Hindawi Case Reports in Infectious Diseases Volume 2020, Article ID 9545243, 6 pages https://doi.org/10.1155/2020/9545243

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

Rashmi Dhital , Anish Paudel, Nidrit Bohra, and Ann K. Shin

Reading Hospital and Medical Center, Tower Health System, West Reading, PA, USA

Correspondence should be addressed to Rashmi Dhital; [email protected]

Received 5 December 2019; Revised 2 February 2020; Accepted 4 February 2020; Published 20 February 2020

Academic Editor: Raul Colodner

Copyright © 2020 Rashmi Dhital et al. &is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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. CTchest 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. &e patient continued to have fever 2 days after admission (max: 102.8°F). Preliminary blood cultures grew Gram- ° negative rods. &e patient continued to have temperature spikes on the 3rd day of antibiotics (Tmax 101.5 F). Blood cultures revealed oxidase-positive nonfermenting rods. &e patient’s antibiotic was changed to IV meropenem on the 4th day of hos- pitalization. Ultimately, on the seventh day of hospitalization, the blood culture was confirmed from outside lab as Herbaspirillum seropedicae. &e 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.

1. Introduction 1.1. Case History. A 58-year-old woman with a medical history of non-small-cell lung cancer (NSCLC) with ma- Herbaspirillum seropedicae are Gram-negative oxidase- lignant left pleural effusion (with RETmutation under phase positive nonfermenting rods of Betaproteobacteria class, 1 trial with pralsetinib), nonbacterial thrombotic endo- commonly found in the rhizosphere of maize and rice, carditis, and pulmonary embolism presented to the hospital which promote plant growth via biological nitrogen fixa- with fevers, chills, and rigors for 2 days. At presentation, she tion and phytohormone production [1, 2]. More recently, was febrile with a temperature of 101 F and tachycardic at some Herbaspirillium species have transitioned from en- 114 beats/minute. Physical examination revealed a Port-A- vironment (water, contaminated soil, plant internal tissues, catheter on the right upper chest. Coarse breath sounds were and root nodules) to human hosts, mostly as opportunistic auscultated on the right upper lung field. Labs revealed (pathogenic) bacteria. Cases of human colonization and anemia with the hemoglobin level of 6.4 (ref: 12.0–16.0 g/dl), infection have mostly been noted in cystic fibrosis and leukopenia with the white blood cell (WBC) count of 1.7 (ref immunocompromised cancer patients [3–8] and also in 4.8–10.8 10E3/ul), mild neutropenia with the absolute some patients without an apparent immunosuppressed neutrophil count (ANC) of 1353 cells per microliter, an state [9–11]. elevated C-reactive protein (CRP) level of 22.52 (ref range 2 Case Reports in Infectious Diseases

