Childbirth after perioperative systemic therapy in patients with breast cancer: a retrospective single institutional study in Japan.

BACKGROUND: The number of breast cancer patients of childbearing age has been increasing. Therefore, we investigated the characteristics and the childbearing status of the patients who received systemic therapy for breast cancer during their childbearing age to better understand the clinical impact of childbirth. METHODS: Female patients with breast cancer younger than 40 years old who underwent surgery and received perioperative systemic therapy from 2007 to 2014 were included in this study. We compared the characteristics of patients with and without childbirth after treatment. RESULT: Of 590 patients, 26 delivered a child, and 355 did not bear a child during the median observation period of 8.1 years, whilst 209 had unknown childbirth data. The childbirth group had a lower mean age at surgery (32.2 vs. 35.1, P < 0.001). The proportion of patients who desired childbirth and used assisted reproductive technology was significantly higher in the childbirth group (65.4 vs. 23.9% and 45.2 vs. 5.1%, respectively, P < 0.001). The patients in the childbirth group had significantly less advanced disease (P = 0.002). In the childbirth group, the age at childbirth was significantly older in patients who received combined endocrine therapy and chemotherapy (40.8 years) than in patients who received either alone (endocrine therapy: 36.9 years, chemotherapy: 36.7 years, P = 0.04). However, survival was not different between those with and without childbirth. CONCLUSION: It is critical to recognize the desire for childbirth in patients with breast cancer who are receiving systemic therapy and to provide them with necessary fertility information before treatment to support their decision-making.

[A Case of Breast Apocrine Carcinoma in Which Eribulin Was Effective].

A 79-year-old woman presented with a chief complaint of a palpated tumor on her right axilla. The right breast tumor size was 18mm and the axillary lymph node size was 30 mm, as detected with ultrasonography. Pathological findings indicated the presence of an ER(-), Pg R(-), HER2-negative apocrine carcinoma. The presence of axillary lymph node metastasis was diagnosed from the apocrine carcinoma. Eribulin(1.5mg)was administered 3 times before surgery. Tumors were significantly reduced. The Bt+Ax(Patey procedure)dissection was performed until Level 2. The pathological findings of the tumor revealed coagulation, necrosis, and the remaininglimited cancer lesions in the periphery zone. No remainingcancer cells were detected in the lymph nodes. The breast apocrine carcinoma was determined as a special type of invasive cancer. Although the prognosis is positive, the current case was considered highly malignant with a 50% positive Ki-67 rating. Although eribulin was effective, it seems that this case requires strict follow-up observations.

Central control of bone remodeling by neuromedin U.

Bone remodeling, the function affected in osteoporosis, the most common of bone diseases, comprises two phases: bone formation by matrix-producing osteoblasts and bone resorption by osteoclasts. The demonstration that the anorexigenic hormone leptin inhibits bone formation through a hypothalamic relay suggests that other molecules that affect energy metabolism in the hypothalamus could also modulate bone mass. Neuromedin U (NMU) is an anorexigenic neuropeptide that acts independently of leptin through poorly defined mechanisms. Here we show that Nmu-deficient (Nmu-/-) mice have high bone mass owing to an increase in bone formation; this is more prominent in male mice than female mice. Physiological and cell-based assays indicate that NMU acts in the central nervous system, rather than directly on bone cells, to regulate bone remodeling. Notably, leptin- or sympathetic nervous system-mediated inhibition of bone formation was abolished in Nmu-/- mice, which show an altered bone expression of molecular clock genes (mediators of the inhibition of bone formation by leptin). Moreover, treatment of wild-type mice with a natural agonist for the NMU receptor decreased bone mass. Collectively, these results suggest that NMU may be the first central mediator of leptin-dependent regulation of bone mass identified to date. Given the existence of inhibitors and activators of NMU action, our results may influence the treatment of diseases involving low bone mass, such as osteoporosis.

