Raoultella ornithinolytica infection is a new type of infectious disease that has emerged globally, with the overall incidence currently showing an increasing trend. R. ornithinolytica is a common respiratory, urinary, and bloodstream infection that follows catheter placement and artificial joint replacement [5,6,7,8]. This occurs because the bacteria form a biofilm on the inner surface of artificial implants such as catheters leading to HAIs [9]. In some cases, appendicitis, liver abscess, bacteremia and septic shock have been reported [10, 11] with some infections also causing oral ulcers and facial nerve palsy [12]. In the present case, the patient had abnormally enlarged superficial lymph nodes. These clinical manifestations associated with R. ornithinolytica infection have not been reported previously. The occurrence of similar cases should therefore be monitored closely to provide sufficient data to better understand the clinical features and risk factors of this type of infection.
In many of the cases reported to date, R. ornithinolytica has been considered as an opportunistic pathogen that rarely infected humans. These infections are most prevalent in individuals with impaired immune function. In the present case, the patient had no history of abnormal immune function and we infer that her disease was due to an opportunistic infection caused by contact with soil or plants whilst picking strawberries. In previous case reports [1, 3, 5, 8, 9, 11], MALDI-TOF MS technology was used to identify the R. ornithinolytica infections. However, in our case, due to cost constraints, the clinical laboratory of our hospital is not equipped with the equipment needed to carry out MALDI-TOF MS analyses. Blood culture has several disadvantages as it requires a large volume of blood (20–30 ml), takes a long time to obtain results, is susceptible to contamination, and prone to false negative results due to culture conditions. We therefore finally used next generation sequencing analysis to identify the pathogenic microorganisms in the surrounding blood and then compared them with the pathogenic microorganism database to detect possible pathogenic sources. This technique only requires 5–8 mL of blood samples and we consider that it has the potential to rapidly identify clinical pathogens.
Raoultella ornithinolytica has been shown to express β-lactamase and is therefore not sensitive to clinical routine antibiotic intervention [13]. Case reports in retrospective studies have shown that 80% of R. ornithinolytica strains are resistant to amoxicillin, 17% to amoxicillin-carat tretinoin, 15% to piperacillin/tazobactam, 12% to quinolones, 10% to third-generation cephalosporins, 7% to aminoglycosides and 7% to carbapenems [9, 14]. In recent years, some case reports have also described new isolates carrying the extended-spectrum β-lactamase gene [15, 16]. In our case, the antibiotic treatment regimen (cefixime → amoxicillin and potassium clavulanate → moxifloxacin and ganciclovir) was adjusted several times, although its clinical efficacy was poor. But the infection was effectively controlled after 6 days of treatment with meropenem. However, it is worth noting that there have been reports of new cases of infections resistant to carbapenems [17, 18].
Raoultella ornithinolytica also has the hdc gene that encodes for histidine decarboxylase, an enzyme with catalyzes the conversion of histidine to histamine. Therefore, infected patients may develop skin symptoms related to allergic reactions such as skin flushing, itching, and maculopapular formation [19, 20]. These clinical manifestations were confirmed in our case, and therefore in addition to appropriate antibiotics, antihistamine therapy was also necessary to successfully treat the patient.
In patients with these diseases it must also be noted that there may be some treatment limitations as follows. Firstly, because no pathogenic bacteria were found in body fluid cultures in our case, further drug susceptibility tests could not be carried out. Next-generation sequencing also failed to identify a clear drug-resistant gene locus and could not provide us with guidance for further adjustment of antibiotic therapy. Under the premise that the use of cephalosporins, penicillin, and quinolone antibiotics had not worked, we finally administered the carbapenem drug, meropenem to our patient. Secondly, before the next-generation sequencing results identified the pathogen we could only indirectly diagnose and provide empirical treatment based on the patient’s medical history, symptoms, signs, and the results of routine examinations. As a consequence, the allergic rash was mistakenly regarded as a rash caused by a viral infection and therefore ganciclovir was added to the treatment regime.
Although previous case reports have mainly suggested that R. ornithinolytica infections are more likely to occur in immunocompromised persons, our case indicates that the bacteria may also infect healthy people in the community. The clinical characteristics of the onset of infection in healthy individuals are not only infection-related symptoms, but also symptoms of allergic reactions to bacterial components, which are quite different from those reported previously for immunocompromised infections. We also found in our case, that although R. ornithinolytica did not have a clear drug resistance gene, the pathogenic bacteria were not sensitive to common clinical antibiotic treatments and administration of carbapenem drugs was required to treat the infection. As a novel clinical pathogen that is able to spread gradually, R. ornithinolytica should not be regarded as miscellaneous bacteria that can only contaminate tissue samples. Physicians should be aware of its risk to cause a community infection with high drug resistance leading to an increased risk of death from sepsis. Clinical manifestations should therefore be identified quickly and appropriate control measures initiated at an early stage. Broad-spectrum antibiotics combined with antihistamine treatment could be considered before accurate microbiological results are obtained.