Nosocomial Aspergillosis Research Articles

Invasive aspergillosis in liver transplant recipients.

Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries. We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions. The incidence of IA in LT recipients is low (1.8%), while mortality is high (∼50%). It occurs mainly early (<3 months) after LT. Some risk factors have been identified before (corticosteroid, renal, and liver failure), during (massive transfusion and duration of surgical procedure), and after transplantation (intensive care unit stay, re-transplantation, re-operation). Diagnosis can be difficult and therefore requires full radiological and clinicobiological collaboration. Accurate identification of Aspergillus species is recommended due to the cryptic species, and susceptibility testing is crucial given the increasing resistance of Aspergillus fumigatus to azoles. It is recommended to reduce the dose of tacrolimus (50%) and to closely monitor the trough level when introducing voriconazole, isavuconazole, and posaconazole. Surgery should be discussed on a case-by-case basis. Antifungal prophylaxis is recommended in high-risk patients. Environmental preventative measures should be implemented to prevent outbreaks of nosocomial aspergillosis in LT recipient units. IA remains a very serious disease in LT patients and should be promptly sought and, if possible, prevented by clinicians when risk factors are identified.

Aspergillus wound infection in an immune-competent patient – A case report

• Abdominal surgical site aspergillosis can be seen in an immunocompetent patient. • Surgical site aspergillosis is a form of cutaneous aspergillosis. • Prevention of surgical site aspergillosis combines clinical and environmental considerations. • Therapy involves medical and surgical approach for optimal outcomes. Abdominal aspergillosis is a life-threatening, opportunistic fungal infection that mainly affects immunocompromised patients. In this report, we present a case of abdominal surgical site aspergillosis in an immunocompetent patient. A 74-year-old immune-competent woman that had a prolonged hospitalization in the Intensive Care (ICU) Unit with several abdominal surgeries and multiple antibiotic treatment regimens. The abdomen remained open between interventions. 21 days following ICU admission a diagnosis of surgical site aspergillosis was made, treated with systemic and topical antifungal treatment. While nosocomial aspergillosis typically affects immunocompromised patients, immunocompetent patients also become susceptible when the skin barrier is broken and tissue is exposed to the environment. Treatment consisted with surgical debridement and systemic antifungal therapy. This case provides an example of extensive and rare surgical infection.

Blockade Of PD-1 Attenuated Postsepsis Aspergillosis Via The Activation of IFN-γ and The Dampening of IL-10.

Nosocomial aspergillosis in patients with sepsis has emerged in the past few years. Blockade of PD-1/PD-L pathway has tended to become a promising therapeutic strategy as it improved the outcome of bacterial sepsis and postsepsis secondary fungal infection. Recently, the controversial effects of PD-1 blockade on infectious diseases, including aspergillosis, have been demonstrated; therefore, the efficacy of anti-PD-1 drug still remains to be elucidated. Cecal ligation and puncture (CLP) was conducted as a mouse sepsis model. Aspergillus fumigatus spores were intravenously inoculated on day 5 post-CLP, when the immune cells succumbed to exhaustion. Amphotericin B was medicated together with or without anti-PD-1 treatment after Aspergillus infection. Amphotericin B alone was not effective to treat the CLP-mice with secondary aspergillosis. In contrast, antifungal medication with the adjunctive anti-PD-1 treatment attenuated the fungal burdens in blood and internal organs, and improved the survival rate of the mice with secondary aspergillosis. These outcomes of PD-1 blockade were concurring with the enhanced CD86 expression on splenocytes, the augmented serum IFN-γ, and the dampened IL-10. Activated T cells from anti-PD-1-treated mice also highly increased IFN-γ and diminished IL-10 production. The blockade of PD-1 on postsepsis aspergillosis presumably reinvigorated exhausted antigen-presenting cells and T cells by upregulating CD86 expression and IFN-γ production, and dampened IL-10 production, which consequently leaded to the attenuation of secondary aspergillosis. The adjunctive anti-PD-1 therapy may become a promising strategy for the advanced immunotherapy against lethal fungal infection.

