Download Antimicrobial activities of tosufloxacin against Streptococcus

J Infect Chemother (2005) 11:253–255
DOI 10.1007/s10156-005-0397-8
© Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2005
NOTE
Kenji Suzuki · Toshiyuki Fujisawa · Mayuki Nakashima
Risa Hamasaki
Antimicrobial activities of tosufloxacin against Streptococcus pneumoniae,
Haemophilus influenzae, and Moraxella branhamella catarrhalis isolated
from otolaryngological infectious diseases
Received: January 5, 2005 / Accepted: June 29, 2005
Abstract In 2003, the Japan Society for Infectious Diseases
in Otolaryngology conducted its third nationwide survey of
clinical isolates from otolaryngological infectious diseases.
We selected three primary causative organisms of otolaryngological infectious diseases, Streptococcus pneumoniae,
Haemophilus influenzae, and Moraxella Branhamella
catarrhalis, and evaluated their sensitivities to tosufloxacin
(TFLX), a new oral quinolone, because the survey revealed
a rise in drug-resistant strains, suggesting potential problems with the antibiotics commonly used against these organisms. The minimum inhibitory concentration (MIC)90
values of TFLX against S. pneumoniae, H. influenzae, and
M. catarrhalis were 0.25 mg/ml, £0.06 mg/ml, and £0.06 mg/ml
respectively, and TFLX was shown to be as effective as
or superior to other new quinolones. In addition, TFLX
showed sufficient antimicrobial effects against frequently
detected drug-resistant bacteria such as penicillin-resistant
S. pneumoniae (PRSP) and b-lactamase-negative, ampicillin-resistant strains of H. influenzae (BLNAR). Furthermore, only a few strains of bacteria showed resistance
to TFLX.
Key words Otolaryngological infectious · Streptococcus
pneumoniae · Haemophilus influenzae · Moraxella
(Branhamella) catarrhalis · Susceptibility · Tosufloxacin
(TFLX)
The Japan Society for Infectious Diseases in Otolaryngology has conducted three nationwide surveys to gather data
on clinically isolated bacteria and their sensitivities to antibacterial agents,1–4 and the results of the surveys have shown
a rise in drug-resistant strains. Especially, the third survey,
K. Suzuki (*) · T. Fujisawa · M. Nakashima · R. Hamasaki
Department of Otolaryngology, Second Hospital, Fujita Health
University School of Medicine, 3-6-10 Otobashi, Nakagawa-ku,
Nagoya 454-8509, Japan
Tel. +81-52-323-5647; Fax +81-52-331-6843
e-mail: [email protected]
conducted in 2003, showed increases in penicillin-resistant
Streptococcus pneumoniae (PRSP)/penicillin-intermediate
resistant S. pneumoniae (PISP) strains among S. pneumoniae, and increases in b-lactamase-negative, ampicillinresistant Haeurophilus influenzae (BLNAR) strains among
H. influenzae,4 indicating the clinical importance of antibiotics that have sufficient antibacterial activity against these
resistant strains.
In this study, we evaluated the strains of three primary causative organisms of otolaryngological infectious
diseases; S. pneumoniae (156 strains), H. influenzae (191
strains), and Moraxella Branhamella catarrhalis (50 strains),
isolated during the third nationwide survey conducted by
the Japan Society for Infectious Diseases in Otolaryngology. These strains accounted for almost 60% of all clinical
isolates found during the survey, and significant increases in
resistant strains among these species were reported. This
third survey was conducted from January 2003 to May 2003
in collaboration with a total of 137 medical institutions,
including the otolaryngology departments of 31 universities, their affiliated facilities, and private clinics throughout
Japan. The clinical isolates were collected from patients
(aged 0 to 82 years) who visited participating institutions
for the treatment of acute suppurative otitis media, acute
sinusitis, acute tonsillitis, and peritonsillar abscess, excluding patients with a history of surgical treatment. The sensitivity of tosufloxacin (TFLX), a new quinolone antibiotic,
was evaluated by measuring the minimum inhibitory concentration (MIC), using the standard method defined by the
