, Alder J, Thauvin-Eliopoulos C, Moellering RC Jr, Eliopoulos GM. Induction of daptomycin heterogeneous susceptibility in Staphylococcus aureus by exposure to vancomycin. Antimicrob Agents Chemother. 2006;50:1581–5.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE. Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus. J Infect Dis. 2007;195:202–11.PubMedCrossRefGoogle Scholar
  51. 51.
    Mendes RE, Deshpande LM, Castanheira M, DiPersio J, Saubolle MA, Jones RN. First report of cfr-mediated resistance to linezolid in human staphylococcal clinical isolates recovered in the United States. Antimicrob Agents Chemother. 2008;52:2244–6.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Garrison MW, Kawamura NM, Wen MM. Ceftaroline fosamil: a new cephalosporin active against resistant Gram-positive organisms including MRSA. Expert Rev Anti Infect Ther. 2012;10:1087–103.PubMedCrossRefGoogle Scholar
  53. 53.
    Cunningham M, Guardiani E, Kim HJ, Brook I. Otitis media. Future Microbiol. 2012;7:733–53.PubMedCrossRefGoogle Scholar
  54. 54.
    Brook I, Frazier EH, Thompson DH. Aerobic and anaerobic microbiology of external otitis. Clin Infect Dis. 1992;15:955–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Kaye KS, Pogue JM. Infections caused by resistant gram-negative bacteria: epidemiology and management. Pharmacotherapy. 2015;35:949–62.PubMedCrossRefGoogle Scholar
  56. 56.
    Rossolini GM, Mantengoli E. Treatment and control of severe infections caused by multiresistant Pseudomonas aeruginosa. Clin Microbiol Infect. 2005;11(Suppl 4):17–32.PubMedCrossRefGoogle Scholar
  57. 57.
    Safdar N, Handelsman J, Maki DG. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis. Lancet Infect Dis. 2004;4:519–27.PubMedCrossRefGoogle Scholar
  58. 58.
    Brook I, Wexler HM, Goldstein EJ. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev. 2013;26:526–46.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Busch DF, Kureshi LA, Sutter VL, et al. Susceptibility of respiratory tract anaerobes to orally administered penicillins and cephalosporins. Antimicrob Agents Chemother. 1976;10:713–20.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Acuna C, Rabasseda X. Amoxicillin-sulbactam: a clinical and therapeutic review. Drugs Today (Barc). 2001;37:193–210.CrossRefGoogle Scholar
  61. 61.
    Finegold SM. In vitro efficacy of beta-lactam/beta-lactamase inhibitor combinations against bacteria involved in mixed infections. Int J Antimicrob Agents. 1999;12(Suppl 1):S9–14.PubMedCrossRefGoogle Scholar
  62. 62.
    Goldstein EJC, Citron DM. Resistance trends in antimicrobial susceptibility of anaerobic bacteria, Part I and Part II. Clin Microbiol Newslett. 2011;33:1–14.CrossRefGoogle Scholar
  63. 63.
    Strehl E, Kees F. Pharmacological properties of parenteral cephalosporins: rationale for ambulatory use. Drugs. 2000;59(Suppl 3):9–18.PubMedCrossRefGoogle Scholar
  64. 64.
    Boyanova L, Kolarov R, Mitov I. Recent evolution of antibiotic resistance in the anaerobes as compared to previous decades. Anaerobe. 2015;31:4–10.PubMedCrossRefGoogle Scholar
  65. 65.
    Hecht DW. Prevalence of antibiotic resistance in anaerobic bacteria: worrisome developments. Clin Infect Dis. 2004;39:92–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Goldstein EJC, Citron DM, Cole RE, et al. Cefoxitin in the treatment of aerobic/anaerobic infections: prospective correlation of in vitro susceptibility methods with clinical outcome. Hosp Pract Symp Suppl. 1990;25(Suppl 4):38–45.CrossRefGoogle Scholar
  67. 67.
    Hellinger WC, Brewer NS. Carbapenems and monobactams: imipenem, meropenem, and aztreonam. Mayo Clin Proc. 1999;74:420–34.PubMedCrossRefGoogle Scholar
  68. 68.
