Impurity profiling of Cefteram pivoxil based on Fourier transform ion cyclotron resonance MS.

Profiling impurities for the active pharmaceutical ingredients (APIs) is an indispensable step in drug development process. Nowadays, high resolution mass spectrometry is the first choice for determining the chemical formula of organic impurities. However, merely base on the accurate mass to screen the formula is obviously not a flawless method. In this paper, a reliable strategy based on Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was presented to profile the related impurities. Firstly, Cefteram pivoxil was subjected to forced degration under hydrolytic (acidic and basic), oxidative, photolytic and thermal conditions according to ICH guidelines. Then, a highly specific and efficient HPLC-FT-ICR MS compatible method was developed and it was used to separate and characterize the process related substances and the major degradation products in Cefteram pivoxil. Next, isotopic fine structures (IFSs) of all impurities were acquired to decisively determine their elemental composition. Finally, the possible chemical structures of impurities were predicted by combining the information of accurate mass, retention time, IFSs and characteristic fragmentation ions. As a result, a total of 20 related substances including 6 process related substances and 14 degradation products were identified and characterized. To the best of our knowledge, 13 of these related substances were not reported in the previous literature. It indicates that the developed strategy is accurate and standard independent to determine the chemical formulae of organic impurities in APIs. In conclusion, the impurity profiles obtained in this study are critical to the quality control and stability study of Cefteram pivoxil. Moreover, the developed method can be used as a versatile workflow to profile the impurities in APIs in the future, especially for the unknown impurities.

Consensus guidance of nebulizer therapy for acute rhinosinusitis.

The guidance deals with the recommended applications, procedures, and safety management of nebulizer therapy for acute rhinosinusitis. In Japan, nebulizer therapy for sinusitis has been covered by public health insurance since 1958 and has been commonly carried out nationwide. The Japan Society for Infection and Aerosol in Otorhinolaryngology and the Oto-Rhino-Laryngological Society of Japan set up a working group to draw up a consensus guidance on nebulizer therapy for acute rhinosinusitis. The device for nebulizer therapy are classified into jet, ultrasound, and mesh types. In Japan, cefmenoxime hydrochloride (CMX) was approved for use in nebulizer therapy since 1996. The widening of the obstructed lesions such as large polyps prior to nebulizer therapy were recommended. The numbers of times of nebulizer therapy is recommended for three times in a week for at least for 2 weeks (cure rate: 68%, eradication ratio: 48%). Concerns should be pay for the changes of activity of medicine due to the mixing and bacterial contamination. Pseudomonas cepacia growing in a short even in both saline and distilled water leads to contamination at high concentrations by 2 days. Nebulizer therapy is an effective treatment based on a drug delivery system (DDS) to the nasal and paranasal cavities. The therapy effectively increases the local drug concentration by promptly and uniformly delivering drugs to a targeted local site. The therapy is safe with less systemic absorption and with few adverse reactions.

A super-infection in the cornea caused by Stemphylium, Acremonium, and α-Streptococcus.

BACKGROUND: Polymicrobial keratitis with fungus and bacteria can lead to blindness and is challenging to treat. Here, we introduce a case of fungal keratitis caused by two different strains in addition to definite bacterial super-infection caused by an α-Streptococcus sp., and describe the importance of microscopic examination. CASE PRESENTATION: A 74-year-old woman, who had a past history of infection with leprosy, presented with conjunctival hyperaemia, pain, and corneal opacity in her right eye. Under the presumptive diagnosis of infectious keratitis, corneal scrapings were stained by various reagents and inoculated on several agar plates. Microscopic findings of the scrapings revealed fungi and a small number of Gram-positive cocci. Multiple anti-fungal therapies with levofloxacin ophthalmic solution were administered. Although empiric treatment was initially effective, keratitis recurred 10 days after its initiation. Repeated corneal scraping revealed an abundance of Gram-positive chain cocci and a small amount of fungi, resulting in the switching of an antibiotic medication from levofloxacin to moxifloxacin and cefmenoxime. Keratitis resolved gradually after the conversion. Stemphylium sp., Acremonium sp., and α-Streptococcus sp. were simultaneously isolated from the corneal scrapings. CONCLUSIONS: To the best of our knowledge, this is the first case of fungal keratitis caused by Stemphylium sp., and also the first case of super-infection in the cornea caused by two different fungi and one bacterium. Microscopic examination of the corneal scrapings was beneficial in rapid decision of changing to appropriate drug according to the dominancy of pathogenicity.

