[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2009].

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 2655 strains including 810 strains of Gram-positive bacteria, 1635 strains of Gram-negative bacteria, and 210 strains of anaerobic bacteria obtained from 30 medical institutions during 2009 was examined. The results were as follows; (1) MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multidrug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). (2) MEPM maintained potent and stable antibacterial activity against Pseudomonas aeruginosa. The proportion of MEPM-resistant strains to ciprofloxacin-resistant strains or imipenem-resistant strains were 53.1% and 58.0% respectively. (3) The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (26 strains) in enterobacteriaceae. And the proportion of metallo-beta-lactamase strains was 2.0% (6 strains) in P. aeruginosa. (4) Of all species tested, there were no species except for Bacteroides fragilis group, which MIC90 of MEPM was more than 4-fold higher than those in our previous study. Therefore, there is almost no significant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 14 years passed after available for commercial use in Japan.

Expression of CD38 with intracellular enzymatic activity: a possible explanation for the insulin release induced by intracellular cADPR.

CD38 is a transmembrane glycoprotein expressed in multiple cell types, including pancreatic ß cells. It can serve as an enzyme that catalyzes the metabolism of two different Ca(2+)-mobilizing compounds, cyclic adenosine diphosphoribose (cADPR) and nicotinic acid adenine dinucleotide phosphate. One of these metabolites, cADPR, is known to be involved in glucose-induced insulin secretion from pancreatic ß cells. Although the essential role of CD38 for endogenous cADPR synthesis has been established, the relationship between the proposed extracellular enzymatic activity of CD38 and the intracellular Ca(2+) modulation caused by the intracellular cADPR accumulation has not yet been fully explained. For a better understanding of the role of CD38 in the insulin secretion machinery, analysis of the intracellular localization of this molecule in pancreatic ß cells is essential. In an attempt to provide a method to probe the N-terminal and C-terminal of CD38 separately, we generated an insulin-secreting MIN6 murine pancreatic ß cell line expressing a human CD38 bearing an N-terminal FLAG epitope tag. We found a weak but consistent expression of the FLAG epitope outside of the cells, indicating the presence of a small amount of CD38 with cytoplasmic enzymatic activity. MIN6 cells transfected with human CD38 exhibited increased glucose-induced insulin release. In addition, anti-FLAG cross-linking further enhanced the insulin release, suggesting that the N-terminal of CD38 expressed on the cell surface functions as a receptor for an unknown ligand and triggers positive signals for insulin secretion.

Study of the measurement of serum extracellular domain of HER-2/neu protein with CLIA method.

OBJECTIVE: Immunohistochemistry (IHC) and Fluorescent In Situ Hybridization (FISH) are important technologies to examine the protein expression and gene amplification of human epidermal growth factor receptor type 2/neu (HER-2/neu), respectively, in breast cancer tumors; however, tumor samples are not always available for examination. Therefore, an easy and sensitive examination to detect HER2-overexpressed tumors should be developed. The extracellular domain of HER-2/neu protein (HER2ECD) has been reported to be observed in the serum of many patients with metastatic breast cancer. In this study we assessed the clinical usefulness of serum HER2ECD (sHER2ECD) as a biological marker in breast cancer. METHOD: We measured sHER2ECD levels in 108 patients with breast cancer using the ADVIA Centaur assay system, and conventional tumor markers, i.e. CEA and CA15-3, using enzyme or chemiluminescent immunoassay. The sHER2ECD levels were compared with the levels of tumor markers and clinical characteristics. RESULTS: Patients with primary breast cancer who had four or more lymph nodes involved (n=6) showed significantly higher sHER2ECD values than those with no nodes involved (n=57, p<0.05) and those with 1 to 3 nodes involved (n=15, p<0.01). In the IHC-positive group, the positive rate of sHER2ECD was higher than those of CA15-3 or CEA. In metastatic breast cancer, the combination of sHER2ECD and CA15-3 showed the highest positive rate (81.5%). In all 3 patients with HER2-overexpressed cancer showing a partial response (PR) or complete response (CR) to trastuzumab therapy, sHER2ECD levels declined after treatment (39.9 to 58.7%). CONCLUSION: The sHER2ECD assay by the CLIA method may be useful for the diagnosis and monitoring of metastatic/recurrent breast cancer.

