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Espacios. Vol. 37 (Nº 27) Año 2016. Pág. 15

Costs of treatment to control fungal nosocomial infections in a public hospital of the Brazilian Unified System Health

Costos de tratamiento para controlar las infecciones nosocomiales por hongos en un hospital público del Sistema Único de Salud

Walquíria Barcelos de FIGUEIREDO 1; Simone AQUINO 2; Marcos Roberto PISCOPO 3

Recibido: 12/05/16 • Aprobado: 22/06/2016

Contents

1. Introduction

2. Literature revision

3. Methodology

4. Results and discussion

5. Conclusions

References

1. Introduction

1.1. Nosocomial Infection by Candida spp.

In Brazilian public hospitals the empirical antifungal treatment based on clinical evidence is a common practice. The growing incidence of fungal infections, mainly Candida spp. and Aspergillus spp., has been shown in epidemiological studies involving hospitals and their intensive care units, particularly in transplanted patients. This is reflected in the inclusion of antifungal therapy in empirical therapy regimens (Colombo et al., 2006; Marchetti et al., 2007). In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy (Salomão et al., 2011). Nevertheless, cost considerations remain critically important, especially since increasing demand for high-cost antifungals (e.g. LAmB, Caspofungin and Voriconazole) is exerting a significant strain on limited hospital budgets (Dixon et al., 2004; Moeremans et al., 2006).

Nosocomial infections (NI) are more severe in high technology hospital units, which hold acutely ill patients for intensive life support. Intensive Care Unit (ICU) high mortality rates, usually from 9 to 38%, can reach 60% due to nosocomial infection occurrence (Colpan, 2005). Prolonged hospital stays may also have collaborated with the occurrence of bloodstream infections. The capacity of yeasts to attach to a wide range of inanimate surfaces (such as those of intravascular devices) and to form biofilms in glycosylated solutions seems to protect them from immune responses and antimicrobial agents (Kojic and Darouiche, 2004).

A prospective study performed by Oliveira et al. (2010) aimed to determine the NI incidence in an ICU of a Brazilian University Hospital. The authors described 383 NIs (20.3%) with the hospitalization average of 19.3 days for patients with NI. The period of 20.2 days was observed for those with colonization by resistant microorganisms and the mortality was 39.5% among patients. The most common non-resistant microorganisms responsible for the NI were Candida albicans, Escherichia coli and Pseudomonas aeruginosa. Candida species accounted for 8–10% of all bloodstream infections. These fungi are the most common cause of fungal bloodstream infections in hospitalized patients (Morgan et al., 2005).

According to Mímica et al. (2009) the increase of infection cases related to catheter occurs worldwide. They found 4.7% of C. albicans. C. albicans is the main agent of fungal infections in humans. Recently, C.non-albicans species are emerging and, it has been associated to increased expression of virulence factors (Tamura et al., 2007). A study made in the West of France by Tamura et al. (2007) showed that one 193 strains of Candida spp. were isolated in 186 patients. C. albicans accounted for 54.9%, C. glabrata for 18.7%, C. parapsilosis for 12.9%, C. tropicalis for 4.7% and C. krusei for 4.1% of these isolates. The leading predisposing factors for candidemia were the use of broad-spectrum antibiotics (75.8%), central venous catheter (72.6%), cancer or hematologic malignancy (47.3%), recent surgery (42.5%) and, total parenteral nutrition (37.6%). One hundred and fifty-four patients received antifungal therapy; most of them were treated with Fluconazole as first-line agent. Overall mortality was 49% and it was significantly higher in patients with septic shock, advanced age, and absence of catheter removal (Talarmin et al., 2009). The risk factors for fungal infections are numerous and include the use of broad-spectrum antimicrobial drugs, steroids, early or advanced ages, chemotherapy, malignant diseases, the use of catheters, organ transplantation, disease severity, renal failure, hospital length of stay and mechanical ventilation (Richardson and Lass-Flörl, 2008).

