Feasibility of using point prevalence surveys to assess antimicrobial utilisation in public hospitals in South Africa: a pilot study and implications

Objectives: There is currently a lack of data regarding antimicrobial use among public hospitals in South Africa. This is a concern given their growing use and increasing antimicrobial resistance rates in South Africa. Consequently, the objectives of this study were to firstly determine the appropriateness of point prevalence survey (PPS) data collection instruments for performing antimicrobial utilization studies among public sector hospitals in South Africa; secondly, to determine current antimicrobial utilization in a public sector hospital, and thirdly evaluate the prescribing of antimicrobials with those contained within the national Essential Medicines List and Standard Treatment Guidelines (EML/STGs). The findings will be used to guide future activities in South Africa.

Methods: A PPS was conducted in Dr George Mukhari Academic Hospital. For each in-patient ward, all patients’ files were completely surveyed on a single day. The number of patients who were on antimicrobials served as the numerator and the denominator comprised the total number of patients in the ward.

Results: 39 wards and 512 patient files were surveyed. The overall prevalence of antimicrobial use was 37.7%, highest in the ICUs. Beta lactamase inhibitors and antimicrobials for tuberculosis were the most prevalent antimicrobials. More than two thirds (83%) of antimicrobial treatment was modified following culture sensitivity test results when requested, and 98% of antimicrobials prescribed were contained within the current EML/STGs. In 10.8% of occasions, antimicrobials appear to have been prescribed other than for treatment, i.e. no systemic infection. There were concerns though with the lack of IV to oral switching.

Conclusion: The PPS method offers a standardized tool that can be used to identify targets for quality improvement. However, there were concerns with the time taken to conduct PPS studies, which is an issue in resource limited settings. This is being addressed alongside concerns with the lack of IV to oral switching.     

Antigen delivery to dendritic cells by poly(propylene sulfide) nanoparticles with disulfide conjugated peptides: Cross-presentation and T cell activation

Vaccines aiming to activate cytotoxic T cells require cross-presentation of exogenous antigen by antigen-presenting cells (APCs). We recently developed a synthetic nanoparticle vaccine platform that targets lymph node-resident dendritic cells (DCs), capable of mounting an immune response to conjugated antigen. Here, we explore routes of processing and the efficiency of MHC I cross-presentation of OVA peptides conjugated using both reducible and non-reducible linkages, exploring the hypothesis that reduction-sensitive conjugation will lead to better antigen cross-presentation. Both clathrin and macropinocytic pathways were implicated in nanoparticle uptake by colocalization and inhibitor studies. Cross-presentation by DCs was demonstrated by direct antibody staining and in vitro stimulation of CD8(+) T cells from OT-I mice and was indeed most efficient with the reduction-sensitive conjugation. Similarly, we observed IFN-γ production by CD4(+) T cells from OT-II mice. Finally, immunization with the OVA peptide-bearing nanoparticles resulted in in vivo proliferation and IFN-γ production by adoptively transferred CD8(+) OT-I T cells and was also most efficient with reduction-sensitive linking of the peptide antigen. These results demonstrate the relevance of the poly(propylene sulfide) nanoparticle vaccine platform and antigen conjugation scheme for activating both cytotoxic and helper T cell responses.     

Pneumococcal polysaccharide vaccination induces polysaccharide-specific B cells in adult peripheral blood expressing CD19CD20CD3CD70CD27IgMCD43CD5

Pneumococcal polysaccharide vaccines have been used to elicit a protective anti-pneumococcal polysaccharide antibody response against Streptococcus pneumoniae in healthy individuals. Identifying human B cells which respond to T-cell independent type-2 antigens, such as pneumococcal polysaccharides, has been challenging. We employed pneumococcal polysaccharides directly conjugated to fluorophores in conjunction with flow cytometry to identify the phenotype of B cells that respond to pneumococcal polysaccharide vaccination. We have previously identified that the majority of pneumococcal polysaccharide-selected cells responding to vaccination are CD27⁺IgM⁺ (IgM⁺ memory) cells. In this study, we further characterized pneumococcal polysaccharide-selected cells in the peripheral blood to better identify how the various B cell phenotypes responded 7 and 30 days post-immunization. We show that 7 days post-immunization the majority of pneumococcal polysaccharide-selected IgM⁺ memory cells (PPS14⁺ 56.5%, PPS23F⁺ 63.8%) were CD19⁺CD20⁺CD27⁺IgM⁺CD43⁺CD5^+/−CD70⁻, which was significantly increased compared to pre-immunization levels. This phenotype is in alignment with recent publications describing human B-1 cells. PPS-responsive B cells receded to pre-immunization levels by day-30. These findings suggest that this B-1 like cell population plays an important role in early responses to S. pneumoniae infection and possibly other T-cell independent type-2 antigens in humans     

