Volume 39, Issue 13 December 2012
2573
A case of bisphosphonate-related osteonecrosis of the jaw (Stage 0) successfully treated with
Sitafloxacin
Tetsuya Ikeda and Naoyuki Kohno*
Summary
In recent years, many authors have published reports on bisphosphonate-related osteonecrosis of the
jaw (BRONJ). However, many clinicians have been confused by these reports because of the diagnostic
criteria for BRONJ and because there are no definitive treatment guidelines. In this paper, we report on a
patient who had BRONJ (Stage 0) after dental extraction. She was successfully treated with the antibiotic
sitafloxacin (STFX). A 73-year-old female had been taking 35 mg of alendronate per week for 24 months
for the treatment of osteoporosis. She underwent extraction of the left mandibular second molar; and,
despite the post-operative administration of several antibiotics, the wound would not heal. One month
after the extraction, the patient was still suffering from incomplete extraction site healing, and was
diagnosed with BRONJ Stage 0, although there was no bone exposure observed. STFX 200 mg/day was
administered for two weeks, followed by 100 mg per day for one week. At three weeks after
administration, the extraction site wound was completely healed. Also, the MIC of bacteria isolated,
cultured and identified from the pus of the present case was measured, and it was found that STFX has
superior anti-bacterial properties to those of other antibiotics. Based on this, we considered SFTX to be
efficacious against BRONJ.
……………………………………………………………………………
Introduction
We experienced a case who underwent tooth
Bisphosphonate (BP) agents are widely used in
extraction 24 months after the commencement
treating diseases such as solid tumor bone
of BP therapy, and who was still suffering from
metastases, multiple myeloma, hypercalcaemia
incomplete healing of an extraction wound even
due to malignant tumors, and osteoporosis,
one month after the procedure, and in which
because they have a bone turnover suppression
healing was achieved after three weeks of
action 1, 2). Meanwhile, in the last few years
administration
of
sitafloxacin
(STFX).
there have been a large number of reports on
Additionally, we are reporting on an
bisphosphonate-related osteonecrosis of the
investigation into the antibacterial properties of
jaw (BRONJ) with symptoms similar to
STFX against bacteria which were isolated and
intractable osteomyelitis of the jaw bone, which
cultured from the pus from the present case.
is often observed in patients to whom BP
agents are administered 3-5).
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*Ear, Nose and Throat Department, and the Mandibular and Dental Surgery Department, Kyorin
University Hospital
Contact: Tetsuya Ikeda, Ear, Nose and Throat Department, and the Mandibular and Dental Surgery
Department, Kyorin University Hospital
6-20-2, Arakawa, Mitaka, Tokyo, 181-8611
2574
Cancer and Chemotherapy
I. Case
A 73-year-old female
Past history: Administered alendronate for 24 months by
a nearby orthopedic surgery specialist for osteoporosis
Current history: On a pre-treatment x-ray (Fig. 1a), an
image of resorption in the periphery of the tooth root of the
left mandibular second molar was found. Following
diagnosis of the patient with periodontitis, the patient
underwent extraction of the above-mentioned tooth,
followed by one-week administration of cefditoren pivoxil
(CDTR-PI), and minocycline (MINO) for approximately 5
days. Discharge from the extraction wound site and pain
continued even four weeks from the time of extraction (Fig.
2a); therefore, the patient was diagnosed with BRONJ
Stage 0, and 200 mg per day of STFX was administered for
2 weeks (Fig. 2b), followed by one week at 100 mg, after
which the wound was observed to be healed with no bone
exposure (Fig. 1b and 2c.)
STFX is a new quinolone group oral antibiotic which is
indicated for infectious diseases in the fields of pulmonary
medicine, otolaryngology, and dentistry and stomatology.
Also, this drug has strong antibacterial properties against
intra-oral Streptococcus and intra-oral anaerobic bacteria (6)
and this drug also has high permeability through gum tissue
(7)
. Since STFX was highly efficacious against BRONJ in the
present case, we measured the minimum inhibitory
concentration (MIC) against bacteria which were isolated
and cultured from the present case. We followed reports
from Murray et al (8) in carrying out the identification assay
on bacterial sample from the pus from the disease site.
Moreover, we followed the Clinical and Laboratory
Standards Institute (CLSI) method in measuring the MIC of
various antibiotics against bacteria isolated from the pus. In
other words we employed a micro-volume liquid dilution
method for aerobic bacteria and an agar plate dilution
method for anaerobic bacteria. We used the following 10
antibiotics: STFX, levofloxacin, azithromycin, clarithromycin,
amoxicillin, cefcapene, cefdinir, meropenem, minocycline
and clindamycin.
The results identified a total of 5 bacteria types, namely 2
types of aerobic bacteria (Streptococcus anginosus and
Streptococcus constellatus) and 3 types of anaerobic
bacteria (Prevotella buccae, Fusobacterium nucleatum and
Porphyromonas asaccharolytica) (Table 1). The MIC of
STFX against these isolated bacteria was from 0.015µg/ml
to 0.06µg/ml, and STFX showed the highest antibacterial
properties compared to other antibiotics.
II. Discussion
In recent years, there have been a large number of reports
on BRONJ in Japan, and the position paper issued by the
BP related jaw bone necrosis investigation committee (9)
has certain guidelines for the evaluation and treatment
policies of BRONJ. However, since patients will not be
diagnosed with BROJ unless 8 weeks of jaw bone exposure
is observed, there is a possibility that there will be delay in
response leading to late treatment. Based on this, our
department considers that the Stage 0 is an important
disease period, and we determine that a patient is in
BRONJ Stage 0 if a BP agent was administered to the
patient even for a short period and if incomplete healing of
the gum wound is observed, and we administer STFX to
such patients. As it is clearly seen in the present
investigation, STFX is observed to have highly favorable
antibacterial properties against BONJ (Table 1). Also, STFX
is considered to be a drug which has high permeability
through jaw bone tissue; therefore STFX is an antibiotic of
the last resort if other antibiotics are not efficacious. Hosaka
et al. reported that the MIC of STFX against periodontal
disease-related bacteria was 0.25µg/ml (6). Since the
present investigation found that BRONJ pathogenic
bacteria have the same qualities as those of periodontal
disease-related bacteria, we consider that the results
showed superior antibacterial properties of STFX in the
same way as in the report by Hosaka et al. We anticipated
that STFX is particularly and remarkably efficacious in the
clinic for patients at Stage 0 with whom bone exposure is
not observed, such as in the present case. Additionally, the
patient in the present case suffered from osteoporosis, and
we anticipate that STFX is also efficacious against BRONJ
due to injectable BP agents administered to patients
suffering from malignant tumors.
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