Klebsiella pneumoniae Invasive Syndrome without Liver Abscess: A Case Report

Introduction

Klebsiella pneumoniae invasive syndrome (KPIS) is a rare but increasingly recognized clinical entity, primarily reported in East and Southeast Asia. It is caused by hypervirulent strains of Klebsiella pneumoniae, which are distinct from classical strains, due to their ability to cause severe, community-acquired, disseminated infections in otherwise healthy individuals [1]. Unlike classical Klebsiella infections – which typically affect immunocompromised hosts and present as localized conditions, such as pneumonia or urinary tract infections – hypervirulent strains of Klebsiella pneumoniae can lead to metastatic involvement of multiple organs, often mimicking malignancy and posing diagnostic challenges, especially in non-endemic regions [2].

KPIS is commonly associated with bacteremia and complications, such as liver abscess, endophthalmitis, meningitis, and necrotizing fasciitis, and carries a poor prognosis if not diagnosed early [1]. Its virulence is driven by phenotypic and genetic factors, including hypermucoviscosity, expression of capsular serotypes K1 and K2, and virulence genes, such as fimH (fimbrial adhesion), kfu (iron uptake), and alls (allantoin metabolism) [3]. Mortality rates vary widely, from approximately 10% in antibiotic-sensitive infections to over 24% in those caused by resistant strains [4].

The global incidence of Klebsiella pyogenic liver abscess ranges from 1.1 to 17.6 cases per 100 000 people [5]. In East Asia, rates are particularly high – 12 to 18 per 100 000 – compared with just 1 to 4 per 100 000 in Europe and North America [6]. Approximately 80% of reported cases originate from Taiwan [7,8], although sporadic cases are increasingly seen in Western countries, often among migrant populations, suggesting a growing global spread.

Here, we describe an unusual case of KPIS in an immunocompetent adult from a non-endemic region, who presented with multiple metastatic lesions in the brain, spleen, vertebrae, and joints – findings that were strongly suggestive of disseminated malignancy on initial impressions. Notably, there was no evidence of hepatic involvement, which is uncommon given that liver abscess is typically the primary focus from which the organism spreads to distant sites, usually following acquisition via the fecal-oral route. This case underscores the importance of maintaining a high index of suspicion for KPIS in otherwise healthy individuals presenting with malignancy-like disseminated lesions. It also highlights the diagnostic challenges in resource-limited settings, where advanced molecular tools such as PCR or whole-genome sequencing to identify hypervirulence genes (eg, rmpA, aerobactin, magA) may not be readily available – making simpler diagnostic methods, like the string test, essential for early detection.

This case report has been reported in line with the SCARE checklist [9].

Case Report

A 45-year-old man presented to the Emergency Department of a government hospital in Delhi with acute-onset right-sided weakness, facial asymmetry, and abnormal speech, which had begun approximately 12 h prior to arrival and had progressively worsening since.

Nearly 2 to 3 weeks before this episode, he had developed a small, non-febrile abscess (approximately 1 cm2) over the dorsum of the right elbow, which was drained at a private clinic. He was prescribed oral antibiotics but was unable to recall the name of the medication, nor was the documentation available. The patient described them as “white tablets” taken 3 times daily, with instructions to complete a 5-day course. However, he discontinued the medication after 2 days, as his symptoms had resolved. The rest of the past medical history was non-significant: the patient did not recall any recent trauma, travel, yard work, animal bites, or recent hospitalization.

Approximately 1 week after the elbow abscess drainage, he began experiencing intermittent mild fevers, associated with chills and rigors. A few days later he developed lower back pain and asymmetric arthralgia, affecting the left knee and elbow. During this period, he intermittently consumed the leftover antibiotics from earlier, along with over-the-counter analgesics and paracetamol, that relieved the symptoms temporarily. Despite symptom recurrences, he was unable to seek medical care due to work commitments, until the abrupt onset of neurological deficits that prompted an emergency evaluation.

At the time of presentation, the patient was conscious and oriented, with a fever of 38.9 °C, pulse rate of 101 beats/min, respiratory rate of 17 breaths/min, and blood pressure within normal range. Local examination revealed a vague vertebral and paravertebral tenderness near the L5–S1 levels, and tenderness around the left knee and calf. No associated swelling or redness were noted. A well-healed, non-inflamed scar was present over the right elbow. On neurological examination, he had weakness in the lower half of the left face, with sparing of eyebrow movements. Muscle strength was graded 1/5 in the right upper limb and 3/5 in the right lower limb, with brisk reflexes and an extensor plantar response on the right. There was an associated sensory loss in the same distribution. No signs of meningeal irritation were noted. Fundoscopic examination did not reveal any abnormalities. Abdominal examination revealed mild left upper quadrant tenderness, without any palpable organomegaly. The rest of the physical examination was unremarkable.

