This study was conducted at the Aichi Cancer Center (ACC), a 500-bed tertiary care facility in Aichi, Japan. The center has 23 clinical departments and admits approximately 11,000 patients annually. Specifically, 15 departments are in charge of inpatients: plastic and reconstructive surgery, hematology and cell therapy, thoracic surgery, thoracic oncology, gastroenterological surgery, gastroenterology, orthopedic surgery, head and neck surgery, breast oncology, neurosurgery, urology, gynecological oncology, radiation oncology, diagnostic and interventional radiology, and clinical oncology. The Antimicrobial Stewardship Team (AST) comprises one ID specialist (increased to two from April 1, 2021), a pharmacist, two laboratory technicians, and an infection control nurse.
This was a single-institution retrospective observational study conducted over 48 months between April 1, 2018, and March 31, 2022.
The interventions evaluated in this study were implemented in two phases:
Phase 1: Pre-intervention period (April 1, 2018 to March 31, 2020).
Phase 2: Implementation of ASP and establishment of ID consultation service (April 1, 2020 to March 31, 2022).
The inclusion criteria were all inpatients with positive blood cultures between April 1, 2018 and March 31, 2022.
On weekdays, ID specialists promptly communicated positive blood culture results to the primary physician team to ensure appropriate empiric therapy. Over the weekend, the laboratory or ID specialists did not communicate positive blood culture results to the primary physician team but reported them the following weekday. In cases where Staphylococcus aureus (S. aureus) or Candida spp. were detected, an ID consultation was suggested and the patients were examined at the bedside.
Moreover, audits were conducted thrice weekly at the AST conferences for all patients on (i) specific anti-methicillin-resistant S. aureus agents—vancomycin, teicoplanin, daptomycin, linezolid; and (ii) particular broad-spectrum antibiotics—cefepime, cefozopran, piperacillin–tazobactam, imipenem–cilastatin, meropenem, and doripenem. Patients who had already received an ID consultation were excluded from the audit. For AST conferences, the pharmacist retrieved data of patients who received specific antimicrobials, from ACC’s electronic medical record system. The laboratory technicians shared the latest microbiological information pertaining to these patients with the other AST members. Upon identifying drug-resistant organisms in the patient, the infection control nurse quickly alerted the manager of the ward where the patient was admitted and provided necessary infection control measures. ID specialists oversaw the comprehensive management of each professional’s role in this process. All cases reviewed at the conferences were documented in the electronic medical record. For patients judged by the AST as requiring either modification of antimicrobial therapy or further additional culture tests due to insufficient testing, feedback was provided to the primary physician team on the audit day, either by phone call or a note in the patients’ medical record. All audited patients were monitored daily on weekdays until the completion of their specific antimicrobial therapy or for the duration of follow-up required by the AST. The AST contacted the primary physician teams whenever necessary. From April 2021, the audits were extended to all weekdays, and fluoroquinolones were added to the targeted antimicrobial list. For patients who were deemed to require bedside evaluation by the ID specialists due to challenges in diagnosing and determining treatment for IDs based solely on review of medical record information by the AST conference, the ID specialists contacted the primary physician team to propose an ID consultation.
ID consultation service
Dedicated ID specialists provided patient consultation from primary physician teams in the 15 aforementioned departments on all weekdays.
For all patients with positive blood cultures, the following information was collected from ACC’s electronic medical record system for each episode: age, sex, department, date of blood culture, fluid collection, microorganism detection, diagnosis, 30-day all-cause mortality, and whether the ID specialists provided feedback. The ACC database provided information regarding the number of specimen submissions, AS reviews, and ID consultations. We accessed these data on August 5, 2023 for research purposes.
The diagnosis was determined from medical record descriptions, and missing descriptions were categorized as unknown. When the infection focus was clear, the diagnosis was not classified as febrile neutropenia, regardless of the presence of neutropenia. The term “multiple infection” was defined as the presence of two distinct ID conditions without a clear determination of which caused the bacteremia. The two-set blood culture rate was defined as (number of two sets/total sets) × 100, while the blood culture positivity rate was defined as (number of positive sets/total sets) × 100. Positive blood culture episodes with unknown outcome were excluded from the calculation of all-cause 30-day mortality. Respiratory specimens included sputum, pharyngeal mucus, nasal mucus, oral mucus, lung tissue, and bronchial lavage fluid. Gastrointestinal specimens encompassed stool, bile, and pancreatic fluid. Genitourinary specimens consisted of urine and vaginal secretions. Puncture fluid specimens comprised pleural fluid, ascitic fluid, spinal fluid, joint fluid, and bone marrow fluid. Other materials included catheter tips and wound cultures, drain cultures, and cultures obtained from various sources.
Primary outcome measures
The primary outcome presented the proportion of patients with an unknown diagnosis documented in the medical record per positive blood culture.
Secondary outcome measures
Secondary outcomes assessing the impact of ASP and ID consultations on diagnostic testing included the following: (i) number of each type of culture specimen submitted per 1000 patient-days of hospitalization, (ii) blood culture two-set rate, and (iii) blood culture positivity rate. Culture specimens for inpatients included blood, respiratory, gastrointestinal, and genitourinary specimens, puncture fluid, other materials, and total specimens. Culture specimens used for screening were excluded from the study. Moreover, to determine the prognostic impact of our intervention, we evaluated the all-cause 30-day mortality rate of patients with blood culture-positive episodes. Second and subsequent episodes of bacteremia in the same patient during the study period were included in the mortality rate. In addition, the mortality rate included all deaths, including those caused by cancer and IDs.
Pearson’s Chi-square and Fisher’s exact tests were used for categorical variables, while the Wilcoxon rank-sum test was used to analyze continuous variables. The primary endpoints and 30-day mortality rates were compared between the pre- and post-intervention periods (April 1, 2018 to March 31, 2020 and April 1, 2020 to March 31, 2022, respectively). The secondary endpoints other than the 30-day mortality rate were examined using an interrupted time series. Due to the exploratory nature of this study, no adjustments were made for multiple comparisons. A p value less than 0.05 was considered statistically significant. Analyses were performed using the R software, version 4.2.0 (The R Foundation for Statistical Computing, Vienna, Austria) and SPSS version 28 (IBM Corp., Armonk, NY, USA).
This study was approved by the Institutional Review Board of the ACC Hospital (approval number: 2023-0-161) and was conducted according to the principles of the Declaration of Helsinki. The requirement for informed consent was waived by the Institutional Review Board of ACC Hospital because this study only used data collected in clinical practice.