Antimicrobial stewardship in the Western Cape: A situational analysis of existing facility-level initiatives.

BACKGROUND: Antimicrobial resistance (AMR) is a growing problem worldwide. With the current occurrence of pan-resistant bacterial infections and a paucity of novel antimicrobials in development, the world has entered a post-antibiotic era, in which previously treatable, common infections can become fatal. Antimicrobial stewardship (AMS), defined as 'co-ordinated interventions to ensure appropriate and rational use of antimicrobials', aims to decrease rates of AMR. OBJECTIVES: To co-ordinate AMS in Western Cape Province. The National Department of Health (NDoH) has identified AMS as a key strategic objective, and the Western Cape has formed a provincial AMS committee. However, not much is known regarding current AMS activities in health facilities in the province. METHODS: A self-administered, email questionnaire was sent to specific staff at all district, regional and tertiary hospitals in the 6 health districts of the Western Cape - 47 facilities in total, of which 35 (74.4%) responded. Respondents included pharmacists, managers, doctors, nurses, infection prevention and control practitioners, as well as quality assurance practitioners. The number of facilities implementing AMS were determined, as well as the composition of AMS committees and the nature and frequency of team activities. Barriers to facility-level AMS were explored. Support and outreach activities were assessed, as well as facilities' needs and expectations of the provincial AMS committee. RESULTS: Approximately half of all responding hospitals (n=19; 54.3%) had active AMS committees. Double the proportion of metropolitan (83.3%) than rural facilities (39.1%) had committees. Stewardship activities included antimicrobial prescription chart reviews and audits, AMS ward rounds, antimicrobial restriction policies and training. Most committees included a pharmacist and an infection prevention and control practitioner. More than a third of hospitals (36.1%) did not review their antimicrobial consumption data on a regular basis. Just over half of the hospitals (n=18; 51.4%) did not review AMR patterns. CONCLUSIONS: Despite the need for effective AMS, there is limited information on AMS in South Africa. Most assistance is required in rural areas and smaller hospitals with low numbers of staff and greater numbers of transient rotating junior staff. Information management support, multidisciplinary teamwork and clinical governance are required to enable regular and ongoing AMS in facilities. Rural and smaller facilities require greater support to establish effectively functioning AMS committees.

Repeat injuries in childhood.

BACKGROUND: Injury remains a leading cause of childhood morbidity and mortality in the developing world. The probability of injury occurrence is influenced by agent, host and environmental factors. Studies of repeat injuries in childhood therefore provide insight into factors in the epidemiological triad predisposing children to injury. OBJECTIVES: To determine the proportion of children and the factors associated with repeat presentations to the Red Cross War Memorial Children's Hospital Trauma Unit (RCWMCH TU) in Cape Town, South Africa, for all non-transport-related injuries in childhood. METHODS: This was a retrospective cohort study using data from the RCWMCH TU. We included children aged 0 - 10 years with first presentation from January 1997 to June 2013 and followed up until the earlier of age 13 years or June 2016. We assessed individual and population-level factors associated with repeat injury using multilevel Poisson regression analysis. Child dependency ratios were derived from the 2011 National Census. RESULTS: Between 1997 and 2013, 72 490 children aged <10 years (59% male) presented to the RCWMCH TU for the first time with injuries. After the initial injury, 9 417 (13%) presented with a repeat injury by 2016 and before age 13 years. After adjusting for health subdistrict, distance from RCWMCH TU and age at first presentation, factors associated with reduced repeat presentation were injury identified as due to abuse (adjusted incidence rate ratio (aIRR) 0.6; 95% confidence interval (CI) 0.4 - 0.7), fluid burn (aIRR 0.6; 95% CI 0.6 - 0.7), foreign body ingestion (aIRR 0.7; 95% CI 0.7 - 0.9), and moderate and severe (v. minor) initial injury (aIRR 0.9; 95% CI 0.8 - 0.9 and aIRR 0.7; 95% CI 0.6 - 0.8, respectively), while boys were more likely to have repeat injury presentations (aIRR 1.4; 95% CI 1.4 - 1.5). CONCLUSIONS: Repeat presentations were substantial and associated with male gender. They occurred less commonly after fluid burn injuries, foreign body ingestion and moderate to severe injuries. Children with intentional injuries were also less likely to have a repeat presentation. Further research is indicated for childhood injuries with greater propensity to repeat, including non-height falls and sport-related injuries. Secondary injury prevention education should not neglect patients with unintentional and minor injuries. These results strengthen the hypothesis that injuries arise as a result of sustained exposure to agent, host and environmental risk factors.

