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BACKGROUND: The rise in injection drug use in the USA has led to an increase in injection site infections. We performed a national survey of people who use drugs to evaluate common drug use preparation, harm reduction practices, and experiences with injection site infections. METHODS: A survey was disseminated to members of the Survey of Key Informants' Patients Program from 2021 to 2022 and distributed to patients 18 years or older newly entering one of 68 substance use disorder treatment programs across the USA with a primary diagnosis of an opioid use disorder. Participants were surveyed about practices when preparing and using drugs, along with self-reported infections and drug use complications. RESULTS: 1289 participants responded to the survey. Sexually transmitted infections were common, with 37.6% reporting ever having had any sexually transmitted infection. Injection-associated infections had affected 63.4% of participants who had ever used injection drugs. Many respondents reported not seeking professional medical assistance for infection management, including 29% draining abscesses without seeking medical care and 22.8% obtaining antibiotics through non-healthcare sources. Non-sterile injection practices included sharing needles with others who were febrile or ill (18%), using needles previously used to drain wounds/abscesses (9.9%) for subsequent injection drug use, and licking needles (21.2%). CONCLUSION: Patients entering treatment for opioid use disorder reported a high burden of infectious diseases. A number of easily-modifiable high risk behaviors for developing injection-related infections were identified. Efforts are needed to disseminate targeted harm reduction education to PWID on how to reduce their risks for injection-related infections.
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Infecciones por VIH , Trastornos Relacionados con Opioides , Abuso de Sustancias por Vía Intravenosa , Humanos , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología , Programas de Intercambio de Agujas , Reducción del Daño , Absceso , Composición de Medicamentos , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/complicaciones , Infecciones por VIH/complicacionesRESUMEN
BACKGROUND: The American Heart Association has sponsored both guidelines and scientific statements that address the diagnosis, management, and prevention of infective endocarditis. As a result of the unprecedented and increasing incidence of infective endocarditis cases among people who inject drugs, the American Heart Association sponsored this original scientific statement. It provides a more in-depth focus on the management of infective endocarditis among this unique population than what has been provided in prior American Heart Association infective endocarditis-related documents. METHODS: A writing group was named and consisted of recognized experts in the fields of infectious diseases, cardiology, addiction medicine, and cardiovascular surgery in October 2021. A literature search was conducted in Embase on November 19, 2021, and multiple terms were used, with 1345 English-language articles identified after removal of duplicates. CONCLUSIONS: Management of infective endocarditis in people who inject drugs is complex and requires a unique approach in all aspects of care. Clinicians must appreciate that it requires involvement of a variety of specialists and that consultation by addiction-trained clinicians is as important as that of more traditional members of the endocarditis team to improve infective endocarditis outcomes. Preventive measures are critical in people who inject drugs and are cured of an initial bout of infective endocarditis because they remain at extremely high risk for subsequent bouts of infective endocarditis, regardless of whether injection drug use is continued.
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Consumidores de Drogas , Endocarditis Bacteriana , Endocarditis , American Heart Association , Endocarditis/diagnóstico , Endocarditis/tratamiento farmacológico , Endocarditis/etiología , Endocarditis Bacteriana/tratamiento farmacológico , HumanosRESUMEN
BACKGROUND: Staphylococcus aureus represents the leading cause of complicated bloodstream infections among persons who inject drugs (PWID). Standard of care (SOC) intravenous (IV) antibiotics result in high rates of treatment success but are not feasible for some PWID. Transition to oral antibiotics may represent an alternative treatment option. METHODS: We evaluated all adult patients with a history of injection drug use hospitalized from January 2016 through December 2021 with complicated S. aureus bloodstream infections, including infective endocarditis, epidural abscess, vertebral osteomyelitis, and septic arthritis. Patients were compared by antibiotic treatment (standard of care intravenous [SOC IV] antibiotics, incomplete IV therapy, or transition from initial IV to partial oral) using the primary composite endpoint of death or readmission from microbiologic failure within 90 days of discharge. RESULTS: Patients who received oral antibiotics after an incomplete IV antibiotic course were significantly less likely to experience microbiologic failure or death than patients discharged without oral antibiotics (P < .001). There was no significant difference in microbiologic failure rates when comparing patients who were discharged on partial oral antibiotics after receiving at least 10 days of IV antibiotics with SOC regimens (P > .9). CONCLUSIONS: Discharge of PWID with partially treated complicated S. aureus bacteremias without oral antibiotics results in high rates of morbidity and should be avoided. For PWID hospitalized with complicated S. aureus bacteremias who have received at least 10 days of effective IV antibiotic therapy after clearance of bacteremia, transition to oral antibiotics with outpatient support represents a potential alternative if the patient does not desire SOC IV antibiotic therapy.
