In search of the best method to detect carriage of carbapenem-resistant Pseudomonas aeruginosa in humans: a systematic review.

BACKGROUND: Detection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) in humans is important to prevent transmission. However, the most optimal culture method to detect CR-PA is unknown. This systematic review aims to determine which culture method is most sensitive and which culture methods are used to detect CR-PA in humans. Second, to establish the most feasible culture method taking into account the turnaround time (TAT), and third, to provide an overview of the sampling sites used to detect carriage. METHODS: We systematically searched the electronic databases Embase, Medline Ovid, Cochrane, Scopus, CINAHL, and Web of Science until January 27, 2023. All diagnostic accuracy studies comparing two or more culture methods to detect CR-PA and recent outbreak or surveillance reports on CR-PA carriage or infection in humans, which describe culture methods and their results, were eligible for inclusion. We used QUADAS-2 guideline for diagnostic accuracy studies and the STROBE or ORION guideline for outbreak-surveillance studies to assess the risk of bias. RESULTS: Six diagnostic accuracy studies were included. An enrichment broth was found to increase the detection of CR-PA. Using an enrichment broth extended the TAT by 18-24 h, yet selective media could reduce the TAT by 24 h compared to routine media. In total, 124 outbreak-surveillance studies were included, of which 17 studies with surveillance samples and 116 studies with clinical samples. In outbreak-surveillance studies with surveillance samples, perianal, rectal swabs or stools were the most common sampling site/specimen (13/17, 76%). A large variety was observed in whether and which kind of enrichment broth and selective media were used. CONCLUSIONS: We found a benefit of using an enrichment step prior to inoculation of the material onto selective media for the detection of CR-PA. More research is needed to determine the most sensitive sampling site and culture method. TRAIL REGISTRATION: This study was registered in the PROSPERO International prospective register of systematic reviews (registration number: CRD42020207390, http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42020207390 ).

Multidrug-Resistant Bacteria Colonization in Patients Admitted to Dr. Cipto Mangunkusumo Hospital Jakarta, Indonesia.

BACKGROUND: Antibiotic resistance is the main problem in infectious disease management. Multidrug-resistant (MDR) bacteria could be carried by admitted patients and become a source of spread in the hospital, causing infections in other patients or the patients themselves. However, the screening of MDR bacteria has not been a standard in developing countries. This study aimed to get the prevalence of MDR bacteria colonization in patients on admission to Dr. Cipto Mangunkusumo Hospital. METHODS: Selective liquid media with added antibiotics were used for culturing the MDR bacteria. While admitted to the hospital, subjects were sampled and interviewed to fill out a questionnaire. The screening specimens used for this study were throat, navel, rectal, nasal, and armpit swabs. During hospitalization, hospital-acquired infections (HAIs) were recorded. RESULTS: Of 100 patients included in the study, the prevalence of MDR bacteria colonization on admission was 63% (n=63) with the prevalence of CR-GNB, ESBL-PE, and MRSA were 11%, 54%, and 11%, respectively. Two-thirds of the patients with HAIs (n=8/12) were colonized with MDR bacteria. Factors associated with MDR bacteria colonization were the recent use of invasive medical devices and comorbidity, while a factor associated with CR-GNB colonization was the recent use of antibiotics. CONCLUSION: The prevalence of MDR bacteria colonization in patients on admission to Dr. Cipto Mangunkusumo Hospital in 2022 was 63% (n=63), of which 12.68% (n=8) experienced HAIs during hospitalization. MDR bacteria colonization was associated with the recent use of invasive medical devices and comorbidity. History of antibiotic use was associated with CR-GNB colonization.

Consideration of the Cycle Threshold Values from Real-Time RT-PCR SARS-CoV-2 Interpretation for the Clinicians: Analysis of 339 Positive Cases from a Referral Laboratory in Jakarta, Indonesia.

