Role of Raltegravir in HIV-1 Management

OBJECTIVE: To review the literature concerning the role of raltegravir in the treatment of HIV-1 in antiretroviral (ARV)-experienced and ARV-naïve patients. DATA SOURCES: A PubMed search was conducted for published data through March 2012 using the search terms raltegravir, MK-0518, and integrase strand transfer inhibitor. An additional search of International Pharmaceutical Abstracts for unpublished data, including data from the Infectious Diseases Society of America, the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society, and the Interscience Conference on Antimicrobial Agents and Chemotherapy, was conducted using similar search terms. STUDY SELECTION AND DATA EXTRACTION: In vitro and in vivo Phase 2, Phase 3, and postmarketing studies available in English, evaluating antiretroviral regimens that contain raltegravir for the treatment of HIV-1 infection in both ARV-naïve and ARV-experienced patients, were evaluated. Studies assessing raltegravir pharmacokinetics and pharmacodynamics were included for review. DATA SYNTHESIS: The nucleoside-based regimen of raltegravir with tenofovir/emtricitabine provides an effective first-line treatment option. However, nucleoside-sparing regimens appear unfavorable in ARV-naïve subjects and should be reserved for patients with limited treatment options. Raltegravir used with optimized background therapy provides an alternative regimen for ARV-experienced patients. This review describes the available in vitro and in vivo data on raltegravir potency, defined as the ability to achieve undetectable viral load, and safety profile, as well as comparison to standard HIV-1 therapies. CONCLUSIONS: Raltegravir has demonstrated potent antiretroviral activity against HIV-1 in both ARV-naïve and ARV-experienced subjects, with the benefits of a favorable adverse effect profile and minimal drug interactions. Raltegravir must be dosed twice daily, as once daily raltegravir displays decreased virologic efficacy compared to twice daily dosing. However, the ongoing development of new integrase strand transfer inhibitors may provide potent once daily regimens

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Morbidity and Mortality of Serratia marcescens Bacteremia During the Substance Use Epidemic

BACKGROUND: Serratia marcescens is an Enterobacterales species present throughout the environment causing a range of infections. Historically, Serratia marcescens has been associated with persons who inject drugs (PWID) but literature is scarce. OBJECTIVES: To compare treatment characteristics and clinical outcomes between PWID and Non-PWID with Serratia marcescens bacteremia. METHODS: This was a retrospective cohort study of patients hospitalized with Serratia marcescens bacteremia from January 1, 2013 through December 31, 2019 at a tertiary medical center. Patients were included if they were 18 years and older and had at least one positive blood culture for Serratia marcescens. RESULTS: Of the 67 patients who met inclusion, 14 were identified as PWID (21%) and 53 were non-PWID (79%). PWID were younger (median age in years, PWID = 32; non-PWID = 67) and less likely to have renal disease (PWID 7%; non-PWID 34%). PWID had a higher incidence of infective endocarditis (IE) (PWID 48%; non-PWID 0%) and were more likely to receive combination antimicrobial therapy (PWID 29%; non-PWID 2%). All-cause mortality at 12 months was comparable between groups (PWID 21%; Non-PWID 21%). CONCLUSION: We demonstrate long term outcomes of PWID are comparable to non-PWID despite PWID being a younger cohort with less comorbidities. Clinicians should have high suspicion of IE in PWID with Serratia marcescens bacteremia

Infective Endocarditis During the Infectious Diseases and Substance Use Disorder Syndemic: A Six-Year Case Series

Treatment for infective endocarditis (IE) has not been extensively studied in the setting of rising injection drug use. There were 12 cases of IE at the Maine Medical Center between 2013 and 2018. The patient characteristics, treatment regimens, and outcomes were retrospectively analyzed

Uncomplicated Streptococcal Bacteremia: The Era of Stepdown to Oral Antibiotic Therapy?

BACKGROUND: The purpose of this study was to compare the clinical outcomes of adults with uncomplicated streptococcal bacteremia who received either oral stepdown (PO) or continued intravenous (IV) therapy. METHODS: This was a retrospective, single-center, cohort study, including adults admitted with Streptococcal bloodstream infection between January 1, 2013, and December 31, 2020. Only patients with uncomplicated Streptococcal bloodstream infections were included. Patients transitioned to oral therapy within 5 days from bacteremia onset were compared to patients receiving continued IV therapy. The primary outcome was clinical failure, defined by either 90-day hospital readmission or mortality. Secondary outcomes included hospital length of stay (LOS) and antibiotic-related adverse events (AAEs). RESULTS: Of the 264 patients included, 42% were transitioned to oral step-down therapy. Group B Streptococcus (22.7%) was the most common isolate. The most common sources of infection were skin and soft tissue (35%) and pulmonary (25%). Intensive care unit stay was more common in the continued IV therapy group (22.2%) compared to the step-down PO group (5.4%). The frequency of clinical failure was similar in continued IV therapy and step-down PO (24.2% vs 18.0%, p= 0.23). The IV group had longer LOS (median, [IQR]) compared to the PO group (7 [5-13.5] vs 4 [3-5] days, p\u3c 0.001). AAEs were similar between the two groups (1.3% vs 1.8%, p=0.74). CONCLUSION: Stepdown to oral therapy may be appropriate for the treatment of uncomplicated Streptococcal bacteremia with consideration of factors such as patient comorbidities, type of infection, source control and clinical progress

Limited clinical utility of follow-up blood cultures in patients with streptococcal bacteremia: an opportunity for blood culture stewardship

