Kazunori Seo

Clinical efficacy of peramivir in adult patients with seasonal influenza during the winter of 2012 in Japan

Peramivir is an intravenously administered neuraminidase inhibitor for influenza. The clinical efficacy of peramivir remains unclear because it is used in a limited number of countries. We compared the clinical efficacy of peramivir with that of oseltamivir in influenza patients during the 2012–2013 season.

Characteristics of Serum Endocan Levels in Infection

Objectives Endocan is a newly recognized biomarker of sepsis. However, there have been no studies of the trends in endocan levels during infection and their associations with other clinical factors. The aim of this study was to assess the time course of endocan levels and the associations of endocan with clinical factors during infection by comparison with other biomarkers. Methods Serum samples and blood cultures were obtained from patients who were diagnosed with infection from June 2013 to March 2014. Serum endocan, C-reactive protein (CRP), and procalcitonin (PCT) levels during four periods during infection were measured (day 0, day 1-2, day 3-5, and day 6-10). Results A total of 78 patients were enrolled in this study. The median endocan level decreased by only 23% during infection, whereas both serum CRP and PCT levels decreased by more than 80%. Endocan levels were correlated to neither CRP levels nor PCT levels in each period. Endocan levels at day 0 in patients with bacteremia were higher than those without bacteremia (1.09 ng/mL vs 0.82 ng/mL, P=0.002), but neither CRP levels nor PCT levels at day 0 were different between the two groups. Areas under the receiver operator characteristic (ROC) curves of endocan, CRP, and PCT at day 0 were 0.662, 0.343, and 0.563, respectively. Positive blood cultures tended to be related to high endocan levels, but not significantly (odds ratio: 4.24, 95% CI: 0.99-10.34, P=0.05). Conclusions In bacteremic cases, serum endocan levels in bacteremia tended to be higher than in non-bacteremic cases. Although endocan level was not identified as a prognostic factor of bacteremia, further prospective study concerning the relationship between serum endocan level and bacteremia would be needed.

Infective endocarditis due to Enterobacter cloacae resistant to third- and fourth-generation cephalosporins

We report the case of using a long-term combination of meropenem and amikacin to treat infective endocarditis caused by Enterobacter cloacae resistant to third- and fourth-generation cephalosporins. Multi-drug resistant Gram-negative bacilli, such as the E. cloacae in our study, may become possible pathogens of infective endocarditis. Our experience with this case indicates that long-term use of a combination of β-lactam and aminoglycosides might represent a suitable management option for future infective endocarditis cases due to non-Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella spp. (HACEK group) Gram-negative bacilli such as ours.

Increase of 25-hydroxyvitamin D levels after initiation of combination antiretroviral therapy

Although vitamin D deficiency in HIV patients reported worldwide, the mechanisms and the effect of combination antiretroviral therapy (cART) on vitamin D levels are unclear. Patients were 50 male Japanese with HIV who visited Teikyo University Hospital, Tokyo, Japan. Patients were divided into those receiving cART (cART-experienced group, n = 30) and those who had not received cART (cART-naïve group, n = 20). Patients in the cART-experienced group had received treatment with cART for more than one year and those in the cART-naïve group were just about to start cART at study entry. Patients underwent measurement of serum 25-hydroxyvitamin D (25(OH)D) levels and assessment of clinical factors twice at one year intervals. At study entry, 23 (76.7%) in the cART-experienced group and 19 (95.0%) in the cART-naïve group had vitamin D insufficiency or deficiency. Mean 25(OH)D values were significantly higher in the cART-experienced group (25.2 ng/ml vs. 19.3 ng/ml, p = 0.01). However, levels of 25(OH)D at one year increased more in the cART-naïve group (-1.1 ng/ml vs. 5.0 ng/ml, p = 0.01), with mean 25(OH)D values in the cART-naïve group increasing to match those in the cART-experienced group. HIV infected patients who initiated cART showed increases in vitamin D levels in one year.

