Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

Clinical Utility of Quantitative CT Analysis for Fissure Completeness in Bronchoscopic Lung Volume Reduction: Comparison between CT and Chartis™

OBJECTIVE: The absence of collateral ventilation (CV) is crucial for effective bronchoscopic lung volume reduction (BLVR) with an endobronchial valve. Here, we assessed whether CT can predict the Chartis™ results. MATERIALS AND METHODS: This study included 69 patients (mean age: 70.9 ± 6.6 years; 66 [95.7%] males) who had undergone CT to assess BLVR eligibility. The Chartis™ system (Pulmonox Inc.) was used to check CV. Experienced thoracic radiologists independently determined the completeness of fissures on volumetric CT images. RESULTS: The comparison between the visual and quantitative analyses revealed that 5% defect criterion showed good agreement. The Chartis™ assessment was performed for 129 lobes; 11 (19.6%) of 56 lobes with complete fissures on CT showed positive CV, while this rate was significantly higher (40 of 49 lobes, i.e., 81.6%) for lobes with incomplete fissures. The size of the fissure defect did not affect the rate of CV. Of the patients who underwent BLVR, 22 of 24 patients (91.7%) with complete fissures and three of four patients with incomplete fissures (75%) achieved target lobe volume reduction (TLVR). CONCLUSION: The quantitative analysis of fissure shows that incomplete fissures increased the probability of CV on Chartis™, while the defect size did not affect the overall rates. TLVR could be achieved even in some patients with relatively large fissure defect, if they showed negative CV on Chartis™.

Determining Genotypic Drug Resistance by Ion Semiconductor Sequencing With the Ion AmpliSeq™ TB Panel in Multidrug-Resistant Mycobacterium tuberculosis Isolates

BACKGROUND: We examined the feasibility of a full-length gene analysis for the drug resistance-related genes inhA, katG, rpoB, pncA, rpsL, embB, eis, and gyrA using ion semiconductor next-generation sequencing (NGS) and compared the results with those obtained from conventional phenotypic drug susceptibility testing (DST) in multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates. METHODS: We extracted genomic DNA from 30 pure MDR-TB isolates with antibiotic susceptibility profiles confirmed by phenotypic DST for isoniazid (INH), rifampin (RIF), ethambutol (EMB), pyrazinamide (PZA), amikacin (AMK), kanamycin (KM), streptomycin (SM), and fluoroquinolones (FQs) including ofloxacin, moxifloxacin, and levofloxacin. Enriched ion spheres were loaded onto Ion PI Chip v3, with 30 samples on a chip per sequencing run, and Ion Torrent sequencing was conducted using the Ion AmpliSeq TB panel (Life Technologies, USA). RESULTS: The genotypic DST results revealed good agreement with the phenotypic DST results for EMB (Kappa 0.8), PZA (0.734), SM (0.769), and FQ (0.783). Agreements for INH, RIF, and AMK+KM were not estimated because all isolates were phenotypically resistant to INH and RIF, and all isolates were phenotypically and genotypically susceptible to AMK+KM. Moreover, 17 novel variants were identified: six (p.Gly169Ser, p.Ala256Thr, p.Ser383Pro, p.Gln439Arg, p.Tyr597Cys, p.Thr625Ala) in katG, one (p.Tyr113Phe) in inhA, five (p.Val170Phe, p.Thr400Ala, p.Met434Val, p.Glu812Gly, p.Phe971Leu) in rpoB, two (p.Tyr319Asp and p.His1002Arg) in embB, and three (p.Cys14Gly, p.Asp63Ala, p.Gly162Ser) in pncA. CONCLUSIONS: Ion semiconductor NGS could detect reported and novel amino acid changes in full coding regions of eight drug resistance-related genes. However, genotypic DST should be complemented and validated by phenotypic DSTs.

