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Sepsis Due to Pandoraea sputorum Infection After Multiple Trauma in a Non-Cystic Fibrosis Patient: A Case Report from Southeast China

Authors Ma Z , Zou X, Lin J, Zhang C, Xiao S

Received 9 September 2022

Accepted for publication 17 November 2022

Published 2 December 2022 Volume 2022:15 Pages 7043—7052

DOI https://doi.org/10.2147/IDR.S388520

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Héctor Mora-Montes



Zhiyi Ma,1,* Xin Zou,1,* Jinhao Lin,2,* Chunchun Zhang,3 Shuhua Xiao4

1Department of Pulmonary and Critical Care Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Longyan People’s Hospital, Longyan, People’s Republic of China; 3Department of Laboratory Medicine, Longyan People’s Hospital, Longyan, People’s Republic of China; 4Department of Intensive Care Unit, Longyan People’s Hospital, Longyan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jinhao Lin, Department of Pulmonary and Critical Care Medicine, Longyan People’s Hospital, No. 31 Denggaoxi Road, Longyan, People’s Republic of China, Tel +865973102968, Email [email protected]

Abstract: Pandoraea sputorum (P. sputorum) infection is of great concern as these gram-negative bacillus species are multidrug-resistant and usually isolated from the patients’ respiratory tract suffering from cystic fibrosis (CF). A few cases of infection have also been reported in non-CF patients due to its rare pathogenic nature with unclear and overlapping clinical, biochemical, and microbiological characteristics with other species. Here, we report an unusual case of a 46-year-old non-CF female, who presented with multiple pelvic fractures, acute traumatic brain injury, multiple rib fractures, and multiple burns (18% of the total body surface area, II°) by the collapse of a brick kiln, suffered from P. sputorum sepsis due to wound infection. Pandoraea species were isolated both from her blood and wound secretion. Antibiotic susceptibility testing indicated susceptibility to imipenem, tetracyclines, sulfamethoxazole, and ampicillin/sulbactam but resistance to meropenem, quinolones, aminoglycosides, and other beta-lactams. 16S ribosomal RNA (rRNA) PCR assays and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to confirm the bacteria as P. sputorum. After effective anti-infection of intravenous antibiotics (imipenem 1.0 Q8H with tigecycline 50 mg Q12H for 14 days), wound care, and other comprehensive treatment for two months, the patient improved and was discharged from the hospital eventually. After reviewing the literature, we observed that the susceptibility results of Pandoraea species were often multidrug-resistant and had a unique pattern of being resistant to meropenem but sensitive to imipenem. Biofilm formation, carbapenemase production, and unique gene procession differed from the environmental isolates could help explain its resistance. This case report highlights the potential virulence of Pandoraea species as a pathogen in patients with no underlying disease. Although they are often multi-resistant, imipenem can be a preferred treatment for Pandoraea species in the earliest identification steps.

Keywords: Pandoraea sputorum, sepsis, multidrug-resistant, non-cystic fibrosis, multiple trauma

Introduction

Initially, Coenye et al1 described the characteristic features of Pandoraea species as aerobic, non-spore-forming, non-nitrate-reducing, non-lactose-fermenting, Gram-negative rods with a single polar flagellum that are mostly isolated from cystic fibrosis (CF) patients. To date, 7 named Pandoraea species and 4 unnamed genomospecies have been identified.1–3 The source of Pandoraea species’ isolation is vast; it can be isolated even from environmental samples such as soil, water, and powdered milk, as well as from patients’ clinical samples like wound sites, blood, lung tissue, and urine.4–6 Six clinically relevant Pandoraea Species (Pandoraea apista, Pandoraea norimbergensis, Pandoraea pulmonicola, Pandoraea pnomenusa, Pandoraea sputorum, and Pandoraea fibrosis) have been isolated from human specimens, which were predominantly from the respiratory tract of cystic fibrosis (CF) patients in European and North America.4–8 Their potential harm is still unclear and under-investigated, they have been demonstrated to cause decreased lung function and cross-infection activity in patients with CF.3,4 In addition to lung colonization, a few cases of invasive infections in different sites were also reported worldwide, mostly in non-CF patients with underlying diseases.5 Above all, the Pandoraea species has grabbed the attention of clinicians due to its high resistance to multiple drugs and and invasive fatality if patients have not received appropriate antibiotics.9,13,19 Here, we investigated a case of a 46-year-old female patient without underlying disease infected with sepsis by Pandoraea sputorum (P. sputorum) after multiple pelvic fractures and burns. The Pandoraea species were isolated from both her blood samples and wound secretion. Further detection using the 16S ribosomal RNA (rRNA) gene sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed the bacteria as P. sputorum. Informed consent was obtained from the patient to publish this case report and accompanying images, and institutional review board (IRB) approval was granted.

