Strategies to reduce infectious complication using epidemiologic data analysis in liver transplant recipients.

BACKGROUND: Infectious complications are major factors for morbidity and mortality in liver transplant recipients. To establish a proper strategy to reduce infectious complications, we analyzed epidemiologic and risk factors for post-transplant infections. METHODS: We analyzed the medical records of 231 consecutive liver transplant recipients from December 2007 to November 2011, including at least 1-year follow up, for comparison with those from 1996 to 2005. RESULTS: Among 231 patients, 126 (54.5%) experienced 244 infectious episodes, a rate of 1.05 per patient. Among overall mortality of 9.9% (23/231), infections were more prevalent (P = .04). Predominant infections were postoperative intra-abdominal problems (36.1%), peritonitis (15.2%), pneumonia (13.5%), bacteremia (4.1%), wound complications (1.6%), viral etiologies (18.0%), and other causes (11.5%). Causative organisms were bacterial (68.9%), viral (14.7%), fungal (7.0%), and unproven ones (9.4%). Multivariate analysis of risks for infection showed significant impacts of Model for End-stage Liver Disease score [P = .027; odds ratio (OR), 1.04], post-transplant biliary complications (P < .001; OR, 3.50), and rejection episodes (P = .023; OR, 3.39). Mortality was related to retransplantation (P = .003), post-transplant dialysis (P = .006), and infection (P = .056) upon univariate analysis, none of which were significant in multivariate analysis. Compared with data from the previous period, overall and infection-related mortality decreased from 24.5% to 9.9% and 52.9% to 26.1%, respectively. There were no significant changes in the types of infection or rate of drug-resistant bacteria, but candidal infections and cytomegalovirus reactivations were more prevalent. CONCLUSION: Our data showed current perioperative antimicrobial regimens need not be changed: however, new strategies are needed to reduce infectious complications after liver transplantation, to reduce biliary complications and to properly manage rejection episodes.

Diagnostic value of 18F-FDG PET/CT in patients with fever of unknown origin.

This study investigates the diagnostic value of (18) F-fluorodeoxyglucose positron emission tomography/computed tomography ((18) F-FDG PET/CT) in patients with 109 classical fever of unknown origin (FUO). Of the 48 (18) F-FDG PET/CT scans, 41 (85.4%) were interpreted as abnormal, and 25 (52.1% of all scans) were considered clinically helpful. The final cause of fever was determined in 41 patients (85.4%); infection (25%), malignancy (12.5%), non-infectious inflammatory disease (16.7%) and miscellaneous causes (31.3%). (18) F-FDG PET/CT contributed to the final diagnosis of FUO in 65.8%.

Antiviral prophylaxis versus preemptive therapy to prevent cytomegalovirus infection and related death in liver transplantation: a retrospective study with propensity score matching.

BACKGROUND: Cytomegalovirus (CMV), the most significant viral infection in liver transplant recipients, is addressed by 2 methods: Preemptive therapy (PT) or universal prophylaxis (UP). METHODS: We analyzed medical records including at least 1 year follow-up of patients who underwent liver transplantation from 2006 to 2009 in 3 tertiary hospitals. PT was used in 2 hospitals (PT group), whereas UP with valganciclovir for 3 months was adopted in the other hospital (UP group). The 2 groups were matched using propensity scoring by perioperative variables. We performed a 1:1 comparison of the efficacy of UP and PT. RESULTS: We analyzed 634 liver transplant patients, including 562 matched subjects. Baseline characteristics and underlying liver status were comparable. CMV immunoglobulin G of recipients was positive in 98.9% of the PT group and 99.3% of the UP group. CMV viremia episodes that required administration of an antiviral agent occurred in 26 (9.3%) PT and 37 (13.2%) UP subjects (P = .18). CMV-related mortalities were similar (0.7% vs 1.8%; P = .45), but all-cause mortality was higher in the PT group (18.5% vs 13.2%; P = .08). CONCLUSION: The efficacy of PT was similar to UP to prevent CMV disease and related mortality among a group at moderate risk for CMV infection.

Carbapenem-resistant Acinetobacter baumannii: diversity of resistant mechanisms and risk factors for infection.

