Keywords
melioidosis - liver and splenic abscess -
Burkholderia pseudomallei
Introduction
Burkholderia pseudomallei, a Gram-negative bacterium, is the causative agent of the systemic infection known
as melioidosis. In South East Asia, particularly in Thailand, it is a frequent cause
of septicemia, accounting for 20% of all cases of community-acquired septicemia.[1] Melioidosis is endemic in northern Australia, where it is considered a major public
health concern, as well as in many parts of Southeast Asia, including Thailand, Vietnam,
and Malaysia. In the Indian subcontinent, it has become increasingly recognized, particularly
in regions like southern India. However, it remains underdiagnosed and relatively
less understood compared to other endemic areas.[2]
B. pseudomallei is found in soil and water and can infect humans through inoculation, inhalation,
or ingestion.[3] In endemic areas individuals exposed to soil and surface waters are more prone to
infections due to B. pseudomallei, but active disease primarily occurs in patients with underlying predisposing conditions
like diabetes mellitus, renal disease, alcoholism, liver cirrhosis, chronic lung disease,
malnutrition, and use of immunosuppressive agents. Melioidosis presents as a febrile
illness ranging from septicemia to localized abscess formation especially in the lungs,
liver, spleen, skeletal muscle, and prostate.[4]
Melioidosis cases have been reported from the southern coastal region of India, but
only few cases of liver and splenic abscess have been reported from India. Melioidosis
should always be considered in cases with liver with splenic abscess that are not
responsive to standard antibiotics. Given the high mortality rate, prompt identification
and thorough treatment are essential in this situation.[5]
Case Report
A 61-year-old male came with fever since 2 months, cough with expectoration, generalized
weakness, and weight loss since 1 month. He was a known diabetic (type 2) on oral
hypoglycemic agents. Also, he had coronavirus disease 2019 infection 2 months prior
to these symptoms. He had bone and brain abscesses and pneumonia with pleural effusion
10 years back. He had no history of tuberculosis or travel.
On admission, he was started on empirical antibiotic treatment (piperacillin/tazobactam
and amikacin) and other supportive measures. His total leukocyte count was 9000 cu.mm
with 67.2% neutrophils and 21.9% lymphocytes on admission. Renal and liver function
tests were within normal limits except for raised gamma-glutamyl transferase ([Table 1]).
Table 1
Blood investigations
|
Blood investigations:
|
|
|
Total WBC count
|
9000/cu.mm
|
|
Differential count:
|
|
|
Neutrophils
|
67.2%
|
|
Lymphocytes
|
21.9%
|
|
Platelet count
|
329000/ cu.mm
|
|
CRP
|
173.10 mg/L
|
|
SGOT
|
25 U/L
|
|
SGPT
|
40 U/L
|
|
Gamma-glutamyl transferase
|
95 U/L
|
|
Plasma glucose random
|
281 mg/dL
|
|
Echinococcus (hydatid cyst) IgG
|
Negative
|
|
Amoebiasis antibodies - IgG
|
Negative
|
Abbreviations: CRP, C- reactive protein; IgG, Immunoglobulin G; SGOT, Serum glutamic
oxaloacetic transaminase test; SGPT, Serum glutamate pyruvate transaminase test; WBC,
White blood cell.
Computed tomography (CT) abdomen showed irregular multiloculated hypodense lesion
in segment IVa of liver measuring 5 × 4 × 3.9 cm. It showed enhancing septae, suggestive
of abscess. The spleen was enlarged measuring 16 cm. It showed multiple hypodense
lesions suggestive of abscesses, largest measuring 6 × 2.6 cm, which showed rupture
into the subcapsular space ([Fig. 1]).
Fig. 1 Computed tomography (CT) abdomen showing one loculated hypodense lesion with irregular
inner margin noted in the right lobe of the liver.
CT thorax showed mild broncheictatic changes. No pleural effusion.
Ultrasound-guided percutaneous aspiration of the liver abscess was done which revealed
thick pus. The pus aspirate was inoculated into blood agar and MacConkey agar. After
48 to 72 hours of aerobic incubation at 37°C, large, dry, wrinkled colonies were grown
on blood agar and MacConkey agar ([Fig. 2]). Gram's stain from these colonies showed Gram-negative rods with typical bipolar
“safety-pin” appearance indicating Burkholderia species ([Fig. 3]). The colonies also showed positive oxidase and catalase reaction. The isolated
colonies were processed in VITEK 2 automated culture system and the organism was identified
as B. pseudomallei. The organism was susceptible to carbapenems and cotrimoxazole. The patient was started
on meropenem and cotrimoxazole, which was continued for 2 weeks and later oral cotrimoxazole
was prescribed for the eradication phase. He was also shifted to intravenous insulin
from oral hypoglycemic agents due to steroid-induced hyperglycemia. His symptoms gradually
resolved and the follow-up CT abdomen after 6 months showed complete resolution of
liver and splenic abscesses.
