Aspergillosis coinfection in patients with proven mucormycosis.

Although research on aspergillosis and mucormycosis confection is important to optimize antifungal therapy, data on this issue is scarce. Thus, we systematically investigated aspergillosis coinfection in patients with proven mucormycosis. Medical records of adult patients with proven mucormycosis whose formalin-fixed paraffin-embedded (FFPE) tissue sections were available, in a tertiary hospital from August 2007 to July 2023 were retrospectively reviewed to assess coinfection with aspergillosis. We noted cultures of fungi from sterile and non-sterile sites and performed polymerase chain reaction (PCR) assays on FFPE tissues to detect Aspergillus- and Mucorales-specific DNA. Sixty-seven patients with proven mucormycosis, including 12 (18%) with a positive culture of the mucormycosis agent from sterile site cultures, were enrolled. Fungal cultures from sterile and non-sterile sites revealed Aspergillus spp. growth in nine (13%) of the 67 patients, including two sterile and seven non-sterile cultures. The fungal PCR analysis from the FFPE sections was positive for Aspergillus-specific PCR in five (7%) and positive for both Aspergillus- and Mucorales-specific PCR results in eight (12%). Overall, 21 (31%) of the 67 patients with proven mucormycosis had microbiologic and/or molecular evidence of aspergillosis coinfection. Positive blood or bronchoalveolar lavage fluid galactomannan results were more common in the coinfection group (67% [14/21]) than in the mucormycosis group (37% [17/46], P = .024). No significant difference in mortality between the two groups was observed. Approximately one-third of patients with proven mucormycosis exhibited molecular and/or microbiologic evidence of aspergillosis coinfection. Further research is needed to identify patients with aspergillosis and mucormycosis coinfections, for optimal antifungal therapy.

The study aims to investigate the coinfection between mucormycosis and aspergillosis. Key findings reveal that approximately 31% of patients demonstrated evidence of coinfection, which emphasizes the importance of considering both pathogens in diagnosis and treatment decisions.

Complete genome sequencing of three methicillin-resistant Staphylococcus aureus isolated from the blood of patients with persistent bacteremia.

We report the complete genome sequences of three molecular types of methicillin-resistant Staphylococcus aureus (MRSA) clinical strains isolated from the blood of three patients diagnosed with persistent MRSA bacteremia: KNIH_5618 (ST5-t5076-SCCmecII), KNIH_5844 (ST72-t664-SCCmecIV), and KNIH_6268 (ST89-t375-SCCmecII). These genome sequences contribute to an enhanced understanding of the underlying causes of persistent MRSA infection.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.

BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

Immunity Against Measles in Korean Autologous Hematopoietic Stem Cell Transplant Recipients.

The seropositivity of measles antibodies among 261 autologous stem cell transplant recipients (ASCTs) in Korea, assessed approximately 1-2 years after transplant (median, 11 months; interquartile range, 9-14), was significantly lower than age- and sex-matched control healthcare workers (83.1% [217/261] vs. 90.3% [539/597], P = 0.002). The findings underscore the vulnerability of adult ASCT recipients to measles. Clinicians should prioritize testing for measles IgG after ASCT and consider vaccination for ASCT recipients who remain seronegative 2 years after ASCT.

Clinical and microbiological characteristics of persistent Staphylococcus aureus bacteremia, risk factors for mortality, and the role of CD4+ T cells.

This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4+ T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4+ T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4+ T cells might play a pivotal role in SAB PB.

Risk factors for vancomycin treatment failure in heterogeneous vancomycin-intermediate Staphylococcus aureus bacteremia.

The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older (P < 0.001) and more frequently had solid cancer (P = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent (P < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index (P = 0.01) and Acute Physiology and Chronic Health Evaluation II scores (P < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated Staphylococcus aureus (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.

Effectiveness of ceiling-mounted ultraviolet-C lamps: An experimental study in a biocontainment unit of a tertiary care hospital.

