Hyo-Lim Hong

Viral Infection Is Not Uncommon in Adult Patients with Severe Hospital-Acquired Pneumonia

Background Viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We investigated the role and distribution of viruses in adult with severe HAP who required intensive care. Methods From March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture. Results A total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321). Conclusions Viral pathogens are not uncommon in adult patients with severe HAP who required ICU admission. Since viral pathogens may cause severe HAP and could be a potential source of viral transmission, further investigation is required to delineate the role of viral pathogens in severe HAP.

Is caspofungin really an effective treatment for Pneumocystis jirovecii pneumonia in immunocompromised patients without human immunodeficiency virus infection? Experiences at a single center and a literature review

Abstract Caspofungin, an antifungal agent that acts on the cell wall by inhibiting β-1,3-glucan synthesis, is likely to be effective for treating Pneumocystis pneumonia, because one of the identifying characteristics of Pneumocystis jirovecii is the presence of β-1,3-glucan in its cell wall. Previous case reports in which the efficacy of caspofungin was found to be favourable have supported this hypothesis. However, of 4 HIV-negative patients who received caspofungin as a salvage regimen at Asan Medical Center, none showed a response. Our negative experience opposes the optimistic view of caspofungin use for Pneumocystis pneumonia expressed in previous reports.

Risk factors for mortality in patients with invasive mucormycosis.

Background Mucormycosis is an uncommon and life-threatening fungal infection. The clinical predictors of outcome were evaluated in patients with invasive mucormycosis. Materials and Methods We retrospectively reviewed histologically proven cases of invasive mucormycosis in our institution from 1996 to 2012. Results A total of 64 patients were analyzed. The median age was 59 years (interquartile range [IQR], 50-67), and 32 patients (50%) were male. The most common underlying diseases were diabetes mellitus (67%), hematologic malignancy (22%), and solid cancer (19%). The most common infection sites were the rhino-orbito-cerebral area (56%) and the lungs (31%). The 180-day all-cause mortality was 33%. Disseminated infection was associated with increased mortality (hazard ratio [HR]: 169.74, 95% confidence interval [CI]: 6.41 to 4492.64; P = 0.002). Pulmonary infection (HR: 0.08, 95% CI: 0.01 to 0.66; P = 0.02) and complete surgical removal of infected tissue (HR: 0.12, 95% CI: 0.02 to 0.64; P = 0.01) were associated with decreased mortality. Conclusions These results suggest that patients with mucormycosis had a lower risk of mortality if they developed a pulmonary infection, rather than a disseminated infection and with complete debridement of infected tissue.

Usefulness of Cellular Analysis of Bronchoalveolar Lavage Fluid for Predicting the Etiology of Pneumonia in Critically Ill Patients

Background The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in pneumonia has not been adequately evaluated. This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit. Methods BAL fluid cellular analysis was evaluated in 47 adult patients who underwent bronchoscopic BAL following less than 24 hours of antimicrobial agent exposure. The abilities of BAL fluid total white blood cell (WBC) counts and differential cell counts to differentiate between bacterial and viral pneumonia were evaluated using receiver operating characteristic (ROC) curve analysis. Results Bacterial pneumonia (n = 24) and viral pneumonia (n = 23) were frequently associated with neutrophilic pleocytosis in BAL fluid. BAL fluid median total WBC count (2,815/µL vs. 300/µL, P<0.001) and percentage of neutrophils (80.5% vs. 54.0%, P = 0.02) were significantly higher in the bacterial pneumonia group than in the viral pneumonia group. In ROC curve analysis, BAL fluid total WBC count showed the best discrimination, with an area under the curve of 0.855 (95% CI, 0.750–0.960). BAL fluid total WBC count ≥510/µL had a sensitivity of 83.3%, specificity of 78.3%, positive likelihood ratio (PLR) of 3.83, and negative likelihood ratio (NLR) of 0.21. When analyzed in combination with serum procalcitonin or C-reactive protein, sensitivity was 95.8%, specificity was 95.7%, PLR was 8.63, and NLR was 0.07. BAL fluid total WBC count ≥510/µL was an independent predictor of bacterial pneumonia with an adjusted odds ratio of 13.5 in multiple logistic regression analysis. Conclusions Cellular analysis of BAL fluid can aid early differential diagnosis of bacterial pneumonia from viral pneumonia in critically ill patients.

