Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης

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A 53-year-old male presented to the Emergency Department (ED) with a chief complaint of 3 days of subjective fevers and generalized myalgias. He is originally from Haiti and last visited 1 year prior. His medical history includes uncontrolled diabetes mellitus; his most recent hemoglobin A1C was 11.9%. In the ED his vitals were notable for fever to 104°F, tachycardia to 145, and hypotension that required large-volume resuscitation. Laboratory results showed leukopenia (white blood cells, 2.8 TH/µL) with 78% polymorphonuclear cells and 10% bands and thrombocytopenia (62 TH/µL). Hemoglobin was normal at 13.8 g/dL. Liver tests showed mild elevations of aspartate aminotransferase (60 U/L), alanine aminotransferase (74 U/L), alkaline phosphatase (258 U/L), and direct bilirubin (2.1 mg/dL). Electrolytes and creatinine were unrevealing. Serum glucose was elevated at 304 mg/dL, and lactate was elevated at 2.7 mmol/L. Chest X-ray was normal. Blood cultures were drawn. An abdominal ultrasound showed a 2.9-cm posterior right hepatic lobe mass and 2.2-cm soft-tissue density-filling defect in the right hepatic vein consistent with partial thrombosis. On a computed tomographic (CT) scan of the abdomen and pelvis, the liver mass appeared cystic with some peripheral higher attenuation and was likely an abscess (Figure 1). There was no evidence of gallstones or biliary abnormalities on either the abdominal ultrasound or CT scan. He was started on broad-spectrum antibiotics and sent to interventional radiology for drainage of the liver collection; 10 cc of thick, bloody fluid was drained. Injection of contrast into the abscess cavity demonstrated connection with the hepatic veins. The organism that grew from the blood and liver collection is shown in Figure 2.

Figure 1.

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Computed tomographic scan of the abdomen and pelvis showing a cystic liver lesion with some peripheral higher attenuation, likely an abscess.

Figure 2.

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Isolate grown on MacConkey agar. Photo by: Ana Friedman MT (ASCP).

What is the diagnosis?

A 53-Year-Old Haitian Male Presenting With a Liver Abscess

Diagnosis: Hypervirulent Klebsiella pneumoniae, with hypermucoviscous phenotype.

Shortly after the interventional radiology procedure, the patient developed worsening fever to 105°F, septic shock, and multiorgan failure, including acute respiratory distress syndrome that required intubation, renal failure, and disseminated intravascular coagulation. Surveillance blood cultures remained positive for 72 hours and cleared on hospital day 4.

When the susceptibility of Klebsiella pneumoniae returned as pansensitive (except ampicillin), the antibiotics were narrowed to ceftriaxone. Given the propensity of this organism to invade the central nervous system, meningitis doses of ceftriaxone were used. Although the patient eventually made a full recovery, he required prolonged hospitalization due to complications including hepatic vein thrombosis, septic pulmonary and ocular emboli, and a loculated right pleural effusion.

Community-acquired pyogenic liver abscesses caused by K. pneumoniaewith a hypermucoviscous phenotype were first reported from Taiwan 3 decades ago [1], with the disease entity increasingly recognized throughout East Asia [2]. However, as shown here, cases may be increasing worldwide [3]. The prevalence of hypermucoviscous strains was higher for cases of K. pneumoniae infection causing liver abscess compared to other sites of infection (98% vs 17%) [4]. This emerging disease is characterized by a primary liver abscess that is often complicated with bacteremia and sepsis. The hypermucoviscous phenotype has been associated with metastatic disease, with a particular proclivity for the central nervous system, including endophthalmitis, meningitis, and brain abscess [5]. These organisms demonstrate extremely high viscosity, determined by a string test of the colony cultured in the laboratory. The string test is performed by touching a colony with a loop and pulling up; a test result is considered positive when a string of ≥5 mm is observed. Currently, the string test is not routinely performed in our microbiology laboratory. However, rapid detection of hypermucoviscosity by means of this inexpensive and readily available test can alert the clinician to the possibility of hypervirulent K. pneumoniae, thereby improving patient outcomes for this emerging and severe disease.

Seventy-seven serotypes of K. pneumoniae can be differentiated based on different capsular polysaccharides [6]. Klebsiella pneumoniae serotypes K1 and K2 have emerged as the main serotypes associated with community-acquired primary liver abscesses. These serotypes are more virulent than others, which may in part be due to decreased recognition of their capsular polysaccharides by macrophages and decreased phagocytosis by neutrophils [7]. K1 and K2 isolates are more often hypermucoviscous than non-K1 and K2 isolates [8]. Plasmid-encoded genes such as rmpA(regulator of mucoid phenotype gene A) and magA (mucoid-associated gene A) have been associated with this hypermucoviscous phenotype [9]. Strains with the hypermucoviscous phenotype are more resistant to complement-mediated serum killing than those without this phenotype. Klebsiella pneumoniae strains positive for either gene show significant association with purulent infections in the liver and invasive disease [9]. Other virulence factors have also been identified, but the exact interplay between the different virulence factors is not completely understood [10].

The case presented here was part of a retrospective case series from 2015 to 2017 at Cambridge Health Alliance, an academic community healthcare system that includes Cambridge and Everett hospitals. Four patients with solitary K. pneumoniae liver abscess were identified. All patients presented from the community and none had an underlying biliary etiology. Country of origin was mainly from East Asia, with 2 patients from Vietnam and 1 patient from Cambodia. Only the patient described here was born outside of Asia. All patients had diabetes mellitus type 2. Three patients required intensive care unit level of care due to severity of illness; however, no patients had in-hospital mortality. Only the patient described here showed evidence of metastatic infection. All isolates grown on agar exhibited hypermucoviscosity with a positive string test. Of the 2 isolates sent for genetic sequencing, both contained the rmpA gene.

To our knowledge, this is the first case of a liver abscess caused by the hypermucoviscous strain of K. pneumoniae in a patient from Haiti. While this strain is typically described in patients from East Asia, it is emerging worldwide. Clinicians should be aware that a K. pneumoniae strain with a positive string test portends a virulent infection associated with liver abscesses and metastatic complications, with a particular propensity for the central nervous system. We recommend that microbiology laboratories standardize a protocol to perform the string test on any hypermucoviscous-appearing K. pneumoniae isolate with notification of a positive result to the infectious disease team.

Notes

Acknowledgments. We thank the laboratory and microbiology staff at Cambridge Health Alliance (Dr Rebecca Osgood, Ken Atwell, and Ana Fridman) and the patients included.

Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.