Multifocal Cellulitis due to Disseminated Neisseria Gonorrhoeae in a Male Patient

We report a rare case of disseminated gonococcal infection in a 37-year-old man presenting with multifocal cellulitis. The patient presented with fever and painful swelling of the right foot and left hand, and was admitted to our hospital. CT scanning of the extremities revealed multifocal cellulitis. Transthoracic echocardiography findings were normal, and piperacilin/tazoactam therapy was initiated. On antibiotic day 4, Neisseria gonorrhoeae was cultured from a purulent effusion collected from a focal site. Chlamydia trachomatis was detected in urine samples by PCR. We made the diagnosis of multifocal cellulitis due to N. gonorrhoeae in a patient with chlamydia urethritis. The antibiotic agent was changed from piperacilin/tazobactam to ceftriaxone. Levofloxacin was also administered for chlamydia urethritis. By admission day 14, all lesions had resolved and administration of antibiotic agents was terminated. Disseminated gonococcal infection, although rare, should be included in the differential diagnosis of all sexually active patients who present with multifocal cellulitis - also a rare condition, particularly in light of the fact that in recent times, patterns of sexual activity have changed, which was a pertinent factor in this case.

Liver Abscess With a Markedly High Level of Carbohydrate Antigen 19-9

Serological tumor markers are useful for detection of malignancies and evaluation of disease progression. However, some markers are rarely elevated in patients with benign diseases and without malignancies. We herein present a case of a liver abscess with a highly elevated carbohydrate antigen (CA 19-9) level in both the serum and abscess fluid. The serological level of CA 19-9 decreased with treatment. Although CA 19-9 is known to be a specific tumor marker, high serum levels of CA 19-9 can be observed in patients with pyogenic liver abscesses. CA 19-9 may also be a marker for treatment response in patients with liver abscesses.

Inhibition of osteoblast differentiation by ritonavir

Osteoporosis is one of the chronic complications seen in human immunodeficiency virus (HIV)-infected patients, and affects patients at high prevalence. The causes of osteoporosis in HIV-infected patients are multiple, and include chronic HIV infection, living habits such as smoking and alcohol consumption, and antiretroviral drug use. Among antiretroviral drugs, protease inhibitors have been reported to be associated with osteoporosis. However, it remains to be determined how anti-HIV drugs affect osteoblast differentiation. In the current study, MC3T3-E1 cells, a mouse osteoblastic cell line, were cultured in osteoblast differentiation medium with or without different protease inhibitors (ritonavir, lopinavir, darunavir or atazanavir), and alkaline phosphatase (ALP) activity and the expression of Runt-related transcription factor 2 (Runx2) were analyzed. The ALP activity in MC3T3-E1 cells cultured with ritonavir was significantly reduced compared with that in cells in only osteoblast inducer reagent, indicating that ritonavir inhibited osteoblast differentiation. Meanwhile, ALP activity was not reduced in cells cultured with any of the other inhibitors. In addition, ritonavir inhibited the expression of Runx2, a key regulator of osteoblast differentiation, in the early period of osteoblast differentiation. To the best of our knowledge, this is the first study to demonstrate that ritonavir inhibits osteoblast differentiation in vitro. The present findings may explain the mechanism of osteopenia induced by combination antiretroviral therapy involving protease inhibitors.

Co-colonization with Neisseria species is a risk factor for prolonged colonization with multidrug-resistant Acinetobacter baumannii in the respiratory tract

