Showing papers in "Open Forum Infectious Diseases in 2018"
TL;DR: There is wide variability in the sepsis rate and outcomes in ICU patients around the globe, and independent risk factors for in-hospital death included older age, higher simplified acute physiology II score, comorbid cancer, chronic heart failure, cirrhosis, use of mechanical ventilation or renal replacement therapy, and infection with Acinetobacter spp.
Abstract: Background There is a need to better define the epidemiology of sepsis in intensive care units (ICUs) around the globe. Methods The Intensive Care over Nations (ICON) audit prospectively collected data on all adult (>16 years) patients admitted to the ICU between May 8 and May 18, 2012, except those admitted for less than 24 hours for routine postoperative surveillance. Data were collected daily for a maximum of 28 days in the ICU, and patients were followed up for outcome data until death, hospital discharge, or for 60 days. Participation was entirely voluntary. Results The audit included 10069 patients from Europe (54.1%), Asia (19.2%), America (17.1%), and other continents (9.6%). Sepsis, defined as infection with associated organ failure, was identified during the ICU stay in 2973 (29.5%) patients, including in 1808 (18.0%) already at ICU admission. Occurrence rates of sepsis varied from 13.6% to 39.3% in the different regions. Overall ICU and hospital mortality rates were 25.8% and 35.3%, respectively, in patients with sepsis, but it varied from 11.9% and 19.3% (Oceania) to 39.5% and 47.2% (Africa), respectively. After adjustment for possible confounders in a multilevel analysis, independent risk factors for in-hospital death included older age, higher simplified acute physiology II score, comorbid cancer, chronic heart failure (New York Heart Association Classification III/IV), cirrhosis, use of mechanical ventilation or renal replacement therapy, and infection with Acinetobacter spp. Conclusions Sepsis remains a major health problem in ICU patients worldwide and is associated with high mortality rates. However, there is wide variability in the sepsis rate and outcomes in ICU patients around the globe.
235 citations
TL;DR: Amebiasis has emerged as an important infection among returning travelers, immigrants, and men who have sex with men residing in developed countries and should be considered before corticosteroid therapy to decrease complications.
Abstract: Amebiasis, due to the pathogenic parasite Entamoeba histolytica, is a leading cause of diarrhea globally. Largely an infection of impoverished communities in developing countries, amebiasis has emerged as an important infection among returning travelers, immigrants, and men who have sex with men residing in developed countries. Severe cases can be associated with high case fatality. Polymerase chain reaction-based diagnosis is increasingly available but remains underutilized. Nitroimidazoles are currently recommended for treatment, but new drug development to treat parasitic agents is a high priority. Amebiasis should be considered before corticosteroid therapy to decrease complications. There is no effective vaccine, so prevention focuses on sanitation and access to clean water. Further understanding of parasite biology and pathogenesis will advance future targeted therapeutic and preventative strategies.
214 citations
TL;DR: A case of multidrug-resistant Acinetobacter baumannii infection treated with bacteriophages is presented and bacteriophile therapy as an option to treat multi-drug-resistant bacterial infections is investigated.
Abstract: In the era of antibiotic resistance, alternative treatment options for multidrug-resistant bacterial infections are being explored. We present a case of multidrug-resistant Acinetobacter baumannii infection treated with bacteriophages. Clinical trials are needed to further investigate bacteriophage therapy as an option to treat multidrug-resistant bacterial infections.
152 citations
TL;DR: Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB; and Progressive multifocal leukoencephalopathy is a particular concern with natalIZumab.
Abstract: Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.
98 citations
TL;DR: It is suggested that OPAT may be safe and effective for PWID, with rates of OPAT completion, mortality, and catheter-related complications comparable to rates among patients without a history of IDU.
Abstract: Hospitalizations for people who inject drugs (PWID) with infectious complications requiring prolonged antibiotic therapy are increasing in the context of the opioid epidemic. Although outpatient parenteral antimicrobial therapy (OPAT) is routinely offered to patients without a history of injection drug use (IDU), PWID are often excluded from consideration of OPAT. To better assess the evidence base for the safety and effectiveness of OPAT for PWID, we conducted a review of the published literature. Results suggest that OPAT may be safe and effective for PWID, with rates of OPAT completion, mortality, and catheter-related complications comparable to rates among patients without a history of IDU. Rates of hospital readmissions may be higher among PWID, but instances of misuse of the venous catheter were rarely reported. More research is needed to study the safety and effectiveness of OPAT among PWID, as well as studying the combination of OPAT and addiction treatment.
94 citations
Temple University1, Cornell University2, Montefiore Medical Center3, University of Pittsburgh4, Thomas Jefferson University Hospital5, Rutgers University6, University of Maryland, Baltimore7, Indiana University Health8, University of Georgia9, Saint Joseph's University10, University of the Sciences11, Christiana Care Health System12
TL;DR: Ceftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.
