Scholarly article on topic 'Characteristics, clinical outcomes and factors influencing mortality of patients with melioidosis in southern Thailand: A 10-year retrospective study'

Characteristics, clinical outcomes and factors influencing mortality of patients with melioidosis in southern Thailand: A 10-year retrospective study Academic research paper on "Health sciences"

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Abstract of research paper on Health sciences, author of scientific article — Chaitong Churuangsuk, Sarunyou Chusri, Thanaporn Hortiwakul, Boonsri Charernmak, Kachornsakdi Silpapojakul

Abstract Objective To study characteristics, clinical outcomes and factors influencing mortality of patients afflicted with melioidosis. Methods We retrospectively analyzed 134 patients, with a microbiologically-confirmed diagnosis of melioidosis, during the period from January 2002 to June 2011 at Songklanagarind Hospital, a tertiary care hospital in southern Thailand. Results The prevalence of melioidosis among admitted patients was 36.8 per 100000 in patients. The median age was 49 years and they were predominantly male. The most common underlying disease was diabetes mellitus (47.01%). The majority of cases (50%) had localized infection. The rates of multifocal, bacteremic, and disseminated infections were 12.7%, 23.1%, and 14.2%, respectively. The lungs were the most common organ afflicted, resulting in infection (24.63%). Splenic abscess as well as liver abscess accounted for 20.90% and 19.40%, respectively. A total of one eighth of the patients had septic shock at presentation. The overall mortality rate was 8.96%. The factors influencing mortality were pneumonia, septic shock, a positive blood culture for Burkholderia pseudomallei, superimposing with nosocomial infection and inappropriate antibiotic administration. Conclusions Melioidosis is not uncommon in southern Thailand. The mortality of patients with pneumonia, bacteremia and septic shock is relatively high. Appropriate antibiotics, initially, will improve outcomes.

Academic research paper on topic "Characteristics, clinical outcomes and factors influencing mortality of patients with melioidosis in southern Thailand: A 10-year retrospective study"

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Asian Pacific Journal of Tropical Medicine

journal homepage: http://ees.elsevier.com/apjtm

Original research http://dx.doi.org/10.1016/j.apjtm.2016.01.034

Characteristics, clinical outcomes and factors influencing mortality of patients with melioidosis in southern Thailand: A 10-year retrospective study

Chaitong Churuangsuk1, Sarunyou Chusri1'2*, Thanaporn Hortiwakul1, Boonsri Charernmak1, Kachornsakdi Silpapojakul1

1Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand 2Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand

ARTICLE INFO

ABSTRACT

Article history: Received 15 Dec 2015 Received in revised form 20 Dec 2015

Accepted 30 Dec 2015 Available online 11 Jan 2016

Keywords: Melioidosis Southern Thailand Burkholderia pseudomallei

Objective: To study characteristics, clinical outcomes and factors influencing mortality of patients afflicted with melioidosis.

Methods: We retrospectively analyzed 134 patients, with a microbiologically-confirmed diagnosis of melioidosis, during the period from January 2002 to June 2011 at Songklanagarind Hospital, a tertiary care hospital in southern Thailand. Results: The prevalence of melioidosis among admitted patients was 36.8 per 100000 in patients. The median age was 49 years and they were predominantly male. The most common underlying disease was diabetes mellitus (47.01%). The majority of cases (50%) had localized infection. The rates of multifocal, bacteremic, and disseminated infections were 12.7%, 23.1%, and 14.2%, respectively. The lungs were the most common organ afflicted, resulting in infection (24.63%). Splenic abscess as well as liver abscess accounted for 20.90% and 19.40%, respectively. A total of one eighth of the patients had septic shock at presentation. The overall mortality rate was 8.96%. The factors influencing mortality were pneumonia, septic shock, a positive blood culture for Burkholderia pseudomallei, superimposing with nosocomial infection and inappropriate antibiotic administration.

Conclusions: Melioidosis is not uncommon in southern Thailand. The mortality of patients with pneumonia, bacteremia and septic shock is relatively high. Appropriate antibiotics, initially, will improve outcomes.

1. Introduction

Melioidosis, an infection caused by Burkholderia pseudo-mallei (B. pseudomallei), is an endemic in Southeast Asia and northern Australia [1]. The clinical manifestations vary from benign local skin and soft tissue infection to sepsis or septic shock [2]. In northeastern Thailand, melioidosis mostly accounts for the common cause of community-acquired septicemia [3]. The mortality rate remains high despite effective antibiotics regimens in the intensive phase of treatment [4]. For patients who had apparently been cured, recurrence occurred mostly within a year. This is another important problem [5].

