• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.228-234
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• 2006

Background : Acinetobacter baumannii is an important pathogen associated with nosocomial infections in intensive care units, and is responsible for nosocomial pneumonia, UTI, bacteremia, etc. The main concern is that this pathogen is often resistant to many antimicrobial agents, particularly to carbapenem. This study compared the clinical those of ICU admitted patients with the carbapenem resistant A. baumannii isolated from the sputum with characteristics of patients with carbapenem sensitive A. baumannii. Methods : A total of 49 patients with A. baumannii from a sputum culture who were admitted to the ICU from January to December 2003 were enrolled in this study. This study evaluated the demographic variables, mortality, APACHE II score, comorbidity, antibiotics used, hospital and ICU stay, Clinical Pulmonary Infection Score, and mechanical ventilation. A retrospective analysis was made by a review of the patients' medical records. Results : Carbapenem sensitive and resistant A. baumannii was isolated from 23 patients and 26 patients respectively. Univariate analysis revealed renal disease, the use of carbapenem and aminoglycoside to be statistically significant factors for carbapenem resistance. Multivariate analysis revealed carbapenem use(p=0.024; OR, 8.17; CI 1.32 to 50.68) to be positively associated with carbapenem resistance, and aminoglycoside use(p=0.026; OR, 0.18; CI, 0.04 to 0.82) to be negatively associated with carbapenem resistance. There was no significant difference in mortality between the carbapenem sensitive and resistant group(30 vs 42%. P=0.39). Conclusion : The occurrence of carbapenem resistant A. baumannii is positively associated with carbapenem use and negatively associated with aminoglycoside use. Carbapenem resistance in the sputum culture did not affect the mortality rate.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.209-217
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• 2007

Purpose: Multidrug resistance (MDR) of the cancer cells related to mdr1 gene expression can be effectively treated by selective short hairpin RNA for mdr1 gene (shMDR). Sodium/iodide symporter (NIS) gene is well known to have both reporter and therapeutic gene characteristics. We have co-transfected both shMDR and NIS gene into colon cancer cells (HCT15 cell) expressing MDR and Tc-99m sestamibi and I-125 uptake were measured. In addition, cytotoxic effects of doxorubicin and I-131 therapy were also assessed after transfection. Material and Methods: At first, shMDR was transfected with liposome reagent into human embryonic kidney cells (HEK293) and HCT cells. shMDR transfection was confirmed by RT-PCR and western blot analysis. Adenovirus expressing NIS (Ad-NIS) gene and shMDR (Ad-shMDR) were co-transfected with Ad-NIS into HCT15 cells. Forty-eight hours after infection, inhibition of P-gycoprotein (Pgp) function by shMDR was analyzed by a change of Tc-99m sestamibi uptake and doxorubicin cytotoxicity, and functional activity of induced NIS gene expression was assessed with I-125 uptake assay. Results: In HEK293 cells transfected with shMDR, mdr1 mRNA and Pgp protein expressions were down regulated. HCT15 cells infected with 20 MOI of Ad-NIS was higher NIS protein expression than control cells. After transfection of 300 MOI of Ad-shMDR either with or without 10 MOI of Ad-NIS, uptake of Tc-99m sestamibi increased up to 1.5-fold than control cells. HCT15 cells infected with 10 MOI of Ad-NIS showed approximately 25-fold higher I-125 uptake than control cells. Cotransfection of Ad-shMDR and Ad-NIS resulted in enhanced cytotoxic by doxorubicin in HCT15 cells. I-131 treatment on HCT15 cells infected with 20 MOI of Ad-NIS revealed increased cytotoxic effect. Conclusion: Suppression of mdr1 gene expression, retention of Tc-99m sestamibi, enhanced doxorubicin cytotoxicity and increases in I-125 uptake were achieved in MDR expressing cancer cell by co-transfection of shMDR and NIS gene. Dual therapy with doxorubicin and radioiodine after cotransfection shMDR and NIS gene can be used to overcome MDR.