Clostridium perfringens alpha-toxin induces the release of IL-8 through a dual pathway via TrkA in A549 cells.

A characteristic feature of gas gangrene with Clostridium perfringens (C. perfringens) is the absence of neutrophils within the infected area and the massive accumulation of neutrophils at the vascular endothelium around the margins of the necrotic region. Intravenous injection of C. perfringens alpha-toxin into mice resulted in the accumulation of neutrophils at the vascular endothelium in lung and liver, and release of GRO/KC, a member of the CXC chemokine family with homology to human interleukin-8 (IL-8). Alpha-toxin triggered activation of signal transduction pathways causing mRNA expression and production of IL-8, which activates migration and binding of neutrophils, in A549 cells. K252a, a tyrosine kinase A (TrkA) inhibitor, and siRNA for TrkA inhibited the toxin-induced phosphorylation of TrkA and production of IL-8. In addition, K252a inhibited the toxin-induced phosphorylation of extracellular regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). PD98059, an ERK1/2 inhibitor, depressed phosphorylation of ERK1/2 and nuclear translocation of nuclear factor kappa B (NF-κB) p65, but SB203580, a p38 MAPK inhibitor, did not. On the other hand, PD98059 and SB203580 suppressed the toxin-induced production of IL-8. Treatment of the cells with PD98059 resulted in inhibition of IL-8 mRNA expression induced by the toxin and that with SB203580 led to a decrease in the stabilization of IL-8 mRNA. These results suggest that alpha-toxin induces production of IL-8 through the activation of two separate pathways, the ERK1/2/NF-κB and p38 MAPK pathways.

In vivo role of aldehyde reductase.

BACKGROUND: Aldehyde reductase (AKR1A; EC 1.1.1.2) catalyzes the reduction of various types of aldehydes. To ascertain the physiological role of AKR1A, we examined AKR1A knockout mice. METHODS: Ascorbic acid concentrations in AKR1A knockout mice tissues were examined, and the effects of human AKR1A transgene were analyzed. We purified AKR1A and studied the activities of glucuronate reductase and glucuronolactone reductase, which are involved in ascorbic acid biosynthesis. Metabolomic analysis and DNA microarray analysis were performed for a comprehensive study of AKR1A knockout mice. RESULTS: The levels of ascorbic acid in tissues of AKR1A knockout mice were significantly decreased which were completely restored by human AKR1A transgene. The activities of glucuronate reductase and glucuronolactone reductase, which are involved in ascorbic acid biosynthesis, were suppressed in AKR1A knockout mice. The accumulation of d-glucuronic acid and saccharate in knockout mice tissue and the expression of acute-phase proteins such as serum amyloid A2 are significantly increased in knockout mice liver. CONCLUSIONS: AKR1A plays a predominant role in the reduction of both d-glucuronic acid and d-glucurono-γ-lactone in vivo. The knockout of AKR1A in mice results in accumulation of d-glucuronic acid and saccharate as well as a deficiency of ascorbic acid, and also leads to upregulation of acute phase proteins. GENERAL SIGNIFICANCE: AKR1A is a major enzyme that catalyzes the reduction of d-glucuronic acid and d-glucurono-γ-lactone in vivo, besides acting as an aldehyde-detoxification enzyme. Suppression of AKR1A by inhibitors, which are used to prevent diabetic complications, may lead to the accumulation of d-glucuronic acid and saccharate.

The impact of obesity and endocrine therapy on the prognosis of premenopausal women with hormone receptor-positive breast cancer: A single-institute retrospective study.

