Risk factors for mortality in patients with Pseudomonas aeruginosa bacteremia; retrospective study of impact of combination antimicrobial therapy.

BACKGROUND: Whether the combination of antimicrobial therapy is a factor in mortality in Pseudomonas aeruginosa bacteremia remains to be elucidated. This study investigated the risk factors for mortality in P. aeruginosa bacteremia patients and the influence of adequate antimicrobial therapy and combination therapy on clinical outcomes. METHODS: This retrospective study analyzed data of 234 patients with P. aeruginosa bacteremia at a 1,200-bed tertiary teaching university hospital in South Korea between January 2010 and December 2012. Factors associated with mortality were determined. Mortality was compared in patients with adequate empirical and targeted combination therapy, and monotherapy, and inappropriate therapy. RESULTS: A total of 141 (60.3%) patients were given appropriate empirical antibiotic treatment (combination therapy in 38 and monotherapy in 103). Among 183 patients (78.2%) who finally received appropriate targeted treatment, 42 had combination therapy and 141 had monotherapy. The percentage of patients receiving empirical combination therapy was slightly, but not significantly higher, in the survivor group than in the nonsurvivor group (17.0% [31/182] vs. 13.5% [7/52], p = 0.74). A similar tendency was demonstrated for targeted combination therapy (19.8% [36/182] vs. 11.5% [6/52], respectively; p = 0.31). However, in a subgroup analysis of data from patients (n = 54) with an absolute neutrophil count less than 500/mm3, the patients who had appropriate empirical or targeted combination therapy showed better outcomes than those who underwent monotherapy or inappropriate therapy (p < 0.05). Mechanical ventilation (odds ratio [OR], 6.93; 95% confidence interval [CI], 2.64-18.11; p = 0.0001), the use of a central venous catheter (OR, 2.95; 95% CI, 1.35-6.43; p = 0.007), a high Acute Physiology and Chronic Health Evaluation II score (OR, 4.65; 95% CI, 1.95-11.04; p = 0.0001), and presence of septic shock (OR, 2.91; 95% CI, 1.33-6.38; p = 0.007) were independent risk factors for 14-day mortality. CONCLUSIONS: Disease severity was a critical factor for mortality in our patients with P. aeruginosa bacteremia. Overall, combination therapy had no significant effect on 14-day mortality compared with monotherapy. However, appropriate combination therapy showed a favorable effect on survival in patients with febrile neutropenia.

Liver abscess due to Klebsiella pneumoniae: risk factors for metastatic infection.

INTRODUCTION: Klebsiella pneumoniae-associated liver abscess (KPLA) is often accompanied by extrahepatic complications. We investigated the clinical features and outcomes of patients with and without metastatic infections and compared the 2 groups. METHODS: We retrospectively reviewed the medical records of 161 patients with KPLA who were admitted to 2 tertiary referral hospitals in Korea. RESULTS: In total, 9.9% had a metastatic infection. The most commonly involved distant sites were the eyes (n = 7) and the lungs (n = 6). In multivariate analysis, diabetes mellitus as an underlying disease (odds ratio (OR) 2.30, 95% confidence interval (CI) 1.05-9.51; p = 0.03) and a platelet count < 80,000/mm(3) (OR 11.60, 95% CI 2.53-53.26; p = 0.002) were associated with metastatic infection. Extended-spectrum beta-lactamase (ESBL) production was not observed in K. pneumoniae from patients with metastatic infection, whereas 3.4% of the bacteria in patients without metastatic infection had ESBL production. However, this difference was not statistically significant (p = 0.45). The in-hospital mortality rate was not significantly different (0% vs. 2.8%; p = 0.52). By multivariate analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score was independently associated with mortality among patients with KPLA (OR 1.5, 95% CI 1.12-2.00; p = 0.006). CONCLUSIONS: Clinicians must be aware of potential metastatic infections in patients with KPLA, especially if they have diabetes mellitus and thrombocytopenia. The APACHE II score was predictive of mortality in patients with KPLA.

Effect of characteristics on the clinical course at the initiation of treatment for human immunodeficiency virus infection using dimensionality reduction.

