Antibiotic resistance in primary care in Austria - a systematic review of scientific and grey literature

<p>Abstract</p> <p>Background</p> <p>Antibiotic resistance is an increasing challenge for health care services worldwide. While up to 90% of antibiotics are being prescribed in the outpatient sector recommendations for the treatment of community-acquired infections are usually based on resistance findings from hospitalized patients. In context of the EU-project called "APRES - the appropriateness of prescribing antibiotic in primary health care in Europe with respect to antibiotic resistance" it was our aim to gain detailed information about the resistance data from Austria in both the scientific and the grey literature.</p> <p>Methods</p> <p>A systematic review was performed including scientific and grey literature published between 2000 and 2010. Inclusion and exclusion criteria were defined and the review process followed published recommendations.</p> <p>Results</p> <p>Seventeen scientific articles and 23 grey literature documents could be found. In contrast to the grey literature, the scientific publications describe only a small part of the resistance situation in the primary health care sector in Austria. Merely half of these publications contain data from the ambulatory sector exclusively but these data are older than ten years, are very heterogeneous concerning the observed time period, the number and origin of the isolates and the kind of bacteria analysed. The grey literature yields more comprehensive and up-to-date information of the content of interest. These sources are available in German only and are not easily accessible. The resistance situation described in the grey literature can be summarized as rather stable over the last two years. For <it>Escherichia coli </it>e.g. the highest antibiotic resistance rates can be seen with fluorochiniolones (19%) and trimethoprim/sulfamethoxazole (27%).</p> <p>Conclusion</p> <p>Comprehensive and up-to-date antibiotic resistance data of different pathogens isolated from the community level in Austria are presented. They could be found mainly in the grey literature, only few are published in peer-reviewed journals. The grey literature, therefore, is a very valuable source of relevant information. It could be speculated that the situation of published literature is similar in other countries as well.</p

Emergence of methicillin resistance predates the clinical use of antibiotics

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus—a notorious human pathogen—appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development

Non-detection of Chlamydia species in carotid atheroma using generic primers by nested PCR in a population with a high prevalence of Chlamydia pneumoniae antibody

BACKGROUND: The association of Chlamydia pneumoniae with atherosclerosis is controversial. We investigated the presence of C. pneumoniae and other Chlamydia spp. in atheromatous carotid artery tissue. METHODS: Forty elective carotid endarterectomy patients were recruited (27 males, mean age 65 and 13 females mean age 68), 4 had bilateral carotid endarterectomies (n= 44 endarterectomy specimens). Control specimens were taken from macroscopically normal carotid artery adjacent to the atheromatous lesions (internal controls), except in 8 cases where normal carotid arteries from post mortem (external controls) were used. Three case-control pairs were excluded when the HLA DRB gene failed to amplify from the DNA. Genus specific primers to the major outer membrane protein (MOMP) gene were used in a nested polymerase chain reaction (nPCR) in 41 atheromatous carotid specimens and paired controls. PCR inhibition was monitored by spiking with target C. trachomatis. Atheroma severity was graded histologically. Plasma samples were tested by microimmunofluorescence (MIF) for antibodies to C. pneumoniae, C. trachomatis and C. psittaci and the corresponding white cells were tested for Chlamydia spp. by nPCR. RESULTS: C. pneumoniae was not detected in any carotid specimen. Twenty-five of 38 (66%) plasma specimens were positive for C. pneumoniae IgG, 2/38 (5%) for C. trachomatis IgG and 1/38 (3%) for C. psittaci IgG. CONCLUSIONS: We were unable to show an association between the presence of Chlamydia spp. and atheroma in carotid arteries in the presence of a high seroprevalence of C. pneumoniae antibodies in Northern Ireland

Higher incidence of persistent chronic infection of Chlamydia pneumoniae among coronary artery disease patients in India is a cause of concern

