Follow-up COVID-19 PCR result up to day 5 with clinical features predicts positivity for inconclusive results.

Introduction: False-positive inconclusive polymerase chain reaction (PCR) results against severe acute respiratory syndrome coronavirus 2 were not low and have potentially harmful effects. We aimed to find parameters to differentiate positive cases from false-positive ones, and suggest an optimal scheme and follow-up period for inconclusive results. Methods: Cases with inconclusive PCR tests among healthcare personnel from February 2020 to June 2021 were classified as confirmed positive, clinically positive, and clinically negative groups, which were compared. The diagnostic accuracy of follow-up tests and composites of clinical and laboratory data were analyzed. Results: Symptoms, contact history, and lower cycle threshold of the N gene were more common in the COVID-19 positive group. The scoring schemes combining symptom and contact history with follow-up PCR results had higher sensitivities than the PCR tests only modality. Follow-up tests up to 5 days combined with symptoms and contact history could discriminate between positive and negative cases. Conclusion: A follow-up PCR test up to day 5 with clinical features might predict positivity and shorten the quarantine period in most healthcare personnel.

Incidence and seasonality of respiratory viruses causing acute respiratory infections in the Northern United Arab Emirates.

BACKGROUND: The data on the seasonality of respiratory viruses helps to ensure the optimal vaccination period and to monitor the possible outbreaks of variant type. OBJECTIVES: This study was designed to describe the molecular epidemiology and seasonality of acute respiratory infection (ARI)-related respiratory viruses in the United Arab Emirates (UAE). METHODS: Both upper and lower respiratory specimens were collected for the analysis from all the patients who visited the Sheikh Khalifa Specialty Hospital (SKSH) with ARI for over 2 years. The multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) test was used to detect respiratory viruses, which include human adenovirus, influenza virus (FLU) A and B, respiratory syncytial virus, parainfluenza viruses, human rhinovirus (HRV), human metapneumovirus, human enterovirus, human coronavirus, and human bocavirus. RESULTS: A total of 1,362 respiratory samples were collected from 733 (53.8%) male and 629 (46.2%) female patients with ARI who visited the SKSH between November 2015 and February 2018. The rRT-PCR test revealed an overall positivity rate of 37.2% (507/1362). The positive rate increased during winter; it was highest in December and lowest in September. FLU was the most frequently detected virus (273/1362 [20.0%]), followed by human rhinovirus (146/1362 [10.7%]). The FLU positivity rate showed two peaks, which occurred in August and December. The peak-to-low ratio for FLU was 2.26 (95% confidence interval: 1.52-3.35). CONCLUSIONS: The pattern of FLU in the UAE parallels to that of temperate countries. The trend of the small peak of FLU in the summer suggests a possibility of semi-seasonal pattern in the UAE.

Differences in Colistin-resistant Acinetobacter baumannii Clinical Isolates Between Patients With and Without Prior Colistin Treatment.

BACKGROUND: The increasing morbidity and mortality rates associated with Acinetobacter baumannii are due to the emergence of drug resistance and the limited treatment options. We compared characteristics of colistin-resistant Acinetobacter baumannii (CR-AB) clinical isolates recovered from patients with and without prior colistin treatment. We assessed whether prior colistin treatment affects the resistance mechanism of CR-AB isolates, mortality rates, and clinical characteristics. Additionally, a proper method for identifying CR-AB was determined. METHODS: We collected 36 non-duplicate CR-AB clinical isolates resistant to colistin. Antimicrobial susceptibility testing, Sanger sequencing analysis, molecular typing, lipid A structure analysis, and in vitro synergy testing were performed. Eleven colistin-susceptible AB isolates were used as controls. RESULTS: Despite no differences in clinical characteristics between patients with and without prior colistin treatment, resistance-causing genetic mutations were more frequent in isolates from colistin-treated patients. Distinct mutations were overlooked via the Sanger sequencing method, perhaps because of a masking effect by the colistin-susceptible AB subpopulation of CR-AB isolates lacking genetic mutations. However, modified lipid A analysis revealed colistin resistance peaks, despite the population heterogeneity, and peak levels were significantly different between the groups. CONCLUSIONS: Although prior colistin use did not induce clinical or susceptibility differences, we demonstrated that identification of CR-AB by sequencing is insufficient. We propose that population heterogeneity has a masking effect, especially in colistin non-treated patients; therefore, accurate testing methods reflecting physiological alterations of the bacteria, such as phosphoethanolamine-modified lipid A identification by matrix-assisted laser desorption ionization-time of flight, should be employed.