Preparation of Fine Particles with Improved Solubility Using a Complex Fluidized-Bed Granulator Equipped with a Particle-Sizing Mechanism.

A new type of fluidized-bed granulator equipped with a particle-sizing mechanism was used for the preparation of fine particles that improved the solubility of a poorly water-soluble drug substance. Cefteram pivoxyl (CEF) was selected as a model drug substance, and its solution with a hydrophilic polymer, hydroxypropyl cellulose (HPC-L), was sprayed on granulation grade lactose monohydrate (Lac). Three types of treated particles were prepared under different conditions focused on the spraying air pressure and the amount of HPC-L. When the amount of HPC-L was changed, the size of the obtained particles was similar. However, particle size distribution was dependent on the amount of HPC-L. Its distribution became more homogenous with greater amounts of HPC-L, but the particle size distribution obtained by decreasing the spraying air pressure was not acceptable. By processing CEF with HPC-L using a complex fluidized-bed granulator equipped with a particle-sizing mechanism, the dissolution ratio was elevated by approximately 40% compared to that of unprocessed CEF. Moreover, in the dissolution profile of treated CEF, the initial burst was suppressed, and nearly zero order release was observed up to approximately 60% in the dissolution profile. This technique may represent a method with which to design fine particles of approximately 100 µm in size with a narrow distribution, which can improve the solubility of a drug substance with low solubility.

Clinical Characteristics and Bacteriological Profile of Moraxella Keratitis.

PURPOSE: Moraxella species are rare causative pathogens of severe sight-threatening keratitis. The aim of this study was to analyze the clinical presentation, predisposing risk factors, in vitro antimicrobial susceptibility, and treatment associated with Moraxella keratitis. METHODS: We retrospectively reviewed 30 culture-proven cases of Moraxella keratitis from multiple centers in Japan. RESULTS: The mean age of the patients was 58.4 ± 23.4 years. The most common ocular conditions were contact lens wearing (5 patients, 16.7%) and trauma (3 patients, 10.0%). Seven patients had diabetes mellitus. Sixteen patients exhibited hypopyon in association with the corneal focus. Ring-shaped infiltration was found in 9 patients (30.0%), and irregular or amoebic-shaped infiltration was observed in 13 patients (43.3%). Eight patients (26.7%) showed small round infiltrates. All Moraxella isolates were sensitive to fluoroquinolones and aminoglycosides. All were treated with a combination ophthalmic solution containing a fluoroquinolone, tobramycin, and cefmenoxime. Although no patients developed corneal perforation, the response to treatment was slow in all cases; the mean treatment period was 41.9 days. CONCLUSIONS: In Japan, Moraxella keratitis occurs in patients with contact lens wear, trauma, and diabetes mellitus. It presents as a small, round, ring-shaped, irregularly shaped, or amoebic-shaped focus. Moraxella species exhibit good susceptibility to fluoroquinolones and aminoglycosides. Because the treatment response may be very slow, these agents should be continued for a long period of time.

Combination effect of antibiotics against bacteria isolated from keratitis using fractional inhibitory concentration index.

PURPOSE: To study the in vitro interaction of fluoroquinolones such as levofloxacin (LVFX), gatifloxacin (GFLX), or moxifloxacin (MFLX) in combination with tobramycin (TOB) or cefmenoxime (CMX) against clinical isolates of bacteria from keratitis. METHODS: The activity of each drug alone was determined by an agar dilution method. Checkerboard synergy testing was then performed against 47 isolates, including Staphylococcus species, Streptococcus species, and Pseudomonas aeruginosa. Antimicrobial combinations were classified as synergistic, additive, indifferent, or antagonistic, according to their fractional inhibitory concentration. RESULTS: The average fractional inhibitory concentration indexes of combined use of LVFX/CMX or GFLX/CMX in Staphylococcus species and Streptococcus species, and LVFX/CMX, GFLX/CMX, MFLX/CMX in gram-negative rods were low. The additive activity of the following drug combinations were seen in more than 70% of isolates: LVFX/CMX and GFLX/CMX against gram-positive cocci and LVFX/CMX, GFLX/CMX, MFLX/CMX against gram-negative rods. No consistent synergistic or antagonistic effect was observed with the combinations used. CONCLUSION: The combination of LVFX/CMX or GFLX/CMX was predominantly additive for all tested isolates.

