A Case of Rahnella aquatilis Bacteraemia After the Receipt of an Unlicensed Intravenous Vitamin Infusion, the First to be Reported in the UK

TL;DR

A healthy woman developed a rare bacterial infection after receiving an unlicensed IV vitamin infusion, marking the first UK case of Rahnella aquatilis bacteraemia linked to this source.

Contribution

This is the first reported case in the UK linking R. aquatilis bacteraemia to an unlicensed intravenous vitamin infusion.

Findings

A previously healthy woman developed R. aquatilis bacteraemia following an unlicensed IV vitamin infusion.

The case highlights the potential risks of unregulated intravenous vitamin treatments.

The infection is linked to presumed contamination of the infusion.

Abstract

Rahnella aquatilis is a Gram-negative bacterium commonly found in the environment. Previously associated with food spoilage, it has in the past been responsible for causing infection in humans, usually as an opportunistic pathogen. We report a case of a previously healthy female who was diagnosed with R. aquatilis bacteraemia. Careful history-taking confirmed she had received an intravenous infusion of presumed-contaminated vitamins immediately prior to presentation. As the global beauty-industry continues to expand, we should be vigilant of future similar cases.

Full text

1. Introduction

Rahnella aquatilis is a facultatively anaerobic Gram-negative bacillus that is a member of the order Enterobacterales and member of the family Yersininaceae [1]. Typically isolated from the environment (often fresh water hence ‘aquatilis') [1, 2], it has also been described as a causative pathogen in bloodstream [3–6] and urinary tract infections [2, 7] usually, but not always, in the setting of an immunocompromised host [8]. Endocarditis has also been reported in a paediatric patient with congenital heart disease [9]. The full clinical spectrum of disease caused by this organism is not yet understood, due to the paucity of literature describing such cases. However, it seems that the pathogen could cause overwhelming sepsis [3, 6, 10].

We describe the case of an immunocompetent female who was diagnosed with a R. aquatilis bacteraemia after presenting with features of septic shock. A thorough history revealed that the patient was likely to have acquired the bacteraemia from a vitamin infusion administered by a freelance beauty practitioner working in a beauty clinic. The case, the first to be reported in the UK, highlights the risks of bloodstream infections associated with such procedures.

2. Case Report

A 39-year-old immunocompetent female, with no past medical history except for breast augmentation surgery 16 years previously, presented to the emergency department (ED) with an acute history of right-sided abdominal pain, vomiting and diarrhoea. She also described dysuria, but no chest pain or significant shortness of breath. On examination, she exhibited signs of sepsis, with low blood pressure (91/41 mmHg), tachycardia (heart rate 128 beats per minute) and fever (temperature 40.7°C). Oxygenation and respiratory rate were within normal limits.

Bloods on admission are shown in Table 1. Of note, the patient was leucopenic on admission, primarily showing neutropenia and lymphopenia. It is unclear whether these results were spurious; the neutropenia resolved on bloods sent the following day (although this may have been reactive to the bloodstream infection). Computed tomography (CT) scan pulmonary angiogram abdomen and pelvis revealed bilateral lower lobe pulmonary segmental consolidation only. She was commenced on empirical antibiotics with piperacillin-tazobactam 4.5 g 8 hourly and a single dose of gentamicin. Her clinical status quickly deteriorated, and she required inotropic support in an intensive care setting. At this point, the medical team responsible for her care made the provisional diagnosis of urosepsis.

The patient had two sets of peripheral blood cultures (aerobic and anaerobic bottle) taken within the first 4 h of her admission. After initial processing, both demonstrated the presence of Gram-negative bacilli on gram staining (the first set in both anaerobic and aerobic bottles, with growth at 11 h, and the second set in the aerobic bottle only, with growth at 22 h). On the same evening of the initial gram stain result, using matrix-assisted laser desorption/ionisation (MALDI-TOF), the organism grown in both sets of blood culture bottles was identified as R. aquatilis (MALDI score of 2.32 and 2.29 for the organism in the first and second blood culture, respectively). The MALDI-TOF software package used was the Bruker Maldi-HDT IVD Sirius.

