Authors: Zarif Kazi, Asbah Rahman, Branden Biegert, Jordan Daloya, Chanaka Seneviratne
Categories: Case Report, Meningitis, Delayed diagnosis, Hemorrhoidectomy complication, Bacteremia, Escherichia coli
Source: IDCases
Authors: Zarif Kazi, Asbah Rahman, Branden Biegert, Jordan Daloya, Chanaka Seneviratne
Escherichia coli meningitis is a rare cause of meningitis in adults. Overall, mortality due to meningitis is improving, but remains high for gram negative bacteria. It often progresses rapidly, and even if treated appropriately, can lead to long-term complications. An emerging concern is bacterial resistance to the empiric antibiotic regimen used in meningitis. The effect of adjunct dexamethasone on reducing mortality or preventing complications remains inconclusive. Here, we discuss a case of severe E. coli meningitis in a 56-year-old woman after a hemorrhoidectomy, leading to brain herniation and cardiac arrest.
Bacterial meningitis is an uncommon infection in the United States. Typical causes in adults include Streptococcus pneumoniae and Neisseria meningitidis, with Listeria monocytogenes more common in patients over 50.The pathogenesis of E. coli meningitis involves several mechanisms, particularly ones that aid in the penetration of the blood-brain barrier (BBB). A study published in Nature discussed the E. coli virulence factor IbeA, which interacts with the host Caspr1 transmembrane protein. The researchers hypothesized that this interaction helps in the penetration of the BBB [1]. Another study had reported that cytotoxic necrotizing factor-1, another virulence factor, causes activation of RhoA-dependent pathways which contributes to invasion [2]. Furthermore, it has been suggested that E. coli uses host signaling pathways, including epidermal growth factor receptor (EGFR) and sphingosine 1-phosphate (S1P) pathways, in the penetration of BBB [3], [4]. Once E. coli penetrates the BBB, the bacteria causes an inflammatory response with release of cytokines such as IL-1β, TNF-α and IL-6. This inflammatory response can lead to pathological changes in cells within the CNS [5].
Recent neurosurgical intervention is the largest risk factor for developing this infection from E. coli [6]. Additional risk factors include immunocompromise, alcoholism, urinary tract infections, pneumonia, bacteremia, strongyloidiasis, and septic arthritis [7], [8]. A study from 2022 found that E. coli was a more prevalent cause of meningitis in patients over 80 years old [9]. The classic triad consists of fever, nuchal rigidity, and a change in mental status, often sudden onset, and older patients are more likely to present with this triad. Classic signs such as Kernig and Brudzinski signs are often absent.
The mainstay of treatment for meningitis is prompt initiation of antibiotics. Lumbar puncture is required for a diagnosis to be established and cerebrospinal fluid culture is the gold standard. Several sources, including the CDC, have the approximate mortality of bacterial meningitis at 15–20 %, whereas one study at a tertiary center in Spain calculated the mortality rate at 53 % [10]. Here, we present a case of delayed diagnosis of E. coli meningitis after hemorrhoidectomy.
A female in her 50 s with a past medical history of gastritis and a recent hemorrhoidectomy, one week prior, presented with an acute mental status change for several hours. The day after her hemorrhoidectomy, she began to complain of abdominal pain, and 4 days before presentation, she began having neck pain. It gradually intensified and two days prior to admission, she presented to the emergency department with headache, back pain, abdominal pain and vomiting. No signs of meningismus were noted on the physical exam and she was sent home with a diagnosis of viral syndrome. Since the discharge, she continued having neck pain, headache, vomiting, fever, and she was sleeping more than normal. On the day of admission, the patient was able to cook herself breakfast in the morning and she had a normal conversation with her family. At baseline, she was able to live independently, ambulate unassisted, and work as a nurse. When the patient's son saw her in the afternoon, he found the patient lying in the bed on her side with left-sided facial weakness. She was not able to accomplish simple tasks and was unable to answer questions, but no shaking movements, urinary or bowel incontinence, or tongue lacerations were noted.
