RESUMEN
Staphylococcus aureus (S. aureus) is a challenging bacterial pathogen which can cause a range of diseases, from mild skin infections, to more serious and invasive disease including deep or organ space surgical site infections, life-threatening bacteremia, and sepsis. S. aureus rapidly develops resistance to antibiotic treatments. Despite current infection control measures, the burden of disease remains high. The most advanced vaccine in clinical development is a 4 antigen S. aureus vaccine (SA4Ag) candidate that is being evaluated in a phase 2b/3 efficacy study in patients undergoing elective spinal fusion surgery (STaphylococcus aureus suRgical Inpatient Vaccine Efficacy [STRIVE]). SA4Ag has been shown in early phase clinical trials to be generally safe and well tolerated, and to induce high levels of bactericidal antibodies in healthy adults. In this review we discuss the design of SA4Ag, as well as the proposed clinical development plan supporting licensure of SA4Ag for the prevention of invasive disease caused by S. aureus in elective orthopedic surgical populations. We also explore the rationale for the generalizability of the results of the STRIVE efficacy study (patients undergoing elective open posterior multilevel instrumented spinal fusion surgery) to a broad elective orthopedic surgery population due to the common pathophysiology of invasive S. aureus disease and commonalties of patient and procedural risk factors for developing postoperative S. aureus surgical site infections.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Infecciones Estafilocócicas/prevención & control , Vacunas Estafilocócicas/uso terapéutico , Infección de la Herida Quirúrgica/prevención & control , Antígenos Bacterianos/administración & dosificación , Bacteriemia/prevención & control , Ensayos Clínicos como Asunto , Procedimientos Quirúrgicos Electivos , Humanos , Procedimientos Ortopédicos , Staphylococcus aureus , Infección de la Herida Quirúrgica/microbiologíaRESUMEN
BACKGROUND: Staphylococcus aureus surgical-site infections (SSIs) are a major cause of poor health outcomes, including mortality, across surgical specialties. Despite current advances as a result of preventive interventions, the disease burden of S. aureus SSI remains high, and increasing antibiotic resistance continues to be a concern. Prophylactic S. aureus vaccines may represent an opportunity to prevent SSI. METHODS: A review of SSI pathophysiology was undertaken in the context of evaluating new approaches to developing a prophylactic vaccine to prevent S. aureus SSI. RESULTS: A prophylactic vaccine ideally would provide protective immunity at the time of the surgical incision to prevent initiation and progression of infection. Although the pathogenicity of S. aureus is attributed to many virulence factors, previous attempts to develop S. aureus vaccines targeted only a single virulence mechanism. The field has now moved towards multiple-antigen vaccine strategies, and promising results have been observed in early-phase clinical studies that supported the recent initiation of an efficacy trial to prevent SSI. CONCLUSION: There is an unmet medical need for novel S. aureus SSI prevention measures. Advances in understanding of S. aureus SSI pathophysiology could lead to the development of effective and safe prophylactic multiple-antigen vaccines to prevent S. aureus SSI.
Asunto(s)
Infecciones Estafilocócicas/prevención & control , Vacunas Estafilocócicas/uso terapéutico , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/prevención & control , Profilaxis Antibiótica , Ensayos Clínicos como Asunto , Farmacorresistencia Bacteriana , Humanos , Control de Infecciones/métodos , Staphylococcus aureus/patogenicidadRESUMEN
BACKGROUND: Based on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60-64 years of age have been published. The same study also included a cohort of adults aged 18-49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18-49 years of age compared with adults 60-64 years of age for whom PCV13 is approved. METHODS: Adults naive to PPSV23 were grouped by age into 2 cohorts: 18-49 years (n=899; further stratified by age into 3 subgroups 18-29, 30-39, and 40-49 years) and 60-64 years (n=417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated. RESULTS: In adults aged 18-49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60-64 years. Immune responses were highest in the youngest age subgroup (18-29 years). Local reactions and systemic events were more common in adults 18-49 years compared with 60-64 years and were self-limited. CONCLUSION: Immune responses to PCV13 are robust in adults ≥18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections.
