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Jae-Cheol Kwon,
Si-Hyun Kim,
Sun Hee Park,
Su-Mi Choi,
Dong-Gun Lee,
Jung-Hyun Choi,
Jin-Hong Yoo,
Yoo-Jin Kim,
Seok Lee,
Hee-Je Kim,
Seok-Goo Cho,
Jong-Wook Lee,
Woo-Sung Min
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ABSTRACT: BACKGROUNDAIMS: Hepatic or splenic lesions in hematologic patients are not defined well because they are not easy to evaluate due to limitations of invasive procedures. Management typically depends on the clinical diagnosis with few microbiological data.
We reviewed the medical records of consecutive hematologic patients with hepatic or splenic lesions in the infectious diseases unit from April 2009 to December 2010 at the Catholic Hematopoietic Stem Cell Transplantation Center in Korea.
Twenty-six patients were identified. Their mean age was 46.0 ± 14.7 years, and 16 (61.5%) were male. Underlying diseases were acute myelogenous leukemia (n = 15, 57.7%) and myelodysplastic syndrome (n = 6, 23.1%). Among the nine nontuberculous infectious lesions, two bacterial, six fungal, and one combined infection were identified. The numbers of confirmed, probable, and possible tuberculosis (TB) cases were one, three, and four, respectively. Two patients had concurrent pulmonary TB. QuantiFERON-TB Gold In-Tube (QFT-GIT, Cellestis Ltd.) was positive in seven cases, among which six were diagnosed with TB. The sensitivity and specificity of QFT-GIT were 75% and 81.3%. Nine (34.6%) were defined as noninfectious causes.
Causes of hepatic or splenic lesion in hematologic patients were diverse including TB, non-TB organisms, and noninfectious origins. TB should be considered for patients not responding to antibacterial or antifungal drugs, even in the absence of direct microbiological evidence. QFT-GIT may be useful for a differential diagnosis of hepatosplenic lesions in hematologic patients.
The Korean Journal of Internal Medicine 03/2013; 28(2):187-96.
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Si-Hyun Kim, Jae-Cheol Kwon,
Su-Mi Choi,
Dong-Gun Lee,
Sun Hee Park,
Jung-Hyun Choi,
Jin-Hong Yoo,
Byung-Sik Cho,
Ki-Seong Eom,
Yoo-Jin Kim,
Hee-Je Kim,
Seok Lee,
Chang-Ki Min,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min
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ABSTRACT: Escherichia coli and Klebsiella pneumoniae are main pathogens in neutropenic fever even if the proportion of Gram-positive cocci is increasing. Extended-spectrum β-lactamases (ESBL)-producing organisms are an emerging problem in nosocomial infection. Nevertheless, until now, information about risk factors for the acquisition and clinical outcomes of bacteremia due to ESBL-producing organisms is limited in neutropenic patients. From medical records collected between January 2007 and December 2008, we identified a total of 101 consecutive patients who developed bacteremia due to E. coli (n = 87) or K. pneumoniae (n = 14). Twenty-six (26 %) cases of bacteremia were caused by ESBL-producing organisms. A hospital stay of >2 weeks during the 3 months preceding bacteremia [adjusted odds ratio (OR), 5.887; 95 % confidence interval (CI), 1.572-22.041] and the use of broad-spectrum cephalosporins in the 4 weeks prior to bacteremia (adjusted OR, 6.186; 95 % CI, 1.616-23.683) were significantly related to the acquisition of ESBL. Twenty-four (92 %) of the ESBL-producing organisms were susceptible to either piperacillin-tazobactam or amikacin. Aminoglycosides (amikacin or isepamicin) were the main appropriate antimicrobial agents used against the ESBL-producing isolates during the initial empirical treatment (16/22, 73 %). However, the 30-day mortality rates for ESBL bacteremia and non-ESBL bacteremia were not significantly different (15 vs 5 %; p = 0.199). As alternatives to carbapenem, piperacillin-tazobactam plus amikacin or isepamicin combinations may be effective empirical therapeutic options for patients with neutropenic fever who are at high risk of developing bacteremia with ESBL-producing pathogens.
