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



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.


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.

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Enterococcus hirae primarily causes zoonosis [1, 2], with human infections being relatively rare. Nevertheless, pyelonephritis [3,4,5], infective endocarditis [6,7,8,9,10,11], and biliary tract infections [5, 12] due to E. hirae have been reported in human patients. Although E. hirae has been found to cause these severe diseases in humans, few cases have been reported because of the difficulty in identifying the bacteria, and the lack of comprehensive reports on clinical characteristics and treatments [3].

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 FA Plus, BacT/ALERT 3D [bioMérieux Inc.]). On day 4, a transthoracic echocardiogram revealed no evidence of infective endocarditis. On day 5, final culture results revealed E. hirae by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (MALDI Biotyper [Bruker Daltonics]) and VITEK2 Compact (bioMérieux Inc.). The minimum inhibitory concentrations measured by MicroScan WalkAway 96 Plus and PC1J panel(Beckman Coulter Inc.) for this strain were as follows: penicillin G 0.25 μg/mL, ampicillin 0.25 μg/mL, vancomycin 1 μg/mL, levofloxacin ≤ 0.5 μg/mL, teicoplanin ≤ 2 μg/mL, and linezolid 2 μg/mL (Table 1). We switched to ampicillin IV (2 g every 6 h). Blood cultures performed on day 5 were negative. Because his low-grade 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.

Fig. 1
figure 1

Contrast-enhanced computed tomographic images revealing heterogeneous enhancement of both kidneys in A, and a liver with a blunt edge and irregular surface in B

Table 1 Antimicrobial susceptibility of the Enterococcus hirae isolated from blood culture in this case

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 ((("Enterococcus hirae"[Mesh]) OR ("Enterococcus hirae"[TW]) OR (hirae[TIAB])) AND ((Bacteremia[MH]) OR (bacteremia*[TIAB] OR bacteraemia*[TIAB]))) OR ((("Enterococcus hirae"[Mesh]) OR ("Enterococcus hirae"[TW]) OR (hirae[TIAB])) AND Humans[MH]), and the Embase database using the keywords (('bacteremia'/exp OR 'gram negative sepsis'/exp OR bacteraemia* OR bacteremia*) AND ('enterococcus hirae'/exp OR hirae)) OR (('enterococcus hirae'/exp OR hirae) AND [humans]/lim). PubMed and Embase searches generated 170 and 229 articles, respectively. Of these, 158 and 218 articles from PubMed and Embase, respectively, were excluded because they were not case reports (Fig. 2). We searched Google Scholar and identified eight more human cases. Manuscripts not written in English were excluded. Finally, we reviewed 21 articles that included 31 strains from human sources.

Fig. 2
figure 2

Literature review flow chart

Discussion and conclusion

Enterococcus hirae was first identified by Farrow et al. in 1985 [16]. It has been reported that although animal species such as chickens, rats, birds, and cats are commonly found to be infected [1, 2], human infections are relatively rare [17]. Only 31 human cases of E. hirae have been reported (Table 2). Of these, urinary tract infections [3,4,5, 12, 14, 18], biliary tract infections [5, 12], and infective endocarditis [6,7,8,9,10,11] accounted for the majority of cases, with catheter-related bloodstream infections [12, 19], peritonitis [20, 21], splenic abscess [22], and pneumonia [17] also being reported. Patients were predominantly male (n = 20, 64.5%), similar to predominance in infections caused by other Enterococcus spp. [23], Furthermore, no age trend was observed (median: 63 years) [23]. The common underlying diseases were diabetes mellitus (n = 12, 39%), liver cirrhosis (n = 4, 13%), and chronic kidney disease (n = 4, 13%). Occurrence of diabetes mellitus and liver cirrhosis was consistent with previous reports of Enterococcus spp. Malignant tumors were found to be less common [23]. This case of a middle-aged male with underlying alcoholic cirrhosis and chronic kidney disease was consistent with the trend uncovered in the literature review.

Table 2 Summary of the previously reported human cases with Enterococcus hirae

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 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.

Table 3 Summary of antimicrobial susceptibility in the previously reported human cases with Enterococcus hirae

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.

Availability of data and materials

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E. hirae :

Enterococcus hirae




Matrix-assisted laser desorption ionization-time of flight mass spectrometry


White blood cell


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The manuscript was seen and approved by all the authors and is not under consideration elsewhere. All the authors contributed to the work in this report. TN collected clinical data and wrote the initial draft of the manuscript. TN, KI, and FK performed the review of the literature. KI, TM, YU, and NM supervised and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Tomoaki Nakamura.

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Nakamura, T., Ishikawa, K., Matsuo, T. et al. Enterococcus hirae bacteremia associated with acute pyelonephritis in a patient with alcoholic cirrhosis: a case report and literature review. BMC Infect Dis 21, 999 (2021).

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