Repeated Measurements Are Necessary for Evaluating Accurate Diurnal Rhythm Using a Self-Intraocular Pressure Measurement Device.

PURPOSE: To investigate how many tests need to be performed to adequately assess intraocular pressure (IOP) diurnal change using a self-measuring rebound tonometer among glaucoma patients. SUBJECTS AND METHODS: Adult patients with primary open-angle glaucoma were included. IOP was measured in the morning (6 AM to 9 AM), afternoon (12 PM to 3 PM), and at night (6 PM to 9 PM) for seven consecutive days. Twenty-four (7 males and 17 females, mean age 59.5 ± 11.0 years) patients who successfully measured IOP at least three times per day during the correct time periods for four days were subjected to analysis. RESULTS: The IOP rhythm was significantly greater on the first day of measurement (6.6 ± 3.6 mmHg) than that averaged during subsequent days (4.4 ± 2.2 mmHg). The time of the highest and lowest IOP measurements on the first day of IOP measurement and during the entire measurement period coincided in 72.9% and 64.6% of cases, respectively. The concordance rate of the highest IOP time between the whole measurement period and each measurement day was less than 60%. CONCLUSION: The diurnal IOP rhythm measured by the patients themselves was not consistent, and multiple days of measurements may be necessary to correctly assess diurnal IOP rhythm.

Investigation of visual and physical factors associated with inadequate instillation of eyedrops among patients with glaucoma.

PURPOSE: The aim of this study was to investigate the frequency of eyedrop instillation failure and its related physical and visual function factors among glaucoma patients who used hypotensive eyedrops daily. SUBJECTS AND METHODS: Patients with a history of self-instillation of one or more ocular hypotensive ophthalmic solutions for six or more months were enrolled. Definitions of instillation failure were eyedrop instillation other than on the eye surface; eyedrop contact with eyelashes; eyedrop bottle tip contact with the eyelashes, eye surface or ocular adnexa; or two or more drops instilled with one instillation trial. To clarify factors related to instillation failure, we used visual function tests and investigated cervical spine extension angles during instillation, pinching strength, physical ataxia (evaluated using the Scale for the Assessment and Rating of Ataxia), motor dysfunction of the upper limbs (evaluated using the Disabilities of the Arm, Shoulder and Hand questionnaire), and vision quality (evaluated using the National Eye Institute Visual Function Questionnaire 25). RESULTS: Of 103 total subjects, 61.2% satisfied the definition of instillation failure. Instillation of the eyedrop other than at the cul-desac (76.2%) was the most frequent reason for failure, followed by contact of the tip of the eyedrop bottle (22.2%) and instillation of the same or more than two eyedrops in a single attempt (11.1%). Advanced age, a shallow cervical spine extension angle, weak pinching strength, poor motor dysfunction of the upper limbs, the degree of ataxia, poor best-corrected visual acuity, and visual field scores were significant risk factors for instillation failure. Vision quality may have some relation to instillation failure. CONCLUSION: It is highly recommended that instillation failure be routinely investigated even among patients with adequate experience using eyedrops and that correct therapies are chosen in a patient-based fashion.

Inhibition of TLR9-NF-κB-mediated sterile inflammation improves pressure overload-induced right ventricular dysfunction in rats.

AIMS: Recent accumulating evidence suggests that sterile inflammation plays a crucial role in the progression of various cardiovascular diseases. However, its contribution to right ventricular (RV) dysfunction remains unknown. The aim of this study was to elucidate whether toll-like receptor 9 (TLR9)-NF-κB-mediated sterile inflammation plays a critical role in the pathogenesis of RV dysfunction. METHODS AND RESULTS: We performed main pulmonary artery banding (PAB) in rats to induce RV pressure overload and dysfunction. On Day 14 after PAB, the pressure overload impaired RV function as indicated by increased RV end-diastolic pressure concomitant with macrophage infiltration and fibrosis, as well as maximal activation of NF-κB and TLR9. Short-term administration (days 14-16 after PAB) of a specific TLR9 inhibitor, E6446, or an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) significantly attenuated NF-κB activation. Furthermore, long-term administration of E6446 (treatment: days 14-28) or PDTC (prevention: days -1 to 28; treatment: days 14 to 28) improved RV dysfunction associated with mitigated macrophage infiltration and fibrosis in right ventricle and decreased serum brain natriuretic peptide levels. CONCLUSION: Inhibition of TLR9-NF-κB pathway-mediated sterile inflammation improved PAB-induced RV dysfunction in rats. This pathway plays a major role in the progression of pressure overload-induced RV dysfunction and is potentially a novel therapeutic target for the disorder.

