Hypermucoviscous capsular 1 (K1) serotype Klebsiella pneumoniae necrotising fasciitis and metastatic endophthalmitis

Abstract

A 48-year-old man presented with a non-healing wound on his left foot after stepping on a nail. He self-medicated with amoxicillin, but the wound progressed prompting consult. On examination, his left foot was diffusely swollen with surrounding erythema, areas of gangrene, foul-smelling purulent discharge and subcutaneous emphysema. He was managed as a case of necrotising fasciitis and underwent emergent amputation. Three days after amputation, he developed a sudden and progressive blurring of vision, swelling and conjunctival erythema, with purulent discharge and the presence of hypopyon on the left eye. He was then managed as a case of endophthalmitis of the left eye and underwent pars plana vitrectomy. All cultures (blood, tissue and vitreous fluid) grew pan-susceptible hypermucoviscous Klebsiella pneumoniae, with positive string tests and confirmed by multilocus gene sequencing and sequence type analysis. He gradually improved with intravenous antibiotics, but only regained light perception in the left eye.

Background

Monomicrobial necrotising fasciitis due to hypermucoviscous (hv) Klebsiella pneumoniae has strong association with diabetes mellitus and a strong propensity to disseminate to multiple sites including the eye, causing endogenous endophthalmitis.^1–5 Endophthalmitis is a rare but severe ocular inflammation due to an infection of the vitreous cavity, which may lead to irreversible vision loss when not treated promptly.^6–10 We report the first documented case in the Philippines on monomicrobial necrotising fasciitis with metastatic endophthalmitis.

Case presentation

A 48-year-old man presented with a 2-week history of a non-healing wound on his left foot from a puncture wound sustained on stepping on a nail at work. He did not seek consult and instead performed wound care and self-medicated with amoxicillin for 2 weeks, which did not provide relief of symptoms. In the interim, the wound progressed, prompting him to consult our emergency room. He had no other known comorbidities, an unremarkable family history and worked as a construction worker.

On admission, his vital signs were within normal limits. His random blood sugars were in the range of 400–450 mg/dL. The left foot was cold to touch with absent distal pulses (dorsalis pedis and posterior tibial). It had diffuse swelling, erythema, areas of gangrene, foul-smelling purulent discharge and subcutaneous emphysema (figure 1) extending up to the leg consistent with radiographic findings. The rest of the physical examination findings were unremarkable. The patient was managed as a case of necrotising fasciitis of the left foot extending up to the leg. Blood cultures were taken and empiric vancomycin (1 g intravenously every 12 hours) and piperacillin-tazobactam (4.5 g intravenously every 8 hours) were given. Arterial duplex scan of the lower extremities was not done due to financial constraints. He was immediately brought to the operating room for an emergent above-the-knee amputation as the left foot and leg were clinically non-viable. The initial intraoperative and postoperative courses were uneventful.

Figure 1.

Gross photograph of the patient’s left foot showing an area of diffuse swelling and erythema of the entire foot, with gangrenous and necrotic tissue with foul-smelling discharge at the medial dorsal aspect.

Three days after the amputation, he complained of sudden and progressive blurring of vision, swelling and conjunctival erythema of the left eye. This was subsequently followed by the development of purulent discharge from the left eye. On gross examination, there was presence of hypopyon (figure 2). An emergency referral to the ophthalmology service was facilitated.

Figure 2.

Gross photograph comparing the patient’s right and left eyes (top); the left eye on closer view demonstrates swelling, conjunctival erythema, purulent drainage and the presence of hypopyon (bottom).

Investigations

All cultures (blood, tissue and vitreous fluid) grew pan-susceptible K. pneumoniae. All isolates were positive on string test, consistent with the hv phenotype (figure 3).

Figure 3.

Vitreous fluid isolate showing a positive string test of greater than 5 mm string displacement, consistent with the hypermucoviscous phenotype.

Multilocus sequence typing was done, following the protocols of Diancourt et al,¹¹ on our isolates from three sites (wound, blood and eye). Briefly, seven housekeeping genes were amplified using PCR; products were sent to Macrogen Korea for sequencing. Unrooted tree using 42 sequence types and the sample was generated using MEGA V.7.0¹² and visualised using Microreact.¹³ Each gene was then referenced to the Multilocus sequence typing database (http://bigsdb.pasteur.fr/klebsiella/klebsiella.html) to determine the variant of each locus.^14–18

Treatment

The patient was given empiric piperacillin-tazobactam (4.5 g intravenously every 8 hours) and vancomycin (1 g intravenously every 12 hours) on presentation. An emergent above-the-knee amputation was done for immediate source control. Both piperacillin-tazobactam and vancomycin were discontinued on day 4 based on culture results, and we shifted the antibiotics to ceftazidime (2 g intravenously every 8 hours).

