COVID-19-Associated Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Case Series in a Portuguese Hospital.

Invasive pulmonary aspergillosis (IPA) has become a recognizable complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs). Alveolar damage in the context of acute respiratory distress syndrome (ARDS) appears to be the culprit in facilitating fungal invasion in COVID-19 patients, leading to a COVID-19-associated pulmonary aspergillosis (CAPA) phenomenon. From November 2020 to 15 February 2021, 248 COVID-19 patients were admitted to our ICUs, of whom ten patients (4% incidence) were classified as either probable (six) or possible (four) CAPA cases. Seven patients had positive cultural results: Aspergillus fumigatus sensu stricto (five), A. terreus sensu stricto (one), and A. welwitschiae (one). Five patients had positive bronchoalveolar lavage (BAL) and galactomannan (GM), and two patients had both positive cultural and GM criteria. All but two patients received voriconazole. Mortality rate was 30%. Strict interpretation of classic IPA definition would have resulted in eight overlooked CAPA cases. Broader diagnostic criteria are essential in this context, even though differentiation between Aspergillus colonization and invasive disease might be more challenging. Herein, we aim to raise awareness of CAPA in view of its potential detrimental outcome, emphasizing the relevance of a low threshold for screening and early antifungal treatment in ARDS patients.

Short Communication: HIV and Tuberculosis Co-Infection Among Migrants in Portugal: A Brief Study on Their Sociodemographic, Clinical, and Genomic Characteristics.

HIV and tuberculosis (TB) are among the global deadliest diseases. Migrant populations are particularly vulnerable to these infections. Yet, literature is still scarce on the epidemiology of HIV-TB co-infection among migrants. In this study, we characterized native and migrant HIV patients followed in Portuguese hospitals, who were diagnosed with TB, regarding their sociodemographic, clinical, and genomic characteristics. Among 67 patients with HIV and TB diagnoses, there were 24 migrants, most from sub-Saharan Africa. Most patients had CD4+ T cell counts below 350 cells/µL, and were diagnosed simultaneously for HIV and TB. When compared to natives, migrants presented a higher proportion of non-B HIV-1 infections. Patients infected with these non-B HIV-1 strains presented higher viral loads, which can have an important impact for the transmissibility and pathogenicity of both diseases. Future studies should investigate different HIV strains and consequences for TB and HIV transmission and disease outcomes, especially among vulnerable populations.

Contribution of efflux to colistin heteroresistance in a multidrug resistant Acinetobacter baumannii clinical isolate.

PURPOSE: The mechanisms underlying colistin heteroresistance in Acinetobacter baumannii are not fully understood. Here, we investigated the role of efflux in colistin-heteroresistant populations of a multidrug-resistant (MDR) A. baumannii clinical isolate. METHODOLOGY: Three colistin-resistant A. baumannii strain variants isolated from the same clinical sample were studied for the presence of heteroresistance to colistin by drug susceptibility testing, genotyping and drug resistance target mutation analysis. The existence of active efflux was studied by synergism assays with efflux inhibitors, real-time efflux activity measurements and analysis of the mRNA transcriptional levels of selected efflux pump genes in response to colistin. RESULTS: All of the strain variants belong to the ST218, clonal complex 92, international clonal lineage II. Different colistin susceptibility levels were observed among the three strain variants, indicating that colistin-heteroresistant subpopulations were being selected upon exposure to colistin. No mutations were found in the genes lpxACD and pmrAB, which are associated with colistin resistance. The results showed the existence of synergistic interactions between efflux inhibitors and colistin and ethidium bromide. Real-time efflux assays demonstrated that the three strain variants had increased efflux activity that could be inhibited in the presence of the inhibitors. The efflux pump genes adeB, adeJ, adeG, craA, amvA, abeS and abeM were found to be overexpressed in the strain variants in response to colistin exposure. CONCLUSION: This study shows that efflux activity contributes to colistin heteroresistance in an MDR A. baumannii clinical isolate. The use of efflux inhibitors as adjuvants of the therapy can resensitize A. baumannii to colistin and prevent the emergence of drug resistance.