Demolition activities in a healthcare facility: results from a fungal surveillance after extraordinary preventive measures

ObjectivesAspergillus spp could be responsible of nosocomial aspergillosis in immunocompromised patients. In 2018, it was decided to demolish a building of Careggi Hospital (Florence, Italy), the Chief Medical Officer ordered a 9-months-long air and surface microbiological sampling and extraordinary preventive measures. Study designA 9-months-long prospective study. MethodsAfter mapping the at-risk areas, air and surface samples were collected in different locations: in corridors, in rooms (high efficiency particulate air filter (HEPA) filtered or not), and outdoors. The samples were collected during the critical phases of the demolition. Air temperature and weather conditions were determined and recorded at the beginning of each sampling. ResultsSeventy-eight air samples and 72 surface samples were collected. The results showed highest contamination at time zero (before extraordinary preventive measures) and in the wards without HEPA filtered air. No specific prophylaxis strategy was implemented at our hospital for immunocompromised patients, and no cases of aspergillosis were recorded. ConclusionsOur results showed that extraordinary protective measures, the use of air treatment systems, and a continuous monitoring could be associated with decreased Aspergillus air contamination during construction, renovation, or demolition works.

Renovation in hospitals: a case study of source control ventilation in work zones

ABSTRACTApproximately half of the nosocomial aspergillosis outbreaks in hospitals have been associated with renovation activities. When disturbed, spores encapsulated in building materials can be aerosolized and transported throughout the healthcare facility causing potentially fatal complications, particularly among elderly and immunocompromised patients. Thus, a series of experiments were conducted in an actual hospital to observe containment and removal of airborne particulates with respect to ventilation arrangement and directional airflow. Computational models were then developed to further study the spread of contamination during a hospital renovation project. Results of this study suggest that although directional airflow (negative pressure) was effective in containing particulates across an open doorway between patient and contaminated spaces, turbulence caused by door motion and the location of the exhaust grilles affected the transport of particulates in the work zone. A new source-control ventilation strategy is proposed where the arrangement of supply and exhaust air ventilation is optimized to more effectively contain and remove airborne particulates within hospital work zones. Results indicate that the location of supply and exhaust air relative to the contaminant source can increase particulate removal by an additional 26%, or roughly the effect of doubling work zone air changes – without added operations and maintenance (O&M) costs.

A 2-year comparative study of mold and bacterial counts in air samples from neutral and positive pressure rooms in 2 tertiary care hospitals

Immunocompromised patients are at risk of invasive fungal infection. These high-risk patients are nursed in protective isolation to reduce the risk of nosocomial aspergillosis while in hospital-ideally in a positive pressure single room with high-efficiency particulate air filtration. However, neutral pressure rooms are a potential alternative, especially for patients requiring both protective and source isolation. This study examined mold and bacterial concentrations in air samples from positive and neutral pressure rooms to assess whether neutral pressure rooms offer a similar environment to that of positive pressure rooms in terms of mold concentrations in the air. Mold concentrations were found to be similar in the positive and neutral pressure room types examined in this study. These results add to the paucity of literature in this area.

L’infection aspergillaire peut-elle être une complication du drainage pleural ?

Four cases of nosocomial aspergillosis are described where the responsibility of pleural drainage is advocated. Infection was pulmonary once, pleural three times. Pleural suction had been long lasting with incomplete re-expansion of the lung and major air leaks. The hypothesis of the responsibility of pleural drainage in the advent of aspergillosis is reinforced by the revision of medical papers, which leads to the conviction that similar cases have been described yet, even though the mechanism of the contamination had not been understood. Prevention needs to limitate the lasting of the suction, especially if there are major air leaks. Cure needs total re-expansion of the lung and suppression of any pleural cavity, even if a thoracoplasty is needed. An anti-fungal therapy is not always needed.

Ultraviolet irradiation: An effective inactivation method of Aspergillus spp. in water for the control of waterborne nosocomial aspergillosis

Invasive aspergillosis is the second most common cause of nosocomial fungal infections and occurring mainly by Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger. There is evidence that nosocomial aspergillosis may be waterborne. This study was conducted to evaluate the ultraviolet (UV) irradiation efficiency in terms of inactivating the most important Aspergillus species in water since these are potential sources for nosocomial aspergillosis. A continuous flow UV reactor which could be used as a point-of-use (POU) system was used to survey Aspergillus inactivation by UV irradiation. The inactivation efficiency of UV fluence (4.15–25 mJ/cm2) was measured by determination of fungal density in water before and after radiation. Because turbidity and iron concentration are two major water quality factors impacting UV disinfection effectiveness, the potential influence of these factors on UV inactivation of Aspergillus spp. was also measured. The 4 log inactivation for A. fumigatus, A. niger and A. flavus at a density of 1000 cfu/ml was achieved at UV fluences of 12.45 mJ/cm2, 16.6 mJ/cm2 and 20.75 mJ/cm2, respectively. The inactivation efficiency for lower density (100 cfu/ml) was the same as for the higher density except for A. flavus. The removal efficiency of Aspergillus spp. was decreased by increasing the turbidity and iron concentration. UV disinfection could effectively inactivate Aspergillus spores from water and eliminate potential exposure of high-risk patients to fungal aerosols by installation of POU UV systems.

