A Rare Cause of Empyema and Bacteremia Due to Species in Alcoholic Cirrhosis Patients: A Case Report and Comprehensive Review of Literature

Introduction

Shewanella spp. are glucose-nonfermenting gram-negative mo-tile bacilli whose most important phenotypic characteristic is the production of hydrogen sulfide [1]. The first description of this species was provided in 1931 by Derby and Hammer [2]. Shewanella spp. have been reported to cause otitis media [3], ocular infections [4], skin and soft tissue infections [5], and bacteremia. Patients with such infections are considered to have a good prognosis [6]. Cases of death due to empyema caused by Shewanella spp. are rare. In addition, there are only a few reports on Shewanella infection’s risk factors, severity, susceptibility to antibiotics, and prognosis. The present report is of a 78-year-old man with alcoholic cirrhosis presenting with bacteremia and empyema due to infection with Shewanella spp.

Case Report

In this study, we report a case of empyema and bacteremia due to Shewanella spp. and present a literature review. A 78-year-old man with post-treatment alcoholic cirrhosis (Child-Pugh B) and methicillin-resistant Staphylococcus aureus bacteremia 3 weeks prior to admission presented to our emergency room with high fever and dyspnea. He had eaten raw fish (sashimi) 1 week prior to admission. On admission, vital signs were as follows: clear consciousness; temperature, 37.0°C; blood pressure, 98/68 mmHg; pulse rate, 100/min; respiratory rate, 22/min; and oxygen saturation, 96% on room air. On physical examination, lung sounds were attenuated in the right lower lung field. A systolic murmur was auscultated at the left sternal border of the second intercostal space. The abdomen was slightly distended, with percussion tenderness of the liver and mildly distended veins in the inferior abdominal wall. Edema, sclerosis, erythema, and tenderness bilaterally from the thighs to the dorsum of the feet were noted. Laboratory data were as follows: white blood cell count, 7000/μL (neutrophils, 88.0%; lymphocytes, 6.5%; and monocytes, 5.0%); hemoglobin, 11.9 g/dL; total protein, 7.0 g/dL; albumin, 2.9 g/dL; blood urea nitrogen, 41.0 mg/dL; creatinine, 1.04 mg/dL; total bili-rubin, 4.9 mg/dL; alkaline phosphatase, 587 U/L; lactate dehydrogenase, 1041 U/L; aspartate aminotransferase, 29 U/L; alanine aminotransferase, 23 U/L; γ-glutamyl transpeptidase, 129 mg/dL; sodium, 132 mEq/L; potassium, 3.8 mEq/L; chlorine, 96 mEq/L; ammonia, <15 μg/dL; activated partial thromboplastin time, 38.2 s; and C-reactive protein, 25.2 mg/dL. Chest and abdominal computed tomography (CT) on admission revealed right-sided pleural effusion, pleural thickening, and ascites (Figure 1). Hemorrhagic but non-purulent pleural fluid was aspirated, and a Gram stain revealed the presence of gram-negative rods. The pleural fluid analysis showed a pH of 7.0, 2.2 g/dL of total protein, 1.1 g/dL of albumin, 845 U/L of lactate dehydrogenase, <2 mg/dL of glucose, 18.2 U/L of adenosine deaminase, 16 μg/mL of hyaluronic acid, and 16 850/ μL of white blood cells (neutrophils 99.5%, lymphocytes 0.5%).

On the day of admission, we inserted a chest tube to drain the empyema on the right side and started piperacillin/tazobactam (4.5 g every 8 h) and vancomycin. Cultures of blood and pleural effusion were positive for Shewanella algae, as identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF-MS; Bruker Daltonics, Germany). Antimicrobial susceptibility is shown in Table 1. We switched to ceftriaxone (1 g every 24 h) on hospitalization day 4. On hospitalization day 12, a chest CT revealed a new pleural effusion on the left side; therefore, we performed a left thoracentesis. The left-sided pleural fluid was characterized as a transudative pleural effusion, and the culture was negative. On hospitalization day 17, we performed a right thoracentesis, which was culture negative. We stopped pleural drainage on hospitalization day 21. Subsequently, on hospitalization day 33, the patient developed aspiration pneumonia, and the antibiotic was changed to meropenem (1 g every 8 h). On hospitalization day 53, the patient died of aspiration pneumonia (Figure 2).

