Evaluation of the relationship between linezolid exposure and hyponatremia.

INTRODUCTION: Aims of this study were (a) to assess the development ratio of hyponatremia during treatment with linezolid and (b) to evaluate the relationship between the risk of hyponatremia and linezolid exposure and patient background. METHOD: Clinical data including linezolid serum concentrations and serum sodium values were collected at Toyama University Hospital and Kyorin University Hospital. Data from 89 patients were used for the analysis, and a nadir serum sodium level ≤130 mmol/L during the treatment with linezolid was defined as hyponatremia. Mann-Whitney's U test was used to evaluate the effects of the area under the time-concentration curve (AUC) of linezolid at the nadir sodium level, clinical characteristics (e.g. laboratory data), and baseline serum sodium levels on the development of hyponatremia. RESULTS: The hyponatremia was occurred in 21 of 89 patients (23.6%). Data are compared for baseline and nadir serum sodium levels of patients with and without hyponatremia. In both groups, nadir serum sodium levels were significantly different from those of the baseline values (P < 0.05). The values of AUC0-12, accumulated AUC, baseline serum sodium levels and age were significantly different between patients with and without hyponatremia (P < 0.05). CONCLUSIONS: Linezolid exposure, age, and baseline sodium levels were detected as the risk factors for linezolid-related hyponatremia. Our findings suggest that regular monitoring of serum sodium levels is desirable during treatment with linezolid, especially for the elderly and patients with low serum sodium levels before the start of linezolid administration.

A study on the management of acute respiratory tract infection in adults.

Antimicrobials are commonly used to treat acute respiratory tract infection in adults. Furthermore, their overuse has raised concern. We conducted a field survey study that included 170 medical institutions from January 2008 to June 2010. The purpose of this study was to clarify the relationship between the rate of antimicrobial use and patient outcomes with each indication. The study included 1753 patients diagnosed with acute respiratory tract infection. Antimicrobials were used for treatment of 1420 of these patients, whereas 333 cases were not treated with antimicrobials. After 3 days of treatment, patients administered antimicrobials experienced a higher improvement rate than those who did not receive antimicrobial treatment (92.2% vs. 83.3%, p < 0.0001). However, after 7 days of treatment, the rates of improvement for patients in both groups were similar (95.0% and 93.4%, respectively, p = 0.2391). In addition, according to the criteria for the usage of antimicrobials described in the Japanese Respiratory Society guidelines for the management of respiratory tract infection in adults, the patients were classified into the 3 categories (6 indication factors for antimicrobial use): Grade 1, ≤ 2 factors; Grade 2, 3-4 factors; Grade 3, 5-6 factors). The indication factors considered were the following: 1) temperature; 2) purulent sputum or nasal discharge; 3) tonsillar enlargement and tonsillolith/white puss; 4) middle otitis/sinusitis; 5) inflammatory reaction; and 6) high-risk patients. The results indicate that the improvement observed after 3 days of treatment in Grade 2 and Grade 3 patients was significantly higher with antimicrobial treatment than without antimicrobial treatment. In conclusion, the administration of antimicrobials is not recommended in younger patients with no underlying disease. However, the use of antimicrobials is required in patients with a higher relative risk that corresponds to the presence of ≥ 3 of the 6 indication factors for antimicrobial use.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2006)].

From October 2006 to September 2007, we collected the specimen from 356 patients with lower respiratory tract infections in 14 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 414 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 407 strains were examined. The isolated bacteria were: Staphylococcus aureus 64, Streptococcus pneumoniae 96, Haemophilus influenzae 87, Pseudomonas aeruginosa (non-mucoid) 52, P. aeruginosa (mucoid) 11, Klebsiella pneumoniae 20, and Moraxella catarrhalis 44. Of 64 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 27 (42.2%) and 37 (57.8%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 microg/ml or less. Against MRSA, vancomycin and linezolid showed the most potent activity and inhibited the growth of all the strains at 1 microg/ml. Carbapenems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 microg/ml or less. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.125 and 0.5 microg/ml, respectively. In contrast, there were high-resistant strains (MIC: over 128 microg/ml) for erythromycin (45.8%) and clindamycin (20.8%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 microg/ml or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 microg/ml. Against P. aeruginosa (non-mucoid), tobramycin had the most potent activity and its MIC90 was 2 microg/ml. Against K. pneumoniae, cefozopran was the most potent activity and inhibited the growth of all the strains at 0.063 microg/ml or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 microg/ml or less. The approximately half the number (50.6%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 49.2% and 28.1% of all the respiratory infections, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. pneumoniae (29.2%), S. aureus (20.8%), and H. influenzae (12.9%). H. influenzae (25.0%) and P. aeruginosa (21.7%) also were frequently isolated from the patients with chronic bronchitis. Before the antibacterial agent administration, the bacteria frequently isolated from the patients were S. pneumoniae (27.5%) and H. influenzae (22.5%). The bacteria frequently isolated from the patients treated with macrolides was P. aeruginosa, and its isolation frequently was 39.4%.

