Prospective longitudinal analysis of antibody response after standard and booster doses of SARS-COV2 vaccination in patients with early breast cancer.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants brought waves of pandemics with breakthrough infections in vaccinated individuals. We analyzed the antibody responses after primary and booster vaccination in healthy controls (HC) and patients with early breast cancer (BC). Methods: In this prospective longitudinal cohort study, the binding activity of serum antibody level against spike proteins and antigens of SARS-CoV-2 variants was measured within 21 days after each vaccination in the BC group and HC group. Results: All participants, 40 in the BC and 20 in the HC group, had increased antibody response after vaccination. BC group, however, had weaker humoral responses than the HC group (IgG: 1.5, 2.3, 2.5-folds in BC vs. 1.9, 3.6, 4.0-folds in HC after each dose; IgA: 2.1, 3.0, 3.6-folds in BC vs. 4.2, 10.4, 5.2-folds in HC after each dose, respectively). Those under concurrent cytotoxic chemotherapy had weaker antibody response than the non-cytotoxic treatment group and HC. Adjunct use of steroids and age were not significant risk factors. The levels of binding antibody against the Delta and the Omicron (BA1) variants were lower than the wild-type, especially in BC. Conclusion: In the waves of new sub-variants, our study suggests that an additional dose of vaccinations should be recommended according to the anti-cancer treatment modality in patients with BC who had received booster vaccination.

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. 1-4 These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. 2,5,6 A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. 7,8 Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 515 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we found that CH was associated with severe Covid-19 outcomes (OR=1.9, 95%=1.2-2.9, p=0.01). We further explored the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH was significantly associated with risk of Clostridium Difficile (HR=2.0, 95% CI: 1.2-3.3, p=6×10 -3 ) and Streptococcus/Enterococcus infections (HR=1.5, 95% CI=1.1-2.1, p=5×10 -3 ). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.

Outbreak investigation of Serratia marcescens neurosurgical site infections associated with a contaminated shaving razors.

BACKGROUND: Surgical site infection (SSI) is the most common healthcare-associated infection. We report an outbreak of neurosurgical site infections caused by Serratia marcescens after craniotomy in a tertiary care hospital. METHODS: Between August 6 and 21, 2018, five cases of early-onset SSI caused by S. marcescens after craniotomy were recorded in a 1786-bed tertiary care hospital. Cultures were collected from potential environmental sources and healthcare workers. Whole-genome sequencing (WGS) was used to investigate the genetic relationships among S. marcescens isolates. RESULTS: The outbreak involved five patients; S. marcescens was isolated from the cerebrospinal fluid, pus, tissue, and blood samples from these patients. S. marcescens was also isolated from shaving razors and brushes. All S. marcescens isolates from the infected patients and razors showed the same resistance patterns on antibiotic-susceptibility tests. WGS revealed close clustering among four of five isolates from the patients and among three of four isolates from the razors. No additional patient developed S. marcescens infection after we stopped using the razors for scalp shaving. CONCLUSIONS: We report an outbreak of neurosurgical site infections after craniotomy, which was associated with shaving razors contaminated by S. marcescens. Shaving scalps with razors should be avoided to prevent SSI.

Prospective evaluation of a rapid antimicrobial susceptibility test (QMAC-dRAST) for selecting optimal targeted antibiotics in positive blood culture.

OBJECTIVES: MALDI-TOF MS has been successfully used for empirical antibiotic selection. However, limited data are available regarding the usefulness of MALDI-TOF MS in common resistant organisms compared with rapid antimicrobial susceptibility testing (AST). We prospectively evaluated the usefulness of rapid AST, compared with MALDI-TOF MS, for optimal antibiotic selection by infectious disease (ID) physicians in patients with bacteraemia including polymicrobial infection. METHODS: Three hundred and fifty-nine patients with positive blood culture were included for analysis. ID physicians prospectively decided on antibiotic regimens with consensus at each timepoint of receiving results of Gram stain, MALDI-TOF MS and rapid AST, the last of which was performed using QMAC-dRAST. RESULTS: ID physicians with MALDI-TOF MS results chose optimal targeted antibiotics in 255 (71.0%) cases, with appropriate antibiotic selection in 303 (84.4%) cases. The proportion of optimal targeted antibiotic selection and appropriate antibiotic selection was significantly lower for resistant strains than for susceptible strains [62.5% versus 79.2% (P < 0.001) and 68.2% versus 100% (P < 0.001), respectively]. QMAC-dRAST results led to optimal antibiotic treatment in 95 (91.3%) of the 104 cases receiving non-optimal targeted antibiotics. Optimal targeted treatments based on QMAC-dRAST results were possible in 322 (98.2%) of the 328 cases with monobacterial infection and in 345 (96.1%) of the 359 cases with monobacterial and polymicrobial infection. CONCLUSIONS: MALDI-TOF MS has a high chance of failure in guiding ID physicians to optimal antibiotics, especially against resistant organisms. With increasingly common resistant organisms, rapid AST is needed to identify optimal targeted antibiotics early in bacteraemia.

