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.

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.

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 ).

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.

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.

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.

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.

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.

Gaps in antimicrobial stewardship programmes in Asia: a survey of 10 countries.

Objectives: To determine antimicrobial stewardship (AMS) programme practices in Asian secondary- and tertiary-care hospitals. Methods: AMS programme team members within 349 hospitals from 10 countries (Cambodia, India, Indonesia, Japan, Malaysia, Pakistan, the Philippines, Taiwan, Thailand and Vietnam) completed a questionnaire via a web-based survey link. The survey contained questions as to whether 12 core components deemed essential for AMS programmes were implemented. Results: Overall, 47 (13.5%) hospitals fulfilled all core AMS programme components. There was a mean positive response rate (PRR) of 85.6% for the responding countries in relation to a formal hospital leadership statement of support for AMS activities, but this was not matched by budgeted financial support for AMS activities (mean PRR 57.1%). Mean PRRs were ≥80.0% for the core AMS team comprising a physician or other leader responsible for AMS activities, a pharmacist and infection control and microbiology personnel. Most hospitals had access to a timely and reliable microbiology service (mean PRR 90.4%). Facility-specific antibiotic treatment guidelines for common infections (mean PRR 78.7%) were in place more often than pre-authorization and/or prospective audit and feedback systems (mean PRR 66.5%). In terms of AMS monitoring and reporting, PRRs of monitoring specific antibiotic use, regularly publishing AMS outcome measures, and the existence of a hospital antibiogram were 75.1%, 64.4% and 77.9%, respectively. Conclusions: Most hospitals participating in this survey did not have AMS programmes fulfilling the requirements for gold standard AMS programmes in hospital settings. Urgent action is required to address AMS funding and resourcing deficits.

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.

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.

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.

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.

Performance of Xpert MTB/RIF and sputum microscopy compared to sputum culture for diagnosis of tuberculosis in seven hospitals in Indonesia.

Introduction: Tuberculosis (TB) is a major public health concern in Indonesia, where the incidence was 301 cases per 100,000 inhabitants in 2020 and the prevalence of multi-drug resistant (MDR) TB is increasing. Diagnostic testing approaches vary across Indonesia due to resource limitations. Acid-fast bacilli (AFB) smear is widely used, though Xpert MTB/RIF has been the preferred assay for detecting TB and rifampicin resistance since 2012 due to higher sensitivity and ability to rapidly identify rifampicin resistance. However, <1,000 Xpert instruments were available in Indonesia as of 2020 and the Xpert supply chain has suffered interruptions. Methods: We compared the performance of Xpert MTB/RIF and AFB smear to facilitate optimization of TB case identification. We analyzed baseline data from a cohort study of adults with pulmonary TB conducted at seven hospitals across Indonesia. We evaluated sensitivity and specificity of AFB smear and Xpert MTB/RIF using Mycobacterium tuberculosis (Mtb) culture as the gold standard, factors associated with assay results, and consistency of Xpert MTB/RIF with drug susceptibility test (DST) in detecting rifampicin resistance. Results: Sensitivity of AFB smear was significantly lower than Xpert MTB/RIF (86.2 vs. 97.4%, p-value <0.001), but specificity was significantly better (86.7 vs. 73.3%, p-value <0.001). Performance varied by hospital. Positivity rate for AFB smear and Mtb culture was higher in subjects with pulmonary cavities and in morning sputum samples. Consistency of Xpert MTB/RIF with DST was lower in those with rifampicin- sensitive TB by DST. Discussion: Additional evaluation using sputa from primary and secondary Indonesian health centers will increase the generalizability of the assessment of AFB smear and Xpert MTB/RIF performance, and better inform health policy. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT027 58236].

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.

Multimodal intervention to reduce acquisition of carbapenem-non-susceptible Gram-negative bacteria in intensive care units in the National Referral Hospital of Indonesia: An interrupted time series study.

