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Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

Background Pulmonary mucormycosis (PM) represents a serious burden in terms of morbidity and mortality in immunocompromised patients. Studies of prognostic factors in patients with PM are limited and have involved small numbers of patients. Methods Adult patients diagnosed with proven and probable PM according to the modified definitions of the EORTC/MSG 2008 in a tertiary hospital in Seoul, South Korea, between 2008 and 2019 were retrospectively enrolled. Results A total of 49 patients including 31 (63%) with proven PM and 18 (37%) with probable PM were enrolled. The 90-day mortality rate was 49% (24/49). Neutropenia, thrombocytopenia, use of voriconazole at clinical suspicion, positivity of non-sterile culture, use of steroid and treatment without surgery were more common in fatal cases than non-fatal cases. Voriconazole use at clinical suspicion for invasive mould pneumonia (OR 6.91, P = .01) and prolonged neutropenia (OR 4.86, P = .03) were independent risk factors for mortality. Voriconazole use at clinical suspicion was associated with positive galactomannan (GM) assay (OR 5.93, P = .02) and history of invasive pulmonary aspergillosis (OR, 6.88, P = .05). Conclusion About half of the patients with PM died within 90 days of diagnosis, and fatal outcomes were common in patients with prolonged neutropenia and empirical voriconazole use. Caution is needed in using voriconazole even in patients with positive GM results and prior histories of invasive pulmonary aspergillosis in whom PM cannot be ruled out by differential diagnosis.

Background: Due to the low sensitivity of mould culture, clinicians usually depend on the histomorphologic diagnosis of invasive mould infection for empirical antifungal therapy. However, definite diagnosis is not always possible based on the mould morphology. We thus compared the histomorphologic diagnosis with immunohistochemistry (IHC)- and culture-based diagnosis.Methods: All adult patients who underwent tissue biopsy and in whom the histomorphologic diagnosis revealed invasive mould infection were enrolled at a tertiary hospital, Seoul, South Korea, between 1992 and 2014 (retrospectively) and 2015 and 2019 (prospectively). Their histomorphologic diagnoses were classified as two categories: (1) acute-angled branching, septate hyphae with parallel walls and a uniform width ('morphologic aspergillosis') and (2) right-angled branching pauciseptate, broader and ribbon-like hyphae with nonparallel walls ('morphologic mucormycosis').Results: A total of 113 patients were finally analysed and their histomorphologic diagnoses were classified as follows: 51 (45%) with morphologic aspergillosis, 62 (55%) with morphologic mucormycosis. Of the 51 patients with morphologic aspergillosis, 46 (90%) received the same diagnosis based on culture and/or IHC, and the remaining five (10%) gave positive IHC result for mucormycosis. Of the 62 patients with morphologic mucormycosis, 60 (97%) had the same diagnosis based on culture and/or IHC, and the remaining two (3%) yielded a positive aspergillus culture or a positive IHC result for aspergillosis, respectively.Conclusions: The majority of histomorphologic diagnoses appear to be consistent with definitive diagnoses based on sterile culture and IHC tests. However, about 10% of 'morphologic aspergillosis' diagnoses were mucormycosis cases.

Objective To investigate the accuracy of immunohistochemistry (IHC) tests for distinguishing between mucormycosis and aspergillosis and compare the clinical characteristics of mucormycosis patients according to galactomannan (GM) results. Methods We evaluated diagnostic performance of IHC test with tissue sections of patients with culture-proven invasive fungal infection. In addition, we conducted PCR assay with tissue sections of mucormycosis patients with positive GM results to evaluate the possibility of co-infection. Results In culture-proven mucormycosis (n = 13) and aspergillosis (n = 20), the sensitivity and specificity of IHC test were both 100% for mucormycosis and 85% and 100%, respectively, for aspergillosis. Among the 53 patients who met the modified criteria for proven mucormycosis and had GM assay results, 24 (45%) were positive. Compared with those with negative GM results (n = 29), mucormycosis patients with positive GM results had significantly higher incidence of gastrointestinal tract infections (6/24 [25%] vs 0/29 [0%], P = .006) and were more likely to be histomorphologically diagnosed as aspergillosis (7/24 [29%] vs 2/29 [7%], P = .06). PCR assay amplified both Aspergillus- and Mucorales-specific DNA in 6 of these 24 cases. Conclusions Immunohistochemistry tests seem useful for compensating for the limitations of histomorphologic diagnosis in distinguishing between mucormycosis and aspergillosis. Some proven mucormycosis patients with positive GM results had histopathology consistent with aspergillosis and gastrointestinal mucormycosis. In addition, about one quarter of these patients revealed the evidence of co-infection with aspergillosis by PCR assay.