In vitro assessment of the cytotoxicity of six topical antibiotics to four cultured ocular surface cell lines.

To determine the cytotoxicity of antibiotic eyedrops to ocular surface cells using a semi-quantitative method, a range of commercially available antibiotic eyedrops were assessed by using three corneal cell lines and one conjunctival cell line. All antibiotic solutions were free of benzalkonium chloride. Cell viability was determined by the MTT assay and neutral red assay following the exposure of cells to the undiluted, 2- and 10-fold diluted drugs for 10, 30, and 60 min. Toxicity was compared using % cell viability score (%CVS) . The tested eyedrops and values of %CVS50 and %CVS40/80 were Bestron(®) (cefmenoxime, 100, 94) , Panimycin(®) (dibekacin, 86, 58) , Noflo(®) (norfloxacin, 90, 50) , Cravit(®) (levofloxacin, 86, 46) , Tosfulo(®) (tosufloxacin, 57, -3) , and Vigamox(®) (moxifloxacin, 57, -6) . Cell viability markedly increased after dilution. For instance, cell viability assayed by MTT was > 80% for all the measurements in antibiotics diluted 10-fold, and the rate of the measurements showing > 80% cell viability decreased to 43% (31 out of 72 measurements) in the solutions diluted 2-fold. Of the drugs tested, Bestron(®) containing cefmenoxime showed the weakest toxicity. Vigamox(®) containing moxifloxacin and Tosuflo(®) containing tosufloxacin were more toxic when compared with the other antibiotics. CVS was useful for the comparison of the cytotoxicity of the drugs.

[Drug sensitivity of causative agents in ocular infection of external adnexa and anterior segments--multicenter study of causative agents and drug sensitivity of ocular infection by the Japanese Association for Ocular Infection part II].

PURPOSE: To report the drug sensitivity of causative agents produced by ocular infection of external adnexa and anterior segments investigated by the nationwide survey conducted by Japanese Association for Ocular Infection between September, 2007 and August, 2008. SUBJECTS AND METHODS: Among all strains isolated, causative and presumed causative agents were selected according to the criteria described, and drug sensitivity tests were conducted by minimum inhibitory concentrations (MIC) with 10 kinds of antimicrobial agents including 5 fluoroquinolones. RESULTS: Among 281 causative isolates, cefmenoxime (CMX) showed the highest sensitivity, followed by fluoroquinolones. Staphylococci and Streptococci were more sensitive to fluoroquinolones when compared to the others. Haemophilus influenzae was very sensitive to all fluoroquinolones. Corynebacterium spp. and Propionibacterium acnes were most sensitive to CMX and erythromycin respectively. CONCLUSION: CMX and fluoroquinolones showed generally good sensitivity among causative pathogens of ocular infection.

New Sensitization to House Dust Mites in Cefteram-Induced Occupational Asthma: A Case Report

Occupational asthma (OA) can improve after cessation of exposure; however, some patients suffer from persistence or aggravation of their asthmatic symptoms. Here we report a case of a new sensitization to house dust mites during the follow-up period in a 37-year-old female patient with OA induced by cefteram pivoxil powder (cefteram powder). She was previously diagnosed with OA caused by inhalation of cefteram powder. Consequently, she left her job and had been well for 9 subsequent years. She began to experience aggravation of her rhinitis and asthmatic symptoms again several months prior to presentation. Her skin-prick test results had converted to strongly positive responses to two types of house dust mites. The serum levels of eosinophil cationic protein (ECP) and the total and specific immunoglobulin (Ig)E levels against the two types of house dust mites were elevated. An inhalation challenge test with Dermatophagoides farinae was performed, and significant bronchoconstriction (21.1% reduction in the forced expiratory volume in the first second) with asthma symptoms was observed at 10 minutes. To our knowledge, this is the first case demonstrating a new sensitization to house dust mites in a patient with OA caused by cefteram powder. Regular monitoring, including skin-prick tests and measurement of specific serum IgE/ECP levels, may help to screen potential cases.

[Evaluation of antimicrobial prophylaxis after normal delivery].

