Yoshio Takesue

Practice guidelines for therapeutic drug monitoring of voriconazole: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

Arbekacin (ABK) was approved and widely used in Japan for treatment of patients infected with MRSA, and TDM was introduced in clinical practice. The Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring decided to develop a clinical practice guidelines for TDM of ABK for the following reasons. First, although the daily dose of 150e200 mg was approved in Japan, recent PK- PD studies revealed that higher serum concentration is required to achieve better clinical efficacy and several findings concerning the usefulness of higher dosage regimen have obtained recently. Second, although maximal concentrations that obtained immediately after the end of administration (Cmax )w as generally adopted, the serum concentration at 1 h after initiation of administration (peak serum con- centration (Cpeak)) proved to be more suitable as an efficacy indicator of aminoglycosides. Lastly, as ABK is approved only in Japan, no international practice guideline for TDM has not been available in ABK to date. This guideline evaluated the scientific data associated with serum ABK monitoring and provided rec- ommendations based on the available evidence. Potential limitations of this guideline, however, include the findings that few prospective clinical trials of TDM of ABK are available in the treatment of MRSA infections and that most of the published literature describes observational studies.

Nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy in 2007: general view of the pathogens' antibacterial susceptibility.

For the purpose of nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens collected from patients in Japan, the Japanese Society of Chemotherapy conducted a third year of nationwide surveillance during the period from January to April 2008. A total of 1,097 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 987 strains (189 Staphylococcus aureus, 211 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 187 Haemophilus influenzae, 106 Moraxella catarrhalis, 126 Klebsiella pneumoniae, and 162 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 β-lactams (four penicillins, three penicillins in combination with β-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including a ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). The incidence of methicillin-resistant S. aureus (MRSA) was as high as 59.8%, and those of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) were 35.5 and 11.8%, respectively. Among H. influenzae, 13.9% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 26.7% to be β-lactamase-non-producing ABPC-resistant (BLNAR), and 5.3% to be β-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5%) of β-lactamase-producing strains was suspected in Moraxella catarrhalis isolates. Four (3.2%) extended-spectrum β-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5%) of P.aeruginosa were found to be metallo β-lactamase-producing strains, including three (1.9%) suspected multidrug-resistant strains showing resistance to imipenem, amikacin, and ciprofloxacin. Continual national surveillance of the antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

Combined Assessment of β- d -Glucan and Degree of Candida Colonization before Starting Empiric Therapy for Candidiasis in Surgical Patients

The purpose of the study was to investigate whether examination for plasma β-d-glucan, a cell wall constituent of fungi, is useful for selecting surgical patients with Candida colonization who would benefit from empiric antifungal therapy. We administered fluconazole to postoperative patients with Candida colonization who have risk factors for candidemia and complained of persistent fever despite prolonged antibacterial therapy. We then analyzed the clinical outcomes regarding the number of sites colonized with Candida spp. and plasma β-d-glucan. Of the 32 patients positive for β-d-glucan, 15 (46.9%) responded to the empiric therapy; only 9% of those who were negative responded (p < 0.01). In the multiple logistic regression analysis, being positive for β-d-glucan was a significant factor predicting response, with an adjusted odds ratio of 12.9 in patients with Candida colonization [95% confidence interval (CI) 2.07–80.73) (p < 0.01). In addition, the number of sites colonized with Candida spp. was a significant factor predicting response, with an estimated exposure odds ratio of 7.57 for those who were colonized at three or more sites compared with those colonized at one site (95% CI 1.20–47.70) (p = 0.031). In patients with Candida colonization, assessment of β-d-glucan was useful for deciding whether to start empiric therapy for suspected candidiasis in surgical patients.