BACKGROUND: We aimed to evaluate the performance of ceiling-mounted UV-C lamps. METHODS: This study was conducted in an empty room with UV-C lamps in the biocontainment unit of a tertiary care hospital in South Korea. Each pathogen (Staphylococcus aureus, Escherichia coli, Candida krusei, Bacillus cereus, and Mycobacterium peregrinum) was inoculated on blood agar plates and placed in 20 selected places from the UV-C lamp, and irradiation was applied for 15 min. As a control group, the bacterial solution was diluted 10,000 times and UV was not applied. RESULTS: A mean ± SD of 5.95 ± 0.91 log reduction was observed with UV irradiation compared with the control. The log reduction was greatest for S. aureus [median, 7.05 (IQR, 6.49-7.26)] and least for M. peregrinum [median, 4.88 (IQR, 4.58-5.24)]. The degree of log reduction was inversely proportional to the square of the distance from the UV-C lamp (R2 = -0.12, P < .001). CONCLUSIONS: In this study, ceiling-mounted UV-C demonstrated effective disinfection of at least 4-log reduction of the test organisms within a 4-m distance. Mounted UV-C lighting is a considerable option for improving surface disinfection.

Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection.

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.

Quantitative interferon-gamma releasing assay in predicting tuberculosis in South Korean military: a retrospective cohort study.

OBJECTIVE: The interferon-gamma releasing assay (IGRA) has been widely used to diagnose latent tuberculosis infection (TBI). However, there are limited data on the association between performance in the IGRA and risk of tuberculosis disease (TBD), as well as on the appropriate IGRA threshold for initiating TBI treatment. METHODS: The analysis was performed using the IGRA results in the Korean Military Manpower Administration database (January 2017 to December 2021), and TBD cases reported to the Korean Military Medical Command (January 2017 to June 2023). All Korean candidates for 18-month military service underwent the IGRA in the pre-enlistment examination, and enlistees who tested positive (≥0.35 IU/mL) were advised to receive TBI treatment before enlistment. RESULTS: From 2017 to 2021, 1 647 941 individuals were screened, with 29 574 testing positive for IGRA. Excluding nonenlistees namely individuals with TBD before enlistment, 19 387 individuals were IGRA positive and 1 356 324 IGRA negative. Of the positives, 4351 were excluded due to discontinued or ongoing TBI treatment at or after enlistment. During follow-up of 9219 untreated and 5818 treated positive individuals and 1 356 324 negatives, TBD occurred in 22 of the IGRA-positive individuals (97.5/100 000 person-years [95% CI, 61.1-147.7]), predominantly in the untreated group (18 cases, 130.1/100 000 person-years [95% CI, 77.1-205.7]) compared to the treated group (4 cases, 45.9/100 000 person-years [95% CI 12.5 - 117.4]), whereas 57 cases occurred in the IGRA-negative group (2.8/100 000 person-years [95% CI, 2.2-3.6]). Elevating the cutoff of IGRA from 0.35 IU/mL to 1.33 IU/mL increased positive predictive value (0.2% vs. 0.4%, p 0.03), with insignificant loss of sensitivity (24% vs. 20%, p 0.69) and decreased numbers needing treatment from 790.5 to 415.3. DISCUSSION: Elevated IGRA levels before enlistment are associated with risk of TBD during military service. It is worth considering raising the IGRA threshold for treatment of TBI in cohorts of healthy, young military individuals.

Comparison of the Clinical Outcomes Between Early and Delayed Transplantation After SARS-CoV-2 Infection.

Our study analyzed 95 solid organ transplant (SOT) and 78 hematopoietic stem cell transplant (HSCT) recipients with prior coronavirus disease 2019 (COVID-19). Patients who underwent transplantation within 30 days of COVID-19 infection comprised the early group, and those who underwent transplantation post-30 days of COVID-19 infection comprised the delayed group. In the early transplantation group, no patient, whether undergoing SOT and HSCT, experienced COVID-19-associated complications. In the delayed transplantation group, one patient each from SOT and HSCT experienced COVID-19-associated complications. Additionally, among early SOT and HSCT recipients, two and six patients underwent transplantation within seven days of COVID-19 diagnosis, respectively. However, no significant differences were observed in the clinical outcomes of these patients compared to those in other patients. Early transplantation following severe acute respiratory syndrome coronavirus 2 infection can be performed without increased risk of COVID-19-associated complications. Therefore, transplantation needs not be delayed by COVID-19 infection.