Changes in Glaucoma Medication during the Past Eight Years and Future Directions in Japan Based on an Insurance Medical Claim Database.

PURPOSE: To investigate changes in the status of glaucoma care between 2006 and 2013 and to predict future directions of glaucoma care in Japan. SUBJECTS AND METHODS: Japanese subjects registered in the largest national insurance claim database in Japan from 2006 to 2013 were analyzed. Estimations of the number of glaucoma patients during the past eight years and of the number of future patients were calculated. Changes in prescription trends among the same patients in the three-year period after initiating antiglaucoma medication were also investigated. RESULTS: There was a total of 3,016,000 subjects in the database. The proportion of glaucoma patients increased consistently from 2.5% in 2006 to 4.5% in 2013. This trend was predicted to continue until 2025, followed by a constant decrease with age. The most frequently prescribed antiglaucoma medications were prostaglandin analogues (PGs); however, in recent years, fixed combination therapy has emerged as a major treatment. Among 2856 newly diagnosed glaucoma patients; 94.7% of the patients initially received a single medication, but 25% of the patients received additional medications within 3 years. CONCLUSIONS: The prevalence of glaucoma patients has significantly increased during the past eight years. The number of antiglaucoma medications continuously increased during the treatment period.

[DIAN/DIAN-J/DIAN-TU].

The Dominantly Inherited Alzheimer's Network (DIAN) observational study compared pathophysiological markers between mutation carriers and non-carriers in autosomal dominant Alzheimer's disease. This study revealed that changes in the biomarkers in the mutation carrier's brain start as early as 20 or even 25 years prior to the onset of symptoms. Doctors of the DIAN-Japan team have successfully implemented the DIAN study in Japan (DIAN-J) with effort and enthusiasm. The DIAN-J study is completely compatible with the DIAN study. All members of the DIAN-J team were certified by the NIH and Washington University. The DIAN researchers started a prevention trial (DIAN-TU) testing two monoclonal antibodies in 2013. Together with the DIAN global members including the Japanese team, they will start the new DIAN-TU NexGen Trial testing a BACE inhibitor in 2017. The API study is another clinical trial of anti-amyloid monoclonal antibody therapy for family members of patients with early-onset familial AD who carry the PSEN1 E280A mutation. This study has shown the same biomarker changes that were reported in the DIAN study.

Effectiveness of timely intraoperative iodine irrigation during cataract surgery.

PURPOSE: To determine the antiseptic efficacy of timely intraoperative iodine irrigation during cataract surgery. METHODS: A total of 198 eyes of 99 cataract surgery patients were studied. The eyes were randomly assigned to treatment with or without timely intraoperative iodine irrigation of the surgical field with an iodine compound equivalent to 0.33 % povidone-iodine. In eyes in the timely intraoperative iodine irrigation group, the ocular surface was irrigated twice intraoperatively-before the initial incision and before insertion of the intraocular lens (IOL). The efficacy of the antiseptic treatment was evaluated by culture tests using scrapings of the surface of the sclerocornea and conjunctiva to the left of the incision and by broad-range real-time PCR for bacterial 16S ribosomal DNA using scrapings from the right side of the incision. RESULTS: Following intraoperative application of the iodine, bacteria were not detected in cultures of the samples. For the control eyes without timely iodine irrigation, cultures of samples from five and two eyes were positive before the initial incision and before IOL insertion, respectively. The bacterial DNA copy number before the initial incision was 1.7 ± 0.5 × 103, which was significantly lower than that of the control eyes (1.7 ± 0.6 × 104). For both groups of eyes, the bacterial DNA copy number was significantly lower before the IOL insertion depending on the time course. When the antiseptic effect of the iodine irrigation and time course on bacterial DNA copy number was analyzed using generalized mixed linear regression, both were found to be significantly effective. No significant intraoperative epithelial defect was observed. The postoperative corneal endothelial cell count did not differ significantly between the two groups of eyes. CONCLUSIONS: Timely iodine irrigation can serve as a simple and useful adjunctive disinfection step in cataract surgery.

