ABSTRACT
There are limited reports on the effectiveness of promoting pharmacist-led management of candidemia in tertiary care hospitals without a full-time infectious disease specialist. We aimed to assess the effectiveness of promoting pharmacist-led management of candidemia in a tertiary care hospital without a full-time infectious disease specialist and to determine the type of support provided by pharmacists in the antimicrobial stewardship team. This retrospective cohort study evaluated patients with Candida spp. detected in blood cultures between April 2013 and March 2024 at our hospital. To compare the effect of bundled intervention on patients with candidemia, patients enrolled during the periods from April 2013 to March 2018 and April 2018 to March 2024 were classified in the pre- and post-antimicrobial stewardship team pharmacist intervention groups, respectively. There were no significant differences in the baseline clinical characteristics or Candida spp. distribution between the two groups. Compliance to the candidemia treatment bundle significantly improved in the post-antimicrobial stewardship team pharmacist intervention group (4.5% vs 39.6%); however, there was no difference between the two groups in 30-day mortality. The antimicrobial stewardship team pharmacist primarily contributed by recommending treatment initiation, drug selection, and checking for bundle compliance. Pharmacist-led management of candidemia did not improve outcomes for patients with candidemia in a tertiary care hospital with no full-time infectious disease specialist. However, this management may have helped improve the quality of antifungal therapy in terms of drug selection, dosing, and drug interactions, thus contributing to improved candidemia treatment bundle compliance.
Key Words: management, candidemia, antimicrobial stewardship team, pharmacist, tertiary care hospital
INTRODUCTION
Candidemia is an infection with a high mortality rate.1,2 When treating this infection, the presence of complications and organ infection must be properly assessed, and blood culture negativity must be confirmed before the treatment duration is determined. Although guidelines vary in content, bundled interventions are recommended for treating candidemia.1,2 Promoting candidemia treatment bundles shown to improved treatment outcomes.3,4
Guidelines recommend the appropriate use of antimicrobial and antifungal drugs by infectious disease specialists and pharmacists.5 In Japan, the effectiveness of antimicrobial stewardship team (AST) support for candidemia has been reported in secondary and tertiary medical institutions with infectious disease specialists,6,7 but there are limited reports of AST activities in tertiary medical institutions without full-time infectious disease specialists.8
Therefore, this study investigated the effectiveness of promoting pharmacist-led management of candidemia in a tertiary care hospital without a full-time infectious disease specialist. We also aimed to determine the type of support provided by pharmacists in the AST.
METHODOLOGY
Overview of pharmacist-led candidemia management activities at our hospital
Our hospital is a tertiary care hospital with 704 sickbeds. The hospital has no hematology department and no full-time infectious disease specialist. The AST was established in April 2018, and management of candidemia was initiated.
The AST comprises an emergency specialist, urologist, gastrointestinal surgeon, pediatrician, part-time infectious disease specialist, full-time pharmacist, nurse, and clinical laboratory technician. The role of the part-time infectious disease specialist included attending weekly morning conferences for blood culture-positive patients and weekly consultation responses for difficult cases; they were not involved in any other aspect of the management of candidemia.
The AST comprises five pharmacists (two pharmacists are certified as both Infection Control Pharmacy Specialist and Infectious Disease Chemotherapy Pharmacist, and one pharmacist is certified as an Infectious Disease Chemotherapy Pharmacist), one of whom is dedicated full-time to AST responsibilities. At the core of the team is a full-time pharmacist, who conducts daily morning conferences for patients with positive blood cultures and oversees their follow-up care. The team also performs prospective audit and feedback of patients receiving broad-spectrum antibiotics, such as carbapenems, piperacillin-tazobactam, and fluoroquinolones. One of the key interventions implemented by the team is a bundled approach to the management of patients with candidemia. The candidemia management bundles recommended by the hospital are presented in Table 1.
Table 1.
