Poorly controlled HIV infection increases the risk of opportunistic infections. We are presenting here a case of an HIV patient who was non-compliant with highly active antiretroviral therapy (HAART) regimen and who developed a diarrheal illness secondary to enteroinvasive Escherichia coli (EIEC) infection. The patient presented with severe gastrointestinal symptoms including frank bloody diarrhea, and febrile illness. He was eventually diagnosed with EIEC infection. We discuss the challenges faced in managing this patient and the potential consequences of medication noncompliance in the context of HIV.

Keywords: HIV, AIDS, non-compliant to HIV medication, opportunistic infection, enteroinvasive E. coli, HAART

HIV, human immunodeficiency virus; AIDS, acquired immune deficiency syndrome; EIEC, enteroinvasive E. coli; HAART, highly active antiretroviral therapy; ETEC, enterotoxigenic Escherichia coli; IDSA, infectious diseases society of America; ISTM, International society of travel medicine

Infectious gastroenteritis is a universally major cause of morbidity and mortality. It is important to identify the causative pathogen of diarrhea in acutely ill patients to determine the targeted therapy for their treatment. Escherichia coli constitutes a main cause of diarrhea outbreaks and may be very invasive such as the case of enteroinvasive E. coli (EIEC) that can cause tissue destruction and inflammation like shigellosis.¹ Strict adherence to antiretroviral therapy is crucial for effective management of HIV infection ensuring viral suppression and healthy immune function. Noncompliance may lead to immunosuppression and increased susceptibility to opportunistic infections and contribute to higher mortality.^2,3 In this case report, we present an HIV patient who developed EIEC infection due to non-compliance with antiretroviral medication. Enteroinvasive Escherichia coli (EIEC) is a potentially fatal bacterial infection that can be very severe in immunocompromised HIV patients who are not receiving HAART.

A 40-year-old male patient with human immunodeficiency virus (HIV) infection who has been noncompliant with his HAART regimen over the past 2 years presents to the emergency department with abdominal pain, bloody diarrhea, nausea, and vomiting that have been ongoing for the last 7-8 days. He was also having fever and back pain. On examination, the patient was ill, with poor dentition and mild to moderate tenderness in the lower abdomen without rebound, guarding or rigidity. On blood work up, White Blood Cell count was 8900 (normal, 3.5-10.5 K/uL), with severely depressed Helper T- Lymphocyte CD4 count of 59 (normal, 490-1740 cells/uL). Gastrointestinal panel with BioFire was able to detect Enteroinvasive E coli (EIEC). Blood cultures were negative. The patient was admitted and was initiated on Intravenous ceftriaxone 2 grams every 24 hours. Furthermore, the patient received supportive care including intravenous fluids and electrolyte replacement to manage his dehydration. During the hospital stay, the diarrhea improved within 48 hours, and he started feeling better. He received a 5-day treatment course for the infection and was educated on the importance of adhering to antiretroviral therapy and the risk of opportunistic infection due to compromised immune system. The patient was discharged with a referral to HIV care clinic for ongoing management with highly active antiretroviral therapy (HAART).

Escherichia coli are a regular part of the normal flora of the large intestine and constitute the predominant aerobic organism of normal fecal flora. E. coli strains usually constitute no harm to the host if they do not have genetic elements encoding for virulence.¹ Once they receive a bacteriophage or plasmid DNA that encodes for invasion, they become pathogenic and cause an array of diseases from a simple watery diarrhea to a severe inflammatory dysentery. Enterohemorrhagic E. coli (EHEC) such as E. coli O157:H7 can cause bloody diarrhea and Hemolytic uremic syndrome. Enterotoxigenic Escherichia coli (ETEC) strains produce enterotoxins that may be cytotoxic or cytotonic, and as such, enhancing the loss of water and electrolytes. It is the most common cause of traveler’s diarrhea. Enteropathogenic E. coli (EPEC) causes diarrhea but produces no toxins or invasion factors. E. coli strains that have invasion factors causing inflammation similarly to Shigella are known as Enteroinvasive E. coli (EIEC). The invasive capacity of EIEC is related to a plasmid that is very significantly similar to the invasion plasmid in Shigella.^4,5 It can pass into the intestinal wall to cause severe diarrhea.