Abstract: Background Multidrug-resistant Pseudomonas aeruginosa infections remain common in hospitals worldwide. We investigated the outcomes associated with the use of ceftolozane-tazobactam for the treatment of these infections. Methods Data were collected retrospectively from 20 hospitals across the United States about adults who received ceftolozane-tazobactam for the treatment of multidrug-resistant P aeruginosa infections of any source for at least 24 hours. The primary outcome was a composite of 30-day and inpatient mortality, and secondary outcomes were clinical success and microbiological cure. Multivariable regression analysis was conducted to determine factors associated with outcomes. Results Two-hundred five patients were included in the study. Severe illness and high degrees of comorbidity were common, with median Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 19 (interquartile range [IQR], 11-24) and median Charlson Comorbidity Indexes of 4 (IQR, 3-6). Delayed initiation of ceftolozane-tazobactam was common with therapy started a median of 9 days after culture collection. Fifty-nine percent of patients had pneumonia. On susceptibility testing, 125 of 139 (89.9%) isolates were susceptible to ceftolozane-tazobactam. Mortality occurred in 39 patients (19%); clinical success and microbiological cure were 151 (73.7%) and 145 (70.7%), respectively. On multivariable regression analysis, starting ceftolozane-tazobactam within 4 days of culture collection was associated with survival (adjusted odds ratio [OR], 5.55; 95% confidence interval [CI], 2.14-14.40), clinical success (adjusted OR, 2.93; 95% CI, 1.40-6.10), and microbiological cure (adjusted OR, 2.59; 95% CI, 1.24-5.38). Conclusions Ceftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.
78 citations
TL;DR: Scientific evaluation of the potential clinical benefit of bacteriophages as antibiofilm treatment in PJI is now feasible and required.
Abstract: Local injection of a bacteriophages mix during debridement, antibiotics and implant retention ("DAIR") was performed to treat a relapsing Staphylococcus aureus chronic prosthetic joint infection (PJI). This salvage treatment was safe and associated with a clinical success. Scientific evaluation of the potential clinical benefit of bacteriophages as antibiofilm treatment in PJI is now feasible and required.
78 citations
TL;DR: Inappropriate antibiotic prescribing is common for the treatment of UTIs and further interventions are necessary to improve outpatient antibiotic prescribing for UTIs.
Abstract: Background In 2011, The Infectious Diseases Society of America released a clinical practice guideline (CPG) that recommended short-course antibiotic therapy and avoidance of fluoroquinolones for uncomplicated urinary tract infections (UTIs). Recommendations from this CPG were rapidly disseminated to clinicians via review articles, UpToDate, and the Centers for Disease Control and Prevention website; however, it is unclear if this CPG had an impact on national antibiotic prescribing practices. Methods We performed a retrospective cohort study of outpatient and emergency department visits within a commercial insurance database between January 1, 2009, and December 31, 2013. We included nonpregnant women aged 18-44 years who had an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for a UTI with a concurrent antibiotic prescription. We performed interrupted time series analyses to determine the impact of the CPG on the appropriateness of the antibiotic agent and duration. Results We identified 654 432 women diagnosed with UTI. The patient population was young (mean age, 31 years) and had few comorbidities. Fluoroquinolones, nonfirstline agents, were the most commonly prescribed antibiotic class both before and after release of the guidelines (45% vs 42%). Wide variation was observed in the duration of treatment, with >75% of prescriptions written for nonrecommended treatment durations. The CPG had minimal impact on antibiotic prescribing behavior by providers. Conclusions Inappropriate antibiotic prescribing is common for the treatment of UTIs. The CPG was not associated with a clinically meaningful change in national antibiotic prescribing practices for UTIs. Further interventions are necessary to improve outpatient antibiotic prescribing for UTIs.
76 citations
TL;DR: This work presents a novel schematic that incorporates both people living with HIV and people at risk, making it effectively “status-neutral” in that it proposes the same approach for engagement, regardless of one’s HIV status.
Abstract: Recent biomedical advances inspire hope that an end to the epidemic of HIV is in sight. Adopting new approaches and paradigms for treatment and prevention in terms of both messaging and programming is a priority to accelerate progress. Defining the key sequential steps that comprise engagement in HIV care has provided a useful framework for clinical programs and motivated quality improvement initiatives. Recently, the same approach has been applied to use of pre-exposure prophylaxis for HIV prevention. Building on the various prevention and care continua previously proposed, we present a novel schematic that incorporates both people living with HIV and people at risk, making it effectively "status-neutral" in that it proposes the same approach for engagement, regardless of one's HIV status. This multidirectional continuum begins with an HIV test and offers 2 divergent paths depending on the results; these paths end at a common final state. To illustrate how this continuum can be utilized for program planning as well as for monitoring, we provide an example using data for New York City men who have sex with men, a population with high HIV incidence and prevalence.
71 citations
TL;DR: Despite the availability of new DAA regimens and changes in restrictions of these therapies, absolute denials of DAA Regimens by insurers have remained high and increased over time, regardless of insurance type.
