Seong Yeon Park

Aspergillus galactomannan antigen assay in bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis

OBJECTIVES A recently developed bronchoalveolar lavage (BAL) galactomannan (GM) assay shows promising results. We evaluated the diagnostic performance of this assay and analyzed risk factors for false-positive results. METHODS A prospective cohort study was performed in a tertiary hospital over a 9-month period. We reviewed all adult patients who underwent GM assays of BAL. Patients were categorized with proven, probable, or possible invasive pulmonary aspergillosis (IPA) according to revised EORTC/MSG definitions. Each patient with a false-positive BAL GM result was matched with three patients with true-negative BAL GM result, and the risk factors for false-positive BAL GM results were determined. RESULTS Of 359 enrolled patients, 22 (6%) were diagnosed with IPA (1 proven, 17 probable, and 4 possible). Of the 22 patients with IPA, 17 (77%) had already received antifungal agents before the BAL GM assay was conducted. At an index cutoff value of ≥0.5, the BAL GM assay had a sensitivity of 64% (95% CI 41%-83%) and a specificity of 89% (95% CI 85%-92%). However, at an index cutoff value of ≥0.2, the BAL GM assay had a sensitivity of 86% (95% CI 65%-97%) and a specificity of 74% (95% CI 69%-79%). Of the 52 patients with positive BAL GM assay (≥0.5), 25 (7%) were false-positives. Univariate and multivariate analysis revealed that treatment with piperacillin-tazobactam or ampicillin-sulbactam was associated with false-positive BAL GM results. CONCLUSIONS The BAL GM assay appears promising for the diagnosis of IPA. However, treatment with certain antibiotics may interfere with the results of the BAL GM assay.

Diagnostic Performance of the Cytomegalovirus (CMV) Antigenemia Assay in Patients with CMV Gastrointestinal Disease

Of 149 patients with suspected cytomegalovirus (CMV) gastrointestinal disease, 51 (36%) confirmed cases, 6 (4%) probable cases, and 64 (45%) instances of non-CMV gastrointestinal disease were analyzed using the CMV antigenemia assay; 22 patients (5%) with indeterminate gastrointestinal disease were excluded. The sensitivity and specificity of the CMV antigenemia assay (defined as detection of > or =1 positive cells per 200,000 leukocytes) for diagnosis of CMV gastrointestinal disease were 54% (95% confidence interval, 41%-68%) and 88% (95% confidence interval, 77%-94%), respectively.

Serum and Bronchoalveolar Lavage Fluid Galactomannan Assays in Patients with Pulmonary Aspergilloma

The sensitivities of the serum and bronchoalveolar lavage galactomannan (GM) assays in 48 patients with pulmonary aspergilloma were 38% (13 of 34; 95% confidence interval [CI], 22%-56%) and 92% (33 of 36; 95% CI, 78%-98%), respectively. The positivity of serum GM assays was significantly higher in patients with hemoptysis than in those without hemoptysis (52% vs 9%; P=.02).

Clinical significance of Propionibacterium acnes recovered from blood cultures : Analysis of 524 episodes

ABSTRACT Of 522 patients with Propionibacterium acnes bacteremia (PAB), 18 (3.5%) had clinically significant PAB. Of these 18 patients, 10 (55.6%) had hospital-acquired bacteremia and 6 (33.3%) had undergone invasive procedures before development of PAB. One patient with a ventricular septal defect presented with infective endocarditis. After the exclusion of 1 patient whose outcome was not available, the overall mortality rate was 5.9% (1/17).

