Introduction

The genus Raoultella, which belongs to the Enterobacteriaceae family, encompasses encapsulated Gram-negative, oxidase-negative, catalase-positive, aerobic, and non-motile bacilli¹,². Initially, it was classified in the genus Klebsiella. However, in 2001, with phylogenetic testing including 16S rRNA and rpoB sequence analysis, the genus Klebsiella was further divided into two genera: the genus Raoultella and cluster II of the genus Klebsiella was transferred and renamed within the new genus³. Currently, Raoultella planticola and Raoultella ornithinolytica are the most important species because of their association as pathogenic agents¹,².

R. ornithinolytica has been found in water environments, soil, insects, fish, ticks, and termites, but human infections are rare². The first human infection caused by R. ornithinolytica was reported in 2009⁴ and it is currently considered an emerging pathogen of community and hospital-acquired infection, particularly in patients with immunodeficiencies, malignancies, anatomic abnormalities, or after invasive procedures²,⁵. Gastrointestinal and hepatobiliary infections are among the most frequently reported infections in the literature. However, urinary tract infections, wound and skin infections, bacteremia, respiratory infections, bone and joint infections, central nervous system infections, mediastinitis, pericarditis, conjunctivitis, and otitis have also been reported in adults²,⁵,⁶. Pediatric infections with R. ornithinolytica are exceedingly rare, and only six cases have been reported previously⁷-¹¹, of which two cases were reported for urinary tract infection¹⁰,¹¹. Here, we describe a case of R. ornithinolytica urinary tract infection in a pediatric patient with T-cell precursor acute lymphoblastic leukemia.

Clinical case

A 9-year-old male patient was brought to the emergency department because of emetic syndrome, asthenia, adynamia, and weakness, without fever. A medical history of T-cell precursor acute lymphoblastic leukemia was recorded. Mild to moderate dehydration was identified with no other physical findings. Laboratory tests revealed moderate hypokalemia (2.8 mEq/L), pancytopenia (white blood cell count of 400 cells/mm³, red blood cell count of 2.84 million cells/mm³, platelet count of 23,000 cells/mm³), severe neutropenia (50 cells/mm³), lymphopenia (340 cells/mm³), and hemoglobin of 6.7 g/dL, requiring red blood cell and platelet transfusions. C-reactive protein was 5.6 mg/dL, while liver enzymes and kidney function tests were normal. Fresh, spontaneous urine was collected. A urinalysis revealed negative nitrites, positive leukocytes, positive blood, 10 white blood cells/hpf, 250 red blood cells/hpf, 1+ bacteria, with the remaining parameters within normal limits. Urine and blood samples were sent for culture and sensitivity, and intravenous empiric treatment with cefepime (150 mg/kg/day) was initiated. Gram-negative bacillus and Gram-positive cocci were detected in the Gram-strain of the urine. The colony number was 100,000 cfu/mL for both bacteria on the CHROMagar Orientation Medium™ (Becton Dickinson, Germany). Through VITEK^® 2×L (Biomerieux, France), the urine culture isolate was identified as Raoultella ornithinolytica and Enterococcus faecalis, and antimicrobial susceptibilities were tested. The R. ornithinolytica and E. faecalis demonstrated susceptibility to all tested antibiotics, including ampicillin-sulbactam (Table 1). The blood culture set (two aerobic and two anaerobic bottles) was negative. Treatment was changed to intravenous ampicillin-sulbactam (50 mg/kg) every 6 h to complete a total duration of 7 days of treatment. The patient's clinical condition improved, and all symptoms resolved. After appropriate antibiotic treatment and achievement of negative urine culture, the patient was discharged.

Discussion

Here, we report the seventh case in a pediatric patient and the third pediatric case of urinary tract infection caused by R. ornithinolytica. As in this case (male child with T-cell precursor acute lymphoblastic leukemia), all the six previously published pediatric cases were diagnosed in patients with either immunodeficiency (asplenia)⁷, malignancies (retinoblastoma and acute myeloid leukemia)⁸,⁹, anatomical abnormalities (bilateral vesicoureteral reflux and hydronephrosis)¹⁰,¹¹, or other comorbidities (IgA nephropathy)⁹. This clinical pattern is in line with the most extensive series of R. ornithinolytica infections in adults, which described comorbidities in more than 50% of patients⁵,¹². Therefore, more extensive studies are needed to a better understanding of the clinical features of R. ornithinolytica in childhood to confirm which comorbidities are risk factors.

Only one of the previously reported pediatric cases showed polymicrobial infection: a case of a febrile 8-year-old female patient with a history of retinoblastoma, neurogenic bladder, and frequent urinary tract infections⁸. Blood and urine cultures yielded R. ornithinolytica and Proteus mirabilis⁸. The present report describes a polymicrobial urinary tract infection (R. ornithinolytica and E. faecalis). Regarding the most extensive series of R. ornithinolytica infections, Chun et al. (2015) and Seng et al. (2016) described 31% and 17% polymicrobial infection in adults associated with E. faecalis in 19% and 16%, respectively⁵,¹². Whether polymicrobial infections are related to more or less severe disease in R. ornithinolytica infection is an interesting hypothesis that requires further investigation.

Interestingly, although Raoultella spp. exhibited intrinsic resistance to ampicillin (similarly to some Klebsiella species) because of chromosomally encoded beta-lactamases², we achieved a satisfactory treatment using ampicillin-sulbactam. This outcome could be explained by Walckenaer et al. findings, who observed that a combination of amino- and carboxypenicillin with clavulanic acid makes R. ornithinolytica environmental isolates susceptible to these molecules¹³. As ampicillin-sulbactam is an aminopenicillin combination with an inhibitor of bacterial beta-lactamase (as well as clavulanic acid), these characteristics support our results. In any case, this hypothesis must be confirmed in further studies.

Finally, in Colombia, only a few previous studies have reported Raoultella spp. infections. In 2012, Molano et al. described bacterial isolations of urinary tract infection in women with urethral catheters from Bogotá city and Soacha municipality and found R. ornithinolytica < 3% of the urine cultures¹⁴. Later, in 2016, Márquez-Herrera et al. described the clinical characteristics of patients with carbapenemase-producing Klebsiella isolates in a tertiary pediatric hospital between 2012 and 2015 in Bogotá, reporting only one case of "Klebsiella ornithinolytica" bacteremia in a patient with nephrotic syndrome¹⁵. The last report was published in 2017, where Ramírez-Quintero et al. described a 41-year-old female patient from Medellín city with community-acquired R. planticola bacteremia of gastrointestinal origin¹⁶. While the first two studies used API 20E and VITEK (probably VITEK Legacy), respectively, as phenotypic identification systems¹⁴,¹⁵, Ramírez-Quintero et al. used the VITEK 2 system¹⁶. Moreover, Park et al. evaluated the ability of three phenotypic systems (VITEK 2, MicroScan, and API 20E) to identify R. ornithinolytica and found that only VITEK 2 was able to identify all the isolates correctly¹⁷. Thus, since we used the VITEK2 system, our microbiological identification was accurate and reliable.

In conclusion, this case report describes a polymicrobial urinary tract infection (R. ornithinolytica and E. faecalis) in a pediatric patient with T-cell precursor acute lymphoblastic leukemia, which was successfully treated with ampicillin-sulbactam. We highlight the importance of considering R. ornithinolytica as an emerging pathogen in pediatric patients and the use of reliable diagnostic methods for accurate microbiological identification.