Analysis of Bordetella pertussis agglutinin titers during an outbreak of pertussis at a university in Japan.

In 2007, a large outbreak of pertussis occurred at a university in Japan. Initially, a student, suffering from nocturnal cough and post-tussive vomiting for 3 weeks was diagnosed with pertussis. During the subsequent outbreak, 361 university students and staff members presented with a primary complaint of a cough. In the present study, we analyzed bacterial agglutinin titers against two Bordetella pertussis strains, Yamaguchi (epidemic strain) and Tohama (vaccine strain), in 310 patients with a cough and evaluated its diagnostic accuracy for adolescent and adult pertussis. These serological analyses showed a significant difference (P<0.001) in the levels of Yamaguchi agglutinin titer, but not in those of Tohama agglutinin titer, between patient and healthy adult groups. Therefore, the bacterial agglutination assay against strain Yamaguchi may be a useful tool for diagnosis of adolescent and adult pertussis, especially in young adults, when an agglutinin titer cutoff value of >or=160x is used in combination with clinical symptoms and other clinical laboratory tests.

Automated assay for determining cellular cholesterol using a random access chemistry analyser.

BACKGROUND: We have previously reported an ultrasensitive fluorometric assay for measuring cellular cholesterol. Although this technique is reliable, the use of the assay has limitations due to the requirement for special equipment. It is therefore difficult to apply this assay for the routine determination of cellular cholesterol. METHODS: A colorimetric assay to measure cellular cholesterol was established that utilizes reagents widely used for the measurement of cholesterol in blood samples in conjunction with a random access chemistry analyser ARCHITECT c8000 that is also common in clinical laboratories. RESULTS: This colorimetric assay showed excellent linearity and recovery. The within-run coefficients of variation were less than 2.5%. The sensitivity of this method, with its detection limit of 1.29 mumol/L, was found to be superior to that of the fluorometric assay we have developed previously. In platelets obtained from patients with diabetes, both the free cholesterol and cholesterol ester content were significantly increased. CONCLUSIONS: Using this technique, measurement of cellular cholesterol could be performed routinely without the requirement for special reagents and equipment.

[Evaluation of the factor which has an influence on red blood cell deformability in patients with end-stage renal disease].

To explore the calcium homoeostasis of red blood cells (RBC) in patients with end-stage renal disease (ESRD), which plays an important role in RBC deformability and survival, we measured free calcium-ion concentration of RBC([Ca2+]i). [Ca2+]i was measured by fluorescent spectrophotometry using fura-2. The subjects constituted 5 groups; normal controls(C group), patients with diabetes mellitus(DM) without renal failure (DM group), ESRD patients with DM (HD-DM group), non-diabetic ESRD patients with lower intact parathyroid hormone (i-PTH)(HD-NDM-A group), and with higher i-PTH(HD-NDM-B group). [Ca2] i was significantly higher in the HD-NDM group than in the C group, in the HD-DM group than in the DM group, in the DM group than in the C group, in the HD-DM group than in the HD-NDM group, and in the HD-NDM-B group than in the HD-NDM-A group. There was a significant positive correlation between i PTH and [Ca2+]i, and between C-PTH and [Ca2+]i. In stepwise multivariate regression analysis, ESRD, DM, and secondary hyperparathyroidism (SHPT) appeared as independent determinants of [Ca2+]i. [Ca2+]i was significantly decreased after a hemodialysis session comparing to that of before the session. These data indicate that [Ca2+] i of RBC is elevated in ESRD probably due to uraemia, DM, and SHPT.

[Behavioral approach to facilitate appropriate use of antibiotics].