Abstract: Background Despite the availability of new direct-acting antiviral (DAA) regimens, changes in DAA reimbursement criteria, and a public health focus on hepatitis C virus (HCV) elimination, it remains unclear if public and private insurers have increased access to these therapies over time. We evaluated changes in the incidence of absolute denial of DAA therapy over time and by insurance type. Methods We conducted a prospective cohort study among patients who had a DAA prescription submitted from January 2016 to April 2017 to Diplomat Pharmacy, Inc., which provides HCV pharmacy services across the United States. The main outcome was absolute denial of DAA prescription, defined as lack of fill approval by the insurer. We calculated the incidence of absolute denial, overall and by insurance type (Medicaid, Medicare, commercial), for the 16-month study period and each quarter. Results Among 9025 patients from 45 states prescribed a DAA regimen (4702 covered by Medicaid, 1821 Medicare, 2502 commercial insurance), 3200 (35.5%; 95% confidence interval, 34.5%-36.5%) were absolutely denied treatment. Absolute denial was more common among patients covered by commercial insurance (52.4%) than Medicaid (34.5%, P < .001) or Medicare (14.7%, P < .001). The incidence of absolute denial increased across each quarter of the study period, overall (27.7% in first quarter to 43.8% in last quarter; test for trend, P < .001) and for each insurance type (test for trend, P < .001 for each type). Conclusions Despite the availability of new DAA regimens and changes in restrictions of these therapies, absolute denials of DAA regimens by insurers have remained high and increased over time, regardless of insurance type.
70 citations
TL;DR: It is suggested that ID consultation may be beneficial for patients with some MDRO infections and significantly associated with reductions in 30-day and 1-year mortality for resistant S. aureus and Enterobacteriaceae, and 30- day mortality for polymicrobial infections.
Abstract: Background Multidrug-resistant organism (MDRO) infections are associated with high mortality and readmission rates. Infectious diseases (ID) consultation improves clinical outcomes for drug-resistant Staphylococcus aureus bloodstream infections. Our goal was to determine the association between ID consultation and mortality following various MDRO infections. Methods This study was conducted with a retrospective cohort (January 1, 2006-October 1, 2015) at an academic tertiary referral center. We identified patients with MDROs in a sterile site or bronchoalveolar lavage/bronchial wash culture. Mortality and readmissions within 1 year of index culture were identified, and the association of ID consultation with these outcomes was determined using Cox proportional hazards models with inverse weighting by the propensity score for ID consultation. Results A total of 4214 patients with MDRO infections were identified. ID consultation was significantly associated with reductions in 30-day and 1-year mortality for resistant S. aureus (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36-0.63; and HR, 0.73, 95% CI, 0.61-0.86) and Enterobacteriaceae (HR, 0.41; 95% CI, 0.27-0.64; and HR, 0.74; 95% CI, 0.59-0.94), and 30-day mortality for polymicrobial infections (HR, 0.51; 95% CI, 0.31-0.86) but not Acinetobacter or Pseudomonas. For resistant Enterococcus, ID consultation was marginally associated with decreased 30-day mortality (HR, 0.81; 95% CI, 0.62-1.06). ID consultation was associated with reduced 30-day readmission for resistant Enterobacteriaceae. Conclusions ID consultation was associated with significant reductions in 30-day and 1-year mortality for resistant S. aureus and Enterobacteriaceae, and 30-day mortality for polymicrobial infections. There was no association between ID consultation and mortality for patients with resistant Pseudomonas, Acinetobacter, or Enterococcus, possibly due to small sample sizes. Our results suggest that ID consultation may be beneficial for patients with some MDRO infections.
TL;DR: Widespread infection prevention and antimicrobial stewardship initiatives, in combination with new treatment options, may be required to reduce the burden of carbapenem resistance in health care settings.
Abstract: Background Infections caused by Gram-negative pathogens resistant to carbapenems have limited treatment options and are associated with increased morbidity and mortality We evaluated the rates, infection sources, and pathogen types associated with carbapenem-nonsusceptible (Carb-NS) Gram-negative isolates in intensive care unit (ICU) and non-ICU settings in a large US hospital database Methods We conducted a retrospective cross-sectional analysis of carbapenem susceptibility of all nonduplicate isolates of Gram-negative pathogens collected from January 1, 2017, to December 31, 2017, at 358 US hospitals in the BD Insights Research Database Carb-NS isolates included all pathogens reported at the institutional level as intermediate or resistant Results Of 312 075 nonduplicate Gram-negative isolates, 10 698 (34%) were Carb-NS Respiratory samples were the most frequent source of Carb-NS isolates (352%); skin/wound accounted for 236% Pseudomonas aeruginosa was the most common Carb-NS pathogen (585% of isolates), and about 30% were Enterobacteriaceae The highest rates of Carb-NS were found in Acinetobacter spp (356%) and P aeruginosa (146%) The rate of Carb-NS was significantly higher in ICU (54%) vs non-ICU settings (27%; P < 0001 in univariate analysis) This difference remained significant in multivariable analysis after adjusting for infection and hospital characteristics (odds ratio, 135; 95% confidence interval, 117-156; P < 0001) Conclusions Infections caused by Carb-NS isolates pose a significant clinical problem across different sources of infection, species of pathogen, and hospital settings Widespread infection prevention and antimicrobial stewardship initiatives, in combination with new treatment options, may be required to reduce the burden of carbapenem resistance in health care settings
TL;DR: In patients with MSSA bacteremia where cephalosporins are used as firstline therapy, the CzIE was associated with increased 30-day mortality, and Clinicians should be cautious when using cefazolin as first line therapy for these infections.
