Epidemiology and genetic diversity of Burkholderia pseudomallei from Riau Province, Indonesia.

Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, that is common in tropical and subtropical countries including Southeast Asia and Northern Australia. The magnitude of undiagnosed and untreated melioidosis across the country remains unclear. Given its proximity to regions with high infection rates, Riau Province on Sumatera Island is anticipated to have endemic melioidosis. This study reports retrospectively collected data on 68 culture-confirmed melioidosis cases from two hospitals in Riau Province between January 1, 2009, and December 31, 2021, with full clinical data available on 41 cases. We also describe whole genome sequencing and genotypic analysis of six isolates of B. pseudomallei. The mean age of the melioidosis patients was 49.1 (SD 11.5) years, 85% were male and the most common risk factor was diabetes mellitus (78%). Pulmonary infection was the most common presentation (39%), and overall mortality was 41%. Lung as a focal infection (aOR: 6.43; 95% CI: 1.13-36.59, p = 0.036) and bacteremia (aOR: 15.21; 95% CI: 2.59-89.31, p = 0.003) were significantly associated with death. Multilocus sequence typing analysis conducted on six B.pseudomallei genomes identified three sequence types (STs), namely novel ST1794 (n = 3), ST46 (n = 2), and ST289 (n = 1). A phylogenetic tree of Riau B. pseudomallei whole genome sequences with a global dataset of genomes clearly distinguished the genomes of B. pseudomallei in Indonesia from the ancestral Australian clade and classified them within the Asian clade. This study expands the known presence of B. pseudomallei within Indonesia and confirms that Indonesian B. pseudomallei are genetically linked to those in the rest of Southeast Asia. It is anticipated that melioidosis will be found in other locations across Indonesia as laboratory capacities improve and standardized protocols for detecting and confirming suspected cases of melioidosis are more widely implemented.

A comparative analysis between next-generation sequencing and conventional culture method to detect empyema-associated microorganisms: A systematic review.

Empyema poses a significant global health concern, yet identifying responsible bacteria remains elusive. Recent studies question the efficacy of conventional pleural fluid culture in accurately identifying empyema-causing bacteria. The aim of this study was to compare diagnostic capabilities of next-generation sequencing (NGS) with conventional pleural fluid culture in identifying empyema-causing bacteria. Five databases (Google Scholar, Science Direct, Cochrane, Research Gate, and PubMed) were used to search studies comparing conventional pleural fluid culture with NGS for identifying empyema-causing bacteria using keywords. Positive results identified through conventional pleural fluid culture and NGS were extracted. In addition, bacterial profiles identified by NGS were also documented. Joanna-Briggs Institute (JBI) critical appraisal tool was employed to assess quality of included studies. Descriptive analysis was employed to present outcome of interests. From five databases, three studies, with 354 patients, were included. Findings from three studies showed that NGS outperformed conventional pleural fluid culture in detecting empyema-causing bacteria even in culture-negative samples. Moreover, dominant bacterial profiles identified through NGS included Streptococcus pneumoniae, Staphylococcus aureus, and anaerobic bacteria. In conclusion, NGS outperforms conventional pleural fluid culture in detection empyema-causing bacteria, yet further studies with larger samples and broader bacterial profiles are needed to increase confidence and urgency in its adoption over conventional pleural fluid culture.

Efficacy of pretomanid-containing regiments for drug-resistant tuberculosis: A systematic review and meta-analysis of clinical trials.

Concerns regarding the rise of drug-resistant tuberculosis (DR-TB) infections and the need for new drugs with shorter treatment time and fewer side effects have been voiced by the World Health Organization (WHO). The WHO revised its guideline to treat multidrug resistant tuberculosis (MDR-TB) with a 6-month course of BPaLM (bedaquiline, pretomanid, linezolid and moxifloxacin) in 2022. However, a thorough study and meta-analysis of available evidence is required due to the limited confidence of the evidence confirming the effectiveness of pretomanid-containing regiments. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of pretomanid-containing regiments in treating DR-TB patients. Data from six search engines were searched using inclusion criteria based on the PICOS framework. The keywords of pretomanid and tuberculosis or their alternatives were used. Using RoB2 Cochrane risk-of-bias tool for randomized clinical trials, data were independently extracted and the quality of the data was evaluated. Odds ratio (OR) and heterogeneity tests were used and the findings were presented in ORs and forest plots. A total of four studies with 237 patients was included in the final analysis and 204 (86%) patients had favorable outcome (cured) and 33 (14%) was not cured. Pretomanid-containing regimen (OR: 46.73; 95%CI: 11.76-185.7) and BPaLM/BPaL (OR: 41.67; 95%CI: 8.86-196.73) regimens were associated with favorable outcome (cured). This meta-analysis indicates that the pretomanid-containing regimen and the BPaLM/BPaL regimen could increase the chance to have favorable outcome in DR-TB patients.

