Impact of 18F-FDG-PET/CT on the management of Staphylococcus aureus bacteraemia: A retrospective observational study / Impacto de la 18F-FDG-PET/TC en el manejo de la bacteriemia por Staphylococcus aureus: resultados de un estudio retrospectivo observacional

Objectives: To assess the impact of 18F-FDG-PET/CT on the diagnosis and management of patients with Staphylococcus aureus bacteraemia (SAB). Methods: Post hoc analysis of a prospective cohort of consecutive adult patients diagnosed with SAB (January 2013–December 2017). Patients who underwent 18F-FDG-PET/CT at the discretion of the attending physician were included. Endpoints were the identification of previously unknown infectious foci and changes in clinical management, defined as changes in the duration or class of antibiotic therapy, a surgical procedure on the source of infection or a change in the decision to remove or retain an implantable device. Results: We included 39 patients (median age: 69 years, IQR: 60–79). Fifteen (39%) patients did not have an infectious focus identified before 18F-FDG-PET/CT. Thirty new infectious foci were detected in 22/39 (56%) patients. In 11/15 (73%) patients without an identified focus at least one infectious focus was detected by 18F-FDG-PET/CT. In 22/26 (85%) patients with implantable devices, 18F-FDG-PET/CT confirmed or ruled out infection or detected local complications. Out of 13 device infections, 10 were detected by 18F-FDG-PET/CT (7/10 for the first time). In 19/39 (49%) patients 18F-FDG-PET/CT results led to changes in clinical management (15 changes in antibiotic therapy, 2 device removals, 2 surgical procedures, 1 avoidance of a surgical procedure). Conclusions: 18F-FDG-PET/CT may be a useful asset in the management of selected SAB cases, allowing the identification of previously undetected infectious foci and optimization of therapy, particularly in patients with endovascular devices. Indication should be made on a case-by-case basis.(AU)

Objetivos: Evaluar el impacto de la 18F-FDG-PET/TC en el diagnóstico y manejo de los pacientes con bacteriemia por Staphylococcus aureus (BSA). Métodos: Análisis post hoc de una cohorte prospectiva de pacientes adultos consecutivos con BSA (enero 2013-diciembre 2017). Se incluyeron aquellos pacientes en los que se realizó una 18F-FDG-PET/TC a criterio del médico tratante. Los criterios de valoración fueron la identificación de nuevos focos infecciosos y los cambios en el manejo clínico (definidos como modificaciones en la duración o clase del tratamiento antibiótico, intervención quirúrgica sobre el foco infeccioso o cambios en la decisión de retirar o mantener un dispositivo implantable). Resultados: Se incluyeron 39 pacientes (edad media: 69 años; RIC: 60-79). En 15 (39%) pacientes no se había identificado un foco infeccioso antes de la 18F-FDG-PET/TC. Se identificaron 30 nuevos focos infecciosos en 22/39 (56%) pacientes. En 11/15 (73%) pacientes sin un foco infeccioso identificado la 18F-FDG-PET/TC detectó al menos un foco infeccioso. En 22/26 (85%) pacientes con dispositivos implantables la 18F-FDG-PET/TC permitió confirmar/descartar infección del dispositivo o detectar complicaciones locales. Diez de 13 infecciones de dispositivos fueron detectadas por 18F-FDG-PET/TC (7/10 desconocidas previamente). En 19/39 (49%) pacientes los hallazgos en la 18F-FDG-PET/TC conllevaron cambios en el manejo clínico (15 modificaciones de tratamiento antibiótico, 2 retiradas de dispositivo, 2 intervenciones quirúrgicas, un procedimiento quirúrgico evitado). Conclusiones: La 18F-FDG-PET/TC puede ser de utilidad en la BSA, ya que permite identificar nuevos focos infecciosos y modificar el manejo clínico, sobre todo en pacientes con dispositivos endovasculares. La indicación ha de individualizarse en cada paciente.(AU)

Impact of 18F-FDG-PET/CT on the management of Staphylococcus aureus bacteraemia: a retrospective observational study.

