The epidemiologic and economic impact of varicella and herpes zoster vaccination in South Korea: A mathematical modelling study.

BACKGROUND: In South Korea, the National Immunization Program has included one-dose varicella vaccination for 1-year-olds since 2005. This study examines the potential impact of introducing a two-dose varicella vaccination for children, along with zoster vaccination for adults, using either the zoster vaccine live (ZVL) or recombinant zoster vaccine (RZV). METHODS: The investigation considered four strategies in a base case scenario. The first involved introducing zoster vaccination for 60-year-olds, with a 60 % coverage. The second strategy combined zoster vaccination with a second-dose varicella vaccination for 4-year-olds, with a 90 % coverage. An age-structured model spanning 50 years was employed, assuming a zoster vaccine catch-up campaign over the initial 5 years. Cost-effectiveness analyses were conducted, assessing incremental cost-effectiveness ratios (ICERs), incremental net monetary benefits (INMBs), and net loss under different ages at zoster vaccination (50, 60, 65, and 70 years) and varying willingness-to-pay (WTP) levels from ₩40 million ($34,998) to ₩84 million ($74,000). RESULTS: All strategies were cost-effective and significantly reduced herpes zoster (HZ) incidence, preventing approximately 3,077,000 to 7,609,000 cases, depending on the chosen strategy. The combined strategy prevented around 4,950,000 varicella and 653,000 HZ cases additionally. RZV outperformed ZVL by preventing twice as many HZ cases and offering greater QALY gains. However, ZVL was more cost-effective due to its lower cost. Probabilistic sensitivity analyses revealed that RZV became more cost-effective at higher WTP thresholds, exceeding ₩60.9 million ($53,193) in terms of ICER and ₩62.5 million ($54,591) for INMBs and net loss. The optimal age for zoster vaccination was 60 years concerning ICER but 50 years regarding INMB. CONCLUSIONS: Combining RZV with a two-dose varicella vaccination strategy reduced the disease burden and improved QALY more effectively, though ZVL remained more cost-effective at lower WTP levels. Decisions regarding vaccination policies should be balanced between the public health needs and WTP levels.

One-year antibody durability induced by EuCorVac-19, a liposome-displayed COVID-19 receptor binding domain subunit vaccine, in healthy Korean subjects.

OBJECTIVE: EuCorVac-19 (ECV-19), an adjuvanted liposome-displayed receptor binding domain (RBD) COVID-19 vaccine, previously reported interim Phase 2 trial results showing induction of neutralizing antibodies 3 weeks after prime-boost immunization. The objective of this study was to determine the longer-term antibody response of the vaccine. METHODS: To assess immunogenicity 6 and 12 months after vaccination, participants in the Phase 2 trial (NCT04783311) were excluded if they: 1) withdrew, 2) reported COVID-19 infection or additional vaccination, or 3) exhibited increasing Spike (S) antibodies (representing possible non-reported infection). Following exclusions, of the 197 initial subjects, anti-S IgG antibodies and neutralizing antibodies were further assessed in 124 subjects at the 6-month timepoint, and 36 subjects at the 12-month timepoint. RESULTS: Median anti-S antibody half-life was 52 days (interquartile range [IQR]:42-70), in the "early" period from 3 weeks to 6 months, and 130 days (IQR:97-169) in the "late" period from 6 to 12 months. There was a negative correlation between initial antibody titer and half-life. Anti-S and neutralizing antibody responses were correlated. Neutralizing antibody responses showed longer half-lives; the early period had a median half-life of 120 days (IQR:81-207), and the late period had a median half-life of 214 days (IQR:140-550). CONCLUSION: These data establish antibody durability of ECV-19, using a framework to analyze COVID-19 vaccine-induced antibodies during periods of high infection.

Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine.

BACKGROUND: Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. METHODS: Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19-75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 µg RBD), 96 received low-dose ECV19 (10 µg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). RESULTS: Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization. CONCLUSIONS: ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as # NCT04783311.

Estimation of single-dose varicella vaccine effectiveness in South Korea using mathematical modeling.

In South Korea, despite the implementation of a universal single-dose vaccination program for children aged 12-15 months in 2005, the varicella incidence rate remains significant. Prior case-control studies have reported that currently used varicella vaccines are extremely inefficacious. We estimated vaccine effectiveness (VE) by fitting a dynamic transmission model to age-specific varicella incidence data from 2007 to 2015 and available vaccine coverage data. The initial vaccine efficacy and primary failure rates were estimated to be 61.1% and 38.9%, respectively. The average duration of protection was 21.4 years. The mean VE [(1-relative risk) %] for the simulated data of 2004-2014 birth cohorts decreased from 59.8% to 50.7% over 9 years. This mathematical modeling study demonstrated that the single-dose vaccine exhibits moderate effectiveness, and a high proportion of primary failure could be a main cause of breakthrough infections. Therefore, a two-dose vaccination strategy should be considered.

