Hypermucoviscous Klebsiella pneumoniae invasive syndrome in a patient with diabetes without liver abscess

Abstract

Klebsiella pneumoniae is part of the human gastrointestinal microbiota. It is also a well-known cause of community and nosocomial infections, involving mainly the lung and urinary tract. An invasive syndrome with liver abscess due to a new hypervirulent strain of K. pneumoniae was recently described. Several cases have been reported, mainly in Asia. Here, we show a case of a patient with an extrahepatic involvement affecting the lung and prostate.

Background

Klebsiella pneumoniae is an enterobacterium that occurs in the human gastrointestinal tract. It is also involved in several community and nosocomial infections. In recent years, a new K. pneumoniae hypervirulent strain has been reported to cause invasive liver abscess syndrome. This strain increases morbidity and mortality due to its hypermucoviscous phenotype. It usually causes invasive community-acquired infections. Liver abscesses with metastatic infections are the main characteristic of this syndrome. However, hypermucoviscous K. pneumoniae invasive syndrome (HvKPS) without liver involvement has seldom been reported. Herein, we report a case of a patient with diabetes who had multiple cavitated lung lesions and prostatic abscesses due to a hypermucoviscous strain of K. pneumonia without liver involvement.

Case presentation

A 61-year-old Hispanic man was admitted to the emergency department with a 4-day history of intense anal pain, constipation and abdominal distention. Also, he had a fever and shivering for the last 24 hours. The patient mentioned that he had polyuria, polydipsia and fatigue in the past 6 months.

His medical history was relevant for intense smoking (40 packs/year), chronic venous insufficiency, pre-diabetes for the last 10 years treated only with metformin with poor adherence and benign prostatic hyperplasia. He had no recent hospital admissions, nor had he been overseas for the previous 2 years.

A standard mental status and no signs of respiratory distress were revealed in the physical exams. However, the O₂ saturation was 87% without supplemental oxygen, with 22 breaths/min. Blood pressure was 113/65 mm Hg, heart rate was 130 beats/min and the temperature was 38.7°C. Bilateral crackles were revealed in the thoracic auscultation. The abdomen of the patient was painful but without peritoneal signs and the rectal examination was regular.

Investigations

Analysis of blood components were ordered. Bilateral pulmonary ground-glass opacities and multiple peripheral pulmonary nodules were shown in a thoracic X-ray and a thoracoabdominal CT scan showed. The largest nodule had the main axis of 1.3 cm with a cavitated component (figure 1). Interestingly, the liver was normal without focal lesions and there were no signs of intestinal inflammation or enlarged retroperitoneal lymph nodes. However, the prostate was enlarged and it had multiple hypodense nodules, the largest with the main axis of 1.6 cm (figure 2).

Figure 1.

First CT scan of the chest at admission.

Figure 2.

Prostate with multiple nodules.

Blood analysis had an elevated white cell count (16.7×10⁹ /L with 94% neutrophils and 2% of bands) and elevated inflammatory markers (C reactive protein 35.3 mg/dL and procalcitonin 13.5 ng/dL). He also had hyperglycaemia 581 mg/dL with a glycohemoglobin of 11.5%. Therefore, a diagnosis of diabetes mellitus was made. Blood ketones were negative and arterial blood gas had an acute respiratory alkalosis with non-anion gap metabolic acidosis.

Urinalysis was unremarkable, prostate-specific antigen was 0.53 ng/dL and urine culture was positive for K. pneumoniae. Blood and sputum cultures were also positive for K. pneumoniae.

Additionally, the galactomannan (GM), (1,3)-β-d-glucan test, QuantiFERON, HIV test, Respiratory Panel BIOFIRE FILMARRAY, urinary histoplasma, pneumococcal and legionella antigen were ordered. All of them were negative, except for GM (12.10 ng/mL).