Annals of Hematology 11/2012; · 2.62 Impact Factor
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ABSTRACT: The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has been increased not only in the hospital but also in the community worldwide. This study was aimed to characterize ESBL- producing E. coli isolates and to investigate the molecular epidemiology of community isolates in comparison with hospital isolates at a single center in Korea.
A total of 142 ESBL-producing E. coli isolates were collected at Daejeon St Mary's Hospital in Korea from January 2008 to September 2009. The ESBLs were characterized by PCR sequencing using specific primers. The genetic relatedness was determined by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).
Of 142 isolates, 139 were positive for CTX-M type ESBLs; CTX-M-14 (n = 69, 49.6 %), CTX-M-15 (n = 53, 38.1 %) and both CTX-M-14 and -15 (n = 17, 12.2 %). CTX-M-14 and CTX-M-15 were detected in both community and hospital isolates whereas isolates producing both CTX-M14 and-15 were mainly identified in the hospital. CTX-M producing E. coli isolates were genetically heterogeneous, revealing 75 distinct PFGE types. By MLST, 21 distinctive STs including 5 major STs (ST131, ST405, ST38, ST10, and ST648) were identified. Major STs were distributed in both community and hospital isolates, and ST131 was the predominant clone regardless of the locations of acquisition. No specific major STs were confined to a single type of ESBLs. However, ST131 clones were significantly associated with CTX-M-15 and the majority of them were multidrug-resistant. Distinctively, we identified a hospital epidemic caused by the dissemination of an epidemic strain, ST131-PFGE type 10, characterized by multidrug resistance and co-producing both CTX-Ms with OXA-1 or TEM-1b.
The epidemiology of ESBL-producing E. coli is a complex and evolving phenomenon attributed to the horizontal transfer of genetic elements and clonal spread of major clones, predominantly ST131. The multidrug resistant ST131 clone producing CTX-M-15 has emerged as a major clone in both the community and hospital, suggesting the widespread of this epidemic clone in Korea.
BMC Infectious Diseases 06/2012; 12:149. · 3.12 Impact Factor
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Jae-Cheol Kwon,
Si-Hyun Kim,
Sun Hee Park,
Su-Mi Choi,
Dong-Gun Lee,
Jung-Hyun Choi,
Jin-Hong Yoo,
Yoo-Jin Kim,
Seok Lee,
Hee-Je Kim,
Jong-Wook Lee,
Woo-Sung Min
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ABSTRACT: The aim of this study was to investigate therapeutic outcomes and assess factors associated with therapeutic outcomes in hematologic patients with invasive pulmonary aspergillosis (IPA).
We analyzed all consecutive cases of IPA in adults with hematologic diseases from January 2008 to January 2009 at a Catholic Hematopoietic Stem Cell Transplantation (HSCT) Center in Seoul, Korea.
A total of 54 patients were identified. Underlying diseases were acute myelogenous leukemia (n=25), acute lymphoblastic leukemia (n=10), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=3), multiple myeloma (n=3), severe aplastic anemia (n=2) and other hematologic diseases (n=4). Twenty six patients (48.2%) were assessed as having a favorable response, of which 16 patients (29.6%) showed complete response. Overall 12-week mortality and IPA attributable mortality were 38.9% (n=21) and 33.3% (n=18), respectively. In multivariate analysis, uncontrolled underlying disease (odds ratio [OR], 7.31; 95% confidence interval [CI], 1.49~35.94; p=0.014) was associated with an unfavorable response, and for 12-week mortality, uncontrolled underlying disease (OR, 11.79; 95% CI, 1.49~93.46; p=0.020) and hypoalbuminemia (OR, 9.89; 95% CI, 1.42~68.99; p=0.021) were significantly poor prognostic factors.
IPA still remains as a poor therapeutic outcome, especially in patients with refractory hematologic diseases.