Alveolar soft part sarcoma metastatic to the mandible: A report and review of literature.

Alveolar soft part sarcoma (ASPS) is a rare neoplasm constituting less than 1% of all soft tissue sarcomas. It tends to occur in the deep soft tissues of the lower extremities, however approximately 5-12% of cases are primary to the head and neck region. ASPS metastatic to the oral cavity is rare, with only four documented cases in the literature. Here, we present the case of a 29-year-old woman with ASPS metastatic to the mandible. To the best of our knowledge, this represents only the 5th documented case of ASPS metastatic to the oral cavity, and more specifically, the 3rd documented case of mandibular metastasis.

LEAD COMPOSITE VS. NONLEAD PROTECTIVE GARMENTS: WHICH ARE BETTER? A MULTIVENDOR COMPARISON.

This study aims to provide more insight in attenuation characteristics and corresponding lead (Pb) equivalences of a broad range of commercially available lead composite and nonlead protective garments. Thirty garments of five manufacturers (listed as 0.25-0.35-0.50 mm Pb equivalent) were tested. Transmission values were determined at 70, 90 and 110 kVp using an inverse broad beam geometry. Pb equivalence was determined using lead sheets as reference material. A substantial variability in photon transmission across garments was found. Differences between lead composite and nonlead garments were not statistically significant. Depending on tube voltage, between 9 and 12 out of 30 garments had a lower Pb equivalence than the indicated value. This work shows that lead equivalence as indicated on a garment's label may overestimate its protective performance. Depending on the application a more thorough verification of the effectiveness of protective garments at the desired kVp is warranted.

Strong reduction of spectral heterogeneity in gold bipyramids for single-particle and single-molecule plasmon sensing.

Single metal nanoparticles are attractive biomolecular sensors. Binding of analyte to a functional particle results in a plasmon shift that can be conveniently monitored in a far-field optical microscope. Heterogeneities in spectral properties of individual particles in an ensemble affect the reliability of a single-particle plasmon sensor, especially when plasmon shifts are monitored in real-time using a fixed irradiation wavelength. We compare the spectral heterogeneity of different plasmon sensor geometries (gold nanospheres, nanorods, and bipyramids) and correlate this to their size and aspect-ratio dispersion. We show that gold bipyramids exhibit a strongly reduced heterogeneity in aspect ratio and plasmon wavelength compared to commonly used gold nanorods. We show that this translates into a significantly improved homogeneity of the response to molecular binding without compromising single-molecule sensitivity.

Streptococcus pasteurianus septicemia.

Streptococcus pasteurianus is part of the normal flora of the intestine. It has also been isolated from various infection sites. However, to date it has not been reported as a cause of fulminant septicemia and death. We report the post-mortem findings in a splenectomized hemophiliac patient with cirrhosis and concurrent human immunodeficiency virus (HIV), hepatitis B and hepatitis C infections.

Screening and clinical management of prostate cancer. A cross-national comparison.