Febrile Respiratory Illness Associated with Human Adenovirus Type 55 in South Korea Military, 2014-2016

An outbreak of febrile respiratory illness associated with human adenovirus (HAdV) occurred in the South Korea military during the 2014-15 influenza season and thereafter. Molecular typing and phylogenetic analysis of patient samples identified HAdV type 55 as the causative agent. Emergence of this novel HAdV necessitates continued surveillance in military and civilian populations.

In vitro antimicrobial synergy of colistin with rifampicin and carbapenems against colistin-resistant Acinetobacter baumannii clinical isolates.

Increased use of colistin in a clinical setting had resulted in the emergence of colistin-resistant (CoR) Acinetobacter baumannii. Combination therapy has been studied as a new approach to treat infections caused by A. baumannii. Here, we investigated the in vitro antimicrobial synergistic activities of several antimicrobial agent combinations against CoR A. baumannii. A total of 41 non-duplicate clinical isolates of CoR A. baumannii from a tertiary care hospital in Korea were prospectively collected from April 2012 to December 2014. As a control group, 41 carbapenem-resistant but colistin-susceptible (CoS) A. baumannii strains were also evaluated. Minimum inhibitory concentrations (MICs) of antimicrobial agents were determined by Etest in triplicate, and in vitro synergy tests were performed by the Etest MIC:MIC ratio method. Synergistic activity was determined as the sum of each antimicrobial agent's fractional inhibitory concentration evaluated (ΣFIC): synergy, ≤0.5; indifference, >0.5-4; and antagonism, >4. Synergistic activities were more frequently observed in the CoR group than the CoS group for combinations of colistin-rifampicin (80.5% vs. 14.6%, P< 0.0001), colistin-meropenem (85.4% vs. 4.9%, P< 0.0001), and colistin-imipenem (46.3% vs. 2.4%, P< 0.0001). Combination with rifampicin or meropenem lowered colistin MICs against CoR A. baumannii clinical isolates to the susceptible range (≤ 2 µg/mL) more frequently (61.0%, 25/41, both) than combination with imipenem (29.3%, 12/41). Clinical trials are needed to prove the in vivo efficacy of those antimicrobial combinations that exhibited significant in vitro antimicrobial synergistic effects against CoR A. baumannii.

Vitamin D Status in South Korean Military Personnel with Acute Eosinophilic Pneumonia: A Pilot Study.

BACKGROUND: A relationship between low vitamin D levels and the development or outcomes of respiratory diseases has been identified. However, there is no data on the vitamin D status in patients with acute eosinophilic pneumonia (AEP). We evaluated the vitamin D status in patients with AEP among South Korean military personnel. METHODS: We prospectively compared the serum levels of total 25-hydroxyvitamin D [25(OH)D], 25(OH)D3, and 25(OH)D2 among patients with AEP, pulmonary tuberculosis (PTB), and community-acquired pneumonia (CAP). RESULTS: In total, 65 patients with respiratory diseases, including AEP (n=24), PTB (n=19), and CAP (n=22), were identified. Of the 24 patients with AEP, 2 (8%) had deficient total 25(OH)D levels (<10 ng/mL), 17 (71%) had insufficient total 25(OH)D levels (≥10 to <30 ng/mL), and only 5 (21%) had sufficient total 25(OH)D levels (≥30 to <100 ng/mL). The difference in the total 25(OH)D levels among patients with AEP, PTB, and CAP was not statistically significant (p=0.230). The median levels of total 25(OH)D, 25(OH)D3, and 25(OH)D2 were 22.84, 22.84, and 0.00 ng/mL, respectively, and no differences in the 25(OH)D level were present among patients with AEP, PTB, and CAP with the exception of the total 25(OH)D level between patients with AEP and PTB (p=0.042). CONCLUSION: We have shown that low vitamin D levels are frequently found in patients with AEP and are comparable with those in patients with PTB and CAP.

Epidemiology and Characteristics of Metallo-ß-Lactamase-Producing Pseudomonas aeruginosa.