Therefore, the research question that guided this study was: How the costs of antifungal drugs affect the therapeutic choice in the ICU in a tertiary public hospital?

The purpose of this present study was evaluated the profile of antifungal treatment and the costs spent in an ICU of the largest Brazilian public hospital, located in São Paulo city, in the period from July to December 2013. The results were compared with results from other national and international therapeutic protocols used in private hospitals in cases of NI caused by Candida spp.

2. Literature revision

2.1. Nosocomial Fungal Infection

Several studies have demonstrated the importance of Candida spp. as an agent for septicemia. In Brazil, Colombo et al. (2006) who reported that Candida spp. was also the fourth most frequently isolated pathogen found similar results. The same authors showed that the incidence of candidemia is almost twice, comparing to different countries, as demonstrated in Table 1.

Table 1. Incidence of candidemia (rate/ 1,000 admissions) in the period 1998 – 2004.

Source: Adapted from Colombo et al., 2006.

Candida species are the fourth leading cause of nosocomial bloodstream infections in the United States, accounting for 8% of all bloodstream infections acquired in hospitals. At least half of these infections occur among patients in critical care units. Total nosocomial infection rates at all anatomic sites are 2.5–10%. If nosocomial bloodstream infections represent 10% of all nosocomial infections, and if 8% of the latter are caused by Candida species, then the absolute number of cases would range from 7,000 to 28,000 annually (Edmond et al., 1999).

To determine the exact prescription of an antifungal drug, the susceptibility test is necessary, because the response to therapy varies among different species of fungi. Candida species. C. albicans, C. tropicalis and C. parapsilosis are usually susceptible to Fluconazole, while C. glabrata is generally susceptible dose-dependent or resistant to Fluconazole. C. krusei is usually intrinsically resistant to Fluconazole (Shah et al. 2011). In the United States, C. glabrata has increased as a cause of IC, reaching to 25% with a concomitant growth in Fluconazole resistance from 9 to 14% (Pfaller et al., 2009). 

In Latin America, the prevalence of fungal infection varies according to the species of Candida, but also with environmental conditions. In a tertiary care center in Bogotá, Colombia, 18 cases of candidemia were ascertained. C. parapsilosis contamination was found in plastic containers used for transient intravenous (IV) medication storage at the bedside, plastic bags reused for the transportation of IV medicines and cotton used for disinfection of IV ports. It was associated with poor infection-control practices were likely responsible for the outbreak. In another study, it was associated with the colonization of C. tropicalis, C. albicans and C. parapsilosis in health care workers (Granados et al., 2008).

According to Nunes (2009), C. albicans is the most common cause of nosocomial infection in Brazil. This author registered 114 blood infections by Candida spp in his study. C. albicans was the most frequent specie found (47.4 %), followed by C. parapsilosis (32.5 %), C. tropicalis (14.0 %), C. glabrata (5.3 %) and C. krusei (0.9 %). There is a concept that candidemias due to C. glabrata are rare in Brazil, and C. tropicalis and C. parapsilosis account for the large majority (70 %) of non-albicans species. The author reported that the explanation for rare occurrence of C. glabrata in Brazil is not clear, but the wide geographic variability of species distribution suggests that other factors than the use of Fluconazole may be significant, including demographic characteristics (older age of patients).

The growing appearance of Candida species resistant to azole confirms the importance of monitoring possible changes in the distribution of pathogenic species and in the sensitivity pattern. Both C. albicans andC. tropicalis showed resistance to itraconazole. Resistance to Fluconazole and to 5-fluocytosine was detected, respectively, in C. krusei and C. tropicalis samples. The successful treatment of these infections depends on the identification of the species and on the sensitivity pattern to antifungal agents (Mímica et al., 2009).

According to Nunes (2009) the choice of antifungal should be determined by susceptibility testing but the empirical antifungal therapy has become the standard of care in patients with persistent fever despite treatment with broad-spectrum antibiotics (Pfaller et al., 2011).