OBJECTIVES: The objectives of the study were to identify the current standards of clinical practice regarding prostate cancer screening in western Europe, Canada, and the United States, and to highlight major characteristics of current prostate cancer screening programs or patterns of practice. METHODS: We performed a semi-structured interview by means of a self-administered questionnaire sent by fax to 26 institutes pertaining to the International Network of Agencies for Health Technology Assessment. RESULTS: None of the countries surveyed had a formal national screening policy. Despite that, all the countries answering the questionnaire had discretionary, public-financed screening practices. Moreover, some scientific and professional organizations recommended population screening for prostate cancer, and few of the surveyed countries offered it as experimental practice within a randomized controlled trial. Survey results showed variation regarding screening policies, in particular test of choice, age cut-off points, and treatment prescribed for positive test results. CONCLUSIONS: Despite the lack of conclusive evidence on the benefits of prostate cancer screening, the availability of simple and easy-to-administer tests has lead to an enormous variation on screening policies around the world. Practice variations also affect prostate cancer therapy.

Enterobacterial repetitive intergenic consensus polymerase chain reaction typing of isolates of Enterobacter cloacae from an outbreak of infection in a neonatal intensive care unit.

BACKGROUND: Enterobacter cloacae has become a common cause of nosocomial infections. This study was designed to investigate the pattern of spread of E cloacae during an outbreak in a neonatal intensive care unit. METHODS: Enterobacterial repetitive intergenic consensus polymerase chain reaction was used to examine 111 E cloacae isolates from 17 patients, including 81 from surveillance cultures, 23 from endotracheal tubes, 3 from eyes, and 1 each from blood, urine, skin, and throat. Antibiotic susceptibility profiles were also obtained. RESULTS: Infection with E cloacae resulted from endogenous bacteria and from horizontal transmission. One group of 61 isolates, a third of which were obtained from clinical specimens, was uniformly susceptible to imipenem and ciprofloxacin only. A second group of 50 isolates, only 18% of which were obtained from clinical specimens, was susceptible to all antibiotics tested except for aminopenicillins and first-generation cephalosporins. CONCLUSION: These data indicate that (1) patient-to-patient spread is an important cause of E cloacae infection in the neonatal intensive care unit and (2) highly antibiotic-resistant E cloacae may emerge during an outbreak.

Clonal diversity of vancomycin-resistant enterococci from an outbreak in a tertiary care university hospital.

BACKGROUND: Enterococci have become important nosocomial pathogens and now account for approximately 12% of nosocomial infections. Enterococci can be transferred from patient to patient and from health care personnel to patient. We investigated the clonal diversity of vancomycinresistant enterococci (VRE) causing an outbreak of infections and attempted to determine the patterns of spread of these bacteria in a university hospital. METHODS: Ribotyping was used to examine the clonal diversity of 50 VRE isolates, including 23 from wounds, 14 from urine, 8 from blood, 3 from the rectum, 1 from drainage, and 1 from the cornea. RESULTS: Nine patients were infected with Enterococcus faecalis, 10 with Enterococcus faecium, 3 with both E faecalis and E faecium, and 1 with Enterococcus avium. The results suggest that the sources of the VRE infections included endogenous strains and strains acquired by transmission from attending staff or from the environment. Three patients were infected by both nosocomial and endogenous strains. CONCLUSIONS: These data suggest that the collection and analysis of several isolates from repeated specimens is necessary to obtain a fuller understanding of the epidemiology and population structure of antibiotic-resistant enterococci.

Effects of renal cytoprotective agents on erythrocyte membrane stability.

To elucidate potential mechanisms of ischemic renal injury, investigators often use drugs that interfere with specific pathological pathways and study their protective efficacy in in vitro models of ischemia, such as isolated renal proximal tubules subjected to hypoxia. However, the protective effects of certain drugs may depend on non-specific membrane-stabilizing properties. We have studied the effects of several drugs on membrane integrity using osmotic lysis of erythrocytes as a model system. Freshly isolated rabbit erythrocytes were subjected to a hypotonic shock, and the protective effects of various calcium channel blockers, phospholipase inhibitors, free fatty acids, the NO-synthase inhibitor L-NAME, the amino acid glycine and its receptor-analogue strychnine, and two chloride channel blockers were examined. Most agents protected erythrocytes against hypotonic hemolysis when added to the medium in the same concentration range as used in suspensions of hypoxic proximal tubules. Only the protective agents that proposedly act via a blockade of chloride influx (glycine, strychnine and the chloride channel blockers), did not attenuate hypotonic hemolysis. The erythrocyte hemolysis assay may provide an easy and rapid method to screen for non-specific membrane-stabilizing effects of potentially cytoprotective agents.

