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The use and abuse of antibiotics are directly related to the development of drug resistance, a global public health problem. Whereas the majority of research focus is on the use and misuse of antibiotics in drug resistance development, little is known about improper disposal, as a source of contamination in the environment that includes groundwater, especially in informal settlements. This study sought to determine antibiotic use and disposal in informal settlements in Kisumu, Kenya. A random cross-sectional sample of 447 households in selected informal settlements of Kisumu, Kenya was studied. A structured questionnaire was issued to persons heading households. The prevalence of antibiotic use was 43% (n = 193). Among these people, 74% (n = 144) had consulted a health worker in a healthcare facility for a prescription. Respondents did not always complete doses but kept the remainder for the next time they would become ill (54%). About 32% disposed of the remainder of the antibiotics in pit latrines and compost pits (10%) while 4% disposed through burning. Antibiotic use was fairly high despite a low level of awareness of the health effects of consuming water contaminated with antibiotics (35%) (n = 156); p = 0.03. Misuse and inappropriate disposal of antibiotics as identified may lead to a higher risk of antibiotic resistance, increasing the disease burden in the informal settlements.

Over the last few years, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) unleashed a global public health catastrophe that had a substantial influence on human physical and mental health, the global economy, and socio-political dynamics. SARS-CoV-2 is a respiratory pathogen and the cause of ongoing COVID-19 pandemic, which testified how unprepared humans are for pandemics. Scientists and policymakers continue to face challenges in developing ideal therapeutic agents and vaccines, while at the same time deciphering the pathology and immunology of SARS-CoV-2. Challenges in the early part of the pandemic included the rapid development of diagnostic assays, vaccines, and therapeutic agents. The ongoing transmission of COVID-19 is coupled with the emergence of viral variants that differ in their transmission efficiency, virulence, and vaccine susceptibility, thus complicating the spread of the pandemic. Our understanding of how the human immune system responds to these viruses as well as the patient groups (such as the elderly and immunocompromised individuals) who are often more susceptible to serious illness have both been aided by this epidemic. COVID-19 causes different symptoms to occur at different stages of infection, making it difficult to determine distinct treatment regimens employed for the various clinical phases of the disease. Unsurprisingly, determining the efficacy of currently available medications and developing novel therapeutic strategies have been a process of trial and error. The global scientific community collaborated to research and develop vaccines at a neck-breaking speed. This review summarises the overall picture of the COVID-19 pandemic, different mutations in SARS-CoV-2, immune response, and the treatment modalities against SARS-CoV-2.

Summary: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles

The 2017-2018 listeriosis outbreak in South Africa warranted testing forThe study assessed the performance of the commonly used tests in our setting to accurately identifyThe study was conducted in a public health laboratory in South Africa. Cultured isolates from food and environmental samples were tested both prospectively and retrospectively between August 2018 and December 2018. Isolates were phenotypically identified using tests for detecting β-haemolysis, Christie-Atkins-Munch-Peterson, alanine arylamidase (AlaA), mannosidase, and xylose fermentation. Listeria monocytogenes isolates were identified using automated systems, Microscan Walkaway Plus 96, Vitek® MS, Vitekβ-haemolysis and Christie-Atkins-Munch-Peterson tests gave delayed positivity or were negative forNo test was ideal in differentiating

Despite a substantial decline in childhood mortality rates in South Africa (SA), progress in neonatal mortality reduction has been much slower. Severe bacterial infections remain a leading cause of neonatal morbidity and a direct cause of 13.1% of neonatal deaths among babiesgt;1 kg. The incidence of hospital-acquired infections, antimicrobial resistance and outbreaks of infections in SA neonatal units is substantial, and is possibly higher than the currently available estimates. The SA Neonatal Sepsis Task Force was launched in Port Elizabeth, SA, on 13 September 2019 to provide technical advice and guidance on surveillance for neonatal sepsis, infection prevention, case management, antimicrobial stewardship and containment of neonatal unit outbreaks.

