SciELO - Scientific Electronic Library Online

 
vol.5 issue2Low-dose adrenocorticotropin test in patients with the Acquired Immunodeficiency Syndrome author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

Indicators

Related links

Share


Brazilian Journal of Infectious Diseases

Print version ISSN 1413-8670On-line version ISSN 1678-4391

Braz. j. infect. dis vol.5 no.2 Salvador Apr. 2001

http://dx.doi.org/10.1590/S1413-86702001000200001 

In vitro Activity of Fluoroquinolones (Gatifloxacin, Levofloxacin and Trovafloxacin) and Seven Other Antibiotics Against Streptococcus pneumoniae

 

Nicodemo A.C., Mendes C.M.F., Oplustil C.P. and Sinto S.

Medical Investigation Laboratory (LIM – 54) – University of São Paulo Medical School, São Paulo, São Paulo, Brazil.

 

 

In recent years, the level of resistance of S. pneumoniae to beta-lactam and/or macrolides has increased around the world including some countries in South America. Because of this resistance, it is necessary to test the therapeutic alternatives for treating this pathogen, including the newer quinolones. This study was carried out in order to compare the in vitro activity of fluoroquinolones gatifloxacin, levofloxacin and trovafloxacin, to penicillin G, amoxicillin, amoxicillin-clavulanate, cufuroxime sodium, ceftriaxone, azithromycin and clarithromycin, against 300 strains of S. pneumoniae. Of the 300 samples tested, 18.6% were not susceptible to penicillin (56 strains) and 7% (21 strains) were resistant to the second generation cephalosporin. Among the macrolides, resistance ranged from 6.7% for clarithromycin to 29.6% for azithromycin. Susceptibility to the newer quinolones was 100% including the 56 strains not susceptible to penicillin. Among the 10 antibiotics evaluated, the fluoroquinolones gatifloxacin, levofloxacin, and trovafloxacin displayed high levels of in vitro activity against S. pneumoniae.
Key Words: S. pneumoniae antimicrobial resistance, susceptibility testing in vitro, respiratory tract infections, pneumococci.

 

 

The new fluoroquinolones are the result of a significant improvement in the basic chemical structure of this class of synthetic antibiotics. The resulting improvement in antimicrobial activity and pharmacokinetic features make these drugs useful as monotherapy for the treatment of upper and lower community-acquired respiratory tract infections [1]. The use of these drugs is particularly useful in countries where there is a high incidence of respiratory tract infections due to beta-lactam and/or macrolide antibiotic resistant strains.

The resistance of S. pneumoniae to penicillin and other antimicrobial drugs was first noted in Australia and Papua, New Guinea in the 1960s, spread to South Africa in the 1970s, and then to many countries in Europe, specially Eastern Europe, Africa and Asia in the 1980s [2]. Resistant S. pneumoniae greatly increased in the United States during the last decade [3-6], and has been observed in some Latin American countries [7], including Brazil [8, 9]. The treatment of serious diseases caused by S. pneumoniae is now a considerable challenge to clinicians.

In this study, we evaluated the in vitro minimum inhibitory concentration (MIC) of gatifloxacin, levofloxacin, trovafloxacin and 7 other antimicrobial agents including penicillin G, amoxicillin, amoxicillin-clavulanate, cefuroxime sodium, ceftriaxone, azithromycin and clarithromycin, against 300 strains of clinical specimens isolated from the respiratory tract, blood, and other usually sterile sites or fluids.

 

Material and Methods

Strains confirmed as S. pneumoniae, according to standard procedures [10], were screened to verify their susceptibility to penicillin by using 1 mg oxacillin disks.

The strains identified as having diminished susceptibility to penicillin (halos £ 19 mm) were submitted to E-test (AB Biodisk, Sweden) assays to determine the minimal inhibitory concentration (MIC) to penicillin. Samples with results of £ 0.06 mg/ml were considered susceptible, samples with results from 0.06 mg/ml to 1.0 mg/ml were considered of intermediate susceptibility, and samples with results of ³ 2 mg/ml were considered penicillin-resistant (high level). The susceptibility categorization followed the National Committee for Clinical Laboratory Standards (NCCLS) guidelines [11].

The E-test method was also used to evaluate the 9 other antimicrobial agents selected for this study (amoxicillin, amoxicillin-clavulanate, cefuroxime sodium, ceftriaxone, azithromycin, clarithromycin, levofloxacin, trovafloxacin and gatifloxacin). The concentration of the antimicrobial agents available in the E-test varies from 0.002 mg/ml to 256 mg/ml.

 

Results

The in vitro activities of penicillin G, amoxicillin, amoxicillin-clavulanate, cefuroxime sodium, ceftriaxone, azithromycin, clarithromycin, levofloxacin, trovafloxacin, and gatifloxacin against the 300 strains of S. pneumoniae are summarized in Table 1 and the results are expressed as MIC50 and MIC90 (mg/ml).

