In vivo efficacy and pharmacokinetics of biapenem in a murine model of ventilator-associated pneumonia with Pseudomonas aeruginosa

Biapenem (BIPM) has high bactericidal activity against Pseudomonas aeruginosa and similar activity in vitro as meropenem (MEPM). We used a murine model to examine the efficacy of biapenem against ventilator-associated pneumonia (VAP) caused by P. aeruginosa. Mice were treated by intraperitoneal injection with 100 mg/kg BIPM or MEPM every 12 h beginning 12 h after inoculation with P. aeruginosa. Survival was evaluated for 7 days, and 24 h after infection, lung histopathology was analyzed and the number of viable bacteria in the lungs and blood was counted. In addition, the pharmacokinetics of BIPM and MEPM were analyzed after the initial treatment. BIPM and MEPM significantly prolonged survival compared to control (P < 0.05). The lungs of mice treated with BIPM or MEPM had significantly fewer viable bacteria (3.54 ± 0.28 vs. 3.77 ± 0.14 log(10) CFU/ml) than in the lungs of control mice (6.65 ± 0.57 log(10) CFU/ml) (P < 0.05). Furthermore, viable bacteria were not detected in the blood of mice treated with BIPM or MEPM (control 2.85 ± 0.85 log(10) CFU/ml) (P < 0.05). Histopathological examination of lung specimens indicated that BIPM and MEPM prevent the progression of lung inflammation, including alveolar neutrophil infiltration and hemorrhage. The % time above MIC for BIPM and MEPM was 15.4% and 18.3% in plasma and 19.8% and 19.8% in lungs, respectively. These results show that BIPM and MEPM significantly prolongs survival and reduces the number of viable bacteria in a murine model of VAP caused by P. aeruginosa. Therefore, BIPM might be a potent and effective treatment for VAP caused by this bacterium.     

The efficacy and safety of high-dose arbekacin sulfate therapy (once-daily treatment) in patients with MRSA infection

The efficacy and safety of once-daily high-dose arbekacin sulfate therapy for methicillin-resistant Staphylococcus aureus (MRSA) infection were evaluated, with analysis of their relationship to blood drug levels. The study was conducted in patients with pneumonia or sepsis, the cause of which was suspected to be MRSA, who were admitted to the Nagasaki University Hospital or its affiliated hospitals between January 2009 and December 2010. The initial drug dose was set at a level expected to yield the goal peak of 20 μg/ml and a trough level of less than 2 μg/ml, using the Habekacin Therapeutic Drug Monitoring analysis software. Thirteen patients were enrolled: 10 patients had pneumonia and 3 patients had sepsis. Patient mean age was 72.0 years; mean initial drug dose was 269.2 mg. Clinical efficacy at completion of treatment and bacterial eradication-reduction were achieved in 66.7% (6/9) and 62.5% (5/8) of patients, respectively. Incidence of adverse reactions was 38.5% (5/13). In analysis of efficacy in relationship to serum drug levels, the peak drug level was 22.7 ± 5.50 μg/ml, on average, and 15 μg/ml or higher in all 6 responders. Also, in patients with renal dysfunction, it seemed to be essential to ensure a certain peak drug level and to control the trough level appropriately. Although the number of patients was limited, once-daily high-dose arbekacin sulfate therapy may be highly effective, without posing any major safety problems. Further larger-scale studies are needed.     

Secondary traumatic stress and associated factors among Japanese nurses working in hospitals

Nurses can experience secondary traumatic events while caring for patients. However, the severity of this issue is underestimated in Japan. To evaluate the prevalence and factors associated with secondary traumatic stress among general hospital nurses, we carried out a cross-sectional study at a general hospital in August 2006. The rate of experiencing secondary trauma was 90.3% (159 of 176 nurses; 52.1% response rate). The median score of the Impact of Event Scale-Revised was 4.0 (range, 0-56). In multiple regression analyses, variables correlated with the Impact of Event Scale included neuroticism, trauma severity and feelings of self-reproach. It is necessary to develop support systems for nurses at risk for secondary traumatic stress.     