Tuberculosis and Respiratory Diseases 03/2012; 72(3):284-92.
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ABSTRACT: Monitoring the response to therapy for invasive aspergillosis (IA) is essential for the management of patients with hematologic diseases. We evaluated the correlation between the outcome of real-time nucleic acid sequence-based amplification (RTi-NASBA) for Aspergillus 18S rRNA and the clinical outcome of IA. A total of 157 serum samples from 29 patients with IA were tested for RTi-NASBA. The treatment response and mortality were compared with the NASBA outcome (whether the NASBA value was converted to negative or not) at 12 weeks after the start of antifungal therapy. At 12 weeks, there was a moderate correlation between the treatment failure and persistently positive NASBA (κ = 0.482; P = 0.019). Deaths attributable to IA were more prevalent in patients without negative conversion of NASBA than in those with negative conversion (50% vs 5%; P = 0.013). Significant factors of treatment failure at 12 weeks were the status of hematologic disease (nonremission; P = 0.041) and the NASBA outcome (failure of negative conversion; P = 0.024). Survival was significantly better in patients with negative conversion of NASBA than those with persistently positive values (P = 0.036). This study suggests that the serial monitoring of RTi-NASBA could be useful for prediction of the clinical outcome in hematologic patients with IA.
Journal of Korean medical science 01/2012; 27(1):10-5. · 0.84 Impact Factor
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ABSTRACT: This is a case report on a 35-year-old man with acute myelogenous leukemia who presented fever and intermittent mucoid loose stool to the emergency center. He had been taking voriconazole for invasive pulmonary aspergillosis. The flexible sigmoidoscopy was consistent with the diagnosis of pseudomembranous colitis.
Yonsei medical journal 09/2011; 52(5):863-5. · 0.77 Impact Factor
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ABSTRACT: To define the risk factors and clinical outcomes of community-onset bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBLEC), we analyzed 50 consecutive cases of community-onset bacteremia caused by ESBLEC at a secondary hospital in South Korea from 2005 to 2010. Risk factors were assessed by conducting a case-double control study in which cases were compared with (1) control patients with community-onset bacteremia due to non-ESBLEC, and (2) those with community-onset bacteremia not caused by E. coli. Clinical outcome was assessed among patients with community-onset E. coli bacteremia. Community-onset bacteremia due to ESBLEC accounted for 6.7% of all community-onset E. coli bacteremia. In addition, an increasing proportion of ESBLEC among patients without any healthcare risk factors was observed. Comparison with both control groups revealed that the recent use of antibiotics (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.5-12.3) was an independent risk factor for ESBL acquisition. Factors influencing the 30-day mortality were a high Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR, 1.5; 95% CI, 1.1-2.0) and severe sepsis or septic shock (OR, 26.6; 95% CI, 1.5-470.7) and malignancy (OR, 11.9; 95% CI, 1.1-134.8). Increased mortality was not statistically associated either with ESBL production or with inappropriate empirical therapy. ESBLEC has emerged as a significant cause of community-onset bacteremia in this hospital, suggesting that ESBLEC are widely disseminated in the South Korean community.
Microbial drug resistance (Larchmont, N.Y.) 08/2011; 17(4):537-44. · 1.99 Impact Factor
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Si-Hyun Kim,
Dong-Seok Yim,
Su-Mi Choi, Jae-Cheol Kwon,
Seunghoon Han,
Dong-Gun Lee,
Chulmin Park,
Eun-Young Kwon,
Sun Hee Park,
Jung-Hyun Choi,
Jin-Hong Yoo
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ABSTRACT: Voriconazole is a triazole agent with excellent antifungal activity against Aspergillus species. However, despite its potential advantages, the occurrence of unpredictable toxicities might be critical in immunocompromised patients. The aim of this study was to analyze risk factors for voriconazole-related severe adverse events (SAEs).
This prospective observational study was conducted in Korean patients with hematological malignancies and invasive aspergillosis on intravenous voriconazole therapy between June 2008 and April 2009.