Delayed diagnosis of extrapulmonary tuberculosis presenting as fever of unknown origin in an intermediate-burden country.

BACKGROUND: Tuberculosis (TB), especially extrapulmonary tuberculosis (EPTB), is an important cause of fever of unknown origin (FUO) in TB-burdened areas. Little information is known about patients with EPTB with clinical features presenting as FUO and about the factor of delaying the diagnosis. METHODS: We retrospectively analyzed EPTB patients who were referred with FUO at 3 university-affiliated hospitals over 8 years (2010-2017). The subjects were assigned to groups of early diagnosis and delayed diagnosis within 3 days of an initial comprehensive evaluation from the referral. Clinical and laboratory variables were compared between the groups. RESULTS: A total of 95 patients with febrile EPTB were included. Localizing symptoms and/or signs suggestive of anatomy were identified in 62.1% of the patients. Concurrent lung involvement by TB was presented by 49.5% (47/95) of the patients, and only 23.4% of them showed typical findings of pulmonary TB on simple chest X-ray. Most of the patients showed abnormal lesions on cross-sectional CT (98.9%) and MRI (100%). The clinical variables and blood test results of patients were not significantly different between the two groups. The less typical imaging finding of EPTB on CT (38.5% vs. 79.0%) and MRI (37.5% vs. 79.0%) in the delayed diagnosis group was a risk factor for delayed diagnosis. CONCLUSION: Febrile EPTB referred as FUO showed nonspecific clinical manifestations. The active application of cross-sectional imaging tests according to clinical clues or randomly in the absence of local manifestations, combined with invasive diagnostic approaches even for atypical presentations may lead to an earlier diagnosis of febrile EPTB.

Correlation between Pneumonia Severity and Pulmonary Complications in Middle East Respiratory Syndrome.

This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.

Direct rapid antibiotic susceptibility test (dRAST) for blood culture and its potential usefulness in clinical practice.

PURPOSE: The direct rapid antibiotic susceptibility test (dRAST), based on analysing changes in bacterial micro-colonies under antibiotic conditions, detects antibiotic resistance within 6 h of direct smear examination results. This study aimed to assess the accuracy of dRAST and evaluate its potential usefulness for improving selection of appropriate antibiotic in real clinical practice settings. METHODOLOGY: We evaluated the accuracy of dRAST by comparing the antibiotic treatments that should have been administered based on dRAST results and the broth microdilution (BMD) test and its potential usefulness via simulation. RESULT: For 49/52 (94.2 %) patients with Gram-positive bacteraemia and 66/67 (98.5 %) patients with Gram-negative bacteraemia, antibiotics indicated by dRAST results were the same as those indicated by the BMD test. Among 34 patients with ineffective and suboptimal treatment, 19 (55.9 %) of patients could have received optimal treatment 1 to 2 days earlier with dRAST results. Among 33 patients given unnecessary broad-spectrum antibiotics, 1 to 2 days earlier de-escalation could have been possible for 27 (81.8 %) patients based on dRAST results. CONCLUSION: The introduction of dRAST could increase the use of optimal antibiotics and reduce unnecessary broad-spectrum antibiotic use in the early period of bacteraemia.

Epidemiology and Clinical Characteristics of Zika Virus Infections Imported into Korea from March to October 2016.

Zika is a re-emerging, mosquito-borne viral infection, which has been recently shown to cause microcephaly and Guillain-Barré syndrome. Since 2015 the number of infected patients has increased significantly in South America. The purpose of this study was to identify the epidemiologic and clinical characteristics of patients with Zika virus (ZIKV) infections in Korea. Patients who had visited areas of risk and tested positive in the ZIKV reverse transcriptase polymerase chain reaction (RT-PCR) in blood, urine, or saliva specimens were included. The first Korean case of ZIKV infection was reported in March 2016, and 14 cases had been reported by October 2016. The median age of the patients was 34 years (19-64 years). Ten patients had been exposed in Southeast Asia and 4 in Latin America. Rash was the most common symptom (92.9%; 13/14), followed by myalgia (50.0%; 7/14), and arthralgia (28.6%, 4/14). There were no neurologic abnormalities and none of the patients was pregnant. Results of biochemical tests were normal. Positivity rates of RT-PCR for ZIKV in serum, urine, and saliva were 53.8%, 100.0%, and 83.3%, respectively in the first week of symptoms. In conclusion, 14 patients with ZIKV infections were reported in Korea by October 2016 and all of them had mild clinical symptoms.