Interventions and candidemia management in our hospital
| Antifungal drug support programs | Actions |
| Interventions for patients with positive blood cultures for yeast-like fungi | 1. Check blood culture results every morning (If the blood culture turns out positive after the afternoon, an antimicrobial stewardship team [AST] dedicated pharmacist will receive a consultation response from the patient’s doctor.) 2. Confirm appropriate empirical treatment 3. Recommend appropriate drugs and tests if no treatment is being administered |
| Assessments performed by the AST pharmacists | 1. Follow-up every 1–5 days depending on the patient’s treatment progress, severity, and frequency of blood sampling 2. Adjust drug dose according to renal function and Therapeutic Drug Monitoring results 3. Modify drugs according to target organ and susceptibility 4. Evaluate drug interactions (mainly azoles) 5. Recommend any missing tests to achieve the bundle compliance 6. If refractory, consult a part-time infectious disease specialist |
| Guideline-based candidemia treatment bundle1,2 | 1. Central venous catheter removal within 24 hours of diagnosis (The time when the blood culture became positive was considered the diagnosis time.) 2. Ophthalmological examination 3. Transthoracic echocardiography 4. Repeat blood culture 5. Confirm negative blood culture 6. Administer treatment for 14 days after confirmation of negative blood culture |
Data collection and evaluation items
All data were collected retrospectively from electronic medical records. The key items assessed included patient characteristics, risk factors for candidemia, Candida species, diagnosis, and initial treatment. The primary outcome was compliance with the treatment bundle. Secondary outcomes included 30-day mortality due to candidemia, transition to oral therapy, and pharmacist support. The AST pharmacist interventions were evaluated based on recommendations for treatment initiation and discontinuation, drug selection, dose modification, loading dose design (caspofungin or fluconazole), route of administration, and testing recommendations. Bundle elements such as “confirmed negative blood culture” and “14 days of treatment after negative blood culture” can only be achieved in surviving patients. To exclude patients who died or dropped out before completing bundle elements that should be achieved after treatment initiation, a subpopulation analysis was performed on patients who survived >30 days after positive blood culture.
Statistical analysis
JMP Pro 18.0.1 (SAS Institute Inc, Cary, NC, USA) was used to conduct the statistical analysis. The Mann–Whitney U test was used to compare continuous variables, and Fisher’s exact test was used to compare nominal variables. Statistical significance was set at P < 0.05.
Kaplan-Meier curves were generated to assess survival for up to 30 days, and the log-rank test was used to identify differences between the groups.
As a supplemental analysis, we employed an interrupted time series approach to assess trends in bundle completion rates with AST pharmacist intervention. Changes in levels and trends were analyzed using a segmented regression model. The model included outcomes as dependent variables and indicators for pre-intervention, post-intervention, time elapsed since the start of the study, and time since the intervention as independent variables. The offset was the natural logarithm of either the cumulative number of patients per 4-month period or the number of bundle items targeted. No transition period or comparison group was included. For the interrupted time series analysis, we utilized generalized linear models with a Poisson distribution. The analysis included 15 data points from the pre-intervention phase and 17 from the post-intervention phase, excluding the period from April to July 2019 (during which no candidemia cases occurred).
RESULTS
Patients’ characteristics
Between April 2013 and March 2024, Candida spp. were detected in the blood cultures of 112 patients. After excluding 10 patients who died before their blood cultures became positive, 6 patients who were not treated as end-of-life care at the time their blood cultures became positive, and 4 patients who were transferred to other hospitals for treatment, 92 patients were included in the analysis (Figure 1). The pre- and post-AST pharmacist intervention groups comprised 44 and 48 patients, respectively. The patient characteristics in both groups are shown in Table 2. No significant differences were observed in patient characteristics between the two groups, except for β-D-glucan levels.
Fig. 1.
Patient selection scheme
AST: antimicrobial stewardship team
Table 2.
