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Official websites use. Share sensitive information only on official, secure websites. Corresponding author. Nevertheless, IFIs are usually neglected and underdiagnosed. IFIs should be considered as a public-health problem and major actions should be taken to tackle them and their associated costs. This was a retrospective, transversal study carried-out in four Mexican hospitals. All IFIs occurring during were included. Incidence rates and estimation of antifungal therapy's expenditure for one year were calculated. Adjustments for costs of AKI were done. Two-hundred thirty-eight cases were included. The overall incidence of IFIs was 4. Invasive candidiasis showed the highest incidence rate 1. AKI increased the cost of antifungal therapy 4. Costs estimations allow to assess cost-avoidance strategies to increase targeted driven therapy and decrease adverse events and their costs. Invasive fungal infections IFIs affect more than 1. The principal reasons for misdiagnosing are the absence of diagnostic tools plus insufficient training of health-care staff. The lack of diagnostic tests based on culture and non-culture techniques, can lead to overuse of empirical therapy, mainly for individuals with hematological diseases and critically ill patients. IFIs should be considered as a public health problem, therefore a number of major actions should be taken to address these infections and their associated costs. In this study, we report the incidence rates of IFIs in four Mexican hospitals, describe the economic cost associated with IFIs therapy and the impact of adverse events such as acute kidney injury, liver damage, and ICU stay. Mexico has a divided health system where public health care is furthered divided into people with and without social insurance. The SP consists of well defined benefit packages and medicines that provides coverage only for certain services such as preventive medicine and primary care, national vaccination program, HIV infection care, and catastrophic medical expenditures associated with certain conditions such as critical care, neonatal care, congenital disorders, certain malignancies, hepatitis C infection, stem-cell, and solid-organ transplants with different limitations regarding age. Four hospitals located in different states around the country that provide medical attention to patients without social security were included. The National Cancer Institute INCan of Mexico City is a bed tertiary care center focused on the treatment of adult oncological patients who are referred mostly from the central part of the country for medical attention. It provides service only to adults, without gynecology and obstetrics department. The patients pay the hospital length of stay LOS and procedures according to the assigned SEL, the rest is absorbed by the hospital. All expenses are paid according to the SEL. Patients are referred from the middle and east part of the country. In all the hospitals, patients with diseases not covered by SP or catastrophic diseases pay hospital expenses according to the SEL, and purchase medications not provided by the hospital at full cost. All IFIs occurring during were identified using the databases of each participating hospital. Clinical data was recovered from medical records. This included demographic information, previous comorbidities, type of IFI, antifungal type used, duration, and indication, as well as, outcomes such as development of acute kidney injury AKI , liver damage LD , ICU admission, hospital LOS, and mortality. Data regarding costs of antifungal drugs, hospital, and ICU stay were provided by each participant hospital for each patient. In Mexico, hospitals buy certain authorized antifungal drugs at pre-established prices during public tenders Supplementary material, Table S1. Estimate expenses for antifungals were calculated based on the prices paid by each hospital Table S1. All identified IFI-cases without clinical data available were not included for either clinical nor cost analysis, however they were included for incidence rates calculation. Only proven and probable IFIs were used to estimate incidence rates. These were calculated by type and an overall incidence rate for all types of IFIs. The incidence rates were estimated using the number of discharges and patients-days during An estimation of the total expenditure in antifungal therapy during one year in Mexico was performed based on the number of hospital discharges during last information available. This study data is presented as proportion, median and interquartile range IQR depending on the type of data. For categorical data comparisons, Pearson's chi-square or Fisher's exact test were used as appropriate and for ordinal and quantitative variables, Mann—Whitney or Kruskal—Wallis tests were used as indicated. A total of cases were included in the analysis. Estimated proportion using cases with information available about this outcome. Unspecified IFIs refers to diagnosis by histopathology without etiological identification. B Distribution of IFIs by clinical context. The overall, IFI incidence was 4. IC had the highest incidence rates 1. Taking into account the total Mexican population Fluconazole and echinocandins were the two most frequently indicated antifungal drug as initial therapy Table 1. Only three out of individuals did not receive the indicated antifungal therapy. Data presented as median and IQR. Data analyzed with Kruskal—Wallis test. Post hoc analysis was done with Dunn's test. These adverse events, in a multivariate binary regression analysis, were associated with death, independently of ICU stay, age, and sex Table S5. The cost per unit of IV fluconazole and oral formulation varied between 0. However, the cost varied depending on the type of antifungal drug used. The presence of AKI increased 4. However, the costs increased between and fold when the analysis was restricted to survivors, for non-NF and NF possible IFIs, respectively Table 