Liver Abscess In Taiwan Research Articles

Molecular and Clinical Characterization of Multidrug-Resistant and Hypervirulent Klebsiella pneumoniae Strains from Liver Abscess in Taiwan.

Hypervirulent Klebsiella pneumoniae strains are the major cause of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug-resistant and hypervirulent (MDR-HV) K. pneumoniae strains have emerged due to hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobial-susceptible strains further underwent whole-genome sequencing (WGS) and in vivo mice lethality tests. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC β-lactamase genes. WGS revealed that two hypervirulent strains had evolved to an MDR phenotype due to mutation in the ramR gene and the acquisition of an SHV-12-bearing plasmid, respectively. Both these MDR-HV strains retained high virulence compared to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA.

Correlation between proton pump inhibitors and risk of pyogenic liver abscess.

Little is known about the relationship between proton pump inhibitors use and pyogenic liver abscess. The objective of this study was to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess in Taiwan. This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. Subjects aged 20 to 84 who experienced their first episode of pyogenic liver abscess were enrolled as the case group (n=1372). Randomly selected subjects aged 20 to 84 without pyogenic liver abscess were enrolled as the control group (n=1372). Current use, early use, and late use of proton pump inhibitors was defined as subjects whose last one tablet for proton pump inhibitors was noted ≤30days, between 31 to 90days and ≥91days before the date of admission for pyogenic liver abscess. Subjects who never received a prescription for proton pump inhibitors were defined as nonusers of proton pump inhibitors. A multivariable unconditional logistic regression model was used to measure the odds ratio and 95% confidence interval to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess. After adjusting for confounders, the adjusted odds ratio of pyogenic liver abscess was 7.59 for subjects with current use of proton pump inhibitors (95% confidence interval 5.05, 11.4), when compared with nonusers. Current use of proton pump inhibitors is associated with a greater risk of pyogenic liver abscess.

The emerging problems of Klebsiella pneumoniae infections: carbapenem resistance and biofilm formation.

Klebsiella pneumoniae is an opportunistic pathogen that commonly causes nosocomial infections in the urinary tract, respiratory tract, lung, wound sites and blood in individuals with debilitating diseases. Klebsiella pneumoniae is still a cause of severe pneumonia in alcoholics in Africa and Asia, and the predominant primary pathogen of primary liver abscess in Taiwan and Southeast Asia, particularly in Asian and Hispanic patients, and individuals with diabetes mellitus. In the United States and Europe, K. pneumoniae infections are most frequently associated with nosocomial infections. The emergence of antibiotic-resistant strains of K. pneumoniae worldwide has become a cause of concern where extended-spectrum β-lactamases (ESBLs) and carbapenemase-producing strains have been isolated with increasing frequency. The pathogen's ability to form biofilms on inserted devices such as urinary catheter has been proposed as one of the important mechanisms in nosocomially acquired and persistent infections, adding to the increased resistance to currently used antibiotics. In this review, infections caused by K. pneumoniae, antibiotic resistance and formation of biofilm will be discussed.

Zolpidem Use Associated With Increased Risk of Pyogenic Liver Abscess

The purpose of this study was to explore the association between zolpidem use and pyogenic liver abscess in Taiwan.This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. We identified 1325 patients aged 20 to 84 years with the first-attack of pyogenic liver abscess as the cases, and 5082 patients without pyogenic liver abscess matched with sex, age, comorbidities, and index year of hospitalization for pyogenic liver abscess as the controls. Patients whose last remaining 1 tablet for zolpidem was noted ≤7 days before the date of admission for pyogenic liver abscess were defined as current use of zolpidem. Patients whose last remaining 1 tablet for zolpidem was noted >7 days before the date of admission for pyogenic liver abscess were defined as late use of zolpidem. Patients who never received 1 prescription for zolpidem were defined as never use of zolpidem. A multivariable unconditional logistic regression model was used to measure the odds ratio (OR) and 95% confidence interval (CI) to explore the association between zolpidem use and pyogenic liver abscess.After adjustment for possible confounding variables, the adjusted OR of pyogenic liver abscess was 3.89 for patients with current use of zolpidem (95% CI 2.89, 5.23), when compared with those with never use of zolpidem. The adjusted OR decreased to 0.85 for those with late use of zolpidem (95% CI 0.70, 1.03), but without statistical significance.Current use of zolpidem is associated with the increased risk of pyogenic liver abscess. Physicians should take the risk of pyogenic liver abscess into account when prescribing zolpidem.

