Long-term safety and survival with gefitinib in select patients with advanced non-small cell lung cancer: Results from the US IRESSA Clinical Access Program (ICAP).

BACKGROUND: This is the first report of long-term (>10 years) safety, tolerability, and survival data on patients with non-small cell lung cancer (NSCLC) who received treatment with gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. METHODS: Patients with advanced NSCLC (N = 191) who entered the IRESSA Clinical Access Program (ICAP) (June 2011 to January 2013) and had previously obtained a clinical benefit from gefitinib therapy (including patients who had received gefitinib since 2001) were analyzed for adverse events (AEs). A subset of patients (n = 79) underwent retrospective chart review to capture demographic, safety, and survival data. RESULTS: Seventy-five of 191 patients (39%) remained on long-term gefitinib therapy as of September 2016. Overall, serious AEs (SAEs) were reported in 64 patients (34%), the majority of which were attributed to underlying disease or comorbidities; only 3 patients (1.6%) had SAEs that were considered as possibly gefitinib-related. In the retrospective chart review cohort, 70% of patients were women; 58% were former smokers, and 30% were never-smokers; 56% were diagnosed with adenocarcinoma, and 13% were diagnosed with squamous carcinoma. Although EGFR mutational status was tested in only 17 patients (22%), it was assumed that most tumors were EGFR-mutation-positive. The median duration of gefitinib therapy was 11.1 years (7.8 years before and 3.5 years during ICAP), with 10-year and 15-year survival rates of 86% and 59%, respectively, from the initiation of therapy. CONCLUSIONS: A subset of long-term NSCLC survivors who were receiving gefitinib had an excellent long-term safety profile. Although it is assumed that most of these patients' tumors harbor EGFR mutations, molecular studies of available tumor specimens are planned to uncover the features that predict long-term survival. Cancer 2018;124:2407-14. © 2018 American Cancer Society.

Rationale and design of ASPIRE-ICU: a prospective cohort study on the incidence and predictors of Staphylococcus aureus and Pseudomonas aeruginosa pneumonia in the ICU.

BACKGROUND: The epidemiology of ICU pneumonia caused by Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) is not fully described, but is urgently needed to support the development of effective interventions. The objective of this study is to estimate the incidence of S. aureus and P. aeruginosa ICU pneumonia and to assess its association with patient-related and contextual risk factors. METHODS: ASPIRE-ICU is a prospective, observational, multi-center cohort study nested within routine surveillance among ICU patients in Europe describing the occurrence of S. aureus and P. aeruginosa ICU pneumonia. Two thousand (2000) study cohort subjects will be enrolled (50% S. aureus colonized) in which specimens and data will be collected. Study cohort subjects will be enrolled from a larger surveillance population, in which basic surveillance data is captured. The primary outcomes are the incidence of S. aureus ICU acquired pneumonia and the incidence of P. aeruginosa ICU acquired pneumonia through ICU stay. The analysis will include advanced survival techniques (competing risks and multistate models) for each event separately as well as for the sub-distribution of ICU pneumonia to determine independent association of outcomes with risk factors.. A risk prediction model will be developed to quantify the risk for acquiring S. aureus or P. aeruginosa ICU pneumonia during ICU stay by using a composite score of independent risk factors. DISCUSSION: The diagnosis of pathogen-specific ICU pneumonia is difficult, however, the criteria used in this study are objective and comparable to those in the literature. TRIAL REGISTRATION: This study is registered on clinicaltrials.gov under identifier NCT02413242 .

Individual-Level and Partner-Level Predictors of Newly Diagnosed HIV Infection Among Black and White Men Who Have Sex with Men in Baltimore, MD.

Black MSM continue to be the group most disproportionately impacted by HIV in the United States. This study assesses the relationship between partner-level and respondent-level characteristics and newly diagnosed HIV infection among a sample of MSM. Ego-centric data were gathered using venue-based time-space sampling on 335 men who reported on a total of 831 male anal sex partners. In multivariate analyses, age of partner, HIV status of partner, and respondent having had an STD in the past twelve months were associated with a newly diagnosed HIV infection among black MSM. Efforts for black MSM are needed that aim to increase HIV and STD testing, foster open communication between partners about HIV status, and address social determinants of health.

Receipt of palivizumab before birth hospitalization discharge among preterm infants in the United States.