Long-term results of seton drainage on complex anal fistulae in patients with Crohn's disease

Background: The aim of this study was to assess the long-term (greater than 2 years) results of seton drainage on anal fistulae in patients with Crohns disease. Methods: Between September 1990 and September 1999, 32 patients with Crohns disease underwent seton drainage for complex anal fistulae. The median follow-up time in these patients was 62 months (range, 25–133 months). In 10 patients (31.3%), recurrent perineal abscesses occurred with inlying seton drainage, and these were drained by re-insertion of the seton. A Malecot catheter was also inserted in 8 patients with recurrence. Results: The overall success rate of long-term seton usage was 87.5%. The subsequent associated procedure was simple seton removal (n = 9), secondary core-out fistulectomy (n = 7), or lay-open fistulotomy (n = 4). Eleven patients still had the seton in place. Recurrence developed in 3 patients (33%) who underwent simple seton removal and in 2 patients (18.2%) who underwent the secondary core-out procedure or fistulotomy. At the last follow-up examination, continence had not changed in 28 (87.5%) of the 32 patients. No change in continence was experienced by 10 of the 11 patients who underwent secondary fistulotomy or the secondary core-out procedure. Conclusions: Long-term seton drainage for complex anal fistula in Crohns disease is efficacious in both treating sepsis and preserving anal sphincter function. A relatively good result was achieved by the secondary core-out procedure or fistulotomy at the time of seton removal.

Antimicrobial susceptibility and molecular characteristics of 857 methicillin-resistant Staphylococcus aureus isolates from 16 medical centers in Japan (2008–2009): nationwide survey of community-acquired and nosocomial MRSA

This study is a nationwide survey of all clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, including community-acquired MRSA (CA-MRSA), in Japan. A total of 857 MRSA clinical isolates were collected from the 16 institutions throughout Japan that participated in the survey (2008-2009). The drug susceptibility and staphylococcal cassette chromosome mec (SCCmec) typing and the presence of specific pathogenic genes were evaluated. The isolates comprised SCCmec type II (73.6%), type IV (20%), and type I (6%). The percentage of SCCmec type IV isolates was significantly higher in outpatients than in inpatients. Most of the isolated strains were sensitive to vancomycin (VCM, MIC ≤2 μg/mL), linezolid (MIC ≤4 μg/mL), and teicoplanin (MIC ≤8 μg/mL). Although most strains were sensitive to VCM, the MIC value of VCM for SCCmec type II strains was higher than that for SCCmec type IV strains. Only 4 (2.3%) of 171 SCCmec type IV strains were Panton-Valentine leukocidin (lukS/F-PV)-positive. Thus, this result indicates a unique feature of SCCmec type IV strains in Japan. The information in this study not only is important in terms of local public health but will also contribute to an understanding of epidemic clones of CA-MRSA.

Bacterial translocation in patients with Crohn's disease undergoing surgery.

AbstractPURPOSE: Much evidence, derived from experimental studies, suggests that bacterial translocation indeed occurs, yet its clinical significance is still a matter of controversy in humans. The aims of this study were to determine the prevalence of bacterial translocation in patients with Crohn’s disease undergoing laparotomy and to identify any association with postoperative septic complications or systemic inflammatory response syndrome. METHODS: Mesenteric lymph node and peripheral blood samples from 42 patients with Crohn’s disease undergoing laparotomy were collected for bacteriologic assessments. RESULTS: Bacterial translocation to mesenteric lymph node was identified in 20 patients (48 percent). The most common organism was Escherichia coli (27 percent). Blood cultures were positive in 2 of 20 patients in whom translocation to lymph node was identified. Bacterial translocation was associated with a greater than two-fold increase in the incidence of postoperative septic complications (35 vs.14 percent), but this difference was not significant. In the analysis of the occurrence of systemic inflammatory response syndrome, a significantly higher incidence continued until the third postoperative day in patients with vs. those without bacterial translocation. In a logistic regression analysis, bacterial translocation had a significant effect on the occurrence of systemic inflammatory response syndrome, even though septic complications were taken into account. CONCLUSIONS: Bacterial translocation to mesenteric lymph node predisposed patients with Crohn’s disease undergoing laparotomy to systemic inflammatory response syndrome.