Optimal Duration of Antibiotic Therapy in Patients With Hematogenous Vertebral Osteomyelitis at Low Risk and High Risk of Recurrence

BACKGROUND The optimal duration of antibiotic treatment for hematogenous vertebral osteomyelitis (HVO) should be based on the patients risk of recurrence, but it is not well established. METHODS A retrospective review was conducted to evaluate the optimal duration of antibiotic treatment in patients with HVO at low and high risk of recurrence. Patients with at least 1 independent baseline risk factor for recurrence, determined by multivariable analysis, were considered as high risk and those with no risk factor as low risk. RESULTS A total of 314 patients with microbiologically diagnosed HVO were evaluable for recurrence. In multivariable analysis, methicillin-resistant Staphylococcus aureus infection (adjusted odds ratio [aOR], 2.61; 95% confidence interval [CI], 1.16-5.87), undrained paravertebral/psoas abscesses (aOR, 4.09; 95% CI, 1.82-9.19), and end-stage renal disease (aOR, 6.58; 95% CI, 1.63-26.54) were independent baseline risk factors for recurrence. Therefore, 191 (60.8%) patients were classified as low risk and 123 (39.2%) as high risk. Among high-risk patients, there was a significant decreasing trend for recurrence according to total duration of antibiotic therapy: 34.8% (4-6 weeks [28-41 days]), 29.6% (6-8 weeks [42-55 days]), and 9.6% (≥8 weeks [≥56 days]) (P = .002). For low-risk patients, this association was still significant but the recurrence rates were much lower: 12.0% (4-6 weeks), 6.3% (6-8 weeks), and 2.2% (≥8 weeks) (P = .02). CONCLUSIONS Antibiotic therapy of prolonged duration (≥8 weeks) should be given to patients with HVO at high risk of recurrence. For low-risk patients, a shorter duration (6-8 weeks) of pathogen-directed antibiotic therapy may be sufficient.

Rapid diagnosis of tuberculous peritonitis by T cell-based assays on peripheral blood and peritoneal fluid mononuclear cells.

OBJECTIVES The utility of a newly-developed Mycobacterium tuberculosis-specific enzyme-linked immunosorbent spot (ELISPOT) assay for diagnosis of tuberculous peritonitis (TBP) has not been fully assessed. METHODS All patients with suspected TBP in a tertiary care hospital in an intermediate TB burden country were prospectively enrolled over a 30-month period. ELISPOT assays were performed on peripheral mononuclear cells (PBMC) and mononuclear cells from peritoneal fluid (PF-MC). RESULTS Sixty-four patients with suspected TBP were enrolled. Of these, 30 (47%) were classified as having TBP (27 confirmed and 3 probable cases), and 25 (39%) were classified as not having active tuberculosis. The remaining 9 (14%) with possible TBP were excluded from the final analysis. Five (8%) of the total 64 patients gave indeterminate PBMC ELISPOT results and 7 (18%) of 39 patients who underwent PF-MC ELISPOT assay revealed indeterminate PF-MC ELISPOT results. The sensitivity and specificity, respectively, of the tested methods for diagnosing TBP were as follows: PBMC ELISPOT (≥ 6 spots), 86% and 67%; PF-MC ELISPOT (≥ 14 spots), 92% and 86%; PF-MC ELISPOT/PBMC ELISPOT ratio (≥ 2), 75% and 93%; and PF ADA levels (≥ 38 IU/L), 95% and 100%. The areas under the receiver operating characteristics curves were as follows: PF-MC ELISPOT, 0.96; PF ADA, 0.96; PBMC ELISPOT, 0.88; and PF-MC ELISPOT/PBMC ELISPOT ratio, 0.87, respectively. CONCLUSIONS Although the ELISPOT assay does not outperform PF ADA, the ELISPOT assay using PBMC and PF-MC is a useful adjunct for diagnosing TBP, especially for a rule-in test when PF/MC/PBMC ELISPOT ratio (≥ 2) is used. However, the relatively high proportion of indeterminate results limits test utility, so further studies are needed to develop an optimized assay prototype.

