Oh-Hyun Cho

Viral Infection in Patients with Severe Pneumonia Requiring Intensive Care Unit Admission

RATIONALE The role of viruses in pneumonia in adults and the impact of viral infection on mortality have not been elucidated. Previous studies have significant limitations in that they relied predominantly on upper respiratory specimens. OBJECTIVES To investigate the role of viral infection in adult patients with pneumonia requiring intensive care unit (ICU) admission. METHODS A retrospective analysis of a prospective cohort was conducted in a 28-bed medical ICU. Patients with severe community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP) were included in the study. MEASUREMENTS AND MAIN RESULTS A total of 198 patients (64 with CAP, 134 with HCAP) were included for analysis. Of these, 115 patients (58.1%) underwent bronchoscopic bronchoalveolar lavage (BAL), 104 of whom were tested for respiratory viruses by BAL fluid reverse-transcription polymerase chain reaction (RT-PCR). Nasopharyngeal specimen RT-PCR was performed in 159 patients (84.1%). Seventy-one patients (35.9%) had a bacterial infection, and 72 patients (36.4%) had a viral infection. Rhinovirus was the most common identified virus (23.6%), followed by parainfluenza virus (20.8%), human metapneumovirus (18.1%), influenza virus (16.7%), and respiratory syncytial virus (13.9%). Respiratory syncytial virus was significantly more common in the CAP group (CAP, 10.9%; HCAP, 2.2%; P = 0.01). The mortalities of patients with bacterial infections, viral infections, and bacterial-viral coinfections were not significantly different (25.5, 26.5, and 33.3%, respectively; P = 0.82). CONCLUSIONS Viruses are frequently found in the airway of patients with pneumonia requiring ICU admission and may cause severe forms of pneumonia. Patients with viral infection and bacterial infection had comparable mortality rates.

Rapid Diagnosis of Tuberculous Meningitis by T Cell—Based Assays on Peripheral Blood and Cerebrospinal Fluid Mononuclear Cells

BACKGROUND The role of the new Myocbacterium tuberculosis-specific enzyme-linked immunosorbent spot (ELISPOT) assay for diagnosis of tuberculous meningitis (TBM) has not yet been fully assessed. Here, we conducted a prospective, blinded, observational study to evaluate the diagnostic accuracy of this assay, compared with the conventional tests, for diagnosing TBM. METHODS All adult patients with suspected TBM were enrolled at a tertiary care hospital (Seoul, South Korea) during a 12-month period. ELISPOT assays were performed on peripheral mononuclear cells and mononuclear cells from cerebrospinal fluid (CSF). RESULTS Eighty-nine patients with suspected TBM were enrolled. Of these, 31 (35%) were classified as having TBM (10 confirmed, 6 highly probable, and 15 probable cases), and 55 (62%) were classified as not having active tuberculosis. The remaining 3 (3%) with possible TBM were excluded from the final analysis. The sensitivities and specificities, respectively, of the tested methods for diagnosing TBM were as follows: CSF adenosine deaminase level >5.8 U/L, 89% (95% confidence interval [CI], 69%-98%) and 73% (95% CI, 58%-84%); peripheral mononuclear cells ELISPOT, 71% (95% CI, 51%-86%) and 57% (95% CI, 42%-70%); and CSF mononuclear cells ELISPOT assay, 59% (95% CI, 36%-79%) and 89% (95% CI, 72%-98%). The combined sensitivity of an adenosine deaminase level >5.8 U/L or a positive peripheral mononuclear cells ELISPOT assay result was 94% (95% CI, 79%-99%), conferring a negative likelihood ratio of 0.14 (95% CI, 0.03-0.55) when both test results were negative. CONCLUSION ELISPOT assays using peripheral mononuclear cells and CSF mononuclear cells are useful adjuncts to the current tests for diagnosing TBM, particularly when used in combination with the assessment of adenosine deaminase level in CSF.

Paradoxical responses in non-HIV-infected patients with peripheral lymph node tuberculosis

OBJECTIVES We evaluated the clinical characteristics and risk factors for the paradoxical response (PR) in non-HIV-infected patients with peripheral lymph node tuberculosis (TB). METHODS Medical records of non-HIV-infected patients aged > or =16 years with peripheral lymph node TB treated in a tertiary hospital between January 1997 and August 2007 were analysed. PR was defined as clinical or radiological worsening of pre-existing TB lesions, or development of new lesions in a patient who had received anti-TB therapy for at least 2 weeks. RESULTS Three hundred patients with lymph node TB were included. Of these, 235 patients (78%) had confirmed TB; the remaining 65 (22%) had probable TB and were excluded from the final analysis. Among the 235 study patients, their mean age (+/-standard deviation) was 37.6 (+/-13.9) years and 175 (75%) were female. PR occurred in 54 (23%; 95% confidence interval 18-28%) patients, at a median onset time of 8 weeks (interquartile range, 4-14 weeks) after starting anti-TB medication. In multivariate analysis, younger age (OR 0.96), male gender (OR 2.60), and the presence of local tenderness at the time of diagnosis (OR 2.90) were independently associated with PR. CONCLUSION PR was relatively common, occurring in one-fifth of non-HIV-infected patients with peripheral lymph node TB, and was associated with younger age, male gender, and the presence of local tenderness.

