Journal of Antimicrobial Chemotherapy (2000) 45, 709–717
JAC
Correspondence
Penicillin resistance in pneumococci
J Antimicrob Chemother 2000; 45: 710–711
David Felminghama*, Yese Tesfaslasiea,
Carol Burleyb and Robert G. Mastertonc
a S. pneumoniae exhibiting low-level penicillin resistance
GR Micro Ltd, 7–9 William Road, London
NW1 3ER; bHoechst Marion Roussel,
Broadwater Park, Denham, Uxbridge UB9 5HP;
c amoxycillin–clavulanate. Furthermore, a large proportion
Department of Clinical Microbiology,
Western General Hospital, Crewe Road,
Edinburgh EH4 2XU, UK
*Corresponding author. Tel: 44-171-388-7320;
Fax: 44-171-388-7324;
E-mail: d.felmingham@grmicro.co.uk
Sir,
We read with interest the recent leading article by Legg &
Bint1 but cannot agree with all of the authors’ conclusions.
During the 1997–1998 winter season, an antimicrobial
susceptibility surveillance study of community-acquired
lower respiratory tract isolates of Streptococcus pneu-
moniae was conducted. The isolates were collected from
27 centres in the United Kingdom and Republic of Ireland.
All isolates were sent to a central testing laboratory
(GR Micro Ltd, London, UK) where their identity was
confirmed using a combination of Gram’s stain morphol-
ogy, lack of catalase activity, susceptibility to ethylhydro-
cupreine and solubility in bile salts. MICs of a range of
antimicrobials were determined using the NCCLS broth
microdilution method with interpretation of the data
undertaken for all compounds, except ciprofloxacin, using
NCCLS breakpoint MIC.2,3 Interpretation breakpoints for
use when testing the activity of ciprofloxacin against S.
pneumoniae are not provided by the NCCLS. Therefore,
those published for non-fastidious species (S  1, I  2,
R  4 mg/L), which correspond to those suggested by the
BSAC, were used.4 The results, and their interpretation,
are presented in the Table. Penicillin resistance amongst
isolates of S. pneumoniae is following a different pattern of
evolution in the geographically separated areas of Great
Britain and Ireland. During the study period, 90.9% of
663 combined isolates of S. pneumoniae collected from 21
centres in Great Britain were fully susceptible to penicillin,
3.5% exhibited low-level resistance (MIC 0.12–1 mg/L)
and 5.6% high-level resistance (MIC  2 mg/L). In the
same period, only 72.1% of 154 combined isolates collected
from six centres in Ireland were fully susceptible to peni-
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© 2000 The British Society for Antimicrobial Chemotherapy
cillin, with 4.5% exhibiting low-level resistance and 23.4%
high-level resistance. Whatever the source, more of the
isolates were classified as susceptible to amoxycillin/
clavulanate than to penicillin as a result of the higher
breakpoints for amoxycillin ( clavulanate), which reflect
the greater activity of the compound against strains of
(Table).5 Whatever the geographical location, suscepti-
bility to cefotaxime was similar to or better than that to
of the isolates of S. pneumoniae exhibiting high-level
resistance to penicillin were interpreted as being of inter-
mediate susceptibility (MIC 1 mg/L) to cefotaxime with the
possibility of a clinical response to higher dosage of this
parenteral cephalosporin. Overall, resistance to the macro-
lides (clarithromycin MIC  1 mg/L) was seen in 10.7% of
isolates from Great Britain and 7.1% of those from Ireland.
With regard to the fluoroquinolones, 64% of isolates from
Great Britain and 63.6% from Ireland were susceptible
(MIC  1 mg/L) to ciprofloxacin whereas 99.8% and
100%, respectively, were susceptible to levofloxacin (MIC
 2 mg/L) (Table). However, MICs of both ciprofloxacin
and levofloxacin showed an essentially unimodal distribu-
tion for all isolates of S. pneumoniae, with mode values of
1 mg/L for both compounds. Only six isolates (0.7%) had
ciprofloxacin MICs and two isolates (0.2%) had ofloxacin
MICs of  8 mg/L. Legg & Bint1 draw attention to the fact
that levofloxacin has shown efficacy in treating a variety of
respiratory tract infections, which has been confirmed in a
number of published clinical studies.6 Our study shows that
despite the selective pressure brought about by the use of
ciprofloxacin and ofloxacin for the treatment of respiratory
tract and other infections during the past decade, there is
no evidence of widespread evolution of quinolone resist-
ance amongst isolates of S. pneumoniae. Therefore, we
cannot agree with the conclusion drawn by Legg & Bint1
either of the likelihood of the short- to medium-term
evolution of resistance as a result of the acquisition of
sequential mutational events, or of the wisdom of reserving
the fluoroquinolones, with improved activity against S.
pneumoniae, for use in the empirical therapy of lower
respiratory tract infections caused by isolates of the organ-
ism already exhibiting resistance to penicillin or other
antimicrobials. Far better, in our opinion, that these new
compounds be used generally for the treatment of lower
respiratory tract infection, so as to increase the diversity of
bacterial targets attacked and thus to reduce any pressure
for the selection and maintenance of multiply-resistant
isolates.
 Correspondence

Table. Antimicrobial susceptibility of isolates of Streptococcus pneumoniae collected from centres throughout
Great Britain (England, Wales and Scotland) and Ireland (Northern Ireland and the Republic of Ireland) during
the 1997–1998 winter season

Susceptible Intermediate Resistant

Location Antimicrobial agent MIC50 MIC90 Range (%) (%) (%)

Great Britain penicillin 0.03 0.06 0.015–4 90.9 3.5 5.6

(n  663) amoxycillin/clavulanate 0.03 0.06 0.015–4 94.3 0.6 5.1
cefaclor 1 2 0.25–32 90.9 3.5 5.6
cefotaxime 0.06 0.12 0.06–8 94.4 3.9 1.7
clarithromycin 0.06 8 0.06–32 89.3 – 10.7
ciprofloxacin 1 2 0.5–32 64 31.1 4.9
levofloxacin 1 1 0.25–16 99.4 0.3 0.3

Ireland penicillin 0.03 4 0.015–4 72.1 4.5 23.4

(n  154) amoxycillin/clavulanate 0.03 4 0.015–4 75.3 1.3 23.4
cefaclor 1 32 0.5–32 72.1 4.5 23.4
cefotaxime 0.06 1 0.06–4 76.6 17.5 5.9
clarithromycin 0.06 0.06 0.06–32 92.9 – 7.1
ciprofloxacin 1 2 0.5–4 63.6 27.9 8.5
levofloxacin 1 2 0.25–2 100 – –

Interpretative breakpoint MICs (mg/L): penicillin, S  0.06, I  0.12, R  2; amoxycillin/clavulanate, S  0.5, I  1, R  2; cefaclor, predicted by
penicillin; cefotaxime, S  0.05, I  1, R  2; clarithromycin, S  0.25, I  0.05, R  1; ciprofloxacin, S  1, I  2, R  4; levofloxacin, S  2, I  4,
R  8.

Acknowledgements 3. NCCLS. (1998). Performance Standards for Antimicrobial

We wish to express our gratitude to all those microbiolo-
gists, and their staff, who collaborated in this study. The
study was funded by Hoechst Marion Roussel, Denham,
UK.
References
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in their place? Journal of Antimicrobial Chemotherapy 44, 425–7.
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