Heungsup Sung

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.

Candida haemulonii and Closely Related Species at 5 University Hospitals in Korea: Identification, Antifungal Susceptibility, and Clinical Features

Background. Candida haemulonii, a yeast species that often exhibits antifungal resistance, rarely causes human infection. During 2004-2006, unusual yeast isolates with phenotypic similarity to C. haemulonii were recovered from 23 patients (8 patients with fungemia and 15 patients with chronic otitis media) in 5 hospitals in Korea. Methods. Isolates were characterized using D1/D2 domain and ITS gene sequencing, and the susceptibility of the isolates to 6 antifungal agents was tested in vitro. Results. Gene sequencing of the blood isolates confirmed C. haemulonii group I (in 1 patient) and Candida pseudohaemulonii (in 7 patients), whereas all isolates recovered from the ear were a novel species of which C. haemulonii is its closest relative. The minimum inhibitory concentration (MIC) ranges of amphotericin B, fluconazole, itraconazole, and voriconazole for all isolates were 0.5-32 microg/mL (MIC(50), 1 microg/mL), 2-128 microg/mL (MIC(50), 4 microg/mL), 0.125-4 microg/mL (MIC(50), 0.25 microg/mL), and 0.03-2 microg/mL (MIC(50), 0.06 microg/mL), respectively. All isolates were susceptible to caspofungin (MIC, 0.125-0.25 microg/mL) and micafungin (MIC, 0.03-0.06 microg/mL). All cases of fungemia occurred in patients with severe underlying diseases who had central venous catheters. Three patients developed breakthrough fungemia while receiving antifungal therapy, and amphotericin B therapeutic failure, which was associated with a high MIC of amphotericin B (32 microg/mL), was observed in 2 patients. Conclusions. Candida species that are closely related to C. haemulonii are emerging sources of infection in Korea. These species show variable patterns of susceptibility to amphotericin B and azole antifungal agents.

Non‐tuberculous mycobacterial infections of the skin: A retrospective study of 29 cases

The incidence of infections caused by non‐tuberculous mycobacteria has increased in recent years, due to a rise in dermatological procedures and a greater prevalence of immunosuppression in the general population. This study investigated the clinical and microbiological findings of non‐tuberculous mycobacterial skin infections. The study population included 29 patients from whom non‐tuberculous mycobacteria were cultured after isolation from skin biopsy materials, cutaneous abscesses or exudates. Clinical, microbiological and epidemiological data were collected from each patient. Eight patients were immunocompromised while 21 were not. Precipitating factors such as acupuncture, filler injection, surgical procedures and other traumatic events preceded infection in 13 (including 11 normal hosts and two immunocompromised hosts) of the 29 patients. Multiple skin lesions were present in eight patients (including three normal hosts and five immunocompromised hosts). In eight patients (including four immunocompromised hosts), symptoms were accompanied by tenosynovitis, osteomyelitis and myositis. Mycobacterium abscessus was isolated from nine patients, Mycobacterium fortuitum was isolated from nine patients, Mycobacterium chelonae was isolated from six patients, Mycobacterium marinum was isolated from two patients, a Mycobacterium avium complex member was isolated from two patients, and Mycobacterium haemophilum was isolated from one patient. Ten of the 24 cases caused by rapidly growing organisms (i.e. M. chelonae, M. abscessus and M. fortuitum groups) were precipitated by skin injuries such as acupuncture, filler infection and other medical procedures. Increases in skin medical procedures, including both acupuncture and esthetic interventions, explain the increasing incidence of these organisms. Immunocompromised patients tended to develop multiple skin lesions and deep tissue infections.