OBJECTIVE: This study aims to determine predischarge palivizumab receipt prevalence among infants ≤ 36 weeks' gestational age. STUDY DESIGN: This retrospective cohort study used hospital discharge records from the Premier Perspective database (Premier Inc., Charlotte, NC) of infants ≤ 36 weeks' gestational age who were discharged home after birth hospitalization during the November-March respiratory syncytial virus (RSV) seasons from 2006 to 2011. Descriptive statistics were performed and logistic regression was employed to identify differences in categorical variables. RESULTS: Among infants ≤ 36 weeks' gestational age discharged home during the RSV seasons, 21.4 to 27.0% had a record of palivizumab receipt before discharge. Among infants ≤ 30 weeks' gestational age, palivizumab receipt was 82.3 to 88.8%. Receipt varied considerably at the hospital level, from 0 to 100%. CONCLUSION: This study improves our understanding of characteristics associated with predischarge palivizumab administration. The identified gaps in recommended care can help inform future implementation of palivizumab and other interventions to help improve the health of high-risk preterm infants in the United States.

Medically attended respiratory syncytial virus infections in adults aged ≥ 50 years: clinical characteristics and outcomes.

BACKGROUND: Few studies have examined respiratory syncytial virus (RSV) infections in adults. We assessed the characteristics and outcomes of RSV relative to other viral infections. METHODS: Patients ≥ 50 years old with acute respiratory illness were recruited for studies of influenza vaccine effectiveness from 2004 through 2010. Nasopharyngeal swabs from enrollees were analyzed for the presence of RSV and other respiratory viruses by multiplex reverse transcription polymerase chain reaction. Clinical data were obtained from interview and medical records. RESULTS: A total of 2225 samples were tested across all seasons. The mean age was 64.2 (SD, 10.7) years; the mean interval from illness onset to sample collection was 4 (SD, 2.2) days. One or more viruses were detected in 1202 (54%) participants. In a multivariable logistic regression model, RSV was associated with ages 65-79 years (vs 50-64 years), symptoms of cough, nasal congestion and wheezing, and longer interval from illness onset to clinical encounter. RSV was not associated with the presence of chronic obstructive pulmonary disease or congestive heart failure in univariate analyses. Hospital admission within 30 days after illness onset was less common among patients with RSV compared to those with influenza (unadjusted odds ratio = 0.54 [95% confidence interval, .29-1.01], P = .06). CONCLUSIONS: RSV is a common cause of acute respiratory illness in adults aged ≥ 50 years; the risk of infection increases with age. Delays in healthcare seeking and reduced risk of hospital admission in patients with RSV suggest a milder course of illness relative to influenza.

Age-specific prevalence of Epstein-Barr virus infection among individuals aged 6-19 years in the United States and factors affecting its acquisition.

BACKGROUND: Data on the age-specific prevalence of Epstein-Barr virus (EBV) infection are relevant for determining when to administer a prophylactic vaccine. Comparison of demographic groups could identify factors associated with its acquisition. METHODS: The National Health and Nutrition Examination Surveys (NHANES) examine a representative sample of the US population. Serum specimens from NHANES participants 6-19 years old were tested for EBV antibody by enzyme immunoassay (EIA). A random portion was also tested by indirect immunofluorescence (IFA). Prevalence estimates and risk-factor comparisons used demographic data and sampling weights in logistic regression models. RESULTS: Serum specimens collected between 2003 and 2010 from 9338 individuals participating in NHANES were tested. The concordance between EIA and IFA findings was 96.7%. The overall age-adjusted EBV antibody prevalence declined from 72% in 2003-2004 to 65% in 2009-2010 (P = .027). The prevalence in 2009-2010 by age group was as follows: 6-8 years, 50%; 9-11 years, 55%; 12-14 years, 59%; 15-17 years, 69%; and 18-19 years, 89%. Within each race/ethnicity group, younger age, health insurance coverage, higher household income, and education level were significantly associated with a lower prevalence of EBV antibody. CONCLUSIONS: The EBV antibody prevalence declined in US individuals aged 6-19 years from 2003-2004 to 2009-2010, mainly because of the decrease among non-Hispanic white participants. The declining antibody prevalence over time and the consistently high observed prevalence among participants aged 12-19 years support broad use of EBV vaccine before 12 years of age.