Risk factors and clinical impact of COVID-19-associated pulmonary aspergillosis: Multicenter retrospective cohort study.

BACKGROUND/AIMS: The risk factors and clinical impacts of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remain controversial, and no data have been reported in Korea. This study aimed to investigate the epidemiology and importance of CAPA diagnostic efforts and to identify the predictors of CAPA and the impacts on clinical outcomes. METHODS: Between January 2020 and May 2021, data of severely to critically ill COVID-19 patients were extracted from seven hospitals of the Catholic Medical Center through a clinical data warehouse. Corticosteroid use was subcategorized into total cumulative dose, early 7-day dose, mean daily dose, and duration of use. RESULTS: A total of 2,427 patients were screened, and 218 patients were included. CAPA was diagnosed in 4.6% (10/218) of all hospitalized and 11.2% (10/89) of intensive care unit patients. Total cumulative dose (over 1,000 mg as methylprednisolone) and daily high-dose corticosteroid use (over 60 mg/day) were independent predictors but not early 7-day high-dose corticosteroid use (over 420 mg/week) (odds ratio [OR], 1.731; 95% confidence interval [CI], 0.350 to 8.571) nor prolonged use (OR, 2.794; 95% CI, 0.635 to 13.928). In-hospital overall mortality was 11.9% (26 of 218). CAPA itself did not affect the outcome; rather, daily high-dose steroid use significantly increased the 30-day mortality (hazard ratio, 5.645; 95% CI, 1.225 to 26.091). CONCLUSION: CAPA was not uncommon, especially in critically ill patients. Daily high-dose corticosteroid use was the predictor of CAPA and associated with high mortality rates. High-dose corticosteroids use after early inflammatory phase should be avoided, and active surveillance methods for CAPA are essential for those high-risk patients.

Intracerebral Hemorrhage due to Thrombosis with Thrombocytopenia Syndrome after Vaccination against COVID-19: the First Fatal Case in Korea.

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage. Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.

Estimating the basic reproductive number of varicella in South Korea incorporating social contact patterns and seroprevalence.

Varicella, which is caused by the varicella zoster virus (VZV), is a common infectious disease affecting children. Varicella vaccines have been used for decades; however, vaccination policies vary across countries because of differences in VZV epidemiology. The basic reproductive number R0a transmissibility measure parameter, also differs from country to country. In this study R0 for varicella was estimated in South Korea using the contact rate matrix derived from averaged POLYMOD contact data, the Korean population, and proportionality factor fitted to the Korean VZV seroprevalence R0 for varicella in South Korea was estimated to be 5.67 (95% CI: 5.33, 6.33). Therefore, to reach the herd immunity threshold, the critical vaccine coverage should be greater than 82.4% with a perfect vaccine, or the primary vaccine failure proportion should be less than 17.6% with 100% coverage. Because of the relatively low seroconversion rate and rapidly waning immunity after one-dose vaccination in South Korea, the herd immunity threshold is difficult to attain with only a one-dose vaccine. Two doses of vaccination may be necessary to effectively interrupt varicella transmission and maintain herd immunity in South Korea. The study results can help guide the decision-making on an effective varicella vaccination policy in South Korea.

The impact of two-dose varicella vaccination on varicella and herpes zoster incidence in South Korea using a mathematical model with changing population demographics.

BACKGROUND: In South Korea, one-dose varicella vaccination was introduced to the National Immunization Program in 2005, but varicella outbreaks have continued to occur. Therefore, a two-dose vaccination strategy is considered. METHODS: We developed an age-structured deterministic compartment model using Korean population projection data. The impact of adding a second dose of varicella vaccine on varicella and herpes zoster (HZ) epidemiology was assessed under four different vaccine effectiveness (VE) scenarios (base, moderate, lowest, highest) and the optimal timing of the second vaccine dose (18 months, 4, 5, or 6 years of age) was examined over the period 2020-2065. RESULTS: A two-dose vaccination schedule reduced the cumulative varicella incidence by > 90% compared to no vaccination, regardless of the VE. The additional reduction attributable to a second dose compared to a single dose was greatest (82%) with the lowest VE scenario. A second dose at 6 years of age reduced the varicella incidence at a population level, whereas a second dose at 18 months of age reduced the varicella incidence primarily in the target birth cohorts. Routine vaccination at the age of 18 months with a catch-up vaccination of 6-year-olds was the optimal strategy for birth cohort and population-level control. HZ incidence continued to increase under no vaccination scenario, which represents the effect of aging population. Under a two-dose scenario, the additional increase in HZ incidence attributable to the reduced exogenous boosting was small relative to a one-dose scenario and a further reduction in HZ cases was observed. CONCLUSION: A two-dose varicella vaccination schedule would significantly reduce varicella and HZ incidence in the long term. A second dose at the age of 18 months with a catch-up vaccination of 6-year-olds would be optimal for controlling varicella in South Korea.

