Antibiotic knowledge, attitudes, and practices: new insights from cross-sectional rural health behaviour surveys in low- and middle-income South-East Asia

Introduction: Low- and middle-income countries (LMICs) are crucial in the global response to antimicrobial resistance (AMR), but diverse health systems, healthcare practices, and cultural conceptions of medicine can complicate global education and awareness-raising campaigns. Social research can help understand LMIC contexts but remains underrepresented in AMR research. Objective: To (1) describe antibiotic-related knowledge, attitudes, and practices of the general population in two LMICs and to (2) assess the role of antibiotic-related knowledge and attitudes on antibiotic access from different types of healthcare providers. Design: Observational study: cross-sectional rural health behaviour survey, representative on the population level. Setting: General rural population in Chiang Rai (Thailand) and Salavan (Lao PDR), surveyed between November 2017 and May 2018. Participants: 2141 adult members (≥18 years) of the general rural population, representing 712,000 villagers. Outcome measures: Antibiotic-related knowledge, attitudes, and practices across sites and healthcare access channels. Findings: Villagers were aware of antibiotics (Chiang Rai: 95.7%; Salavan: 86.4%; p<0.001) and drug resistance (Chiang Rai: 74.8%; Salavan: 62.5%; p<0.001), but the usage of technical concepts for antibiotics was dwarfed by local expressions like “anti-inflammatory medicine” in Chiang Rai (87.6%; 95% confidence interval [CI]: 84.9–90.0) and “ampi” in Salavan (75.6%; 95% CI: 71.4–79.4). Multivariate linear regression suggested that attitudes against over-the-counter antibiotics were linked to 0.12 additional antibiotic use episodes from public healthcare providers in Chiang Rai (95% CI: 0.01 – 0.23) and 0.53 in Salavan (95% CI: 0.16 – 0.90). Conclusions: Locally specific conceptions and counter-intuitive practices around antimicrobials can complicate AMR communication efforts and entail unforeseen consequences. Overcoming “knowledge deficits” alone will therefore be insufficient for global AMR behaviour change. We call for an expansion of behavioural AMR strategies towards “AMR-sensitive interventions” that address context-specific upstream drivers of antimicrobial use (e.g. unemployment insurance) and complement education and awareness campaigns

Randomized clinical trial: Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition

Background & aims: Staphylococcus aureus decolonization has proven successful in prevention of S. aureus infections and is a key strategy to maintain venous access and avoid hospitalization in patients receiving home parenteral nutrition (HPN). We aimed to determine the most effective and safe long-term S. aureus decolonization regimen. Methods: A randomized, open-label, multicenter clinical trial was conducted. Adult intestinal failure patients with HPN support and carrying S. aureus were randomly assigned to a ‘continuous suppression’ (CS) strategy, a repeated chronic topical antibiotic treatment or a ‘search and destroy’ (SD) strategy, a short and systemic antibiotic treatment. Primary outcome was the proportion of patients in whom S. aureus was totally eradicated during a 1-year period. Secondary outcomes included risk factors for decolonization failure and S. aureus infections, antimicrobial resistance, adverse events, patient compliance and cost-effectivity. Results: 63 participants were included (CS 31; SD 32). The mean 1-year S. aureus decolonization rate was 61% (95% CI 44, 75) for the CS group and 39% (95% CI 25, 56) for the SD group with an OR of 2.38 (95% CI 0.92, 6.11, P = 0.07). More adverse effects occurred in the SD group (P = 0.01). Predictors for eradication failure were a S. aureus positive caregiver and presence of a (gastro)enterostomy. Conclusion: We did not demonstrate an increased efficacy of a short and systemic S. aureus decolonization strategy over a continuous topical suppression treatment. The latter may be the best option for HPN patients as it achieved a higher long-term decolonization rate and was well-tolerated (NCT03173053)

¹⁸F-FDG PET/CT Optimizes Treatment in <i>Staphylococcus Aureus</i> Bacteremia and Is Associated with Reduced Mortality.

