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COVID-19, caused by SARS-CoV-2, is characterised by a broad spectrum of symptom severity that requires varying amounts of care according to the different stages of the disease. Intervening at the onset of mild to moderate COVID-19 symptoms in the outpatient setting would provide the opportunity to prevent progression to a more severe illness and long-term complications. As early disease symptoms variably reflect an underlying excessive inflammatory response to the viral infection, the use of anti-inflammatory drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs), in the initial outpatient stage of COVID-19 seems to be a valuable therapeutic strategy. A few observational studies have tested NSAIDs (especially relatively selective COX-2 inhibitors), often as part of multipharmacological protocols, for early outpatient treatment of COVID-19. The findings from these studies are promising and point to a crucial role of NSAIDs for the at-home management of people with initial COVID-19 symptoms.
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COVID-19 , Virosis , Humanos , SARS-CoV-2 , Antiinflamatorios/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéuticoRESUMEN
Background and Aim: While considerable success has been achieved in the management of patients hospitalized with severe coronavirus disease 2019 (COVID-19), far less progress has been made with early outpatient treatment. We assessed whether the implementation of a home treatment algorithm-designed based on a pathophysiologic and pharmacologic rationale-and including non-steroidal anti-inflammatory drugs, especially relatively selective cyclooxygenase-2 inhibitors and, when needed, corticosteroids, anticoagulants, oxygen therapy and antibiotics-at the very onset of mild COVID-19 symptoms could effectively reduce hospital admissions. Methods: This fully academic, matched-cohort study evaluated outcomes in 108 consecutive consenting patients with mild COVID-19, managed at home by their family doctors between January 2021 and May 2021, according to the proposed treatment algorithm and in 108 age-, sex-, and comorbidities-matched patients on other therapeutic schedules (ClinicalTrials.gov: NCT04854824). The primary outcome was COVID-19-related hospitalization. Analyses were by intention-to-treat. Results: One (0.9%) patient in the "recommended" cohort and 12 (11.1%) in the "control" cohort were admitted to hospital (P = 0.0136). The proposed algorithm reduced the cumulative length of hospital stays by 85% (from 141 to 19 days) as well as related costs (from 60.316 to 9.058). Only 9.8 patients needed to be treated with the recommended algorithm to prevent one hospitalization event. The rate of resolution of major symptoms was numerically-but not significantly-higher in the "recommended" than in the "control" cohort (97.2 vs. 93.5%, respectively; P = 0.322). Other symptoms lingered in a smaller proportion of patients in the "recommended" than in the "control" cohort (20.4 vs. 63.9%, respectively; P < 0.001), and for a shorter period. Conclusion: The adoption of the proposed outpatient treatment algorithm during the early, mild phase of COVID-19 reduced the incidence of subsequent hospitalization and related costs.
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BACKGROUND: Effective home treatment algorithms implemented based on a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalisation of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health system. METHODS: This academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians between October 2020 and January 2021 in Northern and Central Italy, according to the proposed recommendation algorithm, with outcomes for 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalisation. Analyses were by intention-to-treat. FINDINGS: All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the 'recommended schedule' cohort and 14 [7-30] days in the matched 'control' cohort (p = 0·033). Other symptoms persisted in a lower percentage of patients in the 'recommended' than in the 'control' cohort (23·3% versus 73·3%, respectively, p<0·0001) and for a shorter period (p = 0·0107). Two patients in the 'recommended' cohort were hospitalised compared to 13 (14·4%) controls (p = 0·0103). The prevention algorithm reduced the days and cumulative costs of hospitalisation by >90%. INTERPRETATION: Implementation of an early home treatment algorithm failed to accelerate recovery from major symptoms of COVID-19, but reduced the risk of hospitalisation and related treatment costs. Given the study design, additional research would be required to consolidate the proposed treatment recommendations. FUNDING: Fondazione Cav.Lav. Carlo Pesenti.
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The last decade has been characterized by the emergence of CA-MRSA strains associated with the production of Panton-Valentine leukocidin. We report a case of necrotizing pneumonia and septic shock caused by CA-MRSA, in which early recognition of the syndrome and appropriate treatment with two toxin-suppressing antibiotics improved the patient's outcome.