The changing epidemiology of herpes zoster over a decade in South Korea, 2006-2015.

BACKGROUND: In South Korea, the population is rapidly aging and the prevalence of comorbidities has increased. We investigated longitudinal changes in the herpes zoster (HZ) considering demographic changes and comorbidities in the era of universal single-dose varicella vaccination. METHODS: We used the population-based database of the National Health Insurance Service in South Korea, with approximately 50 million subscribers during 2006-2015. HZ cases were identified using ICD-10 codes and comorbid conditions were also collected. Incidence rates (IRs) and incidence rate ratios (IRRs) per year were calculated adjusting for age, sex, comorbidities and socioeconomic status, and the temporal trends were examined using segmented negative binomial regression analysis. RESULTS: Over a decade, the adjusted HZ IR increased significantly from 4.23 to 9.22 per 1000 person-years (adjusted IRR 1.05, 95% confidence interval [CI] 1.04-1.06). However, during 2012-2015, the increasing trends decelerated (adjusted IRR per year 1.01, 95% CI 0.98-1.04) and slope changes differed by age. There was a declining trend in children under 9 years, sustained increase in adults aged 30-39 years, and near-plateau in those aged 50-69 years. Nonetheless, the age distribution of HZ incidence did not change over a decade, with the peak in adults aged 60-79 years. HZ-associated hospitalization rates also increased, with a deceleration in the increasing trends during 2012-2015. CONCLUSIONS: The HZ burden increased independently of demographic changes and prevalence of comorbidities. However, different trajectories by age group necessitate continuous HZ surveillance for better understanding of these changes, and to provide evidence for development of preventive strategies.

Reply letter: trends in varicella and herpes zoster epidemiology before and after the implementation of universal one-dose varicella vaccination over one decade in South Korea, 2003-2015.

In the letter, Lai SW suggested that the cost-benefit of two-dose varicella vaccines should be considered since universal one-dose vaccination effectively reduced varicella incidence in Taiwan. However, the vaccination impact was different between South Korea and Taiwan. In South Korea, only a moderate reduction in varicella incidence was observed after implementing universal one-dose vaccination. Such difference possibly reflects the relatively high background varicella incidence in South Korea. As substantial variability in varicella epidemiology exists across countries, an optimal vaccination strategy may differ in each country. Despite the effectiveness of one-dose vaccine being moderate, primary vaccine failure and rapidly waning immunity are major concerns. Therefore, two-dose vaccination would be a reasonable choice for effectively preventing virus transmission in South Korea.

History of Syphilis and Gonorrhea in Korea.

In Korea, systematic management of sexually transmitted infections (STIs), including syphilis and gonorrhea, began only after the end of the Korean War. Since the enactment of the Law on Prevention of Communicable Diseases of 1954, STI has been managed and regularly monitored in high risk group. However, the major turning point was the implementation of the Special Law on Prostitution, which was enacted in September 2004. The national policy on STI management had also changed from management of core groups by mandatory to voluntary examinations and treatment of patients by health examinations. The national surveillance system for STI was introduced in 2000 by the revision of the Prevention of Communicable Diseases Act of 1999. The incidence of STI had increased in the 1960s, but began to decline at the 1970s. In the 21st century, the incidence of STI has been increasing again. Currently, more thorough methods of STI management are needed in Korea.

Epidemiology and Antifungal Susceptibility Profile of Aspergillus Species: Comparison between Environmental and Clinical Isolates from Patients with Hematologic Malignancies.

