Corrigendum: Degenerate Beta autoregressive model for proportion time-series with zeros or ones: an application to antimicrobial resistance rate using R shiny app.

[This corrects the article DOI: 10.3389/fpubh.2022.969777.].

Comparison of integron mediated antimicrobial resistance in clinical isolates of Escherichia coli from urinary and bacteremic sources.

BACKGROUND: Antimicrobial resistance (AMR) is a global threat driven mainly by horizontal gene transfer (HGT) mechanisms through mobile genetic elements (MGEs) including integrons. The variable region (VR) of an integron can acquire or excise gene cassettes (GCs) that confer resistance to antibiotics based on the selection pressure. Escherichia coli plays a significant role in the genetic transfer of resistance determinants to other Gram-negative bacteria. Current study is aimed to detect and compare integron-mediated resistance in clinical isolates of E. coli. Unique isolates of E. coli from urine or blood cultures were studied for their antimicrobial resistance patterns and integrons were detected using polymerase chain reaction assays followed by Sanger sequencing of GCs. RESULTS: During the study period, a total of 470 E. coli isolates were obtained, 361 (76.8%) from urinary and 109 (23.1%) from bacteremic sources. Class 1 integrons were detected in 66 (18.2%) and 26 (23.8%) isolates respectively. Urinary isolates of E. coli harbouring Class 1 integrons demonstrated significantly higher rates of resistance (p < 0.05) for most antibiotics (12/16, 75%) compared to integron negative isolates. Although not statistically significant, similar differences were observed in bacteremic isolates. Among the urinary isolates, 27 (40.9%) had a VR, in which the most common GC array detected was DfrA17-AadA5 (n = 14), followed by DfrA5 (n = 4) and DfrA12 (n = 3). Among bacteremic isolates, only 4 (15.3%) had a VR, all of which were carrying DfrA17. The detected GC array correlated with the respective isolates' phenotypic resistance patterns. CONCLUSION: We found a strong correlation between integron positivity and trimethoprim resistance among E. coli from urinary sources. Although higher rates of resistance were observed in bacteremic isolates, they mostly carried empty integrons.

Evaluation of clinical, diagnostic features and therapeutic outcome of neurobrucellosis: a case series and review of literature.

AIM: In this study, we aimed to discuss the clinical features, laboratory findings, treatment and outcome of seven cases of neurobrucellosis from a tertiary care center and review the available global literature. MATERIALS AND METHODS: The diagnosis of neurobrucellosis was established using the following criteria in our setting: (1) signs and symptoms of neurological infection with examination of cerebrospinal fluid (CSF) revealing signs of meningitis, (2) isolation of Brucella spp. from blood and/or CSF and/or antibody titer ≥1:160 in serum using standard agglutination test (SAT) and/or the presence of anti-Brucella antibodies in CSF and/or detection of Brucella spp.-specific DNA from CSF using PCR. A literature search was performed to review previous cases of neurobrucellosis published worldwide during the last 30 years. RESULTS: The proportion of neurobrucellosis was 2.8% in our setting. Fever with headache and altered sensorium were the major presenting complaints. Brucella melitensis was isolated from blood culture in 6 patients. From the literature search, a total of 221 cases of neurobrucellosis were reviewed and analyzed. Meningitis (32.6%), loss of hearing (25.8%) and encephalitis (14.9%) were the most common clinical features. Involvement of cranial nerves, polyradiculopathy and paraplegia were the major complications found in patients with neurobrucellosis. CONCLUSIONS: Neurobrucellosis should always be considered in the differential diagnosis of befitting neurological, rheumatological, and neuropsychiatric presentations in endemic regions for brucellosis. To prevent morbidity and mortality associated with neurobrucellosis, a multimodal diagnostic approach is essential for early and accurate diagnosis and effective treatment.

Self-reported survey on infection prevention and control structures in healthcare facilities part of a national level healthcare associated infection surveillance network in India, 2019.