Nasal and conjunctival screening prior to refractive surgery: an observational and cross-sectional study.

OBJECTIVES: To investigate bacterial flora of clinically healthy conjunctiva and nasal cavity among patients prior to refractive surgery, as well as the characteristics of patients with methicillin-resistant Staphylococcus aureus (MRSA) colonisation. DESIGN: Observational and cross-sectional study. SETTING: A single-centre study in Japan. PARTICIPANTS: 120 consecutive patients pre-refractive surgery. PRIMARY AND SECONDARY OUTCOME MEASURES METHODS: Samples were obtained from the right conjunctival sac and the nasal cavity of 120 consecutive patients prior to refractive surgery and were then measured for the levels of the minimum inhibitory concentration (MIC) of antibiotics. Patients were interviewed regarding their occupation, family living situation and any personal history of atopic dermatitis, asthma, smoking or contact lens wear. RESULTS: Propionibacterium acnes (P. acnes) (32.5%) and Staphylococcus epidermidis (4.2%) were detected from the conjunctival sac. S. epidermidis was the most commonly isolated (68.3%) in the nasal cavity. Of the 30 patients (25.0%) with colonisation by S. aureus, 2 patients, both of whom were healthcare workers with atopic dermatitis, were found to be positive for MRSA in the nasal cavity. A history of contact lens wear, asthma or smoking, as well as patient gender and age, was not associated with MRSA colonisation. CONCLUSIONS: There were only 2 patients who were colonised with MRSA, both of whom were healthcare workers with atopic dermatitis. P. acnes was predominantly found in the conjunctival sac. Further study is needed to investigate the involvement between nasal and conjunctival flora, and risk factors for infectious complications.

[Antimicrobial Effects of Iodine-Polyvinyl Alcohol Ophthalmic and Eye Washing Solution (PA * IODO) with Special Reference to its Temperature, Concentration and Time and its Preservation Stability].

PURPOSE: Temperature, concentration and time are the three factors that affect the inactivation capacity of iodine antiseptics. We investigated the effect of these factors on the microbe inactivation of Iodine-Polyvinyl Alcohol ophthalmic and eye washing solution (PA * IODO), and also investigated the preservation conditions on stability of the inactivation activity of the PA * IODO. METHODS: Test microbes were mixed with PA * IODO, varying the three factors. The live microbes were counted after each reaction. The effects of plugging and preservation temperature were investigated to determine the preserving stability. RESULTS: The inactivation capacity of PA * IODO tended to decrease in almost all microbes tested at 4 degrees C. Twenty times or less diluted PA * IODO killed almost all microbes completely. The time effect was more marked in viruses. Plugging and low-temperature made iodine concentration in diluted PA * IODO remain relatively high. CONCLUSIONS: The concentration of PA * IODO affected the inactivation ability more than the temperature and time, although all the three factors correlated positively to the inactivation. For preservation the diluted PA * IODO needed plugging and low temperature.

Susceptibility of various oral antibacterial agents against extended spectrum ß-lactamase producing Escherichia coli and Klebsiella pneumoniae.