Differential diagnosis

First, a diagnosis of community-acquired multifocal pneumonia and prostatic abscesses was made in the context of a patient with undiagnosed diabetes mellitus. The blood cultures and the serum GM were positive in the first 24 hours. Therefore, we started meropenem and isavuconazole. However, the respiratory and haemodynamic status of the patient deteriorated in the first 48 hours, requiring advanced airway management and vasoactive drugs.

The patient had complicated and persistent bacteraemia for 5 days despite adequate antimicrobial treatment, with negative blood cultures until the 6th day after admission. Given the positive serum GM, we conducted bronchoscopy with bronchoalveolar lavage (BAL) 48 hours after admission to confirm the diagnosis of invasive aspergillosis. The patient received three doses of isavuconazole at that moment, as this was started immediately after the positive serum GM. Both cultures and GM were negative in BAL and a repeated serum GM was negative on the 5th day of admission.

The urine, blood and sputum cultures were positive for pan-susceptible K. pneumoniae. A hypermucoviscous strain was confirmed with a positive string test on the colonies from the culture media on MacConkey agar.

Treatment

The patient received appropriate antimicrobial treatment within the first 2 hours from admission. However, he developed acute respiratory distress syndrome and septic shock after 2 days, requiring mechanical ventilation and vasoactive drugs in the intensive care unit (ICU). He required mechanical ventilation for 9 days and he achieved glycaemic control goals with an insulin drip in the ICU.

At first, he received meropenem, azithromycin, isavuconazole and vancomycin. We performed another CT scan of the chest on the 8th day and larger cavitated pulmonary lesions were revealed (figure 3). However, considering the positive cultures and the negative confirmation for aspergillosis, we tailored antimicrobial treatment with high-dose ceftriaxone (4 g/day) and levofloxacin (750 mg/day) to reach lung cavitations 1 week after the initial antimicrobial scheme.

Figure 3.

CT scan of the chest at first week from admission.

The patient was discharged on the 20th day from admission. He continued with long-acting insulin, and he completed a 6 week antimicrobial treatment with ceftriaxone and levofloxacin as an outpatient. The patient remained without fever and recovered at home. We looked after him every 15 days with laboratory analysis for 2 months (table 1). Additionally, we performed CT scans of the chest on the 1st, 5th and 14th months after admittance (figure 4). Marked improvements were shown in the laboratory analysis and CT scans of the chest.

Table 1.

Laboratory data

Variable	On admission	Eighth day	Day of discharge	End of antibiotic treatment (45th day)	Reference range
White cell count (×109 /L)	16.7	14	7.3	7.4	3.5–10
Haemoglobin (g/L)	141	90	81	114	145–185
Platelet count (×109 /L)	121 000	331 000	368 000	280 000	150 000–450 000
Lactate dehydrogenase (U/L)	223	145	159	144	122–222
C reactive protein (mg/dL)	35.3	18.08	6.79	0.06	0–0.50
Erythrocyte sedimentation rate (mm/h)	120			38	10–20

Figure 4.

Sequence of CT scans of the chest at 1st, 5th and 14th month from admission.

Discussion

Nowadays, K. pneumoniae invasive syndrome is an entity identified worldwide, with more than 900 cases reported so far. First, it was described in Asian countries as reported cases of liver abscess due to hypervirulent K. pneumoniae. However, seldom has this entity been described without liver involvement. Herein, we describe a case of a patient with diabetes with lung and prostatic hypermucoviscous K. pneumoniae infection.¹

K. pneumoniae is a gram-negative bacterium belonging to the Enterobacteriaceae family. It can affect the lungs, the urinary tract, soft tissues and the bloodstream. The classic infection caused by K. pneumoniae is mainly found in immunosuppressed patients. However, HvKPS affects younger, healthier, immunocompetent patients and develops a more severe disease.²

Usually, this strain only causes infection affecting the liver, forming multiple abscesses. Metastatic infection has been described as endophthalmitis, meningitis, brain abscesses, lumbar or cervical spondylitis, discitis, endocarditis, necrotising fasciitis, arthritis and abscesses on the lung, spleen, prostate, psoas muscle and kidneys.^{3 4} In our patient, it is possible that the origin of the infection was the prostate because his main and first complain was anal pain. He had multiple abscesses in the prostate and a positive urine culture for K. pneumoniae.

