Spread Of Antibiotic-resistant Organisms Research Articles

The challenges of defining the human nasopharyngeal resistome.

The nasopharynx is an important microbial reservoir for the emergence and spread of antibiotic-resistant organisms. The nasopharyngeal resistome is an extensive, adaptable reservoir of antibiotic-resistance genes (ARGs) within this niche. Metagenomic sequencing decodes the genetic material of all organisms within a sample using next-generation technologies, permitting unbiased discovery of novel ARGs and associated mobile genetic elements (MGEs). The challenges of sequencing a low-biomass bacterial sample have limited exploration of the nasopharyngeal resistome. Here, we explore the current understanding of the nasopharyngeal resistome, particularly the role of MGEs in propagating antimicrobial resistance (AMR), explore the advantages and limitations of metagenomic sequencing technologies and bioinformatic pipelines for nasopharyngeal resistome analysis, and highlight the key outstanding questions for future research.

Evaluating Healthcare Worker Movements and Patient Interactions Within ICU Rooms

Background: Contamination of healthcare workers and patient environments likely play a role in the spread of antibiotic-resistant organisms. The mechanisms that contribute to the distribution of organisms within and between patient rooms are not well understood, but they may include movement patterns and patient interactions of healthcare workers. We used an innovative technology for tracking healthcare worker movement and patient interactions in ICUs. Methods: The Kinect system, a device developed by Microsoft, was used to detect the location of a person’s hands and head over time, each represented with 3-dimensional coordinates. The Kinects were deployed in 2 intensive care units (ICUs), at 2 different hospitals, and they collected data from 5 rooms in a high-acuity 20-bed cardiovascular ICU (unit 1) and 3 rooms in a 10-bed medical-surgical ICU (unit 2). The length of the Kinect deployment varied by room (range, 15–48 days). The Kinect data were processed to included date, time, and location of head and hands for all individuals. Based on the coordinates of the bed, we defined events indicating bed touch, distance 30 cm (1 foot) from the bed, and distance 1 m (3 feet) from the bed. The processed Kinect data were then used to generate heat maps showing density of person locations within a room and summarizing bed touches and time spent in different locations within the room. Results: The Kinect systems captured In total, 2,090 hours of room occupancy by at least 1 person within ~1 m of the bed (Table 1). Approximately half of the time spent within ~1 m from the bed was at the bedside (within ~30 cm). The estimated number of bed touches per hour when within ~1 m was 13–23. Patients spent more time on one side of the bed, which varied by room and facility (Fig. 1A, 1B). Additionally, we observed temporal variation in intensity measured by person time in the room (Fig. 1C, 1D). Conclusions: High occupancy tends to be on the far side (away from the door) of the patient bed where the computers are, and the bed touch rate is relatively high. These results can be used to help us understand the potential for room contamination, which can contribute to both transmission and infection, and they highlight critical times and locations in the room, with a potential for focused deep cleaning.Funding: NoneDisclosures: None

ANTIBIOTIC SUSCEPTIBILITY PATTERN AND PHENOTYPIC CHARACTERIZATION OF EXTENDED-SPECTRUM-BETALACTAMASE-PRODUCING Enterobacteriaceae ISOLATED FROM VARIOUS CLINICAL SAMPLES