Background: The value of positive follow-up blood cultures (FUBCs) in streptococcal bacteremia has not been well defined. Therefore, we explored the frequency of and risk factors for positive FUBC in a retrospective cohort of patients with streptococcal bacteremia. Methods: Adults ≥18 years of age, admitted with at least 1 positive blood culture for Results: In our single-center cohort, we identified 590 patients with streptococcal bacteremia, and 314 patients met inclusion criteria. Ten patients had FUBC with Conclusions: Follow-up blood cultures among patients with streptococcal BSI are rarely positive. Clinicians could consider limiting follow-up blood cultures in patients at low risk for deep-seated streptococcal infections, persistent bacteremia, or endovascular infection

Mortality, morbidity, and cardiac surgery in Injection Drug Use (IDU)-associated versus non-IDU infective endocarditis: The need to expand substance use disorder treatment and harm reduction services.

BACKGROUND: The addiction crisis is widespread, and unsafe injection practices among people who inject drugs (PWID) can lead to infective endocarditis. METHODS: A retrospective analysis of adult patients with definite or possible infective endocarditis admitted to a tertiary care center in Portland, Maine was performed over three-year period. Our primary objective was to examine differences in demographics, health characteristics, and health service utilization between injection drug use (IDU)-associated infective endocarditis and non-IDU infective endocarditis. The association between IDU and mortality, morbidity (defined as emergency department visits within 3 months of discharge), and cardiac surgery was examined. Bivariate and multivariate analyses were performed. A subgroup descriptive analysis of PWID was also performed to better examine substance use disorder (SUD) characteristics, treatment with medication for opioid use disorder (MOUD) and health service utilization. RESULTS: One-hundred and seven patients were included in the study, of which 39.2% (n = 42) had IDU-associated infective endocarditis. PWID were more likely to be homeless, uninsured, and lack a primary care provider. PWID were notably younger and had less documented comorbidities, however had similar in-hospital mortality rates (10% vs. 14%, p = 0.30), ED visits (50% vs. 54%, p = 0.70) and cardiac surgery (33% vs. 26%, p = 0.42) compared to those with non-IDU infective endocarditis. Ninety-day mortality was less among PWID (19.0% vs. 36.9%, p = 0.05). IDU was not associated with morbidity (adjusted odds ratio (AOR) 0.73, 95% CI 0.18-3.36), 90-day mortality (AOR 0.72, 95% CI 0.17-3.01), or cardiac surgery (AOR 0.15, 95% CI 0.03-0.69). Ninety-day mortality among PWID who received MOUD was lower (3% vs 15%, p = 0.45), as were ED visits (10% vs. 41%, p = 0.42) compared to those who did not receive MOUD. CONCLUSIONS: Our results highlight existing differences in health characteristics and social determinants of health in people with IDU-associated versus non-IDU infective endocarditis. PWID had less comorbidities and were significantly younger than those with non-IDU infective endocarditis and yet still had similar rates of cardiac surgery, ED visits, and in-hospital mortality. These findings emphasize the need to deliver comprehensive health services, particularly MOUD and other harm reduction services, to this marginalized population

Mortality, morbidity, and cardiac surgery in Injection Drug Use (IDU)-associated versus non-IDU infective endocarditis: The need to expand substance use disorder treatment and harm reduction services.

BACKGROUND: The addiction crisis is widespread, and unsafe injection practices among people who inject drugs (PWID) can lead to infective endocarditis. METHODS: A retrospective analysis of adult patients with definite or possible infective endocarditis admitted to a tertiary care center in Portland, Maine was performed over three-year period. Our primary objective was to examine differences in demographics, health characteristics, and health service utilization between injection drug use (IDU)-associated infective endocarditis and non-IDU infective endocarditis. The association between IDU and mortality, morbidity (defined as emergency department visits within 3 months of discharge), and cardiac surgery was examined. Bivariate and multivariate analyses were performed. A subgroup descriptive analysis of PWID was also performed to better examine substance use disorder (SUD) characteristics, treatment with medication for opioid use disorder (MOUD) and health service utilization. RESULTS: One-hundred and seven patients were included in the study, of which 39.2% (n = 42) had IDU-associated infective endocarditis. PWID were more likely to be homeless, uninsured, and lack a primary care provider. PWID were notably younger and had less documented comorbidities, however had similar in-hospital mortality rates (10% vs. 14%, p = 0.30), ED visits (50% vs. 54%, p = 0.70) and cardiac surgery (33% vs. 26%, p = 0.42) compared to those with non-IDU infective endocarditis. Ninety-day mortality was less among PWID (19.0% vs. 36.9%, p = 0.05). IDU was not associated with morbidity (adjusted odds ratio (AOR) 0.73, 95% CI 0.18-3.36), 90-day mortality (AOR 0.72, 95% CI 0.17-3.01), or cardiac surgery (AOR 0.15, 95% CI 0.03-0.69). Ninety-day mortality among PWID who received MOUD was lower (3% vs 15%, p = 0.45), as were ED visits (10% vs. 41%, p = 0.42) compared to those who did not receive MOUD. CONCLUSIONS: Our results highlight existing differences in health characteristics and social determinants of health in people with IDU-associated versus non-IDU infective endocarditis. PWID had less comorbidities and were significantly younger than those with non-IDU infective endocarditis and yet still had similar rates of cardiac surgery, ED visits, and in-hospital mortality. These findings emphasize the need to deliver comprehensive health services, particularly MOUD and other harm reduction services, to this marginalized population