Quantifying guideline adherence in mucormycosis management using the EQUAL score

Mucormycosis is a difficult‐to‐diagnose life‐threatening disease with high morbidity and mortality. Adherence to guidelines that lead through complex management and support clinical decisions is however rarely reported. By applying the EQUAL Score, our study evaluates the management of mucormycosis at the University Hospital of Cologne, Germany.


| INTRODUC TI ON
Mucormycosis is a difficult-to-diagnose life-threatening disease with high morbidity and mortality. Clinical patterns are diverse and span from pneumonia to sinusitis, but other organs may be involved too.
Haematogenous dissemination and contiguous invasion of adjacent organs are characteristics explaining dire prognosis. 1 Guidelines lead through the complex management pathways and support clinical decisions. 7,8 However, mucormycosis guideline adherence is rarely reported. The difficulty quantifying adherence may be one reason. In 2018, the European QUALity (EQUAL) Score was derived from current guidelines and converts guideline recommendations into score points. 8,9 By applying the EQUAL Score, our study evaluates the management of mucormycosis at the University Hospital of Cologne, Germany. The study is part of a teaching project at our university, as previously described. 10

| Patients
We performed a retrospective chart review of patients with mucor-  (Table 1). This study was carried out in accordance with the ethical principles reflected in the Declaration of Helsinki. 11

| Documentation
Available cases were retrieved from the inpatient hospital informa-  (Table 2). Quality indicators were defined as diagnostic (max. 11 to 18 points depending on available specimen and/or biopsy), treatment (max. 8 points) and follow-up procedures (max. 6 points).
The maximum EQUAL Mucormycosis Score counts thus between 25 and 32 points. 9 All records were double-checked by an infectious diseases physician for missing values or inconsistency (PK and SCM), and queries were issued until resolved.

| Teaching
Documentation, interpretation of results and authoring of the paper were part of an established teaching concept on scientific writing at the University of Cologne embedded into the Medical School Research Track as described previously. 10 Twelve students participated in this project. After documentation of mucormycosis cases, students were taught drafting an original manuscript during a oneday course. The draft was revised by PK, SCM, JSt, FO, FF, JSG, FK and OAC.

| Statistics
Categorical variables are presented as frequencies and percentages, while continuous variables are presented as median and interquartile range, as appropriate, after variable distribution was evaluated with Shapiro-Wilk test. The latter were compared using Mann-Whitney U test. A two-tailed P-value < .05 was defined as statistically significant. Statistical computation and design of

| Economics
Clinical data were merged with economic data using a hospital con-  (Table 3).

| RE SULTS
The overall mucormycosis incidence rate of this retrospective cohort study was 0.06/1000 admissions.

| Patient characteristics
Of 29 patients identified, two were excluded due to insufficient data quality leading to 27 study participants documented retrospectively.  Note: Data are n (%). Twenty-nine patients were identified via screening. Two excluded due to missing data.
Diagnostic yield of fungal culture was 18.5% (n = 5); all these isolates were identified to species level and underwent susceptibility testing.
Twelve cases were defined proven by histopathology, 15 cases probable mycological evidence by culture or PCR in non-sterile according to the current EORTC/MSGERC consensus definitions of invasive fungal diseases (IFDs). 12 Median score achieved for diagnosis of mucormycosis was 7.0 (IQR: 6.0-12.0) out of 18.

| Economics
As demonstrated in

| D ISCUSS I ON
In this retrospective study at the University Hospital of Cologne, Germany, the overall mucormycosis incidence rate was 0.06/1000 admissions. This concurs with the reported general incidence of mucormycosis in Europe ranging from 0.006 to 0.2/1000 admissions. 13,14 Mould active prophylaxis was performed in 44.4% of patients who either had expected neutropenia for more than 10 days, or who had received allogeneic stem cell transplantation. The rate is similar to the 45.5% in the EQUAL Score validation study. 9 Median score achieved for diagnosis of mucormycosis was 7.0 Three of 27 patients (11.1%) died within seven days after diagnosis, eight within the first months-accounting for a total mortality of 48.1%. This is in accordance with previously reported studies showing 44% to 72.2%. 9,15 We conclude that the EQUAL Score may not be an appropriate tool for patients who die within the first days after diagnosis.
In these patients, treatment and follow-up management cannot be evaluated.
Cost data and economic analysis have shown higher resource consumption in the haematology group associated with higher average length of stay. Due to different main diagnosis and resource utilisation in both groups, we identified wide ranges of costs per case. There is an apparent need for detailed cost and reimbursement evaluations for such patients.
Results of this study are limited due to its retrospective character and relatively small patient number compared to other case series. 1,4,16 However, first application of the EQUAL Score within a small case series facilitates experience of its feasibility and insights in management at our own hospital. We decided to only include patients with electronic case files, which were introduced in 2011 at our hospital. Lacking reference populations for comparison are a further limitation as the score has not been applied to other patients yet. Studies with greater sample sizes are needed to verify our results in the future.
Data collected in this retrospective analysis represents a real-life scenario of clinical routine care. As performed previously, 10 we were able to combine our scientific approach with medical student teaching.
We observed management of mucormycosis aligning with current guidelines and hope to encourage other groups to use the EQUAL Score in routine clinical settings. Ultimately, we may learn whether guideline adherence in mucormycosis management improves patient outcome.

ACK N OWLED G M ENTS
The authors thank Susanna Proske and Susann Blossfeld for technical assistance.

CO N FLI C T O F I NTE R E S T
PK has received non-financial scientific grants from Miltenyi Biotec

E TH I C A L A PPROVA L
The authors confirm that the ethical policies of the journal, as noted in the author's guideline page, have been adhered to. Data collection was conducted in accordance with guidelines outlined by the