High-precision plant height measurement by drone with RTK-GNSS and single camera for real-time processing.

Conventional crop height measurements performed using aerial drone images require 3D reconstruction results of several aerial images obtained through structure from motion. Therefore, they require extensive computation time and their measurement accuracy is not high; if the 3D reconstruction result fails, several aerial photos must be captured again. To overcome these challenges, this study proposes a high-precision measurement method that uses a drone equipped with a monocular camera and real-time kinematic global navigation satellite system (RTK-GNSS) for real-time processing. This method performs high-precision stereo matching based on long-baseline lengths (approximately 1 m) during the flight by linking the RTK-GNSS and aerial image capture points. As the baseline length of a typical stereo camera is fixed, once the camera is calibrated on the ground, it does not need to be calibrated again during the flight. However, the proposed system requires quick calibration in flight because the baseline length is not fixed. A new calibration method that is based on zero-mean normalized cross-correlation and two stages least square method, is proposed to further improve the accuracy and stereo matching speed. The proposed method was compared with two conventional methods in natural world environments. It was observed that error rates reduced by 62.2% and 69.4%, for flight altitudes between 10 and 20 m respectively. Moreover, a depth resolution of 1.6 mm and reduction of 44.4% and 63.0% in the error rates were achieved at an altitude of 4.1 m, and the execution time was 88 ms for images with a size of 5472 × 3468 pixels, which is sufficiently fast for real-time measurement.

Equilibrium space and a pseudo linearization of nonlinear systems.

This paper attempts to extend the concept of the equilibrium point to what is called equilibrium space, which can adapt to a system in which there exists an infinite number of equilibrium points. In the context of Lyapunov's linearization method extended for the equilibrium space, this paper proposes a pseudo linearization, from which we can derive a linear representation for a nonlinear system. The equilibrium state of this pseudo linearization and its stability are shown to be the same as that of the original nonlinear system. As an example of the applicability, the proposed pseudo linearization is applied to derive a discrete-time model for a control moment gyroscope system from a nonlinear continuous-time model. Simulation results show that the discrete-time model derived using the proposed pseudo linearization yields responses that are closer to that of the continuous-time model than the discrete-time model derived by the well-known forward-difference method and the conventional pseudo linear representation method, even with a large sampling interval.

Clinical Surveillance of Candidemia at Our Hospital.

Treatment of Candidemia has become increasingly complicated as more and more non-albicans Candida species are being isolated in recent years.We launched an investigation of the species, the MIC value, and the state of administration of antifungal drugs for all the cases with Candida spp. confirmed by blood cultures for the 7-year period from 2012 to 2018 at our hospital. In total, 192 cases were found and 206 strains of Candida species were isolated. Overall, 49.5% of the 206 isolated strains were Candida albicans (102 strains), followed by Candida glabrata (40 strains, 19.4%), and Candida parapsilosis (38 strains, 18.4%). The most frequently used antifungal drug for the initial dose was MCFG (120 cases, 59.2%), while the most frequently switched antifungal agent was L-AMB. Cases with an inappropriate end-of-treatment time represented 58.7% of all the cases.We investigated the Candidemia situation at our hospital for a period of seven years. We believe that it is important for medical institutions to gather detailed data on candidemia at their own hospitals. Likewise, the hospital's Infection Control Team/Antimicrobial Stewardship Team should inform the physicians-in-charge about the appropriate diagnosis and treatment based on the data obtained.

Efficacy of steroid therapy on adult patients with severe pneumonia.

