Seok H, et al. Infect Chemother. 2020 Mar;52(1):19-30. https://doi.org/10.3947/ic.2020.52.1.19

Background: Invasive fungal disease (IFD) is common in solid organ transplant (SOT) recipients and contributes to high morbidity and mortality. Although kidney transplantation (KT) is a commonly performed SOT, data on the risk factors for IFD-related mortality are limited. Methods: A 1:2 retrospective case-control study was performed in an experienced single center in the Republic of Korea. We reviewed the electronic medical records of patients with IFD after KT between February 1995 and March 2015. Results: Of 1963 kidney transplant recipients, 48 (2.5%) were diagnosed with IFD. The median interval from KT to IFD diagnosis was 172 days. Invasive aspergillosis (IA) was the most common, followed by invasive candidiasis (IC). Diabetes mellitus (DM) (odds ratio (OR) 3.72, 95% confidence interval (CI) 1.34–10.31, p = 0.011) and acute rejection (OR 3.41, 95% CI 1.41–8.21, p = 0.006) were associated with IFD development. In the subgroup analyses, concomitant bacterial infection was associated with IC development (OR 20.10, 95% CI 3.60–112.08, p = 0.001), and delayed graft function was associated with IA occurrence (OR 10.60, 95% CI 1.05–106.84, p = 0.045). The 12-week mortality rate in all patients was 50.0%. Mortality rates were significantly higher in older patients (adjusted hazard ratio (aHR) 1.06, 95% CI 1.02–1.11, p = 0.004), or those with DM (aHR 2.61, 95% CI 1.02–6.68, p = 0.044), deceased donor transplantation (aHR 2.68, 95% CI 1.03–6.95, p = 0.043), lymphocyte-depleting antibody usage (aHR 0.26, 95% CI 0.08–0.80, p = 0.019), acute rejection (aHR 0.38, 95% CI 0.15–0.97, p = 0.044), and concomitant bacterial infection (aHR 8.76, 95% CI 1.62–47.51, p = 0.012). Conclusions: A total of 50% of IFD cases occurred six months or later after transplantation. The IFD-related mortality rate was high in kidney transplant recipients despite the low incidence. DM and acute rejection were associated with high mortality, as well as IFD development. As old age, deceased donor transplantation, lymphocyte-depleting antibody usage, and concomitant bacterial infection are risk factors for IFD-related mortality, efforts for its early diagnosis and appropriate treatment are required.

Kim SH, et al. J Korean Med Sci. 2022 Apr;37(18):e134. https://doi.org/10.3346/jkms.2022.37.e134

We investigated fosfomycin susceptibility in Escherichia coli clinical isolates from South Korea, including community-onset, hospital-onset, and long-term care facility (LTCF)-onset isolates. The resistance mechanisms and genotypes of fosfomycin-resistant isolates were also identified. Finally, the in vitro efficacy of combinations of fosfomycin with other antibiotics were examined in susceptible or extended spectrum β-lactamase (ESBL)-producing E. coli isolates. The fosfomycin resistance rate was 6.7% and was significantly higher in LTCF-onset isolates than community-onset and hospital-onset isolates. Twenty-one sequence types (STs) were identified among 19 fosfomycin-resistant E. coli isolates, showing diverse genotypes. fosA3 was found in only two isolates, and diverse genetic variations were identified in three genes associated with fosfomycin resistance, namely, GlpT, UhpT, and MurA. Some fosfomycin-resistant E. coli isolates carried no mutations. In vitro time-kill assays showed that fosfomycin alone did not exhibit an excellent killing activity, compared with ciprofloxacin in susceptible isolates and with ertapenem in ESBL producers. However, combining fosfomycin with cefixime or piperacillin-tazobactam eradicated susceptible or ESBL-producing isolates, respectively, even with 0.5× minimum inhibitory concentrations. Overall, we found a relatively high fosfomycin resistance rate in E. coli isolates from South Korea. Based on their genotypes and resistance mechanisms, most of the fosfomycin-resistant E. coli isolates might occur independently. Antibiotic combinations with fosfomycin could be a suitable therapeutic option for infections caused by E. coli isolates.

We developed a novel computer program, the Intelligent Sepsis Management System, based on Sepsis-3 definitions and 2016 Surviving Sepsis Campaign guidelines and performed a quasi-experimental pre-post study to assess its effect on compliance with the Surviving Sepsis Campaign guidelines and outcomes in patients with sepsis and septic shock. During the pre-period, patients were managed with usual care. During the post-period, patients were managed using the Intelligent Sepsis Management System upon arrival at the emergency department. A total of 631 patients were enrolled (pre-period, 316; post-period, 315). The overall compliance with the Surviving Sepsis Campaign guidelines’ bundle improved (pre-period 10.8% vs. post-period 54.6%; p < 0.001). The post-period showed significantly lower 30-day mortality than the pre-period (pre-period 37.3% vs. post-period 29.5%; p = 0.037), but was not a protective factor for 30-day mortality, with an adjusted hazard ratio (95% confidence interval) of 0.75 (0.55–1.04) (p = 0.151). The associated factors for 30-day mortality were age, sequential organ failure assessment score, overall compliance, and lactate levels. The 30-day mortality was significantly lower in the compliance group than in the non-compliance group (27.2% vs. 36.5%; p = 0.002). After implementation of the Intelligent Sepsis Management System, overall compliance with the Surviving Sepsis Campaign guidelines improved and was associated with reduced 30-day mortality. However, we could not verify the causal effect of this system on 30-day mortality.

A prospective cohort study was conducted to evaluate the effect of vitamin D deficiency on sepsis. A total of 129 patients were enrolled. The median age was 74 years old, with a median SOFA score of 7; septic shock was observed in 60 patients. The median vitamin D level in the overall population was 13 ng/mL. A total of 96 patients had vitamin D deficiency, whereas 62 patients were described to have severe vitamin D deficiency. Severe vitamin D deficiency significantly increased the 14-day mortality (adjusted hazard ratio (aHR) 2.57; 95% confidence interval [CI]: 1.03–6.43; p = 0.043), 28-day mortality (aHR 2.28; 95% CI: 1.17–4.45; p = 0.016), and in-hospital mortality (aHR 2.11; 95% CI: 1.02–4.36; p = 0.044). In Kaplan–Meier analysis, the severe vitamin D deficiency group had significantly higher 14-day and 28-day mortality rates compared with the non-deficient group. Evaluating the vitamin D levels in sepsis patients may become necessary in an aging society. Severe vitamin D deficiency can independently affect poor prognosis related to sepsis. Further studies are needed to evaluate whether vitamin D supplementation in sepsis patients with vitamin D deficiency can help improve the prognosis of sepsis in addition to improving bone mineral metabolism.