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Bacteriemia , Consumidores de Drogas , Infecciones Estafilocócicas , Abuso de Sustancias por Vía Intravenosa , Adulto , Humanos , Antibacterianos , Staphylococcus aureus , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Bacteriemia/microbiología , Estudios RetrospectivosRESUMEN
BACKGROUND: African American women have an elevated risk for experiencing depressive symptoms, and discrimination, stress, and coping contribute to symptoms of depression. AIMS: We aimed to examine the associations between discrimination, stress, and coping on symptoms of depression among young African American mothers. METHODS: In this retrospective study, we utilized a hierarchical linear regression to explore the effects of perceived racial discrimination, stress, and general and discrimination-related coping responses on depressive symptoms in a sample of African American mothers (N = 250). The data were drawn from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure study (InterGEN), a study conducted between 2014 and 2019 and based in Connecticut. RESULTS: After accounting for maternal age, level of education, and income, greater perceived racial discrimination (p = .03), higher levels of stress (p < .001), greater engagement in avoidance coping (p < .001), and use of passive coping responses to discrimination (p = .04) were uniquely associated with increased depressive symptoms. Other forms of coping, specifically, problem-solving and support seeking, did not appear to influence depressive symptoms in this sample. CONCLUSION: The findings highlight the negative impact of discrimination, heightened stress, and maladaptive coping on the emotional health of young African American mothers.
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BACKGROUND: The Benefits and Barriers Model proposes both benefits and barriers associated with nonsuicidal self-injury (NSSI) and that a negative association with the self plays a key role in the initial selection of and acute motivation for NSSI. The current investigation builds upon previous findings by assessing the added benefit of targeting self-criticism in the treatment of NSSI. METHODS: Sample included 40 participants (30 females; Mage = 14.92) enrolled in dialectical behavior therapy for adolescents within a partial hospitalization program. All study participants received dialectical behavior therapy for adolescents, and those randomized to the experimental condition received an additional brief cognitive intervention developed to decrease self-criticism. RESULTS: There was no evidence of an indirect effect of targeting self-criticism upon NSSI at post-treatment via post-treatment self-criticism (b = -0.98, p = .543); however, there was evidence of a significant interaction between treatment condition and self-criticism at pretreatment in the prediction of NSSI at post-treatment (b = 0.33, p = .030). Analyses of simple slopes indicated the conditional direct effect of targeting self-criticism varied as a function of patient's level of self-criticism at the onset of treatment, such that individuals -1 SD below the mean (b = -5.76, p = .037) and at average pretreatment levels of self-criticism (b = -4.09, p = .042), but not + 1 SD above the mean (b = -2.42, p = .056), experienced fewer incidents of NSSI at post-treatment. CONCLUSIONS: The results of this investigation support the added benefit of targeting self-criticism in the treatment of NSSI for adolescents.
