Recent reports suggest that mosaic-like sequences within the mtr (multiple transferable resistance) efflux pump locus of Neisseria gonorrhoeae likely originating from commensal Neisseria sp. by transformation can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within the mtrR gene encoding the transcriptional repressor (MtrR) of the mtrCDE efflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (Wadsworth et al. 2018. MBio. doi.org/10.1128/mBio.01419-18). We performed detailed genetic and molecular studies to define the mechanistic basis for why such strains can exhibit decreased susceptibility to MtrCDE antimicrobial substrates including Azi. We report that a strong cis-acting transcriptional impact of a single nucleotide change within the -35 hexamer of the mtrCDE promoter as well gain-of-function amino acid changes at the C-terminal region of MtrD can mechanistically account for the decreased antimicrobial susceptibility of gonococci with a mosaic-like mtr locus.IMPORTANCE Historically, after introduction of an antibiotic for treatment of gonorrhea, strains of N. gonorrhoeae emerge that display clinical resistance due to spontaneous mutation or acquisition of resistance genes. Genetic exchange between members of the Neisseria genus occurring by transformation can cause significant changes in gonococci that impact the structure of an antibiotic target or expression of genes involved in resistance. The results presented herein provide a framework for understanding how mosaic-like DNA sequences from commensal Neisseria that recombine within the gonococcal mtr efflux pump locus function to decrease bacterial susceptibility to antimicrobials including antibiotics used in therapy of gonorrhea.

BACKGROUND: One of the promising current approaches to curb malaria lies in genetic vector control, the implementation of which will require an improved understanding of the movement of genetic constructs among mosquito populations. To predict potential gene flow from one area to another, it is important to begin to understand mosquito dynamics outside of the commonly-sampled village areas, and thus how genes may move between villages. This study assessed the presence and relative abundance of mosquitoes in a 6-km corridor between two villages in western Burkina Faso. METHODS: The area surrounding the villages was mapped and the road between them was used as the basis of a transect along which to sample. Five collection points were placed along this transect. To investigate both larval and adult mosquito presence, multiple sampling approaches were used surrounding each point: searching for larval sites in an area of 500 m radius, swarm sampling, human landing catches (HLC), CDC light traps and backpack aspiration catches of potential resting sites. Sampling took place twice: in September and October 2015. RESULTS: Adult mosquitoes from six species of Anopheles and three other genera were found along the whole transect. Anopheles gambiae (s.l.) was the most abundant followed by Anopheles nili and Anopheles coustani. Larvae of Anopheles spp. were found in small pools of surface water along the whole transect, though their presence increased with human proximity. HLC and aspiration were the most efficient methods of collecting adult mosquitoes along the whole transect, indicating that there are both host-seeking and resting mosquitoes well away from core village areas. In contrast, swarms of male mosquitoes, thought to be the principle mating locations of Anopheles spp. mosquitoes in West Africa, were only found close to the core village areas. CONCLUSIONS: This preliminary study indicates that Anopheles spp. mosquitoes are both present and breeding in low human-density areas along transit axes and provides both a relative evaluation of methods for use in these areas and evidence that gene flow between Sahelian population centres is likely. More robust and structured studies are nevertheless needed to come with stronger conclusions.

Recent reports suggest that mosaic-like sequences within the mtr (multiple transferable resistance) efflux pump locus of Neisseria gonorrhoeae, likely originating from commensal Neisseria sp. by transformation, can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within the mtrR gene encoding the transcriptional repressor (MtrR) of the mtrCDE efflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (C. B. Wadsworth, B. J. Arnold, M. R. A. Satar, and Y. H. Grad, mBio 9:e01419-18, 2018, https://doi.org/10.1128/mBio.01419-18). We performed detailed genetic and molecular studies to define the mechanistic basis for why such strains can exhibit decreased susceptibility to MtrCDE antimicrobial substrates, including Azi. We report that a strong cis-acting transcriptional impact of a single nucleotide change within the -35 hexamer of the mtrCDE promoter as well gain-of-function amino acid changes at the C-terminal region of MtrD can mechanistically account for the decreased antimicrobial susceptibility of gonococci with a mosaic-like mtr locus.IMPORTANCE Historically, after introduction of an antibiotic for treatment of gonorrhea, strains of N. gonorrhoeae emerge that display clinical resistance due to spontaneous mutation or acquisition of resistance genes. Genetic exchange between members of the Neisseria genus occurring by transformation can cause significant changes in gonococci that impact the structure of an antibiotic target or expression of genes involved in resistance. The results presented here provide a framework for understanding how mosaic-like DNA sequences from commensal Neisseria that recombine within the gonococcal mtr efflux pump locus function to decrease bacterial susceptibility to antimicrobials, including antibiotics used in therapy of gonorrhea.