Sequence type 23 and sequence type 65 are the main strains of hypervirulent K. pneumoniae.⁵ These strains have critical virulence factors that make them hypermucoviscous strains, such as siderophore systems used for iron intake and high capsular polysaccharide production by capsular polysaccharide 1 and 2 types. Virulence factors allow K. pneumoniae to avoid phagocytosis and the complement system.^{4 6} These strains grow as adherent colonies. In our case, we could not determine the specific strain of K. pneumoniae due to lack of necessary equipment to do so. Although, we were able to perform a string test to confirm the phenotype. The strains can be observed on agar plates by a ‘string test’, which consists of stretching the colonies and getting a string>5 mm in length.⁷

The transmission of hypermucoviscous K. pneumoniae is unclear. The proposed mechanisms are ingestion of contaminated water or food, person-to-person transmission or animal-to-person transmission.⁸ Predilection for liver involvement is unknown. It is believed that hypermucoviscous K. pneumoniae strains can enter portal circulation through the bowel.⁹ Clinically, most patients present with fever, shivering, abdominal pain, nausea and vomiting. Females are more frequently affected than males. The right lobe of the liver tends to be more affected with abscess formations (65%), and a metastatic infection happens in 8%–24% of the patients.¹⁰

Although the classic HvKPS has liver abscesses, some cases have been described as an extrahepatic disease without liver abscesses, such as isolated muscle abscesses, necrotising fasciitis, osteomyelitis, septic arthritis, renal abscess, meningitis and prostate and bloodstream infections without abscesses.^11–18 Further research is needed to unravel why some patients present with the typical phenotype while others do not.

HvKPS infections often have a community origin, as occurred in our patient. However, there have been some reports linked to healthcare settings. Gu et al reported an outbreak in one hospital in China of a carbapenem-resistant HvKPS that caused fatal ventilator-associated pneumonia in five patients.¹⁹ The emergence of this strain constitutes a substantial threat to human health because it is both hypervirulent and multidrug resistant.

As it has been established with other infections that cause abscesses, the management of HvKPS needs adequate source control and appropriate antibiotic treatment. No clinical trials were performed to assess which drugs have the best activity for this strain. However, high susceptibility to commonly used antibiotics was reported in most studies.^{6 20} A Guo et al demonstrated that non-HvKPS isolates were more resistant than HvKPS.²¹ In this case report, the K. pneumoniae isolate was susceptible to all antibiotics.

Currently, treatment options are based on local epidemiology and pharmacokinetic/pharmacodynamic parameters to reach the infection site. We mainly decided to use combination therapy to ensure a beta-lactam for treating bacteraemia and a quinolone because of its good prostate/cavitations penetration. A 6-week regimen has been proposed for cases with multiple abscesses, such as ours.

Here, we show a case of an extrahepatic presentation of HvKPS syndrome with bloodstream infection and abscesses in the lung and prostate. We started empiric antibiotics and after we obtained positive urinary, sputum and blood cultures for hypermucoviscous K. pneumoniae, we tailored the antibiotic treatment to ceftriaxone and levofloxacin. The patient completed a 6-week course antibiotic regimen with a good clinical and antimicrobial response.

Learning points.

• Hypermucoviscous K. pneumoniae invasive syndrome (HvKPS) may occur without liver abscess as in our patient with diabetes with prostatic and lung involvement.

• HvKPS strain is frequently susceptible to most used antibiotics.

• Long antibiotic treatment is needed when multiple abscesses are diagnosed to achieve a cure defined as negative cultures, negative inflammatory markers and abscess image improvement.

• Considering that HvKPS is now considered a global pathogen, a high suspicion index is necessary for appropriate treatment once the diagnosis is made.

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