The origin of sequence type 72 community-associated methicillin-resistant Staphylococcus aureus (MRSA) and fusidic acid (FA) resistant sequence type 5 MRSA: Analysis of FA resistance and spa type in a single center in South Korea.

INTRODUCTION: We investigated the prevalence of fusidic acid (FA) resistance in MSSA and MRSA stratified by sequence (ST) and spa types, and determined the prevalence of FA resistance mechanisms. METHODS: From August 2014 to April 2020, S. aureus blood isolates were collected in Asan Medical Center, Seoul, South Korea. Antimicrobial susceptibility tests were performed using broth microdilution and interpreted according to EUCAST's FA criteria. We performed spa typing for fusA mutation presence and acquired FA resistance determinants (fusB, fusC, and fusD) by PCR. RESULTS: Of the 590 MRSA isolates, 372 were FA resistant, and among 425 MSSA isolates, 136 were resistant. Of the 380 ST5-MRSA isolates, 350 were FA resistant, whereas only 1 of 14 ST5-MSSA isolates was FA resistant. Conversely, of the 163 ST72-MRSA isolates, only 8 were resistant, whereas 37 of 42 ST72-MSSA were resistant. The fusA mutation (80%) was the most common determinant. The one FA resistant ST5-MSSA isolate belonged to the t2460 spa type, the most common spa type (24 of 35 isolates) of FA resistant ST5-MRSA. In addition, t324 and t148, which are minor spa types of ST72-MSSA, were susceptible to FA, in contrast to other ST72-MSSA spa types, and the major spa type of ST72-MRSA (110 of 163 isolates). CONCLUSIONS: FA resistance was common in ST5-MRSA and ST72-MSSA, and rare in ST5-MSSA and ST72-MRSA. Our findings suggest that minor clones of ST5-MSSA isolates, with the fusA mutation and minor clones of ST72-MSSA susceptible to FA, may have evolved to harbor the mecA gene.

Clinical safety of remdesivir therapy in COVID-19 patients with renal insufficiency.

Though remdesivir benefits COVID-19 patients, its use in those with renal dysfunction is currently limited due to concerns about possible toxic effects of accumulated sulfobutylether-ß-cyclodextrin (SBECD) on liver and kidney. We examined renal and hepatic function for a month in renally-impaired COVID-19 patients who were treated or not treated with remdesivir to assess the safety of the drug. A retrospective study was performed in adult COVID-19 patients with glomerular filtration rates of <30 ml/min/1.73 m2 at admission to a tertiary care hospital between November 2020 and March 2022. Data on serum creatinine and liver chemistry were collected serially. A total of 101 patients with impaired renal function were analyzed, comprising 64 remdesivir-treated patients and 37 who did not receive any antiviral agent. Although remdesivir-treated patients were more likely to be infected with the Omicron variant (79.7% vs. 48.6%), baseline characteristics did not differ significantly between the two groups. Among patients who initially did not require dialysis, 18.4% (7/38) of remdesivir-treated patients developed acute kidney injury (AKI) at days 4-6, compared with 51.7% (15/29) of non-remdesivir-treated patients. Liver injury severity worsened in 3.1% (2/64) of remdesivir-treated patients and 5.4% (2/37) of non-remdesivir-treated patients at days 4-6. In addition, there was no significant increase in AKI and liver injury over time in remdesivir-treated patients, and there were no cases of discontinuation of remdesivir due to adverse reactions. Concerns regarding the safety of SBECD should not lead to hasty withholding of remdesivir treatment in renally-impaired COVID-19 patients.

Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants.

Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer-correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false-negative rates (cPass-BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F-BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed-effects model suggested superior titer-correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.

Molecular Characteristics and Prevalence of Rifampin Resistance in Staphylococcus aureus Isolates from Patients with Bacteremia in South Korea.

