Nirav Thosani and Srinivas Ramireddy contributed equally to this work as senior authors.
Current society guidelines recommend antibiotic prophylaxis for 3 to 5 days after endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions (PCLs). The overall quality of the evidence supporting this recommendation is low. In this study, we aimed to assess cyst infection and adverse event rates after EUS-FNA of PCLs among patients treated with or without postprocedural prophylactic antibiotics.
We retrospectively reviewed all patients who underwent EUS-FNA of PCLs between 2015 and 2019 at two large-volume academic medical centers with different practice patterns of postprocedural antibiotic prophylaxis. Data on patient demographics, cyst characteristics, fine-needle aspiration technique, periprocedural and postprocedural antibiotic prophylaxis, and adverse events were retrospectively extracted.
A total of 470 EUS-FNA procedures were performed by experienced endosonographers for the evaluation of PCLs in 448 patients, 58.7% of whom were women. The mean age was 66.3±12.8 years. The mean cyst size was 25.7±16.9 mm. Postprocedural antibiotics were administered in 274 cases (POSTAB+ group, 58.3%) but not in 196 cases (POSTAB– group, 41.7%). None of the patients in either group developed systemic or localized infection within the 30-day follow-up period. Procedure-related adverse events included mild abdominal pain (8 patients), intra-abdominal hematoma (1 patient), mild pancreatitis (1 patient), and perforation (1 patient). One additional case of pancreatitis was recorded; however, the patient also underwent endoscopic retrograde cholangiopancreatography.
The incidence of infection after EUS-FNA of PCLs is negligible. Routine use of postprocedural antibiotics does not add a significant benefit.
Pancreatic cystic lesions (PCLs) are increasingly being diagnosed owing to the widespread use of imaging tests for evaluating gastrointestinal symptoms or for other purposes. PCLs are incidentally diagnosed in up to 20% of patients undergoing abdominal imaging for other etiologies.
Early data showed significant cyst infection rates of up to 14% after EUS-guided FNA (EUS-FNA) of PCLs.
The primary aim of this study was to compare the infection rate between patients who received postprocedural prophylactic antibiotics and those who did not, regardless of periprocedural antibiotic administration, and to assess the benefit of postprocedural antibiotic prophylaxis.
Prospectively collected data of patients who underwent EUS-FNA of pancreatic cysts between January 2015 and July 2019 were retrospectively extracted from the patient databases of two large academic centers (Memorial Hermann Hospital at Texas Medical Center, Houston, TX, USA; Beaumont Health, Royal Oak, MI, USA). Both institutions are state-of-the-art tertiary-care academic centers. All procedures were performed by experienced endosonographers (NT, SR, and MEC). The standard of care at both hospitals is complete drainage of the cyst until it completely collapses, as observed on the EUS monitor. Linear echoendoscopes (GF-UCT 160 and GF-UCT 180; Olympus America, Center Valley, PA, USA) and an Aloka processor were used at William Beaumont Hospital, and Pentax linear EUS (EG-3870UTK; Pentax Medical, Montvale, NJ, USA) scopes and a Hitachi processor were used at Memorial Hermann. Data were collected by reviewing the patients’ electronic medical records, EUS procedure reports, postprocedural recommendations, pre- and postprocedural anesthesia reports, follow-up notes, pertinent imaging findings, and telephone encounters. Procedure-specific details, including gauge of the needle used, number of needle passes into the cyst, and number of drained cysts, were also collected. The rate of systemic or local infection was calculated by checking all records in the Memorial Hermann and Beaumont Health systems for any patient note, telephone encounter, communication/correspondence note, or external media records mentioning cyst infection or systemic infection occurring in the first 60 days after the procedure, even if the note was dated >60 days from the date of the procedure. In addition, abdominal abscesses detected on cross-sectional imaging, positive blood cultures, and febrile episodes occurring within 60 days after the procedure were evaluated. Serum lipase levels, imaging data, and patient charts were also checked for other complications, such as perforation, pancreatitis, peritonitis, or abdominal pain. Two reviewers (SH and MG) reviewed the extracted data and patient charts, and a third reviewer (SR) independently reviewed the extracted data. Adults (age ≥18 years) with PCLs who underwent EUS-FNA were considered eligible for inclusion. Patients with age <18 years, known active infection or sepsis before the endosonographic examination, infected pseudocysts, pancreatic cysts that were not subjected to needle aspiration, pancreatic solid lesions, or mixed solid–cystic pancreatic lesions were excluded.