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Acetamidas/uso terapéutico , Antibacterianos/uso terapéutico , Clindamicina/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Oxazolidinonas/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Acetamidas/administración & dosificación , Acetamidas/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antifúngicos/uso terapéutico , Caspofungina , Clindamicina/administración & dosificación , Clindamicina/farmacología , Terapia Combinada , Infecciones Comunitarias Adquiridas/microbiología , Quimioterapia Combinada , Equinocandinas/uso terapéutico , Femenino , Hemofiltración , Humanos , Hidrocortisona/uso terapéutico , Linezolid , Lipopéptidos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Persona de Mediana Edad , Necrosis , Oxazolidinonas/administración & dosificación , Oxazolidinonas/farmacología , Terapia por Inhalación de Oxígeno , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/terapia , Aspergilosis Pulmonar/complicaciones , Aspergilosis Pulmonar/tratamiento farmacológico , Respiración Artificial , Choque Séptico/tratamiento farmacológico , Choque Séptico/etiología , Choque Séptico/terapia , Infecciones Estafilocócicas/microbiologíaRESUMEN
We report on a patient who presented at our hospital with fever, headache, neck pain, partial nuchal rigidity and decreased vision of the left eye. The clinical history, biochemical and instrumental exams performed suggested meningitis but the final hypothesis achieved was an unusual case of Neuro-Behcet-Disease (NBD) without orogenital ulcerations at presentation and with normal MRI findings, whose course was complicated by fatal cerebral venous sinus thrombosis and intracranial haemorrhage. The post-mortem results confirmed the diagnosis. This is a rare case confirmed by anatomo-pathological findings where NBD can present itself as an acute meningeal syndrome that mimics central nervous system infections, making diagnosis difficult and delaying treatment.
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Síndrome de Behçet/complicaciones , Trastornos Cerebrovasculares/etiología , Meningitis Aséptica/etiología , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/inmunología , Encéfalo/irrigación sanguínea , Encéfalo/patología , Edema Encefálico/etiología , Hemorragia Cerebral/etiología , Diagnóstico Diferencial , Resultado Fatal , Femenino , Antígenos HLA-B/análisis , Antígeno HLA-B51 , Humanos , Imagen por Resonancia Magnética , Meningitis Bacterianas/diagnóstico , Especificidad de Órganos , Trombosis de los Senos Intracraneales/etiología , Trombofilia/etiología , Vasculitis/etiologíaRESUMEN
Two travelers returning to Italy from southern Egypt were hospitalized with a fever of unknown origin. Test results showed infection with Alkhurma virus. The geographic distribution of this virus could be broader than previously thought.
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Virus de la Encefalitis Transmitidos por Garrapatas/clasificación , Enfermedad del Bosque de Kyasanur/diagnóstico , Animales , Secuencia de Bases , Mordeduras y Picaduras , Egipto , Virus de la Encefalitis Transmitidos por Garrapatas/genética , Virus de la Encefalitis Transmitidos por Garrapatas/aislamiento & purificación , Humanos , Italia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Factores de Riesgo , Viaje , Proteínas no Estructurales Virales/genéticaRESUMEN
BACKGROUND: The treatment of severe bloodstream infections (sepsis, endocarditis, and infections of vascular prostheses) caused by Gram-positive microorganisms is made even more difficult by the emergence of resistant strains. The introduction of new antibiotics with activity against these strains has created new opportunities, but many controversial issues remain. CONTROVERSIAL ISSUES: The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group - a panel of multidisciplinary experts - was to define recommendations for some controversial issues using an evidence-based and analytical approach. The controversial issues concerned the duration of therapy and role of aminoglycosides and teicoplanin in the treatment of Gram-positive bacterial endocarditis, the optimal use of the new antibiotics in the treatment of bloodstream infections caused by resistant Gram-positive strains, and the use of microbiological techniques (i.e., bactericidal serum testing and synergy testing) and of pharmacokinetic data (e.g., monitoring of plasma levels of antibiotics) in the treatment of difficult-to-treat Gram-positive bloodstream infections. METHODS: A systematic literature search of randomized controlled trials and/or non-randomized studies was performed mainly using the MEDLINE database. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle-Ottawa Quality Assessment Scale for non-randomized studies. The GRADE method for grading the quality of evidence and strength of recommendation was applied.