Comparative Evaluation of the Loop-Mediated Isothermal Amplification Assay for Detecting Pulmonary Tuberculosis

BACKGROUND: Early detection of tuberculosis (TB) is challenging in resource-poor settings because of limited accessibility to molecular diagnostics. The aim of this study was to evaluate the performance of the loop-mediated isothermal amplification kit (TB-LAMP) for TB diagnosis compared with conventional and molecular tests. METHODS: A total of 290 consecutive sputum samples were collected from May till September, 2015. All samples were processed using the N-Acetyl-L-cysteine (NALC) NaOH method and tested by smear microscopy, solid and liquid culture, real-time PCR, and TB-LAMP. RESULTS: The sensitivity of TB-LAMP for smear-positive and smear-negative samples with culture positivity was 92.0% and 58.8%, respectively. TB-LAMP was positive in 14.9% of TB culture-negative samples; however, all those samples were also positive by real-time PCR. In addition, none of the samples positive for nontuberculous mycobacteria by culture were positive by TB-LAMP. The overall agreement between TB-LAMP and real-time PCR was good; however, the concordance rate was significantly lower for real-time PCR positive samples with Ct values of 30–35. CONCLUSIONS: TB-LAMP could replace smear microscopy and increase TB diagnostic capacity when Xpert MTB/RIF is not feasible because of poor infrastructure.

Impact of Time Delay in Processing Blood Sample on Next Generation Sequencing for Transcriptome Analysis

No abstract available.

Epidemiology and Clinical Characteristics of Zika Virus Infections Imported into Korea from March to October 2016

Zika is a re-emerging, mosquito-borne viral infection, which has been recently shown to cause microcephaly and Guillain-Barré syndrome. Since 2015 the number of infected patients has increased significantly in South America. The purpose of this study was to identify the epidemiologic and clinical characteristics of patients with Zika virus (ZIKV) infections in Korea. Patients who had visited areas of risk and tested positive in the ZIKV reverse transcriptase polymerase chain reaction (RT-PCR) in blood, urine, or saliva specimens were included. The first Korean case of ZIKV infection was reported in March 2016, and 14 cases had been reported by October 2016. The median age of the patients was 34 years (19–64 years). Ten patients had been exposed in Southeast Asia and 4 in Latin America. Rash was the most common symptom (92.9%; 13/14), followed by myalgia (50.0%; 7/14), and arthralgia (28.6%, 4/14). There were no neurologic abnormalities and none of the patients was pregnant. Results of biochemical tests were normal. Positivity rates of RT-PCR for ZIKV in serum, urine, and saliva were 53.8%, 100.0%, and 83.3%, respectively in the first week of symptoms. In conclusion, 14 patients with ZIKV infections were reported in Korea by October 2016 and all of them had mild clinical symptoms.

Drug Resistance Patterns of Multidrug- and Extensively Drug-Resistant Tuberculosis in Korea: Amplification of Resistance to Oral Second-line Drugs

We aimed to analyze the drug resistance patterns of multidrug-resistant and extensively drug-resistant tuberculosis (TB) and the difference of drug resistance among various settings for health care in Korea. The data of drug susceptibility testing in 2009 was analyzed in order to secure sufficient number of patients from various settings in Korea. Patients were categorized by types of institutions into four groups, which comprised new and previously treated patients from public health care centers (PHC), the private sector, and Double-barred Cross clinics (DBC). The resistance rates to first-line drugs were uniformly high in every group. While the resistance rates to second-line drugs were not as high as first-line drugs, there was a pattern that drug resistance rates were lowest for PHC and highest for DBC. The differences of the resistance rates were more prominent for oral second-line drugs. Our findings implied that drug resistance to oral second-line drugs was significantly amplified during multidrug-resistant-TB treatment in Korea. Therefore, an individualized approach is recommended for treating drug-resistant-TB based on susceptibility testing results to prevent acquisition or amplification of drug resistance.

Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B

PURPOSE: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. MATERIALS AND METHODS: Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. RESULTS: Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. CONCLUSION: We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.

Recent update in HIV vaccine development

Despite the tremendous efforts to develop a successful human immunodeficiency virus (HIV) vaccine, the quest for a safe and effective HIV vaccine seems to be remarkably long and winding. Disappointing results from previous clinical trials of VaxGen's AIDSVAXgp120 vaccine and MRKAd5 HIV-1 Gag/Pol/Nef vaccine emphasize that understanding the correlates of immune protection in HIV infection is the key to solve the puzzle. The modest vaccine efficacy from RV144 trial and the successive results obtained from the correlate of risk analysis have reinvigorated the HIV vaccine research field leading to various novel strategies. This paper will review the brief history and recent advances in HIV vaccine development.

