Meghan F. Davis

Household transmission of meticillin-resistant Staphylococcus aureus and other staphylococci

Although the role of pets in household transmission of meticillin-resistant Staphylococcus aureus (MRSA) has been examined previously, only minor attention has been given to the role of the abiotic household environment independent of, or in combination with, colonisation of pets and human beings to maintain transmission cycles of MRSA within the household. This report reviews published work about household transmission of S aureus and other staphylococci and describes contamination of household environmental surfaces and colonisation of pets and people. Household microbial communities might have a role in transfer of antimicrobial resistance genes and could be reservoirs for recolonisation of people, although additional research is needed regarding strategies for decontamination of household environments. Household-based interventions should be developed to control recurrent S aureus infections in the community, and coordination between medical and veterinary providers could be beneficial.

Feather Meal: A Previously Unrecognized Route for Reentry into the Food Supply of Multiple Pharmaceuticals and Personal Care Products (PPCPs)

Antimicrobials used in poultry production have the potential to bioaccumulate in poultry feathers but available data are scarce. Following poultry slaughter, feathers are converted by rendering into feather meal and sold as fertilizer and animal feed, thereby providing a potential pathway for reentry of drugs into the human food supply. We analyzed feather meal (n = 12 samples) for 59 pharmaceuticals and personal care products (PPCPs) using EPA method 1694 employing liquid chromatography tandem mass spectrometry (LC/MS/MS). All samples tested positive and six classes of antimicrobials were detected, with a range of two to ten antimicrobials per sample. Caffeine and acetaminophen were detected in 10 of 12 samples. A number of PPCPs were determined to be heat labile during laboratory simulation of the rendering process. Growth of wild-type E. coli in MacConkey agar was inhibited by sterilized feather meal (p = 0.01) and by the antimicrobial enrofloxacin (p < 0.0001) at levels found in feather meal. Growth of a drug-resistant E. coli strain was not inhibited by sterilized feather meal or enrofloxacin. This is the first study to detect antimicrobial residues in feather meal. Initial results suggest that more studies are needed to better understand potential risks posed to consumers by drug residues in feather meal.

Dose imprecision and resistance: free-choice medicated feeds in industrial food animal production in the United States.

Background Industrial food animal production employs many of the same antibiotics or classes of antibiotics that are used in human medicine. These drugs can be administered to food animals in the form of free-choice medicated feeds (FCMF), where animals choose how much feed to consume. Routine administration of these drugs to livestock selects for microorganisms that are resistant to medications critical to the treatment of clinical infections in humans. Objectives In this commentary, we discuss the history of medicated feeds, the nature of FCMF use with regard to dose delivery, and U.S. policies that address antimicrobial drug use in food animals. Discussion FCMF makes delivering a predictable, accurate, and intended dose difficult. Overdosing can lead to animal toxicity; underdosing or inconsistent dosing can result in a failure to resolve animal diseases and in the development of antimicrobial-resistant microorganisms. Conclusions The delivery of antibiotics to food animals for reasons other than the treatment of clinically diagnosed disease, especially via free-choice feeding methods, should be reconsidered.

An ecological perspective on U.S. industrial poultry production: the role of anthropogenic ecosystems on the emergence of drug-resistant bacteria from agricultural environments

The industrialization of food animal production, specifically the widespread use of antimicrobials, not only increased pressure on microbial populations, but also changed the ecosystems in which antimicrobials and bacteria interact. In this review, we argue that industrial food animal production (IFAP) is appropriately defined as an anthropogenic ecosystem. This paper uses an ecosystem perspective to frame an examination of these changes in the context of U.S. broiler chicken production. This perspective emphasizes multiple modes by which IFAP has altered microbiomes and also suggests a means of generating hypotheses for understanding and predicting the ecological impacts of IFAP in terms of the resistome and the flow of resistance within and between microbiomes.