Initial laboratory investigations revealed neutrophilic leukocytosis (18 600/mm3 with 84% neutrophils), elevated C-reactive protein (320 mg/L), erythrocyte sedimentation rate (82 mm/h), procalcitonin (1.4 μg/dL), and serum ferritin (1690 μg/L). Liver function tests showed a total bilirubin of 1.4 mg/dL, alanine aminotransferase of 63 IU/L, aspartate aminotransferase of 37 IU/L, and alkaline phosphatase of 200 IU/L. Renal parameters were within normal limits. Urinalysis was unremarkable. Blood and urine cultures were obtained upon admission and showed no growth within the next 72 h. HIV, HBsAg, and HCV serologies were negative, as was the interferon-gamma release assay.

Initial imaging with chest X-ray and abdominal ultrasound revealed no abnormalities. Contrast-enhanced magnetic resonance imaging (MRI) of the brain revealed multiple hemorrhagic foci, with the most prominent being at the gray-white matter junction of the left frontoparietal region, with surrounding edema and mass effect, raising suspicion of septic emboli or hemorrhagic metastases (Figure 1A). MRI of the spine identified a lytic lesion at the L5–S1 vertebrae (Figure 1B). A positron emission tomography-computed tomography (PET-CT) scan revealed hypermetabolic osteolytic lesions at C5–C6 and L5–S1, with pre- and paravertebral collections extending along the psoas and iliopsoas muscles, with intraspinal extension (Figure 1C). Additional lesions were also visualized in the spleen (Figure 1D) and right kidney, along with a fluid collection near the left knee joint (Figure 1E). Transthoracic echocardiogram and Carotid Doppler ultrasound did not reveal any abnormalities. A transesophageal echocardiogram could not be obtained, due to unavailability at the institution.

Aspirates from the left knee joint and the paravertebral collection were sent for analysis and culture. Synovial fluid showed a total leukocyte count of 750 cells/mm3, with 45% neutrophils; however, no organisms were isolated, and cytology was negative for acid-fast bacilli and malignant cells. Culture of the paravertebral aspirate grew non-extended-spectrum beta-lactamase-producing (non-ESBL) Klebsiella pneumoniae, susceptible to most of the routinely used antibiotics. A string test was positive, with a length of about 8 mm, suggestive of a hypermucoviscous phenotype. Genetic testing for hypervirulence-associated genes was not performed, due to lack of availability at the facility.

The patient was initially treated empirically with intravenous vancomycin and gentamicin, which were later de-escalated to amoxicillin-clavulanic acid, based on the sensitivity reports (Table 1). Supportive management included positional measures and mannitol to reduce cerebral edema. Clinical improvement was observed over the next few days, with resolution of fever, joint pain, and backache. Serial monitoring of inflammatory markers showed a steady decline, with an erythrocyte sedimentation rate of 24 mm/h and C-reactive protein level of 30 mg/L by the time of discharge. Leukocyte counts had normalized, and a follow-up PET-CT showed significant regression of all the foci. Given the improvement in the patient’s condition, repeat MRI and repeat aspiration of the septic foci for cultures were deemed unnecessary. A repeat set of blood cultures drawn 3 days before the discharge remained negative. Neurologically, the patient had demonstrated gradual improvement, with the help of inpatient physiotherapy. Upon discharge, after 2 weeks of hospitalization, the muscle power had improved to 4/5 in both the right upper and lower limbs, with no additional deficits. Antibiotic therapy was continued for a total duration of 6 weeks. Upon follow-up at 12 weeks after discharge, the patient was doing well, with return of neurological function to baseline.

Discussion

Klebsiella pneumoniae is a gram-negative, non-motile, rod-shaped bacterium belonging to the Enterobacteriaceae family. While traditionally recognized as a nosocomial pathogen, it has increasingly emerged as a cause of severe community-acquired infections, especially in immunocompromised individuals, such as those with diabetes mellitus, malignancies, or chronic cardiopulmonary or hepatic disease [8]. It is capable of causing a broad spectrum of infections, including pneumonia, urinary tract infections, liver abscesses, meningitis, and endophthalmitis. Among these, KPIS, also known as invasive liver abscess syndrome, is particularly notable for its metastatic potential, with secondary involvement of the central nervous system, eyes, lungs, and osteoarticular structures being well-documented [3]. Classically, liver abscesses serve as the primary focus of infection in KPIS. However, increasing evidence suggests that hypervirulent strains can disseminate from non-hepatic sites, even in immunocompetent hosts without traditional risk factors.