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Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/tratamiento farmacológico , Bacterias Grampositivas/efectos de los fármacos , Antibacterianos/farmacología , Bacteriemia/microbiología , Ensayos Clínicos como Asunto , Farmacorresistencia Bacteriana , Endocarditis Bacteriana/microbiología , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Infections are today by far the most common complication affecting patients with chronic kidney disease and particularly those undergoing chronic haemodialysis. Numerous antimicrobial-resistant pathogens have emerged among patients with chronic kidney disease. These patients are hospitalized with greater frequency than the general population and the number of hospitalizations has been shown to correlate with higher infection rates. This review will briefly discuss the most common infections in patients undergoing chronic haemodialysis, the clinical relevance of antimicrobial resistance in these patients, and their therapeutic options.
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Infecciones Bacterianas/epidemiología , Fallo Renal Crónico/terapia , Diálisis Renal , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Bacteriemia/microbiología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Proteínas Bacterianas/metabolismo , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/microbiología , Catéteres de Permanencia/efectos adversos , Comorbilidad , Farmacorresistencia Bacteriana Múltiple , Endocarditis Bacteriana/epidemiología , Endocarditis Bacteriana/etiología , Enterobacteriaceae/enzimología , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Enterococcus/aislamiento & purificación , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Huésped Inmunocomprometido , Fallo Renal Crónico/epidemiología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Resistencia a la Vancomicina , beta-Lactamasas/metabolismoAsunto(s)
Infecciones Bacterianas/diagnóstico , Pericarditis/microbiología , Amicacina/uso terapéutico , Infecciones Bacterianas/diagnóstico por imagen , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/cirugía , Ecocardiografía/métodos , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pericarditis/diagnóstico por imagen , Pericarditis/tratamiento farmacológico , Pericarditis/cirugía , Providencia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of the ADONE (ADherence to ONE pill) study was to verify the effect of a reduced number of pills on adherence and quality of life (QoL) in HIV-infected patients on highly active antiretroviral therapy (HAART). DESIGN: Prospective, multicenter, study. METHODS: Patients chronically treated with emtricitabine (FTC) + tenofovir (TDF) + efavirenz (EFV) or lamivudine (3TC) +TDF +EFV and with a HIV-RNA < 50 copies/mL were switched to the single-pill fixed-dose regimen (FDR) of FTC +TDF +EFV. Data were collected with SF-36 using visual analog scales. Results of the final (6 months) primary as-treated analysis are reported. RESULTS: 212 patients (77.4% males) of mean age 45.8 years were enrolled; 202 completed the study. One month post switch to FDR the adherence rate increased significantly to 96.1% from a baseline value of 93.8% (P < 0.01). The increase was steadily maintained throughout the study (96.2% at 6 months). QoL improved over time from 68.8% to 72.7% (P = 0.042) as well, and was significantly associated with the perception of health status, presence of adverse events (AEs) and number of reported AEs (P < 0.0001). QoL significantly influenced adherence (P < 0.0001). During FDR use the mean CD4 count increased from 556 to 605 cells/muL (P < 0.0001). At the end of follow-up 98% of patients maintained HIV-RNA level < 50 copies/mL and 100% <400 copies/mL. Four patients stopped therapy because they were lost to follow-up and 6 because of AEs (insomnia/nervousness 4, allergy 1, difficulties swallowing pills 1). CONCLUSION: By substituting a one-pill once-a-day HAART, we observed an improvement of both adherence and QoL while maintaining high virologic and immunologic efficacy. HAART simplicity is an added value that favors adherence and may improve long-term success.
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BACKGROUND: Antiviral drugs of the category of nucleoside reverse transcriptase inhibitors (NRTIs), largely used for the treatment of HIV infection, can have toxic effects on mitochondria. We performed a cross-sectional study on mitochondrial toxicity in a randomized group of patients belonging to a larger randomized study on different NRTI-based once-daily regimens by quantifying mitochondrial DNA (mtDNA), three different mitochondrial RNAs (mtRNAs) and functional parameters in highly purified peripheral CD4+ and CD8+ T-cells. METHODS: A total of 49 previously treatment-naive patients treated for a mean of 15 months with efavirenz plus didanosine plus lamivudine (group 1), or tenofovir disoproxil fumarate plus lamivudine (group 2), or didanosine plus abacavir (group 3) were considered. The groups were matched for sex, age, CDC classification, risk factor for HIV, nadir CD4+ T-cell count and baseline viral load. mtDNA and mtRNA were quantified by using real-time PCR assays. RESULTS: No patient showed any clinical symptom; however, the amount of mtDNA in CD4+ and CD8+ T-cells was significantly lower in groups 1 and 3; similarly, the expression of different mtRNAs in both CD4+ and CD8+ T-cells showed significant differences that were dependent upon the drug used. No differences were found in mitochondrial membrane potential and mitochondrial mass in peripheral lymphocytes. The amount of total HIV DNA in CD4+ T-cells did not differ among the groups, who displayed a similar immune reconstitution and control of the virus. CONCLUSIONS: An efficient didanosine-containing once-daily therapy can have more mitochondrial toxicity than regimens devoid of this drug.