Discussion

We encountered a case of a patient with liver cirrhosis who developed Shewanella spp. empyema and bacteremia. Consumption of raw fish may have been a risk factor for this case. Our patient had a poor prognosis because of his underlying disease and complications; however, Shewanella infections may have a better outcome with effective drainage and appropriate antimicrobial treatment.

In general, Shewanella spp. infection is caused by exposure to marine products or seawater and mainly presents as necrotizing soft tissue infection and bacteremia [7]. In particular, immunocompromised patients may develop primary bacteremia with a fulminant course [1]. We conducted a literature review of cases of Shewanella infection with bacteremia. Five authors independently reviewed the relevant titles and abstracts in the database records, retrieved full texts for eligibility assessment, and extracted information from these cases. To account for changes in nomenclature, we performed a search using the keywords “shewanella,” “alteromonas putrefaciens,” and “pseudomonas putrefaciens” in the PubMed, Embase, and Ichushi electronic databases, up to January 2021.

We retrieved a total of 330 articles (80 from PubMed, 99 from Embase, and 151 from Ichushi). After removing records not reporting bacteremia due to Shewanella spp., and articles not written in English or Japanese, 158 articles remained. After removing duplicates and performing full-text evaluations of these 158 articles, 66 articles, with data on a total of 124 patients, were included in our review (Figure 3).

The results of the literature review and the case list are presented in Tables 2 and 3 [7–69].

Of the published cases, 35 were from the United States of America, 28 were from South Africa, 16 were from Japan, and 12 were from Taiwan. An analysis of all 124 patients from the studies revealed that 39 (31%) were infected with S. algae, 7 (6%) with Shewanella haliotis, 77 (62%) with Shewanella putrefaciens, and 1 (1%) with Shewanella xiamenensis. The reported cases had a median age of 61.6 (56.0–75.0) years. Where sex was reported, 75/93 (81%) of the infected patients were male.

In terms of portal of entry, skin lesions, seen in 21/35 patients (60%), constituted the most common portal, while an oral portal of entry was the second most common, seen in 9/35 patients (26%). The consumption of raw fish was assumed to be the cause of infection in the present case. There have been numerous reports of Shewanella spp. being detected in fish [71]; however, there are no direct reports confirming

Shewanella infection in humans resulting from the consumption of fish. Nevertheless, given that many of the individuals with Shewanella infection reported in the literature had a history of fish consumption, the possibility remains. However, it remains necessary to demonstrate whether Shewanella isolated from infected human specimens and Shewanella identified from fish used for consumption are indeed the same.

In this literature review, Shewanella species were identified using the API 20 NE system (bioMerieux, France) in 41/93 patients (44%), 16S rRNA gene sequencing analysis (Macrogen, Korea) in 24/93 patients (26%), VITEK 2 GN (bioMerieux, France) in 10/93 patients (11%), ID 32 GN (bioMerieux, France) in 10/93 patients (11%), and MALDI-TOF-MS (bioMerieux, France) in 8/93 patients (9%). However, previous studies have reported that the API 20 NE system, ID 32 GN, VITEK 2 GN, and MALDITOF-MS cannot distinguish S. algae from S. haliotis or S. putrefaciens [6,10,13]. Indeed, in the case reported by Yan et al, an identification of S. putrefaciens was conferred by culture and molecular identification of bacteria in the specimen, while next-generation sequencing technology (NGS, Genskey Medical Technology Co., Ltd, Beijing, China) identified the bacteria as S. algae [72]. Furthermore, since Shewanella chilikensis and Shewanella carassii are phylogenetically related to S. algae, they may also be misidentified [73]. In another study, 16S rRNA gene sequencing analysis was found to be more accurate than MALDI-TOF-MS in distinguishing between S. algae and S. haliotis [74]. In the present case, Shewanella was identified using MALDI-TOF-MS alone, and we could not distinguish between S. algae and S. haliotis.