BACKGROUND: Healthcare associated infections (HAIs) are prevalent and difficult to treat worldwide. Most HAIs can be prevented by effective implementation of Infection Prevention and Control (IPC) measures. A survey was conducted to assess the existing IPC practices across a network of Indian Hospitals using the World Health Organization designed self-assessment IPC Assessment Framework (IPCAF) tool. METHODS: This was a cross sectional observation study. Thirty-two tertiary care public and private facilities, part of the existing Indian HAI surveillance network was included. Data collected was analyzed by a central team at All India Institute of Medical Sciences, New Delhi, a tertiary care hospital of India. The WHO questionnaire tool was used to understand the capacity and efforts to implement IPC practices across the network. RESULTS: The overall median score of IPCAF across the network was 620. Based on the final IPCAF score of the facilities; 13% hospitals had basic IPC practices, 28% hospitals had intermediate and 59% hospitals had advanced IPC practices. The component multimodal strategies had the broadest range of score while the component IPC guidelines had the narrowest one. CONCLUSIONS: Quality improvement training for IPC nurses and healthcare professionals are needed to be provided to health facilities.

Degenerate Beta autoregressive model for proportion time-series with zeros or ones: An application to antimicrobial resistance rate using R shiny app.

Background: Antimicrobial resistance has emerged as one of the foremost public health troubles of the 21st century. This has ended in a public health disaster of the global situation, which threatens the exercise of present-day remedy. There is an urgent requirement for a cost-effective strategy to reduce antimicrobial resistance. Infectious disease control researchers most often analyze and predict antimicrobial resistance rate data that includes zeros or ones. Commonly used time-series analysis such as autoregressive moving average model is inappropriate for such data and may arrive at biased results. Objective: This study aims to propose a time-series model for continuous rates or proportions when the interval of series includes zeros or ones and compares the model with existing models. Data: The Escherichia coli, isolated from blood cultures showing variable susceptibility results to different antimicrobial agents, has been obtained from a clinical microbiology laboratory of a tertiary care hospital, Udupi district, Karnataka, during the years between 2011 and 2019. Methodology: We proposed a Degenerate Beta Autoregressive model which is a mixture of continuous and discrete distributions with probability mass at zero or one. The proposed model includes autoregressive terms along with explanatory variables. The estimation is done using maximum likelihood with a non-linear optimization algorithm. An R shiny app has been provided for the same. Results: The proposed Degenerate Beta Autoregressive model performed well compared to the existing autoregressive moving average models. The forecasted antimicrobial resistance rate has been obtained for the next 6 months. Conclusion: The findings of this article could be beneficial to the infectious disease researchers to use an appropriate time-series model to forecast the resistance rate for the future and to have better or advance public health policies to control the rise in resistance rate.

Acute kidney injury and its outcomes in melioidosis.

BACKGROUND: Melioidosis is a potentially fatal tropical infection caused by Burkholderia pseudomallei. Kidney involvement is possible, but has not been well described. AIM: This study aimed to assess the risk of acute kidney injury (AKI) and its outcomes in melioidosis. METHODS: A retrospective observational cohort study was performed. Case records of consecutive patients with culture-confirmed melioidosis, observed from January 1st, 2012 through December 31st, 2019 were analysed for demographics, presence of comorbidities, including chronic kidney disease (CKD), diabetes mellitus (DM), and presence of bacteraemia, sepsis, shock, AKI, and urinary abnormalities. The outcomes we studied were: mortality, need for hospitalisation in an intensive care unit (ICU), duration of hospitalization. We then compared the outcomes between patients with and without AKI. RESULTS: Of 164 patients, AKI was observed in 59 (35.98%), and haemodialysis was required in eight (13.56%). In the univariate analysis, AKI was associated with CKD (OR 5.83; CI 1.140-29.90, P = 0.03), bacteraemia (OR 8.82; CI 3.67-21.22, P < 0.001) and shock (OR 3.75; CI 1.63-8.65, P = 0.04). In the multivariate analysis, CKD (adjusted OR 10.68; 95% CI 1.66-68.77; P = 0.013) and bacteraemia (adjusted OR 8.22; 95% CI 3.15-21.47, P < 0.001) predicted AKI. AKI was associated with a greater need for ICU care (37.3% vs. 13.3%, P = 0.001), and mortality (32.2% vs. 5.7%, P < 0.001). Mortality increased with increasing AKI stage, i.e. stage 1 (OR 3.52, CI 0.9-13.7, P = 0.07), stage 2 (OR 6.79, CI 1.92-24, P = 0.002) and stage 3 (OR 17.8, CI 5.05-62.8, P < 0.001), however kidney function recovered in survivors. Hyponatremia was observed in 138 patients (84.15%) and isolated urinary abnormalities were seen in 31(18.9%). CONCLUSIONS: AKI is frequent in melioidosis and occurred in 35.9% of our cases. Hyponatremia is likewise common. AKI was predicted by bacteraemia and CKD, and was associated with higher mortality and need for ICU care; however kidney function recovery was observed in survivors.