Postoperative Enteritis Caused by Methicillin-Resistant Staphylococcus aureus

We examined the clinical features of 14 men (mean age 72 years) with postoperative enteritis caused by methicillin-resistantStaphylococcus aureus (MRSA). The patients had all undergone surgery for the treatment of digestive diseases and had received antibiotic prophylaxis consisting of an extended-spectrum cephem. Diarrhea appeared a mean of 3.3 days postoperatively and lasted for 5 days on average. In severe cases organ insufficiency was involved. Coagulase-positive staphylococci were the predominant organisms isolated from watery diarrhea. In 13 of 14 patients, coagulase type II isolates producing enterotoxins A, C and toxic shock syndrome toxin-1 (TSST-1) withenterotoxin A, C, andtst genes were isolated. These strains were sensitive to vancomycin and arbekacin; however, they were highly resistant to many other antibiotics. We also investigated the effects of a glucocorticoid hormone and gamma globulin on production of tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) obtained from healthy volunteers. TNF-α and IL-2 production was enhanced by TSST-1 and the supernatant of Iscove-modified dulbecco medium, in which coagulase type II isolates producing enterotoxins A, C and TSST-1 with enterotoxin A, C were cultured for 24h. Both glucocorticoid hormone and gama globulin suppressed TNF-α and IL-2 production, thus suggesting that these drugs may be effective in treating postoperative MRSA enteritis.

A brief course of colon preparation with oral antibiotics.

P < 0.05). The surgical site infection rate was 18% in group 1 and 13% in group 2. Organisms isolated from the sites of postoperative infections were not identical with those from the peritoneal fluid. This relatively brief course preparation minimized the emergence of resistant strains. However, in spite of the colonic bacterial burden and the intraoperative inoculation in the patients with mechanical cleansing alone, their incidence of subsequent infections was comparable to that of patients who were administered oral antibiotics provided that the prophylactic antibiotic was administered for 3 days after surgery.

The effectiveness of perineal rectosigmoidectomy for the treatment of rectal prolapse in elderly and high-risk patients

We report herein on the follow-up of ten consecutive patients who underwent perineal rectosigmoidectomy, and discuss the indications, surgical technique, and outcomes of this procedure. The median age of the patients was 79 years, with a range of 26 to 85 years, and eight patients had complicating medical conditions. Of five patients who underwent this procedure for a recurrent prolapse after another type of perineal procedure, four had previously undergone the Thiersch operation combined with the Gant-Miwa technique. The mean length of the excised rectum and sigmoid colon was 22.1 cm. Pain was minimal or absent in all patients and oral intake was commenced after 2 days. There were no mortalities, but anastomotic leakage occurred in one patient. The mean follow-up period was 3.5 years. Only one patient developed recurrent rectal prolapse 24 months after the operation. Of seven patients who underwent concomitant levatoroplasty for incontinence, five became fully continent within 3 weeks after the operation, while the remaining two improved after 2 months. We propose that perineal rectosigmoidectomy is indicated for patients who have suffered an early recurrence of prolapse after another transperineal repair; elderly or highrisk patients with incontinence; male patients; and patients with an incarcerated or gangrenous prolapsed rectal segment.

A study on postoperative enteritis caused by methicillin-resistant Staphylococcus aureus

We investigated the production of staphylococcal enterotoxin (SE) with respect to coagulase types by methicillin-resistant Staphylococcus aureus (MRSA). A total of 138 strains of MRSA, which were isolated from clinical materials in the surgical ward between 1983 and 1990, were studied. Coagulase type IV strains produced SE A only, whereas coagulase type II strains were classified into four groups by SE production: SE B producing strains (32.7%), SE C producing strains (29.8%), SE B and C coproducing strains (12.5%), and SE A and C coproducing strains (25.0%). Almost all of the organisms (nine of ten) which were isolated from the feces of patients with MRSA enteritis were SE A and C coproducing strains. The coincidence in time of the prevalence of MRSA enteritis and the isolation SE A and C coproducing strains also demonstrated that these strains caused MRSA enteritis. Although SE C producing strains and SE A and C coproducing strains were simultaneously prevalent in 1990, the former tended to be sensitive while the latter tended to be resistant to minocycline. Considering the variety of antibiotic sensitivity in coagulase type II strains, it is thus considered to be of critical importance for epidemiologic purposes to further characterize isolates by SE typing.