Susceptibility of β-Lactam Antibiotics and Genetic Mutation of Drug-Resistant Mycobacterium tuberculosis Isolates in Korea / 결핵및호흡기질환

Background@#Mycobacterium tuberculosis (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with a β-lactamase inhibitor clavulanate, was effective in MDR and XDR tuberculosis (TB). However, clavulanate can only be used in drugs containing amoxicillin in Korea. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients. @*Methods@#The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets blaC, blaI, ldtA, ldtB, dacB2, and crfA were analyzed by PCR and DNA sequencing. @*Results@#The MIC90 values of amoxicillin and meropenem with clavulanate in drug-resistant Mtb isolates were 64 and 16, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation of was found in the blaC gene related to β-lactam antibiotics high susceptibility. @*Conclusion@#Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

Performance of chromID Clostridium difficile Agar Compared with BBL C. difficile Selective Agar for Detection of C. difficile in Stool Specimens

We evaluated the performance of a new chromogenic medium for detection of Clostridium difficile, chromID C. difficile agar (CDIF; bioMerieux, France), by comparison with BBL C. difficile Selective Agar (CDSA; Becton Dickinson and Company, USA). After heat pre-treatment (80degrees C, 5 min), 185 diarrheal stool samples were inoculated onto the two media types and incubated anaerobically for 24 hr and 48 hr for CDIF and for 48 hr and 72 hr for CDSA. All typical colonies on each medium were examined by Gram staining, and the gram-positive rods confirmed to contain the tpi gene by PCR were identified as C. difficile. C. difficile was recovered from 36 samples by using a combination of the two media. The sensitivity with CDIF 48 hr was highest (100%) and was significantly higher than that with CDIF 24 hr (58.3%; P<0.001), because samples with a low burden of C. difficile tended to require prolonged incubation up to 48 hr (P<0.001). The specificity of CDIF 24 hr and CDIF 48 hr (99.3% and 90.6%, respectively) was significantly higher than that of CDSA 48 hr and CDSA 72 hr (72.5% and 67.1%, respectively; P<0.001). CDIF was effective for detecting C. difficile in heat-pretreated stool specimens, thus reducing unnecessary testing for toxin production in non-C. difficile isolates and turnaround time.

A Case of Polycythemia Vera with a JAK2V617F Mutation Combined with Smoldering Myeloma / 대한내과학회지

The lymphoproliferative disease multiple myeloma and the myeloproliferative disease polycythemia vera have different pathogenic mechanisms and different natural courses. Thus, the concomitant development of these two diseases in the same individual is rare. In most previously reported cases of both diseases, one disease was assumed to be a secondary malignancy caused by chemotherapy for the other primary disease. Our case was diagnosed as smoldering myeloma based on increased bone marrow plasma cell numbers and monoclonal gammopathy during a regular follow-up visit for JAK2V617F mutation-positive polycythemia vera, which had not been treated except with phlebotomy. This case provides useful clues for understanding the pathogenesis of these two hematological malignancies and the association between them. Here, we report a case of polycythemia vera with a JAK2V617F mutation combined with smoldering myeloma and discuss the clinical significance and pathogenic association between these disorders of different lineages, along with a literature review.

Successful treatment of steroid resistant hypereosinophilic syndrome with low-dose CsA

No abstract available.

Performance Assessment of Advansure(TM) MDR-TB Genoblot Assay Kit for Anti-tuberculosis Drug Susceptibility Test