Clinical characteristic of patients included in the analysis
| Characteristic | Pre-AST pharmacist intervention group (n = 44) | Post-AST pharmacist intervention group (n = 48) | P-value |
| Age, years (IQR) | 75.5 (65.7–85.0) | 77.0 (69.2–83.0) | 0.956 |
| Sex (female) | 25 (56.8%) | 22 (45.8%) | 0.306 |
| Height, cm (IQR) | 152.4 (147.9–162.7) | 158 (147.8–164.3) | 0.277 |
| Body weight, kg (IQR) | 46.2 (39.2–61.5) | 49.6 (43.2–55.6) | 0.320 |
| Body mass index, kg/m2 (IQR) | 19.4 (16.3–24.2) | 20.1 (16.9–22.5) | 0.984 |
| Charlson Comorbidity Index (IQR) | 6 (5.0–9.7) | 6 (5.0–9.0) | 0.785 |
| Pitt Bacteremia Score (IQR) | 3 (1.0–5.0) | 2 (1.0–3.7) | 0.473 |
| ICU admission | 14 (31.8%) | 12 (25.0%) | 0.495 |
| Use of anti-Pseudomonas aeruginosa active drugs within 1 weeka,b | 16 (36.4%) | 21 (43.8%) | 0.527 |
| Surgery within 28 daysb | 7 (15.9%) | 9 (18.8%) | 0.787 |
| Artificial respirator useb | 8 (18.2%) | 8 (16.7%) | 1.000 |
| Immunosuppressive therapy within 1 monthb,c | 0 (0%) | 1 (2.1%) | 1.000 |
| Anticancer drugs within 1 monthb | 7 (15.9%) | 4 (8.3%) | 0.341 |
| Catecholamine useb | 5 (11.4%) | 8 (16.7%) | 0.556 |
| Central venous catheter (including CV port)b | 31 (70.5%) | 28 (58.3%) | 0.279 |
| Use of steroidsb | 7 (15.9%) | 3 (6.3%) | 0.185 |
| Total parenteral nutritionb | 25 (56.8%) | 24 (50.0 %) | 0.537 |
| Renal replacement therapyb | 9 (20.5%) | 5 (10.4%) | 0.247 |
| Febrile neutropeniab | 3 (6.8%) | 0 (0%) | 0.105 |
| Solid tumor | 19 (43.2%) | 17 (35.4%) | 0.523 |
| Blood tumor | 0 (0%) | 1 (2.1%) | 1.000 |
| COVID-19 | 0 (0%) | 0 (0%) | 1.000 |
| Time to positive blood culture, hour (IQR) | 41.0 (26.0–54.5) | 41.5 (30.2–58.0) | 0.487 |
| White blood cell, 103/μL (IQR) | 8.6 (6.2–13.3) | 9.0 (6.6–11.7) | 0.845 |
| Platelet, 104/μL (IQR) | 16.5 (12.0–25.4) | 18.7 (13.0–27.1) | 0.342 |
| C-reactive protein, mg/dL (IQR) | 7.2 (4.4–12.2) | 9.6 (5.4–16.5) | 0.098 |
| Serum creatinine, mg/dL (IQR) | 0.69 (0.52–1.32) | 0.89 (0.59–1.50) | 0.188 |
| eGFR, mL/min/1.73 m2 (IQR) | 65.9 (38.4–102.7) | 56.8 (31.8–88.6) | 0.279 |
| β-D-glucan, pg/mLd | 34.6 (13.7–107.9) (n=31) |
154.8 (46.3–426.6) (n=30) |
0.006 |
| Candida spp.e | |||
| C. albicans | 16 | 17 | 0.509 |
| C. glabrata | 15 | 15 | |
| C. parapsilosis | 7 | 7 | |
| C. tropicalis | 3 | 5 | |
| C. krusei | 0 | 2 | |
| C. guilliermondii | 3 | 1 | |
| Other less common species | 0 | 3 | |
| Diagnosis | |||
| Catheter-related bloodstream infection | 31 | 27 | 0.550 |
| Mediastinitis | 2 | 1 | |
| Infectious endocarditis | 1 | 2 | |
| Intra-abdominal infection | 3 | 8 | |
| Urinary tract infectionf | 4 | 6 | |
| Decubitus ulcer with infection | 0 | 2 | |
| Unknown | 3 | 4 | |
| Initial therapeutic drug | |||
| Fosfluconazole | 9 | 7 | 0.469 |
| Echinocandins | 35 | 38 | |
| Liposomal amphotericin B | 0 | 2 | |
| Itraconazole | 0 | 1 | |
AST: antimicrobial stewardship team
CV: central venous
ICU: intensive care unit
IQR: interquartile range
eGFR: estimated glomerular filtration rate
aCarbapenem, piperacillin, tazobactam/piperacillin, fluoroquinolone, aminoglycoside, cefepime, cefoperazone/sulbactam, cefozopran, ceftazidime
b Time point for blood culture
c Biologics, Janus kinase inhibitors, and calcineurin inhibitors
dWithin 72 hours from the time of blood culture collection
e Two species of Candida were detected in two patients in the post-AST group.
f This was defined as follows: no other suspicion of infection; bacteria detected on blood and urine cultures are consistent; presence of pyuria, urinary turbidity, or urinary tract obstruction; the attending specialist diagnoses a urinary tract infection.