BACKGROUND: Higher body mass index (BMI) is associated with worse prognosis in pre- and postmenopausal patients with breast cancer (BC). However, there is insufficient evidence regarding the optimal adjuvant endocrine therapy for obese premenopausal women with hormone receptor (HR)-positive BC. AIM: To evaluate the impact of obesity and adjuvant endocrine therapy on prognosis in premenopausal patients with BC. METHODS AND RESULTS: We retrospectively reviewed the medical record of premenopausal women who received curative surgery for clinical stage I-III HR-positive BC from 2007 to 2017. Patients were classified into five groups according to BMI: underweight (UW), normal weight (NW), obese 1 degree (OB1), obese 2 degree (OB2), and obese 3 degree (OB3) categories. The primary analysis was a comparison of BC-specific survival (BCSS) according to BMI (UW/NW vs. OB1-3) and adjuvant endocrine therapy (with or without ovarian function suppression [OFS]). Of 13 021 patients, the data of 3380 patients were analyzed. BCSS in OB1-3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40-4.02: p = .0009). In OB1-3 patients who received tamoxifen (TAM), BCSS was significantly worse than that in UW/NW patients (p = .0086); however, a significant difference was not shown in patients who received TAM and OFS (p = .0921). CONCLUSION: High BMI was associated with worse prognosis in premenopausal patients with HR-positive BC who received adjuvant TAM. The role of OFS as adjuvant endocrine therapy remains unclear, and further studies are required to explore the adequate management of obese premenopausal patients.

Automatic parameter optimization in epsilon-filter for acoustical signal processing utilizing correlation coefficient.

epsilon-filter can reduce most kinds of noise from a single-channel noisy signal while preserving signals that vary drastically such as speech signals. It can reduce not only stationary noise but also nonstationary noise. However, it has some parameters whose values are set empirically. So far, there have been few studies to evaluate the appropriateness of the parameter settings for epsilon-filter. This paper employs the correlation coefficient of the filter output and the difference between the filter input and output as the evaluation function of the parameter setting. This paper also describes the algorithm to set the optimal parameter value of epsilon-filter automatically. To evaluate the adequateness of the obtained parameter, the mean absolute error is calculated. The experimental results show that the adequate parameter in epsilon-filter can be obtained automatically by using the proposed method.

[Clinical analysis of precaution against atrial fibrillation following cardiac surgery: landiolol or amiodarone?].

Atrial fibrillation following cardiac surgery remains as a most common complication. Tachycardia with atrial fibrillation just after the operation could lead to cardiac deterioration. Although we have to control tachycardia, we often have great difficulties in managing these arrhythmias. Many reports have showed landiolol, ultra short-acting beta1 blocker, and amiodarone were effective against postoperative atrial fibrillation. However there has been no report on comparison between these 2 drugs. As excessively sympathetic activity might cause atrial fibrillation, landiolol was introduced into our therapy concomitant with the sedative. Our investigation confirmed that both landiolol and amiodarone were effective in preventing atrial fibrillation, and that the timing of transition from intravenous administration to oral intake was acceptable. When landiolol was administered, enough attention should be paid to the patients whose left ventricular function was low. The patients in whom atrial fibrillation occurred under landiolol therapy showed tendency of lower heart rate in comparison with the patients under amiodarone therapy.

Noise reduction utilizing cross time-frequency epsilon-filter.

A time-frequency epsilon-filter (TF epsilon-filter) is an advanced epsilon-filter applied to complex spectra along the time axis. It can reduce most kinds of noise while preserving a signal that varies frequently such as a speech signal. The filter design is simple and it can effectively reduce noise. It is applicable not only to small amplitude stationary noise but also to large amplitude nonstationary noise. However, when the filter is applied to the noise that varies much frequently along the time axis, TF epsilon-filter cannot reduce noise without the signal distortion. This paper introduces an advanced method for noise reduction that applies epsilon-filter to complex spectra not only along the time axis but also along the frequency axis labeled cross TF epsilon-filter. It can reduce the noise where the neighboring frequency bins have similar powers. To show the effectiveness of the proposed method, some comparative experiments are also given, such as the performance of noise reduction and the robustness concerning input signal-to-noise ratio and parameter changes.