The prevalence of human taeniasis has decreased in Korea. The stool egg positive proportion decreased from 1.9% in 1971 to 0% in 2004 in nationwide surveys. The neurocysticercosis (NCC) is also presumed to decrease. However, detailed information regarding the recent status of NCC in Korea is lacking. We retrospectively reviewed NCC cases from 1990 to 2016 at Asan Medical Center, a 2700-bed tertiary referral hospital in Korea. We identified patients based on clinical symptoms, brain imaging, pathology and serological assay. The cases were classified as parenchymal, extraparenchymal, and mixed NCC. Eighty-one patients were included in the analysis. The mean age was 54.5 years, and 79.0% were male. The number of NCC cases was highest from 1995 to 1999, and continuously decreased thereafter. Forty (49.4%) patients had parenchymal NCC, while 25 (30.9%) patients had extraparenchymal NCC, and 16 (19.8%) patients had mixed NCC. The seizure and headache were most common symptom of parenchymal NCC and extraparenchymal NCC respectively. Hydrocephalus was more common in extraparenchymal NCC, and patients with extraparenchymal NCC were more likely to require a ventriculoperitoneal shunt. Cases of NCC are decreasing accordingly with human taeniasis and lesion location was the most important determinant of clinical presentation and outcome of NCC in Korea.

Methods for distinguishing catheter-related candidemia (CRC) from non-CRC before catheter removal remain limited. We thus evaluated the diagnostic performance of differential time to positivity (DTP) to diagnose CRC in neutropenic cancer patients with suspected CRC. Of the 35 patients enrolled, 15 (43%) with CRC (six definite and nine probable) and 17 (49%) with non-CRC were finally analyzed. Based on the receiver operating characteristic curve, the optimal cutoff value of DTP for diagnosing CRC was ≥1.45 hours with the sensitivity 80% (95% confidence interval [CI], 51–95) and specificity 100% (95% CI, 80–100), respectively.

This study aimed to compare the clinical characteristics and outcomes of patients with isolated respiratory and extrarespiratory mucormycosis.Adult patients diagnosed with proven or probable invasive mucormycosis in a tertiary hospital in South Korea, between 1999 and 2020 were retrospectively reviewed. We compared the clinical, mycological characteristics, and outcomes of patients with isolated respiratory mucormycosis (IRM) and those with extrarespiratory mucormycosis (ERM).A total of 44 patients including 32 (72%) with IRM, and 12 (27%) with ERM were enrolled. Of these, 38 (86%) were classified as proven and 6 (14%) as probable invasive mucormycosis according to the EORTC/MSG criteria. Univariate analysis exhibited that old age, surgery, and intensive care unit were associated with ERM, and multivariable analysis revealed that variable associated with ERM was intensive care unit (aOR 9.80; 95% CI 2.07-46.35; P = 0.004). There were no significant differences in 90-day mortality between patients with IRM and ERM (38% vs 50%, P = 0.45). In multivariable analysis, neutropenia (aOR 6.88; 95% CI 1.67-28.27; P = 0.01) was an independent risk factor for 90-day mortality.More than a quarter of patients with mucormycosis had extrarespiratory manifestations, especially in patients who were admitted to intensive care unit. The mortality of the patients with ERM was comparable to that of the patients with IRM, although the patients with ERM received ICU care more frequently.

