Introduction

KPIS describes an uncommon clinical condition characterized by a primary liver abscess associated with extrahepatic metastatic infection, especially meningitis, necrotising fasciitis, or endophthalmitis [1]. Community-acquired KPIS cases are increasingly reported especially from Asian countries like Taiwan, South Korea, Singapore, and Hong Kong. KPIS is commonly associated with K1 or K2 serotypes.

IE due to gram negative bacilli is unusual and klebsiella-induced IE is rare. Klebsiella endocarditis carries significant higher risk of mortality than other types of endocarditis. Delayed diagnosis increases mortality rate up to about 50%, despite commencement of wide-spectrum antibiotic therapy [2]. This case report highlights the rarity of community acquired KPIS complicated with IE successfully treated with six weeks monotherapy intravenous ceftriaxone.

Case report

A 60 year old lady with long-standing poorly controlled type II diabetes mellitus with no known heart disease presented to emergency department with intermittent fever, malaise for two weeks, associated with right hypochondriac pain and episodic non-billous vomiting. Additionally, she also experienced five days history of jaundice and tea colored urine.

On examination, she was septic looking, lethargy, jaundice, with poor peripheral perfusion. Temperature was 39.3 °C, blood pressure was 90/52mmHg, heart rate 108 beats/minute with regular pulse, respiratory rate was 38 breaths/minute, while oxygen saturation was 98% under room air. Abdomen examination revealed tender right hypochondriac with volunteering guarding. Cardiovascular and lungs examination were unremarkable on initial assessment. Complete blood count showed leukocytosis with white blood cell count of 21.8 × 103/µL (differential of 93.5% neutrophils), hemoglobin of 10.5 g/dl, and thrombocytopenia with platelet count of 126 × 103/µL. Capillary blood glucose was 24.7mmol/L, with venous blood gas exhibited compensated metabolic acidosis (pH 7.42, bicarbonate 12.8mmol/L, base excess − 6.8mmol/L) and serum ketone 4.2mmol/L consistent with diabetic ketoacidosis (DKA). Other blood test results including raised C reactive protein (CRP) 287.6 mg/L (normal range, <5 mg/L), corrected sodium 133mmol/L, total bilirubin 67µmol/L (direct bilirubin 41µmol/L, indirect bilirubin 26µmol/L), alanine aminotransferase (ALT) 64U/L, aspartate aminotransferase (AST) 82U/L, alkaline phosphatase (ALP) 390U/L, serum albumin 18 g/L, other electrolytes, renal profile and coagulation profile were within normal range. Hemoglobin A1C (HbA1C) came back deranged 11.7% (normal range, < 6.5%). Electrocardiogram (ECG) showed sinus tachycardia, chest x ray was unremarkable with clear lung fields. Fluid resuscitation and insulin infusion was initiated to manage her DKA, which resolved on the subsequent day. Vasopressor was started in emergency department and was tapered off over the next 48 h. Intravenous cefotaxime and metronidazole were commenced in emergency department for suspicious intra-abdominal sepsis. Urgent ultrasound abdomen revealed an ill-defined heterogenous hypoisoechoic collection at segment II/III of liver, measuring 5.2 cm x 6.4 cm x 10.2 cm (Fig. 1A) and distended gallbladder measured 15.2 cm, thickened gallbladder wall with echogenic debris within (Fig. 1C). Otherwise, common bile duct and intrahepatic ducts were not dilated. There was no evidence of focal splenic lesion or perinephric collection. Ultrasound guided pigtail drainage of gallbladder empyema drained 30 cc pus, and she was transferred to medical ward after the procedure. Pus, urine, and blood cultures obtained were positive for Klebsiella pneumonia with similar sensitivity (susceptibility testing demonstrated sensitivity to most antibiotics, including amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, and ceftriaxone). Four separated sets of blood culture taken thereafter yielded negative growth. On day five of admission, cardiovascular examination noted newly detected pansystolic murmur over mitral region. Subsequent echocardiogram exhibited oscillating mass attached to anterior mitral valve leaflet measured 0.72cm2 (Fig. 2A). Patient remained afebrile for the rest of hospitalization with gradual resolution of leukocytosis and decreasing CRP. After consultation with the infectious disease team, the antibiotic coverage was changed to ceftriaxone one gram twice daily for a total of six weeks duration with additional gentamicin coverage. Intravenous gentamicin was halted after five days due to acute kidney injury, with increment of serum creatinine from 89µmol/L to 289µmol/L. Renal function normalized subsequently with cessation of gentamicin. Follow-up echocardiogram at six weeks (Fig. 2C) and three month after completion of antibiotics showed complete resolution of mitral valve vegetation. hepatic and gallbladder collection (Fig. 1C, D). Follow-up echocardiograms were not able to be conducted in closer constant interval due to limited resources. Patient was keeping well during review in general medical clinic 6 months after discharge, with no symptoms and signs of heart failure.

Fig. 1
figure 1

A C Ultrasound abdomen revealed an ill-defined heterogenous hypoisoechoic collection (white arrow) at segment II/III of liver, measuring 5.2 cm x 6.4 cm x 10.2 cm and distended gallbladder, thickened gallbladder wall with echogenic debris within. B D Repeated ultrasound abdomen after completion of antibiotic showing resolved liver abscess and gallbladder empyema

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Fig. 2
figure 2

A Transthoracic echocardiogram image showing 0.72cm2 oscillating mass (white arrow) attached to anterior mitral valve leaflet. B C Repeated transthoracic echocardiogram at 4 and 6 weeks post treatment showed shrunken (white arrow) and complete resolution of the mitral valve vegetation

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Discussion

Approximately 1.2% of native valve endocarditis cases are caused by Klebsiella [3]. Clinically, KPIS is defined as primary pyogenic liver abscess associated with metastatic infections. Brain abscess, suppurative meningitis, endophthalmitis and necrotizing fasciitis are the commonly reported sites of metastasis [1]. The incident is higher in Asia and common among patients with diabetes mellitus, liver cirrhosis, hepatobiliary disease, asplenia, neoplasia, chronic alcoholism and corticosteroids usage [4]. In this case, poorly controlled diabetes is the identified risk for KPIS.

