Evidence of Placental Villous Inflammation and Apoptosis in Third-Trimester Symptomatic SARS-CoV-2 Maternal Infection.

PURPOSE: In view of conflicting reports on the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to infect placental tissue, this study aimed to further evaluate the impact of inflammation and placental damage from symptomatic third-trimester maternal COVID-19 infection. MATERIALS AND METHODS: This case-control study included 32 placenta samples each from symptomatic COVID-19 pregnancy and normal non-COVID-19 pregnancy. The villous placental area's inflammatory expression [angiotensin converting enzyme-2 (ACE-2), transmembrane protease serine-2 (TMPRSS2), interferon-γ (IFN-γ), interleukin-6 (IL-6), and SARS-CoV-2 spike protein] and apoptotic rate were examined using immunohistochemistry and Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Comparison and correlation analysis were used based on COVID-19 infection, placental SARS-CoV-2 spike protein evidence, and maternal severity status. RESULTS: Higher expressions of TMPRSS2, IFN-γ, and trophoblast apoptotic rate were observed in the COVID-19 group (p<0.001), whereas ACE-2 and IL-6 expressions were not significantly different from the control group (p>0.05). Additionally, SARS-CoV-2 spike protein was detected in 8 (25%) placental samples of COVID-19 pregnancy. COVID-19 subgroup analysis revealed increased IFN-γ, trophoblast, and stromal apoptosis (p<0.01). Moreover, the results of the current study revealed no correlation between maternal COVID-19 severity and placental inflammation as well as the apoptotic process. CONCLUSION: The presence of SARS-CoV-2 spike protein as well as altered inflammatory and apoptotic processes may indicate the presence of placental disturbance in third-trimester maternal COVID-19 infection. The lack of correlation between placental disruption and maternal severity status suggests the need for more research to understand the infection process and any potential long-term impacts on all offsprings born to COVID-19-infected pregnant women.

Management of wounds in diabetes by administering allicin and quercetin in emulsion form as wound medicine in diabetic rat models.

Wounds in diabetes is a complex problem that requires effective treatment at a high cost. Adjuvant therapy from natural bioactive elements can be an alternative to overcome problems in diabetic wound healing disorders. Allicin and quercetin are natural bioactive substances contained in several fruit or vegetable plants that have various pharmacological effects. The purpose of this study was to determine the effect of allicin and quercetin in emulsion form as wound medicine in helping the wound healing process. Diabetic wistar rats with wounds on their backs measuring 1 × 1 cm were divided into four treatment groups which were given wound medicine once a day for seven days according to their distribution. The wound healing process was evaluated on the third and seventh day. Data were observed and analyzed using appropriate statistical tools. Measurement of wound healing indicators was carried out by examining wound contraction and histopathological examination showing that the treatment group given the allicin and quercetin formula experienced an improvement compared to the treatment group without allicin and quercetin. Allicin and quercetin increase the percentage of wound contraction, increase the density of blood vessels and the epithelialization process in the wound so that the wound healing process becomes faster. In conclusion, allicin and quercetin can be effective adjuvant therapies in helping wound healing in diabetes. Wound medication in the form of an emulsion is an effective choice, because it can maintain the stability of the allicin and quercetin content and can make the wound environment moist.

Metagenome and Resistome Analysis of Beta-Lactam-Resistant Bacteria Isolated from River Waters in Surabaya, Indonesia.

Antimicrobial agents are administered to humans and livestock, and bacterial antimicrobial resistance (AMR) and antimicrobial agents are released into the environment. In this study, to investigate the trend of AMR in humans, livestock, and the environment, we performed a metagenomic analysis of multidrug-resistant bacteria with CHROMagar ESBL in environmental river water samples, which were collected using syringe filter units from waters near hospitals, downtown areas, residential areas, and water treatment plants in Surabaya, Indonesia. Our results showed that Acinetobacter, Pseudomonas, Aeromonas, Enterobacter, Escherichia, and Klebsiella grew in CHROMagar ESBL; they were most frequently detected in water samples from rivers surrounding hospitals contaminated with various AMR genes (ARGs) in high levels. These results identified bacteria as ARG reservoirs and revealed that hospitals could be sources for various ARGs disseminated into the environment. In conclusion, this study details a novel metagenomic analysis of collected bacteria in environmental water samples using a syringe filter unit for an AMR epidemiological study based on the One Health approach.