Added Value of Magnetic Resonance Imaging in Staging of Malignant Pleural Mesothelioma

PURPOSE: We investigated the possible added value of magnetic resonance imaging (MR) in staging of malignant pleural mesothelioma (MPM) compared to computed tomography (CT). MATERIALS AND METHODS: We retrospectively enrolled 20 patients (M;F = 14:6; mean age, 53.5 yrs) who diagnosed as MPM by histology and underwent CT and MR at initial evaluation from Jan 1997 to Dec 2012. Two radiologists performed clinical staging by using CT alone or MR alone in consensus. In patients underwent surgery (n = 13), we evaluated the diagnostic accuracy of CT and MR in terms of staging compared to surgical staging. In all patients, we compared clinical staging of CT only and CT with MR. RESULTS: The diagnostic accuracy for T staging of CT only was 23.1% (3/13) and that of combined CT and MR was 38.5% (5/13), respectively. Among 13 patients underwent surgery, surgical stage was higher than combined CT and MR stage in 5 patients, but lower in 3 patients. CT only and combined CT and MR agreed in 85.0% (17/20). In cases of disagree (15.0%, 3/20), combined CT and MR showed higher stage than CT only. CONCLUSION: Combined CT and MR increases the diagnostic accuracy in staging of MPM compared to CT only and is important in determining the appropriate treatment in patients being considered for surgery.

Epidemiology and Clinical Features of Post-Transplant Bloodstream Infection: An Analysis of 222 Consecutive Liver Transplant Recipients

BACKGROUND: Bloodstream infection (BSI) is a significant cause of morbidity and mortality in liver transplant (LT) recipients. This study aimed to investigate the epidemiology and clinical features of post-transplant BSI in LT recipients. MATERIALS AND METHODS: The microbiology, frequency, and outcome of post-transplant BSI in the first year after LT were retrospectively analyzed in 222 consecutive patients who had received liver transplants at a single center between 2005 and 2011. The risk factors for post-transplant BSI and death were evaluated. RESULTS: During a 1-year period after LT, 112 episodes of BSI occurred in 64 of the 222 patients (28.8%). A total of 135 microorganisms were isolated from 112 BSI episodes including 18 polymicrobial episodes. The median time to BSI onset ranged from 8 days for Klebsiella pneumoniae to 101 days for enterococci, and the overall median for all microorganisms was 28 days. The most frequent pathogens were Enterobacteriaceae members (32.5%), enterococci (17.8%), yeasts (14.0%), Staphylococcus aureus (10.3%), and Acinetobacter baumannii (10.3%); most of them showed resistance to major antibiotics. The major sources of BSI were biliary tract (36.2%), abdominal and/or wound (28.1%), and intravascular catheter (18.5%) infections. The independent risk factors for post-transplant BSI were biliary complications (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.29 to 6.59, P = 0.010) and longer hospitalization in the intensive care unit (OR: 1.04, 95% CI: 1.00 to 1.08, P < 0.001) after LT. BSI was an independent risk factor for death (hazard ratio [HR]: 3.92, 95% CI: 2.22 to 6.91, P < 0.001), with a poorer survival rate observed in patients with BSI than in those without BSI (1-year survival rate: 60.0% versus 89.5%, respectively, P < 0.001) after LT. The strongest predictors for death in patients with BSI were hepatocellular carcinoma (HR: 3.82, 95% CI: 1.57 to 9.32, P = 0.003), candidemia (HR: 3.71, 95% CI: 1.58 to 8.71, P = 0.003), polymicrobial bacteremia (HR: 3.18, 95% CI: 1.39 to 7.28, P = 0.006), and post-transplant hemodialysis (HR: 2.44, 95% CI: 1.02 to 5.84, P = 0.044). CONCLUSIONS: BSI was a frequent post-transplant complication, and most of the causative pathogens were multi-drug resistant. Biliary complications and BSIs resulting from biliary infection are major problems for LT recipients. The prevention of BSI and biliary complications is critical in improving prognosis in liver transplant recipients.

