Herbaspirillum Infection in Humans: A Case Report and Review of Literature

Introduction. Herbaspirillum seropedicae are Gram-negative oxidase-positive nonfermenting rods of Betaproteobacteria class, commonly found in rhizosphere. More recently, some Herbaspirillium species have transitioned from environment to human hosts, mostly as opportunistic (pathogenic) bacteria. We present a 58-year-old female with non-small-cell lung cancer (NSCLC) who presented with pneumonia and was found to have Herbaspirillum seropedicae bacteremia. Case History. A 58-year-old woman with NSCLC on Pralsetinib presented with fevers and rigors for 2 days. Coarse breath sounds were auscultated on the right upper lung field. Labs revealed leukopenia and mild neutropenia. CT chest revealed right upper lobe pneumonia. She was admitted for sepsis secondary to pneumonia and placed on broad spectrum antibiotics with intravenous piperacillin-tazobactam and vancomycin. The patient continued to have fever 2 days after admission (max: 102.8°F). Preliminary blood cultures grew Gram-negative rods. The patient continued to have temperature spikes on the 3rd day of antibiotics (Tmax 101.5°F). Blood cultures revealed oxidase-positive nonfermenting rods. The patient's antibiotic was changed to IV meropenem on the 4th day of hospitalization. Ultimately, on the seventh day of hospitalization, the blood culture was confirmed from outside lab as Herbaspirillum seropedicae. The patient started feeling better and defervesced after about 24 hours. Discussion. More recently, Herbaspirillum spp. have been recovered from humans. Our patient had Herbaspirillum bacteremia, and reported regularly cleaning her pond and weeding her garden with possible exposure to this environmental proteobacterium. Herbaspirillum may be more prevalent than earlier thought owing to misidentification. With the institution of appropriate antimicrobial therapy, the outcomes seem mostly favorable.


Introduction
Herbaspirillum seropedicae are Gram-negative oxidasepositive nonfermenting rods of Betaproteobacteria class, commonly found in the rhizosphere of maize and rice, which promote plant growth via biological nitrogen fixation and phytohormone production [1,2]. More recently, some Herbaspirillium species have transitioned from environment (water, contaminated soil, plant internal tissues, and root nodules) to human hosts, mostly as opportunistic (pathogenic) bacteria. Cases of human colonization and infection have mostly been noted in cystic fibrosis and immunocompromised cancer patients [3][4][5][6][7][8] and also in some patients without an apparent immunosuppressed state [9][10][11].

Case History.
A 58-year-old woman with a medical history of non-small-cell lung cancer (NSCLC) with malignant left pleural effusion (with RET mutation under phase 1 trial with pralsetinib), nonbacterial thrombotic endocarditis, and pulmonary embolism presented to the hospital with fevers, chills, and rigors for 2 days. At presentation, she was febrile with a temperature of 101 F and tachycardic at 114 beats/minute. Physical examination revealed a Port-Acatheter on the right upper chest. Coarse breath sounds were auscultated on the right upper lung field. Labs revealed anemia with the hemoglobin level of 6 .00) mg/dl, and an elevated creatinine level of 1.56 mg/dl (baseline creatinine of 1 mg/dl). CT chest revealed right upper lobe pneumonia, scattered small pulmonary nodules consistent with metastatic disease, and stable bony metastatic disease of the anterior left 6th rib. She was admitted for sepsis secondary to pneumonia and placed on broad spectrum antibiotics with intravenous piperacillin-tazobactam and vancomycin. She received 2 units of packed red cell transfusion with stable hemoglobin thereafter. Urine analysis was unremarkable. Urine legionella and streptococcus pneumonia antigens were negative. e patient continued to have fever 2 days after admission (max: 102.8 F). Preliminary blood cultures done at our hospital at Day 2 of hospitalization revealed Gram-negative rods. CT abdomen and pelvis revealed small volume of ascites and jejunal wall thickening with mild adjacent mesenteric edema, suggestive of enteritis. CT chest revealed persistent right upper lobe pneumonia. e patient continued to have temperature spikes on the 3rd day of antibiotics (T max 101.5 F). Blood cultures revealed oxidase-positive nonfermenting rods. e organism was not clearly identified in our lab, and the specimen was sent to Central Pennsylvania Alliance Laboratory for identification by DNA sequencing using MALDI (matrix-assisted laser desorption/ionization) technique. e patient's antibiotic was changed to IV meropenem on the 4th day of hospitalization. Port was removed and catheter tip culture was sent, which came out to be negative.
Ultimately, on the seventh day of hospitalization, the blood culture was identified from outside lab as Herbaspirillum seropedicae (which was susceptible to all tested antibiotics including amikacin, cefepime, ceftazidime, ciprofloxacin, aztreonam, levofloxacin, meropenem, piperacillin/tazobactam, and ticarcillin/clavulanate). e patient started feeling better and defervesced after about 24 hours of being on meropenem. e patient was discharged with a midline catheter to continue IV meropenem for a total of 14 days and follow-up for outpatient monitoring. e WBC count at discharge was 5.1 × 10 µ/L, ANC was 3978 cells/ microliter, and CRP was 6.36 mg/dl. On further questioning to assess for risk factors, the patient reported taking care of her pond and regularly cleaning weeds.