Impact TB co-infections on immune tolerance among people living with HIV: a systematic review.

BACKGROUND: The high-burden regions of Sub-Saharan Africa, which accounted for greater than 70% of the HIV epidemic, are disproportionately affected by the high rates of TB coinfection. This might be explained by, the low immune tolerance of the population due to malnutrition and chronic infections aggravating immune suppression. In this review, we discuss the immunopathogenesis of this common co-infection that causes significant morbidity and mortality in people living with HIV globally. METHODS: We used published studies using a two-step search strategy. Initial search of Pub Med Central and Google Scholar was undertaken followed by an analysis of the keywords. A second search using all the reference list of all identified reports and articles was searched for additional studies. Literature published as of January 1, 1981, that meets the inclusion criteria were considered. Qualitative data was extracted from papers included in the review. RESULT: Mortality occurs at both ends of the immunological spectrum of TB at one end HIV uninfected patient dies from asphyxiation from acute massive hemoptysis due to cavitary TB; at the other end, and far more frequently HIV-infected patient with disseminated TB dies from overwhelming infection with less evidence of focal pathology. There is no clear sign that the HIV-TB epidemic is slowing, especially considering the emergence of increasingly drug-resistant strains of MTB. A major challenge for the future is to discover immune correlates of TB protection and TB disease risk. Failure to define this conclusively has hindered TB prevention strategies, including the design of new TB vaccines to replace BCG, which provides only shortlived efficacy, prevents severe forms of the extra-pulmonary disease and is contraindicated in PLHIV. CONCLUSION: Understanding TB and HIV infection through immunological advances needs to be combined to describe the complex interactions between TB and HIV and the effects of ART. The complex interactions between the individual components of innate and acquired immune responses to TB and HIV infection is also likely to be the next step forward.

The use of antibiotic prophylaxis in patients undergoing urologic procedures in an academic hospital Surabaya: A retrospective study.

INTRODUCTION: Prophylactic antibiotics in urological procedures are essential to prevent postoperative infections. A different approach in selecting antibiotic prophylaxis according to the type of procedure is needed. METHODOLOGY: A retrospective study was carried out at an academic hospital in Surabaya, Indonesia, by collecting medical records of patients who underwent urologic procedures within 2019- 2020, including microbiological data. RESULT: One hundred seventy-nine urological procedures were assessed. Antibiotic prophylaxis was administered in the clean-contaminated and clean procedures (93.2% and 6.8%, respectively). Ceftriaxone was commonly used (69.3%), single-dose, one day before the surgery. Gram-negative bacteria were widely found in the urinary culture of patients (75.2%). E. coli, K. pneumoniae, and P. aeruginosa were dominating with low susceptibility to cephalosporins. ESBL-producing bacteria were E. coli (64%) and K. pneumoniae (89%). CONCLUSIONS: The 3rd generation cephalosporins (ceftriaxone) are mostly used in urological procedures despite the low susceptibility against this antibiotic in cultured E coli, P. aeruginosa, and K. pneumonia. The aminoglycosides have relatively good activity and have been suggested in several guidelines for urologic procedures, such as prostate and urinary tract stone procedures. It is crucial to consider the incision site, type of procedure, and bacterial profile in the hospital to propose antibiotic prophylaxis guidelines.

HAART induced inflammation, toxicity and its determinants among HIV positive children in Addis Ababa, Ethiopia.