Metallo-ß-lactamase-producing Pseudomonas aeruginosa (MPPA) is an important nosocomial pathogen that shows resistance to all ß-lactam antibiotics except monobactams. There are various types of metallo-ß-lactamases (MBLs) in carbapenem-resistant P. aeruginosa including Imipenemase (IMP), Verona integron-encoded metallo-ß-lactamase (VIM), Sao Paulo metallo-ß-lactamase (SPM), Germany imipenemase (GIM), New Delhi metallo-ß-lactamase (NDM), Florence imipenemase (FIM). Each MBL gene is located on specific genetic elements including integrons, transposons, plasmids, or on the chromosome, in which they carry genes encoding determinants of resistance to carbapenems and other antibiotics, conferring multidrug resistance to P. aeruginosa. In addition, these genetic elements are transferable to other Gram-negative species, increasing the antimicrobial resistance rate and complicating the treatment of infected patients. Therefore, it is essential to understand the epidemiology, resistance mechanism, and molecular characteristics of MPPA for infection control and prevention of a possible global health crisis. Here, we highlight the characteristics of MPPA.

Outcomes of early administration of cidofovir in non-immunocompromised patients with severe adenovirus pneumonia.

The benefits of treatment with antiviral therapy for severe adenovirus (AdV) pneumonia are not well established. We described the clinical characteristics and treatment outcomes of early cidofovir treatment of severe AdV pneumonia in non-immunocompromised patients. We retrospectively reviewed the medical records of all patients diagnosed with severe AdV pneumonia between 2012 and 2014. A total of seven non-immunocompromised patients with severe AdV pneumonia were identified, and all isolates typed (n = 6) were human AdV-B55. All patients had progressive respiratory failure with lobar consolidation with or without patchy ground glass opacity. Three patients required vasopressors and mechanical ventilation. All patients had abnormal laboratory findings including: leukopenia, thrombocytopenia, or elevated liver enzymes. After admission, all patients received antiviral therapy with cidofovir, and the median time from admission to cidofovir administration was 48 h and median the time from onset of symptoms to cidofovir administration was 7.1 days. After cidofovir administration, complete symptomatic improvement occurred after a median of 12 days and radiographic resolution occurred after a median of 21 days. Consequently, all patients completely improved without complications. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection.

Clinical implications of correlation between peripheral eosinophil count and serum levels of IL-5 and tryptase in acute eosinophilic pneumonia.

BACKGROUND: The peripheral eosinophil count (PEC) tends to increase during the course of acute eosinophilic pneumonia (AEP), and an initially elevated PEC is associated with milder disease. However, there is a lack of data regarding these phenomena and inflammatory process of AEP. METHODS: We prospectively evaluated serial changes in serum interleukin (IL)-5 levels and the correlation between the initial level of IL-5 and the PEC to investigate whether the initial PEC indicates a resolving state of inflammation. We also evaluated serum tryptase levels to investigate the possibility of involvement of mast cell activity in AEP. RESULTS: Twenty-one AEP patients were included, and all patients improved within 10 days after corticosteroid treatment. The median initial serum IL-5 level among all patients was 561.0 pg/mL, which decreased to zero at 10 days of follow-up (n = 15, P < 0.001). The median initial serum tryptase level (detectable in 20 of 21 patients) was 3.7 ng/mL and decreased to a median of 1.1 ng/mL at 10 days of follow-up (n = 15, P < 0.001). The initial serum IL-5 and C-reactive protein levels were positively correlated (P = 0.009, r = 0.556), and the initial serum IL-5 level was inversely correlated with the initial PEC (P = 0.004, r = -0.603). CONCLUSIONS: Our data suggest that IL-5 is an important cytokine involved in the recruitment of eosinophils from peripheral blood into the lungs, that an initially elevated PEC is associated with a resolving state of inflammation, and that mast cells are potentially involved in the inflammatory process of AEP.

Performance evaluation of new automated hepatitis B viral markers in the clinical laboratory: two quantitative hepatitis B surface antigen assays and an HBV core-related antigen assay.

We evaluated quantitative hepatitis B surface antigen (qHBsAg) assays and a hepatitis B virus (HBV) core-related antigen (HBcrAg) assay. A total of 529 serum samples from patients with hepatitis B were tested. HBsAg levels were determined by using the Elecsys (Roche Diagnostics, Indianapolis, IN) and Architect (Abbott Laboratories, Abbott Park, IL) qHBsAg assays. HBcrAg was measured by using Lumipulse HBcrAg assay (Fujirebio, Tokyo, Japan). Serum aminotransferases and HBV DNA were respectively quantified by using the Hitachi 7600 analyzer (Hitachi High-Technologies, Tokyo, Japan) and the Cobas AmpliPrep/Cobas TaqMan test (Roche). Precision of the qHBsAg and HBcrAg assays was assessed, and linearity of the qHBsAg assays was verified. All assays showed good precision performance with coefficients of variation between 4.5% and 5.3% except for some levels. Both qHBsAg assays showed linearity from 0.1 to 12,000.0 IU/mL and correlated well (r = 0.9934). HBsAg levels correlated with HBV DNA (r = 0.3373) and with HBcrAg (r = 0.5164), and HBcrAg also correlated with HBV DNA (r = 0.5198; P < .0001). This observation could provide impetus for further research to elucidate the clinical usefulness of the qHBsAg and HBcrAg assays.