A survey on distribution and toxigenicity of Aspergillus flavus from indoor and outdoor hospital environments

In the present study, genetic diversity and mycotoxin profiles of Aspergillus flavus isolated from air (indoors and outdoors), levels (surfaces), and soils of five hospitals in Southwest Iran were examined. From a total of 146 Aspergillus colonies, 63 isolates were finally identified as A. flavus by a combination of colony morphology, microscopic criteria, and mycotoxin profiles. No Aspergillus parasiticus was isolated from examined samples. Chromatographic analyses of A. flavus isolates cultured on yeast extract-sucrose broth by tip culture method showed that approximately 10% and 45% of the isolates were able to produce aflatoxin B(1) (AFB(1)) and cyclopiazonic acid (CPA), respectively. Around 40% of the isolates produced sclerotia on Czapek-Dox agar. The isolates were classified into four chemotypes based on the ability to produce AF and CPA that majority of them (55.5%) belonged to chemotype IV comprising non-mycotoxigenic isolates. Random amplified polymorphic DNA (RAPD) profiles generated by a combination of four selected primers were used to assess genetic relatedness of 16 selected toxigenic and non-toxigenic isolates. The resulting dendrogram demonstrated the formation of two separate clusters for the A. flavus comprised both mycotoxigenic and non-toxigenic isolates in a random distribution. The obtained results in this study showed that RAPD profiling is a promising and efficient tool to determine intra-specific genetic variation among A. flavus populations from hospital environments. A. flavus isolates, either toxigenic or non-toxigenic, should be considered as potential threats for hospitalized patients due to their obvious role in the etiology of nosocomial aspergillosis.

Hospital environment and invasive aspergillosis in patients with hematologic malignancy

To determine whether there is a correlation between sources of Aspergillus spores in a high-efficiency particulate air (HEPA)-filtered environment and nosocomial invasive aspergillosis (IA), we performed a detailed environmental assessment and case review. From April to October 2004, 626 bioaerosol samples, 1,257 surface samples, and 607 water samples were obtained from 74 HEPA-filtered air hospital rooms occupied by 458 patients with hematologic malignancies. Samples were collected prospectively from the room before and after cleaning within 1 hour of patient admission or discharge. Aspergillus spp was isolated from 21 surface samples and 46 bioaerosol samples. Interestingly, Aspergillus spp was not isolated from any water samples. Aspergillus spp was isolated from 21 surface samples and 46 bioaerosol samples. Interestingly, Aspergillus spp were not isolated from any water samples. The majority (90%) of the positive bioaerosol samples had ≤ 10 colony-forming units of Aspergillus/m3 of air. Only 2 patients developed nosocomial IA. No correlations were found between Aspergillus species isolated from the hospital rooms and those causing IA. The risk of hematologic malignancy patients acquiring nosocomial aspergillosis from water or HEPA-filtered air is very low.

Correlation between the incidence of nosocomial aspergillosis and room reconstruction of a haematological ward

Invasive pulmonary aspergillosis (IPA) represents ~ a major cause of morbidity and mortality in patients I with impaired function of the immune system such as in patients with acute myeloid leukaemia (AML). We investigated the in uence of the patients’ room occu- pancy and the sanitary facilities with regard to the inci- dence of IPA after reconstruction of a haematological ward. This is a retrospective cohort-control study in patients with newly diagnosed AML. Thirty ve patients were treated before and 28 patients in the time after the reconstruction works. The median time of neutropenia was 18.5 days vs. 19.5 days. Twelve patients before and 11 patients after the reconstruction developed IPA (p = 0.794). The incidence of IPA did not decrease after a reduction in the patients’ occupancy and improvement of the sanitary equipment. This study emphasises the presumed importance of optimal physical barriers, e.g. air ltration and/or antimycotic prophylaxis in high-risk patients.