Global data on the epidemiology and susceptibility of Aspergillus are crucial in the management of invasive aspergillosis. Here, we aimed to determine the characteristics of clinical and environmental Aspergillus isolates, focusing mainly on hematologic malignancy patients. We prospectively collected all consecutive cases and clinical isolates of culture-positive proven/probable invasive aspergillosis patients from January 2016 to April 2018 and sampled the air inside and outside the hospital. Cryptic species-level identification of Aspergillus, antifungal susceptibilities, and cyp51 gene sequencing were performed, and clinical data were analyzed. This study was conducted as part of the Catholic Hematology Hospital Fungi Epidemiology (CAFÉ) study. A total of 207 proven/probable invasive aspergillosis and 102 clinical and 129 environmental Aspergillus isolates were included in this analysis. The incidence of proven/probable invasive aspergillosis was 1.3 cases/1,000 patient-days during the study period. Cryptic Aspergillus species accounted for 33.8%, with no differences in proportions between the clinical and environmental isolates. Section Nigri presented a high proportion (70.5%) of cryptic species, mainly from A. tubingensis and A. awamori: the former being dominant in environmental samples, and the latter being more common in clinical isolates (P < 0.001). Of 91 A. fumigatus isolates, azole-resistant A. fumigatus was found in 5.3% of all A. fumigatus isolates. Three isolates presented the TR34/L98H mutation of the cyp51A gene. Patients with invasive aspergillosis caused by azole-resistant A. fumigatus showed 100% all-cause mortality at 100 days. This study demonstrates the significant portion of cryptic Aspergillus species and clinical implications of azole resistance and underscores the comparison between clinical and environmental isolates.

Trends in varicella and herpes zoster epidemiology before and after the implementation of universal one-dose varicella vaccination over one decade in South Korea, 2003-2015.

Background: In South Korea, the one-dose varicella vaccine was included in the National Immunization Program for children aged 12-15 months in 2005, and the vaccine coverage reached >95%. The impact of varicella vaccination on varicella and herpes zoster (HZ) was investigated, accounting for demographic changes over time.Methods: We calculated the crude and age-sex standardized incidence rates (IRs) and age-specific IRs of varicella and HZ from 2003 to 2015, using the National Health Information Database including approximately 50 million Koreans. The annual incidence rate ratios (IRRs) were calculated using a negative binomial regression analysis, adjusting for age and sex.Results: The crude varicella IR steadily declined by 67%, from 5.70/1000 to 1.87/1000 person years (IRR per year: 0.91; 95% CI 0.89-0.93), but the adjusted IRs showed a significant decline only during 2010-2015 (adjusted IRR per year: 0.90; 95% CI 0.88-0.93). The greatest decline was found in children ≤4 years of age, whereas the IR increased until 2011 and then declined afterward in children aged 5-9 years, who represented the highest incidence age group in 2013-2015. The crude HZ IR increased from 2.67/1000 to 9.80/1000 person years (IRR per year: 1.12; 95% CI 1.10-1.15), and the adjusted IR also followed the same trend. A similar increasing trend was observed before and after universal vaccination.Conclusions: One-dose varicella vaccination was moderately effective in preventing varicella, but this strategy was insufficient to interrupt varicella transmission in children. Furthermore, the HZ incidence dramatically increased over this decade. The current vaccination strategy against varicella-zoster disease should be reconsidered.

Erratum: Carbapenem-Resistant Enterobacteriaceae: Prevalence and Risk Factors in a Single Community-Based Hospital in Korea.

This corrects the article on p. 166 in vol. 48, PMID: 27659436.

A Case of Life-Threating Streptococcus suis Infection Presented as Septic Shock and Multiple Abscesses.

Streptococcus suis is a zoonotic pathogen that can cause severe systemic infections in humans as well as swine. In recent decades, the number of S. suis infections in humans has increased, particularly in Southeast Asia. Although most cases of S. suis human infections are reported as sporadic, a few outbreaks have been noted. Interestingly, these outbreaks have been proposed to be associated with concomitant outbreaks in swine. In Korea, four sporadic and non-fatal cases of S. suis infection have been reported. We herein report a case of life-threating S. suis infection with sepsis for the first time in Korea. The patient was a healthy pig farmer, and the gastrointestinal tract was considered the route of infection. This case emphasized the need for awareness and recognition of S. suis as a zoonotic pathogen.

Catheter-Related Trichosporon asahii Bloodstream Infection in a Neutropenic Patient with Myelodysplastic Syndrome.

Because primary antifungal prophylaxis is widely used for immunocompromised hosts, the incidences of unusual fungal infections have increased. Trichosporon asahii has emerged as an important life-threatening opportunistic systemic pathogen because of the increased use of cytotoxic or immunosuppressant agents, along with high mortality rates. Here, we describe a case of catheter-related T. asahii bloodstream infection with multiple septic skin nodules in both the arms and legs of the patient who was in the neutropenic period after allogeneic stem cell transplantation for myelodysplastic syndrome treated with prophylactic ciprofloxacin and itraconazole. We successfully treated her with intravenous voriconazole for more than a month without any complications. Clinicians should consider breakthrough Trichosporon infections when clinical progress in an immunocompromised patient with unexplained infection signs and symptoms does not improve despite proper treatment with antibiotics or various antifungal agents. In addition, voriconazole can be a good treatment choice for achieving better treatment results and prognosis.