In Japan, as a measure to prevent puerperal infection, oral antimicrobial prophylaxis has been conducted after delivery in many maternity clinics. However, there are only a few reports on the evidence supporting the validity of antimicrobial prophylaxis following normal delivery. There is concern that unnecessary antimicrobial administration may be conducted in such clinics. In the present study, the puerperal females after normal delivery were placed on different treatments. A group of females received no oral antimicrobial administration. The remaining females were given cefteram pivoxil (CFTM-PI) in the two different doses. In this manner, we evaluated usefulness of antimicrobial prophylaxis. We compared three treatment groups with respect to the incidence of infection for the period until the first week after discharge, and obtained the following results: non-antimicrobial prophylaxis group (group A), 5.83%; antimicrobial prophylaxis group (group B), 1.77%; antimicrobial prophylaxis group (group C), 0%. In group B, the puerperal females were orally given CFTM-PI in a total daily dose of 300 mg, three times daily for three days. In group C, the puerperal females were orally given CFTM-PI in a total daily dose of 300 mg, three times daily for five days. The incidence of infection was the lowest in group C which was followed by group B and group A in this order and the significant intergroup difference was recognized (p=0.004). We also compared the total counts of bacteria, aerobes and anaerobes in lochia on the fifth day during the puerperal period with those on the first day in each treatment group. The decrease in bacterial count was the largest in group C, which was followed by group B and group A in this order. Compared with the total bacterial counts obtained on the first day, those obtained on the fifth day decreased significantly (p<0.001). The results of the present study showed usefulness of antimicrobial prophylaxis after normal delivery. As one of the factors, a significant decrease in the count of bacteria in lochia seems to contribute toward producing the satisfactory outcome.

Pharmacokinetics and bioequivalence studies of cefteram pivoxil in healthy Chinese volunteers.

A simple, sensitive and specific method has been developed for the determination of cefteram in human plasma. Sample preparation was accomplished through protein precipitation with 20% trichloroacetic acid (v/v) and chromatographic separation was performed on a C18 column at 25 degrees C. The mobile phase consisted of methanol-aqueous 20 mM ammonium acetate (18:82, v/v) at flow rate of 1.0 mL/min. Wavelength was set at 235 nm. The lower limit of quantification was 0.04 microg/mL and the assay exhibited a linear range of 0.04-3.2 microg/mL (r=0.9996). The relative recoveries of cefteram from human plasma at three different concentrations were more than 90%. The method was successfully applied to investigate the bioequivalence between two kinds of cefteram pivoxil preparations (test vs reference) in 24 healthy Chinese volunteers. After a single 100 mg dose for the test and reference product, the resulting means of major pharmacokinetic parameters such as AUC(0-t), AUC(0-infinity), Cmax and Tmax of cefteram pivoxil were 4.75 +/- 1.35 vs 4.76 +/- 1.29 microg h/mL, 4.89 +/- 1.36 vs 4.91 +/- 1.29 microg h/mL, 1.65 +/- 0.45 vs 1.73 +/- 0.45 microg/mL and 1.48 +/- 0.59 vs 1.73 +/- 0.45 h, respectively, indicating that these two kinds of preparations were bioequivalent.

Pharmacokinetic and bioequivalence comparison of a single 100-mg dose of cefteram pivoxil powder suspension and tablet formulations: a randomized-sequence, open-label, two-period crossover study in healthy Chinese adult male volunteers.

BACKGROUND: Cefteram pivoxil (CFTM-PI) is an oral antibiotic available in powder suspension and tablet formulations indicated in China for the treatment of bacterial infections. Although these 2 formulations are marketed in China, published information regarding their pharmacokinetics and bioequivalence in the Chinese population is not available. OBJECTIVE: The aim of this study was to compare the pharmacokinetics and bioequivalence of the powder suspension (test) and tablet (reference) formulations of CFTM-PI 100 mg available in China. METHODS: This single-dose, randomized-sequence, open-label, 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 100-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Plasma was assayed using a high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to 6 hours (AUC(0-6)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were obtained at intervals over the 6-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (80%-125%) as established by the US Food and Drug Administration (FDA). Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). RESULTS: Twenty-four Chinese male subjects (mean [range] age,24.2 [23-32] years;weight,64.3 [58-67] kg; height, 172 [167-185] cm) enrolled; all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-6;), and AUC(0-infinity) were 96.5 to 120.1, 95.7 to 110.2, and 96.2 to 110.4, respectively (all, P>0.05). Similar results were found for the data without log-transformation. No AEs occurred or were reported during the study. CONCLUSIONS: In this small study in healthy Chinese adult male volunteers, a single 100-mg dose of the powder-suspension formulation was bioequivalent to a single 100-mg dose of the tablet formulation based on the US FDA's regulatory definition (rate and extent of absorption). Both formulations were well tolerated.

