Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries.

Early development of the microbiome has been shown to affect general health and physical development of the infant and, although some studies have been undertaken in high-income countries, there are few studies from low- and middle-income countries. As part of the BARNARDS study, we examined the rectal microbiota of 2,931 neonates (term used up to 60 d) with clinical signs of sepsis and of 15,217 mothers screening for blaCTX-M-15, blaNDM, blaKPC and blaOXA-48-like genes, which were detected in 56.1%, 18.5%, 0% and 4.1% of neonates' rectal swabs and 47.1%, 4.6%, 0% and 1.6% of mothers' rectal swabs, respectively. Carbapenemase-positive bacteria were identified by MALDI-TOF MS and showed a high diversity of bacterial species (57 distinct species/genera) which exhibited resistance to most of the antibiotics tested. Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae/E. cloacae complex, the most commonly found isolates, were subjected to whole-genome sequencing analysis and revealed close relationships between isolates from different samples, suggesting transmission of bacteria between neonates, and between neonates and mothers. Associations between the carriage of antimicrobial resistance genes (ARGs) and healthcare/environmental factors were identified, and the presence of ARGs was a predictor of neonatal sepsis and adverse birth outcomes.

Transmission of multidrug-resistant Gram-negative bacteria from colonized mothers to their infants: a systematic review and meta-analysis.

BACKGROUND: Neonatal sepsis remains a leading cause of neonatal mortality. Maternal bacterial colonization plays a major role in transmission to the infant, with potential for subsequent development of neonatal sepsis with maternally derived strains. AIM: To review the molecular evidence supporting transmission of multidrug-resistant Gram-negative bacteria (MDR-GNB) from colonized mothers to their infants and the risk factors for MDR-GNB transmission. METHODS: PubMed and Scopus were searched for studies investigating the mechanisms, risk factors for and/or scale of transmission of MDR-GNB from colonized mothers to their infants. Random effects meta-analyses were performed to determine pooled proportions of MDR-GNB transmission and the neonatal outcomes of transmission. FINDINGS: Eight studies were included in the narrative description and six in the meta-analysis. Five studies used pulsed-field gel electrophoresis to assess relatedness of isolates from colonized mothers and their infants. Pooled proportion of MDR-GNB transmission from colonized mothers to their infants was 27% (95% confidence interval (CI): 8-47%). Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae were the most frequently studied MDR-GNB pathogens transmitted between mother-infant pairs. Following mother-to-infant transmission of an MDR-GNB pathogen, the pooled proportion for the outcome of neonatal colonization was 19% (95% CI: 3-35%). CONCLUSION: This systematic review strongly supports MDR and/or ESBL Enterobacteriaceae transmission from colonized mothers to their infants, with subsequent infant colonization. The risk factors contributing to transmission of MDR-GNB between colonized mothers and their infants warrants further research.

Optimizing antibiotic prescribing: collective approaches to managing a common-pool resource.

BACKGROUND: Antimicrobial resistance (AMR) is one of the greatest threats in 21st century medicine. AMR has been characterized as a social dilemma. A familiar version describes the situation in which a collective resource (in this case, antibiotic efficacy) is exhausted due to over-exploitation. The dilemma arises because individuals are motivated to maximize individual payoffs, although the collective outcome is worse if all act in this way. OBJECTIVES: We aim to outline the implications for antimicrobial stewardship of characterizing antibiotic overuse as a social dilemma. SOURCES: We conducted a narrative review of the literature on interventions to promote the conservation of resources in social dilemmas. CONTENT: The social dilemma of antibiotic over-use is complicated by the lack of visibility and imminence of AMR, a loose coupling between individual actions and the outcome of AMR, and the agency relationships inherent in the prescriber role. We identify seven strategies for shifting prescriber behaviour and promoting a focus on the collectively desirable outcome of conservation of antibiotic efficacy: (1) establish clearly defined boundaries and access rights; (2) raise the visibility and imminence of the problem; (3) enable collective choice arrangements; (4) conduct behaviour-based monitoring; (5) use social and reputational incentives and sanctions; (6) address misalignment of goals and incentives; and (7) provide conflict resolution mechanisms. IMPLICATIONS: We conclude that this theoretic analysis of antibiotic stewardship could make the problem of optimizing antibiotic prescribing more tractable, providing a theory base for intervention development.