The dilemma faced by patients who undergo single embryo transfer

Purpose  The aim of this study was to identify the factors that contribute to the decision to choose single embryo transfer (SET). Methods  Two hundred and nine patients who underwent ART treatment in our clinics between April 2006 and May 2007 were enrolled in this study. All patients had elected to undergo SET before the start of each treatment cycle; a questionnaire was administered to all patients prior to the SET procedure. Results  The mean age of the patients was 34.6 years old (range: 24–45 years). The mean number of redundant embryos was 3.7 (range: 1–17), and the pregnancy rate per embryo transfer was 25.7%. A total of 121 patients (57.9%) who underwent SET returned their questionnaires. Based on the results of questionnaire, 56.2% of patients who received SET waived their right to choose between single and double embryo transfer. Among patients who selected SET, 67.6% believed that the pregnancy rate resulting from double embryo transfer (DET) is significantly greater than that associated with SET, and 25% of patients wanted to have twins. The majority of patients (80.9%) who underwent SET understood that multi-fetal pregnancy increases the risk of complications during gestation and delivery. Among all patients who completed the questionnaire, 72.8% believed that the number of transferred embryos should not be controlled by law. Conclusions  The results of the present study show that greater than one-half of patients who underwent SET were faced with a dilemma––the difficult choice between their own desires and their clinician’s recommendation.     

A study of the effect of an extremely low oxygen concentration on the development of human embryos in assisted reproductive technology

Purpose  

To determine whether embryos cultured with a low oxygen level (2%) brought about beneficial effects on the outcome of ART.     

Identification of Legionella londiniensis isolated from hot spring water samples in Shizuoka, Japan, and cytotoxicity of isolates

As part of an epidemiological study on legionellosis, we attempted to isolate Legionella spp. from hot spring water and were able to isolate L. londiniensis HYKF-90505 (=JCM 16338), confirming that L. londiniensis inhabits hot spring water in Japan. To investigate the disease potential of L. londiniensis, we examined its ability to grow intracellularly within Acanthamoeba sp. JAC/E1 strain. The isolated HYKF-90505 was able to grow within Acanthamoeba sp. JAC/E1 strain, and we confirmed also that the HYKF-90505 strain showed cytotoxicity for cultured cells such as J774.1 (JCRB0018). However, in a culture of human U937 cells, the bacterial count was not increased by the intracellular growth of the HYKF-90505 strain. Cells infected for 24 h and stained using the Giménez method showed no intracellular growth of the HYKF-90505 strain. Thus, the isolate appears to be weakly pathogenic to humans.     

Spatial distribution of cell adhesion molecules on the peritoneal surface in the cecal perforation‐induced peritonitis

For understanding the immunological functions of the peritoneum, spatial localization of integrins and their ligands was studied by immuno‐SEM on the peritoneal surface of mice with cecal perforation‐induced peritonitis. The cecal peritoneum 24 hr after perforation was stained with specific antibodies against LFA‐1, Mac‐1, VLA‐4, ICAM‐1, VCAM‐1, and fibronectin diluted with cold University of Wisconsin (UW) solution in conjunction with immuno‐gold labeling. The spatial localization of those cell adhesion molecules was detected by backscatter electron (BSE) imaging with field emission scanning electron microscope (FESEM). Numerous leukocytes with diverse surface ultrastructure were observed on the peritoneal surface by FESEM. Some leukocytes were in contact with mesothelial cells, and others adhered to the exposed underlying connective tissue. The BSE imaging showed the ubiquitous distribution of Mac‐1 on all membrane domains of leukocytes, i.e., cell body, ruffles, and microvilli. In contrast, predominant expressions of LFA‐1 and VLA‐4 were discernible on ruffles/microvilli of some leukocytes. The mesothelial cells remaining in the inflamed area expressed both ICAM‐1 and VCAM‐1 on their microvilli. The fibronectin was detected on presumable collagen fibers and/or fibrin over the exposed smooth muscle layer as well as on fibrin extending between leukocyte aggregation. The spatial microlocalization of integrins was clarified on the leukocytes emigrated in peritonitis, and their ligands were detected on the inflamed peritoneum. Anat Rec 264:219–227, 2001. © 2001 Wiley‐Liss, Inc.     

Phlegmasia cerulea dolens in a patient with chronic myelogenous leukemia—a case report

Phlegmasia cerulea dolens (PCD), a rare condition caused by deep venous thrombosis of the extremities and characterized by sudden massive edema, severe intractable pain, and purple ecchymoses, may result in arterial and venous compromise, amputation, and death. The causes of PCD vary and there is no consensus regarding optimal treatment. We describe what we believe is the first reported case of PCD in a patient with chronic myelogenous leukemia. The condition was treated successfully with thromboembolectomy performed after temporary placement of an inferior vena cava filter to prevent intraoperative pulmonary embolism. The thromboembolectomy specimen consisted of leukemic tumor emboli.