BACKGROUND: real-time RT-PCR was recommended by WHO for COVID-19 diagnosis. The cycle threshold (Ct) values were expected to have an association with clinical manifestation. However, the diagnostic modalities such as quantitative molecular detection and virus isolation were not yet available for the routine test. This study has been conducted to analyze the relationship between the Ct values of qualitative rRT-PCR and the clinical manifestation and to describe the factors determining the result. METHODS: from March to April 2020, specimens were sent to our laboratory from different healthcare centers in Jakarta. The patient's characteristic and clinical manifestation were extracted from the specimen's epidemiology forms. The specimens extracted and tested using rRT-PCR, and the Ct value were collected. The data were analyzed using the appropriate statistic test. RESULTS: from 339 positive results, the mild to moderate case was 176 (52%) and the severe cases was 163 (48%). Female was dominant in the mild to moderate cases (58%), while the male was prevalent in the severe cases (60%). The median age for mild to moderate case was 35 years old and severe cases was 49 years old. Statistical analysis found relationship between both group with gender (p = 0.001) and age (p < 0.001), but not with the Ct value. CONCLUSION: many variables in specimen sampling and processing could affect the Ct value result. In addition, the disease's severity was depended with the host immune response, regardless the number of virus. There was suggested no significant difference between the Ct values of mild-moderate and severe COVID-19, and thus should not be loosely interpreted.

Procalcitonin (PCT)-guided antibiotic stewardship in Asia-Pacific countries: adaptation based on an expert consensus meeting.

Introduction Recently, an expert consensus on optimal use of procalcitonin (PCT)-guided antibiotic stewardship was published focusing mainly on Europe and the United States. However, for Asia-Pacific countries, recommendations may need adaptation due to differences in types of infections, available resources and standard of clinical care. Methods Practical experience with PCT-guided antibiotic stewardship was discussed among experts from different countries, reflecting on the applicability of the proposed Berlin consensus algorithms for Asia-Pacific. Using a Delphi process, the group reached consensus on two PCT algorithms for the critically ill and the non-critically ill patient populations. Results The group agreed that the existing evidence for PCT-guided antibiotic stewardship in patients with acute respiratory infections and sepsis is generally valid also for Asia-Pacific countries, in regard to proposed PCT cut-offs, emphasis on diagnosis, prognosis and antibiotic stewardship, overruling criteria and inevitable adaptations to clinical settings. However, the group noted an insufficient database on patients with tropical diseases currently limiting the clinical utility in these patients. Also, due to lower resource availabilities, biomarker levels may be measured less frequently and only when changes in treatment are highly likely. Conclusions Use of PCT to guide antibiotic stewardship in conjunction with continuous education and regular feedback to all stakeholders has high potential to improve the utilization of antibiotic treatment also in Asia-Pacific countries. However, there is need for adaptations of existing algorithms due to differences in types of infections and routine clinical care. Further research is needed to understand the optimal use of PCT in patients with tropical diseases.

Optimal Amikacin Levels for Patients with Sepsis in Intensive Care Unit of Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

BACKGROUND: Amikacin is one of the antibiotics of choice for sepsis and septic shock. Pharmacokinetic of amikacin can be influenced by septic condition with subsequent effect on its pharmacodynamic. At Cipto Mangunkusumo Hospital (RSCM), Jakarta, adult patients in the ICU were given standard amikacin dose of 1 g/day, however the achievement of optimal plasma level had never been evaluated. This study aimed to evaluate whether the optimal plasma level of amikacin was achieved with the use of standard dose in septic conditions. METHODS: all septic patients admitted to the intensive care unit of a national tertiary hospital receiving standard dose of 1g/day IV amikacin during May-September 2015 were included in this study. Information of minimum inhibitory concentration MIC was obtained from microbial culture. Cmax of amikacin was measured 30 minutes after administration and optimal level was calculated. Optimal amikacin level was considered achieved when Cmax/MIC ratio >8. RESULTS: average Cmax achieved for all patients was 86.4 (43.5-238) µg/mL with 87% patients had Cmax of >64 µg/mL.MIC data were available for 7 of 23 patients. MICs for identified pathogens were 0.75 - >256 µg/mL (K. pneumonia), 0.75 - >256 µg/mL(A. baumanii), 1.5 - >256 µg/mL (P. aeruginosa)and 0.75 - 16 µg/mL(E. coli). Four out of seven patients achieved optimal amikacin level. CONCLUSION: despite high Cmax, only half of the patients achieved optimal amikacin level with highly variable Cmax. This study suggests that measurement of Cmax and MIC are important to optimize septic patients management.

