Typhoid intestinal perforation (TIP) is a late complication of typhoid fever that typically occurs two weeks after initial symptoms in people who are not diagnosed and treated with effective antibiotic therapy. In endemic areas, antimicrobial resistance to first-line drugs used to treat typhoid fever, including fluoroquinolones, continues to increase. ^{1 – 3} This drug resistance can lead to treatment failure and complications, including TIP. While rarely diagnosed in high income countries, TIP remains a leading cause of emergency abdominal surgery among children in resource-limited settings including typhoid-endemic regions of sub-Saharan Africa and southeast Asia. ^{4 , 5} While most non-traumatic pediatric intestinal perforations are related to typhoid and located in the terminal ileum, associated gallbladder necrosis has occasionally been observed. ^{6 – 14} The presence of E. coli bacteremia further complicates management. ¹⁵

An adolescent male with no significant past medical or surgical history was transferred to a regional mission hospital in Niger with surgical expertise with a one-week history of fever, constipation, vomiting, decreased appetite, and severe abdominal pain. He received three days of metronidazole at an outside health center before transfer.

On admission, he was afebrile with blood pressure 100/60 mmHg, heart rate 140 beats/minute, oxygen saturation 95% on room air, and weight of 27 kg. Physical examination revealed abdominal distention with rebound tenderness consistent with peritonitis. Initial laboratory results showed a white blood cell count of 5,200 × 10 ³/μL, hemoglobin 9.3 g/dL, hematocrit 26.5%, sodium 127 mEq/L, potassium 3.9 mEq/L, and serum creatinine 0.9 mg/dL. Malaria rapid diagnostic test was negative. A blood culture was collected before empiric antibiotic treatment with intravenous ceftriaxone (100 mg/kg IV daily) and intravenous metronidazole (30 mg/kg/day divided every 8 hours). Bedside abdominal ultrasound showed turbid free fluid in his pelvis. Given the concern for enteric perforation causing peritonitis, he was taken to the operating room emergently for exploratory laparotomy.

A standard vertical midline incision was made, 900cc of succus was aspirated, and extensive exudate was removed. Three distal ileal full thickness perforations and eight pre-perforations consistent with typhoid fever were found, requiring an ileocecectomy. The gallbladder fundus had areas of necrosis, so a cholecystectomy was performed with suture ligation of both the cystic artery and cystic duct with 3-0 silk ties. An end ileostomy and mucous fistula were then matured with 3-0 Vicryl suture. The fascia was left open, and the skin was closed for a planned return to the operating room in 48 hours due to high intraabdominal contamination. At repeat washout, significant purulence was irrigated from all four quadrants, the gallbladder bed had no bile leak, and no new perforations were seen. A second return to the operating room 48 hours later revealed cloudy fluid and no new perforations, but a new area of necrosis was visualized along the right lower quadrant abdominal wall and debrided. A drain was placed into the right paracolic gutter lateral to the stoma, and the abdomen was closed with retention sutures.

Postoperatively, the patient was admitted to the intensive care unit for further care and then transferred to a regular surgical bed seven days after admission. His ileostomy was functional two days after his initial operation, and he tolerated oral intake on post-operative day five. His course was complicated by a superficial surgical site infection and wound dehiscence, which was treated with antibiotics and local wound care.

Blood culture obtained at admission returned positive after five days for ESBL-producing Escherichia coli. Due to local drug availability and cost constraints, ceftriaxone was discontinued and intravenous chloramphenicol (100mg/kg/day divided into four doses) was initiated based on susceptibility results. However, persistent purulent drainage was noted from the midline wound despite surgical washout and appropriate wound care, raising concerns about a clinical response.

Although meropenem was considered the preferred treatment based on the susceptibility profile, it was initially unavailable in the region. Meropenem was able to be obtained and initiated on hospital day 13 at a dose of 20mg/kg every 8 hours. Notably, the patient had remained afebrile for several days prior, and the antibiotic change was prompted more by ongoing purulence than by overt clinical deterioration. Following the switch to meropenem, the patient’s wound began to show signs of improvement.

The patient was ultimately discharged on postoperative day 23 to a nutritional rehabilitation center. His discharge weight was 24.6kg, down from an admission weight of 27 kg. He was doing well without further complications at his first follow-up visit 16 days after discharge.

TIP remains a leading cause of pediatric and adult non-traumatic emergency abdominal surgery in Niger. ^{4 , 5} Due to limitations in diagnostic capabilities in many regions where typhoid is endemic, TIP is commonly diagnosed by surgeons based on clinical history and visualization of the perforation(s) on the anti-mesenteric side of the small bowel, most commonly located in terminal ileum. ^{16 – 18} TIP pathology is thought to result from S. Typhi replication within the Peyer’s patches, causing inflammation, ulceration and necrosis, eventually progressing to a full thickness perforation. ¹⁹ Several published cases highlight the occurrence of typhoid-related perforations outside of the expected ileal region, largely gallbladder necrosis due to acalculous cholecystitis. ^{6 – 14} The pathogenesis of gallbladder necrosis and gallbladder perforation, in the context of typhoid, relates to S. Typhi bacterial invasion of the epithelial wall. ^{20 , 21} In this case, the ESBL-resistant E. coli was likely an intestinal commensal bacterium that caused secondary bacteremia after ileal perforation. This highlights a growing concern for community-acquired antimicrobial resistance, particularly given that ceftriaxone is the first line antibiotic in the hospital setting for suspected TIP. Meropenem can be difficult or impossible to obtain in rural areas and is cost prohibitive to many families. To our knowledge, this is the first report of ESBL-resistant E. coli bacteremia in a patient with acute acalculous cholecystitis and TIP. The presence of ESBL-resistant E. coli in a patient with no significant past medical or surgical history is alarming given the widespread reliance on ceftriaxone as a first-line treatment for suspected TIP in many endemic regions. Many typhoid endemic areas do not have blood culture testing available, and if they do, antimicrobial sensitivity testing is limited. It is therefore likely that this case represents a larger population of TIP patients with multidrug-resistant infections that are not diagnosed due to a lack of testing capacity.

TIP remains a leading cause of pediatric and adult non-traumatic emergency abdominal surgery in Niger, and TIP incidence will likely increase as drug resistance also rises. Other complications of typhoid fever will also likely become more common, including gallbladder necrosis seen in this patient, and carry a high risk of mortality. These factors underscore the urgent need for measures to prevent typhoid fever in endemic areas, including improvements in water and sanitation and TCV introduction.

Parental written informed consent was obtained prior to enrollment in the TIP observational study.