1Department of Gastroenterology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China; 2Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China

Correspondence: Liuyang Hu, Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China, Email [email protected]

Abstract: Species of Pantoea are mainly environmental strains and plant pathogens, rarely causing human infections. Here, we describe two cases of hemodialysis catheter-related bloodstream infection caused by Pantoea in patients with uremia. To our knowledge, this is the first reported case of catheter related bloodstream infection caused by Pantoea dispersa (P. dispersa) in hemodialysis patients, as well as the first case of bloodstream infection caused by Pantoea anthophila (P. anthophila). Multiple blood cultures from the catheter showed the presence of Pantoea, and the isolated P. dispersa and P. anthophila were found to be highly sensitive to various antibiotics. Prompt use of antibiotics and catheter lock with gentamicin or amikacin led to rapid recovery of the patients, avoiding the economic burden of catheter replacement. Infections caused by Pantoea might be underestimated as methods such as VITEK® MS system often result in misidentification. Therefore, we recommend using advanced techniques such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or 16S ribosomal RNA analysis to detect more cases of Pantoea infections. By sharing these cases, we hope to increase awareness among clinicians about the potential pathogenicity of Pantoea in hemodialysis patients. It is crucial to strengthen noting the primary concern for sources of infection with Pantoea species (plant and environmental exposures) to prevent outbreaks of Pantoea-related bloodstream infections in hospitals.

Keywords: hemodialysis catheter-related bloodstream infections, nosocomial bloodstream, pantoea genus, pantoea dispersa, pantoea anthophila

Introduction

Pantoea is a rare, gram-negative opportunistic pathogen. Species of this genus are usually isolated from soil, fruits, and vegetables.1,2Pantoea occasionally causes human infections, including joint infections,3 urinary tract infections,4 and bloodstream infections,5 often in association with penetrating plant-related injuries or immunosuppression and indwelling vascular devices.1,5Pantoea genus contain 20 different species, with P. agglomerans being the most common species associated with human infections and recently described as causing hospital outbreaks.6,7 Although P. dispersa is considered to have low virulence, it can be fatal in infants, postoperative patients, and those with immunocompromised conditions, and only a limited number of clinical cases of disseminated P. dispersa bloodstream infections have been described.8P. anthophila has low pathogenicity characteristics, and the first case of urinary tract infection caused by P. anthophila was described by Zhang et al,4 with no reports of this microorganism causing bloodstream infections in humans. It has been observed that bloodstream infections events are significantly associated with hemodialysis vascular access.9 Common pathogens causing bloodstream infections in hemodialysis are often gram-positive cocci (Staphylococcus aureus and Enterococcus),10 while gram-negative bacteria and fungi are less common. Here, we describe two cases of hemodialysis patients with Pantoea-induced bloodstream infections related to dialysis catheters. To our knowledge, this is the first reported case of catheter related bloodstream infection caused by P. dispersa in hemodialysis patients, as well as the first case of bloodstream infection caused by P. anthophila.

Case Presentation Case 1

A 59-year-old female patient was diagnosed with uremia in 2020. After undergoing a right internal jugular central venous catheter placement, she received regular hemodialysis twice a week. In 2021, during the hemodialysis process, the patient repeatedly experienced insufficient blood flow, with a maximum blood flow of 160 mL/min. Despite repeated thrombolytic therapy, the effect was unsatisfactory. During the next month, the patient was admitted to the Nephrology Department of People’s Hospital of Guangxi Zhuang Autonomous Region due to fever and chills during hemodialysis. The routine physical examination on admission included a temperature of 38.6°C, a pulse rate of 87 beats/min, and a blood pressure of 110/76 mmHg. The laboratory examination revealed white blood cell count of 5.90×109/L, hemoglobin of 73 g/L, platelet count of 123×109/L. C-reactive protein of 101.22 mg/L (normal values 0–5 mg/L), procalcitonin of >100.00 ng/mL (normal values 0–0.05 ng/mL), ferritin of 505.0 ug/L, urea of 16.42 mmol/L, creatinine of 617.20 umol/L. Clinicians suspected long-term hemodialysis catheter infection and sent an aerobic and anaerobic culture bottle of catheter blood culture for examination. The patient received intravenous anti infection treatment with piperacillin tazobactam 2.25g Q8h and catheter lock with gentamicin. On the fourth day of hospitalization, two catheter blood cultures showed P. dispersa, which was only resistant to cefazolin and sensitive to other antibiotics (Table 1). Therefore, piperacillin-tazobactam was continued for the anti-infective treatment. After 6 days of hospitalization, the patient had no fever, C-reactive protein and procalcitonin decreased significantly, and a repeat catheter blood culture was negative. On the eighth day of hospitalization, the patient was able to undergo hemodialysis smoothly after catheter thrombolysis, avoiding the economic burden of catheter replacement. After 17 days of hospitalization, the patient’s condition improved and discharged. During the one-year follow-up period, no further infections were observed.