Serotype Distribution and Antimicrobial Susceptibilities of Invasive Streptococcus pneumoniae Isolates from Adults in Korea from 1997 to 2012.

In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period.

The purpose and appropriateness of carbapenem use in a single university hospital, 2009-2013.

This is a retrospective review study to investigate changes in carbapenem consumption and to evaluate the proportion of inappropriate empirical use of carbapenem in the months of September and October of 2009, 2011, and 2013 in a single university-affiliated hospital. Total carbapenem use was classified into 3 categories: prophylactic, directed, and empirical. If an empirical prescription was continued without documentation of any eligible etiologic microorganism, we defined this as 'inappropriate' use. We also considered it 'inappropriate' when a patient's culture revealed no pathogen and the patient was initially not in severe sepsis or septic shock and did not have a history of admission to a health-care facility or of colonization with a pathogen eligible for carbapenem within 3 months. The total amount was 48.1, 51.1, and 91.0 defined daily doses/1000 patient-days in 2009, 2011, and 2013, respectively. Empirical use accounted for 78.4% of all prescriptions. The proportion of inappropriate empirical use ranged from 15.0 to 38.9% of the empirical carbapenem prescriptions.

Inappropriate continued empirical vancomycin use in a hospital with a high prevalence of methicillin-resistant Staphylococcus aureus.

Vancomycin is frequently inappropriately prescribed, especially as empirical treatment. The aim of this study was to evaluate (i) the amount of inappropriate continued empirical vancomycin use as a proportion of total vancomycin use and (ii) the risk factors associated with inappropriate continued empirical vancomycin use. We reviewed the medical records of adult patients who had been prescribed at least one dose of parenterally administered vancomycin between January and June 2012, in a single tertiary care hospital. When empirically prescribed vancomycin treatment was continued after 96 h without documentation of beta-lactam-resistant Gram-positive microorganisms in clinical specimens with significance, the continuation was considered inappropriate, and the amount used thereafter was considered inappropriately used. We identified risk factors associated with inappropriate continued empirical vancomycin use by multiple logistic regression. During the study period, the amount of parenterally administered vancomycin prescribed was 34.2 defined daily doses (DDDs)/1,000 patient-days (1,084 prescriptions for 971 patients). The amount of inappropriate continued empirical vancomycin use was 8.5 DDDs/1,000 patient-days, which represented 24.9% of the total parenterally administered vancomycin used (8.5/34.2 DDDs/1,000 patient-days). By multivariate analyses, inappropriate continued empirical vancomycin use was independently associated with the absence of any documented etiological organism (adjusted odds ratio [aOR], 1.60 [95% confidence interval {CI}, 1.06 to 2.41]) and suspected central nervous system (CNS) infections (aHR, 2.33 [95% CI, 1.20 to 4.50]). Higher Charlson's comorbidity index scores were inversely associated with inappropriate continued empirical vancomycin use (aHR, 0.90 [95% CI, 0.85 to 0.97]). Inappropriate continued empirical vancomycin use represented 24.9% of the total amount of vancomycin prescribed, which indicates room for improvement.

Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis: a comparison with bacteremia caused by Enterobacteriaceae.

BACKGROUND: This study was performed to detect risk factors for Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis. METHODS: A retrospective case-control study was designed to identify risk factors for P. aeruginosa bacteremia in cirrhotic patients. The cases were cirrhotic patients with P. aeruginosa bacteremia and the controls were cirrhotic patients with Enterobacteriaceae bacteremia. RESULTS: Sixty-one cases and the same number of controls were enrolled. In a multivariate analysis, younger age {adjusted odds ratio (aOR) per one year: 0.96, 95% confidence interval: 0.93 - 0.99}, nosocomial acquisition (aOR 3.87, 95% confidence interval: 1.50 - 9.94), preexisting biliary disease (aOR 4.79, 95% confidence interval: 1.92 - 10.47), and recent exposure to immunosuppressive agent (aOR 3.10, 95% confidence interval: 1.23 - 7.82) were associated with P. aeruginosa bacteremia. In the case group the frequency of appropriate initial antibiotic regimens was considerably lower than in the control group: 29.5% vs. 65.6% (P <0.01). However, thirty day mortality did not differ significantly between cases and controls (19.7% vs. 24.6%). CONCLUSIONS: Nosocomial acquisition, preexisting biliary disease, and recent use of immunosuppressive agents are strong predictive factors for P. aeruginosa bacteremia in cirrhotic patients.