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Terapia Conductual Dialéctica , Conducta Autodestructiva , Adolescente , Femenino , Humanos , Motivación , Autoevaluación (Psicología) , Conducta Autodestructiva/terapiaRESUMEN
BACKGROUND: Patients with opioid use disorder (OUD) are frequently admitted for invasive infections. Medications for OUD (MOUD) may improve outcomes in hospitalized patients. METHODS: In this retrospective cohort of 220 admissions to a tertiary care center for invasive infections due to OUD, we compared 4 MOUD treatment strategies: methadone, buprenorphine, methadone taper for detoxification, and no medication to determine whether there were differences in parenteral antibiotic completion and readmission rates. RESULTS: The MOUDs were associated with increased completion of parenteral antimicrobial therapy (64.08% vs 46.15%; odds ratio [OR] = 2.08; 95% CI, 1.23-3.61). On multivariate analysis, use of MOUD maintenance with either buprenorphine (OR = 0.38; 95% CI, .17-.85) or methadone maintenance (OR = 0.43; 95% CI, .20-.94) and continuation of MOUD on discharge (OR = 0.35; 95% CI, .18-.67) was associated with lower 90-day readmissions. In contrast, use of methadone for detoxification followed by tapering of the medication without continuation on discharge was not associated with decreased readmissions (OR = 1.87; 95% CI, .62-5.10). CONCLUSIONS: Long-term MOUDs, regardless of selection, are an integral component of care in patients hospitalized with OUD-related infections. Patients with OUD should have arrangements made for MOUDs to be continued after discharge, and MOUDs should not be discontinued before discharge.
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Infecciones Bacterianas/tratamiento farmacológico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Adulto , Anciano , Antibacterianos/administración & dosificación , Antifúngicos/administración & dosificación , Infecciones Bacterianas/etiología , Infecciones Bacterianas/prevención & control , Buprenorfina/uso terapéutico , Continuidad de la Atención al Paciente , Consumidores de Drogas/psicología , Consumidores de Drogas/estadística & datos numéricos , Femenino , Humanos , Infecciones Fúngicas Invasoras/epidemiología , Infecciones Fúngicas Invasoras/etiología , Infecciones Fúngicas Invasoras/prevención & control , Masculino , Cumplimiento de la Medicación/psicología , Metadona/uso terapéutico , Persona de Mediana Edad , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Trastornos Relacionados con Opioides/complicaciones , Trastornos Relacionados con Opioides/psicología , Readmisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/psicología , Centros de Atención Terciaria/estadística & datos numéricos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
HAMLET is a complex of human α-lactalbumin (ALA) and oleic acid and kills several Gram-positive bacteria by a mechanism that bears resemblance to apoptosis in eukaryotic cells. To identify HAMLET's bacterial targets, here we used Streptococcus pneumoniae as a model organism and employed a proteomic approach that identified several potential candidates. Two of these targets were the glycolytic enzymes fructose bisphosphate aldolase (FBPA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Treatment of pneumococci with HAMLET immediately inhibited their ATP and lactate production, suggesting that HAMLET inhibits glycolysis. This observation was supported by experiments with recombinant bacterial enzymes, along with biochemical and bacterial viability assays, indicating that HAMLET's activity is partially inhibited by high glucose-mediated stimulation of glycolysis but enhanced in the presence of the glycolysis inhibitor 2-deoxyglucose. Both HAMLET and ALA bound directly to each glycolytic enzyme in solution and solid-phase assays and effectively inhibited their enzymatic activities. In contrast, oleic acid alone had little to no inhibitory activity. However, ALA alone also exhibited no bactericidal activity and did not block glycolysis in whole cells, suggesting a role for the lipid moiety in the internalization of HAMLET into the bacterial cells to reach its target(s). This was verified by inhibition of enzyme activity in whole cells after HAMLET but not ALA exposure. The results of this study suggest that part of HAMLET's antibacterial activity relates to its ability to target and inhibit glycolytic enzymes, providing an example of a natural antimicrobial agent that specifically targets glycolysis.