The beginning of human immunodeficiency virus (HIV) infection treatment depends on various factors, which are significantly correlated with the initial CD4 cell number. However, a covariate correlation between these factors may not reflect the correct outcome variable. Thus, we evaluated the effects of a combination of fixed factors (reduced dimensions), which determine when to start treatment for the first time, on short-term outcome, long-term outcome, and survival, considering correlations between factors. Multiple correspondence analysis was performed on variables obtained from 925 patients who participated in a Korean HIV/acquired immunodeficiency syndrome cohort study (2006-2017). Five reduced dimension groups were derived according to clinical data, viral load, CD4 cell count at diagnosis, initial antiretroviral therapy, and others. The dimension group with high initial viral loads (55,000 copies/mL) and low CD4 cell counts (< 200 cells/mm3) should start treatment promptly after diagnosis. Groups with high initial CD4 cell counts (> 350 cells/mm3) that did not require immediate treatment according to previous guidelines had a higher failure rate for long-term relative CD4 recovery. Our results highlight the importance of early diagnosis and treatment to positively influence long-term disease outcomes, even if the initial immune status is poor, given the patient's combination of early diagnostic symptoms.

Cancer Incidence Among Adults With HIV in a Population-Based Cohort in Korea.

Importance: In combination with a decreased risk of AIDS-defining cancers and improved survival of people infected with HIV, the burden of non-AIDS-defining cancer has increased markedly. Although a substantial number of studies have measured the cancer risk among people with HIV in developed countries, little research has been conducted on the risk of cancer in HIV-infected people in Asia. Objective: To examine the cancer incidence and the estimated risk of cancer among people in Korea infected with HIV compared with the general population. Design, Setting, and Participants: This retrospective cohort study evaluated patients without cancer newly diagnosed with HIV from January 1, 2006, to December 31, 2018, using a nationwide population-based claims database embedded in the National Health Insurance Service database. Data were analyzed between December 6, 2021, and February 28, 2022. Exposures: Infection with HIV. Main Outcomes and Measures: Cancer incidence and standardized incidence rate (SIR) through indirect standardization. Results: A total of 11 552 individuals without cancer (10 444 male [90.4%]; mean [SD] age, 39.9 [11.2] years) diagnosed with HIV were identified. The SIR for all cancers was 1.68 (95% CI, 1.50-1.87) in men and 1.26 (95% CI, 0.89-1.64) in women. In men, the highest SIRs were for Kaposi sarcoma (SIR, 349.10; 95% CI, 196.10-502.20) and anal cancer (SIR, 104.20; 95% CI, 55.56-149.90). The incidence of non-Hodgkin lymphoma (SIR, 15.62; 95% CI, 11.85-19.39), Hodgkin lymphoma (SIR, 16.67; 95% CI, 4.32-29.02), and oropharyngeal cancer (SIR, 2.97; 95% CI, 1.36-4.58) in men infected with HIV was higher than in the general population. In women infected with HIV, an increased incidence of cervical cancer (SIR, 4.98; 95% CI, 1.29-8.66) and non-Hodgkin lymphoma (SIR, 11.78; 95% CI, 2.35-21.21) compared with the general population was observed. The SIR of thyroid cancer in patients with HIV was lower than in the general population in both men (SIR, 0.63; 95% CI, 0.27-0.99) and women (SIR, 0.48; 95% CI, 0.06-0.90). Conclusions and Relevance: In this cohort study, cancer risks, especially AIDS-defining cancer and virus-related cancer, were elevated in people with HIV. Efforts for cancer prevention, screening, and better accessibility to medical care in HIV-infected people are warranted.

Comparative Evaluation of Standard E TB-Feron ELISA and QuantiFERON-TB Gold Plus Assays in Patients with Tuberculosis and Healthcare Workers.

