Characteristics and Clinical Outcomes of Extended-Spectrum beta-lactamase-producing Klebsiella pneumoniae Bacteremia in Cancer Patients

Eliel Nham,Kyungmin Huh,조선영,Doo Ryeon Chung,Kyong Ran Peck,이남용,Cheol-In Kang 대한감염학회 2020 Infection and Chemotherapy Vol.52 No.1

Background: Cancer patients can be at a higher risk of infection due to drug-resistant bacteria than the general population for various reasons. We performed a retrospective study to evaluate possible risk factors and outcomes of extended-spectrum beta-lactamaseproducing Klebsiella pneumoniae (ESBL-KP) bacteremia in cancer patients. Materials and Methods: Cases were divided into two groups based on whether or not the isolated strain produced ESBL and multivariable regressions were done to identify possible risk factors of ESBL-KP bacteremia and mortality. For ESBL-producing strain, additional molecular analysis was done. Results: 278 cases with KP bacteremia were identified between 2010 and 2012, of which ESBLproducers were 50 (18%). The presence of percutaneous drainage catheter [odds ratio (OR) 4.99, P <0.001] and prior exposure to certain classes of antibiotics including third-generation cephalosporin (OR 2.14, P = 0.03) had significant associations with ESBL-KP bacteremia. Individuals who died within 14 days after the onset of KP bacteremia were more likely to have higher mean Pitt bacteremia score (1.56 in survival group vs. 3.43 in mortality group, P <0.001), hemodialysis (OR 17.03, P = 0.01) and chronic liver disease (OR 5.57, P = 0.01). Although 14-day mortality was higher with ESBL production (OR 2.76, P = 0.04), no significant differences in 30- day mortality (OR 1.67, P = 0.20) and other morbidity indices were observed. 49 ESBL-KP isolates, 65.4% of them produced CTX-M-14 and CTX-M-15 enzymes, and ST711 was the most common. Conclusion: There were several differences in clinical characteristics between ESBL-KP and nonESBL-KP bacteremia in cancer patients, similar to previous reports including non-cancer patients.

Low Neutralizing Activities to the Omicron Subvariants BN.1 and XBB.1.5 of Sera From the Individuals Vaccinated With a BA.4/5-Containing Bivalent mRNA Vaccine

Eliel Nham,Jineui Kim,Jungmin Lee,Heedo Park,Jeonghun Kim,Sohyun Lee,Jaeuk Choi,Kyung Taek Kim,Jin Gu Yoon,Soon Young Hwang,Joon Young Song,Hee Jin Cheong,Woo Joo Kim,Man-Seong Park,Ji Yun Noh 대한면역학회 2023 Immune Network Vol.23 No.6

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster. Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.

Concurrent Subacute Thyroiditis and Graves’ Disease After COVID-19: A Case Report

Nham Eliel,Song Eyun,Hyun Hakjun,Seong Hye,Yoon Jin Gu,Noh Ji Yun,Song Joon Young,Cheong Hee Jin,Kim Woo Joo 대한의학회 2023 Journal of Korean medical science Vol.38 No.18

There are many reports of subacute thyroiditis (SAT) that occurred after the coronavirus disease 2019 (COVID-19), but no such case has been reported in Korea. Moreover, the simultaneous occurrence of SAT and Graves’ disease (GD) is rare. Here, we describe a patient who developed SAT and GD after the second episode of COVID-19. A 27-year-old woman with no known history of thyroid disease presented with fever, upper respiratory tract symptoms, and painful neck swelling. Thyroid function tests revealed thyrotoxicosis, and thyroid ultrasound showed heterogeneous echogenicity of enlarged thyroid glands. Her initial clinical presentation was consistent with SAT after viral infection, with typical neck tenderness and spontaneous improvement of thyrotoxicosis without antithyroid drug use. However, this case had some atypical features, such as an elevated thyroid-stimulating immunoglobulin level, relapse of thyrotoxicosis in short-term follow-up, and increased Tc-99m pertechnetate uptake, suggesting the coexistence of GD. About two months after methimazole (15 mg/day) was prescribed, she was lost to follow up again. We report the first case of unusual co-occurrence of SAT and GD following COVID-19.