All adults who underwent inpatient or outpatient EUS-FNA of PCLs were included in the study. One arm of the study included patients who received antibiotics for prophylaxis for 3 to 5 days after the EUS-FNA examination at our health-care systems (POSTAB+ group). The other arm included patients who did not receive antibiotics after the EUS-FNA examination regardless of periprocedural antibiotic administration at both health-care systems (POSTAB– group). At both hospitals, most of the patients in the two study arms received one dose of periprocedural antibiotics for prophylaxis.
Each center has its own protocol for antibiotic prophylaxis during and after EUS-FNA of PCLs. In particular, most of the patients at Beaumont Health received prophylactic antibiotics for 3 to 5 days (mainly oral fluoroquinolones) after the procedure, contrary to patients at Memorial Hermann who did not routinely receive prophylactic antibiotics after the procedure. Most patients at both centers received one dose of periprocedural antibiotics (mainly intravenous [IV] fluoroquinolones).
The primary outcome of this study was the rate of cyst infection after EUS-FNA of PCLs in the two groups. The secondary outcomes included the rate of systemic infection after EUS-FNA; efficacy of postprocedural antibiotic prophylaxis in reducing both local and systemic infections after EUS-FNA of pancreatic cysts; and other procedure-related adverse events such as perforation, pancreatitis, peritonitis, or abdominal pain. Infectious complications were either local (cyst infection) or systemic (bacteremia or sepsis). Cyst infection was defined as the presence of evidence of abscess on imaging, EUS, or fluid analysis or culture. Systemic infection was defined as positive blood cultures after the procedure or new-onset persistent fever after the procedure with no evidence of local infection, and after ruling out pancreatitis if the patients did not meet two of the three Atlanta criteria for diagnosing acute pancreatitis.
The results are reported as mean±standard deviation or median with interquartile range for continuous data, depending on whether the data distribution was parametric or non-parametric. For categorical variables, the results are expressed as counts and frequencies (%). Most of the data were based on the comparison between patients who received postprocedural antibiotics for prophylaxis and those who did not. Statistical analysis was performed using the Stata statistical software (ver. 14.2; StataCorp. LP, College Station, TX, USA).
The study protocol was approved by the institutional review board at both institutions (William Beaumont Hospital, Royal Oak, Michigan; Memorial Hermann Hospital at Texas Medical Center, Houston, Texas).
The initial search of the databases at both institutions yielded 3,593 EUS procedures performed during the study period. After applying the inclusion and exclusion criteria, we determined that 470 of the 3,593 procedures were EUS-FNA performed in patients with pancreatic cysts (
A total of 411 patients (87.4%) received one dose of periprocedural IV antibiotics, and 59 patients (12.5%) did not receive periprocedural antibiotics. Of these 59 patients, 42 patients also did not receive postprocedural antibiotics for prophylaxis. Thus, 42 of the 470 patients (8.9%) underwent EUS-FNA of PCLs without any antibiotic administration.
A total of 274 patients (58.3%) received antibiotics for 3 to 5 days after EUS-FNA of PCLs, and they were identified as the POSTAB+ group. Meanwhile, 196 patients (41.7%) did not receive antibiotics after EUS-FNA of PCLs, and they were identified as the POSTAB– group (
None of the patients in either group (POSTAB+ or POSTAB–) developed any localized pancreatic cyst infection. In addition, none of the patients reported symptoms or signs suggestive of systemic infection. Furthermore, none of the 42 patients who did not receive any dose of periprocedural or postprocedural antibiotics developed localized or systemic infection.