Bundle attainment and treatment effectiveness
Compliance rates for the candidemia treatment bundles are presented in Table 3. The post-AST pharmacist intervention group demonstrated significantly higher rates of compliance compared to the pre-AST pharmacist intervention group in several key components, including blood culture retesting, confirmation of negative blood culture, treatment for at least 14 days after negative blood culture, and transthoracic echocardiography. The overall implementation rate of all six bundle elements increased from 4.5% in the pre-AST pharmacist intervention group to 39.6% in the post-AST pharmacist intervention group. The difference between the two groups remained consistent when the analysis was limited to patients who survived >30 days after positive blood cultures.
Table 3.
Treatment bundle compliance rates before and after AST interventions
| Treatment administered | Pre-AST pharmacist intervention group (n = 44) | Post-AST pharmacist intervention group (n = 48) | P-value |
| CVC removal within 24 hours of diagnosis | 26/31 (83.9%) | 22/28 (78.6%) | 0.741 |
| Ophthalmological examination | 32 (72.7%) | 41 (85.4%) | 0.197 |
| Transthoracic echocardiography | 6 (13.6%) | 32 (66.7%) | <0.001 |
| Blood culture retesting | 33 (75%) | 45 (93.8%) | 0.018 |
| Negative blood culture confirmation | 30/33 (68.2%) | 43 (89.6%) | 0.018 |
| Treatment for at least 14 days after a negative blood culture | 16 (36.4%) | 31 (64.6%) | 0.011 |
| Bundle compliance rate (all six items)a | 2 (4.5%) | 19 (39.6%) | <0.001 |
| Subpopulation analysis of patients who survived >30 days after a positive blood culture | Pre-AST pharmacist intervention group (n = 33) | Post-AST pharmacist intervention group (n = 35) | P-value |
| CVC removal within 24 hours of diagnosis | 19/22 (86.4%) | 17/22 (77.3%) | 0.698 |
| Ophthalmological examination | 23 (69.7%) | 33 (94.3%) | 0.105 |
| Transthoracic echocardiography | 5 (15.2%) | 25 (71.4%) | <0.001 |
| Blood culture retesting | 24 (72.7%) | 34 (97.1%) | 0.006 |
| Negative blood culture confirmation | 23 (69.7%) | 34 (97.1%) | 0.003 |
| Treatment for at least 14 days after a negative blood culture | 15 (45.5%) | 28 (80.0%) | 0.005 |
| Bundle compliance rate (all six items)a | 2 (6.1%) | 17 (48.6%) | <0.001 |
AST: antimicrobial stewardship team
CVC: central venous catheter
a For patients who did not have a CVC inserted, only five items were measured.
Although no statistically significant changes in level or slope were observed across the intervention periods, interrupted time series analyses indicated trends toward improvement in overall bundle completion rates (Supplementary Figure S1, Table S1). The 30-day mortality rates were 25% (11/44) in the pre-AST pharmacist intervention group and 27.1% (13/48) in the post-AST pharmacist intervention group, with no statistically significant difference between the two groups (Fisher’s exact test, P = 1.00). Kaplan–Meier curves for 30-day mortality (Figure 2) also showed no significant difference (Log-rank test, P = 0.112). Data on persistent positive blood culture rates, oral drug transition rates, and duration of treatment for patients with candidemia are presented in Table 4.
Fig. 2.
Thirty-day mortality in patients with candidemia
AST: antimicrobial stewardship team
Table 4.
Therapeutic effects on candidemia
| Effect | Pre-AST pharmacist intervention group (n = 44) | Post-AST pharmacist intervention group (n = 48) | P-value |
| Persistent positive blood culturea | 10/33 (30.3%) | 4/45 (8.9%) | 0.080 |
| Oral drug transition | 5 (11.4%) | 10 (20.8%) | 0.267 |
| Length of treatment, days (IQR) | 15.5 (12.3–22.5) | 18 (14.0–25.8) | 0.240 |
AST: antimicrobial stewardship team
IQR: interquartile range
a Only cases in which blood culture retesting were included.