Table 1 Antimicrobial Susceptibility of P. Dispersa and P. Anthophila

Case 2

A 57-year-old female patient was diagnosed with uremia in 2020 and underwent regular hemodialysis three times a week after right internal jugular central venous catheter placement. In 2024, she was admitted to the Nephrology Department of People’s Hospital of Guangxi Zhuang Autonomous Region due to chills during the dialysis process for one week. Her temperature was 36.5°C, blood pressure: 110/76 mmHg. Laboratory tests showed white blood cell count of 6.18×109/L, hemoglobin of 123 g/L, albumin of 37.1 g/L, urea of 19.90 mmol/L, creatinine of 921 umol/L, cystatin C of 4.87 mg/L, uric acid of 421 umol/L, C-reactive protein of 72.54 mg/L, procalcitonin 11.90 of ng/mL, erythrocyte sedimentation rate (ESR) of 97.00 mm/h. The patient experienced chills during the dialysis process in the past week, and elevated C-reactive protein and procalcitonin, suggesting catheter-related infection. Two aerobic and two anaerobic culture bottle of catheter blood were sent for culture, and piperacillin-tazobactam 2.25g was administered every 8 hours for anti-infective treatment. Gentamicin was used for catheter lock after dialysis. On the second day of admission, the patient developed a fever (temperature 37.8°C) and chills. All four blood cultures grew a Gram-negative bacterium (Figure 1A) and showed yellow, smooth colonies (Figure 1B), which were confirmed as P. anthophila by MALDI-TOF MS (Figure 1C and D) and 16S rRNA gene sequencing. Therefore, the diagnosis of P. anthophila catheter-related bloodstream infection was confirmed. The antimicrobial susceptibility test conducted within 48 hours of a positive blood culture showed that the pathogen was susceptible to all tested antibiotics (Table 1). Although the drug susceptibility results indicated sensitivity to piperacillin-tazobactam currently being used, the patient had a fever and infection indicator procalcitonin increased to 22.40 ng/mL, suggesting poor response to the anti-infective treatment. According to the drug susceptibility results, the antibiotic regimen was switched to amikacin 0.3g intravenous drip daily and catheter lock after dialysis, combined with levofloxacin injection 0.5g every other day for anti-infective treatment. The patient was discharged after 14 days of hospitalization without removing the central venous catheter.

Figure 1 Isolation and identification of P. anthophila. (A) Gram stain of positive blood cultures showed Gram-negative bacteria; (B) Yellow, smooth colonies on Columbia blood agar after being cultured at 37°C, 5% CO2 for 24 h; (C) The spectrogram with protein molecular mass of the strain acquired by MALDI-TOF MS; (D) Spectra comparison of the strain with that of known strains in a database matched to P. anthophila DSM 23080T with a high confidence level.

Discussion

Pantoea is a genus of Gram-negative bacteria in the family of Enterobacteriaceae, which has recently been separated from the genus Enterobacter. It is found in sewage, plants, feces, and soil. Many human infections are associated with plant-related injuries. Contaminated blood products, intravenous fluids, total parenteral nutrition, and anesthetics are also associated with Pantoea infections.6,7,11 It typically causes hospital-acquired infections in immunocompromised, elderly, and dialysis patients. As mentioned above, recent reports have suggested a correlation between P. agglomerans and severe peritoneal dialysis-related peritonitis,12 but little is known about its association with hemodialysis. In hemodialysis patients, the use of central venous catheters increases the risk of infection compared to arteriovenous fistulas.1