Bone and joint infection as a predictor of community-acquired methicillin-resistant Staphylococcus aureus bacteraemia: a comparative cohort study

BACKGROUND A new clone of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), sequence type (ST) 72-staphylococcal chromosomal cassette mec (SCCmec) type IV/IVA without the Panton-Valentine leucocidin (PVL) genes, has been the major clonal type in Korea since 2007. However, there have been no evaluations of the clinical features, risk factors and outcomes associated with CA-MRSA bacteraemia in Korea. METHODS Adult patients with community-acquired S. aureus bacteraemia (SAB) were enrolled between 1 January 2004 and 31 September 2012. We compared the clinical features and outcomes of CA-MRSA bacteraemia with those of community-acquired methicillin-susceptible S. aureus (CA-MSSA) bacteraemia and evaluated the risk factors for CA-MRSA infection. A microbiological study of the CA-MRSA isolates was also conducted. RESULTS In total, 169 patients were included, i.e. 31 (18%) patients with CA-MRSA bacteraemia and 138 (82%) patients with CA-MSSA bacteraemia. Bone and joint infection [45.2% (14/31) versus 22.5% (31/138); adjusted OR, 2.61; 95% CI, 1.09-6.21] was an independent predictor of CA-MRSA bacteraemia. There were no significant differences in relapse of bacteraemia and mortality within 12 weeks after SAB between the two groups. ST72-SCCmec type IV/IVA without the PVL genes was the most common genotype, especially among bone and joint infections (64%, 9/14) as well as among the CA-MRSA isolates (71%, 22/31). CONCLUSIONS CA-MRSA accounted for 18% of community-acquired SAB and was significantly associated with bone and joint infection. Our study suggests that CA-MRSA should be considered in patients with bone and joint infection and that empirical therapy against MRSA should be included.

Immune reconstitution inflammatory syndrome in neutropenic patients with invasive pulmonary aspergillosis

OBJECTIVES Clinical and radiologic deterioration is sometimes observed during neutrophil recovery in patients with invasive pulmonary aspergillosis (IPA). This deterioration can be caused by immune reconstitution inflammatory syndrome (IRIS) as well as by progression of the IPA. However, there is limited data on IRIS in neutropenic patients. METHODS Over a 6-year period, adult patients with neutropenia who met the criteria for probable or proven IPA by the revised EORTC/MSG definition were retrospectively enrolled. IRIS was defined as de novo appearance or worsening of radiologic pulmonary findings temporally related to neutrophil recovery, with evidence of a decrease of 50% in serum galactomannan level. RESULTS Of 153 patients, 36 (24%, 95% CI 18%-31%) developed IRIS during neutrophil recovery. More of these patients received voriconazole than did those with non-IRIS (42% vs. 25%, P = 0.05). Thirty- and ninety-day mortalities were lower in the patients with IRIS than in those with non-IRIS (11% vs. 33%, P = 0.01, and 33% vs. 58%, P = 0.01, respectively). CONCLUSION IRIS is relatively common among neutropenic patients with IPA, occurring in about one quarter of such patients. It is associated with voriconazole use and has a good prognosis.

Cytomegalovirus infection after acute rejection therapy in seropositive kidney transplant recipients

Acute rejection (AR) after solid organ transplantation has been known to be a risk factor for cytomegalovirus (CMV) infection. However, data regarding the risk for CMV infection during and after anti‐rejection therapy are limited. This study investigated whether the risk of CMV infection and disease within 6 months of kidney transplantation (KT) increases in CMV‐seropositive KT recipients who develop AR.

