RESUMEN
BACKGROUND: Antimicrobial stewardship (AMS) teams are responsible for performing an AMS programme in their hospitals that aims to improve the quality of antibiotic use. Measuring the quality of antimicrobial use is a core task of a stewardship team. Measurement provides insight into the current quality of antibiotic use and allows for the establishment of goals for improvement. Yet, a practical description of how such a quality measurement using quality indicators (QIs) should be performed is lacking. OBJECTIVES: To provide practical guidance on how a stewardship team can use QIs to measure the quality of antibiotic use in their hospital and identify targets for improvement. SOURCES: General principles from implementation science, peer-reviewed publications, and experience from clinicians and researchers with AMS experience. CONTENT: We provide step-by-step guidance on how AMS teams can use QIs to measure the quality of antibiotic use. The principles behind each step are explained and illustrated with the description and results of an audit of patients receiving outpatient parenteral antimicrobial therapy in four Dutch hospitals. IMPLICATIONS: Improving the quality of antibiotic use is impossible without first gaining insight into that quality by performing a measurement with validated QIs. This step-by-step practice example of how to use quality indicators in a hospital will help AMS teams to identify targets for improvement. This enables them to perform their AMS programme more effectively and efficiently.
Asunto(s)
Antiinfecciosos , Programas de Optimización del Uso de los Antimicrobianos , Humanos , Indicadores de Calidad de la Atención de Salud , Pacientes Ambulatorios , Antiinfecciosos/uso terapéutico , Antibacterianos/uso terapéutico , HospitalesRESUMEN
Influenza-specific cell-mediated immune (CMI) responses can protect from influenza, but may be decreased in CVID-patients since defects in CMI responses have been demonstrated in CVID-patients. Therefore CMI responses were evaluated in 15 CVID-patients and 15 matched healthy controls (HC) by determining frequencies of interferon (IFN)γ-producing PBMC, and frequencies of IFNγ-, interleukin (IL)-2- and tumour necrosis factor (TNF)α-producing CD4+ and CD8+ T-cells before and after influenza vaccination using IFNγ enzyme-linked immunospot (IFNγ-ELISpot) and flow cytometry. Humoral responses were determined using haemagglutination inhibition assay. In CVID-patients the number of spotforming PBMC in the IFNγ-ELISpot did not increase following influenza vaccination, in contrast to HC. In flow cytometry, the frequencies of IFNγ-producing T-cells decreased in CVID-patients after influenza vaccination, while in HC the frequencies of IFNγ-production flow cytometry increased. Concluding, CMI responses following influenza vaccination are hampered in CVID-patients compared to HC. Additional protective strategies against influenza other than vaccination are warranted.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Inmunodeficiencia Variable Común/inmunología , Inmunidad Celular , Vacunas contra la Influenza/inmunología , Vacunación , Adulto , Anciano , Anticuerpos Antivirales/biosíntesis , Relación CD4-CD8 , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Ensayo de Immunospot Ligado a Enzimas , Femenino , Citometría de Flujo , Pruebas de Inhibición de Hemaglutinación , Humanos , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/biosíntesis , Vacunas de Productos Inactivados/inmunología , Vacunas de Subunidad/inmunologíaRESUMEN
Yearly influenza vaccination is recommended for patients with humoral primary immunodeficiency (hPID). However, humoral responses following vaccination can be expected to be reduced in these patients. The efficacy of influenza vaccination in patients with hPID, anti-influenza antibody responses was assessed in 26 patients with hPID and 26 matched healthy controls (HC) using hemagglutination inhibition assay. Following vaccination, geometric mean titers (GMT) significantly increased for all influenza strains in the HC group, but only for A/H1N1 in the patient group. Fold increase in anti-influenza titer and seroprotection rates were lower for patients than for HC for A/H3N2 and A/H1N1, leading to postvaccination titer > or =40 in only 29% and 83% vs. 77% and 100%, respectively. Previous vaccination in patients and treatment with IVIg did not result in a higher rate of postvaccination titer > or =40. In conclusion, patients with hPID show hardly any humoral response following influenza vaccination.