Beyond surveillance: a role for respondent-driven sampling in implementation science.

We are now in the fourth decade of the human immunodeficiency virus (HIV) pandemic. Several novel prevention tools have been identified, and prevalence and incidence have declined in many settings. A remaining challenge is the delivery of preventive interventions to hard-to-reach populations, including men who have sex with men and injection drug users. Leaders in the field of HIV have called for a new focus on implementation science, which requires a shift in thinking from individual randomized controlled trials to cluster-randomized trials. Multiple challenges need to be addressed in the conduct of cluster-randomized trials, including: 1) generalizability of the study population to the target population, 2) potential contamination through overlap/exchange of members of control and intervention clusters, and 3) evaluation of effectiveness at multiple levels of influence. To address these key challenges, we propose a novel application of respondent-driven sampling-a chain-referral strategy commonly used for surveillance-in the recruitment of participants for the evaluation of a cluster-randomized trial of a community intervention. We illustrate this application with an empirical example of a cluster-randomized trial that is currently under way to assess the effectiveness of men's wellness centers in improving utilization of HIV counseling and testing among men who have sex with men in India.

Postoperative Staphylococcus aureus Infections in Patients With and Without Preoperative Colonization.

Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies. Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors. Design, Setting, and Participants: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio. Exposure: Preoperative S aureus colonization. Main Outcomes and Measures: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models. Results: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs. Conclusions and Relevance: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.

Partner characteristics and undiagnosed HIV seropositivity among men who have sex with men only (MSMO) and men who have sex with men and women (MSMW) in Baltimore.

This study examined the relationship between HIV risk behaviors, partner characteristics, and undiagnosed seropositivity among men who have sex with men and women (MSMW) and men who have sex with men only (MSMO). BESURE-MSM2 is a venue-based cross-sectional HIV surveillance study conducted among MSM in 2008. Stratified log-binomial regression was used to assess adjusted prevalence ratios of undiagnosed seropositivity among 103 MSMW and 296 MSMO (N = 399). Among MSMO, race/ethnicity, age, having had a sexually transmitted infection, concurrency, and having a black/African American male partner were associated with undiagnosed seropositivity. Among MSMW, having five or more male partners, having a main male partner, and having a main female partner were associated with undiagnosed seropositivity. Our findings underscore the importance of partner characteristics in understanding HIV transmission. HIV programs for men with both male and female partners are needed to address the unique partnership dynamics of MSMW.

The geography of heterosexual partnerships in Baltimore city adults.

BACKGROUND: Human immunodeficiency virus/sexually transmitted disease (HIV/STD) risk is determined in part by sexual network characteristics, which include spatial parameters. Geography and proximity of partner selection are important factors, which may explain neighborhood-level differences in HIV/STD morbidity. To study the effects of neighborhood factors on HIV/STD transmission in high-density urban areas, the geography of partner selection must be understood. METHODS: The Baltimore site of the National HIV Behavioral Surveillance system surveyed adults reporting one or more heterosexual partnerships. Spatial assortativity was defined as both partners residing in the same or adjacent census tracts and based on participant report. HIV core areas were defined as the census tracts in the top quartile for standardized HIV/AIDS case rates. RESULTS: Participants (n = 307) provided data on 776 recent sexual partnerships, and geographic information were obtained for 510 partnerships (66%). Almost half (47%) reported choosing spatially assortative partners. Participants who lived in high HIV-prevalence areas were more likely to choose spatially assortative partners than residents of lower prevalence areas after adjusting for partnership type, gender, and number of partners. Although this population exhibited assortative mixing in all types of partnerships, racial and age assortativities were not associated with choosing spatially assortative partners. CONCLUSIONS: Over 15 years ago, STD clinic patients in Baltimore were found to seek partners within close proximity. We confirm these results in a non-STD clinic population, indicating a continuing need for neighborhood approaches to intervention programs in urban areas.

Factors associated with increased vaccination in 2009 H1N1 school-located influenza vaccination programs.

