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Background Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates. Methods Susceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility. Results A total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06 μg/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC ≤0.25 μg/mL. Conclusions Single marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials.

Neisseria gonorrhoeae is an urgent public health threat due to the emergence of antibiotic resistance. As most isolates in the United States are susceptible to at least one antibiotic, rapid molecular antimicrobial susceptibility tests (ASTs) would offer the opportunity to tailor antibiotic therapy, thereby expanding treatment options. With genome sequence and antibiotic resistance phenotype data for nearly 20,000 clinical N. gonorrhoeae isolates now available, there is an opportunity to use statistical methods to develop sequence-based diagnostics that predict antibiotic susceptibility from genotype. N. gonorrhoeae, therefore, provides a useful example illustrating how to apply machine learning models to aid in the design of sequence-based ASTs. We present an overview of this framework, which begins with establishing the assay technology, the performance criteria, the population in which the diagnostic will be used, and the clinical goals, and extends to the choices that must be made to arrive at a set of features with the desired properties for predicting susceptibility phenotype from genotype. While we focus on the example of N. gonorrhoeae, the framework generalizes to other organisms for which large-scale genotype and antibiotic resistance data can be combined to aid in diagnostics development.

Objective:To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.Design:Prospective observational study.Setting:Neonatal intensive care unit (NICU).Methods:We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.Results:A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.Conclusions:In comparison to fast outbreaks, outbreaks that are “slow and sustained” may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.

Wastewater-based epidemiology is a promising public health tool that can yield a more representative view of the population than case reporting. However, only about 80% of the U.S. population is connected to public sewers, and the characteristics of populations missed by wastewater-based epidemiology are unclear. To address this gap, we used publicly available datasets to assess sewer connectivity in the U.S. by location, demographic groups, and economic groups. Data from the U.S. Census American Housing Survey revealed that sewer connectivity was lower than average for American Indian and Alaskan Native, White, non-Hispanic, older, not in poverty, and larger households, but smaller geographic scales revealed local variations from this national connectivity pattern. For example, data from the U.S. Environmental Protection Agency showed that sewer connectivity was positively correlated with income in Minnesota, Florida, and California. Data from the U.S. Census American Community Survey and Environmental Protection Agency also revealed geographic areas with low sewer connectivity, such as Alaska, the Navajo Nation, Minnesota, Michigan, and Florida. However, with the exception of the U.S. Census data, there were inconsistencies across datasets. Using mathematical modeling to assess the impact of wastewater sampling inequities on inferences about epidemic trajectory at a local scale, we found that in some situations, even weak connections between communities may allow wastewater monitoring in one community to serve as a reliable proxy for an interacting community with no wastewater monitoring, when cases are widespread. A systematic, rigorous assessment of sewer connectivity will be important for ensuring an equitable and informed implementation of wastewater-based epidemiology as a public health monitoring system.

Our data suggest that the high-virulence ensemble of the STEC O104:H4 outbreak strain remains a global threat because genomically similar strains cause disease worldwide but that the horizontal acquisition of O-antigen gene clusters has diversified the O-antigens of strains belonging to ST678. Thus, the identification of these highly pathogenic strains is masked by diverse and rare O-antigens, thereby confounding the interpretation of their potential risk.

Rapid identification of new SARS-CoV-2 variants is a critical component of the public health response to the COVID-19 pandemic. However, we lack a quantitative framework to assess the expected performance of sampling strategies in varying epidemic contexts. To address this gap, we used a multi-patch stochastic model of SARS-CoV-2 spread in New York City to evaluate the impact of the volume of testing and sequencing, geographic representativeness of sampling, location and timing of variant emergence, and relative variant transmissibility on the time to first detection of a new variant. The strategy of targeted sampling of likely emergence locations offered the most improvement in detection speed. Increasing sequencing capacity reduced detection time more than increasing testing volumes. The relative transmissibility of the new variant and the epidemic context of variant emergence also influenced detection times, showing that individual surveillance strategies can result in a wide range of detection outcomes, depending on the underlying dynamics of the circulating variants. These findings help contextualize the design, interpretation, and trade-offs of genomic surveillance strategies.