PURPOSE: To evaluate a low-cost multimodal intervention on the acquisition of carbapenem-non-susceptible Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa by patients in low-resource intensive care units. MATERIALS AND METHODS: We performed a quasi-experimental study in a referral hospital in Jakarta, Indonesia: pre-intervention phase 1 (2013-2014), intervention phase 2 (2014-2015) and post-intervention phase 3 (2015-2016). The intervention was hand hygiene promotion and environmental cleaning and disinfection combined with patient disinfection and cohorting. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, which was assessed by active microbiological surveillance and analysed with a multilevel Poisson segmented regression model. RESULTS: In phase 1 (387 patients), the acquisition rate was 4.3/100 days for carbapenem-non-susceptible A. baumannii versus 1.1/100 days for both K. pneumoniae and P. aeruginosa. There was a significant step change from phase 1 to phase 3 (361 patients) in the acquisition of carbapenem-non-susceptible strains, the incidence rate ratio (IRR) was 0.343 (99%CI: 0.164-0.717). This significant change was mainly due to reduced acquisitions of resistant A. baumannii (IRR 0.4, 99%CI: 0.181-1.061). Negative confounding was observed. CONCLUSION: A multimodal intervention to prevent acquisition of resistant pathogens is feasible and may be effective in ICUs in lower-middle income countries.

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.

New approach for the identification of potentially toxigenic Corynebacterium sp. using a multiplex PCR assay.

In diphtheria laboratory examinations, the PCR test can be applied to isolates and clinical specimens. This study aimed to develop a PCR assay to identify the species and toxigenicity of diphtheria-causing bacteria, including the prediction of some NTTB types. Seven reference isolates, four synthetic DNA samples, 36 stored isolates, and 487 clinical samples used for PCR optimization. The PCR results was confirmed by DNA sequence analysis. The results of the PCR examination of the 7 reference isolates and 36 stored isolates were similar to the results obtained using conventional methods as gold standard, both for diphtheria-causing and non-diphtheria-causing bacteria. The validation of the PCR results using DNA sequence analysis showed that there was no mispriming or misamplification. The multiplex PCR assay developed in this study could correctly identify the species and toxigenicity of diphtheria-causing bacteria, including the prediction of some NTTB types not yet covered by established PCR methods.

Biofilm-Producing Bacteria and Risk Factors (Gender and Duration of Catheterization) Characterized as Catheter-Associated Biofilm Formation.

BACKGROUND: A catheter-associated urinary tract infection (CA-UTI) is preceded by biofilm formation, which is related to several risk factors such as gender, age, diabetic status, duration of catheterization, bacteriuria before catheterization, virulence gene factor, and antibiotic usage. AIMS: This study aims to identify the microbial composition of catheter samples, including its corresponding comparison with urine samples, to determine the most important risk factors of biofilm formation and characterize the virulence gene factors that correlate with biofilm formation. METHODS: A longitudinal cross-sectional study was conducted on 109 catheterized patients from September 2017 to January 2018. The risk factors were obtained from the patients' medical records. All catheter and urine samples were cultured after removal, followed by biomass quantification. Isolate identification and antimicrobial susceptibility testing were performed using the Vitex2 system. Biofilm-producing bacteria were identified by the Congo Red Agar (CRA) method. A PCR test characterized the virulence genes of dominant bacteria (E. coli). All data were collected and processed for statistical analysis. RESULTS: Out of 109 catheterized patients, 78% of the catheters were culture positive, which was higher than those of the urine samples (37.62%). The most common species isolated from the catheter cultures were Escherichia coli (28.1%), Candida sp. (17.8%), Klebsiella pneumoniae (15.9%), and Enterococcus faecalis (13.1%). E. coli (83.3%) and E. faecalis (78.6%) were the main isolates with a positive CRA. A statistical analysis showed that gender and duration prior to catheterization were associated with an increased risk of biofilm formation (p < 0.05). CONCLUSION: E. coli and E. faecalis were the most common biofilm-producing bacteria isolated from the urinary catheter. Gender and duration are two risk factors associated with biofilm formation, therefore determining the risk of CAUTI. The presence of PapC as a virulence gene encoding pili correlates with the biofilm formation. Biofilm-producing bacteria, female gender, duration of catheterization (more than five days), and PapC gene presence have strong correlation with the biofilm formation. To prevent CAUTI, patients with risk factors should be monitored by urinalysis tests to detect earlier the risk of biofilm formation.