Balancing the risks to individual and society: a systematic review and synthesis of qualitative research on antibiotic prescribing behaviour in hospitals.

BACKGROUND: Antimicrobial resistance is a global health threat, partly driven by inappropriate antibiotic prescriptions for acute medical patients in hospitals. AIM: To provide a systematic review of qualitative research on antibiotic prescribing decisions in hospitals worldwide, including broad-spectrum antibiotic use. METHODS: A systematic search of qualitative research on antibiotic prescribing for adult hospital patients published between 2007 and 2017 was conducted. Drawing on the Health Belief Model, a framework synthesis was conducted to assess threat perceptions associated with antimicrobial resistance, and perceived benefits and barriers associated with antibiotic stewardship. FINDINGS: The risk of antimicrobial resistance was generally perceived to be serious, but the abstract and long-term nature of its consequences led physicians to doubt personal susceptibility. While prescribers believed in the benefits of optimizing prescribing, the direct link between over-prescribing and antimicrobial resistance was questioned, and prescribers' behaviour change was frequently considered futile when fighting the complex problem of antimicrobial resistance. The salience of individual patient risks was a key barrier to more conservative prescribing. Physicians perceived broad-spectrum antibiotics to be effective and low risk; prescribing broad-spectrum antibiotics involved low cognitive demand and enabled physicians to manage patient expectations. Antibiotic prescribing decisions in low-income countries were shaped by a context of heightened uncertainty and risk due to poor microbiology and infection control services. CONCLUSIONS: When tackling antimicrobial resistance, the tensions between immediate individual risks and long-term collective risks need to be taken into account. Efforts to reduce diagnostic uncertainty and to change risk perceptions will be critical in shifting practice.

Lowbury Lecture 2007: infection prevention and control strategies for tuberculosis in developing countries - lessons learnt from Africa.

The World Health Organization ranks South Africa among the top ten of high-burden countries for tuberculosis (TB). The Western Cape Province has the highest prevalence of TB in the country. Studies performed in healthcare facilities both at Tygerberg Hospital and from Kwa-Zulu Natal province indicate a significant risk for nosocomial transmission of tuberculosis. An audit of provision for infection prevention and control (IPC) programmes revealed that although there were adequate supplies of protective clothing, the greatest need was for training and understanding of IPC principles among healthcare workers. In establishing national IPC guidelines for TB in South Africa, it has become evident that most of these were derived from existing guidelines in developed countries. Though the principles were sound, the practices were not realistic for developing economies and generally not implemented in healthcare facilities. Factors that influence a robust TB management programme are poverty, concurrent human immunodeficiency virus infection, overcrowding, ignorance of the disease and a varied level of health service delivery. It is recommended that a foundation of sound knowledge should be established upon which best practices should be built within the framework of good IPC principles.

The antimicrobial activity of copper and copper alloys against nosocomial pathogens and Mycobacterium tuberculosis isolated from healthcare facilities in the Western Cape: an in-vitro study.