Identifying opportunities for antimicrobial stewardship through a point prevalence survey in an Indian tertiary-care teaching hospital.

OBJECTIVES: Unregulated and inappropriate use of antimicrobial agents has been a major driver of antimicrobial resistance with a dangerous impact on health issues in developing nations. We report an audit of antimicrobial use patterns in a tertiary-care teaching hospital in order to identify opportunities for antimicrobial stewardship. METHODS: A point prevalence survey was conducted to study the use of ten selected antibiotics in various adult inpatient facilities. Patient characteristics as well as indications and patterns of antibiotic prescription were recorded. RESULTS: A total of 188 patients received any one of the survey antibiotics, accounting for 43% of patients admitted under the study specialties. Of the 188 patients, 59% were admitted in non-intensive care unit settings. The median (interquartile range) duration of hospitalisation during the survey was 8 (4.75) days. Intra-abdominal infections (75; 40%) and respiratory infections (41; 22%) were the most common reasons for admission. Empirical antibiotic use was observed in 66% of patients. Antimicrobial use without any microbiological test was evidenced in 32 patients (17%). Significant differences were noted between medical and surgical specialties in choice of antibiotic, dosage and utilisation of microbiological tests. CONCLUSIONS: High empirical antibiotic use, poor transition from empirical to rational use, and underutilisation of microbiological tests were noted. The choice of antibiotics differed among specialties. Inappropriate dosing was greater in surgical specialties, especially with aminoglycosides. Adherence to local antibiotic policy, optimal dosing and audit of reserved antibiotic use can be useful approaches to strengthen antimicrobial stewardship programmes.

Implications of environmental and pathogen-specific determinants on clinical presentations and disease outcome in melioidosis patients.

BACKGROUND: Melioidosis is gaining recognition as an emerging infectious disease with diverse clinical manifestations and high-case fatality rates worldwide. However, the molecular epidemiology of the disease outside the endemic regions such as northeast part of Thailand and northern Australia remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Clinical data and B. pseudomallei isolates obtained from 199 culture-confirmed cases of melioidosis diagnosed during 2006-2016 in South India were used to elucidate the host and pathogen specific variable virulence determinants associated with clinical presentations and disease outcome. Further, we determined the temporal variations and the influence of ecological factors on B.pseudomallei Lipopolysaccharide (LPS) genotypes causing infections. Severe forms of the disease were observed amongst 169 (85%) patients. Renal dysfunction and infection due to B.pseudomallei harboring BimABm variant had significant associations with severe forms of the disease. Diabetes mellitus, septicemic melioidosis and infection due to LPSB genotype were independent risk factors for mortality. LPSB (74%) and LPSA (20.6%) were the prevalent genotypes causing infections. Both genotypes demonstrated temporal variations and had significant correlations with rainfall and humidity. CONCLUSION/SIGNIFICANCE: Our study findings suggest that the pathogen specific virulence traits under the influence of ecological factors are the key drivers for geographical variations in the molecular epidemiology of melioidosis.

Perceived differences between intensivists and infectious diseases consultants facing antimicrobial resistance: a global cross-sectional survey.

To identify differences in perception on multi-drug-resistant (MDR) organisms and their management at intensive care units (ICU). A cross-sectional survey was conducted. A proposal addressing a pathogen priority list (PPL) for ICU, arising from the TOTEM study, was compared with a sample of global experts in infections in critically ill patients. The survey was responded by 129 experts. Globally, ESBL Enterobacteriaceae, followed by carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Klebsiella pneumoniae, were the main concerns. Some differences in opinion were identified between 63 (49%) ICU physicians (ICU/anesthesiology) and 43 (33%) infectious disease consultants (ID physicians/microbiologists). The pathogens most concerning in the ICU for intensivists were ESBL Enterobacteriaceae (38%) versus carbapenem-resistant A. baumannii (48.3%) for ID consultants, (p < 0.05). Increasing number of ID consultants over intensivists (26% vs 14%) reported difficulty in choosing initial therapy for carbapenem-resistant A. baumannii. For intensivists, the urgent measures to limit development of antibiotic resistance were headed by cohort measures (26.3%) versus increasing nurse/patient ratio (32.5%) for ID consultants, (p < 0.05). Regarding effectiveness to prevent MDR development and spread, education programs (42.4%) were the priority for intensivists versus external consultation (35.7%) for ID consultants. Finally, both groups agreed that carbapenem resistance was the most pressing concern (> 70%) regarding emerging resistance. Differences in priorities regarding organisms, infection control practices, and educational priorities were visualized between ID/clinical microbiologists and ICU/anesthesiologists. Multi-disciplinary collaboration is required to achieve best care for ICU patients with severe infections.