Metastatic infection is an important complication of Staphylococcus aureus bacteremia (SAB). Early diagnosis of metastatic infection is crucial, because specific treatment is required. However, metastatic infection can be asymptomatic and difficult to detect. In this study, we investigated the role of 18 F-FDG PET/CT in patients with SAB for detection of metastatic infection and its consequences for treatment and outcome. Methods: All patients with SAB at Radboud University Medical Center were included between January 2013 and April 2016. Clinical data and results of 18 F-FDG PET/CT and other imaging techniques, including echocardiography, were collected. Primary outcomes were newly diagnosed metastatic infection by 18 F-FDG PET/CT, subsequent treatment modifications, and patient outcome. Results: A total of 184 patients were included, and 18 F-FDG PET/CT was performed in 105 patients, of whom 99 had a high-risk bacteremia. 18 F-FDG PET/CT detected metastatic infectious foci in 73.7% of these high-risk patients. In 71.2% of patients with metastatic infection, no signs and symptoms suggesting metastatic complications were present before 18 F-FDG PET/CT was performed. 18 F-FDG PET/CT led to a total of 104 treatment modifications in 74 patients. Three-month mortality was higher in high-risk bacteremia patients without 18 F-FDG PET/CT performed than in those in whom 18 F-FDG PET/CT was performed (32.7% vs. 12.4%, P = 0.003). In multivariate analysis, 18 F-FDG PET/CT was the only factor independently associated with reduced mortality ( P = 0.005; odds ratio, 0.204; 95% confidence interval, 0.066-0.624). A higher comorbidity score was independently associated with increased mortality ( P = 0.003; odds ratio, 1.254; 95% confidence interval, 1.078-1.457). Conclusion: 18 F-FDG PET/CT is a valuable technique for early detection of metastatic infectious foci, often leading to treatment modification. Performing 18 F-FDG PET/CT is associated with significantly reduced 3-mo mortality

Traditional management of ear, nose and throat (ENT) diseases in Central Kenya

Diseases of ear, nose and throat (ENT) often have serious consequences including hearing impairment, and emotional strain that lower the quality of life of patients. In Kenya, upper respiratory infections are among the most common infections encountered in outpatient facilities. Some of these infections are becoming difficult to control because some of the causing microorganisms have acquired antibiotic resistance and hence the need to develop new drugs with higher efficacy. Ethnobotanical studies have now been found to be instrumental in improving chances of discovering plants with antimicrobial activity in new drug development. In Kenya the majority of local people are turning to herbal remedies for primary health care needs. In most cases the sources of these remedies are undocumented and the knowledge about them passed orally form generation to generation, hence under threat of disappearing with current rates of modernisation. This study explored the traditional remedies used in managing various ENT diseases in seven districts of the Central Province of Kenya. The most common ENT conditions managed using traditional therapies include: common cold, cough, tonsillitis, otitis-media, chest pains and asthma. The results indicate that 67 species belonging to 36 plant families were utilized in this region. These plants were of varying habits; herbs (37.3%), shrubs (34.4%), trees (25.4%) as well as some grasses and sedges (3%). The traditional preparations were found to be made mainly from leaves (49%), roots (20.5%) and barks (12.5%). For each of the ENT conditions multiple species are utilized mainly as individual preparations but occasionally as polyherbal concoctions. In the case of common cold for example, 30 different species are used. Plants reported in this survey are important candidates for antimicrobial tests against ENT disease causing micro-organisms, especially those with antibiotic resistance

Antibody landscapes after influenza virus infection or vaccination.

We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.This is the author’s version of the work. It will be under embargo for 6 months following publication. It is posted here by permission of the AAAS for personal use, not for redistribution. The final version is available from AAAS in Science at http://www.sciencemag.org/content/346/6212/996.long

High prevalence of methicillin resistant Staphylococcus aureus in the surgical units of Mulago hospital in Kampala, Uganda