Proton pump inhibitor use significantly increases the risk of cryptogenic liver abscess: a population-based study.

Proton pump inhibitors (PPIs) increase gastric pH and impair defence mechanisms against ingested pathogens, which may result in the overgrowth of virulent Klebsiella pneumoniae in the intestine and subsequent liver abscess. We investigated the possible association between PPIs use and cryptogenic liver abscess in Taiwan. We conducted a population-based case-control study using data from the National Health Insurance Research Database. A total of 958 adult cases of liver abscess and 3832 age- and sex-matched control patients were enrolled during 2000-2010. Conditional logistic regression was used to estimate the adjusted odds ratios (ORs) in patients using PPIs before cryptogenic liver abscess. The adjusted OR associating current use of PPIs (prescription within thepast 30days) with cryptogenic liver abscess was 4.7 [95% confidence interval (CI), 2.9-7.8], and recent use of PPIs (prescription within the past 31-90days) with cryptogenic liver abscess was 2.9 (95% CI, 1.4-6.1). A dose-response relationship was apparent for cumulative dose of PPIs within 90days. Adjusted OR was highest among the patients receiving PPIs more than 60 cumulative defined daily dose (OR=6.5, 95% CI, 2.8-14.9). Proton pump inhibitor therapy within the past 90days was associated with an increased risk of cryptogenic liver abscess.

Clinical Manifestations and Risk Factors of Amebic Liver Abscess in Southeast Taiwan Compared with Other Regions of Taiwan

Amebic liver abscess (ALA) had previously been endemic in Taiwan, particularly in the southern region, although its occurrence in the southeastern area was unknown. Thus, we conducted a retrospective study for southeastern Taiwan. We identified 14 patients who were diagnosed with ALA between July of 1995 and July of 2008. These patients were predominantly male and older in age. Most patients lived in rural areas (85.7%). Alcoholism (78.6%) and diabetes (35.7%) were risk factors for ALA. No human immunodeficiency virus (HIV) infections were detected. The most common clinical symptoms were fever (100%) and abdominal pain (100%). Short mean durations of symptoms, high bilirubin levels, and low albumin levels were also noted. Most patients (92.86%) had a single lesion, particularly in the right liver lobe (71.4%). Six patients also had secondary Klebsiella pneumoniae bacterial infections. Clinicians should be aware of the different risk factors in different regions when diagnosing amebic liver abscess in Taiwan.

Clinical characteristics and economic consequence of Klebsiella pneumoniae liver abscess in Taiwan

Klebsiella pneumoniae liver abscess (KPLA) has emerged as an endemic disease in Taiwan, and its prevalence has been increasing in east Asian countries in the past three decades. The utilization of healthcare resources associated with KPLA is assumed to be substantial, and may be of future concern. This study investigated the clinical characteristics and economic burden of KPLA in Taiwan in 2011 and 2012. Adult patients with KPLA were identified retrospectively in a tertiary medical center in Taiwan from January 2011 to December 2012. The clinical characteristics, total and daily hospitalization expenditure, and the risk factors for the costs of KPLA were analyzed. Among patients with KPLA, the median cost was $5290.80 in US dollars, and the mean cost was $6337.50 ± $4363.40. Length of hospital stay was the only independent risk factor for the high total hospitalization expenditure. The duration of antibiotic use was nearly the same as the length of hospital stay. The prolonged stay in the general ward (≥21 days) also contributed to the high total cost of hospitalization. The independent risk factors for the high average daily cost of hospitalization were a higher Charlson Comorbidity Index and the requirement of intensive care on admission. The current study is the first to demonstrate the high economic burden resulting from KPLA in a medical center in Taiwan. Standardizing the treatment protocol for KPLA inpatients and introducing an outpatient parenteral antimicrobial therapy center to reduce the length of stay may reduce costs, whereas development of a vaccine may be necessary to tackle endemic KPLA in the future.

