Case of endogenous endophthalmitis caused by Klebsiella pneumoniae with magA and rmpA genes in an immunocompetent patient

Case of endogenous endophthalmitis caused by Klebsiella pneumoniae with magA and rmpA genes in an immunocompetent patient

J Infect Chemother (2013) 19:326–329 DOI 10.1007/s10156-012-0468-6 CASE REPORT Case of endogenous endophthalmitis caused by Klebsiella pneumoniae wi...

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J Infect Chemother (2013) 19:326–329 DOI 10.1007/s10156-012-0468-6

CASE REPORT

Case of endogenous endophthalmitis caused by Klebsiella pneumoniae with magA and rmpA genes in an immunocompetent patient Akira Sawada • Shinya Komori • Kazunari Udo Shinsuke Suemori • Kiyofumi Mochizuki • Mitsuru Yasuda • Kiyofumi Ohkusu



Received: 24 May 2012 / Accepted: 10 August 2012 / Published online: 20 September 2012 Ó Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2012

Abstract We report a case of endogenous endophthalmitis caused by Klebsiella pneumoniae in an immunocompetent patient. A 73-year-old man with acute epididymitis who had no history of diabetes mellitus developed endogenous endophthalmitis. The patient underwent anterior vitrectomy and intracapsular cataract extraction with intravitreal injections of both vancomycin and ceftazidime. After the surgery, he was treated with topical and intravenous antibiotics; however, the left eye perforated and was enucleated. Culture from vitreous biopsy specimens grew as K. pneumoniae, which was positive for both magA and rmpA. K. pneumoniae should be considered as a pathogen that can cause severe endogenous endophthalmitis in patients with urinary tract infection. The severity of the disease may be related to the virulence genes. Keywords Endogenous endophthalmitis  Klebsiella pneumoniae  Acute epididymitis  magA  rmpA

A. Sawada (&)  S. Komori  K. Udo  S. Suemori  K. Mochizuki Department of Ophthalmology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan e-mail: [email protected] M. Yasuda Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan K. Ohkusu Department of Microbiology, Gifu University Graduate School of Medicine, Gifu, Japan

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Introduction Endogenous bacterial endophthalmitis results from a blood-borne spread of bacteria with entrance into the intraocular space. It is associated with underlying medical conditions such as diabetes, gastrointestinal disorders, renal failure, heart disease, and malignancies in up to 90 % of the patients [1, 2]. Diabetes is a significant risk factor for the development of endogenous endophthalmitis and poor visual outcome [3]. However, a case series of cultureproven endogenous endophthalmitis has been reported in apparently healthy and immunocompetent individuals [4]. Earlier studies have reported that the most common bacterial organism causing endogenous bacterial endophthalmitis was Staphylococcus aureus [1]. In East Asia, it is more commonly (in 37–70 % of infections) caused by gram-negative organisms, particularly Klebsiella spp. [5]. Among the gram-negative organisms, Klebsiella pneumoniae is known to be the species most frequently responsible for endogenous bacterial endophthalmitis, especially in East Asian countries [2, 5]; e.g., K. pneumoniae was found in 48.4 % of infections [2]. Despite early diagnosis and treatment, the visual prognosis remains poor [1, 2, 5]. Lee et al. [2] reported that K. pneumoniae-associated endogenous endophthalmitis had significantly poorer visual outcomes than those with gram-positive cocci-associated endophthalmitis. Fung et al. [6] reported that K. pneumoniae serotype K1 was significantly associated with liver abscesses with the complication of endophthalmitis. Infections by the K. pneumoniae K1 and K2 capsular serotypes, the mucoid phenotypes, followed by their aerobactin production, were important determinants of virulence [7]. In addition, a close relationship of the mucoviscosity-associated (magA) gene and/or regulator of mucoid phenotype (rmpA) gene to the

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K. pneumoniae hypermucoviscosity phenotype has been pointed out [8]. We present here a case of endogenous K. pneumoniae endophthalmitis with acute epididymitis in an immunocompetent patient; both the magA and rmpA genes were identified in vitreous specimens.