Genetic and phenotypic of Pseudomonas aeruginosa sensitive to meropenem antibiotics after exposure to meropenem.

Background and Objectives: Pseudomonas aeruginosa, drug-resistant, causes health infections. Resistance to the preferred therapy meropenem is a serious threat. This study aimed to analyze changes in meropenem minimum inhibitory concentration (MIC), changes in ampC, mexA, and oprD gene expression, and the correlation between MIC and ampC, mexA, and oprD gene expression after meropenem exposure. Materials and Methods: Ten isolates of P. aeruginosa from the Clinical Microbiology Department, Faculty of Medicine, Universitas Indonesia were used. After the bacteria were shown to be sensitive to meropenem phenotypically, intrinsic resistance genes were detected using PCR. After meropenem exposure on Days 5 and 12, sensitivity testing was carried out with the concentration gradient method and RNA was detected using real-time RT-PCR. Results: All P. aeruginosa isolates that were phenotypically sensitive to meropenem had the ampC, mexA, and oprD genes. An increase in MIC, an increase in ampC and mexA gene expression, and a decrease in oprD gene expression were observed after meropenem exposure. There was a very strong and significant correlation (p ≤ 0.05) between MIC and oprD gene expression after Day 12 of meropenem exposure. Conclusion: Although there were no significant differences in MIC and ampC, mexA, and oprD gene expression between Day 5 and Day 12, there was a very strong and significant correlation between MIC and oprD gene expression on Day 12 (p ≤ 0.05). This indicates that decreasing oprD gene expression has the potential to increase meropenem resistance in Pseudomonas aeruginosa.

Evaluation of SARS-CoV-2 quantification from oropharyngeal swabs, nasopharyngeal swabs, and naso-oropharyngeal swabs: A cross-sectional study.

The current naso-oropharyngeal swab for SARS-CoV-2 detection faces several problems, such as waste issues and its use for quantitative studies. This study aimed to evaluate the total RNA and viral loads from different upper respiratory tract swabs types and whether SARS-CoV-2 quantification can use the current internal control for normalization. This cross-sectional study collected positive specimens with single oropharyngeal or nasopharyngeal swabs and naso-oropharyngeal swabs. The samples were extracted, tested with qualitative RT‒PCR, and then tested with quantitative RT‒PCR. The RNA eluate was measured for the total RNA concentration. The total RNA concentration, viral load, and RNaseP Ct values were collected and analysed statistically. The positive results came from 41 oropharyngeal swabs, 34 nasopharyngeal swabs, and 36 naso-oropharyngeal swabs. The total RNA increased significantly from oropharyngeal swabs to nasopharyngeal swabs to naso-oropharyngeal swabs. Significant differences in RNaseP Ct values between groups and their correlations with total RNA were found. In addition, the increase in the total RNA and the RNaseP Ct values were unrelated to the viral load. The physical features in the naso-oropharyngeal area and the swabbing procedures could affect the total RNA but not the viral load. However, since the virus particles could present inside and outside human cells, the increase in collected human cells may not always be followed by the viral load increase. Normalization using the RNaseP Ct value became unnecessary due to the factors mentioned above. Therefore, a careful approach is needed in viral load studies of swab specimens.

Antimicrobial resistance among common bacterial pathogens in Indonesia: a systematic review.

Background: The WHO Global Antimicrobial Resistance Surveillance System (GLASS) aims to describe antimicrobial resistance (AMR) patterns and trends in common bacterial pathogens, but data remain limited in many low and middle-income countries including Indonesia. Methods: We systematically searched Embase, PubMed and Global Health Database and three Indonesian databases for original peer-reviewed articles in English and Indonesian, published between January 1, 2000 and May 25, 2023, that reported antimicrobial susceptibility for the 12 GLASS target pathogens from human samples. Pooled AMR prevalence estimates were calculated for relevant pathogen-antimicrobial combinations accounting for the sampling weights of the studies (PROSPERO: CRD42019155379). Findings: Of 2182 search hits, we included 102 papers, comprising 19,517 bacterial isolates from hospitals (13,647) and communities (5870). In hospital settings, 21.6% of Klebsiella pneumoniae isolates, 18.3% of Escherichia coli isolates, 35.8% of Pseudomonas aeruginosa isolates and 70.7% of Acinetobacter baumannii isolates were carbapenem-resistant; 29.9% of Streptococcus pneumoniae isolates were penicillin-resistant; and 22.2% of Staphylococcus aureus isolates were methicillin-resistant. Hospital prevalence of carbapenem-resistant K. pneumoniae and E. coli, and penicillin-resistant S. pneumoniae increased over time. In communities, 28.3% of K. pneumoniae isolates and 15.7% of E. coli isolates were carbapenem-resistant, 23.9% of S. pneumoniae isolates were penicillin-resistant, and 11.1% of S. aureus isolates were methicillin-resistant. Data were limited for the other pathogens. Interpretation: AMR prevalence estimates were high for critical gram-negative bacteria. However, data were insufficient to draw robust conclusions about the full contemporary AMR situation in Indonesia. Implementation of national AMR surveillance is a priority to address these gaps and inform context-specific interventions. Funding: Wellcome Africa Asia Programme Vietnam.