Clinical isolates of meticillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Candida albicans and Mycobacterium tuberculosis (MTB) were tested against copper (Cu) and its alloys. Stainless steel and polyvinylchloride (PVC) were used as controls. The amount of Cu required to inhibit test isolates at room temperature (24 degrees C) and at 4 degrees C was determined. At room temperature, Cu, DZR Brass (Cu 62%, Pb 2.5%, arsenate 0.13% and Zn 22.5%) and Brass 70/30 (Cu 70% and zinc 30%) inhibited C. albicans and K. pneumoniae at 60 min; nickel silver (NiAg) inhibited C. albicans at 60 min and K. pneumoniae at 270 min. P. aeruginosa was inhibited by Brass 70/30 and nickel silver (NiAg) at 180 min and at 270 min by Cu and DZR. Cu and DZR inhibited A. baumannii at 180 min while the other alloys were effective at 360 min. Stainless steel and PVC showed little or no inhibitory activity. Two M. tuberculosis strains, one isoniazid resistant (R267) and the other multidrug resistant (R432), demonstrated growth inhibition with Cu of 98% and 88% respectively compared with PVC; the other alloys were less active. Time to positivity (TTP) for R267 was >15 days with Cu and 11 days for the other alloys; with R432 it was 5 days. Effective inhibition of nosocomial pathogens and MTB by Cu and alloys was best when the Cu content was >55%.

HIV risk exposure among South African children in public health facilities.

The study investigates the risk exposure to HIV infection among South African children aged 2-9 years served by public health services. Together with their biological mothers, 3471 children and were recruited from inpatient and outpatient children in the Free State Province. Blood samples were taken by professional nurses and a history taken of exposure factors associated with HIV transmission. DNA testing was used to confirm biological maternity where the child was HIV-positive and the mother HIV-negative. Mother-child pairs were stratified by mother's HIV status. Exposure factors related to the child's HIV status were examined in each stratum using a chi-square test. Independent factors were then included in a multiple logistic regression model. Having an HIV-positive mother was strongly related to HIV infection in children (OR: 310; 95%CI: 148-781). However, seven HIV-positive children had HIV-negative mothers. Transmission in this group was significantly associated with breastfeeding by a non-biological mother (OR: 437; 95%CI: 53-5020), being fed with expressed breast milk from a milk room (OR: 37.6; 95%CI: 6.2-259.0), dental injection history (OR: 31.5; 95%CI: 4.5-189.4) and visits to a dentist (OR: 26.9; 95%CI: 4.4-283.5). Although mother-to-child-transmission is shown to be the primary mode of HIV transmission in South African children, the few HIV-positive children infected by other modes of transmission suggest a potential risk of non-vertical HIV infections. These infections can be prevented through education and improved infection-control procedures.

An international survey of cleaning and disinfection practices in the healthcare environment.

BACKGROUND: Antimicrobial resistance has become an urgent global health priority. Basic hygiene practices and cleaning and disinfection of the hospital environment are key in preventing pathogen cross-transmission. AIM: To our knowledge no studies have assessed the worldwide differences in cleaning and disinfection practices in healthcare facilities. The electronic survey described here was developed in order to evaluate differences in healthcare facility cleaning practices around the world. METHODS: The International Society of Antimicrobial Chemotherapy (ISAC, formerly ISC), Infection Prevention and Control work group developed a survey with 30 multiple-choice questions. The questions were designed to assess the current cleaning practices in healthcare settings around the world. FINDINGS: A total of 110 healthcare professionals, representing 23 countries, participated in the online survey. In 96% of the facilities a written cleaning policy was present. Training of cleaning staff occurred in 70% of the facilities at the start of employment. Cleaning practices and monitoring of these practices varied. CONCLUSIONS: The survey enabled assessment and recognition of widely differing global practices in approaches to environmental cleaning and disinfection. Development of guideline recommendations for cleaning and disinfection could improve practices and set minimum standards worldwide.

Infection control practices in public dental care services: findings from one South African Province.