• Journal of Yeungnam Medical Science
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• v.28 no.2
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• pp.133-144
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• 2011

Background: Tigecycline (TIG), a new broad-spectrum glycylcycline with anti-multidrug-resistant-(MDR)-pathogen activity, was launched in March 2009 in South Korea, but there are insufficient clinical studies on its use in the country. As such, this study was performed to analyze cases of severe MDR-pathogen-caused infections treated with TIG. Methods: Patients treated with TIG within the period from May 2009 to June 2010 were enrolled in this study. Their clinical and microbiologic data were reviewed retrospectively. Results: Twenty-one patients were treated with TIG for complicated skin and soft-tissue infections (cSSTIs) (42.9%), complicated intra-abdominal infections (cIAIs) (38.1%), or pneumonia (19.1%) caused by MDR pathogens like carbapenem-resistant $Acinetobacter$ $baumannii$ (76.2%), methicillin-resistant $Staphylococcus$ $aureus$ (61.9%), extended-spectrum beta-lactamase-producing $Escherichia$ $coli$ and $Klebsiella$ $pneumoniae$ (38.1%), and penicillin-resistant $Enterococcus$ species (33.3%). Thirteen patients (61.9%) had successful clinical outcomes while five (23.8%) died within 30 days. The rate of clinical success was highest in cSSTI (77.8%), followed by cIAI (50%) and pneumonia (50%), and the mortality rate was highest in pneumonia (50%), followed by cIAI (25%) and cSSTI (11.1%), Conclusion: Tigecycline therapy can be an option for the treatment of severe MDR-pathogen-caused infections in South Korea, Due to its high risk of failure and mortality, however, prudence is required in its clinical use for the treatment of severe infections like nosocomial pneumonia.

• Journal of Life Science
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• v.26 no.7
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• pp.835-846
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• 2016

Chemo-resistance is the biggest issue of effective cancer therapy. ABCG2 is highly correlated with multi-drug resistance, and represent a typical phenotype of multiple cancer stem-like cells. Accumulating evidence recently reported that oncolytic viruses represent a new strategy for multiple aggressive cancers and drug resistant cancers including cancer stem cell-like cells and ABCG2 expressing cells. In this study, we generated an evolutionally engineered vaccinia virus, SLJ-496, for drug-resistant cancer therapy. We first showed that SLJ-496 treatment enhanced tumor affinity using cytopathic effect assay, plaque assay, as well as cell viability assay. Next, we clearly demonstrated that in vitro SLJ-496 treatment represents significant cytotoxic effect in multiple cancers including colorectal cancer cells (HT-29, HCT-116, HCT-8), gastric cancer cells (AGS, NCI-N87, MKN-28), Hepatocellular carcinoma cells (SNU-449, SNU-423, SNU-475, HepG2), as well as mesothelioma cell (NCI-H226, NCI-H28, MSTO-221h). Highly ABCG2 expressing HT-29 cells represent cancer stem like phenotype including stem cell marker expression, and self-renewal bioactivities. Interestingly, we demonstrated that in vitro treatment of SLJ-496 showed significant cytotoxicity effect, as well as viral replication capacity in ABCG2 overexpressing cell. In addition, we also demonstrated the cytotoxic effect of SLJ-496 in Adriamycin-resistant cell lines, SNU-620 and ADR-300. Taken together, these findings provide us a pivotal clue that cancer therapy using SLJ-496 vaccinia virus might be new therapeutic strategy to overcome ABCG2 expressing cancer stem-like cell and multiple chemo-resistance cancer cells.

• Journal of Korean Academy of Nursing
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• v.39 no.2
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• pp.186-197
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• 2009

Purpose: This study was done to investigate nurses' knowledge of, and compliance with the multidrug-resistant organism (MDRO) infection control guidelines. Methods: A survey questionnaire was developed based on the institutional and national guidelines and was administered to a convenience sample of 306 nurses in a university hospital. Results: The mean score for knowledge was 33.87 (percentage of correct answers: 82.61%). The percentages of correct answers for basic concepts, route of transmission, hand washing/protective devices and environment management were 74.27%, 94.29%, 92.90% and 75.54% respectively. The mean compliance score was 4.15 (range: 1-5). The compliance scores for education, communication, contact precaution, disinfection, surveillance culture, and hand washing were 3.29, 4.05, 4.20, 4.50, 4.40 and 4.48 respectively. Nurses indicated "lack of time (30.06%)", "lack of means (10.78%)" and "lack of knowledge (9.48%)" as reasons for noncompliance. Conclusion: While most educational programs have focused on hand washing or use of protective devices to prevent transmission of MDRO in acute care settings, hospital nurses' knowledge of the basic concepts of MDRO and environmental management has remained insufficient. Nurses are relatively non-compliant to the guidelines in the areas of education (staff, patient, family) and communication. Comprehensive educational programs are needed to decrease hospital infection rates and to improve the health of patients.