Recently, the American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention advised against performing the interferon-γ-release assay (IGRA) test for individuals with a low risk of TB, and also recommended retesting low-risk individuals with an initial positive IGRA result. However, to evaluate both sensitivity and specificity of available tests, we compared the performance of the Standard E TB-Feron (TBF) and QuantiFERON-TB Gold Plus (QFT-Plus) assays in healthcare workers (HCWs) and tuberculosis (TB) patients. We also retrospectively investigated diabetes mellitus (DM) comorbidity among the enrolled TB patients. We prospectively collected samples from 177 HCWs and 48 TB patients. The TBF and QFT-Plus tests were performed and analyzed according to the manufacturers' instructions. We also defined IGRA results between 0.2 and 0.7 IU/mL as 'borderline'. The agreement rate between TBF and QFT-Plus was 92.0% (207/225) with a Cohen's kappa value of 0.77 (95% CI, 0.68-0.87). While the majority (26/31, 83.9%) of borderline TBF results were in HCWs, the majority (14/19, 73.7%) of borderline QFT-Plus results were in TB patients. Discordant results were found in 18 samples, with TBF-positive/QFT-Plus-negative or indeterminate results in 11 HCWs and seven TB patients. After resampling from 10 HCWs (seven borderline-positive and three positive results, all <1.0), six reverted to negative. The prevalence of DM comorbidity was very high (35.4%). In summary, TBF showed substantial agreement with the QFT-Plus assay but had a higher positivity rate in both HCWs and TB patients. The negative conversion rate was high (60%) among HCWs whose initial (TB Ag-nil) result was <1.0.

Orientia tsutsugamushi induced endothelial cell activation via the NOD1-IL-32 pathway.

Orientia tsutsugamushi (OT), the causative agent of scrub typhus, is an obligate intracellular bacterium. In order to verify the inflammatory responses involved in the pathogenesis of scrub typhus, we assessed the cytokine profile of the human endothelial cell line, ECV304, after OT infection. We noted that CCL5, CCL17, IL-1alpha, IL-6, IL-8, IL-10, IL-15, TNF-alpha and TNF-beta were strongly induced in response to OT. Additionally, IL-32, the candidate modulator for the induction of IL-6 and IL-8, was increased significantly with OT infection and these increases coincided with NOD1 pathway activation. Thus, we hypothesized that NOD1 pathway and IL-32 might act on cytokine release in endothelial cells as a modulator of the inflammation caused by OT infection. NOD1 siRNA resulted in a reduction in IL-32 levels, and also reduced IL-1beta, IL-6, IL-8, and ICAM-1 expression in OT-infected ECV304 cells. These changes in IL-1beta, IL-6, IL-8, and ICAM-1 induced by NOD1 knockdown were reversed as the result of IL-32 treatment. This indicated that OT infection activated the NOD1 pathway followed by IL-32 secretion, thus resulting in the production and expression of IL-1beta, IL-6, IL-8, and ICAM-1. Therefore, IL-32 might perform a role upstream of the inflammatory reaction in endothelial cells of OT infection.

A case report of crescentic glomerulonephritis associated with Hantaan virus infection.

Although various glomerular diseases in hantavirus infection have been reported, an association between hantavirus infection and crescentic glomerulonephritis has not been described. Herein, we report a case of immune complex-mediated crescentic glomerulonephritis in a 70-year-old man with Hantaan virus infection.

Impact of Enterococcal Bacteremia in Liver Transplant Recipients.

BACKGROUND: Enterococcus species are a common cause of bacteremia in liver transplant recipients. Vancomycin-resistant enterococci (VRE) have become an important cause of nosocomial infection. In this study, we analyzed the incidence, antibiotic resistance, and outcomes of enterococcal bacteremia in living donor liver transplant recipients and the risk factors for VRE. PATIENTS AND METHODS: This single-center, retrospective review included 536 patients who underwent liver transplant between January 2008 and December 2017. RESULTS: Among 536 patients, 42 (7.8%) experienced a total of 58 enterococcal bacteremic episodes (37 Enterococcus faecium, 17 Enterococcus faecalis, 2 Enterococcus casseliflavus, 1 Enterococcus. avium, and 1 Enterococcus raffinosus). Most cases of enterococcal bacteremia (46/58, 79.3%) occurred within 6 months after transplant; among the 26 cases of VRE bacteremia, 50% occurred within 1 month after transplant. E. faecium isolates had the highest rate of vancomycin resistance (25/37, 67.5%), whereas all E. faecalis isolates were susceptible to vancomycin. According to multivariate analysis, post-transplant dialysis (odds ratio, 3.95; 95% CI, 1.51-10.34; P = .005) and length of post-transplant hospital stay (odds ratio, 1.03; 95% CI, 1.009-1.04; P = .004) were significantly associated with VRE bacteremia. One-year mortality was 31% (13/42) among recipients with enterococcal bacteremia, 5.0% (20/384) among nonbacteremic patients, and 11.1% (10/90) among patients with nonenterococcal bacteremia (P < .001). CONCLUSION: In this study, enterococcal bacteremia showed high incidence in liver transplant recipients, especially with vancomycin resistance, occurred in early period after transplant, and was associated with increased mortality. High rates of resistance to vancomycin warrant further efforts to manage enterococcal infection in liver transplant recipients at our center.

