Blood Culture Tests Reveal Fistula Infection In Febrile Patients
Overview
In this study, the researchers aimed to elucidate the importance of blood culture testing following pancreatoduodectomy (PD), a complex surgical procedure. The investigation focused on the rates of blood culture sampling and positivity during febrile episodes (FEs) in PD patients spanning from 2016 to 2021.
FEs were defined as instances where patients exhibited a body temperature of 38.0°C or higher, occurring on or after the 4th postoperative day. The origin of fever was retrospectively diagnosed, categorizing FEs as either pancreatic fistula (PF)-related or PF-unrelated. Factors associated with blood culture positivity were also examined.
Out of 339 PD patients, 99 experienced a total of 202 FEs. Blood culture testing was conducted for 160 FEs in 89 patients, yielding sampling and positivity rates of 79.2% and 17.5% per episode, respectively, and 89.9% and 28.1% per patient, respectively. Of these episodes, 36 were deemed PF-related, while 124 were categorized as PF-unrelated. Significantly lower blood culture positivity was observed in PF-related FEs compared to PF-unrelated ones (1/36 vs. 27/124, respectively, p= 0.006).
Furthermore, blood culture positivity was notably higher in patients with cholangitis, catheter-related bloodstream infection, and urinary tract infection compared to PF-related FEs. Multivariate analysis revealed a negative association between blood culture positivity and PF-related FEs, and a positive association with accompanying symptoms such as shivering, Pitt Bacteremia Score, and preoperative biliary drainage.
In conclusion, PD patients displayed relatively elevated blood culture positivity rates, suggesting the potential to differentiate between PF-related and PF-unrelated FEs based on these findings.
Introduction
Pancreatoduodenectomy (PD) stands as the gold standard procedure for addressing malignant and borderline malignant conditions in the periampullary region. Despite a commendable reduction in postoperative mortality rates to below 4% owing to advancements in surgical techniques and perioperative care, morbidity remains notably high, hovering around 40%, even in renowned high-volume medical centers. One common hallmark of post-PD complications is the onset of fever.
Given the significance of fever as a potential indicator of underlying complications, routine blood culture testing upon the emergence of fever, typically defined as a temperature of 38.0°C or higher, has become a standard practice in many medical institutions, including ours. Such testing serves the dual purpose of accurately identifying the causative infectious agents, thereby facilitating targeted antibiotic therapy and minimizing the indiscriminate use of broad-spectrum antibiotics.
However, the efficacy of routine blood culture testing in the post-PD setting has been a subject of debate. While it undoubtedly aids in pinpointing infectious organisms, the low positivity rate of blood cultures raises concerns regarding its efficiency vis-à-vis patient burden and testing costs. Previous studies exploring the utility of blood cultures in various postoperative scenarios have yielded mixed results, casting doubt on its universal applicability.
Notably, the complexity of PD and its associated complications, such as pancreatic fistula, intra-abdominal abscess, ascending cholangitis, pneumonia, and catheter-related bloodstream infections, underscores the unique nature of this surgical procedure. Consequently, the significance of blood culture testing after PD may differ from that of other surgeries, necessitating a dedicated investigation into its relevance and utility in this specific patient population.
To address this gap in knowledge, our study aimed to elucidate the significance of blood culture testing in the postoperative period following PD, recognizing the inherent challenges and complexities associated with this highly invasive surgical intervention. By shedding light on the role of blood culture testing in this context, we aspire to optimize postoperative management strategies and enhance patient outcomes in this challenging clinical scenario.
Method
A retrospective review was conducted on the medical records of consecutive patients who underwent pancreaticoduodenectomy (PD) for periampullary diseases at the Department of Gastroenterological Surgery, Aichi Cancer Center, between 2016 and 2021. The study aimed to identify factors associated with positive blood cultures in these patients.
Febrile episodes (FE) were defined as instances of fever reaching 38.0°C or higher occurring between the 4th postoperative day and discharge. Patients with FE underwent two sets of blood culture tests, unless sample collection was challenging. Fever origins were retrospectively diagnosed and classified as PF-related or PF-unrelated based on defined criteria. PF-related FEs were associated with postoperative pancreatic fistula (CRPOPF) or biochemical leakage (BCL), evident through imaging techniques. PF-unrelated FEs were diagnosed based on clinical manifestations, imaging findings, and laboratory tests.
