Shigella sonnei bacteraemia in a cystic fibrosis patient: case report and literature review

>Introduction Shigellosis has a gastrointestinal presentation of variable severity in which bacteraemia is uncommon. We describe the first reported case of Shigella sonnei bacteraemia and intestinal coinfection with Clostridioides difficile in a cystic fibrosis patient. The literature on S. sonnei bacteraemia in adult and paediatric populations is also reviewed. Case presentation A 29-year-old male with cystic fibrosis presented with profuse acute watery diarrhoea, abdominal pain, shivering and fever. The patient showed mixed cardiogenic and septic shock. Despite antibiotic therapy, volume replacement therapy and vasoactive drugs, the patient showed biventricular dysfunction and multiple organ failure requiring implantation of an intra-aortic balloon pump (IABP) with extracorporeal membrane oxygenation (ECMO). C. difficile and S. sonnei were detected in the stools. Escherichia coli was identified in the blood by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, although after re-evaluation with biochemical and antiserum agglutination tests, the isolate was confirmed as S. sonnei. After adjustment of the antibiotic therapy to vancomycin, meropenem, amikacin and metronidazole and continuing with ECMO and IABP support for 8 days, the patient improved and was finally discharged after 44 days. Conclusion S. sonnei bacteraemia is an unusual entity that should be kept in mind because of the severity of its presentation and high mortality. In acute gastroenteritis and fever, especially in paediatric patients under 5 years old and adults with criteria for immunosuppression or chronic diseases, blood and stool cultures provide simple information that is nonetheless very important for the management and prognosis of these patients.


InTROduCTIOn
The genus Shigella belongs to the family Enterobacteriaceae and comprises four species: Shigella dysenteriae, Shigella flexneri, Shigella boydii and Shigella sonnei. Infections vary from asymptomatic presentations and self-limiting gastroenteritis to dysentery with fever, abdominal cramps and blood and/or mucus in diarrhoea [1]. Unlike other members of family Enterobacteriaceae, Shigella spp. do not penetrate the lamina propria of the intestinal mucosa, so that bacteraemia is very infrequent, especially in the case of S. boydii and S. sonnei [2]. This report describes a rare case of bacteraemia caused by S. sonnei and intestinal coinfection with Clostridioides difficile in an adult cystic fibrosis patient treated at our medical centre, and provides a summary of the existing literature on S. sonnei bacteraemia in paediatric and adult populations. A 29-year-old Spanish male diagnosed with cystic fibrosis (mutation ∆F508 of the CFTR gene), complicated by exocrine pancreatic insufficiency, bilateral bronchiectasis and repeated respiratory infections, was admitted to the emergency department. The patient reported 12 h of profuse diarrhoea with up to 10-15 liquid stools without mucus, blood or other In the emergency room, intensive volume replacement was started, administering up to 2000 ml of saline solution. Empirical antibiotic therapy with ceftriaxone IV and metronidazole IV was also started. As the patient did not respond, he was transferred to the intensive care unit (ICU).

CASE REPORT
Upon arrival in the ICU, the APACHE II severity score was 32 and the SAPS II score was 53, and the patient required orotracheal intubation with mechanical ventilation for 4 days. In addition, he received continuous serum perfusion, norepinephrine (0.25 µg/kg min −1 ) and continued with antibiotic therapy. Transthoracic echocardiography showed severe biventricular dysfunction and dobutamine 10 µg/kg min −1 and vasopressin 0.7 µg/kg min −1 were added. Despite this, the patient remained in shock with multiorgan failure, so that femoro-femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) together with an intra-aortic balloon pump (IABP) were put in place for 8 days. Antimicrobial therapy was changed to meropenem plus metronidazole plus amikacin.
Samples for stool culture, C. difficile toxin detection and blood cultures were taken and sent to the Microbiology Laboratory prior to antibiotherapy.
The species most frequently found in bacteraemia are S. flexneri and S. dysenteriae, with the first being the most virulent [2]. Although all Shigella species produce the plasmidencoded enterotoxin, ShET2 [15], and S. flexneri produces the chromosomal enterotoxin, ShET1 [16], only the Shiga toxin has been shown to play an important role in the onset of the pathology. This toxin is generated by S. dysenteriae, and in specific cases by S. sonnei and S. flexneri [17,18]. Nevertheless, according to the literature, Shigella bacteraemia is less likely to be due to the toxin or other virulence factors in specific strains than to patient comorbidities that predispose to systemic invasion [2,19,20].
The scientific literature was reviewed and 43 documented cases of S. sonnei bacteraemia were found containing demographic, clinical and microbiological data (Table 1). Of those 43 cases, 20 were in children (46.5 %) and 23 were in adults (53.5 %). Nineteen of the 20 paediatric patients were under 5 years old (95 %) and 12 (60 %) presented some risk factor, with malnutrition being the most common (5 patients), followed by maternal infection caused by S. sonnei prior to birth (4 patients), sickle cell anaemia (2 patients) and acute lymphoid leukaemia (1 patient). Mortality was 20 %, which was considerably lower than the 46 % mortality previously attributed to bacteraemia caused by the genus Shigella in the paediatric population [13]. This could be explained by the lower virulence of S. sonnei relative to S. flexneri and S. dysenteriae, the main causative organisms of bacteraemia [2]. Of the 23 adult cases, 18 (78.3 %) had risk factors such as diabetes (5 patients), malignancies (4 patients), AIDS (3 patients) or solid organ transplantation (1 patient). Some had significant immunosuppression and severity scores, which helped raise the mortality rate to 30.4 %, a priori higher than the estimated 21 % for bacteraemia caused by the genus Shigella in adults [2].
Almost all the cases of S. sonnei bacteraemia described presented with previous diarrhoea, with the exception of six patients: three children and three adults. The most common type of diarrhoea in both populations was watery diarrhoea, rather than diarrhoea with the presence of blood and/or mucus, which is typical of intestinal shigellosis [1].
To the best of our knowledge, this is the first reported case of Shigella bacteraemia in a cystic fibrosis patient coinfected with C. difficile. A possible cause of this bacteraemia may have been malnutrition, since our patient had exocrine pancreatic insufficiency as a complication of cystic fibrosis. Some authors [2,13,20] have reported that malnutrition may facilitate an invasive presentation because it produces decreased secretion of immunoglobulins, complement and other proteins involved in opsonization and lysis of micro-organisms, as well as increasing transferrin saturation [2,20]. The normal immunological values obtained in our patient, however, would seem to rule out the hypothesis of malnutrition as facilitating this presentation. On the other hand, coinfection with C. difficile would probably contribute to intestinal barrier damage and facilitate the translocation of S. sonnei to the blood. The association of the two toxins (C.difficile and S. sonnei) would probably have exacerbated the seriousness of the case, leading to septic and cardiogenic shock and acute renal failure in the patient.
With regard to the microbiological diagnosis, a limitation of MALDI-TOF mass spectrometry is its inability to identify the genus Shigella and differentiate it from E. coli, because the genera Escherichia and Shigella are practically identical at the ribosomal protein level [21]. As a result, it is necessary to use traditional diagnostic techniques, such as biochemical and serological tests or sequencing, for identification.
In conclusion, it is important to emphasize that although S. sonnei bacteraemia is a rare entity, it should be borne in mind because of the severity of its presentation and high mortality. Therefore, in acute gastroenteritis and fever, especially in paediatric patients under 5 years old and adults with criteria for immunosuppression or chronic diseases, blood and stool cultures provide simple information that is very important for the management and prognosis of these patients.