• Journal of Korean Critical Care Nursing
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• v.3 no.1
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• pp.67-78
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• 2010

Purpose: This study was done to investigate knowledge of and compliance with the multidrug-resistant organism (MDRO) infection control guidelines among student nurses on clinical practicum, Methods: survey questionnaire on MORO infection control was administered to a convenience sample of 259 nursing students from 3 different nursing schools Results: The mean knowledge score was 28.01/39 (71.82%). The percentages of correct answers for basic concepts, route of transmission, hand washing/ protective devices and environment management, were 55.40, 81.14, 84.94 and 69.17 respectively. The mean compliance score was 3.83/5. The compliance scores for education, communication, contact precaution, environment management, and hand washing were 3.06, 3.33, 3.86, 4.50, 3.92 and 4.29 respectively. 96.9% of subjects knew that they should wash hands after touching MORO patient while only 22.8% of subjects knew how to collect samples for VRE surveillance culture, The highest compliant item was hand washing after touching MORO patient. The Lo-west compliant item was referring to infection control manual. Conclusion: Comprehensive MDRO infection control education programs for nursing students should be developed to decrease MORO infection.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• Pediatric Infection and Vaccine
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• v.10 no.2
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• pp.167-177
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• 2003

Purpose : To know the trends of antimicrobial susceptibility is critical for antimicrobial treatment. We studied the organisms isolated from blood, urine, stool, and cerebrospinal fluid from 1997 to 2001 to reveal the trends of their antimicrobial susceptibility. Methods : We conducted a retrospective study with isolates obtained from 0~18 year old outpatients and inpatients from 1997 to 2001 at Department of Pediatrics, Hanil general hospital. We gathered the data through the laboratory test files and the origin of microorganisms cultured from blood, urine, stool and cerebrospinal fluid and their antimicrobial susceptibility. Results : Microorganisms were isolated from 226(3.3%) out of 6,974 blood cultures, 365 (8.0%) out of 4,549 urine cultures, 50(1.9%) out of 2,593 stool cultures and 9(1.4%) in 655 cerebrospinal fluid cultures. The most frequently isolated organisms from blood cultures was Staphylococcus epidermidis(33.5%) which was followed by Staphylococcus aureus(19.7%), Escherichia coli(13.8%), and Burkholderia cepacia(9.0%). Among the urine cultures, E. coli was the most common(74.7%) which was followed by Group D Enterococcus(11.3%), Klebsiella pneumoniae(7.1%) and Proteus mirabilis(2.5%). The positive stool cultures all yield Salmonella species. Group D Salmonella was obtained most frequently. Among the positive cerebrospinal fluid cultures, Group B Streptococcus was isolated most frequently. Among the 40 cases of S. aureus in blood cultures, 27 cases were methicillin-resistant. The rates of susceptibility for amikacin, ceftizoxime and ceftriaxone of E. coli isolated from blood cultures were 80%, 100% and 60% in 1997 and 60%, 80% and 60% in 2001. The rates of susceptibility for amikacin, ceftizoxime and ceftriaxone of K. pnumoniae isolated from urine cultures. were 80%, 100% and 80% in 1997 and 50%, 83% and 50% in 2001 Enterococcus was isolated from 6.7% to 15.8% and vancomycin-resistant Enterococcus was observed in 17% of Group D Enterococcus isolated from urine cultures. The rates of susceptibility for amikacin, ceftizoxime and ceftriaxone of Group D Salmonella were 96%, 96% and 92% during the study period. Conclusion : Among the blood cultures S. epidermidis, S. aureus, E. coli and B. cepacia were isolated in order of frequency and among the urine cultures E. coli, Group D Enterococcus, K. pneumoniae and P. mirabilis were isolated in order of frequency. During the study period there was no big difference in major organisms isolated from blood and urine. The methicillin-resistant S. aureus was observed in 67% of S. aureus isolated from blood cultures but vancomycin-reistant S. aureus or vancomycin intermediate resistant S. aureus was not observed. The rates of susceptibility to amikacin and the third generation cephalosporin of E. coli isolated from blood cultures and K. pneumoniae from urine cultures have decreased. The isolation rates of Group D Enterococcus and vancomycin resistant Enterococcus have increased.

