J Korean Med Sci.  2007 Feb;22(1):20-25. 10.3346/jkms.2007.22.1.20.

In vitro Activities of Oral Cephem and Telithromycin Against Clinical Isolates of Major Respiratory Pathogens in Japan

• Shimizu A
• Maebashi K
• Niida M
• Mikuniya T
• Hikida M
• Ubukata K

• KMID: 1713224
• DOI: http://doi.org/10.3346/jkms.2007.22.1.20

Abstract

The in vitro antibacterial activities of oral cephem antibiotics and ketolide telithromycin against major respiratory pathogens possessing beta-lactam-resistant mutations (within the pbp gene) and/or macrolide-resistant genes (erm and mef) were examined in clinical isolates collected at 66 institutes in all over the Japan between 2002 and 2003. Telithromycin showed the strongest antibacterial activity against methicillinsusceptible Staphylococcus aureus strains with and without macrolide-resistant genes, such as ermA or ermC gene. All the cephem antibiotics showed potent antibacterial activity against Streptococcus pyogenes, with minimum inhibitory concentrations (MICs) of 0.015 mg/L or lower. Cefdinir had a much higher MIC90 against genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) than cefditoren and cefcapene (8 mg/L cefdinir vs. 1 mg/L cefditoren and cefcapene). The majority of gPRSP harbored either ermB or mefA, and the antibacterial activity of telithromycin against these strains was decreased however some susceptibility was still sustained. Cefditoren exerted the strongest antibacterial activity against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, with an MIC90 of 0.5 mg/L. These results underline the importance of checking the susceptibility and selecting an appropriate antibiotic against target pathogens.

Keyword

cefditoren; telithromycin; Microbial Sensitivity Tests; Minimum Inhibitory Concentration; beta-Lactams

MeSH Terms

Streptococcus pyogenes/*drug effects
Streptococcus pneumoniae/*drug effects
Staphylococcus aureus/*drug effects
Microbial Sensitivity Tests
Methicillin Resistance
Ketolides/*pharmacology
Humans
Haemophilus influenzae/*drug effects
Cephalosporins/*pharmacology
Administration, Oral

Reference

1. Ubukata K. Problems associated with high prevalence of multidrug-resistant bacteria in patients with community-acquired infections. J Infect Chemother. 2003. 9:285–291.

2. Ubukata K, Iwata S, Sunakawa K. In vitro activities of new ketolide, telithromycin, and eight other macrolide antibiotics against Streptococcus pneumoniae having mefA and ermB genes that mediate macrolide resistance. J Infect Chemother. 2003. 9:221–226.

3. Inoue M, Lee NY, Hong SW, Lee K, Felmingham D. PROTEKT 1999-2000: a multicentre study of the antibiotic susceptibility of respiratory tract pathogens in Hong Kong, Japan and South Korea. Int J Antimicrob Agents. 2004. 23:44–51.

4. Roberts MC, Sutcliffe J, Courvalin P, Jensen LB, Rood J, Seppala H. Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob Agents Chemother. 1999. 43:2823–2830.

5. Hasegawa K, Chiba N, Kobayashi R, Murayama SY, Iwata S, Sunakawa K, Ubukata K. Rapidly increasing prevalence of beta-lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae type b in patients with meningitis. Antimicrob Agents Chemother. 2004. 48:1509–1514.

6. Morosini MI, Canton R, Loza E, del Campo R, Almaraz F, Baquero F. Streptococcus pyogenes isolates with characterized macrolide resistance mechanisms in Spain: in vitro activities of telithromycin and cethromycin. J Antimicrob Chemother. 2003. 52:50–55.

7. Farrell DJ, Morrissey I, Bakker S, Felmingham D. Molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae and Streptococcus pyogenes isolated from the PROTEKT 1999-2000 study. J Antimicrob Chemother. 2002. 50:Suppl S1. 39–47.

8. Sunaoshi K, Nakayama E, Kobayashi R, Suzuki E, Tajima T, Ubukata K. Antibiotic susceptibility and T type identification of Streptococcus pyogenes isolated from pediatric outpatients with pharyngotonsillitis. Jpn J Chemother. 2004. 52:401–407.

9. Ubukata K, Chiba N, Hasegawa K, Kobayashi R, Iwata S, Sunakawa K. Antibiotic susceptibility in relation to penicillin-binding protein genes and serotype distribution of Streptococcus pneumoniae strains responsible for meningitis in Japan, 1999 to 2002. Antimicrob Agents Chemother. 2004. 48:1488–1494.

10. Lina G, Quaglia A, Reverdy ME, Leclercq R, Vandenesch F, Etienne J. Distribution of genes encoding resistance to macrolides, lincosamides, and streptogramins among staphylococci. Antimicrob Agents Chemother. 1999. 43:1062–1066.

11. Ross JI, Eady EA, Cove JH, Cunliffe WJ, Baumberg S, Wootton JC. Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family. Mol Microbiol. 1990. 4:1207–1214.

12. Schmitz FJ, Petridou J, Milatovic D, Verhoef J, Fluit AC, Schwarz S. In vitro activity of new ketolides against macrolide-susceptible and -resistant Staphylococcus aureus isolates with defined resistance gene status. J Antimicrob Chemother. 2002. 49:580–582.

13. Canton R, Loza E, Morosini MI, Baquero F. Antimicrobial resistance amongst isolates of Streptococcus pyogenes and Staphylococcus aureus in the PROTEKT antimicrobial surveillance programme during 1999-2000. J Antimicrob Chemother. 2002. 50:Suppl S1. 9–24.

14. Okubo T, Iyobe S, Fujiki Y, Sagai H. Antimicrobial activities of macrolides against recent clinical isolates, and analysis of resistant mechanisms. Jpn J Antibiot. 2003. 56:163–170.

15. Hsueh PR, Teng LJ, Wu TL, Yang D, Huang WK, Shyr JM, Chuang YC, Wan JH, Yan JJ, Lu JJ, Wu JJ, Ko WC, Chang FY, Yang YC, Lau YJ, Liu YC, Lee CM, Leu HS, Liu CY, Luh KT. Telithromycin and fluoroquinolone-resistant Streptococcus pneumoniae in Taiwan with high prevalence of resistance to macrolides and beta-lactams: SMART program 2001 data. Antimicrob Agents Chemother. 2003. 47:2145–2151.

16. Peric M, Bozdogan B, Jacobs MR, Appelbaum PC. Effects of efflux mechanism and ribosomal mutations on macrolide susceptibility of Haemophilus influenzae clinical isolates. Antimicrob Agents Chemother. 2003. 47:1017–1022.

17. Sanchez L, Pan W, Vinas M, Nikaido H. The acrAB homolog of Haemophilus influenzae codes for a functional multidrug efflux pump. J Bacteriol. 1997. 179:6855–6857.