The spread of antibiotic resistant organisms and those producing extended spectrum -lactamases (ESBL) has become a health care problem worldwide in communities and hospitals, as it leads to more complicated infections, longer duration of treatment, and increases in patient mortality. In the present study, we analyzed 226 clinical samples in order to assess the spread of ESBL-producing Enterobacteriaceae. 196 Enterobacteriaceae were identified and classified as members of the genera Pantoea, Klebsiella, Escherichia, Enterobacter, Serratia, Proteus, Citrobacter, and Raoultella. The results of susceptibility testing of isolated strains to 19 antibiotics showed that the most part of the isolates were highly resistant (p.0.01) to the tested -lactams: penicillins and penicillin like antibiotics (amoxicillin, ticarcillin and amoxicillin-clavulanic acid), first-generation cephalosporins (cephalexin), and second generation cephalosporins (cefoxitin). 60.20% of the Enterobacteriaceae isolates were multi-drug resistant (MDR) strains. Resistant isolates to third generation cephalosporins were tested for ESBL by tree methods, concluding its presence in 29.59% of the isolates by double-disk synergy test, 27.55% by the disk approximation method and by 31.63% double-disk test. High levels of MDR strains and ESBL- producing Enterobacteriaceae in our study suggest the need for applying specific infection control measures, and rational antibiotic use to reduce the selection pressure and prevent dissemination of resistant bacteria.

CARRIAGE OF MULTI-DRUG RESISTANT UROBACTERIA BY ASYMPTOMATIC PREGNANT WOMEN IN YENAGOA, BAYELSA STATE, NIGERIA.

Background:Urinary Tract Infections (UTIs) in pregnancy are associated with significant morbidity for both mother and baby but its early detection and treatments can prevent unfavorable complications in pregnancy. This study therefore determined the prevalence of asymptomatic bacteriuria and antimicrobial resistance profile of the urinary bacteria among pregnant women in Yenagoa, Bayelsa State, Nigeria.Materials and Methods:Mid-stream urine samples were collected from 201 apparently healthy pregnant women attending antenatal clinics in Yenagoa. The samples were analyzed and the organisms identified using standard microbiological methods. Haemolysin production by the organisms was screened and their antimicrobial susceptibility was performed using standard assay methods.Results:A high significant bacteriuria of 119 (59.2%) was predominantly recovered from the pregnant women in their second and third trimesters. The bacteria isolated; Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus species had 36 – 67% of haemolysin producers. The bacteria exhibited a very high resistance to most of the antibiotics tested but the resistance to ceftazidime, gentamicin and ciprofloxacin was 28 – 67%. All the Staphylococcus species exhibited 90% and 85% resistance to cefoxitin (methicillin resistant) and vancomycin respectively. An 89 - 100% of the bacteria exhibited multiple antibiotic resistance and 72.3% of the screened bacteria phenotypically expressed Extended-Spectrum Beta-lactamase production.Conclusion:The high prevalence of significant bacteriuria with high multi-drug resistance among the study pregnant women call for regular education on proper personal hygiene and the need for early screening for UTIs during antenatal clinics as means of controlling the spread of antibiotic resistant organisms and complications in pregnancy.

Antibiotic resistant pathogen outbreak investigation: an interdisciplinary module to teach fundamentals of evolutionary biology

The evolution of resistance to antibiotics provides a timely and relevant topic for teaching undergraduate students evolutionary biology. Here, we present a module incorporating modified sequencing data from eight antibiotic resistant pathogen outbreaks in hospital settings with bioinformatics and phylogenetic analyses. This module uses whole genome sequencing data from hospital outbreaks investigated by the Centers for Disease Control and Prevention to provide examples of antibiotic resistance spread. Students work in groups to analyze outbreak data to identify the bacterial species and antibiotic resistance genes, to infer a phylogenetic tree examining relatedness among isolates, and to determine a possible source of the outbreak. Students then compile their results in individual reports and provide recommendations for preventing the further spread of antibiotic resistant organisms. In addition to providing genomic outbreak data, we include a teaching concepts guide discussing three integral components of the module: how evolutionary biology concepts of natural selection and competition impact antibiotic resistance; outbreak investigation information to aid in phylogenetic analysis and creation of recommendations; and instructions for the bioinformatics protocol. Completion of this module provides students an opportunity to think critically about the evolution of resistance, practice bioinformatics techniques, and relate evolutionary biology to current events.

Fitness costs associated with the acquisition of antibiotic resistance.

