Excess mortality, length of stay and cost attributable to candidaemia

doi:10.1016/j.jinf.2009.08.020

Journal of Infection

Volume 59, Issue 5, November 2009, Pages 360-365

https://doi.org/10.1016/j.jinf.2009.08.020 Get rights and content

Summary

Background

There were 1967 reports of Candida species isolated from blood specimens in 2007 in the UK (excluding Scotland). Such infections are particularly common in the intensive care unit (ICU). The impact of candidaemia on mortality, length of stay (LOS) and cost in a UK hospital was examined.

Methods

A retrospective analysis of candidaemia episodes and appropriate matched controls was undertaken based on data from the ICU, high dependency units and hospital wards at Wythenshawe Hospital in Manchester. The study covered the period November 2003–February 2007.

Results

In total, 48 case-patients of candidaemia and 81 control-patients were identified. The attributable mortality due to candidaemia varied from 21.5% to 34.7%. Candidaemia patients spend on average 5.6 days more in the ICU than matched patients and generate mean additional costs of at least £8252 per patient, £16,595 in adults only.

Conclusion

Candidaemia remains a severe disease associated with high attributable mortality in the UK. In addition, candidaemia leads to additional ICU length of stay and costs. The implication is an attributable cost of at least £16.2 million with 683 deaths attributable to candidaemia per year in the UK.

Introduction

Infections due to Candida species are common and Candida species are the predominant fungal nosocomial pathogens, especially in the intensive care unit (ICU).1, 2 Data from the UK show that Candida species are the eighth most common cause of hospital-acquired bloodstream infections.³ A study at six UK hospitals⁴ found the rate of candidaemia to be more than 3 cases per 100,000 bed days while a recent prospective survey in Scotland reported an incidence rate of 4.8 cases per 100,000 population per year.⁵ The latest data from the Health Protection Agency indicate that a total of 1967 reports of Candida species were made in 2007 by laboratories in England, Wales and Northern Ireland (representing more than 90% of the UK population) confirming an increasing trend during the last decade.⁶ A recent retrospective study in our own ICU has shown that the incidence of candidaemia changed from 4.9/1000 ICU admissions in 2004–10.1 and 9.1/1000 ICU admissions in 2005 and 2006 respectively (unpublished). The rise in the incidence of candidaemia is due to many factors such as an increase in intensive care, greater use of invasive technologies, intravascular catheters and an increasing use of antibiotics.⁷

Candidaemia has been shown to be associated with an increased length of hospital stay, higher mortality, and greater costs8, 9 although the number of studies capturing these types of data is limited.⁹ In a matched case-control study in the USA, the excess length of stay was 10.1 days in adults and 21.1 days in paediatric patients,¹⁰ and in a UK study, attributable 30-day mortality was reported as 26.4%.⁴

How much excess mortality is really attributable to candidaemia remains a topic for debate.¹¹ This is due to the underlying comorbidities and risk factors that generally characterise patients infected with Candida.11, 7 Given that these patients will have a poor prognosis, it is often extremely difficult to discriminate between mortality attributable directly to the bloodstream infection and the mortality that is actually caused by the underlying condition.11, 7

Therefore we designed a matched case-control study based on data from our own hospital in order to estimate attributable mortality in addition to the impact of candidaemia on length of stay and costs due to an episode of candidaemia by comparing patients with candidaemia with hospitalised patients without candidaemia who were otherwise similar.

Section snippets

Methods

A retrospective analysis was undertaken of candidaemia in patients admitted to Wythenshawe Hospital between the 10th November 2003 and the 8th February 2007. The hospital's audit committee approved the study.

Wythenshawe Hospital forms part of the University Hospital of South Manchester NHS Foundation Trust. It is an acute teaching trust, covering the geographical area of South Manchester, South Trafford, North East Cheshire and West Stockport. The population it serves is approximately 250,000.

Results

There were a total of 48 cases and 81 controls when considering all patients. Approximately 1/3 of patients were over 70 years of age and five (10%) were premature infants. In the case of ICU patients the number of cases and controls was 40 and 68 respectively. The most common species was Candida albicans (32–66.7%) followed by Candida glabrata (7–14.6%). In five cases, multiple species types were identified. Key demographic details of cases (Candida albicans – 25 (62.5%) and Candida glabrata –

Discussion

The main findings of our case-control study during the period 2004–2006 are that significant mortality and costs are attributable to candidaemia when matched with comparable non-candidaemia patients. This higher attributable mortality applies to all patients and those who received care in the ICU. These results are consistent with the conclusions of most published studies and a systematic review of matched cohort and case-control studies.¹¹ In our study the attributable mortality was reduced

Acknowledgement

This study was supported by Astellas Pharma Ltd, UK. The authors would also like to express their gratitude to the medical, scientific & secretarial staff of microbiology lab, the audit department and the medical staff of our ICUs & Christine Harris (Prof. Denning's secretary), for their help in obtaining the data.