Fig. 2 Colony morphology in blood agar (A) and MacConkey agar (B) and MacConkey agar showing large, dry wrinkled colonies of Burkholderia pseudomallei.
Fig. 3 Gram staining showing Gram-negative bacilli with typical bipolar safety pin appearance
indicating Burkholderia pseudomallei.
Discussion
Melioidosis, caused by the bacterium B. pseudomallei, presents a diverse range of clinical manifestations, with hepatic involvement being
a particularly challenging and intriguing aspect. This discussion explores the nuances
of melioidosis in the context of hepatic abscesses, shedding light on its clinical
presentation, diagnostic challenges, and treatment strategies. Various studies from
India highlight the diversity of clinical presentation seen with melioidosis. The
most common clinical manifestations include fever, pneumonia, multiorgan abscesses,
septicemia, and occasionally neurological and joint involvement.[6]
[7]
[8]
The lung is the most commonly affected organ. Abscesses in the liver and spleen could
be limited to disseminated cases. Liver abscess due to melioidosis can mimic pyogenic
liver abscess or cryptic tuberculosis. Hence, melioidosis was known as “The remarkable
imitator” and the great masquerader.[5]
[9]
[10] Splenic involvement is very rare in cases of liver abscess due to Entamoeba histolytica
and pyogenic bacteria, which should alert one to the possibility of melioidosis. In
Thailand, 95% of splenic abscesses are due to B. pseudomallei.[4]
[11] A study conducted by Raj et al also accounts for a greater frequency of splenic
and liver abscess compared to other organ sites in melioidosis cases.[12]
In our case, the predisposing factor for melioidosis was diabetes mellitus. Diabetes
mellitus was the most common predisposing factor in various other Indian studies.[6]
[7] Various other risk factors like disease occurrence in rainy season, male sex, and
age > 45 years also correlates with other studies.[13]
[14] Our case also presented in the month of July, during the rainy season.
In each organ, several abscesses are more frequent than a single abscess. Study by
Iyer et al also revealed multiple abscesses in liver and spleen similar to our case.[15] CT scan findings usually include liver abscesses with a “honeycomb” pattern of multiseptate,
multiloculated lesions. These “honeycomb” appearance on a CT scan are described as
being highly predictive of melioidosis.[16]
Definitive diagnosis can be made by culture of B. pseudomallei from clinical specimens along with accurate identification of organism using automated
systems. Few conventional identification methods like the presence of Gram-negative,
oxidase positive bacilli with bipolar staining pattern or safety pin appearance, and
rough wrinkled pink colonies with metallic sheen after prolonged incubation on MacConkey's
agar and with unusual susceptibility pattern (susceptible to amoxicillin-clavulanic
acid and resistant to aminoglycosides and colistin) can hint toward B. pseudomallei.[6]
[13]
Culture-based diagnostic tests remain the gold standard; however, they are time consuming,
prone to misidentification, and may not always yield positive results due to the inappropriate
use of broad-spectrum antibiotics. Serological tests such as hemagglutination lack
sensitivity and specificity owing to high seropositivity rates in endemic areas. polymerase
chain reaction-based assays are excellent alternatives for the rapid diagnosis of
melioidosis.[8]
The treatment of melioidosis includes an intravenous intensive phase and an eradication
phase. Ceftazidime or carbapenems are used in the intensive phase (10–14 days) and
trimethoprim-sulfamethoxazole (TMP-SMX) or doxycycline or amoxicillin-clavulanic acid
alone or in combination are employed for the eradication phase lasting for 3 to 6
months.[17] In our case, B. pseudomallei was resistant to ceftazidime, hence the patient was started on intravenous meropenem
and trimethoprim-sulfamethoxazole initially for 2 weeks during the intensive phase.
A randomized trial indicated that combining ceftazidime and cotrimoxazole together
reduced mortality.[18] The eradication phase consisted of treatment with oral trimethoprim-sulfamethoxazole
for 6 months.[19]
Conclusion
This case report highlights the diagnostic challenges posed by cases of prolonged
fever with diverse clinical manifestations and overlapping symptoms, which are unresponsive
to traditional antibiotics and antitubercular agents. Better awareness among clinicians
and microbiologists can allow in early diagnosis and prompt management, which can
significantly reduce the morbidity and mortality associated with this disease. In
certain situations it may be prudent to consider B. pseudomallei as a cause of abscess involving multiple organ systems.