Clinical and bacteriological characteristics of Klebsiella pneumoniae causing liver abscess with less frequently observed multi-locus sequences type, ST163, from Singapore and Missouri, US

Klebsiella pneumoniae is the major cause of liver abscesses in several Asian countries. Differences in the type of circulating Klebsiella strains and/or the genetic make up of the host seem to be plausible explanations for this. Two recent K. pneumoniae strains isolated from patients with liver abscess, one from Missouri in the US, and a second one from Singapore, were fully characterized by molecular typing, association of virulent genes, neutrophil phagocytosis, susceptibility to serum killing, and lethality in mice. Both strains had mucoid colony morphology and were similar in multilocus sequence type (ST-163), drug-susceptibility profile, resistance to phagocytosis and susceptibility to serum killing. Although ST-163 is a single nucleotide variant (SNV) to the major ST-23, which is specific to serotype K1 K. pneumoniae that causes liver abscess in Taiwan, these two isolates differ in capsular serotype. One was serotype K1 and the other K29. Since a serotype K35 with ST163 was reported previously to cause peritonitis, serotype K29 with SNV to ST-23 was not impossible. Pulsed field gel electrophoresis by XbaI digestion showed different restriction patterns. The virulence-associated genes rmpA and aerobactin were only present in the serotype K1 isolate from Singapore and not in the serotype K29 isolate from Missouri. The serotype K1 isolate was also more virulent to mice. The reasons underlying the high prevalence of ST-23 or its SNV in K. pueumonaie liver abscesses is worth further investigation.

Impact of advanced age on inpatients with pyogenic liver abscess in Taiwan: A nationwide claim-based analysis

Background Pyogenic liver abscess (PLA) is seen as an endemic disease in population of Taiwan. The impact of advanced age on inpatients with PLA remains unclear. Methods Data was collected and analyzed from claims of discharges by inpatients with PLA, using the National Health Insurance Research Database of 2007. Results A total of 2319 subjects and 2651 related discharges were enrolled, including 939 subjects/1077 discharges ≥65 years and 1380 subjects/1574 discharges <65 years. Subjects ≥65 years had significantly higher ratios of females to males, nephropathy, biliary tract diseases, liver cirrhosis and gastroenterological cancers than those <65 years. Hepatic/intra-hepatic duct cancers accounted for the most comorbid gastroenterological cancers. Discharged of subjects ≥65 years had longer hospital stays, more in-hospital death/critical discharge, and a higher ratio of acute low respiratory conditions (ALRC) and urological infections than those of subjects <65 years ( p < 0.05). The inpatient costs for subjects ≥65 years were significantly higher than those for subjects age<65 years in blood products, hemodialysis and total hospitalization. Co-morbidities, such as nephropathy, biliary tract diseases, liver cirrhosis, gastroenterological cancers, ALRC and urological infections were predictive variables associated with age ≥65 years in patients with PLA, as were being female and in-hospital death/critical discharge. Nephropathy and gastroenterological cancers were predictive variables associated with poor prognosis (in-hospital death/critical discharge) in both PLA patients age < and ≥65 years ( p < 0.05). Diabetes mellitus featured predominantly, but had no impact on distribution and prognosis. Conclusion Advanced age (≥65 years) had an impact on the aforementioned characteristics and predictive variables in inpatients with PLA. Physicians should pay attention and treat aged PLA patients with greater care, especially those cares with comorbid nephropathy or gastroenterological cancers.

Molecular Typing and Virulence Analysis of Serotype K1 Klebsiella pneumoniae Strains Isolated from Liver Abscess Patients and Stool Samples from Noninfectious Subjects in Hong Kong, Singapore, and Taiwan

Serotype K1 Klebsiella pneumoniae with multilocus sequence type 23 (ST23) has been strongly associated with liver abscess in Taiwan. Few data regarding the strain types and virulence of this serotype from other Asian countries are available. Serotype K1 K. pneumoniae strains isolated from liver abscess and stool samples from subjects hospitalized in Hong Kong, Singapore, and Taiwan hospitals were examined. Forty-seven serotype K1 isolates were identified: 26 from liver abscess samples and 21 from stool samples. MLST revealed 7 sequence types: 85.1% (40 of 47 isolates) belonged to ST23, 1 isolate belonged to ST163 (a single-locus variant of ST23), and 2 isolates were ST249 (a 3-locus variant of ST23). New STs, namely, ST367, ST425, and ST426, were allocated to 3 of 4 isolates from stool samples. The virulence of these strains was determined by neutrophil phagocytosis and mouse infection models. Except for two ST23 isolates, all Klebsiella pneumoniae isolates were resistant to phagocytosis. Resistance to serum killing varied in isolates of ST23, while all non-ST23 strains were susceptible to serum killing except one with ST249 from a liver abscess. All hypervirulent isolates with a 50% lethal dose of <10(2) CFU were from ST23, were resistant to phagocytosis and serum killing, and also carried both virulence-associated genes, rmpA and aerobactin. Multilocus sequence typing genotype 23 was the most prevalent sequence type among serotype K1 K. pneumoniae isolates from both liver abscess and stool samples in the Asia Pacific region. Serotype K1 K. pneumoniae isolates with capsule expression leading to phagocytic resistance and with the aerobactin gene were associated with hypervirulence.