As concerns arise that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concurrent colistin administration, we evaluated the effect of colistin on vancomycin efficacy against MRSA via in vitro and in vivo studies. Among MRSA blood isolates collected in a tertiary-care hospital, we selected representative strains from community-associated MRSA strains (CA-MRSA; ST72-MRSA-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA; ST5-MRSA-SCCmec II). USA CA-MRSA (USA300), HA-MRSA (USA100), N315 (New York/Japan clone), and a MRSA standard strain (ATCC 43300) were used for comparison. We performed checkerboard assays to identify changes in the vancomycin MIC of MRSA following colistin exposure and evaluated the effect of a vancomycin-colistin combination using time-kill assays. We also assessed the in vivo antagonistic effect by administering vancomycin, colistin, and a combination of these two in a neutropenic murine thigh infection model. In the checkerboard assays, vancomycin MICs of all MRSA strains except N315 were increased by from 0.25 to 0.75 μg/ml following colistin exposure. However, the time-kill assays indicated antagonism only against ST5-MRSA and USA100, when the vancomycin concentration was twice the MIC. In the murine thigh infection model with ST5-MRSA and USA100, vancomycin monotherapy reduced the number of CFU/muscle >1 log10 compared to a combination treatment after 24 h in ST5-MRSA, indicating an antagonistic effect of colistin on vancomycin treatment. This study suggests that exposure to colistin may reduce the susceptibility to vancomycin of certain MRSA strains. Combination therapy with vancomycin and colistin for multidrug-resistant pathogens might result in treatment failure for concurrent MRSA infection.

AIM To develop and validate a radiomics-based model for predicting response to neoadjuvant chemotherapy (NAC) using baseline computed tomography (CT) images in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS A radiomics signature for predicting pathological complete response (pCR) was developed using radiomics features selected by a random forest classifier on baseline CT images, and imaging predictors were identified in the training set (87 patients). By incorporating imaging predictors and radiomics signature, an imaging-based model was constructed using multivariate logistic regression analysis and validated in an independent validation set consisting of 48 patients with CT from outside institutions. The performance and clinical usefulness of the imaging-based model for predicting pCR were evaluated using area under the receiver operating characteristic curve (AUC) and decision curve analysis. Using a cut-off determined in the training set, the positive likelihood ratios of the imaging-based model were calculated and compared with imaging and histological predictors. RESULTS The radiomics signature was developed based on six stable radiomics features. An imaging-based model incorporating radiomics signature, tumour shape, tumour size, and clinical stage showed good performance for predicting pCR in both the training (AUC, 0.85; 95% confidence interval [CI], 0.78–0.93) and validation (AUC, 0.75; 95% CI, 0.60–0.86) sets, providing a larger net benefit in decision curve analysis. The imaging-based model showed a higher positive likelihood ratio (1.91) for pCR than imaging and histological predictors (1.33–1.63). CONCLUSIONS The radiomics-based model using baseline CT images may predict the response of patients with MIBC to NAC.

We describe the case of a patient with severe fever with thrombocytopenia syndrome (SFTS) complicated by SFTS-associated encephalopathy who was successfully treated with 4-day plasma exchange followed by two-time convalescent plasma therapy. During plasma exchange, the plasma cytokines interferon-α and inducible protein-10 gradually decreased without change of plasma viral load. However, plasma viral load gradually decreased after convalescent plasma therapy. This case provides important insights for understanding the mechanisms of experimental therapy in severely affected SFTS patients.

As concerns arise that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concurrent colistin administration, we evaluated the effect of colistin on vancomycin efficacy against MRSA via in vitro and in vivo studies. Among MRSA blood isolates collected in a tertiary-care hospital, we selected representative strains from community-associated MRSA strains (CA-MRSA; ST72-MRSA-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA; ST5-MRSA-SCCmec II). USA CA-MRSA (USA300), HA-MRSA (USA100), N315 (New York/Japan clone), and a MRSA standard strain (ATCC 43300) were used for comparison. We performed checkerboard assays to identify changes in the vancomycin MIC of MRSA following colistin exposure and evaluated the effect of a vancomycin-colistin combination using time-kill assays. We also assessed the in vivo antagonistic effect by administering vancomycin, colistin, and a combination of these two in a neutropenic murine thigh infection model. In the checkerboard assays, vancomycin MICs of all MRSA strains except N315 were increased by from 0.25 to 0.75 μg/ml following colistin exposure. However, the time-kill assays indicated antagonism only against ST5-MRSA and USA100, when the vancomycin concentration was twice the MIC. In the murine thigh infection model with ST5-MRSA and USA100, vancomycin monotherapy reduced the number of CFU/muscle >1 log(10) compared to a combination treatment after 24 h in ST5-MRSA, indicating an antagonistic effect of colistin on vancomycin treatment. This study suggests that exposure to colistin may reduce the susceptibility to vancomycin of certain MRSA strains. Combination therapy with vancomycin and colistin for multidrug-resistant pathogens might result in treatment failure for concurrent MRSA infection.