Optimal management of steroid therapy for severe pneumonia is an urgent issue. One hundred forty-eight elderly patients enrolled in our study were treated for severe pneumonia in a university hospital in Tokyo from 1998 through 2002. Steroid drugs were given to 82 patients (55.4%), whereas 66 (44.6%) received no steroids. Based on this main division, retrospective analyses were performed with regard to patient characteristics, antimicrobial agents, use or nonuse of mechanical ventilators, and prognoses. Significant difference was not seen in age, sex, underlying disease, isolated pathogens, and artificial respirator between the steroid and nonsteroid groups. Partial pressure of oxygen in arterial blood/fraction of inspired oxygen (Pao(2)/Fio(2)) ratio was significantly lower in the steroid (227.2 +/- 96.9) compared with the nonsteroid group (271.6 +/- 86.4) (P < 0.01). Prognoses were evaluated 21 days after treatment initiation. Significant differences appeared: First, the average cure rate of patients who took steroids within 3 days after starting treatment was 62.7%, whereas the rate was 12.9% (P < 0.001) in those who did not take steroids earlier than the 4th day. The cure rate of the nonsteroid group was 39.3% (P < 0.001). Second, the total dose of steroids (methylprednisolone) given within 7 days was less in cured cases (774 +/- 749 mg) than in noncured cases (1,190 +/- 768 mg) (P < 0.05). In conclusion, steroids should be administered in the early stage after onset of pneumonia, and large doses of steroids becomes a compounding factor in the prognosis of pneumonia.

[Susceptibility surveillance of clinical isolates to fluoroquinolone antimicrobial agents from 2003 to 2008: post-marketing study of prulifloxacin].

Yearly changes in the susceptibility of clinical isolates to ulifloxacin (UFX) and other fluoroquinolones were examined through surveys over 3 periods. In the first survey, 534 strains derived from 19 species were collected from clinical specimens during 6 months from December 2003 to May 2004. In the same way, 805 strains were collected from December 2005 to May 2006 in the second survey, and 863 strains were from December 2007 to May 2008 in the third survey. Over these 3 study periods, the susceptibilities of fluoroquinolones against methicillin-susceptible Staphylococcus aureus and Escherichia coli were decreased. The isolation frequency of levofloxacin-nonsusceptible strain was increased from 0% to 11.8% and from 14.6% to 20.8%, respectively. MIC90s of UFX against these pathogens were also increased, but its MIC90 for E. coli was 2 to 4 times lower than that of levofloxacin. On the other hand, the susceptibility of strains of Klebsiella pneumoniae to UFX was increased. Among the fluoroquinolones tested, UFX showed the most potent activity against Pseudomonas aeruginosa, and no changes in the MIC90s occurred during the surveillance. Although one strain of Streptococcus pneumoniae isolated in the third study period showed levofloxacin-resistance (MIC, 8 microg/mL), there were nearly no changes in the MIC90s of any agents tested including UFX against S. pneumoniae during the surveillance. As for other bacterial species, a tendency to increase in resistance to UFX was not observed. The activity of UFX against Salmonella spp. and Shigella spp. was superior/equal to those of fluoroquinolones tested.

Stepwise PathNet: a layer-by-layer knowledge-selection-based transfer learning algorithm.

Some neural network can be trained by transfer learning, which uses a pre-trained neural network as the source task, for a small target task's dataset. The performance of the transfer learning depends on the knowledge (i.e., layers) selected from the pre-trained network. At present, this knowledge is usually chosen by humans. The transfer learning method PathNet automatically selects pre-trained modules or adjustable modules in a modular neural network. However, PathNet requires modular neural networks as the pre-trained networks, therefore non-modular pre-trained neural networks are currently unavailable. Consequently, PathNet limits the versatility of the network structure. To address this limitation, we propose Stepwise PathNet, which regards the layers of a non-modular pre-trained neural network as the module in PathNet and selects the layers automatically through training. In an experimental validation of transfer learning from InceptionV3 pre-trained on the ImageNet dataset to networks trained on three other datasets (CIFAR-100, SVHN and Food-101), Stepwise PathNet was up to 8% and 10% more accurate than finely tuned and from-scratch approaches, respectively. Also, some of the selected layers were not supported by the layer functions assumed in PathNet.

Immunological analysis and pathological examination of gnotobiotic mice monoassociated with Mycoplasma pneumoniae.