Objectives In this study, we examined the impact of epigenetic modifications on host gene functioning by assessing the expression of seven candidate genes in three separate groups including healthy, multidrug-resistant (MDR) TB-HIV co-infected and HIV-1 positive individuals. Methods Ten patients with MDR TB and HIV-1 co-infection on TB and HIV therapy and a cohort comprised of 10 newly diagnosed individuals with HIV-1 infection were recruited from the TB and HIV clinics at the Charlotte Maxeke Johannesburg Academic Hospital. Notably, the HIV-1 positive individuals were not placed on antiretroviral therapy (ART) at the time of recruitment and blood collection. A third group consisting of 10 healthy participants without MDR TB or HIV infection was recruited from the University of the Witwatersrand. Blood samples collected from all three cohorts were employed for extraction of plasma, total RNA and genomic DNA. Results Our data indicated that the expression of DNA methyltransferase 1 (DNMT1) and Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) genes was significantly increased in HIV-1 positive patients and was lowest in MDR TB-HIV co-infected patients. By contrast, histone acetyltransferase (HAT), histone deacetylase (HDAC), protein tyrosine kinase (PtkA) and protein tyrosine phosphatase (PtpA) mRNA expression levels were substantially enhanced in HIV-1 infected and were lowest in healthy individuals. Conversely, Dicer expression levels were comparable among all three study groups. Conclusion Promising preliminary data emanating from this investigation may potentially be used for generation of novel vaccines and therapeutic compounds capable of neutralising MDR TB-HIV and HIV-1 infection.

International audience; BackgroundAn outbreak of listeriosis was identified in South Africa in 2017. The source was unknown.MethodsWe conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018.ResultsA total of 937 cases were identified, of which 465 (50%) were associated with pregnancy; 406 of the pregnancy-associated cases (87%) occurred in neonates. Of the 937 cases, 229 (24%) occurred in patients 15 to 49 years of age (excluding those who were pregnant). Among the patients in whom human immunodeficiency virus (HIV) status was known, 38% of those with pregnancy-associated cases (77 of 204) and 46% of the remaining patients (97 of 211) were infected with HIV. Among 728 patients with a known outcome, 193 (27%) died. Clinical isolates from 609 patients were sequenced, and 567 (93%) were identified as sequence type 6 (ST6). In a case–control analysis, patients with ST6 infections were more likely to have eaten polony (a ready-to-eat processed meat) than those with non-ST6 infections (odds ratio, 8.55; 95% confidence interval, 1.66 to 43.35). Polony and environmental samples also yielded ST6 isolates, which, together with the isolates from the patients, belonged to the same core-genome multilocus sequence typing cluster with no more than 4 allelic differences; these findings showed that polony produced at a single facility was the outbreak source. A recall of ready-to-eat processed meat products from this facility was associated with a rapid decline in the incidence of L. monocytogenes ST6 infections.ConclusionsThis investigation showed that in a middle-income country with a high prevalence of HIV infection, L. monocytogenes caused disproportionate illness among pregnant girls and women and HIV-infected persons. Whole-genome sequencing facilitated the detection of the outbreak and guided the trace-back investigations that led to the identification of the source.

Various microbial species have developed mechanisms that allow them to survive and propagate in the presence of potent therapeutic molecules that would normally inactivate their replication cycle and eradicate them. In most cases, the development or acquisition of genetic mutations bearing drug-resistance traits facilitate emergence of drug-resistant pathogens. Infection by drug-resistant strains leads to poor clinical outcomes in infected individuals. Other factors responsible for emergence of drug-resistant strains include long-term monotherapy, lack of adherence to treatment plan, and incorrect diagnosis, drug prescription and usage thereof. Development of novel and potent therapeutic molecules may eradicate drug resistance. However, the extended period of time required for drug testing and licensing undermines the urgency of combating drug-resistant diseases. Therefore this chapter aims to specifically examine the beneficial clinical outcomes of employing combination therapy as an effective method of treating and preventing the emergence of drug-resistant viral pathogens.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) cause significant infections and pose a threat to the viability of available antibiotics. Understanding the epidemiology of these infection...

Purpose of review Less than two decades into the 21st century, the world has already witnessed numerous large epidemics or pandemics. These events have highlighted inadequacies in both national and international capacity for outbreak prevention, detection, and response. Here, we review some of the major challenges from a policy perspective. Recent findings The most important challenges facing policymakers include financing outbreak preparedness and response in a complex political environment with limited resources, coordinating response efforts among a growing and diverse range of national and international actors, accurately assessing national outbreak preparedness, addressing the shortfall in the global biomedical workforce, building surge capacity of both human and material resources, balancing investments in public health and curative services, building capacity for outbreak-related research and development, and reinforcing measures for infection prevention and control. Summary In recent years, numerous epidemics and pandemics have caused not only considerable loss of life but also billions of dollars of economic loss. Although the events have served as a wake-up call and led to the implementation of relevant policies and counter-measures, such as the Global Health Security Agenda, many questions remain and much work to be done. Wise policies and approaches for outbreak control exist, but will require the political will to implement them.