Epidemiological Characteristics of Methicillin-Resistant Staphylococcus aureus Isolates from Children with Eczematous Atopic Dermatitis Lesions

ABSTRACT In this study, we investigated the rate of colonization of skin of children with atopic dermatitis (AD) by methicillin-resistant Staphylococcus aureus (MRSA) and characterized the isolates. Active skin lesions in pediatric AD patients were cultured with Rodac Staph (Komed, Korea). S. aureus isolates were examined for drug susceptibilities, analyzed for the eta, etb, tst, and pvl genes, and typed using agr polymorphism, pulsed-field gel electrophoresis of SmaI-restricted chromosomal DNA, and staphylococcal cassette chromosome mec (SCCmec) typing. Eighty-seven (75.4%) of 115 patients had cultivable S. aureus isolates, 16 of which (18.3%) were MRSA. All MRSA isolates were susceptible to chloramphenicol, rifampin, cotrimoxazole, and ciprofloxacin. While methicillin-susceptible S. aureus (MSSA) isolates were composed of 23 isolates of singular types and nine clusters comprising 48 isolates, MRSA isolates were typed into three clones: eight isolates of pulsotype A-agr-1-SCCmec IV, five isolates of pulsotype B-agr-3-SCCmec IIb-etb positive, and three isolates of pulsotype C-agr-3-SCCmec IV. Three SCCmec IVA MRSA isolates were tst positive, but none were positive for the pvl or eta gene. Among 71 MSSA isolates, 7 isolates were tst positive, 6 of which were pulsotype F-agr-3, and 9 of 10 agr-4 isolates were eta positive. The average ages of patients carrying MSSA, SCCmec IVA MRSA, and SCCmec IIb MRSA were 7.7 ± 4.6, 3.1 ± 1.5, and 8.2 ± 3.1 years, respectively. Among the patients carrying MRSA, two patients had been treated with oral antimicrobials, and one had been admitted to the hospital 18 months previously. In conclusion, community-acquired MRSA isolates of a few clones colonized the skin of patients with AD without risk factors for the acquisition of hospital-acquired MRSA, which suggested that the skin of children with AD may represent a significant reservoir of MRSA colonization in the community.

Comparison of Anyplex II RV16 with the xTAG Respiratory Viral Panel and Seeplex RV15 for Detection of Respiratory Viruses

ABSTRACT A novel multiplex real-time PCR approach (Anyplex II RV16 [RV16]; Seegene, South Korea) was compared with a multiplex endpoint PCR kit (Seeplex RV15 ACE detection kit [RV15]; Seegene) and a liquid bead-based assay (xTAG respiratory viral panel [xTAG]; Abbott, United States). Of nasopharyngeal swabs or aspirates and bronchoalveolar lavage fluid samples submitted for RV15 testing, 199 retrospectively collected positive specimens and 283 prospectively collected specimens were further tested with RV16 and xTAG. A true-positive result was defined as a positive result from all three methods or RV16 and xTAG or RV15 and xTAG. For specimens with discrepant results, monoplex PCR and sequencing of the target viruses were performed. In total, 300 virus-positive specimens yielded 386 viruses. When the bocavirus results were excluded, the overall sensitivities of RV16, RV15, and xTAG were 95.2%, 93.3%, and 87.2%, respectively (95% confidence intervals, 93.0 to 97.4%, 90.8 to 95.8%, and 83.8 to 90.6%, respectively). RV16 was more sensitive than xTAG for coronavirus OC43/HKU1 (100% versus 26.1%; P < 0.0001) and adenovirus (100% versus 79.5%; P < 0.01) but was less sensitive than xTAG for rhinovirus/enterovirus (89.4% versus 97.9%; P < 0.05). RV16 demonstrated higher sensitivity than RV15 for the detection of adenovirus (100% versus 82.1%; P < 0.05). The specificities of all three methods ranged from 98.6% to 100%. Sequencing analysis of 64 rhinovirus-positive samples revealed that RV16 accurately differentiated between rhinovirus and enterovirus. RV16 most frequently missed rhinovirus C. In conclusion, the overall sensitivity of RV16 was better than that of xTAG. However, improvement of the sensitivity for rhinovirus is required.

Clinical and radiological features of invasive pulmonary aspergillosis in transplant recipients and neutropenic patients.

S.Y. Park, S.‐H. Kim, S.‐H. Choi, H. Sung, M.‐N. Kim, J.H. Woo, Y.S. Kim, S.‐K. Park, J.‐H. Lee, K.‐H. Lee, S.‐G. Lee, D.J. Han, S.‐O. Lee. Clinical and radiological features of invasive pulmonary aspergillosis in transplant recipients and neutropenic patients.
Transpl Infect Dis 2010: 12: 309–315. All rights reserved

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.