BACKGROUND: Because of the long time required for conventional drug susceptibility test (DST) for rifampin and isoniazid, development of rapid DSTs is necessary. Recently, the AdvanSure(TM) MDR-TB GenoBlot Assay kit (LG Life Science, Korea), using reverse hybridization line blot assay, was developed. We compared this kit with Genotype(R) MTBDRplus (HAIN Lifescience, Germany) and conventional DST. METHODS: Of the DNAs preserved after performing DST by using Genotype(R), we selected 144 samples having conventional DST results. The experiments with both the kits were performed according to the manufacturers' instructions. For the samples for which discrepant results were obtained, sequencing was performed if the DNA was available. Conventional DST was performed at the Korean Institute of Tuberculosis by using the absolute concentration method. RESULTS: For rifampin, the findings obtained using both the kits were the same with concordance rates of 98.6% (142/144) compared to conventional DST. Of the 2 discrepant findings, one was very major error and the other was major error. For isoniazid, compared to conventional DST, concordance rates of AdvanSure(TM) and Genotype(R) were 95.8%(138/144) and 95.1%(137/144) respectively. Of the 6 discrepant findings between conventional method and Advansure(TM), 5 were very major error and one was major error. All the 7 discrepant findings between conventional method and Genotype(R) were very major error. CONCLUSIONS: The findings obtained using AdvanSure(TM) showed high concordance with those obtained using Genotype(R) and conventional DST. This kit has a higher rate of detection of isoniazid resistance because it includes probes for an additional target (ahpC).

A variant acute promyelocytic leukemia with t(11;17) (q23;q12); ZBTB16-RARA showing typical morphology of classical acute promyelocytic leukemia

A subgroup of acute leukemia with morphology resembling acute promyelocytic leukemia (APL) shows variant translocations involving RARA and has a different morphology from that of classical APL. The variant APL with t(11;17)(q23;q12); ZBTB16-RARA subgroup has been reported to have leukemic cells with regular nuclei, many granules, absence of Auer rods, an increased number of Pelgeroid neutrophils, strong myeloperoxidase (MPO) activity, and all-trans-retinoic-acid (ATRA) resistance. Here, we report a case of variant APL with t(11;17)(q23;q12); ZBTB16-RARA showing typical morphological features of classical APL, including numerous Auer rods and faggot cells. The leukemic cells expressed CD13, CD33, CD117, human leukocyte antigen (HLA)-DR, and cytoplasmic-MPO on the immunophenotyping study. The diagnosis was confirmed by cytogenetic and molecular studies. To distinguish variant APL cases from classical APL cases, regardless of whether morphologically the findings are consistent with those of classical APL, combining morphologic, immunophenotypic, cytogenetic, and molecular studies before chemotherapy is very important.

JAK2 V617F mutation in myelodysplastic syndrome, myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable, refractory anemia with ring sideroblasts with thrombocytosis, and acute myeloid leukemia

BACKGROUND: The JAK2 V617F mutation has been noted in the cases of polycythemia vera, essential thrombocythemia, and primary myelofibrosis patients. This mutation occurs less frequently in acute myeloid leukemia (AML) and other hematologic diseases, such as myelodysplastic syndrome (MDS); myelodysplatic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U); and refractory anemia with ring sideroblasts with thrombocytosis (RARS-T). METHODS: Patients diagnosed with hematologic diseases other than MPN who visited Seoul St Mary's Hospital from January 2007 to February 2010 were selected. A total of 43 patients were enrolled in this study: 12 MDS, 9 MDS/MPN-U, 7 RARS-T, and 15 AML patients. The diseases were diagnosed according to the 2008 WHO classification criteria. Data obtained from JAK2 V617F mutation analysis and cytogenetic study as well as complete blood count and clinical data were analyzed. RESULTS: Of the 43 patients, 6 (13.9%) harbored the JAK2 V617F mutation. The incidence of the JAK2 V617F mutation in each patient group was as follows: 8.3% (1/12), MDS; 22.2% (2/9), MDS/MPN-U; 14.3% (1/7), RARS-T; and 13.3%, (2/15) AML. The platelet count was higher than 450x10(9)/L in 3 of the 6 patients (50%) harboring the JAK2 V617F mutation, and it was in the normal range in the remaining 3 patients. Among the 6 patients, 1 MDS and 1 MDS/MPN-U patients had the 46,XX,del(20)(q11.2) karyotype. CONCLUSION: The JAK2 V617F mutation is associated with an increased platelet count in MDS, MDS/MPN-U, RARS-T, and AML patients. Cytogenetic abnormalities of del(20)(q11.2) occurred in 1/3 of patients with the JAK2 V617F mutation but further studies are required to confirm this association.

A Case of Ectopic ACTH Syndrome Caused by Wilms Tumor

No abstract available.