Noise reduction combining time-frequency epsilon-filter and M-transform.

This paper introduces noise reduction combining time-frequency epsilon-filter (TF epsilon-filter) and time-frequency M-transform (TF M-transform). Musical noise is an offensive noise generated due to noise reduction in the time-frequency domain such as spectral subtraction and TF epsilon-filter. It has a deleterious effect on speech recognition. To solve the problem, M-transform is introduced. M-transform is a linear transform based on M-sequence. The method combining the time-domain epsilon-filter (TD epsilon-filter) and time-domain M-transform (TD M-transform) can reduce not only white noise but also impulse noise. Musical noise is isolated in the time-frequency domain, which is similar to impulse noise in the time domain. On these prospects, this paper aims to reduce musical noise by improving M-transform for the time-frequency domain. Noise reduction by using TD M-transform and the TD epsilon-filter is first explained to clarify its features. Then, an improved method applying M-transform to the time-frequency domain, namely TF M-transform, is described. Noise reduction combining the TF epsilon-filter and TF M-transform is also proposed. The proposed method can reduce not only high-level nonstationary noise but also musical noise. Experimental results are also given to demonstrate the performance of the proposed method.

Noise reduction combining time-domain epsilon-filter and time-frequency epsilon-filter.

A time-domain epsilon-filter (TD epsilon-filter) is a nonlinear filter that can reduce noise while preserving a signal that varies drastically, such as a speech signal. Although the filter design is simple, it can effectively reduce noise. It is applicable not only to stationary noise but also to nonstationary noise. It cannot, however, be applied when the amplitude of noise is relatively large. This paper introduces an advanced method for noise reduction that applies an epsilon-filter to complex spectra, namely a time-frequency epsilon-filter (TF epsilon-filter). This paper also introduces noise reduction combining a TD epsilon-filter and a TF epsilon-filter. An advanced method called a variable time-frequency epsilon-filter is also proposed. First, the algorithm of the TD epsilon-filter is explained to clarify the problem. Then, the algorithms of the proposed methods are explained. By utilizing an epsilon-filter in the frequency domain, the proposed method can reduce not only noise that has a relatively small amplitude but also noise that has a relatively large amplitude. Experimental results are also given to demonstrate the performance of the proposed methods in comparison to the results of some conventional methods.

[A case of liver failure associated with liver damage due to mFOLFOX 6 after resection for multiple liver metastases from colorectal cancer].

A case of colorectal cancer in a 60-year-old man became resectable after downstaging was achieved with mFOLFOX 6 for multiple liver metastases from colorectal cancer. The patient received 8 cycles of mFOLFOX 6 on the basis of a diagnosis of multiple liver metastases in the right and left lobes and a single metastasis in the right lung. After chemotherapy, the liver metastases showed partial response, and the lung metastasis stable disease. Because the lung metastasis was controlled and radical cure of the liver metastases was thought possible by resection, we performed right lobectomy of the liver. Postoperative progress was good, and we then planned a staged partial resection of the lung. However,on postoperative day 28, the patient was hospitalized again with liver dysfunction, which evolved into liver failure, in spite of conservative treatment. The patient died on postoperative day 95. The needle biopsy specimens of the liver taken on readmission showed bile duct occlusion, portal hypertension, and perisinusoidal fibrosis, and histopathology of the surgical non-tumoral liver specimen showed the same findings. We think that liver failure was triggered by resection of the liver which had been damaged by mFOLFOX 6. Recently, liver damage due to oxaliplatin was reported, and evaluation of liver injury is considered important before liver resection for colorectal liver metastases with neoadjuvant FOLFOX.