Background Pauci-bacillary pulmonary tuberculosis (TB) can be delayed to diagnose and start anti-TB therapy, especially in immunocompromised patients. We therefore evaluated the clinical and radiologic features of these delayed cases. Methods Immunocompromised adult patients with pauci-bacillary pulmonary TB were retrospectively enrolled in a tertiary hospital in an intermediate–TB burden country over a 5-year period. We defined “missed TB” or “not-missed TB” patients as those who started anti-TB therapy after or before positive mycobacterial culture results, respectively. Results Of 258 patients, 134 (52%) were classified in the missed TB group, and 124 (48%) in the not-missed TB group. Positive results of molecular tests including MTB polymerase chain reaction and/or Xpert TB/RIF were only obtained in the not-missed TB group (54/106, 54%). The median diagnostic delay in the missed TB group was longer than in the other group (30 vs 6 days; P < .001). In the missed TB group, the most common working diagnoses were pneumonia (46, 34%) and lung metastasis of malignancy (40, 30%). Typical radiologic findings for TB, such as upper lobe predominance and centrilobular nodules with tree-in-bud appearance, were less common in the missed TB group than in the other group. Old age (odds ratio [OR], 1.03), solid organ transplant (OR, 3.46), solid tumor (OR, 3.83), and hematologic malignancy (OR, 4.04) were independently associated with missed TB. Conclusions Care is needed to differentiate pauci-bacillary TB, especially in immunocompromised patients with the mentioned risk factors, even without the usual radiologic features of TB. Additional rapid diagnostic tests to rule out pauci-bacillary TB are urgently needed.

Although there was no specific finding in peripheral blood smears performed on the second day after doxycycline administration in clinically suspected human granulocytic anaplasmosis (HGA) patients, we re-examed the peripheral blood smears performed at the time of admission and found morulaes in neutrophils. This case shows that the detection of morulae in a blood smear can be helpful in the diagnosis of HGA, especially in the acute phase of illness, prior to empirical antibiotic administration. Keywords: Human granulocytic anaplasmosis, Morulae, Diagnosis

Background Ocular involvement of candidemia can result in serious complications, including vision loss. This study investigated the risk factors for ocular involvement in patients with candidemia and the outcomes of treatment. Methods Episodes of candidemia in hospitalized adults who underwent ophthalmic examinations within 2 weeks of candidemia onset between January 2014 and May 2017 were retrospectively reviewed. Their demographic characteristics, antifungal treatments, and visual outcomes were evaluated. Results During the study period, 438 adults were diagnosed with candidemia, with 275 (62.8%) undergoing ophthalmic examinations within 2 weeks. Of these 275 patients, 59 (21.5%) had fundoscopic abnormalities suggestive of ocular involvement, including 51 with chorioretinitis and eight with Candida endophthalmitis. Eleven patients were symptomatic. Persistent candidemia (adjusted odd ratio [aOR], 2.55; 95% confidence interval [CI], 1.29–5.08; P = 0.01), neutropenia during the preceding 2 weeks (aOR, 2.92; 95% CI, 1.14–7.53; P = 0.03), and C. albicans infection (aOR, 2.15; 95% CI, 1.09–4.24; P = 0.03) were independently associated with ocular involvement. Among the 24 patients with neutropenia, 41.7% had ocular involvements at the initial examination. Ophthalmologic examination even before the neutrophil recovery was positive in one-third of neutropenic patients. Out of the 37 patients in whom ocular outcomes after 6 weeks were available, 35 patients showed favorable or stable fundoscopic findings. Two patients had decreased visual acuity despite the stable fundoscopic finding. Conclusion Neutropenia within two weeks of candidemia was a risk factor for ocular involvement. More than 80 percent of patients with ocular involvements were asymptomatic, emphasizing the importance of routine ophthalmic examinations. The median 6 weeks of systemic antifungal treatment resulted in favorable outcomes in 89.2% of patients.