Case report A 73-year-old nondiabetic man who had a history of lumbar spinal canal stenosis underwent prostate surgery at another hospital. After the surgery, he was treated with cefdinir (300 mg/day) and loxoprofen, a nonsteroidal antiinflammatory drug. Ten days later, he was examined at an eye clinic because of a 4-day history of blurred vision in the left eye and nausea. His visual acuity was light perception in the left eye and 20/20 in the right eye. The intraocular pressure was 14 mmHg in the right eye and 40 mmHg in the left eye. He was diagnosed with uveitis with secondary glaucoma and was referred to us for further therapy on the same day. Slit-lamp examination showed severe ciliary injection, corneal edema, and severe inflammation with a hypopyon in the anterior chamber of his left eye (Fig. 1). His left fundus could not be examined in detail because of hazy media. Ultrasonography of the posterior segment showed moderately dense infiltrations in the vitreous cavity, and the electroretinogram was completely extinguished in his left eye. His right eye was normal. With a tentative diagnosis of suspected endogenous endophthalmitis, he underwent emergency anterior vitrectomy and intracapsular cataract extraction with intravitreal injections of vancomycin (1 mg/eye) and ceftazidime (2 mg/eye). He was also treated with topical 0.5 % levofloxacin and 0.5 % cefmenoxime, 0.3 % ofloxacin ointment, and intravenous cefpirome (2 g/day). The vitreous aspirate showed a few gram-negative rods. On the following day, we began to determine the primary extraocular origin of the infection because there was no history of ocular trauma and ocular surgery. Physical examination showed a body temperature of 37.2 °C with testicular tenderness. Scrotal magnetic resonance imaging revealed bilateral testicular enlargement and the presence of a moderate hydrocele. No abnormalities were detected by chest roentgenography and computed tomography of the brain, chest, and liver. Laboratory tests demonstrated an elevated leukocyte count of 19,320/ll with 90 % of polymorphonuclear cells, a C-reactive protein level of 16.15 mg/dl, alkaline phosphatase level of 923 IU/l, c-glutamyl-transpeptidase level of 302 IU/l, creatinine level of 1.38 mg/dl, and blood urea nitrogen level of 32.4 mg/ml. The level of hemoglobin A1C was 5.6 %. Urinalysis

Fig. 1 External slit-lamp photograph of the left eye. The conjunctiva is erythematous and chemotic, and the cornea was thickened with inflammatory debris on its endothelium. The anterior chamber is severely irritated with a hypopyon

revealed a pH of 5.5, 1 ? protein, 1 ? white blood cell, 3 ? red blood cells, and 1 ? gram-negative bacilli. These findings led to a diagnosis of acute epididymitis. Two days after admission, the cefpirome was discontinued and replaced by imipenem (1 g/day) for 2 weeks. His ocular inflammation worsened, and the corneal wound ruptured 3 days after the first surgery. With the consent of the patient, his left eye was enucleated 2 days later. The same topical antibiotics were continued after the enucleation. The imipenem was switched to oral levofloxacin 500 mg daily for 7 days. Thereafter, the acute epididymitis gradually improved. Subsequently, cultures from vitreous biopsy specimens obtained during both vitrectomy and enucleation grew K. pneumoniae, which was positive for both the magA and rmpA genes. Polymerase chain reaction (PCR) was performed to amplify the magA and the rmpA genes, as previously described [2]. K. pneumoniae was found to be susceptible to piperacillin, ceftazidime, aztreonam, ceftriaxone, imipenem/cilastatin, amikacin, gentamicin, minocycline, levofloxacin, and vancomycin, and was resistant to sulbactam sodium/ampicillin sodium, and ampicillin (Table 1). Both blood and urine cultures on admission to our hospital were negative.