References (20)

C.C. Kibbler et al.
Management and outcome of bloodstream infections due to Candida species in England and Wales
J Hosp Infect
(2003)
S.I. Blot et al.
Effects of nosocomial candidemia on outcomes of critically ill patients
Am J Med
(2002)
J. Bille et al.
Changing face of health-care associated fungal infections
Curr Opin Infect Dis
(2005)
M. Morris et al.
Echinocandins in the management of invasive fungal infections, part 1
Am J Health-Syst Pharm
(2006)
N.I.N.S.S. Partnership
Surveillance of hospital-acquired bacteraemia in English hospitals 1997–2002
(2002)
F. Odds et al.
One year prospective survey of Candida bloodstream infections in Scotland
J Med Microbiol
(2007)
HPA. Candidaemia in England, Wales and Northern Ireland: 2007 – overall trend in reports (www.hpa.org.uk) (accessed on...
M.E. Falagas et al.
Attributable mortality of candidemia: a systematic review of matched cohort and case-control studies
Eur J Clin Microbiol Infect Dis
(2006)
B. Spellberg et al.
Current treatment strategies for disseminated candidiasis
Clin Infect Dis
(2006)
J. Morgan et al.
Excess mortality, hospital stay, and cost due to candidaemia: a case-control study using data from population-based candidaemia surveillance
Infect Control Hosp Epidemiol
(2005)

There are more references available in the full text version of this article.

Cited by (71)