<1.00) mg/dl, and an elevated creatinine level of 1.56 mg/dl cleaning her pond and weeding her garden with possible (baseline creatinine of 1 mg/dl). CT chest revealed right exposure to this environmental proteobacterium, support- upper lobe pneumonia, scattered small pulmonary nodules ing this change in dynamics from environmental bacterium consistent with metastatic disease, and stable bony meta- to opportunistic pathogen. However, it is not entirely clear static disease of the anterior left 6th rib. She was admitted for why the patient only defervesced and improved after 24 sepsis secondary to pneumonia and placed on broad spec- hours of switching piperacillin/tazobactam to meropenem, trum antibiotics with intravenous piperacillin-tazobactam even though her culture report suggested sensitivity to and vancomycin. She received 2 units of packed red cell piperacillin/tazobactam. New genomic data findings suggest transfusion with stable hemoglobin thereafter. Urine anal- that the transition from environmental to pathogenic led to ysis was unremarkable. Urine legionella and streptococcus the loss and acquisition of specific genes to allow coloni- pneumonia antigens were negative. zation and survival in new environments. &e strains that &e patient continued to have fever 2 days after admission have been infectious to humans have lost the genes for (max: 102.8 F). Preliminary blood cultures done at our hos- nitrogen fixation and acquired genes for lipopolysaccharide pital at Day 2 of hospitalization revealed Gram-negative rods. biosynthesis with the addition of sialic acids to evade the CT abdomen and pelvis revealed small volume of ascites and immune system [1]. jejunal wall thickening with mild adjacent mesenteric edema, We reviewed the literature for available Herbaspirillum suggestive of enteritis. CT chest revealed persistent right cases and identified 9 published studies from 2005 to 2019 upper lobe pneumonia. &e patient continued to have tem- (Table 1), with Herbaspirillum bacteremia, cellulitis or perature spikes on the 3rd day of antibiotics (Tmax 101.5 F). pneumonia. Tan and Oehler reported Herbaspirillum bac- Blood cultures revealed oxidase-positive nonfermenting rods. teremia and cellulitis in a patient with aquatic exposure [8]. &e organism was not clearly identified in our lab, and the Ziga et al. reported Herbaspirillum bacteremia in a 2-year- specimen was sent to Central Pennsylvania Alliance Labo- old girl with a history of acute lymphoblastic leukemia (ALL) ratory for identification by DNA sequencing using MALDI after induction chemotherapy and stem cell transplant [6]. (matrix-assisted laser desorption/ionization) technique. &e Chen et al. reported Herbaspirillum bacteremia in an ALL patient’s antibiotic was changed to IV meropenem on the 4th patient on chemotherapy after taking sugarcane juice [12]. day of hospitalization. Port was removed and catheter tip Regunath et al. described a case of bacteremia caused by culture was sent, which came out to be negative. gentamicin-resistant Herbaspirillum in an immunocompe- Ultimately, on the seventh day of hospitalization, the tent adult male farmer [11]. Suwantarat et al. reported the blood culture was identified from outside lab as Herbas- first fatal case-related H. seropedicae bacteremia secondary pirillum seropedicae (which was susceptible to all tested to pneumonia in an immunocompromised 65-year-old man antibiotics including amikacin, cefepime, ceftazidime, with end-stage renal disease and multiple myeloma [13]. ciprofloxacin, aztreonam, levofloxacin, meropenem, piper- Abreu-Di Berardino et al. described Herbaspirillum hut- acillin/tazobactam, and ticarcillin/clavulanate). &e patient tiense pneumonia in a patient with essential thrombocytosis started feeling better and defervesced after about 24 hours of [9]. Liu et al. reported Herbaspirillum huttiense bacteremia being on meropenem. &e patient was discharged with a in an elderly patient with no obvious immune suppression, midline catheter to continue IV meropenem for a total of 14 who later went on to develop a pneumonia, where despite days and follow-up for outpatient monitoring. &e WBC adequate treatment, microbiological eradication was not count at discharge was 5.1 × 10 µ/L, ANC was 3978 cells/ easily achieved, and septicemia lasted for several days along microliter, and CRP was 6.36 mg/dl. On further questioning with sputum culture positivity for Herbaspirillum huttiense 2 to assess for risk factors, the patient reported taking care of months later [10]. her pond and regularly cleaning weeds. Chemaly et al. investigated a potential cluster of hospital- based Herbaspirillum infections in cancer patients at the 2. Discussion University of Texas MD Anderson Cancer Center, initially identified as Burkholderia cepacia complex and subsequently &e first described species of the genus Herbaspirillum was reidentified as Herbaspirillum species by the Cystic Fibrosis the bacterium Herbaspirillum seropedicae, which was found Foundation Burkholderia cepacia Research Laboratory and colonizing the roots and aerial parts of important crops [1]. Repository (BcRLR) at the University of Michigan. &e More recently, Herbaspirillum spp. have been recovered authors identified a total of 8 patients with bacteremia and from the blood and sputum/bronchoalveolar lavage of pa- pneumonia with cultures positive for Herbaspirillum species tients with cystic fibrosis and pneumonia [4, 6, 11] and from between July 2011 and August 2012 (including 5 clusters and blood in patients with leukemia [6, 7, 12], aplastic anemia 3 additional cases identified prospectively). 5 of the 8 pa- [7], multiple myeloma [13], and cellulitis [8]. Our patient is a tients were females and the median age was 53 years (2–67 58-year-old woman with NSCLC on RET-inhibitor pralse- years) [7]. tinib who presented with right upper lobe pneumonia and Spilker et al. reported a 26-year-old male with moderate had blood culture positive for oxidase-positive non- to severe lung disease with Gram-negative rod bacteremia at fermenting Gram-negative rod, which was confirmed as hospital day 23. &e patient was admitted for methicillin- Herbaspirillium only on Day 7 of hospitalization by which resistant staphylococcus aureus (MRSA) and Pseudomonas time the patient was already improving with meropenem pneumonia, and cultures were initially misidentified as therapy. On retrospect, our patient had been regularly Burkholderia cepacia complex [4]. &e authors analyzed aeRprsi netosDiseases Infectious in Reports Case

