[Mutant prevention concentrations of garenoxacin against Streptococcus pneumoniae isolates from otorhinolaryngological infections].

The minimum inhibitory concentrations (MICs) and the mutant prevention concentrations (MPCs) of garenoxacin (GRNX), were compared to those of levofloxacin (LVFX), and moxifloxacin (MFLX) against 78 Streptococcus pneumoniae isolates from otorhinolaryngological infections in Japan during the period January 2007 to June 2007. The MIC and MPC for 90% of the isolates (MIC90 and MPC90) of GRNX were 0.06 and 0.12 microg/mL, respectively, and were the lower values than LVFX and MFLX MIC90s and MPC90s. The ratios of MPC/MIC of GRNX were the lower values than those of LVFX and MFLX.

[Antimicrobial susceptibility surveillance of recent isolates from otorhinolaryngological infections to garenoxacin and other antimicrobial drugs].

The antimicrobial susceptibility of 339 isolates from the otorhinolaryngological infections at the otorhinolaryngological departments at 27 universities in Japan, as well as their 108 affiliated hospitals and practitioners during January 2007 to June 2007 was determined to garenoxacin (GRNX), levofloxacin, moxifloxacin, azithromycin, cefditoren, and cefcapene applicable for otorhinolaryngological infections. The in vitro activities of these drugs against the isolates were compared. The quinolones including GRNX were potently active against Streptococcus pneumoniae including penicillin-intermediate and -resistant strains (PISP and PRSP), Streptococcus pyogenes and methicillin-susceptible Staphylococcus aureus, except for MRSA, a major causative pathogens for otorhinolaryngological infection. When MIC ranges, MIC50, MIC80 and MIC90 of three quinolones were compared, it was considered that GRNX was the most active of them. GRNX was potently active against Haemophilus influenzae and Moraxella catarrhalis same as that of other quinolones tested. In conclusion, GRNX exhibits a potently active against fresh isolates from otorhinolaryngological infections, and has an effective potential in the treatment of otorhinolaryngological infections.

Topical ofloxacin for chronic suppurative otitis media and acute exacerbation of chronic otitis media: optimum duration of treatment.

OBJECTIVE: To assess the optimum duration of topical ofloxacin therapy for chronic otitis media and to compare the response between patients with chronic suppurative otitis media (CSOM) and acute exacerbation of chronic otitis media (AE). STUDY DESIGN: Prospective observational study. SETTING: Five university hospitals and 30 affiliated institutions. PATIENTS: A total of 294 patients who presented to the participating institutions with CSOM were enrolled. Among them, 268 patients were evaluable for safety and 237 were evaluable for efficacy (64 with CSOM and 173 with AE . INTERVENTION: Ofloxacin otic solution was administered for as long as 4 weeks. MAIN OUTCOME MEASURES: Clinical and bacteriologic assessment was done weekly during the treatment period. The clinical response was assessed on the basis of the symptom scores. RESULTS: There were no differences between CSOM and AE patients with respect to sex, age, and severity. The most common bacterial isolate from middle ear discharge was Staphylococcus aureus. The clinical response rates in patients with CSOM and AE were 39.1% and 61.3% after 2 weeks of treatment and 57.8% and 75.1% after 4 weeks, respectively, and the bacterial eradication rate was 91.0% at 2 weeks and 94.6% at 4 weeks. Detection of new fungal infection did not increase as the duration of therapy was prolonged. No serious adverse events were reported. CONCLUSIONS: The duration of treatment was shorter and the clinical response was higher in AE patients than in CSOM patients. The standard topical ofloxacin regimen for chronic otitis media should consist of a 2-week course from the aspect of bacteriologic efficacy, although patients showing insufficient symptomatic improvement after 2 weeks may benefit from another 1 or 2 weeks of therapy. Administration of this drug for as long as 4 weeks can increase the clinical efficacy without causing safety problems.

WITHDRAWN: Mutant prevention concentrations of garenoxacin against Streptococcus pneumoniae isolates from otorhinolaryngological infections.

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Genetic characteristics and clonal dissemination of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae strains isolated from the upper respiratory tract of patients in Japan.