Diagnosis of abdominal tuberculosis by T-cell-based assays on peripheral blood and peritoneal fluid mononuclear cells

OBJECTIVES Diagnosing abdominal tuberculosis (TB) remains a challenge. A recently developed RD-1 gene-based assay for diagnosing tuberculosis infection shows promising results. We evaluated the diagnostic usefulness of this assay compared with conventional tests in patients with suspected abdominal TB in clinical practice. METHODS All patients with suspected abdominal TB were prospectively enrolled in a tertiary hospital during a 1-year period. In addition to the conventional tests for diagnosing TB, the IFN-gamma-producing T-cell response to ESAT-6 and CFP-10 by ELISPOT assay using peripheral blood mononuclear cells (PBMC) and peritoneal fluid mononuclear cells (PF-MC) were performed. RESULTS Forty eight patients with suspected abdominal TB were enrolled. Of these patients, 30 (63%) were classified as abdominal TB including 14 TB peritonitis (12 confirmed + 1 probable + 1 possible), 6 abdominal TB lymphadenitis (3 confirmed + 3 probable), 4 hepatic TB (3 confirmed + 1 possible), 2 intestinal TB (1 confirmed + 1 probable), 3 renal TB (1 confirmed + 2 probable), and 1 pancreatic TB (1 confirmed). Eighteen (38%) were classified as not TB. ELISPOT assay using PBMC was performed on samples from all 48 subjects. The sensitivity and specificity of the PBMC ELISPOT assay were 89% (95% CI, 71-98%) and 78% (95% CI, 52-94%), respectively. In the 11 patients in whom PF-MC ELISPOT assay was performed, it was positive in 5 of 6 patients with TB peritonitis, and negative in all 5 patients with not TB. CONCLUSIONS The ELISPOT assay using PBMC and PF-MC is a useful adjunct to the current tests for diagnosing abdominal TB.

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).

Diagnostic usefulness of a T-cell-based assay for osteoarticular tuberculosis

BACKGROUND Although diagnosing osteoarticular tuberculosis (TB) remains a challenge, a recently developed Mycobacterium tuberculosis-specific ELISPOT assay for diagnosing TB infection has shown promising results. We performed a prospective, blinded, observational study to compare its diagnostic usefulness with those of conventional tests in patients with suspected osteoarticular TB. METHODS All patients presenting at a tertiary hospital between April 2008 and September 2009 with suspected osteoarticular TB were enrolled. In addition to conventional tests for TB, we used ELISPOT assays to measure the IFN-gamma response to ESAT-6 and CFP-10 in T-cells in samples of peripheral blood mononuclear cells (PBMC). Patients with suspected osteoarticular TB were classified by diagnostic category. RESULTS Of the 65 patients with suspected osteoarticular TB, 5 (8%) were excluded due to inconclusive diagnoses. Of the remaining 60 patients, 23 (38%) were classified as having confirmed TB, 3 (5%) as having probable TB, 2 (3%) as having possible TB, and 32 (53%) as not having active TB. Five (8%) patients with probable or possible TB were excluded from the final analysis. Of the 23 patients with confirmed osteoarticular TB, 15 (65%) had TB spondylitis, 4 (17%) had TB arthritis, 2 (9%) had prosthetic joint infection, and 2 (9%) had extra-spinal TB. The sensitivities of the tuberculin skin test (> or =10 mm) and the ELISPOT assay for active osteoarticular TB were 80% (95% confidence interval [CI], 58%-92%) and 100% (95% CI, 85%-100%) (P = 0.04), respectively and their specificities were 68% (95% CI, 51%-81%) and 58% (95% CI, 41%-74%) (P = 0.60), respectively. CONCLUSION A negative ELISPOT assay using PBMC may be a useful test for excluding a diagnosis of active osteoarticular TB.