Multidrug-resistant Acinetobacter baumannii (MDRAB) colonization increases the risk of bacterial spread in the hospital setting. The impact of clinical factors, including antibiotic use, on prolongation of MDRAB colonization has not been investigated. Patients with respiratory tract MDRAB detected using culture were enrolled in this study. Long-term colonizers and short-term colonizers were defined as patients whose colonization periods were >30 days or ≤30 days, respectively. Clinical data were abstracted from medical records. MDRAB was isolated in 34 patients. There were 13 long-term colonizers and 9 short-term colonizers. Twelve patients were lost to follow-up and excluded from the study. There were no significant differences in average leukocyte counts, numbers of antibiotic classes administered, duration of antibiotic use in the 30 days following colonization, or rates of central catheterization or mechanical ventilation between the 2 groups. Long-term colonizers carried Neisseria species (spp.) more frequently in the 30 days following colonization than short-term colonizers (7/13 vs 1/9, p = 0.01); however, this was not the case prior to colonization with MDRAB (5/13 vs 1/9, p = 0.33). The 90-day MDRAB colonization rates for Neisseria-negative patients and Neisseria-positive patients were 10.0% and 83.3%, respectively (P < 0.01). Prolonged MDRAB colonization in the respiratory tract was associated with Neisseria spp. co-colonization.

The clinical value of cystatin C as a marker of renal function in HIV patients receiving dolutegravir

Dolutegravir (DTG) is an integrase strand transfer inhibitor that is used for the treatment of HIV infection. DTG inhibits organic cation transporter 2 on the basolateral side of proximal tubule cells of the kidney and leads to increased serum creatinine levels without true renal function deterioration. In HIV patients who receive DTG, an alternative test to serum creatinine measurement is needed to determine the correct renal function. We retrospectively evaluated 18 HIV-infected men who had received combination antiretroviral therapy (cART), including DTG, and who had available data on serum creatinine and cystatin C levels. We used paired t-test to assess the changes in estimated glomerular filtration rate (eGFR) calculated by serum creatinine or cystatin C level, after the start of cART. In all 18 patients, only 2 cases were naive, whereas 16 cases switched treatment. Based on serum creatinine level, eGFR significantly changed from 67.9 (61.2-95.7) ml/min per 1.73 m2 [medians and interquartile ranges ] to 63.6 (55.5-83.7) ml/min per 1.73 m2 (p = .0004). Conversely, eGFR was almost unchanged [79.8 (77.7-82.5) to 80.0 (77.1-82.5) ml/min per 1.73 m2; p = .132] when serum cystatin C level was used for estimation. In HIV patients receiving DTG, measurement of serum cystatin C as an alternative renal function test might be clinically valuable because it is not affected by DTG administration.

Hyaluronic Acid concentration in pleural fluid: diagnostic aid for tuberculous pleurisy.

Background A high concentration of hyaluronic acid in pleural fluid is suggestive of malignant mesothelioma. However, a relatively high concentration of hyaluronic acid was also seen in the pleural fluid of patients with benign inflammatory diseases. To show the utility of measuring hyaluronic acid levels in pleural fluid to diagnose tuberculous pleurisy, we compared the clinical features and levels of hyaluronic acid in the pleural fluid of patients with and without tuberculous pleurisy. Methods We enrolled 27 patients with infective pleurisy admitted at Teikyo University Hospital from January 2010 to December 2013. Ten patients were diagnosed with tuberculous pleurisy, and 17 with non-tuberculous pleurisy. We reviewed the clinical features and data of all 27 patients and compared the two groups. We analyzed and compared the concentration of hyaluronic acid and adenosine deaminase in their pleural fluid. Results Patients with tuberculous pleurisy tended to have significantly higher concentrations of hyaluronic acid and adenosine deaminase in their pleural fluid (tuberculous pleurisy patients vs. other infective pleurisy patients: hyaluronic acid (× 103 ng/mL); 42.9 ± 23.3 vs. 16.8 ± 17.9, P = 0.003, adenosine deaminase (IU/L); 89.7 ± 33.3 vs. 74.0 ± 90.9, P = 0.032). Receiver operating characteristic analysis revealed no significant difference in the area under the curve of hyaluronic acid and adenosine deaminase volumes in pleural fluid, suggesting their equivalent value as major diagnostic tools for tuberculosis pleurisy. Conclusions Hyaluronic acid concentration in pleural fluid can be a valuable tool for the diagnosis of tuberculous pleurisy.