We evaluated the recent prevalence of antimicrobial-resistant Haemophilus influenzae isolated from the upper respiratory tracts (URT) of patients in Japan. Mutations in the ftsI gene, which encodes penicillin binding protein 3 (PBP3), and the clonal dissemination of the resistant strains were also investigated. A total of 264 H. influenzae isolates were collected from patients with URT infections. According to the criteria of the Clinical and Laboratory Standards Institute for the susceptibility of H. influenzae to ampicillin (AMP), the isolates were distributed as follows: 161 (61.0%) susceptible strains (MIC < or = 1 microg/ml), 37 (14.0%) intermediately resistant strains (MIC = 2 microg/ml), and 66 (25.0%) resistant strains (MIC > or = 4 microg/ml). According to PCR-based genotyping, 172 (65.1%) of the isolates had mutations in the ftsI gene and were negative for the beta-lactamase (bla) gene. These 172 isolates were thus defined as genetically beta-lactamase-negative ampicillin-resistant (gBLNAR) strains. The ftsI mutant group included 98 (37.1%) strains with group I/II mutations in the variable mutated region (group I/II gBLNAR) and 74 (28.0%) strains with group III mutations in the highly mutated region (group III gBLNAR). Eighty-seven (33.0%) of the isolates were genetically beta-lactamase-negative ampicillin-susceptible (gBLNAS) strains. The group III gBLNAR strains showed resistance to beta-lactams. Only five strains (1.9%) were positive for a bla gene encoding TEM-type beta-lactamase. The three clusters consisting of 16 strains found among the 61 BLNAR strains (MIC > or = 4 microg/ml and without the bla gene) showed identical or closely related DNA restriction fragment patterns. Those isolates were frequently identified among strains with a MIC to AMP of 16 microg/ml. The current study demonstrates the apparent dissemination and spread of a resistant clone of H. influenzae among medical centers in Japan. The gBLNAR strains show a remarkable prevalence among H. influenzae isolates, with the prevalence increasing with time. This fact should be taken into account when treating URT infections.

Study of nasopharyngeal bacterial flora. Variations in nasopharyngeal bacterial flora in schoolchildren and adults when administered antimicrobial agents.

Changes in nasopharyngeal bacterial flora in adults with acute upper respiratory tract infection on administration of antimicrobial agents were investigated, and how these changes contrasted with those in children. Many patients with acute sinusitis due to allergies, and patients with malignancy and diabetes mellitus were included in the investigation. The detection rates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the major bacteria of acute otitis media (AOM), were 22%, 10%, and 7% respectively, which were significantly lower than those for children. Gram stain examination of nasopharyngeal swab samples showed a significant relation between leukocyte infiltration and the detection amount of S. pneumoniae (P = 0.0086). A significant relation (P = 0.0134) was also observed when H. influenzae was simultaneously detected. No significant change in the three major AOM bacteria present in nasopharyngeal bacterial flora after administration of antimicrobial agents was observed. However, all S. pneumoniae and H. influenzae detected after antimicrobial agent administration had the beta-lactam-resistance gene. It was observed that a significant improvement in leukocyte infiltration occurred 6 to 10 days after antimicrobial agent administration. In contrast, a significant improvement in children was observed at 2 to 5 days. In the adult subjects, this improvement was probably due to spontaneous remission rather than the effect of the antimicrobial agents. Although investigation of the long-term administration of antimicrobial agents was also conducted, its benefits for the patients were not elucidated.

Study of upper respiratory tract bacterial flora: first report. Variations in upper respiratory tract bacterial flora in patients with acute upper respiratory tract infection and healthy subjects and variations by subject age.

With the appearance of penicillin-resistant Streptococcus pneumoniae, there has been increasing debate concerning antimicrobial treatments for acute upper respiratory tract infection (AURTI) and acute otitis media in children. This study compares the nasopharyngeal bacterial flora in patients with AURTI (AURTI group; 710 subjects) and healthy subjects (HS group; 380 subjects). The comparisons were made between subjects aged 6 years or younger (0-6 subgroup: 330 subjects), between 7 and 74 years (7-74 subgroup: 668 subjects), and 75 years and older (92 subjects), because the subjects were subgrouped as described above dependent on the maturity of the protective immunity. In the HS group 7-74 subgroup, viridans group streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and Corynebacterium sp. with a detection rate of 10% or more were classified as normal nasal flora (NNF), and Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were classified as drum cavity pathogens (DCP). In the 0-6 subgroup, although the detection rate for DCP bacteria in the AURTI group tended to be high, it did not reach a significant difference, whereas the detection rate for NNF bacteria was significantly lower. This trend was also observed to some degree in the other age subgroup. In the 0-6 subgroup, leukocyte infiltration observed with a microscope indicated the closest relationship between S. pneumoniae detection rate and detection quantity. These results suggest that in the 0-6 subgroup the tendency for patients with AURTI to have NNF bacteria as well as DCP bacteria should be taken into consideration.

