Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the ...subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.
Summary
During recent years, inappropriate antifungal use has contributed to the global increase in antifungal resistance and has played a role in the shift in the aetiology of invasive fungal ...infections. Moreover, overuse of antifungals may also lead to higher toxicity associated with unnecessary medication exposure and to increased healthcare costs. Antifungal stewardship (AFS) programmes consist of multidisciplinary interventions, led by specialists in infectious disease, microbiology and pharmacy that cooperate and communicate with the major prescribing departments in order to optimise antifungal therapies evaluating the indication, dose, streamlining and duration. Herein, we review the available evidence for the use of AFS and their impact on health economics. We also describe our AFS program, the successive steps we followed and the main difficulties we found.
Objectives
Information on the recently COVID‐19‐associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus ...disease 2019 (COVID‐19), and review the published literature from Western countries.
Methods
Prospective study (March to May, 2020) that included all COVID‐19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used.
Results
COVID‐19‐associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non‐immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA‐related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all‐cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%.
Conclusions
COVID‐19‐associated pulmonary aspergillosis must be considered a serious and potentially life‐threatening complication in patients with severe COVID‐19 receiving immunosuppressive treatment.
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant bacteria (MDR). In this study, the biofilm-forming capability of 209 MDR strains ...(Escherichia coli n = 106, Klebsiella pneumoniae n = 78, and Enterobacter spp. n = 25) isolated from rectal swabs in the first 48 hours before or after kidney (93 patients), liver (60 patients) or kidney/pancreas transplants (5 patients) were evaluated by using a microplate assay. Thirty-nine strains were isolated before transplant and 170 strains were isolated post-transplant. Overall, 16% of E. coli strains, 73% of K. pneumoniae strains and 4% Enterobacter strains showed moderate or strong biofilm production. Nine strains isolated from infection sites after transplantation were responsible of infections in the first month. Of these, 4 K. pneumoniae, 1 E. coli and 1 Enterobacter spp. strains isolated pre-transplant or post-transplant as colonizers caused infections in the post-transplant period. Our results suggest that in vitro biofilm formation could be an important factor for adhesion to intestine and colonization in MDR K. pneumoniae strains in SOT recipients, but this factor appears to be less important for MDR E. coli and Enterobacter spp.
•Daptomycin initial dosage was adequate in 68.3% (43/63) of patients.•High variability in daptomycin use and serum levels was observed.•A trough serum level (Cmin) of <3.18 mg/L was independently ...related to poor outcome.•Therapeutic drug monitoring might be useful to optimise daptomycin doses and outcome.
Therapeutic drug monitoring (TDM) could optimise daptomycin use. However, no validated serum target levels have been established. This prospective study at a tertiary centre including hospitalised patients receiving daptomycin aimed to evaluate the adequacy of daptomycin doses in a real-life study, assess interpatient variability in serum levels, identify predictive factors for non-adequate serum levels and assess their clinical impact. Blood samples trough (Cmin) and peak (Cmax) levels were drawn ≥3 days post-treatment initiation. Serum daptomycin concentrations were determined by HPLC. Outcome was classified as: (i) favourable, if clinical improvement or cure occurred with no adverse events; or (ii) poor, in the case of no clinical response, recurrence, related mortality or if adverse events were detected. Sixty-three patients (63.5% male; median age 63.0 years) were included. The most common indications for daptomycin use were bacteraemia (46.0%), complicated skin and soft-tissue infection (30.2%) and endovascular infection (15.9%). The initial dosage was adequate in 43 patients (68.3%), low in 14 (22.2%) and high in 6 (9.5%). Large interindividual variability in serum levels was observed, with a median Cmin of 10.6 mg/L (range 1.3–44.7 mg/L) and median Cmax of 44.0 mg/L (range 3.0–93.7 mg/L). Multivariate analysis showed that Cmin < 3.18 mg/L was independently related to poor outcome (OR = 6.465, 95% CI 1.032–40.087; P = 0.046). High variability in daptomycin use and serum levels was detected. Specific serum targets were identified as risk factors for poor outcome. TDM might be useful to optimise daptomycin doses and to avoid therapeutic failure.
The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of ...210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.
Nocardiosis at the turn of the century Minero, Maricela Valerio; Marín, Mercedes; Cercenado, Emilia ...