Currently, only a limited number of clinical cases of Pantoea genus bacteria have been described. Therefore, there is insufficient information about its pathogenic mechanisms. Infections caused by Pantoea may be underestimated, as a previous report documented that the VITEK® MS system falsely identified over 10% of Pantoea clinical isolates as species of the Enterobacter genus.13 Isolates of Pantoea dispersa were misidentified as Klebsiella ozaenae by MALDI Biotyper® and were ultimately identified as Pantoea dispersa by 16S rRNA analysis.14 Most reported cases that we identified in the literature were detected by MALDI-TOF MS, and half of them were diagnosed by 16S rRNA gene sequencing.8,14 More cases of infections caused by the Pantoea genus might be revealed with advancing technical methods, such as MALDI-TOF-MS or 16S rRNA analysis. A retrospective study on bloodstream infections caused by Pantoea in Italy from 2018 to 2023 demonstrated that Pantoea isolates showed high sensitivity to all antibiotics except ampicillin (63.2%), colistin (73.7%), and piperacillin/tazobactam (84.2%).15 The 28-day all-cause mortality rate for Pantoea bloodstream infections was 5.3%.15 In our case, the Pantoea dispersa was sensitive to all tested antibiotics except cefazolin, and P. anthophila was sensitive to all tested antibiotics. From a microbiological perspective, although Pantoea has multiple sensitivities, broad-spectrum antibiotics are mainly used for the treatment of Pantoea bloodstream infections.15 The most commonly used antibiotic treatments of bloodstream infections by Pantoea species for adults were piperacillin/tazobactam (21.4%), while pediatric patients were treated with meropenem (40%) and aminoglycosides (40%).15 Fortunately, our patient survived because appropriate antibiotic therapy was rapidly started. These results were similar to those of previous reports.16,17

A total of eight cases of infections by Pantoea in hemodialysis patients, including ours, have previously been reported, as shown in Table 2. Previous reported 6 cases were caused by P. agglomerans, and our cases are the first case of P. dispersa and P. anthophila-related hemodialysis-associated bloodstream infection. The epidemiological and clinical characteristics of P. dispersa and P. anthophila are still unclear. All 8 patients used central venous catheter to hemodialysis. The general recommendation for catheter-related infections is catheter removal, but in the context of hemodialysis, initial conservative treatment is attempted to preserve the venous access in the absence of other dialysis pathways. Currently, all 8 cases of Pantoea-related hemodialysis-associated bloodstream infections have had a good prognosis, with only 2 cases requiring catheter removal and the remaining 6 cases retaining the central venous catheter. In 2020, Borrego Garcia et al reported 3 cases of P. agglomerans caused a bloodstream infection outbreak in hemodialysis patients, all of whom had retained their internal jugular venous catheter.18 The patients showed improvement in infection status after receiving 10 days of post-dialysis treatment with meropenem. Correct disinfection of the tap water distribution system and hemodialysis circuit, as well as the implementation of updated aseptic measures for handling catheters, prevented the need for catheter replacement and the occurrence of new cases.18 In our case, prompt use of antibiotics and catheter lock with gentamicin or amikacin led to rapid recovery of the patients, avoiding the economic burden of catheter replacement.

Table 2 Previous Cases of Hemodialysis Infection Caused by Pantoea

Conclusion

In conclusion, we report two cases of catheter-related bloodstream infections in hemodialysis patients caused by Pantoea dispersa and Pantoea anthophila, respectively. Based on our experience, early detection of the pathogen, prompt use of antibiotics and catheter lock with gentamicin or amikacin led to rapid recovery of the patients, avoiding the economic burden of catheter. It is crucial to strengthen noting the primary concern for sources of infection with Pantoea species (plant and environmental exposures) to prevent outbreaks of Pantoea-related bloodstream infections in hospitals.

Data Sharing Statement

The datasets used and analysed during the current study available from the corresponding author on reasonable request.

Ethics Approval and Patient Consent

Written informed consents were obtained from both patients for the publication of the case details. The study was approved by the medical ethics committee of The People’s Hospital of Guangxi Zhuang Autonomous Region and obtained The People’s Hospital of Guangxi Zhuang Autonomous Region’s approval for publish the case details.

Acknowledgments

We would like to acknowledge the reviewers for their helpful comments on this paper.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This study was supported by the Guangxi Natural Science Foundation under Grant No. 2024GXNSFBA010122 and Guangxi Natural Science Foundation under Grant No. 2023GXNSFBA026068.

Disclosure

The authors declare no conflict of interest in this work.

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