Pulmonary mucormycosis in the aftermath of critical COVID-19 in an immunocompromised patient:Mind the diagnostic gap

Mucormycosis has recently been recognized as a severe complication of COVID-19 with high fatality rates. We report a fatal case of COVID-19 associated mucormycosis (CAM) in a non-diabetic immunocompromised patient, who was first misdiagnosed and treated for COVID-19 associated aspergillosis (CAPA). The risk factors and initial clinical presentation of CAPA and CAM are similar, but CAM has a more aggressive course and CAPA and CAM are treated differently. Dedicated diagnostic workup is essential to ensure early treatment of CAM with surgical debridement and targeted antifungal therapy

Clinical characteristics of pyogenic vertebral osteomyelitis, and factors associated with inadequate treatment response

Objectives: Pyogenic vertebral osteomyelitis (PVO) is associated with a high burden of disease. Our study aimed to describe characteristics at presentation of PVO, the risk of inadequate treatment response (ITR), relapse, and death, and to determine risk factors for ITR. Methods: Patients with an ICD-10 discharge code for PVO and admission to a major Danish university hospital between November 2016 and April 2019 were included. ITR was defined as clinical, microbiological, and/or radiological progression during treatment. Data were collected through review of medical records, and logistic regression was used to determine adjusted odds ratios (aOR). Results: Of 106 patients included, 87% presented with pain in the spine, 97% elevated CRP, 14% severe sepsis, and 13% with a history of previous spinal surgery. 39% were infected with Staphylococcus aureus and 9% with Escherichia coli. 31% responded inadequately to treatment, and risk factors for ITR were previous spinal surgery (aOR 19.29; 95% confidence interval (CI) 2.20–169.08), severe sepsis (aOR 4.59; 95% CI 1.28–15.41), and infection with Escherichia coli (aOR 8.10; 95% CI 1.71–38.45). 13% experienced relapse within the first 2 years, while the 1-year crude mortality was 12%. Conclusion: Staphylococcus aureus is still the main pathogen in PVO patients, and the risks of relapse and mortality remain high. Factors found to be associated with ITR were previous spinal surgery, severe sepsis, and infection with Escherichia coli

Adverse Events Associated with Universal versus Targeted Antifungal Prophylaxis among Lung Transplant Recipients—A Nationwide Cohort Study 2010–2019

Background: Invasive fungal infections in lung transplant (LTX) recipients cause substantial morbidity, but the best strategy for prevention has not yet been determined. We evaluated adherence to and rates of adverse events of universal versus targeted prophylaxis. Methods: All LTX recipients in the Danish National LTX Centre (2010–2019) were included. Before July 2016, universal voriconazole prophylaxis was used. After July 2016, only high-risk patients received targeted prophylaxis with posaconazole and inhaled amphotericin B. Proportions of triazole discontinuation, side-effects, off-target calcineurin-inhibitor (CNI) levels, and acute rejection were compared between the two periods. Results: Universal and targeted prophylaxis was initiated in 183/193 and 6/102 patients, respectively. Only 37% completed > 9 of the intended 12 weeks of voriconazole; 72% of discontinuations were due to hepatotoxicity. In the universal vs. targeted prophylaxis period, 89% vs. 72% (p p p p < 0.001) had acute rejection associated with low CNI episodes. Conclusions: Universal voriconazole prophylaxis was associated with high rates of discontinuation, mainly caused by hepatotoxicity. In comparison to the targeted posaconazole period, more patients had low CNI levels and acute rejection in the universal voriconazole period

<i>Achromobacter </i>spp. in a Cohort of Non-Selected Pre-and Post-Lung Transplant Recipients

Achromobacter is an opportunistic pathogen that mainly causes chronic lung infections in cystic fibrosis (CF) patients and is associated with increased mortality. Little is known about Achromobacter spp. in the lung transplant recipient (LTXr) population. We aimed at describing rates of Achromobacter spp. infection in LTXr prior to, in relation to, and after transplantation, as well as all-cause mortality proportion in infected and uninfected LTXr. We included 288 adult LTXr who underwent lung transplantation (LTX) between 1 January 2010 and 31 December 2019 in Denmark. Bronchoalveolar lavage was performed at regular intervals starting two weeks after transplantation. Positive cultures of Achromobacter spp. were identified in nationwide microbiology registries, and infections were categorized as persistent or transient, according to the proportion of positive cultures. A total of 11 of the 288 LTXr had transient (n = 7) or persistent (n = 4) Achromobacter spp. infection after LTX; CF was the underlying disease in 9 out of 11 LTXr. Three out of the four patients, with persistent infection after LTX, also had persistent infection before LTX. The cumulative incidence of the first episode of infection one year after LTX was 3.8% (95% CI: 1.6–6.0). The incidence rates of transient and persistent infection in the first year after LTX were 27 (12–53) and 15 (5–37) per 1000 person-years of follow-up, respectively. The all-cause mortality proportion one year after LTX was 27% in the Achromobacter spp. infected patients and 12% in the uninfected patients (p = 0.114). Achromobacter spp. mainly affected LTXr with CF as the underlying disease and was rare in non-CF LTXr. Larger studies are needed to assess long-term outcomes of Achromobacter spp. in LTXr

Invasive Aspergillosis among Lung Transplant Recipients during Time Periods with Universal and Targeted Antifungal Prophylaxis—A Nationwide Cohort Study

The optimal prevention strategy for invasive aspergillosis (IA) in lung transplant recipients (LTXr) is unknown. In 2016, the Danish guidelines were changed from universal to targeted IA prophylaxis. Previously, we found higher rates of adverse events in the universal prophylaxis period. In a Danish nationwide study including LTXr, for 2010–2019, we compared IA rates in time periods with universal vs. targeted prophylaxis and during person-time with vs. person-time without antifungal prophylaxis. IA hazard rates were analyzed in multivariable Cox models with adjustment for time after LTX. Among 295 LTXr, antifungal prophylaxis was initiated in 183/193 and 6/102 during the universal and targeted period, respectively. During the universal period, 62% discontinued prophylaxis prematurely. The median time on prophylaxis was 37 days (IQR 11–84). IA was diagnosed in 27/193 (14%) vs. 15/102 (15%) LTXr in the universal vs. targeted period, with an adjusted hazard ratio (aHR) of 0.94 (95% CI 0.49–1.82). The aHR of IA during person-time with vs. person-time without antifungal prophylaxis was 0.36 (95% CI 0.12–1.02). No difference in IA was found during periods with universal vs. targeted prophylaxis. Prophylaxis was protective of IA when taken. Targeted prophylaxis may be preferred over universal due to comparable IA rates and lower rates of adverse events