Many hospitals have infection control education programs to facilitate the appropriate use of antimicrobial agents. Even with these efforts, however, it is not rare to encounter irregular prescriptions. In order to solve this discrepancy between knowledge and actual behavior, we chose an alternative approach to improve the decision making process. Recent advances in information technology have made it possible to not only instantly integrate various bacterial examination results using a computer, but to simultaneously carry out the statistical analyses at a much lower cost. We employed a client-server system to accomplish these tasks in Kagawa University Hospital. By connecting CCD camera-equipped microscopes to the system directly, image uploading has become a single-clicking job. Various microbial examination data were automatically transferred to the system once they became available in analytical devices such as BacT/ALERT 3D, VITEK, and an MIC analyzer. These data were presented to hospital doctors in well-designed web windows without delay. By removing psychological barriers to access laboratory examination data, statistics, and relevant information, more doctors seemed to independently follow scientific processes to choose antimicrobial agents. The daily behavior of hospital doctors has also been influenced by the system, e. g., pasting the microscopic images onto clinical records, or starting Gram staining in their own wards. These subtle but fundamental changes will eventually alter the way they make prescription decisions. The computer system was also useful for the infection control team to monitor and detect nosocomial infections, which has become essential to carry out its daily activities.

A combination therapy of ethanol injection and radiofrequency ablation under general anesthesia for the treatment of hepatocellular carcinoma.

AIM: To summarize the effects of laparoscopic ethanol injection and radiofrequency ablation (L-EI-RFA), thoracoscopic (T-EI-RFA) and open-surgery assisted EI-RFA (O-EI-RFA) under general anesthesia for the treatment of hepatocellular carcinoma (HCC). METHODS: Time-lag performance of RFA after ethanol injection (Time-lag PEI-RFA) was performed in all cases. The volume of coagulated necrosis and the applied energy for total and per unit volume coagulated necrosis were examined in the groups treated under general (group G) or local anesthesia (group L). RESULTS: The results showed that the total applied energy and the applied energy per unit volume of whole and marginal, coagulated necrosis were significantly larger in group G than those in the group L, resulting in a larger volume of coagulated necrosis in the group G. The rate of local tumor recurrence within one year was extremely low in group G. CONCLUSION: These results suggest that EI-RFA, under general anesthesia, may be effective for the treatment of HCC because a larger quantity of ethanol and energy could be applied during treatment under painfree condition for the patients.

Inhibition of Src reduces gemcitabine-induced cytotoxicity in human pancreatic cancer cell lines.

In the present study, we examined the role of Src in gemcitabine-induced cell growth suppression in human pancreatic cancer cell lines. In two human pancreatic cancer cell lines, PK-9 and MIA PaCa-2, we found that a selective Src protein tyrosine kinase inhibitor, PP2, inhibited gemcitabine-induced cell growth suppression. When dominant negative src cDNA was constitutively expressed in PK-9 cells (PK-9-Src-DN), the degree of gemcitabine-induced cell growth suppression was decreased compared with that of mock-transfected PK-9 cells. The mechanism of the inhibitory effect of gemcitabine-induced cytotoxicity was found to be the suppression of apoptosis, which was downregulated in PK-9-Src-DN cells. These results indicate that Src mediates signals that culminate in suppressing cell growth and survival in the presence of gemcitabine, at least in particular cell lines.

Successful treatment of hypovascular advanced hepatocellular carcinoma with lipiodol-targetting intervention radiology.

