Klebsiella invasive syndrome: a challenging diagnosis

Abstract

Klebsiella invasive syndrome is a rare condition that typically presents as a liver abscess with metastatic infection, with mortality rates as high as 14% potentially due to diagnostic delay by clinicians. Here, we present a case of a woman in her 60s, who presented with symptoms and signs consistent with meningitis, imaging findings suggestive of possible leptomeningeal carcinomatosis a long with areas of lung consolidation and abdominal nodules and lymphadenopathy, presumably metastatic malignancy. We diagnosed Klebsiella invasive syndrome and treated it conservatively with medical management, including a long course of intravenous antibiotic therapy and supportive care. This is an infrequently encountered clinical entity with potentially fatal consequences, and we hope to add to the existing literature on the subject and drive home the point that it should be considered in the differential diagnoses in the appropriate clinical scenario.

Background

Klebsiella pneumoniae is a gram-negative bacillus typically implicated in the causation of Klebsiella related hospital-acquired pneumonia. A hypervirulent strain of the bacterium causes the invasive Klebsiella syndrome, which is a less-commonly encountered clinical entity and has been described to have varied presentations. There have been incidences of Klebsiella pneumoniae invasive syndrome (KPIs)¹ that started as a primary liver abscess^2–4 with dissemination to the meninges and endophthalmitis, described in East Asia. There are around 20 case reports of this syndrome described in the USA, however, the incidence is on the rise. In our case, we describe a KPIs⁵ in an immunocompetent patient presenting with meningitis and dissemination of infection to the liver and lungs. The severity of the presentation, high associated mortality rates (4%–14%),⁶ and the low incidence of KPIs in the USA⁷ highlight the need to have a high index of suspicion in the appropriate clinical setting.

Case presentation

The patient is an East Asian immigrant female in her 60s, without any recent history of travel, who presented to the emergency department with a throbbing headache for 7 days and fever, chills and confusion for 2 days. The headache was associated with nausea, nonbloody nonbilious vomiting and abdominal pain. She had a medical history of hypertension on nifedipine. She also had a history of rectal prolapse, which required manual faecal disimpaction daily. Social history and family history were reviewed but noncontributory. She was febrile to 101.9°F (38.83C), tachycardic (heart rate around 120 beats per min, sinus rhythm) and tachypnoeic (26 respirations per min). On examination, she was awake but disoriented, had neck rigidity with positive Kernig and Brudzinski signs, reflexes 2+ and negative Babinski. There were bilateral crackles on auscultation. The abdomen was soft, and mildly distended with diffuse tenderness and normoactive bowel sounds.

Investigations

Initial blood work sent on admission showed leucocytosis (22x 10ˆ9/L) with 88% neutrophils and 8% bands. Lactic acid was 2.5 mmol/L. Random blood glucose was 472 mg/dL with a hemoglobin A1c of 10.6%. She was also hyponatraemic with a serum sodium of 121 mg/dL and hypochloraemic, serum chloride was 94 mEq/L. Urinalysis was suggestive of a urinary tract infection with 4+ bacteriuria, positive leucocyte esterase and nitrite, and urine cultures sent at the time grew extended spectrum beta lactamase (ESBL) producing Escherichia coli. Blood cultures grew hypermucoviscous variant of Klebsiella species (figure 1). A chest radiograph showed multilevel patchy and nodular airspace opacities (figure 2). A CT abdomen and pelvis with contrast (figures 3 and 4) done on day 1 revealed a hepatic vein thrombus and bilateral pleural-based heterogeneous mass-like consolidations scattered throughout the lungs, bilateral pulmonary nodules, multiple hypodense liver nodules concerning for metastasis. An MRI brain (figure 5) done on day 1 showed multiple intraparenchymal and leptomeningeal nodules with rim enhancement suggestive of leptomeningeal carcinomatosis. Cerebrospinal fluid (CSF) analysis was significant for elevated white cell count at 26.4 x10ˆ9/L, red cell count of 3.3 x10ˆ12/L, actic acid at 11.7 mmol/L, elevated protein in CSF at 273 mg/dL and low CSF glucose at 25 mg/dL. CSF cultures were negative possibly due to antibiotic administration prior to lumbar puncture. Over the course of her hospitalisation, she also developed a loculated right sided pleural effusion, as seen on MRI abdomen on day 9 (figure 6), which was of malignant versus infectious aetiology. The MRI abdomen on days 9 and 13 (figure 7) showed persistent hyperenhancement in the liver, with a cluster of liver abscesses. Eventually a hepatic nodule was biopsied 2 weeks later, once she showed clinical improvement, which showed organising fibroinflammatory tissue and fibropurulent debris with reactive or regenerative changes in the adjacent liver parenchyma, suggestive of abscess, no neoplastic cells were identified.

Figure 1.

Mucoid colonies of Klebsiella pneumonia on blood agar.

Figure 2.

Diffuse patchy opacities on chest X-ray (day 1).

Figure 3.

Chest abdomen/pelvis without contrast (day 1)—right lower lobe mass (arrow) like consolidation 2.3×2.1 cm.

Figure 4.

Chest abdomen/pelvis without contrast (day 1)—multiple hypodense hepatic nodular densities.

Figure 5.

MRI brain (day1)—peripherally enhancing lesion in the right para midline cerebral peduncle.

Figure 6.

Mri abdomen (day 9)—malignant loculated pleural effusion.

Figure 7.

Mri abdomen (day 13)—multiple satellite lesions in the liver.