2.2. Antifungal drug costs

Since the 1990s Rentz and colleagues (1998) have warned that an important aspect to be considered in relation to episodes of candidemia is the cost of the patient care. They showed that in the United States, the cost of private care for each patient with candidemia was US$ 44,536. Today candidemia still persists as a public health problem in tertiary hospitals all over the world (Colombo and Guimarães, 2003). Nevertheless, it is pointed out that costs have high influence for the determination the choice of antifungal drugs. Unfortunately, the pharmacoeconomic impact of antifungal therapeutic drug monitoring has not been formally investigated. However, the cost of these assays is less than the cost of a single day of antifungal therapy with one of the new compounds and certainly less than that of any patient complication associated with inappropriate antifungal drug exposures (Colombo and Guimarães, 2003; Freifeld et al., 2011).

Ha et al. (2012) in a study in South Korea found that the total cost for the treatment of candidemia was US$ 4,743 per patient (mean). The length of stay (LOS) was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switching to second-line agents for any reason was the only modifiable risk factor of increased costs and LOS. Consequently, choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia. When choosing the antifungal agent, the presence (or absence) of neutropenia, severe sepsis or septic shock and recent exposure to azole drugs should be considered. In severe sepsis and septic shock patients, caspofungin has been suggested as the first choice drug, and liposomal amphotericin B and voriconazole (in patients not previously exposed to azoles) have been suggested as alternative drugs (Flückiger et al., 2006). 

In multicenter clinical trial conducted by Walsh et al. (2004), Caspofungin (Caspo) was shown to be non-inferior to LAmB for empirical therapy in febrile neutropenic patients. The authors concluded that Caspofungin is a suitable alternative to LAmB for empirical antifungal treatment. However, given the differential costs of between these agents, related health economic data would be essential to establish the role of Caspofungin as the latest addition to the empirical antifungal armamentarium.

The decision making the best antifungal for empirical use is mostly based on available efficacy and safety data. Salomão et al. (2011) concluded that the high susceptibility of Candida species to Fluconazole found in the blood cultures, in association with the low cost and toxicity of Fluconazole may support the selection of this antifungal agent. But in critically ill adults with risk factors for invasive candidiasis, empirical Fluconazole therapy fails to clearly improve the outcome when compared with placebo.

Jansen et al. (2006) analyzed the cost-effectiveness of Voriconazole in comparison to Conventional Amphotericin B (CAmB) deoxycholate for the treatment of invasive aspergillosis in Germany. Average survival of patients treated with Voriconazole was 174.4 life-weeks, compared with 119.4 life-weeks for CAmB. The mean total costs per patient with Voriconazole, were € 30,026 (US$ 41,640) compared with € 26,669 (US$ 36,985) for CAmB. Based on this research results, Voriconazole is cost-effective for treatment of invasive aspergillosis, in comparison to Amphotericin B. Standardization by survival resulted in costs of € 172 (US$ 238.53) per life-week for the Voriconazole arm, and € 222 (US$ 307.87) per life-week for the CAmB arm. The corresponding costs per life-week were € 151 (US$ 209.41) for the Voriconazole arm, and € 218 (US$ 302.32) for the CAmB arm. Voriconazole is also more cost-effective first-line treatment than CAmB. The incremental costs per life week gained with Voriconazole in comparison to CAmB was € 62 (US$ 85.98), that is, € 3,224 (US$ 4,471) per life-year gained (Bohme et al., 2003). Wenzel et al. (2005) reported similar findings with the average total treatment costs per patient was 10% lower in the Voriconazole arm (US$ 30,664) than in the CAmB arm (US$ 34,144).

Al-Badriyeh et al. (2009) performed a large randomized clinical trial, evaluating Voriconazole versus liposomal Amphotericin B (LAmB) as empirical therapy in febrile neutropenia. The authors, recommended Voriconazole as a suitable alternative to LAmB in Australia. However, for therapy of established or suspected Candida spp. infection in severely ill patients, recentreviews suggest echinocandins as the first option andamphotericin B formulations as an alternative (Salomão et al., 2011).