Acquisition of antibiotic resistance is a relevant problem for human health. The selection and spread of antibiotic-resistant organisms not only compromise the treatment of infectious diseases, but also the implementation of different therapeutic procedures as organ transplantation, advanced surgery or chemotherapy, all of which require proficient methods for avoiding infections. It has been generally accepted that the acquisition of antibiotic resistance will produce a general metabolic burden: in the absence of selection, the resistant organisms would be outcompeted by the susceptible ones. If that was always true, discontinuation of antibiotic use would render the disappearance of resistant microorganisms. However, several studies have shown that, once resistance emerges, the recovery of a fully susceptible population even in the absence of antibiotics is not easy. In the present study, we review updated information on the effect of the acquisition of antibiotic resistance in bacterial physiology as well as on the mechanisms that allow the compensation of the fitness costs associated with the acquisition of resistance.

Impact of Methicillin-Resistant Staphylococcus aureus Colonization on Transfer to a Nursing Home

BackgroundStudies on the spread of antibiotic-resistant organisms across a network of facilities often rely on measures of infection rates, however, little is known about the impact that colonization may have on whether patients require additional care after discharge. To understand the impact of MRSA colonization on transfers to nursing homes (NH), we used surveillance tests for methicillin-resistant Staphylococcus aureus (MRSA) which have been performed for patients admitted to US Veterans Affairs (VA) hospitals since October 1, 2007.MethodsWe identified first admissions into a VA facility from January 1, 2000 to July 1, 2011, restricting our analysis to patients first admitted into a hospital after MRSA surveillance was initiated on October 1, 2007. Patients were included if they had an admission test and at least one additional test during their stay. Importation was defined by a positive MRSA surveillance test within 12 hours of admission, and acquisition was defined as a negative test within 12 hours of admission followed by a positive test. Primary outcome was NH transfer, with all other events censored. We classified MRSA colonization as either importation or acquisition, and ran a cox proportional hazard model, treating acquisition as a time-varying covariate. Because the time of first positive test is unlikely to coincide with the time of acquisition, we estimated acquisition time as the midpoint between the negative and positive test times. Baseline covariates included importation, gender and age.ResultsIncluded were 243,553 admissions with a total of 5,548 (2.3 %) transfers to NH, 12,399 (5.1 %) importations and 3,064 (1.3 %) acquisitions. Gender was not associated with NH transfer, but age was associated with increased risk of NH transfer (HR 1.36, 95% CI 1.25–1.49 for 55 age 70, and HR 1.84, 95% CI 1.68–2.01 for age 70). Additionally, importation (HR 1.19, 95% CI 1.09–1.31) and acquisition (HR 1.28, 95% CI 1.09–1.49) were associated with increased rate of NH transfer.ConclusionMRSA colonization is associated with increased risk of NH transfer following hospital admission. Additionally, acquisition of MRSA seems to result in a slightly elevated risk of NH transfer compared with those who are colonized at the time of hospital admission.Disclosures All authors: No reported disclosures.

A US View on Antimicrobial Stewardship in Animal Agriculture

Antimicrobial resistance was declared a serious threat to global public health by the World Health Organization. Actions have been taken to improve antimicrobial use, especially in settings such as hospitals. However, a large amount of antimicrobials are administered to food-producing animals, posing a risk of spread of antibiotic-resistant organisms to humans through contaminated retail meat, or by direct contact with animals. In the USA, efforts are in place to limit the use of antimicrobials for growth enhancement as opposed to disease prevention or treatment purposes. Additionally, the US Administration is calling for improved surveillance capabilities for the monitoring of antimicrobial use in livestock and for the tracking of antimicrobial resistance through the National Antimicrobial Resistance Monitoring System, as well as for development of antimicrobial alternatives for use in food production. The restaurant industry and meat suppliers are also committing to decreasing the amounts of antimicrobials used in animal food production.