BackgroundDoxycycline post-exposure prophylaxis (DoxyPEP) has demonstrated efficacy for prevention of bacterial sexually transmitted infections. To inform policy decisions on the use of DoxyPEP for gonorrhea prevention, we used a mathematical model to investigate its impact on resistance dynamics and the burden of infection in men who have sex with men (MSM).Methods and FindingsUsing a deterministic compartmental model of gonorrhea transmission in an MSM population, we introduced DoxyPEP at various uptake levels (10-75%) and compared 20-year prevalence and resistance dynamics relative to those at baseline (i.e., no DoxyPEP introduction). Uptake of DoxyPEP resulted in initial drops in the prevalence and incidence of gonorrhea infection, but also accelerated the spread of doxycycline resistance, with increasing DoxyPEP use driving steeper initial declines followed by faster spread of resistance. This resulted in the total loss of DoxyPEP’s clinical efficacy within 1-2 decades in almost all scenarios explored. The magnitude by which DoxyPEP initially reduced the prevalence of infection was constrained by the extent of pre-existing doxycycline resistant strains in the population.De novoemergence of doxycycline resistance did not influence these dynamics. Additionally, the implementation of DoxyPEP had minimal impact on extending the clinically useful lifespan of ceftriaxone monotherapy.ConclusionsModel findings suggest DoxyPEP can be an effective but short-term solution for reducing the burden of gonorrhea infection, as its selection for doxycycline-resistant strains results in loss of its prophylaxis benefit. Increasing levels of DoxyPEP uptake and higher starting prevalence of doxycycline resistance resulted in faster loss of its efficacy and had little change on extending the clinical lifespan of ceftriaxone for treatment ofN. gonorrhoeaeinfections.

The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we compared the SARS-CoV-2 viral kinetics of firstvs. second infections, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a lower peak viral concentration and faster clearance time, especially in individuals who received a vaccine dose between their first and second infection. Furthermore, a person’s relative (rank-order) viral clearance time, compared to others infected with the same variant, was similar across first and second infections; that is, individuals who had a relatively fast clearance time in their first infection tended to also have a relatively fast clearance time in their second infection. These findings provide evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person’s relative ability to clear SARS-CoV-2 infection that persists across sequential infections.

BACKGROUND: Neisseria gonorrhoeae poses an urgent public health threat because of increasing antimicrobial resistance; however, much of the circulating population remains susceptible to historical treatment regimens. Point-of-care diagnostics that report susceptibility could allow for reintroduction of these regimens, but development of such diagnostics has been restricted to ciprofloxacin, for which susceptibility can be predicted from a single locus. We aimed to define genetic variants associated with susceptibility to penicillin and tetracycline. METHODS: We collected publicly available global whole-genome sequencing data (n=12 045) from clinical N gonorrhoeae isolates, with phenotypic resistance data for penicillin (n=6935), and tetracycline (n=5727). Using conditional genome-wide association studies, we defined genetic variants associated with susceptibility to penicillin and tetracycline. We excluded isolates that could not be classified as either susceptible or resistant. To validate our results, we assembled 1479 genomes from the US Centers for Disease Control and Prevention (CDC)’s Gonococcal Isolate Surveillance Project, for which urethral specimens are collected at sentinel surveillance sites across the USA. We evaluated the sensitivity and specificity of susceptibility-associated alleles using Clinical & Laboratory Standards Institute breakpoints for susceptibility and non-resistance in both the global and validation datasets. FINDINGS: In our conditional penicillin genome-wide association study, the presence of a genetic variant defined by a non-mosaic penA allele without an insertion at codon 345 was associated with penicillin susceptibility and had the highest negative effect size (β) of significant variants (p=5·0×10(–14), β –2·5). In combination with the absence of bla(TEM), this variant predicted penicillin susceptibility with high specificity (99·8%) and modest sensitivity (36·7%). For tetracycline, the wildtype allele at rpsJ codon 57, encoding valine, was associated with tetracycline susceptibility (p=5·6×10(–16), β –1·6) after conditioning on the presence of tetM. The combination of rpsJ codon 57 allele and tetM absence predicted tetracycline susceptibility with high specificity (97·2%) and sensitivity (88·7%). INTERPRETATION: As few as two genetic loci can predict susceptibility to penicillin and tetracycline in N gonorrhoeae with high specificity. Molecular point-of-care diagnostics targeting these loci have the potential to increase available treatments for gonorrhoea. FUNDING: National Institute of Allergy and Infectious Diseases, the National Science Foundation, and the Smith Family Foundation.