A Case of Recurrent Breast Cancer Identified by Pulmonary Tumor Thrombotic Microangiopathy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare, cancer-related, pulmonary complication that causes hypoxia and pulmonary hypertension. We report on a 42-year-old woman who was diagnosed with recurrent breast cancer that was detected due to the presence of PTTM. Eleven months after surgery for heterochronous bilateral cancer of the left breast, she developed progressive dyspnea but computerized tomography showed no pulmonary thromboembolism, and a transthoracic echocardiography revealed mild pulmonary hypertension. She was diagnosed with PTTM by cytology from pulmonary artery catheterization and perfusion lung scintigraphy. Also, the patients complained of back pain after admission, bone scintigraphy showed multiple bone metastases. Despite the early diagnosis of PTTM, her platelet count decreased, her performance status rapidly deteriorated, and her dyspnea worsened. Thus, we could not treat her with chemotherapy. She died due to respiratory failure 19 days after admission. To the best of our knowledge, this is the first report of recurrent breast cancer identified by the manifestation of PTTM. Although PTTM is a rare phenomenon, it should be considered in the differential diagnosis of acute dyspnea or pulmonary hypertension in patients with breast cancer. Furthermore, upon diagnosis, the patient should be referred to a cardiologist as soon as possible.

Yeast Ca(2+)-signal transduction inhibitors isolated from Dominican amber prevent the degranulation of RBL-2H3 cells through the inhibition of Ca(2+)-influx.

A new norlabdane compound, named kujigamberol has previously been isolated from Kuji amber (but not from Baltic amber) by activity guided fractionation. However, there has been no study of biological compounds in Dominican amber. Biological activities were examined using the hypersensitive mutant yeast (zds1Δ erg3Δ pdr1Δ pdr3Δ) with respect to Ca(2+)-signal transduction, enzymes and rat basophilic leukemia (RBL)-2H3 cells. The structures were elucidated on the basis of spectral analysis including high resolution (HR)-EI-MS, 1D NMR and 2D NMR. Three diterpenoid compounds, 5(10)-halimen-15-oic acid (1), 3-cleroden-15-oic acid (2) and 8-labden-15-oic acid (3), which are different from the bioactive compounds in Kuji and Baltic ambers, were isolated from Dominican amber. They inhibited both calcineurin (CN) (IC50=40.0, 21.2 and 34.2µM) and glycogen synthase kinase-3ß (GSK-3ß) (IC50=48.9, 43.8 and 41.1µM) which are involved in the growth restored activity against the mutant yeast. The most abundant compound 2 showed inhibitory activity against both degranulation and Ca(2+)-influx in RBL-2H3 cells. The compounds having the growth restoring activity against the mutant yeast have potential as anti-allergic compounds.

[Surveillance of susceptibility of clinical isolates to panipenem between 2000 and 2003].

For the post-marketing surveillance of panipenem/betamipron (PAPM/BP, Carbenin), MICs of injectable beta-lactam antibacterials including PAPM against clinical isolates from 15 medical institutions all over Japan are measured yearly and the incidence rates of resistance in various species are also evaluated. In the first surveillance from June 2000 to March 2001, 1,356 isolates of 28 species were tested, 1,221 isolates of the same 28 species were tested in the second surveillance from April 2001 to March 2002, and 1,403 isolates of the same 28 species were tested in the third surveillance from April 2002 to March 2003. No remarkable changes in the activity of PAPM were observed in these surveillances spanning three years. The activity of PAPM in this study was comparable to that in the studies conducted before Carbenin was launched. This result suggests that PAPM still maintains potent activity. In these surveillances spanning three years, the incidence rates of resistance in various species were as follows (2000.6-2001.3 --> 2001.4-2002.3 --> 2002.4-2003.3): methicillin-resistant Staphylococcus aureus (39.3% --> 43.9% --> 47.3%), penicillin-intermediate Streptococcus pneumoniae (48.9% --> 44.2% --> 25.7%), penicillin-resistant S. pneumoniae (PRSP, 13.8% --> 26.3% --> 43.2%), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (0.9% --> 0% --> 1.4%), ESBL-producing Klebsiella pneumoniae (3.4% --> 1.3% --> 3.1%), beta-lactamase-producing Haemophilus influenzae (19.2% --> 8.9% --> 42.9%), beta-lactamase-negative ampicillin-resistant H. influenzae (BLNAR, 22.1% --> 30.7% --> 33.0%), and metallo-beta-lactamase-producing Pseudomonas aeruginosa (1.0% --> 4.4% --> 1.0%). PAPM showed the most potent activity among tested drugs against PRSP, whose incidence rate increased notably. BLNAR, whose incidence rates also increased, exhibited low susceptibility to all tested drugs and metallo-beta-lactamase-producing P. aeruginosa also exhibited high resistance. The findings of this surveillance indicate that it is necessary to pay careful attention to the trends of resistant bacteria such as PRSP, BLNAR, and metallo-beta-lactamase producing strains.