CHARACTERIZATION AND LARGE-SCALE EXPRESSION OF THE RECOMBINANT CYSTEINE PROTEINASE FROM ADULT CLONORCHIS SINENSIS

Cysteine proteinases play important roles in the pathogenesis of several parasitic infections and have been proposed as targets for the structure-based approach of drug design. As the first step toward applying this strategy to design inhibitors as antiparasitic agents for Clonorchis sinensis, we overexpressed and characterized the 24-kDa cysteine proteinase from adult worms. First, the partial cysteine proteinase gene from C. sinensis was cloned by performing reverse transcription polymerase chain reaction (RT-PCR) with degenerate oligonucleotide primers derived from conserved cysteine proteinase sequences. The 5′ and the 3′ regions of the cysteine proteinase gene were amplified using the PCR protocol for the rapid amplification of cDNA ends–polymerase chain reaction (RACE-PCR). The cDNA has an open reading frame of 981 bp, and the deduced amino acid sequence shares similarity with the cathepsin L–like cysteine proteinases from Schistosoma mansoni, Paragonimus westermani metacercaria, Fasciola hepatica, and human cathepsin L by 52%, 47%, 34%, and 29%, respectively. The cysteine proteinase was then overexpressed in the yeast Pichia pastoris as an active enzyme on a large-scale basis (19.7 mg/L). The active recombinant enzyme was purified from culture media using a Ni2+–NTA–agarose affinity column and gel filtration chromatography. This 24-kDa recombinant protein exhibited a substrate preference for Z-Phe-Arg-AMC (benzyloxycarbonyl-l-phenylalanyl-l-arginine-7-amino-4-methyl-coumarin) compared with Z-Arg-Arg-AMC, and the activity was inhibited by E-64 (l-trans-epoxysuccinylleucylamido(4-quanidino)butane).

Risk factors for hospital-acquired pneumonia caused by carbapenem-resistant Gram-negative bacteria in critically ill patients: a multicenter study in Korea

We performed a case-control study to identify risk factors of carbapenem-resistant Gram-negative bacteria (CRGNB) as an increasing cause of hospital-acquired pneumonia (HAP). The study included critically ill adult patients with HAP whose microbial etiology was identified at eight tertiary centers in Korea between June 2008 and December 2009. Eighty two patients with 86 isolates of CRGNB (62 Acinetobacter baumannii, 14 Pseudomonas aeruginosa, and 10 Stenotrophomonas maltophilia) were included in the case group, and 122 patients with carbapenem-susceptible Gram-negative bacteria were included in the control group. Diabetes mellitus (adjusted odds ratio [aOR] 2.82, 95% confidence interval [95% CI] 1.25-6.38), radiologic score ≥5 (aOR 4.56, 95% CI 2.36-8.81), prior fluoroquinolone (aOR 2.39. 95% CI = 1.07-5.35), or carbapenem usage (aOR 2.82, 95% CI 1.75-17.83) were found to be independent risk factors. Fluoroquinolone and carbapenem should be cautiously used to avoid HAP caused by CRGNB.

The burden of nosocomial staphylococcus aureus bloodstream infection in South Korea: a prospective hospital-based nationwide study

BackgroundWe estimated the nationwide burden of nosocomial S. aureus bloodstream infection (SA-BSI), a major cause of nosocomial infection, in South Korea.MethodsTo evaluate the nationwide incidence of nosocomial SA-BSI, cases of SA-BSI were prospectively collected from 22 hospitals with over 500 beds over 4?months. Data on patient-days were obtained from a national health insurance database containing the claims data for all healthcare facilities in South Korea. The additional cost of SA-BSI was estimated through a matched case?control study. The economic burden was calculated from the sum of the medical costs, the costs of caregiving and loss of productivity.ResultsThree hundred and thirty nine cases of nosocomial SA-BSI were included in the study: 254 cases of methicillin-resistant SA-BSI (MRSA-BSI) and 85 cases of methicillin-susceptible SA-BSI (MSSA-BSI). Death related to BSI occurred in 81 cases (31.9%) of MRSA-BSI and 12 cases (14.1%) of MSSA-BSI. The estimated incidence of nosocomial MRSA-BSI was 0.12/1,000 patient-days and that of nosocomial MSSA-BSI, 0.04/1,000 patient-days. The estimated annual cases of nosocomial BSI were 2,946 for MRSA and 986 for MSSA in South Korea. The additional economic burden per case of nosocomial SA-BSI was US

Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea.

20,494 for MRSA-BSI and