Pyogenic liver abscess in our case was complicated with septic shock on presentation, contributing to Quick Pitt bacteremia score of 2 (vasopressin use and tachypnoeic), associated with significant in-hospital mortality [5]. Ultrasound of abdomen revealed gallbladder empyema which was drained. Blood, pus and urine culture subsequently turnout growing Klebsiella pneumoniae. Bloodstream infection developed within two days of admission along with low antimicrobial resistance implies community-acquired Klebsiella infection in this case. New onset murmur on day 5 of admission implies hepatobiliary sepsis as primary source of infection with hematogenous dissemination and infective endocarditis occurred later. Pathogenic strain analysis especially capsular type and virulent plasmid gene analyses were not performed due to lacking adequate laboratory facilities. String test was not proceeded in this setting due to the limited specificity. Clinically, the Klebsiella pneumoniae species has demonstrated that it is highly virulent and contributed to invasive syndromes. [6]

Diagnosis of IE is crucial to monitor both treatment responsiveness and disease complications including systemic embolism, heart failure, valvular abscess as well as infective aneurysm. The presence of a new murmur raised the suspicious of infective endocarditis, which was further confirmed with transthoracic echocardiogram mitral valve was affected in this case, in line with systemic review by Ioannou et al. exhibiting aortic and mitral valves as the most involved intracardiac sites in Klebsiella endocarditis [4].

To date, guidelines on optimal antimicrobial regimen of non-Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella (HACEK) species gram-negative bacilli IE is lacking due to rarity of the disease. American Heart Association (AHA) advocates combination antibiotic therapy with a β-lactam (penicillins, cephalosporins, or carbapenems) and either an aminoglycoside or fluoroquinolone for at least 6 weeks in non-HACEK IE [7]. Combination therapy with a beta-lactam and an aminoglycoside agent in this severely ill patient with Klebsiella pneumoniae bacteremia and septic shock is strongly advocated [8]. In this case, intravenous ceftriaxone and gentamicin were commenced initially. Intravenous ceftriaxone is the recommended choice of antibiotic in guidelines to manage both Klebsiella pneumoniae IE and liver abscess for its excellent tissue and body fluid penetration [7, 8]. Hypoalbuminemia is expected in this critically ill patient with shock due to transcapillary escape of albumin to extravascular space. Downregulated hepatic synthesis of albumin during severe sepsis is another contributing factor to hypoalbuminemia [9]. The frequency of ceftriaxone was increased considering hypoalbuminemia, as its pharmacokinetic profile displays high protein binding of 83 to 96%. Notable raised in volume of distribution (Vd) and clearance (CL) in patients with hypoalbuminaemia is associated with failure of ceftriaxone to attain the pharmacodynamic targets for therapy [9]. Gentamicin was withheld on day five of treatment in light of derangement in kidney function. Fortunately, acute kidney injury recovered with cessation of gentamicin. Both liver abscess and mitral valve vegetation resolved completely by week sixth despite monotherapy with intravenous ceftriaxone. Opinions from infectious diseases specialist and cardiologist were sought considering increased toxicity risks from antimicrobial regimen, the risks of drug-drug interactions and high mortality rate from non-HACEK gram-negative bacilli IE. Follow up under cardiology clinic three months later showed resolution of mitral regurgitation without evidence of recurrent endocarditis.

Table 1 KPIS with IE reported in various centers
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Looking into other cases of KPIS complicated with IE [10,11,12,13,14,15], diabetes mellitus is the most common associated risk factor. Other risk factors observed are immunocompromised state like end stage renal disease and chronic alcoholic. Not surprisingly, K1 is the most frequent recorded serotype associated with KPIS related IE, followed by K2 serotype. This is consistent with review on KPIS by Siu et al. [1]. Liver abscess and pneumonia are the most mentioned sources of infection, with subsequent metastatic infection affecting mitral and aortic valves. Distinct with other cases, Izzo et al. postulates implantable cardioverter-defibrillator (ICD) endocarditis as primary infection with liver abscess and pneumonia as complications of metastatic infection [13]. Central nervous system (CNS) [11, 12] and intramuscular abscesses [11, 14] are the most described site of metastatic infection, followed by endophthalmitis, and spine vertebral osteomyelitis. Similar as our patient, most of the cases reported treatment with at least 6 weeks of antibiotic. Cephalospirin and carbapenam group of antibiotics are the most preferred antibiotics, in combination with aminoglycoside or fluoroquinolone antibiotic. Drainage of liver abscess was indicated in most of the cases [10, 11, 13, 14]. In the present case, liver abscess was conservatively managed while gallbladder empyema was drained via pigtail catheter. Mortality was reported in two KPIS associated IE cases. A case reported by Hwang et al. diagnosed KPIS retrospectively from blood culture result after patient succumbed, further highlights the important of diagnostic suspicion for metastatic infection when dealing with Klebsiella pneumoniae infection.

Conclusion

Concomitant extrahepatic IE should raise concerns in daily practice for patients with Klebsiella pneumoniae liver abscesses, despite the rarity of Klebsiella endocarditis. KPIS with IE is associated with a high mortality rate. In the absence of diagnostic suspicion, antibiotic treatment regimens may be shortened, and adverse effects from IE infection may ensue.