Enterococcus hirae bacteremia associated with acute pyelonephritis in a patient with alcoholic cirrhosis: a case report and literature review

Background Infections caused by Enterococcus hirae are common in animals, with instances of transmission to humans being rare. Further, few cases have been reported in humans because of the difficulty in identifying the bacteria. Herein, we report a case of pyelonephritis caused by E. hirae bacteremia and conduct a literature review on E. hirae bacteremia. Case presentation A 57-year-old male patient with alcoholic cirrhosis and neurogenic bladder presented with fever and chills that had persisted for 3 days. Physical examination revealed tenderness of the right costovertebral angle. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) of the patient’s blood and urine samples revealed the presence of E. hirae, and pyelonephritis was diagnosed. The patient was treated successfully with intravenous ampicillin followed by oral linezolid for a total of three weeks. Conclusion The literature review we conducted revealed that E. hirae bacteremia is frequently reported in urinary tract infections, biliary tract infections, and infective endocarditis and is more likely to occur in patients with diabetes, liver cirrhosis, and chronic kidney disease. However, mortality is not common because of the high antimicrobial susceptibility of E. hirae. With the advancements in MALDI-TOF MS, the number of reports of E. hirae infections has also increased, and clinicians need to consider E. hirae as a possible causative pathogen of urinary tract infections in patients with known risk factors.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently emerged as an important diagnostic tool, characterized by its high speed, ease of use, and low per sample cost compared to those of conventional diagnostic tools [13]. Therefore, greater progress in the analysis of a variety of bacterial species that have been difficult to identify in the past is expected [13]. In a case of urinary tract infection, E. hirae was rapidly and correctly identified using MALDI-TOF MS, without any complementary tests [14]. Here, we report a case of bacteremia secondary to pyelonephritis caused by E. hirae identified by MALDI-TOF MS, which was successfully treated with ampicillin followed by linezolid. Furthermore, we conducted a literature review on bacteremia caused by E. hirae.

Case presentation
A 57-year-old male with a history of neurogenic bladder caused by cerebral palsy presented to our emergency department with fever and chills that had persisted for 3 days. He had a history of alcoholic cirrhosis classified as Child-Pugh class C treated with rifaximin, lactulose, and branched-chain amino acid supplementation. The patient reported daily consumption of 500 mL of Shochu (a traditional Japanese distilled spirit). He had no allergies or significant family history. He was unemployed and denied any recent contact with animals. The patient was diagnosed with a urinary tract infection at a nearby clinic and was prescribed oral cefcapene 2 days before admission. The patient was conscious on admission with a Glasgow Coma Scale of E4V5M6, body temperature of 36.9 °C, blood pressure of 104/52 mmHg, pulse rate of 82/min, respiratory rate of 20/min, and oxygen saturation of 95% on room air. On physical examination, tenderness of the right costovertebral angle was noted. Laboratory findings revealed a normal white blood cell (WBC) count of 6,000 /μL, hemoglobin level of 12.3 g/dL, platelet count of 48,000 /μL, creatinine level of 0.92 mg/dL, serum albumin level of 2.9 g/dL, total bilirubin level of 2.7 mg/ dL, and C-reactive protein level of 13 mg/dL. Urinalysis showed protein 2 + , occult blood 2 + , and WBC 2 + . Urine Gram staining revealed gram-positive chains with phagocytosis. Contrast-enhanced computed tomography of the abdomen revealed mild swelling of the kidneys, increased surrounding fat tissue density, and a dull edge and uneven surface of the liver (Fig. 1). We first administered 1 g of intravenous (IV) ceftriaxone every 24 h. On day 2, we added 2 g of IV ampicillin every 4 h because streptococci were cultured from blood and urine samples obtained on admission (BacT/  ALERT    fever persisted, we switched to oral linezolid 600 mg every 12 h on day 11, considering possible drug fever. Thereafter, the patient defervesced and was discharged on day 15. He completed a course of oral linezolid for 3 weeks in total, and his condition resolved without any relapse of symptoms at the 10-month follow-up.

Methods of literature review
Two authors independently reviewed the titles and abstracts of database records, retrieved full texts for eligibility assessment, and extracted data from these case reports. We ran searches on the PubMed database (up to May 2020) using the keywords (
In this review, one case of death due to biliary tract infection caused by E. hirae was reported [12]. The mortality rate (n = 1, 3%) from E. hirae infection was similar      to or lower than that of other Enterococcus spp. infections (23%) [23]. However, the accumulation of E. hirae infections warrants accurate evaluation. Three cases of E. hirae infection recurred during treatment [6,7,21], and two of the three recurrent cases involved infective endocarditis. In a report comparing 3308 cases of infective endocarditis caused by non-Enterococcus spp. with 516 cases of infective endocarditis caused by Enterococcus spp. collected prospectively from 35 centers in Spain, recurrence was significantly higher in cases of infective endocarditis caused by Enterococcus spp. (3.5% vs. 1.7%) [28]. There were nine reported cases of E. hirae urinary tract infections with no recurrences or deaths.
The susceptibility of E. hirae to antimicrobial agents is similar to that of E. faecalis, which is susceptible to penicillin. Table 3 shows the antimicrobial susceptibility of E. hirae infections in humans. Although some Table 3 Summary of antimicrobial susceptibility in the previously reported human cases with Enterococcus hirae  reports have reported high resistance to gentamicin [29], of the 21 antimicrobial-susceptible cases in this review, only four (19%) were gentamicin-resistant, and high-level gentamicin resistance cases were not reported. The relatively low mortality and antimicrobial resistance suggest that E. hirae is more similar to E. faecalis than E. faecium. In the present case, the patient could not tolerate ampicillin due to drug allergy and was successfully treated with linezolid after confirming susceptibility. Resistance to clindamycin and gentamicin has been reported repeatedly, and the possibility of resistance should be considered when these drugs are used. The accumulation of human clinical data is warranted to generate an accurate evaluation. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was developed in the 1980s and was accurate in 80-95% of bacterial isolates [13]. Species-level identifications have been obtained and have been widely used in recent years [13]. A study validated the accuracy of MALDI-TOF MS for the identification of Enterococcus spp. compared with the gold standard rpoA gene sequencing method for the identification of bacteria of environmental origin. The occurrence of Enterococcus spp., including E. hirae, in wild birds was correctly identified by MALDI-TOF MS [30]. Before the advent of MALDI-TOF-MS, E. hirae may have been underdiagnosed because of the limitations of the diagnostic method [3]. This review found that there has been an increase in reporting of E. hirae since 2015 following the advent of MALDI-TOF MS.
Enterococcus hirae is a newly recognized causative pathogen of urinary tract infections, especially in patients with underlying diseases. Clinical data such as risk factors, clinical manifestations, and antimicrobial susceptibility are lacking, and more cases should be accumulated following accurate identification.
In summary, the number of E. hirae infections reported has increased following the development of MALDI-TOF MS. Although E. hirae may have a low virulence, as do other enterococci, clinicians need to consider E. hirae as a causative pathogen of urinary tract infection.