Carbapenem-resistant Acinetobacter baumannii (CRAB) are an increasing infectious threat in hospitals. We investigated the clinical epidemiology of CRAB infections vs. colonization in patients, and examined the mechanisms of resistance associated with elevated minimum inhibitory concentrations (MICs) for carbapenems. From January to June 2009, 75 CRAB strains were collected. CRAB infection was significantly associated with malignancy and a high APACHE II score. The most dominant resistance mechanism was ISAba1 preceding OXA-51, producing strains with overexpression of efflux pump. Strains carrying blaOXA-23-like enzymes had higher carbapenem MICs than those carrying blaOXA-51-like enzymes; however, the presence of multiple mechanisms did not result in increased resistance to carbapenems. There was no difference in the resistance mechanisms in strains from infected and colonized patients. The majority of strains were genetically diverse by DNA macrorestriction although there was evidence of clonal spread of four clusters of strains in patients.

High mortality associated with Acinetobacter species infection in liver transplant patients.

BACKGROUND: Acinetobacter species have become increasingly important nosocomial pathogens worldwide and can result in a wide range of infections, including bacteremia, pneumonia, urinary tract infection, peritonitis, among others. The aim of this study was to investigate clinical characteristics, mortality, and outcomes among liver transplant recipients with Acinetobacter species infections. METHODS: We retrospectively analyzed 451 subjects who had undergone living donor liver transplantations between January 2001 and May 2010. Pandrug-resistant (PDR) Acinetobacter species were defined as resistant to all commercially available antibiotics except colistin. RESULTS: Infectious complications due to Acinetobacter species appeared in 26 patients (5.8%) with a total of 37 episodes. Of the species identified, 34 were Acinetobacter baumannii and 3 Acinetobacter Iwoffiii. The presumed sources of infection were the biliary tract (n = 21, 56.8%), lung (n = 7, 18.9%), intra-abdomen (n = 6, 16.2%), catheter (n = 2, 5.4%), and urinary tract (n = 1, 3.6%). Among the 37 Acinetobacter species, 75.7% (28/37) were PDR species. Age, duration of intensive care unit stay, Child-Pugh score, and Model for End-stage Liver Disease score were not significant risk factors for Acinetobacter species infection. However, the overall mortality among patients with Acinetobacter species infections was 50% (13/26), which was significantly higher than that among those free of infection (50% vs 11.5%, P < .05). Multivariate analysis using a Cox regression model showed that inappropriate antimicrobial treatment was a significant independent risk factor for mortality among patients with Acinetobacter species infections (hazard Ratio = 4.19, 95% confidence interval 1.1-18.7; P = .06). CONCLUSION: Patients with Acinetobacter species infections after liver transplantation show a significantly worse prognosis. PDR Acinetobacter species have been a major problem in our center.

AKR1B10 is associated with smoking and smoking-related non-small-cell lung cancer.

This prospective study explored the relationship between expression of AKR1B10 mRNA and various clinical parameters in non-small-cell lung cancer (NSCLC) in terms of its validation as a marker for NSCLC. Tumour tissue samples were collected from 229 patients with NSCLC. Tissue samples from adjacent non-malignant lung tissue (> 5 cm from the tumour) of 89 of these patients and samples from 20 patients with benign lung disease were used as controls. Quantitative reverse transcription- polymerase chain reaction showed significantly higher levels of AKR1B10 mRNA expression in NSCLC tumour tissue than in adjacent non-malignant lung tissue and benign lung tissue. Statistically significant factors for AKR1B10 mRNA over-expression were found to be male gender, smoking, squamous cell carcinoma and moderate or poor cell differentiation. It is concluded that AKR1B10 seems to have potential as a prognostic marker for NSCLC and warrants further investigation.

Acute cytomegalovirus pneumonia and hepatitis presenting during acute HIV retroviral syndrome.

Cytomegalovirus (CMV) disease is a frequent opportunistic infection that usually occurs in the late stages of HIV infection as a result of reactivation of a latent infection. We report a case of a 23-year-old man with acute retroviral syndrome complicated by coexisting CMV pneumonia and CMV hepatitis, which were documented by histopathological examination. His CMV pneumonia and hepatitis were assumed to be primary CMV diseases owing to the absence of CMV IgG antibody. To the best of our knowledge, this is the first case of simultaneous CMV pneumonia and hepatitis occurring as primary CMV diseases during primary HIV infection. This case indicates that invasive CMV diseases such as pneumonia and hepatitis should be considered even in patients with primary HIV infection.