SARS-CoV-2 antibody titers may serve as a correlate for immunity and could inform optimal booster timing. The relationship between antibody titer and protection from infection was evaluated in 2,323 vaccinated individuals from the National Basketball Association who had antibody levels measured from 9/12/2021—12/31/2021. Cox-proportional hazards models were used to estimate risk of infection within 90-days of serologic testing by titer level (800 AU/mL) and individuals were censored on date of booster receipt. The cohort was 78.2% male, 68.1% aged ≤ 40 years, and 56.4% vaccinated (primary series) with the Pfizer-BioNTech mRNA vaccine. Among the 2,248 individuals not yet boosted at testing, those with titers 800 AU/mL. Serologic titers could inform individual COVID-19 risk and booster scheduling.

The evolution of the obligate human pathogen Neisseria gonorrhoeae has been shaped by selective pressures from diverse host niche environments as well as antibiotics. The varying prevalence of antibiotic resistance across N. gonorrhoeae lineages suggests that underlying metabolic differences may influence the likelihood of acquisition of specific resistance mutations. We hypothesized that the requirement for supplemental CO(2), present in approximately half of isolates, reflects one such example of metabolic variation. Here, using a genome-wide association study and experimental investigations, we show that CO(2)-dependence is attributable to a single substitution in a β-carbonic anhydrase, CanB. CanB(19E) is necessary and sufficient for growth in the absence of CO(2), and the hypomorphic CanB(19G) variant confers CO(2)-dependence. Furthermore, ciprofloxacin resistance is correlated with CanB(19G) in clinical isolates, and the presence of CanB(19G) increases the likelihood of acquisition of ciprofloxacin resistance. Together, our results suggest that metabolic variation has impacted the acquisition of fluoroquinolone resistance.

The CLEAR Trial recently found that decolonization reduced infections and hospitalizations in MRSA carriers in the year following hospital discharge. In this secondary analysis, we explored whether decolonization had a similar benefit in the subgroup of trial participants who harbored USA300, using two different definitions for the USA300 strain-type.

Increasing levels of antibiotic resistance in many bacterial pathogen populations is a major threat to public health. Resistance to an antibiotic provides a fitness benefit when the bacteria is exposed to this antibiotic, but resistance also often comes at a cost to the resistant pathogen relative to susceptible counterparts. We lack a good understanding of these benefits and costs of resistance for many bacterial pathogens and antibiotics, but estimating them could lead to better use of antibiotics in a way that reduces or prevents the spread of resistance. Here, we propose a new model for the joint epidemiology of susceptible and resistant variants, which includes explicit parameters for the cost and benefit of resistance. We show how Bayesian inference can be performed under this model using phylogenetic data from susceptible and resistant lineages and that by combining data from both we are able to disentangle and estimate the resistance cost and benefit parameters separately. We applied our inferential methodology to several simulated datasets to demonstrate good scalability and accuracy. We analysed a dataset ofNeisseria gonorrhoeaegenomes collected between 2000 and 2013 in the USA. We found that two unrelated lineages resistant to fluoroquinolones shared similar epidemic dynamics and resistance parameters. Fluoroquinolones were abandoned for the treatment of gonorrhoea due to increasing levels of resistance, but our results suggest that they could be used to treat a minority of around 10% of cases without causing resistance to grow again.