Rifampin resistance (RIF-R) in Staphylococcus aureus (S. aureus) with rpoB mutations as one of its resistance mechanisms has raised concern about clinical treatment and infection prevention strategies. Data on the prevalence and molecular epidemiology of RIF-R S. aureus blood isolates in South Korea are scarce. We used broth microdilution to investigate RIF-R prevalence and analyzed the rpoB gene mutation in 1615 S. aureus blood isolates (772 methicillin-susceptible and 843 methicillin-resistant S. aureus (MRSA)) from patients with bacteremia, between 2008 and 2017. RIF-R prevalence and antimicrobial susceptibility were determined. Multilocus sequence typing was used to characterize the isolate's molecular epidemiology; Staphylococcus protein A (spa), staphylococcal cassette chromosome mec (SCCmec), and rpoB gene mutations were detected by PCR. Among 52 RIF-R MRSA isolates out of 57 RIF-R S. aureus blood isolates (57/1615, 0.4%; 5 methicillin-susceptible and 52 MRSA), ST5 (44/52, 84.6%), SCCmec IIb (40/52, 76.9%), and spa t2460 (27/52, 51.9%) were predominant. rpoB gene mutations with amino acid substitutions showed that A477D (17/48, 35.4%) frequently conferred high-level RIF resistance (MIC > 128 mg/L), followed by H481Y (4/48, 8.3%). RIF-R S. aureus blood isolates in South Korea have unique molecular characteristics and are closely associated with rpoB gene mutations. RIF-R surveillance through S. aureus-blood isolate epidemiology could enable effective therapeutic management.

Clinical impact of metformin exposure during Staphylococcus aureus bacteremia in patients with diabetes mellitus.

PURPOSE: Increasing evidence has suggested that metformin may play positive roles in a wide range of infectious diseases. This study aimed to investigate the clinical impact of metformin exposure during Staphylococcus aureus bacteremia (SAB) in patients with diabetes. METHODS: A 3-year observational cohort study of 452 patients (aged ≥ 16 years) with SAB was performed at a tertiary care hospital. Metformin exposure was defined as receiving metformin during SAB, regardless of metformin use before the onset of bacteremia. RESULTS: Of 452 patients, 51 (11.3%) were classified in Group A (diabetes with metformin exposure), 115 (25.4%) in Group B (diabetes without metformin exposure), and 286 (63.3%) in Group C (no diabetes). The 30-day mortality rate in Group A was significantly lower than that in Group B (3.9% [2/51] versus 14.8% [17/115]; p = 0.04) and lower than that in Group C (3.9% [2/51] versus 17.1% [49/286]; p = 0.02). The mortality rates did not differ between Group B and Group C (14.8% [17/115] versus 17.1% [49/286]; p = 0.57). The rates of persistent and recurrent bacteremia were comparable among the three groups. Multivariate analysis indicated that metformin exposure was significantly associated with reduced mortality (adjusted odds ratio, 0.20; 95% confidence interval, 0.04-0.88; p = 0.03). CONCLUSIONS: Metformin exposure during SAB appears to be an independent predictor of survival in patients with diabetes.

Routine ophthalmologic examination in Klebsiella pneumoniae bacteremia is not necessary: incidence of and risk factors for ocular involvement.

Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.

Clinical characteristics of COVID-19 rebound after nirmatrelvir-ritonavir or molnupiravir therapy: A prospective cohort study.