 

 

The MIC90 for gatifloxacin for the 300 analyzed strains was 0.19 mg/ml ranging from 0.016 mg/ml to 0.5 mg/ml. The susceptibility for penicillin using 1 mg oxacillin disks demonstrated that 103 of 300 strains were not susceptible (halo £ 19 mm). The E-test of these 103 strains showed that 47 were susceptible to penicilin (MIC £ 0.06 mg/ml), 50 strains presented intermediated level resistance (MIC 0.1 mg/ml to 1.0 mg/ml), and 6 strains presented high level resistance (MIC ³ 2 mg/ml); thus, 56 (18.6%) of the strains were considered penicillin resistant. We verified 7% of resistance to the second generation cephalosporin, and only 1 strain was not susceptible to ceftriaxone. Regarding the macrolides, resistance ranged from 6.7% for clarithromycin to 29.6% for azithromycin. The susceptibility to the new quinolones was 100%, including the 56 strains not susceptible to penicillin, with both MIC50 and MIC90 lower for trovafloxacin and gatifloxacin, respectively, when compared to levofloxacin. Among the 10 antibiotics evaluated gatifloxacin, levofloxacin and trovafloxacin displayed enhanced in vitro activity against S. pneumoniae.

 

Discussion

The results of this study, as summarized in Table 1, are in accordance with other studies [12, 13] and support the inclusion of the newest quinolones as monotherapy for the treatment of respiratory and other invasive infections caused by S. pneumoniae. Their use should be considered mainly in countries with a high frequecy of respiratory tract infections due to resistant strains.

The improved pharmacokinetic profile of this generation of quinolones permits the use of a single daily dose and a switch of therapy. However, the fluoroquinolones should be chosen for situations in which they offer a clear therapeutic advantage over other classes of antibiotics, rather than being selected for routine empirical use because of their broad spectrum of action [14]. The rational and appropriate use of these drugs is important in order to minimize the development of resistance and to ensure the maximum benefit from this class of antibiotics.

 

References

1. Nicodemo A.C., Nicodemo E.L., Idrahin K.Y. Oral levofloxacin in the treatment of community-acquired pneumonia. Braz J Infect Dis 2000;4:61-6.         [ Links ]

2. Bartlett J.G., Breiman R.F., Mandell L.A., et al. Community-acquired pneumonia in adults: Guidelines for management. Clin Infect Dis 1998;26:811-38.         [ Links ]

3. Hofmann J., Cetron M.S., Farley M.M., et al. The prevalence of drug-resistant Streptococcus pneumoniae in Atlanta. N Engl J Med 1995;333: 481-6.         [ Links ]

4. Butler J.C., Hofmann J., Cetron M.S., et al. The continued emergence of drug-resistant Streptococcus pneumoniae in the United States: an up-date from the Centers for Disease Control and Prevention's Pneumococcal sentinel Surveillance System. J Infect Dis 1996;174:986-93.         [ Links ]

5. Doern G.V., Bueggemann A., Holley H.P.,Jr, Rauch A.M. Antimicrobial resistance of Streptococcus pneumoniae recovered from out patients in the United States during the winter months of 1994 to 1995: results of a 30 center national surveillance study. Antimicrob Agents Chemother 1996;40:1208-13.         [ Links ]

6. Thorsnsberry C., Ogilve P., Khan J., et al. Surveillance of Antimicrobial Resistance in Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in the United States in 1996-1997 Respiratory Season. Diagn Microbiol Infect Dis 1997;29:249-57.         [ Links ]

7. Kertesz D.A., Di Fabio J.L., Brandileone M.C.C., et al. Invasive Streptococcus pneumoniae infection in Latin American children: results of the Pan American Health Organization Surveillance Study. Clin Infect Dis 1998;26:1355-61.         [ Links ]

8. Sessegolo J.F., Levin A.S.S., Levy C.E., et al. Distribuition of serotypes and antimicrobial resistance of Streptococcus pneumoniae strains isolated in Brazil from 1988 to 1992. J Clin Microbiol 1994;32:906-11.         [ Links ]

9. Brandileone M.C.C., Vieira V.S.D., Casagrande S.T., et al. Characteristics of isolates Streptococcus pneumoniae from middle aged and elderly adults in Brazil: capsular serotypes and antimicrobial sensitivity with invasive infections. Bras J Infect Dis 1998;2:90-6.         [ Links ]

10. Fackland R.R., Washington II J.A. Streptococcus and related catalase-negative Gram positive cocci. In A Balows, W.J. Hausler Jr., K.L. Herman, H.D. Isenberg, and H.J. Shadomy [eds.] Manual of clinical microbiology. American Society for Microbiology, Washington, DC, 1991;238-57.         [ Links ]

11. National Committee for Clinical Laboratory Standards (NCCLS). Performance Standards for Antimicrobial Susceptibility Testing; Ninth Informational Supplement. M100-S9, 1999 vol. 19 no 1, 90-1.         [ Links ]

12. Plouffe J.F., County F. Pneumonia study group. Levofloxacin in vitro activity against bacteremic isolates of Streptococcus pneumoniae. Diagn Microbiol Infect Dis 1996;25:43-5.         [ Links ]

13. Doern G.V., Pfaller M.A., Erwin M.E., et al. The prevalence of fluoroquinolone resistance among clinically significant respiratory tract isolates of Streptococcus pneumoniae in the United States and Canada – 1997 results from the SENTRY Antimicrobial Surveillance Program. Diag Microbiol Infect Dis 1998; 32:313-6.         [ Links ]

14. Hooper D. Expanding uses of fluoroquinolones: opportunities and challenges. Ann Intern Med 1998;129: 908-10.         [ Links ]

 

 

Received on 16 December 2000; revised 15 March 2001.
Address for correspondence: Dr. Antônio Carlos Nicodemo, MD - Rua Barata Ribeiro, 398, cj. 32, São Paulo, SP, Brazil. Zip Code 01308-000. Phone/Fax: (11) 214-4251/259-1318. E-mail: acnicode@zip.net.com.br

Creative Commons License All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License