The Global Spread of Healthcare-Associated Multidrug-Resistant Bacteria: A Perspective From Asia

Since antibiotics were first used, each new introduced class has been followed by a global wave of emergent resistance, largely originating in Europe and North America where they were first used. Methicillin-resistant Staphylococcus aureus spread from the United Kingdom and North America across Europe and then Asia over more than a decade. Vancomycin-resistant enterococci and Klebsiella pneumoniae carbapenemase-producing K. pneumoniae followed a similar path some 20 years later. Recently however, metallo-β-lactamases have originated in Asia. New Delhi metallo-β-lactamase-1 was found in almost every continent within a year of its emergence in India. Metallo-β-lactamase enzymes are encoded on highly transmissible plasmids that spread rapidly between bacteria, rather than relying on clonal proliferation. Global air travel may have helped facilitate rapid dissemination. As the antibiotic pipeline offers little in the short term, our most important tools against the spread of antibiotic resistant organisms are intensified infection control, surveillance, and antimicrobial stewardship.

Human Food Chain and Microorganisms: A Case of Co-Evolution

Human Food Chain and Microorganisms: A Case of Co-Evolution

Resistant Organisms and Otitis Media

To the Editors: Treatment of AOM in the current era of high prevalence of antibiotic-resistant Streptococcus pneumoniae is a great concern and an issue of controversy. A major step towards reducing nonjudicious antibiotic treatment of this infection has been the recognition that antibiotic treatment can be postponed and even omitted in many cases. Yet antibiotic prescriptions for this indication are currently still very frequent, and nonjudicious treatment of this disease continues to contribute to the increase in resistance rate among pathogens. One frequently measured outcome is nasopharyngeal carriage of resistant pathogens after different antibiotic treatments, because such a carriage constitutes a potential source of spread of resistant pathogens in the community. In the study by Toltzis et al,1 4 antimicrobial regimens frequently used in the treatment of acute otitis media (AOM) (amoxicillin, ceftriaxone, cefprozil and azithromycin) were compared, and the outcomes of nasopharyngeal colonization by penicillin-nonsusceptible S. pneumoniae (PNSSP) and in particular penicillin-resistant S. pneumoniae (PRSP) were measured. Although the relative proportion of PRSP of all S. pneumoniae isolated was higher in the amoxicillin group, no significant difference was observed in the prevalence rate of PRSP among the children treated with all 4 regimens during the follow-up period (up to 30 days), when the 4 treatment groups were compared. Neither was there any difference in PRSP carriage rates between the treatment groups. In fact, the only antibiotic that reduced PNSSP carriage was amoxicillin. Because about 33% of PNSSP and 66% of PRSP in the United States are also macrolide-resistant,2,3 missing information in the report by Toltzis et al that is crucial is the carriage rate of macrolide-resistant and multidrug-resistant S. pneumoniae during the period after treatment. In fact, because one of the treatment arms was azithromycin, it is surprising that macrolide resistance (and multidrug resistance) rates were not reported or at least that the reason why they were not reported was not provided. In communities in which macrolide resistance of S. pneumoniae is low, this may not be significant, but in populations with higher prevalence rates (as has been reported in the United States and many countries in Europe), this information is essential. Toltzis et al4 calculated both the simple odds ratio (ORs) and the conditional odds ratio (ORc). Because there was no change in the absolute number of PRSP isolates in each group and thus of the prevalence rate of PRSP, and even the change in PNSSP rates were not significant, the pairwise comparisons of ORs indeed did not detect any differences between the groups (P > 0.29). A recent review5 emphasized how misleading the use of ORc alone can be in interpreting data on carriage and spread of antibiotic-resistant organisms. Toltzis et al used the ORc to claim that acquisition of PRSP was higher in the amoxicillin-treated group, whereas the data show that in the amoxicillin-treated group absolute numbers of PNSP decreased. However, both PNSP and PSSP decreased, but PRSP as a subgroup did not change; the proportion of PRSP increased. The acquisition rate of PNSP or any other subgroup was not measured. In fact, without the use of molecular measures, or at least serotyping, one cannot really calculate acquisition or eradication rates of S. pneumoniae given that both spontaneous and antibiotic-induced eradication and acquisition of new strains are common. Therefore the conclusions drawn by the authors (that amoxicillin administration, compared with the other 3 regimens, resulted in a larger shift toward PRSP colonization and might promote the dissemination of the nonsusceptible phenotype) do not correspond to their results. To date, the published data still support the use of high dose amoxicillin given at high doses (90–100 mg/kg/d, with or without clavulanate)6,7 as the primary treatment of AOM. This regimen is still regarded as optimal when considering both the efficacy of the antimicrobial regimen and the population dynamics associated with carriage and spread of antibiotic-resistant S. pneumoniae. Ron Dagan, MD Soroka University Medical Center The Faculty of Health Science Ben-Gurion University of the Negev Beer-Sheva, Israel Gili Regev-Yochay, MD Ethan Rubinstein, MD Sheba Medical Center Tel-Hashomer, Israel