Although mycoplasmal pneumonia has been generally considered to be a disease with good prognosis, a pathogenic host immune response has been associated with its occurrence. In the present study, the pathogenic significance of the immune response was examined using germ-free mice either infected intranasally with Mycoplasma pneumoniae or inoculated with M. pneumoniae antigens (soluble antigen and partially purified antigen). In gnotobiotic mice monoassociated with M. pneumoniae, 10(4) c.f.u. M. pneumoniae per lung were isolated 2-28 days after infection. Inflammatory changes with infiltration of lymphocytes were histopathologically detected in the perivascular area at 2 and 7 days after infection. In the mice intranasally inoculated with soluble antigen or partially purified antigens (F6 and F10 antigens), infiltration of neutrophils and lymphocytes was histopathologically detected at 2 days after inoculation. Severe pneumonia with tissue destruction was observed in the mice inoculated with F6 antigen. A gamma interferon (IFN-gamma) dominant response in endogenous cytokine expression was observed in all the treated mice. These results indicate that inflammatory changes in the lung tissue were prolonged in gnotobiotic mice monoassociated with M. pneumoniae compared with mice inoculated with M. pneumoniae antigen. In addition, it was shown that IFN-gamma plays an important role in the pathogenesis of pneumonia in mice either infected with M. pneumoniae or inoculated with its antigen. In particular, the F6 antigen has been considered to be an important virulence factor in terms of induction of tissue injury causing infiltration of lymphocytes and neutrophils in the lung, suggesting a close interaction between the immune response and the occurrence of M. pneumoniae pneumonia.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2005)].

From October 2005 to September 2006, we collected the specimen from 366 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 411 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 406 strains were examined. The isolated bacteria were: Staphylococcus aureus 70, Streptococcus pneumoniae 85, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 46, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 21, and Moraxella subgenus Branhamella catarrhalis 40. Of 70 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 38 (54.3%) and 32 (45.7%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of 37 strains (97.4%) at 0.063 microg/ml or less. Against MRSA, arbekacin and vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/ml. Carbapenems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 microg/ml or less. Faropenem also had a preferable activity and inhibited the growth of all the strains at 0.25 microg/ml. In contrast, there were high-resistant strains (MIC: over 128 microg/ml) for erythromycin (38.1%) and clindamycin (22.6%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 microg/ml or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 microg/ml. Against P. aeruginosa (non-mucoid), arbekacin had the most potent activity and its MIC90 was 8 microg/ml. Against K. pneumoniae, cefozopran was the most potent activity and inhibited the growth of all the strains at 0.063 microg/ml or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 2 microg/ml or less. The approximately half the number (53.6%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 44.3% and 29.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (15.4%), S. pneumoniae (23.4%), and H. influenzae (21.3%). S. aureus (25.4%) and S. pneumoniae (18.0%) also were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.0%) and H. influenzae (21.4%). The bacteria frequently isolated from the patients treated with macrolides were S. pneumoniae and P. aeruginosa, and their isolation frequencies were each 35.3%.

An HIV-infected Patient with Confirmed Overlapping Complications of Severe Amebic Colitis and CMV Enteritis.

We herein report a case of simultaneous amebic colitis and cytomegalovirus (CMV) enteritis in an HIV-infected patient. The patient was a 40-year-old man who developed bloody stool and diarrhea. We diagnosed him with severe amebic colitis associated with HIV infection and administered metronidazole. While his symptoms began to improve, the patient then developed CMV enteritis. We administered ganciclovir, and his symptoms improved. However, despite control of the infection, stenosis of the descending colon caused intestinal obstruction, and colostomy was performed. This case shows the importance of considering the possibility of simultaneous infection when gastrointestinal symptoms appear in people infected with HIV.

Effects of tributyltin on the immune system of Japanese flounder (Paralichthys olivaceus).

