Pseudomonas otitidis bacteremia in an immunocompromised patient with cellulitis: case report and literature review.

BACKGROUND: Pseudomonas otitidis belongs to the genus Pseudomonas and causes various infections, including ear, skin, and soft tissue infections. P. otitidis has a unique susceptibility profile, being susceptible to penicillins and cephalosporins but resistant to carbapenems, due to the production of the metallo-ß-lactamase called POM-1. This revealed genetic similarities with Pseudomonas aeruginosa, which can sometimes lead to misidentification. CASE PRESENTATION: We report the case of a 70-year-old Japanese male who developed cellulitis and bacteremia during chemotherapy for multiple myeloma. He was initially treated with meropenem, but blood culture later revealed gram-negative bacilli identified as P. otitidis using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Carbapenem resistance was predicted from previous reports; therefore, we switched to dual therapy with levofloxacin and cefepime, and favorable treatment results were obtained. CONCLUSION: This is the first reported case of P. otitidis cellulitis and bacteremia in an immunocompromised patient. Carbapenems are typically used in immunocompromised patients and P. otitidis is often resistant to it. However, its biochemical properties are similar to those of Pseudomonas aeruginosa; therefore, its accurate identification is critical. In the present study, we rapidly identified P. otitidis using MALDI-TOF MS and switched from carbapenems to an appropriate antimicrobial therapy, resulting in a successful outcome.

Evaluation of clinical utility of novel coronavirus antigen detection reagent, Espline® SARS-CoV-2.

BACKGROUND: To prevent the novel coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to perform early identification and isolation of people shedding the infectious virus in biological materials with high viral loads several days prior to symptom onset. Rapid antigen tests for infectious diseases are useful to prevent the pandemic spread in clinical settings. METHODS: We evaluated a SARS-CoV-2 antigen test, Espline® SARS-CoV-2 reagent, with reverse transcription polymerase chain reaction (RT-PCR) as reference test, using 129 nasopharyngeal swab specimens collected from COVID-19 hospitalized patients or from patients suspected having COVID-19-like symptoms. Out of these, 63 RT-PCR positive and 66 RT-PCR negative specimens were identified. RESULTS: Among 63 RT-PCR positive specimens, 25 were positive in the Espline test. Test sensitivity was estimated based on the 532.4 copies/reaction of SARS-CoV-2 RNA obtained through receiver operating characteristic analysis. When the specimens were classified based on time since symptom onset, Espline test sensitivity were 73.3% and 29.2% in specimens collected before day 9 and after day 10, respectively. CONCLUSION: Although the overall sensitivity of the Espline® SARS-CoV-2 reagent compared with RT-PCR is less, this antigen test can be useful in identifying people with high risk of virus transmission with high viral loads in order to prevent the pandemic and is useful for diagnosing COVID-19 within 30 min.

Immunochromatographic test for the detection of SARS-CoV-2 in saliva.

We evaluated the rapid immunochromatographic test for severe acute respiratory coronavirus 2 (SARS-CoV-2) antigen detection using 16 saliva specimens collected from 6 COVID-19 hospitalized patients, and detected N-antigen in 4 of 7 RT-PCR positive specimens. This POCT detected SARS-CoV-2 antigen in saliva and would be useful for COVID-19 diagnosis.

Clinical validation of quantitative SARS-CoV-2 antigen assays to estimate SARS-CoV-2 viral loads in nasopharyngeal swabs.

BACKGROUND: Expansion of the testing capacity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important issue to mitigate the pandemic of coronavirus disease-2019 (COVID-19) caused by this virus. Recently, a sensitive quantitative antigen test (SQT), Lumipulse® SARS-CoV-2 Ag, was developed. It is a fully automated chemiluminescent enzyme immunoassay system for SARS-CoV-2. METHODS: In this study, the analytical performance of SQT was examined using clinical specimens from nasopharyngeal swabs using reverse transcription polymerase chain reaction (RT-PCR) as a control. RESULTS: Receiver operating characteristic analysis of 24 SARS-CoV-2-positive and 524 -negative patients showed an area under the curve of 0.957 ± 0.063. Using a cut-off value of 1.34 pg/ml, the sensitivity was 91.7%, the specificity was 98.5%, and the overall rate of agreement was 98.2%. In the distribution of negative cases, the 99.5 percentile value was 1.03 pg/ml. There was a high correlation between the viral load calculated using the cycle threshold value of RT-PCR and the concentration of antigen. The tendency for the antigen concentration to decrease with time after disease onset correlated with that of the viral load. CONCLUSIONS: Presented results indicate that SQT is highly concordant with RT-PCR and should be useful for the diagnosis of COVID-19 in any clinical setting. Therefore, this fully automated kit will contribute to the expansion of the testing capability for SARS-CoV-2.

Sex difference in clinical presentation of patients with infectious mononucleosis caused by Epstein-Barr virus.