<p>Abstract</p> <p>Background</p> <p>There is growing evidence that <it>Chlamydia pneumoniae </it>may be involved in the pathogenesis of atherosclerosis, as several studies have demonstrated the presence of the organism in atherosclerotic lesions. <it>C. pneumoniae </it>infections, which are especially persistent infections, have been difficult to diagnose either by serological methods or isolation of the organism from the tissue. Nucleic Acid Amplification tests (NAATs) has emerged as an important method for detecting <it>C. pneumoniae</it>. Inspite of high prevalence of <it>C. pneumoniae </it>specific antibodies in coronary heart disease patients, direct detection of <it>C. pneumoniae </it>in circulating blood of coronary artery disease (CAD) patients by sensitive nucleic acid amplification tests nested PCR (nPCR), multiplex PCR (mPCR) has not been carried out is required. Further correlation of the presence of <it>C. pneumoniae </it>in blood of CAD patients with <it>C. pneumoniae </it>specific IgA and IgG antibodies, which may indicative of the status of infection with the progression of atherosclerosis. This will help in order to prepare strategies for the antibiotic intervention to avoid the progression towards CAD.</p> <p>Methods</p> <p>Venous blood was obtained from 91 CAD patients and 46 healthy controls. Nucleic acid amplification tests <it>viz</it>. nested -, semi-nested – and multiplex PCR were used for detection of <it>C. pneumoniae</it>. ELISA carried out prevalence of <it>C. pneumoniae </it>specific IgG and IgA antibodies.</p> <p>Results</p> <p>29.67% (27/91) patients were positive for <it>C. pneumoniae </it>using nested PCR. The sensitivity and specificity of semi-nested and multiplex PCR were 37.03%, 96.96% and 22.22%, 100% with respect to nested PCR. Positive nPCR patients were compared with presence of <it>C. pneumoniae </it>specific IgA, IgA+IgG and IgG antibodies. Among 27 (29.67%) nPCR <it>C. pneumoniae </it>positive CAD patients, 11(12%) were IgA positive, 13(14.2%) were IgA+IgG positive and only1 (1.1%) was IgG positive. A significant presence of <it>C. pneumoniae </it>was detected in heavy smokers, non-alcoholics and with family histories of diabetes and blood pressure group of CAD patients by nPCR.</p> <p>Conclusion</p> <p>The results indicate synergistic association of <it>C. pneumoniae </it>infection and development of CAD with other risk factors. We also detected increased positivity for <it>C. pneumoniae </it>IgA than IgG in nPCR positive CAD patients. Positive nPCR findings in conjunction with persisting high <it>C. pneumoniae </it>specific antibody strongly suggest an ongoing infection.</p

Association of circulating Chlamydia pneumoniae DNA with cardiovascular disease: a systematic review

BACKGROUND: Chlamydia pneumoniae antigens, nucleic acids, or intact organisms have been detected in human atheroma. However, the presence of antibody does not predict subsequent cardiovascular (CV) events. We performed a systematic review to determine whether the detection of C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) was associated with CV disease. METHODS: We sought studies of C. pneumoniae DNA detection in PBMC by polymerase chain reaction (PCR) among patients with CV disease or other clinical conditions. We pooled studies in which CV patients were compared with non-diseased controls. We analyzed differences between studies by meta-regression, to determine which epidemiological and technical characteristics were associated with higher prevalence. RESULTS: Eighteen relevant studies were identified. In nine CV studies with control subjects, the prevalence of circulating C. pneumoniae DNA was 252 of 1763 (14.3%) CV patients and 74 of 874 (8.5%) controls, for a pooled odds ratio of 2.03 (95% CI: 1.34, 3.08, P < 0.001). Prevalence was not adjusted for CV risk factors. Current smoking status, season, and age were associated with C. pneumoniae DNA detection. High prevalence (>40%) was found in patients with cardiac, vascular, chronic respiratory, or renal disease, and in blood donors. Substantial differences between studies were identified in methods of sampling, extraction, and PCR targets. CONCLUSIONS: C. pneumoniae DNA detection was associated with CV disease in unadjusted case-control studies. However, adjustment for potentially confounding measures such as smoking or season, and standardization of laboratory methods, are needed to confirm this association

Rapid cross-border emergence of NDM-5-producing Escherichia coli in the European Union/European Economic Area, 2012 to June 2022

Whole genome sequencing data of 874 Escherichia coli isolates carrying blaNDM-5 from 13 European Union/ European Economic Area countries between 2012 and June 2022 showed the predominance of sequence types ST167, ST405, ST410, ST361 and ST648, and an increasing frequency of detection. Nearly a third (30.6%) of these isolates were associated with infections and more than half (58.2%) were predicted to be multidrug-resistant. Further spread of E. coli carrying blaNDM-5 would leave limited treatment options for serious E. coli infections