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Infecciones por VIH/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa , Adenina/administración & dosificación , Adenina/efectos adversos , Adenina/análogos & derivados , Adulto , Alquinos , Terapia Antirretroviral Altamente Activa , Benzoxazinas/administración & dosificación , Benzoxazinas/efectos adversos , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/virología , Estudios Transversales , Ciclopropanos , ADN Mitocondrial/análisis , ADN Mitocondrial/genética , Didanosina/administración & dosificación , Didanosina/efectos adversos , Didesoxinucleósidos/administración & dosificación , Didesoxinucleósidos/efectos adversos , Esquema de Medicación , Femenino , VIH/genética , Infecciones por VIH/virología , Humanos , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Masculino , Mitocondrias/genética , Mitocondrias/virología , Organofosfonatos/administración & dosificación , Organofosfonatos/efectos adversos , ARN/análisis , ARN/genética , ARN Mitocondrial , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , TenofovirRESUMEN
BACKGROUND: Antibiotic prophylaxis of patients believed to be at a risk of developing infective endocarditis has been recently revisited with limited indications compared with the previous body of knowledge in use by the medical community. As a consequence, most of the healthcare specialists in cardiology and infectious diseases have doubts related to the enormous change that has been proposed. In this study, we report the results of an Italian consensus of experts in cardiology and infectious diseases, with the aim to offer a national document that illustrates the reasons for such a change through the review of the basis of infective endocarditis prophylaxis, the historical background, and the reasons for the change, providing practical conclusions and illustrating grey areas. METHODS: The main guidelines published on the topic of antibiotic prophylaxis for infective endocarditis were discussed as well as the risk of anaphylaxis. Overall, the group agreed that the evidence for prophylaxis is weak and limited to few case-control studies, expert opinion, clinical experience, and descriptive studies. RESULTS: The 'downgrading' of the indications for prophylaxis is mainly due to a cultural change and a more critical attitude towards available published data. Although the group acknowledge the critical view of the previously published guidelines, it seems to be more practical to consider the issue of prophylaxis without the evidence required by guidelines but rather as a consensus document based on the available data. CONCLUSION: Contemporary guidelines on infective endocarditis prophylaxis challenge previous recommendations based on a low level of evidence. The main recommendation of the study group is to underline that prophylaxis may often be based on adequate education without the administration of antibiotics, which only remains suggested, following the usual practice, in patients with heart diseases, when the risk of a complicated prognosis following infective endocarditis may be anticipated.
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Profilaxis Antibiótica/normas , Cardiología/tendencias , Endocarditis Bacteriana/prevención & control , Humanos , Italia , Guías de Práctica Clínica como Asunto , Riesgo , Sociedades Médicas , IncertidumbreAsunto(s)
Antibacterianos/uso terapéutico , Endocarditis Bacteriana/prevención & control , Guías de Práctica Clínica como Asunto , Animales , Profilaxis Antibiótica/métodos , Endocarditis Bacteriana/epidemiología , Endocarditis Bacteriana/etiología , Endocarditis Bacteriana/mortalidad , Medicina Basada en la Evidencia , Humanos , Italia/epidemiología , Guías de Práctica Clínica como Asunto/normas , Medición de Riesgo , Factores de Riesgo , Sociedades MédicasRESUMEN
The recent origin and great evolutionary potential of HIV imply that the virulence of the virus might still be changing, which could greatly affect the future of the pandemic. However, previous studies of time trends of HIV virulence have yielded conflicting results. Here we used an established methodology to assess time trends in the severity (virulence) of untreated HIV infections in a large Italian cohort. We characterized clinical virulence by the decline slope of the CD4 count (n = 1423 patients) and the viral setpoint (n = 785 patients) in untreated patients with sufficient data points. We used linear regression models to detect correlations between the date of diagnosis (ranging 1984-2006) and the virulence markers, controlling for gender, exposure category, age, and CD4 count at entry. The decline slope of the CD4 count and the viral setpoint displayed highly significant correlation with the date of diagnosis pointing in the direction of increasing virulence. A detailed analysis of riskgroups revealed that the epidemics of intravenous drug users started with an apparently less virulent virus, but experienced the strongest trend towards steeper CD4 decline among the major exposure categories. While our study did not allow us to exclude the effect of potential time trends in host factors, our findings are consistent with the hypothesis of increasing HIV virulence. Importantly, the use of an established methodology allowed for a comparison with earlier results, which confirmed that genuine differences exist in the time trends of HIV virulence between different epidemics. We thus conclude that there is not a single global trend of HIV virulence, and results obtained in one epidemic cannot be extrapolated to others. Comparison of discordant patterns between riskgroups and epidemics hints at a converging trend, which might indicate that an optimal level of virulence might exist for the virus.
