Lourdes Rodriguez, MD

Infecitous Diseases Unit, Guillermo

Almenara Hospital, Lima, Peru

lourdesrod@gmail.com

(511)3242983, ext. 44717

Nosocomial Bloodstream Infections Due to Candida spp. at a Tertiary Care Center in Lima, Peru: Species Distribution and Clinical Features

Lourdes Rodriguez1, Luis R Illescas1, Rafael Ramirez1, Beatriz Bustamante2,3, Alberto Diaz1 and Jose Hidalgo1

1Hosp. Guillermo Almenara Irigoyen, 2Hosp. Nac. Cayetano Heredia; 3Inst A von Humboldt-UPCH, Lima, Peru

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• Candidemia is a frequent finding in nosocomial bloodstream infection at our institution, a large, urban hospital in a middle income country.

• The incidence, mortality and species distribution is comparable to that found in other Latin American, North American and European centers.

• A large proportion of our cases came from non-ICU settings, but this is probably related to the low number of ICU beds at this hospital.

BACKGROUND & METHODS

Background: Candida sp. has become one of the major worldwide pathogens in nosocomial bloodstream infections. In recent years, reports from multiple parts in the world show this trend consistently. Our series describes the clinical epidemiology and presentation of candidemia at a Peruvian referral hospital.Methods Prospective study at a large tertiary care hospital in Lima, Peru. Candida sp. isolates identified by hospital laboratory between July 2012 and December 2013 (18 months) were included in the present study. Microbiological and clinical information was collected for each isolate.Results: Seventy four episodes of candidemia were reported during the study period. Candida was the fourth most common pathogen isolated from blood cultures. The median age of patients with candidemia was 58 years (0–100), and 43 (58.1%) of them were males. Ten (13.5%) episodes occurred in children (5.4% younger than 1 year, and 8.1% between 1 and 18 years), thirty (40.5%) episodes in adults between 19 and 60 years old, and 34 (45.9%) episodes in elderly subjects. The overall incidence was 1.18 cases per 1,000 admissions. In 69 of 74 isolates, the laboratory identified the species of Candida. Species identification was tested again with molecular techniques. Non-albicans candidas were predominant (71%), although C. tropicalis was the most common species (30.4 %), followed by C. albicans (29.0%), C. parapsilosis (15.9%), C. glabrata (15.9%), C. guillermondii (7.2%).

Isolates recovered were most commonly from the ICU (n=17, 23.1%), followed by cultures from surgical wards (n=12, 16.9%). Recent surgery (n=29, 39.2%), and hemodialysis (14, 18.9%) were the most frequent associated conditions, with fever the most common clinical finding in 52 cases (70.3%). Forty-seven cases (63.5%) in this series received antifungal treatment based on blood culture finding. Eleven patients (14.9%) received empirical treatment. The overall 30-day survival was 56.8% (treated subjects, 68.1%; not-treated patients, 37%, p=0.0094).Conclusion: Candidemia is a frequent finding in nosocomial bloodstream infection at our institution, a large, urban hospital in a middle income country. The incidence, mortality and species distribution is comparable to that found in other Latin American, North American and European centers. A large proportion of our cases came from non-ÍCU settings, but this is probably related to the low number of ICU beds at this hospital.

ABSTRACT

CONCLUSIONS

1. Wille MP, Guimarães T, Furtado GH, Colombo AL. Historical trends in the epidemiology of candidaemia: analysis of an 11-year period in a tertiary care hospital in Brazil. Mem Inst Oswaldo Cruz. 2013; 108(3)288-92.

2. Nucci M, Thompson-Moya L, Guzman-Blanco M, Tiraboschi IN, Cortes JA, et al; Grupo Proyecto Épico. [Recommendations for the management of candidemia in adults in Latin America. Grupo Proyecto Épico]. Rev Iberoam Micol. 2013; 30(3 Suppl 1):179-88.

3. Colombo AL, Cortes JA, Zurita J, Guzman-Blanco M, Alvarado Matute T, et al. Recommendations for the diagnosis of candidemia in Latin America. Rev Iberoam Micol. 2013; 30(3):150-7.

4. Nucci M, Queiroz-Telles F, Alvarado-Matute T, Tiraboschi IN, Cortes J, et al; Latin American Invasive Mycosis Network. Epidemiology of candidemia in Latin America: a laboratory-based survey. PLoS One. 2013; 8(3):e59373.

5. Bustamante B, Martins MA, Bonfietti LX, Szeszs MW, Jacobs J, et al. Species distribution and antifungal susceptibility profile of Candida isolates from bloodstream infections in Lima, Peru. J Med Microbiol. 2014; 63(Pt 6):855-60.

RESULTS

Contact Info

REFERENCES

Background: Candida sp. has become one of the major worldwide pathogens in nosocomial bloodstream infections. In recent years, reports from multiple parts in the world show this trend consistently. These studies have included also Latin American countries (Wille et al, Nucci et al), and one reported Peruvian data from another hospital (Bustamante et al). Our series describes the clinical epidemiology and presentation of candidemia at a Peruvian referral hospital.