The Global Action Plan on antimicrobial resistance calls for the use of antimicrobial medicines in human and animal health to be optimized, in tandem with a strengthening of the knowledge and evidence base through surveillance and research. However, there is a paucity of consumption data for African countries such as South Africa. Determining antimicrobial consumption data in low-resource settings remains a challenge. This article describes alternative mechanisms of assessing antimicrobial consumption data, such as the use of Intercontinental Marketing Services (IMS) data and contract data arising from tenders (an open Request for Proposal, RFP), as opposed to the international norms of daily defined doses per 100 patient-days or per 1000 population. Despite their limitations, these serve as indicators of antimicrobial exposure at the population level and represent an alternative method for ascertaining antimicrobial consumption in human health. Furthermore, South Africa has the largest antiretroviral treatment programme globally and carries a high burden of tuberculosis. This prompted the inclusion of antiretroviral and anti-tuberculosis antibiotic consumption data. Knowledge of antimicrobial utilization is imperative for meaningful future interventions. Baseline antimicrobial utilization data could guide future research initiatives that could provide a better understanding of the different measures of antibiotic use and the level of antibiotic resistance. Keywords: Antimicrobial governance, DOTS, Antibiotic consumption, Developing country, Antimicrobial exposure

The occurrence of invasive fungal diseases, particularly in immunocompromised patients, is life-threatening and increases the economic burden. The rising problem of multi-drug resistance is becoming a major concern for clinicians. In addition, a repertoire of antifungal agents is far less in number than antibacterial drugs. To combat these problems, combination therapy has gained a lot of interest. We previously reported the synergistic interaction of some mono- and bis-dihydropyrimidinone and thione derivatives with fluconazole and amphotericin B for combination antifungal therapy. In this study we used the same approach and synthesized different azole and non-azole derivatives of mono-(M) and bis-(B) chalcones and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drug – fluconazole (FLC) – against seven FLC susceptible and three FLC resistant clinically isolated Candida albicans strains. Based on the minimum inhibitory concentration results, the bis-derivatives showed lower MIC values compared to their mono-analogues. Both fractional inhibitory concentration index and isobologram results revealed mostly synergistic, additive or indifferent interactions between the tested compounds and FLC against different Candida isolates. None of the tested compounds showed any effect on energy dependent R6G efflux, revealing that they do not reverse the mechanism of drug efflux. However, surprisingly, these compounds profoundly decreased ergosterol biosynthesis and showed down regulation of ERG11 gene expression, which is the possible mechanism of reversal of azole drug resistance by these compounds. These results provide a platform for further research to develop pyrimidinone/thione ring containing compounds as promising new antifungal agents, which could be used in antifungal combination therapy.

Background: Mycobacterium tuberculosis (Mtb) is an airborne pathogenic microorganism that causes tuberculosis (TB). This pathogen invades lung tissues causing pulmonary infections and disseminates into other host organs. The Bacillus Calmette-Guerin (BCG) vaccine is employed to provide immune protection against TB; however, its efficacy is dependent on the age, immune status and geographic location of vaccinated individuals. Advanced diagnostic approaches such as GeneXpert MTB/RIF® and line probe assays (LPAs) have allowed rapid detection of drug-resistant, multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains. However, in sub-Saharan Africa, public and private health institutions are further burdened by the high prevalence of Human Immunodeficiency Virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) and TB co-infections across different age groups. Epigenetic mechanisms have been widely exploited by Mtb and HIV to bypass the host’s innate and adaptive immune responses, leading to microbial proliferation and disease manifestation. In the current study, we investigated the impact of epigenetic mechanisms in regulating target gene expression in healthy and patients co-infected with MDR TB-HIV.

Tuberculosis (TB) infection caused by Mycobacterium tuberculosis (Mtb) is still a persistent global health problem, particularly in developing countries. The World Health Organization (WHO) reported a mortality rate of about 1.8 million worldwide due to TB complications in 2015. The Bacillus Calmette-Guerin (BCG) vaccine was introduced in 1921 and is still widely used to prevent TB development. This vaccine offers up to 80% protection against various forms of TB; however its efficacy against lung infection varies among different geographical settings. Devastatingly, the development of various forms of drug-resistant TB strains has significantly impaired the discovery of effective and safe anti-bacterial agents. Consequently, this necessitated discovery of new drug targets and novel anti-TB therapeutics to counter infection caused by various Mtb strains. Importantly, various factors that contribute to TB development have been identified and include bacterial resuscitation factors, host factors, environmental factors and genetics. Furthermore, Mtb-induced epigenetic changes also play a crucial role in evading the host immune response and leads to bacterial persistence and dissemination. Recently, the application of GeneXpert MTB/RIF® to rapidly diagnose and identify drug-resistant strains and discovery of different molecular markers that distinguish between latent and active TB infection has motivated and energised TB research. Therefore, this review article will briefly discuss the current TB state, highlight various mechanisms employed by Mtb to evade the host immune response as well as to discuss some modern molecular techniques that may potentially target and inhibit Mtb replication.