Diagnostic and antibiotic use practices among COVID-19 and non-COVID-19 patients in the Indonesian National Referral Hospital.

BACKGROUND: Little is known about diagnostic and antibiotic use practices in low and middle-income countries (LMICs) before and during COVID-19 pandemic. This information is crucial for monitoring and evaluation of diagnostic and antimicrobial stewardships in healthcare facilities. METHODS: We linked and analyzed routine databases of hospital admission, microbiology laboratory and drug dispensing of Indonesian National Referral Hospital from 2019 to 2020. Patients were classified as COVID-19 cases if their SARS-CoV-2 RT-PCR result were positive. Blood culture (BC) practices and time to discontinuation of parenteral antibiotics among inpatients who received a parenteral antibiotic for at least four consecutive days were used to assess diagnostic and antibiotic use practices, respectively. Fine and Grey subdistribution hazard model was used. RESULTS: Of 1,311 COVID-19 and 58,917 non-COVID-19 inpatients, 333 (25.4%) and 18,837 (32.0%) received a parenteral antibiotic for at least four consecutive days. Proportion of patients having BC taken within ±1 calendar day of parenteral antibiotics being started was higher in COVID-19 than in non-COVID-19 patients (21.0% [70/333] vs. 18.7% [3,529/18,837]; p<0.001). Cumulative incidence of having a BC taken within 28 days was higher in COVID-19 than in non-COVID-19 patients (44.7% [149/333] vs. 33.2% [6,254/18,837]; adjusted subdistribution-hazard ratio [aSHR] 1.71, 95% confidence interval [CI] 1.47-1.99, p<0.001). The median time to discontinuation of parenteral antibiotics was longer in COVID-19 than in non-COVID-19 patients (13 days vs. 8 days; aSHR 0.73, 95%Cl 0.65-0.83, p<0.001). CONCLUSIONS: Routine electronic data could be used to inform diagnostic and antibiotic use practices in LMICs. In Indonesia, the proportion of timely blood culture is low in both COVID-19 and non-COVID-19 patients, and duration of parenteral antibiotics is longer in COVID-19 patients. Improving diagnostic and antimicrobial stewardship is critically needed.

Characteristics and clinical outcomes of patients with pre-delta, delta and omicron SARS-CoV-2 infection in Indonesia (2020-2023): a multicentre prospective cohort study.

