Validation of Drug Resistance in Pneumonia (DRIP) Score as Empirical Antibiotic Failure Predictor in Community-Acquired Pneumonia Patients in Cipto Mangunkusumo Hospital.

BACKGROUND: The incidence of CAP due to Drug-Resistant Pathogen (DRP) requires broad-spectrum antibiotic therapy, Drugs Resistance in Pneumonia (DRIP) score can predict these cases. The use of the DRIP score can prevent antibiotic failure and long hospitalization, but validation is needed so that the DRIP score can be used according to the local community at Cipto Mangunkusumo National Central Public Hospital. METHODS: This research is a retrospective cohort study in CAP patients who were hospitalized during the period January 2019 to June 2020. Data were taken from medical records. Failure of empiric antibiotics occurs when one of these criteria is found: patient mortality, ICU transfer, and escalation of antibiotics as well as length of stay. RESULTS: 480 patients met the criteria. There were 331 patients (69%) with a DRIP score of <4 and 149 patients (31%) with a DRIP score of≥4. A total of 283 patients (59%) of antibiotic failures were detailed in 174 patients with a DRIP score <4 and 109 patients DRIP score ≥4. DRIP calibration using the Hosmer-Lemeshow test obtained p-value= 0.667 (p>0.05). AUC observations on the ROC curve obtained 0.651 (95% CI; 0.601-0.700). CONCLUSION: The DRIP score has low accuracy performance and calibration value in predicting empirical antibiotic failure and poor discriminatory value.

Identifying Predictors of Mortality in Sepsis Patients with Malignancy: A Retrospective Cohort Study.

BACKGROUND: Sepsis is a major problem that contributes to a high mortality rate. Its mortality is especially high in patients with malignancy. One study reported that sepsis patients with malignancy have a 2.32 times higher risk of mortality compared to patients without malignancy. For this reason, factors that influence mortality in sepsis patients with malignancy become especially important to provide effective and efficient therapy. This study aims to identify factors that influence mortality in sepsis patients with malignancy. METHODS: This study is a retrospective cohort study using medical records of sepsis patients with malignancy who were treated at Cipto Mangunkusumo Hospital from 2020 to 2022. A bivariate analysis was carried out and followed by a logistic regression analysis on variables with p-value<0.25 on the bivariate analysis. RESULTS: Among the 350 eligible sepsis subjects with malignancy, there was an 82% mortality rate (287 subjects). Bivariate and multivariate analyses revealed significant associations between mortality and both SOFA score (adjusted Odds Ratio of 5.833, 95%CI 3.214-10.587) and ECOG performance status (adjusted Odds Ratio of 3.490, 95%CI 1.690-7.208). CONCLUSION: SOFA score and ECOG performance status are significantly associated with sepsis patient mortality in malignancy cases.

Observational Study on Secondary Bacterial Infection and the Use of Antibiotics in COVID-19 Patients Treated in a Tertiary Referral Hospital.

BACKGROUND: Data on secondary bacterial infection in patients with COVID-19 in Indonesia are still limited, while the use of empirical antibiotics continues to increase. This study aims to determine the secondary bacterial infection rate in hospitalized COVID-19 patients and factors related to secondary bacterial infection. METHODS: This is a retrospective cohort study on hospitalized COVID-19 patients undergoing treatment at Cipto Mangunkusumo Hospital from March 2020 to September 2020. Secondary bacterial infection is defined as the identification of a bacterial pathogen from a microbiological examination. RESULTS: From a total of 255 subjects, secondary infection was identified in 14.5%. Predictors of secondary infection were early symptoms of shortness of breath (OR 5.31, 95% CI 1.3 - 21.5), decreased consciousness (OR 4.81, 95% CI 1.77 - 13.0), length of stay > 12 days (OR 8.2, 95% CI 2.9 - 23.3), and central venous catheter placement (OR 3.0, 95% CI 1.1 - 8.0) The most common pathogen of secondary bacterial infection is Acinetobacter sp. (n=9; 28%). Empirical antibiotics were administered to 82.4% of subjects with predominant use of macrolides (n=141; 32.4%). CONCLUSION: The secondary bacterial infection rate in COVID-19 was 14.5% and is associated with dyspnea, decreased consciousness, length of stay >12 days, and central venous catheter placement. The use of antibiotics in COVID-19 reaches 82.4% and requires special attention to prevent the occurrence of antibiotic resistance.

Revisiting the Overlooked Infection: Rickettsioses.