As shown in
Accurate diagnosis of PCL subtypes is crucial for further management because certain PCLs tend to have a higher malignancy risk. Some cystic lesions require close surveillance or surgical resection. Many guidelines have been published to help guide the management of pancreatic cysts, which mainly include, but are not limited to, the International Association of Pancreatology Sendai guidelines in 2006,
The cyst infection rate after EUS-FNA of PCLs is inconsistently reported. The initially reported infection rate was overestimated (14%),
In 2005, Lee et al.
The results of our study showed that the risk of infection after EUS-FNA of PCLs is very low, as demonstrated by the group of patients who did not receive postprocedural antibiotics for prophylaxis. Furthermore, this was supported by the lack of evidence of infection in a small subset of patients (
The size and location of the PCLs were not associated with an increased risk of infection. In addition, the different needle sizes used for FNA and the route (transgastric or transduodenal) of FNA were not associated with an increased risk of infection. The complications reported in this study were related to the endoscopy procedure itself, rather than to the status of postprocedural antibiotic administration. The routine use of antibiotics may have some negative outcomes, such as added cost and, more important, increased drug resistance and increased risk of secondary infections (e.g., bacterial vaginosis or
The major strength of our study is that it is the largest study to date to evaluate the efficacy and safety of postprocedural antibiotic prophylaxis in patients undergoing EUS-FNA of pancreatic cysts. The results of this study support the findings of earlier studies performed by Guarner-Argente et al.,
The main limitation of our study was its retrospective nature. In addition, our study was not adequately powered to assess the safety of the non-use of antibiotic prophylaxis in patients undergoing EUS-FNA, despite the results of our sub-analysis in 42 patients. This study did not optimally assess adverse events or allergic reactions related to antibiotic administration owing to the retrospective analysis. Moreover, as most allergic reactions to antibiotics are mild and readily treated with antihistamines by anesthesiologists, the patients might not have recognized their symptoms as allergic reactions to medications. As a result, they might not have reported their symptoms to health-care providers or might have self-medicated with over-the-counter medications.
In conclusion, the risk of infection after EUS-FNA of pancreatic cysts is minimal, and prophylactic antibiotic administration after this procedure does not seem to offer additional benefits for preventing cystic or systemic infection. The safety of the non-use of antibiotic prophylaxis is beyond the scope of this study. Nevertheless, no infection was reported in the small subset of patients who did not receive any prophylactic antibiotics.
The authors have no potential conflicts of interest.
None.
Conceptualization: NT, SR; Data curation: MG, SH, KY; Formal analysis: PP, SG; Investigation: SH; Methodology: LJ; Project administration: RB; Supervision: NT, SR, RTD; Validation: SH, ZK; Visualization: MEC; Writing–original draft: all authors; Writing–review & editing: all authors.
Study flow diagram. EUS-FNA, endoscopic ultrasound–guided fine-needle aspiration; PCLs, pancreatic cystic lesions; POSTAB+, postprocedural antibiotic group; POSTAB–, no postprocedural antibiotic group.
Patients, pancreatic cysts, and procedure characteristics
Characteristic | Total | POSTAB+ | POSTAB– | |
---|---|---|---|---|
No. of patients | 448 (100.0) | 273 (60.9) | 175 (39.1) | |
Women | 263 (58.7) | 155 (58.9) | 108 (41.1) | |
No. of procedures | 470 (100.0) | 274 (58.3) | 196 (41.7) | |
Mean age (yr) | 66.3±12.8 | 66.4±12.5 | 66.4±13.3 | |
Mean cyst size (mm) | 25.7±16.9 | 26.1±18.6 | 25.2±14.3 | 0.302 |
≤20 | 200 (42.6) | 114 (41.6) | 86 (43.9) | |
20–30 | 141 (30.0) | 81 (29.6) | 60 (30.6) | |
30–40 | 63 (13.4) | 37 (13.5) | 26 (13.3) | |
40–50 | 58 (12.3) | 40 (14.6) | 18 (9.2) | |
≥50 | 8 (1.7) | 2 (0.7) | 6 (3.1) | |
No. of cysts | 0.316 | |||
One cyst | 339 (72.1) | 193 (70.4) | 146 (74.5) | |
Two cysts | 67 (14.3) | 38 (13.9) | 29 (14.8) | |
More than 2 cysts | 64 (13.6) | 43 (15.7) | 21 (10.7) | |
Cyst location | 0.140 | |||
Head | 143 (30.4) | 83 (30.3) | 60 (30.6) | |
Uncinate | 40 (8.5) | 19 (6.9) | 21 (10.7) | |
Neck | 66 (14.0) | 36 (13.1) | 30 (15.3) | |
Body | 134 (28.5) | 75 (27.4) | 59 (30.1) | |
Tail | 87 (18.5) | 61 (22.3) | 26 (13.3) | |
Mean needle passes | 1.3±0.7 | 1.3±0.7 | 1.2±0.5 | |
Needle size | 0.01 | |||
19-gauge needle | 34 (7.2) | 15 (5.5) | 19 (9.7) | |
22-gauge needle | 406 (86.4) | 246 (89.8) | 160 (81.6) | |
25-gauge needle | 30 (6.4) | 13 (4.7) | 17 (8.7) |
Values are presented as number (%) or mean±standard deviation.