We report a similar unusual case of KPIS in an otherwise healthy individual, with no hepatic involvement. The likely portal of entry was a small, seemingly benign skin abscess over the right elbow, which had been inadequately treated. While gram-positive organisms like Staphylococcus aureus and Streptococcus pyogenes are the usual culprits in such presentations, our case underscores the pathogenic potential of K. pneumoniae.

The patient presented with acute neurological deficits mimicking stroke. Imaging revealed multiple lesions at the gray-white matter junction, with associated vasogenic edema. High-grade fever and markedly elevated inflammatory markers raised concerns for a disseminated infectious or inflammatory process. Initial differential diagnosis included disseminated tuberculosis (given the regional prevalence), systemic fungal infections, and metastatic malignancy. However, a negative interferon-gamma release assay, along with normal chest imaging and abdominal ultrasound, made these less likely. Blood and the knee joint aspirate cultures remained sterile, likely due to prior antibiotic self-medication. Further PET-CT imaging revealed widespread lesions involving the spleen, kidney, left knee, and spine. A definitive diagnosis was made following biopsy of a paravertebral abscess, which revealed no malignant cells but cultured non-ESBL K. pneumonia, with a positive string test, indicating a hypermucoviscous phenotype consistent with a hypervirulent strain.

Several recent cases highlight the virulent potential of K. pneumoniae to cause disseminated infections, even in immunocompetent individuals. Acosta et al described a 61-year-old Hispanic man with undiagnosed diabetes who developed multiple metastatic pulmonary nodules originating from a prostatic infection, without liver involvement [10]. Chae et al reported a 49-year-old immunocompetent Korean man who initially presented with leg swelling and pain, later found to have widespread abscesses – including in the anorectal region, kidneys, lungs, brain, and cervical spine – with no hepatic lesions; the isolate was a K1 serotype positive for hypervirulence genes [11]. Similarly, another fatal case of KPIS was reported in Thailand, in which a 71-year-old man with diabetes had developed cervical epidural abscess and rhombencephalitis, without hepatic or genitourinary involvement and no identifiable primary source [12]. These findings support the growing recognition that KPIS can arise from extrahepatic sources alone and can affect patients without conventional risk factors.

The patient in the present case was treated in accordance with the principles of antimicrobial stewardship. Empirical therapy with vancomycin and gentamicin was initiated, then de-escalated to amoxicillin-clavulanic acid following confirmation of pathogen susceptibility. The optimal route of antibiotic administration in KPIS remains debatable, with studies indicating that oral antibiotics can be as effective as intravenous therapy in treating community-acquired Klebsiella liver abscesses [13]. Drainage of accessible abscesses should be considered, to accelerate recovery. In line with current guidelines recommending prolonged treatment for disseminated K. pneumoniae infections [14,15], our patient received a 6-week course of antibiotics – comprising 2 weeks of intravenous therapy during hospitalization, followed by oral therapy for the remaining duration after discharge.

This case underscores several key considerations. KPIS can occur in immunocompetent hosts and should be considered in cases of unexplained systemic inflammation with multifocal abscesses. Hepatic involvement, while characteristic, is not essential for diagnosis. In resource-limited settings, where molecular diagnostics may not be readily available, clinical judgment – supported by culture data and imaging – is paramount. A positive string test is highly indicative of hypervirulent K. pneumoniae and should be routinely performed when disseminated infections with septic emboli are suspected.

Conclusions

KPIS is a rare, invasive condition characterized by disseminated septic emboli, typically associated with a primary infection site, most commonly a liver abscess. For reasons not yet fully understood, the syndrome is most prevalent in Taiwan and neighboring regions, although cases are increasingly being reported worldwide.

In our case, the patient developed multiple septic emboli several weeks after a minor skin abscess, ultimately leading to an embolic stroke – despite the absence of a liver abscess or other traditional risk factors for Klebsiella infection. This atypical presentation highlights the highly virulent nature of K. pneumoniae. Clinicians should maintain a high index of suspicion when a febrile patient presents with multisystem involvement and evidence of metastatic lesions. When genotypic testing is unavailable, a positive string test can serve as a useful surrogate marker for identifying hypervirulent strains.