The prevalence of human Rickettsioses cases in Indonesia is unknown and could probably be underestimated. The high prevalence of seropositive Rickettsia sp. was reported in small mammals (as vectors) and humans. In Indonesia, a recent study in patients with acute fever revealed that the prevalence of Rickettsioses is 10%. Many cases of Rickettsioses were often misdiagnosed with dengue fever, enteric fever, or leptospirosis due to their overlapping clinical manifestation. The limitation of point of care testing in Indonesia hindered the adequacy of diagnosis confirmation. Appropriate empirical or definitive treatment with macrolide, mainly doxycycline, is preferable compared to other broad-spectrum antibiotics, such as cephalosporin or quinolones. Moreover, when left untreated, Rickettsioses may deteriorate progressively to fatal outcomes, such as meningitis, sepsis, and even death. The awareness of health care practitioners, the availability of confirmatory rapid diagnostic tests and adequate treatment choices are important in eradicating this disease.

Prognostic accuracy of the quick Sequential Organ Failure Assessment (qSOFA)-lactate criteria for mortality in adults with suspected bacterial infection in the emergency department of a hospital with limited resources.

BACKGROUND: Routine use of the Sequential Organ Failure Assessment (SOFA) score to prognosticate patients with sepsis is challenged by the requirement to perform numerous laboratory tests. The prognostic accuracy of the quick SOFA (qSOFA) without or with lactate criteria has not been prospectively investigated in low and middle income countries. We assessed the performance of simplified prognosis criteria using qSOFA-lactate criteria in the emergency department of a hospital with limited resources, in comparison with SOFA prognosis criteria and systemic inflammatory response syndrome (SIRS) screening criteria. METHODS: This prospective cohort study was conducted between March and December 2017 in adult patients with suspected bacterial infection visiting the emergency department of the Indonesian National Referral Hospital. Variables from sepsis prognosis and screening criteria and venous lactate concentration at enrolment were recorded. Patients were followed up until hospital discharge or death. Prognostic accuracy was measured using area under the receiver operating characteristic curve (AUROC) of each criterion in the prediction of in-hospital mortality. RESULTS: Of 3026 patients screened, 1213 met the inclusion criteria. The AUROC of qSOFA-lactate criteria was 0.74 (95% CI 0.71 to 0.77). The AUROC of qSOFA-lactate was not statistically significantly different to the SOFA score (AUROC 0.75, 95% CI 0.72 to 0.78; p=0.462). The qSOFA-lactate was significantly higher than qSOFA (AUROC 0.70, 95% CI0.67 to 0.74; p=0.006) and SIRS criteria (0.57, 95% CI0.54 to 0.60; p<0.001). CONCLUSIONS: The prognostic accuracy of the qSOFA-lactate criteria is as good as the SOFA score in the emergency department of a hospital with limited resources. The performance of the qSOFA criteria is significantly lower than the qSOFA-lactate criteria and SOFA score.This abstract has been translated and adapted from the original English-language content. Translated content is provided on an "as is" basis. Translation accuracy or reliability is not guaranteed or implied. BMJ is not responsible for any errors and omissions arising from translation to the fullest extent permitted by law, BMJ shall not incur any liability, including without limitation, liability for damages, arising from the translated text.

Case report: two confirmed cases of human Seoul virus infections in Indonesia.

BACKGROUND: Seoul virus (SEOV) is a member of hantavirus family, which is transmitted to humans by Rattus rattus and Rattus norvegicus. Diagnosing SEOV infection is difficult because the clinical presentations are often undifferentiated with other viral or bacterial infections and assays to test antibodies seroconversion and RNA detection are not available in resource-limited setting like Indonesia. CASE PRESENTATION: We report two confirmed cases of SEOV infection from Indonesia. Here, we illustrate the clinical presentations, hematology and biochemistry profiles, and outcomes of the two cases. Phylogenetic analysis revealed that SEOV sequences have highest homology to isolates obtained from rodents in Indonesia. CONCLUSIONS: This report highlights the importance of considering SEOV infection in febrile patients with lymphopenia, thrombocytopenia, and elevation of liver enzyme despite the absence of hemorrhagic manifestations and renal syndromes. The public health importance of rodent-borne diseases such as SEOV infection urges an integrated epidemiological surveillance both in humans and rodents in Indonesia.

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.

The role of the glucocorticoid receptor and its impact on steroid response in moderate-severe COVID-19 patients.