Biofilm formation and genotyping of Candida haemulonii, Candida pseudohaemulonii, and a proposed new species (Candida auris) isolates from Korea

Emergence of Candida haemulonii and closely related species at five Korean hospitals has been recently described. We examined biofilm formation by these isolates and assessed their genotypic relatedness by pulsed-field gel electrophoresis (PFGE). This study is the first to show that all bloodstream isolates of Candida pseudohaemulonii can form significant biofilms in glucose-containing medium. PFGE of NotI-digested genomic DNA revealed that C. pseudohaemulonii isolates recovered from seven patients in two hospitals shared five patterns, and that 15 isolates of a proposed new species (Candida auris) obtained from patients at three hospitals shared seven patterns, suggesting that some of these isolates may be related to clonal transmission.

Long-term intake of Korean red ginseng in HIV-1-infected patients: development of resistance mutation to zidovudine is delayed.

We have observed that CD4+ T cell counts in human immunodeficiency virus (HIV)-1-infected patients treated with only Korean red ginseng (KRG) are maintained or even increased for a prolonged period. In the present study, we investigated whether the development of resistance mutations in reverse transcriptase (RT) to zidovudine (ZDV) is delayed by combined therapy with KRG and ZDV. Nested polymerase chain reaction (PCR) and direct sequencing methods were used to define RT codons 41, 67, 70, 210, 215 and 219 of the HIV-1 pol gene in DNA from peripheral blood mononuclear cells (PBMC) samples from 18 patients. Nine of these eighteen patients were in the KRG group and had been treated with KRG for 60 +/- 15 months (range: 38-82) and ZDV, and nine were in the control group and had been treated with ZDV only. The patients in the KRG group had been treated with ZDV for 75 +/- 24 months, and CD4+ T cell counts were maintained from 239 +/- 85 to 234 +/- 187 microliters-1 (P > 0.05) during the study period, whereas the patients in the control group had been treated with ZDV for 51 +/- 31 months, and their CD4+ T cell counts decreased from 272 +/- 97 to 146 +/- 154 microliters-1 (P < 0.01). In samples within 24 months of ZDV therapy, the overall incidence of 6 resistance mutations to ZDV was 4.2% and 47% in the KRG and control group (P < 0.01), respectively. In samples after 24 months of therapy, the incidence was 21.7% and 56.3% in the KRG and control group (P < 0.01), respectively. These data suggest that the maintenance of CD4+ T cell counts by ZDV and KRG-intake for a prolonged period might be indirectly associated with delayed development of resistance to ZDV by KRG-intake.

Outcomes of Moderate-to-Severe Pneumocystis Pneumonia Treated with Adjunctive Steroid in Non-HIV-Infected Patients

ABSTRACT While it is well-known that adjunctive corticosteroid use improves the outcome of moderate-to-severe Pneumocystis jirovecii pneumonia (PcP) in patients with human immunodeficiency virus (HIV), there are limited data on its efficacy in non-HIV-infected patients with PcP. Patients undergoing fiber-optic bronchoscopy with bronchoalveolar lavage for suspected PcP from January 2007 through December 2010 were reviewed retrospectively. We compared demographics, clinical characteristics, and outcomes in 88 non-HIV-infected patients with moderate-to-severe PcP with (n = 59) and without (n = 29) adjunctive corticosteroid use. Outcomes of PcP were assessed by respiratory failure and 30-day and 90-day all-cause mortality. Survival curves were analyzed by the Kaplan-Meier method and estimated by the log rank test. All-cause mortality of moderate-to-severe PcP at 90 days was lower in the solid-organ transplant recipients than in all other patients (6/26 [23%] versus 34/62 [55%], respectively; P = 0.006), and mortality at 30 days was lower in patients with hematologic malignancies than in all other patients (4/26 [15%] versus 24/62 [39%], respectively; P = 0.03). The outcomes of PcP were not significantly different in moderate-to-severe PcP patients with and without adjunctive corticosteroid use, regardless of recent corticosteroid use. Survival analysis of PcP patients with and without corticosteroid use by the Kaplan-Meier method also did not reveal any difference (log rank test; P = 0.81). There again was no difference within the subgroup of PcP patients with solid-organ transplants. Adjunctive corticosteroid use may not improve the outcome of moderate-to-severe PcP in non-HIV-infected patients.