Association of Carotid Plaque Lp-PLA2 with Macrophages and Chlamydia pneumoniae Infection among Patients at Risk for Stroke

BACKGROUND: We previously showed that the burden of Chlamydia pneumoniae in carotid plaques was significantly associated with plaque interleukin (IL)-6, and serum IL-6 and C-reactive protein (CRP), suggesting that infected plaques contribute to systemic inflammatory markers in patients with stroke risk. Since lipoprotein-associated phospholipase A2 (Lp-PLA(2)) mediates inflammation in atherosclerosis, we hypothesized that serum Lp-PLA(2) mass and activity levels and plaque Lp-PLA(2) may be influenced by plaque C. pneumoniae infection. METHODOLOGY/PRINCIPAL FINDINGS: Forty-two patients underwent elective carotid endarterectomy. Tissue obtained at surgery was stained by immunohistochemistry for Lp-PLA(2) grade, macrophages, IL-6, C. pneumoniae and CD4+ and CD8+ cells. Serum Lp-PLA(2) activity and mass were measured using the colorimetric activity method (CAM) and ELISA, respectively. Serum homocysteine levels were measured by HPLC. Eleven (26.2%) patients were symptomatic with transient ischemic attacks. There was no correlation between patient risk factors (smoking, coronary artery disease, elevated cholesterol, diabetes, obesity, hypertension and family history of genetic disorders) for atherosclerosis and serum levels or plaque grade for Lp-PLA(2). Plaque Lp-PLA(2) correlated with serum homocysteine levels (p = 0.013), plaque macrophages (p<0.01), and plaque C. pneumoniae (p<0.001), which predominantly infected macrophages, co-localizing with Lp-PLA(2). CONCLUSIONS: The significant association of plaque Lp-PLA(2) with plaque macrophages and C. pneumoniae suggests an interactive role in accelerating inflammation in atherosclerosis. A possible mechanism for C. pneumoniae in the atherogenic process may involve infection of macrophages that induce Lp-PLA(2) production leading to upregulation of inflammatory mediators in plaque tissue. Additional in vitro and in vivo research will be needed to advance our understanding of specific C. pneumoniae and Lp-PLA(2) interactions in atherosclerosis

Qualitative and Quantitative Detection of Chlamydophila pneumoniae DNA in Cerebrospinal Fluid from Multiple Sclerosis Patients and Controls

A standardized molecular test for the detection of Chlamydophila pneumoniae DNA in cerebrospinal fluid (CSF) would assist the further assessment of the association of C. pneumoniae with multiple sclerosis (MS). We developed and validated a qualitative colorimetric microtiter plate-based PCR assay (PCR-EIA) and a real-time quantitative PCR assay (TaqMan) for detection of C. pneumoniae DNA in CSF specimens from MS patients and controls. Compared to a touchdown nested-PCR assay, the sensitivity, specificity, and concordance of the PCR-EIA assay were 88.5%, 93.2%, and 90.5%, respectively, on a total of 137 CSF specimens. PCR-EIA presented a significantly higher sensitivity in MS patients (p = 0.008) and a higher specificity in other neurological diseases (p = 0.018). Test reproducibility of the PCR-EIA assay was statistically related to the volumes of extract DNA included in the test (p = 0.033); a high volume, which was equivalent to 100 µl of CSF per reaction, yielded a concordance of 96.8% between two medical technologists running the test at different times. The TaqMan quantitative PCR assay detected 26 of 63 (41.3%) of positive CSF specimens that tested positive by both PCR-EIA and nested-PCR qualitative assays. None of the CSF specimens that were negative by the two qualitative PCR methods were detected by the TaqMan quantitative PCR. The PCR-EIA assay detected a minimum of 25 copies/ml C. pneumoniae DNA in plasmid-spiked CSF, which was at least 10 times more sensitive than TaqMan. These data indicated that the PCR-EIA assay possessed a sensitivity that was equal to the nested-PCR procedures for the detection of C. pneumoniae DNA in CSF. The TaqMan system may not be sensitive enough for diagnostic purposes due to the low C. pneumoniae copies existing in the majority of CSF specimens from MS patients