Sean Loughlin Why has concern regarding healthcare-associated infections (HAIs) escalated in recent years? | Donna Swenson One reason is simply because awareness of the problem has increased. The problem has existed for a long time, but people are more aware of it because of media attention, particularly in regard to duodenoscopes. Also, medical devices have become far more complex than they used to be, which has raised questions about how to reprocess reusable devices effectively. Finally, we are seeing problems with antibiotic-resistant bacteria. Bacteria have evolved; we've been attacking them, but they have developed defense mechanisms. As a result, our antibiotics aren't as effective as they used to be. | Michelle Alfa Some HAIs that are related to reservoirs or contaminated medical devices are preventable, and awareness of this has increased. So, we're seeing more attention given to the concept of exogenous infections, where the organisms are being introduced from the environment or from contaminated medical devices into the patient while they're in the hospital. This is very different from endogenous infections where the patient's own normal flora are causing an infection. I would agree that multiantibiotic-resistant organisms are one of the reasons that we're more aware of the issue, and that's because we can specifically track these multiresistant microorganisms and know that they are more likely coming from an exogenous source. Because of their unusual antimicrobial resistance profile, it triggers an infection control investigation. If a hospital has five cases of carbapenem-resistant Enterobacteriaceae (CRE), this suggests there may be a point-source issue. Finally, the world is “flat” in terms of the spread of infectious diseases—essentially we're only “one flight away” from the next multiantibiotic-resistant organism being on our doorstep. We certainly don't want such multiresistant organisms entering our healthcare facilities and causing HAIs. So we have to be vigilant, ensuring early detection, monitoring, tracking, and preventing the spread of multiresistant organisms as quickly as possible. | Ann Gaffey Patient safety has always been a top priority for hospitals, and we all are quite aware of the 1999 Institute of Medicine (IOM) report, To Err is Human: Building a Safer Health System, which focused on preventing patient harm, as well as subsequent data that have been presented. So, we have more information to look at. At a local level, we see the advantages of incident and event reporting systems. Also, data that are being fed into the patient safety organizations are helping us to identify and address these issues. Recognition has increased that patient safety should really be top of mind for folks who are looking at HAIs and other events that could cause patient harm. | Matt Arduino Awareness of HAIs really didn't gain traction in the community until the publication of the IOM report in 1999, which stated that about 98,000 deaths a year result from preventable events and errors in healthcare facilities, of which HAIs are a part. In 1999, this translated to about $29 billion a year. Since that report, we now have public reporting through the Department of Health & Human Services (HHS), which also has an action plan for reducing infections. We have the Centers for Medicare & Medicaid Services requirement for conditions of participation for facilities to report data. However, a problem is that not all HAIs are captured through those mechanisms. | Lisa Waldowski Other aspects that have resulted in increased attention include medical device and equipment recalls, along with regulatory and federal agencies making the prevention of HAIs a priority by updating their respective guidelines, as well as communications through advisories, alerts, and other related materials. In addition, the terminology has changed from “hospital-acquired infections” to “healthcare-associated infections,” which underscores the fact that this problem is not isolated to hospitals.