Shiga toxin-producingE. coli(STEC) can give rise to a range of clinical outcomes from diarrhea to the life-threatening systemic condition, hemolytic uremic syndrome (HUS). Although STEC O157:H7 is the serotype most frequently associated with HUS, a major outbreak of HUS occurred in 2011 in Germany, and was caused by a rare serotype, STEC O104:H4. Prior to 2011 and since the outbreak, STEC O104:H4 strains have only rarely been associated with human infections. From 2012 to 2020 intensified STEC surveillance was performed in Germany where subtyping of ∼8,000 clinical isolates by molecular methods including whole genome sequencing was carried out. A rare STEC serotype O181:H4 associated with HUS was identified and, like the STEC O104:H4 outbreak strain, this strain belongs to sequence type (ST) 678. Genomic and virulence comparisons revealed that the two strains are phylogenetically related and differ principally in the gene cluster encoding their respective lipopolysaccharide O-antigens but exhibit similar virulence phenotypes. In addition, five other serotypes belonging to ST678 from human clinical infection, such as OX13:H4, O127:H4, OgN-RKI9:H4, O131:H4, and O69:H4, were identified from diverse locations worldwide.ImportanceOur data suggest the high virulence ensemble of the STEC O104:H4 outbreak strain remains a global threat because genomically similar strains cause disease worldwide, but that horizontal acquisition of O-antigen gene clusters has diversified the O-antigens of strains belonging to ST678. Thus, identification of these highly pathogenic strains is masked by diverse and rare O-antigens, thereby confounding the interpretation of their potential risk.

Early in the COVID-19 pandemic, outpatient clinics throughout the US shifted toward virtual care to limit viral transmission in the office. However, as health care facilities have reopened, evidence about the risk of acquiring respiratory viral infections in medical office settings remains limited. To inform policy for reopening outpatient care settings, we analyzed rates of potential airborne disease transmission in medical office settings, focusing on influenza-like illness. We quantified whether exposed patients (that is, those seen in a medical office after a patient with influenza-like illness) were more likely to return with a similar illness in the next two weeks compared with nonexposed patients seen earlier in the day. Patients exposed to influenza-like illness in the medical office setting were more likely than nonexposed patients to revisit with a similar illness within two weeks (adjusted absolute difference: 0.7 per 1,000 patients). Similar patterns were not observed for exposure to urinary tract infection and back pain as noncontagious control conditions. These results highlight the potential threat of reopening outpatient clinics during the pandemic and the value of virtual visits for patients with suspected respiratory infections.

The etiologic agent of gonorrhea, Neisseria gonorrhoeae, has become resistant to each of the first line antibiotics used to treat it. However, most isolates in the US remain susceptible to ciprofloxacin, leading to the hypothesis that a diagnostic that accurately reports susceptibility to ciprofloxacin may allow its reintroduction into clinical use. One diagnostic approach is to identify codon 91 in gyrA, where coding for the wildtype serine is associated with ciprofloxacin susceptibility and phenylalanine with resistance. Here, we found that escape from this diagnostic method can occur through gyrA F91S reversion and expansion of pre-existing ciprofloxacin non-susceptible N. gonorrhoeae lineages with gyrA 91S. Furthermore, we found that mutations conferring ciprofloxacin resistance in gyrA 91S isolates led to cross-resistance with zoliflodacin, an antibiotic in phase 3 trial for treatment of gonorrhea. These findings define N. gonorrhoeae mutations that should be monitored via surveillance systems, particularly in populations and regions deploying gyrA 91-based diagnostics, and demonstrate how diagnostics that guide antibiotic therapy can have unintended consequences.

