Article

Impact of First-Line Antifungal Agents on the Outcomes and Costs of Candidemia

Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.45). 04/2012; 56(7):3950-6. DOI: 10.1128/AAC.06258-11
Source: PubMed

ABSTRACT Candida species are the leading causes of invasive fungal infection among hospitalized patients and are responsible for major economic burdens. The goals of this study were to estimate the costs directly associated with the treatment of candidemia and factors associated with increased costs, as well as the impact of first-line antifungal agents on the outcomes and costs. A retrospective study was conducted in a sample of 199 patients from four university-affiliated tertiary care hospitals in Korea over 1 year. Only costs attributable to the treatment of candidemia were estimated by reviewing resource utilization during treatment. Risk factors for increased costs, treatment outcome, and hospital length of stay (LOS) were analyzed. Approximately 65% of the patients were treated with fluconazole, and 28% were treated with conventional amphotericin B. The overall treatment success rate was 52.8%, and the 30-day mortality rate was 47.9%. Hematologic malignancy, need for mechanical ventilation, and treatment failure of first-line antifungal agents were independent risk factors for mortality. The mean total cost for the treatment of candidemia was $4,743 per patient. Intensive care unit stay at candidemia onset and antifungal switch to second-line agents were independent risk factors for increased costs. The LOS was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switch to second-line agents for any reasons was the only modifiable risk factor of increased costs and LOS. Choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia.

Download full-text

Full-text

Available from: Kyong Hwa Park, Apr 10, 2014
0 Followers
 · 
123 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we developed a self-assembled biodegradable polyglutamic acid (PGA)-based formulation of amphotericin B (AmB) and evaluated its in vitro antifungal potential against Candida albicans. The AmB-loaded PGA nanoparticles were prepared in-house and had a mean size dimension of around 98±2 nm with a zeta potential of -35.2±7.3 mV. Spectroscopic studies revealed that the drug predominantly acquires an aggregated form inside the formulation with an aggregation ratio above 2. The PGA-based AmB formulation was shown to be highly stable in phosphate-buffered saline as well as in serum (only 10%-20% of the drug was released after 10 days). The AmB-PGA nanoparticles were less toxic to red blood cells (<15% lysis at an AmB concentration of 100 μg/mL after 24 hours) when compared with Fungizone(®), a commercial antifungal product. An MTT assay showed that the viability of mammalian cells (KB and RAW 264.7) was negligibly affected at AmB concentrations as high as 200 μg/mL. Histopathological examination of mouse kidney revealed no signs of tissue necrosis. The AmB-PGA formulation showed potent antimicrobial activity similar to that of Fungizone against C. albicans. Interestingly, AmB-bearing PGA nanoparticles were found to inhibit biofilm formation to a considerable extent. In summary, AmB-PGA nanoparticles showed highly attenuated toxicity when compared with Fungizone, while retaining equivalent active antifungal properties. This study indicates that the AmB-PGA preparation could be a promising treatment for various fungal infections.
    International Journal of Nanomedicine 03/2015; 10:1769-90. DOI:10.2147/IJN.S63155 · 4.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A copolymer was used as a platform for solubilisation of an anti-leishmanial agent. A non-covalent complex of amphotericin B (AmB) and poly(vinylpyrrolidone-co-methacrylic acid) (PVM) sodium salt was prepared from a N-hydroxysuccinimide (NHS) active ester precursor polymer in an effort to improve the therapeutic index of AmB. Leishmaniasis is a neglected disease that can be effectively treated with AmB. Unfortunately AmB is poorly soluble and highly prone to aggregation and degradation. It is also toxic and the lipid formulations of AmB that can mediate this toxicity are too expensive and unstable to use in resource-limited regions of the world. We hypothesised that replacement of the lipids with an appropriate water-soluble polymer would be a viable strategy to address the issues of AmB solubility, toxicity and cost of the final medicine. Copolymer precursors of PVM were prepared using different ratios of the monomers, N-1-vinyl-2-pyrrolidone and N-methacryloxysuccinimide. Complexation of AmB was achieved by hydrolysis of the NHS moiety as a DMSO solution of the copolymer precursor and AmB was diluted with sodium hydroxide and water. The free AmB was removed from the AmB–PVM complex, and then freeze dried to give water-soluble (2 mg mL−1 AmB equivalents) complexes with AmB loadings ranging from 20 to 30 wt%. The AmB–PVM complex reduced the toxicity of AmB towards mammalian cells (THP-1 and KB cells) while retaining its activity against intracellular L. major amastigotes in macrophages derived from THP-1 cells. The EC50 of the complex ranged between 0.08 and 0.18 μg mL−1 which is quite similar to clinical AmB (Fungizone®) (0.06 ± 0.01 μg ml−1). Our results show that there is potential to develop safe and effective AmB–polymer complexes to treat leishmaniasis.
    01/2013; 4(3):584-591. DOI:10.1039/C2PY20425H
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of our study is to test procalcitonin (PCT) as surrogate marker of identification of Candida spp. by blood culture (BC) and real-time-polymerase chain reaction (PCR), whether alone or in association with bacteria, in septic patients. We performed a single-centre retrospective study. We reviewed the clinical charts of patients with a diagnosis of severe sepsis or septic shock treated at our general intensive care unit from March 2009 to March 2013. We analysed all diagnostic episodes consisting of BC, real-time PCR assay and dosage of PCT. We registered age, sex, white blood count, sequential organ failure assessment score and type of admission between medical or surgical. When inclusion criteria were met more than once, we registered the new diagnostic episode as subsequent diagnostic episode. The diagnostic performance of PCT to predict Candida spp. identification alone or in mixed infections by either BC or PCR was tested using the receiver-operative characteristic curve. Logistic regression was constructed using presence of Candida spp. as the dependent variable. A total of 260 diagnostic episodes met the inclusion criteria. According to BC results classification, a significantly lower value of PCT was observed in Candida spp. BSI (0.99 ng/ml, 0.86 - 1.34) than in BSI caused by bacteria (16.7 ng/ml, 7.65 - 50.2) or in mixed infections (4.76 ng/ml, 2.98 - 6.08). Similar findings were observed considering PCR results. A cut-off of ≤ 6.08 ng/ml for PCT yielded a sensitivity of 86.8%, a specificity of 87.4%, a positive predictive value of 63.9%, a negative predictive value (NPV) of 96.3% and an area under the curve of 0.93 for Candida spp. identification by BC. A similar high NPV for a cut-off ≤ 6.78 ng/ml was observed considering the classification of diagnostic episodes according to PCR results, with an AUC of 0.85. A subsequent diagnostic episode was independently associated with Candida spp. detection either by BC or PCR. PCT could represent a useful diagnostic tool to exclude the detection of Candida spp. by BC and PCR in septic patients.
    BMC Anesthesiology 02/2014; 14(1):9. DOI:10.1186/1471-2253-14-9 · 1.33 Impact Factor

Similar Publications