Corresponding author: Sarunyou Chusri, Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. Tel: +66 74 451 483 Fax: +66 74 451 033 E-mail: sarunyouchusri@hotmail.com

Peer review under responsibility of Hainan Medical University.

Previous studies in northeastern Thailand defined several factors, which included age, underlying diseases of patients, the severity of clinical manifestations and antibiotic regimens; these factors influenced mortality and recurrence [4,5].

The incidence in the southern regions of Thailand were relatively low, compared to those in the northeastern regions [6]. In addition to the higher prevalence of B. pseudomallei in soil, higher rates of virulent biotype were prevalent in northeastern Thailand [7]. The aim of this study is to establish clinical characteristics, outcomes and factors influencing mortality of the patients with melioidosis in southern Thailand.

2. Materials and methods

2.1. Study design, study site, population and ethical consideration

This retrospective, cross-sectional study was conducted in Songklanagarind Hospital, an 800-bed university hospital in

1995-7645/Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Songkhla province, located in southern Thailand. All patients (>1 year old) of Songklanagarind Hospital who had a microbiologically-confirmed diagnosis during the periods from January 2002 to June 2011 were enrolled. Ethical permission was obtained from the research ethical committee of the Faculty of Medicine at the Prince of Songkla University.

2.2. Data collection

Demographic data, clinical manifestations together with treatment including antibiotic regimens were collected from the Hospital Information System, a computerized database system of Songklanagarind Hospital, and analyzed for the risk factors for mortality.

Focal infection was defined by 1 site of infection. Multifocal was defined by multiple sites of focal infection, without bacteremia. Bacteremia was defined by positive blood culture with, or without 1 site of focal infection, while disseminated melioidosis was defined by positive blood cultures with at least two, or more focal infections. Septic shock was described as the presence of hypotension without response to fluid replacement, and associated with hypoperfusion and organ dysfunction. Newly diagnosed diabetes mellitus cases were defined as patients who did not have any treatment including oral hypogly-cemic agents, insulin and life style modifications.

Occupations, which were suspected risk factors for melioi-dosis, were classified into two groups according to the chances of exposure to B. pseudomallei from the soil and water. These were divided into high exposure and low exposure occupations. Death was defined by patients who died during initial therapy or during intensive therapy.

2.3. Data analysis and statistic

For descriptive statistics, median with inter-quartile range was used for non-normal distribution and continuous data, while frequency with percentage was used for categorical data. In terms of analytic statistics, for continuous variables, the MannWhitney U test was used, and for categorical variables, either the X2 test with Yates' correction or Fisher's exact test was used. Logistic regression analysis was used to identify independent risk factors for mortality. A P-value of less than 0.05 was considered statistically significant difference. R program was used for analysis with package 'commend', 'ICE' and 'epicalc'.

3. Results

of patients (89.55%) were treated with parenteral antibiotics as inpatients at Songklanagarind Hospital (Table 1).

A total of 95 (78.51%) patients had a fever prior to admission. Septic shock accounted for 12.40% of patients at initial diagnosis and 21.67% of the patients during hospitalization. A total of 20.83% of the patients required admission into the intensive care unit. A total of 15 patients (12.50%) were superimposed with nosocomial infection. In terms of distribution of infection, 50% of the patients had a localized infection. Multifocal infection, bacteremia, and disseminated infection were 12.69%, 23.13%, and 14.18% respectively.

Overall, there were 12 (8.96%) deaths during hospitalization. After successful treatment, no patient died from any other documented causes. A total of 2 patients died within 2 d, after admission, before laboratory confirmation of the causative organism. Median of time for defervescence was 8 d (Table 2). A total of thirty-three (24.63%) patients presented with community-acquired pneumonia, while only 13 of the 33 patients developed respiratory failure including acute respiratory distress syndrome. Splenic abscess and liver abscess presented in 28 (20.90%) and 26 (19.40%) patients respectively, in the primary diagnosis; however, drainage was required in only 5 patients in splenic abscess, and 2 patients underwent splenec-tomy. Only one patient with liver abscess underwent abscess drainage.