The clinical characteristics of the rebound phenomenon after antiviral therapy in patients with Coronavirus disease-2019 (COVID-19) are largely unknown. There are few data comparing the rebound phenomenon after molnupiravir therapy to that after nirmatrelvir-ritonavir therapy. We investigated the incidence and risk factors associated with COVID-19 rebound after nirmatrelvir-ritonavir or molnupiravir therapy during the Omicron era. This prospective cohort study enrolled patients with mild-to-moderate COVID-19 who received nirmatrelvir-ritonavir or molnupiravir. We conducted weekly questionnaires of symptom scores from day 0 to day 28, with an additional day when patients experienced reappearing symptoms. We defined COVID-19 rebound as when patients experienced a 50% increase in symptom scores compared to the lowest symptom score between days 0 and 14. Among the 150 patients, 93 (62%) and 57 (38%) received nirmatrelvir-ritonavir therapy and molnupiravir, respectively. Of these, 11 patients (7.3%; 95% CI, 3.1-11.5) experienced COVID-19 rebound. The median duration from antiviral therapy to rebound was 12 days. Patients with clinical rebound had a higher symptom score at antiviral therapy initiation than those without (median, 5 vs 4; P = .02). There was no significant difference in the clinical rebounds associated with nirmatrelvir-ritonavir and molnupiravir therapy (5.4% vs 10.5%; P = .39). Approximately one-tenth of patients with mild-to-moderate COVID-19 who received antiviral therapy experienced rebound phenomena after treatment. Regardless of antiviral therapy type, high initial symptom scores were associated with a more frequent rebound phenomenon.

False positive Aspergillus galactomannan assay results caused by specific parenteral nutrition.

In September 2022, the proportion of clinically false positive results with high index values for the galactomannan (GM) assay increased dramatically in our hospital and remained high until November 2022. We aimed to identify the possible causative agent that led to the dramatic increase in false positivity in GM assay. A case-control-control study was conducted, and patients admitted to two intensive care units between September and November 2022 were included. We defined each time point at which the GM assay was conducted in a patient as an episode and classified episodes into strong-positive (≥10.0 index; case), positive (control), and negative (<0.5 index; control) groups. We compared the medications administered in three groups and measured GM levels in relevant medications, including parenteral nutrition (PN). In total, 118 episodes in 33 patients were classified into three groups. There were 46 negative, 23 positive, and 49 strong-positive episodes, and there was a significant difference in the use of Winuf® PNs (P < .001) between the three groups. Forty episodes (82%) in the strong-positive group received Winuf®, compared with three (6.5%) in the negative group and one (4.3%) in the positive group (P < .001). All samples of Winuf® PNs used in the five patients whose GM results were repeatedly strong-positive were strongly positive for GM. False positivity in GM assay can be caused by the administration of specific PNs. A thorough investigation of prescribed medications should be considered when there is an abrupt increase in the proportion of strong-positive or positive GM results.

Clinical Characteristics of and Risk Factors for Subsequent Carbapenemase-producing Enterobacterales (CPE) Bacteraemia in Rectal CPE Carriers.

BACKGROUND: Due to high mortality and limited treatment options, the rise in carbapenemase-producing Enterobacterales (CPE) has become a major concern. This study aimed to evaluate the incidence and characteristics of subsequent CPE bacteraemia in rectal CPE carriers and investigate the risk factors for CPE bacteraemia compared with non-carbapenemase-producing (non-CP) Enterobacterales bacteraemia. METHODS: A retrospective analysis was conducted on adult patients who were confirmed to have CPE colonisation by stool surveillance culture at a tertiary hospital from January 2018 to February 2022. All episodes of Enterobacterales bacteraemia up to 6 months after CPE colonisation were identified. RESULTS: Of 1174 patients identified as rectal CPE carriers, 69 (5.8%; 95% CI 4.6-7.3%) experienced subsequent CPE bacteraemia during the 6 months after the diagnosis of CPE colonisation. Colonisation by a Klebsiella pneumoniae carbapenemase (KPC) producer (or CP-K. pneumoniae), colonisation by multiple CPE species, chronic kidney disease and haematological malignancy were independently associated with CPE bacteraemia in CPE carriers. When CPE carriers developed Enterobacterales bacteraemia, the causative agent was more frequently non-CP Enterobacterales than CPE (63.6% vs. 36.4%). Among these patients, colonisation with a KPC producer, CPE colonisation at multiple sites, shorter duration from colonisation to bacteraemia (< 30 days) and recent intraabdominal surgery were independent risk factors for CPE bacteraemia rather than non-CP Enterobacterales bacteraemia. CONCLUSIONS: In CPE carriers, non-CP Enterobacterales were more often responsible for bacteraemia than CPE. Empirical antibiotic therapy for CPE should be considered when sepsis is suspected in a CPE carrier with risk factors for CPE bacteraemia.