Background: Highly Active Antiretroviral therapy (HAART) plays significant role in reduction of mortality among children infected with HIV. Despite the inevitable impact of HAART on inflammation and toxicity, there is limited evidence on its impact among children in Ethiopia. Moreover, evidence on contributing factors to toxicity has been poorly described. Hence, we evaluated HAART induced inflammation and toxicity among children taking HAART in Ethiopia. Method: This cross-sectional study was conducted among children (<15 years old) taking HAART in Ethiopia. Stored plasma samples and secondary data from a previous study on HIV-1 treatment failure were used for this analysis. By 2018, a total of 554 children were recruited from randomly selected 43 health facilities in Ethiopia. The different levels of liver (SGPT), renal (Creatinine) and hematologic toxicity (Hemoglobin) toxicity were assessed using established cut-off value. Inflammatory biomarkers (CRP and vitamin-D) were also determined. Laboratory tests were done at the national clinical chemistry laboratory. Clinical and baseline laboratory data were retrieved from the participant's medical record. Questionnaire was also administered to study guardians to assess individual factors to inflammation and toxicity. Descriptive statistics was used to summarize the characteristics of the study participants. Multivariable analysis was conducted and considered significant at P < 0.05. Result: Overall 363 (65.6%) and 199 (36%) of children taking HAART in Ethiopia developed some level of inflammation and vitamin-D in-sufficiency, respectively. A quarter of the children 140 (25.3%) were at Grade-4 liver toxicity while renal toxicity were 16 (2.9%). A third 275 (29.6%) of the children also developed anemia. Children who were on TDF+3 TC + EFV, those who were not virally suppressed and children with liver toxicity were at 17.84 (95%CI = 16.98, 18.82), 2.2 (95%CI = 1.67, 2.88) and 1.20 (95%CI = 1.14, 1.93) times risk of inflammation, respectively. Children on TDF+3 TC + EFV, those with CD4 count of <200 cells/mm3 and with renal toxicity were at 4.10 (95%CI = 1.64, 6.89), 2.16(95%CI = 1.31, 4.26) and 5.94 (95%CI = 1.18, 29.89) times risk of vitamin-D in-sufficiency, respectively. Predictors of liver toxicity were history of HAART substitution (AOR = 4.66; 95%CI = 1.84, 6.04) and being bedridden (AOR = 3.56; 95%CI = 2.01, 4.71). Children from HIV positive mother were at 4.07 (95%CI = 2.30, 6.09) times risk of renal toxicity while the different type of HAARTs had different level of risk for renal toxicity AZT+3 TC + EFV (AOR = 17.63; 95%CI = 18.25, 27.54); AZT+3 TC + NVP (AOR = 22.48; 95%CI = 13.93, 29.31); d4t+3 TC + EFV (AOR = 4.34; 95%CI = 2.51, 6.80) and d4t+3 TC + NVP (AOR = 18.91; 95%CI = 4.87, 27.74) compared to those who were on TDF+3 TC + NVP. Similarly, children who were on AZT+3 TC + EFV were at 4.92 (95%CI = 1.86, 12.70) times risk of anemia compared to those who were on TDF+ 3 TC + EFZ. Conclusion: The high level of HAART induced inflammation and liver toxicity among children calls for the program to consider safer regimens for pediatric patients. Moreover, the high proportion of vitamin-D in-sufficiency requires program level supplement. The impact of TDF+3 TC + EFV on inflammation and vitamin-D deficiency calls for the program to revise this regimen.

Burden of HIV, HBV and syphilis among children in urban Ethiopia: Community-based cross-sectional study.

BACKGROUND: Children have largely been ignored in the fight against sexually transmitted infection (STI). Among children, STI is reported to be a globally emerging public health challenge. We evaluated the burden of HIV, hepatitis B virus (HBV) and syphilis among children (< 15 years old) and its determinants in urban Ethiopia. METHODS: For this study, we used data from the Ethiopian Population-based HIV Impact Assessment (EPHIA), collected through a nationally representative, community-based study conducted in Ethiopia from October 2017 to April 2018. We used plasma samples from 4729 children. Moreover, we linked the data and analysed them alongside their respective mothers. Child and maternal HIV status was determined using the national testing algorithm. Plasma samples from children were also tested for syphilis and HBV surface antigen. A descriptive analysis was done followed by bivariable analysis with 95% confidence interval (CI) at a significance level of p < 0.05. We finally evaluated predictors of STIs using regression analysis. RESULTS: HIV, HBV and syphilis prevalence rates among urban children in Ethiopia were 0.36%, 1.48% and 0.28%, respectively. Children living in Gambella and Addis Ababa had a 6.41-fold (95% CI: 3.20-9.88) and 4.20-fold (95% CI: 3.24-5.46) higher risk of HIV infection compared with those in Dire Dawa. Children of HIV-positive mothers had a 10.31-fold (95% CI: 3.20-18.19) higher risk of HIV infection, and if those mothers were not taking highly active antiretroviral therapy (HAART), the risk was 7.27 times higher (95% CI: 2.57-12.64). Those who were from HIV-positive mothers with viral load ≥ 1000 copies/mL had a 18.64-fold (95% CI: 6.36-31.24) higher risk of HIV infection and those with a history of breastfeeding had a 3.27-fold (95% CI: 1.11-5.67) higher risk. Children from Addis Ababa had a 3.26-fold (95% CI: 1.64-6.66) higher risk of HBV infection compared with those from Dire Dawa. Moreover, for those from HIV-positive mothers and whose mother was not taking HAART, the risk of HBV transmission was 6.37 (95% CI: 2.20-19.96) and 3.62 (95% CI: 1.27-11.29), respectively. Children living in Gambella, Somali, Afar and Tigray had a 7.21-fold (95% CI: 2.30-18.68), 3.10-fold (95% CI: 1.28-3.74) and 1.32-fold (95% CI: 1.11-3.38) higher risk of acquiring active syphilis compared with those living in Dire Dawa, respectively. Those from HIV-positive mothers also had a 4.22-fold (95% CI: 1.16-8.39) higher risk of acquiring active syphilis. CONCLUSION: The burden of HIV, HBV and syphilis was high among children in urban Ethiopia. The key determinants for the high burden of HIV, syphilis and HBV were maternal factors including maternal HIV status and breastfeeding. This might be due to the challenges associated with mother-to-child transmission. Hence, the programme shall focus on the elimination of the triple infections of HIV, syphilis and HBV.