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Lactalbúmina/química , Lípidos/química , Proteínas de la Leche/química , Leche Humana/química , Ácidos Oléicos/química , Streptococcus pneumoniae/citología , Adenosina Trifosfato/química , Desoxiglucosa/química , Fructosa-Bifosfato Aldolasa/química , Glucosa/química , Gliceraldehído 3-Fosfato Deshidrogenasa (NADP+)/química , Glucólisis , Humanos , Viabilidad Microbiana , Ácido Oléico/química , Proteómica , Proteínas Recombinantes/químicaRESUMEN
BACKGROUND: Persons who inject drugs (PWID) are at risk of invasive infections; however, hospitalizations to treat these infections are frequently complicated by against medical advice (AMA) discharges. This study compared outcomes among PWID who (1) completed a full course of inpatient intravenous (IV) antibiotics, (2) received a partial course of IV antibiotics but were not prescribed any antibiotics on AMA discharge, and (3) received a partial course of IV antibiotics and were prescribed oral antibiotics on AMA discharge. METHODS: A retrospective, cohort study of PWID aged ≥18 years admitted to a tertiary referral center between 01/2016 and 07/2019, who received an infectious diseases consultation for an invasive bacterial or fungal infection. RESULTS: 293 PWID were included in the study. 90-day all-cause readmission rates were highest among PWID who did not receive oral antibiotic therapy on AMA discharge (nâ =â 46, 68.7%), compared with inpatient IV (nâ =â 43, 31.5%) and partial oral (nâ =â 27, 32.5%) antibiotics. In a multivariate analysis, 90-day readmission risk was higher among PWID who did not receive oral antibiotic therapy on AMA discharge (adjusted hazard ratio [aHR],â 2.32; 95% confidence interval [CI], 1.41-3.82) and not different among PWID prescribed oral antibiotic therapy on AMA discharge (aHR,â .99; 95% CI, .62-1.62). Surgical source control (aHR,â .57; 95% CI, .37-.87) and addiction medicine consultation (aHR,â .57; 95% CI, .38-.86) were both associated with reduced readmissions. CONCLUSIONS: Our single-center study suggests access to oral antibiotic therapy for PWID who cannot complete prolonged inpatient IV antibiotic courses is beneficial.
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Consumidores de Drogas , Preparaciones Farmacéuticas , Abuso de Sustancias por Vía Intravenosa , Adolescente , Adulto , Antibacterianos/uso terapéutico , Estudios de Cohortes , Humanos , Estudios Retrospectivos , Abuso de Sustancias por Vía Intravenosa/complicacionesRESUMEN
The opioid epidemic has increased hospital admissions for serious infections related to opioid abuse. Our findings demonstrate that addiction medicine consultation is associated with increased treatment for opioid use disorder (OUD), greater likelihood of completing antimicrobial therapy, and reduced readmission rates among patients with OUD and serious infections requiring hospitalization.
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Medicina de las Adicciones , Trastornos Relacionados con Opioides/complicaciones , Readmisión del Paciente/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Adulto , Anciano , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/etiología , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/microbiología , Estudios Retrospectivos , Centros de Atención Terciaria , Adulto JovenRESUMEN
Streptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx.
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Anticuerpos Antibacterianos/biosíntesis , Proteínas Bacterianas/inmunología , Vacunas Neumococicas/administración & dosificación , Neumonía Neumocócica/prevención & control , Streptococcus pneumoniae/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/genética , Administración Intranasal , Animales , Proteínas Bacterianas/administración & dosificación , Proteínas Bacterianas/genética , Toxinas Bacterianas/administración & dosificación , Toxinas Bacterianas/genética , Toxinas Bacterianas/inmunología , Enterotoxinas/administración & dosificación , Enterotoxinas/genética , Enterotoxinas/inmunología , Proteínas de Escherichia coli/administración & dosificación , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/inmunología , Femenino , Expresión Génica , Inmunidad Humoral/efectos de los fármacos , Inmunización , Inmunoglobulina G/biosíntesis , Inyecciones Intradérmicas , Ratones , Ratones Endogámicos BALB C , Nasofaringe/efectos de los fármacos , Nasofaringe/inmunología , Nasofaringe/microbiología , Neumonía Neumocócica/inmunología , Neumonía Neumocócica/microbiología , Neumonía Neumocócica/mortalidad , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/genética , Análisis de Supervivencia , Simbiosis/efectos de los fármacos , Vacunas ConjugadasRESUMEN
BACKGROUND: Group A streptococcus (GAS) commonly colonizes the oropharynx and nonintact skin. However, colonization has been little studied and the role of biofilm formation is unclear, as biofilm experiments to date have not been conducted under conditions that mimic the host environment. METHODS: In this study we grew GAS biofilms on human keratinocytes under various environmental conditions and used this model to evaluate colonization, invasive disease and natural transformation. RESULTS: GAS grown on epithelial cells, but not biofilms grown on abiotic surfaces, produced biofilms with characteristics similar to in vivo colonization. These biofilm bacteria showed a 100-fold higher bacterial burden of nasal-associated lymphoid tissue in mice than broth-grown bacteria, and were not virulent during septic infection, which was attributed in part to down-regulation of genes typically involved in localized and invasive disease. We also showed for the first time that GAS were naturally transformable when grown in biofilms and during colonization of NALT in vivo. CONCLUSIONS: These findings provide novel model systems to study biofilm formation of GAS in vitro and in vivo, suggest an important role for biofilm formation during GAS colonization, and provide an explanation for the known genome diversity within the GAS population.