Development of the choices and acquisition of antibiotics model from a descriptive study of a Lay Honduran population

Antibiotic resistance is a global public health problem that is accelerated by overuse and misuse of antibiotics. In today's world of increasing international travel and exchange of goods, the spread of antibiotic resistant organisms is a growing threat. Despite significant antibiotic use in developing nations, research to describe and curtail inappropriate use is limited. In this study, the investigators developed a model of antibiotic use, choices and acquisition of antibiotics model, from a study of a lay population in Honduras. A representative sample of 939 rural and urban Hondurans completed the Preguntas Para El Uso de Antibiotics questionnaire to determine how the participant made choices about antibiotic use. The study indicated that the rural participants used significantly fewer antibiotics than the urban participants and that the demographic indicators did not show a significant difference in antibiotic use in those of lower socioeconomic status. In addition, the participants reported that they seek out professional advice and care rather than self-prescribing. Implications for educational and empowerment programs based on the model are discussed.

Acquired immunoparalysis in paediatric intensive care: prospective observational study

The increase in high technology medicine, complex surgical techniques, and use of immunosuppressive agents means that more patients are managed with broad spectrum antibiotics. Such regimens may contribute to the...

Antimicrobial Stewardship at The Toronto Hospital

Infectious diseases continue to plague humankind, and the treatment of infections continues to consume a significant proportion of health care resources. Although antibiotics have saved countless lives and have transformed the treatment of infectious diseases, increasing levels of antibiotic resistance present a serious emerging public health threat. Antibiotic resistance results in morbidity and mortality from treatment failures and increased health care costs (1). Current costs to treat infections with antibiotic-resistant organisms are estimated by the Centers for Disease Control and Prevention, Atlanta, Georgia to be over $4 billion annually in the United States (2). Increasing resistance raises concerns about the inability to treat certain infections, bringing about the dawn of the ‘postantibiotic’ era. Overuse and inappropriate use of antibiotics are widely believed to be responsible for the increasing level of antibiotic resistance (3-5). Although antibiotic resistance is encountered everywhere, particular problems exist in health care institutions. Many of the organisms that are part of the normal flora may pose a significant threat, as an invasive pathogen, to patients whose resistance is lowered by virtue of age, chemotherapy, transplantation or immunosuppression. The hospital milieu, especially in intensive care units, burn units, neonatal units, hematology-oncology units and other special care units, provides an epidemiological pressure cooker for the emergence and dissemination of antibiotic-resistant organisms. The frequent use of antibiotics, high use of invasive devices and frequent hospitalization in these patient populations adds the necessary ingredients to this pressure cooker environment. Approaches to controlling the development and spread of antibiotic-resistant organisms have been outlined in several documents and reports (2,5-10). Three major strategies are employed to achieve this end: surveillance to identify the trends of resistance, improving appropriate antimicrobial usage (antimicrobial stewardship), and reducing cross transmission of multiresistant organisms through enhanced infection control precautions and reducing environmental contamination. These strategies may be considered in the context of the classic host-microbe-drug relationship as depicted in Figure 1. We describe the approaches to antibiotic stewardship that have been used at The Toronto Hospital (TTH) over the past seven years. The Toronto Hospital is a 1200-bed tertiary care medical school-affiliated hospital with over 34,000 visits per year. In 1991, the annual expenditure for antimicrobial agents was over $3 million. At this time the Pharmacy and Therapeutics Committee recommended the creation of a new pharmacy position (Drug Utilization Co-ordinator) to monitor drug use with a focus on appropriate antimicrobial prescribing. The An-