    Aldridge K, Aldridge KE, Ashcraft D, et al. Multicenter survey of the changing in vitro antimicrobial susceptibilities of clinical isolates of Bacteroides fragilis group, Prevotella, Fusobacterium, Porphyromonas, and Peptostreptococcus species. Antimicrob Agents Chemother. 2001;45:1238–43.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Paterson DL, Depestel DD. Doripenem. Clin Infect Dis. 2009;49:291–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Nicolau DP, Carmeli Y, Crank CW, et al. Carbapenem stewardship: does ertapenem affect Pseudomonas susceptibility to other carbapenems? A review of the evidence. Int J Antimicrob Agents. 2012;39:11–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Jorgensen JH, Maher LA, Howell AW. Activity of meropenem against antibiotic-resistant or infrequently encountered gram-negative bacilli. Antimicrob Agents Chemother. 1991;35:2410–4.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Kattan JN, Villegas MV, Quinn JP. New developments in carbapenems. Clin Microbiol Infect. 2008;14:1102–11.PubMedCrossRefGoogle Scholar
  73. 73.
    Keating GM, Perry CM. Ertapenem: a review of its use in the treatment of bacterial infections. Drugs. 2005;65:2151–78.PubMedCrossRefGoogle Scholar
  74. 74.
    Snydman DR, Jacobus NV, McDermott LA, et al. Update on resistance of Bacteroides fragilis group and related species with special attention to carbapenems 2006-2009. Anaerobe. 2011;17:147–51.PubMedCrossRefGoogle Scholar
  75. 75.
    Liu CY, Huang YT, Liao CH, et al. Increasing trends in antimicrobial resistance among clinically important anaerobes and Bacteroides fragilis isolates causing nosocomial infections: emerging resistance to carbapenems. Antimicrob Agents Chemother. 2008;52:3161–8.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Wexler HM. Susceptibility testing of anaerobic bacteria: myth, magic, or method? Clin Microbiol Rev. 1991;4:470–84.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Bush K. Beta-Lactamases of increasing clinical importance. Curr Pharm Des. 1999;5:839–45.PubMedGoogle Scholar
  78. 78.
    Appelbaum PC, Spangler SK, Pankuch GA, et al. Characterization of a beta-lactamase from Clostridium clostridioforme. J Antimicrob Chemother. 1994;33:33–40.PubMedCrossRefGoogle Scholar
  79. 79.
    Pumbwe L, Chang A, Smith RL, et al. Clinical significance of overexpression of multiple RND-family efflux pumps in Bacteroides fragilis isolates. J Antimicrob Chemother. 2006;58:543–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Snydman DR, Jacobus NV, McDermott LA, et al. Lessons learned from the anaerobe survey: historical perspective and review of the most recent data (2005-2007). Clin Infect Dis. 2010;50(Suppl 1):S26–33.PubMedCrossRefGoogle Scholar
  81. 81.
    Snydman DR, Jacobus NV, McDermott LA, et al. Multicenter study of in vitro susceptibility of the Bacteroides fragilis group, 1995 to 1996, with comparison of resistance trends from 1990 to 1996. Antimicrob Agents Chemother. 1999;43:2417–22.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Snydman DR, Jacobus NV, McDermott LA, et al. National survey on the susceptibility of Bacteroides fragilis Group: report and analysis of trends for 1997-2000. Clin Infect Dis. 2002;35:S126–34.PubMedCrossRefGoogle Scholar
  83. 83.
    Balbi HJ. Chloramphenicol: a review. Pediatr Rev. 2004;25:284–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Goldstein EJC, Citron DM, Merriam CV. Linezolid activity compared to those of selected macrolides and other agents against aerobic and anaerobic pathogens isolated from soft tissue bite infections in humans. Antimicrob Agents Chemother. 1999;43:1469–74.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Williams JD, Maskell JP, Shain H, et al. Comparative in-vitro activity of azithromycin, macrolides (erythromycin, clarithromycin and spiramycin) and streptogramin RP 59500 against oral organisms. J Antimicrob Chemother. 1992;30:27–37.PubMedCrossRefGoogle Scholar
  86. 86.
    Goldstein EJC, Lewis RP, Sutter VL, et al. Treatment of pleuropulmonary and soft-tissue Infections with erythromycin. JAMA. 1979;242:435–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Sanai Y, Persson GR, Starr JR, et al. Presence and antibiotic resistance of Porphyromonas gingivalis, Prevotella intermedia, and Prevotella nigrescens in children. J Clin Periodontol. 2002;29:929–34.PubMedCrossRefGoogle Scholar
  88. 88.
    Feigin RD, Pickering LK, Anderson D, et al. Clindamycin treatment of osteomyelitis and septic arthritis in children. Pediatrics. 1975;55:213–23.Google Scholar
  89. 89.