Support provided by the AST pharmacists
The main areas of support provided by the AST pharmacists to patients with candidemia included recommendations for treatment initiation, selection of drugs at initiation, and determination of loading dose (Table 5). Recommendations for tests to ensure compliance with the candidemia treatment bundle requirements, such as echocardiography and ophthalmological tests, were made in almost all cases.
Table 5.
Recommendations from the AST pharmacists and acceptance rates
| Recommendation | Blood culture conference or pre-conference recommendations | During transitional follow-up |
| Commencement of treatment | 30/31 (96.8%) | — |
| Escalationa | 0/0 | 0/0 |
| De-escalationa | 3/3 (100%) | 7/7 (100%) |
| Drug selection | 29/29 (100%) | 3/3 (100%) |
| Increase doseb | 2/2 (100%) | 5/5 (100%) |
| Decrease doseb | 0/0 | 3/3 (100%) |
| Determination of loading dosec | 5/5 (100%) | 6/6 (100%) |
| Drug interaction management | 0/0 | 6/6 (100%) |
| Inspection recommendationsd | 40/43 (93.0%) | 4/4 (100%) |
AST: antimicrobial stewardship team
aDefined in Figure S2
bAssociated with changes in organ function or renal replacement therapy
cChanges to caspofungin or fluconazole
dTests to ensure compliance with the candidemia treatment bundle requirements, such as echocardiography and ophthalmological tests
DISCUSSION
This study examined the effectiveness of pharmacist-led management of candidemia in a hospital that does not have a full-time infectious disease specialist. With severe infections such as Staphylococcus aureus bacteremia,9 Pseudomonas aeruginosa bacteremia,10 and candidemia,11 early consultation with an infectious disease specialist is associated with reduced mortality and improved patient outcomes; therefore, early and appropriate therapeutic intervention is crucial. However, Japan has a shortage of infectious disease specialists, and most specialists work at university hospitals.12 Therefore, pharmacists must play a central role in ASTs in many hospitals, and their intervention in infectious disease treatment is important.13,14
The mortality associated with candidemia is considerably high, with international studies reporting rates between 10% and 50%.1,2 In reports from Japan, the mortality rate is estimated to be approximately 20% to 60%, although it varies widely from one report to another.6-8 National guidelines recommend bundle management to improve the prognosis of candidemia. Reports from Japan also indicate that promoting the candidemia treatment bundle improves clinical outcomes.3 A candidemia treatment bundle, based on the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases guidelines,1,2 was developed at our hospital (Table 1), and its effectiveness was studied.
Although the promotion of candidemia management by the pharmacist-led AST significantly increased compliance with the candidemia treatment bundle, no significant differences in 30-day mortality rates were observed. The candidemia treatment bundle (all six items) compliance rate improved significantly from the pre-AST pharmacist intervention group (4.5%) to the post-AST pharmacist intervention group (39.6%); however, the compliance rate remained low. This may be related to the high mortality rate from candidemia. The treatment bundle includes negative blood culture confirmation followed by 14 days of treatment. Therefore, it is difficult to achieve the bundle if the patient dies before negative blood culture confirmation or within 14 days after the confirmation. In addition, tests may not be performed for patients with severe symptoms and scheduled for end-of-life care. However, when the analysis was limited to patients who survived 30 days or more after a positive blood culture, compliance with the candidemia treatment bundle (all six items) improved. Although there were slight differences in the bundle content, the completion rate in Kawaguchi et al’s report,7 which was based on a university hospital with an on-site infectious disease specialist, was approximately 50%, a comparable level. Considering that the bundle completion rate in Takesue et al’s report was 21.4%,3 our pharmacist-led initiative is highly valuable. Furthermore, although the report by Murakami et al,8 based on a tertiary medical institution without an infectious disease specialist, did not include the overall bundle completion rate, it focused solely on physician-led AST. Our study’s inclusion of the diagnostic process of echocardiography, and the fact that it was conducted as a pharmacist-led AST, are significant.