Vaccination Rates of Hospitalized Patients at High Risk of Severe COVID-19: A Single-Center Cross-Sectional Study

Nham Eliel,Hyun Hakjun,Seong Hye,Yoon Jin Gu,Noh Ji Yun,Song Joon Young,Kim Woo Joo,Cheong Hee Jin 대한감염학회 2022 Infection and Chemotherapy Vol.54 No.4

We investigated coronavirus disease 2019 (COVID-19) vaccination rate in patients admitted to chronic pulmonary disease, cardiovascular disease, chronic kidney disease, and cancer wards in the third week of April 2022 to determine the immunity level of these vulnerable groups. Compared to the general population, our study subjects had lower vaccination rates, except for higher percentages of boosted individuals in patients with chronic pulmonary disease and cardiovascular disease. This tendency was most pronounced in cancer patients, less than half of whom were boosted. Patients with cancer should be encouraged to complete their COVID-19 vaccination.

COVID-19 Vaccination in Korea: Past, Present, and the Way Forward

Nham Eliel,Song Joon Young,Noh Ji Yun,Cheong Hee Jin,Kim Woo Joo 대한의학회 2022 Journal of Korean medical science Vol.37 No.47

Since its first emergence in late 2019, severe acute respiratory syndrome coronavirus-2 has claimed more than 6.5 million lives worldwide and continues to infect hundreds of thousands of people daily. To combat this once-in-a-century disaster, several vaccines have been developed at unprecedented speeds. Novel vaccine platforms (messenger ribonucleic acid vaccines and adenoviral vector vaccines) have played a major role in the current pandemic. In Korea, six vaccines, including a domestically developed recombinant vaccine, have been approved. As in other countries, vaccines have been proven to be safe and highly effective in Korea. However, rare serious adverse events and breakthrough infections have undermined public trust in the vaccines, even while the benefits of vaccination far outweigh the risks. The rise of the omicron variant and the subsequent increase in excess mortality demonstrated that while vaccines are a key component of the pandemic response, it alone can fail without non-pharmaceutical interventions like masking and social distancing. The pandemic of coronavirus disease has revealed both the strengths and weaknesses of our healthcare system and pandemic preparedness. When the next pandemic arrives, improved risk communication and vaccine development should be prioritized. To enable timely vaccine development, it is essential to make strategic and sufficient investments in vaccine research and development.

Severe Thrombocytopenia in a Patient with COVID-19

Nham Eliel,고재훈,Jeong Byeong-Ho,Huh Kyungmin,Cho Sun Young,Kang Cheol-In,Chung Doo Ryeon,Peck Kyong Ran 대한감염학회 2020 Infection and Chemotherapy Vol.52 No.3

Coronavirus disease 2019 (COVID-19) outbreak is spreading rapidly all over the world, being a major threat to public health. Since clinical feature of COVID-19 has not been fully evaluated yet, empirical antibacterial agents are frequently combined for the treatment of COVID-19 in addition to antiviral agents, concerning co-existing bacterial pathogens. We experienced a case of severe thrombocytopenia with epistaxis and petechiae, while treating a COVID-19 patient with ceftriaxone, levofloxacin, and lopinavir/ritonavir. The platelet count decreased to 2,000/mm3 and recovered after discontinuation of the three suspected drugs. In treating a potentially fatal emerging infectious disease, empirical and/or experimental approach would be unavoidable. However, the present case suggests that the possibility of adverse effects caused by polypharmacy should also be carefully considered.

COVID-19 Vaccination Rates in Patients With Chronic Medical Conditions: A Nationwide Cross-Sectional Study

Nham Eliel,Kim Young-Eun,Jung Jaehun,Kim Dong Wook,Jang Hoyeon,Hyun Hakjun,Seong Hye,Yoon Jin Gu,Noh Ji Yun,Song Joon Young,Kim Woo Joo,Cheong Hee Jin 대한의학회 2022 Journal of Korean medical science Vol.37 No.45

As most individuals acquire immunity to severe acute respiratory syndrome coronavirus 2, South Korea declared a return to normalcy a few months ago. However, epidemic waves continue because of endlessly emerging variants and waning immunity. Health authorities are focusing on those at high risk of severe coronavirus disease 2019 to minimize damage to public health and the economy. In this regard, we investigated the vaccination rates in patients with various chronic medical conditions by examining the national health insurance claims data and the national immunization registry. We found that patients with chronic medical conditions, especially those of higher severity, such as malignancy, had vaccination rates approximately 10–20% lower than those of the general population. Public health authorities and healthcare providers should try to vaccinate these patients to avoid preventable morbidity and mortality.