OBJECTIVE: We evaluated whether being in drug use treatment improves linkage to HIV medical care for HIV-infected drug users. We assessed whether an evidence-based intervention for linkage to care ['ARTAS'] works better for HIV-infected drug users who had been in drug use treatment than those who had not. DESIGN: Randomized trial. METHODS: 295 Participants in the Antiretroviral Treatment Access Study ['ARTAS'] trial were followed for time to first HIV medical care. Drug use (injected and non-injected drugs) in the last 30days and being in drug treatment in the last 12 months were assessed by audio-CASI. We used a proportional hazards model of time to care in drug users with and without drug treatment, adjusting for barriers to care, AIDS symptoms, and demographic factors. We tested whether drug treatment modified the intervention effect by using a drug use/drug treatment*intervention interaction term. RESULTS: Ninety-nine participants (30%) reported drug use in the 30days before enrollment. Fifty-three (18%) reported being in a drug treatment program in the last 12 months. Drug users reporting methadone maintenance became engaged in care in less than half the time of drug users without a treatment history [HR 2.97 (1.20, 6.21)]. The ARTAS intervention effect was significantly larger for drug users with a treatment history compared to drug users without a treatment history (AHR 5.40, [95% CI, 2.03-14.38]). CONCLUSIONS: Having been in drug treatment programs facilitated earlier entry into care among drug users diagnosed with HIV infection, and improved their response to the ARTAS linkage intervention.

We analyzed highly pathogenic avian influenza A(H5N1) viruses isolated from humans infected in Egypt during 2007-2011. All analyzed viruses evolved from the lineage of subtype H5N1 viruses introduced into Egypt in 2006; we found minimal evidence of reassortment and no exotic introductions. The hemagglutinin genes of the viruses from 2011 formed a monophyletic group within clade 2.2.1 that also included human viruses from 2009 and 2010 and contemporary viruses from poultry; this finding is consistent with zoonotic transmission. Although molecular markers suggestive of decreased susceptibility to antiviral drugs were detected sporadically in the neuraminidase and matrix 2 proteins, functional neuraminidase inhibition assays did not identify resistant viruses. No other mutations suggesting a change in the threat to public health were detected in the viral proteomes. However, a comparison of representative subtype H5N1 viruses from 2011 with older subtype H5N1 viruses from Egypt revealed substantial antigenic drift.

Adverse events following immunization (AEFI) reported to the national Vaccine Adverse Event Reporting System (VAERS) represent true causally related events, as well as events that are temporally, but not necessarily causally related to vaccine. OBJECTIVE: We sought to determine if the causal relationships between the vaccine and the AEFI reported to VAERS could be assessed through expert review. DESIGN: A stratified random sample of 100 VAERS reports received in 2004 contained 13 fatal cases, 19 cases with non-fatal disabilities, 39 other serious non-fatal cases and 29 non-serious cases. Experts knowledgeable about vaccines and clinical outcomes, reviewed each VAERS report and available medical records. MAIN OUTCOME MEASURES: Modified World Health Organization criteria were used to classify the causal relationship between vaccines and AEFI as definite, probable, possible, unlikely or unrelated. Five independent reviewers evaluated each report. If they did not reach a majority agreement on causality after initial review, the report was discussed on a telephone conference to achieve agreement. RESULTS: 108 AEFIs were identified in the selected 100 VAERS reports. After initial review majority agreement was achieved for 83% of the AEFI and 17% required further discussion. In the end, only 3 (3%) of the AEFI were classified as definitely causally related to vaccine received. Of the remaining AEFI 22 (20%) were classified as probably and 22 (20%) were classified as possibly related to vaccine received; a majority (53%) were classified as either unlikely or unrelated to a vaccine received. CONCLUSIONS: Using VAERS reports and additional documentation, causality could be assessed by expert review in the majority of VAERS reports. Assessment of VAERS reports identified that causality was thought to be probable or definite in less than one quarter of reports, and these were dominated by local reactions, allergic reactions, or symptoms known to be associated with the vaccine administered.

We report on the genetic analysis of 213 highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry in Vietnam between 2007 and 2010. Phylogenetic analyses of the viral genomes revealed 38 distinct viral genotypes, 29 were novel and 9 were reported in Vietnam or neighboring countries in recent years. Viruses from only six genotypes persisted beyond one season or year. Thus, most reassortant viruses were transient, suggesting that such genotypes lacked significant fitness advantages. Viruses with clade 2.3.2.1 HA were re-introduced into Vietnam in 2009 and their prevalence rose steeply towards the end of 2010. Clade 2.3.4-like viruses (genotype V) were predominant in northern Vietnam and caused the majority of zoonotic infections, whereas clade 1.1 (genotype Z) viruses were only detected in the Mekong delta region, in southern Vietnam. Antigenic analysis of representative viruses from the four clades indicated substantial drift.