Of the 25 patients enrolled, eight (32%) showed voriconazole-related SAEs, which included hepatotoxicities (n=5), cardiac tachyarrhythmias (n=2), and neurotoxicity (n=1). Sex, age, underlying hematological malignancies, voriconazole dose, the co-administration of a proton pump inhibitor, and CYP2C19 genotype were not found to be related to the occurrence of SAEs. However, trough plasma concentrations of voriconazole were found to be significantly higher in the patients with an SAE: median 6.32 mg/l (interquartile range (IQR) 2.86-9.71 mg/l) vs. median 2.15 mg/l (IQR 0.92-4.00 mg/l); p=0.011. Receiver operating characteristic curve analysis identified a cut-off trough concentration for SAEs of 5.83 mg/l (sensitivity 62.5% and specificity 94.1%). Furthermore, multivariate analysis showed that a trough concentration of ≥ 5.83mg/l was the only significant independent risk factor of an SAE.
This study shows that therapeutic drug monitoring is indicated in patients with a voriconazole-related SAE and that dose adjustment is required if the trough concentration of voriconazole exceeds 5.83 mg/l.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 08/2011; 15(11):e753-8. · 2.17 Impact Factor
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ABSTRACT: The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (C(trough)) and microorganism- specific (AUC24/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever.
One thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC24/MIC>125 [or 345] and C(trough)>10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC24/MIC>125 [or 345] using logistic analysis.
The standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC24/MIC>125 [or 345] and C(trough)>10 [or 20] mg/L, respectively.
The current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered.
Yonsei medical journal 07/2011; 52(4):616-23. · 0.77 Impact Factor
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Sun Hee Park,
Su-Mi Choi,
Dong-Gun Lee,
Jung-Hyun Choi,
Si-Hyun Kim, Jae-Cheol Kwon,
Jin-Hong Yoo,
Hee-Je Kim,
Seok Lee,
Ki-Seong Eom,
Woo-Sung Min
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ABSTRACT: Invasive aspergillosis (IA) remains an important cause of mortality in acute leukaemia patients. Previous studies reported that serum galactomannan (GM) levels correlate strongly with IA outcomes in patients with haematological cancers. This study aimed to clarify the usefulness of serial GM testing for outcome evaluation of IA in acute leukaemia patients. We retrospectively analysed 58 acute leukaemia patients who had IA during neutropenic period after chemotherapy and whose serum GM was serially monitored until discharge or death. The kappa correlation coefficient was used to determine the strength of correlation between GM and clinical outcome (survival or death) of IA. The correlation between clinical outcome and GM kinetics was good at week 6 [κ = 0.663, 95% confidence interval (CI): 0.465-0.861] and excellent at week 12 (κ = 0.819, 95% CI: 0.667-0.91). Survival was significantly better in patients whose GM values normalised than in patients with persistently positive GM (P < 0.0001) regardless of whether neutropenia resolved or acute leukaemia responded to chemotherapy. In neutropenic patients with acute leukaemia, serum GM correlated strongly with survival outcome of IA. This finding further supports the usefulness of the GM index as a surrogate marker for assessing IA outcome and the need for serial GM testing in therapeutic monitoring.
Mycoses 05/2011; 54(6):523-30. · 2.25 Impact Factor
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ABSTRACT: We investigated molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) isolated at 10 intensive care units (ICUs) in Korea. MRSA isolates from bacteremia and nasal colonization were collected prospectively from October 2008 through May 2009 at 10 University-affiliated hospital ICUs. A total of 83 and 175 MRSA strains were isolated from bacteremia and nasal colonization, respectively. Acquired group accounted for 69.9% (n = 58) of bacteremia and 73.1% (n = 128) of nasal colonization. Pulsed-field gel electrophoresis (PFGE) type B (SCCmec type II/ST5) was dominant in the acquired group followed by PFGE type D (SCCmec type IVA/ST72; a community genotype). Seven of 58 (12.1%) acquired bacteremia and 15 of 128 (11.8%) acquired nasal colonizations had SCCmec type IVA/ST72 genotype, which indicated that the community genotype had already emerged as a cause of ICU acquired MRSA infection or colonization. Antibiotic resistance rates to ciprofloxacin, tetracycline, clindamycin and trimethoprim/ sulfamethoxazole were 84.4%, 67.1%, 78.1%, and 12.0%, respectively. Susceptibility to ciprofloxacin best predicted a community genotype (sensitivity 96.5%; specificity 96.9%; odds ratio 861; 95% confidence interval 169-4,390, P < 0.001) and the positive predictive value was 90.2%. Among 23 nasal re-colonized strains, 7 MRSA strains (30.4%) were different from the originally colonized strains on the basis of PFGE types.