Abstract: Background Recent studies have favored the use of cefazolin over nafcillin for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. The clinical influence of the cefazolin inoculum effect (CzIE) in the effectiveness of cephalosporins for severe MSSA infections has not been evaluated. Methods We prospectively included patients from 3 Argentinian hospitals with S. aureus bacteremia. Cefazolin minimum inhibitory concentrations (MICs) were determined at standard (105 colony-forming units [CFU]/mL) and high (107 CFU/mL) inoculum. The CzIE was defined as an increase of MIC to ≥16 µg/mL when tested at high inoculum. Whole-genome sequencing was performed in all isolates. Results A total of 77 patients, contributing 89 MSSA isolates, were included in the study; 42 patients (54.5%) had isolates with the CzIE. In univariate analysis, patients with MSSA exhibiting the CzIE had increased 30-day mortality (P = .034) and were more likely to have catheter-associated or unknown source of bacteremia (P = .033) compared with patients infected with MSSA isolates without the CzIE. No statistically significant difference between the groups was observed in age, clinical illness severity, place of acquisition (community vs hospital), or presence of endocarditis. The CzIE remained associated with increased 30-day mortality in multivariate analysis (risk ratio, 2.65; 95% confidence interval, 1.10-6.42; P = .03). MSSA genomes displayed a high degree of heterogeneity, and the CzIE was not associated with a specific lineage. Conclusions In patients with MSSA bacteremia where cephalosporins are used as firstline therapy, the CzIE was associated with increased 30-day mortality. Clinicians should be cautious when using cefazolin as firstline therapy for these infections.
TL;DR: This is the largest rapid entry cohort described in the United States and suggests that rapid entry is feasible and could have a positive impact on HIV transmission at the population level.
Abstract: Background Rapid entry programs (REPs) improve time to antiretroviral therapy (ART) initiation (TAI) and time to viral suppression (TVS). We assessed the feasibility and effectiveness of a REP in a large HIV clinic in Atlanta, Georgia, serving a predominately un- or underinsured population. Methods The Rapid Entry and ART in Clinic for HIV (REACH) program was implemented on May 16, 2016. We performed a retrospective cohort study with the main independent variable being period of enrollment: January 1, 2016, through May 15, 2016 (pre-REACH); May 16, 2016, through July 31, 2016 (post-REACH). Included individuals were HIV-infected and new to the clinic with detectable HIV-1 RNA. Six-month follow-up data were collected for each participant. Survival analyses were conducted for TVS. Logistic and linear regression analyses were used to evaluate secondary outcomes: attendance at first clinic visit, viral suppression, TAI, and time to first attended provider visit. Results There were 117 pre-REACH and 90 post-REACH individuals. Median age (interquartile range [IQR]) was 35 (25-45) years, 80% were male, 91% black, 60% men who have sex with men, 57% uninsured, and 44% active substance users. TVS decreased from 77 (62-96) to 57 (41-70) days (P < .0022). Time to first attended provider visit decreased from 17 to 5 days, and TAI from 21 to 7 days (P < .0001), each remaining significant in adjusted models. Conclusions This is the largest rapid entry cohort described in the United States and suggests that rapid entry is feasible and could have a positive impact on HIV transmission at the population level.
TL;DR: The majority of physicians surveyed treated PWID and reported myriad obstacles to providing care, so public health and health care systems should consider ways to support ID physicians caring for PWID, including guidelines for providing complex care, including safe provision of multiweek parenteral antibiotics.
Abstract: Background In the context of the opioid epidemic, injection drug use (IDU)-related infections are an escalating health issue for infectious diseases (ID) physicians in the United States. Methods We conducted a mixed methods survey of the Infectious Diseases Society of America's Emerging Infections Network between February and April 2017 to evaluate perspectives relating to care of persons who inject drugs (PWID). Topics included the frequency of and management strategies for IDU-related infection, the availability of addiction services, and the evolving role of ID physicians in substance use disorder (SUD) management. Results More than half (53%, n = 672) of 1273 network members participated. Of these, 78% (n = 526) reported treating PWID. Infections frequently encountered included skin and soft tissue (62%, n = 324), bacteremia/fungemia (54%, n = 281), and endocarditis (50%, n = 263). In the past year, 79% (n = 416) reported that most IDU-related infections required ≥2 weeks of parenteral antibiotics; strategies frequently employed for prolonged treatment included completion of the entire course in the inpatient unit (41%, n = 218) or at another supervised facility (35%, n = 182). Only 35% (n = 184) of respondents agreed/strongly agreed that their health system offered comprehensive SUD management; 46% (n = 242) felt that ID providers should actively manage SUD. Conclusions The majority of physicians surveyed treated PWID and reported myriad obstacles to providing care. Public health and health care systems should consider ways to support ID physicians caring for PWID, including (1) guidelines for providing complex care, including safe provision of multiweek parenteral antibiotics; (2) improved access to SUD management; and (3) strategies to assist those interested in roles in SUD management.