Background: Limited data exist from southeast Asia on the impact of SARS-CoV-2 variants and inactivated vaccines on disease severity and death among patients hospitalised with COVID-19. Methods: A multicentre hospital-based prospective cohort was enrolled from September 2020 through January 2023, spanning pre-delta, delta, and omicron periods. The participant hospitals were conveniently sampled based on existing collaborations, site willingness and available study resources, and included six urban and two rural general hospitals from East Nusa Tenggara, Jakarta, and North Sumatra provinces. Factors associated with severe disease and day-28 mortality were examined using logistic and Cox regression. Findings: Among 822 participants, the age-adjusted percentage of severe disease was 26.8% (95% CI 22.7-30.9) for pre-delta, 50.1% (44.0-56.2) for delta, and 15.2% (9.7-20.7) for omicron. The odds of severe disease were 64% (18-84%) lower for omicron than delta (p < 0.001). One or more vaccine doses reduced the odds of severe disease by 89% (65-97%) for delta and 98% (91-100%) for omicron. Age-adjusted mortality was 11.9% (8.8-15.0) for pre-delta, 24.4% (18.8-29.9) for delta and 9.6% (5.2-14.0) for omicron. The day-28 cumulative incidence of death was lower for omicron (9.2% [5.6-13.9%]) than delta (28.6% [22.0-35.5%]) (p < 0.001). Severe disease on admission was the predominant prognostic factor for death (aHR34.0 [16.6-69.9] vs mild-or-moderate; p < 0.001). After controlling for disease severity on admission as an intermediate, the risk of death was 48% (32-60%) lower for omicron than delta (p < 0.001); and 51% (38-61%; p < 0.001) lower for vaccinated participants than unvaccinated participants overall, and 56% (37-69%; p < 0.001) for omicron, 46% (-5 to 73%; p = 0.070) for pre-delta (not estimable for delta). Interpretation: Infections by omicron variant resulted in less severe and fatal outcomes than delta in hospitalised patients in Indonesia. However, older, and unvaccinated individuals remained at greater risk of adverse outcomes. Funding: University of Oxford and Wellcome Trust.

Detection of carbapenemase encoding genes in Enterobacteriace, Pseudomonas aeruginosa, and Acinetobacter baumanii isolated from patients at Intensive Care Unit Cipto Mangunkusumo Hospital in 2011.

AIM: to determine the prevalence of carbapenemase encoding genes (blaIMP-1, blaVIM-2, blaKPC-2, blaOXA-48, and blaNDM-1) of carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumanii isolated from the intensive care unit patients as pathogens, in Cipto Mangunkusumo hospital (ICU-RSCM) in 2011. METHODS: we examined the carbapenemase encoding genes in the clinical microbiology laboratory (LMK FKUI/RSCM). Duplex- and simplex PCR methods were conducted to detect the resistant genes. RESULTS: we found 4 (5%) P. aeruginosa strains carry blaIMP-1 gene and all were isolated from sputum specimens. The prevalence of carbapenem resistant among Gram-negative bacilli isolated from ICU-RSCM, are Enterobacteriaceae 27.6%, P. aeruginosa 21.9%, and A. baumannii 50.5%. The New Delhi Metallo--lactamase encoding gene (blaNDM-1) was detected in 1 K. pneumonia isolated from sputum as well. The other genes, i.e. blaKPC-2, blaVIM-2, and blaOXA-48 were not found in any isolates. The absence of other genes indicated that other mechanisms may play a role in the occurrence of carbapenem resistance in pathogens isolated in ICU-RSCM. CONCLUSION: this study confirmed that the prevalence of carbapenems resistant Gram-negative bacilli in ICU-RSCM in 2011 was high. The carbapenemase encoding genes, which were detected among the carbapenems resistant Gram-negative bacilli, were blaIMP-1 and blaNDM-1.

Comparison of Culture Results between Specimens from Corneal Scraping with Microhomogenization and Corneal Swab in Moderate and Severe Bacterial Corneal Ulcers.

The purpose of this study was to compare the bacterial culture results from corneal infiltrate specimens collected using two different methods, corneal scraping followed by microhomogenization and corneal swab. This is a comparative crosssectional study, with 18 participants undergoing corneal specimen collection using each of the 2 sampling techniques. The results from the scraping and swab methods were separated and then compared using data analysis. The proportion of Gram stain results that matched the culture results for the scraping-microhomogenization technique was 6/13 (46.2%), and the proportion of Gram stain results that matched the culture results for the swab technique was 5/13 (38.5%) (McNemar test P value, 1.000; P > 0.05). The proportion of positive cultures obtained using the scraping-microhomogenization technique was 13/18 (72.2%), and the proportion of positive cultures obtained using the swab technique was 9/18 (50%) (McNemar test P value, 0.219; P > 0.05). The Kappa suitability test value for comparison of the scraping-microhomogenization technique to the corneal swab was 0.333. The specimens collected by corneal scraping followed by microhomogenization had a higher positive bacterial culture rate than those collected by corneal swab, but the results were not statistically significant. IMPORTANCE This study aimed to compare the culture results between scraping specimens with microhomogenization and corneal smears in patients with moderate to severe bacterial corneal ulcers. This study could be a guideline for treating bacterial corneal ulcers.