With the increase in extended spectrum ß-lactamase (ESBL)-producing bacteria in the community, cases are often seen in which treatment of infectious diseases with oral antimicrobial agents is difficult. Therefore, we measured the antimicrobial activities of 14 currently available oral antimicrobial agents against ESBL-producing Escherichia coli and Klebsiella pneumoniae. Based on the standard of the Clinical and Laboratory Standards Institute (CLSI), E. coli showed high susceptibility rates of 99.4% to faropenem (FRPM). In terms of fluoroquinolones, the susceptibility rate of E. coli to levofloxacin (LVFX) was low at 32.2%, whereas it showed a good susceptibility rate of 93.1% to sitafloxacin (STFX). With respect to other antimicrobial agents, susceptibility rates to fosfomycin (FOM) and colistin (CL) were more than 90% each, whereas rates of the two antimicrobial agents expected as therapeutic agents, minocycline (MINO) and sulfamethoxazole-trimethoprim (ST), were low at 62.4% and 44.3%, respectively. Based on the CLSI standard, K. pneumoniae showed high susceptibility rates to ceftibuten (CETB) (91.89%), LVFX (86.49%), and STFX (94.6%), indicating that K. pneumoniae showed higher rates than those of E. coli, particularly to fluoroquinolones. Comparison of susceptibility rates according to E. coli genotype showed that many antimicrobial agents existed to which the CTX-M-9 group showed high susceptibility rates. However, there were many agents to which the CTX-M-1 group showed low susceptibility rates, particularly to CETB (51.1%) and LVFX (17.0%). Although there was no significant difference by genotype between FRPM, STFX, and FOM, a significant difference was observed between LVFX, MINO, and ST. Antibiotic-resistant bacteria with highly pathogenic strains have spread in the community, appropriate use of oral antimicrobial agents is required.

Epidemiology of Escherichia coli, Klebsiella species, and Proteus mirabilis strains producing extended-spectrum ß-lactamases from clinical samples in the Kinki Region of Japan.

In the present study, nonduplicate, clinical isolates of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli, Klebsiella spp, and Proteus mirabilis were collected during a 10-year period from 2000 to 2009 at several hospitals in the Kinki region, Japan. The detection rate of E coli markedly increased from 0.24% to 7.25%. The detection rate of Klebsiella pneumoniae increased from 0% to 2.44% and that of P mirabilis from 6.97% to 12.85%. The most frequently detected genotypes were the CTX-M9 group for E coli, the CTX-M2 group for K pneumoniae, and the CTX-M2 group for P mirabilis. E coli clone O25:H4-ST131 producing CTX-M-15, which is spreading worldwide, was first detected in 2007. The most common replicon type of E coli was the IncF type, particularly FIB, detected in 466 strains (69.7%). Of the K pneumoniae strains, 47 (55.3%) were of the IncN type; 77 P mirabilis strains (96.3%) were of the IncT type. In the future, the surveillance of various resistant bacteria, mainly ESBL-producing Enterobacteriaceae, should be expanded to prevent their spread.

[Determination 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 I].

PURPOSE: To determine the causative agents of ocular infection of external adnexa and anterior segments due to selected criteria. SUBJECTS AND METHODS: Between September 22, 2007 and August 25, 2008, 890 bacterial strains were collected from 476 patients in 18 facilities nationwide participating in the Drug Sensitivity for Ocular Infection Study Group. Usual aerobic and anaerobic cultures, enrichment cultures, smears, and measurements of bacterial quantity were performed and the determination of causative agents was made from the results of smears and culture, the presence of polymorphonuclear cells and bacterial quantity. The selection was divided into two categories, causative agents and presumed causative agents. Staphylococcus aureus, Moraxella bacilli, Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Neisseria gonorrhoeae were distinctively considered as specified bacteria. RESULTS: Among 890 strains, 18.8% were determined to be causative agents, and 15.1% were determined to be presumed causative agents. Among the bacteria detected in normal flora, 2.0% of Staphylococcus epidermidis, 2.6% of Propionibacterium acnes, and 38.3% of Corynebacterium spp. were determined to be causative agents. CONCLUSION: To determine the causative agents, the results of smears and bacterial quantity should be considered together with culture results. Bacteria constituting normal flora have the potential of becoming causative agents.

[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.

Laboratory surveillance for prospective plasmid-mediated AmpC beta-lactamases in the Kinki region of Japan.