Discussion
e first described species of the genus Herbaspirillum was the bacterium Herbaspirillum seropedicae, which was found colonizing the roots and aerial parts of important crops [1]. More recently, Herbaspirillum spp. have been recovered from the blood and sputum/bronchoalveolar lavage of patients with cystic fibrosis and pneumonia [4,6,11] and from blood in patients with leukemia [6,7,12], aplastic anemia [7], multiple myeloma [13], and cellulitis [8]. Our patient is a 58-year-old woman with NSCLC on RET-inhibitor pralsetinib who presented with right upper lobe pneumonia and had blood culture positive for oxidase-positive nonfermenting Gram-negative rod, which was confirmed as Herbaspirillium only on Day 7 of hospitalization by which time the patient was already improving with meropenem therapy. On retrospect, our patient had been regularly cleaning her pond and weeding her garden with possible exposure to this environmental proteobacterium, supporting this change in dynamics from environmental bacterium to opportunistic pathogen. However, it is not entirely clear why the patient only defervesced and improved after 24 hours of switching piperacillin/tazobactam to meropenem, even though her culture report suggested sensitivity to piperacillin/tazobactam. New genomic data findings suggest that the transition from environmental to pathogenic led to the loss and acquisition of specific genes to allow colonization and survival in new environments. e strains that have been infectious to humans have lost the genes for nitrogen fixation and acquired genes for lipopolysaccharide biosynthesis with the addition of sialic acids to evade the immune system [1].
We reviewed the literature for available Herbaspirillum cases and identified 9 published studies from 2005 to 2019 (Table 1)   were Herbaspirillum seropedicae, and 2 were Herbaspirillum putei, and the remaining eighteen isolates could not be speciated [4]. Prior to the correct identification of Herbaspirillum at the BcRLR for the above 28 specimen, they had been identified as Burkholderia cepacia complex in 19 (68%) and Ralstonia in 4 (14%). Most patients appeared to have had transient respiratory tract colonization with Herbaspirillum except for bacteremia in one patient and a chronic respiratory tract infection in another [4]. Tetz and Tetz, for the first time, identified Herbaspirillum frisingense from the bladder of a human patient with urinary tract infection (UTI). Furthermore, genome analysis revealed numerous factors such as adhesins, urease, hemolysin D, and pilin that contribute to the bacterium's virulence in UTIs. e authors suggested that further research of this Herbaspirillum spp would aid in better understanding of its implication in UTI [14]. Similarly, Wu et al. performed a comprehensive analysis of urinary microenvironment of bladder cancer and identified Herbaspirillum as one of the species associated with an increased risk of progression, suggesting its potential role in risk stratifying bladder cancer [15].
As evidenced by the above studies, Herbaspirillum is an emerging pathogen and may be more prevalent than earlier thought owing to misidentification for organisms like Burkholderia cepacia complex due to phylogenetic and phenotypic resemblance [4,6,7,13]. Antimicrobial susceptibilities may serve as a means for differentiating Herbaspirillum species from Burkholderia cepacia complex because the latter are usually multidrug resistant, whereas Herbaspirillum is not. With the institution of appropriate antimicrobial therapy, the outcomes seem mostly favorable and the bacteria appear to be easily eradicated, except in 1 case reported by Liu et al. Misidentification as Burkholderia complex can have serious implications for clinical care, and distinction between these is important due to different resistance profiles and different therapeutic implications. e increased availability of newer molecular methods (e.g., MALDI-TOF MS) should allow laboratories to correctly identify this organism and reduce misidentification by established microbial identification systems.

Conflicts of Interest
e authors declare that they have no conflicts of interest.