Evaluation of the Seeplex(R) Meningitis ACE Detection Kit for the Detection of 12 Common Bacterial and Viral Pathogens of Acute Meningitis

BACKGROUND: Bacterial meningitis is an infectious disease with high rates of mortality and high frequency of severe sequelae. Early identification of causative bacterial and viral pathogens is important for prompt and proper treatment of meningitis and for prevention of life-threatening clinical outcomes. In the present study, we evaluated the value of the Seeplex Meningitis ACE Detection kit (Seegene Inc., Korea), a newly developed multiplex PCR kit employing dual priming oligonucleotide methods, for diagnosing acute meningitis. METHODS: Analytical sensitivity of the kit was studied using reference strains for each pathogen targeted by the kit, while it's analytical specificity was studied using the human genome DNA and 58 clinically well-identified reference strains. For clinical validation experiment, we used 27 control cerebrospinal fluid (CSF) samples and 78 clinical CSF samples collected from patients at the time of diagnosis of acute meningitis. RESULTS: The lower detection limits ranged from 101 copies/microL to 5x101 copies/microL for the 12 viral and bacterial pathogens targeted. No cross-reaction was observed. In the validation study, high detection rate of 56.4% was obtained. None of the control samples tested positive, i.e., false-positive results were absent. CONCLUSIONS: The Seeplex Meningitis ACE Detection kit showed high sensitivity, specificity, and detection rate for the identification of pathogens in clinical CSF samples. This kit may be useful for rapid identification of important acute meningitis-causing pathogens.

Prevalence and Clinical Characteristics of Pulmonary Arterial Hypertension in Human Immunodeficiency Virus-Infected Patients / 대한내과학회지

BACKGROUND/AIMS: Human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) is a complication of HIV infection. Due to improvements in HIV survival rates following the introduction of highly active antiretroviral therapy, HIV-PAH has become an important cause of HIV-related morbidity. Thus, the objective of this study was to explore the prevalence and characteristics of HIV-PAH. METHODS: Ninety-two patients were enrolled in the study from March to August 2010. We investigated clinical characteristics and performed echocardiography. HIV-PAH was defined as having a mean pulmonary arterial pressure (mPAP) > or = 25 mmHg based on Mahan's equation, without lung disease or heart disease. The HIV-PAH-possible group was defined as having a tricuspid regurgitation velocity (TRV) of 2.9-3.4 m/s and a pulmonary arterial systolic pressure (PASP) of 37-50 mmHg. RESULTS: Fifteen patients (16.3%) met the criteria of HIV-PAH based on mPAP. With respect to TRV, six patients met the criteria of the HIV-PAH-possible group. Based on the criteria of mPAP, the duration of HIV infection was not different with or without HIV-PAH. HIV RNA titers and CD4 T cell counts tended to be higher in HIV-PAH patients (8,607 +/- 11 vs. 1,067 +/- 64 copies/mL, p = 0.371; 471 +/- 148 vs. 499 +/- 252 cells/mm3, p = 0.680, respectively). Echocardiographic indices of the right ventricle were significantly deteriorated in the HIV-PAH group as compared with the non-HIV-PAH group (TASPE: 20.52 vs. 23.2, p = 0.001; Tei index: 0.42 vs. 0.39, p = 0.037). In a multivariate regression analysis, HIV activity factors (HIV duration, HIV RNA titer, and CD4 cell count) were not associated with echocardiographic indices of PAH (mPAP, PASP, and pulmonary vascular resistance). CONCLUSIONS: In this study, the prevalence of HIV-PAH was comparable to that of previous studies.

Prevalence and Clinical Characteristics of Pulmonary Arterial Hypertension in Human Immunodeficiency Virus-Infected Patients / 대한내과학회지

BACKGROUND/AIMS: Human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) is a complication of HIV infection. Due to improvements in HIV survival rates following the introduction of highly active antiretroviral therapy, HIV-PAH has become an important cause of HIV-related morbidity. Thus, the objective of this study was to explore the prevalence and characteristics of HIV-PAH. METHODS: Ninety-two patients were enrolled in the study from March to August 2010. We investigated clinical characteristics and performed echocardiography. HIV-PAH was defined as having a mean pulmonary arterial pressure (mPAP) > or = 25 mmHg based on Mahan's equation, without lung disease or heart disease. The HIV-PAH-possible group was defined as having a tricuspid regurgitation velocity (TRV) of 2.9-3.4 m/s and a pulmonary arterial systolic pressure (PASP) of 37-50 mmHg. RESULTS: Fifteen patients (16.3%) met the criteria of HIV-PAH based on mPAP. With respect to TRV, six patients met the criteria of the HIV-PAH-possible group. Based on the criteria of mPAP, the duration of HIV infection was not different with or without HIV-PAH. HIV RNA titers and CD4 T cell counts tended to be higher in HIV-PAH patients (8,607 +/- 11 vs. 1,067 +/- 64 copies/mL, p = 0.371; 471 +/- 148 vs. 499 +/- 252 cells/mm3, p = 0.680, respectively). Echocardiographic indices of the right ventricle were significantly deteriorated in the HIV-PAH group as compared with the non-HIV-PAH group (TASPE: 20.52 vs. 23.2, p = 0.001; Tei index: 0.42 vs. 0.39, p = 0.037). In a multivariate regression analysis, HIV activity factors (HIV duration, HIV RNA titer, and CD4 cell count) were not associated with echocardiographic indices of PAH (mPAP, PASP, and pulmonary vascular resistance). CONCLUSIONS: In this study, the prevalence of HIV-PAH was comparable to that of previous studies.