Background In the United States, children aged Methods We conducted an observational study with a cohort of 124 759 children aged Results Children received a mean of 6.8 (95% confidence interval [CI]: 6.7–6.9) antibiotic courses by age 5, and 91% (95% CI: 90%–92%) of children had received at least 1 antibiotic course by age 5. Most antibiotic courses (71%; 95% CI: 70%–72%) were associated with respiratory infections. Presence of a pulmonary/respiratory, otologic, and/or immunological comorbidity substantially increase a child's odds of being in the top 20% of antibiotic recipients. Children with at least 1 of these conditions received a mean of 10.5 (95% CI: 10.4–10.6) antibiotic courses by age 5. Conclusions Privately insured children in the United States receive many antibiotics early in life, largely due to respiratory infections. Antibiotic dispensing varies widely among children, with more antibiotics dispensed to children with pulmonary/respiratory, otologic, and/or immunological comorbidities.

Methicillin-resistant

This study compares the incidence of SARS-CoV-2 infection in players and staff of the National Basketball Association (NBA) who did vs those who did not receive a COVID-19 vaccine booster dose.

Protein glycosylation systems are widely recognized in bacteria, including members of the genus

Immunity is a multifaceted phenomenon. For T cell-mediated memory responses to SARS-CoV-2, it is relevant to consider their impact both on COVID-19 disease severity and on viral spread in a population. Here, we reflect on the immunological and epidemiological aspects and implications of pre-existing cross-reactive immune memory to SARS-CoV-2, which largely originates from previous exposure to circulating common cold coronaviruses. We propose four immunological scenarios for the impact of cross-reactive CD4+ memory T cells on COVID-19 severity and viral transmission. For each scenario, we discuss its implications for the dynamics of herd immunity and on projections of the global impact of SARS-CoV-2 on the human population, and assess its plausibility. In sum, we argue that key potential impacts of cross-reactive T cell memory are already incorporated into epidemiological models based on data of transmission dynamics, particularly with regard to their implications for herd immunity. The implications of immunological processes on other aspects of SARS-CoV-2 epidemiology are worthy of future study., How does the discovery of SARS-CoV-2 cross-reactive T cells in unexposed individuals change our understanding of the COVID-19 pandemic? In this Perspective, the authors provide a thought experiment to explain why the discovery of cross-reactive T cells may affect disease severity in individuals, but is unlikely to change our estimate of the herd immunity threshold.

Summary Background Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible and broader mitigation measures must be implemented. Methods To estimate the comparative efficacy of individual quarantine and active monitoring of contacts to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit a model to the incubation period distribution (mean 5·2 days) and to two estimates of the serial interval distribution: a shorter one with a mean serial interval of 4·8 days and a longer one with a mean of 7·5 days. To assess variable resource settings, we considered two feasibility settings: a high-feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and a low-feasibility setting with 50% of contacts traced, a 2-day average delay, and 50% effective isolation. Findings Model fitting by sequential Monte Carlo resulted in a mean time of infectiousness onset before symptom onset of 0·77 days (95% CI −1·98 to 0·29) for the shorter serial interval, and for the longer serial interval it resulted in a mean time of infectiousness onset after symptom onset of 0·51 days (95% CI −0·77 to 1·50). Individual quarantine in high-feasibility settings, where at least 75% of infected contacts are individually quarantined, contains an outbreak of SARS-CoV-2 with a short serial interval (4·8 days) 84% of the time. However, in settings where the outbreak continues to grow (eg, low-feasibility settings), so too will the burden of the number of contacts traced for active monitoring or quarantine, particularly uninfected contacts (who never develop symptoms). When resources are prioritised for scalable interventions such as physical distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. Even under the shorter serial interval, if physical distancing reduces the reproductive number to 1·25, active monitoring of 50% of contacts can result in overall outbreak control (ie, effective reproductive number Interpretation Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission to make data-driven policy decisions regarding the cost–benefit comparisons of individual quarantine versus active monitoring of contacts. To the extent that these interventions can be implemented, they can help mitigate the spread of SARS-CoV-2. Funding National Institute of General Medical Sciences, National Institutes of Health.