Infection control practices which increase the risk of blood-borne virus transmission with associated dental practice in one South African province were studied. All 24 state dental clinics were observed for adequate provision to carry out good infection prevention and control (IPC) practice, 75 staff including dentists, nurses and dental assistants were interviewed to assess IPC knowledge and 23 dental procedures were observed. Significant findings were the difference between knowledge and practice, despite adequate provisions for safe infection control practice. The lack of protective eye wear during a dental procedure, not washing hands between patients, not disassembling an item prior to disinfection or sterilization, and not using a sterile drill for each patient were identified. A rapid method for detection of occult blood was used as a marker for inadequate IPC practice. Contaminated dental items of equipment just prior to patient use in 25% of equipment tested and 37% of surfaces and surrounding areas in the dental clinics and units were recorded. This study concludes that, despite provision for safe dental practice available in state dental clinics, there was a lack of knowledge application in clinical practice. The risk of blood-borne virus transmission in a population with high human immunodeficiency virus (HIV) prevalence cannot be ignored.

Infectious disease exposures and outbreaks at a South African neonatal unit with review of neonatal outbreak epidemiology in Africa.

BACKGROUND: Hospitalized neonates are vulnerable to infection, with pathogen exposures occurring in utero, intrapartum, and postnatally. African neonatal units are at high risk of outbreaks owing to overcrowding, understaffing, and shared equipment. METHODS: Neonatal outbreaks attended by the paediatric infectious diseases and infection prevention (IP) teams at Tygerberg Children's Hospital, Cape Town (May 1, 2008 to April 30, 2016) are described, pathogens, outbreak size, mortality, source, and outbreak control measures. Neonatal outbreaks reported from Africa (January 1, 1996 to January 1, 2016) were reviewed to contextualize the authors' experience within the published literature from the region. RESULTS: Thirteen outbreaks affecting 148 babies (11 deaths; 7% mortality) over an 8-year period were documented, with pathogens including rotavirus, influenza virus, measles virus, and multidrug-resistant bacteria (Serratia marcescens, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci). Although the infection source was seldom identified, most outbreaks were associated with breaches in IP practices. Stringent transmission-based precautions, staff/parent education, and changes to clinical practices contained the outbreaks. From the African neonatal literature, 20 outbreaks affecting 524 babies (177 deaths; 34% mortality) were identified; 50% of outbreaks were caused by extended-spectrum ß-lactamase-producing Klebsiella pneumoniae. CONCLUSIONS: Outbreaks in hospitalized African neonates are frequent but under-reported, with high mortality and a predominance of Gram-negative bacteria. Breaches in IP practice are commonly implicated, with the outbreak source confirmed in less than 50% of cases. Programmes to improve IP practice and address antimicrobial resistance in African neonatal units are urgently required.

Manual cleaning of hospital mattresses: an observational study comparing high- and low-resource settings.

BACKGROUND: Hospital-associated infections (HAIs) are more frequently encountered in low- than in high-resource settings. There is a need to identify and implement feasible and sustainable approaches to strengthen HAI prevention in low-resource settings. AIM: To evaluate the biological contamination of routinely cleaned mattresses in both high- and low-resource settings. METHODS: In this two-stage observational study, routine manual bed cleaning was evaluated at two university hospitals using adenosine triphosphate (ATP). Standardized training of cleaning personnel was achieved in both high- and low-resource settings. Qualitative analysis of the cleaning process was performed to identify predictors of cleaning outcome in low-resource settings. FINDINGS: Mattresses in low-resource settings were highly contaminated prior to cleaning. Cleaning significantly reduced biological contamination of mattresses in low-resource settings (P < 0.0001). After training, the contamination observed after cleaning in both the high- and low-resource settings seemed comparable. Cleaning with appropriate type of cleaning materials reduced the contamination of mattresses adequately. Predictors for mattresses that remained contaminated in a low-resource setting included: type of product used, type of ward, training, and the level of contamination prior to cleaning. CONCLUSION: In low-resource settings mattresses were highly contaminated as noted by ATP levels. Routine manual cleaning by trained staff can be as effective in a low-resource setting as in a high-resource setting. We recommend a multi-modal cleaning strategy that consists of training of domestic services staff, availability of adequate time to clean beds between patients, and application of the correct type of cleaning products.

Biotyping of Haemophilus using API 10S--an epidemiological tool?

