Feasibility of informing syndrome-level empiric antibiotic recommendations using publicly available antibiotic resistance datasets.

Background: Antibiotics are often prescribed empirically to treat infection syndromes before causative bacteria and their susceptibility to antibiotics are identified. Guidelines on empiric antibiotic prescribing are key to effective treatment of infection syndromes, and need to be informed by likely bacterial aetiology and antibiotic resistance patterns. We aimed to create a clinically-relevant composite index of antibiotic resistance for common infection syndromes to inform recommendations at the national level. Methods: To create our index, we used open-access antimicrobial resistance (AMR) surveillance datasets, including the ECDC Surveillance Atlas, CDDEP ResistanceMap, WHO GLASS and the newly-available Pfizer ATLAS dataset. We integrated these with data on aetiology of common infection syndromes, existing empiric prescribing guidelines, and pricing and availability of antibiotics. Results:  The ATLAS dataset covered many more bacterial species (287) and antibiotics (52) than other datasets (ranges = 8-11 and 16-32 respectively), but had a similar number of samples per country per year. Using these data, we were able to make empiric prescribing recommendations for bloodstream infection, pneumonia and cellulitis/skin abscess in up to 44 countries. There was insufficient data to make national-level recommendations for the other six syndromes investigated. Results are presented in an interactive web app, where users can visualise underlying resistance proportions to first-line empiric antibiotics for infection syndromes and countries of interest. Conclusions: We found that whilst the creation of a composite resistance index for empiric antibiotic therapy was technically feasible, the ATLAS dataset in its current form can only inform on a limited number of infection syndromes. Other open-access AMR surveillance datasets are largely limited to bloodstream infection specimens and cannot directly inform treatment of other syndromes. With improving availability of international AMR data and better understanding of infection aetiology, this approach may prove useful for informing empiric prescribing decisions in settings with limited local AMR surveillance data

Antibiotic de-escalation experience in the setting of emergency department: A retrospective, observational study

Background: Antimicrobial de-escalation (ADE) is a part of antimicrobial stewardship strategies aiming to minimize unnecessary or inappropriate antibiotic exposure to decrease the rate of antimicrobial resistance. Information regarding the effectiveness and safety of ADE in the setting of emergency medicine wards (EMW) is lacking. Methods: Adult patients admitted to EMW and receiving empiric antimicrobial treatment were retrospectively studied. The primary outcome was the rate and timing of ADE. Secondary outcomes included factors associated with early ADE, length of stay, and in-hospital mortality. Results: A total of 336 patients were studied. An initial regimen combining two agents was prescribed in 54.8%. Ureidopenicillins and carbapenems were the most frequently empiric treatment prescribed (25.1% and 13.6%). The rate of the appropriateness of prescribing was 58.3%. De-escalation was performed in 111 (33%) patients. Patients received a successful de-escalation on day 2 (21%), 3 (23%), and 5 (56%). The overall in-hospital mortality was 21%, and it was significantly lower among the de-escalation group than the continuation group (16% vs 25% p = 0.003). In multivariate analysis, de-escalation strategies as well as appropriate empiric and targeted therapy were associated with reduced mortality. Conclusions: ADE appears safe and effective in the setting of EMWs despite that further research is warranted to confirm these findings

Improving empirical antibiotic treatment:The role of diagnostic accuracy and surveillance

Antimicrobial Resistance (AMR) is a global health and development threat quickly worsening, especially in low-middle and middle-income countries. Overuse of antibiotics and inappropriate antibiotic treatment are the main drivers of AMR. The thesis describes the use of the urinary dipstick and the adherence to clinical guidelines as ways to improve the diagnostic process of urinary tract infection (UTI) and sepsis, respectively. An improved diagnostic process steers the prescription of the right antibiotic at the right time. Empirical antibiotic treatment requires insight into the prevailing prevalence of AMR, which population-based surveillance provides, in general, more accurate data compared to laboratory-based surveillance. In Southeast Asian countries where the prevalence of AMR is high, there are limited surveillance activities precluding guidance to empirical antibiotic treatment. The thesis discusses findings from current AMR surveillance in Indonesia, showing an extremely high prevalence of AMR in bacterial isolates from urine samples of patients suspected of UTI, threatening rational choices for empirical treatment. The thesis introduces the technique of Lots Quality Assurance Sampling as a way to make AMR surveillance more efficient while obtaining relevant local data to facilitate the choice of an appropriate antibiotic treatment strategy and steer empirical treatment guidelines and antimicrobial stewardship efforts

Strengthening antimicrobial resistance surveillance in Indonesia:Strategies for surveillance of uropathogens

Antimicrobial resistance (AMR) represents one of the most important threats to global health. Inappropriate use of antibiotics is a key driver of AMR. Surveillance is one important approach for tackling AMR, in order to: (1) inform empirical antibiotic therapy, (2) monitor trends in AMR and antibiotic use, and (3) inform policy at national and international levels. However, there are multiple challenges when implementing AMR surveillance, including cost, logistics, availability of relevant and timely information of AMR, and laboratory capacity. Novel approaches are thus needed that require minimum resources to produce high-quality and relevant surveillance data. Uropathogens are the most common bacteria causing infections in hospitals and in the community, and are commonly treated with empirical antibiotics. AMR in uropathogens is associated with increasing morbidity and mortality. This thesis assesses surveillance practices in the Asia-Pacific region, including Indonesia, and investigates the use of rapid threshold surveillance approaches, in particular Lot Quality Assurance Sampling (LQAS), for AMR surveillance among uropathogens. The research highlights the importance of unbiased population-based sampling in the out-patient setting, and the need for quality-assured laboratory processes. LQAS-based AMR surveillance should be considered when implementing surveillance for obtaining locally relevant AMR data

