The battle against fungi: lessons in antifungal stewardship from COVID 19 times

The COVID-19 pandemic has highlighted the detrimental effect of secondary pathogens in patients with a primary viral insult. In addition to superinfections with bacterial pathogens, invasive fungal infections were increasingly reported. The diagnosis of pulmonary fungal infections has always been challenging; however, it became even more problematic in the setting of COVID-19, particularly regarding the interpretation of radiological findings and mycology test results in patients with these infections. Moreover, prolonged hospitalization in ICU, coupled with underlying host factors. such as preexisting immunosuppression, use of immunomodulatory agents, and pulmonary compromise, caused additional vulnerability to fungal infections in this patient population. In addition, the heavy workload, redeployment of untrained staff, and inconsistent supply of gloves, gowns, and masks during the COVID-19 outbreak made it harder for healthcare workers to strictly adhere to preventive measures for infection control. Taken together, these factors favored patient-to-patient spread of fungal infections, such as those caused by Candida auris, or environment-to-patient transmission, including nosocomial aspergillosis. As fungal infections were associated with increased morbidity and mortality, empirical treatment was overly used and abused in COVID-19-infected patients, potentially contributing to increased resistance in fungal pathogens. The aim of this paper was to focus on essential elements of antifungal stewardship in COVID-19 for three fungal infections, COVID-19-associated candidemia (CAC), -pulmonary aspergillosis (CAPA), and -mucormycosis (CAM).

Evaluation of the Abbott Panbio™ COVID-19 antigen detection rapid diagnostic test among healthcare workers in elderly care.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been especially dangerous for elderly people. To reduce the risk of transmission from healthcare workers to elderly people, it is of utmost importance to detect possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive healthcare workers as early as possible. We aimed to determine whether the Abbott Panbio™ COVID-19 antigen detection rapid diagnostic test (Ag-RDT) could be used as an alternative to reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The second aim was to compare the cycle threshold (Ct) in RT-qPCR with the results of the Ag-RDT. METHODS: A prospective diagnostic evaluation of the Abbott Panbio™ COVID-19 Ag-RDT among healthcare workers across three elderly care facilities as well as home-based elderly care workers who met clinical criteria for COVID-19 during the second wave of the COVID-19 pandemic. Per healthcare worker, the first nasopharyngeal swab was obtained to perform the Ag-RDT and the second swab for RT-qPCR. A Ct-value of < 40 was interpreted as positive, ≥ 40 as negative. RESULTS: A total of 683 healthcare workers with COVID-19 symptoms were sampled for detection of SARS-CoV-2 by both Ag-RDT and RT-qPCR. Sixty-three healthcare workers (9.2%) tested positive for SARS-CoV-2 by RT-qPCR. The overall sensitivity of Ag-RDT was 81.0% sensitivity (95%CI: 69.6-88.8%) and 100% specificity (95%CI: 99.4-100%). Using a cut-off Ct-value of 32, the sensitivity increased to 92.7% (95% CI: 82.7-97.1%). Negative Ag-RDT results were moderately associated with higher Ct-values (r = 0.62) compared to positive Ag-RDT results. CONCLUSION: The Panbio™ COVID-19 Ag-RDT can be used to quickly detect positive SARS-CoV-2 healthcare workers. Negative Ag-RDT should be confirmed by RT-qPCR. In case of severe understaffing and with careful consideration, fully vaccinated healthcare workers with Ag-RDT negative results could work with a mask pending PCR results.

Reply to Viner, A.; Ayrey, S. Comment on "Scheepers et al. Comparative Performance Testing of Respirator versus Surgical Mask Using a Water Droplet Spray Model. Int. J. Environ. Res. Public Health 2021, 18, 1599".

The response to our publication by Andrew Viner and Stewart Ayrey is much appreciated [...].

SARS-CoV-2 Risk Quantification Model and Validation Based on Large-Scale Dutch Test Events.

In response to the outbreak of SARS-CoV-2, many governments decided in 2020 to impose lockdowns on societies. Although the package of measures that constitute such lockdowns differs between countries, it is a general rule that contact between people, especially in large groups of people, is avoided or prohibited. The main reasoning behind these measures is to prevent healthcare systems from becoming overloaded. As of 2021 vaccines against SARS-CoV-2 are available, but these do not guarantee 100% risk reduction and it will take a while for the world to reach a sufficient immune status. This raises the question of whether and under which conditions events like theater shows, conferences, professional sports events, concerts, and festivals can be organized. The current paper presents a COVID-19 risk quantification method for (large-scale) events. This method can be applied to events to define an alternative package of measures replacing generic social distancing.

Reply to Viner, A.;Ayrey, S. Comment on “Scheepers et al. Comparative Performance Testing of Respirator versus Surgical Mask Using a Water Droplet Spray Model. Int. J. Environ. Res. Public Health 2021, 18, 1599”

When searching for ‘total inward leakage’ on Google, the first hit refers to a statement by the National Institute of Occupational Safety and Health [3]: “Total inward leakage (TIL) is an estimate of the performance of a respirator, which is measured as the leakage of contaminants through the filter media and through the face-seal interface and exhalation valve of respiratory protective devices under laboratory conditions. There is a lack of consensus on the most appropriate test method to measure TIL”. [...]it is not useful to discuss this with respect to its application in EN149:2001 [2]. For other tasks, good quality surgical masks provide sufficient protection. Since our paper was published, two additional systematic reviews have analyzed the current collection of studies, including the more recent studies.

Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial.

OBJECTIVES: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. METHODS: HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919). RESULTS: In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78-1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72-1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99-1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication. CONCLUSIONS: During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19.

Hand hygiene compliance and its drivers in long-term care facilities; observations and a survey.

BACKGROUND: Hand hygiene is an important measure to prevent healthcare-associated infections in long-term care facilities. OBJECTIVES: To evaluate compliance with hand hygiene recommendations by different nursing professionals in long-term care facilities and to investigate determinants potentially influencing hand hygiene and whether these differed between the different cadres of staff. METHODS: We conducted two sub-studies: we measured hand hygiene compliance of 496 professionals in 14 long-term care facilities (23 wards) through direct observation using World Health Organisation's 'five moments of hand hygiene' observation tool. In addition, we performed a survey to examine determinants that may influence hand hygiene and to determine differences between different cadres of staff. We used a principal component analysis approach with varimax rotation to explore the underlying factor structure of the determinants. RESULTS: We found an overall mean hand hygiene compliance of 17%. There was considerable variation between wards (5-38%) and between specific World Health Organization hand hygiene moments. In addition, hand hygiene compliance varied widely within and between different cadres of staff. The determinant analysis was conducted on 177 questionnaires. For all nursing professionals, we found multiple determinants in four domains: 'social context and leadership', 'resources', 'individual healthcare professional factors' and 'risk perception'. In two domains, several barriers were perceived differently by nursing assistants and nurses. In the domain 'social context and leadership', this included (1) how the manager addresses barriers to enable hand hygiene as recommended and (2) how the manager pays attention to correct adherence to the hand hygiene guidelines. In the 'risk perception' domain, this included a resident's risk of acquiring an infection as a result of the nursing professional's failure to comply with the hand hygiene guidelines. CONCLUSION: Hand hygiene compliance was low and influenced by multiple factors, several of which varied among different cadres of staff. When designing interventions to improve hand hygiene performance in long-term care facilities, strategies should take into account these determinants and how they vary between different cadres of staff. We recommend exploring hand hygiene determinants at ward level and among different cadres of staff, for example by using our exploratory questionnaire. TRIAL REGISTRATION: Registration number 50-53000-98-113, 'Compliance with hand hygiene in nursing homes: go for a sustainable effect' on ClinicalTrials.gov. Date of registration 28-6-2016.

BSAC Vanguard Series: The future of infection prevention and control: how COVID is already transforming our approach to antimicrobial resistance.

COVID -19 stimulated enormous focus on, and change in, infection prevention and control (IPC), not just in the healthcare sector but also among the general public. While global cooperation and guidance are important, there is also an essential role and benefit from national policies that respect local circumstances and cultural differences. Hospitals will have a new role and data sharing and cooperation between areas such as acute and long-term care will be even more important. Further integration of infection control, microbiology and infectious diseases staff in IPC teams is needed. The digital and AI revolutions have roles to play in how and where patients are seen and diagnosed. The built environment may have longer-term influence on changing the behaviour of health professionals than education and training. One constant is the need for highly trained, flexible and motivated staff in these IPC teams.