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Infecciones por VIH/virología , VIH/patogenicidad , Virulencia/genética , Evolución Biológica , Recuento de Linfocito CD4 , Brotes de Enfermedades , Infecciones por VIH/patología , Humanos , Italia/epidemiología , Modelos Lineales , Métodos , Riesgo , Factores de TiempoRESUMEN
Candida species are an uncommon cause of infective endocarditis (IE). Given the rarity of this infection, the epidemiology, prognosis, and optimal therapy of Candida IE are poorly defined. We conducted a prospective, observational study at 18 medical centers in Italy, including all consecutive patients with a definite diagnosis of IE admitted from January 2004 through December 2007.A Candida species was the causative organism in 8 cases of prosthetic valve endocarditis (PVE), 5 cases of native valve endocarditis (NVE), 1 case of pacemaker endocarditis, and 1 case of left ventricular patch infection. Candida species accounted for 1.8% of total cases, and for 3.4% of PVE cases. Most patients (86.6%) had a health care-associated infection. PVE associated with a health care contact occurred after a median of 225 days from valve implantation. Ten patients (66.6%) were treated with caspofungin alone or in combination with other antifungal drugs. The overall mortality rate was 46.6%. Mortality was higher in patients with PVE (5 of 8 cases, 62.5%) than in patients with NVE (2 of 5 patients, 40%). A better outcome was observed in patients treated with a combined medical and surgical therapy.Candida IE should be classified as an emerging infectious disease, usually involving patients with intravascular prosthetic devices, and associated with substantial related morbidity and mortality. Candida PVE usually is a late-onset disease, which becomes clinically evident even several months after an initial episode of transient candidemia.
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Candida/aislamiento & purificación , Candidiasis/microbiología , Endocarditis/microbiología , Prótesis Valvulares Cardíacas/microbiología , Infecciones Relacionadas con Prótesis/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Candida/clasificación , Candidiasis/tratamiento farmacológico , Candidiasis/epidemiología , Caspofungina , Niño , Preescolar , Equinocandinas/uso terapéutico , Endocarditis/tratamiento farmacológico , Endocarditis/epidemiología , Femenino , Prótesis Valvulares Cardíacas/efectos adversos , Humanos , Italia/epidemiología , Lipopéptidos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The clinical profile and outcome of nosocomial and non-nosocomial health care-associated native valve endocarditis are not well defined. OBJECTIVE: To compare the characteristics and outcomes of community-associated and nosocomial and non-nosocomial health care-associated native valve endocarditis. DESIGN: Prospective cohort study. SETTING: 61 hospitals in 28 countries. PATIENTS: Patients with definite native valve endocarditis and no history of injection drug use who were enrolled in the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) from June 2000 to August 2005. MEASUREMENTS: Clinical and echocardiographic findings, microbiology, complications, and mortality. RESULTS: Health care-associated native valve endocarditis was present in 557 (34%) of 1622 patients (303 with nosocomial infection [54%] and 254 with non-nosocomial infection [46%]). Staphylococcus aureus was the most common cause of health care-associated infection (nosocomial, 47%; non-nosocomial, 42%; P = 0.30); a high proportion of patients had methicillin-resistant S. aureus (nosocomial, 57%; non-nosocomial, 41%; P = 0.014). Fewer patients with health care-associated native valve endocarditis had cardiac surgery (41% vs. 51% of community-associated cases; P < 0.001), but more of the former patients died (25% vs. 13%; P < 0.001). Multivariable analysis confirmed greater mortality associated with health care-associated native valve endocarditis (incidence risk ratio, 1.28 [95% CI, 1.02 to 1.59]). LIMITATIONS: Patients were treated at hospitals with cardiac surgery programs. The results may not be generalizable to patients receiving care in other types of facilities or to those with prosthetic valves or past injection drug use. CONCLUSION: More than one third of cases of native valve endocarditis in non-injection drug users involve contact with health care, and non-nosocomial infection is common, especially in the United States. Clinicians should recognize that outpatients with extensive out-of-hospital health care contacts who develop endocarditis have clinical characteristics and outcomes similar to those of patients with nosocomial infection. PRIMARY FUNDING SOURCE: None.