Multicenter Study of the Risk Factors and Outcomes of Bloodstream Infections Caused by Carbapenem-Non-Susceptible Acinetobacter baumannii in Indonesia.

The prevalence of bacteremia caused by carbapenem-non-susceptible Acinetobacter baumannii (CNSAB) continues to increase, and it is associated with a high mortality rate. Early recognition of infection and mortality determinants risk factors is necessary for adequate antibiotic administration. We aimed to determine the risk factors and outcomes of CNSAB bacteremia in Indonesia. A multicenter case-control study was conducted in three referral hospitals in Indonesia. Data were collected retrospectively from January 2019 to December 2021. Cases were defined as patients with bacteremia where CNSAB was isolated from the blood, while the controls were patients with bacteremia caused by carbapenem-susceptible A. baumannii (CSAB). Risk factors for bacteremia and mortality associated with CNSAB bacteremia were determined using univariates analysis (chi-squared and Student's t-test or Mann-Whitney test) and multivariate logistic regression analysis. A total of 144 bacteremia patients were included, of whom 72 patients were for each case and control group. The final model of multivariate regression analysis revealed that bacteremia source from the lower respiratory tract (adjusted odds ratio (aOR): 3.24; 95% CI: 1.58-6.63, p = 0.001) and the use of central venous catheter (aOR: 2.56; 95% CI: 1.27-5.18; p = 0.009) were independent risk factors for CNSAB bacteremia. Charlson Comorbidity Index ≥ 4 (aOR: 28.56; 95% CI: 3.06-265.90, p = 0.003) and Pitt Bacteremia Score ≥ 4 (aOR: 6.44; 95% CI: 1.17-35.38; p = 0.032) were independent risk factors for mortality due to CNSAB bacteremia. Only high Pitt Bacteremia Score was an independent risk factor for mortality of CSAB bacteremia. In conclusion, we identified the risk factors for CNSAB-associated bacteremia and the risk factors for death, which are relevant for empiric therapy and infection control prevention, as well as prognosis evaluation of patients with bloodstream infections.

The susceptibility pattern and distribution of blaOXA-23 genes of clinical isolate Acinetobacter baumannii in a tertiary hospital, Indonesia.

INTRODUCTION: Acinetobacter baumannii, a pathogen of concern in hospitals worldwide, has diverse antimicrobial resistance mechanisms leading to limiting the antibiotic options and carbapenemase enzyme production is one of the common mechanisms in carbapenem resistance. The epidemiology and resistance pattern of clinical isolates are critical in developing a prevention and treatment strategy. The aim of this was to determine the prevalence and resistance pattern of carbapenem non-susceptible strains (CNS) A. baumannii at Arifin Achmad General Hospital, Pekanbaru, Indonesia. METHODOLOGY: Data were retrieved from the culture and susceptibility test results from various clinical specimens from January 2015 to December 2019. A susceptibility test was conducted using Vitek 2 Compact following the manufacturer's protocol. To explore the genetic profile of CNS A. baumannii, we amplified the blaOXA-23 and blaOXA-51 genes, carbapenemase producing genes, using a duplex polymerase chain reaction (PCR) among 24 isolates Chi-squared was used to assess the factors associated with the presence of CNS A. baumannii. RESULTS: Between 2015-2019, 1.263 A. baumannii isolates were tested and the prevalence of CNS A. baumannii was 50%. The trend decreased from 53% in 2016 to 45% in 2019. The proportion of CNS A. baumannii was higher among samples from patients treated in the Intensive Care Unit (ICU) compared to non-ICU (p < 0.001). The CNS A. baumannii was also more frequently detected from sputum than from non-sputum samples (p = 0.009). CNS A. baumannii were highly resistant to almost all antibiotics and the highest susceptibility was to amikacin, tigecycline, and trimethoprim/sulfamethoxazole with 64%, 53%, and 43%, respectively. The blaOXA-23 gene was detected in 92% of tested CNS A. baumannii isolates. CONCLUSIONS: The prevalence of CNS A. baumannii is high at Arifin Achmad Hospital Riau, Indonesia. This is also supported by the high prevalence of the blaOXA-23 gene among tested isolates. Based on the antibiotic susceptibility pattern there are limited antibiotic choices for CNS A. baummannii urging the strengthening of antimicrobial stewardship programs in the country.