The shared microbiota of humans and companion animals as evaluated from Staphylococcus carriage sites

BackgroundStaphylococcus aureus and other coagulase-positive staphylococci (CPS) colonize skin and mucous membrane sites and can cause skin and soft tissue infections (SSTIs) in humans and animals. Factors modulating methicillin-resistant S. aureus (MRSA) colonization and infection in humans remain unclear, including the role of the greater microbial community and environmental factors such as contact with companion animals. In the context of a parent study evaluating the households of outpatients with community MRSA SSTI, the objectives of this study were 1) to characterize the microbiota that colonizes typical coagulase-positive Staphylococcus spp. carriage sites in humans and their companion pets, 2) to analyze associations between Staphylococcus infection and carriage and the composition and diversity of microbial communities, and 3) to analyze factors that influence sharing of microbiota between pets and humans.ResultsWe enrolled 25 households containing 56 pets and 30 humans. Sampling locations were matched to anatomical sites cultured by the parent study for MRSA and other CPS. Bacterial microbiota were characterized by sequencing of 16S ribosomal RNA genes. Household membership was strongly associated with microbial communities, in both humans and pets. Pets were colonized with a greater relative abundance of Proteobacteria, whereas people were colonized with greater relative abundances of Firmicutes and Actinobacteria. We did not detect differences in microbiota associated with MRSA SSTI, or carriage of MRSA, S. aureus or CPS. Humans in households without pets were more similar to each other than humans in pet-owning households, suggesting that companion animals may play a role in microbial transfer. We examined changes in microbiota over a 3-month time period and found that pet staphylococcal carriage sites were more stable than human carriage sites.ConclusionsWe characterized and identified patterns of microbiota sharing and stability between humans and companion animals. While we did not detect associations with MRSA SSTI, or carriage of MRSA, S. aureus or CPS in this small sample size, larger studies are warranted to fully explore how microbial communities may be associated with and contribute to MRSA and/or CPS colonization, infection, and recurrence.

One Reservoir: Redefining the Community Origins of Antimicrobial-resistant Infections

This article reviews the evidence concerning the emergence of community-acquired MRSA and highlights the relevance of reservoirs of antimicrobial resistance in humans and animals in the community environment. Although hospital use of antimicrobials has been assumed to generate the highest risk of resistance and transmission of resistant infections, the greater load of antimicrobial use is found in food animal production. The authors conclude that it is important to assess accurately and evaluate the interactions between hospital and community; improve surveillance for resistance of community origin, including agriculture; and to implement policies that prevent increases in community reservoirs of antibiotic resistance.

Methicillin-Resistant Staphylococcus aureus ST9 in Pigs in Thailand

Background Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial and community-associated pathogen. Recently, livestock-associated MRSA (LA-MRSA) has emerged and disseminated in Europe and North America and now constitutes a considerable zoonotic burden in humans with risk factors of pig exposure, whereas the extent of the livestock reservoir is relatively unknown on other continents. Methodology/Principal Findings From March through April 2011, MRSA was identified in pigs from 3 out of 30 production holdings in Chang Mai Province, Thailand. Representative isolates were subjected to molecular characterization and antimicrobial susceptibility testing; all isolates had genotypic and phenotypic characteristics of LA-MRSA previously characterized in the region: they belonged to ST9, lacked the lukF-lukS genes encoding Panton-Valentine leukocidin, and were resistant to multiple non-β-lactam antimicrobials. However, unlike other Asian LA-MRSA-ST9 variants, they were spa type t337 and harbored a different staphylococcal cassette chromosome mec IX. Conclusions/Significance A novel MRSA-ST9 lineage has been established in the pig population of Thailand, which differs substantially from LA-MRSA lineages found in other areas of the continent. The emergence of novel LA-MRSA lineages in the animal agriculture setting is worrisome and poses a serious threat to global public health.