Case Presentation

On August 12th, 2018, a 46-year-old female patient was admitted to the emergency ward of the People’s Hospital (Longyan, China) due to severe trauma caused by the collapse of a brick kiln. She had no history of any chronic or infectious diseases earlier. An initial physical examination found that her vital signs were stable and within normal range. She was still conscious but with limited activity. Further examination revealed that her whole body was burned with blisters (2% of the abdomen, 3% of the right waist, 4% of the back, 7% of the legs, and 2% of the arms). Her right eyelid was turned and exploited, while her left forehead skin and labium were exuded with blood because of the contusion. The back side of her left hand was injured, with exposure of bones and tendons. Her iliac region was also swollen with skin bruises and congestion, she felt obvious pain, and her pelvic extrusion and separation tests were positive. An emergency computer tomography (CT) of her brain, chest, and abdomen was recommended. Chest CT showed mild dilation in the right middle lobe, the right lower lobe, and the left lower lobe (Figure 1). Blood analysis showed a white blood cell (WBC) count of 8.13×109/L, hemoglobin (HGB) of 130g/L, and platelet (PLT) count of 174 ×109/L. After clinical examination and imaging studies, she was diagnosed to have multiple fractures (right sacral promontory, bilateral superior pubic ramus, right inferior pubic ramus, right 1–5th rib), multiple lacerations (scalp, right canthus, right eyelid), acute traumatic craniocerebral injury, superficial skin contusion (right zygomatic, left frontal), and multiple burns (II°, 18% of the total body surface area [TBSA]). A comprehensive treatment of debridement, analgesics, anti-infection (levofloxacin 0.4 QD+ cefazolin 1.0 Q12H, I.V.), hemostasis, tetanus prevention, wound exposure, and rehydration was carried out on the first day. On hospital day 2, her blood pressure dropped to 85/50mmHg, and HGB reached a nadir of 104g/L. We suspected the patient was in a state of hemorrhagic shock due to intra-abdominal hemorrhage and pelvic fracture and transferred her to the intensive care unit (ICU) immediately. She received enhanced dilatation and rehydration treatment, anti-infection (ceftazidime 1.0 Q8H + levofloxacin 0.4 QD, I.V. for 11 days), analgesia, nutritional support, single room isolation, appropriate braking, wound disinfection, external application of burn cream, and exposure treatments. Her situation improved gradually, with stable blood pressure. But she had an intermittent moderate fever (38.2°C of the highest level) without any symptoms of respiratory or urinary tract infection. There was still much exudation from the wound on her back and upper right leg. Bilateral blood samples were collected to culture both aerobic and anaerobic bacteria on the 7th day. Her blood analysis still showed a normal WBC count of 3.75×109/L, an elevated CRP of 145 mg/L, and a mildly elevated PCT of 0.81 ng/mL. Four days later, her first blood culture reports revealed the presence of bacterial Pandoraea species (Figure 2). In vitro susceptibility testing with the Vitek2 compact system (bioMerieux, Marcy-I’Etoile, France): interpreted according to the 2018 Clinical and Laboratory Standards Institute (CLSI) criteria for non-fermentative isolates: showed the isolate to be only sensitive to sulfamethoxazole, imipenem, and ampicillin/sulbactam (Table 1). On hospital day 12, her body temperature rose to a higher level of 38.9°C. The second bilateral blood sample for bacterial culture was collected again. Repeat blood analysis still showed a normal white blood cell count of 4.21×109/L, an elevated C-reactive protein (CRP) of 93.7 mg/L, and mildly elevated procalcitonin (PCT) of 0.74 ng/mL. A repeat CT scan of the chest and abdomen showed no new pulmonary shadows but still obvious soft tissue edema and subcutaneous swelling in the right abdominal wall and the right iliac region. The bacterial Pandoraea species presented in her blood was considered the responsible pathogen for her infection. On hospital day 13, we changed her anti-infection treatment to imipenem 1.0 Q8H + tigecycline 50 mg Q12H I.V. Four days later, her second blood culture reports again confirmed the presence of Pandoraea species, which were sensitive to the three antibiotics mentioned above and minocycline (Table 1). The source of her sepsis was presumed to be wound-associated, as no respiratory or urinary infection happened during the hospital day. On day 18, bacteria culture and the high-throughput gene detection of pathogenic microorganisms were performed using the samples from her wound secretion. Although the results of high-throughput gene sequencing of pathogenic microbial DNA only showed DNA sequences of Staphylococcus epidermidis and Candida parapsilosis, Pandoraea species was again cultured six days after sample collection (Table 1). 16S ribosomal RNA (rRNA) gene sequencing of bacteria from her first blood culture sample confirmed it as Pandoraea species, which has the first-highest similarity to Pandoraea sputorum (99.89%), the second-highest similarity to Pandoraea vervacti (99.66%), and the third-highest similarity to Pandoraea oxalalivorans (99.66%). The MALDI-TOF MS method was further applied to confirm it as Pandoraea sputorum. No bacteria were isolated from her blood sample collected on the hospital days 17th and 23rd. After 14 days of treatment with appropriate anti-infection and wound care, the patient’s condition improved with a normal body temperature, a normal CRP of 6.0mg/L, a normal PCT of 0.11ng/mL, and scanty wound exudation (Figure 3). Her situation was stable enough to shift her to the Department of Burn and Plastic Surgery to continue her wound reparation. Two months later, she was discharged from our hospital, her wounds and fractures healed, and she could move freely. The clinical manifestations, significant examination results, and related antibiotic treatments have been presented as a timeline (Figure 4).