We report a case of hypovascular advanced hepa-tocellular carcinoma (HCC) successfully treated with a novel combination therapy of percutaneous ethanol-lipiodol injection (PELI) and intervention radiology (IVR), lipiodol-targetting IVR (Lipi-IVR). The present case had a hypovascular HCC (3 cm in diameter) located in the S6 region of the liver. Although the tumor was not detectable at all by both of early and late phase of helical dynamic computed tomography (CT), it could be detected by ultrasonography (US) as a low echoic space occupying lesion (SOL) beside the gallbladder and right kidney. Serum levels of alpha fetoprotein (AFP) and AFP-L3 were extremely high. Combination therapy of PELI, firstly reported in our department, and IVR (PELI and IVR, lipiodol-targetting IVR) was performed twice for the treatment. PELI could effectively visualize the location of the tumor for IVR treatment and show the presence of a thin blood vessel branching from the right hepatic artery flowing into the lipiodol deposit. After treatment, the serum levels of AFP and AFP-L3 were rapidly decreased to normal and maintained for more than eight months. Thus, this case expressing the tremendous effect might give us insight into the effectiveness of the novel combination therapy of PELI and IVR for the treatment of hypovascular HCC.

Smoking, fasting serum insulin, and obesity are the predictors of carotid atherosclerosis in relatively young subjects.

The purpose of this study was to identify predictors of atherosclerosis in a healthy young cohort comprised of 241 subjects who underwent a regular employee medical check-up at Ohshima National Sanatorium over a 9-month period. All subjects underwent carotid ultrasound examinations to determine maximal common carotid artery intima media thickness. In addition, serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, blood urea nitrogen, creatinine, glucose, and insulin were evaluated. The subjects were relatively young (mean age, 44 years; range, 18 to 62 years), with 130 females (54%) and 111 males (46%). Maximal common carotid artery intima media thickness was predicted by smoking habit, body mass index, fasting blood sugar, fasting serum insulin, and systolic blood pressure (F(5,235) = 52.8, P < 10(-5)). There was clear separation in common carotid artery intima media thickness values based on body mass index, smoking, and fasting serum insulin, and somewhat more overlap with systolic blood pressure and fasting blood sugar. These findings suggest that smoking and high values of body mass index, fasting serum insulin, systolic blood pressure, and fasting blood sugar are warning factors for early atherosclerosis development, and could conceivably serve as the basis of diagnostic screening. Smoking is particularly deleterious, as smokers with high body mass index, high fasting serum insulin, or high systolic blood pressure tend to have larger common carotid artery intima media thickness values than would have been predicted by consideration solely of the individual risk factors.

Src transduces signaling via growth hormone (GH)-activated GH receptor (GHR) tyrosine-phosphorylating GHR and STAT5 in human leukemia cells.

Most human leukemia cells are shown to express growth hormone receptor (GHR) and some of them proliferate in response to GH. We demonstrate that Src contributes to GHR-mediated signal transduction via STAT5 activation in F-36P human leukemia cells stimulated with GH. The tyrosine phosphorylation levels of GHR and STAT5 induced by GH decreased in the presence of PP2 Src kinase inhibitor. When GHR and wild-type Src were co-expressed in COS7 cells, GHR was markedly tyrosine phosphorylated as well as when Jak2 was co-expressed with GHR, but not when kinase-inactive Src co-expressed. The treatment of F-36P cells with the antisense src oligonucleotides, which selectively decreased the Src expression, reduced the rhGH-induced tyrosine phosphorylation of the STAT5 activation sites.

Japanese standard reference material for JDS Lot 2 haemoglobin A1c. I: Comparison of Japan Diabetes Society-assigned values to those obtained by the Japanese and USA domestic standardization programmes and by the International Federation of Clinical Chemistry reference laboratories.