A detailed analysis of bundle components (Table 3) revealed the specific aspects of care most impacted by pharmacist-led AST. The most significant improvements were seen in procedures that pharmacists could review and recommend without strict deadlines, such as transthoracic echocardiography, repeat blood cultures, and negative blood culture confirmation. These items align closely with the pharmacist’s main activities, such as inspection recommendations (Table 5). Conversely, “central venous catheter removal within 24 hours” showed the least improvement. This may be because this item was already implemented at a relatively high rate (83.9%) pre-intervention. Unlike electronic orders, it requires a physician-dependent procedure, has a strict 24-hour time limit that can be missed during weekends or nights (when pharmacist intervention may be delayed), and involves complex clinical decision-making in severe cases (eg, patients on high-dose catecholamines). Similarly, “treatment for at least 14 days after a negative blood culture” (36.4% to 64.6%), while improved, was not fully achieved. This highlights a limitation of intervention timing; if a pharmacist notices a premature discontinuation (eg, on day 13) retrospectively, it is difficult to recommend restarting therapy. These findings suggest that items requiring strict time adherence and physician-dependent procedures (central venous catheter removal) or retrospective review (treatment duration) are challenging to manage solely through case-by-case pharmacist intervention. To further improve compliance, these individual interventions must be supplemented by continuous, hospital-wide education and awareness campaigns regarding the candidemia bundle.
Six possible reasons for the lack of significant reductions in the 30-day mortality rates may be proposed. (1) The rates of central venous catheter removal within 24 hours of diagnosis, ophthalmological examination, and blood culture retesting were considerably high compared to those previously reported,6-8 even before the AST pharmacist intervention was implemented. Candidemia may have been appropriately treated to some extent even before the AST pharmacist intervention. (2) Treatment rates were significantly higher in the post-AST pharmacist intervention group within 14 days of negative blood culture results than in the pre-AST pharmacist intervention group. However, treatment duration was similar between the two groups. (3) The increase in echocardiography examination rates was associated with a significant improvement in bundle compliance rates. The complication rate of endocarditis resulting from candidiasis is 2% to 8% in patients with candidemia, and it is rare.15-17 In the present study, only one case (2.2%) of infectious endocarditis was noted in the pre-AST pharmacist intervention group, while two cases (4.2%) were identified in the post-AST pharmacist intervention group. (4) The number of patients treated during the study period and included in the analysis was small. Takesue et al analyzed a large number of cases and reported that compliance to the candidemia treatment bundle led to improved clinical outcomes.3 Other studies involving a small number of cases reported that improved compliance to treatment bundles did not improve 30-day mortality rates.6-8 (5) The coronavirus disease 2019 pandemic occurred in the period after the AST intervention was implemented. Although the present study did not include any patients who tested positive for coronavirus disease 2019, the prevalence of this disease may have had an unforeseen impact on the outcomes because the hospital has been designated as a medical institution for Class II infectious diseases. (6) β-D-glucan levels were higher in the post-AST pharmacist intervention group compared to the pre-AST pharmacist intervention group.
Previous research has shown that high β-D-glucan levels are associated with higher mortality rates.18,19 Therefore, it is possible that this may have negated the effect of the AST pharmacist intervention.
Support from AST pharmacists for candidemia treatment mainly consisted of recommendations for drug selection, dose adjustment, and checking for bundle compliance. The content of support from pharmacists was similar to that reported in other countries, where healthcare systems and pharmacists’ remit differ.20,21 Our hospital had a high support acceptance rate, suggesting that a pharmacist-led AST is an important component in a hospital that does not have an infectious disease department. The cooperation between various departments contributed to the high proposal acceptance rate, as the AST included doctors from several departments and could participate in the blood culture conferences every morning. Since April 2020, the AST pharmacist has provided education regarding infectious disease treatment to residents at the hospital; we consider that a good relationship has been established with the AST pharmacist, particularly among younger doctors.
The drugs used to treat candidemia pose a number of challenges. For example, several drug interactions with azoles must be addressed appropriately.22 A loading dose is recommended for fluconazole, voriconazole, and caspofungin, and the patient’s renal function and weight are relevant to dose setting. Appropriate dosage adjustment by a pharmacist is necessary, especially in critically ill patients, because pharmacokinetic parameters may change daily.
This study had several limitations. First, the study was a single-agency management of candidemia initiative. Currently, and for various reasons, hospital medical staff are under-resourced,12,23,24 and the number of medical staff available for involvement in the management of candidemia varies widely from facility to facility. Therefore, extrapolating these findings to initiatives at other facilities may not be possible. Second, the drugs available in Japan differ from those available in other countries. Consequently, the choice of antifungal drugs and methods of administration may differ, leading to differences in interventions provided by pharmacists. Finally, the number of patients included in the study was small.