Medicine (Baltimore)
88, Issue:
4
Journal Article
Peer reviewed
Open access
Nocardia species is an uncommon pathogen that affects both immunosuppressed and immunocompetent patients. The clinical and microbiologic spectrum of nocardiosis has changed recently due to the ...widespread use of cotrimoxazole prophylaxis, the emergence of new types of immunosuppressed patients, and the improved identification of isolates using molecular techniques. Nocardia asteroides was traditionally considered the predominant organism, and prophylaxis with cotrimoxazole was considered almost universally protective. We conducted the current study to determine the incidence of nocardiosis and its microbiologic and clinical characteristics in a general hospital over the last 12 years. We reviewed the clinical records of all patients in whom Nocardia species was isolated from clinical specimens between 1995 and 2006. Nocardia isolates were identified by standard procedures and by 5' end 16S rRNA gene polymerase chain reaction (PCR) and sequencing. Susceptibility to cotrimoxazole, minocycline, imipenem, linezolid, and amikacin was determined by the broth microdilution method following the guidelines of the Clinical and Laboratory Standards Institute.The incidence of Nocardia infections did not increase significantly during the study period (0.39/100,000 inhabitants in 1995-1998 and 0.55/100,000 inhabitants in 2003-2006). Nocardia was recovered from 43 patients. Six were considered to be colonized. The colonizing species were N. farcinica, N. nova, and N. asteroides. All colonized patients had severe underlying pulmonary conditions and were treated with antimicrobials (6 patients) or corticosteroids (4 patients). Invasive nocardiosis was diagnosed in 37 patients (86.5% were men, and their mean age was 55.8 +/- 17.3 yr). The most common underlying condition in our institution was human immunodeficiency virus (HIV) infection (10 patients; 27%), followed by chronic obstructive pulmonary disease (8 patients; 21.6%), autoimmune diseases (8 patients; 21.6%), solid organ transplantation (7 patients; 18.9%), and cancer (4 patients; 10.8%). The most important risk factor for nocardiosis was corticosteroid administration (23 patients; 62.2%). Nocardiosis affected the lungs in 26 cases (70.3%), the skin in 3 cases (8.1%), and the central nervous system in 2 cases (5.4%). It was disseminated in 5 cases (13.5%) and caused otomastoiditis in 1 (2.7%). The species identified were N. cyriacigeorgica (32.4%), N. farcinica (24.3%), N. otitidiscaviarum (10.8%), N. veterana (8.1%), N. nova (5.4%), N. abscessus (5.4%), N. asiatica (2.7%), N. beijingensis (2.7%), N. brasiliensis (2.7%), N. carnea (2.7%), and Nocardia species (2.7%).Linezolid and amikacin were uniformly active against all the isolates, whereas 29.7% of isolates showed intermediate susceptibility to minocycline (minimum inhibitory concentration = 2 mg/L), 10.8% were resistant to cotrimoxazole, and 5.4% were resistant to imipenem. Nocardiosis occurred while the patients were on cotrimoxazole prophylaxis in 8 cases (21.6%). The strains isolated from these patients were susceptible to cotrimoxazole in 5 cases (62.5%) and resistant in 3 (37.5%). Overall, 13 patients died (35.1%); related mortality was 21.6% (8 patients). We conclude that HIV infection has become the most common underlying condition for invasive nocardiosis in our institution, followed by chronic lung disease. Previous use of corticosteroids was the main risk factor and was present in more than half the patients. New species of Nocardia have been identified, and administration of cotrimoxazole prophylaxis should no longer be considered highly reliable protection against nocardiosis. Larger studies of nocardiosis are required to better identify risk factors associated with mortality, and alternative and more effective methods of prevention must be developed.
The purpose of this study was to determine among patients with candidemia the real rate of ophthalmoscopy and the impact of performing ocular assessment on the outcome of the disease. We performed a ...post hoc analysis of a prospective, multicenter, population-based candidemia surveillance program implemented in Spain during 2010-2011 (CANDIPOP). Ophthalmoscopy was performed in only 168 of the 365 patients with candidemia (46%). Ocular lesions related to candidemia were found in only 13/168 patients (7.7%), of whom 1 reported ocular symptoms (incidence of symptomatic disease in the whole population, 0.27% 1/365). Ophthalmological findings led to a change in antifungal therapy in only 5.9% of cases (10/168), and performance of the test was not related to a better outcome. Ocular candidiasis was not associated with a worse outcome and progressed favorably in all but 1 evaluable patient, who did not experience vision loss. The low frequency of ophthalmoscopy and ocular involvement and the asymptomatic nature of ocular candidiasis, with a favorable outcome in almost all cases, lead us to reconsider the need for systematic ophthalmoscopy in all candidemic patients.
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