Persistent Catheter-Related Staphylococcus aureus Bacteremia after Catheter Removal and Initiation of Antimicrobial Therapy

Objectives Catheter-related Staphylococcus aureus bacteremia (CRSAB) occasionally persists despite catheter removal and initiation of appropriate antimicrobial therapy. The aim of this study was to determine the incidence, risk factors, and outcomes of persistent CRSAB after catheter removal and initiation of antimicrobial therapy. Methods Consecutive patients with CRSAB were prospectively included from over a 41-month period. We compared the clinical features, 40 bacterial virulence genes, and outcomes between patients with persistent CRSAB (i.e., bacteremia for >3 days after catheter removal and initiation of appropriate antimicrobial therapy) and non-persistent CRSAB. Results Among the 220 episodes of CRSAB, the catheter was kept in place in 17 (6%) and removed in 203 (94%) cases. In 43 (21%) of the 203 episodes, bacteremia persisted for >3 days after catheter removal and initiation of antimicrobial therapy. Methicillin resistance (Odds ratio [OR], 9.01; 95% confidence interval [CI], 3.05–26.61; P<0.001), non-catheter prosthetic devices (OR, 5.37; 95% CI, 1.62–17.80; P = 0.006), and renal failure (OR, 3.23; 95% CI, 1.48–7.08; P = 0.003) were independently associated with persistent CRSAB. Patients with persistent CRSAB were more like to experience complication than were those with non-persistent CRSAB (72% vs. 15%; P<0.001). Among all episodes due to methicillin-resistant S. aureus, persistent CRSAB isolates were associated with accessory gene regulator (agr) group II (P = .04), but presence of other bacterial virulence genes, distribution of vancomycin minimum inhibitory concentration distribution, and frequency of vancomycin heteroresistance did not differ between the groups. Conclusions In patients with CRSAB, bacteremia persisted in 21% of cases despite catheter removal and initiation of antimicrobial therapy. Methicillin resistance, renal failure, and non-catheter prosthetic devices were independent risk factors for persistent CRSAB, which was associated with a higher rate of complications.

Fluoroquinolone resistance of Streptococcus pneumoniae isolates causing invasive disease: special focus on zabofloxacin.

The present study examined the in vitro activity of various antibiotics including zabofloxacin, against isolates responsible for invasive pneumococcal diseases. Between 1997 and 2008, a total of 208 isolates were collected from sterile fluids, including blood (n=196, 94.2%), pleural fluid (n=5, 2.4%), cerebrospinal fluid (n=5, 2.4%), and ascites (n=2, 1.0%). Zabofloxacin showed the lowest MIC50 (0.015μg/mL) and MIC90 (0.025μg/mL) values of all the tested antibiotics. Rates of isolates resistant to penicillin (MIC ≥8μg/mL), ceftriaxone (MIC ≥4μg/mL) and levofloxacin (MIC ≥8μg/mL) were 3.4%, 0.4% and 2.0%, respectively. Four isolates (2.0%) were resistant to levofloxacin, and zabofloxacin showed low MICs (range, 0.025-0.125μg/mL). Zabofloxacin shows potent in vitro activity against S. pneumoniae isolates that caused invasive disease, even strains that are resistant to levofloxacin.

Clinical characteristics of hospital-onset Pneumocystis pneumonia and genotypes of Pneumocystis jirovecii in a single tertiary centre in Korea

BackgroundPneumocystis pneumonia (PCP) may develop as a clinical manifestation of nosocomial pneumonia by means of either reactivation of resident P. jirovecii or de novo infection. However, there have been no studies describing the clinical characteristics of hospital-onset PCP.MethodsA retrospective review of medical records was performed to identify episodes of hospital-onset PCP in a tertiary care centre in Korea between May 2007 and January 2013. We investigated whether human-to-human contact during hospitalisation contributed to PCP development by molecular analysis of the genes encoding mitochondrial large ribosomal subunit (mtLSU) rRNA and dihydropteroate synthase (DHPS) and a review of hospitalisation history.ResultsDuring the study period, 129 patients (130 episodes) were diagnosed with PCP. Of these, respiratory specimens from 94 patients during 95 PCP episodes were available for analysis. Sixteen episodes (16.8%) were categorised as hospital-onset PCP. There was a trend toward a higher proportion of haematological malignancy (43.8% [7/16] vs. 20.3% [16/79]; P = 0.058) in patients with hospital-onset PCP compared to patients with community-onset PCP. mtLSU genotype 1 was the most common, occurring in 41 (43.2%) patients. There were four possible cases of nosocomial transmission. Mutation in DHPS was not observed in any PCP episode.ConclusionsPCP can be one of the causes of nosocomial pneumonia, although the mode of acquisition and transmission of P. jirovecii remains uncertain. mtLSU genotype 1 is the predominant P. jirovecii strain in Korea.