Background Genomic epidemiology studies of gonorrhea in the United States have primarily focused on national surveillance for antibiotic resistance, and patterns of local transmission between demographic groups of resistant and susceptible strains are unknown. Methods We analyzed a convenience sample of genome sequences, antibiotic susceptibility, and patient data from 897 gonococcal isolates cultured at the New York City (NYC) Public Health Laboratory from NYC Department of Health and Mental Hygiene (DOHMH) Sexual Health Clinic (SHC) patients, primarily in 2012–2013. We reconstructed the gonococcal phylogeny, defined transmission clusters using a 10 nonrecombinant single nucleotide polymorphism threshold, tested for clustering of demographic groups, and placed NYC isolates in a global phylogenetic context. Results The NYC gonococcal phylogeny reflected global diversity with isolates from 22/23 of the prevalent global lineages (96%). Isolates clustered on the phylogeny by patient sexual behavior (P < .001) and race/ethnicity (P < .001). Minimum inhibitory concentrations were higher across antibiotics in isolates from men who have sex with men compared to heterosexuals (P < .001) and white heterosexuals compared to black heterosexuals (P < .01). In our dataset, all large transmission clusters (≥10 samples) of N. gonorrhoeae were susceptible to ciprofloxacin, ceftriaxone, and azithromycin, and comprised isolates from patients across demographic groups. Conclusions All large transmission clusters were susceptible to gonorrhea therapies, suggesting that resistance to empiric therapy was not a main driver of spread, even as risk for resistance varied across demographic groups. Further study of local transmission networks is needed to identify drivers of transmission., We used Neisseria gonorrhoeae genomes together with clinical and demographic data to study transmission in New York City. Our results indicate transmission across demographic groups and suggest that antibiotic resistance is not the main driver of gonorrhea spread.

The sexually transmitted infection gonorrhea, caused by the Gram-negative bacterium Neisseria gonorrhoeae, can cause urethritis, cervicitis, and systemic disease, among other manifestations. N. gonorrhoeae has rapidly rising incidence along with increasing levels of antibiotic resistance to a broad range of drugs including first-line treatments. The rise in resistance has led to fears of untreatable gonorrhea causing substantial disease globally. In this review, we will describe multiple approaches being undertaken to slow and control this spread of resistance. First, a number of old drugs have been repurposed and new drugs are being developed with activity against Neisseria gonorrhoeae. Second, vaccine development, long an important goal, is advancing. Third, new diagnostics promise rapid detection of antibiotic resistance and a shift from empiric to tailored treatment. The deployment of these new tools for addressing the challenge of antibiotic resistance will require careful consideration to provide optimal care for all patients while extending the lifespan of treatment regimens.

Background The mechanisms driving the recent decline in outpatient antibiotic prescribing are unknown. We estimated the extent to which reductions in the number of antibiotic prescriptions filled per outpatient visit (stewardship) and reductions in the monthly rate of outpatient visits (observed disease) for infectious disease conditions each contributed to the decline in outpatient antibiotic prescribing in Massachusetts between 2011 and 2015. Methods Outpatient medical and pharmacy claims from the Massachusetts All-Payer Claims Database were used to estimate rates of antibiotic prescribing and outpatient visits for 20 medical conditions and their contributions to the overall decline in antibiotic prescribing. Trends were compared with those in the National Ambulatory Medical Care Survey (NAMCS). Results Between 2011 and 2015, the January and July antibiotic-prescribing rates per 1000 individuals in Massachusetts declined by 18.9% and 13.6%, respectively. The monthly rate of outpatient visits per 1000 individuals in Massachusetts declined (P Conclusions The decline in antibiotic prescribing in Massachusetts was driven both by a decline in observed disease and improved antibiotic stewardship, in agreement with national trends. A focus on infectious disease prevention should be considered alongside antibiotic stewardship as a means to reduce antibiotic prescribing.