Infection Control Measures to Prevent Invasive Mould Diseases in Hematopoietic Stem Cell Transplant Recipients

Invasive mould diseases, particularly aspergillosis, are important causes of morbidity and mortality in allogeneic stem cell transplant recipients. Mould spores are ubiquitous in the environment. Guidelines established by the Centers for Disease Control (CDC) and other authoritative organizations focus on approaches to reduce exposure to mould spores. These recommendations include avoidance of areas and activities expected to result in high levels of mould spores (e.g., construction, gardening) and use of specially designed units (protected environments) where additional standards (e.g., HEPA-filtered rooms) are in place to minimize mould exposure. These recommendations are based on consensus criteria and limited clinical data largely derived from single-center retrospective studies. In addition, highly immunocompromised stem cell transplant recipients are commonly managed as outpatients, where engineering standards of the inpatient protected environment are not feasible. In the absence of an outbreak with an identified environmental source (e.g., a contaminated air vent), it is not possible to reliably distinguish community-acquired from nosocomial aspergillosis. Adherence to infection control guidelines, acknowledging their limitations, combined with evidence-based targeted antifungal prophylaxis for the highest risk transplant recipients, is likely to be the most effective approach to prevent invasive mould diseases.

Efficacité des mesures environnementales dans la prévention de l’aspergillose invasive nosocomiale liée aux travaux : bilan de cinq années d’expérience

Invasive hospital-acquired aspergillosis (IA) is responsible for lethal outbreaks. In 2002, an interdisciplinary team was created in the teaching hospital of Rouen in order to organize the surveillance of construction sites by the implementation of environmental measures of prevention. The aim of our study was to estimate the efficiency of these measures using an indirect indicator, reflecting the incidence of the cases of invasive nosocomial aspergillosis (AI): the consumption of antifungals. From the nominative prescriptions established, we studied the medical files about 210 patients to track down the number of IA cases in intensive care unit (ICUI) and in pediatric hematology-oncology units between 2002 and 2006. The incidence of the cases was put in parallel with the various periods of level 5-risk works during these five years. The relative risk of appearance of the disease was calculated. In pediatric haematology-oncology unit, 35 cases were diagnosed on 99 medical files which have been studied and in ICU 19 cases were classified on 93 studied files. The follow-up of the incidence in both units stake in parallel with the periods of level 5-risk works does not show increase of the number of cases. The calculated relative risk indicates the same result: the level 5-risk works are not a factor facilitating the appearance of invasive aspergillosis cases. This study shows the importance of the environmental measures of prevention during the periods of works within services for risk. The coordination of the actors within an interdisciplinary cell seems thus essential for the prevention of AIN.

Nosocomial aspergillosis and building construction

Healthcare-associated infections (HAI) with Apergillus pose a serious threat to those most severely immune suppressed patients. Outbreaks of nosocomial aspergillosis have occurred mainly among neutropenic patients, but with several important exceptions. HAI due to aspergillosi has occurred in association with environmental disturbances including but not limited to: hospital construction, maintenance, demolition and renovation; contaminated fireproofing materials; air filters in hospital ventilation systems, and via contaminated carpeting. It behooves those in the practice of patient care to prevent these situations before they occur, as opposed to dealing with them once they happen. The framework of the six links in the infectious disease process will be used to examine healthcare-associated invasive aspergillosis: causative agent, portal of entry, susceptible host, portal of exit, reservoir and mode of transmission. Two particular interventions: the Protective Environment (PE), and the Infection Control Risk Assessment (ICRA), will be outlined. Building construction projects and the number of neutropenic patients are likely to continue to increase. Therefore, future directions need to focus on reducing the susceptibility of the susceptible host and reducing the exposure to Aspergillus from environmental sources. In addition, recently released guidelines with control measures aimed at reducing environmental exposure to Aspergillus need to be further studied.

Detection of fungal development in closed spaces through the determination of specific chemical targets

In addition to the biodegradation problems encountered in buildings, exposure of their occupants to moulds is responsible for numerous diseases: infections (invasive nosocomial aspergillosis), immediate or delayed allergies, food-borne infections and different types of irritation. In this context, the aim of our work has been to determine specific chemical tracers for fungal development on construction materials. More generally, by detecting a specific chemical fingerprint of fungal development, our objective was to propose a microbiological alert system which could control systems and/or procedures for the microbiological treatment of indoor areas. We therefore characterized the chemical emissions from six types of construction material contaminated artificially by moulds. Chemical fingerprints were established for 19 compounds arising specifically from fungal metabolism: 2-ethylhexanoic acid methyl ester, 1-octen-3-ol, 3-heptanol, 3-methyl-1-butanol, 2-methyl-1-butanol, 1,3-octadiene, 2-(5H)-furanone, 2-heptene, α-pinene, 2-methylisoborneol, 4-heptanone, 2-methylfuran, 3-methylfuran, dimethyldisulfide, methoxybenzene, a terpenoid and three sesquiterpenes. Determining the origin of these compounds and their specific links with a growth substrate or fungal species made it possible to judge the pertinence of choosing these compounds as tracers. Thus the detecting specific volatile organic compounds emitted as from the second day of fungal growth demonstrated that this approach had the advantage of detecting fungal development both reliably and rapidly before any visible signs of contamination could be detected.