Pyogenic Liver Abscess as Endemic Disease, Taiwan

Pyogenic liver abscess has become a health problem in Taiwanese society. However, the extent of this problem has remained unclear because of the lack of a population-based study. We therefore performed a nationwide analysis of pyogenic liver abscess in Taiwan from 1996 through 2004. We analyzed 29,703 cases from the Taiwan National Health Insurance database and 506 cases from National Taiwan University Hospital. Our analysis showed that the annual incidence of pyogenic liver abscess increased steadily from 11.15/100,000 population in 1996 to 17.59/100,000 in 2004. Diabetes, malignancy, renal disease, and pneumonia were associated with a higher risk for the disease. By contrast, death due to pyogenic liver abscess decreased over time, although population-based abscess-related death increased slightly. Renal disease, malignancy, pneumonia, and heart disease correlated with higher death rates; Klebsiella pneumoniae infection and therapeutic procedures were related to lower death rates. Diabetes did not significantly change death rates for the 506 patients from the hospital.

Reply to Yu et al., Fung and Siu, and Lin et al

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A clinical survey ofKlebsiella pneumoniae virulence and genotype in pyogenic liver abscess

Primary Klebsiella pneumoniae liver abscess with metastatic complications is a globally emerging infectious disease and is the leading cause of liver abscess in Taiwan. Host immunity and bacterial virulence, especially of the capsular polysaccharide type, are important in determining clinical manifestations. Investigators retrospectively studied the K pneumoniae genotype and capsular serotype from patients with 37 strains of liver abscess; no correlation was noted with genotype, and many genetically different strains caused liver abscess. Although K pneumoniae is prevalent in patients with diabetes, it can attack healthy or alcoholic people as well. Additional studies are needed to explore the mechanisms of bacterial virulence and to optimize treatment strategies. Physicians should be alert to the illness and its complications.

Pyogenic Liver Abscess Caused by Burkhoderia pseudomallei in Taiwan

Pyogenic liver abscess in Taiwan is a well-known disease entity, commonly associated with a single pathogen, Klebsiella pneumoniae. Melioidosis is an endemic disease in Taiwan that can manifest as multiple abscesses in sites including the liver. We report three cases of liver abscesses caused by Burkholderia pseudomallei. The first patient was a 54-year-old diabetic woman, who presented with liver abscess and a left subphrenic abscess resulting from a ruptured splenic abscess, co-infected with K. pneumoniae and B. pseudomallei. The second patient, a 58-year-old diabetic man, developed bacteremic pneumonia over the left lower lung due to B. pseudomallei with acute respiratory distress syndrome, and relapsed 5 months later with bacteremic abscesses of the liver, spleen, prostate and osteomyelitis, due to lack of compliance with prescribed antibiotic therapy. The third patient was a 61-year-old diabetic man with a history of travel to Thailand, who presented with jaundice and fever of unknown origin. Liver and splenic abscesses due to B. pseudomallei were diagnosed. A high clinical alertness to patients' travel history, underlying diseases, and the presence of concomitant splenic abscess is essential to early detection of the great mimicker, melioidosis. The treatment of choice is intravenous ceftazidime for at least 14 days or more. An adequate duration of maintenance oral therapy, with amoxicillin-clavulanate or trimethoprim-sulfamethoxazole for 12-20 weeks, is necessary to prevent relapse. Liver abscess in Taiwan is most commonly due to K. pneumoniae, but clinicians should keep in mind that this may be a presenting feature of melioidosis.