CONCLUSION
Pharmacist-led management of candidemia did not improve treatment outcomes for patients with candidemia in a tertiary care hospital that had no full-time infectious disease specialist. However, this strategy may have helped improve the quality of antifungal therapy in terms of drug selection, dosing, and drug interactions, thus contributing to improved candidemia treatment bundle compliance.
ACKNOWLEDGEMENTS
Ethics considerations
This study was approved by institutional review board of Kariya Toyota General Hospital (approval number, 904).
Consent to participate
In accordance with national ethical guidelines, the requirement for informed consent was waived and an opt-out process was implemented.
Consent for publication
Not applicable.
Author contributions
All authors have met the International Committee of Medical Journal Editors (ICMJE) authorship criteria and have given final approval for submission of the final version. Teruhisa Kinoshita, Shoko Sahara, Atsuya Kondo, and Keisuke Oka: Writing of original draft. Yuki Kondo, Yoichi Ishitsuka, and Norio Takimoto: Review and editing. Yuki Kondo, Yoichi Ishitsuka, and Keisuke Oka: Supervision.
Declaration of conflicting interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Miscellaneous acknowledgments
We would like to express our sincere gratitude to the antimicrobial stewardship team at Kariya Toyota General Hospital for their assistance in preparing this paper. We would like to thank Editage (www.editage.com) for English language editing.
Supplementary Material
Abbreviation
- AST
antimicrobial stewardship team
Funding Statement
The authors received no financial support for the research, authorship, and/or publication of this article.
REFERENCES
- 1.Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50. doi: 10.1093/cid/civ933 [DOI] [PMC free article] [PubMed]
- 2.Cornely OA, Bassetti M, Calandra T, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012;18(suppl 7):19–37. doi: 10.1111/1469-0691.12039 [DOI] [PubMed]
- 3.Takesue Y, Ueda T, Mikamo H, et al. Management bundles for candidaemia: the impact of compliance on clinical outcomes. J Antimicrob Chemother. 2015;70(2):587–593. doi: 10.1093/jac/dku414 [DOI] [PMC free article] [PubMed]
- 4.Hoenigl M, Salmanton-García J, Egger M, et al. Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study. Lancet Infect Dis. 2023;23(6):751–761. doi: 10.1016/S1473-3099(22)00872-6 [DOI] [PubMed]
- 5.Dellit TH, Owens RC, McGowan JE Jr, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159–177. doi: 10.1086/510393 [DOI] [PubMed]
- 6.Samura M, Hirose N, Kurata T, et al. Support for fungal infection treatment mediated by pharmacist-led antifungal stewardship activities. J Infect Chemother. 2020;26(3):272–279. doi: 10.1016/j.jiac.2019.09.016 [DOI] [PubMed]
- 7.Kawaguchi H, Yamada K, Imoto W, et al. The effects of antifungal stewardship programs at a tertiary-care teaching hospital in Japan. J Infect Chemother. 2019;25(6):458–462. doi: 10.1016/j.jiac.2019.01.015 [DOI] [PubMed]
- 8.Murakami M, Komatsu H, Sugiyama M, et al. Antimicrobial stewardship without infectious disease physician for patients with candidemia: A before and after study. J Gen Fam Med. 2018;19(3):82–89. doi: 10.1002/jgf2.159 [DOI] [PMC free article] [PubMed]
- 9.Vogel M, Schmitz RP, Hagel S, et al. Infectious disease consultation for Staphylococcus aureus bacteremia — A systematic review and meta-analysis. J Infect. 2016;72(1):19–28. doi: 10.1016/j.jinf.2015.09.037 [DOI] [PubMed]
- 10.Chiong F, Wasef MS, Liew KC, et al. The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bactaeremia in adults: a retrospective cohort study. BMC Infect Dis. 2021;21(1):671. doi: 10.1186/s12879-021-06372-5 [DOI] [PMC free article] [PubMed]