One hundred and ninety-nine strains of Haemophilus isolates were biotyped by Kilian's method(1) and a modified API 10S strip and the results compared. One hundred percent correlation was found between the two systems. The ONPG test proved of value in differentiating between Haemophilus influenzae and Haemophilus parainfluenzae when there was growth factor disc failure.

Distribution and transferability of plasmids encoding trimethoprim resistance in urinary pathogens from Greece.

Of 505 strains of Enterobacteriaceae responsible for significant bacteriuria and isolated from hospital patients in two Greek cities in 1989, 151 strains (30%) were resistant to trimethoprim (MIC greater than or equal to 4 mg/L) and 220 (44%) were resistant to sulphamethoxazole (MIC greater than or equal to 64 mg/L); 127 (84%) of the trimethoprim-resistant strains exhibited high-level resistance (MIC greater than 1024 mg/L) and 121 (80%) were additionally resistant to four or more other antibiotics. Plasmids were detected in 141 (93%) of the trimethoprim-resistant strains. Trimethoprim resistance was encoded on self-transmissible plasmids in 79 (52%) of the resistant strains, and in a further seven strains (5%), plasmids coding for trimethoprim resistance could be mobilised by X+ factor. Co-transfer of various other antimicrobial resistances with trimethoprim resistance was observed, tetracycline resistance being the most common. The low degree of linkage observed between trimethoprim resistance and resistance to streptomycin and spectinomycin suggests that Tn7 is relatively uncommon in Greece. Classification of trimethoprim-resistance plasmids on the basis of their antimicrobial-resistance patterns and molecular mass revealed 39 different profiles. Overall, these findings differ from those from other European countries where the prevalence of transferable high-level trimethoprim resistance is low and where chromosomal Tn7-encoded trimethoprim resistance is common.

How to cost and fund an infection control programme.

Infection control (IC) services in the United Kingdom are provided as part of the microbiology services and therefore they have not, to date, been costed separately. This paper addresses the cost of providing the service, the savings that accrue from the IC policies in a hospital and, finally, the cost of infective episodes and outbreaks. The point of the exercise is to enable readers to cost their own services and separate the IC and microbiology budgets while maintaining the provision of service under one department.

Infection control programmes--are they cost-effective?

Infection control (IC) programmes are cost-effective in the long-term but much depends on the available resources and the support from management. The funding of IC programmes at present is linked to the Microbiology Department and a separate budget needs to be established. The best use of resources is to apply a risk assessment to each situation which presents and to adapt protocols accordingly. For example, the treatment of a carrier or an infected patient with methicillin-resistant Staphylococcus aureus cost 374 pounds and 2454 pounds, respectively in 1993, the major portion of the cost being due to an increased length of stay which was two days and 10 days, respectively. It is more cost-effective to treat carriers. The other cost-effective investment is in education and reinforcement of simple messages. Formal lectures seem to be the least effective way of producing long-term effect; frequent ward visits or contacts are most effective. Also, there is better compliance when there is a perceived risk to the staff themselves. The availability of the IC team to advise helps reduce waste and therefore cost. This is particularly true of antibiotic usage where it was noted that without guidance, the antibiotic usage increased by 2000 pounds per month when compared to a similar period in the previous year. The available provisions for IC programmes in the UK are utilized exceptionally well when compared with other countries.

New strategies for the use of mupirocin for the prevention of serious infection.

Nasal mupirocin has an important role to play in the prevention of Staphylococcus aureus infection by eliminating nasal carriage of this organism. Indeed, in many countries nasal mupirocin is one of the mainstays for controlling outbreaks of methicillin-resistant S. aureus. Eradication of nasal S. aureus with mupirocin has been shown to be effective in preventing postoperative infections in patients undergoing cardiothoracic surgery and in preventing exit-site infections in patients undergoing haemodialysis. It has been proposed that the use of mupirocin should be extended to other situations, such as the prevention of postoperative infections in patients undergoing implant surgery and the prevention of bacteraemias in high-risk patients. Clinical trials are needed to establish the efficacy of mupirocin in these situations. Both low-level and high-level resistance have been reported during treatment with nasal mupirocin. Low-level resistance does not represent a significant clinical problem but high-level resistance resulting from indiscriminate use may give grounds for concern. Further review of these issues is required. As with any antibiotic, mupirocin should be used judiciously, as part of an integrated programme of infection control.