Infectious complications in living-donor liver transplant recipients: a 9-year single-center experience.

BACKGROUND: Infectious complications following living-donor liver transplantation (LDLT) remain a major cause of morbidity and mortality. We analyzed the frequency and type of infectious complications according to the post-transplantation period, and their risk factors with regard to morbidity and mortality. METHODS: We retrospectively analyzed 208 subjects who had undergone LDLT during a 9-year period. RESULTS: The rate of infection was 1.69 per patient during the study period. The predominant infections were intra-abdominal infections (37.6%), primary bacteremia (17.4%), and pneumonia (14.5%). Within the first post-transplant month, 140 (39.9%) infections were detected, and catheter-related coagulase-negative staphylococci (44) were the most common infectious agents. During the 2-6-month post-transplant period, 109 infectious episodes occurred (31.1%), and Enterococcus sp. (n=16) related to biliary infection was the most frequent isolate. After the sixth month, 96 infectious episodes (29%) occurred, and biliary tract-related Escherichia coli (n=19) was the major causative organism. The overall mortality was 24.5% (51/208); 1-year survival rate was 88% (196/208). Post-transplant infection-related mortality was 52.9% (27/51). Biliary tract complications, such as biliary stenosis or leakage, significantly increased the mortality (P=0.01); however, reoperation (retransplantation or resurgery for biliary tract obstruction/leakage or to control bleeding) significantly reduced the mortality (P=0.01). CONCLUSIONS: Our data showed that early catheter removal would mainly aid in reducing infectious complications in the 1-month post-transplantation period. Aggressive management, including reoperation, would lower the mortality in the LDLT recipients.

The sensory interactions of organic acids and various flavors in ramen soup systems.

This study was conducted to investigate the sensory interactions between various organic acids and flavorants in 3 types of ramen soup ('beef,' seafood, and 'kimchi') when types and levels of organic acids (citric, malic, and lactic) varied. For 'beef' and seafood ramen soup, weak suprathreshold levels of acids (0.0039% to 0.0071%) were applied to the system and medium suprathreshold of acids (0.0128% to 0.0299%) were applied to the kimchi ramen soup. The amount of acid applied to each system was chosen based on the equiweight level. Descriptive analyses were performed separately for each ramen soup system using 8 trained panelists. A total of 11, 13, and 12 flavor descriptors were generated for 'beef,' seafood, and 'kimchi' soup, respectively. Analysis of variance was conducted to evaluate the effect of organic acid on the sensory characteristics of ramen soup. Principal component analysis was conducted to summarize the relationship between the soup samples and attributes. The effect of organic acids on the flavor attributes of ramen soup was dependent on the soup system as well as adding levels of acid. Addition of lactic acid power (at 0.0066%) in 'beef'ramen soup showed enhancement effect on the sour, salty, beefy, 'mushroom' flavor, and fermented soybean paste soup flavor, whereas lactic acid powder (at 0.0071%) showed enhancement effect only on the sour and fermented soybean paste soup flavor in seafood ramen soup due to the strong 'hot' flavor characteristics of the soup. In kimchi ramen soup, flavor attributes congruent to sourness were enhanced by the addition of organic acids to the system.

Multicenter surveillance study for nosocomial infections in major hospitals in Korea. Nosocomial Infection Surveillance Committee of the Korean Society for Nosocomial Infection Control.

BACKGROUND: The goals of a surveillance for nosocomial infections (NIs) are to observe the magnitude and characteristics of NIs and to plan and evaluate policies and guidelines of infection control. This study was designed to determine the rate and distribution of NIs and their causative pathogens in Korean hospitals. METHODS: Prospective surveillance was performed at 15 acute care hospitals with more than 500 beds during a 3-month period from June to August 1996. The case-finding methods were laboratory-based surveillance for patients in the general wards and a direct review of medical charts done regularly for all the patients in the intensive care units. RESULTS: A total of 3162 NIs were found among 85,547 discharged patients, with an overall nosocomial infection rate of 3.70 per 100 patients discharged. Urinary tract infections constituted 30.3% of all NIs. Other infections were pneumonias, 17.2%, surgical site infections, 15.5%, and primary bloodstream infections, 14.5%. The infection rate was the highest in neurosurgery (14.21), followed by neurology (8. 62) and ontology services (6.70). The infection rate in intensive care units was higher than it was in the general wards (10.74 vs 2. 57, P =.001). The commonly isolated organisms were Staphylococcus aureus (17.2%), Pseudomonas aeruginosa (13.8%), and Escherichia coli (12.3%). CONCLUSIONS: This first multicenter surveillance study provided extensive information on the current status and trends of NIs in major hospitals in Korea. The results may contribute to the evaluation of infection control programs and the development of effective strategies in these hospitals.