In the United States, school-located influenza vaccination (SLIV) programs have increased significantly in recent years. In June 2010, the Office of Inspector General issued a report regarding 38 elementary school H1N1 SLIV programs conducted in 6 localities in November/December 2009. By locality, there was a mean of 14 to 46 first doses of vaccine administered per 100 students. The locality that conducted programs in early November had a higher uptake rate than localities with later programs (46 vs 21 per 100 students; p < 0.01). Among localities with programs in mid- to late-November, the locality with programs after school hours had a lower uptake rate than the two localities with programs during school hours (16 vs. 28, p = 0.05 and 16 vs. 30, p < 0.01, respectively). These data suggest that future SLIV programs may achieve higher uptake rates if conducted during school hours with advance parental consent and when parental demand is highest.

Persistent Cardiometabolic Health Gaps: Can Therapeutic Care Gaps Be Precisely Identified from Electronic Health Records.

The objective of this study was to determine the strengths and limitations of using structured electronic health records (EHR) to identify and manage cardiometabolic (CM) health gaps. We used medication adherence measures derived from dispense data to attribute related therapeutic care gaps (i.e., no action to close health gaps) to patient- (i.e., failure to retrieve medication or low adherence) or clinician-related (i.e., failure to initiate/titrate medication) behavior. We illustrated how such data can be used to manage health and care gaps for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and HbA1c for 240,582 Sutter Health primary care patients. Prevalence of health gaps was 44% for patients with hypertension, 33% with hyperlipidemia, and 57% with diabetes. Failure to retrieve medication was common; this patient-related care gap was highly associated with health gaps (odds ratios (OR): 1.23-1.76). Clinician-related therapeutic care gaps were common (16% for hypertension, and 40% and 27% for hyperlipidemia and diabetes, respectively), and strongly related to health gaps for hyperlipidemia (OR = 5.8; 95% CI: 5.6-6.0) and diabetes (OR = 5.7; 95% CI: 5.4-6.0). Additionally, a substantial minority of care gaps (9% to 21%) were uncertain, meaning we lacked evidence to attribute the gap to either patients or clinicians, hindering efforts to close the gaps.

Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection.

It is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.

The expanding epidemics of HIV type 1 among men who have sex with men in low- and middle-income countries: diversity and consistency.

Men who have sex with men (MSM) have borne a disproportionate burden of human immunodeficiency virus (HIV) infection and remain a markedly underresourced population globally. To better describe HIV epidemics among MSM in low- and middle-income countries, the authors conducted a systematic review of published and unpublished literature available after January 1, 2000 (2000-2009). A total of 133 HIV prevalence studies from 50 countries met the search criteria. Data were used to develop an algorithmic approach to categorize these epidemics. The authors found that the HIV epidemic in low- and middle-income countries may be described using the following 4 scenarios: 1) settings where MSM are the predominant contributor to HIV cases; 2) settings where HIV transmission among MSM occurs in the context of epidemics driven by injection drug users; 3) settings where HIV transmission among MSM occurs in the context of well-established HIV transmission among heterosexuals; and 4) settings where both sexual and parenteral modes contribute significantly to HIV transmission. The authors focused on Peru, Ukraine, Kenya, and Thailand to describe the diversity across and similarities between proposed epidemic scenarios. This scenario-based categorization of HIV epidemics among MSM may assist public health agencies and civil societies to develop and implement better-targeted HIV prevention programs and interventions.

Prevalence of HIV infection and prior HIV testing among young men who have sex with men. The Baltimore young men's survey.

Data are presented from the Baltimore Young Men's Survey, a cross-sectional, venue-based sample survey of risks associated with HIV and report of a prior HIV test, conducted between 1996 and 2000, and enrolling 843 young men who have sex with men (MSM) aged 15-29 years. HIV prevalence was 12.1% overall and racial disparities in HIV prevalence were pronounced (range, 2.9% among non-Hispanic whites to 27.1% among non-Hispanic blacks). Risks independently associated with being HIV-positive were: being between 26 and 29 years of age, being non-Hispanic black or of other/mixed race, having had 20 or more lifetime male sex partners, having been diagnosed with a sexually transmitted disease (STD), and not being currently enrolled in school. The majority of participants (78.9%) reported a prior HIV test. In multivariate analysis, being older, having had five or more lifetime male sex partners, having had anal intercourse with males, reporting an STD diagnosis, and reporting recent unprotected anal sex were associated with report of a prior HIV test. Prevention efforts must address high HIV prevalence among young non-Hispanic black MSM and must make testing and effective counseling for young MSM readily available.

