A case of bacterial keratitis caused by multi-drug-resistant Shewanella algae without marine exposure.

Shewanella are Gram-negative rods and marine pathogens. Here, we report a case of bacterial keratitis caused by Shewanella algae without marine exposure. A 66-year-old man with suspected pneumonia was sent to the emergency department from a nursing hospital. He had been in there for 2 years in a vegetative state and could not close his eyes voluntarily. Neither the patient nor his family had experienced any marine exposure. Keratitis was suspected in his right eye. Gram-negative rods grew from swab culture and identified as S. algae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA sequencing. The patient was treated with topical tobramycin, moxifloxacin and ofloxacin as well as steroids for 14 days, and the keratitis improved. S. algae is a rare human pathogen, and most human infections involve marine exposure. This is the second report of bacterial keratitis caused by S. algae worldwide and the first in Asia.

INTRODUCTION

Shewanella spp. are facultatively anaerobic, Gram-negative, motile rods first described by Derby and Hammer in 1931 [1, 2]. They are typical marine pathogens found in marine, cold water environments and deep sea sediments [3]. Human infections by Shewanella spp. are very rare, although the number of reports has increased recently [4]. Most human infections caused by Shewanella spp. have a marine association, such as infection from trauma while fishing. There are more than 20 known Shewanella species. The species reported most frequently as human pathogens are Shewanella putrefaciens and S. algae [4]. Since first identification of S. algae in 1992, various human infections caused by S. algae have been published worldwide, including bacteremia, skin and soft tissue infection, peritonitis, pericarditis and bone infections [4]. In Korea, reported S. algae infections have caused endophthalmitis, tenosynovitis, peritonitis and bacteremia [5-7]; all cases were related to marine environments, including trauma while fishing, slipping on the beach and eating raw fish. Here, we report a case of keratitis caused by multi-drug-resistant S. algae that was not related to a marine environment.

CASE REPORT

A 66-year-old man was sent to the emergency department from a nursing hospital because of desaturation. He had been hospitalized for more than 2 years in an unconscious state due to a cervical spine injury. He was unable to close his eyes voluntarily. Neither the patient nor his family had a history of marine exposure. At admission, pneumonia was suspected, and conjunctival injection, purulent discharge and central white opacity were detected in his right eye. He was admitted to the respiratory department, and treatment with piperacillin–tazobactam was started for pneumonia. An ophthalmologist examined the patient at the bedside. Examination of his right eye revealed 6.0 × 5.0 mm corneal opacity and hyphema with hypopyon in the anterior chamber. Fundus examination was impossible due to corneal haziness. Corneal swabs were sent for Gram staining, bacterial culture and antimicrobial sensitivity testing, KOH mount smear and fungal culture. Empirical treatment with tobramycin, moxifloxacin and ofloxacin eye drops was started. The KOH smear and Gram stain were negative. After a 2-day incubation, medium-sized gray and dark pink colonies grew on blood agar plate and chocolate agar plate (Fig. 1). Other types of colony did not grow on the plate. S. algae was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the Vitek system (bioMérieux, Marcy-L’Étoile, France). 16S rRNA sequencing revealed 99.93% (1410/1411 bp) identity with S. algae JCM 21037(T) (GenBank accession number BALO01000089). Susceptibility testing of the isolate indicated susceptible to amikacin, aztreonam, cefepime, ceftazidime, colistin and gentamicin, resistant to cefotaxime, imipenem, piperacillin and piperacillin/tazobactam, and intermediate to ciprofloxacin, levofloxacin and meropenem. We added steroid eye drops to control the inflammation and continued the antibiotic eye drops. After 14 days, his keratitis had improved.

Figure 1

Shewanella algae colonies grown on chocolate (left) and blood (right) agar plates.

DISCUSSION

Microbial keratitis is inflammation of the cornea caused by bacteria, fungi, or protists. The main causative bacteria are Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae and Serratia species [8]. Bacterial keratitis caused by Shewanella species is extremely rare. Only one case of S. algae infection has been reported worldwide; this was in the USA in 2019 [9]. In Korea, there has been one case of S. algae endophthalmitis but no reported keratitis cases [7]. We report the second case of S. algae keratitis worldwide and the first in Asia. Colonies of Shewanella species on medium are convex, circular, and smooth and produce an unusual brown to tan pigment, in contrast to the white colonies of the major keratitis pathogens S. aureus and P. aeruginosa [2]. The colonies we observed were also medium-sized circular smooth colonies that were dark pink to brown on both blood agar plate and chocolate agar plate (Fig. 1). This should inform clinicians of the unusual colony morphology, which differs from that of the major keratitis pathogens observed in clinical microbiology laboratory.

This case has two exceptional aspects. First, the isolate was resistant to multiple drugs. There are no criteria for antimicrobial susceptibility testing of Shewanella species in international guidelines, such as the Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing. Therefore, we used the criteria for P. aeruginosa, which is a related strain. The antimicrobial susceptibility tests showed resistance to cefotaxime, piperacillin, piperacillin/tazobactam, and carbapenem and intermediate to quinolone, which shows more resistant tendency than previous reported isolates. In a 2013 review of 239 cases since 1973, 82%, 94%, 94% and 98% of Shewanella species were susceptible to imipenem, ciprofloxacin, piperacillin and piperacillin/tazobactam, respectively [10]. In our case, S. algae was multi-drug resistant, rendering it difficult to treat, which can lead to treatment failure. Furthermore, the types of antibiotics that can be used in eye drops are limited, decreasing the treatment options.

Second, the patient had no history of seawater exposure. Shewanella infections are often associated with marine exposure [5, 7]. Our patient had been hospitalized in a nursing hospital for more than 2 years, and his family had no relation to the sea. Consequently, we did not suspect S. algae infection in this patient sooner. It is necessary to consider whether there are S. algae infection routes other than marine exposure. We did not perform other culture such as stool culture, therefore it was not possible to confirm that S. algae existed in the patient as colonization. Although S. algae mainly inhabit the marine environment, there is a possibility of infection even if the patient did not have marine exposure. S. algae is found naturally in wildlife including seawater as well as soil, fish, meat, and dairy product [6]. There have been several cases of eye infections without marine exposure in previously published reports (Table 1). Although no other investigation has been conducted to find the source of the infection, it should be thought that various environment including care giving staff and ingestion of seafood also can be the sources of infection.

Table 1

Eye infections caused by Shewanella species

Year	Age	Sex	Species	Clinical manifestation	Underlying condition	Marine exposure	Country	Reference number
2007	58	M	Shewanella putrefaciens	Keratitis	s/p LASIK	None	USA	[11]
2013	27	M	Shewanella algae	Endophthalmitis	None	Trauma during fishing	Korea	[7]
2014	25	M	S. putrefaciens	Endophthalmitis	None	Trauma with a fishhook	India	[9]
2019	75	M	S. putrefaciens	Keratitis	None	None	Korea	[12]
2019	75	M	S. algae	Keratitis	Chronic dry eye syndrome, glaucoma	None	USA	[9]

As in this case, clinical isolates can be extremely rare species with high levels of drug resistance and can involve an atypical patient history. For best clinical practice, clinicians need to keep an eye on the laboratory results after ordering cultures.

This is the second report of bacterial keratitis caused by multi-drug resistant S. algae worldwide and the first in Asia. Clinicians must track microbiology test results to determine appropriate antimicrobial treatment.