Clinical Features of Re-Emerging Hepatitis A: An Analysis of Patients Hospitalized during an Urban Epidemic in Korea

From April 2008 to November 2008, many cases of hepatitis A were reported in Seoul and Gyeonggi Province in Korea. Furthermore, the rate of severe or fulminant hepatitis have significantly increased during the latest epidemic (13.4% vs. 5.2%, p=0.044). Therefore, widespread use of vaccine is warranted to reduce the burden of hepatitis A in Korea.

Characterization of Class 1 Integrons in Metallo-beta-lactamase-producing Pseudomonas aeruginosa / 대한임상미생물학회지

BACKGROUND: The genes of metallo-beta-lactamase (MBL), a powerful carbapenemase, are carried as a part of the mobile gene cassettes inserted into integrons playing an important role in rapid dissemination of antibiotic resistance genes among bacterial isolates. In this study, we investigated carbapenemase genes and class 1 integrons integrated into the gene cassettes in imipenem-non susceptible P. aeruginosa. METHODS: From July 2006 to March 2008, 81 consecutive, non-duplicate, imipenem-non susceptible P. aeruginosa were isolated at Chungnam National University Hospital in Chungcheong province of Korea. The modified Hodge and double disk synergy tests were conducted for the screening of carbapenemase and MBL production, respectively, and PCR and DNA sequencing were performed for the detection of carbapenemase genes and class 1 integron gene cassettes. We also employed the repetitive element sequence-based (Rep)-PCR method for an epidemiologic study. RESULTS: MBLs were detected in 13.6% (11/81) of imipenem-non susceptible P. aeruginosa. Ten isolates were found to carry blaIMP-1, whereas 1 isolate was found to carry a blaVIM-2. All of the IMP-1-producing strains harbored 4.0 kb class 1 integron containing chloramphenicol, aminoglycoside, and beta-lactam- resistant genes. However, blaIMP-1 was not detected at class 1 integron. A 2.5 kb class 1 integron harboring blaVIM-2 was detected in a VIIM-2- producing strain. One identical pattern was observed in ten IMP-1 producing strains. CONCLUSION: IMP-1 producing P. aeruginosa strains are currently distributed throughout Chungcheong province of Korea. In particular, all of the strains harbored class 1 integrons containing variant antibiotic resistance gene cassettes.

Recurrent Coccidioidomycosis Manifesting as Osteomyelitis in Korea

Coccidioidomycosis is a fungal infection that results from inhaling the airborne arthroconidia of the Coccidioides species. It is an endemic disease in the southwest part of North America and rarely diagnosed in Korea. As tourism to endemic areas and the number of immunocompromised patients have been increasing, the incidence of this infection has increased in non-endemic areas. Treatment is usually successful with antifungal agents; however, recurrence is common. It is difficult to decide when to discontinue the antifungal treatment especially in non-endemic areas where doctors are not familiar with the disease. We report a case of recurrent coccidioidomycosis manifesting as osteomyelitis after the treatment of the patient for disseminated coccidioidal infection. The complement fixation test was a useful tool for the assessment of patient response and to evaluate suspected recurrence.

Recurrent Coccidioidomycosis Manifesting as Osteomyelitis in Korea

Coccidioidomycosis is a fungal infection that results from inhaling the airborne arthroconidia of the Coccidioides species. It is an endemic disease in the southwest part of North America and rarely diagnosed in Korea. As tourism to endemic areas and the number of immunocompromised patients have been increasing, the incidence of this infection has increased in non-endemic areas. Treatment is usually successful with antifungal agents; however, recurrence is common. It is difficult to decide when to discontinue the antifungal treatment especially in non-endemic areas where doctors are not familiar with the disease. We report a case of recurrent coccidioidomycosis manifesting as osteomyelitis after the treatment of the patient for disseminated coccidioidal infection. The complement fixation test was a useful tool for the assessment of patient response and to evaluate suspected recurrence.