A global priority list of the TOp TEn resistant Microorganisms (TOTEM) study at intensive care: a prioritization exercise based on multi-criteria decision analysis.

The World Health Organization (WHO) proposed a global priority pathogen list (PPL) of multidrug-resistant (MDR) bacteria. Our current objective was to provide global expert ranking of the most serious MDR bacteria present at intensive care units (ICU) that have become a threat in clinical practice. A proposal addressing a PPL for ICU, arising from the WHO Global PPL, was developed. Based on the supporting data, the pathogens were grouped in three priority tiers: critical, high, and medium. A multi-criteria decision analysis (MCDA) was used to identify the priority tiers. After MCDA, mortality, treatability, and cost of therapy were of highest concern (scores of 19/20, 19/20, and 15/20, respectively) while dealing with PPL, followed by healthcare burden and resistance prevalence. Carbapenem-resistant (CR) Acinetobacter baumannii, carbapenemase-expressing Klebsiella pneumoniae (KPC), and MDR Pseudomonas aeruginosa were identified as critical organisms. High-risk organisms were represented by CR Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae. Finally, ESBL Serratia marcescens, vancomycin-resistant Enterococci, and TMP-SMX-resistant Stenotrophomonas maltophilia were identified as medium priority. We conclude that education, investigation, funding, and development of new antimicrobials for ICU organisms should focus on carbapenem-resistant Gram-negative organisms.

Ventilator-associated events versus ventilator-associated respiratory infections-moving into a new paradigm or merging both concepts, instead?

Despite ventilator-associated respiratory infections (VARI) are reported as the most common and fatal complications related to mechanical ventilation (MV), they are not the unique occurrences. The new classification of ventilator-associated events (VAE) proposed by the centers for disease control and prevention (CDC) enhance the spectra of complications due to MV including both infection-related and non-infectious events. Both VAEs and VARIs are associated with prolonged duration of MV, longer stay in hospital and in the intensive care unit (ICU) and more antibiotic consumption, nonetheless patients with VAEs have worst outcomes. The VARI and VAE algorithms are focused on different targets and the correlation between both classifications is shown to be poor. The diagnostic criteria of the traditional classification have limited accuracy and the non-infectious complications may be misinterpreted as VARI. While the VAE surveillance enhances the spectra of MV complications but excludes less severe VARIs. Noninfective events explain up to 30% of VAEs, the main causes being atelectasis, acute respiratory distress syndrome, pulmonary edema and pulmonary embolism. The bundles assessing VAE are associated with less incidence of VAP and improved outcomes but they fail to reduce the rates of VAE. Automated VAE surveillance is efficient and useful as a quality indicator in the ICU while the differences in the interpretation of VARI criteria limit its role in the design of global protocols and preventive strategies. We suggest that a more comprehensive strategy should combine both algorithms with emphasis on clinical outcomes.

Invasive nontyphoidal Salmonella disease in southern India: a 5-year experience from a tertiary care hospital

Background/aim: The current study was carried out to describe the clinical presentation, antimicrobial susceptibility pattern, and outcome of invasive nontyphoidal Salmonella disease (iNTS) in a tertiary care center. Materials and methods: A 5-year hospital-based retrospective study was carried out on blood culture-confirmed cases of iNTS. Medical records of patients were reviewed to obtain information on demography, clinical manifestations, comorbidities, complications, immune status, treatment, and clinical outcome. Results: A total of 40 blood culture-confirmed cases of iNTS were diagnosed during the study period. Among these 40 isolates, 9 (22.5%) were identified as Salmonella Typhimurium. Fever (67.5%) with gastrointestinal disturbance (40%) was the most common clinical presentation. The majority of the patients were immunosuppressed (75%). All isolates were susceptible to all the antimicrobials tested. Ceftriaxone (92.5%) was the most common antimicrobial used in our setting. A total of 15% patients died during the hospital stay. Conclusion: We conclude that iNTS disease is a severe infection prevailing in India with a high mortality rate. Anemia and diabetes were the two most common comorbidities. Though all NTS organisms isolated were sensitive to all the antimicrobials tested, we suggest that continued surveillance is necessary to monitor the presence of multidrug-resistant strains.