Prevalence of Latent Tuberculosis Infection among Health Care Workers in South Korea: A Multicenter Study

Background We investigated the prevalence of latent tuberculosis infection (LTBI) among the health care workers (HCWs) and analyzed its risk factors in South Korea. Methods A standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant and tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay, and chest radiography were performed. Results A total of 493 participants, 152 (30.8%) doctors and 341 (69.2%) nurses were enrolled in eight tertiary referral hospitals. The mean age of the subjects was 30.6 years old, and 383 (77.7%) were female. Of the 152 doctors, 63 (41.4%) and 36 (23.7%) were positive by TST and by QTF-GIT, respectively, and among the 341 nurses, 119 (34.9%) and 49 (14.4%) had positive TST and QFT-GIT results, respectively. Overall, the agreement between the two tests was 0.22 by the chance corrected proportional agreement rate (kappa coefficient) in 493 subjects. Experience of working in tuberculosis (TB)-related departments was significantly associated with positive LTBI test results by QFT-GIT assay, not by TST. In multivariate analysis, only age was independently associated with increased risk of a positive TST result, while age and experience of working in TB-related departments (odds ratio, 2.29; 95% confidence interval, 1.01-5.12) were independently associated with increased risk of a positive QFT-GIT result. Conclusion A high prevalence of LTBI was found among South Korean HCWs. Considering the association between the experience of working in TB-related departments and high risk of LTBI, QFT-GIT may be a better diagnostic test for LTBI than TST in HCWs.

Chest computed tomography is more likely to show latent tuberculosis foci than simple chest radiography in liver transplant candidates.

Although the detection and treatment of latent tuberculosis infections (LTBIs) in transplant candidates are essential, current diagnostic methods for LTBIs are limited, especially in immunocompromised subjects. Pretransplant chest computed tomography (CT) may reveal more LTBI foci and thus predict the development of posttransplant tuberculosis (TB) more efficiently; however, this hypothesis has not yet been investigated. Thirty‐six liver transplantation (LT) recipients who developed TB (the TB group) and 144 LT recipients who did not develop TB (the control group) were retrospectively enrolled into a study with a nested case‐control design, and their clinical characteristics and radiological findings were compared. Tuberculin skin tests (TSTs) were not performed, and none of these patients had been treated for LTBIs. Thirty‐six of 2549 LT recipients (1.4%) were diagnosed with TB after LT (median = 10 months, range = 1‐80 months). Twenty‐eight patients (77.8%) successfully completed the treatment. There were no significant differences in the clinical characteristics of the 2 groups. Abnormal CT findings (40.0% versus 17.3%, P = 0.018) and chest X‐ray (CXR) findings (25.0% versus 11.8%, P = 0.044) suggestive of healed TB were significantly more frequent in the TB group versus the control group. Of the 10 patients who underwent chest CT and developed TB, 5 (50%) showed abnormal findings only on chest CT scans, whereas their CXR results were normal. In conclusion, a pretransplant chest CT scan is more likely to show an LTBI than a CXR in those with post‐LT TB. The usefulness of chest CT along with traditional methods such as TSTs for LTBI screening should be further investigated. Liver Transpl 17:963–968, 2011.

Bloodstream infections caused by qnr-positive Enterobacteriaceae: clinical and microbiologic characteristics and outcomes

The clinical significance of plasmid-mediated quinolone resistance determinant qnr has not been well characterized. We investigated the clinical and microbiologic characteristics and outcomes of bloodstream infections (BSIs) caused by qnr-positive Enterobacteriaceae. We prospectively collected 351 nonduplicate consecutive blood isolates of Enterobacter spp. and Klebsiella pneumoniae. qnr genes were detected by polymerase chain reaction and confirmed by sequencing. The medical records of patients were retrospectively reviewed. qnr genes were detected in a total of 26 isolates. A comparison of these 26 qnr-positive and 297 qnr-negative Enterobacteriaceae BSIs in adult patients showed that the population characteristics and clinical features of BSIs were similar between the qnr-positive and qnr-negative groups. However, patients with hematologic malignancies, solid organ transplant recipients, and BSIs caused by strains with multiple antimicrobial resistance, including extended-spectrum beta-lactamase (ESBL) resistance, were more common in the qnr-positive group. Previous antibiotic therapy and prior use of trimethoprim-sulfamethoxazole or aminoglycosides were significantly associated with BSIs caused by qnr-positive strains. In the multivariate analysis, prior use of trimethoprim-sulfamethoxazole (odds ratio [OR], 5.55; 95% confidence interval [CI], 1.47-20.94) and having an underlying disease other than solid tumor (OR, 4.06; 95% CI, 15.07) were independently associated with qnr-positive Enterobacteriaceae BSIs. There was no significant difference in 30-day mortality rates between the qnr-positive and qnr-negative groups (15.4% [4/26] versus 13.8% [41/297], P = 0.77). Although qnr determinants were significantly associated with multiple antimicrobial resistance including ESBL resistance, they did not affect clinical outcomes of BSIs.

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.