Urinary iodine and sodium status of urban Korean subjects: a pilot study.

OBJECTIVES: We estimated iodine status of Korean population by determining the concentration of spot urinary iodine (UI) with a reliable method based on the Sandell-Kolthoff reaction. MATERIALS AND METHODS: A total of 540 urine samples from apparently healthy subjects were collected, and UI, urinary sodium (UNa), and urinary creatinine (UCr) were determined from those samples and analyzed with age. RESULTS: There were significant decreases in either UI (P<0.0001), UI/UCr ratio (P=0.0001), UNa (P<0.0001), or UNa/Cr ratio (P=0.0001) in younger subjects than older ones. The median value of UI was 267.6 µg/L, but the median UI of the younger group (191.8 µg/L) was significantly decreased compared to that of the older group (383.9 µg/L). CONCLUSIONS: This study showed that the median of UI in Korean urban population was in a more than adequate iodine nutritional state, but UI was significantly different between the younger age group and the older age group.

Diagnostic performances of HE4 and CA125 for the detection of ovarian cancer from patients with various gynecologic and non-gynecologic diseases.

OBJECTIVES: We compared diagnostic performance of CA125 and HE4 in various gynecologic and non-gynecologic diseases. DESIGN AND METHODS: Sera from 176 patients with various diseases were collected, and CA125 and HE4 levels were compared. ROC curves were constructed to estimate the diagnostic performance. RESULTS: Levels of both markers were elevated in ovarian cancer. CA125 was also high in benign gynecologic diseases, but HE4 was not. CA125 levels of pregnant women were higher than those of control group, and HE4 was increased in chronic renal diseases. The sensitivity for discriminating ovarian cancer from healthy or benign conditions was 44.8% for HE4 and 55.2% for CA125 at 95% specificity. The ROC-AUC values for HE4 and CA125 were 0.85 and 0.87 respectively. CONCLUSIONS: HE4 demonstrated comparable diagnostic performances to CA125, though each marker had its own strengths and weaknesses. Combining CA125 and HE4 might be more advantageous than either one alone.

Serum high mobility group box-1 (HMGB1) is closely associated with the clinical and pathologic features of gastric cancer.

BACKGROUND: High mobility group box-1 (HMGB1) is a newly recognized factor regulating cancer cell tumorigenesis, expansion and invasion. We investigated the correlation between the serum HMGB1 levels and the clinical and pathologic features of gastric cancer and evaluated the validity of HMGB1 as a potential biomarker for the early diagnosis of gastric cancer. METHODS: A total of 227 subjects were classified into 5 disease groups according to the 'gastritis-dysplasia-carcinoma' sequence of gastric carcinogenesis and their serum levels of HMGB1 were analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Clinical parameters, International Union Against Cancer (UICC) TNM stage, cancer size, differentiation or lymphatic invasion, vascular or perineural invasion and prognosis were used as analysis variables. RESULTS: The serum HMGB1 levels were significantly different among disease groups (ANOVA, p < 0.05) and HMGB1 levels tended to increase according to the progression of gastric carcinogenesis. Serum HMGB1 levels were significantly associated with depth of invasion, lymph node metastasis, tumor size, and poor prognosis (p < 0.05). However, HMGB1 levels were not associated with patient gender or age, differentiation of tumor cells, or lymphatic, vascular and perineural invasion, or the existence of distant metastasis in advanced cancer (p > 0.05). The sensitivity and specificity of serum HMGB1 was 71% and 67% (cut-off value of 5 ng/ml) for the diagnosis of early gastric cancer, and 70% and 64% (cut-off value of 4 ng/ml) for the diagnosis of high-risk lesions, respectively. These values were greater than those for carcinoembryonic antigen (CEA) (30-40% of sensitivity). CONCLUSION: HMGB1 appears to be a useful serological biomarker for early diagnosis as well as evaluating the tumorigenesis, stage, and prognosis of gastric cancer.