SETTING Knowledge about spoligotyping families of drug-susceptible and drug-resistant Mycobacterium tuberculosis circulating in the Johannesburg area, South Africa, is lacking. OBJECTIVE To determine the genetic diversity of M. tuberculosis isolates circulating in the Johannesburg area and to compare the results with both national and international databanks. DESIGN Five hundred cultured M. tuberculosis isolates from within the greater Johannesburg metropolitan area collected from January 2009 to December 2010 were obtained from the National Health Laboratory Services (NHLS) Mycobacteriology Referral Laboratory, Johannesburg, in MGIT vials. The isolates were specimens from individuals with tuberculosis (TB) symptoms and known TB patients submitted to the NHLS for routine mycobacterial culture and drug susceptibility testing. The isolates were genotyped using spoligotyping. RESULTS Spoligotyping generated 62 shared types, with 92% (458/500) of the sample size matching pre-existing shared types. Of the 62 shared types, eight families were predominant (clustering from 16 to 132), representing 64% (340/500) of the sample. The Beijing family (135/500) predominated (P < 0.001). CONCLUSION TB incidence in Johannesburg does not appear to be due to clonality, but is rather due to diverse circulating strains, namely the Beijing family, followed by the S, Latin American-Mediterranean and T families.

Introduction: Antimicrobial resistant bacterial infections are widespread globally and increases in antimicrobial resistance presents a major threat to public health. Pseudomonas aeruginosa is an opportunistic healthcare-associated pathogen with high rates of morbidity and mortality and an extensive range of resistance mechanisms. This study describes the antibiotic susceptibility profiles of P. aeruginosa isolates from patients with bacteraemia submitted by sentinel laboratories in South Africa from 2014 to 2015. Methodology: Organism identification and antimicrobial susceptibility testing were done using automated systems. Molecular methods were used to detect common resistance genes and mechanisms. Results: Overall the susceptibility was high for all antibiotics tested with a decrease over the two-year period. There was no change in the MIC50 and MIC90 breakpoints for all antibiotics from 2014 to 2015. The MIC50 was within the susceptible breakpoint range for most antibiotics and the MIC90 was within the susceptible breakpoint range for colistin only. Phenotypically carbapenem non-susceptible isolates harboured the following plasmid-mediated genes: blaVIM (n = 81, 12%) and blaGES (n = 6, 0.9%); blaNDM (n = 4, 0.6%) and blaOXA-48 and variants (n = 3, 0.45%). Porin deletions were observed in one meropenem non-susceptible isolate only, and multi-drug resistance efflux pumps were expressed in the majority of the non-susceptible isolates investigated. BlaVEB-1, blaIMP and blaKPC were not detected. Conclusion: The prevalence of resistance to commonly used antibacterial agents was low for P. aeruginosa isolates and similarly, tested resistance mechanisms were detected in a relatively small proportion of isolates. Findings in this study represent baseline information for understanding antimicrobial susceptibility patterns in P. aeruginosa isolates from blood. Our surveillance report may assist in contributing to hospital treatment guidelines.

Background The diagnosis of tuberculous meningitis (TBM) can be extremely difficult in the absence of culture confirmation. Cerebrospinal fluid (CSF) adenosine deaminase (ADA) can potentially assist in this regard, although its current value remains unclear. The literature on the usefulness of CSF ADA in TBM diagnosis is inconsistent, especially from an analytical point of view. Methods A retrospective analysis of clinical and laboratory data relating to all CSF ADA requests during 2009 and 2010 in a South African quaternary healthcare setting was performed. A CSF ADA cut-off for TBM diagnosis was calculated using receiver operating characteristic curve analysis. The performance of CSF ADA in different infective and non-infective categories was assessed. Results In total, 3548 CSF ADA requests were considered over the 2-year period. Of these, 1490 were for patients for whom both a CSF ADA and a mycobacterial culture were requested. The optimal cut-off was calculated at 2.0 U/L (AUC = 0.86; 95% CI = 0.82 – 0.89; p-value