[Surveillance of susceptibility of clinical isolates to cefpodoxime between 2000 and 2003].

For the post-marketing surveillance of cefpodoxime proxetil (CPDX-PR, Banan), MICs of oral cephem antibacterials including CPDX against clinical isolates from 15 medical institutions all over Japan are measured yearly and the incidence rates of resistance in various species are also evaluated. In the first surveillance from June 2000 to March 2001, 1,091 isolates of 22 species were tested, 993 isolates of the same 22 species were tested in the second surveillance from April 2001 to March 2002, and 1,115 isolates of the same 22 species were tested in the third surveillance from April 2002 to March 2003. No remarkable changes in the activity of CPDX were observed against most of the species in these surveillances spanning three years and in comparison with that in the studies conducted before Banan was launched. In the study, CPDX as well as other cephem antibacterials showed a gradual decrease in activity against all the strains of Streptococcus pneumoniae and Haemophilus influenzae in proportion to the increase in the incidence rates of penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase-negative ampicillin-resistant H. influenzae (BLNAR). A small percentage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, which are high-resistant strains, were isolated. The findings of this surveillance indicate that it is necessary to pay careful attention to the trends of resistant bacteria such as PRSP, BLNAR, and ESBL-producing strains.

[Surveillance of susceptibility of clinical isolates to cefmetazole between 2000 and 2003].

For the post-marketing surveillance of cefmetazole (CMZ, Cefmetazon), MICs of injectable beta-lactam antibacterials including CMZ against clinical isolates from 15 medical institutions all over Japan are measured yearly and the incidence rates of resistance in various species are also evaluated. In the first surveillance from June 2000 to March 2001, 574 isolates of 13 species were tested, 548 isolates of the same 13 species were tested in the second surveillance from April 2001 to March 2002, and 654 isolates of the same 13 species were tested in the third surveillance from April 2002 to March 2003. No remarkable changes in the activity of CMZ were observed in these surveillances spanning three years. The activity of CMZ in this study was comparable to that in the studies conducted before Cefmetazon was launched. This result suggests that CMZ still maintains potent activity. Changes in percent resistance of each species to CMZ (MIC of CMZ > or = 32 microg/ml) were as follows: methicillin-susceptible Staphylococcus aureus (MSSA, 0.0% --> 0.0% --> 0.0%), methicillin-resistant Staphylococcus aureus (MRSA, 72.9% --> 87.2% --> 88.7%), Staphylococcus epidermidis (18.5% --> 31.6% --> 14.3%), coagulase-negative Staphylococcus spp. (CNS, 13.3% --> 18.2% --> 21.4%), Escherichia coli (3.6% --> 0.8% --> 2.1%), Klebsiella pneumoniae (3.4% --> 3.8% --> 2.1%), Klebsiella oxytoca (0.0% --> 0.0% --> 0.0%), Proteus mirabilis (2.3% --> 2.1% --> 0.0%), Proteus vulgaris (13.6% --> 6.7% --> 0.0%), Morganella morganii (7.3% --> 0.0% --> 14.0%), Providencia spp. (12.5% --> 0.0% --> 18.2%), Peptostreptococcus spp. (0.0% --> 0.0% --> 0.0%), Bacteroides fragilis (10.3% --> 10.8% --> 17.1%), Bacteroides spp. (78.6% --> 87.5% --> 62.5%). The Change in percent resistance of MRSA, other CNS, and B. flagiris tended to increase. It is necessary to pay much attention to trends observed in these species. Compared to other drugs tested, against MSSA, the activity of CMZ was inferior to that of CEZ, CTM, and FMOX and superior to that SBT/CPZ. Against MRSA, S. epidermidis, and CNS, the tested drugs exhibited little activity. Against Gram-negative bacteria, the activity of CMZ was almost superior to that of CEZ and CTM, and inferior to that of FMOX. Against B. flagiris and other Bacteroides spp., the activity of CMZ was almost superior to that of CEZ and CTM, and comparable to or inferior to that of SBT/CPZ and FMOX.