Background Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM. Material and Methods For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machine-learning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. Results The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machine-learning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P

Background There is a growing concern on infections with multiple organisms including fungi in patients with mucormycosis. However, limited data are available on co-infection in patients with mucormycosis. Methods Patients with proven mucormycosis were retrospectively enrolled at a tertiary hospital from July 2009 to January 2019. Proven mucormycosis was defined as positive fungal culture result for mucormycosis from a sterile biopsy specimen and/or histologic evidence of tissue invasion of hyphae with positive mucormycosis immunohistochemistry test result. We reviewed other pathogens isolated from sterile or non-sterile sites before and after 7 days from the biopsy for infected tissue that suggested invasive fungal infection. Results A total of 61 patients with proven mucormycosis were analyzed. The primary site of infection was as follows; lung (n = 38, 62.3%), rhino-sinus (n = 21, 34.4%), and orbito-cerebral (n = 15, 24.6%). Based on sterile culture results, 4 patients (6.6%) had the evidence of co-infection with other fungi including Candida species (from 3 cases; C. albicans from 1, C. glabrata from 1 and C. krusei from 1), A. flavus (1), and F. solani (1), and 23 patients (37.7%) had the evidence of co-infection with bacteria including E. faecium (VRE) (8), P. aeruginosa (5),coagulase-negative staphylococci (5), methicillin-susceptible S. aureus (4) and others. Based on non-sterile culture results, 10 patients (16.4%) had the evidence of co-infection with fungi other than mucormycosis including Aspergillus species (5, A. fumigatus from 1, Aspergillus not fumigatus from 1 and A. oryzae from 1), Candida species (5, C. albicans from 2, C. tropicalis from 2 and C. glabrata from 1), Penicillium species (1), S. cerevisiae (1) and P. jirovecii (1), and 24 patients (39.3%) had evidence of bacterial co-infection including S. maltophilia (5), methicillin-resistant S. aureus (5), E. faecium (VSE) (3), K. pneumonia (3), P. aeruginosa (3), and others. Conclusion Bacterial or fungal co-infections appear to frequently occur as appreciated before in patients with mucormycosis. These data provide us important information to select empirical antifungal and antibacterial agents. Disclosures All authors: No reported disclosures.

Background There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen. Methods We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment. Results In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2). Conclusion This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.

Background: Interferon (IFN)-γ-releasing assay for diagnosing tuberculosis (TB) has shown promise; however, there are only a few reports on usefulness of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral osteomyelitis. Methods: All patients presenting at a tertiary hospital between January 2010 and July 2016 with suspected TB vertebral osteomyelitis were retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We used QFT-GIT to measure the IFN-γ response to ESAT-6, CFP-10 and TB7.7. Results: A total of 141 patients were enrolled; 32 (23%) were categorized as having confirmed TB, (1%) as probable TB, 14 (10%) as possible TB and 93 (66%) as not TB. Of these, 16 patients with probable and possible TB were excluded from the final analysis. Chronic granulomas with/without necrosis, acid-fast bacilli stain, M. tuberculosis polymerase chain reaction and cultures for M. tuberculosis were positive in 14 (44%), 12 (38%), 22 (69%) and 28 (88%) patients, respectively, among the 32 patients with confirmed TB. The overall sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive result, and likelihood ratio for a negative result of the QFT-GIT for TB vertebral osteomyelitis were 91% (95% confidence interval [CI], 75–98%), 65% (95% CI, 54–75%), 50% (95% CI, 42–58%), 95% (95% CI, 86–98%), 2.59 (95% CI, 1.89–3.55) and 0.14 (95% CI, 0.05–0.43), respectively. Conclusion: The QFT-GIT appears to be a useful adjunct test for diagnosing TB vertebral osteomyelitis because the negative test results may be useful for excluding a diagnosis of active TB vertebral osteomyelitis.