    Klainer AS. Clindamycin. Med Clin North Am. 1987;71:1169–75.PubMedCrossRefGoogle Scholar
  90. 90.
    Paap CM, Nahata MC. Clinical pharmacokinetics of antibacterial drugs in neonates. Clin Pharmacokinet. 1990;19:280–318.PubMedCrossRefGoogle Scholar
  91. 91.
    Gorbach SL. Antibiotics and Clostridium difficile. N Engl J Med. 1999;341:1690–1.PubMedCrossRefGoogle Scholar
  92. 92.
    Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intraabdominal infections in adults and children: guidelines by the Surgical Infection Society and The Infectious Diseases Society of America. Clin Infect Dis. 2010;50:133–64.PubMedCrossRefGoogle Scholar
  93. 93.
    Brook I. Spectrum and treatment of anaerobic infections. J Infect Chemother. 2016;22:1–13.PubMedCrossRefGoogle Scholar
  94. 94.
    Chow AW, Patten V, Guze LB. Susceptibility of anaerobic bacteria to metronidazole: relative resistance of non-spore forming gram-positive bacilli. J Infect Dis. 1975;131:182–5.PubMedCrossRefGoogle Scholar
  95. 95.
    Rustia M, Shubik P. Experimental induction of hematomas, mammary tumors and other tumors with metronidazole in noninbred Sas: WRC (WT)BR rats. J Natl Cancer Inst. 1979;63:863–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Cohen SM, Ertürk E, Von Esch AM, et al. Carcinogenicity of 5-nitrofurans, 5-nitroimidazoles, 4-nitrobenzenes, and related compounds. J Natl Cancer Inst. 1973;51:403–17.PubMedCrossRefGoogle Scholar
  97. 97.
    Beard CM, Noller KL, O’Fallon WM, et al. Lack of evidence for cancer due to use of metronidazole. N Engl J Med. 1979;301:519–22.PubMedCrossRefGoogle Scholar
  98. 98.
    Townsend ML, Pound MW, Drew RH. Tigecycline: a new glycylcycline antimicrobial. Int J Clin Pract. 2006;60:1662–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Goldstein EJC, Citron DM, et al. Comparative in vitro susceptibilities of 396 unusual anaerobic strains to tigecycline and eight other antimicrobial agents. Antimicrob Agents Chemother. 2006;50:3507–13.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Jacobus NV, McDermott LA, Ruthazer R, et al. In vitro activities of tigecycline against the Bacteroides fragilis group. Antimicrob Agents Chemother. 2004;48:1034–6.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Edmiston CE, Krepel CJ, Seabrook GR, et al. In vitro activities of moxifloxacin against 900 aerobic and anaerobic surgical isolates from patients with intra-abdominal and diabetic foot infections. Antimicrob Agents Chemother. 2004;48:1012–6.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Stein GE, Goldstein EJ. Fluoroquinolones and anaerobes. Clin Infect Dis. 2006;42:1598–607.PubMedCrossRefGoogle Scholar
  103. 103.
    United States Food and Drug Administration. FDA News Release: FDA updates warnings for fluoroquinolone use. July 26, 2016.
  104. 104.
    Oh H, Hedberg M, Edlund C. Efflux-mediated fluoroquinolone resistance in the Bacteroides fragilis group. Anaerobe. 2002;8:277–82.CrossRefGoogle Scholar
  105. 105.
    Tyrrell KL, Citron DM, Warren YA, et al. In-vitro activity of TD-1792, a multivalent glycopeptide-cephalosporin antibiotic, against 377 strains of anaerobic bacteria and 34 strains of Corynebacterium species. Antimicrob Agents Chemother. 2012;56:2194–7.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Finch RG. Antibacterial activity of quinupristin/dalfopristin. Rationale for clinical use. Drugs. 1996;51:31–7.PubMedCrossRefGoogle Scholar
  107. 107.
    Brook I, Gober E. Emergence of beta-lactamase-producing aerobic and anaerobic bacteria in the oropharynx of children following penicillin chemotherapy. Clin Pediatr. 1984;23:338–42.CrossRefGoogle Scholar
  108. 108.
    Wexler HM. Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev. 2007;20(4):593–621.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Itzhak Brook
    • 1
    • 2
  1. 1.Department of PediatricsGeorgetown University School of MedicineWashington, DCUSA
  2. 2.Department of MedicineGeorgetown University School of MedicineWashington, DCUSA

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