Establishment of Safety Monitoring System for Vaccines Not Included in the National Immunization Program in Korea

Nham Eliel,Yoon Jin Gu,Choi Min Joo,Seo Yu Bin,Lee Jacob,Choi Won Suk,Hyun Hakjun,Seong Hye,Noh Ji Yun,Song Joon Young,Kim Woo Joo,Cheong Hee Jin 대한의학회 2024 Journal of Korean medical science Vol.39 No.5

Background: In Korea, there are no surveillance programs for vaccines that are not included in the national immunization program (NIP), and vaccine safety monitoring in the adult population is inadequate. This study aimed to establish a safety monitoring system for nonNIP vaccines in adults. Methods: Frequently administered non-NIP vaccines were selected. Individuals were included if they received at least one of the selected vaccines at a participating institution and provided informed consent. Solicited and unsolicited adverse events were monitored using questionnaires sent through text messages on days 1, 3, 7, 28, and 90 post-vaccination. Selected adverse events of special interest (AESIs) were monitored monthly by retrospective review of electronic medical records. Causality was assessed according to the Korea Disease Control and Prevention Agency guidelines. Results: Four vaccines (tetanus-diphtheria-pertussis [Tdap], pneumococcal conjugate 13-valent [PCV13], live zoster vaccine [ZVL], and recombinant zoster vaccine [RZV]) were selected, and their safety profiles were monitored at four tertiary hospitals and 10 primary care clinics. The response rates of the questionnaires on post-vaccination days 1, 7, 28, and 90 were 99.2%, 93.6%, 81.0%, and 48.7%, respectively. Of 555 AESI identified over 10 months, 10 cases received one of the selected non-NIP vaccines within 90 days of the event. Conclusion: We are establishing the first safety monitoring system for selected non-NIP vaccines in Korea since September 2022 and report its progress as of July 2023. However, continuous government support is essential for its maintenance and improvement.

Severity-Adjusted Dexamethasone Dosing and Tocilizumab Combination for Severe COVID-19

홍진영,고재훈,양진영,하소영,Eliel Nham,허경민,조선영,강철인,정두련,백진양,손유민,박효정,이범기,허희재,강은숙,서지영,정치량,백경란 연세대학교의과대학 2022 Yonsei medical journal Vol.63 No.5

Purpose: Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease(COVID-19) needs to be investigated. Materials and Methods: A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasonein combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery. Results: A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in thedexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinicalrecovery, compared to the Dexa group (p=0.024). In multivariable analyses, peak FiO2 within 3 days and tocilizumab combinationwere consistently significant for 30-day recovery (all p<0.05). The DexaToci group showed a significantly steeper decreasein FiO2 (-4.2±2.6) than the Dexa group (−2.7±2.6; p=0.021) by hospital day 15. The duration of oxygen requirement was significantlyshorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p=0.006). Infectious complications andcellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescencestage were not different between the two groups. Conclusion: A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improvedclinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.

Clinical Characteristics and Risk Factors for Mortality in Critical Coronavirus Disease 2019 Patients 50 Years of Age or Younger During the Delta Wave: Comparison With Patients > 50 Years in Korea

Shi Hye Jin,Nham Eliel,Kim Bomi,Joo Eun-Jeong,Cheong Hae Suk,Hong Shin Hee,Hyun Miri,Kim Hyun ah,Jang Sukbin,Rhee Ji-Young,Kim Jungok,Kim Sungmin,Cho Hyun Kyu,Wi Yu Mi,Cheon Shinhye,Kim Yeon-Sook,Lim 대한의학회 2022 Journal of Korean medical science Vol.37 No.22

Background: Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea. Methods: We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients’ electronic medical records were reviewed to identify clinical characteristics. Results: During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m2 . Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754–18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439–35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321–37.357), and combined blood stream infection (OR, 7.092; 95% CI, 1.061–18.181) were identified as independent predictors of mortality in total patients. Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group. The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m2 ), and the one remaining patient died from a secondary infection. Conclusion: About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m2 ) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.