The effect of corticosteroid therapy in COVID-19 patients is mediated by its suppressive effect on the regulations of inflammatory response. However, its clinical outcome is often unpredictable. This study aimed to explore the role of glucocorticoid receptors in corticosteroid response in Moderate-Severe COVID-19 patients. In this cross-sectional study, we attempted to find the relationship between the expression of the glucocorticoid receptor (encoded by NR3C1), the variation of glucocorticoid receptors isoform, and the mutations of glucocorticoid receptors exon with clinical response to corticosteroids. In addition, the relationship between glucocorticoid receptors expression and the expression of IκBα (encoded by NFKBIA) and glucocorticoid-induced leucine zipper protein (GILZ; encoded by TSC22D3) as steroid pathways was also evaluated. Thirty-four COVID-19 patients were studied. Blood was drawn before and on day 5 of corticosteroid treatment. Glucocorticoid receptors expression, isoform, and mutation were determined by RNA sequencing from white blood cells. Based on the improvement of clinical and oxygen status, patients were classified into responder and non-responder groups. Of thirty-four patients, 23 (67.6%) showed excellent responses to corticosteroids, and 11 (32.4%) were non-responders. The NR3C1 gene expression was significantly higher in the responsive group at baseline and after five days of glucocorticoid treatment. Isoform variant and mutation of glucocorticoid receptors did not correlate with clinical response. The expression of IκBα and GILZ correlated positively with glucocorticoid receptors expression. This study elucidates the relationship between glucocorticoid receptor expression with therapeutic responses to corticosteroids in moderate-severe COVID-19.

Blood culture utilization and epidemiology of antimicrobial-resistant bloodstream infections before and during the COVID-19 pandemic in the Indonesian national referral hospital.

BACKGROUND: There is a paucity of data regarding blood culture utilization and antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs). In addition, there has been a concern for increasing AMR infections among COVID-19 cases in LMICs. Here, we investigated epidemiology of AMR bloodstream infections (BSI) before and during the COVID-19 pandemic in the Indonesian national referral hospital. METHODS: We evaluated blood culture utilization rate, and proportion and incidence rate of AMR-BSI caused by WHO-defined priority bacteria using routine hospital databases from 2019 to 2020. A patient was classified as a COVID-19 case if their SARS-CoV-2 RT-PCR result was positive. The proportion of resistance was defined as the ratio of the number of patients having a positive blood culture for a WHO global priority resistant pathogen per the total number of patients having a positive blood culture for the given pathogen. Poisson regression models were used to assess changes in rate over time. RESULTS: Of 60,228 in-hospital patients, 8,175 had at least one blood culture taken (total 17,819 blood cultures), giving a blood culture utilization rate of 30.6 per 1,000 patient-days. A total of 1,311 patients were COVID-19 cases. Blood culture utilization rate had been increasing before and during the COVID-19 pandemic (both p < 0.001), and was higher among COVID-19 cases than non-COVID-19 cases (43.5 vs. 30.2 per 1,000 patient-days, p < 0.001). The most common pathogens identified were K. pneumoniae (23.3%), Acinetobacter spp. (13.9%) and E. coli (13.1%). The proportion of resistance for each bacterial pathogen was similar between COVID-19 and non-COVID-19 cases (all p > 0.10). Incidence rate of hospital-origin AMR-BSI increased from 130.1 cases per 100,000 patient-days in 2019 to 165.5 in 2020 (incidence rate ratio 1.016 per month, 95%CI:1.016-1.017, p < 0.001), and was not associated with COVID-19 (p = 0.96). CONCLUSIONS: In our setting, AMR-BSI incidence and etiology were similar between COVID-19 and non-COVID-19 cases. Incidence rates of hospital-origin AMR-BSI increased in 2020, which was likely due to increased blood culture utilization. We recommend increasing blood culture utilization and generating AMR surveillance reports in LMICs to inform local health care providers and policy makers.

Enhanced bedside mortality prediction combining point-of-care lactate and the quick Sequential Organ Failure Assessment (qSOFA) score in patients hospitalised with suspected infection in southeast Asia: a cohort study.

BACKGROUND: Simple, bedside prediction of infection-related mortality in low-resource settings is crucial for triage and resource-utilisation decisions. We aimed to evaluate mortality prediction by combining point-of-care venous lactate with the quick Sequential Organ Failure Assessment (qSOFA) score in adult patients admitted to hospital with suspected infection in southeast Asia. METHODS: We performed a cohort study by prospectively enrolling patients aged 18 years or older who had been admitted to hospital within the previous 24 h for suspected infection (with at least three documented systemic manifestations of infection according to the 2012 Surviving Sepsis Campaign) at Sunpasitthiprasong Hospital in Ubon Ratchathani, Thailand (derivation cohort). Venous lactate concentration was determined by a point-of-care device and multiple scores were developed. We then evaluated candidate 28-day mortality prediction models combining qSOFA and the lactate scores. A final model was compared with the qSOFA score, a lactate score, and a modified Sequential Organ Failure Assessment (SOFA) score for mortality discrimination using the area under the receiver operating characteristic curve (AUROC). Mortality discrimination of the qSOFA-lactate score was then verified in an external, prospectively enrolled, multinational cohort in southeast Asia. FINDINGS: Between March 1, 2013, and Jan 26, 2017, 5001 patients were enrolled in the derivation cohort; 4980 had point-of-care lactate data available and were eligible for analysis, and 816 died within 28 days of enrolment. The discrimination for 28-day mortality prediction of a qSOFA-lactate score combining the qSOFA score and a lactate score was superior to that of the qSOFA score alone (AUROC 0·78 [95% CI 0·76-0·80] vs 0·68 [0·67-0·70]; p<0·0001) and similar to a modified SOFA score (0·77 [0·75-0·78]; p=0·088). A lactate score alone had superior discrimination compared with the qSOFA score (AUROC 0·76 [95% CI 0·74-0·78]; p<0·0001). 815 patients were enrolled in the external validation cohort and 792 had point-of-care lactate data and were included in the analysis; the qSOFA-lactate score (AUROC 0·77 [95% CI 0·73-0·82]) showed significantly improved 28-day mortality discrimination compared with the qSOFA score alone (0·69 [0·63-0·74]; p<0·0001). INTERPRETATION: In southeast Asia, rapid, bedside assessments based on point-of-care lactate concentration combined with the qSOFA score can identify patients at risk of sepsis-related mortality with greater accuracy than the qSOFA score alone, and with similar accuracy to a modified SOFA score. FUNDING: National Institutes of Health, Wellcome Trust.

