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      Prevalence of extended-spectrum-β-lactamase-producing Enterobacteriaceae: first systematic meta-analysis report from Pakistan

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          Abstract

          Background

          South-Asia is known as a hub for multidrug-resistant (MDR) bacteria. Unfortunately, proper surveillance and documentation of MDR pathogens is lacking in Pakistan. The alarming increase in the prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is a serious problem. From this perspective, we analysed published data regarding ESBL-producing Enterobacteriaceae in different regions of Pakistan.

          Methods

          A meta-analysis was performed to determine the prevalence of ESBL-producing Enterobacteriaceae in Pakistan. A Web-based search was conducted in electronic databases, including PubMed, Scopus and PakMedi Net (for non-indexed Pakistani journals). Articles published (in either indexed or non-indexed journals) between January 2002 and July 2016 were included in the study. Relevant data were extracted, and statistical analysis was performed using the Metaprop command of STATA version 14.1.

          Results

          A total of 68 studies were identified from the electronic data base search, and 55 of these studies met our inclusion criteria. Pakistan’s overall pooled proportion of ESBL-producers was 0.40 (95% CI: 0.34–0.47). The overall heterogeneity was significant (I2 = 99.75%, p < 0.001), and significant ES = 0 (Z = 18.41, p < 0.001) was found. OXA, SHV, TEM and CTX-M were the most commonly found gene variants for ESBLs in these studies.

          Conclusion

          The prevalence of ESBL-producing Enterobacteriaceae is high in Pakistan. Little is known about the annual frequency of ESBLs and their prevalence in different provinces of Pakistan. No data are available regarding ESBL frequency in Baluchistan. This underscores an urgent demand for regular surveillance to address this antimicrobial resistance problem. Surveillance to better understand the annual ESBL burden is crucial to improve national and regional guidelines.

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          Most cited references97

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          Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic.

          Staphylococcus aureus is an important cause of skin and soft-tissue infections (SSTIs), endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis. Methicillin-resistant S. aureus (MRSA) isolates were once confined largely to hospitals, other health care environments, and patients frequenting these facilities. Since the mid-1990s, however, there has been an explosion in the number of MRSA infections reported in populations lacking risk factors for exposure to the health care system. This increase in the incidence of MRSA infection has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). CA-MRSA strains differ from the older, health care-associated MRSA strains; they infect a different group of patients, they cause different clinical syndromes, they differ in antimicrobial susceptibility patterns, they spread rapidly among healthy people in the community, and they frequently cause infections in health care environments as well. This review details what is known about the epidemiology of CA-MRSA strains and the clinical spectrum of infectious syndromes associated with them that ranges from a commensal state to severe, overwhelming infection. It also addresses the therapy of these infections and strategies for their prevention.
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            Metaprop: a Stata command to perform meta-analysis of binomial data

            Background Meta-analyses have become an essential tool in synthesizing evidence on clinical and epidemiological questions derived from a multitude of similar studies assessing the particular issue. Appropriate and accessible statistical software is needed to produce the summary statistic of interest. Methods Metaprop is a statistical program implemented to perform meta-analyses of proportions in Stata. It builds further on the existing Stata procedure metan which is typically used to pool effects (risk ratios, odds ratios, differences of risks or means) but which is also used to pool proportions. Metaprop implements procedures which are specific to binomial data and allows computation of exact binomial and score test-based confidence intervals. It provides appropriate methods for dealing with proportions close to or at the margins where the normal approximation procedures often break down, by use of the binomial distribution to model the within-study variability or by allowing Freeman-Tukey double arcsine transformation to stabilize the variances. Metaprop was applied on two published meta-analyses: 1) prevalence of HPV-infection in women with a Pap smear showing ASC-US; 2) cure rate after treatment for cervical precancer using cold coagulation. Results The first meta-analysis showed a pooled HPV-prevalence of 43% (95% CI: 38%-48%). In the second meta-analysis, the pooled percentage of cured women was 94% (95% CI: 86%-97%). Conclusion By using metaprop, no studies with 0% or 100% proportions were excluded from the meta-analysis. Furthermore, study specific and pooled confidence intervals always were within admissible values, contrary to the original publication, where metan was used.
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              Novel classes of antibiotics or more of the same?

              The world is running out of antibiotics. Between 1940 and 1962, more than 20 new classes of antibiotics were marketed. Since then, only two new classes have reached the market. Analogue development kept pace with the emergence of resistant bacteria until 10-20 years ago. Now, not enough analogues are reaching the market to stem the tide of antibiotic resistance, particularly among gram-negative bacteria. This review examines the existing systemic antibiotic pipeline in the public domain, and reveals that 27 compounds are in clinical development, of which two are new classes, both of which are in Phase I clinical trials. In view of the high attrition rate of drugs in early clinical development, particularly new classes and the current regulatory hurdles, it does not seem likely that new classes will be marketed soon. This paper suggests that, if the world is to return to a situation in which there are enough antibiotics to cope with the inevitable ongoing emergence of bacterial resistance, we need to recreate the prolific antibiotic discovery period between 1940 and 1962, which produced 20 classes that served the world well for 60 years. If another 20 classes and their analogues, particularly targeting gram-negatives could be produced soon, they might last us for the next 60 years. How can this be achieved? Only a huge effort by governments in the form of finance, legislation and providing industry with real incentives will reverse this. Industry needs to re-enter the market on a much larger scale, and academia should rebuild its antibiotic discovery infrastructure to support this effort. The alternative is Medicine without effective antibiotics. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
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                Author and article information

                Contributors
                samyyiaabrar@gmail.com
                shahidahussain100@gmail.com
                stat4u@gmail.com
                noorulain.799@gmail.com
                hayat.phd.mmg@pu.edu.pk
                saba.mmg@pu.edu.pk
                Journal
                Antimicrob Resist Infect Control
                Antimicrob Resist Infect Control
                Antimicrobial Resistance and Infection Control
                BioMed Central (London )
                2047-2994
                20 February 2018
                20 February 2018
                2018
                : 7
                : 26
                Affiliations
                [1 ]ISNI 0000 0001 0670 519X, GRID grid.11173.35, Department of Microbiology and Molecular Genetics, , University of the Punjab, ; Lahore, Pakistan
                [2 ]Citilab and Research center, Lahore, Pakistan
                [3 ]ISNI 0000 0001 0670 519X, GRID grid.11173.35, College of Statistical and Actuarial Sciences, , University of the Punjab, ; Lahore, Pakistan
                Article
                309
                10.1186/s13756-018-0309-1
                5819302
                29484173
                f8bce4b7-223b-41e2-b77b-8856f7cbaa01
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 November 2017
                : 26 January 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Infectious disease & Microbiology
                mdr,esbls,enterobacteriaceae,meta-analysis,pakistan
                Infectious disease & Microbiology
                mdr, esbls, enterobacteriaceae, meta-analysis, pakistan

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