Invasive pneumococcal disease among hospitalized children aged 28 days to 60 months in Jarkarta.

Streptococcus pneumoniae is a leading cause of morbidity and mortality among children worldwide. Prevention of invasive pneumococcal disease (IPD) with a pneumococcal conjugate vaccine (PCV) is an effective approach to reduce the burden of pneumococcal disease. Nationwide epidemiological data is required prior to considering universal pneumococcal immunization for Indonesia. This preliminary study aimed to quantify the burden of IPD among hospitalized children at Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta. We studied 205 subjects aged 28 days to 60 months who were admitted with the diagnosis of pneumonia, meningitis, sepsis, and suspected occult bacteremia. Streptococcus pneumoniae was isolated from 1 of 205 blood specimens, giving an IPD proportion of 0.5%. The IPD case in this study was a 3-month-old baby with meningitis and bilateral lobar pneumonia. The Quellung test demonstrated serotype 7F. The isolate was susceptible to amoxicillin and Cotrimoxazole. Incidence of IPD could not be calculated due to low number of cases; this underscores the importance of surveillance of pneumococcal disease in Indonesia.

Case series in Indonesia: B.1.617.2 (delta) variant of SARS-CoV-2 infection after a second dose of vaccine.

BACKGROUND: The B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in Maharashtra in late 2020 and has rapidly expanded across India and worldwide. It took only 2 mo for this variant to spread in Indonesia, making the country the new epicenter of the delta variant as of July 2021. Despite efforts made by accelerating massive rollouts of current vaccines to protect against infection, cases of fully-vaccinated people infected with the delta variant have been reported. AIM: To describe the demographic statistics and clinical presentation of the delta variant infection after the second dose of vaccine in Indonesia. METHODS: A retrospective, single-centre case series of the general consecutive population that worked or studied at Faculty of Medicine, Universitas Indonesia with confirmed Delta Variant Infection after a second dose of vaccine from 24 June and 25 June 2021. Cases were collected retrospectively based on a combination of author recall, reverse transcription-polymerase chain reaction (RT-PCR), and whole genome sequencing results from the Clinical Microbiology Laboratory, Faculty of Medicine, Universitas Indonesia. RESULTS: Between 24 June and 25 June 2021, 15 subjects were confirmed with the B.1.617.2 (delta) variant infection after a second dose of the vaccine. Fourteen subjects were vaccinated with CoronaVac (Sinovac) and one subject with ChAdOx1 nCoV-19 (Oxford-AstraZeneca). All of the subjects remained in home isolation, with fever being the most common symptom at the onset of illness (n = 10, 66.67%). The mean duration of symptoms was 7.73 d (± 5.444). The mean time that elapsed from the first positive swab to a negative RT-PCR test for SARS-CoV-2 was 17.93 d (± 6.3464). The median time that elapsed from the second dose of vaccine to the first positive swab was 87 d (interquartile range: 86-128). CONCLUSION: Although this case shows that after two doses of vaccine, subjects are still susceptible to the delta variant infection, currently available vaccines remain the most effective protection. They reduce clinical manifestations of COVID-19, decrease recovery time from the first positive swab to negative swab, and lower the probability of hospitalization and mortality rate compared to unvaccinated individuals.

The role of exclusive breastfeeding on sIgA and lactoferrin levels in toddlers suffering from Acute Respiratory Infection: A cross-sectional study.

Secretion of Immunoglobulin A (sIgA) and lactoferrin is a nutrient content in breast milk that can increase immunity in preventing infectious diseases such as Acute Respiratory Infection (ARI). This research aims to determine the role of exclusive breastfeeding (EBF) on sIgA and Lactoferrin levels in toddlers suffering from ARI. A cross-sectional study was conducted on 124 toddlers under five from January-July 2021. Toddlers were selected using a purposive technique sampling from three Community Health Centers in Central Jakarta. Data were analyzed using t-test and ANOVA. The history of immunization, EBF, and frequency of ARI was significantly associated with levels of sIgA and lactoferrin. Parity only correlated with sIgA but not with lactoferrin levels. Maternal and toddlers' age, gender, and nutritional status were not significantly related to sIgA and lactoferrin levels. There is a significant (p-value <0.001) difference in the mean protein sIgA and lactoferrin levels in toddlers who were given EBF with ARI frequency <2 times and toddlers who were given EBF with ARI frequency ≥2 times. Toddlers who were exclusively breastfed with ARI frequency <2 times had higher levels of sIgA and lactoferrin (188901.77 pg/ml and 262.32 ng/ml, respectively) compared to infants given EBF with ARI frequency ≥2 times (136683.47 pg/ml and 181.49 ng/ml, respectively). History of immunization was also significantly (p-value <0.05) associated with levels of sIgA and lactoferrin in infants with ARI. The content of sIgA and lactoferrin in breast milk and immunization can increase the body's immune system in toddlers suffering from ARI.