Traditional testing methods are slow, labor intensive, and sometimes fail to reveal the etiology of a patient’s gastrointestinal symptoms. While Shiga toxin-producing E. coli strains (STEC) can be diagnosed by detecting Shiga toxins via molecular or immunoassays, enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroinvasive E. coli (EIEC), and enteroaggregative E. coli (EAEC) need other diagnostic modalities. In 1 study, while the majority of the E. coli isolates were lysine decarboxylase positive, all EIEC isolates were lysine decarboxylase negative.⁶ BioFire and BD have FDA approved multiplex molecular GI panels for the detection of different pathogenic E. coli strains. The organisms can be detected using nucleic acid tests, including multiplex panels. The use of BioFire® FilmArray® Gastrointestinal (GI) Panel (BioFire Diagnostics, LLC, Salt Lake City, UT) eliminates limitations from conventional methods by providing faster, more accurate, and comprehensive results.⁷

EIEC is rare in the U.S. but may cause outbreaks. EIEC is related to Shigella species, and both can cause similar gastrointestinal diseases. EIEC does not produce enterotoxins. EIEC may be differentiated from Shigella principally by the fact that EIEC strains ferment glucose and xylose. It causes diarrhea by invading the epithelial cells of the colon. Acute inflammatory response and direct tissue invasion of the intestinal epithelial cells are characteristic of this highly virulent Shigella-like E. coli. EIEC invades the intestinal cell, multiplies intracellularly, and extends into the adjacent intestinal cells. The same genes facilitate pathogenesis of both EIEC and Shigella.⁸ Patients may experience fever, abdominal cramps, and sometimes tenesmus with scanty stool containing blood and mucus. Dysentery or bloody diarrhea may happen although uncommonly. Clinical guidelines are not clear about the role of antimicrobial treatment for gastroenteritis due to this infection.

Most of the time, diarrheal illnesses are self-limited. Host defense plays a major role in the pathogenesis of enteroinvasive E coli. This defense is usually deficient in the young and the elderly, reflecting the epidemiology of this diarrheal illness and its severity in this age group. Infection with this pathogen produces an inflammatory cell response that is responsible for the diarrhea symptoms. The immune response mechanisms that contribute to the control of diarrheal disease are important. Cytokines play an important role in controlling the homoeostasis of the immune system. In one study,⁹ increased levels of TNF-α and IL-6 were associated with decreased durations of EPEC infection and increased ETEC durations. Increased IL-4 and IFN-γ levels were associated with decreased and increased durations of both EPEC and ETEC infections respectively. Increased IL-10 levels were related to increased and decreased durations of asymptomatic and symptomatic EPEC infections, respectively, and increased durations of ETEC infections.

HIV infected patients commonly suffer from diarrhea. In patients with AIDS, recurrence of infection is common, and may cause chronic diarrhea.^10,11 A case of enteroinvasive E. coli bacteremia has been described in an AIDS patient who was having diarrhea, fever, and who was improving each time he received antibacterial therapy. However, he developed symptoms of septicemia prior to the diagnosis of bacteremia with EIEC.¹² In HIV infection, there is dysregulation of cytokines, and this abnormal cytokine production contributes to the impairment of cell-mediated immunity. For instance, in HIV-1 infection, the production of T-helper type 1 cytokines, like interleukin (IL)-2, and antiviral interferon (IFN)-gamma, is decreased, whereas production of T helper type 2 cytokines, IL-4, IL-10, proinflammatory cytokines (IL-1, IL-6, IL-8) and tumor necrosis factor (TNF)-alpha, is increased. Cytokines such as TNF-alpha, TNF-beta, IL-1 and IL-6 are considered HIV inductive because they stimulate HIV-1 replication in T cells and monocyte-derived macrophages, IL-2, IL-7 and IL-15 upregulate HIV-1 in T cells, and macrophage-colony stimulating factor. HIV-suppressive cytokines include IFN-alpha, IFN-beta and IL-16, which inhibit HIV-1 replication in T cells and monocyte-derived macrophages and IL-10 and IL-13, which inhibit HIV-1 in monocyte-derived macrophages.¹³ Thus the important role of highly active antiretroviral therapy in regulating cytokine production and as such controlling the severity of diarrheal illness.