TL;DR: Pneumococci, M pneumoniae, and viruses are the most common pathogens associated with CAP requiring hospital admission, and they all have a similar incidence that increases with age.
Abstract: This work was funded by the Icelandic Center for Research, Rannis (grant number 100436021), the Landspitali University Hospital Science Fund, and the University of Iceland Research Fund.
TL;DR: It is demonstrated the successful and safe implementation of a pilot oral penicillin challenge program for cancer patients with low-riskPenicillin allergies, increasing the use of penicillus and narrow-spectrum beta-lactams post-testing.
Abstract: Antibiotic allergies are reported by up to 1 in 4 cancer patients, almost 50% of which are considered low risk and precede the cancer diagnosis. We demonstrate the successful and safe implementation of a pilot oral penicillin challenge program for cancer patients with low-risk penicillin allergies, increasing the use of penicillin and narrow-spectrum beta-lactams post-testing.
TL;DR: Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.
Abstract: Background
Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection.
TL;DR: It is shown how the next-generation sequencing approach can be used for the early detection of emerging pathogens and to improve the understanding of enterovirus circulation in humans.
Abstract: Background Enteroviruses are common human pathogens occasionally associated with severe disease, notoriously paralytic poliomyelitis caused by poliovirus. Other enterovirus serotypes such as enterovirus A71 and D68 have been linked to severe neurological syndromes. New enterovirus serotypes continue to emerge, some believed to be derived from nonhuman primates. However, little is known about the circulation patterns of many enterovirus serotypes and, in particular, the detailed enterovirus composition of sewage samples. Methods We used a next-generation sequencing approach analyzing reverse transcriptase polymerase chain reaction products synthesized directly from sewage concentrates. Results We determined whole-capsid genome sequences of multiple enterovirus strains from all 4 A to D species present in environmental samples from the United Kingdom, Senegal, and Pakistan. Conclusions Our results indicate complex enterovirus circulation patterns in human populations with differences in serotype composition between samples and evidence of sustained and widespread circulation of many enterovirus serotypes. Our analyses revealed known and divergent enterovirus strains, some of public health relevance and genetically linked to clinical isolates. Enteroviruses identified in sewage included vaccine-derived poliovirus and enterovirus D-68 stains, new enterovirus A71 and coxsackievirus A16 genogroups indigenous to Pakistan, and many strains from rarely reported serotypes. We show how this approach can be used for the early detection of emerging pathogens and to improve our understanding of enterovirus circulation in humans.
TL;DR: A systematic review of the cost-effectiveness studies of palivizumab is presented and the main highlights of a round table discussion with clinical, payer, economic, research method, and other experts are described.
Abstract: Respiratory syncytial virus (RSV) infection is the most common cause of lower respiratory tract infection and the leading cause of hospitalization among young children, incurring high annual costs among US children under the age of 5 years. Palivizumab has been found to be effective in reducing hospitalization and preventing serious lower respiratory tract infections in high-risk infants. This paper presents a systematic review of the cost-effectiveness studies of palivizumab and describes the main highlights of a round table discussion with clinical, payer, economic, research method, and other experts. The objectives of the discussion were to (1) review the current state of clinical, epidemiology, and economic data related to severe RSV disease; (2) review new cost-effectiveness estimates of RSV immunoprophylaxis in US preterm infants, including a review of the field's areas of agreement and disagreement; and (3) identify needs for further research.
TL;DR: With antiretroviral therapy initiation, higher WC increases in the RAL arm compared with PIs were more pronounced in female and black participants, and a more advanced baseline HIV disease state was a strong predictor of larger abdominal increases.
Abstract: Background This study investigates the association of clinical and demographic predictors with abdominal fat gain, measured using waist circumference (WC) and self-reported abdominal size. Methods We analyzed data from ACTG A5257, a clinical trial that randomized treatment-naive HIV-infected participants to 1 of 3 antiretroviral regimens: raltegravir (RAL) or the protease inhibitors (PIs) atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r), each in combination with tenofovir disoproxil fumarate/emtricitabine. Associations of treatment and baseline/demographic characteristics with 96-week WC change were assessed using repeated-measures models. Ordinal logistic regression was used to examine the associations of predictors with week 96 self-reported abdominal changes. Results The study population (n = 1809) was 76.0% male and predominantly black non-Hispanic (41.9%) and white non-Hispanic (34.1%). Mean baseline WC was 90.6 cm, with an average 96-week increase of 3.4 cm. WC increases were higher in the RAL arm compared with DRV/r (P = .0130). Females experienced greater increases in WC on RAL vs ATV/r than males (P = .0065). Similarly, a larger difference in WC change was found for RAL vs DRV/r for black vs nonblack individuals (P = .0043). A separate multivariable model found that in addition to the treatment regimen, higher baseline viral load and lower CD4+ were also associated with WC increases. Conclusions With antiretroviral therapy initiation, higher WC increases in the RAL arm compared with PIs were more pronounced in female and black participants, and a more advanced baseline HIV disease state was a strong predictor of larger abdominal increases. Understanding factors predisposing individuals to abdominal fat gain could inform health management after therapy initiation.