Asunto(s)
Anticuerpos Antivirales/sangre , Síndromes de Inmunodeficiencia/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Vacunas contra la Influenza/efectos adversos , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Vacunas de Subunidad/inmunologíaRESUMEN
The glutamate-rich protein (GLURP) of P. falciparum is the target of cytophilic antibodies which are significantly associated with protection against clinical malaria. A phase 1 clinical trial was conducted in healthy adult volunteers with the long synthetic peptide (LSP) GLURP(85-213) combined with either Aluminum Hydroxide (Alum, 18 volunteers) or Montanide ISA 720 (ISA, 18 volunteers) as adjuvants. Immunizations with 10, 30 or 100 microg GLURP(85-213) were administered subcutaneously at days 0, 30, and 120. Adverse events occurred more frequently with increasing dosage of GLURP(85-213) LSP and were more prevalent in the ISA group. Serious vaccine-related adverse events were not observed. The vaccine induced dose-dependent cellular and humoral immune responses, with high levels of (mainly cytophilic IgG1) antibodies that recognize parasites by immunofluorescence (IFA). Plasma samples collected 30 days after the last immunization induced a dose-dependent inhibition of parasite growth in vitro in the presence of monocytes. In conclusion, immunizations with GLURP(85-213) LSP formulations induce adverse events but can be administered safely, generating antibodies with capacity to mediate growth-inhibitory activity against P. falciparum in vitro.
Asunto(s)
Anticuerpos Antiprotozoarios/biosíntesis , Vacunas contra la Malaria/administración & dosificación , Malaria Falciparum/inmunología , Malaria Falciparum/prevención & control , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , Adolescente , Adulto , Animales , Anticuerpos Antiprotozoarios/inmunología , Relación Dosis-Respuesta Inmunológica , Femenino , Humanos , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/inmunología , Vacunas contra la Malaria/efectos adversos , Vacunas contra la Malaria/inmunología , Malaria Falciparum/parasitología , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Fragmentos de Péptidos/inmunología , Plasmodium falciparum/crecimiento & desarrollo , Proteínas Protozoarias/metabolismoRESUMEN
Clinical trials are an essential step in evaluation of safety and efficacy of malaria vaccines, and human experimental malaria infections have been used for evaluation of protective immunity of Plasmodium falciparum malaria. In this study, a quantitative real-time polymerase chain reaction was used to measure P. falciparum malaria parasitemia in non-immune volunteers who had been experimentally infected by mosquito bites. Based on a remarkably small variation in the kinetics of parasitemia, a statistical model was developed that provides detailed estimates of pre-patent periods and parasite multiplication of blood stages. Using this model, we could predict results on vaccine efficacy for 1) pre-erythrocytic vaccines in the asymptomatic incubation period and 2) asexual stage vaccines after a limited number of multiplication cycles. The model shows that stage-specific vaccines even with limited efficacy can be highly efficacious when used in combination. This P. falciparum challenge method significantly adds to the potential to evaluate efficacy of candidate malaria vaccines before going into field trials.
Asunto(s)
Vacunas contra la Malaria , Malaria Falciparum/prevención & control , Modelos Biológicos , Parasitemia/parasitología , Plasmodium falciparum/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Animales , Anopheles/parasitología , Sangre/parasitología , Ensayos Clínicos Fase II como Asunto , Humanos , Vacunas contra la Malaria/administración & dosificación , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Plasmodium falciparum/crecimiento & desarrollo , Proyectos de InvestigaciónRESUMEN
OBJECTIVE: This study evaluated the effect of multiple-dose efavirenz on the steady-state pharmacokinetics of the combination of indinavir (800 mg) and low-dose ritonavir (100 mg) twice a day, in which ritonavir is used to increase indinavir plasma concentrations. METHODS: Eighteen healthy male volunteers participated in this multiple-dose, 1-arm, 2-period interaction study. They took a combination of 800 mg indinavir and 100 mg ritonavir with food for 15 days. From days 15 to 29, a once-daily administration of 600 mg efavirenz was added to the combination. Pharmacokinetics of indinavir and ritonavir on days 15 and 29 were compared. RESULTS: Fourteen volunteers completed the study. The addition of efavirenz resulted in significant reductions (P <.01) in indinavir area under the curve (AUC, -25%), trough concentration (C(min), -50%), and maximum concentration (C(max), -17%). All indinavir C(min) levels on day 29 remained equivalent to or above the mean C(min) value described for the regimen of 800 mg indinavir three times a day, without ritonavir (0.15 mg/L). Changes in ritonavir AUC, C(min), and C(max) were -36%, -39%, and -34%, respectively. Pharmacokinetics of efavirenz on day 29 were comparable with published data. CONCLUSIONS: The addition of efavirenz to a combination of 800 mg indinavir and 100 mg ritonavir twice daily results in significant decreases in AUC, C(max), and especially C(min) of indinavir. The dose of indinavir or ritonavir should be increased to maintain similar indinavir drug levels after addition of efavirenz to the indinavir-ritonavir combination. Dose modifications may not be needed in antiretroviral-naive human immunodeficiency virus-infected patients if the reference C(min) of the regimen of 800 mg indinavir 3 times a day is considered to be adequate.