Rare Fatal Event of Multidrug-resistant Shigella Septicemia and Cryptococcal Meningitis in an Immunocompromised Host

Abstract

Bacteriemia due to Shigella spp. is a rare event. However, an individual with impaired immunity remains at risk of such invasion where the infective dose is as low as 10 viable bacilli. This case report describes one such fatal event where a 40-year-old immunocompromised male presented to a tertiary-level healthcare facility with a history of diarrhea for 10 days and seizures. Prompt microbiological workup established multidrug-resistant Shigella flexneri septicemia and cryptococcal meningitis.

INTRODUCTION

Clinical spectrum of dysentery due to Shigella species (Shigella dysenteriae, Shigella sonnei, Shigella flexneri, and Shigella boydii) ranges from mild watery to bloody mucoid diarrhea, abdominal cramps, and fever with complications of toxic megacolon, hemolytic–uremic syndrome, renal failure, anemia, and post-reactive arthritis. A small percentage, especially pediatric, elderly, and immunocompromised, may develop bacteremia. As a leading cause of diarrheal disease-related deaths, Z This report presents a rare fatal case of Shigella flexneri septicemia along with cryptococcal meningitis in an human immunodeficiency virus (HIV)-reactive male from the plains of the Himalayan state of Uttarakhand, India.

CASE REPORT

A 40-year-old male, resident of Rishikesh, presented to the emergency department with complaints of seizures. Further history elicited febrile illness, abdominal cramps, loose stools, and melena for 10 days, associated with nausea and vomiting. On-examination, abdomen was soft but tender. On admission, the patient was hypotensive, tachycardic, and febrile (102°F). Day zero investigations indicated leucopenia, normocytic normochromic anemia, raised C-reactive protein (CRP), and acute kidney injury (AKI) [Table 1].

Table 1.

Day zero haematology and biochemistry parameters

Parameter	Day zero values	Reference range
Hb	8.6	14–17 g/dL
TLC	4000	4000–11,000/mm3
Neutrophil	76	44–68
Lymphocyte	20	25–48
Red blood cell	3.05	4.5–5.5 million/µL
Packed cell volume	26.7	40–50%
MCV	87.5	83–99
MCH	28.2	27–32
MCHC	32.2	31.5–34.5
Platelet	120	150–400
RDW	16.1	11.6–14.1
CRP	208	0–5 mg/L
ESR	110	0–15 mm
SGPT	30	17–59 U/L
SGOT	33	04–50 U/L
ALP	238	38–126 U/L
Serum urea	131	19–43 mg/dL
Serum creatinine	2.5	3.5–5.1 mg/dL
Total cholesterol	50	150–200 mg/dL

Hb=Hemoglobin, TLC=Total leukocyte count, MCV=Mean corpuscular volume, MCH=Mean corpuscular hemoglobin, MCHC=Mean corpuscular hemoglobin concentration, RDW=Red cell distribution width, CRP=C-reactive protein, ESR=Erythrocyte sedimentation rate, SGPT=Serum glutamic pyruvic transaminase, SGOT=Serum glutamic oxaloacetic transaminase, ALP=Alkaline phosphatase

Peripheral blood film examination showed mild anisopoikilocytosis, predominantly normocytic, and normochromic population of cells, along with a few microcytes. The working diagnosis on admission was acute febrile illness with viral meningitis and pre-renal AKI. The patient was started on intravenous (IV) fluids, antiemetics, probiotics, antipyretics, antiepileptics, ceftriaxone 1 g IV bidaily (BD), and metronidazole 100 mg IV BD. Over the next 6 days (although CRP levels declined significantly), the patient had bleeding per rectum, for which colonoscopy was planned but deferred with risk of increased intracranial pressure. Stool was unavailable for culture as the patient was kept nil per oral. One unit of packed red blood cells was transfused to the patient in view of anemia. On day 7, the patient developed drowsiness, and the condition deteriorated (sharp increase in total leucocyte count and upward shift in CRP) [Figure 1].

Figure 1.

Total leucocyte count and C-reactive protein levels during the course of treatment

At this point, paired blood cultures (time-to-positivity of 12 h) yielded Shigella group (Gram-negative Identification/antibiotic susceptibility testing card 406; Vitek-2, BioMérieux) identified as S. flexneri (MAST^TM ASSURE Antiserum; Bootle, Merseyside, UK), resistant to beta-lactams (third- and fourth-generation cephalosporin and aztreonam), fluoroquinolones (FQs), susceptible to carbapenems and beta-lactamase inhibitor combinations. Consequently, antibiotics were escalated to Piperacillin–Tazobactam.