The Effect of Intensive Therapy Using Nebulized Antibiotics after Endoscpic Sinus Surgery / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: There are some difficulties and dilemmas in treating patients who show acute recurrent infection or persistent inflammation after sinus surgery. Recently, nebulized antibiotic therapy was recommended as another treatment option for these patients. Our study was to evaluate the effect of nebulized antibiotic therapy in these patients. SUBJECTS AND METHOD: We selected 38 adult patients who had received endoscopic surgery previously. They were patients of the refractory group who have showed persistent purulent rhinorrhea despite treatment for 2 months after sinus surgery and the acute exacerbation group who have showed repeated worsening of their symptoms more than 3 times for 6 months. Cultures were taken from all cases and proper oral antibiotics were used based on their culture results. Oral antibiotics were stopped during the nebulized antimicrobial therapy. Nebulized antibiotics therapy was performed 5 times a week for 4 weeks with cefmenoxime hydrochloride using ultrasonic nebulizer. The symptom score and endoscopic appearance were checked also before and 1, 2 and 3 months after the treatment. RESULTS: In 38 patients, 6 patients were excluded due to follow up loss or voluntary stop of treatment and 32 patients were available. S. aureus, P. aeruginosa and coagulase-negative Staphylococcus were most common organisms in all patients. The symptom score and endoscopic appearance after the treatment showed significant improvement. No complication was found in all cases. CONCLUSION: Nebulized antibiotic therapy might be considered as another therapeutic option for patients with refractory or acute exacerbation of chronic rhinosinusitis after endoscopic sinus surgery.

Ceftezole, a cephem antibiotic, is an alpha-glucosidase inhibitor with in vivo anti-diabetic activity.

Using a high throughput-compatible assay to screen for potential alpha-glucosidase inhibitors, we found that the beta-lactam antibiotic ceftezole exhibited potent alpha-glucosidase inhibitory activity. In in vitro alpha-glucosidase assays, ceftezole was shown to be a reversible, non-competitive inhibitor of yeast alpha-glucosidase with a Ki value of 5.78 x 10(-7) M when the enzyme mixture was pretreated with ceftezole. Using an in vivo streptozotocin-induced mouse model, we confirmed that blood glucose levels decreased by 30% 20 min after ceftezole treatment (10 mg/kg/day). Expression levels of glycogen synthase kinase-3, peroxisome proliferator-activated receptor-gamma, and uncoupling protein-3 mRNA were also slightly decreased compared to controls following ceftezole treatment. Taken together, these in vivo and in vitro results suggest that ceftezole may be a clinically useful anti-diabetic compound.

In vitro synergistic effects of double combinations of beta-lactams and azithromycin against clinical isolates of Neisseria gonorrhoeae.

In Japan, Neisseria gonorrhoeae, a sexually transmitted pathogen, has recently shown significant resistance to various antimicrobial agents. In this study, a checkerboard method was utilized to investigate the in vitro activities of cefixime (CFIX), cefteram (CFTM), or amoxicillin (AMPC) in combination with azithromycin (AZM) against 25 clinical isolates of N. gonorrhoeae. Synergy, defined as a fractional inhibitory concentration (FIC) index of less than or equal to 0.50, was observed in 32% of isolates with CFIX+AZM, 12% of isolates with CFTM+AZM, and 4% of isolates with AMPC+AZM. Moreover, partial synergy, defined as an FIC index of greater than 0.50 and less than 1, was observed in 44% of isolates with CFIX+AZM, 68% of isolates with CFTM+AZM, and 52% of isolates with AMPC+AZM. In particular, as a result of the combination of CFIX and AZM, for all isolates, significant reductions were observed in the median CFIX minimum inhibitory concentration (MIC; from 0.25 to 0.008 microg/ml; P < 0.0001) and the median AZM MIC (from 0.12 to 0.03 microg/ml; P < 0.0001). However, antagonism, defined as an FIC index of greater than 1, was observed in only 4% of the isolates with both CFIX+AZM and CFTM+AZM, while it was seen in 12% of the isolates with AMPC+AZM. To our knowledge, this is the first study to demonstrate that the in vitro activity of CFIX against N. gonorrhoeae can be significantly enhanced in combination with AZM.

Enhancement of antimicrobial activities of cefteram or clavulanic acid/amoxicillin against cefixime-resistant Neisseria gonorrhoeae in the presence of clarithromycin or azithromycin.