The role of mediator suppressor of cytokine signaling (SOCS), toll-like receptor 3 (TLR-3) and nuclear factor kappa B (NFκB) on cytokine production during dengue virus infection.

Inability to understand the pathogenesis of severe dengue, in particular the control mechanism of immune responses, has led to high mortality rate for patients with dengue shock syndrome (DSS). The aim of this study was to determine the control mechanism of cytokine production by mediator suppressor of cytokine signaling (SOCS), toll-like receptor 3 (TLR-3) and nuclear factor kappa B (NFκB) during DENV infection. Peripheral blood mononuclear blood cells (PBMC), isolated from healthy individuals, were infected with dengue virus (DENV)-2 strain SJN-006 Cosmopolitan genotype (isolated from Bali, Indonesia). The relative gene expression of SOCS-3, TLR-3, NFκB, and the cytokine genes (interleukin (IL)-6, IL-8, interferon inducible protein 10 (IP-10), and macrophage inflammatory protein-1 beta (MIP-1ß)) were measured using qRT-PCR at 6, 12 and 24 hours post infection (hpi). Student t-test and Mann-Whitney test were used to compare the gene expressions while causal correlations were analyzed using regression test and path analyses. DENV-2 infection increased the gene expression of SOCS-3, TLR-3, and NFκB after 12 and 24 hpi. The expression of IL-6, IL-8, IP-10, and MIP-1ß genes was increased and peaked at different times post-infection. NFκB and SOCS-3 genes likely have role in the upregulation of IL-8 and IL-6 gene expression, respectively. MIP-1ß gene expression was significantly induced by both NFκB and SOCS-3. In conclusion, our study suggested that SOCS-3, TLR-3, and NFκB are important in regulating the production of IL-6, IL-8, IP-10, MIP-1ß during early phase of DENV-2 infection. This enriches our understanding on pathogenesis pathway of DENV-associated cytokine storm.

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.

Antibiotic Resistance in Non-Typhoidal Salmonella enterica Strains Isolated from Chicken Meat in Indonesia.

The increase in antibiotic resistance in non-typhoidal Salmonella enterica (NTS) has been confirmed in Indonesia by this study. We confirmed the virulence genes and antimicrobial susceptibilities of clinical NTS (n = 50) isolated from chicken meat in Indonesia and also detected antimicrobial resistance genes. Of 50 strains, 30 (60%) were non-susceptible to nalidixic acid (NA) and all of them had amino acid mutations in gyrA. Among 27 tetracycline (TC) non-susceptible strains, 22 (81.5%) had tetA and/or tetB. The non-susceptibility rates to ampicillin, gentamicin or kanamycin were lower than that of NA or TC, but the prevalence of blaTEM or aadA was high. Non-susceptible strains showed a high prevalence of virulence genes compared with the susceptible strains (tcfA, p = 0.014; cdtB, p < 0.001; sfbA, p < 0.001; fimA, p = 0.002). S. Schwarzengrund was the most prevalent serotype (23 strains, 46%) and the most frequently detected as multi-antimicrobial resistant. The prevalence of virulence genes in S. Schwarzengrund was significantly higher than other serotypes in hlyE (p = 0.011) and phoP/Q (p = 0.011) in addition to the genes above. In conclusion, NTS strains isolated from Indonesian chicken had a high resistance to antibiotics and many virulence factors. In particular, S. Schwarzengrund strains were most frequently detected as multi-antimicrobial resistant and had a high prevalence of virulence genes.