Mycobacterium kansasii (M. kansasii) is a major cause of non-tuberculous mycobacterial pulmonary disease in the South African gold-mining workforce, but the source of infection and molecular epidemiology are unknown. This study investigated the presence of M. kansasii in gold and coal mine and associated hostel water supplies and compared the genetic diversity of clinical and environmental isolates of M. kansasii. Five M. kansasii and ten other potentially pathogenic mycobacteria were cultured mainly from showerhead biofilms. Polymerase chain reaction-restriction analysis of the hsp65 gene on 196 clinical and environmental M. kansasii isolates revealed 160 subtype I, eight subtype II and six subtype IV strains. Twenty-two isolates did not show the typical M. kansasii restriction patterns, suggesting that these isolates may represent new subtypes of M. kansasii. In contrast to the clonal population structure found amongst the subtype I isolates from studies in other countries, DNA fingerprinting of 114 clinical and three environmental subtype I isolates demonstrated genetic diversity amongst the isolates. This study demonstrated that showerheads are possible sources of M. kansasii and other pathogenic non-tuberculous mycobacterial infection in a gold-mining region, that subtype I is the major clinical isolate of M. kansasii strain and that this subtype exhibits genetic diversity.

South Africa implemented Xpert MTB/RIF as the initial diagnostic test for pulmonary tuberculosis (TB). Xpert MTB/RIF's accuracy for diagnosing extrapulmonary tuberculosis (EPTB) was investigated. EPTB specimens ( n = 7,916) from hospitalized patients received over a 6-month period at a high-throughput TB referral laboratory in Johannesburg were investigated. Large-volume specimens were centrifuged, tissue biopsy specimens homogenized, and all specimens checked for growth of contaminating bacteria on blood agar. Contaminated samples received NALC-NaOH ( N -acetyl- l -cysteine–sodium hydroxide) decontamination prior to liquid culture. Residual specimens (volumes > 1 ml) after inoculation of culture ( n = 1,175) were tested using the Xpert MTB/RIF sputum protocol. Using culture as the reference, Xpert MTB/RIF's overall sensitivity was 59% (95% confidence interval [95% CI], 53% to 65%) and specificity was 92% (CI, 90% to 94%), with the highest sensitivities of 91% (95% CI, 78% to 97%) for pus, 80% (95% CI, 56% to 94%) for lymph node aspirates, and 51% (95% CI, 44% to 58%) for fluids (ascitic, 59%; pleural, 47%). A difference in sensitivities was noticed between specimens classified as having a thick (87% [95% CI, 76% to 94%]) versus clear (watery) (48% [95% CI, 36% to 61%]) appearance. This was unchanged with traces of blood (52% [95% CI, 44% to 60%]) or precentrifugation (57% [95% CI, 28% to 82%]) among clear specimens. Xpert MTB/RIF generated an additional 124 specimen results that were contaminated by Mycobacterial Growth Indicator Tubes (MGIT; 10.5%) and diagnosed rifampin (RIF) resistance earlier (9.6% [25/260]). Xpert MTB/RIF's performance on EPTB specimens provides very promising results and should be considered for incorporation into national TB guidelines. Xpert MTB/RIF is less affected by contaminating bacteria and reduces laboratory labor and diagnostic delay compared to traditional methods.

Background Prevalence surveillance methodology is the systematic observation of the occurrence and distribution of healthcare-associated infections (HCAIs) so that appropriate actions can be taken. Aim The objectives of a prevalence survey with an international validated methodology were to determine the prevalence of HCAIs for the first time in Argentina, and to provide data which could be used for international benchmarking. Methods In 2008, an HCAI prevalence survey was carried out in 39 hospitals in seven of 23 provinces in Argentina, with methodology identical to that employed by the Hospital Infection Society in the third prevalence survey of HCAIs in acute hospitals in the British Isles. Data collected were processed and analysed at the Northern Ireland Healthcare-Associated Infection Surveillance Centre at Belfast. Findings A total of 4249 patients were surveyed; 480 of these had at least one HCAI, resulting in a prevalence of 11.3% of patients. Male prevalence was 13.6% and female 9.0%. The most common HCAIs were pneumonia (3.3%), urinary tract infection (3.1%), surgical site infection (2.9%), primary bloodstream infection (1.5%), and soft tissue infections (1.2%). Among the 1027 patients who underwent surgery, the prevalence of surgical site infection was 10.2%. The prevalence of meticillin-resistant Staphylococcus aureus was 1.1%, accounting for 10.0% of all HCAI isolates. The results for Argentina show higher HCAI rates compared with corresponding findings for England, Wales, Northern Ireland and South Africa. Conclusion This survey will contribute to the prioritization of resources and help to inform Departments of Health and hospitals in the continuing effort to reduce HCAIs.