Similarly to visceral organ abscess, isolated superficial lymph node infection, along with intra-abdominal lymph node infection accounted for 9.70% and 2.24% of the patients respectively. In addition to this, less required aspiration. A total of twenty (14.93%) patients had rheumatologic manifestations involving joints (14 patients with septic arthritis), bones (7 patients with osteomyelitis), muscles (5 patients with muscle abscess) and 5 patients with a combination of the above. Patients, who had septic arthritis required intervention, including surgical drainage and simple aspiration. Genitourinary infection including prostatic abscesses (4.48%) and renal abscess (5.97%), along with parotid gland abscess (3.73%), were less common primary diagnoses (Table 3).

Amongst these patients, indirect hemagglutination antibody against B. pseudomallei test was performed in 8 (5.97%) patients, and the titer showed less than, or equal to 1:20 in 1 patient, 1:160 in 1 patient, 1:640 in 4 patients, 1:1 280 in 2 patients, and more than, or equal to 1:2 560 in 1 patient (data not shown).

On the univariate analysis, gender and age of the patients did not affect the mortality. The high exposure occupations, including rice farmers, gardeners and planters, were not related

During the 10-year study period (2002-2011), a total of 134 patients, with a microbiologically-confirmed diagnosis of melioidosis, were recruited. The prevalence of inpatients with melioidosis was 36.8 per 100000 inpatients. The median age of affected patients was 49 years with the first and third quartile of 34 years and 58 years respectively. A total of 69.40% of the patients were men. In total, 29.10% of the patients were classified as high risk occupations for melioidosis.

The majority of cases were diagnosed throughout the year, rather than just during the rainy season. At least one underlying disease was documented in 99 (73.88%) of patients, and the most common predisposing condition was diabetes mellitus. Renal failure and abnormal hemoglobin disease were identified in 8 (5.97%) and 7 (5.22%) patients respectively. The majority

Table 1

Demographic data of 134 patients with melioidosis.

Characteristics

No. of patients (%)

Sex: male

Age in years

Occupation: high risk

Underlying diseases

At least 1 underlying disease

Diabetes mellitus

Chronic kidney disease

Thalassemia

Malignancy

CMT/Steroid/Immunosuppressant Outpatient cases Inpatient cases

93 (69.40) 49 (34, 58) 39 (29.10)

99 (73.88) 63 (47.01) 8 (5.97) 7 (5.22) 11 (8.21) 14 (10.45) 14 (10.45) 120 (89.55)

Table 2

Clinical data of 134 patients with melioidosis.

Characteristic No. of patients (%)

Fever prior to admission 95 (78.51)

Septic shock prior to admission 15 (12.40)

Septic shock during admission 26 (21.67)

Intensive care unit admission 25 (20.83)

Superimposed with nosocomial infection 15 (12.50)

Distribution of infection

Localized 67 (50.00)

Multifocal 17 (12.69)

Bacteremia 31 (23.13)

Disseminated infection 19 (14.18)

Death during intensive phase of treatment 12 (8.96)

Time for defervescence in days, median(IQR) 8 (4, 15)

with a higher mortality. The underlying conditions including diabetes mellitus, chronic kidney disease, thalassemia or hemoglobin diseases, malignancy and application of steroids or immunosuppressant, were not associated with a higher mortality rate. Septic shock prior to, and during admission was significantly associated with a higher mortality rate with an OR of 29.14 (7.02, 121.02), and 68.20 (8.20, 567.33) (P < 0.001), respectively. Bacteremia, disseminated infection and pulmonary involvement were also significantly related to a higher mortality. Intensive care unit admission was 100% mortality (Table 4).

On the other hand, the initial treatment with antibiotics, another than ceftazidime, or carbapenems, did raise the mortality. It was, however, emphasized that these antibiotics were replaced with ceftazidime and carbapenems a few days after the culture was reported. Patients who were initially treated with carbapenems did not show a lower mortality when compared with an initial treatment with ceftazidime.

4. Discussion

The prevalence and mortality of melioidosis among admitted patients in Songklanagarind Hospital was relatively low. The majority of cases had localized infection, with the lungs being the most commonly involved organ. The factors influencing mortality were pneumonia septic shock, positive blood culture for B. pseudomallei, superimposing with nosocomial infection and inappropriate antibiotic administration.

Although melioidosis was the most common cause of community-acquired septicemia, and an important pathogen, causing community-acquired pneumoniain in northeastern Thailand, the clinical data of this disease in southern Thailand is sparse [3]. The incidence of inpatients with melioidosis in this study (36.8:100000 inpatients) was similar to the reports from the central, eastern and northern parts of Thailand [6,8,9]. The incidence of this study was relatively low compared with the previous study in northeastern Thailand [6], along with those of the Northern Territory of Australia [10]. However, it was higher than those in Vietnam [11].