On arrival to the emergency room, the patient was non-verbal, not following any commands, had eyes rolling to the back of her head, and had a brief episode of left-sided gaze deviation. Her vitals were notable for hypotension, a heart rate of 160 beats per minute in sinus rhythm, respiratory rate of 24 breaths per minute, and a temperature of 104.1 F. Her physical exam was notable for neck stiffness, photophobia, and positive Kernig and Brudzinski signs. She also had livedo reticularis on her legs. No apparent facial weakness was identified, and the remainder of the exam was not significant.
The patient underwent CT angiography of the head and neck for altered mental status, which showed no acute intracranial findings or large vessel occlusion. She was started on empiric meningitis coverage with ampicillin, ceftriaxone, vancomycin, acyclovir, dexamethasone, and IV fluid resuscitation.
Initial blood work showed an elevated lactate of 7.6 mmol/L with creatinine of 1.9 mg/dL, showing signs of poor perfusion. Her white blood cells were 9.2 K/uL with 6 % bands. Influenza, RSV, and COVID tests were negative. She also had a platelet count of 44 K/uL (normal > 150 K/uL) with no known history of thrombocytopenia. TTP was also considered but ruled out due to normal hemoglobin, ADAMTS13 activity, lack of schistocytes, and complement levels. The patient was admitted to the medical intensive care unit.
Lumbar puncture showed a white blood cell count of 105 cells/uL and 85 cells/uL neutrophils, a total protein of 654 mg/dL, and glucose < 10 mg/dL. Gram stain resulted in gram-negative cocci and E. coli was detected by PCR. Blood cultures also returned positive for E. coli. Treatment was narrowed to only Ceftriaxone 2 g BID and Ciprofloxacin 400 mg BID as sensitivity was not known. Clinically, the patient remained unstable; her mental status did not improve, and her vitals continued to be tenuous. Twelve hours after admission, the patient became hypotensive, apneic and went into cardiac arrest. CT head done post-arrest showed downward cerebellar tonsillar herniation of approximately 9 mm and ultimately, a few days after her arrest, the patient expired.
Hemorrhoidectomy is generally a short and simple procedure and rarely causes serious complications. Currently, the literature does not describe bacterial meningitis as a direct complication of a hemorrhoidectomy. However, a case report described bacterial meningitis as a complication of a spontaneous ischiorectal abscess [11]. Although uncommon, abscesses, including ischiorectal abscesses, are relatively uncommon complications following hemorrhoidectomy, occurring in approximately 0.8 % of cases [12].
Bacteremia is a known complication of hemorrhoidectomy as the anorectal mucosa is highly vascularized and dense microbially [13]. An analysis on the bacterial colonies in the anal wounds after open hemorrhoidectomy showed that E. coli was the most common organism identified [14]. This can suggest that during the surgical excision of the hemorrhoidal tissue, the disruption of the mucosal barrier allows endogenous flora to access the bloodstream, of which E. coli is one of the most common organisms. Another study also showed that colonization with multidrug-resistant bacteria further increased the risk of infection [15].
Meningitis is a rare but known complication of bacteremia. For example, a study assessing for S. aureus meningitis as a complication S. aureus bacteremia showed that only 0.8 % of the patients developed meningitis as a complication of non-surgical S. aureus bacteremia [16]. In the case of meningitis as a complication of hemorrhoidectomy, no definitive mechanism has been described, but a potential pathway of transmission is hematogenous spread. The site of surgical incision in the anorectal mucosa provides a site for the entry of bacteria present in the skin flora. The bacteria can then proceed to disseminate into the bloodstream. Once bacteremia has occurred, certain pathogens are capable of CNS invasion through specific mechanisms that allow them to interact with the BBB. As described in the introduction, E. coli has mechanisms that allow for this, leading to meningeal invasion. A summary of the proposed mechanism is shown in Fig. 1.Fig. 1Potential transmission pathway for meningitis from hemorrhoidectomy.Fig. 1
This case unfortunately highlights the importance of prompt diagnosis and treatment of meningitis. Despite presenting two days prior to her acute mental status change, the patient had no symptoms concerning for meningismus nor did she have any symptoms of the classic triad. Although it was on the list of differentials of the emergency room team, the suspicion was low. The patient also had generalized abdominal pain after her hemorrhoidectomy which was not adequately explored. The procedure was the likely source of her meningitis and the myriad of symptoms she presented with were due to her developing bacteremia.