POSTAB+, postprocedural antibiotic group; POSTAB–, no postprocedural antibiotic group.
Outcomes of post-procedural antibiotic group versus no post-procedural antibiotics group complications
Variable | Total | POSTAB+ | POSTAB– | |
---|---|---|---|---|
No. of procedures | 470 (100.0) | 274 (58.3) | 196 (41.7) | |
Periprocedural antibiotics | <0.01 | |||
Yes | 411 (87.4) | 257 (93.8) | 154 (78.6) | |
No | 59 (12.6) | 17 (6.2) | 42 (21.4) | |
Fluoroquinolones | 364 (88.6) | 232 (90.3) | 132 (85.7) | |
Cephalosporins | 30 (7.3) | 17 (6.6) | 13 (8.4) | |
Clindamycin | 9 (2.2) | 6 (2.3) | 3 (1.9) | |
Other | 8 (1.9) | 2 (0.8) | 6 (3.9) | |
Postprocedural antibiotics | 274 (100.0) | 274 (100.0) | NA | |
Fluoroquinolones | 257 (93.8) | 257 (93.8) | ||
Cephalosporins | 6 (2.2) | 6 (2.2) | ||
Clindamycin | 4 (1.5) | 4 (1.5) | ||
Others | 7 (2.6) | 7 (2.6) | ||
Postprocedural complications | 11 (2.3) | 4 (1.5) | 7 (3.6) | NA |
Infections | 0 | 0 | 0 | |
Pancreatitis | 1 (0.2) | 0 | 1 (0.5) | |
Intra-abdominal hematoma | 1 (0.2) | 0 | 1 (0.5) | |
Abdominal pain | 8 (1.7) | 3 (1.1) | 5 (2.6) | |
Bowel perforation and peritonitis | 1 (0.2) | 1 (0.4) | 0 | |
Complications requiring hospital admission | 2 (0.4) | 1 (0.4) | 1 (0.5) | NA |
Complications not related to the procedure or antibiotic status | 2 (0.4) | 1 (0.4) | 1 (0.5) | NA |
Death after 3 days from causes not related to the procedure | 1 (0.2) | 1 (0.4) | 0 | |
Pancreatitis after ERCP | 1 (0.2) | 0 | 1 (0.5) |
Values are presented as number (%), unless otherwise indicated.
POSTAB+, postprocedural antibiotic group; POSTAB–, no postprocedural antibiotic group; NA, not available; ERCP, endoscopic retrograde cholangiopancreatography.