Extended-spectrum beta-lactamases, plasmid-mediated AmpC beta-lactamases (PABLs), and plasmid-mediated metallo-beta-lactamases confer resistance to many beta-lactams. In Japan, although several reports exist on the prevalence of extended-spectrum beta-lactamases and metallo-beta-lactamases, the prevalence and characteristics of PABLs remain unknown. To investigate the production of PABLs, a total of 22,869 strains of 4 enterobacterial species, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis, were collected during six 6-month periods from 17 clinical laboratories in the Kinki region of Japan. PABLs were detected in 29 (0.13%) of 22,869 isolates by the 3-dimensional test, PCR analysis, and DNA sequencing analysis. PABL-positive isolates were detected among isolates from 13 laboratories. Seventeen of 13,995 (0.12%) E. coli isolates, 8 of 5,970 (0.13%) K. pneumoniae isolates, 3 of 1,722 (0.17%) K. oxytoca isolates, and 1 of 1,182 (0.08%) P. mirabilis isolates were positive for PABLs. Of these 29 PABL-positive strains, 20 (69.0%), 6 (20.7%), 2 (6.9%), and 1 (3.4%) carried the genes for CMY-2, DHA-1, CMY-8, and MOX-1 PABLs, respectively. Pattern analysis of randomly amplified polymorphic DNA and pulsed-field gel electrophoretic analysis revealed that the prevalence of CMY-2-producing E. coli strains was not due to epidemic strains and that 3 DHA-1-producing K. pneumoniae strains were identical, suggesting their clonal relatedness. In conclusion, the DHA-1 PABLs were predominantly present in K. pneumoniae strains, but CMY-2 PABLs were predominantly present in E. coli strains. The present findings will provide significant information to assist in preventing the emergence and further spread of PABL-producing bacteria.

Monte Carlo simulation for evaluation of the efficacy of carbapenems and new quinolones against ESBL-producing Escherichia coli.

Extended-spectrum beta-lactamase (ESBL)-producing bacteria are known to be resistant to penicillins, cephalosporins, and monobactams because of their substrate specificity, and these bacteria are sensitive only to a narrow range of antimicrobial agents. The present study was undertaken to evaluate the efficacy of carbapenems and the new quinolones against ESBL-producing Escherichia coli, using a Monte Carlo simulation based on the pharmacokinetic/pharmacodynamic (PK/PD) theory. The time above MIC (TAM, %) served as the PK/PD parameter for carbapenems, with the target level set at 40%. The AUC/MIC served as the PK/PD parameter for the new quinolones, with the target level set at more than 125. In the analysis of drug sensitivity, the MIC50 of all carbapenems other than imipenem was low (0.03 microg/ml), while the MIC50 of the new quinolones was higher (1-2 microg/ml). The probability of achieving the PK/PD target with carba penems after two doses at the usual dose level, as determined by the Monte Carlo simulation, was high for each of the carbapenems tested (99.0% for biapenem, 99.60% for meropenem, and 95.03% for doripenem), except for imipenem. Among the new quinolones, the highest probability of achieving the PK/PD target was obtained with pazufloxacin (42.90%). Thus, the results of the present study have revealed that carbapenems are effective at the regular dose and can be used as the first-choice antibiotics for ESBL-producing E. coli because the resistance ratios for carbapenems are low compared to those of the new quinolones.

Susceptibility comparisons of normal preoperative conjunctival bacteria to fluoroquinolones.