Table 1 Antibiotic Susceptibility of Pandoraea Species from Blood and Wound Secretion Samples in Our Case

Figure 1 The first chest CT scan of the patient when she was sent to the emergency.

Figure 2 Bacteria colony of Pandoraea species cultured on Columbia blood plate for 48 hours.

Figure 3 Wound situation of the patient before and after treatment. (A) Skin wound of the lower back; (B) skin wound of the right thigh; (C and D) Skin wound of the lower back after 2-months’ treatment.

Figure 4 The treatment timeline showed clinical manifestations, significant examination results, and related antibiotic treatments of the case.

Discussion

The Pandoraea species was first isolated by Coenye et al1 from a mixed population of other well-known CF pathogens. This Pandoraea species belongs to the β-subclass of Proteobacteria, including Pseudomonas. It is closely related to two Gram-negative rods of the genera Burkholderia and Ralstonia species that closely resemble their characteristic features. The source of isolation of Pandoraea species is vast; it can be isolated even from environmental samples such as soil, water, and powdered milk, as well as from patients’ clinical samples like wound sites, blood, lung tissue, and urine.5,6 In most of the epidemiology cases of CF, Pandoraea species was isolated from respiratory samples in Australia, Europe, and America,4,7,8 and very scanty reports are available from Asia, which may consist with the epidemiology of CF and imply that the detection of Pandoraea spp. might be underestimated owing to the difficulty of routine diagnostic tests. Pandoraea species has been considered a significant pathogen because it has the infectious nature of causing cross-infection among CF patients, like other well-known bacteria such as Burkholderia cepacia complex, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa.3,4