TL;DR: RSV causes substantial outpatient illness with lower respiratory tract involvement and the relative risk of a serious outcome was significantly increased in persons aged ≥75 years (vs 60–64 years) and in those with chronic obstructive pulmonary disease or congestive heart failure.
Abstract: Background The epidemiology and burden of respiratory syncytial virus (RSV) illness are not well defined in older adults. Methods Adults ≥60 years old seeking outpatient care for acute respiratory illness were recruited from 2004-2005 through 2015-2016 during the winter seasons. RSV was identified from respiratory swabs by multiplex polymerase chain reaction. Clinical characteristics and outcomes were ascertained by interview and medical record abstraction. The incidence of medically attended RSV was estimated for each seasonal cohort. Results RSV was identified in 243 (11%) of 2257 enrollments (241 of 1832 individuals), including 121 RSV type A and 122 RSV type B. The RSV clinical outcome was serious in 47 (19%), moderate in 155 (64%), and mild in 41 (17%). Serious outcomes included hospital admission (n = 29), emergency department visit (n = 13), and pneumonia (n = 23) and were associated with lower respiratory tract symptoms during the enrollment visit. Moderate outcomes included receipt of a new antibiotic prescription (n = 144; 59%), bronchodilator/nebulizer (n = 45; 19%), or systemic corticosteroids (n = 28; 12%). The relative risk of a serious outcome was significantly increased in persons aged ≥75 years (vs 60-64 years) and in those with chronic obstructive pulmonary disease or congestive heart failure. The average seasonal incidence was 139 cases/10 000, and it was significantly higher in persons with cardiopulmonary disease compared with others (rate ratio, 1.89; 95% confidence interval, 1.44-2.48). Conclusions RSV causes substantial outpatient illness with lower respiratory tract involvement. Serious outcomes are common in older patients and those with cardiopulmonary disease.
TL;DR: Video DOT is an acceptable and important option for measurement of TB treatment adherence and may allow a higher proportion of prescribed treatment doses to be observed, compared with in-person DOT.
Abstract: Background Directly observed therapy (DOT) remains an integral component of treatment support and adherence monitoring in tuberculosis care. In-person DOT is resource intensive and often burdensome for patients. Video DOT (vDOT) has been proposed as an alternative to increase treatment flexibility and better meet patient-specific needs. Methods We conducted a pragmatic, prospective pilot implementation of vDOT at 3 TB clinics in Maryland. A mixed-methods approach was implemented to assess (1) effectiveness, (2) acceptability, and (3) cost. Medication adherence on vDOT was compared with that of in-person DOT. Interviews and surveys were conducted with patients and providers before and after implementation, with framework analysis utilized to extract salient themes. Last, a cost analysis assessed the economic impacts of vDOT implementation across heterogeneous clinic structures. Results Medication adherence on vDOT was comparable to that of in-person DOT (94% vs 98%, P = .17), with a higher percentage of total treatment doses (inclusive of weekend/holiday self-administration) ultimately observed during the vDOT period (72% vs 66%, P = .03). Video DOT was well received by staff and patients alike, who cited increased treatment flexibility, convenience, and patient privacy. Our cost analysis estimated a savings with vDOT of $1391 per patient for a standard 6-month treatment course. Conclusions Video DOT is an acceptable and important option for measurement of TB treatment adherence and may allow a higher proportion of prescribed treatment doses to be observed, compared with in-person DOT. Video DOT may be cost-saving and should be considered as a component of individualized, patient-centered case management plans.
TL;DR: A simple, behavioral nudge in microbiology reporting increased de-escalation and discontinuation of unnecessary broad-spectrum antibiotics highlights the importance of clear, persuasive communication of diagnostic testing in improving antibiotic prescribing behaviors.