BACKGROUND: The Committee on Standardization of Laboratory Testing Related to Diabetes Mellitus of the Japan Diabetes Society (JDS) previously recommended use of the primary calibrator (JDS Lot 1) prepared by the former Committee for Standardization of Glycohemoglobin for standardizing the measurement of haemoglobin A1c (HbA1c). Owing to the depletion of vials of Lot 1 in March 2001, the present committee certified a new reference material, Lot 2, now distributed by the Health Care Technology Foundation (HECTEF). The standardization programme for HbA1c measurement in Japan is currently based on Lot 2, which has values assigned from within Lot 1; the Lot 1 values were consensus values based on assays by laboratories in the Japanese national quality control programme. In this study, for the purpose of international comparison and standardization, Lot 2 was assayed by the JDS reference laboratories, the National Glycoprotein Standardization Program (NGSP) in the USA, and by reference laboratories approved by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). METHOD: The HbA1c values of JDS Lot 2 were transferred from those assigned to Lot 1 using KO500, a high-resolution HPLC method, at three laboratories approved by the JDS committee. Subsequently, vials of JDS Lot 2 were shipped to and assayed by the NGSP in the USA and 10 IFCC reference laboratories. RESULT: The JDS-assigned HbA1c values (from Lot 1) are 4.04 for Level 1, 5.38 for Level 2, 7.32 for Level 3, 9.88 for Level 4, and 12.63 for Level 5, all expressed as a percentage of total haemoglobin. The values obtained by NGSP and the IFCC laboratories gave the following formulas: NGSP value(%)=JDS value(%)+0.3%; IFCC value(%)=1.068xJDS value(%)-1.741%. CONCLUSION: Although the values obtained by the IFCC laboratories are significantly lower than the values assigned to Lot 2 by the JDS, the relationship is linear. In addition, standardization of HbA1c based on JDS Lot 2 is currently at a satisfactory level in Japan. As a result, the reassignment of values for Lot 2 to agree with the IFCC values should be relatively easy and will be done after all relevant parties agree to the change.

Japanese standard reference material JDS Lot 2 for haemoglobin A1c. II: Present state of standardization of haemoglobin A1c in Japan using the new reference material in routine clinical assays.

BACKGROUND: In 2001, the Committee on Standardization of Laboratory Testing Related to Diabetes Mellitus of the Japan Diabetes Society (JDS) prepared and certified a new reference material for haemoglobin A1c (HbA1c), Lot 2. The standardization programme for HbA1c measurement in Japan is currently based on Lot 2, although some laboratories still use the previous material (Lot 1). The values assigned to Lot 2 were based on the consensus values for Lot 1 and should give the same results. Therefore, there should be no difference in the measured values no matter which calibrators are used. The Committee conducted a domestic survey in order to confirm this relationship. METHOD: In November 2002, four samples for HbA1c assay were sent to 795 laboratories as part of a national survey in Japan. Assays were performed using the laboratories' routine clinical methods. The coefficients of variation (CVs) of the reported values from all laboratories for the samples were calculated in order to determine the current level of standardization in Japan. RESULTS: The overall CVs in the measured values for the four samples ranged from 2.7% to 4.0%. Values from laboratories using calibrators based on Lots 1 and 2 were similar. CONCLUSION: The present state of standardization for the routine measurement of HbA1c in Japan, as indicated by the 2002 survey, is excellent. This should aid in the eventual conversion of Lot 2 to IFCC-based values from the results of the 2002 national HbA1c survey.

Cyclosporin A inhibits the early phase of NF-kappaB/RelA activation induced by CD28 costimulatory signaling to reduce the IL-2 expression in human peripheral T cells.

Cyclosporin A (CsA) inhibits interleukin (IL)-2 production, activation and proliferation of human peripheral T cells (HPTC) costimulated with simultaneous engagement of T cell receptor (TCR)/CD3 and CD28. We demonstrated that 10 ng/ml CsA, which reduced the proliferation of HPTC costimulated with anti-CD3 and anti-CD28 by half, prevented NF-AT and NF-kappaB from migrating into the nucleus. Whereas CsA added even 30 min after the costimulation caused NF-AT to remain in the cytoplasm, the delayed addition of CsA could not prevent NF-kappaB from translocating into the nucleus. CsA, which was added to HPTC simultaneously with the engagement of both CD3 and CD28 or the 1-h-delayed engagement of CD28 after prior TCR/CD3-triggering, inhibited NF-kappaB p65/RelA from binding to the target DNA fragment, followed by reduction of HPTC proliferation in response to the costimulation. When CsA was added 30 min after the delayed engagement of CD28 following the prior engagement of TCR/CD3, these inhibitory effects were diminished. Antisense NF-kappaB p65/RelA oligonucleotides inhibited p65/RelA mRNA expression, diminished IL-2 mRNA expression in the costimulated HPTC and reduced HPTC proliferation to the same extent as CsA added simultaneously with the costimulation. The CsA- or antisense p65/RelA oligonucleotide-induced reduction in the proliferation of costimulated HPTC was overcome by the addition of exogenous IL-2. These findings indicate that the major effects of CsA on the early phase of CD28-mediated costimulation in the presence of TCR/CD3 signaling are to inhibit NF-kappaB/RelA from translocating into the nucleus and binding to the target DNA sequence in the IL-2 gene promoter region, which induces IL-2 expression leading to HPTC proliferation.