Central venous catheters (CVCs) are extensively used worldwide. Mechanical, infectious and thrombotic complications are well described with their use and may be associated with prolonged hospitalization, increased medical costs and mortality. CVCs account for an estimated 90% of all catheter-related bloodstream infections (CRBSI) and a host of risk factors for CVC-related infections have been documented. The duration of use of CVCs remains controversial and the length of time such devices can safely be left in place has not been fully and objectively addressed in the critically ill patient. Antimicrobial-impregnated catheters have been introduced in an attempt to limit catheter-related infection (CRI) and increase the time that CVCs can safely be left in situ. Recent meta-analyses concluded that antimicrobial-impregnated CVCs appear to be effective in reducing CRI. The authors conducted a prospective, randomized, double-blind study at Johannesburg Hospital over a 4-year period. The study entailed a comparison of standard triple-lumen versus antimicrobial impregnated CVCs on the rate of CRI. Our aim was to determine whether we could safely increase the duration of catheter insertion time from our standard practice of seven days to 14 days, to assess the influence of the antimicrobial impregnated catheter on the incidence of CRI, and to elucidate the epidemiology and risks of CRI. One hundred and eighteen critically ill patients were included in the study which spanned 34 951.5 catheter hours (3.99 catheter years). It was found that antimicrobial catheters did not provide any significant benefit over standard catheters, which the authors feel can safely be left in place for up to14 days with appropriate infection control measures. The most common source of CRI was the skin. The administration of parenteral nutrition and the site of catheter insertion (internal jugular vein vs subclavian vein) were not noted to be risk factors for CRI. There was no clinical evidence of thrombotic complication in either of the study groups. This study offers direction for the use of CVCs in critically ill patients and addresses many of the controversies that exist.

It has been shown that the inappropriate use of antimicrobial household agents selects for organisms with resistance mechanisms (e.g. efflux pumps), which could lead to the development of antibiotic resistance. The reverse hypothesis, that antibiotic-resistant organisms become tolerant to other antibacterial agents (e.g. disinfectants) due to the action of efflux pumps, has however not been extensively examined. The objective of this study was to establish whether there is a link between antibiotic resistance in potential gastrointestinal pathogens and reduced sensitivity of these organisms to commonly used household antimicrobial agents. In this study, tetracycline and ofloxacin sensitive and resistant Escherichia coli (9 strains) and Salmonella spp. (8 strains) were isolated from poultry and clinical samples. In order to assess whether these bacteria had active efflux pumps, ethidium bromide accumulation assays were performed. Extrusion of the active components of three commercial household agents (triclosan, sodium salicylate, and ortho-phenylphenol) by efflux pumps was tested using spectrophotometric accumulation assays. In order to simulate the kitchen environment, in-use disinfectant testing using the commercial household agents was performed to determine changes in their efficacy due to antibiotic resistance. Active efflux pump activity and extrusion of all three active ingredients was observed only in the antibiotic resistant organisms. The antibiotic sensitive bacteria were also more susceptible than the resistant isolates to the household antimicrobial agents at concentrations below that recommended by the manufacturer. These resistant bacteria could potentially be selected for and result in hard to treat infections.

Healthcare-associated infections have serious implications for both patients and hospitals. Environmental surface contamination is the key to transmission of nosocomial pathogens. Routine manual cleaning and disinfection eliminates visible soil and reduces environmental bioburden and risk of transmission, but may not address some surface contamination. Automated area decontamination technologies achieve more consistent and pervasive disinfection than manual methods, but it is challenging to demonstrate their efficacy within a randomized trial of the multiple interventions required to reduce healthcare-associated infection rates. Until data from multicenter observational studies are available, automated area decontamination technologies should be an adjunct to manual cleaning and disinfection within a total, multi-layered system and risk-based approach designed to control environmental pathogens and promote patient safety.