At the point of the bacterial species identification, a review of the available literature demonstrated that R. aquatilis possesses a chromosomally encoded Ambler Class A extended spectrum beta lactamase (ESBL) enzyme (RAHN-1) [11]. Given this information, the critical condition of the patient, and the confirmed growth of R. aquatilis in blood cultures, piperacillin-tazobactam was empirically escalated to meropenem 1 g 8 hourly (due to concern that the former antibiotic is not reliable in treating other ESBL-producing Enterobacterales bloodstream infections) [12], pending the antibiotic sensitivity profile of the organism to become available.

Antimicrobial sensitivity was performed manually using the Kirby–Bauer method. Antimicrobial susceptibility testing (AST) profiles were determined using disc diffusion on Mueller–Hinton agar (Oxoid). The in vitro sensitivity profile is shown in Table 1. Zone disc diameters were interpreted using the European Committee on Antimicrobial Susceptibility Testing (EUCAST)'s methodology. Our laboratory's first line Enterobacterales AST panel was performed on the first blood culture growth of R. aquatilis; the organism grown from the second set was tested against the ‘urinary Enterobacterales' panel. The urinary panel was used owing to the rarity of the organism and the team's suspicion of the bacteraemia being urinary in origin. It should be noted that whilst most of some antibiotics in the urinary panel are inappropriate for bacteraemia (i.e., pivmecillinam and nitrofurantoin), they may have use in other cases, if needing to treat only urinary tract infection. The isolate was sensitive to amoxicillin-clavulanic acid when tested against the first line antibiotic panel but resistant to the same antibiotic in the second panel. This is likely due to differences in zone diameter interpretation for each panel.

The isolate was confirmed as being an extended-spectrum beta lactamase (ESBL) producer, using the MAST D72C AmpC ESBL CPE detection set.

Rahnella aquatilis is ubiquitous in the environment, and whilst it remains an unusual pathogen in immunocompetent adults, it has previously been associated with line infections in these patients [13]. Considering this, a more detailed exposure history was taken. It transpired that on the afternoon of her presentation to hospital; the patient had visited a beauty clinic where she had received an intravenous infusion of vitamins administered by a freelance practitioner. The patient reported that she had felt well prior to visiting the clinic; however, during the infusion of the second vial of vitamins, she had started to vomit and developed wheeze and shortness of breath. Following this, she returned home, where she continued to vomit and have diarrhoea, before presenting to the ED. The patient denied recent travel or the consumption of unusual or uncooked foods within the preceding 48 h of her admission; however, a detailed account of every food/drink ingested over the days prior to her admission was not taken.

Meropenem was continued; the patient clinically improved, and 7 days after admission to hospital her care was stepped down to a medical ward. The patient did not have an echocardiogram owing to her marked response to antibiotic therapy. Antibiotics were switched to oral ciprofloxacin 500 mg 12 hourly, and she completed a 10-day course of antibiotics in total.

The case was referred to the United Kingdom Health Security Agency (UKHSA), who together with the Care Quality Commission (CQC) and the local authority Health and Safety Team investigated both the practitioner and the beauty clinic. During this investigation, the practitioner was referred to both the General Dental Council (for inappropriate use of protected titles) and the Advertising Standards Agency (for the cosmetic procedures advertised). UKHSA was unfortunately unable to trace the batch of vitamin vials for further testing— thus their contamination remains a presumption—nonetheless, we believe it to be the most likely source of the patient's bacteraemia.