Background Distinguishing aspergillosis from mucormycosis is clinically important as different antifungal agents are required. However, the sensitivity of fungal culture is suboptimal and histomorphologic diagnosis is not always accurate due to morphologic similarities. We investigated the diagnostic performance of immunohistochemistry (IHC) test for diagnosis of aspergillosis and mucormycosis. Methods Patients who met the criteria for mycologically proven aspergillosis or mucormycosis and in whom formalin-fixed, paraffin-embedded tissues were available were enrolled at a tertiary hospital from January 1992 to October 2017. Mycologically proven invasive fungal infections were defined as there were the histologic evidence of tissue invasion of hyphae and the recovery of Aspergillus species or agents of mucormycosis (Rhizopus spp., Cunninghamella spp., Apophysomycesspp., Saksenaea spp., Absidia spp., Mucor spp.) by culture from sterile specimens. Anti-Aspergillus mouse monoclonal antibody (1:50; clone WF-AF-1; LSBio, WA, USA) and anti-Rhizopus arrhizus mouse monoclonal antibody (1:100; clone WSSA-RA-1; LSBio, WA, USA) were used for IHC test, and we evaluated the diagnostic performance of IHC test using sensitivity and specificity. Results A total of 32 invasive fungal infection including 12 proven mucormycosis and 20 proven aspergillosis were analyzed. The fungal species from sterile sites and diagnostic performance of IHC test for these 30 patients were shown in Table 1. Conclusion The IHC test seems to be useful in compensating the limitations of histomorphologic diagnosis in distinguishing between aspergillosis and mucormycosis. Keywords. Aspergillosis; Mucormycosis; Histomorphology; Immunohistochemistry Table 1: Diagnostic Performance of Mucormycosis and Aspergillosis Immunohistochemistry Tests in Proven Mucormycosis and Proven Aspergillosis IHC Test Result Proven Mucormycosis,No. of Cases (n = 12) Proven Aspergillosis,No. of Cases (n = 20) Diagnostic Performance% (95% CI) Mucormycosis Positive 12 0 Sensitivity: 100(70–100) Negative 0 0 Specificity: 100 (80–100) Aspergillosis Positive 0 18 Sensitivity: 90(67–98) Negative 0 2 Specificity: 100(70–100) Abbreviations: CI, confidence interval; IHC, immunohistochemistry. Disclosures S. H. Kim, the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI): Investigator, Grant recipient.

Background Discrepancies between histomorphologic finding and indirect test results such as galactomannan (GM) assay make diagnosis of invasive fungal infection difficult. We investigated the frequency and clinical characterisitics of positive GM assay results in patients with mucormycosis. Methods Patients who met the modified criteria for proven or probable mucormycosis and had serum and/or bronchoalveolar lavage (BAL) fluid GM assay result were enrolled at a tertiary hospital from July 2009 to October 2017. Proven mucormycosis was defined as histologic evidence of tissue invasion of hyphae with positive mucormycosis immunohistochemistry (IHC) test result and the recovery of agents of mucormycosis (Rhizopus spp., Cunninghamella spp., Apophysomyces spp., Saksenaea spp., Absidia spp., Mucor spp.) by culture from sterile specimens. Probable mucormycosis was defined as histologic evidence of tissue invasion of hyphae with positive mucormycosis IHC test result with or without recovery of agents of mucormycosis by culture from nonsterile specimens. Results Among 50 patients of proven or probable mucormycosis, 20 (40%) patients were positive for serum and/or BAL fluid GM assay results; 13 of 20 (65.0%) were positive in serum, nine of 12 (75.0%) were positive in BAL fluid, and two of 12 (16.7%) were positive in both. There were more patients with gastrointestinal infections (4 of 20 [20%] vs. 0 of 30 [0%], P = 0.021) and diagnosed as histomorphologically aspergillosis (6 of 20 [30%] vs. 1 of 30 [3%], P = 0.012) in GM positive group than GM negative group. Conclusion These results suggest that positive GM assay results are not uncommon in mucormycosis. GM assay results from the patients with mucormycosis appear to be related with gastrointestinal infections and histomorphologic diagnosis of aspergillosis. Further studies are needed on the mechanism of positive GM results in patients with mucormycosis and possible coinfection with other fungi such as Aspergillus species in these patients. Disclosures S. H. Kim, the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI): Investigator, Grant recipient