In terms of underlying diseases, hepatobiliary disease may be a result of Shewanella bacteremia [50]. Similarly, in the present literature review, hepatobiliary disease was the most common underlying disease, reported in 38/114 patients (33%). In general, patients with cirrhosis are at risk of bacterial translocation caused by disruption of the intestinal mucosal barrier and suppression of neutrophil function caused by iron overload associated with hepatic dysfunction [11,22,75]. In addition, Shewanella spp. are known to possess siderophores that absorb iron and contribute to proliferation [11]. In our case, the patient had a medical history of Child-Pugh B cirrhosis and appeared to be at risk for Shewanella spp. bacteremia.

Shewanella spp. are susceptible to third- and fourth-generation cephalosporins, aminoglycosides, carbapenems, erythromycin, and quinolones; however, they are reported to be resistant to penicillins [1]. In this review, although we could not identify the antimicrobial susceptibility in all cases, 39/87 patients were treated with third- or fourth-generation cephalosporins (45%), 35/87 with penicillin (40%), and 31/87 with aminoglycosides (36%). On the other hand, a recent review article reported that the genus of Shewanella contains a variety of drug-resistant genetic elements, showing resistance to many drugs, including beta-lactams, quinolones, aminoglycosides, macrolides, and carbapenems [73,76]. In our case, after the results of the pleural fluid culture were revealed, the antibiotic was changed to ceftriaxone. Although ceftriaxone was not included in the susceptibility testing panel conducted, the minimum inhibitory concentration (MIC) for the similar third-generation cephalosporin ceftazidime was 2 μg/ml, and the MIC for the fourth-generation cephalosporin cefepime was ≤2 μg/ ml, indicating susceptibility to cephalosporins. Regarding resistance in this strain, extended spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacterales were screened with a MASTDISCS Combi D68C (Mast Group, Ltd., Bootle, UK) according to the manufacturer’s instructions, which revealed that neither ESBL nor AmpC were produced. Since the strain did not produce the cephalosporinase AmpC, indicating that the strain was not cephalosporin resistant, we considered it was safe to treat with ceftriaxone.

Some studies have reported that the prognosis of Shewanella infection is relatively good, and the mortality rate is low [6,50]. In our review, the mortality rate was approximately 20%, and most types of Shewanella infections were not deep-seated infections but skin and soft tissue infections. Many older patients have multiple underlying diseases. Therefore, prognosis and mortality may depend on the underlying disease, the type of Shewanella infection, appropriate antibiotics, and source control.

Shewanella spp. infections rarely cause empyema. In our review, we found 3 cases of empyema (2 S. algae), and the site of entry of Shewanella infection was unknown for all 3 cases. Two of the 3 patients received drainage and survived. Although our patient died because of aspiration pneumonia, the initial response to treatment with thoracic drainage and antibiotics was favorable. The prognosis of a Shewanella infection, as in this case, may be influenced by the patient’s underlying diseases and overall health condition. To improve treatment outcomes, appropriate antimicrobial therapy and drainage are also important.

This study had several limitations. As mentioned above, 16S rRNA gene sequencing analysis is more accurate than MALDITOF-MS in identifying S. algae; however, 16S rRNA gene sequencing may not be able to separate closely related strains [77]. Therefore, the most appropriate approaches would be qPCR for specific S. algae genes or whole-genome sequencing. Additionally, we could not exclude reporting bias, wherein researchers and clinicians frequently report successfully treated cases rather than mortality in a case series.

Conclusions

We report a case of Shewanella spp. empyema and bacteremia with a history of hepatobiliary disease. Our case highlights that clinicians should recognize Shewanella spp. as a cause of empyema and bacteremia in patients with liver cirrhosis, and that microbiological diagnosis with antibiotic sensitivity testing and treatment should be undertaken urgently to prevent fatal sepsis.