Journal of Korean medical science 05/2011; 26(5):604-11. · 0.84 Impact Factor
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ABSTRACT: Over a 6-year period (March 2000-February 2006), there were 60 vancomycin-resistant Enterococcus faecium (VREF) bloodstream infections (BSIs) in a hematology unit, accounting for 83.3% of all VREF BSIs in the hospital. We investigated 49 VREF isolates causing BSIs in patients with neutropenia to understand the molecular epidemiology at this unit. All isolates had the vanA genotype. Pulsed-field gel electrophoresis typing revealed high clonal diversity (23 types with nine clusters comprising 35 isolates) and 1 predominant type, type A (14/49, 28.6%), persisted at this unit throughout the study period, suggesting the clonal spread of this endemic strain by cross-contamination. Tn1546 types were less heterogeneous, with five main Tn1546 types, two of which (types I and IV) accounted for 67.4% of isolates. This indicates that in addition to clonal spread, the horizontal transfer of Tn1546 played a major role in the nosocomial dissemination of vancomycin resistance. The genetic diversity of VREF increased over time, implying an increasing influx of new strains into the unit and genetic changes, possibly attributable to the horizontal transfer of diverse Tn1546 types. Despite such diversity, all the isolates belonged to clonal complex 17, which is the epidemic clone worldwide, enriched with the esp (35/49, 71.4%) and hyl (24/49, 48.9%) virulence genes. This hospital-adapted clone has become endemic and is well suited to causing BSIs in patients with neutropenia in this unit.
Microbial drug resistance (Larchmont, N.Y.) 12/2010; 17(1):59-65. · 1.99 Impact Factor
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ABSTRACT: Community-associated methicillin resistant Staphylococcus aureus (CAMRSA) infections are increasing. Although gentamicin (GEN) is usually susceptible against CA-MRSA, GEN is rarely considered for treatment as monotherapy. We employed an in vitro pharmacodynamic model (IVPDM) to compare efficacies of GEN against CA-MRSA with two dosing regimens [thrice-daily (TD), once-daily (OD)].
Using two strains of CA-MRSA, we adopted IVPDM comprised of two-compartments with a surface-to-volume ratio of 5.34 cm(-1). GEN regimens were simulated with human pharmacokinetic data of TD and OD. Experiments were performed over 48 hours in triplicate for each strain and dosing regimen.
MICs of GEN for YSSA1 and YSSA15 were 1 and 2 mg/L, respectively. In OD, indices of peak/MIC were > 8.6 at least, in contrast to < 6.4 in TD. A > or = 3-log(10) reduction in CFU/mL was demonstrated prior to 4 hours in TD and OD, and continued until 8 hours for both strains. However, reductions in the colony counts at 24 and 48 hours were significantly larger for OD compared to TD in both strains (p < 0.001). During TD, resistance developed in YSSA1 and small colony variants (SCVs) were documented in YSSA15. No resistance or SCVs were observed during OD in both strains.
TD and OD showed the same killing slopes until 8 hours. After the 24 hours of experiments, OD of GEN would be advantageous not only in having more reductions in colony counts, but also suppressing the development of resistance or SCVs for 48 hours.
Yonsei medical journal 09/2010; 51(5):722-7. · 0.77 Impact Factor