Cold preservation of isolated rabbit proximal tubules induces radical-mediated cell injury.

BACKGROUND: Reactive oxygen species (ROS) are involved in reperfusion injury after preservation. Recent studies in isolated endothelial cells and hepatocytes suggested the occurrence of ROS-mediated injury during the period of cold incubation. In the present study, formation of ROS and subsequent cell injury were studied in freshly isolated rabbit proximal tubules (PTs). METHODS: PTs were incubated in University of Wisconsin (UW) solution, Euro-Collins solution, or a modified Krebs-Henseleit buffer under aerobic conditions for up to 94 hr at 4 degrees C. ROS formation and cell death were assessed as lipid peroxidation (formation of thiobarbituric acid-reactive substances [TBARS]) and release of lactate dehydrogenase, respectively. The involvement of ROS was further investigated in UW solution using compounds that might interfere with ROS formation. In addition, tubules were studied under anaerobic conditions (gassing with 95% N2/5% CO2). RESULTS: Cold preservation of rabbit PTs in any of the solutions under aerobic conditions caused progressive lipid peroxidation and concomitant cell injury. Addition to UW solution of inhibitors of ROS formation, in particular 2,2'-dipyridyl, or removal of oxygen by gassing with 95% N2/5% CO2, prevented lipid peroxidation and protected rabbit PTs against cold injury. Both the nitric oxide (NO) synthase inhibitor L-NAME and dexamethasone, which blocks the inducible NO synthase, were ineffective. The cytoprotectant glycine affected neither TBARS formation nor lactate dehydrogenase release. CONCLUSIONS: Cold preservation of renal PTs under aerobic conditions caused cell injury even in the specially designed preservation solution UW. Cell injury is caused by iron-dependent, NO synthase-independent ROS formation.

Hypoxia decreases calcium influx into rat proximal tubules.

Renal ischemia results in adenosine triphosphate (ATP) depletion, particularly in cells of the proximal tubule (PT), which rely heavily on oxidative phosphorylation for energy supply. Lack of ATP leads to a disturbance in intracellular homeostasis of Na+, K+ and Cl-. Also, cytosolic Ca2+ levels in renal PTs may increase during hypoxia [1], presumably by a combination of impaired extrusion and enhanced influx [2]. However, Ca2+ influx was previously measured using radiolabeled Ca2+ and at varying partial oxygen tension [2]. We have now used to Mn2(+)-induced quenching of fura-2 fluorescence to study Ca2+ influx in individual rat PTs during normoxic and hypoxic superfusion. Normoxic Ca2+ influx was indeed reflected by the Mn2+ quenching of fura-2 fluorescence and this influx could be inhibited by the calcium entry blocker methoxyverapamil (D600; inhibition 50 +/- 2% and 35 +/- 3% for 10 and 100 mumol, respectively). La3+ completely blocked normoxic Ca2+ influx. Hypoxic superfusion or rat PTs did not induce an increase in Ca2+ influx, but reduced this influx to 79 +/- 3% of the normoxic control. We hypothesize that reducing Ca2+ influx during hypoxia provides the cell with a means to prevent cellular Ca2+ overload during ATP-depletion, where Ca2+ extrusion is limited.

The effect of acrylic nails on the measurement of oxygen saturation as determined by pulse oximetry.