5. Also, LD had a 4-fold increase in the cost of antifungal therapy Table 3. Information about the costs of the antifungal therapy and length of hospital stay provided by each hospital and case-specific allowed to determine the mean cost of a day of antifungal therapy and hospital-stay Table 6. These values could vary, depending on the type of antifungal drug more expensive for liposomal amphotericin B and less expensive for generic formulations of fluconazole , required doses, ICU stay, and if the patient died or survived. In order to have an approximated mean cost of the antifungal therapy, all different drug costs for all patients were taken into account, without distinction with regard to the final outcome Table 6. Assumed cost and associated increasing were taken from the results obtained in the clinical and cost analysis presented in previous sections in this manuscript. Taking into account incidence rate of IFIs 4. A total of 6,, hospital discharges were reported by OECD during that year. This estimated burden represents an approximation to the total use of antifungal therapy in Mexico. Hence, this estimate shown above could be even higher. The overall incidence rate of IFIs and more specifically the individual rates of aspergillosis, histoplasmosis, coccidioidomycosis and candidemia are shown here and, with the exception of invasive candidiasis, no similar study has been published in recent years. Prior studies on coccidioidomycosis and histoplasmosis from Mexico have focused on the prevalence of these two infections by using coccidioidin skin testing 15 and not focused in the incidence of active infections. In Mexico, notification of these IFIs to the national health ministry was discontinued in In the current study, we estimated an incidence rate for endemic IFI of 7. Diagnostic improvement in IA has been in part due to the availability of galactomannan antigen detection in specialized reference centers, not only in Mexico, but in other Latin American countries. The four hospitals included in this study have several differences, such as number of beds, patient diversity, geographic location, and policies about the reimbursement of expenses, mainly for antifungal drugs. The data presented in the study is heterogeneous, however, this heterogeneity is a rule more than an exception in Mexican hospitals. Nevertheless, we acknowledge limitations in the estimations showed in the current study, as these four hospitals only represent 0. The diagnosis of possible IFIs, receiving empirical therapy, corresponds to more than half of the cases. This proportion can be the result of several phenomena. A classic example is IC, as blood culture identifies only two to seven out of 10 cases. Second, as the lack of access to better diagnostic tools decreases the possibility of accurate identification of IFIs, this also, may increase overdiagnosis and hence overuse of empiric antifungal drugs, causing unwanted adverse events such as AKI or LD, and higher costs for medical institutions and patients, as shown in this study. Amphotericin B formulations, itraconazole, voriconazole, flucytosine, and fluconazole are in the Essential Medicine List issued by the WHO. However, access to this drug is still problematic, not all patients are covered and, if it is needed, the cost is absorbed by the patient. At least five are licensed to distribute generic fluconazole, and one patent fluconazole. It is known that IFIs are an independent factor for higher associated health care costs. In our study, LOS was almost two-fold longer for aspergillosis and endemic mycosis when compared with reports from other countries. As previous reports have shown, in our study AKI was associated with higher mortality rate during IFIs therapy, usually associated with the use of amphotericin formulations. In this report, other contributing factors to AKI or LD were not assessed, which is a limitation inherent to the study design. Most of the individuals suffering from an IFI require multiple medications to treat comorbidities such as chemotherapy, antiretrovirals, or have underlining AKI such as diabetic patients, and could also be critically ill due to IFI or other conditions. We could not ascertain if AKI was secondary to the use of antifungal therapy since we did not control for other confounders, but we could establish the high burden and impact of AKI in patients with IFI, which justifies increasing focus on preventive measures. Awareness of the burden of IFIs in Mexico and the estimation of the treatment cost per person, allowed us to have an approximate expenditure in antifungal drugs by the health care system. This estimation allows to assess cost-avoidance strategies, such as antifungal prophylaxis, antifungal stewardship, programs improving access to essential drugs and make cost-conscious decisions such as access to more diagnostic tools, to increase diagnostic-driven therapy and decrease unwanted adverse events and their associated cost. DECL contributed to the conception and design of the study, also to the analysis and interpretation of data, and drafting the manuscript. AMO and ACO contributed with critical revision of the manuscript, interpretation of data and drafting the manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Braz J Infect Dis. Find articles by Alexandra Martin-Onraet. Find articles by Adrian Camacho-Ortiz. Find articles by Hiram Villanueva-Lozano. General characteristics of the studied population in four Mexican hospitals. Open in a new tab. Increasing cost associated with AKI development during antifungal therapy. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Other hepatic cirrhosis or other gastrointestinal disease, and neurologic, genitourinary diseases. First antifungal used before having the final diagnosis. Duration of antifungal therapy days, median, IQR. Acute kidney injury b. Liver damage during antifungal treatment LD b. Length of hospital stay days, median, IQR. Mortality rate c. Type of IFI indicating antifungal therapy.