Application of infrequent-restriction-site PCR to clinical isolates of Acinetobacter baumannii and Serratia marcescens.

We applied infrequent-restriction-site PCR (IRS-PCR) to the investigation of an outbreak caused by 23 isolates of Acinetobacter baumannii in an intensive care unit from November 1996 to May 1997 and a pseudoepidemic caused by 16 isolates of Serratia marcescens in a delivery room from May to September 1996. In the epidemiologic investigation of the outbreak caused by A. baumannii, environmental sampling and screening of all health care workers revealed the same species from the Y piece of a mechanical ventilator and the hands of two health care personnel. IRS-PCR showed that all outbreak-related strains were genotypically identical and that three strains from surveillance cultures were also identical to the outbreak-related strains. In a pseudoepidemic caused by S. marcescens, IRS-PCR identified two different genotypes, and among them one genotype was predominant (15 of 16 [93.8%] isolates). Extensive surveillance failed to find any source of S. marcescens. Validation of the result of IRS-PCR by comparison with that of field inversion gel electrophoresis (FIGE) showed that they were completely concordant. These results suggest that IRS-PCR is comparable to FIGE for molecular epidemiologic studies. In addition, IRS-PCR was less laborious and less time-consuming than FIGE. To our knowledge, this is the first report of the application of IRS-PCR to A. baumannii and S. marcescens.

Foodborne outbreaks of human toxoplasmosis.

Two outbreaks of acute toxoplasmosis involving 8 adult patients in Korea were linked to eating uncooked pork. In the first outbreak, 3 patients developed unilateral chorioretinitis within 3 months of eating a meal consisting of raw spleen and liver of a wild pig. In the second outbreak, 5 of 11 soldiers who ate a meal consisting of raw liver of a domestic pig developed lymphadenopathy. All 8 patients had high levels of IgG Toxoplasma gondii antibodies (> or = 1:1024) in the Sabin-Feldman dye test, modified agglutination test incorporating mercaptoethanol, and latex agglutination test. T. gondii IgM antibodies persisted in these patients for several months. Most patients had a favorable response to anti-T. gondii chemotherapy with pyrimethamine and sulfanomides.

Molecular epidemiological analysis of quinolone-resistant Escherichia coli causing bacteremia in neutropenic patients with leukemia in Korea.

We analyzed an outbreak of Escherichia coli bacteremia in eight patients with leukemia in a hematology-oncology unit from July to September 1994. The antibiograms and genotypic patterns of the isolates were different, thus suggesting that the outbreak did not originate from a single clone. However, all the isolates were resistant to quinolones, which led us to examine the microbiological records from 1992 to 1994. The incidence of quinolone-resistant E. coli bacteremia in the hematology-oncology unit ranged from 81.8% to 94.6% during this period. We then analyzed 36 more isolates recovered from late 1994 to 1995. Field inversion gel electrophoresis patterns of these isolates were also different. Analysis of the quinolone resistance determining region in gyrA revealed that all the isolates had a double mutation in gyrA. In conclusion, quinolone-resistant E. coli could be an emerging threat to neutropenic patients with leukemia who receive a quinolone prophylactically, and attention must be paid to this trend of resistance.

A small epidemiological survey for vivax malaria in Kimpo-gun, Kyonggi-do, Korea undertaken after detecting two consecutive cases.

On July and August 1997, two 15-year-old mates of a football team of Tongjin Middle School in northern Kyonggi-do, Korea were consecutively diagnosed as vivax malaria by peripheral blood smear. They had no histories of travelling abroad or drug abuse. They witnessed that other mates in the team were ill of fever in the same period. A small survey was therefore undertaken to determine whether vivax malaria was outbroken locally. A total of 57 students of the team living together in a dormitory was examined for history of fever, presence of splenomegaly, blood smear and anti-P. vivax antibody test by immunofluorescent antibody test (IFAT). Except for the above two patients, only one case revealed a marginal titer of IFAT. No other positive findings of vivax malaria were found. In the results of this local survey, no more cases of vivax malaria were revealed except the two sporadic cases.