Recently, Pandoraea species was observed to be more likely to cause invasive infections in non-CF patients. Only 21 cases of Pandoraea infection (including ours) in non-CF patients were reported. Among the 21 isolated cases, seven were Pandoraea pnomenusa,5,9–12 five were Pandoraea Apista,5,13–15 three were Pandoraea sputorum,16,17 two were Pandoraea norimbergensis,1 and four were unidentified Pandoraea species.5,18,19 Ten (47.6%) were isolated from blood, eight from the respiratory samples, one from the maxillary sinus,5 one from the hemodialysis catheter,16 and one from the skull base14 (see Table 2). To our knowledge, only four non-CF patients infected by Pandoraea species were reported from China. Besides all the above information, our case was considered the third case of Pandoraea sputorum, isolated from non-CF patients worldwide. By reviewing all the cases reported to be infected by Pandoraea species from non-CF patients, we found that most of the cases had underlying susceptibility factors, which allow the host to enter into a situation of mild or severe immunosuppression (such as post-transplantation or underlying diseases), leading to disease susceptibility. Under specific conditions, Pandoraea species opportunistically invade the body and cause infections. However, the patient in our case was healthy and had no underlying disease before onset, which is different from the two cases of bloodstream infection of Pandoraea sputorum reported in previous literatures. Since Pandoraea species were isolated from the blood of the patient and wound secretion, her skin and soft tissue were infected by the microbes present in the environment, and they were considered the source of her sepsis.

Table 2 Case Reports Infected or Colonized with Pandoraea Species in Non-CF Patients

By conventional culture medium method, Pandoraea species are frequently misdiagnosed and misidentified as Burkholderia or Ralstonia species.4,5 Therefore, to avoid such confusion and misdiagnosis, molecular analysis such as 16S rRNA sequence analysis is recommended for further confirmation.1 However, the limitation of this method has been reported when differentiating the Pandoraea species.18 Other scientists have implemented gyrB gene sequences to identify species, but there is a lag in identifying closely related species as well.2,20 Further, some researchers21 have suggested the MALDI-TOF MS as a quicker, easier, and more reliable method for rapidly identifying closely related species. Through 16S rRNA analysis, our study confirmed that Pandoraea species is the causative pathogen. However, we could not further differentiate the species because of its close similarity with P. sputorum (99.89%), P. vervacti (99.66%), and P. oxalalivorans (99.66%). Finally, through the MALDI-TOF MS method, we identified and confirmed the causative strain as Pandoraea sputorum.

The pathogenesis and potential virulence of Pandoraea species are still unclear. Some researchers have found that chronic bronchopulmonary colonization by P. apista or P. sputorum had a close relationship with frequent exacerbations, and a decreased activity of lung function is observed in CF patients.21 Further research has demonstrated that infection of Pandoraea species could induce a robust pro-inflammatory response in lung epithelial cells, with elevated inflammatory markers such as interleukin-6 (IL-6) and interleukin-8 (IL-8).22

Pandoraea species often resist antibiotics such as β-lactam agents, quinolones, and aminoglycosides. However, the susceptibility results vary between different stains. Some of the isolates were reported to be sensitive to trimethoprim-sulphamethoxazole,11,12,15,18 minocycline,17,19 piperacillin/tazobactam,11,17 ampicillin/sulbactam,18 ciprofloxacin,11,17,19 and tetracycline.11,17,18 Interestingly, almost all of the Pandoraea species were reported to be resistant to meropenem but sensitive to imipenem, which was the opposite of most Gram-negative non-fermenting bacteria (see Table 2). Biofilm formation and carbapenemase production by Pandoraea species may be related to increased antibiotic resistance.23 When comparing the genome sequence of clinically isolated P. pnomenusa with the environmental isolates, researchers found that clinical isolates possessed many unique genes that differed from the environmental isolates, which could help to explain its resistance to multiple antibiotics.24 To date, no recommended criteria guideline is available for the susceptibility of Pandoraea species. We used the 2018 CLSI criteria for non-fermentative isolates to judge the results. In our case, the susceptibility results were similar to the data available in the literature.