We investigated the enhancement of the antimicrobial activities of beta-lactams against cefixime (CFIX)-resistant Neisseria gonorrhoeae in the presence of macrolides. Ten strains of CFIX-resistant N. gonorrhoeae, isolated between 2000 and 2003 from male patients with urethritis at Jikei University Affiliated Hospital and its related clinics in the Tokyo metropolitan area, were tested. The fractional inhibitory concentrations of clavulanic acid/amoxicillin (CVA/AMPC), CFIX, or cefteram (CFTM), in the presence of clarithromycin (CAM) or azithromycin (AZM), against these strains were determined. Synergism, partial synergism, or additivity was recognized between CVA/AMPC or CFTM and macrolides against nine strains. Additivity and partial synergism between CFTM and macrolides against nine and ten strains, respectively, were also recognized. On the other hand, antagonism between CFIX and macrolides was recognized. These results indicate that combination antimicrobial chemotherapy, using CFTM or CVA/AMPC with macrolides, is a possible alternative treatment for CFIX-resistant N. gonorrhoeae infections.

[The effect of preoperative topical antibiotics in cataract surgery].

PURPOSE: We studied whether topical antibiotics prevent endophthalmitis after cataract surgery. METHODS: Cefmenoxime hydrochloride (CMX) or artificial tears (AT) were randomly instilled 72 hours before surgery. Conjunctival swab samples were taken before the instillation of eye drops (1) and after the instillation of eye drops (2). Aqueous humor (3) was cultured intraoperatively. RESULTS: Positive cultures were found in the CMX group of eyes in 76.3% of (1) samples, 58.1% of (2) samples, and 6.0% of (3) samples. In the AT group of eyes, positive cultures were found in 78.6% of (1) samples, 63.8% of (2) samples, and 2.9% of (3) samples. CMX was not effective. In the CMX group of eyes, Staphylococcus epidermidis was found in 59 eyes of group (1), 5 eyes of group (2), and 0 eyes of group (3). In the AT group of eyes, S. epidermidis was found in 70 eyes of group (1), 26 eyes of group (2), and 1 eye of group (3). In the cases where S. epidermidis was decreased by CMX topical use Propionibacterium acnes was increased. CONCLUSIONS: There is a possibility that preoperative topical use of CMX can reduce S. epidermidis. On the other hand, it might increase P. acnes. Considering these results and the fact that there was no difference in effectiveness in the aqueous humor cultures, preoperative CMX topical use may not prevent postoperative endophthalmitis except for endophthalmitis due to S. epidermidis.

Effect of Topical Antibiotics to Mouse Model of Acute Rhinosinusitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES : Administration of antibiotics is an essential modality to treat acute rhinosinusitis. Although intranasal inoculation of antibiotics does not have definite bioavailability, it is a very effective method to treat acute rhinosinusitis. We made a mouse model of rhinosinusitis by inoculation of Streptococcus pneumoniae and administrated time-dependent antibiotics or concentration-dependent antibiotics as a topical manner and investigated their effectiveness. SUBJECTS AND METHOD : Fifty 10-week old male C57BL/6 mice were employed for acute rhinosinusitis model. Mice were inoculated with Streptococcus pneumoniae, and from the 6th to 10th day, we made the negative control group by inoculation of normal saline (Group I), the antibiotics group by inoculation of cefmenoxime & vancomycin (Group II), the ofloxacin & tobramycin group (Group III), and the positive control group (Group IV). On the 11th day, all mice were sacrificed and the effectiveness of antibiotics was evaluated by comparison of nasal lavage colony count and neutrophil count of the sinonasal tissue. RESULTS : Minimum bactericidal concentration (MBC) of each antibiotics was cefmenoxime 20 microgram/ml, ofloxacin 80 microgram/ml, tobramycin 25 microgram/ml, vancomycin 12.5 microgram/ml. By nasal lavage, antibiotics inoculation group (Group II, III) had more decreased bacterial growth than the positive control, and it was statistically significant (p=0.037). Comparision between the group administrated with concentration-dependent antibiotics and time-dependent antibiotics, clusters of neutrophil decreased in two groups compared to positive control revealed that the group administered with concentration-dependent antibiotics had fewer clusters of neutrophil than the group administered with time-dependent antibiotics, and it was statistically significant. CONCLUSION : Local inoculation of concentration dependent antibiotics could be a more effective way to treat acute rhinosinusitis induced by Streptococcus pneumoniae than time dependent antibiotics.