Rationalising empirical antibiotics for bloodstream infections: A retrospective study at a South African district-level hospital.

BACKGROUND: Incorrect empirical antibiotic therapy is one of the factors that contribute to poor clinical outcomes and the development of antimicrobial resistance. Knowledge of the local infectious disease burden and antibiotic resistance patterns can assist with development of strategies, updating of guidelines and subsequent improvement in initial empirical therapy. OBJECTIVES: To determine whether the empirical antibiotic choice for treatment of septic episodes at a district-level hospital was appropriate according to national guidelines, and to describe the epidemiological features of the septic episode population being studied and depict their antibiotic susceptibility profile. METHODS: This was a retrospective, descriptive study of adult inpatients with bloodstream infections at Karl Bremer Hospital, Cape Town, South Africa. Laboratory and clinical data were obtained and analysed for the period 1 July 2017 - 30 June 2018. Septic episodes were subdivided into community-acquired bloodstream infection (CABSI) and hospital-acquired bloodstream infection (HABSI) study populations, and empirical antibiotics for both groups were assessed and compared with the adult Standard Treatment Guidelines and Essential Medicines List for South Africa, Hospital Level Care, 2015 edition (STG and EML). RESULTS: Our study sample consisted of 184 septic episodes, isolated from 176 patients. Nearly half of the septic episodes (49.5%) were hospital acquired. Overall guideline adherence in the CABSI population was 88%, compared with 58% in the HABSI population. The reasons for guideline non-adherence in the CABSI population were lack of source-appropriate empirical antibiotics (n=7) and septic episodes where empirical antibiotics were indicated but not prescribed (n=4), while in the HABSI group the main reason was that the patients were treated by community-acquired standards (n=30; 33.0%). The in-hospital mortality rate for a septic episode in this study was 38%. Considering the typical first-line antibiotics used, 77.3% of CABSIs were found to be susceptible to co-amoxiclav (n=75) and 59.8% to ceftriaxone (n=58). With the exclusion of methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii isolates as confounders, HABSIs had a susceptibility of 86% to the piperacillin/tazobactam plus amikacin combination, 81% to ertapenem, 90% to imipenem and 93% to meropenem. CONCLUSIONS: This study demonstrates poor guideline adherence in HABSIs, emphasising the importance of distinguishing between CABSIs and HABSIs. The empirical antibiotics advised by the STG and EML were found to be appropriate in the majority of septic episodes. Future revision and improvement of prescribing practices can assist in rationalising empirical antibiotic decisions.

Recognition of infants at high risk for vertical HIV transmission at delivery in rural Western Cape Province, South Africa

Despite South Africa's substantial reduction in vertical HIV transmission (VHT), national paediatric HIV elimination is not yet attained. National and Western Cape Province (WC) HIV guidelines recommend enhanced postnatal prophylaxis for infants at high risk for VHT, identified in the WC 2015/2016 guidelines by any single high-risk criterion (maternal antiretroviral therapy (ART) <12 weeks, absent/ unsuppressed maternal HIV viral load (HIV-VL) <12 weeks before/including delivery, spontaneous preterm labour, prolonged rupture of membranes, chorioamnionitis). Accuracy of high-risk infant identification is unknown. Objectives. Primarily, to determine the proportion of infants at high risk for VHT, the accuracy of labour-ward risk classification, the criteria determining high-risk statuses and the criteria missed among unrecognised high-risk infants; secondarily, to determine maternal factors associated with high-risk infants. Methods. Infants born to women living with HIV at a rural regional hospital (May 2016 - April 2017) were retrospectively evaluated using data from the labour ward VHT register, standardised maternity case records, National Health Laboratory Service database and WC Provincial Health Data Centre. The study-derived risk status for each infant was determined using documented presence/absence of risk criteria and compared with labour ward assigned risk to determine accuracy. Proportions of high-risk and unrecognised high-risk infants with each high-risk criterion were determined. Maternal characteristics associated with having a high-risk infant were evaluated using multivariable logistic regression. Results. For liveborn infants, labour ward assigned risk classifications were 40% (n=75/188) high risk, 50% (n=94/188) low risk and 10% (n=19/188) unclassified. Study-derived risk was high risk for 69% (n=129/188) and low risk for 31% (n=59/188), yielding a high-risk classification sensitivity of 51% (95% confidence interval (CI) 42 - 60) and specificity of 69% (95% CI 56 - 80). Absent/unsuppressed HIVVL <12 weeks before delivery accounted for 83% (n=119/143) of study-derived high-risk exposures and 81% (n=60/74) of missed high-risk exposures. Fewer mothers of high-risk infants had >4 antenatal visits (38% v. 81%, p<0.01) and first antenatal visit <20 weeks' gestation (57% v. 77%, p=0.01). Only the number of antenatal visits remained associated with having a high-risk infant after adjusting for gestation at first visit and timing of HIV diagnosis and ART initiation: each additional antenatal visit conferred a 39% (95% CI 25 - 50) reduction in the odds of having a high-risk infant. Conclusion. Labour ward risk classification failed to recognise half of high-risk infants. Infant high-risk status as well as non-detection thereof were driven by suboptimal maternal HIV-VL monitoring. Reinforcing visit frequency later in pregnancy may improve antenatal HIV-VL monitoring, and point-of-care HIV-VL monitoring at delivery could improve recognition of virally unsuppressed mothers and their high-risk infants