Optimizing antibiotic use in Indonesia: A systematic review and evidence synthesis to inform opportunities for intervention.

Background: A major driver of antimicrobial resistance (AMR) and poor clinical outcomes is suboptimal antibiotic use, although data are lacking in low-resource settings. We reviewed studies on systemic antibiotic use (WHO ATC/DDD category J01) for human health in Indonesia, and synthesized available evidence to identify opportunities for intervention. Methods: We systematically searched five international and national databases for eligible peer-reviewed articles, in English and Indonesian, published between 1 January 2000 and 1 June 2021 including: (1) antibiotic consumption; (2) prescribing appropriateness; (3) antimicrobial stewardship (AMS); (4) consumers' and providers' perceptions. Two independent reviewers included studies and extracted data. Study-level data were summarized using random-effects model meta-analysis for consumption and prescribing appropriateness, effect direction analysis for antimicrobial stewardship (AMS) interventions, and qualitative synthesis for perception surveys. (PROSPERO: CRD42019134641). Findings: Of 9323 search hits, we included 100 reports on antibiotic consumption (20), prescribing appropriateness (49), AMS interventions (13), and/or perception (25) (8 categorized in >1 domain). The pooled estimate of overall antibiotic consumption was 134.8 DDD per 100 bed-days (95%CI 82.5-187.0) for inpatients and 121.1 DDD per 1000 inhabitants per day (10.4-231.8) for outpatients. Ceftriaxone, levofloxacin, and ampicillin were the most consumed antibiotics in inpatients, and amoxicillin, ciprofloxacin, and cefadroxil in outpatients. Pooled estimates for overall appropriate prescribing (according to Gyssens method) were 33.5% (18.1-53.4) in hospitals and 49.4% (23.7-75.4) in primary care. Pooled estimates for appropriate prescribing (according to reference guidelines) were, in hospitals, 99.7% (97.4-100) for indication, 84.9% (38.5-98.0) for drug choice, and 6.1% (0.2-63.2) for overall appropriateness, and, in primary care, 98.9% (60.9-100) for indication, 82.6% (50.5-95.7) for drug choice and 10.5% (0.8-62.6) for overall appropriateness. Studies to date evaluating bundled AMS interventions, although sparse and heterogeneous, suggested favourable effects on antibiotic consumption, prescribing appropriateness, guideline compliance, and patient outcomes. Key themes identified in perception surveys were lack of community antibiotic knowledge, and common non-prescription antibiotic self-medication. Interpretation: Context-specific intervention strategies are urgently needed to improve appropriate antibiotic use in Indonesian hospitals and communities, with critical evidence gaps concerning the private and informal healthcare sectors. Funding: Wellcome Africa Asia Programme Vietnam.

The impact of aqueous humor polymerase chain reaction and serological test results for establishing infectious uveitis diagnosis: An Indonesian experience.