[Surveillance of susceptibility of clinical isolates to cefmetazole between 2000 and 2002].

The antibacterial activity of cefmetazole (CMZ) against clinical isolates from 15 medical institutions all over Japan was evaluated yearly for two years from June 2000 to March 2002 and compared with that of other parenteral beta-lactams, cefazolin (CEZ), cefotiam (CTM), sulbactam/cefoperazone (SBT/CPZ), and flomoxef (FMOX). In the first surveillance from June 2000 to March 2001, 575 isolates of 13 species were tested, and 548 isolates of the same 13 species were tested in the second surveillance from April 2001 to March 2002. In these surveillances spanning two years, the MIC90s of CMZ against the bacterial species tested hardly differed. Changes in percent resistance of each species to CMZ (MIC of CMZ > or = 32 micrograms/mL) were as follows: methicillin-susceptible Staphylococcus aureus (MSSA, 0%-->0%), methicillin-resistant Staphylococcus aureus (MRSA, 73%-->87%), Staphylococcus epidermidis (19%-->32%), other coagulase-negative Staphylococcus spp. (other CNS, 13%-->18%), Escherichia coli (4%-->1%), Klebsiella pneumoniae (3%-->4%), Klebsiella oxytoca (0%-->0%), Proteus mirabilis (2%-->2%), Proteus vulgaris (14%-->7%), Morganella morganii (7%-->0%), Providencia spp. (17%-->0%), Peptostreptococcus spp. (0%-->0%), Bacteroides fragilis (10%-->11%), and other Bacteroides spp. (79%-->88%). The change in percent resistance of MRSA, S. epidermidis, other CNS, and other Bacteroides spp. tended to increase. In addition, the percent resistance of B. fragilis was 10%. It is necessary to pay much attention to the trends observed in these species. Compared to other drugs tested, against MSSA, the activity of CMZ was inferior to that of CEZ, CTM, and FMOX and superior to that of SBT/CPZ. Against MRSA, S. epidermidis, and CNS, the tested drugs exhibited little activity. Against Gram-negative bacteria, the activity of CMZ was almost superior to that of CEZ and CTM, and inferior to that of FMOX. Against B. fragilis and other Bacteroides spp., the activity of CMZ was almost superior to that of CEZ and CTM, and comparable to or inferior to that of SBT/CPZ and FMOX. No remarkable changes in the activity of CMZ were observed in this study compared with studies conducted before CMZ was launched. This result suggests that CMZ still maintains potent activity.

[Antibacterial activity of panipenem against clinical isolates in 2000 and 2001].