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2004].

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 907 strains of Gram-positive bacteria, 1790 strains of Gram-negative bacteria, and 192 strains of anaerobic bacteria obtained from 30 medical institutions during 2004 was measured. The results were as follows; 1. MIC90 of MEPM for almost all of enterobacteriaceae and Haemophilus influenzae were 4-fold to 32-fold lower than those of other carbapenems. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and H. influenzae. MEPM were active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus. 2. As for Pseudomonas aeruginosa, imipenem (IPM) showed high cross-resistant rate againt meropenem-resistant P. aeruginosa (87.9%). MEPM showed low cross-resistant rate both againt IPM-resistant P. aeruginosa (49.2%) and ciprofloxacin-resistant P. aeruginosa (38.0%). 3. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli, 8.0% (2 strains) in Citrobacter koseri, 2.5% (3 strains) in Klebsiella pneumoniae, 2.5% (2 strains) in Enterobacter cloacae, 0.9% (1 strains) in Serratia marcescens, and 2.2% (2 strains) in Proteus mirabilis. The proportion of metallo-beta-lactamase strains was 1.6% (5 strains) in P. aeruginosa. 4. Of all species tested, Peptostreptococcus spp. was the only species, which MIC90 of MEPM was more than 4-fold higher than that in our previous study using clinical isolates during 2002 (0.25 microg/ml --> 1 microg/ml). Therefore, there is almost no siginificant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem at present, 9 years after available for commercial use.

Analysis of the optimal blood sampling conditions for estimation of hematopoietic progenitor cell count by the SE-9000 automated hematolyzer.

We evaluated the optimal conditions for blood sampling for hematopoietic progenitor cells (HPCs) as estimated by the immature information program of the SE-9000 automated hematology analyzer. The HPC count was most stable when the blood samples were incubated at room temperature with ethylene-diaminetetraacetic acid dipotassium (EDTA-2K) as an anticoagulant. The HPC count should, however, be measured within 4 h after blood collection, even under optimal conditions. In contrast, the CD34+ cell count estimated by flow cytometric analysis was stable for at least 21 h after the blood samples were incubated with EDTA-2K at room temperature or 4 degrees C. When appropriate blood samples were used, the HPC count in the peripheral blood significantly correlated with the CD34+ cell count in the peripheral blood and in the apheresis yields (r = 0.798 and 0.635, respectively); therefore, the HPC count is a reliable predictor for initiation of apheresis procedures to obtain sufficient HPCs for peripheral blood stem cell transplantation.

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2002].

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 899 strains of Gram-positive bacteria, 1500 strains of Gram-negative bacteria, and 158 strains of anaerobic bacteria obtained from 28 medical institutions during 2002 was measured. The results were as follows; 1. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MIC90 of MEPM against Pseudomonas aeruginosa was the lowest of the drugs tested. MEPM showed low cross-resistant rate against both imipenem-resistant P. aeruginosa and ciprofloxacin-resistant P. aeruginosa. MEPM was active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE). 2. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli and 1.9% (2 strains) in Klebsiella pneumoniae. Carbapenems including MEPM were active against these ESBL strains. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem; at present, 7 years after available for commercial use.