Quality of meta-analysis in terms of actual statistical analysis

Meta-analysis is an essential tool that facilitates clinicians, medical experts and decision makers to cope with the information overload in the public and healthcare sectors. The publication of meta-analyses is increasing rapidly every day with less or more of methodological rigour. Clinicians and medical experts depend wholeheartedly on the results and conclusions obtained from analyzing meta-analysis in order to assess the clinical effectiveness of healthcare intervention on a daily basis. Meta-analysis provides a specific estimate of a relationship which may also indicate if there is any need for further research. But the foundational problem of performing the clinically powerful meta-analysis is the guideline for how similar the studies must be in order to meet the inclusion criteria of the meta-analysis and the reliability of its conclusions {ERIC(2010)}. When there are discrepancies in the studies being combined and patient populations being studied, meta-analysis may provide results that are wrong. These may mislead potential users of meta-analysis to give wrong prescriptions to their patients. One requirement is to prepare a validated and reliable checklist that can assess the quality of meta-analysis in terms of reporting, methodology, science and most especially, the actual statistical analysis. Literature review reveals that existing checklists mainly focus on other aspects of quality with little or no attention to the quality of statistical methodology. Consequently, this thesis attempts to cover this gap. OBJECTIVE- To construct an appropriate validated quality instrument. Use the instrument to assess the quality of selected meta-analyses in terms of actual statistical analysis. To assess accuracy and consistency of reported estimates using Lee's methods for checking errors in reported relative risks, odds ratios and confidence intervals{Lee(1999)}. STUDIES - Eligible articles (Meta-analysis of randomised controlled trials) identified in the Cochrane database, Web of Knowledge and Medline databases were used in this project. Eligibility criteria include studies published in English language, as a full report between the periods of 2000-2008, have a comprehensive search strategy and have clear methods of selecting studies for inclusion and performed statistical analysis. We developed a checklist that measures the quality of meta-analysis in terms of actual statistical analysis and used the instrument to assess papers published in both Cochrane and Non-Cochrane reviews. RESULTS: A sample size of 100 papers was obtained using an estimated maximum error bound of 0.1. Studies were allocated equally between Cochrane and Non-Cochrane publications and selections were made from electronic databases. Records of meta-analysis of randomised contolled trials published in English, full text and journal articles between the periods of 2000 - 2008 show that there were 515 results out of 5821 records of meta-analysis published in Cochrane library, 507 out of 1434 records and 130 out of 135 records of meta-analysis published in Web of Knowledge and Medline respectively. Simple random sampling, implemented in R statistical package, was used to select random sample of studies from each database. 83 out of the 100 selected studies met the inclusion criteria - 42 studies from Cochrane reviews and 41 from Non-Cochrane reviews. Reporting and methodology quality are high in the two databases. However, in terms of statistical analysis, both databases are unlikely to explicitly state the design of individual studies combined in the meta- analysis. The Cochrane review is more likely to contact authors of published studies than their Paper-base counterparts. Cochrane reviews are less likely also, to use OQAQ(Overview Quality Assessment Questionnaire) and QUOROM (Quality of Reporting of Meta-analyses)in asssessment of validity of studies than paper reviews. There was no double counting of some aspects of studies identified among Paper-base Journals while we discovered four studies in Cochrane reviews that double counted the control arms. However, there was no simple double counting of studies found in both Cochrane and Non-Cochrane reviews. Lee's checks were performed on the twenty selected studies to verify errors on reported odd ratios, relative risks and confidence intervals. Some studies included in the meta-analysis reported zero events either in the treatment or control groups or both which led to a disparity between our calculated results and the estimates reported by the authors. The addition of a continuity correction factor of 0.5 to each cell of the studies with zero events took care of the disparities. Mabinary sas macro designed by Weir and Senn{weir(2008)} was also used to assess and check the validity of reported odd ratios, relative risks and confidence intervals on both reviews. The results obtained using the macro are consistent with the original reported results in most of the studies. Studies reporting relative risks in both Paper-Base Journals and Cochrane reviews are more likely to disagree with the Lee's requirement on minimum subject size and number of diseased subjects in either exposure groups given the CI, than those reporting odd ratios. These studies also have large outcomes. This seems to suggest that Lee's checks are not reliable for studies reporting relative risks, especially when outcomes are relatively large. CONCLUSION: Cochrane Handbooks and scales relating to specific interventions were mostly used to assess quality of studies in Cochrane reviews. Results showed no statistically significant difference between the reporting and methodological quality of Cochrane and non-Cochrane publications. More improvement is needed in the reportage of the design of included studies in both Cochrane and non-Cochrane reviews. This will help establish if the combined studies and the statistical method used in combining them are compatible. However, double counting of some aspects of studies was found in some meta-analysis selected from Cochrane reviews. Analysis suggests that studies reporting odd ratios are likely to be consistent with Lee's checks than those reporting relative risks. We also showed that Peter Lee's checks involving totals cannot be relied on to assess the quality of studies reporting relative risks