Treatment of Enteroinvasive E. coli is usually supportive care with fluid, electrolyte, and nutritional management. Antibiotics are only reserved for those who have severe illness that lasts greater than 7 days and who continues to have fever and bloody diarrhea. HIV patients, and namely those who are not on HAART, may qualify for antibiotic therapy because they may have more severe or persistent infection, viewing their immunocompromised status. Rifaximin, azithromycin, and ciprofloxacin are currently recommended by the Infectious Diseases Society of America (IDSA) and the International Society of Travel Medicine (ISTM) to treat E. coli diarrheal illness.¹³

This case highlights the complex correlations between HIV infection, non-adherence to antiretroviral therapy and opportunistic infection such as enteroinvasive Escherichia coli. Individuals with compromised immune system are at risk of severe infectious disease and non-compliance to medication exacerbates this risk. To effectively manage such cases, it is imperative to provide comprehensive patient education and support services to ensure continued adherence to antiretroviral therapy which is critical for restoring immune function along with suppressing HIV replication.

This report presents the case of enteroinvasive E. coli diarrheal illness in an immunocompromised patient with AIDS, who did not have the capacity to clear the pathogen on his own, viewing his noncompliance to HAART. It also emphasizes the difficulties encountered in managing enteroinvasive E.coli infection in HIV patients compounded by non-adherence to HIV medication. Effective management requires prompt intervention, suitable antimicrobial treatment and comprehensive approach that addresses the medical factors.

None.

The authors declare that there are no conflicts of interest.

1. Levine MM. Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. J Infect Dis. 1987;155(3):377–389.
2. Glass TR, Sterne JA, Schneider MP, et al. Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality. AIDS. 2015;29(16):2195–2200.
3. Kim JH, Psevdos G, Gonzalez E, et al. All-cause mortality in hospitalized HIV-infected patients at an acute tertiary care hospital with a comprehensive outpatient HIV care program in New York City in the era of highly active antiretroviral therapy (HAART). Infection. 2013;41(2):545–551.
4. Hale TL, Sansonetti PJ, Schad PA, et al. Characterization of purulence +mid and +mid associated outlet membrane proteins in Shigella flexneri, Shigella sonnei, and Escherichia coli. Infect Immun. 1983;40(1):340–350.
5. Sansonetti PJ, d’Hauteville H, Ecobichon C, et al. Molecular comparison of virulence plasmid in Shigella and enteroinvasive Escherichia coli. Ann Microbiol (Paris). 1983;134A(3):295–318.
6. Toledo, MRF, Trabulsi LR. Correlation between biochemical and serological characteristics of Escherichia coli and results of the Sereny test. J Clin Microbiol. 1983;17(3):419–421.
7. Torres-Miranda D, Akselrod H, Karsner R, et al. Use of BioFire FilmArray gastrointestinal PCR panel associated with reductions in antibiotic use, time to optimal antibiotics, and length of stay. BMC Gastroenterol. 2020;20(1):246.
8. Tulloch EF Jr, Ryan KJ, Formal SB, et al. Invasive enteropathic Escherichia coli dysentery. An outbreak in 28 adults. Ann Intern Med. 1973;79(1):13–17.
9. Long KZ, Rosado JL, Santos JI, et al. Associations between mucosal innate and adaptive immune responses and resolution of diarrheal pathogen infections. Infect Immun. 2010;78(3):1221–1228.
10. Rodolfo EM, Loscar SR, Jossette A, et al. Chronic diarrhea in HIV patient -an uncommon villain: 1514. Am J Gastroenterol. 2018;113:S870.
11. Juferdy K, Simadibrata M, Karyadi T, et al. Diarrhea in HIV Infection. Indonesia J Gastroenterol Hepatol Digest Endoscopy. 2009;10(1):23–28.
12. Bessesen MT, Wang E, Echeverria P, et al. Enteroinvasive Escherichia coli: a cause of bacteremia in patients with AIDS. J Clin Microbiol. 1991;29(11):2675–2677.
13. Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. J Travel Med. 2017;24(Suppl 1):S57–S74.