2.3. Brazilian Health System and Generic Drugs Program

Brazil is a heterogeneous country of continental size, with major regional differences, and a diverse set of socio-economic contexts, with differentiated needs. In parallel, the demands for extended health services are growing at a rapid pace.The Brazilian Unified Health System, called Sistema Único de Saúde (SUS) is effectively one of the world’s largest fully financed health care systems. The SUS established in the Brazilian Constitution of 1988, was an important expression of the Brazilian democratization movement in the 1980s and was, as such, spearheaded by health professionals and civil society movements (Tillvaxtanalys, 2013).

As a result, the SUS holds a series of particular traits: 1) it defines comprehensive, universal preventive and curative care as a constitutional right for 200 million Brazilians, thereby making the SUS one of the largest public health care systems in the world; 2) it stresses decentralized management and provision of health services along with community participation at all administrative levels; and 3) it operates through a particular mix of public and private participation, incentivized and supported even financially by the state itself, in which the private sector enters as a complementary and competing actor, fulfilling some of the tasks that the public sector may not be able to take on (Tillvaxtanalys, 2013).

During the 1990s, the country’s health system has over time evolved along two basic traits, after the creation of SUS. In terms of financing and service delivery, SUS has three subsectors, according to Paim and Teixeira (2007):

1) The public subsector, in which services are financed and provided exclusively by the State, at all levels of government and to which citizens have free access;

2) The private coverage sub-sector, where private actors deliver services, and for which citizens have to pay to gain access; 

3) A mixed (for-profit and non-profit) subsector, in which services, although provided by private actors, could be financed by either public or/and private funds, and to which citizens have free access to all services financed by the state.

The implementation of the SUS has since its inception been complicated by: 1) chronic underfunding; 2) inherent inefficiencies in the public-private service delivery model, essentially manifested in the inability to connect the two sectors; 3) similar shortcomings in the decentralized governance model, where communication and collaboration between different administrative units often are seriously hampered; and 4) a structural concentration of health services to more developed regions (Tillvaxtanalys, 2013).

As for services financed by both public and private actors, citizens will have to pay for treatment in accordance with the difference between the two funding streams. Another component is the emphasis on a highly decentralized administrative structure intended to support optimization, complementarity and public participation at all levels (Paim and Teixeira, 2007). These institutional and financial aspects of the Brazilian health system have direct implications on its infrastructure and the delivery of services. In practice, there is a division of labor, where – somewhat simplified – the public subsector focuses on decentralized primary care, emergency assistance and preventive measures, while hospitals, outpatient clinics, and diagnostic and therapeutic services mainly are in the hands of private actors (Iaquinto, 2012).

The principal objective regarding primary care has been to provide free, universal comprehensive health care to all citizens. These efforts have almost exclusively been carried out by the public sector that, through programs based on the decentralized approach outlined above, also tried to expand coverage to specialist treatment and hospital care, including the pharmaceutical assistance by the SUS. The secondary care constitutes the principal interphase between public and private actors. The SUS is highly dependent on contracts with the private sector, particularly in areas such as diagnostic and therapeutic support services (Paim et al., 2011). Finally, it is in tertiary care that private actors are increasingly predominant. Two thirds (66.4 %) of Brazil’s nearly 6400 hospitals are currently under private – i.e. commercial or philanthropic – regime (Tiago, 2012).

Despite the limitations, the SUS has made considerable progress such as making considerable investments in human resources and technology, including the domestic production of strategic pharmaceutical products. In particular, the former has played a critical role in the development of the Brazilian health system. Increased access to medication has, since its outset, been a central purpose of SUS and thus supported by several governmental programs. The pharmaceutical industryis a good illustration of the challenges and opportunities that the Brazilian health care sector confronts. It has grown at almost 10 % per year over the last decade despite the economic recession (Garrido, 2012). This growth is due to increased access of the population to medications, particularly to generics drugs (Garrido, 2012; Portal Brasil, 2012). Today, generic drugs play an essential role in treating almost 80% of diseases in Brazil.