Table 1: Summary table of published cases of Herbaspirillum infection in humans. Past history/ Likely risk Reason for Response to initial Specimen source Author year, Age/ predisposing Immune factor/inciting admission/Clinical Initial antibiotics antibiotics/ positive for country sex conditions/cancer/ suppression event presentation subsequent antibiotics Herbaspirillum HCST Changed to meropenem and Blood: (i) Fever, seizure colistin at 10 days and Herbaspirillum (ii) After a few days, Empiric changed to huttiense Hypertension Liu 2019, Korea 93/F N/A — hypoxia and chest vancomycin + ceftriaxone for ceftazidime, 2 months later, Advanced age X-ray with encephalitis minocycline, and sputum: pneumonia trimethoprim/ Herbaspirillum sulfamethoxazole huttiense thereafter Aortic wall (i) Generalized thrombosis, visceral deconditioning Abreu-di and cerebral ischemic Sputum: (ii) Dyspnea 10 days Recovered completely berardino 2019, 59/F lesions, N/A — Piperacillin-tazobactam Herbaspirillum after admission, after antibiotics Spain JAK2 + essential huttiense nosocomial thrombocytopenia, pneumonia new DM Drank On Blood: Acute lymphoblastic sugarcane juice Chen 2010, China 48/F chemotherapy Fever, chills Cefmetazole and gatifloxacin Improved Herbaspirillum leukemia before fever and G-CSF huttiense started On the hospital day 23: fever and rigors Changed to Blood: (GNR, Moderate to severe Recent multiple Fevers and rigors, Vancomycin, piperacillin- intravenous initially identified as lung disease, admissions for MRSA, and tazobactam, and tobramyicn ceftazidime and burkholderia cepacia 26/ pancreatic Spilker 2008, USA exacerbation of — Pseudomonas x 20 days Antibiotic tobramycin and oral complex) Later, m insufficiency, respiratory aeruginosa discontinued at 20 days, after trimethoprim- identified as diabetes, and liver symptoms bacteremia FEV1 started to improve sulfamethoxazole Herbaspirillum disease (TMP-SMX), species levofloxacin, and minocycline 3 Table 1: Continued. 4 Past history/ Likely risk Reason for Response to initial Specimen source Author year, Age/ predisposing Immune factor/inciting admission/Clinical Initial antibiotics antibiotics/ positive for country sex conditions/cancer/ suppression event presentation subsequent antibiotics Herbaspirillum HCST Blood: (oxidase- Homeless positive nonlactose- Antibiotics switched Jumped from a Increasing fermenting to cefepime and 49/ Probable hepatic bridge into a erythema and GNR,submitted to Tan 2005, USA — Ampicillin/sulbactam levofloxacin after m cirrhosis freshwater warmth to the left an outside reference initial blood culture canal in central leg (cellulitis) laboratory) positive results Florida for Herbaspirillum seropedicae Blood (Day 1) (from referring facility) Farming in Fever, fatigue, SOB, Ceftriaxone switched identified as rural Missouri, night sweats, to piperacillin- Burkholderia cepacia close contact anorexia, myalgia, tazobactam complex (BCC),later Childhood asthma, with cattle and and headache Dry Azithromycin as Herbaspirillum Regunath 2014, 46/ atypical pneumonia as turkeys, mold cough, right-sided Vancomycin, ceftriaxone, switched to aquaticum or N/A USA M a teenager, and possible rat pleuritic chest pain, and azithromycin Doxycycline Herbaspirillum tonsillectomy excreta and worsening After 12 days of huttiense BAL (Day Drenched in dyspnea Hypoxia treatment, the patient 3): GNR as rain during a (multilobar improved and was Herbaspirillum fishing trip pneumonia) extubated aquaticum or Herbaspirillum huttiense Chemaly 2015, USA All patients improved Cefepime (5 patients), with antibiotic and ceftazidime (1 patient), Source and had negative repeat moxifloxacin (1 patient), Ovarian mechanism of Pseudomonas BSI, blood cultures 48/F Chemotherapy meropenem (1 patient) Blood, Infusaport tip adenocarcinoma the cluster sepsis-CRBSI 1 patient had Diseases Infectious in Reports Case initially Hospital-based unknown recurrence, which Followed by ceftriaxone or cluster of resolved once the port fluoroquinolone Herbaspirillium sp was removed infections initially MRSA pneumonia, 67/F Leukemia Chemotherapy Blood misidentified as B. sepsis-BSI cepacia 58/ High-dose GI bleed GVHD, Leukemia/HSCT Blood M steroid BSI High-dose 55/F Leukemia/HSCT GI GVHD, BSI Blood steroid High-dose Herbaspirillium 2/M Ependymoma Blood steroid Sepsis-BSI aeRprsi netosDiseases Infectious in Reports Case