Asunto(s)
Vacunas Neumococicas/efectos adversos , Vacunas Neumococicas/inmunología , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Estudios de Cohortes , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Proteínas Opsoninas/sangre , Fagocitosis , Vacunas Neumococicas/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
SETTING: Urban inner city human immunodeficiency virus (HIV) clinic. OBJECTIVE: To evaluate tuberculin skin testing (TST) and QuantiFERON-TB Gold (QFT-G) testing in an HIV-infected population relative to the presence of risk factors for latent tuberculosis infection (LTBI). DESIGN: Cross-sectional analysis of the response of a whole blood gamma interferon release assay to early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) antigens and TST relative to known risk factors for LTBI. RESULTS: Of 207 subjects enrolled, four were excluded due to missing data and three specimens yielded discordant results. Ten specimens were indeterminate due to inadequate response to mitogen. All indeterminate results occurred in subjects with CD(4) counts <200 cells/mm(3). Eleven QFT-G results and 13 TST results were positive. The concordance between TST and QFT-G was poor (kappa 0.38). QFT-G results were more likely than TST to be associated with risk factors for LTBI. CONCLUSIONS: QFT-G, but not TST, showed a statistically significant association between the number of risk factors for LTBI and a positive result (OR 1.6). QFT-G testing may be more useful than TST in individuals with HIV infection.
Asunto(s)
Infecciones por VIH/complicaciones , Tuberculosis/complicaciones , Tuberculosis/diagnóstico , Adulto , Anciano , Recuento de Linfocito CD4 , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Closed circular (cc) forms of extrachromosomal HIV DNA are detected in patients with high viral loads; however, it is unclear whether these forms remain if virus replication is suppressed to undetectable levels by combination antiretroviral therapy. A nested primer polymerase chain reaction amplification assay was used to detect the presence of ccDNA containing two long terminal repeat sequences (2-LTR) in PBMC of patients with low or undetectable plasma HIV RNA. Fifty percent of patients with plasma RNA levels <50 copies/ml of blood had detectable 2-LTR DNA. Sequencing of the products identified normal LTR--LTR junctions in the minority of cases with the majority containing anomalies including deletions and insertions. The persistence of HIV ccDNA in patients with no detectable plasma RNA could be consistent with ongoing de novo infection of dividing cells or with stability of this form of DNA in nondividing cells.
Asunto(s)
ADN Circular/genética , ADN Viral/genética , Infecciones por VIH/virología , Duplicado del Terminal Largo de VIH/genética , Leucocitos Mononucleares/virología , ARN Viral/sangre , Secuencia de Bases , VIH-1/genética , VIH-1/fisiología , Humanos , Datos de Secuencia Molecular , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: We attempted to determine the prevalence and predictors of skin disease in a cohort of women with and at risk for HIV infection. METHODS: We analyzed baseline data from a multicenter longitudinal study of HIV infection in women. RESULTS: A total of 2018 HIV-infected women and 557 HIV-uninfected women were included in this analysis. Skin abnormalities were reported more frequently among HIV-infected than uninfected women (63% vs 44%, respectively; odds ratio [OR] 2.10; 95% confidence interval [95% CI], 1.74-2.54). Infected women were also more likely to have more than 2 skin diagnoses (OR, 3.27; 95% CI, 1.31-8.16). Folliculitis, seborrheic dermatitis, herpes zoster, and onychomycosis were more common among HIV-infected women (P < .05). Independent predictors of abnormal findings on skin examination in the infected women were African American race (OR, 1.38; 95% CI, 1.07-1.77), injection drug use (OR, 2.74; 95% CI, 2.11-3.57), CD4(+) count less than 50 (OR, 1.68; 95% CI, 1.17-2.42), and high viral loads (100,000-499,999 = OR, 1.77; 95% CI, 1.32-2.37; > 499,999 = OR, 2.15; 95% CI, 1.42-3.27). CONCLUSION: HIV infection was associated with a greater number of skin abnormalities and with specific dermatologic diagnoses. Skin abnormalities were also more common among women with CD4(+) cell depletion or higher viral load.
Asunto(s)
Infecciones por VIH/complicaciones , Enfermedades de la Piel/complicaciones , Enfermedades de la Piel/epidemiología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Prevalencia , Estados Unidos/epidemiología , Carga Viral , Salud de la MujerRESUMEN
OBJECTIVE: To document the sexual and contraceptive practices of women with HIV infection or who are at risk for infection. DESIGN: Data on the baseline behaviors of 561 HIV-negative and 2040 HIV-positive women were collected as part of the Women's Interagency HIV Study (WIHS). WIHS is a multisite, longitudinal study following the natural history of HIV infection among women in the United States. METHODS: Each participant contributed an interviewer administered, self-report interview including questions on sexual and contraceptive behavior. RESULTS: Women with HIV were less likely to report heterosexual activity in the previous 6 months (65% HIV-positive, 76% HIV-negative). Among sexually active women, there were no differences in the proportion of those reporting vaginal (97% HIV-positive, 98% HIV-negative) or anal sex (12% HIV-positive, 10% HIV-negative), although women with HIV were less likely to report cunnilingus (41% HIV-positive, 70% HIV-negative) and fellatio (48% HIV-positive, 57% HIV-negative). Of women with HIV, 63% always used condoms during vaginal sex (versus 28% HIV-negative), with lower rates reported during other sexual activities. Crack, cocaine, or injecting drug use, reported by 27% of HIV-positive and 35% of HIV-negative women, was associated with inconsistent condom use, independent of serostatus. HIV-positive women who reported using condoms and another contraception method were less consistent condom users (57% consistent versus 67%). CONCLUSIONS: The prevalence of sexual risk behavior in this sample suggests that, although women with HIV exhibit lower levels of sexual risk behavior than uninfected women, many have not been successfully reached with regard to implementing safer behaviors. These findings have implications for more widespread and effective behavioral intervention efforts.