Japanese Society of Chemotherapy (broth microdilution
test) so that the results could be directly compared with the
results of the survey for the objective assessment of the
antibacterial activity of TFLX. We compared the measured
antibacterial activity of TFLX with the antibacterial
activity of three new quinolones (ciprofloxacin [CPFX],
levofloxacin [LVFX], and gatifloxacin [GFLX]) and one
ketolide (telithromycin [TEL]) measured during the third
survey. In addition, the antibacterial activity of TFLX was
also compared with that of penicillin G (PCG) against
S. pneumoniae and that of ampicillin (ABPC) against
H. influenzae.
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Table 1. Drug sensitivity of Streptococcus pneumoniae
Antibiotics
PCG
TFLX
CPFX
LVFX
GFLX
TEL
PSSP (63 strains)
PISP (62 strains)
PRSP (31 strains)
Range
MIC50
MIC90
Range
MIC50
MIC90
Range
MIC50
MIC90
⬉0.06
0.12–0.5
0.5–4
0.5–2
0.25–1
⬉0.06–1
⬉0.06
0.25
2
1
0.5
⬉0.06
⬉0.06
0.25
2
2
0.5
0.125
0.125–1
⬉0.06–0.25
0.25–2
0.25–2
0.06–0.5
⬉0.06–2
0.5
0.25
1
1
0.5
⬉0.06
1
0.25
2
2
0.5
0.25
2–4
0.12–0.25
0.5–2
0.5–2
0.25–1
⬉0.06–0.5
2
0.12
1
1
0.5
0.125
2
0.25
2
2
0.5
0.25
PCG, penicillin G; TFLX, tosufloxacin; CPFX, ciprofloxacin; LVFX, levofloxacin; GFLX, gatifloxacin; TEL, telithromycin; PSSP, penicillinsusceptible S. pneumoniae (MIC of PCG, <0.063 mg/ml; PISP, penicillin-intermediate resistant S. pneumoniae (MIC of PCG, 0.125–1 mg/ml);
PRSP, penicillin-resistant S. pneumoniae (MIC of PCG, >2 mg/ml)
Table 2. Drug sensitivity of Haemophilus influenzae
Antibiotics
ABPC
TFLX
CPFX
LVFX
GFLX
TEL
BLNAS (95 strains)
BLNAR (90 strains)
BLPAR (6 strains)
Range
MIC50
MIC90
Range
MIC50
MIC90
Range
0.125–0.5
⬉0.06
⬉0.06–0.5
⬉0.06–1
⬉0.06–0.5
0.5–8
0.25
⬉0.06
⬉0.06
⬉0.06
⬉0.06
2
0.5
⬉0.06
0.125
0.125
0.125
4
1–32
⬉0.06–0.5
⬉0.06–1
⬉0.06–1
⬉0.06–0.5
0.5–8
2
⬉0.06
⬉0.06
⬉0.06
⬉0.06
2
8
⬉0.06
⬉0.06
⬉0.06
⬉0.06
4
64–256
⬉0.06
⬉0.06
⬉0.06
⬉0.06
1–2
ABPC, ampicilln; TFLX, tosufloxacin; CPFX, ciprofloxacin; LVFX, levofloxacin; GFLX, gatifloxacin; TEL, telithromycin; BLNAS, b-lactamasenegative, ampicillin-sensitive strains of H. influenzae (MIC of ABPC £ 0.5 mg/ml); BLNAR, b-lactamase-negative, ampicillin-resistant strains of
H. influenzae (MIC of ABPC ≥ 1 mg/ml); BLPAR, b-lactamase-positive, ampicillin-resistant strains of H. influenzae (MIC of ABPC ≥ 1 mg/ml)
Table 3. Drug sensitivity of Moraxella (Branhamella) catarrhalis
Antibiotics
TFLX
CPFX
LVFX
GFLX
TEL
b-lactamase (+) (47 strains)
b-lactamase (-) (3 strains)
Range
MIC50
MIC90
Range
⬉0.06
⬉0.06–0.125
⬉0.06–0.125
⬉0.06
⬉0.06–0.5
⬉0.06
⬉0.06
⬉0.06
⬉0.06
0.125
⬉0.06
⬉0.06
0.125
⬉0.06
0.25
⬉0.06
⬉0.06
⬉0.06
⬉0.06
⬉0.06–0.25
TFLX, tosufloxacin; CPFX, ciprofloxacin; LVFX, levofloxacin; GFLX, gatifloxacin; TEL,
telithromycin; b-lactamase(+), production of b-lactamase; b-lactamase(-), irrespective of production of b-lactamase
For the evaluation of antibacterial activity, the isolated
S. pneumonia were classified into three groups, penicillinsusceptible S. pneumoniae (PSSP; MIC of PCG, £0.063 mg/
ml), PISP (MIC of PCG, 0.125–1 mg/ml), and PRSP (MIC of
PCG, ≥2 mg/ml), as defined by the National Committee for
Clinical Laboratory Standards (NCCLS).5 The results are
summarized in Table 1. The MIC90 values of TFLX against
PSSP, PISP, and PRSP were consistently around 0.25 mg/ml,
and TFLX was shown to have the most powerful antimicrobial activity among these new quinolones. In addition, it
was shown that the antibacterial activity of TFLX was
equivalent to that of a ketolide, telithromycin. Furthermore, for the other new quinolones and TEL, there were
strains with MIC90 values of 1–4 mg/ml and 2 mg/ml, respectively, indicating the presence of resistant strains, but there
was no strain suggesting a decrease in the antibacterial
activity of TFLX.