Hand hygiene compliance in Dutch general practice offices.

BACKGROUND: Hand hygiene (HH) is considered one of the most important measures to prevent healthcare-associated infections (HAI). Most studies focus on HH compliance within the hospital setting, whereas little is known for the outpatient setting. The aim of this study was to evaluate compliance with HH recommendations in general practitioners (GPs) office, based on World Health Organization (WHO) guideline. METHODS: An observational study was conducted at five Dutch GPs-practices in September 2017. We measured HH compliance through direct observation using WHO's 'five moments of hand hygiene' observation tool. All observations were done by one trained professional. RESULTS: We monitored a total of 285 HH opportunities for 30 health care workers (HCWs). The overall compliance was 37%. Hand hygiene compliance was 34, 51 and 16% for general practitioners, practice assistants, and nurses, respectively. It varies between 63% after body fluid exposure and no HH performance before-, during and after home visit of a patient (defined as moment 5). The preferred method of HH was soap and water (63%) versus 37% for alcohol-based hand rub (ABHR). The median time of disinfecting hands was 8 s (range 6-11 s) for HCWs in our study. CONCLUSIONS: HH compliance among HCWs in Dutch GPs was found to be low, especially with regard to home visits. The WHO recommended switch from hand wash to ABHR was not implemented by the majority of HCWs in 5 observed GPs offices.

Comparative Performance Testing of Respirator versus Surgical Mask Using a Water Droplet Spray Model.

BACKGROUND: During the SARS-CoV-2 pandemic, there was shortage of the standard respiratory protective equipment (RPE). The aim of this study was to develop a procedure to test the performance of alternative RPEs used in the care of COVID-19 patients. METHODS: A laboratory-based test was developed to compare RPEs by total inward leakage (TIL). We used a crossflow nebulizer to produce a jet spray of 1-100 µm water droplets with a fluorescent marker. The RPEs were placed on a dummy head and sprayed at distances of 30 and 60 cm. The outcome was determined as the recovery of the fluorescent marker on a membrane filter placed on the mouth of the dummy head. RESULTS: At 30 cm, a type IIR surgical mask gave a 17.7% lower TIL compared with an FFP2 respirator. At 60 cm, this difference was similar, with a 21.7% lower TIL for the surgical mask compared to the respirator. When adding a face shield, the TIL at 30 cm was further reduced by 9.5% for the respirator and 16.6% in the case of the surgical mask. CONCLUSIONS: A safe, fast and very sensitive test method was developed to assess the effectiveness of RPE by comparison under controlled conditions.

Not sick enough to worry? "Influenza-like" symptoms and work-related behavior among healthcare workers and other professionals: Results of a global survey.

BACKGROUND: Healthcare workers (HCWs) and non-HCWs may contribute to the transmission of influenza-like illness (ILI) to colleagues and susceptible patients by working while sick (presenteeism). The present study aimed to explore the views and behavior of HCWs and non-HCWs towards the phenomenon of working while experiencing ILI. METHODS: The study was a cross-sectional online survey conducted between October 2018 and January 2019 to explore sickness presenteeism and the behaviour of HCWs and non-HCWs when experiencing ILI. The survey questionnaire was distributed to the members and international networks of the International Society of Antimicrobial Chemotherapy (ISAC) Infection Prevention and Control (IPC) Working Group, as well as via social media platforms, including LinkedIn, Twitter and IPC Blog. RESULTS: In total, 533 respondents from 49 countries participated (Europe 69.2%, Asia-Pacific 19.1%, the Americas 10.9%, and Africa 0.8%) representing 249 HCWs (46.7%) and 284 non-HCWs (53.2%). Overall, 312 (58.5%; 95% confidence interval [CI], 56.2-64.6) would continue to work when sick with ILI, with no variation between the two categories. Sixty-seven (26.9%) HCWs and forty-six (16.2%) non-HCWs would work with fever alone (p<0 .01) Most HCWs (89.2-99.2%) and non-HCWs (80%-96.5%) would work with "minor" ILI symptoms, such as sore throat, sinus cold, fatigue, sneezing, runny nose, mild cough and reduced appetite. CONCLUSION: A future strategy to successfully prevent the transmission of ILI in healthcare settings should address sick-leave policy management, in addition to encouraging the uptake of influenza vaccine.