PURPOSE: To compare the susceptibility and efficacy of 3 fluoroquinolones, (levofloxacin, gatifloxacin, and moxifloxacin) in treating conjunctival bacteria in patients having ocular surgery. SETTING: Osaka University Hospital, Osaka, and Tohoku University Hospital, Miyagi, Japan. METHODS: Eyes of patients were examined preoperatively. Aerobic and anaerobic cultures were obtained from conjunctival swabs. The minimum inhibitory concentrations (MICs) of levofloxacin, gatifloxacin, and moxifloxacin for isolated strains were determined. Using the MIC values, descriptive statistics (median, MIC(50), MIC(90), mode, and range), susceptibility, and efficacy of each fluoroquinolone were calculated for the bacteria isolated, and the data were analyzed statistically. RESULTS: Of the 200 eyes sampled, 163 (81.5%) had positive bacterial growth. From the 163 eyes, 235 bacterial strains were isolated: 116 (49.4%) Propionibacterium acnes; 58 (24.7%) coagulase-negative Staphylococcus (CNS), including 36 methicillin-sensitive CNS (MS-CNS) and 22 methicillin-resistant CNS (MR-CNS); 10 (4.3%) Staphylococcus aureus, including 6 methicillin-sensitive S aureus and 4 methicillin-resistant S aureus (MRSA); and 29 (12.3%) Corynebacterium. Approximately 40% of Staphylococci (22/58 CNS, 37.9%; 4/10 S aureus, 40.0%) were methicillin-resistant. Furthermore, 18 (81.8%) of MR-CNS and all 4 MRSA were fluoroquinolone resistant. The MICs of moxifloxacin and gatifloxacin were statistically significantly lower than those of levofloxacin for CNS and P acnes (P<.05, Kruskal-Wallis test). However, there was no statistically significant difference in the susceptibility patterns of the fluoroquinolones for these strains (P>.05, McNemar test). CONCLUSION: Because many methicillin-resistant and fluoroquinolone-resistant strains were isolated from the conjunctiva preoperatively, clinicians should be mindful of endophthalmitis or ocular infections associated with these strains.

Bacteriologic profile of the conjunctiva in the patients with dry eye.

PURPOSE: To assess the conjunctival bacterial profiles in dry eye and their fluoroquinolone susceptibility patterns. DESIGN: Prospective, observational study. METHODS: Sixty-seven female patients with dry eye (29 with Sjögren syndrome and 38 without Sjögren syndrome) who received artificial tears were enrolled at Osaka University Hospital in Japan. Twenty-three patients received additional topical steroids. Twenty-six puncta were occluded with plugs. Cultures were obtained with conjunctival swabs at the right eye of the subjects. The minimum inhibitory concentrations of isolated strains were determined for the fluoroquinolones (levofloxacin and gatifloxacin). The profiles of conjunctival bacteria of patients with dry eye were compared with those obtained before surgery from 56 female control patients. RESULTS: Eighty-eight strains were isolated (48 strains of Propionibacterium acnes, 26 coagulase-negative Staphylococcus [CNS] species, six Staphylococcus aureus strains, and eight others). Of the 26 CNS strains, 17 (65.4%) were fluoroquinolone resistant, including four (33.3%) of 12 methicillin-sensitive CNS and 13 (92.9%) of 14 methicillin-resistant CNS. All methicillin-sensitive S. aureus strains and P. acnes strains were sensitive to fluoroquinolones; one methicillin-resistant S. aureus strain was resistant. There was no significant difference in the conjunctival isolation rates between patients with dry eye and controls. However, the dry eye group had a significantly higher incidence of fluoroquinolone-resistant methicillin-sensitive CNS and of fluoroquinolone-resistant methicillin-resistant CNS than controls (P = .018 and P = .024, respectively). There were no significant differences in bacteria isolated between subgroups with or without punctal plugs and with or without topical steroids. CONCLUSIONS: Patients with dry eye are more likely to have fluoroquinolone-resistant conjunctival bacteria than controls. These results may help prevent infectious keratoconjunctivitis in patients with dry eye.

Polyclonality of Staphylococcus epidermidis residing on the healthy ocular surface.