At the time of presentation, our patient was severely septic with an elevated lactate and neutrophil band percentage. The patient’s perfusion was compromised as evidenced by her elevated creatinine and the livedo reticularis on her legs causing her skin to appear mottled. Antibiotics were given almost immediately upon presentation but her mental or clinical status never improved during her stay. On blood work, there were some signs of improvement such as normalization of lactate and mild improvement in creatinine. Clinically, the patient never improved and was persistently tachycardic and tachypneic despite intervention.
E. coli is known to be a rare cause of meningitis in adults. A study conducted in Wales and England found that E. coli accounted for 5 % of bacterial meningitis cases among adults [17]. Another study from the Netherlands revealed that E. coli accounts for 1–3 % of cases of meningitis [18]. Mortality rates with gram negative meningitis are higher than gram positive meningitis or Neisseria meningitis. One study at a tertiary center in Spain calculated the mortality rate at 53 % [10]. Gram negative causes of bacterial meningitis is also concerning because of the growing concerns for antibiotic resistance which would not be covered by empiric antibiotic coverage. Fortunately, in our patient, the isolate was susceptible to cephalosporins but there are increasing rates of extended spectrum beta lactamase (ESBL) producing isolates. In the case of ESBL isolates, Ertapenem has shown in animal models to adequately penetrate inflamed meninges in meningitis [18].
Incidence has been decreasing overall. One large prospective cohort study in the Netherlands showed that the incidence of community-acquired bacterial meningitis was 0.94 per 100,000 people. S. pneumoniae was responsible 72 % of the time in people aged 16 and up. The mortality rate overall was 17 %, although it decreased over time. They tested the addition of adjunctive dexamethasone on mortality rate and other unfavourable outcomes (such as hearing loss), and the OR was 0.46 and 0.54 respectively compared to no dexamethasone. Although, no subgroup analysis was performed and the majority of their cases were due to S. pneumoniae (72 %) for which there is already a known benefit [19], [20]. Since 2002, three large trials have been performed to evaluate the role of adjunctive dexamethasone therapy for adults with bacterial meningitis. A European trial showed a reduction in mortality for all suspected bacterial meningitis patients, while trials in Malawi and Vietnam did not. The Vietnam trial did show a decreased rate of mortality for patients with confirmed bacterial meningitis [20], [21], [22]. Currently, S. pneumoniae is the only indication to continue steroids in meningitis.
All of the authors contributed to the literature review and design of the study. Dr. Rahman and Dr. Kazi drafted the initial manuscript and were responsible for the publication process. Dr. Biegert and Dr. Daloya reviewed the manuscript. Dr. Seneviratne performed the final review, approved the submission and was in charge of coordination.
Zarif Kazi: Writing – review & editing, Writing – original draft, Methodology, Conceptualization. Branden Biegert: Writing – review & editing, Conceptualization. Asbah Rahman: Writing – review & editing, Writing – original draft, Methodology, Conceptualization. Chanaka Seneviratne: Supervision, Project administration, Conceptualization. Jordan Daloya: Writing – review & editing, Conceptualization.
IRB approval was not required for this case report.
Written consent was obtained from the patient.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
The authors declare the following financial interests/personal relationships which may be considered as potential competing Zarif Kazi reports article publishing charges was provided by Maimonides Medical Center. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.