Species identification and antifungal susceptibility of uncommon blood yeast isolates
2022, Journal of Microbiology, Immunology and Infection
Accurate identification of Candida species is increasingly important in the era of emergence of Candida auris. We aimed to compare the identification performance of two matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems (Vitek MS and Bruker biotyper MS) and an oligonucleotide array for uncommon blood yeast isolates and demonstrate the susceptibilities among those isolates.
Candida species isolates from blood culture other than Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata, and Candida krusei identified by biochemical methods were collected from multiple hospitals and further identified by an oligonucleotide array based on the internal transcribed spacer-1 (ITS-1) and ITS-2 sequences of the rRNA genes, Vitek MS and Bruker biotyper MS. The minimal inhibitory concentrations (MICs) of these clinical isolates were determined by the Sensititre YeastOne (SYO) system.
Among 136 isolates, Candida guilliermondii was most common (52, 38.2%), followed by C. lusitaniae (13, 9.6%) and C. haemulonii (12, 8.8%). The oligonucleotide array, Vitek MS and Bruker biotyper MS correctly identified 89.7% (122), 90.4% (123), and 92.6% (126) of these isolates, respectively. Elevated minimal inhibitory concentrations (MICs) of fluconazole were observed for C. haemulonii (MIC₉₀: 256 mg/L), and C. guilliermondii (MIC₉₀: 16 mg/L) with 28.4% of uncommon Candida isolates with MIC ≧ 8 mg/L.
For uncommon Candida species, the unmet need for current databases of two commercial MALDI-TOF MS systems is highlighted, and the oligonucleotide array may serve as a supplement.
The Economic Burden of Candidemia and Invasive Candidiasis: A Systematic Review
2020, Value in Health Regional Issues
Citation Excerpt :
The prevalence-based approach was employed in all studies included in this review. Five studies3,4,7-9 used a top-down approach (ie, breaking down to average costs), and 3 studies6,10,11 applied the bottom-up approach (ie, building up average costs in which each component of resource use is estimated and a unit cost derived for each). Only Slavin et al (2004) used total diseases cost to estimate the cost outcome, whereas the remaining studies employed incremental cost method.
Candidemia or invasive candidiasis (IC) is an increasingly common fungal infection and has been associated with high mortality, particularly among the immunocompromised and critically ill. Although several studies have been conducted to estimate the cost of managing candidemia and IC, quality assessment on the methodological aspects of these cost studies was not performed. To date, no systematic review focusing on the economic burden of candidemia and IC has ever been conducted.
The aim of this study was to systematically review the available evidence on the economic burden of candidemia and IC worldwide.
Databases (ie, PubMed, Scopus, EconLit, HEORO, and Ovid/Embase) were searched through June 2018. Two researchers independently assessed the quality of the eligible studies. Costs reported in the included studies were converted to 2016 USD using Campbell and Cochrane Economics Methods Group-the Evidence for Policy and Practice Information (CCEMG–EPPI)-Centre Cost Converter software.
Eight articles were included in this systematic review. The mean total cost per patient with candidemia and IC ranged from $48 487 to $157 574, whereas the mean cost per hospitalization associated with candidemia and IC was from $10 216 to $37 715. All studies were from developed Western countries and reported only direct costs of candidemia and IC. Hospitalization was the main cost driver, contributing to more than half of the total costs.
Quality cost studies on candidemia and IC based on standardized methods to provide informed decision making among healthcare authorities in implementing appropriate strategies is anticipated, in particular in developing countries.
Morbidity and mortality of candidaemia in Europe: an epidemiologic meta-analysis
2019, Clinical Microbiology and Infection
Candidaemia is a serious hazard to hospitalized patients, but European epidemiological data are restricted to national studies focusing on Northern Europe, population-based surveillance programmes or studies conducted in distinct local areas. The aim was to provide current data on the overall burden and epidemiological development of candidaemia in Europe.
A Web of Knowledge™ search was carried out from January 2000 to February 2019. Appropriate data were collected on total cases, study duration, incidence, species distribution and/or mortality rates. Meta-analysis was performed to pool individual studies. Heterogeneity was examined using the I² statistic. Calculations of pooled incidence and mortality rates, subgroup analysis by geographical origin, study period and scenarios were carried out. Daily candidaemia incidence and mortality rates in Europe were extrapolated. Systematic review and meta-analysis were used to determine incidence and mortality of candidaemia in the UN European region. Complete datasets were categorized into population-based and hospital-based epidemiological studies and were analysed separately. Subgroup analyses were performed for geographic distributions and time-dependent developments.
In population-based studies, 43 799 cases of candidaemia were diagnosed in 1 885 271 885 person-years, revealing an overall pooled incidence rate of 3.88/100 000. The highest pooled incidence rate was observed in intensive care units (5.5/1000 admissions, Day 30 mortality rate 37%), followed by tertiary care centres (0.96/1000 admissions, pooled Day 30 mortality rate 38%) and the mixed group of teaching and general hospitals (0.52/1000 admissions, pooled Day 30 mortality rate 37%). European incidence of candidaemia was extrapolated to approximately 79 cases per day, of which an estimated 29 patients might have fatal outcome at Day 30.
Pooled incidence rates, species distribution and outcome of candidaemia differ considerably between clinical groups, European regions and over time. We observed an increasing overall pooled incidence rate of candidaemia and a higher proportion of Candida spp. other than C. albicans in the current decade in population-based data.
Epidemiologic characteristics of adult candidemic patients in a secondary hospital in Kuwait: A retrospective study
2019, Journal de Mycologie Medicale
Candida blood steam infection is a life-threatening disease that seems to be under estimated. Understanding epidemiology of such disease is crucial for improved diagnosis, optimized treatment, and better outcome. Through this retrospective study, we aimed to determine the incidence of candidemia in a secondary care hospital, and to describe the epidemiology and outcome of candidemia among adult patients. The incidence of candidemia for all age groups was 0.24, 0.16 and 0.15 cases/1000 patient-days in 2014, 2015 and 2016 respectively. Among adult patients, 82 cases were identified. The patients had the following clinical characteristics with varying proportions: old age, diabetes, antibiotic exposure, use of vascular catheter, abdominal surgery, ICU hospitalization, haemodialysis, and total parenteral nutrition. All-cause 30-day mortality was 54% and ICU hospitalization was a recognized risk factor for death. The leading causative agents were Candida albicans (32%), and Candida parapsilosis (32%), followed by Candida tropicalis (20%), Candida glabrata (13%) and one each by Candida dubliniensis, Candida famata, and Candida auris. Almost all tested isolates were susceptible to caspofungin and amphotericin B. With regard to fluconazole, C. glabrata showed variable susceptibility. Other species were susceptible except one isolate, each of C. parapsilosis and C. auris. The study highlights the growing importance of non-C. albicans Candida species in the etiology of candidemia. Emergence of C. auris is a warning sign and needs to be closely monitored.
Up-regulation of chemokine CXCL13 in systemic candidiasis
2018, Clinical Immunology
Candida albicans is the leading cause of healthcare associated bloodstream infections. Chemokine CXCL13 is well-known involved in inflammation, but its role in candidemia has not been assessed. Our study firstly demonstrated that serum CXCL13 levels were significantly elevated in candidemic patients compared with bacteremic patients and control subjects by ELISA, and CXCL13 concentrations were positively and significantly correlated with clinical Sequential Organ Failure Assessment (SOFA) scores and several laboratory parameters in patients. Moreover, ROC curve analysis showed the diagnostic efficiency of CXCL13 was superior to CRP and PCT. To further study the role of CXCL13, a mouse model was established. Importantly, the data showed the dramatically elevated levels of CXCL13 in mice serum and infected kidney, were significantly correlated with renal fungal burden and pathology scores. In conclusion, our results indicated that CXCL13 had strong potential as a novel biomarker of diagnosis and prognosis for candidemia.
Association between Candida biofilm-forming bloodstream isolates and the clinical evolution in patients with candidemia: An observational nine-year single center study in Mexico
2018, Revista Iberoamericana de Micologia
Candidemia is one of the most common nosocomial infections globally and it is associated with considerable excess mortality and costs. Abreast, biofilm-forming strains are associated with even higher mortality rates and poor prognosis for the patient.
To evaluate a possible association between the biofilm-forming capability of Candida bloodstream isolates and the clinical evolution in patients with candidemia.
An observational, retrospective study was conducted at a tertiary care university hospital during 9 years (2006–2015). The biofilm quantitation of the Candida bloodstream isolates was determined by crystal violet staining and XTT reduction assay.
A total of 218 cases of candidemia had been diagnosed and 89 isolates were obtained. The mortality rate was 36% and the main risk factors were antibiotic exposure and the use of catheters. Candida tropicalis (52.8%) was the most frequent species, followed by Candida albicans (30.4%), Candida parapsilosis sensu stricto (10.1%), Candida orthopsilosis (3.4%), Candida krusei (2.2%) and Candida glabrata sensu stricto (1.1%). All the strains were biofilm producers, which is an important contribution to the patient's mortality. C. tropicalis showed the highest production of biomass biofilm, whereas C. glabrata exhibited the highest metabolic activity.
This study contributes to expand the knowledge about the local epidemiology of candidemia and highlights the impact of Candida biofilm on patient's outcome.
La candidemia es una de las infecciones nosocomiales más frecuentes globalmente y se encuentra asociada con una elevada mortalidad y coste económico. Las cepas productoras de biopelícula se asocian con elevadas tasas de mortalidad y mal pronóstico para el paciente.
Evaluar una posible asociación entre la capacidad de formación de biopelícula de aislamientos sanguíneos de Candida y la evolución clínica de pacientes con candidemia.
Durante 9 años (2006-2015) se ha llevado a cabo un estudio observacional y retrospectivo en un hospital universitario de tercer nivel de atención. La cuantificación de biopelícula de los aislamientos sanguíneos de Candida se determinó por tinción con cristal violeta y ensayo de reducción de XTT.
Se diagnosticó un total de 218 casos de candidemia y se obtuvieron 89 aislamientos. La tasa de mortalidad fue del 36% y los principales factores de riesgo fueron la exposición a antibióticos y el uso de catéteres. Candida tropicalis (52,8%) fue la especie más frecuente, seguida por Candida albicans (30,4%), Candida parapsilosis sensu stricto (10,1%), Candida orthopsilosis (3,4%), Candida krusei (2,2%) y Candida glabrata sensu stricto (1,1%). Todas las cepas produjeron biopelícula, una contribución importante a la mortalidad de los pacientes. C. tropicalis mostró la producción más alta de biomasa de biopelícula, mientras que C. glabrata exhibió la actividad metabólica más alta.
Este estudio contribuye a expandir el conocimiento de la epidemiología local de la candidemia y resalta el impacto de las biopelículas de Candida en el pronóstico del paciente.