This case report highlights the potential virulence of Pandoraea species as an opportunistic pathogen from the environment in non-CF patients. Identification of these species needs molecular analysis, such as 16s RNA sequencing and MALDI-TOF MS analysis. The limitation is the lack of infection treatment guidelines and no appropriate CLSI susceptibility information for Pandoraea until now. Although different methods and interpretive susceptibility criteria result in unavoidable bias, the antimicrobial susceptibility profiles of Pandoraea species are often multidrug-resistant to antibiotics such as β-lactam agents, quinolones, and aminoglycoside. Almost all the Pandoraea species have a unique pattern of being resistant to meropenem but sensitive to imipenem, which might be a preferred practical treatment choice for Pandoraea species in the earliest identification steps.

Data Sharing Statement

The data is available upon reasonable request to the corresponding author.

Acknowledgment

We thank Medjaden Inc. for the scientific editing of this manuscript.

Funding

There is no funding to report.

Disclosure

The authors report no conflicts of interest in this work.

References

1. Coenye T, Liu L, Vandamme P, LiPuma JJ. Identification of Pandoraea species by 16S ribosomal DNA-based PCR assays. J Clin Microbiol. 2001;39(12):4452–4455. doi:10.1128/jcm.39.12.4452-4455.2001

2. See-Too WS, Ambrose M, Malley R, et al. Pandoraea fibrosis sp. nov., a novel Pandoraea species isolated from clinical respiratory samples. Int J Syst Evol Microbiol. 2019;69(3):645–651. doi:10.1099/ijsem.0.003147

3. Jones AM, Webb AK. Recent advances in cross-infection in cystic fibrosis: Burkholderia cepacia complex, Pseudomonas aeruginosa, MRSA and Pandoraea spp. J R Soc Med. 2003;96 Suppl 43(Suppl43):66–72.

4. Degand N, Lotte R, Decondé Le Butor C, et al. Epidemic spread of Pandoraea pulmonicola in a cystic fibrosis center. BMC Infect Dis. 2015;15(1):583. doi:10.1186/s12879-015-1327-8

5. Daneshvar MI, Hollis DG, Steigerwalt AG, et al. Assignment of CDC Weak Oxidizer Group 2 (WO-2) to the genus pandoraea and characterization of three new pandoraea genomospecies. J Clin Microbiol. 2001;39(5):1819–1826. doi:10.1128/jcm.39.5.1819-1826.2001

6. Lipuma JJ. The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev. 2010;23(2):299–323. doi:10.1128/cmr.00068-09

7. Degand N, Carrère J, Segonds C, et al. Nosocomial outbreak of Pandoraea pulmonicola in a French cystic fibrosis (CF) center. J Cyst Fibros. 2010;9:S34. doi:10.1016/S1569-1993(10)60132-4

8. Ambrose M, Malley RC, Warren SJC, et al. Pandoraea pnomenusa isolated from an Australian patient with cystic fibrosis. Front Microbiol. 2016;7:692. doi:10.3389/fmicb.2016.00692

9. Stryjewski ME, LiPuma JJ, Messier RH, Reller LB, Alexander BD. Sepsis, multiple organ failure, and death due to pandoraea pnomenusa infection after lung transplantation. J Clin Microbiol. 2003;41(5):2255–2257. doi:10.1128/jcm.41.5.2255-2257.2003

10. Falces-Romero I, Gutiérrez-Arroyo A, Romero-Gómez MP. Bacteriemia asociada a catéter por Pandoraea pnomenusa en un paciente pediátrico con leucemia aguda linfoblástica [Catheter-associated bacteremia by Pandoraea pnomenusa in an infant with acute lymphoblastic leukemia]. Med Clin. 2016;147(3):132. Spanish. doi:10.1016/j.medcli.2016.04.009