The emerging HIV epidemic among men who have sex with men in Tamil Nadu, India: geographic diffusion and bisexual concurrency.

In India, men who have sex with men (MSM) remain hidden because anal intercourse was criminalized and marriage socially required. We characterize HIV/STI prevalence among MSM in Tamil Nadu. Eligible participants were recruited using respondent-driven sampling in eight cities (n = 721). Median age was 28, 34% were married and 40% self-identified as homosexual. Median number of male partners in the prior year was 15; 45% reported any unprotected anal intercourse (UAI). HIV, herpes simplex virus-2 (HSV-2), chronic hepatitis B virus (HBV) and syphilis prevalence were 9, 26, 2 and 8%, respectively; among married men, all were higher: 14, 32, 3 and 11% (p < 0.01 for HIV and HSV-2). Less education, HSV-2, more male partners, UAI and not having a main male partner were associated with HIV prevalence. The high STI and UAI prevalence may lead to a burgeoning HIV epidemic among MSM, reinforcing the need for focused preventive measures incorporating complex circumstances.

Association of Staphylococcus aureus Colonization and Pneumonia in the Intensive Care Unit.

Importance: Carriage of Staphylococcus aureus is associated with S aureus infection. However, associations between S aureus carriage and the development of S aureus intensive care unit (ICU) pneumonia (SAIP) have not been quantified accurately, and interpretation of available data is hampered because of variations in definitions. Objective: To quantify associations of patient-related and contextual factors, including S aureus colonization status, with the occurrence of SAIP. Design, Setting, and Participants: This cohort study was conducted in ICUs of 30 hospitals in 11 European countries, geographically spread across 4 regions. Among patients with an anticipated length of stay 48 hours or longer who were undergoing mechanical ventilation at ICU admission, S aureus colonization was ascertained in the nose and lower respiratory tract. From this group, S aureus-colonized and noncolonized patients were enrolled into the study cohort in a 1:1 ratio. Data analysis was performed from May to November 2019. Main Outcomes and Measures: SAIP was defined as any pneumonia during the ICU stay developing 48 hours or more after ICU admission with S aureus isolated from lower respiratory tract specimens or blood samples. The incidence of SAIP was derived in the study cohort and estimated on the weighted incidence calculation for the originating overarching population, while taking competing events into account. Weighted risk factor analysis was performed using Cox multivariable regression. Results: The study cohort consisted of 1933 patients (mean [SD] age, 62.0 [16.0] years); 1252 patients (64.8%) were men, and 950 patients (49.1%) were S aureus carriers at ICU admission. In all, 304 patients (15.7%) developed ICU-acquired pneumonia, of whom 131 patients (6.8%) had SAIP. Weighted SAIP incidences were 11.7 events per 1000 patient-days in the ICU for S aureus-colonized patients and 2.9 events per 1000 patient-days in the ICU for noncolonized patients (overall incidence, 4.9 events per 1000 patient-days in the ICU). The only factor independently associated with SAIP was S aureus colonization status at ICU admission (cause-specific hazard ratio, 3.6; 95% CI, 2.2-6.0; P < .001). There were marked regional differences in SAIP incidence and cause-specific hazard ratios for colonization status. Conclusions and Relevance: SAIP incidence was 4.9 events per 1000 ICU patient-days for patients undergoing mechanical ventilation at ICU admission (or shortly thereafter). The daily risk of SAIP was 3.6 times higher in patients colonized with S aureus at ICU admission compared with noncolonized patients.

Changes in sexual risk behavior as young men transition to adulthood.