As the post-marketing surveillance of panipenem/betamipron (Carbenin), MICs of panipenem (PAPM) against 1355 clinical isolates of 28 species from 15 medical institutions all over Japan from June 2000 to March 2001 were measured using the broth microdilution method approved by the Japanese Society of Chemotherapy and compared with those of parenteral carbapenem antibacterials, imipenem (IPM) and meropenem (MEPM), and parenteral cephem antibacterials, cefozopran, cefepime, and sulbactam/cefoperazone. The activity of PAPM was comparable to that of IPM against almost all species tested. Compared with MEPM, PAPM was more active against Gram-positive bacteria and Bacteroides spp., and less active against Gram-negative bacteria. Compared with the parenteral cephems, PAPM was more active against most of species tested and its MIC ranges were narrower than those of the cephems as were those of other carbapenems. In this surveillance study, the incidence of resistance in various species were as follows: 39.3% for methicillin-resistant Staphylococcus aureus, 47.3% for penicillin-intermediate Streptococcus pneumoniae (PISP), 15.1% for penicillin-resistant S. pneumoniae (PRSP), 0.9% for extended-spectrum beta-lactamase (ESBL) producing Escherichia coli, 3.4% for ESBL producing Klebsiella pneumoniae, 19.2% for beta-lactamase producing Haemophilus influenzae, 24.0% for beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae, and 1.0% for metallo-beta-lactamase producing Pseudomonas aeruginosa. Against these resistant strains, carbapenems including PAPM showed generally more potent activity than cephems. It was noted that PAPM showed the most potent activity against PISP and PRSP, which showed high incidence of 62.4% totally, among tested drugs. Metallo-beta-lactamase producing P. aeruginosa exhibited high resistance and BLNAR H. influenzae also exhibited low susceptibility against all tested drugs. But no remarkable change in the activity of PAPM against other species was observed in this study compared with that in the studies before the marketing of Carbenin. Furthermore, it is necessary to pay much attention to the trend of resistant strains such as PRSP, metallo-beta-lactamase producing bacteria, and BLNAR H. influenzae.

[Antibacterial activity of cefpodoxime against clinical isolates in 2000 and 2001].

As the post-marketing surveillance of cefpodoxime proxetil (Banan), MICs of cefpodoxime (CPDX, an active form of Banan) against 1090 clinical isolates of 22 species from 15 medical institutions all over Japan from June 2000 to March 2001 were measured using the broth microdilution method approved by the Japanese Society of Chemotherapy and compared with those of oral cephem antibacterials, cefaclor, cefdinir, cefditoren, and cefcapene. In this study, remarkable change in the activity of CPDX was observed in Streptococcus pneumoniae and Haemophilus influenzae compared with the susceptibility in the studies before Banan was launched. This cause is considered to be the increase in the incidence of the following resistant strains: penicillin-intermediate S. pneumoniae (47.3%), penicillin-resistant S. pneumoniae (PRSP, 15.1%), and beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae (24.0%), which were scarcely isolated in 1989 when Banan was launched. Other tested drugs also exhibited low activity against these resistant strains. However, CPDX showed comparatively good activity with MIC90 of 2 micrograms/mL against PRSP. Against methicillin-susceptible Staphylococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, and Moraxella catarrhalis, CPDX also showed comparatively good activity with MIC90 of < or = 4 micrograms/mL, which was almost equal to that in the studies before its marketing. Against quinolones-resistant Neisseria gonorrhoeae, CPDX showed excellent activity with MIC90 of 0.5 microgram/mL. Against members of the family Enterobacteriaceae except for Citrobacter freundii, Enterobacter spp., Proteus vulgaris, and Morganella morganii, CPDX showed good activity. However, in Escherichia coli, Klebsiella spp. Proteus spp., and Providencia spp., there are some high-resistant strains to all tested drugs including CPDX. Against Peptostreptococcus spp., MIC90 of CPDX was 8 micrograms/mL and its MIC range was widely distributed from 0.03 to 32 micrograms/mL, which were similar to those in the studies before its marketing. In this study, CPDX showed the decrease in the activity against several species as did other drugs tested, but against most of species tested, CPDX maintained good activity. Furthermore, it is necessary to pay much attention to the trend of resistant strains.