Introduction We aimed to obtain an in-depth understanding on recent antimicrobial resistance trends and molecular epidemiology trends of S . aureus bacteraemia (SAB). METHODS: Thirteen academic centres in South Africa were included from June 2010 until July 2012. S . aureus susceptibility testing was performed on the MicroScan Walkaway. Real-time PCR using the LightCycler 480 II was done for mec A and nuc . SCC mec and spa -typing were finalized with conventional PCR. We selected one isolate per common spa type per province for multilocus sequence typing (MLST). RESULTS: S . aureus from 2709 patients were included, and 1231 (46%) were resistant to methicillin, with a significant decline over the three-year period (p-value = 0.003). Geographical distribution of MRSA was significantly higher in Gauteng compared to the other provinces (P

Malaria is a serious global health problem, and rapid, accurate diagnosis is required to control the disease. An image processing algorithm to automate the diagnosis of malaria on thin blood smears is developed. The image classification system is designed to positively identify malaria parasites present in thin blood smears, and differentiate the species of malaria. Images are acquired using a charge-coupled device camera connected to a light microscope. Morphological and novel threshold selection techniques are used to identify erythrocytes (red blood cells) and possible parasites present on microscopic slides. Image features based on colour, texture and the geometry of the cells and parasites are generated, as well as features that make use of a priori knowledge of the classification problem and mimic features used by human technicians. A two-stage tree classifier using backpropogation feedforward neural networks distinguishes between true and false positives, and then diagnoses the species (Plasmodium falciparum, P. vivax, P. ovale or P. malariae) of the infection. Malaria samples obtained from the Department of Clinical Microbiology and Infectious Diseases at the University of the Witwatersrand Medical School are used for training and testing of the system. Infected erythrocytes are positively identified with a sensitivity of 85% and a positive predictive value (PPV) of 81%, which makes the method highly sensitive at diagnosing a complete sample provided many views are analysed. Species were correctly determined for 11 out of 15 samples.

Objective: To write a guideline for the management and prevention of nosocomial infections in South Africa in view of the following: i) nosocomial infections are a common and increasing problem globally, including South Africa; ii) widely varying standards of prevention and management of these important infections; iii) increasing and emerging antimicrobial resistance among commonly isolated pathogens, and iv) the significant economic burden of these infections on the healthcare system as well as their impact on patient morbidity and mortality. The main aims of the guideline are to provide recommendations for the initial choice of antimicrobial agents and the appropriate management of these infections encompassing the following conditions: i) nosocomial pneumonia, healthcare-associated pneumonia and ventilator-associated pneumonia; (ii) nosocomial bloodstream infections; (iii) nosocomial intravascular infections; (iv) nosocomial urinary tract infections; (v) nosocomial intra-abdominal infections; and (vi)...

The global problem of antimicrobial resistance is particularly pressing in developing countries, where the infectious disease burden is high and cost constraints prevent the widespread application of newer, more expensive agents. Gastrointestinal, respiratory, sexually transmitted, and nosocomial infections are leading causes of disease and death in the developing world, and management of all these conditions has been critically compromised by the appearance and rapid spread of resistance. In this first part of the review, we have summarised the present state of resistance in these infections from the available data. Even though surveillance of resistance in many developing countries is suboptimal, the general picture is one of accelerating rates of resistance spurred by antimicrobial misuse and shortfalls in infection control and public health. Reservoirs for resistance may be present in healthy human and animal populations. Considerable economic and health burdens emanate from bacterial resistance, and research is needed to accurately quantify the problem and propose and evaluate practicable solutions. In part II, to be published next month, we will review potential containment strategies that could address this burgeoning problem.

The presence of the foodborne pathogens, Salmonella spp., Listeria monocytogenes and Campylobacter spp., on 99 fresh and frozen chicken carcasses sourced from various retailers in Gauteng, South Africa, was investigated. Using culture methods, 60.6% of the carcasses were found to be contaminated with one or more pathogens, with 19.2%, 19.2% and 32.3% of the carcasses being found to harbour Salmonella, L. monocytogenes and Campylobacter, respectively. The extent of contamination with one or more pathogens was not significantly different (p>0.1) between fresh or frozen samples or between samples from butcheries, supermarkets or street vendors. Significantly more (p

guidelines for infection control in South Africa and developing countries have been formulated to assist healthcare professionals to deal with five important challenges that face healthcare workers: antimicrobial resistance, nosocomial pneumonia, bloodstream infections caused by intravascular catheters, nosocomial urinary tract infections, and nosocomial intra-abdominal infactions.

Candida parapsilosis was detected in environmental swabs and batches of total parenteral nutrition (TPN) products after routine monitoring. The isolates were analysed using randomly amplified polymorphic DNA (RAPD) to determine clonality and establish the most likely source of contamination. Of 20 isolates analysed, 18 were indistinguishable clonally and were found to be associated with particular work stations. The application of regular testing using a system such as the BacT/Alert, and molecular studies for epidemiological analysis, is of benefit to producers of medical products such as TPN to ensure patient safety.