Pulse oximetry (Spo2) is a simple, noninvasive method that is widely used to determine oxygen saturation in patients undergoing surgical procedures. Artificial acrylic nails have recently become fashionable to strengthen and lengthen nails. This study investigates the effect of unpolished acrylic nails on the measurement of oxygen saturation by pulse oximetry. Data were collected during a 3-month period. Thirty women, average age 32 years (range 18 to 61 years), were recruited at a high-volume nail salon in northwestern Pennsylvania. A baseline pulse oximetry reading was obtained on each subject's natural, unpolished fingernail using a Nellcor N-20/N-20P portable pulse oximeter (Nellcor Incorporated, Hayward, California). A licensed nail technician applied the acrylic compound to the same finger. After the compound had hardened in approximately 5 minutes, a second reading was obtained on the unpolished acrylic nail. The mean pulse oximetry reading at baseline was 97.33% and after acrylic nail application, 97.58%. Using a paired Student's t test, no statistically significant differences existed between readings. This study demonstrates that unpolished acrylic nails do not affect pulse oximetry measurements of oxygen saturation. Patients may not need to remove unpolished acrylic nails before surgery.

Glycine protection against hypoxic injury in isolated rat proximal tubules: the role of proteases.

BACKGROUND: Isolated rat proximal tubules are frequently used as a model to study hypoxic injury. Glycine is a very effective protective agent against hypoxia-induced cell injury in this model. The mechanisms involved in hypoxic renal injury and glycine protection are still debated. We have focused on the role of proteolytic enzymes. METHODS: Isolated rat proximal tubules in suspension were gassed with either 95%O2/5%CO2 or 95%N2/5%CO2 to create normoxic or hypoxic conditions. Cell injury was assessed by the release of LDH. Activity of proteolytic enzymes was measured by quantifying the release of fluorescent 7-amino-4-methylcoumarin from specific substrates, which were added to tubules in suspension or to cytosolic fractions of permeabilized tubules. RESULTS: Fifteen minutes of hypoxia caused cell injury, which was completely prevented by glycine. Activities of serine-, aspartate-, and the calcium-dependent cysteine protease calpain were increased in these hypoxic tubules in suspension, but only calpain activity was attenuated by glycine. Cytosolic fractions obtained by digitonin-permeabilization of hypoxic (15 min) tubules showed increased proteolytic activity of all measured classes of proteases and glycine prevented these increases. In measurements performed at an earlier time point (7.5 min) neither changes in calpain activity nor effects of glycine were detected. Calpain activity was not inhibited directly by glycine. CONCLUSIONS: Hypoxia increases the activity of several classes of proteases. The effects of glycine on protease activation are equivocal, and may merely reflect the potential of glycine to prevent hypoxia-induced lethal membrane injury.

Rise in cytosolic Ca2+ and collapse of mitochondrial potential in anoxic, but not hypoxic, rat proximal tubules.

It has been suggested that ischemic renal proximal tubular cell injury is mediated by an increase in cytosolic calcium concentrations ((Ca2+)i). However, measurements of (Ca2+)i in rat or rabbit proximal tubules exposed to hypoxia or anoxia have yielded ambiguous results. This study explored the possibility that the severity of oxygen deprivation and the energy state of the mitochondria are important determinants of (Ca2+)i. To this end, (Ca2+)i (measured with fura-2) and the mitochondrial membrane potential (measured with rhodamine 123) were studied simultaneously in individual rat proximal tubules in hypoxic and anoxic conditions. (Ca2+)i did not change during hypoxia, but increased rapidly during anoxia. Increases in (Ca2+)i were only observed in parallel with a decrease of rhodamine 123 fluorescence, which indicates a collapse of the mitochondrial membrane potential. The increase in (Ca2+)i during anoxia was prevented by incubating the tubules in a low Ca2+ medium, which did not interfere with the collapse of the mitochondrial membrane potential. Both hypoxic and anoxic incubation led to cell death, as assessed by the fluorescent dye propidium iodide. These results clearly demonstrate that the level of oxygen deprivation is critical in determining changes in (Ca2+)i. Because cell damage occurred in both hypoxic and anoxic conditions. It was concluded that an increase in (Ca2+)i is not a necessary prerequisite for the development of ischemic cell injury.