3. Discussion and Review of the Literature Describing Cases of Human Infection

Throughout their lifetime, humans are likely to have frequent exposure to Rahnella species; high concentrations have been discovered in minced meat, freshwater fish and dairy produce [10]. The bacterium is a potential public health concern; there are reports of it producing the gene for Escherichia coli heat labile toxin, and it is associated with dangerous levels of histamine in fish products. The bacterium has been implicated in the spoilage of food [14]; there are also hypothesised (but microbiologically unconfirmed) accounts of it contaminating bags of total parenteral nutrition (TPN) [15].

We conducted a brief review of the literature describing invasive infection caused by R. aquatilis in humans. Two separate searches were conducted, the first used the terms ‘Rahnella aquatilis' and ‘invasive infection,' and the second ‘Rahnella aquatilis' and ‘human infection.' Both searches returned a combined total of 21 papers. Invasive infection was defined as the presence of bacteria in normally sterile sites (thus would include bacteraemia, invasive skin/soft tissue infection, pyelonephritis and meningitis and exclude nonbacteraemic pneumonia, urinary tract infection or superficial wound infection). Studies that did not describe invasive R. aquatilis infection in humans (n = 5) or not written in English were excluded (n = 1). Fifteen papers met these criteria and are described in Table 2.

Eight of the 16 patients with invasive R. aquatilis infection were immunocompromised. The source of infection in seven patients was related to a possible intravenous line or port infection; three patients' infections were linked to contamination of infusions. Three patients had an entirely unclear source of their infection. Therapy varied in choice of antimicrobial and duration; all patients survived, however.

There are confirmed reports of R. aquatilis causing sepsis in immunocompetent adults after contaminating vitamin infusion vials that have subsequently been infused intravenously [3]. It may be assumed that our exposure to the bacterium will continue to increase as the number of people seeking vitamin infusions increases.

Rahnella species has been discovered in plant roots and rhizospheres [22]. It possesses several virulence factors, including endotoxins [23] and signalling molecules to facilitate quorum sensing, surface motility and biofilm formation [24], amongst others [25].

Previous work has demonstrated that R. aquatilis possesses a chromosomally encoded extended-spectrum Ambler class A beta-lactamase (RAHN-1) [11]; therefore, penicillins and cephalosporins might not be effective for treatment and should be avoided if possible (although cephalosporins have been successfully used as therapy in some cases) [13]. Carbapenems, co-trimoxazole and quinolones can be appropriate empirical therapy. Rahnella species grow well under standard conditions [2]; previously (prior to being listed within commercial API systems/identified through the MALDI-TOF) [3], they have been misidentified as Enterobacter agglomerans.

According to data extracted from UKHSA's Second Generation Surveillance System, from the start of 2021 to September 2023 (when UKHSA's investigation into this case began), Rahnella species or R. aquatilis had been isolated from clinical samples on 29 occasions in NHS hospitals in England and Wales, including blood, sputum, cerebrospinal fluid (CSF) and muscle biopsy. There is no suggestion that this is in exceedance of numbers of cases expected, or that there are links between these infections. These cases are likely to be due to the increased use of MALDI-TOF in NHS laboratories, rather than a sudden increase in infections caused by Rahnella species.

One limitation of this case is its inability to prove that the source of this patient's bacteraemia was the infused vitamin vials, as these were unable to be traced and subsequently sampled. Nonetheless, the timing of her clinical deterioration would fit with the infusion being contaminated with R. aquatilis, and similar cases have been reported in the literature. In view of contaminated foods being a theoretical source of R. aquatilis, in retrospect, an itemised account of her recent food/drink consumption may have been useful, to exclude this as a potential source of her bacteraemia.

This case report highlights the need to consider Rahnella species as significant opportunistic pathogens; they can cause fulminant sepsis in immunocompetent patients. As the United Kingdom's beauty industry develops, with increasing numbers of (both licenced and unlicenced) intravenous vitamin infusions available for use, Rahnella aquatilis and other environmental bacteria are likely to become more well-recognized as potential human pathogens. Furthermore, the synergistic work of clinical microbiologists and public health practitioners is highlighted by this case report.