Environmental factors of nosocomial invasive aspergillosis

随着院内免疫缺陷人群的增多,侵袭性曲霉病的发病率逐年增加.研究显示,院内曲霉感染不仅与宿主自身因素有关,亦和空气、水源、院内施工等环境因素密切相关.了解院内侵袭性曲霉病的流行病学、与环境真菌分布的相关性、环境真菌监控措施对降低其发病率、提高免疫缺陷宿主存活率具有重要意义。

Invasive nosocomial aspergillosis associated with heart failure and complete heart block following recovery from dengue shock syndrome

To report a case of invasive aspergillosis, associated with complete heart block and heart failure, in an immunocompetent child recovering from dengue shock syndrome. Case report and literature review. Pediatric intensive care unit in a tertiary care center. A 9-yr-old boy was admitted to our pediatric intensive care unit with dengue shock syndrome, for which he was successfully managed. During the recovery phase, the child developed recurrence of fever and signs of congestive heart failure. Thereafter, he developed complete heart block and died. Myocardial biopsy revealed myocarditis and invading fungal elements with branching septate hyphae suggestive of Aspergillus. A renal biopsy specimen also showed glomerular invasion with Aspergillus and patchy necrosis. This suggested the diagnosis of invasive aspergillosis. This case highlights an unusual manifestation of invasive aspergillosis in a critically ill immunocompetent child.

Reduced fungal contamination of the indoor environment with the Plasmair™ system (Airinspace)

Aspergillus spp. and other moulds cause life-threatening opportunistic infections in immunocompromised patients. Indoor contamination and construction work that liberate fungal spores are a major source of nosocomial aspergillosis. Dijon hospital is a tertiary care institution in northeast France undergoing construction work beside high-risk clinical units. To determine the impact of this activity, a surveillance programme was implemented one year before building work began in order to establish baseline levels of contamination. Air and surface fungal contamination in adult and paediatric haematology units were prospectively examined following use, or not, of a new air-treatment system with mobile Plasmair units (Airinspace). There were significant reductions in overall fungal contamination for the Plasmair treated rooms for air and surface samples in both clinical units. Plasmair treatment also significantly reduced A. fumigatus in the air. These data suggest that Plasmair units may provide an efficient method of reducing indoor fungal contamination in hospitals.

Maîtrise du risque fongique environnemental dans les établissements de santé

In the attempt of chemoprophylaxis that has been proved to be effective, prevention of hospital-acquired fungal infection is currently based on air-control measures with monitoring of environmental fungal contamination. It is the most important way to significantly reduce the incidence of nosocomial aspergillosis in particular. High-risk patients should thus benefit from air treatment such as high-efficiency particulate air (HEPA) filtration, laminar airflow systems, and high rates of room-air changes, positive pressure, and well-sealed rooms. Prevention strategies should also fight contamination from the many other sources of spore transmission, food, water etc. Monitoring of environmental fungal contamination detects increases in conidia density and assesses the efficiency of air filtration. Monitoring of air and surface fungal loads is highly recommended (i) in hospital units, which benefit from air control measures, and (ii) during specific investigations in the case of Aspergillus infection. We describe the current French regulatory procedures on hospital environmental surveillance. The French Afnor recommendation (NF S 90 351) specifies different tests to evaluate the effectiveness of protective measures during installation of the system and once it is up and running. These tests include specific biocontamination controls. The French hospital guidelines specify that each hospital is responsible for the air and the water they provide to the patient, and that air-control efficiency must be monitored. Optimal environmental monitoring requires efficient and specific methodologies to detect fungal spores in addition to bacteria.

Questions linked to Vonberg R-P, Gastmeier P. Nosocomial aspergillosis in outbreak settings. J Hosp Infect 2006;62:246–254.

Questions linked to Vonberg R-P, Gastmeier P. Nosocomial aspergillosis in outbreak settings. J Hosp Infect 2006;62:246–254.