There are three species of Chrysaora (Scyphozoa: Discomedusae) in the Benguela upwelling ecosystem, not two.

Chrysaora (Pèron Lesueur 1810) is the most diverse genus within Discomedusae, and 15 valid species are currently recognised, with many others not formally described. Since Chrysaora fulgida (Reynaud 1830) was first recognised as occurring off the south west (SW) coast off South Africa, the species has been variously synonymised with Chrysaora hysoscella (Linnaeus 1767) and Chrysaora africana (Vanhöffen 1902). Using DNA evidence alongside multivariate tools to analyse quantitative morphometric and meristic data, as well as information from the cnidome, we unambiguously separate C. fulgida from C. hysoscella; we resurrect C. africana as a valid species and recognise a new species, Chrysaora agulhensis sp. nov. Full descriptions of C. fulgida, C. africana and C. agulhensis sp. nov. are provided. The species have different geographical patterns of distribution around the region, with restricted areas of overlap: C. agulhensis sp. nov. is found along the southern coast of South Africa and over the Agulhas Bank, C. fulgida extends from Cape Point in South Africa to southern Angola, and C. africana can be found from southern Namibia northwards to the Gulf of Guinea. The species can be readily separated in the field by a combination of tentacle/lappet number and shape, colour patterns and the form of the oral arms.

Dietary red palm oil protects the heart against the cytotoxic effects of anthracycline.

Strong anti-neoplastic anthracyclines like daunorubicin (DNR) and doxorubicin (DOX) have high efficacy against systemic neoplasm and solid tumours. However, clinically, they cause chronic cardiomyopathy and congestive heart failure. Red palm oil (RPO) supplementation can protect the heart against ischemic injury. We therefore hypothesize that supplementation with RPO during chemotherapy may protect the heart. Control rats received a standard diet, and the experimental group received RPO in addition for 4 weeks. Each group was subsequently injected with either saline or DNR over a 12-day period towards the end of 4 weeks. Hearts were excised and perfused on a working heart system. Functional parameters were measured. Tissue samples were collected for analysis of mRNA and protein levels. DNR + RPO increased aortic output by 25% (p < 0.05) compared with DNR only. Furthermore, DNR treatment significantly reduced tissue mRNA levels of superoxide dismutase 1 (SOD1) and nitric oxide synthase 1 (NOS1) compared with untreated controls. Protein expression of SOD1 followed the same pattern as mRNA levels. NOS1 protein levels were significantly increased in DNR treated rats when compared with untreated controls. In addition, DNR increased phosphorylation of p38 and Jun N-terminal kinase compared with untreated controls, whereas DNR + RPO completely counteracted this activation. DNR + RPO significantly up regulated the protein extracellular signal-regulated kinase 1 level compared with DNR only. In this model of DNR treatment, RPO is associated with stabilization of important antioxidant enzymes such NOS and SOD, and inhibition of the 'stress' induced mitogen-activated protein kinase pathways. Dietary RPO also maintained function, similar to control, in DNR treated hearts.

