Salmonella meningitis and septicaemia in an non-immunocompromised adult, associated with a cluster of Salmonella Enteritidis PT 14b, Ireland, November 2009.

We report a fatal case of meningitis caused by Salmonella Enteritidis phage type 14b in a middle-aged man who had no history or findings to suggest he was immunocompromised. To our knowledge, this is the first reported case of Salmonella meningitis in an adult in Ireland, and the first case of meningitis in an adult caused by phage type 14b. This case was associated with a nationwide cluster of salmonellosis which is still under investigation at the time of writing.


Introduction
Salmonella infection is recognised as a common cause of gastroenteritis which can result in large outbreaks [1].Acute bacterial meningitis is a rare manifestation of Salmonella infection, and when it does occur, it is most commonly a disease of infants [2,3].In adults, Salmonella meningitis, although rare, is most commonly seen in patients with impaired immunity, particularly in infection with human immunodeficiency virus (HIV) [4,5].
In this report, we describe a case of a non-immunocompromised adult with Salmonella Enteritidis meningitis and severe sepsis, with a rapid onset and a fatal outcome, that occurred in Dublin in November 2009.This case is one of a cluster of at least 15 cases of Salmonella Enteritidis phage type 14b infection in Ireland that started in October 2009 [6; Health Protection Surveillance Centre, personal communication].This variant has also been implicated in over 443 cases, including 14 outbreaks, in the United Kingdom since August 2009 [7,8].

Case description
The patient was a man in his late 40s who had a stable chronic mental illness and lived in a community psychiatric hostel in an urban area, supervised by 24-hour nursing staff.His regular medications included clozapine, amisulpride and valproate.Regular blood tests for potential side effects such as agranulocytosis did not show any abnormalities.He was a regular smoker.There was no abuse of alcohol or intravenous drugs and no known risk factors for HIV infection.
The patient woke in the early morning hours with a headache, which was relieved by treatment with 1 g paracetamol.After a quiet night he was found agitated and feverish six hours later.He was seen by a doctor and, due to rapid deterioration, was transferred by ambulance to the nearby acute hospital as an emergency with a seven-hour history of headache and a two-hour history of fever (38.5 °C), rigors, inability to stand and progressive reduction in level of consciousness.He was admitted to the intensive care unit on the same day.
On admission, a lumbar puncture revealed turbid cerebrospinal fluid, with a milky-brown colour.Three samples of cerebrospinal fluid (CSF) were taken at the time of admission.All of them showed a white blood cell count of >5,000 and a red blood cell count of zero.Microscopy of the CSF, performed urgently, showed abundant Gram-negative bacilli.A blood sample taken on admission showed a leukocyte count of 8.97 x10 9 /L, with a neutrophil count of 8.13 x 10 9 /L.Plasma urea, electrolytes, liver enzymes, total protein and albumin concentration were all within the normal range at that time.
A progressive neutrophilia was documented, with a count of 17.73 x 10 9 /L on day 2, rising to 31.61 x 10 9 /L on day 4 of hospitalisation.The patient developed acute renal failure on day 2 of hospitalisation.
The patient received one dose of 2 g cefotaxime and 2.4 g benzylpenicillin in the emergency department.After Gram-negative organisms were identified in the CSF samples taken on admission, this treatment was discontinued and the patient received 2 g meropenem three times a day and 1 g vancomycin twice a day for the following three days.On day 4 of hospitalisation, cultures from the CSF samples and a series of three blood samples taken on the day of admission grew Salmonella sensitive to cefotaxime, and the patient's treatment was changed to 1 g cefotaxime every four hours.
In view of known association between Salmonella meningitis in adults and immunodeficiency, and despite the absence of risk factors, the patient was tested on day 5 for HIV, hepatitis B virus and hepatitis C virus infections, all of which were negative.Nor were there any incidental clinical signs, radiographic or laboratory findings to suggest underlying malignancy or opportunistic infection.
Despite treatment with appropriate antibiotics and interventions to support failing organ systems, he deteriorated and died five days after admission.The final post mortem report was not available at the time of writing this report.