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Biopelículas/crecimiento & desarrollo , Transferencia de Gen Horizontal , Streptococcus pyogenes/fisiología , Animales , Células Cultivadas , Humanos , Queratinocitos/microbiología , Tejido Linfoide/microbiología , Ratones , Ratones Endogámicos BALB C , Cavidad Nasal/microbiología , Streptococcus pyogenes/genética , Streptococcus pyogenes/crecimiento & desarrollo , Streptococcus pyogenes/patogenicidadRESUMEN
Both Streptococcus pyogenes and Streptococcus pneumoniae are widely thought to rapidly die outside the human host, losing infectivity following desiccation in the environment. However, to date, all literature investigating the infectivity of desiccated streptococci has used broth-grown, planktonic populations. In this study, we examined the impact of biofilm formation on environmental survival of clinical and laboratory isolates of S. pyogenes and S. pneumoniae as both organisms are thought to colonize the human host as biofilms. Results clearly demonstrate that while planktonic cells that are desiccated rapidly lose viability both on hands and abiotic surfaces, such as plastic, biofilm bacteria remain viable over extended periods of time outside the host and remain infectious in a murine colonization model. To explore the level and extent of streptococcal fomite contamination that children might be exposed to naturally, direct bacteriologic cultures of items in a day care center were conducted, which demonstrated high levels of viable streptococci of both species. These findings raise the possibility that streptococci may survive in the environment and be transferred from person to person via fomites contaminated with oropharyngeal secretions containing biofilm streptococci.
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Biopelículas/crecimiento & desarrollo , Fómites/microbiología , Streptococcus pneumoniae/crecimiento & desarrollo , Streptococcus pyogenes/crecimiento & desarrollo , Animales , Línea Celular Tumoral , Células Cultivadas , Femenino , Humanos , Ratones , Ratones Endogámicos BALB CRESUMEN
Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis.
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Biopelículas/crecimiento & desarrollo , Virus de la Influenza A , Infecciones por Orthomyxoviridae/complicaciones , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/metabolismo , Streptococcus pneumoniae/fisiología , Animales , Línea Celular Tumoral , Células Epiteliales/microbiología , Humanos , Ratones , Ratones Endogámicos BALB C , Infecciones Neumocócicas/complicaciones , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sepsis/microbiología , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidadRESUMEN
Background: People who inject drugs (PWID) are at high risk of severe wounds, invasive infections, and overdoses. To date, there are few data on the bacterial and chemical contaminants PWID are exposed to when using illicitly manufactured fentanyls and stimulants. Methods: Previously used injection drug use equipment was recovered in St Louis, Missouri, by harm reduction organizations over a 12-month period. Syringe residue was analyzed for bacterial contaminants by routine culturing followed by whole genome sequencing of single bacterial isolates. Chemical adulterants in syringe residue were identified by liquid chromatography-mass spectrometry. Results: Bacteria were cultured from 58.75% of 160 syringes analyzed. Polymicrobial growth was common and was observed in 23.75% of samples. Bacillus cereus was the most common pathogen present and was observed in 20.6% of syringe residues, followed closely by Staphylococcus aureus at 18.8%. One hundred syringes underwent mass spectrometry, which demonstrated that chemical adulterants were common and included caffeine, diphenhydramine, lidocaine, quinine, and xylazine. Conclusions: Analysis of syringe residue from discarded drug use equipment demonstrates both chemical and biological contaminants, including medically important pathogens and adulterants.