An open pilot study of the efficacy and safety of Polygeline in adult subjects with dengue haemorrhagic fever.

AIM: To observe the efficacy and safety of Polygeline colloid (Haemaccel) in adults with stage I - II of dengue haemorrhagic fever (DHF). METHODS: An open, non-comparative clinical trial. The subjects were male or female between 17 - 55 years old, who fulfilled the criteria of stage I or II of DHF according to WHO and selected with consecutive sampling. Fluid treatments were given following this protocol: polygeline i.v. infusion: 500 ml over first 6 hours and continued with 500 ml for the next 18 hours, and maintained to 1000 mL/24 hours from day-2 until maximum day-5. Ringer's lactate infusion: 1000 mL/18 hours from the first day to maximum day-5, as maintenance. Efficacy and safety of polygeline colloid were evaluated using initial stabilization of haematocrite level, measured as percentage of clinical trial subject who has stabilization of haemodynamic status based on serial haematocrite levels examinations, total parenteral fluid required and length of hospitalization. Statisticial analysis was done using ANOVA test and post hoc analysis using Turkey test. RESULTS: There were 43 subjects who completely participated in this study and included in analysis. From baseline levels, haematocrite decreased in first 6 hours during fluid treatment. This decrement persisted in 48 hours of observation. Statistical analysis with ANOVA test showed the significant differences of haematocrite level during observation (Sum of square between groups 495 and within group 4845, p= 0.000). Post hoc analysis with Turkey test showed significant differences of haematocrite level from baseline level to 48, 72 and 96 hours during observation periods. CONCLUSION: This pilot study showed that polygeline colloid was a safe initial fluid treatment and can be used for maintaining fluid adequacy in adults with stage I-II of DHF.

Utility of SOFA score, management and outcomes of sepsis in Southeast Asia: a multinational multicenter prospective observational study.

BACKGROUND: Sepsis is a global threat but insufficiently studied in Southeast Asia. The objective was to evaluate management, outcomes, adherence to sepsis bundles, and mortality prediction of maximum Sequential Organ Failure Assessment (SOFA) scores in patients with community-acquired sepsis in Southeast Asia. METHODS: We prospectively recruited hospitalized adults within 24 h of admission with community-acquired infection at nine public hospitals in Indonesia (n = 3), Thailand (n = 3), and Vietnam (n = 3). In patients with organ dysfunction (total SOFA score ≥ 2), we analyzed sepsis management and outcomes and evaluated mortality prediction of the SOFA scores. Organ failure was defined as the maximum SOFA score ≥ 3 for an individual organ system. RESULTS: From December 2013 to December 2015, 454 adult patients presenting with community-acquired sepsis due to diverse etiologies were enrolled. Compliance with sepsis bundles within 24 h of admission was low: broad-spectrum antibiotics in 76% (344/454), ≥ 1500 mL fluid in 50% of patients with hypotension or lactate ≥ 4 mmol/L (115/231), and adrenergic agents in 71% of patients with hypotension (135/191). Three hundred and fifty-five patients (78%) were managed outside of ICUs. Ninety-nine patients (22%) died. Total SOFA score on admission of those who subsequently died was significantly higher than that of those who survived (6.7 vs. 4.6, p < 0.001). The number of organ failures showed a significant correlation with 28-day mortality, which ranged from 7% in patients without any organ failure to 47% in those with failure of at least four organs (p < 0.001). The area under the receiver operating characteristic curve of the total SOFA score for discrimination of mortality was 0.68 (95% CI 0.62-0.74). CONCLUSIONS: Community-acquired sepsis in Southeast Asia due to a variety of pathogens is usually managed outside the ICU and with poor compliance to sepsis bundles. In this population, calculation of SOFA scores is feasible and SOFA scores are associated with mortality. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02157259. Registered 5 June 2014, retrospectively registered.