Table 1: Continued. Past history/ Likely risk Reason for Response to initial Specimen source Author year, Age/ predisposing Immune factor/inciting admission/Clinical Initial antibiotics antibiotics/ positive for country sex conditions/cancer/ suppression event presentation subsequent antibiotics Herbaspirillum HCST History of recurrent Radiation Herbaspirillium 3 additional 66/F pneumonia, lung Sputum therapy Sepsis-pneumonia Herbaspirillium sp cancer after continued 18/ Chemotherapy Lymphoma Chemotherapy Blood surveillance M Sepsis-BSI (sporadic) Aplastic anemia/ Herbaspirillium 51/F Tacrolimus Blood, PICC line tip HSCT Sepsis- CRBSI BAL (oxidase- Changed to positive, nonlactose- vancomycin, fermenting GNR), Acute respiratory meropenem, and Multiple myeloma Vancomycin, cefepime, initially identified as Suwantarat 2015, 65/ Steroids and failure and septic gentamicin within 12 ESRD on ciprofloxacin, and Cupriavidus, later as USA M lenalidomide shock Right lower hours However, the hemodialysis micafungin Herbaspirillum lobe pneumonia patient remained Blood: clinically unstable and Herbaspirillum died after 4 days seropedicae Gentamicin added Blood Burkholderia Uncertain Lives after oxidase-positive, cepacia complex As with her parents weakly catalase- susceptibility pattern Acute lymphoblastic Chemotherapy, Ziga 2010, USA 2/F and Fever and diarrhea Cefepime positive, Gram- was not consistent, leukemia HSCT grandparents negative bacillus further identification on a large farm Later, switched to was pursued: meropenem Herbaspirillum sp G-CSF: granulocyte-colony stimulating factor; BAL: bronchoalveolar lavage; GI GVHD: gastrointestinal graft versus host disease; BSI: blood stream infection; CRBSI: catheter-related blood stream infection; HSCT: hematopoietic stem cell infection; GNR: gram-negative rod. 5 6 Case Reports in Infectious Diseases isolates from sputum from over 1,100 cystic fibrosis patients environmental and clinical isolates of Herbaspirillum spp.,” across 8 years (January 2000 to December 2007) and found Journal of Clinical Microbiology, vol. 53, no. 1, pp. 302–308, Herbaspirillum in only 28 patients (<3%) with ages ranging 2015. from 20 months to 5 years, of which 3 isolates were Her- [3] T. Coenye, J. Goris, T. Spilker, P. Vandamme, and baspirillum huttiense, 3 were Herbaspirillum frisingense, 2 J. J. LiPuma, “Characterization of unusual bacteria isolated from respiratory secretions of cystic fibrosis patients and were Herbaspirillum seropedicae, and 2 were Herbaspirillum description of Inquilinus limosus gen. Nov., sp. Nov,” Journal putei, and the remaining eighteen isolates could not be of Clinical Microbiology, vol. 40, no. 6, pp. 2062–2069, 2002. speciated [4]. Prior to the correct identification of Herbas- [4] T. Spilker, A. Z. Uluer, F. M. Marty et al., “Recovery of pirillum at the BcRLR for the above 28 specimen, they had Herbaspirillum species from persons with cystic fibrosis,” been identified as Burkholderia cepacia complex in 19 (68%) Journal of Clinical Microbiology, vol. 46, no. 8, pp. 2774–2777, and Ralstonia in 4 (14%). Most patients appeared to have had 2008. transient respiratory tract colonization with Herbaspirillum [5] W. Chen, Y.-Y. Chen, C.-F Tsai et al., “Incidence and out- except for bacteremia in one patient and a chronic respi- comes of acute respiratory distress syndrome,” Medicine, ratory tract infection in another [4]. vol. 94, no. 43, p. e1849, 2015. Tetz and Tetz, for the first time, identified Herbaspirillum [6] E. D. Ziga, T. Druley, and C.