Study of nasopharyngeal bacterial flora. Second report. Variations in nasopharyngeal bacterial flora in children aged 6 years or younger when administered antimicrobial agents. Part 1.

In our first report, we investigated nasopharyngeal bacterial flora related to penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR) and their relation to acute upper respiratory tract infection (AURTI). This report analyzes the results of a study of nasopharyngeal bacterial flora before the administration of antimicrobial agents in 172 AURTI patients aged 6 years or younger. In addition to Gram staining, microscopic observation, and culturing, a polymerase chain reaction (PCR) method was used to identify PRSP (gPRSP) and BLNAR (gBLNAR) drug-resistant genes. Of the patients analyzed, 90% had acute otitis media (AOM) and were aged 2 years or younger. The antimicrobial agents administered were amoxicillin (34%), clavulanic acid/amoxicillin (11%), cefditren pivoxil (CDTR-PI) (43%), and others (12%). This was particularly true for patients administered CDTR-PI, among whom there were many who had already suffered one or more episodes of AOM by the age of 1 year or younger, and many in which gPRSP were detected (P < 0.01). There was a significant relation between the degree of nasopharyngeal inflammation indicated by leukocyte infiltration images and the amount of S. pneumoniae and H. influenzae detected, which are the main pathogenic bacteria causing AOM (P < 0.01). In addition to leukocyte infiltration images, there were cases in which shedding of ciliated cells was observed and/or giant monocytic cells. Both nasopharyngeal leukocyte infiltration images and/or shed cell findings observed in infant AURTI cases are important indices for the prompt detection of gPRSP and/or gBLNAR and appropriate doses of antimicrobial agents.

Study of nasopharyngeal bacterial flora. Second report. Variations in nasopharyngeal bacterial flora in children aged 6 years or younger when administered antimicrobial agents. Part 2.

This report focuses on changes in the nasopharyngeal bacterial flora before and after administration of antimicrobial agents in 172 cases of acute upper respiratory infection in patients aged 6 years or younger. The antimicrobial agents administered were amoxicillin (AMPC) (34%), clavulanic acid/amoxicillin compound (11%), cefditren pivoxil (CDTR-PI) (43%), and others (12%). Changes in nasopharyngeal bacterial flora were investigated with reexaminations conducted after 2-5 days (day 2-5 subgroup), 6-10 days (day 6-10 subgroup), and 11 days and thereafter. There was a significant reduction in the Streptococcus pneumoniae detected in the group administered AMPC (AMPC group) in the day 2-5 subgroup and the day 6-10 subgroup. There was also a significant decrease in H. influenzae in the group administered CDTR-PI (CDTR-PI group) in the day 2-5 subgroup. From this it was inferred that for the most part significant changes in infectious nasopharyngeal bacteria occurred in the day 2-5 subgroups. However, a significant improvement in the degree of inflammation, as indicated by leukocyte infiltration images for the AMPC group, was observed in the day 2-5 subgroup, and for the CDTR-PI group in the day 6-10 subgroup. On the other hand, in both the antimicrobial agent groups, S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were newly detected at reexamination. Furthermore, a difference in the incidence of these bacteria was observed between the 2 antimicrobial agent groups. It was suggested that such phenomena related to the survival of resistant strains or a recurrence otitis media.

Long-term surgical follow-up of sleep apnea syndrome.

During a 10-year period, 845 patients suspected of having sleep apnea syndrome underwent overnight monitoring at our institution. We report herein the results of a study of 204 surgical patients who responded to a questionnaire survey. Of these 204 cases, 86 (42%) showed a > or = 75% postoperative improvement in the apnea-hypopnea index (AHI) (or AHI < 10) and 48 (24%) showed an improvement of > or = 50%. Based on the data obtained from the questionnaire survey we studied the long-term postoperative improvement as well as the long-term prognosis in terms of the postoperative improvements in AHI and body weight.

Anatomy of oral respiration: morphology of the oral cavity and pharynx.