The key factor for this development is the “Law of Generic Medication” nº 9787/1999 that provides an outspoken support for generic products, priced at least 30 percent lower than the reference drugs. These, and other, policies have had a tremendous impact on the national pharmaceutical industry that has seen annual growth rates of nearly 10 percent for the last decade (Saúde Web, 2011). This suggests that there may be room for expansion and, as already noted, pharmaceuticals is one of the prioritized areas in the recent Brazilian national industrial policy plan (Garrido, 2012).

3. Methodology

The methodology for this prospective case study is described as an exploratory level with qualitative approach. The case study is presented as a more effective method when the form of the question to be answered is made ​​with "how", according to Yin (2010). This study was performed in an Intensive Care Unit (ICU) that consists of 14 beds of a tertiary public hospital in the State of São Paulo, Brazil. The prescription drugs analyzed were collected from 181 registry data dispensing of antifungals drugs administered to ICU patients from July to December 2013, provided by the central hospital pharmacy, where all items are listed per unit and total value used, monthly. The ethical aspects of this research were met with the prior evaluation of the study by the Hospital Ethics Committee under the registration number CAAE 39216814.1.0000.0068 and approved under number 928557, with online protocol number 12900.

Documental analysis was based on patients registry affected by urinary infection caused by multi-drug resistant bacteria and fungi, provided by the Commission Services and Infection Control (SCCIH) and by the laboratory data. The total positive tests of ICU patients for fungal nosocomial infection were from: mid-stream urine samples; patients with permanent bladder catheters; patients using central venous catheters (CVC) and with endotracheal tube.

4. Results and discussion

The nosocomial pathogens isolated from the ICU in the studied period are demonstrated in the Table 2.In this study, the Candida genera corresponded to 14.8% (Candida albicans 7.4% and C. non-albicans 7.4 %) and this result reinforce the literature data that demonstrated that Candida spp. is the fourth cause of nosocomial infections (Colombo et al., 2006; Edmond et al., 1999).

Table 2. The microorganisms isolated from ICU patients in the period of July to December 2013.

Source: Author’s own.

The costs spent with antifungal therapy were US$ 44,743.80 that corresponded to 48 % of total costs with antimicrobial drugs (US$ 93,234.48) in the same period of 2013. The total values for each drug used during six months is shown in Figure 1.

Figure 1. Total values (US$) of antifungal drugs costs spent in the ICU in the second semester of 2013.

Source: Author’s own.

LAmB was the empirical therapy of choice in the Brazilian public hospital studied. The total antifungal drugs prescribed in the studied period was 528 and 50.5% of it was represented by LAmB, followed Fluconazole (34.84%), followed by CAmB and Voriconazole (Figure 2).

Figure 2. Consumption of antifungal drugs prescribed in the second semester in the ICU.

Source: Author’s own.

In August 2013 the LAmB was not available at central pharmacy and it was replaced by CAmB, Fluconazole or Voriconazole treatment (Figure 3).

Figure 3. Monthly costs of antifungal drugs prescribed to patients of ICU (US$).

Source: Author’s own.

This fact led to an additional cost due the use of Voriconazole (approximately US$ 6,973.19), corresponding to 12.75% of costs for antifungal treatment in the semester. As already mentioned, the cost of generic drugs in Brazil has been reduced since the publication of generic drugs Law, which explains the lower values of CAmB, LAmB and Fluconazole. Voriconazole has not yet lowered the cost to the public system, compared to other countries, although it is available through SUS. Due to the high unit cost, therapy with Voriconazole is presented as a replacement for lack of LAmB, but not as a first treatment option (Figure 3).

Our findings indicated that LAmB and Fluconazole are the first and second antifungal drug choice (respectively) in the public hospital of this study. In Brazil, the health professionals use clinical experience as the best evidence available for their clinical decision-making, based on prevalence of Candida albicans. The empirical therapy is still the basis of choice in a public Brazilian hospital, as demonstrated in Figure 4, in a monthly distribution.