Epstein-Barr virus-associated gastric adenocarcinomas among Koreans.

Epstein-Barr virus (EBV)-associated gastric carcinomas have been reported from various regions of the world. Epstein-Barr virus appears to be pathogenetically related to some gastric carcinomas. To determine the incidence of EBV association with gastric carcinomas among Koreans, the authors have studied EBV genome expression in 89 consecutive patients with gastric carcinomas diagnosed at the Catholic University Hospitals in Seoul, Korea, using in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs), and immunohistochemistry for EBV latent membrane proteins (LMP) and CD21 antigen on paraffin sections. Thirty-seven gastric specimens with benign ulcer disease were used controls. EBV-encoded small RNAs were expressed in tumor cell nuclei in 12 patients (13.5%). None of the controls or benign portions of the cases were positive. In the positive cases, all tumor cell nuclei were uniformly stained and the staining intensity was strong. Immunohistochemistry for LMP was positive in 3 of 12 EBERs positive patients and none of EBERs negative patients. EBV latent membrane proteins was localized only in the lymphoid cells infiltrating the tumor in two patients, and tumor cells as well as infiltrating lymphoid cells in one patient. These results indicate that the rate of EBV association with gastric carcinomas in Koreans is relatively high and comparable to other Far Eastern Asian regions. The expression pattern in EBV-associated gastric carcinomas is similar to those of nasopharyngeal carcinomas in which clonality analysis using specific probes to the tandem repeat region of EBV yielded single episomal bands suggesting that EBV infection in EBV-associated gastric carcinomas are also clonal and pathogenetically related to the neoplasm. However, the mechanism of tumorigenesis remains to be elucidated.

In-vitro effects of cefodizime on leucocyte functions and colony formation from granulocyte-monocyte progenitors.

Infections in immunocompromised patients are often difficult to treat, even with currently available antimicrobial agents. An understanding of the effects of antibiotic therapy on the host's immune response is therefore important when deciding on the clinical management of such patients. Antimicrobial agents which lack immunodepressive effects and/or potentiate the immune response are the goal of current research into the treatment of infections in immunocompromised patients. The effects of cefodizime (1-250 micrograms/mL) in vitro on some functional activities of leucocytes and on colony formation by granulocyte monocyte progenitors were studied to investigate the effects of the antibiotic on the host's immune response. A marked enhancement in the lymphocyte transformation reaction was observed in cells exposed to cefodizime. This effect was dose-dependent. Cefodizime had no significant effect on antibody-dependent cell cytotoxicity or on natural killer cell-mediated cytotoxicity. The chemotactic activity of neutrophils was not influenced by the presence of cefodizime (P > 0.05). The phagocytic activity of neutrophils was significantly increased by cefodizime (P > 0.01). Cefodizime significantly stimulated, in a dose-dependent manner, colony formation by granulocyte-monocyte progenitors (P < 0.01). Results suggest that cefodizime has certain stimulatory effects on immunocompetent cells such as enhancing the transformation reaction of lymphocytes, neutrophil phagocytosis and colony formation by granulocyte-monocyte progenitors. Further studies are required to clarify the mechanisms responsible for these effects.

Immunogenicity of Vi capsular polysaccharide vaccine evaluated for three years in Korea.

The immunogenicity of a single dose of Salmonella typhi(S.typhi) Vi capsular polysaccharide(CPS) vaccine was evaluated before, and at 1, 3, 12, and 36 months after vaccination. Eighty-five adults(20-28 years of age) and sixty-four children(8-16 years of age) received a single dose of 25 micrograms Vi CPS vaccine intramuscularly, and antibody titers to Vi CPS were measured by passive hemagglutination. Of 149 vaccinees, 138(92.6%) showed seroconversion at 1 month after vaccination, and then 138 out of 141(97.9%) did at 3 months. Of 137 vaccinees, 116(84.7%) maintained a persistent rise in Vi antibody titer 12 months after vaccination, and 55 out of 100(55.0%) had a 4-fold or greater rise at 36 months. No significant adverse reactions were observed. Booster injection may be needed 3-5 years after vaccination.