CONTEXT: Understanding how young men's sexual risk behaviors change during the transition from adolescence to early adulthood is important for the design and evaluation of effective strategies to reduce the transmission of HIV and other STDs. METHODS: Data from three waves of the National Survey of Adolescent Males (1988, 1991 and 1995) were used to categorize 1,880 respondents into clusters according to sexual risk behaviors. Univariate and bivariate analyses were conducted to assess associations between clusters and rates of self-reported STD diagnoses and positive chlamydia tests. RESULTS: Two dimensions of sexual risk-taking defined the clusters: partner characteristics and condom use. More than 50% of men remained in low-risk groups over time. In the first two waves, 24-32% of men reported engaging in high-risk behaviors (risky partners, condom nonuse); these behaviors were associated with elevated levels of STD outcomes. Nearly 40% of men who entered a high-risk group in the first two waves transitioned to a lower risk group by the third wave. Nine percent of men either engaged in increasingly risky behaviors or maintained membership in high-risk groups; elevated STD rates characterized both trajectories. Low condom use combined with having multiple partners during adolescence was associated with elevated STD rates in the year preceding the third wave; high condom use coupled with having risky partners was not. CONCLUSIONS: The prominence of low-risk behaviors over time suggests that most young men avoid sexual risk-taking. Effective strategies to reduce HIV and STD risk in young men must simultaneously address multiple dimensions of sexual behavior.

Surveillance for control of antimicrobial resistance.

Antimicrobial resistance poses a growing threat to public health and the provision of health care. Its surveillance should provide up-to-date and relevant information to monitor the appropriateness of therapy guidelines, antibiotic formulary, antibiotic stewardship programmes, public health interventions, infection control policies, and antimicrobial development. In Europe, although the European Antimicrobial Resistance Surveillance Network provides annual reports on monitored resistant bacteria, national surveillance efforts are still fragmented and heterogeneous, and have substantial structural problems and issues with laboratory data. Most incidence and prevalence data cannot be linked with relevant epidemiological, clinical, or outcome data. Genetic typing, to establish whether trends of antimicrobial resistance are caused by spread of resistant strains or by transfer of resistance determinants among different strains and species, is not routinely done. Furthermore, laboratory-based surveillance using only clinical samples is not likely to be useful as an early warning system for emerging pathogens and resistance mechanisms. Insufficient coordination of surveillance systems of human antimicrobial resistance with animal surveillance systems is even more concerning. Because results from food surveillance are considered commercially sensitive, they are rarely released publicly by regulators. Inaccurate or incomplete surveillance data delay a translational approach to the threat of antimicrobial resistance and inhibit the identification of relevant target microorganisms and populations for research and the revitalisation of dormant drug-discovery programmes. High-quality, comprehensive, and real-time surveillance data are essential to reduce the burden of antimicrobial resistance. Improvement of national antimicrobial resistance surveillance systems and better alignment between human and veterinary surveillance systems in Europe must become a scientific and political priority, coordinated with international stakeholders within a global approach to reduce the burden of antimicrobial resistance.

Risk prediction for Staphylococcus aureus surgical site infection following cardiothoracic surgery; A secondary analysis of the V710-P003 trial.

BACKGROUND: Identifying patients undergoing cardiothoracic surgery at high risk of Staphylococcus aureus surgical site infection (SSI) is a prerequisite for implementing effective preventive interventions. The objective of this study was to develop a risk prediction model for S. aureus SSI or bacteremia after cardiothoracic surgery based on pre-operative variables. MATERIALS/METHODS: Data from the Merck Phase IIb/III S. aureus vaccine (V710-P003) clinical trial were analyzed. In this randomized placebo-controlled trial, the effect of preoperative vaccination against S. aureus was investigated in patients undergoing cardiothoracic surgery. The primary outcome was deep/superficial S. aureus SSI or S. aureus bacteremia through day 90 after surgery. Performance, calibration, and discrimination of the final model were assessed. RESULTS: Overall 164 out of 7,647 included patients (2.1%) developed S. aureus infection (149 SSI, 15 bacteremia, 28 both). Independent risk factors for developing the primary outcome were pre-operative colonization with S. aureus (OR 3.08, 95% confidence interval [CI] 2.23-4.22), diabetes mellitus (OR 1.87, 95% CI 1.34-2.60), BMI (OR 1.02 per kg/m2, 95% CI 0.99-1.05), and CABG (OR 2.67, 95% CI 1.91-3.78). Although vaccination had a significant (albeit modest) protective effect, it was omitted from the model because its addition did not significantly change the coefficients of the final model and V710-vaccine development has been discontinued due to insufficient efficacy. The final prediction model had moderate discriminative accuracy (AUC-value, 0.72). CONCLUSION: Pre-operative S. aureus colonization status, diabetes mellitus, BMI, and type of surgical procedure moderately predicted the risk of S. aureus SSI and/or bacteremia among patients undergoing cardiothoracic surgery.