Development of Local Birth Weight Reference Based on Gestational Age and Sex in South Kalimantan Province, Indonesia.

Purpose: Percentile reference of babies' birth weight is an effective reference tool for early detection of the risk of neonatal morbidity and impaired growth. However, the lack of minimum local and national perinatal data makes its development in Indonesia difficult. This study aims to develop a local birth weight percentile reference for babies based on gestational age and sex by utilizing local data in South Kalimantan Province which is one of the provinces with the highest neonatal mortality rate in Indonesia. Patients and Methods: All single live newborns who were born and were recorded in 20 primary healthcare centers, between 1 June 2016 and 30 June 2017, were included in the study. Birth weight percentiles of infants were calculated using the weighted average method. The study focused on neonates born with gestational age from 36 to 40 weeks. Results: A local birth weight reference for babies has been developed. According to our local reference, the proportion of male newborns with a birth weight < 10th percentile was higher (7.0%) than the existing Indonesian (4.2-4.3%) and international references (3.3-6.2%). Similarly, the proportion of female newborns with a birth weight <10th percentile was higher (6.5%) than the existing Indonesian references (3.6-4.4%) and the global reference (5.8%) but lower than the Intergrowth 21st project (7.2%). The differences suggest that relative birth weight will likely be underestimated (overestimated) if other percentile references are used for the local population. Conclusion: A local birth weight percentile reference for babies in South Kalimantan Province based on gestational age (36-40 weeks) and sex has been developed. Access to the local data, as baseline information, will allow the compilation and comparison of pregnancy-related outcomes across provinces in Indonesia. Consequently, reliable national perinatal data can be strengthened to establish the national references for newborns' anthropometric measurements.

Possible Cases of SARS-CoV-2 Reinfection In Pekanbaru, Indonesia.

Confirmed and possible reinfection cases of SARS-CoV-2 have been reported from various countries. Here we present two cases of possible SARS-CoV-2 reinfection in Pekanbaru, Indonesia. A 26 years old female and a 27 years old male healthcare workers were first confirmed by PCR with high Ct-value (>35) while presenting no or mild symptoms, respectively. In more than one month since the last negative test results, both patients developed typical COVID-19 symptoms; fever and anosmia. RT-PCR results for SARS-CoV-2 were positive with Ct-value less than 30. The timeframe between 1st and 2nd episode, negative test result between episodes, and epidemiological risk factor strengthened the possibility of reinfection. However, we did not have whole genome sequence (WGS) or viral viability data to further confirm reinfection with different viable virus. The requirement of viral WGS data to confirm true reinfection cases calls for investment in whole genome sequencing platform in public health laboratories. We encourage standardized definition of SARS-CoV-2 reinfection case in order to be able to investigate and observe such cases.

Distribution of Carbapenemase Genes among Carbapenem-Non-Susceptible Acinetobacter baumanii Blood Isolates in Indonesia: A Multicenter Study.

Carbapenem non-susceptible Acinetobacter baumannii (CNSAB) is an important pathogen that causes nosocomial bacteremia among critically ill patients worldwide. The magnitude of antibiotic resistance of A. baumanii in Indonesia is expected to be significant; however, the data available are limited. The aim of this study was to analyze the genetic profiles of CNSAB isolates from patients with bacteremia in Indonesia. CNSAB isolates from blood cultures of bacteremia patients in 12 hospitals in Indonesia were included. The blood cultures were conducted using the BacT/Alert or BACTEC automated system. The CNSAB were identified with either Vitek 2 system or Phoenix platform followed by a confirmation test using a multiplex polymerase chain reaction (PCR) assay, targeting the specific gyrB gene. The carbapenemase genes were detected by multiplex PCR. In total, 110 CNSAB isolates were collected and were mostly resistant to nearly all antibiotic classes. The majority of CNSAB isolates were susceptible to tigecycline and trimethoprim-sulfamethoxazole (TMP-SMX), 45.5% and 38.2%, respectively. The blaOXA-51-like gene was identified in all CNSAB isolates. Out of the total, 83.6% of CNSAB isolates had blaOXA-23-like gene, 37.3% blaOXA-24-like gene, 4.5% blaNDM-1 gene, 0.9% blaIMP-1 gene, and 0.9% blaVIM gene. No blaOXA-48-like gene was identified. The blaOXA-23-like gene was the predominant gene in all except two hospitals. The presence of the blaOXA-24-like gene was associated with resistance to tigecycline, amikacin, TMP-SMX and cefoperazone-sulbactam, while blaOXA-23-like gene was associated with resistance to TMP-SMX and cefoperazone-sulbactam. In conclusion, the blaOXA-23-like gene was the predominant gene among CNSAB isolates throughout Indonesia. A continuous national surveillance system needs to be established to further monitor the genetic profiles of CNSAB in Indonesia.