Figure 4. Monthly amount of prescribed antifungal drugs for the ICU.

Source: Author’s own.

According to Pappas et al. (2009) the additional cost of each case of invasive candidiasis in hospitalized adults is around US$ 40,000. Between Fluconazole and Amphotericin B deoxycholate, one explanation presumes that Amphotericin B deoxycholate was preferred in patients with more serious illnesses. Patients who started on Amphotericin B deoxycholate treatment had underlying cancer, central venous catheters (CVC), or mechanical ventilation more frequently that those who started on Fluconazole, suggesting that Amphotericin B is given to patients in extremely critical conditions (Walsh et al., 2004).

Each country adopts different therapeutic protocols with even internal differences when compared public hospitals to private hospitals. In Korea Echinocandins and LAmB are not admitted as first-line agents against invasive candidiasis or candidemia, where is usually prescribed Fluconazole for the treatment of candidemia. The CAmB is chosen when it is considered necessary for broader spectrum of coverage or for immunocompromised hosts. Some may presume that the loss of cost-effectiveness of CAmB compared to Fluconazole in this study could be partially explained by the increase in other medical treatment costs because disease severity in CAmB group might have been worse (Walsh et al., 2004).

The first economic study that compared Voriconazole to CAmB as primary therapy for definite or probable IA in immunocompromised patients demonstrated that using Voriconazole provided an average cost saving of US$ 3,481 per treated patient. In addition, Voriconazole resulted in a lower cost per survivor (difference of US$ 15,661) and a lower cost per successfully treated patient (difference of US$ 50,024) (Wenzel et al., 2005). In Germany, Voriconazole is more effective, more cost-effective, and it is indicated as first-line treatment for invasive aspergillosis over CAmB. In conclusion, Voriconazole in Germany is a cost effective choice for antifungal treatment. Hence, economic arguments do not interfere with German guidelines that state that Voriconazole is first choice of treatment for invasive aspergillosis (Bohme et al., 2003). All comparative costs data cited by the literature are shown in the Table 3.

Table 3. Cost comparison of antifungal drugs for treatment.

Source: Adapted from Martín-Peña et al., 2013a; Al-Badriyeh et al., 2009b; 
Neoh et al., 2011c; Jansen, et al., 2006d; Wenzel et al., 2005e.

In this present study the unit values of antifungal drugs was of US$ 4.80 for CAmB, US$ 190.55 for LAmB, US$ 0.11 for Fluconazole and US$ 316.96 for Voriconazole (the most expensive antifungal drug).

The findings of the Australian study conducted by Al-Badriyeh et al. (2009) suggest that the first-line therapy of febrile neutropenia with LAmB results in both higher efficacy and lower direct medical costs when compared with Voriconazole. From the Australian perspective, LAmB is a dominant empirical medication over Voriconazole, which contradicts the current Australian practices of recommending Voriconazole as an effective alternative, with economic advantage, to LAmB for empirical use. Nevertheless, caspofungin was more cost-beneficial than LAmB, which contradicts again the current Australian guidelines of recommending LAmB as the first choice for empirical therapy.

In a Brazilian private tertiary hospital named Albert Einstein Hospital (AEH) the protocol using antifungal therapy is based on the patient clinical condition (Table 4).

Table 4. The protocol applied to invasive Candida infections in a private ICU.

Source: Albert Einstein Hospital (AEH, 2012).
Note: NI – Not indicated; NA- No Activity; Alt- Alternative therapy; Fluco- Fluconazole;
CAmB – Conventional Amphotericin B; LAmB – liposomal Amphotericin B;
Anid- Anidulafungin; Mica- Micafungin; Caspo- Caspofungin; Vorico- Voriconazole.