Environmental investigation
In view of the fatal outcome, and despite the fact that no staff member or resident at the hostel had a history of gastroenteritis, stool samples from staff and fellow residents were obtained as part of the public health investigation.In addition to testing samples of food, eggshells and water from the hostel, other food premises where the patient was known or thought to have eaten were inspected, foods sampled and distribution chains traced.Particular attention was paid to foods containing chicken, eggs or egg products of any kind.None of the dozens of stool or food samples grew Salmonella.
The Salmonella species involved was nalidixic acidresistant Salmonella Enteritidis phage type 14b.The same phage type has been identified in a cluster of cases notified to Irish departments of public health since November 2009, all of whom had gastro-enteritis alone and made a full recovery [6].As with the above case, meticulous tracing of relevant foods through the distribution chains was and is being conducted for all cases, but to date the source of infection has not been identified.

Discussion
Human Salmonella infection is categorised into four manifestations: enteric infections, sepsis, non-enteric focal infections (including meningitis) and a chronic carrier state [3].Bacterial meningitis is characterised by acute onset of fever, headache and one of the following signs: neck stiffness, altered consciousness or other meningeal signs [9].
The first case of Salmonella meningitis in the literature was reported in 1907 by Ghon [10].In a study of 7,779 infections identified at the New York Salmonella Centre, meningitis accounted for only 0.8% [3].In adults, Salmonella meningitis is most commonly seen in patients with intercurrent illness [11,12], including particularly immunosuppression associated with HIV [4,5].
Irish legislation requires doctors to send notifications of infectious diseases, including Salmonella infections, to medical officers of health in regional public health departments.Notification of bacterial meningitis from any cause must also be given.These data are collated at the national level by the Health Protection Surveillance Centre (HPSC).In a review of national data for the ten-year period from 2000 to 2009, the number of notifications of bacterial meningitis in Ireland was 1,229 and the number of notifications of Salmonella infection was 4,395, including 88 cases of typhoid and/or paratyphoid.The data from this period include only one case of Salmonella meningitis, a three-weekold baby with S. Dublin (medical officer of health, personal communication).Before this period, Foley et al. published in 1980 one series of three cases of childhood Salmonella meningitis in Ireland; all were infants [13].
Of all Salmonella infections listed in 2008 in the database of enteric infections collected by Enter-net, the European surveillance network for human gastrointestinal infections, Salmonella Enteritidis was by far the most common serotype, while S. Typhi, Oranienburg, Paratyphi and Berta were not listed among the top ten [14].However, the European literature includes only two previous case reports of adults with meningitis due to Salmonella Enteritidis, one of whom was immunocompromised [15,16].Other cases of Salmonella meningitis in adults previously reported in the literature have involved a diversity of serotypes, including at least 19 cases of S. Typhi [17][18][19][20][21][22], two cases of S. Typhimurium [18,11], and one case each of S. Oranienburg [23], S. Virchow [24], S. Paratyphi [21] and S. Berta [25].
The case described here is the only notified case of Salmonella meningitis in an adult in Ireland in the last ten years, and the first published adult case in Ireland.Kauffman et al. reported that Salmonella meningitis, arising in association with a variety of serotypes, may present without preceding symptoms of gastroenteritis [11], as was also true in our case.There were no clinical signs, laboratory or radiographic findings to suggest a compromised immune system in this case.While agranulocytosis is a recognised adverse effect of clozapine, the fact that the patient's white blood cell count was monitored regularly and that he developed a marked neutrophilia indicates that this was not a factor.

Conclusion
We describe the first reported case of Salmonella meningitis in an adult in Ireland, who was not immunocompromised.The association of this fatal case with a phage type that has also been implicated in a large number of sporadic cases and several recent outbreaks in the United Kingdom indicates the need for continuing vigilance in terms of surveillance and investigation to reduce the risk of further such infections with Salmonella Enteritidis PT 14b.