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Atención Ambulatoria , Endocarditis Bacteriana/epidemiología , Adulto , Anciano , Infecciones Comunitarias Adquiridas/diagnóstico por imagen , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/diagnóstico por imagen , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Endocarditis Bacteriana/diagnóstico por imagen , Endocarditis Bacteriana/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal/efectos adversos , Factores de Riesgo , Resultado del Tratamiento , UltrasonografíaRESUMEN
OBJECTIVE: To compare continuous HAART with a CD4 cell-driven scheduled treatment interruption (STI) strategy. METHODS: LOng Term Treatment Interruption study is a randomized, controlled, prospective trial. Patients with CD4 cell counts more than 700 cells/microl were eligible, and the immunologic threshold to resume HAART was 350 cells/microl. The primary end point was the development of an opportunistic disease, death from any cause or the occurrence of diseases, other than opportunistic, requiring hospital admission. Secondary end points were major adverse effects, virologic failures and therapeutic costs. RESULTS: Three hundred and twenty-nine patients were randomized 1: 1. Total follow-up was 1388 person-years (mean 4.2 years). Patients in the STI group stopped therapy for a total of 241 STI cycles, their mean off-therapy period was 65.3% of the follow-up. The primary end point occurred in 12.1% of patients on STI and in 11.6% of controls [odds ratio 1.05; 95% confidence interval 0.54-2.05]. A higher proportion of patients in the STI arm were diagnosed with pneumonia (P = 0.037), whereas clinical events influencing the cardiovascular risk of patients were significantly (P < 0.0001) more frequent among controls. Eight patients (4.8%) in the STI group and 11 (6.7%) controls developed viral resistance [odds ratio 0.79, 95% confidence interval 0.27-1.81]. The mean daily therapeutic cost was 20.29 euro for controls and dropped to 9.07 euro in the STI arm (P < 0.0001). CONCLUSION: The two strategies may be considered clinically equivalent. CD4 cell-guided STIs seem a possible alternative for chronically infected individuals responding to HAART provided that CD4 cell decrements would be steadily maintained above a safe threshold.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Recuento de Linfocito CD4/métodos , Linfocitos T CD4-Positivos/virología , Esquema de Medicación , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Masculino , Estudios Prospectivos , ARN Viral/genética , ARN Viral/inmunología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Adequate antiretroviral exposure during pregnancy is critical to prevent the vertical transmission of HIV and for maternal health. Pregnancy can alter drug kinetics. We assessed the pharmacokinetics of atazanavir/ritonavir (300/100 mg a day) during pregnancy. METHODS: An intensive steady-state 24-h pharmacokinetic profile of atazanavir was performed in the third trimester of pregnancy and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured atazanavir by reverse-phase high-performance liquid chromatography. RESULTS: Seventeen women completed the study. Antepartum, the atazanavir geometric mean area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 28 510 ng.h/l, the maximum observed plasma concentration (Cmax) was 2 591 ng/ml and the 24-h postdose concentration (Ctrough) was 486 ng/ml. The same postpartum parameters were 30 465 ng.h/l, 2 878 ng/ml and 514 ng/ml, respectively. The antepartum to postpartum ratio for AUC0-24 was 0.94 and for Ctrough was 0.96, indicating equivalence, whereas Cmax values were slightly although not significantly lower. The ratio of cord blood/maternal atazanavir concentration in 14 paired samples was 0.13. CONCLUSION: Atazanavir exposure during the third trimester of pregnancy is similar to that observed in the non-pregnant period. Over the whole dosing interval, therapeutic drug concentrations well above the wild-type HIV 90% inhibitory concentration are maintained. Atazanavir crosses the placenta, potentially providing further protection for the newborn. As pregnancy does not appear to alter atazanavir exposure, no dose adjustment is required in pregnant women. Results suggest that atazanavir is a reasonable component of HAART during pregnancy.