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Resistance of Streptococcus pneumoniae to the fluoroquinolones, doxycycline, and trimethoprim-sulfamethoxazole

Author
Daniel M Musher, MD
Section Editor
Daniel J Sexton, MD
Deputy Editor
Sheila Bond, MD

INTRODUCTION

Streptococcus pneumoniae (pneumococcus) is among the most commonly identified bacterial causes of upper and lower respiratory tract infections including pneumonia, otitis media, acute rhinosinusitis, and acute exacerbations of chronic obstruction pulmonary disease (COPD). However, rates of pneumococcal infections are overall declining, in part due to widespread use of pneumococcal vaccinations [1,2].

The fluoroquinolones (often called quinolones) have been used widely to treat adults with these conditions. In 2016, the US Food and Drug Administration (FDA) stated that the serious adverse effects associated with fluoroquinolones generally outweigh the benefits for patients with acute rhinosinusitis (as well as acute bronchitis and uncomplicated urinary tract infections) who have other treatment options [3]. This safety alert is likely to reduce the indiscriminate use of the fluoroquinolones, thereby preserving the susceptibility of pneumococci. (See "Fluoroquinolones", section on 'Restriction of use for uncomplicated infections'.)

Doxycycline and macrolides/azalides (azithromycin or clarithromycin) are used for empiric treatment of pneumonia in adult outpatients [4], acute exacerbation of COPD [5], and acute bacterial rhinosinusitis [6] as alternative agents for patients with penicillin allergy.

Trimethoprim-sulfamethoxazole (TMP-SMX) was commonly used to treat these conditions from the mid-1970s to the mid-1990s, but this combination drug has largely fallen out of favor because of the high rate of pneumococcal resistance.

Pneumococci were uniformly susceptible to all antibiotics used to treat respiratory tract bacterial infections until outbreaks of infection due to antibiotic-resistant pneumococci occurred in South Africa in the late 1970s [7,8]. Although the responsible organisms were called penicillin-resistant pneumococci, they had acquired genetic material that encoded broad resistance both to penicillin and to other commonly used antibiotics. In the ensuing decades, pneumococcal resistance has arisen in a number of clinically relevant classes of antibiotics.