Cytomegalovirus Colitis during Dasatinib Treatment for Patients with Hematologic Malignancy: Case Series and Literature Review.

Dasatinib, a tyrosine kinase inhibitor, is widely used for patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Although the drug has a potent immunosuppressive effect, infectious complications during dasatinib treatment have been reported rarely. We describe five patients who developed cytomegalovirus (CMV) colitis during dasatinib treatment, in whom the colitis was initially confused with other causes. The patients, three with chronic myeloid leukemia, and two with acute lymphoblastic leukemia, were diagnosed with CMV colitis based on endoscopic and histologic findings. The patients who examined blood CMV polymerase chain reaction were all positive. The patients received antiviral therapy in the form of either ganciclovir or valganciclovir, and the overall treatment outcome was fair. These cases suggest that physicians should consider the possibility of CMV reactivation when treating diarrhea and/or hematochezia in patients on dasatinib.

Clinical effectiveness of carbapenems versus alternative antibiotics for treating ESBL-producing Enterobacteriaceae bacteraemia: a systematic review and meta-analysis.

Objectives: The widespread administration of carbapenems to patients with ESBL-producing Enterobacteriaceae bacteraemia (ESBL-B) has accelerated the emergence of carbapenem-resistant Enterobacteriaceae. This study aimed to systematically review recently published data to evaluate the clinical effectiveness of carbapenems, compared with other antibiotics, in the treatment of ESBL-B. Methods: We searched the Ovid-Medline, Ovid-Embase, Cochrane Library and five Korean local databases until January 2016. We selected studies that reported overall mortality in patients with ESBL-B who had been treated with carbapenems and alternatives. Overall mortality was assessed as the primary outcome and sepsis-related mortality and adverse events were analysed as secondary outcomes. Results: Thirty-five publications fulfilled the inclusion criteria. Regarding empirical therapy, there were no significant differences between the groups that received carbapenems and those that received non-carbapenems in relation to overall mortality. Regarding definitive therapy, overall mortality was lower for patients administered carbapenems compared with those administered non-carbapenems [risk ratio (RR) 0.78, 95% CI 0.61-0.98], non-ß-lactam/ß-lactamase inhibitor combinations (non-BL/BLI) (RR 0.71, 95% CI 0.56-0.90) and cephalosporins (RR 0.56, 95% CI 0.42-0.74). There were no differences between the carbapenems and the other antibiotics, namely BL/BLIs, quinolones and aminoglycosides. Conclusions: This meta-analysis showed that BL/BLIs may be promising alternative antibiotics for definitive therapy in patients with ESBL-B. However, the lack of robust data derived from randomized controlled trials limits the conclusions and inferences from the pooled data.

Risk factors and clinical outcomes of breakthrough yeast bloodstream infections in patients with hematological malignancies in the era of newer antifungal agents.

Although yeast bloodstream infections (BSIs) are increasingly being reported in patients with hematological malignancies undergoing antifungal therapy, clinical information regarding breakthrough infections is scarce. The aim of this study was to determine the risk factors for and clinical outcomes of breakthrough yeast BSIs in patients with hematological malignancies in the era of newer antifungal agents. Between 2011 and 2014, all consecutive patients with hematological malignancies who developed yeast BSIs were included in a case-control study wherein breakthrough infections (cases) and de novo infections (controls) were compared. Of 49 patients with yeast BSIs, 21 (43%) met the criteria for breakthrough infections. The proportions of Candida krusei and Candida tropicalis in the cases and controls were significantly different (32% [7/22] vs. 3% [1/29], P = .015; 5% [1/22] vs. 38% [11/29], P = .007, respectively). Acute leukemia, presence of a central venous catheter and neutropenia in the 3 days prior to BSI were significant risk factors for breakthrough infections. Six-week mortality rates was 33% [7/21] in the cases and 43% [12/28] in the controls (P = .564). Refractory neutropenia and the Pitt bacteremia score were independent predictors of 6-week mortality. In conclusion, breakthrough infections accounted for a significant proportion of yeast BSIs in patients with hematological malignancies. However, these infections did not increase the risk of death by themselves. Our results suggest that current clinical management of breakthrough yeast BSIs, which includes switching to a different antifungal class and prompt catheter removal is reasonable.