The development of an alternative growth chart for estimated fetal weight in the absence of ultrasound: Application in Indonesia.

A fetal growth chart is a vital tool for assessing fetal risk during pregnancy. Since fetal weight cannot be directly measured, its reliable estimation at different stages of pregnancy has become an essential issue in obstetrics and gynecology and one of the critical elements in developing a fetal growth chart for estimated fetal weight. In Indonesia, however, a reliable model and data for fetal weight estimation remain challenging, and this causes the absence of a standard fetal growth chart in antenatal care practices. This study has reviewed and evaluated the efficacy of the prediction models used to develop the most prominent growth charts for estimated fetal weight. The study also has discussed the potential challenges when such surveillance tools are utilized in low resource settings. The study, then, has proposed an alternative model based only on maternal fundal height to estimate fetal weight. Finally, the study has developed an alternative growth chart and assessed its capability in detecting abnormal patterns of fetal growth during pregnancy. Prospective data from twenty selected primary health centers in South Kalimantan, Indonesia, were used for the proposed model validation, the comparison task, and the alternative growth chart development using both descriptive and inferential statistics. Results show that limited access to individual fetal biometric characteristics and low-quality data on personal maternal and neonatal characteristics make the existing fetal growth charts less applicable in the local setting. The proposed model based only on maternal fundal height has a comparable ability in predicting fetal weight with less error than the existing models. The results have shown that the developed chart based on the proposed model can effectively detect signs of abnormality, between 20 and 41 weeks, among low birth weight babies in the absence of ultrasound. Consequently, the developed chart would improve the quality of fetal risk assessment during pregnancy and reduce the risk of adverse neonatal outcomes.

Improving the Information Availability and Accessibility of Antenatal Measurements to Ensure Safe Delivery: A Research-Based Policy Recommendation to Reduce Neonatal Mortality in Indonesia.

PURPOSE: Assessing the risks and preventable causes of maternal and neonatal mortality requires the availability of good-quality antenatal information. In Indonesia, however, access to reliable information on pregnancy-related results remains challenging. This research has proposed a research-based policy recommendation to improve availability and accessibility to vital information on antenatal examinations. PATIENTS AND METHODS: Descriptive statistics were used to characterize midwives' capabilities in routinely gathering and recording antenatal information during pregnancy. The investigation was carried out among 19 midwives in South Kalimantan, Indonesia, from April 2016 to October 2017. Antenatal data on 4946 women (retrospective study) and 381 women (prospective study) have been accessed through a scientific and technical training program. RESULTS: To date, lack of timely access to antenatal information has hampered the process of reducing neonatal mortality in Indonesia. The post-training statistical analysis showed that the training has significantly improved midwives' scientific knowledge and technical abilities in providing more reliable data on antenatal measurements. CONCLUSION: Consistent scientific and technical training among midwives is required to update their knowledge and skills, particularly those relating to documenting the results of antenatal examinations at different stages of pregnancy and using that information to assess potential risks and identify necessary interventions. This should also be followed by routine monitoring on the quality of collected antenatal data. This can be one of the enabling actions to achieve the 2030 Sustainable Development Goals target in reducing neonatal mortality in Indonesia.

The Impact of Scientific and Technical Training on Improving Databases' Adequacy for Fetal Growth Chart Development in Limited-Resource Settings: A Case Study in the Province of South Kalimantan, Indonesia.

OBJECTIVES: To assess the impact of scientific and technical training on midwives' abilities in collecting and recording the key performance indicators for fetal growth chart development in limited-resource settings. METHODS: A descriptive design was used to describe midwives' abilities in timely collecting and recording the minimum data required to estimate fetal weight and develop fetal growth chart. The study was conducted among 19 urban and rural midwives in South Kalimantan, Indonesia, between April 2016 and October 2017. The training provided access to antenatal care information on 4,946 women (retrospective cohort study) and 381 women (prospective cohort study). RESULTS: The average amount of recorded antenatal care data on the key performance indicators of fetal growth assessment has been significantly improved (from 33.4% to 89.1%, p-value < 0.0005) through scientific and technical training. CONCLUSIONS: Scientific knowledge and technical abilities have enabled midwives to timely record routine data of the key performance indicators for fetal growth surveillance. Access to this information is vital during different stages of pregnancy. The information can be utilised as evidence-based guidelines to assess fetal risks through fetal weight estimation and to develop fetal growth chart that is currently not available in Indonesian primary healthcare systems.