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Background: To end the HIV and hepatitis C virus (HCV) epidemics, people who use drugs (PWUD) need more opportunities for testing. While inpatient hospitalizations are an essential opportunity to test people who use drugs (PWUD) for HIV and HCV, there is limited research on rates of inpatient testing for HIV and HCV among PWUD. Methods: Eleven hospital sites were included in the study. Each site created a cohort of inpatient encounters associated with injection drug use. From these cohorts, we collected data on HCV and HIV testing rates and HIV testing consent policies from 65 276 PWUD hospitalizations. Results: Hospitals had average screening rates of 40% for HIV and 32% for HCV, with widespread heterogeneity in screening rates across facilities. State consent laws and opt-out testing policies were not associated with statistically significant differences in HIV screening rates. On average, hospitals that reflexed HCV viral load testing on HCV antibody testing did not have statistically significant differences in HCV viral load testing rates. We found suboptimal testing rates during inpatient encounters for PWUD. As treatment (HIV) and cure (HCV) are necessary to end these epidemics, we need to prioritize understanding and overcoming barriers to testing.
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To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets.
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Lípidos/fisiología , Proteínas de la Leche/metabolismo , Leche Humana/química , Streptococcus pneumoniae/fisiología , Biopelículas , Calcio/metabolismo , Muerte Celular , Humanos , Sodio/metabolismoRESUMEN
Importance: US primary care practitioners (PCPs) are the largest clinical workforce, but few provide addiction care. Primary care is a practical place to expand addiction services, including buprenorphine and harm reduction kits, yet the clinical outcomes and health care sector costs are unknown. Objective: To estimate the long-term clinical outcomes, costs, and cost-effectiveness of integrated buprenorphine and harm reduction kits in primary care for people who inject opioids. Design, Setting, and Participants: In this modeling study, the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death, was used to examine the following treatment strategies: (1) PCP services with external referral to addiction care (status quo), (2) PCP services plus onsite buprenorphine prescribing with referral to offsite harm reduction kits (BUP), and (3) PCP services plus onsite buprenorphine prescribing and harm reduction kits (BUP plus HR). Model inputs were derived from clinical trials and observational cohorts, and costs were discounted annually at 3%. The cost-effectiveness was evaluated over a lifetime from the modified health care sector perspective, and sensitivity analyses were performed to address uncertainty. Model simulation began January 1, 2021, and ran for the entire lifetime of the cohort. Main Outcomes and Measures: Life-years (LYs), hospitalizations, mortality from sequelae (overdose, severe skin and soft tissue infections, and endocarditis), costs, and incremental cost-effectiveness ratios (ICERs). Results: The simulated cohort included 2.25 million people and reflected the age and gender of US persons who inject opioids. Status quo resulted in 6.56 discounted LYs at a discounted cost of $203â¯500 per person (95% credible interval, $203â¯000-$222â¯000). Each strategy extended discounted life expectancy: BUP by 0.16 years and BUP plus HR by 0.17 years. Compared with status quo, BUP plus HR reduced sequelae-related mortality by 33%. The mean discounted lifetime cost per person of BUP and BUP plus HR were more than that of the status quo strategy. The dominating strategy was BUP plus HR. Compared with status quo, BUP plus HR was cost-effective (ICER, $34â¯400 per LY). During a 5-year time horizon, BUP plus HR cost an individual PCP practice approximately $13â¯000. Conclusions and Relevance: This modeling study of integrated addiction service in primary care found improved clinical outcomes and modestly increased costs. The integration of addiction service into primary care practices should be a health care system priority.