Discussion Immunocompromised states such as diabetes mellitus, renal failure, and malignancy are associated with a reduced host defense and are risk factors for the development of endogenous endophthalmitis [1, 2, 9, 10]. It has been reported that K. pneumoniae is a common cause of

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J Infect Chemother (2013) 19:326–329

Table 1 Susceptibility testing results of Klebsiella pneumoniae Antimicrobial agent

Minimum inhibitory concentration (lg/ml)

Ampicillin

[16

Piperacillin

B16

Ceftazidime Cefazolin

B1 B8

Cefmetazole

B16

Cefdinir

B1

Imipenem/cilastatin

B1

Aztreonam

B1

Sulbactam/ampicillin

[16

Ceftriaxone

B1

Amikacin

B8

Gentamicin

B2

Cefozopran

B1

Minocycline

B2

Fosfomycin

128

Levofloxacin

B2

Sulfamethoxazole–trimethoprim

B1

Cefpodoxime proxetil

B1

endogenous bacterial endophthalmitis [2]. However, endogenous endophthalmitis caused by K. pneumoniae in immunocompetent patients in Japan is rare, with only three cases reported [11–13]. The mean age of the patients in these reports was 60 years, with a range of 52–71 years. All the cases were men; the primary source of the infection was liver abscess in two cases [12, 13] and septic pulmonary embolism in one case [11]. The visual outcomes in all these cases were poor. Our case was an older man without diabetes mellitus and malignancy, and the outcome was poor. We suggest that delayed diagnosis also leads to poor prognosis [5]. The primary sources of the endogenous K. pneumoniae endophthalmitis were from the hepatobiliary system (77.5 %), followed by the urinary tract (9.9 %), and respiratory system (4.2 %) [14]. Acute epididymitis is characterized by testicular pain and tender swelling of the epididymis [15]. In older men, acute epididymitis may follow prostatic surgery. Escherichia coli, Proteus spp., K. pneumoniae, and Pseudomonas aeruginosa were occasional causes of the epididymis [14]. Chen et al. [16] reported on two diabetic patients with K. pneumoniae renal abscess and endophthalmitis. In our case, we suggest that the infectious source was the acute epididymitis following the prostatic surgery. However, our patient did not have a history of diabetes mellitus, and no urine specimens for repeated cultures were obtained after a course of systemic antibiotics. Additionally, no other culture-documented

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sources of infection, such as cardiac vegetation or liver disease, were identified. Despite the early diagnosis and aggressive intravenous and intravitreal antibiotic therapy, the visual outcome of endogenous K. pneumoniae endophthalmitis was extremely poor, with eventual evisceration or enucleation [14, 17]. Nonetheless, early detection of associated infectious focus with initial systemic investigation is the most important factor in the management of endogenous bacterial endophthalmitis because the treatment of the causative organism and control of the infection source would decrease the burden of bacteremia [2]. Ang et al. [14] reported that the clinical features including those caused by more virulent organisms that are risk factors for poor visual outcome. Infections with K1 and K2 capsular serotype, the hypermucoviscosity phenotype, and the presence of the magA gene contributed to the virulence and metastatic nature of K. pneumoniae [14]. Lin et al. [7] demonstrated poor glycemic control to be a risk factor for susceptibility to serotype K1/K2 K. pneumoniae liver abscesses and complication of endophthalmitis. Although we did not examine the serotype of the K. pneumoniae, the magA gene has been reported to be a component of the K1 capsule [18, 19]. Karama et al. [20] reported that a diabetic patient with endogenous endophthalmitis secondary to a liver abscess caused by K. pneumoniae expressed the magA gene. Hunt et al. [21] demonstrated that magA was a virulence factor in experimental K. pneumoniae endophthalmitis. Lin et al. [22] reported that hypermucoviscosity was highly correlated with the presence of the rmpA gene in urinary tract infection strains, and rmpA may play a role in community-acquired urinary tract infections. Because our PCR results were positive for the magA and rmpA genes, K. pneumoniae is an emerging pathogen that caused catastrophic septic ocular complications. In conclusion, the immediate diagnosis and aggressive systemic treatments including vitrectomy and intravitreal antibiotics against K. pneumoniae are most important for the control of sepsis and restoration of vision. PCR analysis of the hypermucoviscosity phenotype may help in understanding the contribution of a distinctive invasive endophthalmitis caused by K. pneumonia.

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