Protection against hypoxic injury of rat proximal tubules by felodipine via a calcium-independent mechanism.

Most evidence for a key role of calcium entry in hypoxia-induced renal damage stems from studies with calcium channel blockers. In proximal tubules, a primary site of renal ischaemic injury, only phenyl-alkylamines, especially verapamil, have been studied. In the present study the effect of the dihydropyridine felodipine on hypoxic injury in isolated rat proximal tubules was investigated. To discriminate between the block of calcium entry and other effects, the enantiomers and a non-calcium blocking derivative of felodipine (H186/86) were included. Cell membrane injury was assessed by measuring the release of lactate dehydrogenase (LDH). At high concentrations (100 microM) felodipine, H186/86 and the two enantiomers all protected rat proximal tubules against hypoxia-induced injury to the same extent. Absence of extracellular calcium did not offer protection, but rather enhanced hypoxic injury. All dihydropyridines used increased the intracellular potassium concentration during normoxia. Felodipine attenuated the hypoxia-induced loss of cellular potassium. We have tried to mimic the effects of felodipine by using potassium channel blockers. The potassium channel blockers quinidine and glibenclamide afforded some protection against hypoxic injury, although their effects on cellular potassium were equivocal. We conclude that the dihydropyridine calcium channel blocker felodipine protects rat proximal tubules against hypoxic injury via a calcium-independent mechanism. We propose that high levels of intracellular potassium and attenuation of potassium loss during hypoxia are important in this protection.

Analysis of peripheral blood lymphocytes of AIDS and high-risk patients for human cytomegalovirus transforming DNA sequences.

Investigation into the presence of human cytomegalovirus (HCMV) transforming mtrII and mtrIII sequences in peripheral blood lymphocyte (PBL) specimens of AIDS and high-risk patients was carried out by nucleic acid hybridization analyses. These probes were selected because they were viral-specific and lacked homology to normal cellular DNAs. In Southern blot hybridizations carried out under stringent conditions, we detected HCMV mtrII sequences associated with the high-molecular-weight DNAs of PBLs in 17 of 37 patients either with AIDS/Kaposi's sarcoma or at high risk for AIDS. In comparison, only 2 of 17 DNA specimens from PBLs of healthy blood donors showed hybridization to mtrII sequences. The inability to detect hybridization to the mtrIII region in most mtrII-positive specimens suggested a specific retention of mtrII sequences. Our study suggests that the retention of mtrII sequences in high molecular weight DNA may constitute a risk factor for the development/progression of AIDS. Alternatively, the retention of mtrII sequences may occur as a result of enhanced HCMV replication in patients with AIDS or at high risk for AIDS.

A comparative immunogenicity-reactogenicity dose-response study of influenza vaccine.

This study examined the immunogenic and reactogenic responses of influenza vaccine in 29 healthy nonallergic adults at three vaccine dosages: 0.5 mL, 0.1 mL, and 0.05 mL. After immunization a 7-day assessment of adverse reactions was made and serial serum hemagglutination-inhibition (HAI) antibody responses were measured during a 28-day period. The incidence of adverse reactions was significantly decreased in the group receiving 0.1 mL and 0.05 mL compared with the group receiving 0.5 mL of vaccine. After immunization with 0.1 mL or 0.05 mL vaccine increases in serum HAI antibody to A/Leningrad, A/Taiwan, and B/Ann Arbor influenza antigens were seen comparable to those observed after 0.5 mL. However the magnitude of these rises were lower and were directly correlated with the dose of vaccine. Since immunization of egg-sensitive allergic patients with influenza vaccine poses a risk of localized and systemic reactions, a common clinical practice is to prevent such reactions by vaccine dilution. Although the results of the present study suggest that vaccine dilution results in a decrease in adverse reactions, there is also the risk of decrease protective immunity with this procedure and therefore the practice should not be condoned.