Differential diagnosis

The patient’s presentation and lab work on admission was suggestive of Klebsiella bacteraemia/sepsis from meningitis vs urinary source. The imaging findings of leptomeningeal carcinomatosis on MRI brain and pulmonary and hepatic nodules on CT chest abdomen pelvis raised suspicion for an underlying malignancy with metastatic involvement of the brain vs a disseminated infection. The resolution of the patient’s symptoms with antibiotics increased the probability of this being a disseminated infectious process. However, given the patient’s extensive abdominopelvic lymphadenopathy and hepatic vein thrombosis, an underlying malignancy could not be ruled out. She subsequently underwent biopsy of the liver nodules which showed fibropurulent tissue and no malignant cells thus establishing the whole clinical picture to be due to disseminated invasive Klebsiella syndrome. She was newly diagnosed with type 2 diabetes mellitus, which is a predisposing factor for developing an invasive syndrome.⁸

Treatment

The patient received empiric antibiotic therapy with Piperacillin-Tazobactam Vancomycin, ampicillin, and acyclovir for 1 day and aggressive intravenous fluid resuscitation with 30 cc/kg/hour normal saline bolus, for sepsis from meningitis vs urinary tract infection. She was switched to meropenem after urine cultures grew ESBL E. coli and blood cultures grew meropenem-sensitive Klebsiella (figure 8). Acyclovir was discontinued as CSF analysis was suggestive of bacterial meningitis. The patient had markedly elevated blood glucose levels and was treated with an insulin lispro sliding scale. Repeat imaging was performed on day 13 in which there was no resolution of liver nodules, prompting a liver nodule biopsy, which did not show malignancy. Over the course of her hospitalisation, the patient developed a right-sided loculated pleural effusion, for which video-assisted thoracocentesis was considered. The patient and her family opted to await resolution with medical therapy. She was given therapeutic anticoagulation with rivaroxaban for hepatic vein thrombosis. She was discharged with a plan for 4 weeks of intravenous antibiotic therapy and continued anticoagulation.

Figure 8.

Antibiogram for K pneumonia isolate. MIC Interp, minimum inhibitory concentration interpretation; MIC Dilutn, minimum inhibitory concentration dilution; Neg, negative; R, resistant, S, sensitive.

Outcome and follow-up

The patient had a total duration of hospitalisation was 19 days. She had an excellent response to antibiotics with complete resolution of bacteraemia, meningitis, urinary tract infection, and pneumonia. A repeat MRI of the abdomen on day 13 of hospitalisation showed persistent coalescing nodules in her liver, diagnosed as liver abscesses on biopsy. She was discharged home with a peripherally inserted central catheter for intravenous antibiotics. She completed 4 weeks of intravenous antibiotics and was re-evaluated in the clinic. She is now symptom-free and at baseline state of health (figure 9).

Figure 9.

Timeline of events from admission to postdischarge follow-up. CSF, cerebrospinal fluid; CXR, chest X-ray; ESBL, extended spectrum beta lactamase.

Discussion

Klebsiella pneumonia invasive syndrome is an uncommon condition that is defined as a malignant disseminated infection diagnosed as having meningitis or endophthalmitis secondary to Klebsiella liver abscess (KLA) or pneumonia. Malignant infection is rare with a reported incidence of 2% or less in patients with KLA, even in Taiwan, a country with the highest reported burden of KLA.⁹ While Klebsiella pneumonia is common, there have been atypical presentations of the disease, with cases reported in east Asia presenting primarily as a liver abscess.^10–12 There is current literature suggesting that specific hypervirulent strains typically associated with liver abscesses produce hypermucoviscous colonies which hypothetically increase the risk of dissemination.¹³ Extended-spectrum beta lactase-producing bacteria have been associated with hypervirulence,¹⁴ of note, our patient had ESBL E. coli in the Urine. Most cases have been observed in east Asia and there have been only a few cases reported in Europe and the USA particularly in patients, such as ours, who are of Asian descent, suggesting the possibility of a genetic predisposition.^15–17 She had septic emboli in the lung, liver, abdominopelvic lymph nodes and meningitis in the presence of both pneumonia and multiple liver nodules, making it difficult to know the source of the dissemination. Current guidelines suggest percutaneous drainage guided by imaging, which is both diagnostic and therapeutic. In this case, there were no large fluid-filled collections seen on imaging that would be amenable to drainage. Surgical resection was deferred due to rapid resolution of symptoms and the patient opting for medical management. The recommended antibiotic of choice for community-acquired Klebsiella is a cephalosporin.¹⁸ However, in view of the patient’s concurrent ESBL E. coli UTI, she was given meropenem which is also the preferred antibiotic for ESBL positive Klebsiella.¹⁹ Antibiotic therapy for liver abscess is recommended for a period of 4–6 weeks and can be extended if there are persistent radiological findings of infection. Although there is evidence that oral antibiotics may be as effective as intravenous antibiotics,²⁰ our patient was discharged on intravenous antibiotic therapy. Of note, she was also newly diagnosed with type 2 diabetes mellitus, which reiterates the contribution of high blood glucose levels in the development of an invasive syndrome.

Learning points.

• Literature suggests that while Klebsiella pneumoniae invasive syndrome (KPIS) is routinely seen in east Asia, there are few reported incidences in the USA;however, the incidence is on the rise. Thus having a high index of suspicion for KPIS, especially in patients of Asian descent, is important given its fulminant course and possible mortality.

• Klebsiella-related sepsis with meningitis being the initial presentation, severe disseminated septic emboli and hepatic vein thrombosis without the presence of an overwhelming respiratory compromise is an unusual presentation, making it a relevant case report to add to the literature.

• A disseminated infection can mimic a metastatic malignancy, and while a cancer state can predispose to infections, a single infectious entity causing widespread disease should be on the differential.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).