View all citing articles on Scopus

View full text

Article preview

Journal of Infection

Summary

Background

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgement

References (20)

Management and outcome of bloodstream infections due to Candida species in England and Wales

J Hosp Infect

Effects of nosocomial candidemia on outcomes of critically ill patients

Am J Med

Changing face of health-care associated fungal infections

Curr Opin Infect Dis

Echinocandins in the management of invasive fungal infections, part 1

Am J Health-Syst Pharm

Surveillance of hospital-acquired bacteraemia in English hospitals 1997–2002

One year prospective survey of Candida bloodstream infections in Scotland

J Med Microbiol

Attributable mortality of candidemia: a systematic review of matched cohort and case-control studies

Eur J Clin Microbiol Infect Dis

Current treatment strategies for disseminated candidiasis

Clin Infect Dis

Excess mortality, hospital stay, and cost due to candidaemia: a case-control study using data from population-based candidaemia surveillance

Infect Control Hosp Epidemiol

Cited by (71)

Species identification and antifungal susceptibility of uncommon blood yeast isolates

The Economic Burden of Candidemia and Invasive Candidiasis: A Systematic Review

Morbidity and mortality of candidaemia in Europe: an epidemiologic meta-analysis

Epidemiologic characteristics of adult candidemic patients in a secondary hospital in Kuwait: A retrospective study

Up-regulation of chemokine CXCL13 in systemic candidiasis

Association between Candida biofilm-forming bloodstream isolates and the clinical evolution in patients with candidemia: An observational nine-year single center study in Mexico