In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary aspergillosis (CAPA). We identified 85 cases from 22 studies. The frequency of CAPA is currently unknown but ranges between <5% to >30% in different case series; the possibility of colonization rather than invasive disease is the most important confounder. The vast majority of patients with CAPA did not have any of the classic host risk factors, such as immunosuppression from organ transplant or neutropenia, although a significant proportion (46%) had received corticosteroids. Age, pulmonary comorbidities and male sex were associated with higher mortality. Patients treated with voriconazole had numerically lower case-fatality rate. Clinical vigilance for CAPA is advisable in critically ill patients with COVID-19 who are not improving, even those who do not meet classic host criteria for invasive mycoses, especially if they are receiving corticosteroids. A thorough, multi-faceted diagnostic work-up and early initiation of a mold-active triazole may be lifesaving. Further research studies using standardized, uniform definitions of invasive disease and colonization are urgently needed.

Invasive pulmonary aspergillosis (IPA) is increasingly recognized as a complication of severe influenza and coronavirus disease-2019. The extent to which other respiratory viral infections (RVIs) predispose to IPA is unclear. We performed a retrospective review of IPA occurring within 90-days of respiratory syncytial virus (RSV), parainfluenza or adenovirus infections (non-influenza respiratory viral infections; NI-RVI) in patients who underwent solid organ transplant between 1/15/2011 and 12/19/2017. At median post-transplant follow-up of 43.4 months, 221 of 2986 patients (7.4%) developed 255 RSV, parainfluenza or adenovirus infections. IPA complicating these NI-RVIs was exclusively observed in lung and small bowel transplant recipients, in whom incidence was 5% and 33%, respectively. Cumulative prednisone doses &gt;140 mg within 7 days and pneumonia at time of NI-RVI were independent risk factors for IPA (odds ratios: 22.6 (4.5-112) and 7.2 (1.6-31.7), respectively). Mortality at 180-days following NI-RVI was 27% and 7% among patients with and without IPA, respectively (p=0.04). In conclusion, IPA can complicate RSV, parainfluenza and adenovirus infection in lung and small bowel transplant recipients. Future research is needed on the epidemiology of IPA complicating various RVIs. In the interim, physicians should be aware of this complication.

BackgroundDespite reports questioning its efficacy, cefepime remains a first-line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime in this setting.MethodsWe searched the PubMed and EMBASE databases to identify randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published until November 28, 2016.ResultsThirty-two trials, reporting on 5724 patients, were included. Clinical efficacy was similar between study arms (P = .698), but overall mortality was greater among cefepime-treated patients (risk ratio [RR] = 1.321; 95% confidence interval [CI], 1.035–1.686; P = .025). Also of note, this effect seemed to stem from trials using low-dose (2 grams/12 hours, 100 mg/kg per day) cefepime monotherapy (RR = 1.682; 95% CI, 1.038–2.727; P = .035). Cefepime was also associated with increased mortality compared with carbapenems (RR = 1.668; 95% CI, 1.089–2.555; P = .019), a finding possibly influenced by cefepime dose, because carbapenems were compared with low-dose cefepime monotherapy in 5 of 9 trials. Treatment failure in clinically documented infections was also more frequent with cefepime (RR = 1.143; 95% CI, 1.004–1.300; P = .043). Toxicity-related treatment discontinuation was more common among patients that received high-dose cefepime (P = .026), whereas low-dose cefepime monotherapy resulted in fewer adverse events, compared with alternative monotherapy (P = .009).ConclusionsCefepime demonstrated increased mortality compared with carbapenems, reduced efficacy in clinically documented infections, and higher rates of toxicity-related treatment discontinuation. The impact of cefepime dosing on these outcomes is important, because low-dose regimens were associated with lower toxicity at the expense of higher mortality.

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