A Niche for Infectious Disease in Environmental Health: Rethinking the Toxicological Paradigm

Objective In this review we highlight the need to expand the scope of environmental health research, which now focuses largely on the study of toxicants, to incorporate infectious agents. We provide evidence that environmental health research would be strengthened through finding common ground with the tools and approaches of infectious disease research. Data sources and extraction We conducted a literature review for examples of interactions between toxic agents and infectious diseases, as well as the role of these interactions as risk factors in classic “environmental” diseases. We investigated existing funding sources and research mandates in the United States from the National Science Foundation and the National Institutes of Health, particularly the National Institute of Environmental Health Sciences. Data synthesis We adapted the toxicological paradigm to guide reintegration of infectious disease into environmental health research and to identify common ground between these two fields as well as opportunities for improving public health through interdisciplinary research. Conclusions Environmental health encompasses complex disease processes, many of which involve interactions among multiple risk factors, including toxicant exposures, pathogens, and susceptibility. Funding and program mandates for environmental health studies should be expanded to include pathogens in order to capture the true scope of these overlapping risks, thus creating more effective research investments with greater relevance to the complexity of real-world exposures and multifactorial health outcomes. We propose a new model that integrates the toxicology and infectious disease paradigms to facilitate improved collaboration and communication by providing a framework for interdisciplinary research. Pathogens should be part of environmental health research planning and funding allocation, as well as applications such as surveillance and policy development.

Duration of Colonization and Determinants of Earlier Clearance of Colonization With Methicillin-Resistant Staphylococcus aureus

BACKGROUND The duration of colonization and factors associated with clearance of methicillin-resistant Staphylococcus aureus (MRSA) after community-onset MRSA skin and soft-tissue infection (SSTI) remain unclear. METHODS We conducted a prospective cohort study of patients with acute MRSA SSTI presenting to 5 adult and pediatric academic hospitals from 1 January 2010 through 31 December 2012. Index patients and household members performed self-sampling for MRSA colonization every 2 weeks for 6 months. Clearance of colonization was defined as negative MRSA surveillance cultures during 2 consecutive sampling periods. A Cox proportional hazards regression model was developed to identify determinants of clearance of colonization. RESULTS Two hundred forty-three index patients were included. The median duration of MRSA colonization after SSTI diagnosis was 21 days (95% confidence interval [CI], 19-24), and 19.8% never cleared colonization. Treatment of the SSTI with clindamycin was associated with earlier clearance (hazard ratio [HR], 1.72; 95% CI, 1.28-2.30; P < .001). Older age (HR, 0.99; 95% CI, .98-1.00; P = .01) was associated with longer duration of colonization. There was a borderline significant association between increased number of household members colonized with MRSA and later clearance of colonization in the index patient (HR, 0.85; 95% CI, .71-1.01; P = .06). CONCLUSIONS With a systematic, regular sampling protocol, duration of MRSA colonization was noted to be shorter than previously reported, although 19.8% of patients remained colonized at 6 months. The association between clindamycin and shorter duration of colonization after MRSA SSTI suggests a possible role for the antibiotic selected for treatment of MRSA infection.

Immunologic Consequences of Signal Transducers and Activators of Transcription 3 Activation in Human Squamous Cell Carcinoma

Paracrine cross-talk between tumor cells and immune cells within the tumor microenvironment underlies local mechanisms of immune evasion. Signal transducer and activator of transcription 3 (STAT3), which is constitutively activated in diverse cancer types, is a key regulator of cytokine and chemokine expression in murine tumors, resulting in suppression of both innate and adaptive antitumor immunity. However, the immunologic effects of STAT3 activation in human cancers have not been studied in detail. To investigate how STAT3 activity in human head and neck squamous cell carcinoma (HNSCC) might alter the tumor microenvironment to enable immune escape, we used small interfering RNA and small-molecule inhibitors to suppress STAT3 activity. STAT3 inhibition in multiple primary and established human squamous carcinoma lines resulted in enhanced expression and secretion of both proinflammatory cytokines and chemokines. Although conditioned medium containing supernatants from human HNSCC inhibited lipopolysaccharide-induced dendritic cell activation in vitro, supernatants from STAT3-silenced tumor cells reversed this immune evasion mechanism. Moreover, supernatants from STAT3-silenced tumor cells were able to stimulate the migratory behavior of lymphocytes from human peripheral blood in vitro. These results show the importance of STAT3 activation in regulating the immunomodulatory mediators by human tumors and further validate STAT3 as a promising target for therapeutic intervention.