The anatomical states of the oral cavity and pharynx during mouth breathing in children with adenoid hypertrophy and in adults confirmed the speculation that mouth breathing is disadvantageous compared with nose breathing. In addition, comparison of the anatomical state between wakefulness and sleep in normal adults showed slight depression of the tongue root and slight narrowing of the oropharynx and hypopharynx during sleep. Obstructive sleep-disordered breathing occurs due to a variety of factors, such as paranasal sinus disease, tonsil and adenoid hypertrophy, hypertrophy and morphological abnormalities of the soft palate and palatine uvula, low-set soft palate, micrognathia, macroglossia, obesity and tongue root depression. Narrowing or obstruction of the middle pharynx and hypopharynx is more marked in patients with obstructive sleep-disordered breathing than in normal people and is especially marked during sleep. Therefore, morphological (i.e. anatomical) changes during mouth breathing may provide useful information for evaluating the pathology of snoring and sleep apnea.

Current status of bacterial resistance in the otolaryngology field: results from the Second Nationwide Survey in Japan.

The study reported here was a nationwide assessment of otitis media (466 patients with acute suppurative otitis media and 476 with chronic suppurative otitis media), sinusitis (447 with acute sinusitis and 426 with chronic sinusitis), acute tonsillitis (724 patients), and peritonsillar abscess (141 patients) performed between November 1998 and March 1999. Eighty university hospitals, 79 affiliated hospitals, and 103 general practitioners participated. Methicillin-resistant Staphylococcus aureus(MRSA) comprised 15.6% of the 786 isolated strains of S. aureus. MRSA was frequently detected in patients with suppurative otitis media, but was uncommon in those with acute tonsillitis or peritonsillar abscess, and it was more common in those who had already been treated than in those who had not, with a significant difference between the groups. Vancomycin (VCM) showed the highest antimicrobial activity against MRSA and no VCM resistance was detected. Penicillin-sensitive Streptococcus pneumoniae(PSSP), penicillin-intermediate-resistant S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) accounted for 49.6%, 28.5%, and 21.9% of the 228 isolated strains of S. pneumoniae, respectively. PISP and PRSP were frequently detected in children aged 5 years or younger. beta-Lactamase was produced by 96 of the 100 strains (96%) of Moraxella (Branhamella) catarrhalis. The 281 strains of Haemophilus influenzae isolated consisted of 199 beta-lactamase-negative, ampicillin-sensitive (BLNASe) strains (70.8%), 65 beta-lactamase-negative ampicillin-resistant (BLNAR) strains (23.1%), and 17 beta-lactamase-producing strains (6.0%). BLNAR strains were frequently detected in pretreated patients. Of these 281 strains of H. influenzae, 214 had nontypable capsules. In conclusion, the major bacterial species showed resistance to beta-lactams, indicating that care should be taken when selecting an appropriate antimicrobial agent.

Laser midline glossectomy and lingual tonsillectomy as treatments for sleep apnea syndrome.

Preservation treatments for sleep respiratory disorders, such as the use of a dental device and the technique of nasal continuous positive air pressure, cause discomfort to the patient and are not radical treatments. Therefore, we performed operative therapy instead. Laser midline glossectomy was performed to treat constriction at the root of the tongue in 16 patients diagnosed with sleep apnea syndrome. We also tried lingual tonsil excision using the Harmonic Scalpel in three patients with stenosis at the base of the tongue.

Two cases of sleep apnea syndrome caused by primary hypothyroidism.

Two cases of sleep apnea syndrome caused by primary hypothyroidism are reported. The first patient was a 66-year-old man who complained of sleep apnea; his apnea-hypopnea index (AHI) was 50.8, as assessed by all-night monitoring. Hypothyroidism was subsequently suspected when he showed delayed recovery from general anesthesia following surgery involving uvulopalatopharyngoplasty. Hypothyroidism was diagnosed on the basis of blood tests His snoring and apnea improved after 2 months of levothyroxine sodium administration and the AHI fell from 50.8 to 13.0. The second patient was a 73-year-old man with an AHI of 41.3, as assessed by all-night monitoring. Hypothyroidism was diagnosed on the basis of blood tests and was suspected because of his slow speech. He was similarly treated with levothyroxine sodium. The AHI did not decrease after 4 months of treatment. His desaturation rate (rate of O2 saturation < 90%) improved however, from 56.6% to 31.9%, and the symptoms of hypothyroidism also improved markedly. In both patients, elevated creatine phosphokinase, a dull facial expression, peripheral edema and slow speech were recognized, and these symptoms were suggestive of hypothyroidism. The type of sleep apnea was mainly obstructive in both patients.