The Economic Impact of Carbapenem Resistant-Non Lactose Fermenter and Enterobacteriaceae Infections on Hospital Costs in Dr. Soetomo General Academic Hospital Surabaya, Indonesia.

Background: Carbapenem resistant-non lactose fermenter (CR-NLF) and Carbapenem resistant-Enterobacteriaceae (CR-E) bacterial infections are likely to be a global threat to people's health. However, studies on the economic impacts according to the hospital setting are very scarce. The study aimed to explore the impact of CR-NLF (Acinetobacter baumannii = CRAB) & Pseudomonas aeruginosa = CRPA) and CR-E (Escherichia coli = CREC) & Klebsiella pneumoniae = CRKP) infections on hospital costs from a payer perspective among patients admitted to Dr.Soetomo Hospital, Surabaya, Indonesia. Methods: In the retrospective case-control study, medical records of all included patients hospitalized during 2018−2021 were reviewed for CRAB, CRPA, CREC, CRKP, and carbapenem sensitive (CSAB, CSPA, CSEC, CSKP) were collected. We retrieved the data of age, gender, clinical specimen, dates of admission, and discharge status. The outcomes of interest were hospital length of stay and hospitalization cost. Results: The cost for CR-NLFs infections was higher than carbapenem sensitive, $3026.24 versus $1299.28 (p < 0.05). There was no significant difference between CR-E against carbapenem sensitive. It showed that the highest impact of the cost was CRAB, followed by CRPA, CRKP, and CREC. The bed, antibiotics, pharmacy, and diagnostic costs of CR-NLFIs were significantly higher than CR-E. Conclusion: This study showed that the hospital cost and expenditure of CR-NLFs per patient were higher than CS. The hospital cost per patient for CR-NLF was higher than CR-E.

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.

MRSA surveillance programmes worldwide: moving towards a harmonised international approach.

Multinational surveillance programmes for methicillin-resistant Staphylococcus aureus (MRSA) are dependent on national structures for data collection. This study aimed to capture the diversity of national MRSA surveillance programmes and to propose a framework for harmonisation of MRSA surveillance. The International Society of Antimicrobial Chemotherapy (ISAC) MRSA Working Group conducted a structured survey on MRSA surveillance programmes and organised a webinar to discuss the programmes' strengths and challenges as well as guidelines for harmonisation. Completed surveys represented 24 MRSA surveillance programmes in 16 countries. Several countries reported separate epidemiological and microbiological surveillance. Informing clinicians and national policy-makers were the most common purposes of surveillance. Surveillance of bloodstream infections (BSIs) was present in all programmes. Other invasive infections were often included. Three countries reported active surveillance of MRSA carriage. Methodology and reporting of antimicrobial susceptibility, virulence factors, molecular genotyping and epidemiological metadata varied greatly. Current MRSA surveillance programmes rely upon heterogeneous data collection systems, which hampers international epidemiological monitoring and research. To harmonise MRSA surveillance, we suggest improving the integration of microbiological and epidemiological data, implementation of central biobanks for MRSA isolate collection, and inclusion of a representative sample of skin and soft-tissue infection cases in addition to all BSI cases.

Occurrence of Carriage of Multidrug Resistant Enterobacteriaceae among Pregnant Women in the Primary Health Center and Hospital Setting in Surabaya, Indonesia.