Positive blood culture was defined as the detection of pathogenic bacteria in one or more sets of cultures, excluding skin commensals considered as contamination. Interpretation of blood culture results and diagnosis of fever origins were conducted in collaboration with infectious disease specialists and surgeons. The severity of FEs was assessed using the Pitt Bacteremia Score, considering factors such as body temperature, mental status, blood pressure, ventilation requirement, and recent cardiac events. Operative complications were evaluated using the Clavien–Dindo classification system.
In summary, the study reviewed PD patients’ records to analyze factors associated with positive blood cultures, utilizing defined criteria for FE diagnosis, fever origin classification, and severity assessment. Collaboration with specialists ensured accurate interpretation of findings, contributing to comprehensive understanding of postoperative complications in these patients.
Statistical Analysis
In this study, the main objective was to assess blood culture positivity as the primary endpoint following surgical procedures, with a specific focus on postoperative pancreatic fistula-related febrile events (PF-related FEs). To account for the longitudinal aspect of blood culture testing, Generalized Estimating Equations (GEE) were utilized for analysis. Uni- and multivariable GEE models were employed to evaluate the impact of PF-related FEs on blood culture positivity, with various covariates such as age, gender, body mass index, preoperative biliary drainage, Charlson comorbidity index, operative time, operative blood loss, maximum temperature ≥ 39.0°C, timing of FEs postoperatively, presence of shivering symptoms, and the Pitt Bacteremia Score considered in the analyses. Statistical tests including the chi-square test, Fisher’s exact probability test for categorical variables, and the Mann–Whitney U test for continuous variables were conducted. All analyses were conducted using STATA version 16 or SPSS version 21.0 software.
Result
During the observation period, a cohort of 339 patients who underwent pancreaticoduodenectomy (PD) was studied, with 99 of these patients experiencing a total of 202 febrile events (FEs). Blood culture testing was conducted in 160 of these FEs, equating to a per-episode sampling rate of 79.2%. Among these, bacterial species were detected in 33 episodes, with a blood culture positivity rate of 17.5% per episode. Gram-negative bacilli were the most commonly detected bacterial species.
On a patient population level, at least one blood culture test was performed in 89 out of 99 patients, with a sampling rate of 89.9%. Among these patients, a single positive blood culture was confirmed in 25 individuals, resulting in a patient-level positivity rate of 28.1%.
Regarding the origin of fevers, analysis revealed 36 febrile events related to postoperative fluid collections (PF-related) and 124 febrile events unrelated to postoperative fluid collections (PF-unrelated). Blood cultures were positive in only one PF-related FE and 27 PF-unrelated FEs. Notably, blood culture positivity was significantly higher in PF-unrelated FEs compared to PF-related ones.
Speculated origins of PF-unrelated FEs included cholangitis, intra-abdominal abscesses, respiratory infections, catheter-related bloodstream infections (CRBSI), and urinary tract infections. The blood culture positivity rate was notably higher in certain conditions such as cholangitis, CRBSI, and urinary tract infections compared to PF-related FEs.
Factors correlating with blood culture positivity included accompanying symptoms of shivering, a higher Pitt Bacteremia Score, and preoperative biliary drainage. Conversely, the presence of PF-related febrile events was negatively associated with blood culture positivity.
Overall, the study provides insights into the prevalence and origins of febrile events following PD, highlighting the importance of blood culture testing in identifying causative pathogens, particularly in PF-unrelated cases.
Conclusion
A review of 10 publications regarding blood culture collection in postoperative patients revealed varying rates of positivity, generally low, discouraging routine collection due to cost and invasiveness. However, our study, focused on post-pancreaticoduodenectomy (PD) patients, demonstrated significantly higher positivity rates, suggesting potential benefits in antibiotic management. Notably, post-PD fevers commonly stemmed from cholangitis and pancreatic fistula (PF)-related fevers, posing diagnostic challenges. Cholangitis, often reflux-related without typical blood test abnormalities, exhibited higher blood culture positivity, likely due to bacterial reflux into hepatic sinusoids. Conversely, PF-related fevers showed lower positivity, attributed to localized peritoneal inflammation. Yet, blood culture results proved pivotal in select cases, aiding treatment decisions, particularly when drainage feasibility was uncertain. Despite challenges like contamination risk and cost, multivariate analysis highlighted predictors of positive cultures, aiding in decision-making regarding culture necessity. While acknowledging study limitations, including its retrospective nature, the study underscores the potential utility of blood cultures in post-PD patients, guiding antibiotic therapy and distinguishing fever etiology. Further research is warranted to refine criteria for culture collection and identify patient subsets benefiting most.
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