Staphylococcus epidermidis is part of the normal bacterial flora on the ocular surface. The chromosomal DNA of bacterial isolates obtained from the conjunctival sac, upper and lower lid margins, and upper and lower Meibomian glands of healthy volunteers was subjected to SmaI digestion and PFGE to study the genetic diversity of the organisms. Multiple colonies were also examined of S. epidermidis derived from the conjunctival sac of the same subjects. Lastly, commensal bacteria were harvested from the ocular surfaces of four healthy subjects once a month for 6 months, and the genetic background of the S. epidermidis isolates was analysed. It was found that bacterial strains not only from different subjects but also from multiple ocular surface sites of the same subject exhibited different PFGE patterns. In five of 42 subjects multiple colonies of S. epidermidis were isolated from the conjunctival sac; three harboured multiple colonies with different PFGE patterns, and two manifested multiple colonies with identical PFGE patterns. S. epidermidis isolated from the conjunctival sac of the same subjects over a 6-month period exhibited varying PFGE patterns. The data demonstrate the polyclonality of S. epidermidis on the healthy ocular surface.

[Extended-spectrum-beta-lactamase-producing Proteus mirabilis: laboratory-based surveillance in cooperation with 12 clinical laboratories in the Kinki Region of Japan].

We studied 247 strains of Proteus mirabilis collected during the 6 months from November 2003 to April 2004 from 12 clinical laboratories in the Kinki region of Japan for the production of extended-spectrum beta-lactamase (ESBL). Eighteen strains (7.3%) showed MICs for cefpodoxime of > or = 2 microg/mL and 13 strains (5.2%) were positive for the double-disk synergy test. Susceptibility depended on genotype. MICs for cefepime, cefozopran, and cefpirome were high (> or = 8 microg/mL), and that for ceftazidime was low (0.12-0.5 microg/mL). Meropenem showed the lowest MIC (< or = 0.03-0.25 microg/mL) of the calbapenems, while other calbapenems showed somewhat higher values (0.5-2 microg/mL). The MIC of tazobactam/piperacillin was also relatively low (< or = 0.25-1 microg/mL). Analysis of the ESBL genotype by the polymerase chain reaction showed that 12 of 13 strains were CTX-M2 types. CTX-M9 was detected in a single laboratory. The clinical background showed 5 strains in urine samples. Twelve of 13 strains were detected in patients with minimal devices use. No symptoms were found in most cases of established syndrome. Analysis of PCR fingerprint profiles of random amplified polymorphic DNA patterns showed that 6 of 7 strains from hospital 1 showed the same pattern, and 5 of 5 strains from hospital 13 showed the same pattern, suggesting the nosocomial spread of P. mirabilis in each hospital.

[Surveillance of antimicrobial resistance of Streptococcus pneumoniae isolates from the Kinki Region of Japan during 2003/2004. The Surveillance Program of Bacterial Resistance in the Kinki Region of Japan; SBRK].

Three hundred seventy five isolates of Streptococcus pneumoniae were collected from 14 medical institutions in the Kinki region of Japan between November 2003 and February 2004. We determined the minimum inhibitory concentration (MIC) of penicillin G (PCG) and 25 of other antimicrobial agents against these isolates according to the National Committee for Clinical Laboratory Standards (NCCLS). Overall, 71.5% of all isolates were resistant to PCG (intermediate and resistant categories were 51.7% and 19.8%, respectively). For the carbapenems and penem, the rank order of activity was PAPM (MIC90, 0.12 microg/ml) > IPM (0.25 microg/ml) > MEPM (0.5 microg/ml) = FRPM (0.5 microg/ml). For the cephems, the overall rank order of activity was CPR (MIC90, 0.5 microg/ml) = CDTR (0.5 microg/ml) > CTRX (1 microg/ml) = CTX (1 microg/ml) = CZOP (1 microg/ml) = CFPN (1 microg/ml). Rank order activity for six of fluoroquinolones was TFLX = MFLX (MIC90, 0.25 microg/ml) > GFLX (0.5 microg/ ml) = SPFX (0.5 microg/ml) > LVFX (1 microg/ml) > PZFX (4 microg/ml). The rate of resistance to fluoroquinolones per the NCCLS criteria were very low, ranging from 0.7% to 2.6%. Rate of resistance to other antimicrobiotics were CAM, 77.0%; CLDM, 41.7%; TEL, 0%; VCM, 0%; ST, 32.7%, and CP, 21.4%.