However, the patient’s condition deteriorated, and on day 12, contrast-enhanced magnetic resonance imaging) of the brain revealed multiple T2 hyperintense foci in the bilateral gangliocapsular regions, thalami, cerebral peduncles, and superior cerebellar hemispheres with incomplete suppression on fluid-attenuated inversion recovery (FLAIR) and no postcontrast enhancement, suggestive of dilated perivascular spaces with proteinaceous contents. Furthermore, FLAIR hyperintensities along the cortical sulci of both cerebral hemispheres and basal cisterns with mild leptomeningeal enhancement were noted, consistent with meningitis, along with diffuse cerebral edema causing mild sulcal effacement and tiny focus of diffusion restriction along the posterior limb of the right external capsule, in keeping with a small recent infarct [Figure 2a and b].

Figure 2.

(a) Axial T2-weighted (left) and axial post-contrast T1 magnetic resonance image (right) at the level of the basal ganglia showing multiple T2 hyperintense foci in bilateral gangliocapsular regions (arrows). These foci show incomplete suppression on the corresponding fluid-attenuated inversion recovery (FLAIR) images, consistent with dilated perivascular spaces containing proteinaceous material. (b) Axial FLAIR (left) and post-contrast FLAIR images (right) demonstrating hyperintense signal along the cortical sulci in bilateral cerebral hemispheres (arrows), suggestive of leptomeningeal involvement

Following this, cerebrospinal fluid was obtained through lumbar puncture (showing capsulated budding yeast cells on India Ink examination, later identified as Cryptococcus neoformans by Vitek-2, sensitive to Amphotericin B) and simultaneously, HIV testing according to National AIDS Control Organisation strategy 2A was performed (turned out to be Reactive for HIV-1). Unfortunately, before the treatment modification, the patient suffered cardiopulmonary arrest and could not be revived.

DISCUSSION

Shigella down-regulates innate immune response by inhibiting Nuclear Factor kappa-light-chain-enhancer of activated B cells, mitogen-activated protein kinase signaling pathways, and regulates repression of pro-inflammatory cytokines such as interleukin 8, causing susceptibility to re-infection.[1] Tobin-D’Angelo et al. stated 0.64% of Shigella bacteremia in decade-old study with S. flexneri as the most common species, in nearly 51% patients, HIV-positive cases.[2] Another study from the United States (2000–2024) showed 1.7% cases of Shigella bacteremia, predominantly S. flexneri, of which 2.9% died within 30 days of infection (mean age: 65 years, compromised immune status).[3] Mohiuddin et al. reported an apparently healthy 66-year-old woman presenting with diarrhea, febrile episodes, where blood cultures showed S. flexneri, which resolved after antibiotic use.[4] This case highlighted community-acquired Gram-negative sepsis due to S. flexneri (dominant in India with 6.2% prevalence, compared to > 10% in Asia), compounded by Cryptococcal meningitis in an immunocompromised individual. Shigellosis, characterized by ileal, colon, and rectal epithelial disruption, resulting in watery diarrhea accompanied by bloody stools along with fever and abdominal cramps, is a standout pathogen in India, particularly with poor sanitation conditions.[5] Antibiotics, increasingly refractory due to AMR, are, however, prescribed to prevent complications and further environmental transmission.[6] Escalating DR-Shigella spp. FQ from medium (2017) to high-risk priority pathogen (2024) by the World Health Organization reflects the unmitigated menace of this pathogen.[7] From an Indian perspective, Shigella resist 60%–80% FQ (otherwise recommended as first-line treatment by World Health Organization in 2005), followed by 23%–30% third-generation cephalosporins, and least toward carbapenems.[8] One of the prominent reasons for upsurged DR-Shigella, attributed to selection pressure, is explained through irrational haywire antibiotic consumption for self-limiting diarrhoea, facilitating its clonal spread. It is observed that there may be a delay in presentation of septicemia due to Shigella, attributed to inappropriate antibiotic therapy, allowing the organism to propagate in the gastrointestinal tract. Another reason may be the limit of bacteria beyond the lamina propria, and hence a rare cause of bacteremia. Immunocompromised condition, causing loss of immunoglobulins and complement proteins, may facilitate further tissue invasion and consequently bacteremia.[9] What looked like viral meningitis at the time of presentation could have been a gradually progressing Cryptococcus infection. This is the first fatal case of dual Shigella and Cryptococcus infection in an HIV-reactive individual from Uttarakhand.

CONCLUSION

“Open eyes can see only when the mind knows it.” Although rare, healthcare personnel should be aware of Shigella burden and possible bacteremia, threatened distension to Shigellemia, and local antibiogram for better therapeutic intervention, data for which seems scarce in India. Here, whether Shigella or Cryptococcus was the killer, it’s hard to say; highlight the importance of blood and stool cultures (especially given the risk of misidentifying Shigella as atypical Escherichia coli in the absence of serotyping) in suspected cases of diarrhoea associated with malena, particularly in immunocompromised and elderly individuals.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.