Asunto(s)
Analgésicos Opioides , Buprenorfina , Humanos , Análisis Costo-Beneficio , Analgésicos Opioides/uso terapéutico , Buprenorfina/uso terapéutico , Esperanza de Vida , Atención Primaria de SaludRESUMEN
Background: The rise in injection drug use (IDU) has led to an increase in drug-related infections. Harm reduction is an important strategy for preventing infections among people who inject drugs (PWID). We attempted to evaluate the harm reduction counseling that infectious diseases physicians provide to PWID presenting with infections. Methods: An electronic survey was distributed to physician members of the Emerging Infections Network to inquire about practices used when caring for patients with IDU-related infections. Results: In total, 534 ID physicians responded to the survey. Of those, 375 (70%) reported routinely caring for PWID. Most respondents report screening for human immunodeficiency virus (HIV) and viral hepatitis (98%) and discussing the risk of these infections (87%); 63% prescribe immunization against viral hepatitis, and 45% discuss HIV preexposure prophylaxis (PrEP). However, 55% of respondents (n = 205) reported not counseling patients on safer injection strategies. Common reasons for not counseling included limited time and a desire to emphasize antibiotic therapy/medical issues (62%), lack of training (55%), and believing that it would be better addressed by other services (47%). Among respondents who reported counseling PWID, most recommended abstinence from IDU (72%), handwashing and skin cleansing before injection (62%), and safe disposal of needles/drug equipment used before admission (54%). Conclusions: Almost all ID physicians report screening PWID for HIV and viral hepatitis and discussing the risks of these infections. Despite frequently encountering PWID, fewer than half of ID physicians provide safer injection advice. Opportunities exist to standardize harm reduction education, emphasizing safer injection practices in conjunction with other strategies to prevent infections (eg, HIV PrEP or hepatitis A virus/hepatitis B virus vaccination).
RESUMEN
The human nasopharynx is the main reservoir for Streptococcus pneumoniae (the pneumococcus) and the source for both horizontal spread and transition to infection. Some clinical evidence indicates that nasopharyngeal carriage is harder to eradicate with antibiotics than is pneumococcal invasive disease, which may suggest that colonizing pneumococci exist in biofilm communities that are more resistant to antibiotics. While pneumococcal biofilms have been observed during symptomatic infection, their role in colonization and the role of host factors in this process have been less studied. Here, we show for the first time that pneumococci form highly structured biofilm communities during colonization of the murine nasopharynx that display increased antibiotic resistance. Furthermore, pneumococcal biofilms grown on respiratory epithelial cells exhibited phenotypes similar to those observed during colonization in vivo, whereas abiotic surfaces produced less ordered and more antibiotic-sensitive biofilms. The importance of bacterial-epithelial cell interactions during biofilm formation was shown using both clinical strains with variable colonization efficacies and pneumococcal mutants with impaired colonization characteristics in vivo. In both cases, the ability of strains to form biofilms on epithelial cells directly correlated with their ability to colonize the nasopharynx in vivo, with colonization-deficient strains forming less structured and more antibiotic-sensitive biofilms on epithelial cells, an association that was lost when grown on abiotic surfaces. Thus, these studies emphasize the importance of host-bacterial interactions in pneumococcal biofilm formation and provide the first experimental data to explain the high resistance of pneumococcal colonization to eradication by antibiotics.
Asunto(s)
Biopelículas/crecimiento & desarrollo , Portador Sano/microbiología , Células Epiteliales/microbiología , Nasofaringe/microbiología , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/fisiología , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Adhesión Bacteriana , Biomasa , Portador Sano/tratamiento farmacológico , Línea Celular Tumoral , Células Cultivadas , Farmacorresistencia Bacteriana , Células Epiteliales/ultraestructura , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Rastreo , Infecciones Neumocócicas/tratamiento farmacológico , Mucosa Respiratoria/citología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/ultraestructuraRESUMEN
We interviewed persons who inject drugs (PWID) to understand perceptions of pre-exposure prophylaxis (PrEP) to prevent HIV infection. Knowledge of PrEP was poor. Patients felt that PrEP was for sexual intercourse rather than injection drug use, and PWID managed on medications for opioid use disorder felt that they had no need for PrEP.