<p>Abstract</p> <p>Background</p> <p>There is limited data on Methicillin resistant <it>Staphylococcus aureus </it>(MRSA) in Uganda where, as in most low income countries, the routine use of chromogenic agar for MRSA detection is not affordable. We aimed to determine MRSA prevalence among patients, healthcare workers (HCW) and the environment in the burns units at Mulago hospital, and compare the performance of CHROMagar with oxacillin for detection of MRSA.</p> <p>Results</p> <p>One hundred samples (from 25 patients; 36 HCW; and 39 from the environment, one sample per person/item) were cultured for the isolation of <it>Staphylococcus aureus</it>. Forty one <it>S. aureus </it>isolates were recovered from 13 patients, 13 HCW and 15 from the environment, all of which were oxacillin resistant and <it>mecA/femA/nuc</it>-positive. MRSA prevalence was 46% (41/89) among patients, HCW and the environment, and 100% (41/41) among the isolates. For CHROMagar, MRSA prevalence was 29% (26/89) among patients, HCW and the environment, and 63% (26/41) among the isolates. There was high prevalence of multidrug resistant isolates, which concomitantly possessed virulence and antimicrobial resistance determinants, notably biofilms, hemolysins, toxin and <it>ica </it>genes. One isolate positive for all determinants possessed the <it>bhp </it>homologue which encodes the biofilm associated protein (BAP), a rare finding in human isolates. SCC<it>mec </it>type I was the most common at 54% prevalence (22/41), followed by <it>SCCmec </it>type V (15%, 6/41) and <it>SCCmec </it>type IV (7%, 3/41). <it>SCCmec </it>types II and III were not detected and 10 isolates (24%) were non-typeable.</p> <p>Conclusions</p> <p>Hyper-virulent methicillin resistant <it>Staphylococcus aureus </it>is prevalent in the burns unit of Mulago hospital.</p

Crystal Structures Reveal the Multi-Ligand Binding Mechanism of Staphylococcus aureus ClfB

Staphylococcus aureus (S. aureus) pathogenesis is a complex process involving a diverse array of extracellular and cell wall components. ClfB, an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family surface protein, described as a fibrinogen-binding clumping factor, is a key determinant of S. aureus nasal colonization, but the molecular basis for ClfB-ligand recognition remains unknown. In this study, we solved the crystal structures of apo-ClfB and its complexes with fibrinogen α (Fg α) and cytokeratin 10 (CK10) peptides. Structural comparison revealed a conserved glycine-serine-rich (GSR) ClfB binding motif (GSSGXGXXG) within the ligands, which was also found in other human proteins such as Engrailed protein, TCF20 and Dermokine proteins. Interaction between Dermokine and ClfB was confirmed by subsequent binding assays. The crystal structure of ClfB complexed with a 15-residue peptide derived from Dermokine revealed the same peptide binding mode of ClfB as identified in the crystal structures of ClfB-Fg α and ClfB-CK10. The results presented here highlight the multi-ligand binding property of ClfB, which is very distinct from other characterized MSCRAMMs to-date. The adherence of multiple peptides carrying the GSR motif into the same pocket in ClfB is reminiscent of MHC molecules. Our results provide a template for the identification of other molecules targeted by S. aureus during its colonization and infection. We propose that other MSCRAMMs like ClfA and SdrG also possess multi-ligand binding properties

The nasal cavity microbiota of healthy adults

Abstract Background The microbiota of the nares has been widely studied. However, relatively few studies have investigated the microbiota of the nasal cavity posterior to the nares. This distinct environment has the potential to contain a distinct microbiota and play an important role in health. Results We obtained 35,142 high-quality bacterial 16S rRNA-encoding gene sequence reads from the nasal cavity and oral cavity (the dorsum of the tongue and the buccal mucosa) of 12 healthy adult humans and deposited these data in the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI) (Bioproject: PRJNA248297). In our initial analysis, we compared the bacterial communities of the nasal cavity and the oral cavity from ten of these subjects. The nasal cavity bacterial communities were dominated by Actinobacteria, Firmicutes, and Proteobacteria and were statistically distinct from those on the tongue and buccal mucosa. For example, the same Staphylococcaceae operational taxonomic unit (OTU) was present in all of the nasal cavity samples, comprising up to 55% of the community, but Staphylococcaceae was comparatively uncommon in the oral cavity. Conclusions There are clear differences between nasal cavity microbiota and oral cavity microbiota in healthy adults. This study expands our knowledge of the nasal cavity microbiota and the relationship between the microbiota of the nasal and oral cavities.http://deepblue.lib.umich.edu/bitstream/2027.42/109547/1/40168_2014_Article_56.pd

Screening for multi-drug-resistant Gram-negative bacteria: what is effective and justifiable?

Effectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention's effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant Staphylococcus aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised