JAC Advance Access originally published online on July 12, 2006
Journal of Antimicrobial Chemotherapy 2006 58(3):678-679; doi:10.1093/jac/dkl261
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In vitro effects of penicillin and telithromycin on the expression of Streptococcus pneumoniae capsule
Departments of Pediatrics and Medicine, Georgetown University and George Washington University, Schools of Medicine 4431 Albemarle St NW, Washington, DC, USA
*Corresponding author. Tel: +1-301-295-2698; Fax: +1-253-981-8709; E-mail: ib6{at}georgetown.edu
Received 6 April 2006; returned 2 May 2006; revised 2 May 2006; accepted 1 June 2006
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Abstract |
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Objective: To evaluate the effects of subinhibitory concentrations of penicillin and telithromycin on capsular formation by Streptococcus pneumoniae.
Methods: A total of 60 isolates of S. pneumoniae, 20 susceptible, 20 intermediately resistant and 20 resistant to penicillin, were studied. All isolates were susceptible to telithromycin.
Results: All isolates were capsulate when grown without antibiotics. Encapsulation was lower after incubation with telithromycin as compared with penicillin in isolates susceptible to penicillin (20% versus 75%), in those intermediately resistant to penicillin (25% versus 95%) and in isolates fully resistant to penicillin (15% versus 100%) (P < 0.01).
Conclusions: Telithromycin appears to be superior to penicillin in reducing the expression of the capsule by S. pneumoniae.
Keywords: S. pneumoniae , capsular formation , resistance
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Introduction |
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Streptococcus pneumoniae is a common cause of acute otitis media, sinusitis and pneumonia. Isolates that exhibit intermediate susceptibility or full resistance to penicillin are increasingly prevalent reaching 40–50% of the number of isolates and this complicates management of infections caused by this organism.1 Penicillin-resistant S. pneumoniae are also often resistant to other commonly prescribed antibiotics such as macrolides, some cephalosporins and trimethoprim–sulfamethoxazole,2 but 99.5% are susceptible to telithromycin.1,3 Telithromycin is the first ketolide antibacterial approved for the treatment of community-acquired respiratory tract infections.3
The virulence of S. pneumoniae is partly attributed to its capsule, which enables it to escape phagocytosis.4 Interruption of capsule production in S. pneumoniae by the use of transposon mutagenesis renders the organism avirulent.5
Subinhibitory concentrations of clindamycin, which has a mode of antimicrobial activity similar to telithromycin, have been shown to suppress the capsular formation of S. pneumoniae.6 We compared the influence of subinhibitory concentrations of penicillin with telithromycin on the expression of capsule by S. pneumoniae in vitro.
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Materials and methods |
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S. pneumoniae were isolated from endoscopically obtained cultures from patients with acute maxillary sinusitis. The organisms were identified by characteristic colony morphology and alpha-haemolysis, confirmed by susceptibility to ethylhydrocupreine (Optochin®) and bile solubility.7
Routine screening of penicillin susceptibility was carried out with a 1 µg oxacillin disc on sheep blood-supplemented Mueller–Hinton agar. A strain was suspected of penicillin resistance when the zone of inhibition surrounding the disc measured <20 mm after incubation for 24 h with CO2 at 35°C. The MICs of penicillin (Penicillin-G, Bristol-Myers, Squibb, Princeton, NJ, USA) and telithromycin (Sanofi-Aventis, Bridgewater, NJ, USA) for each isolate were determined by the agar dilution method. Mueller–Hinton agar supplemented with 5% sheep blood was used, as recommended by the National Committee for Clinical Laboratory Standards.8 The final inocula contained 1 x 104 to 3 x 104 cfu spot. The MIC was defined as the lowest drug concentration that prevented visible growth or yielded fewer than six discrete colonies.
To investigate the effect of subinhibitory concentrations of penicillin or telithromycin on capsule formation, isolates of S. pneumoniae (106 organisms in 1 mL) were incubated for 48 h at 37°C in 9 mL of Todd–Hewitt broth medium that included the antibiotic at 0.5 MIC. A tube without antimicrobial agents served as a control. The presence of a capsule was evaluated by negative staining with India ink.7 Capsules were observed by light microscopy at 1000x magnification. An isolate was considered to be capsulated if a capsule was seen in more than 75% of 500 bacterial cells. The specimens were coded to prevent observer bias. Statistical analysis was performed by the 
2 test and Fisher exact test.
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Results |
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A total of 60 isolates of S. pneumoniae were included in the study: 20 susceptible, 20 intermediately resistant and 20 fully resistant to penicillin. All isolates were susceptible to telithromycin (MIC 0.025–0.05 mg/L).
All isolates were capsulate when grown without antibiotics. Encapsulation was lower after incubation with telithromycin as compared with penicillin in isolates susceptible to penicillin (20% versus 75%), in those intermediately resistant to penicillin (25% versus 95%) and in isolates fully resistant to penicillin (15% versus 100%) (P < 0.01) (Table 1).
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Discussion |
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In the present study, exposure of S. pneumoniae to telithromycin at 0.5 MIC commonly suppressed the formation of the capsule, whereas a subinhibitory concentration of penicillin was less effective in this respect. The inability of penicillin to suppress capsule formation has previously been demonstrated in experiments in which the concentration of S. pneumoniae in the growth media was >106–107 organisms/mL.9
The growing resistance of S. pneumoniae to penicillin and other antimicrobial agents requires use of alternative effective drugs. More than 99% of penicillin-resistant S. pneumoniae isolates are currently susceptible to telithromycin1,3 and suppression of capsule formation is an additional beneficial quality that might enhance the eradication of the organism. Further studies are warranted to evaluate the ability of telithromycin and other antimicrobials to suppress capsular formation by other pathogens.
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We have no conflicts of interest involving this study.
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References |
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1 Karchmer AW. (2004) Increased antibiotic resistance in respiratory tract pathogens: PROTEKT US—an update. Clin Infect Dis 39:Suppl 3:, S142–50.
2 Jacobs MR. (2004) Streptococcus pneumoniae: epidemiology and patterns of resistance. Am J Med 117:Suppl 3A:, 3–15S.[CrossRef]
3 File TM. (2005) Telithromycin new product overview. J Allergy Clin Immunol 115:S1–13.[Medline]
4
Musher DM, Johnson B Jr, Watson DA. (1990) Quantitative relationship between anticapsular antibody measured by enzyme-linked immunosorbent assay or radioimmunoassay and protection of mice against challenge with Streptococcus pneumoniae serotype 4. Infect Immun 58:3871–6.
5
Watson DA and Musher DM. (1990) Interruption of capsule production in Streptococcus pneumoniae serotype 3 by insertion of transposon Tn916. Infect Immun 58:3135–8.
6 Brook I and Gober AE. (1996) In-vitro effects of penicillin and clindamycin on the expression of Streptococcus pneumoniae capsule. J Med Microbiol 45:505–6.[Abstract]
7 Murray PR, Baron EJ, Jorgensen JH, et al. (2003) Manual of Clinical Microbiology. 8th edn (American Society for Microbiology, Washington, DC).
8 National Committee for Clinical Laboratory Standards. (2003) Methods For Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically: Approved Standard M7-A6. (NCCLS, Wayne, PA, USA).
9 Holloway Y, Boersma WG, Kuttschrütter H, et al. (1993) Detection of pneumococcal capsular antigen in the presence of penicillin in vitro. Scand J Infect Dis 25:317–22.[ISI][Medline]
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