Chinese herbal medicine for chronic heart failure: a multicenter,randomized, double-blind,placebo-controlled trial

ObjectiveThe purpose of this study was to assess the efficacy and safety of Chinese herbal medicine (CHM) in the treatment of chronic heart failure (CHF) patients according to syndrome differentiation.MethodsIn this multicenter, randomized, double-blind, placebo-controlled clinical trial, a total of 220 CHF patients were assigned to receive CHM or placebo granules without decoction according to syndrome differentiation in addition to their standard western treatment for 4 weeks. The change in the left ventricular ejection fraction (LVEF) was the primary outcome, and the changes in the TCM syndrome scores (TCM-SS) and New York Heart Association functional classification (NYHA-FC) were the secondary outcomes.ResultsAfter 4 weeks of treatment, the mean changes in the LVEF (13.1 ± 9.78 vs. 7.34 ± 7.40, P < 0.001) and the TCM syndrome scores (−34.2 ± 24.6 vs. −23.5 ± 25.2, P = 0.002) were better in the CHM group than in the placebo group. After two weeks of treatment, the mean changes in the LVEF (9.26 ± 7.83 vs. 4.72 ± 5.60, P < 0.001) and the TCM syndrome scores (−23.5 ± 18.6 vs. −14.0 ± 15.9, P < 0.001) were better in the CHM group than in the placebo group. In addition, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of CHM versus placebo in the LVEF and TCM syndrome cores (P < 0.001 for all). The distention of the jugular vein (P = 0.021), expectoration (P = 0.044), abdominal distention (P = 0.004), and rib pain (P = 0.005) were significantly less in the CHM group than in the placebo group after two weeks of treatment. Fatigue (P = 0.001), less gas and lazy words (P = 0.001), dizziness (P = 0.003), gasping for breath (P = 0.027), abdominal distention (P = 0.011), nausea (P = 0.001) and emesis (P = 0.012) were significantly less in the CHM group than in the placebo group after treatment for four weeks. After four weeks of treatment, the change in the NYHA functional classification in the CHM group was better than that in the placebo group (P < 0.001). There was one death in the placebo group, and one patient in the CHM group experienced atrial fibrillation.ConclusionCHM treatment according to syndrome differentiation effectively improved the LVEF, TCM-SS, and NYHA-FC in patients with CHF and also appeared to be safe. Thus, CHM treatment could be used as an adjuvant therapy in the treatment of CHF (Clinical trial registration: NCT01939236).     

The effect of the transfusion of stored RBCs on intestinal microvascular oxygenation in the rat

BACKGROUND: Although it is known that the transfusion of stored RBCs does not always improve tissue O(2) consumption under conditions of limited tissue oxygenation, the efficiency of O(2) delivery to the microcirculation by stored RBCs has never been determined. STUDY DESIGN AND METHODS: In a rat hemorrhagic shock model, the effects of resuscitation with fresh or 28-day-old RBCs stored in CPD plasma, saline-adenine-glucose-mannitol, and CPDA-1 plasma were investigated. Systemic hemodynamic and intestinal oxygenation measures were monitored. Intestinal microvascular PO(2) was determined with the O(2)-dependent quenching of palladium-porphyrin phosphorescence, and the RBC deformability was measured with a Laser-assisted optic rotational cell analyzer. RESULTS: Hemodynamic and oxygenation measures were significantly decreased during hemorrhagic shock. Intestinal oxygen consumption and mesenteric venous pO(2) were restored with the transfusion of both fresh and stored RBCs, except for CPD-stored RBCs. The intestinal microvascular pO(2) improved only with the transfusion of fresh RBCs. Deformability of the stored RBCs was significantly decreased. CONCLUSION: In contrast to that of fresh RBCs, the transfusion of stored RBCs did not restore the microcirculatory oxygenation, possibly because of impaired O(2) unloading, but, except for CPD-stored RBCs, the storage-induced changes were not enough to impair intestinal VO(2) and mesenteric venous pO(2).