Effects of tributyltin (TBT) which has been used for antifouling paint of ship's hulls and fishing nets on the immune system in Japanese flounder (Paralichthys olivaceus) were investigated. After short-term exposure to a high level of TBT, leucocytes in the head kidney from 1-year-old flounder were examined for the proportion of neutrophils in total leucocytes. Also examined were their respiratory burst activities using flow cytometry, the reduction of nitroblue tetrazolium (NBT) and lysozyme activities. Furthermore, long-term exposures to a relatively low level of TBT using young flounder were also carried out. The proportion of neutrophils in total leucocytes prepared from head kidney in each fish exposed to TBT at 20 microg/L for 5 days and the reduction of NBT by leucocytes prepared from the same experimental conditions increase compared to the control group. The contents were 42.0+/-6.8 and 52.5+/-6.3%, respectively. Significant differences of the NBT reduction were observed between 0 and 20 microg/L TBT exposure groups. On the other hand, the respiratory burst activity of cells in the exposure group clearly showed a tendency to decrease compared to the control group. Furthermore, high level of TBT also inhibited lysozyme activity which plays an important role for the bacteriocidal procedures. However, similar results were not obtained in the exposure group with a relatively low level of TBT. To determine the immunotoxic effects of TBT, infection experiments using pathogens which are naturally occurring should be further investigated.

A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.

Wiskott-Aldrich syndrome (WAS) is caused by mutations in the gene encoding WAS protein (WASP ). Recently, somatic mosaicism caused by reversions or second-site mutations has been reported in some inherited disorders including WAS. In this article, we describe somatic mosaicism in a 15-year-old WAS patient due to a second-hit mutation in the initiation codon. The patient originally had a single-base deletion (c.11delG; p.G4fsX40) in the WAS (WASP) gene, which resulted in a frameshift and abrogated protein expression. Subsequently, a fraction of T and natural killer (NK) cells expressed a smaller WASP, which binds to its cellular partner WASP-interacting protein (WIP). The T and NK cells were found to have an additional mutation in the initiation codon (c.1A>T; p.M1_P5del). The results strongly suggest that the smaller WASP is translated from the second ATG downstream of the original mutation, and not only T cells but also NK cells carrying the second mutation acquired a growth advantage over WASP negative counterparts. To our knowledge, this is the first report describing somatic mosaicism due to a second-site mutation in the initiation codon of any inherited disorders.

Antigen-specific free immunoglobulin light-chain antibodies: could it be a new diagnostic marker for patients with allergy?

OBJECTIVES: Human free immunoglobulin light chains (FLCs) have long been considered as nonmeaningful spillover remnants from the process of immunoglobulin production; however, recent findings suggest that the antibody activity of FLCs may be involved in the pathology of allergic responses. We therefore assessed the antigen-binding ability of FLCs to evaluate their usefulness as diagnostic markers for patients with allergy. DESIGN AND METHODS: FLCs were separated from the serum samples of patients seropositive against cedar pollen and mice immunized with bovine serum albumin and 1-fluoro-2,4-dinitrobenzene by ultrafiltration and protein G absorption. A sensitive immunoassay confirmed the absence of any IgG in the separated FLC fractions from the human serum samples. RESULTS: Solid-phase immunoassay for cedar pollen showed that none of the human serum samples possessed any antibody activity against the antigen after the removal of whole immunoglobulins. Furthermore, while the immunized mice also showed high antibody titers against the antigens, but the serum specimens showed no residual antibody activity against the antigens after the FLCs were separated from the whole immunoglobulins. CONCLUSIONS: The results of the present study suggested that the FLC fractions may possess little or no antigen-binding activity, and that therefore, they may not serve as useful diagnostic markers in patients with allergy.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2004)].

From October 2004 to September 2005, we collected the specimen from 319 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 383 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 381 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 87, Streptococcus pneumoniae 80, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 35, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 15, Moraxella subgenus Branhamella catarrhalis 30, etc. Of 87 S. aureus strains, those with 2 microg/mL or less of MIC of oxacillin (methicillin-sensitive S. aureus: MSSA) and those with 4 microg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 40 (46.0%) and 47 (54.0%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/mL. Arbekacin (ABK) also showed the potent activity and its MIC90 was 2 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/mL) and inhibited the growth of all the strains at 2 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for ABK (2.5%), erythromycin (37.5%), and clindamycin (38.8%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of all the strains at 0.125 microg/mL. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 microg/mL. Against P. aeruginosa (non-mucoid), amikacin (AMK) had the most potent activity and its MIC90 was 4 microg/mL. The activity of CZOP against the non-mucoid type also was preferable and its MIC90 was 8 microg/mL. Against K. pneumoniae, CZOP, cefmenoxime, cefpirome, flomoxef were the most potent activity and inhibited the growth of all the strains at 0.063 microg/mL. Also, all the agents generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (57.0%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 50.8% and 23.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.6%), S. pneumoniae (24.7%) and H. influenzae (20.1%). S. aureus (20.9%), S. pneumoniae (16.1%), and H. influenzae (16.1%) also were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.3%) and H. influenzae (25.1%). The bacteria relatively frequently isolated from the patients treated with macrolides were P. aeruginosa and the isolation frequency was 43.5%.

Efficient management and maintenance of ultrasonic nebulizers to prevent microbial contamination.

AIM: To seek the cause of Burkholderia cepacia complex (Bcc) infection outbreak and evaluate the efficacy of new methods for nebulizer maintenance. METHODS: We investigated the annual number of Bcc isolates recovered from clinical samples in our hospital between 1999 and 2013. Swab samples were randomly collected for bacterial culture before patient use from 10 each of the two machine types in August 2001; these included 20 samples from each of the following: Drain tubes, operating water chambers, oscillators, and nebulizing chambers. In addition, 10 samples each of nebulizer solutions before and after use were cultured. For environmental investigation, 10 samples were collected from sinks in the nurse stations of the wards where patients positive for Bcc were hospitalized. Numbers of Bcc isolates were compared before and after introduction of new methods for nebulizer maintenance in October 2001. In addition, randomly amplified polymorphic DNA (RAPD) assay was applied to find the genetic divergence of the Bcc isolates obtained from clinical samples and nebulizers. RESULTS: From January 1999 to December 2013, a total of 487 Bcc isolates were obtained from clinical specimens from 181 patients. Notably, 322 (66.1%) Bcc isolates were obtained from clinical specimens from 1999 to 2001, including 244 (115 patients) from sputum and 34 (11 patients) from blood. During this period, 14 isolates were obtained from nebulizer components. Among these, six were derived from nebulizer drain tubes, five from operating water chambers, and one from the oscillator before patient use, and two from nebulizer solutions after patient use. When Bcc was isolated from the nebulizer solution after patient use, Bcc was simultaneously detected in other parts of the nebulizer. Bcc was not isolated from any nebulizer solution before use. RAPD assays revealed similar DNA profiles in isolates obtained from patients and nebulizers. Investigation revealed damaged diaphragms in many nebulizers. The new maintenance methods for nebulizers, including restriction of the usage period, thorough disinfection, and routine check for diaphragm breakage, remarkably reduced Bcc isolation (165 isolates from patients in 12 years and 0 isolate from nebulizers in periodical sampling). In particular, Bcc has been isolated from blood from only one patient since the new methods were introduced. CONCLUSION: Appropriate maintenance of ultrasonic nebulizers is crucial for preventing Bcc contamination of nebulizers and subsequent respiratory tract and blood infections.

Successful treatment of photo-damaged skin of nano-scale atRA particles using a novel transdermal delivery.

We show a novel drug delivery system (DDS) for improved all-trans retinoic acid (atRA) therapy for external treatments of photo-damaged skin. We prepared inorganic-coated atRA nanoparticles, in turn an egg-like structure in nano-scale (Nano-atRA), using boundary-organized reaction droplets. The interfacial properties of organic architectures, in atRA micelles, were used to template the nucleation of inorganic minerals. As a result, irritation and inflammation associated with atRA therapy were substantially reduced due to the complete encapsulation of the carboxylic function. Both irritative symptoms and physicochemical instability of the atRA micelle were improved. Since Nano-atRA which is prepared following to this new DDS system developmentally improved the permeability to the stratum corneum, the remarkable pharmacological effects were resulted in comparison with atRA as such as follows: (1) thicker epidermis than classical atRA treatment and (2) the overexpression of mRNA for heparin-binding epidermal growth factor (HB-EGF) as the provocation epidermal hyperplasia. Furthermore, we found a surprising boost in production of hyaluronan (HA) among the intercellular spaces of the basal and spinous cell layers in epidermis. Nano-atRA technology for atRA therapy could not only efficiently regulate keratinocyte cell proliferation and differentiation, but also markedly produce the additional benefit. Severely injured human skin by chronic ultraviolet irradiation will completely repair due to the accelerated turnover of skin tissue, which is induced by Nano-atRA.