Abstract: Background Systematic and behavioral interventions are needed to improve antibiotic use for common conditions like pneumonia. Methods Single pretest, post-test quasi-experiment in a 4-hospital health system in metropolitan Detroit, Michigan. Hospitalized patients treated with anti-methicillin-resistant Staphylococcus aureus and antipseudomonal antibiotics for respiratory infections from August 1, 2015, through January 31, 2016, and August 1, 2016, through January 31, 2017, were eligible for inclusion. Beginning in May 2016, respiratory cultures with no dominant organism growth and no Pseudomonas sp. or Staphylococcus aureus were reported by the clinical microbiology laboratory as "commensal respiratory flora only: No S. aureus/MRSA [methicillin-resistant Staphylococcus aureus] or P. [Pseudomonas] aeruginosa." Before intervention, these were reported as "commensal respiratory flora." The primary end point was de-escalation or discontinuation of anti-methicillin-resistant Staphylococcus aureus or antipseudomonal therapy. Secondary clinical and safety outcomes included nephrotoxicity and in-hospital, all-cause mortality. Results Two hundred ten patients were included in the study. De-escalation/discontinuation was more commonly performed in the intervention group (39% vs 73%, P < .001). After adjusting for APACHE II and Charlson Comorbidity Index, the intervention comment was associated with a 5.5-fold increased odds of de-escalation (adjusted odds ratio, 5.5; 95% confidence interval, 2.8-10.7). Acute kidney injury was reduced in the intervention phase (31% vs 14%, P = .003). No difference in all-cause mortality was detected between the groups (30% vs 18%, P = .052). Conclusion A simple, behavioral nudge in microbiology reporting increased de-escalation and discontinuation of unnecessary broad-spectrum antibiotics. This highlights the importance of clear, persuasive communication of diagnostic testing in improving antibiotic prescribing behaviors.
TL;DR: A strong inverse association between housing instability and viral suppression across a spectrum of unstable housing arrangements is found.
Abstract: Housing instability negatively impacts outcomes in people [living] with human immunodeficiency virus (PLHIV), yet the effect of diverse living arrangements has not previously been evaluated. Using 6 dwelling types to measure housing status, we found a strong inverse association between housing instability and viral suppression across a spectrum of unstable housing arrangements.
TL;DR: Conclusions Cryptococcosis after ART initiation is common in Africa and patients initiating ART who unmask cryptococcal meningitis are at a high risk of death.
Abstract: Background Increased antiretroviral therapy (ART) availability has been associated with more patients developing cryptococcosis after ART initiation. Despite this changing epidemiology, data regarding cryptococcal meningitis in those already receiving ART are limited. We compared clinical presentations and outcomes among ART-naive and ART-experienced Ugandans. Methods We prospectively enrolled 605 HIV-infected persons with first-episode cryptococcal meningitis from August 2013 to May 2017 who received amphotericin-based combination therapy. We classified participants by ART status and ART duration and compared groups for 2-week survival. Results Overall, 46% (281/605) of participants were receiving ART at presentation. Compared with those not receiving ART, those receiving ART had higher CD4 counts (P .99). However, 47% (24/51) of those receiving ART for ≤14 days died within 2 weeks, compared with 19% (20/105) of those receiving ART for 15-182 days and 26% (32/125) of those receiving ART for >6 months (P 6 months, 87% had HIV viral loads >1000 copies/mL. Conclusions Cryptococcosis after ART initiation is common in Africa. Patients initiating ART who unmask cryptococcal meningitis are at a high risk of death. Immune recovery in the setting of central nervous system infection is detrimental, and management of this population requires further study. Implementing pre-ART cryptococcal antigen screening is urgently needed to prevent cryptococcal meningitis after ART initiation.
TL;DR: Investigation of a pharmacist-led PrEP program is feasible and associated with high rates of patient satisfaction and pharmacist acceptability and no participant has seroconverted.
Abstract: Background HIV pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition, yet significant barriers exist to its prescription and use. Incorporating pharmacists in the PrEP care process may help increase access to PrEP services. Methods Our pharmacist-led PrEP program (P-PrEP) included pharmacists from a university-based HIV clinic, a community pharmacy, and two community-based clinics. Through a collaborative practice agreement, pharmacists conducted PrEP visits with potential candidates for PrEP, according to the recommended CDC guidelines, and authorized emtricitabine-tenofovir disoproxil fumarate prescriptions. Demographics and retention in care over 12 months were summarized and participant satisfaction and pharmacist acceptability with the P-PrEP program were assessed by Likert-scale questionnaires. Results Sixty patients enrolled in the P-PrEP program between January and June 2017 completing 139 visits. The mean age was 34 years (range 20-61 years) and 88% identified as men who have sex with men, 91.7% were men, 83.3% were white, 80% were commercially insured, and 89.8% had completed some college education or higher. Participant retention at 3, 6, 9, and 12 months was 73%, 58%, 43%, and 28%, respectively. To date, no participant has seroconverted. One hundred percent of the participants who completed the patient satisfaction questionnaire would recommend the P-PrEP program. Pharmacists reported feeling comfortable performing point-of-care testing and rarely reported feeling uncomfortable during PrEP visits (3 occasions - 2.2%) or experiencing workflow disruption (1 occasion - 0.7%). Conclusions Implementation of a pharmacist-led PrEP program is feasible and associated with high rates of patient satisfaction and pharmacist acceptability.
TL;DR: Home OPAT may be a safe discharge option in carefully selected patients and persons who inject drugs discharged home were not more likely to have complications than those discharged to a SNF/rehab.