- 11.Takakura S, Fujihara N, Saito T, et al. Improved clinical outcome of patients with Candida bloodstream infections through direct consultation by infectious diseases physicians in a Japanese university hospital. Infect Control Hosp Epidemiol. 2006;27(9):964–968. doi: 10.1086/504934 [DOI] [PubMed]
- 12.Hagiya H. Shortage and unequal distribution of infectious disease specialists in Japan: how can we refine the current situation? PLoS One. 2023;18(10):e0291677. doi: 10.1371/journal.pone.0291677 [DOI] [PMC free article] [PubMed]
- 13.Monmaturapoj T, Scott J, Smith P, Abutheraa N, Watson MC. Pharmacist-led education-based antimicrobial stewardship interventions and their effect on antimicrobial use in hospital inpatients: a systematic review and narrative synthesis. J Hosp Infect. 2021;115:93–116. doi: 10.1016/j.jhin.2021.06.003 [DOI] [PubMed]
- 14.Mahmood RK, Gillani SW, Alzaabi MJ, Gulam SM. Evaluation of inappropriate antibiotic prescribing and management through pharmacist-led antimicrobial stewardship programmes: a meta-analysis of evidence. Eur J Hosp Pharm. 2022;29(1):2–7. doi: 10.1136/ejhpharm-2021-002914 [DOI] [PMC free article] [PubMed]
- 15.Foong KS, Sung A, Burnham JP, et al. Risk factors predicting Candida infective endocarditis in patients with candidemia. Med Mycol. 2020;58(5):593–599. doi: 10.1093/mmy/myz104 [DOI] [PMC free article] [PubMed]
- 16.Hitzenbichler F, Joha T, Simon M, et al. Candida endocarditis in patients with candidemia: a single-center experience of 14 cases. Mycopathologia. 2020;185(6):1057–1067. doi: 10.1007/s11046-020-00492-3 [DOI] [PMC free article] [PubMed]
- 17.Huggins JP, Hohmann S, David MZ. Candida infective endocarditis: a retrospective study of patient characteristics and risk factors for death in 703 United States cases, 2015–2019. Open Forum Infect Dis. 2021;8(2):ofaa628. doi: 10.1093/ofid/ofaa628 [DOI] [PMC free article] [PubMed]
- 18.Giacobbe DR, Esteves P, Bruzzi P, et al. Initial serum (1,3)-β-D-glucan as a predictor of mortality in proven candidaemia: findings from a retrospective study in two teaching hospitals in Italy and Brazil. Clin Microbiol Infect. 2015;21(10):954.e9–954.e17. doi: 10.1016/j.cmi.2015.06.002 [DOI] [PubMed]
- 19.Akazawa H, Fukushima S, Higuchi T, et al. Prognostic Value of Serum (1→3)-β-D-Glucan Levels in Patients with Candidemia Stratified by Compliance with Candida Bundle: A Multicenter Retrospective Cohort Study (2016–2023). Mycopathologia. 2025;190(6):90. doi: 10.1007/s11046-025-00999-7 [DOI] [PMC free article] [PubMed]
- 20.Kara E, Metan G, Bayraktar-Ekincioglu A, et al. Implementation of pharmacist-driven antifungal stewardship program in a tertiary care hospital. Antimicrob Agents Chemother. 2021;65(9):e0062921. doi: 10.1128/AAC.00629-21 [DOI] [PMC free article] [PubMed]
- 21.Lachenmayr SJ, Strobach D, Berking S, Horns H, Berger K, Ostermann H. Improving quality of antifungal use through antifungal stewardship interventions. Infection. 2019;47(4):603–610. doi: 10.1007/s15010-019-01288-4 [DOI] [PubMed]
- 22.Lewis R, Niazi-Ali S, McIvor A, et al. Triazole antifungal drug interactions—practical considerations for excellent prescribing. J Antimicrob Chemother. 2024;79(6):1203–1217. doi: 10.1093/jac/dkae103 [DOI] [PMC free article] [PubMed]
- 23.Ohue T, Togo E, Ohue Y, Mitoku K. Mental health of nurses involved with COVID-19 patients in Japan, intention to resign, and influencing factors. Medicine (Baltimore). 2021;100(31):e26828. doi: 10.1097/MD.0000000000026828 [DOI] [PMC free article] [PubMed]
- 24.Takami H, Kodera Y, Eguchi H, et al. The shortage of surgeons in Japan: results of an online survey of qualified teaching hospitals that take part in the surgical training programs for board certification by the Japan Surgical Society. Surg Today. 2024;54(1):41–52. doi: 10.1007/s00595-023-02697-7 [DOI] [PMC free article] [PubMed]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.