11. Bodendoerfer E, Personnic N, Mestres CA, Wilhelm MJ, Meyer L, Hasse B. Possible prosthetic valve endocarditis by pandoraea pnomenusa and specific virulence mechanisms. Infect Drug Resist. 2021;14:1319–1324. doi:10.2147/idr.s301138

12. Cubides-Diaz DA, Muñoz Angulo N, Martin Arsanios DA, Ovalle Monroy AL, Perdomo-Rodriguez DR, Del-Portillo MP. Pandoraea pnomenusa Superinfection in a patient with SARS-CoV-2 pneumonia: first case in the literature. Infect Dis Rep. 2022;14(2):205–212. doi:10.3390/idr14020025

13. Lin C, Luo N, Xu Q, et al. Pneumonia due to Pandoraea Apista after evacuation of traumatic intracranial hematomas: a case report and literature review. BMC Infect Dis. 2019;19(1):869. doi:10.1186/s12879-019-4420-6

14. Patil NR, Tripathi M, Charaya K, Angrup A, Ahuja C, Mohindra S. Skull base osteomyelitis by Pandoraea apista: an unusual pathogen at unusual location - A case report. Surg Neurol Int. 2021;12:447. doi:10.25259/sni_472_2021

15. Singh S, Sahu C, Patel SS, Garg A, Ghoshal U. Pandoraea apista Bacteremia in a COVID-positive man: a rare coinfection case report from North India. J Lab Physicians. 2021;13(2):192–194. doi:10.1055/s-0041-1730847

16. Monzón T, Valga F, Reichert J, López C. Hemodialysis catheter colonized by Pandoraea sputorum. Nefrologia. 2018;38(6):662–664. doi:10.1016/j.nefro.2017.11.003

17. Xiao X, Tian H, Cheng X, et al. Pandoraea sputorum Bacteremia in a patient who had undergone allogeneic liver transplantation plus immunosuppressive therapy: a case report. Infect Drug Resist. 2019;12:3359–3364. doi:10.2147/idr.s227643

18. Gao J, Wei Q, Shao H, Hui WU. A case report of Pandoraea sp. isolated from neonatal blood culture. J Microbes Infect. 2018;13(6):368–372.

19. Dlewati MM, Aung PP, Park K, Rodriguez JA, Poon KK. Meropenem-resistant pandoraea pneumonia in a critically ill patient With COVID-19. Cureus. 2021;13(11):e19498. doi:10.7759/cureus.19498

20. Coenye T, LiPuma JJ. Use of the gyrB gene for the identification of Pandoraea species. FEMS Microbiol Lett. 2002;208(1):15–19. doi:10.1111/j.1574-6968.2002.tb11053.x

21. Fernández-Olmos A, Morosini MI, Lamas A, et al. Clinical and microbiological features of a cystic fibrosis patient chronically colonized with pandoraea sputorum identified by combining 16S rRNA sequencing and matrix-assisted laser desorption ionization–time of flight mass spectrometry. J Clin Microbiol. 2012;50(3):1096–1098. doi:10.1128/jcm.05730-11

22. Caraher E, Collins J, Herbert G, et al. Evaluation of in vitro virulence characteristics of the genus Pandoraea in lung epithelial cells. J Med Microbiol. 2008;57(1):15–20. doi:10.1099/jmm.0.47544-0

23. Tabatabaei M, Dastbarsar M, Moslehi MA. Isolation and identification of Pandoraea spp. From bronchoalveolar lavage of cystic fibrosis patients in Iran. Ital J Pediatr. 2019;45(1):118. doi:10.1186/s13052-019-0687-x

24. Ee R, Ambrose M, Lazenby J, Williams P, Chan K-G, Roddam L. Genome sequences of two pandoraea pnomenusa isolates recovered 11 months apart from a cystic fibrosis patient. Genome Announc. 2015;3(1):e01389–01314. doi:10.1128/genomeA.01389-14

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