• Pediatric Infection and Vaccine
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• v.7 no.2
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• pp.211-217
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• 2000

Purpose : Salmonellosis including typhoid fever is still prevalent in Korea. Recently it has been reported that the incidence of salmonella gastroenteritis is increasing with a reduction of typhoid fever. We studied the clinical and laboratory features of salmonellosis. Methods : We evaluated the clinical records of 83 patients with salmonellosis who had been confirmed by stool culture from 1994 to 1999. Results : Annual incidence of salmonellosis showed an increasing tendency during recent 4 years. Seasonally, summer(45.8%) was the most prevalent, followed by fall(32.5%). Male to female ratio was 1.4 : 1. In age distribution, 64 cases(77.1%) were under 5 year-old, and 18 cases(21.7%) were younger than 1 year-old. Clinical features included diarrhea(96.4%), fever(91.6%), vomiting(49.4%), bloody stool(42.1%), abdominal pain(40.1%) and tenesmus(12.0%). In serogroups, there was no group A and group B, group C, group D(including 2 cases of S.typhi) and group E were in 41.0%(34 cases), 3.6%(3 csaes), 51.8%(43cases) and 3.6%(3 cases), respectively. In Widal test, 5 cases(13.5%) and 1 case(2.7%) of group B, C and E(total 37 cases) were observed the O titer above 1 : 80 and 1 : 320, respectively. However, in 36 cases of group D, 19 cases(52.7%) and 9 cases(25.0%) were above the O titer 1 : 80 and 1 : 320, respectively. Antibiotics resistant rates to ampicillin, trimethoprim/sulfamethoxazole and chloramphenicol were 23.2%, 10.1% and 51.4%, respectively. Conclusion : Salmonellosis has become a common cause of gastroenteritis in children, especially under the pre-school age. Isolation of salmonella is neccessary for accurate diagnosis of gastroenteritis and typhoid fever. A careful attention of the use of antibiotics is needed to reduce the muilti-drug resistant strains.

• Tuberculosis and Respiratory Diseases
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• v.64 no.1
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• pp.8-14
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• 2008

Background: Acinetobacter infections are difficult to treat as they often exhibit multiple resistance to the antibiotics that are currently available for the treatment of pneumonia. Colistin is active against gram-negative bacteria, including the multiple drug resistant (MDR) Acinetobacter species. However, intravenous administration of colistin was abandoned because of its nephrotoxicity and neurotoxicity. The aims of this study were to examine the efficacy and safety of colistin administered by aerosol in the treatment of pneumonia caused by MDR Acinetobacter baumannii. Methods: We retrospectively reviewed the medical records of patients admitted to the intensive care unit (ICU) from Dec. 2006 to Aug. 2007 who had been diagnosed as suffering from pneumonia due to MDR Acinetobacter baumannii and had been treated with nebulized colistin. Results: 31 patients received aerosolized colistin. The average duration of the treatment was $14{\pm}7$ days and the daily dose of ranged from 225 mg to 300 mg. All patients received concomitant intravenous antimicrobial agents. The average length of the stay in the ICU was $34{\pm}21$ days and in the hospital $58{\pm}52$ days. The overall microbiological eradication was observed in 25 patients (80.6%). 14 of these (56%) were cured, and 11 (44%) were infected with other microorganisms. The overall crude mortality of the ICU was 48%. Nephrotoxicity and significant bronchial constriction did not occur in any patient during neublized colistin treatment. Conclusion: Nebulized colistin may be a safe and effective option in the treatment of pneumonia due to MDR Acinetobacter baumannii. Its role in therapy warrants further investigation in comparative studies.