The isolated H. influenzae were classified into three
groups, b-lactamase-negative, ampicillin-sensitive strains
of H. influenzae (BLNAS; MIC of ABPC, £0.5 mg/ml),
BLNAR (MIC of ABPC, ≥1 mg/ml) and b-lactamasepositive, ampicillin-resistant strains of H. influenzae
(BLPAR; MIC of ABPC, ≥1 mg/ml). The results are summarized in Table 2. The MIC90 values of TFLX against
BLNAS, BLNAR, and BLPAR were consistently £0.06 mg/
ml, and it was shown that the antibacterial activity of TFLX
was equivalent to that of the other new quinolones. The
MIC90 values of TEL were 2–4 mg/ml, and it was shown that
the antibacterial activity of TEL against H. influenzae was
inferior to that of the new quinolones.
The isolated M(B). catarrhalis were classified into two
groups, according to the production of b-lactamase. The
results are summarized in Table 3. The MIC90 values of
TFLX against M(B). catarrhalis were £0.06 mg/ml for both
255
b-lactamase-producing and non-producing strains, and it
was shown that the antibacterial activity of TFLX was
equivalent to that of the other new quinolones. The MIC90
value of TEL was 0.25 mg/ml, slightly lower than that of the
new quinolones.
The MIC90 values of TFLX against the three above primary causative organisms for otolaryngological infectious
diseases were the lowest among the antibacterial agents that
were evaluated, and it was shown that TFLX had sufficient
antibacterial activity against these three organisms. In addition, TFLX was shown to be the antibiotic with the leastresistant strains. Furthermore, the antibacterial activity of
TFLX was shown to be one of the best among the
quinolones used for respiratory infections. This is a very
important factor for selecting a drug. The incidence of
PRSP/PISP among S. pneumoniae increased from 50.9% in
the second survey to 59.6% in the third survey, indicating
the serious impact of these resistant strains on the clinical
use of cephems and macrolides, which are frequently used
to treat tympanitis and sinusitis. In fact, with the rise in the
number of resistant strains, the number of antibiotics that
one can use knowing that they work for sure is decreasing
every year. Therefore, it is believed that agents such as
TFLX, which was shown to be one of the most effective new
quinolones and as effective as TEL against S. pneumoniae,
will play a very important role clinically.
TFLX is recommended as one of the first-line treatment
drugs for tympanitis and sinusitis in adults, in the Prescription guidelines for antibiotics published by the Japanese
Association for Infectious Diseases and the Japanese Society of Chemotherapy.5 The results of the present study
demonstrate the powerful antimicrobial activity of TFLX
and its suitability as an effective treatment drug, and the
results support the use of TFLX as the first-line treatment
drug.
The development of new antibiotics has not kept up with
the development of antibiotic-resistant strains, and now one
cannot expect a steady supply of new antibiotics to fight
these emerging resistant strains. Therefore, it is important
for clinicians to evaluate the use of currently available antibiotics, not only to achieve optimal treatment effects but
also to prevent drug-resistant strains from emerging. TFLX
has potent antibacterial activity against primary causative
organisms such as S. pneumoniae, H. influenzae, and M(B).
catarrhalis, and there are only a few strains resistant to
TFLX. These characteristics make TFLX a very useful
agent for the treatment of infections with primary causative
organisms, and TFLX should be considered as one of the
first-line treatment drugs for these infections.
References
1. Baba S, Ohyama M, Kataura A, Togawa K, Takasaka T, Ichikawa
G, et al. First report on a nationwide survey of clinical isolates from
patients with tympanitis and sinusitis: prevalence of isolates from
patients with tympanitis and sinusitis (in Japanese). J Jpn Soc Infect
Otolaryngol Dis 1996;14:70–83.
2. Baba S, Ohyama M, Kataura A, Togawa K, Takasaka T, Ichikawa
G, et al. Second report of nationwide survey of clinical isolates from
patients with tympanitis and sinusitis: sensitivity of isolates to oral
antibiotics (in Japanese). J Jpn Soc Infect Otolaryngol Dis 1996;
14:84–98.
3. Suzuki K, Nishimura T, Baba S. Current status of bacterial resistance in the otolaryngology field: results from the Second Nationwide Survey in Japan. J Infect Chemother 2003;1:46–52.
4. Nishimura T, Suzuki K, Oda M, Kobayashi T, Yajin K, Yamanaka
N, et al. Report of the results of the third nationwide survey of
clinical isolates from patients with infectious otolaryngological diseases (in Japanese). J Jpn Soc Infect Otolaryngol Dis 2004;22:12–23.
5. Suzuki K. II-10 Otolaryngological infectious diseases. Prescription
guidelines for antibiotics (in Japanese). (edited by The Japanese
Society of Chemotherapy and The Japanese Association for Infectious Diseases) Tokyo: Kyowakikaku; 2001; p. 136–41.