Objectives: The incidence of healthy individuals carrying multidrug resistant Enterobacteriaceae, including extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-E), especially extended-spectrum ß-lactamase producing Escherichia coli (ESBL-EC) and extended-spectrum ß-lactamase producing Klebsiella pneumoniae (ESBL-KP), is increasing worldwide. Although ESBL-E causes early or late onset of neonatal sepsis, the prevalence of ESBL-E carriage among pregnant women in Indonesia is not clear. In the present study, we compared the occurrence of carriage of ESBL-E among pregnant women in a primary health center (PHC) versus two hospitals. Materials and Methods: We collected rectal swab samples from 200 pregnant women who visited a PHC or were admitted to two hospitals in Surabaya, Indonesia from July to October 2018. The ESBL-E strains were isolated from the samples and phenotypically and genotypically analyzed. Results: ESBL-E strains were isolated from 25 (24.8%) pregnant women who visited the PHC and 49 (49.5%) pregnant women who were admitted to the hospitals. The rate of ESBL-E carriage of pregnant women in the hospitals was significantly higher than that in the PHC. Among the 74 isolated ESBL-E strains, ESBL-EC was most frequently isolated (62 strains), followed by ESBL-KP (12 strains). In addition, blaCTX-M-15 was the most frequent ESBL gene type of the isolated ESBL-E strains. Conclusions: Our results revealed the high occurrence of ESBL-E carriage in pregnant women, especially those who were admitted to the hospitals.

The Clinical Pattern and Prevalence of Streptococcus mutans and Streptococcus sobrinus among Adult and Children Patients with Dental Caries

Abstract Objective: To explore the clinical pattern, host factors, and presentation of Streptococcus mutans related to caries incidence among children and adults visiting Universitas Airlangga dental clinic. Material and Methods: This was an observational study with a cross-sectional approach with 50 patients in each group of carious children (6-12 years) and adults (18-35 years). Dental decay samples were taken by sterile excavator, put in a BHI's transport medium, and directly incubated overnight at 37 ºC. The next day, they were sub-cultured microbiologically in Tryptone Yeast Cystine Sucrose Bacitracin (TYCSB) selective medium. Bacterial species and serogroups were examined by PCR. All patient's data were collected from medical records and direct observation. Results: Caries were mostly media type in both children and adults. Oral hygiene (OHIS) in children was higher than in adults but not significantly different according to their DMFT. The highest scores for decay, missed and filled teeth were 16, 8 and 7, with an average of 6.82, 1.22 and 0.63, considered quite high. Conclusion: The prevalence of S. mutans was higher in children's caries than in adults, but among the adult patients the co-incidence of S. mutans and S. sobrinus was associated with higher DMFT. The mutans serotypes e, f, and d were more prevalent among children than adults.

Analysis of the upstream genetic structures of the ISEcp1-blaCTX-M transposition units in Escherichia coli isolates carrying blaCTX-M obtained from the Indonesian and Vietnamese communities.

Extended spectrum ß-lactamase (ESBL)-producing Escherichia coli have been found in healthy individuals in Indonesia and Vietnam. The ISEcp1-blaCTX-M transposition unit of ESBL-producing bacterial isolates has been considered responsible for the production of CTX-M type ESBL and it is important for the dissemination of blaCTX-M . This study aimed to characterize the upstream genetic structure (UGS) of E. coli isolates possessing blaCTX-M-1 group and/or blaCTX-M-9 group genes obtained from healthy individuals in Indonesia and Vietnam. A total of 501 CTX-M type ESBL-producing E. coli isolates possessing blaCTX-M-1 group and/or blaCTX-M-9 group genes were obtained from healthy individuals of the two countries in 2018. The UGSs of the ISEcp1-blaCTX-M transposition unit of the 501 ESBL-producing E. coli isolates were amplified by barcode-adaptor-ligation-mediated PCR and analyzed using the Nanopore sequencer. The obtained sequence information was used to classify the UGSs of the ISEcp1-blaCTX-M transposition unit. From the 501 ESBL-producing E. coli isolates, 502 UGSs were obtained, which were classified into 85 UGS types based on the sequence. ISEcp1 of 359 (71.5%) of the 502 UGSs was disrupted by gene insertion, and ISEcp1-blaCTX-M transposition unit of most (87.1%) of the determined UGSs was confirmed as plasmidic. Only 6 (7.1%) of the 85 UGS types were common to both countries. Our results indicated that many different UGSs of ISEcp1-blaCTX-M transposition units were detected in Indonesia and Vietnam; hence, we suggest that structurally different kinds of plasmids harboring blaCTX-M were separately distributed in the two countries.

The clinical impact of bacterial co-infection among moderate, severe and critically ill COVID-19 patients in the second referral hospital in Surabaya.