Direct effectiveness of pneumococcal polysaccharide vaccine against invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia in elderly population in the era of pneumococcal conjugate vaccine: A case-control study.

BACKGROUND: While herd effects and serotype replacement by childhood pneumococcal protein conjugated vaccines (PCVs) continues to accumulate worldwide, direct effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases in the elderly has been challenged. We estimated the direct effectiveness of PPV23 in the elderly population. METHODS: For a hospital-based case-control study, cases of invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) (adults ≥ 65 years) were identified in 14 hospitals participated in the pneumococcal surveillance program from March 2013 to October 2015, following implementation of PPV23 national immunization program (NIP) for the elderly in the Republic of Korea. Controls matched by age, sex, and hospital were selected at ratios of 1:2 (IPD) or 1:1 (NBPP). Clinical data and vaccination records were collected. Vaccine effectiveness was calculated as (1-adjusted odds ratio) × 100. RESULTS: We enrolled 148 IPD and 557 NBPP cases, and 295 IPD and 557 NBPP controls for analyses. Overall effectiveness of PPV23 against IPD was 28.5% [95% confidence interval (CI) -5.8%-51.6%] and against NBPP was 10.2% (-15.1-30.6) in all patients ≥ 65 years. However, in subgroup analysis of patients aged 65-74 years, PPV23 was protective against IPD [effectiveness 57.4% (19.4-77.5)] and against NBPP [effectiveness 35.0% (2.3-56.7)]. Furthermore, serotype-specific effectiveness of PPV23 against IPD was 90.6% (27.6-98.8) for PPV23-unique serotypes and 81.3% (38.6-94.3) for PPV23 serotypes excluding serotype 3. CONCLUSIONS: This study indicates that PPV23 with broad serotype coverage might be beneficial in preventing IPD and NBPP due to non-PCV13 serotypes in the young-elderly, with potentially increasing effectiveness in the setting of childhood PCV NIP.

Epidemiology and risk factors for bacteremia in 144 consecutive living-donor liver transplant recipients.

PURPOSE: Bacteremia is a major infectious complication associated with mortality in liver transplant recipients. The causative organisms and clinical courses differ between medical centers due to variations in regional bacterial epidemiology and posttransplant care. Further, living donors in Korea contribute to 83% of liver transplants, and individualized data are required to improve survival rates. PATIENTS AND METHODS: We retrospectively analyzed 104 subjects who had undergone living-donor liver transplant from 2005 to 2007. RESULTS: Among the 144 consecutive living-donor liver transplant recipients, 24% (34/144) developed bacteremia, 32% (46/144) developed non-bacteremic infections, and 44% (64/144) did not develop any infectious complications. Forty episodes of bacteremia occurred in 34 recipients. The major sources of bacteremia were intravascular catheter (30%; 12/40), biliary tract (30%; 12/40), and abdomen (22.5%; 9/40). Gram-positive cocci were more common (57.5%; 23/40) than Gram-negative rods (32.5 %; 13/40) and fungi (10%; 4/40). The data revealed that the following factors were significantly different between the bacteremia, non-bacteremic infection, and no infection groups: age (p = 0.024), posttransplant hemodialysis (p = 0.002), ICU stay (p = 0.012), posttransplant hospitalization (p < 0.0001), and duration of catheterization (p < 0.0001). The risk factors for bacteremia were older than 55 years (odds ratio, 6.1; p = 0.003), catheterization for more than 22 days (odds ratio, 4.0; p = 0.009), UNOS class IIA (odds ratio, 6.6; p = 0.039), and posttransplant hemodialysis (odds ratio, 23.1; p = 0.001). One-year survival rates in the bacteremic, non-bacteremic infection, and no infection groups were 73.2%, 91.3%, and 93.5%, respectively. CONCLUSION: Early catheter removal and preservation of renal function should focus for improving survival after transplant.