Comparison of the fatty acid compositions in intraepithelial and infiltrating lesions of the cervix: part II, free fatty acid profiles.

In the second part of this study, the emphasis is on the free fatty acids during cervical carginogenesis, since they may reflect active cell metabolism during this disease process. Lipids were extracted from biopsies of normal epithelial tissue (N) (n=36), cervical intraepithelial lesions (CIL) (n=47), and infiltrating lesions (Ca) (n=47) of the cervix. Samples, from which the free fatty acid compositions were determined, were saponified, methylated and analysed by GLC. In accordance with results obtained on total fatty acid compositions, essential fatty acid deficiency (EFAD) in the intraepithelial lesions, compared with normal tissue (linoleic acid, P< 0.01), and infiltrating lesions compared with intraepithelial lesions (linoleic acid and arachidonic acid, P< 0.01) were observed. High levels of oleic acid were also observed when infiltrating lesions were compared with normal tissue (P < 0.01). As previously mentioned by us in part I of this study, with regard to possible disturbances in metabolic pathways based on the total fatty acid profiles during stages of cervical cancer, EFAD is prevalent during cervical carcinogenesis. This EFAD in cancer cells may result in many defective cell mechanisms, since fatty acids are associated with biochemical events such as lipid peroxidation, signal transduction and immune responses. The high level of oleic acid in cancer cells is known to activate PKC and thus contribute to the continous growth stimulus thought to exist in malignant cells. From a therapeutic viewpoint, substantial changes in the fatty acid composition of the membranes can be produced in cancer cells by selective fatty acid supplementation strategies. At present, modifications of the fatty acid compositions of cell membranes represent an experimental model that has promoted increased understanding of lipid transportation, membrane remodelling, and the relationship between membrane lipids and membrane function. By addressing factors responsible for insufficient essential fatty acid levels, carginogenesis may be prevented or treated. The clinical feasibility of using modification of fatty acids in tumours or cancer by diet or perfusion as an adjunct to standard therapies should be tested.

Evidence that noradrenergic neurons in the A1 and A2 nuclei are lesioned by low doses of 6-OHDA injected into the locus coeruleus.

In order to determine the specificity of a lesion aimed at the locus coeruleus (LC), various doses of 6-hydroxydopamine (6-OHDA), a neurotoxin which selectively lesions catecholaminergic neurons, were bilaterally infused into the LC. The noradrenaline (NA) concentration in the frontal cortex, hippocampus, hypothalamus, LC, A1 and A2 nuclei decreased with increasing doses of 6-OHDA. A 1 microgram dose of 6-OHDA injected bilaterally into the LC caused maximal depletion of the NA concentration in the frontal cortex, hippocampus and A1 and A2 nuclei. A dose of 2 micrograms 6-OHDA caused further depletion of the NA content of the hypothalamus and LC. These findings suggest that A1 and A2 neurons which project to the hypothalamus may have been lesioned or that the noradrenergic projection from the LC to the hypothalamus may be greater than was previously suspected. Alternatively, leakage of 6-OHDA into the cerebrospinal fluid may have occurred at the higher doses, thus directly exposing the hypothalamus to the toxic effects of 6-OHDA.

The effect of intrahippocampal injection of kainic acid on corticosterone release in rats.

The aim of the present study was to investigate whether the hippocampus exerts a modulatory effect on the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Kainic acid was stereotaxically injected into the CA1 pyramidal cell layer of the dorsal hippocampus, causing histological and behavioural changes typical of kainic acid toxicity. The CA3 pyramidal cells of the dorsal hippocampus were selectively lesioned. Rats treated with kainic acid were hyperactive, executed clockwise rotatory movements and displayed epileptic seizures. The acute excitatory effect of kainic acid on glutamatergic receptors in the hippocampus resulted in an elevation in plasma corticosterone levels, suggesting a stimulation of HPA axis activity. Direct or indirect stimulation of the CA1 pyramidal cells of the dorsal hippocampus appeared to have caused the increase in corticosterone secretion.