It is unfortunate that the data of melioidosis in 'land-linked' countries of Thailand including Loa PDR, Myanmar and Cambodia is scarce [12-14]. The previous study showed the paucity of cases of melioidosis occurring in the southern regions of Thailand. This could be explained by a lower prevalence of B. pseudomallei in soil, when compared with that in the northeastern region [6,15]. According to the arabinose assimilation property, one of the determinant indicating virulence, B. pseudomallei was

differentiated into two (2) biotypes, including those with the ability to utilize arabinose (Ara+) and those without the ability to utilize arabinose (Ara-) [16]. The significantly higher ratio of AraB. pseudomallei in environmental isolation from the northeastern region, than other regions, could influence the disease burden [7].

The median age of our study (49 years) was lower than the average ages of previous studies conducted in the northeastern, northern, and eastern parts of Thailand, whereas they were similar to the reports from the tropical northern parts of Australia, Malaysia, Singapore and northern Vietnam [3,8-11,1719]. Similar to this knowledge, most cases were male, which could be because of the fact that males were more often than not involved in outdoor activities leading to exposure from the soil and surface water, more so than females [2,6].

The proportion of patients with high exposure occupations including rice farmers and fruit agriculturists was quite different from the reports of other regions in Thailand except those of the eastern part of Thailand [3,5,6,8,9]. An explanation of this could be that the low proportion of rice farmers amongst the agriculturists in the southern regions. Secondly, the low prevalence of B. pseudomallei in soil could not influence the burden of melioidosis in people exposed to high amounts of soil and water [6,20].

Diabetes mellitus was well established as an important risk factor for melioidosis [3,18,21]. The most likely mechanism for this predisposition was the impairment of neutrophil functions including chemotaxis, phagocytosis, and intracellular killing, whilst the inhibitory effect of insulin on the growth of B. pseudomallei was unacceptable [22]. As pursuant to this knowledge, half of all patients had diabetes mellitus and 29 (45.31%) patients were diagnosed during the first time of admission. Unlike the report from northeastern Thailand, there were only 6 patients who had hematologic disease including thalassemia disease, thalassemia traits, along with other hemoglobin diseases [21].

Fever was the most common presentation. Some patients had no specific organ involvement in so saying, specific organ involvement was sequentially identified in the following days after admission. This encouraged the physicians to conduct a complete physical examination on patients with fevers and with non-specific organ involvement. This finding supported the previous report, which ranged melioidosis as differential diagnosis of acute undifferentiated fever in Thailand [23]. Our study also filled in the lack of data of melioidosis, as the cause of fever of an unknown origin in the endemic area [24].

The incidence of patients with blood stream and disseminated infection were lower than the incidence from other regions of Thailand, and nearly all the incidence from the Northern Territory of Australia, Malaysia and Singapore [3,10,18]. Because the site of study was a referral center, the low proportion of bacteremic patients was suspected primarily from the prescription of antibiotics prior to referral of the patients to our hospital. The possible different virulence of B. pseudomallei isolated in southern Thailand needs to be investigated further.

This study demonstrated pulmonary involvement as the most common manifestation among bacteremic and non-bacteremic patients. Similar to the prospective study in Australia, pneumonic patients in this study were primarily diagnosed rather than after another primary diagnosis [10]. The differences from previous studies were that there were 12 patients with pleural involvement including pleural effusion and empyema thoracis among 33 patients with pulmonary involvement [25-27]. Multi-lobar involvement was

Table 3

Organ involvement of melioidosis.

Organ involvement No. of patients (%)

Lung 33 (24.63)

- Reticular infiltration 6

- Patchy infiltration 12

- Cavity lesion 1

- Pleural effusion 12

- Lobar involvement

Left upper lobe 1

Right upper lobe 4

Right middle lobe 2

- Multilobar involvement 11

- Respiratory failure 13

- Acute respiratory 2

distress syndrome

Liver 26 (19.40)

- Require drainage 1

Spleen 28 (20.90)

- Require drainage 5

- Splenectomy 2

Bone and joints 20 (14.93)

- Osteomyelitis 7

- Muscle abscess 5

- Septic arthritis 14

Skin and soft tissue 25 (18.66)

Prostate gland 6 (4.48)

Kidney 8 (5.97)

Parotid gland 5 (3.73)

Intra-abdominal lymph node 3 (2.24)

Superficial lymph node 13 (9.70)

predominated rather than isolated lower lobar lesions which were described in the report from northern Australia, or confluent upper lobe lesions which were described in the report from northeastern Thailand [25-27]. There were no patients who had initial cavity lung lesion, whilst only 1 patient developed cavity lung lesions, these developed during admission.

