Haemophilus parainfluenza bacteremia post-ERCP and cholecystectomy in a pediatric patient: A case report

Abstract

Haemophilus parainfluenzae is a species that is commonly found in the human respiratory tract. It is an uncommon cause of gastrointestinal infection and bacteremia. Here, we present the case of a 17-year-old boy who developed H. parainfluenzae bacteremia and intraabdominal abscess after endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy followed by elective cholecystectomy within 3 days. The patient was successfully treated with IV ceftriaxone with improvement in symptoms and progressive resolution of his abscess. We report a pediatric case of H. parainfluenzae infection occurring post-ERCP and cholecystectomy, and describe the convergence of two major risk factors for H. parainfluenzae bacteremia in the same pediatric patient.

Case Presentation

A 17-year-old male with a history of five episodes of pancreatitis, heterozygous ΔF508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and heterozygous PRSS1 mutation, presented to the outpatient gastroenterology clinic with a 1-week history of dull abdominal pain. Bloodwork revealed an elevated lipase (155 U/L; 4–39 U/L), normal ALP, total bilirubin, ALT, and GGT. The patient felt comfortable to remain home and was managed as an outpatient with hydration and acetaminophen for pain-control only. Magnetic resonance cholangiopancreatography (MRCP) was performed the following week as an outpatient and reported an atrophic, calcified pancreatic tail, and possible accessory duct in the ventral aspect of the pancreas that fuses with the Santorini duct and drains into the duodenum. The intrahepatic biliary tree, common bile duct, and pancreatic duct were normal in appearance. These findings suggested chronic inflammatory changes in the pancreas and a potential anatomic anomaly in the pancreatic duct. He was scheduled for elective, outpatient endoscopic retrograde cholangiopancreatography (ERCP) 6 months later to further assess for pancreatic divisum.

On the evening before the scheduled procedure, the patient was admitted to hospital with acute epigastric abdominal pain radiating to the back. Laboratory results showed a markedly elevated lipase (837 U/L; 4–39 U/L) and amylase (487 U/L; <102 U/L). The patient was admitted to hospital for pain management overnight. Given the timing of admission, a decision was made to forgo abdominal ultrasound. An ERCP with sphincterotomy was performed the next morning. Upon cannulation of the common bile duct, large volume yellow sludge and associated stone-like debris flowed readily around the sphincterotome. Post procedure, the patient reported moderate improvement in symptoms and the lipase gradually decreased. The pediatric general surgery team was consulted, and given the presence of biliary sludge and debris on ERCP, cholecystectomy was offered. The patient consented, and a laparoscopic cholecystectomy was performed 72 hours after ERCP. At post-operative day 2, the patient’s clinical symptoms had resolved, lipase level was only mildly increased (90 U/L; 4–39 U/L), and the boy was discharged.

Twenty-four hours after discharge, the patient reported acute lethargy and new-onset rigours. He was brought to the emergency department and acutely admitted with fevers (39.2°C), and back and flank pain. Abdominal examination did not reveal peritonitis, but he was acutely tender. Blood work showed moderately elevated lipase (146 U/L; 4–39 U/L), elevated C-reactive protein (CRP) (184 mg/L; <1.8 mg/L), ALT (53 U/L; <25 U/L), GGT (82 U/L; 7–21 U/L), and normal alkaline phosphatase level and total bilirubin. Blood cultures were drawn and returned positive for Haemophilus parainfluenzae bacteremia at 19 hours. An abdominal computed tomography (CT) scan was performed and showed a large, thin-walled, septated collection (8.0 cm × 5.0 cm × 7.9 cm × 7.6 cm) in the left upper quadrant between the splenic hilum and pancreatic tail. The patient was started on ceftriaxone. He was discharged on day 3 with resolved bacteremia, negative blood cultures, improving symptoms and laboratory markers, and instructions to complete 10 days of IV antibiotics for H. parainfluenzae bacteremia. At follow-up 1 week after discharge, he was pain-free, fevers had not returned, his energy was improved, and the fluid collection on abdominal ultrasound had decreased.

Discussion

Haemophilus parainfluenzae is a gram-negative coccobacillus and facultative anaerobic commensal that resides in the oropharynx (1–4). The Haemophilus genus constitutes up to 10% of the upper respiratory tract microbiome, of which H. parainfluenzae represents the predominant species (5). H. parainfluenzae most commonly causes upper and lower respiratory tract infections, but has been associated with endocarditis, septic arthritis, genital tract infections, osteomyelitis, psoas and retroperitoneal abscesses, hepatic abscesses, cholecystitis, and meningitis (2,4,6,7). While our patient responded to a third-generation cephalosporin (ceftriaxone), H. parainfluenzae has several molecular resistance mechanisms to common antibiotics and has been considered as the initial reservoir for β-lactamase plasmids dissemination to other gram-negative bacteria (8). Resistance occurs through the production of β-lactamases, antibiotic efflux, drug inactivation through esterases and methylation that inhibit binding, and production of ribosomal protection proteins, among others (9). There have been emerging case reports of extensively drug-resistant H. parainfluenzae, including a small case-series from Switzerland (10,11).

H. parainfluenzae has been found in the human gastrointestinal tract. This was first reported in a 1981 study of 1,137 fecal samples, where 20.7% were found to be positive for H. parainfluenzae (12). This was again shown in a 1988 study of 450 pediatric patients who had received an appendectomy, where 7.8% contained H. parainfluenzae isolates (13). Colonization from the oropharynx to the gastrointestinal tract may initially occur through the patient swallowing expectorated H. parainfluenzae containing sputum (14). Its colonization here may be further supported by its unique utilization of factor V (NAD) as a substrate for growth (15). Factor V is metabolized and secreted by duodenal bacteria and found in the bile. These factors may particularly encourage the role of H. parainfluenzae in ascending cholangitis (12,16,17). H. parainfluenzae is estimated to cause between 6.6%–11% of biliary tract infections (18,19).