Child-care practices: effects of social change on the epidemiology of infectious diseases and antibiotic resistance.

The increasing number of mothers of young children in the work force and the resultant escalated use of child-care facilities has had a marked effect on the epidemiology of infectious diseases in young children. Children attending child care are at high risk for respiratory and gastrointestinal tract illnesses. The high prevalence of infectious diseases in the child-care setting is accompanied by high usage of antibiotics, which in turn has resulted in spread of antibiotic-resistant organisms. The infectious disease standards of the American Public Health Association/American Academy of Pediatrics guidelines were developed to prevent and limit transmission of infectious diseases in the child-care setting. Adherence to these standards is essential but will not completely eliminate the increased risk of infectious diseases in child-care settings. New challenges need to be addressed to assure that optimal health promotion and disease prevention is practiced in child-care settings. We approach the 21st century with a vast amount of medical knowledge, molecular technology, highly effective vaccines, and powerful antimicrobial agents. However, at the same time we face many unsolved serious problems, such as preventing or controlling the emergence and spread of antibiotic-resistant organisms that adversely affect our ability to treat infectious diseases. Further research is needed concerning the relations between child care, the use of antibiotics, and transmission of antibiotic-resistant organisms in order to design and implement the most effective strategies for preventing or controlling antibiotic resistance. The potential risk for transmission of HIV in the child-care setting also needs to be recognized, and procedures to prevent transmission of blood-borne pathogens need to be followed. Monitoring compliance with national standards for child-care facilities, dissemination of information concerning infectious diseases and use of antibiotics, and development and use of new vaccines are strategies which should be used to help protect the health of children in child-care environments.

Release of genetically modified micro-organisms into the environment

Biotechnology in general, and recombinant DNA technology in particular, has the capacity to change the health and wealth of every individual, but like other major advances in science and technology such as nuclear power and electronics it can also be exploited to mankind's detriment. For this reason and the fact that recombinant DNA technology involves altering the molecules encoding life itself, the subject has given rise to a high level of public debate. Centuries of experience with the release of conventional micro-organisms for sewage treatment, agriculture and food production have shown that the release of large numbers of foreign organisms into an environment does not necessarily cause ecological damage. In fact few of these organisms survive for long periods. The threat of horizontal gene transfer from recombinant organisms to indigenous ones is however very real and mechanisms exist whereby, at least theoretically, any genetically engineered trait can be transferred to any prokaryotic organism and many eukaryotic ones. The rapid spread of antibiotic-resistant organisms since the widespread introduction of antibiotics graphically demonstrates that such a threat is real. There have now been several experiments to determine the effect of environmental release of micro-organisms, both in enclosed areas and in unenclosed sites. Proposals for the use of genetically modified micro-organisms that contain specific gene deletions have had a relatively smooth passage through government approval agencies and public enquiries and some products have been approved for commercial use. In addition a strain of bakers' yeast with an altered control element has also been approved for commercial use in the UK. Genetically modified viruses, especially those containing foreign genes have not received such favourable treatment and have been the subject of heated national and international debate. Many microbiologists are convinced, however, that the use and release of carefully constructed genetically engineered organisms will result in significant benefit, but with little risk to the environment. Ecologists, however, are not so sanguine and in the current ‘green’ political atmosphere their opinions are very influential. Thus most developed countries now have in force a series of very cautious regulations and guidelines for the release of genetically modified micro-organisms.