KLEBSIELLA PNEUMONIAE PRIMARY LIVER ABSCESS IN A NEWLY DIAGNOSED DIABETIC

A 48 year old male presented with cough, fever, and chills for 1 week and right sided pleuritic chest pain of 3 days duration. He had a 20 pack year history of smoking, and abused alcohol. He denied any past medical history including recent travel. He had tachycardia and tachypnea with a fever of 103.5 F. Physical exam was unremarkable. WBC count was 13,100/mm3, with 94% neutrophils. Blood glucose was 181 mg %, Bilirubin 1.9 mg/dL, ALT 140 U/L, AST 175 U/L, alkaline phosphatase 185 U/L and LDH 386 U/L. Chest × ray was suspicious for a right lower lobe infiltrate. The patient was started on Ceftriaxone and Azithromycin for pneumonia. Over the next few days, fever and chills subsided and the pain diminished becoming localized to the right upper quadrant of the abdomen. The liver enzymes improved. Blood cultures sent on admission grew Klebsiellapneumoniae sensitive to all antibiotics except ampicillin. An abdominal CT revealed a 9 × 1 1cm abscess in the right lobe of the liver with multiple small nodules (< 1cm) in the lower lobe of the lungs CT guided catheter drainage of the abscess grew K. pneumoniae with the same antibiotic resistance pattern as in blood. After three weeks of parenteral broad spectrum cephalosporins the patient was discharged on oral antibiotics. Six weeks after admission a repeat abdominal CT revealed a much smaller abscess in the right lobe. The lung nodules resolved. The patient remained asymptomatic and continued to take antibiotics. K. pneumoniae was reported as the most common cause of liver abscess in Taiwan, Singapore and Korea between 1990 and 1999. They still remain a rare cause of liver abscess in North America. Diabetes mellitus is an established risk factor. CT guided drainage and third generation cephalosporins are the suggested treatment. Endopthalmitis, meningitis, septic pulmonary emboli and necrotizing fasciitis are associated complications. With increasing globalization, we may begin to see an increase in K. pneumoniae primary liver abscess outside Asia.

Klebsiella pneumoniae isolates causing liver abscess in Taiwan

Klebsiella pneumoniae has been the leading cause of pyogenic liver abscess in Taiwan during the period from 1985 to 1999, which is different from other countries. The present study investigated the in vitro antimicrobial susceptibilities of 51 K. pneumoniae isolates collected from blood cultures of patients with liver abscess in Taiwan during the period from 1993–1997, and typed by pulsed-field gel electrophoresis (PFGE). All 51 isolates were resistant to ampicillin, but susceptible to other antimicrobial agents. The minimum inhibitory concentrations (MICs) were less than 1 μg/ml for the third- and fourth-generation cephalosporins, monobactam, carbapenems, and ciprofloxacin. In comparison, 62 isolates of K. pneumoniae from community-acquired bacteremic patients without liver abscess had similar antimicrobial susceptibilities, while 142 isolates from patients with hospital-acquired bacteremia without liver abscess were much less susceptible to all of the tested antimicrobial agents. PFGE molecular epidemiologic analysis found 20 out of 51 isolates belonged to eight clusters of genetically related strains, with two or three isolates in each clusters. The other 31 isolates were genetically distinct strains. This study demonstrated that K. pneumoniae isolates which cause liver abscess in Taiwan remained susceptible to a wide range of antimicrobial agents and that they were not genetically related.

Identification of a major cluster of Klebsiella pneumoniae isolates from patients with liver abscess in Taiwan.

Klebsiella pneumoniae has emerged as the leading liver abscess pathogen in Taiwan, with the percentage rising from 30% in the 1980s to over 80% in the 1990s. Most of the patients with K. pneumoniae liver abscess are diabetic and without biliary tract disease. Some patients develop serious extrahepatic complications such as endophthalmitis, meningitis, lung abscess, and necrotizing fasciitis. Pulsed-field gel electrophoresis (PFGE) was used for cluster analysis of 96 isolates from patients with liver abscess and 60 isolates from patients with other diseases. A total of 136 PFGE types were identified. Among the 96 liver abscess-associated isolates, 60 (62.5%) were classified in major cluster A. Cluster A included 41 PFGE types (types 1 to 41) which had a genetic similarity of at least 72.4% +/- 9.4%. The PFGE patterns of cluster A strains are so similar that they could have originated from the same ancestor. This study demonstrates that cluster A plays an important role in the high incidence of K. pneumoniae liver abscess in Taiwan.