          
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Literature review current through: Nov 2017. | This topic last updated: Nov 28, 2017.
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References
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  1. Musher DM, Abers MS, Bartlett JG. Evolving Understanding of the Causes of Pneumonia in Adults, With Special Attention to the Role of Pneumococcus. Clin Infect Dis 2017; 65:1736.
  2. Moberley S, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev 2013; :CD000422.
  3. FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together. http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm (Accessed on May 26, 2016).
  4. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27.
  5. Dever LL, Shashikumar K, Johanson WG Jr. Antibiotics in the treatment of acute exacerbations of chronic bronchitis. Expert Opin Investig Drugs 2002; 11:911.
  6. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngol Head Neck Surg 2015; 152:S1.
  7. Appelbaum PC, Bhamjee A, Scragg JN, et al. Streptococcus pneumoniae resistant to penicillin and chloramphenicol. Lancet 1977; 2:995.
  8. Jacobs MR, Koornhof HJ, Robins-Browne RM, et al. Emergence of multiply resistant pneumococci. N Engl J Med 1978; 299:735.
  9. Zhanel GG, Palatnick L, Nichol KA, et al. Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002. Antimicrob Agents Chemother 2003; 47:1867.
  10. Thomson KS, Chartrand SA, Sanders CC, Block SL. Trovafloxacin, a new fluoroquinolone with potent activity against Streptococcus pneumoniae. Antimicrob Agents Chemother 1997; 41:478.
  11. Blondeau JM. A review of the comparative in-vitro activities of 12 antimicrobial agents, with a focus on five new respiratory quinolones'. J Antimicrob Chemother 1999; 43 Suppl B:1.
  12. Fukuda H, Hiramatsu K. Primary targets of fluoroquinolones in Streptococcus pneumoniae. Antimicrob Agents Chemother 1999; 43:410.
  13. Pestova E, Millichap JJ, Siddiqui F, et al. Non-PmrA-mediated multidrug resistance in Streptococcus pneumoniae. J Antimicrob Chemother 2002; 49:553.
  14. Smith HJ, Nichol KA, Hoban DJ, Zhanel GG. Dual activity of fluoroquinolones against Streptococcus pneumoniae: the facts behind the claims. J Antimicrob Chemother 2002; 49:893.
  15. Brueggemann AB, Coffman SL, Rhomberg P, et al. Fluoroquinolone resistance in Streptococcus pneumoniae in United States since 1994-1995. Antimicrob Agents Chemother 2002; 46:680.
  16. Jorgensen JH, Weigel LM, Swenson JM, et al. Activities of clinafloxacin, gatifloxacin, gemifloxacin, and trovafloxacin against recent clinical isolates of levofloxacin-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother 2000; 44:2962.
  17. Jones RN, Jacobs MR, Sader HS. Evolving trends in Streptococcus pneumoniae resistance: implications for therapy of community-acquired bacterial pneumonia. Int J Antimicrob Agents 2010; 36:197.
  18. Jacobs MR, Good CE, Windau AR, et al. Activity of ceftaroline against recent emerging serotypes of Streptococcus pneumoniae in the United States. Antimicrob Agents Chemother 2010; 54:2716.
  19. Kupronis BA, Richards CL, Whitney CG, Active Bacterial Core Surveillance Team. Invasive pneumococcal disease in older adults residing in long-term care facilities and in the community. J Am Geriatr Soc 2003; 51:1520.
  20. Pletz MW, van der Linden M, von Baum H, et al. Low prevalence of fluoroquinolone resistant strains and resistance precursor strains in Streptococcus pneumoniae from patients with community-acquired pneumonia despite high fluoroquinolone usage. Int J Med Microbiol 2011; 301:53.
  21. Patel SN, McGeer A, Melano R, et al. Susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Antimicrob Agents Chemother 2011; 55:3703.
  22. Scheld WM. Maintaining fluoroquinolone class efficacy: review of influencing factors. Emerg Infect Dis 2003; 9:1.
  23. Pankuch GA, Bozdogan B, Nagai K, et al. Incidence, epidemiology, and characteristics of quinolone-nonsusceptible Streptococcus pneumoniae in Croatia. Antimicrob Agents Chemother 2002; 46:2671.
  24. Ho PL, Yung RW, Tsang DN, et al. Increasing resistance of Streptococcus pneumoniae to fluoroquinolones: results of a Hong Kong multicentre study in 2000. J Antimicrob Chemother 2001; 48:659.
  25. Wang H, Chen M, Xu Y, et al. Antimicrobial susceptibility of bacterial pathogens associated with community-acquired respiratory tract infections in Asia: report from the Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS) study, 2009-2010. Int J Antimicrob Agents 2011; 38:376.
  26. Ho PL, Tse WS, Tsang KW, et al. Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study. Clin Infect Dis 2001; 32:701.
  27. Hoban DJ, Bouchillon SK, Johnson BM, et al. In vitro activity of tigecycline against 6792 Gram-negative and Gram-positive clinical isolates from the global Tigecycline Evaluation and Surveillance Trial (TEST Program, 2004). Diagn Microbiol Infect Dis 2005; 52:215.
  28. Jones RN, Wilson ML, Weinstein MP, et al. Contemporary potencies of minocycline and tetracycline HCL tested against Gram-positive pathogens: SENTRY Program results using CLSI and EUCAST breakpoint criteria. Diagn Microbiol Infect Dis 2013; 75:402.
  29. Nelson ML, Levy SB. Reversal of tetracycline resistance mediated by different bacterial tetracycline resistance determinants by an inhibitor of the Tet(B) antiport protein. Antimicrob Agents Chemother 1999; 43:1719.
  30. Steigbigel NH, Reed CW, Finland M. Susceptibility of common pathogenic bacteria to seven tetracycline antibiotics in vitro. Am J Med Sci 1968; 255:179.
  31. Schaedler RW, Choppin PW, Zabriskie JB. PNEUMONIA CAUSED BY TETRACYCLINE-RESISTANT PNEUMOCOCCI. N Engl J Med 1964; 270:127.
  32. Holt R, Evans TN, Newman RL. Tetracycline-resistant pneumococci. Lancet 1969; 2:545.
  33. Kahlmeter G, Kamme C. Tetracycline-resistant group A streptococci and pneumococci. Scand J Infect Dis 1972; 4:193.
  34. Tetracycline resistance in pneumococci and group A streptococci. Report of an ad-hoc study group on antibiotic resistance. Br Med J 1977; 1:131.
  35. Hitchings GH. Mechanism of action of trimethoprim-sulfamethoxazole. I. J Infect Dis 1973; 128:Suppl:433.
  36. Burchall JJ. Mechanism of action of trimethoprim-sulfamethoxazole. II. J Infect Dis 1973; 128:Suppl: 437.
  37. Simberkoff MS, Lukaszewski M, Cross A, et al. Antibiotic-resistant isolates of Streptococcus pneumoniae from clinical specimens: a cluster of serotype 19A organisms in Brooklyn, New York. J Infect Dis 1986; 153:78.
  38. Henderson FW, Gilligan PH, Wait K, Goff DA. Nasopharyngeal carriage of antibiotic-resistant pneumococci by children in group day care. J Infect Dis 1988; 157:256.
  39. Reeves RR, Musher DM. Antibiotic-resistant pneumococcus in a hemophiliac with AIDS. Hosp Pract 1991; 26:81.
  40. Doern GV, Richter SS, Miller A, et al. Antimicrobial resistance among Streptococcus pneumoniae in the United States: have we begun to turn the corner on resistance to certain antimicrobial classes? Clin Infect Dis 2005; 41:139.
  41. Thornsberry C, Sahm DF, Kelly LJ, et al. Regional trends in antimicrobial resistance among clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States: results from the TRUST Surveillance Program, 1999-2000. Clin Infect Dis 2002; 34 Suppl 1:S4.
  42. Vanderkooi OG, Low DE, Green K, et al. Predicting antimicrobial resistance in invasive pneumococcal infections. Clin Infect Dis 2005; 40:1288.