It is possible to observe that at AEH the antifungal drug called Caspofungin (€ 1,413.10/ US$ 1,959.83) was available, in despite of high costs as a first therapy choice in candidemia and endocarditis (AEH, 2012).

Finally, to extend and to disseminate knowledge on candidemia is a way to spread the need to establish efficient pharmacovigilance programs. It could also establish identity or similarity of the strains present in the hospital environment is an important tool in hospital epidemiology that can direct specific treatment for Candida species, with reduced cost and best therapeutic choice for every patient (Giolo and Svidzinski, 2010). Antifungal susceptibility tests should be performed although, unlike antibiotics, they are not a common clinical practice in medical microbiology (Chang  et al., 2008; Martín-Peña et al., 2013) compared the cost-effectiveness of two different approaches, from a Spanish perspective. The diagnosis-driven antifungal therapy (DDAT) approach is more cost-effective (€ 32,671 or US$ 45,308.14 /episode) than the empirical antifungal therapy (EAT) approach (€ 52,479 or US$ 72,777.88/ episode) in the management of persistent febrile neutropenia (PFN) in hematological patients. This study showed also that Voriconazole in the DDAT approach had a significantly lower acquisition cost (29.7%) than caspofungin and LAmB.

Besides, according to Mota et al. (2008) health authorities must therefore regularize, rationalize and control drug use to minimize inefficiency in pharmaceutical care and to prevent exposing the population to unnecessary health risks.

5. Conclusions

This research adds knowledge on ICU infection in a public Brazilian hospital and emphasizes the importance of the implementation of a program to evaluate in vitro susceptibility of these pathogens to drugs. Monitoring of clinical specimens can be an extremely useful tool as it allows choosing the right drug and the right dose based on pharmacological criteria, to be used for each patient, avoiding both the administration of an overdose, and consequently their undesirable effects, such as the selection of resistant microorganisms with high costs to the health system.

The therapeutic choice depends on the economic balance of the hospital, patient's clinical status, the Candida species or availability of drugs. The Law of generics in Brazil offers economic advantages in choosing LAmB, CAmB and Fluconazole. Voriconazole is currently very expensive to the Brazilian healthcare system (SUS) in the primary care and its use is restricted to emergencies. It was observed that the use of Echinocandins was not an option in the ICU studied, such as Caspofungin and Micafungin and this phenomenon is associated with the high costs of these new antifungal drugs.

 The results of this study contribute to support other studies of nosocomial infection, and to reaffirm the importance of an effective infection control program with the involvement of health professionals and authorities. Their decisions are largely based on available clinical efficacy and safety data and to existing antifungal usage guidelines.

As demonstrated in recent studies there are differences in epidemiology, economics costs and resistance of invasive infections caused by Candida species worldwide. Besides, we should consider that many tourism and business travelling worldwide can spread many Candida resistant species to everywhere, including Brazilian public hospitals. Physicians and hospital managers should take into account other Candida species. They should promote the availability of for choosing antifungal therapy based on susceptibility testing by the DDAT, instead of the empirical therapy. In addition, the financial transfers to a public hospital by Brazilian Unified System Health reinforce the use of cheaper generic antifungal medications, such as Amphotericin B and Fluconazole, which confirms the findings of this study.

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1. Head nurse of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Master in Health Management in Business Administration of Universidade Nove de Julho – UNINOVE. E-mail: walquiria.figueiredo@hc.fm.usp.br.
2. Researcher and Professor of the Professional Master in Management of Health Systems of Universidade Nove de Julho – UNINOVE. Adjunct Editor of the Health Systems Management Jornal – UNINOVE. E-mail: siaq66@uninove.br
3. Researcher and Professor of the Universidade Nove de Julho – UNINOVE in the Doctorate Degree Program in Management and Professional Master's Program in Project Management - UNINOVE. Professor, Department of General Administration and Human Resources at EAESP / FGV. Chief Editor of the magazine and Project Management (GEP) and Member of the Iberoamerican Editorial Board of the Journal of Project Management (IJoPM). E-mail: piscopomr@gmail.com