Methods: Prospective study at a large tertiary care hospital in Lima, Peru. All Candida sp. isolates identified by VITEK 2 automated system at the hospital laboratory between July 2012 and December 2013 (18 months) were included in the present study. Patients medical records were reviewed and relevant information was included in the study database (clinical presentation, demographic information, associated conditions, treatment received, outcomes). Epidemiological rates were calculated following conventional criteria.The isolates were transported to the Mycology Laboratory of Instituto de Medicina Tropical Alexander von Humboldt-Universidad Peruana Cayetano Heredia. CHROMagarTM Candida medium (Difco, USA) was used to evaluate the colony purity and viability and for the presumptive identification of Candida species. Isolates were preserved using both yeast extract-peptone-dextrose broth medium (YEPD) and distilled water at -20ºC and skim milk at -70ºC.At this second laboratory, strain identification was determined using standard methods such as microscopic morphology on corn meal agar+Tween 80, growth at 37°C and 42°C, growth in hypertonic medium, and using an API 20 C AUX system (bioMérieux, Marcy-l’Étoile, France). Additionally to traditional methods, C. albicans, C. parapsilosis complex and C. glabrata complex were identified by sequencing of the ITS ribosomal DNA region by Macrogen (USA) and compared to sequence data available from GenBank.

• Seventy four episodes of candidemia were reported during the study period. Candida was the fourth most common pathogen isolated from blood cultures.

• The median age of patients with candidemia was 58 years (0–100), and 43 (58.1%) of them were males. Ten (13.5%) episodes occurred in children (n=6, 5.4% younger than 1 year, and n=7, 8.1% between 1 and 18 years), thirty (40.5%) episodes in adults between 19 and 60 years old, and 34 (45.9%) episodes in elderly subjects.

• The overall incidence was 1.18 cases per 1,000 admissions. • In 69 of 74 isolates, the laboratory identified the species of Candida. Non-albicans candidas were

predominant (69.6%). • Although both laboratory methods showed mostly concordant identifications, by molecular

identification C. tropicalis was the most frequent species, and C. albicans by Vitek 2 automated system. The frequencies obtained by each method are shown in the figures and table 2.

• The 3 most common species coincide with other reports. C. glabrata appeared with greater frequency in this series compared to previous studies in Latin America.

• Isolates recovered were most commonly from the ICU (n=17, 23.1%), followed by cultures from surgical wards (n=12, 16.9%).

• Recent surgery (n=29, 39.2%), and HD (14, 18.9%) were the most frequent associated conditions.• Fever was the most common clinical finding in 52 cases (70.3%). Sepsis and severe sepsis

presentation were also frequent findings.• Forty-seven cases (63.5%) received antifungal treatment based on blood culture finding. Eleven

patients (14.9%) received empirical treatment. • Overall 30-day survival was 56.8% (treated subjects, 68.1%; not-treated patients, 37%, p=0.0094).

Table 1. MEDICAL CONDITIONS ASSOCIATED TO CANDIDEMIA

(0-90 days prior to diagnosis of candidemia)

Medical condition N %

Recent Surgery 29 39.2

Abdominal 18 24.4

Vascular 3 4.1

Genito-urinary 4 5.4

Gynecological 2 2.7

Cardiac 1 1.4

Neurologic 1 1.4

Invasive procedures 50 67.6

CVC/TPN 19 25.7

Mechanical ventilation 31 41.9

Cancer 11 14.9

Hematological malignancy 4 5.4

Solid tumor 7 9.5

System/Organ Disease 43 58.2

ESRD - Chronic dialysis 14 18.9

Chronic pulmonary disease 8 10.8

Cardiac 7 9.5

Immunological 7 9.5

Neurological 4 5.4

Hepatic 3 4.1

Organ transplantation 8 11.0

Hematopoietic stem cell (allo) 2 2.7

Hematopoietic stem cell (auto) 1 1.4

Graft-versus-host-disease 3 4.1

Solid organ (kidney, liver) 2 2.8

Other condition 7 9.6

Neonatal candidemia 3 4.1

HIV 2 2.7

Burn 1 1.4

Neutropenia 1 1.4

C. albicans, 30.4 %n=21

C. glabrata, 11.6 %n=8

C. guillermondii, 2.9 %n=2

C. parapsilosis, 18.8%

n=13

C. tropicalis, 24.6 %n=17

Others, 2.9 %n=2 C. sp, 8.7 %

n=6

DISTRIBUTION OF EPISODES ACCORDING TO SPECIESOF Candida, VITEK 2

(N= 69)

C. albicans C. glabrata C. guillermondii C. parapsilosis C. tropicalis Others C. sp

C. albicans, 29.0%n=20

C. glabrata, 13.0%n=9

C. guillermondii, 7.2%n=5

C. parapsilosis,15.9%n=11

C. tropicalis30.4 %N=21

C. sp, 4.3 %n=3

DISTRIBUTION OF EPISODES ACCORDING TO SPECIES OF Candida, API 20C AUX AND MOLECULAR IDENTIFICATION

(N= 69)

C. albicans C. glabrata C. guillermondii C. parapsilosis C. tropicalis C. sp

SpeciesVITEK 2

N= 69 (%)

API 20C AUX and

molecular test

N=69 (%)

C. albicans 21 (30.4) 20 (29.0)

C. glabrata 8 (11.6) 9 (13.0)

C. guillermondii 2 (2.9) 5 (7.2)

C. parapsilosis 13 (18.8) 11 (15.9)

C. tropicalis 17 (24.6) 21 (30.4)

C. sp 6 (8.7) 3 (4.3)

Others 2 (2.9) 0

Table 2. COMPARISON OF Candida ISOLATED BY LABORATORY METHOD

Incidence (cases per 1000 adm) 1.18

30-day survival with treatment, % 68.1

30-day survival without treatment, % 37

Fever, n (%) 52 (70.2)

Sepsis, n (%) 25 (33.8)

Severe sepsis, n (%) 24 (32.4)

Median age (yrs) 58

Male (%) 58.1

Table 3. MAIN EPIDEMIOLOGICAL AND CLINICAL RESULTS