H. parainfluenzae has been reported post-ERCP. In 1998, the first case report was published of a 49-year-old man who received an ERCP with sphincterotomy for choledocholithiasis (20). No prophylactic antibiotics were given peri-procedure. Post-operatively, the patient developed severe epigastric pain with an elevated CRP (114 mg/L). A CT scan showed a right-sided retroperitoneal abscess extending from the diaphragm to the right kidney and drainage revealed abundant growth of H. parainfluenzae. The post-operative bacteremia and abdominal fluid collection were directly attributed to H. parainfluenzae seeding, with manipulation through ERCP and sphincterotomy causing sufficient mucosal trauma to introduce H. parainfluenzae from the duodenum and bile. This case stands out as a pediatric case of H. parainfluenza post-ERCP.

Bacteremia following ERCP is an uncommon, but recognized complication. Incidence varies between 1.1%–8.8% (21–24), and causative organisms include oropharyngeal pathogens, particularly streptococci, Escherichia coli, Peptostreptococcus, and Staphylococcus aureus (23,25). The recognition that oropharyngeal pathogens may seed into gastrointestinal mucosal defects introduced by endoscopic procedures is recognized and has prompted guidelines for antibiotic prophylaxis by the American Heart Association and American Society for Gastrointestinal Endoscopy (26,27).

H. parainfluenzae may also be a source of primary intraabdominal infection. A case report from 2002 described a 9.5-year-old male who developed an intraabdominal abscess following an open appendectomy (28). Intraabdominal cultures grew H. parainfluenzae, and the patient improved after treatment with amoxicillin. This patient did not have blood cultures drawn. A second pediatric case report from 1988 reported a 12-month-old boy with chronic granulomatous disease who presented with a multiloculated hepatic abscess that grew H. parainfluenzae (1). Repeated blood cultures failed to show evidence for hematogenous spread. H. parainfluenzae has also been isolated from peritoneal fluid in patients undergoing continuous peritoneal dialysis via peritoneal catheter (29–32).

ERCP and general surgery procedures are often performed in conjunction, such as how our patient was managed. There is one other case report describing a similar H. parainfluenzae bacteremia in a patient requiring ERCP, followed by open cholecystectomy (14). This 2010 report described a 68-year-old woman who developed a post-operative right paracolic H. parainfluenzae abscess; however, this patient had a full 5 weeks elapse between the initial ERCP and elective cholecystectomy.

This case is novel due to multiple risk factors for H. parainfluenzae bacteremia interacting in the same pediatric patient. While this doesn’t present an opportunity to isolate how, specifically, he developed hematogenous seeding, it does present several intriguing possibilities. ERCP involves the passage of a side-viewing endoscope through the oropharynx and into the duodenum, where further manipulation enables cannulation of the sphincter of Oddi. H. parainfluenzae’s residence in the oropharynx may have presented the opportunity for passage along the endoscope, through the esophagus, stomach, and duodenum, and into the bloodstream during sphincterotomy or ascension through the biliary tree (1,3,4). Indeed, H. parainfluenzae has been reported post-ERCP previously, and transit of oropharyngeal pathogens is implicated in other bacteremias associated with upper endoscopic procedures (20,33).

The patient’s abdominal surgery adds another potential source for infection. Patients have had H. parainfluenzae seed into the peritoneal cavities after appendectomy, cholecystectomy, peritoneal dialysis, and choledochojejunostomy (16,21–22,28–32). These cases suggest that H. parainfluenzae likely also resides within the gastrointestinal tract, and procedures involving manipulation of the gastrointestinal mucosa may offer an additional route of entry into the bloodstream or peritoneal cavity. Unfortunately, the nasopharyngeal swab done at the time of the blood culture did not test for H. parainfluenza specifically, underscoring the need for this pathogen to be considered in routine, oropharyngeal pathogen testing. We remain open to the possibility that this patient may have developed H. parainfluenzae bacteremia entirely spontaneously, as has been reported previously (21). However, the proximity of two high-risk procedures in this patient, ERCP and cholecystectomy, strongly implicates the cumulative role of these invasive gastrointestinal manipulations.

Conclusion

We present a case of a pediatric patient who developed H. parainfluenzae bacteremia after two back-to-back procedures involving abdominal manipulation. This case highlights the multiple possible pathophysiologies for development of H. parainfluenzae bacteremia and outlines risk factors, such as procedures involving manipulation of the gastrointestinal tract and endoscopic procedures involving passage through the oropharynx.

Haemophilus parainfluenzae is an uncommon cause of bacteremia, but its resident colonization in the human respiratory and gastrointestinal tracts increase its risk of hematogenous seeding. H. parafluenzae infection should be considered in any patient who presents with post-operative complications of ERCP or abdominal surgery. Emerging multidrug resistance warrants careful antibiotic sensitivity testing to help guide appropriate coverage.

Competing Interests:

The authors have nothing to disclose.

Ethics Approval:

N/A

Informed Consent:

N/A

Registry and the Registration No. of the Study/Trial:

N/A

Animal Studies:

N/A

Funding:

No funding was received for this work.

Peer Review:

This article has been peer reviewed.