Characteristics of aac(6')-Ib-cr Gene in Extended-Spectrum beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolated from Chungnam Area / 대한진단검사의학회지

BACKGROUND: Concomitant quinolone resistance in extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a crucial problem in the clinical management of infections. In foreign countries, the fluoroquinolone acetylating aminoglycoside-(6)-N-acetyltransferase (aac[6']-Ib-cr) gene, a novel plasmid-mediated quinolone resistance determinant has been reported to occur in conjunction with qnr. We aim to investigate the prevalence and characteristics of concomitant aac(6')-Ib-cr and qnr expression in ESBL-producing Escherichia coli and Klebsiella pneumoniae in Korea. METHODS: Between December 2007 and April 2008, we collected 60 and 69 clonally unrelated non-repetitive clinical isolates of ESBL-producing E. coli and K. pneumoniae, respectively. We studied the expressions of 11 types of ESBL-encoding genes, 4 types of 16s rRNA methylase genes; rmtA, rmtB, rmtC and armA, 3 types of qnr genes; qnrA, qnrB, qnrS and aac(6')-Ib. The presence of aac(6')-Ib-cr variants was detected by sequencing. The involvement of integrons was studied using multiplex PCR and sequencing of gene-cassette arrays. Conjugation experiments were performed to confirm plasmid-mediated resistance and the relationships among coharbored genes. RESULTS: We observed a high prevalence of the cr variant (61.1%) of aac(6')-Ib, and the prevalence of this variant in qnr and aac(6')-Ib-coharboring isolates (67.4%) was higher than in qnr-negative isolates (51.7%). The high prevalence of the cr variant was significantly related to the high minimum inhibitory concentrations (MICs) of ciprofloxacin, tobramycin, and amikacin and indicated the statistically significant roles of qnrB, qnrS, rmtA, and rmtB in quinolone and aminoglycoside resistance. CONCLUSIONS: The aac(6')-Ib-cr variants were widespread and showed significant relation to the high-level quinolone and aminoglycoside resistance in ESBL-producing E. coli and K. pneumoniae.

Dissemination of IMP-1 and OXA Type beta-Lactamase in Carbapenem-resistant Acinetobacter baumannii / 대한진단검사의학회지

BACKGROUND: Acinetobacter baumannii is an aerobic, gram-negative, glucose-nonfermenting bacterium, which has emerged as a serious opportunistic pathogen. In recent years, the increasing instance of carbapenem-resistant A. baumannii producing metallo-beta-lactamases (MBLs) or OXAtype beta-lactamases is causing a serious clinical problem. In this study, we investigated the prevalence of Ambler class A, B, and D beta-lactamases and their extended-spectrum derivatives in carbapenem-resistant A. baumannii isolates. METHODS: A total of 31 consecutive, non-duplicate, carbapenem-resistant A. baumannii were isolated from three university hospitals in the Chungcheong province of Korea. The modified Hodge and inhibitor-potentiated disk diffusion tests were conducted for the screening of carbapenemase and MBL production, respectively. PCR and DNA sequencing were performed for the detection of beta-lactamase genes. We also employed the enterobacterial repetitive intergenic consensus (ERIC)-PCR method for the epidemiologic study. RESULTS: Twenty-three of 31 isolates harbored bla(OXA-2) (51.6%), bla(OXA-23) (22.6%), bla(IMP-1) (48.4%),and bla(VIM-2) (3.2%). All of the OXA-2-producing strains also evidenced MBLs. The strains that harbored bla(OXA-23) were isolated only in hospital C, and only in a limited fashion. The ERIC-PCR pattern of the five OXA-23 strains indicated that the isolates were closely related in terms of clonality. The six strains producing IMP-1 isolated from hospital A were confirmed to be identical strains. CONCLUSIONS: A. baumannii strains harboring IMP-1 or OXA-type beta-lactamases are currently widely distributed throughout the Chungcheong province of Korea. The most notable finding in this study was that a bla(OXA-2)-producing A. baumannii harboring MBL, which has not been previously reported, can also lead to outbreaks.