Posture of Patients with Sleep Apnea During Sleep.

The relationship between sleep apnea syndrome (SAS) and posture during sleep has been noted and the beneficial effect of an optimal posture on sleep apnea has been empirically indicated. We investigated this effect in a group of subjects that included obese patients and found that the apnea-hypopnea index (AHI) may be normalized in the lateral position, even among patients severely affected with apnea. Among those with intermediate or lower AHI values, sleeping in a lateral position markedly improved the symptoms, with AHI even approaching the normal range in many patients. A tendency was noted for AHI to rise regardless of posture but in proportion to the increase in body mass index (BMI). In other words, the improvement due to changes in posture became increasingly insignificant with increase in BMI.

Obstructive sleep apnea syndrome in children.

Obstructive sleep apnea syndrome (OSAS) in children is often caused by obstruction of the upper airway due to hypertrophy of the adenoids and palatine tonsils. Between October 1988 and December 1991, 50 children (34 males, 16 females) visited our department due to attacks of sleep apnea and underwent adenotomy or adeno-tonsillectomy. Respiratory monitoring during sleep was performed before and after operation, and the usefulness of the surgery was evaluated. Before operation, 27/ 50 children (54.0%) were diagnosed as having OSAS. Their age distribution showed peaks at the ages of 4 and 5 years and the male:female ratio was 2:1. Concerning the degree of improvement in clinical symptoms after surgery, marked effects were observed in 40/50 patients (80.0%), moderate effects in 7 (14.0%) and slight effects in 3 (6.0%). Concerning the degree of improvement in the apnea index after surgery in the 27 patients with OSAS, marked effects were observed in 22 patients (81.50%), moderate effects in 2 (7.4%), slight effects in 1 (3.7%) and no change in 2 (7.4%).

Obesity and obstructive sleep apnea syndrome.

We investigated the influence of obesity on upper airway obstruction, especially the relationship between obesity and the type of obstruction. The site of obstruction was identified by means of endoscopic examination and dynamic MRI during sleep. Many obese patients have the circumferential type of obstruction.

Dynamic MRI diagnosis of sleep-disordered breathing.

According to the obstructive site, the different types of obstructive-type sleep-disordered breathing are classified as the soft palate type, palatine tonsil type, soft palate and depressed lingual root type, depressed lingual root type and epiglottis type. In this study, we conducted dynamic MRI examinations of the oral, pharyngeal and lingual root sites in patients with obstructive sleep-disordered breathing, and studied the usefulness of MRI as a diagnostic tool for the examination of such obstructive sites.

Influence of sleep respiratory disturbance on nocturnal blood pressure.

We subjected 65 patients to overnight monitoring and continuous nocturnal blood pressure measurement in order to assess the influence of sleep apnea on the circulatory system. Thirty-one patients were compared before and after surgery. The severity of sleep apnea was classified by means of the apnea-hypopnea index (AHI), the duration of exposure to low-level oxygen [calculated as the desaturation time (DT)] and changes in blood pressure (BP). Before surgery, a significant correlation was noted between DT and changes in BP. Therefore, DT was considered useful for assessing the influence of sleep apnea on nocturnal BP. After surgery, an improvement in AHI of > 50% was noted in 19/31 patients (61.3%), a result comparable to that described in the literature. Improvements in DT and change in BP were > 50% in 21/31 (67.7%) and 14/ 31 (45.2%) patients, respectively. With regard to the severity of sleep apnea before surgery, AHI was > or = 50 and DT > or = 40% in 10 and 18 patients, respectively and 19 patients showed changes in BP of > or = 40 mmHg. After surgery, one, five and two patients, respectively, still showed these values. Thus, a beneficial effect of surgery was demonstrated.

Posture of patients with sleep apnea during sleep.

The relationship between sleep apnea syndrome (SAS) and posture during sleep has been noted and the beneficial effect of an optimal posture on sleep apnea has been empirically indicated. We investigated this effect in a group of subjects that included obese patients and found that the apnea-hypopnea index (AHI) may be normalized in the lateral position, even among patients severely affected with apnea. Among those with intermediate or lower AHI values sleeping in a lateral position markedly improved the symptoms, with AHI even approaching the normal range in many patients. A tendency was noted for AHI to rise regardless of posture but in proportion to the increase in body mass index (BMI). In other words, the improvement due to changes in posture became increasingly insignificant with increase in BMI.