Background The decision of catheter removal in neutropenic patients with candidemia is difficult because they usually have surgically implanted catheter, and CRC are less frequent than in non-neutropenic patients. However, there are limited data on distinguishing CRC from non-CRC before catheter removal. We thus evaluated the diagnostic performances of DTP to diagnose CRC in neutropenic cancer patients with suspected CRC. Methods All adult neutropenic cancer patients with candidemia were enrolled in a tertiary care hospital from July 2012 to December 2016. Definite CRC was defined if ≥15 CFU of Candida spp. in a removed catheter tip. Probable CRC was defined if (1) one to 14 CFU in catheter tip, and clinical improvement within 48 hours after catheter removal with antifungal agent therapy or (2) the infection was refractory to antifungal therapy alone but improved within 48 hours after catheter removal. Non-CRC was defined if any of the following conditions were satisfied: (1) catheter tip cultures were negative and a noncatheter source of candidemia was found by culture, (2) the catheter tip cultures within 24 h before the start of antifungal therapy were negative, or (3) the clinical improvement before or without catheter removal. If the above conditions are not met, they were grouped into indeterminate, and were excluded from the final analysis. We defined the DTP as the difference in the time to positivity between blood cultures drawn simultaneously from the central vein and a peripheral vein. Results A total of 35 neutropenic patients with candidemia were enrolled. Of these, 15 patients (43%) with CRC (6 definite and nine probable) and 17 (48.5%) with non-CRC were finally analyzed, excluding threeindeterminate candidemia. On the basis of the receiver operating characteristics (ROC) curve, the optimal cut-off was ≥1.45 hours and the area under the ROC curve was 0.89 (95% CI, 76 to 100) in diagnosing CRC. Of the 15 patients with CRC, 11 (73%) revealed positive DTP, whereas none of the 17 patients with non-CRC exhibits positive DTP. The sensitivity and specificity of DTP for the diagnosis of CRC were 73% (95% CI, 58 to 94) and 100% (95% CI, 71 to 100), respectively. Conclusion DTP appears to be useful to rule in CRC and DTP ≥ 1.45 hours to be the optimal cut-off for CRC in neutropenic cancer patients. Disclosures All authors: No reported disclosures.

Background Interferon-γ releasing assays (IGRAs) are useful for diagnosing LTBI. However, there are limited data on the efficacy of IGRA-based isoniazid (INH) treatment with/without back-up tuberculin skin test (TST) to prevent the development of TB in solid-organ transplant recipients. Methods All adults patients admitted to a KT unit from January 2014 to December 2016 were retrospectively reviewed in a 2,700-bed, tertiary-care hospital in Seoul, South Korea. The IGRA (i.e., QuantiFERON-In-Tube) with/without TST was performed on all recipients before KT, and 9-month INH treatment was given to patients with clinical risk factors for LTBI regardless of IGRA results. Our hospital policy on LTBI diagnosis and treatment was changed as follows. Period 1 (January 2014–September 2015) adopted IGRA-based INH treatment. We administered INH treatment to all patients with positive IGRA results. Period 2 and period 3 adopted IGRA-based followed by back-up TST-based INH treatment. Period 2 (October 2015–December 2015) included the temporary shortage of Mantoux test, so INH treatment was not given to the patients with positive IGRA since back-up TST was not performed. In Period 3 (January 2016–December 2016), we administered INH treatment to the patients with positive IGRA results followed by back-up TST¡Ã10 mm. The development of TB after KT as the primary endpoint was observed from January 2014 to April 2018. Results The study flow is shown in Figure 1. Of the 1,150 KT recipients, 14 (1.2%) developed TB (incidence rate 0.63 per 100 person-years, 95% CI 0.35–1.06). The median time for TB development was 9.4 months (IQR 4.7–14.5). Seven (3.2%) of 216 patients with positive IGRA without INH treatment developed TB, whereas none of 106 patients with positive IGRA with INH treatment developed TB (rate difference 2.43 per 100 person-years, P = 0.008) and 7 (0.8%) of 828 patients with negative or indeterminate IGRA results developed TB (rate difference 2.0 per 100 person-years, P < 0.001). The number needed to treat (NNT) for IGRA-based INH treatment was 31 (95% CI 18–114). Conclusion IGRA-based INH treatment is effective to prevent the development of TB in KT recipients without clinical risk factors for LTBI with reasonable NNT. Disclosures All authors: No reported disclosures.