Minimum standards in laboratories for infection control.

Laboratory services should be available to support every infection control programme, whether in a hospital or community setting. The services will depend upon available resources and the expectation of the clinicians using the services. Equally, resources reflect the level of staff expertise, equipment and finances supporting laboratory practice. All information given to the clinical staff should be sensible, accurate, comprehensible and in keeping with the clinical needs of the healthcare setting. Internal and external quality controls should be rigorous. Not all laboratories are expected to provide an all-encompassing service and therefore primary, secondary and tertiary or referral laboratories should be established where necessary. It is essential to have clear protocols on laboratory usage, mutually agreed between the laboratory and clinical staff to be cost effective.

The effect of disinfectants on perforated gloves.

Three types of gloves, 'Biogel', 'Regent Dispo Surgical' gloves and Ansell gammex were perforated, and contaminated with Escherichia coli or Pseudomonas aeruginosa as test organisms applied either to the hand or the glove surface. The glove surface was decontaminated with alcoholic chlorhexidine ('Hibisol'), methylated spirit, or soap and water. The experiments were performed in triplicate on three separate days. The experiments were designed to study the ability of the three disinfection methods to reduce the bacterial count of 10(6) colony forming units (cfu) ml-1 (applied to perforated gloves or hands) sufficiently to permit the re-use of such gloves for non-sterile ward procedures. The best method of disinfection was using alcoholic chlorhexidine which not only reduced glove surface carriage but also reduced transfer of bacteria to the hands through the perforation in the gloves. Soap and water was the least effective. Escherichia coli was more easily removed than P. aeruginosa. We recommend that non-sterile ward procedures may be carried out even after gloves have been perforated provided alcoholic chlorhexidine is used between each procedure to reduce cross-infection between patients.

A multi-centre evaluation of two chlorhexidine-containing formulations for surgical hand disinfection.

Many experimental methods have been used to assess the efficacy of products intended for surgical hand disinfection. In this study, a modification of the Peterson glove juice method was used to compare two chlorhexidine-based surgical hand disinfectants, 'Hibiscrub' and an experimental formulation, F.6115. The study was performed by four independent laboratories and data merged for analysis. There was found to be no significant difference between the two formulations. The results illustrate that this modified Peterson glove juice method has the potential to form the basis of a standard method for testing surgical hand disinfectants which is both relevant to the practical situation and reproducible in different laboratories.

The continuing problem of 'hospital staphylococci': why?

Nosocomial infections due to staphylococci continue to pose a serious health concern worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is an important and growing cause of staphylococcal infection. The incidence of MRSA varies throughout the world, but is particularly high in Japan where the incidence is four-times that seen in Europe. The emergence of coagulase-negative staphylococci (CNS) has increased as a significant pathogen in infections associated with prosthetic implants. Evidence suggests that hand carriage by hospital staff is one way in which CNS are introduced onto catheters, intravenous lines and other implant devices. Control measures in the UK have concentrated on the reservoirs of infection, with the aim of preventing infection and the resulting morbidity, mortality and economic burden. At the North Middlesex Hospital, London, UK, an aggressive prophylactic policy for MRSA has been employed since 1987. Data show that it is six times cheaper to treat a carrier than it is to treat an infected patient. Prophylaxis therefore provides a more cost-effective way of controlling the spread of MRSA infection. Such stringent control strategies, coupled with increased awareness and adequate funding, are necessary if the spread of resistant bacteria is to be limited.