-A. D. Burnham, “Herbaspirillum frisingense from the bladder of a human patient with urinary species bacteremia in a pediatric oncology patient,” Journal of Clinical Microbiology, vol. 48, no. 11, pp. 4320-4321, 2010. tract infection (UTI). Furthermore, genome analysis [7] R. F. Chemaly, R. Dantes, D. P. Shah et al., “Cluster and revealed numerous factors such as adhesins, urease, he- sporadic cases of Herbaspirillum species infections in patients molysin D, and pilin that contribute to the bacterium’s with cancer,” Clinical Infectious Diseases, vol. 60, no. 1, virulence in UTIs. &e authors suggested that further re- pp. 48–54, 2015. search of this Herbaspirillum spp would aid in better un- [8] M. J. Tan and R. L. Oehler, “Lower extremity cellulitis and derstanding of its implication in UTI [14]. Similarly, Wu bacteremia with Herbaspirillum seropedicae associated with et al. performed a comprehensive analysis of urinary mi- aquatic exposure in a patient with cirrhosis,” Infectious Dis- croenvironment of bladder cancer and identified Herbas- eases in Clinical Practice, vol. 13, no. 5, pp. 277–279, 2005. pirillum as one of the species associated with an increased [9] M. Abreu-Di Berardino, E. Rodr´ıguez-Czaplicki, and risk of progression, suggesting its potential role in risk V. Sanchez-Hell´ ´ın, “Herbaspirillum huttiense pneumonia in a patient with essential thrombocythaemia,” Revista Espanolã stratifying bladder cancer [15]. De Quimioterapia: Publicacioń Oficial de la Sociedad Espanolã As evidenced by the above studies, Herbaspirillum is an de Quimioterapia, vol. 32, no. 1, pp. 83-84, 2019. emerging pathogen and may be more prevalent than earlier [10] C. Liu, M. J. Kwon, M. Kim, J.-H. Byun, D. Yong, and K. Lee, thought owing to misidentification for organisms like “Septicemia caused by Herbaspirillum huttiense secondary to Burkholderia cepacia complex due to phylogenetic and pneumonia,” Annals of Laboratory Medicine, vol. 39, no. 3, phenotypic resemblance [4, 6, 7, 13]. Antimicrobial sus- pp. 340–342, 2019. ceptibilities may serve as a means for differentiating Her- [11] H. Regunath, J. Kimball, L. P. Smith, and W. Salzer, “Severe baspirillum species from Burkholderia cepacia complex community-acquired pneumonia with bacteremia caused by because the latter are usually multidrug resistant, whereas Herbaspirillum aquaticum or Herbaspirillum huttiense in an Herbaspirillum is not. With the institution of appropriate immune-competent adult,” Journal of Clinical Microbiology, antimicrobial therapy, the outcomes seem mostly favorable vol. 53, no. 9, pp. 3086–3088, 2015. [12] J. Chen, Z. Su, Y. Liu et al., “Herbaspirillum species: a potential and the bacteria appear to be easily eradicated, except in 1 pathogenic bacteria isolated from acute lymphoblastic leu- case reported by Liu et al. Misidentification as Burkholderia kemia patient,” Current Microbiology, vol. 62, no. 1, complex can have serious implications for clinical care, and pp. 331–333, 2011. distinction between these is important due to different re- [13] N. Suwantarat, L. T. L. Adams, M. Romagnoli, and sistance profiles and different therapeutic implications. &e K. C. Carroll, “Fatal case of Herbaspirillum seropedicae bac- increased availability of newer molecular methods (e.g., teremia secondary to pneumonia in an end-stage renal disease MALDI-TOF MS) should allow laboratories to correctly patient with multiple myeloma,” Diagnostic Microbiology and identify this organism and reduce misidentification by Infectious Disease, vol. 82, no. 4, pp. 331–333, 2015. established microbial identification systems. [14] V. Tetz and G. Tetz, “Draft genome sequence of the uropa- thogenic Herbaspirillum frisingense strain ureolyticus VT-16- 41,” Genome Announcements, vol. 5, no. 17, pp. e00279–17, Conflicts of Interest 2017. [15] P. Wu, G. Zhang, J. Zhao et al., “Profiling the urinary &e authors declare that they have no conflicts of interest. microbiota in male patients with bladder cancer in China,” Frontiers in Cellular and Infection Microbiology, vol. 8, p. 167, References 2018. [1] H. Faoro, W. K. Oliveira, V. A. Weiss et al., “Genome comparison between clinical and environmental strains of Herbaspirillum seropedicae reveals a potential new emerging bacterium adapted to human hosts,” BMC Genomics, vol. 20, no. 1, p. 630, 2019. [2] A. C. Q. Marques, K. S. Paludo, C. B. Dallagassa et al., “Biochemical characteristics, adhesion, and cytotoxicity of