Hematopoietic chimerism as a predictive marker for the relapse of acute leukemia after allogeneic BMT was evaluated in a prospective study. Monthly assays of hematopoietic chimerism were performed from peripheral blood samples by PCR amplification of short tandem repeats or amelogenin loci. Between December 1997 and June 1999, 33 patients enrolled and 30 were evaluable (two early deaths, one lack of informative bands for chimerism evaluation). There were 14 male and 16 female patients (15 AML and 15 ALL) with a median age of 31 years (range 16-46). Mixed chimerism (MC) was observed at least once in 14 of 30 patients (47%). There was no significant difference between 14 patients who showed MC (MC group) and 16 patients who did not show MC (complete chimerism (CC) group) in terms of age, sex, disease status at BMT, donor type, and the number of bone marrow cells infused. There was no significant difference in the neutrophil and platelet engraftment rates between the two groups. After a median follow up of 10.9 months (range 4.3-22.4), five patients in the CC group and two patients in the MC group relapsed (P = 0.27). All five patients who relapsed in the CC group maintained CC up to 1 month prior to clinical relapse. Our study demonstrated that the patients who showed MC post BMT did not have higher risk of relapse of acute leukemia when compared to patients who did not show MC. Sensitive PCR-based assays for hematopoietic chimerism applied on a monthly basis after allogeneic BMT could not predict relapse of acute leukemia.

We report a first case of biphenotypic blast crisis of unclassified myeloproliferative disorder (MPD). A 20-year-old patient presented with fever, splenomegaly, marked leukocytosis (603 x 10(3)/ micro l), and blasts in the peripheral blood. Since Ph chromosome and bcr-abl gene rearrangement were absent, the diagnosis of an unclassified MPD in the blast crisis phase was established. Immunophenotyping confirmed a biphenotypic crisis of myeloid and T-lymphoid antigens. The patient went into a complete remission after chemotherapy, but marked granulocytic hyperplasia (M:E ratio of 5.7) and 90% cellularity remained. Blast crisis recurred during subsequent intensification chemotherapy and the patient did not go into a complete remission regardless of the intense chemotherapy. The blast crisis transformed from unclassified MPD had a grave prognosis as it responded poorly to chemotherapy. This unique blast crisis is distinguishable from the blast crisis of chronic myelogenous leukemia.

There are few reports about the occurrence of hepatic VOD after BMT for severe aplastic anemia (SAA). We prospectively studied 17 patients with SAA after allogeneic BMT for the occurrence and severity of VOD. Plasma levels of protein C, protein S, antithrombin III, vWF, t-PA and PAI-1 were determined before preparative chemotherapy, on the day of marrow infusion, and on days 7, 14 and 21. VOD occurred in seven patients (41.2%) at a median of day 1 (range, day -2 to 15). Five had mild, and two moderate VOD. Platelet transfusion requirements were higher in the patients with VOD. The plasma levels of natural anticoagulants such as protein C, free protein S and antithrombin III decreased significantly on day 0 from the baseline levels. Plasma levels of t-PA, PAI-1 and vWF increased significantly in the early post-transplant period compared to the baseline levels. The mean plasma levels of t-PA on day 7 (P = 0.016) and PAI-1 on days 0 and 7 (P = 0.016, 0.032) were higher in the patients with VOD. In summary, we observed hypercoagulability and a high incidence of VOD after allogeneic BMT for SAA. Levels of t-PA and PAI-1 were significantly higher in the patients with VOD after BMT.