As in the previous reports, the spleen is the most common source of visceral organ infection, followed by the liver and the genito-urinary organ [28]. Multiple abscesses, in our study, were more prevalent than isolated abscess, while isolated splenic abscess was commonest. These findings were similar to many reports, which demonstrated predominate splenic abscess

among melioidotic patients [3,18,28,29]. Because the splenic infection was rare, the detection of isolated splenic abscess, or splenic abscess in various conditions, in these endemic areas was suggestive to melioidosis [28-30].

During the last decade, the overall fatality rate in the northern and eastern regions of Thailand was similar to those in the northeast of Thailand [8,9,6]. The death rate accounted for only 8.96%, which is relatively lower than the previous study, in several parts of Thailand, and even in Malaysia and Singapore which is located nearby. It is, however, similar to the last 5 years of reports from Darwin, Australia [8,10,6].

This finding raised the aspect that the regional strains of B. pseudomallei in the south of Thailand might have differences in pathogenicity and virulence [15]. In addition, the differences in host genetic and pathogen-host response, which were previously described, have to be studied further [31]. The high proportion of pulmonary involvement was significantly associated with a higher mortality rate, compared with patients without pulmonary involvement. Although the previous study demonstrated the explanation of the low mortality rate, in pneumonic melioidotic patients, was contributed to a low infecting load of B. pseudomallei from inhalation [31], this study showed almost all pneumonic patients had blood stream infections, which caused a higher infecting load than isolated inhalation. However, the predictor of severity, which was determined by individual genetic polymorphism, has to be studied further [32]. The delay in the administration of appropriate antibiotics against B. pseudomallei, which was well established as an important risk factor for the mortality, was also demonstrated in this study [3]. Similarly the treatment concept of other gram negative septicemia, along with the lack of effective bactericidal agents, contributed to the higher death rate [8]. We have demonstrated the incidence, manifestations and mortality of melioidosis in southern Thailand. Pneumonia, septic shock and bacteremia are risk factors for mortality in this study. An early diagnosis, coupled with appropriate antibiotics, during initial and maintenance phases, improve the outcome of the disease. Further investigation into molecular epidemiology, as well as specific host immune response of B. pseudomallei in the south of Thailand, is needed.

Table 4

Risk factors influencing mortality for 134 patients with melioidosis.

Risk factors No. (%) of survivors No. (%) of dead OR P-value

n = 122 n =12 (95%CI)

Sex: male 84 (68.9) 9 (75.0) 0.74 (0.19, 2.88) 0.660

Age in years, median(IQR) 48 (31, 58) 52 (49.2, 56.2) 1.03 (0.99, 1.07) 0.167

High exposure occupation 36 (30.3) 3 (25.0) 0.77 (0.20, 3.01) 0.705

DM 55 (45.1) 8 (66.7) 2.44 (0.70, 8.52) 0.163

Chronic kidney disease 8 (6.6) 0 — —

Thalassemia 7 (5.7) 0 — —

Malignancy 10 (8.2) 1 (8.3) 1.02 (0.12, 8.71) 0.987

CMT/Steroid/Immunosuppressant 12 (9.8) 2 (16.7) 1.83 (0.36, 9.37) 0.466

Septic shock prior to admission 7 (6.4) 8 (66.7) 29.14 (7.02, 121.02) <0.001

Septic shock during admission 15 (13.9) 11 (91.7) 68.20 (8.20, 567.33) <0.001

Intensive care unit admission 13 (12) 12 (100.0) — —

Superimposed with nosocomial infection 10 (9.3) 5 (41.7) 7.00 (1.87, 26.18) 0.004

Distribution of infection

- Localized infection 67 (54.9) 0 — —

- Multifocal infection 15 (12.3) 2 (16.7) 1.43 (0.28, 7.15) 0.666

- Bacteremia/disseminated infection 40 (32.8) 10 (83.3) 10.25 (2.14, 49.00) 0.004

Lung involvement 24 (19.7) 9 (75.0) 12.25 (3.08, 48.73) <0.001

Appropriate antibiotics use 111 (91.0) 3 (37.5) 37.67 (7.29, 238.94) <0.001

Conflict of interest statement

We declare that we have no conflict of interest. References

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