Background: Data on the prevalence of bacterial co-infections among COVID-19 patients are limited, especially in our country, Indonesia. We aimed to assess the rate of bacterial co-infections in hospitalized COVID-19 patients and report the most common microorganisms involved and the antibiotic use in these patients. Methods: This study is a retrospective cohort study, among COVID-19 adult patients admitted to Universitas Airlangga Hospital Surabaya from 14 March-30 September 2020. The bacterial infection is defined based on clinical assessment, laboratory parameters, and microbiology results. Results: A total of 218 patients with moderate to critical illness and confirmed COVID-19 were included in this study. Bacterial infection was confirmed in 43 patients (19.7%). COVID-19 patients with bacterial infections had longer hospital length of stay (17.6 ± 6.62 vs 13.31±7.12), a higher proportion of respiratory failure, intensive care treatment, and ventilator use. COVID-19 patients with bacterial infection had a worse prognosis than those without bacterial infection (p<0.04). The empirical antibiotic was given to 75.2% of the patients. Gram-negative bacteria were commonly found as causative agents in this study (n = 39; 70.37%). Conclusion: COVID-19 patients with bacterial infection have a longer length of stay and worse outcomes. Healthcare-associated infections during intensive care treatment for COVID-19 patients must be carefully prevented.

Differential effects of chromosome and plasmid blaCTX-M-15 genes on antibiotic susceptibilities in extended-spectrum beta-lactamase-producing Escherichia coli isolates from patients with urinary tract infection.

OBJECTIVES: To compare antibiotic susceptibilities between chromosomal and plasmid blaCTX-M-15 locations in urinary tract infection-causing extended-spectrum ß-lactamases-producing Escherichia coli blaCTX-M-15 isolated in Indonesia. METHODS: A total of 84 strains identified as extended-spectrum ß-lactamases-producing E. coli were isolated from patients with urinary tract infection in Indonesia in 2015. Antimicrobial susceptibility tests were performed on these strains using 18 antibiotics, and extended-spectrum ß-lactamase bla genes were detected by polymerase chain reaction. Gene localization of blaCTX-M-15 -positive strains was confirmed by Southern blot hybridization, and epidemiological typing was conducted using multilocus sequence typing. RESULTS: Of 54 strains harboring the blaCTX-M-15 gene, 27 showed localization on chromosome, 20 on plasmid, and seven on chromosome and plasmid. Most multilocus sequence typing sequence types of the 27 strains with chromosomal blaCTX-M-15 were ST405 (25.9%) and ST131 (22.2%) strains, whereas the 20 strains with plasmid-blaCTX-M-15 were mostly ST410 (55.0%). CONCLUSIONS: Extended-spectrum ß-lactamases-producing E. coli blaCTX-M-15 with plasmid genes show significantly higher resistant rates against piperacillin-tazobactam but lower resistant rates against chloramphenicol compared to chromosomal strains in Indonesian patients with urinary tract infection. Mechanistic investigations will be necessary to advance our knowledge of antimicrobial resistance in urinary tract infection.

Correlation of miR-150, hsa-let-7e, and miR- 146a and gene expression of IL-6, IL-8, IP-10, and MIP-1ß during dengue virus infection.

Growing evidence suggests that microRNAs (miRNAs) play a pivotal role in viral infection. The objective of this study was to assess the association between the expression of miR- 150, hsa-let-7e, and miR-146a on cytokine expression during dengue infection. Dengue virus (DENV) strain SJN-006, a serotype 2 DENV strain of the Cosmopolitan genotype, isolated in Bali, Indonesia, was used to infect peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals. The relative gene expressions of miR-150, hsa-let-7e, and miR-146a as well as the gene expression of cytokines (IL-6, IL-8, IP-10, and MIP-1ß) were determined using quantitative real time - polymerase chain reaction (qRT-PCR) at 6, 12 and 24 hours post infection (hpi). Correlations between the microRNAs and cytokines were analyzed by means of causality tests. Our data suggests that miR-150 and hsa-let-7e were significantly higher in infected-PBMCs after 12 hpi compared to the uninfected-PBMCs (p<0.05). The causality tests demonstrated that miR-150 and has-let- 7e were negatively correlated with IL-8 expression, meanwhile miR-146a was the contrast. DENV infection was negatively and positively correlated with miR-150 and hsa-let-7e, respectively, after 24 hpi. In conclusion, our data demonstrates the vital role of miR-150, hsa-let-7e, and miR-146a in regulating IL-8 expression with possible different pathways.