Abstract: Background Opioid use disorder poses a significant public health risk. Persons who inject drugs (PWID) suffer from high mortality and morbidity secondary to serious infectious diseases, often requiring prolonged courses of outpatient parenteral antibiotics. The goal of this study was to determine the outcomes of PWID discharged to home or to a skilled nursing or rehabilitation facility (SNF/rehab) with parenteral antibiotic treatment under an outpatient parenteral antimicrobial therapy (OPAT) program. Methods This is a retrospective observational study. The study population was identified via hospital and OPAT databases using substance use disorder diagnoses and confirmed through chart review. The study population included hospitalized PWID with injection drug use in the preceding 2 years who were discharged between 2010 and 2015 to complete at least 2 weeks of parenteral antibiotics and monitored by the OPAT program. Retrospective chart review was used to describe patient characteristics and outcomes. Results Fifty-two patients met inclusion criteria, 21 of whom were discharged to home and 31 were discharged to a SNF/rehab. Of the patients discharged to home, 17 (81%) completed their planned antibiotic courses without complication. Twenty (64%) patients discharged to a SNF/rehab completed the antibiotic courses without complication. Six (11%) patients had line infections, 6 (11%) had injection drug use relapse, and 12 (23%) required readmission. Conclusions Persons who inject drugs discharged home were not more likely to have complications than those discharged to a SNF/rehab. Home OPAT may be a safe discharge option in carefully selected patients.
TL;DR: Higher vaccination coverage and lower nonmedical exemption rates for MMR and DTaP vaccines in states adopting Advisory Committee on Immunization Practices guidelines for school entry are found.
Abstract: Background Vaccination coverage among children entering kindergarten in the United States is high, but interstate variations exist. The relationship between state immunization laws and vaccination coverage has not been fully assessed. We evaluated associations of state laws on both measles, mumps, and rubella (MMR) and diphtheria, tetanus, and pertussis (DTaP) vaccination coverage and exemptions to school immunization requirements. Methods We conducted a retrospective, longitudinal analysis of the effect of state immunization laws on vaccination coverage and exemptions among US kindergarteners from SY 2008 to SY 2014. The primary outcome measures were state-level kindergarten entry vaccination coverage rates for 2-dose MMR and 4-dose DTaP vaccines. Secondary outcome measures included rates of state-level exemptions (ie, medical, religious, philosophical) to school immunization requirements. Results We found that state policies that refer to Advisory Committee on Immunization Practices recommendations were associated with 3.5% and 2.8% increases in MMR and DTaP vaccination rates. Health Department-led parental education was associated with 5.1% and 4.5% increases in vaccination rates. Permission of religious and philosophical exemptions was associated with 2.3% and 1.9% decreases in MMR and DTaP coverage, respectively, and a 1.5% increase in both total exemptions and nonmedical exemptions, respectively. Conclusions We found higher vaccination coverage and lower nonmedical exemption rates for MMR and DTaP vaccines in states adopting Advisory Committee on Immunization Practices guidelines for school entry. Adherence to these best practices was a successful strategy to increase vaccination coverage and reduce vaccination exemptions.
TL;DR: Within a multidisciplinary model of care, the treatment of HCV-infected PWID with all-oral DAA regimens is safe and highly effective, justifying targeted efforts to enhance access to HCV treatment in this vulnerable and marginalized population.
Abstract: Background Many clinicians and insurance providers are reluctant to embrace recent guidelines identifying people who inject drugs (PWID) as a priority population to receive hepatitis C virus (HCV) treatment. The aim of this study was to evaluate the efficacy of direct-acting antiviral (DAA) HCV therapy in a real-world population comprised predominantly of PWID. Methods A retrospective analysis was performed on all HCV-infected patients who were treated at the Vancouver Infectious Diseases Centre between March 2014 and December 2017. All subjects were enrolled in a multidisciplinary model of care, addressing medical, psychological, social, and addiction-related needs. The primary outcome was achievement of sustained virologic response (undetectable HCV RNA) 12 or more weeks after completion of HCV therapy (SVR-12). Results Overall, 291 individuals were enrolled and received interferon-free DAA HCV therapy. The mean age was 54 years, 88% were PWID, and 20% were HCV treatment experienced. At data lock, 62 individuals were still on treatment and 229 were eligible for evaluation of SVR by intent-to-treat (ITT) analysis. Overall, 207 individuals achieved SVR (90%), with 13 losses to follow-up, 7 relapses, and 2 premature treatment discontinuations. ITT SVR analysis show that active PWID and treatment-naive patients were less likely to achieve SVR (P = .0185 and .0317, respectively). Modified ITT analysis of active PWID showed no difference in achieving SVR (P = .1157) compared with non-PWID. Conclusion Within a multidisciplinary model of care, the treatment of HCV-infected PWID with all-oral DAA regimens is safe and highly effective. These data justify targeted efforts to enhance access to HCV treatment in this vulnerable and marginalized population.