Objective: To assess the clinical value of aqueous humor real-time polymerase chain reaction (RT-PCR) and serological antibody tests among uveitis patients in Indonesian cohort. Methods: In this prospective cohort study, single-plex RT-PCR analysis of aqueous samples from 86 new uveitis patients was performed to detect Mycobacterium tuberculosis, Toxoplasmosis gondii, cytomegalovirus, herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, and rubella virus. Specific serological antibodies for suspected pathogens were also obtained. Comparison of PCR and serological antibodies with the initial and final diagnosis were presented. Results: The diagnostic positivity of aqueous RT-PCR in our cohort was 20% (17/86). The rate of infection as final etiological classification was higher after RT-PCR was performed (45 patients, 52%) compared to initial diagnosis based on clinical presentation alone (38 patients, 44%). In particular, the RT-PCR positivity among patients with infection as the final etiological classification was 33.33% (15/45). A significant difference in the IgG but not IgM toxoplasma value among those with ocular toxoplasmosis as the final diagnosis compared to the other etiologies were observed (3953 (IQR 2707-19562) IU/mL vs 428 (IQR 82-1807) IU/mL; p < 0.0001). Conclusion: RT-PCR analysis of aqueous fluid from uveitis patients helped confirm a third of infectious uveitis cases in Indonesia. In ocular toxoplasmosis, high IgG but not IgM antibody value might help differentiate those with other etiology.

Ceftolozane/Tazobactam In-Vitro Activity against Clinical Isolates from Complicated Intra-Abdominal Infection Patients in Three Indonesian Referral Hospitals.

Complicated intra-abdominal infections (cIAIs) lead to high morbidity and mortality, especially if poorly managed. However, Indonesia's microbial pattern and susceptibility data are limited, especially for new antibiotics. Ceftolozane/tazobactam (C/T) is reported to be a new potent antibiotic against various pathogens. Thus, we aim to investigate C/T in vitro activity against clinical isolates from cIAI patients. This prospective cross-sectional study was conducted in three major referral hospitals in Indonesia, including Dr. Cipto Mangunkusumo Hospital (Jakarta), Dr. Kariadi Hospital (Semarang), and Dr. Soetomo Hospital (Surabaya), enrolling those diagnosed with cIAIs. Blood specimens were collected before or after at least 72 h of the last antibiotic administration. Meanwhile, tissue biopsy/aspirate specimens were collected intraoperatively. These specimens were cultured, followed by a susceptibility test for specific pathogens. The minimum inhibitory concentration (MIC) of isolates was determined according to CLSI M100. Two-hundred-and-eighty-four patients were enrolled from 2019-2021. Blood culture was dominated by Gram-positive bacteria (GPB, n = 25, 52.1%), whereas abdominal tissue culture was dominated by Gram-negative bacteria (GNB, n = 268, 79.5%). The three most common organisms were GNB, including E. coli, K. pneumoniae, and P. aeruginosa. C/T was susceptible in 96.7%, 70.2%, and 94.1% of the E. coli, K. pneumoniae, and P. aeruginosa isolates, respectively. In addition, C/T also remained active against ESBL Enterobacterales and carbapenem-non-susceptible P. aeruginosa. Overall, C/T demonstrates a high potency against GNB isolates and can be considered an agent for carbapenem-sparing strategy for cIAI patients as the susceptibility is proven.

Characteristics of Drug-sensitive and Drug-resistant Tuberculosis Cases among Adults at Tuberculosis Referral Hospitals in Indonesia.

As Indonesia's rifampin resistance testing rates are lower than global testing rates per the 2020 WHO global tuberculosis (TB) report, prevalence of multidrug-resistant TB may be underestimated. Our study aimed to evaluate prevalence and patterns of TB drug resistance (DR) within Indonesia. We conducted a cross-sectional analysis of baseline data collected from 2017-2018 as part of a cohort study of adults with presumed pulmonary TB at 7 DR-TB referral hospitals in Indonesia. Bacteriological examinations (acid-fast bacilli, GeneXpert, sputum culture) and drug-susceptibility testing were performed following the guidelines of the National TB Program. Of 447 participants with complete bacteriological examinations, 312 (69.8%) had positive sputum cultures for Mycobacterium tuberculosis. The proportion of MDR and pre-extensively drug-resistant was higher in previously treated compared with newly diagnosed participants (52.5% [73/139] versus 15% [26/173]). Compared with drug-sensitive case, drug-resistant TB was associated with cavities. Given the difference between rates of DR in TB referral hospitals from our study compared with the WHO survey in 2019 that showed 17.7% and 3.3% DR among previously treated and newly diagnosed participants globally, further characterization of Indonesia's TB epidemiology in the general population is needed. Strategies, including public policies to optimize case finding, strengthen capacity for resistance testing, and prevent loss to follow-up will be critical to reduce the burden of TB in Indonesia.