Asunto(s)
Anticoncepción , Infecciones por VIH/psicología , Conducta Sexual , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Condones , Estudios Transversales , Femenino , Infecciones por VIH/epidemiología , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
In a very short period of time, availability of antiretroviral drugs has increased from one drug with very modest activity to 12 approved drugs with remarkable potency, particularly when used in combination. The additional availability of absolutely quantitative assays with a broad dynamic range to measure plasma HIV-1 RNA has dramatically changed the evaluation of these new antivirals and the management of patients infected with the human immunodeficiency virus (HIV). The approved antiretroviral drugs represent three novel classes including nucleoside analog reverse transcriptase inhibitors, non-nucleoside analog reverse transcriptase inhibitors as well as protease inhibitors. Clinical trials evaluating different combinations of these drugs have resulted in the generation of some basic guidelines for their appropriate use. These guidelines focus on using these drugs in complex, multidrug regimens with the ultimate goal to keep the viral burden, as measured by plasma viral RNA levels, as low as possible and for as long as possible on a drug regimen that is compatible with long-term tolerance and compliance. To maximize the potential of these new drugs and to avoid significant associated toxicities and drug interactions, the treating physician must be completely aware of the pharmacokinetics and unique antiviral properties of these drugs. This review focuses on these unique properties as well as provides general guidelines for their appropriate use.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Ensayos Clínicos como Asunto , Guías como Asunto , Humanos , PronósticoAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA , Tuberculosis/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Infecciones Oportunistas Relacionadas con el SIDA/virología , Antituberculosos/uso terapéutico , Quimioterapia Combinada , Humanos , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Tuberculosis/virologíaRESUMEN
Twenty-seven episodes of Pseudomonas aeruginosa bacteremia in 21 patients with AIDS were evaluated at the Mount Sinai Medical Center in 1987-1992. Of 21 primary episodes, 12 were acquired in the community, 8 were nosocomial, and one was acquired in a nursing home. Sources of bacteremia (i.e., sites of infection; n = 30) included the lungs (12 cases) an indwelling vascular catheter (9), and the upper respiratory tract (5, including 2 cases of sinusitis, 2 cases of malignant external otitis, and 1 case of epiglottis/pharyngeal cellulitis); in 4 cases the source was unknown. White blood cell counts ranged from 0.1 to 26.2 (mean, 4.32) x 10(3)/mm3; in 19 of 26 cases, the absolute neutrophil count was > 1 x 10(3)/mm3. With the exclusion of primary episodes of bacteremia that resulted in death, the rate of relapse was 33.3% (5 of 15 cases). Mortality for the 25 evaluable episodes of bacteremia was 40% (32% for primary infection and 80% for relapse; P = .06); 52.6% of evaluable patients (10 of 19) ultimately died of P. aeruginosa bacteremia. The institution of appropriate therapy at presentation did not positively affect outcome. Rates of response were higher among episodes treated with a drug combination (an antipseudomonal beta-lactam or monobactam antibiotic plus an aminoglycoside) than among those treated with a single agent (P = .036).
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Bacteriemia/microbiología , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Antibacterianos , Bacteriemia/tratamiento farmacológico , Bacteriemia/mortalidad , Quimioterapia Combinada/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/mortalidad , RecurrenciaAsunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Infecciones por VIH/complicaciones , Pentamidina/uso terapéutico , Neumonía por Pneumocystis/prevención & control , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Infecciones Bacterianas/complicaciones , Estudios de Cohortes , Femenino , Humanos , Masculino , Neumonía por Pneumocystis/complicacionesRESUMEN
The case of a 36-year-old man with the acquired immunodeficiency syndrome (AIDS) and a renal aspergilloma is reported. Aspergillus infections are uncommon in patients with AIDS. Isolated renal aspergillomas have rarely been reported in the non-AIDS population (14 cases) and have never been reported in a patient with AIDS. The patient we describe was clinically symptomatic and initially treated medically, but he did not respond to intravenous amphotericin and oral itraconazole. He eventually required nephrectomy; however, there was local recurrence of the aspergilloma postoperatively. We comment on some issues in the spectrum of Aspergillus infections in AIDS and review the literature on the manifestations and treatment of renal aspergillomas.