Following the development of endophthalmitis 3 days after the amputation, an emergency pars plana vitrectomy of the left eye was performed and one dose of intravitreal ceftazidime (2 g) was given intraoperatively. Our patient completed a 10-day course of intravenous ceftazidime.

Outcome and follow-up

He gradually improved with intravenous antibiotics but only regained light perception in the left eye. On discharge, blood sugar levels were within target and his left thigh stump remained dry with good healing.

Discussion

K. pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacteria that can cause urinary tract infections, pneumonia and bacteraemia. It is a recognised causative agent in South-East Asia for hepatic abscesses and necrotising fasciitis.¹ In recent years, literature on Klebsiella has focused on the carbapenem-resistant Enterobacteriaceae (CRE) strains.² On one hand, the CRE species represent a class of multidrug-resistant strains that are common in the hospital setting and long-term care facilities. On the other hand, the hv strains of Klebsiella are distinctly different as community-acquired, highly virulent and essentially susceptible to many antibiotics. The syndrome of metastatic infections from hv K. pneumoniae infections, to a large extent, has been restricted geographically in Asia. Although a few established reports in North America and Europe were documented, interestingly majority of cases have occurred disproportionately in persons of Asian descent.^1–10 The hv strains, especially K1 and K2 capsular serotypes, are highly associated with a wide range of highly complicated and invasive diseases,^8–10 including soft tissue infections such as necrotising fasciitis.¹

The hv strains have become a common cause of necrotising fasciitis in Asia. In Taiwan, the incidence of Klebsiella cases is comparable with the number of cases caused by group A streptococci, with a higher mortality rate in the former (47% vs 19%).¹⁰ Endogenous endophthalmitis via haematogenous dissemination is a devastating complication first described in 1986.¹⁰ Its incidence is less common than exogenous endophthalmitis, which commonly results from trauma or cataract surgery. Primary liver abscesses are the most common primary site, accounting for metastatic spread with an approximate risk as high as 11% of developing endophthalmitis vs 4.8% in patients with bacteraemia.^{7 8} Bilateral involvement occurs in 13%–25%.¹⁰ The most common presenting symptoms include eye pain, swelling, chemosis, and a sudden and rapid onset of blurring of vision. Hypopyon may be seen during physical examination. Prognosis remains dismal despite early and aggressive intraocular antibiotics and source control. Despite the poor visual sequelae, early recognition and treatment may be life-saving from intracranial spread.^{6 7 10}

The hv phenotype can be identified using the string test, in which a colony is lifted via an inoculation wire loop. A positive string test is defined as having a string longer than 5 mm after a colony is stretched on an agar plate.² This phenotype is thought to confer virulence through multiple mechanisms including the ability to resist phagocytosis and the ability to efficiently acquire iron. Despite its propensity to cause a destructive invasive syndrome, hv strains are invariably pan-susceptible to antibiotics.^{2 10} Thus, a finding of broad antibiotic sensitivity in community-acquired Klebsiella strains would therefore provide an indirect evidence of the hv Klebsiella strain. Most reports have identified this new variant as hv K. pneumoniae. However, by taking into account all virulent characteristics as one, the term hypervirulent K. pneumoniae is more appropriate.¹⁰

Most studies have shown that diabetes predisposes patients to hv Klebsiella infections.⁵ It is considered a risk factor but is not a prerequisite to the development of this potentially devastating disease.^{5 10} Therefore, it seems that being of Asian descent, recent travel to Asia and diabetes mellitus are the most important risk factors associated with developing an hv Klebsiella infection.⁷

Until now, the hv strains remain susceptible to a broad range of antimicrobial agents. Our isolate from the three sites (wound, blood and eye), despite its extreme virulence, remained pan-susceptible and consistent with the resistance patterns reported in the literature.² Hence, the management of resistant strains will become more challenging with higher associated morbidity and mortality. The future development of resistant strains coupled with a hypervirulent phenotype will make these strains into ‘superbugs in waiting’ similar to methicillin-resistant Staphylococcus aureus.¹⁰

Learning points.

• Our case illustrated the fulminant course and propensity for metastatic spread of hypermucoviscous Klebsiella infection.

• We should have a high index of suspicion for metastatic endophthalmitis in patients with necrotising fasciitis presenting with eye symptoms.

• The prognosis of endophthalmitis remains dismal despite early antibiotics and aggressive source control.

• Early recognition and treatment for one eye may be life-saving from intracranial spread.

• Our patient’s 2-week delay in seeking hospital care have led to the tragic sequelae of amputation and loss of vision, which remains a common scenario in resource-limited setting.