INTRODUCTION: There are few studies on sex difference in patients with infectious mononucleosis caused by Epstein-Barr virus (EBV-IM). We performed a retrospective study to evaluate the sex difference in clinical presentation of patients with EBV-IM. METHODS: We performed a single-center retrospective study evaluating >14-year-old patients with serologically confirmed EBV-IM during 2006-2017. We compared the patients' age, symptoms, physical findings, and laboratory data between male and female patients. To adjust for confounding factors, we performed a logistic regression analysis based on the results of univariate comparisons. RESULT: Of the 122 eligible patients (56 male and 66 female, ratio: 1:1.2), the median ages were 26 years old (interquartile range [IR], 22-31.5 years old]) and 22 years old (IR, 20-25 years old) for males and females, respectively (p < 0.001). Headache was significantly more prevalent in males (25.0% vs. 10.6%, p = 0.036). Leukocyte count was also significantly higher in males (11,400/mm3 [IR, 7,600-14,100/mm3] vs. 9,400/mm3 [IR, 6,600-11,600/mm3], p = 0.021). The prevalence of periorbital edema (male: 3.6% vs. female: 18.1%, p = 0.012) and severity of transaminase elevation were significantly higher in females. The regression analysis evaluating clinical characteristics of male patients showed that age >30 years old, headache, and leukocyte >11,000/mm3 had high odds ratios. CONCLUSION: Our single-center retrospective study suggests that older age of onset, headache, and leukocytosis are more likely to be characteristics of male patients with EBV-IM. Our study also underscores the importance of periorbital edema as a clue for early diagnosis of EBV-IM, especially in female patients.

Early Anti-SARS-CoV-2 Immunoglobulin G Response May Be Associated with Disease Severity in Patients with COVID-19.

Most coronavirus disease 2019 (COVID-19) cases are mild or asymptomatic, and a substantial minority of patients have severe or critical diseases. There are several reports on the potential risk factors of severe disease, but few reports have reported a relationship between antibody titer and severity in Japan. Antibody-dependent enhancement affects disease progression. We evaluated the IgG responses in COVID-19 patients at our tertiary hospital. The IgG index was the measure of interest. We assigned 1.4 as the cutoff value for a positive result based on the specifications by the manufacturer and observed that patients could be categorized into two groups: the early elevation of IgG and late elevation of IgG (IgG elevated in the first 7 days ± 2 days or more than 10 days after symptom onset) groups. The former comprised early IgG responders (n = 7) and the latter comprised late IgG responders (n = 14), and they were compared. The C-reactive protein and D-dimer concentrations were significantly higher in the early IgG responders on admission (HD 0). The respiratory rate was also higher. The lymphocytes were significantly fewer on day 7 of hospitalization (HD 7). These results suggest that early production of anti-severe acute respiratory syndrome coronavirus 2 IgG may be associated with clinical indicators of severity.

IgG Antibodies, SARS-CoV-2 Load, and Prognostic Indicators in Patients with Severe and Mild COVID-19 in Japan.

We assessed the association of severity of coronavirus disease 2019 (COVID-19) with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load, IgG antibody level, and prognostic indicators.Twenty-one patients hospitalized with COVID-19 were classified as having severe or mild disease on the basis of average respiratory rate during hospitalization (severe: ≥22 breaths/min; mild: <22 breaths/min). Viral load in nasopharyngeal samples, blood levels of C-reactive protein (CRP), lymphocytes, and D-dimer on admission and plasma immunoglobulin G (IgG) index on Day 7±2 after symptom onset were compared in relation to disease severity. Seven patients had severe disease and 14 had mild disease. Those with severe disease had a significantly higher IgG index (median: 3.75 vs 0.56, p=0.01) and CRP (median: 8.6 vs 1.0 mg/dL, p<0.001) and D-dimer levels (median: 1.65 vs 0.75 µg/mL; p=0.002) and a significantly lower lymphocyte count (median: 1,176 vs 666 cells/µL, p=0.005) and viral load (median: 8.7×106 vs 2.3×104 copies/mL, p=0.005). Furthermore, time from symptom onset to virus disappearance was significantly longer in severe patients (median: 24 vs 17 days, p=0.03). A high IgG index in the early phase of the disease was associated with severe disease and might serve as a prognostic indicator.

Combination of a SARS-CoV-2 IgG Assay and RT-PCR for Improved COVID-19 Diagnosis.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is generally diagnosed by reverse transcription (RT)-PCR or serological assays. The SARS-CoV-2 viral load decreases a few days after symptom onset. Thus, the RT-PCR sensitivity peaks at three days after symptom onset (approximately 80%). We evaluated the performance of the ARCHITECT® SARS-CoV-2 IgG assay (henceforth termed IgG assay; Abbott Laboratories, Lake County, IL, USA), and the combination of RT-PCR and the IgG assay for COVID-19 diagnosis. METHODS: In this retrospective study, 206 samples from 70 COVID-19 cases at two hospitals in Tokyo that were positive using RT-PCR were used to analyze the diagnostic sensitivity. RT-PCR-negative (N=166), COVID-19-unrelated (N=418), and Japanese Red Cross Society (N=100) samples were used to evaluate specificity. RESULTS: Sensitivity increased daily after symptom onset and exceeded 84.4% after 10 days. Specificity ranged from 98.2% to 100% for samples from the three case groups. Seroconversion was confirmed from 9 to 20 days after symptom onset in 18 out of 32 COVID-19 cases with multiple samples and from another case with a positive result in the IgG assay for the first available sample. CONCLUSIONS: The combination of RT-PCR and IgG assay improves the robustness of laboratory diagnostics by compensating for the limitations of each method.