BACKROUND: The increasing rates of antimicrobial resistance observed in the nosocomial pathogen Klebsiella pneumoniae are of major public health concern worldwide. OBJECTIVES: To describe the antibiotic susceptibility profiles of K. pneumoniae isolates from bacteraemic patients submitted by sentinel laboratories in five regions of South Africa from mid-2010 to mid-2012. Molecular methods were used to detect the most commonly found extended-spectrum beta-lactamase (ESBL) and carbapenemase resistance genes. METHODS: Thirteen academic centres serving the public healthcare sector in Gauteng, KwaZulu-Natal, Free State, Limpopo and Western Cape provinces submitted K. pneumoniae isolates from patients with bloodstream infections. Vitek 2 and MicroScan instruments were used for organism identification and susceptibility testing. Multiplex polymerase chain reactions (PCRs) were used to detect blaCTX-M, blaSHV and blaTEM genes in a proportion of the ESBL isolates. All isolates exhibiting reduced susceptibility to carbapenems were PCR tested for blaKPC and blaNDM-1 resistance genes. RESULTS: Overall, 68.3% of the 2 774 isolates were ESBL-positive, showing resistance to cefotaxime, ceftazidime and cefepime. Furthermore, 46.5% of all isolates were resistant to ciprofloxacin and 33.1% to piperacillin-tazobactam. The major ESBL genes were abundantly present in the sample analysed. Most isolates (95.5%) were susceptible to the carbapenems tested, and no isolates were positive for blaKPC or blaNDM1 There was a trend towards a decrease in susceptibility to most antibiotics. CONCLUSION: The high proportion of ESBL-producing K. pneumoniae isolates observed, and the prevalence of ESBL genes, are of great concern. Our findings represent a baseline for further surveillance in SA, and can be used for policy and treatment decisions.

The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. volumen 13; número 12

Recent cases of infections caused by glycopeptide-resistant enterococci (GRE) have highlighted the emergence of these organisms in the Republic of South Africa. During May 1998 we conducted a prevalence study in four hospitals in Johannesburg and obtained 184 rectal swabs from patients identified as being at high risk for GRE colonization. Twenty enterococcal isolates showing various glycopeptide resistance genotypes were recovered: 3 Enterococcus faecium vanA isolates, 10 E. faecium vanB isolates, 6 E. gallinarum vanC1 isolates, and 1 E. avium vanA isolate. Macrorestriction analysis was used to demonstrate the clonal spread of GRE strains within hospitals. Evidence also demonstrated the likely persistence of the original E. faecium vanA isolate associated with the first confirmed death contributed to by GRE infection in South Africa in March 1997.

Retrospective antibiotic surveillance data of selected invasive pathogens isolated from blood and cerebrospinal fluid at public sector hospitals in South Africa in 2007 are presented. Antimicrobial susceptibilities were determined according to the 2007 Clinical and Laboratory Standards Institute criteria. Klebsiella pneumoniae remains a highly resistant pathogen, with approximately half of all strains producing extended-spectrum beta-lactamases. All laboratories reported considerable resistance among Acinetobacter spp. Approximately 50-60% of Staphylococcus aureus isolates from blood were resistant to cloxacillin. Among Streptococcus pneumoniae isolates from blood and cerebrospinal fluid, resistance to penicillin ranged from 0% to 6% at most laboratories and 16-42% of isolates were classified with intermediate resistance to penicillin. Resistance to ceftriaxone in S. pneumoniae was rare.

Several pathogenetic processes are involved in the progression to AIDS in HIV-infected individuals. These include a gradual, but ultimately profound, depletion in CD4 lymphocytes, defects in B lymphocytes, neutrophil dysfunction and the breakdown of the integument as a consequence of AIDS-related dermatological conditions such as bacterial and fungal dermatoses and Kaposi's sarcoma. Each of these factors has important implications regarding host susceptibility to nosocomial infections. This review deals with some of the difficulties that are encountered in precisely defining the interrelationships between HIV infection/AIDS and nosocomial sepsis, and some of the controversies that surround respiratory, bloodstream (including central venous catheter-related infections) and gastrointestinal infections that may be acquired within healthcare centres. Because of the lack of accurate, detailed information on this subject, parallels will sometimes be drawn from observations made in other immunologically impaired patient groups and from data examining the rates of community-acquired infections in HIV-infected patients compared to controls. Appropriate and rational infection practice to minimize the risk of acquisition of nosocomial infection is highlighted. Finally, some of the common methodological problems commonly encountered in the current literature regarding nosocomial infections in this population group, and future challenges in the study of these infections, are reviewed.