Foetal weight prediction models at a given gestational age in the absence of ultrasound facilities: application in Indonesia.

BACKGROUND: Birth weight is one of the most important indicators of neonatal survival. A reliable estimate of foetal weight at different stages of pregnancy would facilitate intervention plans for medical practitioners to prevent the risk of low birth weight delivery. This study has developed reliable models to more accurately predict estimated foetal weight at a given gestation age in the absence of ultrasound facilities. METHODS: A primary health care centre was involved in collecting retrospective non-identified Indonesian data. The best subset model selection criteria, coefficient of determination, standard deviation, variance inflation factor, Mallows Cp, and diagnostic tests of residuals were deployed to select the most significant independent variables. Simple and multivariate linear regressions were used to develop the proposed models. The efficacy of models for predicting foetal weight at a given gestational age was assessed using multi-prediction accuracy measures. RESULTS: Four weight prediction models based on fundal height and its combinations with gestational age (between 32 and 41 weeks) and ultrasonic estimates of foetal head circumference and foetal abdominal circumference have been developed. Multiple comparison criteria show that the proposed models were more accurate than the existing models (mean prediction errors between - 0.2 and 2.4 g and median absolute percentage errors between 4.1 and 4.2%) in predicting foetal weight at a given gestational age (between 35 and 41 weeks). CONCLUSIONS: This research has developed models to more accurately predict estimated foetal weight at a given gestational age in the absence of ultrasound machines and trained ultra-sonographers. The efficacy of the models was assessed using retrospective data. The results show that the proposed models produced less error than the existing clinical and ultrasonic models. This research has resulted in the development of models where ultrasound facilities do not exist, to predict the estimated foetal weight at varying gestational age. This would promote the development of foetal inter growth charts, which are currently unavailable in Indonesian primary health care systems. Consistent monitoring of foetal growth would alleviate the risk of having inter growth abnormalities, such as low birth weight that is the most leading factor of neonatal mortality.

Emergence of Melioidosis in Indonesia and Today's Challenges.

A recent modeling study estimated that there could be as many as 20,000 human melioidosis cases per year in Indonesia, with around 10,000 potential deaths annually. Nonetheless, the true burden of melioidosis in Indonesia is still unknown. The Indonesia Melioidosis Network was formed during the first melioidosis workshop in 2017. Here, we reviewed 101 melioidosis cases (99 human and two animal cases) previously reported and described an additional 45 human melioidosis cases. All 146 culture-confirmed cases were found in Sumatra (n = 15), Java (n = 104), Kalimantan (n = 15), Sulawesi (n = 11) and Nusa Tenggara (n = 1). Misidentification of Burkholderia pseudomallei was not uncommon, and most cases were only recently identified. We also evaluated clinical manifestations and outcome of recent culture-confirmed cases between 2012 and 2017 (n = 42). Overall, 15 (36%) cases were children (age <15 years) and 27 (64%) were adults (age ≥15 years). The overall mortality was 43% (18/42). We conducted a survey and found that 57% (327/548) of healthcare workers had never heard of melioidosis. In conclusion, melioidosis is endemic throughout Indonesia and associated with high mortality. We propose that top priorities are increasing awareness of melioidosis amongst all healthcare workers, increasing the use of bacterial culture, and ensuring accurate identification of B. pseudomalleiand diagnosis of melioidosis.

The Impact of Scientific and Technical Training on Improving Routine Collection of Antenatal Care Data for Maternal and Foetal Risk Assessment: A Case Study in the Province of South Kalimantan, Indonesia.

OBJECTIVES: First, to assess the impact of scientific and technical training on midwives' abilities in collecting and recording the results of routine antenatal care examinations. Second, to explore midwives' views with regard to factors affecting their abilities to successfully complete the data documentation tasks. METHODS: The study was conducted in South Kalimantan, Indonesia (April 2016-October 2017). Nineteen urban and rural midwives were selected. Access to antenatal care information on 4,946 women (retrospective cohort study) and 381 women (prospective cohort study) was granted. A descriptive and exploratory design was used to describe midwives' abilities and challenges pertaining to timely collection and recording of results concerning antenatal care examinations. RESULTS: Scientific and technical training has significantly improved the average amount of recorded antenatal care data (from 17.5% to 62.1%, p-value < 0.0005). Lack of awareness, high workload, and insufficient skills and facilities are the main reasons for the database gaps. CONCLUSIONS: The training has equipped midwives with scientific knowledge and technical abilities to allow routine collection of antenatal care data. Provision and adequate use of this information during different stages of pregnancy is crucial as an evidence-based guideline to assess maternal and foetal risk factors to ending preventable mortality.