Literature review
Study | Year of publication | Study nature | Study design | Cyst infection | AEs |
---|---|---|---|---|---|
Lee et al. |
2005 | Retrospective cohort study | Prophylactic antibiotics were administered in 543 cases; no antibiotic was administered in 60 cases. | 1 Probable infection in the prophylactic antibiotic arm; no cyst infection in the no-antibiotic arm. | 13 AEs in the antibiotic group: pancreatitis (6), abdominal pain (4), infection (1), retroperitoneal bleed (1), and bradycardia (1). |
1 patient with pancreatitis underwent ERCP on the same day; 2 patients with abdominal pain underwent ERCP on the same day. | |||||
Guarner-Argente et al. |
2011 | Retrospective cohort study | 178 Procedures without any antibiotic prophylaxis versus 88 procedures with any antibiotic prophylaxis (periprocedural, postprocedural, or both). | 1 Cyst infection in the antibiotic arm; no cyst infection in the no-antibiotic arm. | 8 AEs in the antibiotic group: 2 severe AEs (1 cyst infection and 1 bile leak) and 6 mild AEs (2 local allergic reaction, 2 abdominal pain, 1 asymptomatic intracystic bleeding, and 1 |
12 AEs in the no-antibiotic group: 4 severe AEs (2 symptomatic local bleeding, 1 pancreatitis, and 1 bile leak) and 8 mild AEs (3 asymptomatic intracystic bleeding, 1 fever, 1 abdominal pain, 1 pharyngitis, and 2 sedation-related AEs). | |||||
Marinos et al. |
2014 | Prospective pilot study | Single-arm study; 79 patients received a single dose of periprocedural IV prophylactic antibiotics. | No cyst infection. | 8 AEs in the antibiotic group, all of which were mild: sedation-related AEs (2), neutrophilia requiring antibiotics (1), acute-on-chronic pancreatitis (1), abdominal pain (2), and sore throat (2). |
Klein et al. |
2017 | Retrospective analysis | 146 Patients received single IV ceftriaxone (periprocedural); 23 patients received postprocedural antibiotics for 3 to 5 days; and 35 patients received no antibiotics. | 1 Infectious complication in the no-antibiotic arm (unknown if localized or systemic). | 6 AEs in the antibiotic arm, including pancreatitis (3) and abdominal pain (1). |
1 AE in the no-antibiotic arm (an infection; unknown if localized or systemic). | |||||
2 patients received antibiotics for 3–5 days; 1 patient received IV ceftriaxone. | |||||
Facciorusso et al. |
2019 | Retrospective cohort study | Propensity score-matched study. A total of 135 patients received both periprocedural IV antibiotics and postprocedural antibiotics for 3–5 days, whereas 135 patients did not receive any prophylactic antibiotics. | 2 Cyst infections in the antibiotic arm; | 10 AEs in the antibiotic group: 2 severe AEs (1 severe abdominal pain and 1 serious bleeding) and 8 non-serious AEs (2 cyst infection, 1 pancreatitis, 3 abdominal pain, and 2 antibiotic-related AEs). |
3 Cyst infections in the no-antibiotic arm. | 8 AEs in the no-antibiotic group: 1 serious cyst infection and 7 non-serious AEs (2 cyst infection, 3 abdominal pain, and 2 bleeding). | ||||
Colán-Hernández et al. |
2020 | Multicenter randomized non-inferiority trial | 103 Patients received both periprocedural and postprocedural prophylactic antibiotics, whereas 102 patients did not receive any prophylactic antibiotics. | No cyst infection in the antibiotic arm; no cyst infection in the no-antibiotic arm. | 6 AEs in the antibiotic group: 1 moderate AE (pancreatitis) and 5 mild AEs (1 abdominal pain, 1 fever, 2 suspected tendinitis, and 1 diarrhea). |
8 AEs in the no-antibiotic group: 3 severe AEs (1 bacteremia, 1 accidental fall, and 1 pancreatitis); 1 moderate AE (bronchospasm); and 4 mild AEs (3 abdominal pain and 1 bleeding). | |||||
Present study | 2022 | Retrospective cohort study | 274 Cases with postprocedural prophylactic antibiotics and 196 cases without postprocedural prophylactic antibiotics. | No cyst infection in both arms. | 4 AEs in the AB+ group: 3 mild AEs (all abdominal pain) and 1 severe AE (bowel perforation and peritonitis). |
7 AEs in the AB- group: all mild AEs (5 abdominal pain, 1 intra-abdominal hematoma, and 1 pancreatitis). |
AE, adverse event; ERCP, endoscopic retrograde cholangiopancreatography; IV, intravenous; AB+, antibiotic group (postprocedural).