OBJECTIVES: To assess the impact of 18F-FDG-PET/CT on the diagnosis and management of patients with Staphylococcus aureus bacteraemia (SAB). METHODS: Post hoc analysis of a prospective cohort of consecutive adult patients diagnosed with SAB (January 2013-December 2017). Patients who underwent 18F-FDG-PET/CT at the discretion of the attending physician were included. Endpoints were the identification of previously unknown infectious foci and changes in clinical management, defined as changes in the duration or class of antibiotic therapy, a surgical procedure on the source of infection or a change in the decision to remove or retain an implantable device. RESULTS: We included 39 patients (median age: 69 years, IQR:60-79). Fifteen (39%) patients did not have an infectious focus identified before 18F-FDG-PET/CT). Thirty new infectious foci were detected in 22/39 (56%) patients. In 11/15 (73%) patients without an identified focus at least one infectious focus was detected by 18F-FDG-PET/CT. In 22/26 (85%) patients with implantable devices, 18F-FDG-PET/CT confirmed or ruled out infection or detected local complications. Out of 13 device infections, 10 were detected by 18F-FDG-PET/CT (7/10 for the first time). In 19/39 (49%) patients 18F-FDG-PET/CT results led to changes in clinical management (15 changes in antibiotic therapy, 2 device removals, 2 surgical procedures, 1 avoidance of a surgical procedure). CONCLUSIONS: 18F-FDG-PET/CT may be a useful asset in the management of selected SAB cases, allowing the identification of previously undetected infectious foci and optimization of therapy, particularly in patients with endovascular devices. Indication should be made on a case-by-case basis.

Empirical use of ß-lactam/ß-lactamase inhibitor combinations does not increase mortality compared with cloxacillin and cefazolin in methicillin-susceptible Staphylococcus aureus bacteraemia: a propensity-weighted cohort study.

OBJECTIVES: To evaluate the effectiveness of empirical therapy with ß-lactam/ß-lactamase inhibitor combinations (BL/BLICs) for MSSA bacteraemia. METHODS: We conducted a post hoc analysis of all adult patients with MSSA bacteraemia who were hospitalized at a Spanish university hospital between 2013 and 2018. We compared 30 day mortality among patients receiving initial therapy with BL/BLICs (de-escalated to cloxacillin or cefazolin within 96 h) versus cloxacillin or cefazolin, using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. RESULTS: We evaluated 373 patients with MSSA bacteraemia. Among them, 198 patients met the eligibility criteria, including 127 patients in the BL/BLICs group and 71 patients in the cloxacillin/cefazolin group. Patients in the BL/BLICs group had a higher Charlson comorbidity index (median, 2 [IQR, 1-4.5] versus 2 [IQR, 0-4]); an increased proportion of high-risk sources (i.e. endocarditis, respiratory sources and bacteraemia of unknown origin [34.6% versus 18.3%]); and an earlier start of antibiotic treatment (median, 0 days [IQR, 0-0] versus 1 day [IQR, 1-2]). Thirty day mortality did not significantly differ between the BL/BLICs and the cloxacillin/cefazolin groups (27 patients [21.3%] versus 13 patients [18.3%]; IPTW-adjusted OR = 0.53 [95% CI, 0.18-1.51]). For secondary outcomes, 7 day mortality and 90 day relapse were not statistically different between study groups (8.7% versus 5.6% [P = 0.62] and 6.2% versus 3.8% [P = 0.81], respectively). CONCLUSIONS: BL/BLICs might be an effective empirical treatment for MSSA bacteraemia when de-escalated to cloxacillin or cefazolin within 96 h from the index blood culture.

Mortality in Staphylococcus aureus bacteraemia remains high despite adherence to quality indicators: secondary analysis of a prospective cohort study.

OBJECTIVES: To evaluate the association between compliance with previously published quality indicators (QIs) for the management of Staphylococcus aureus bacteraemia (SAB) and 30-day mortality. METHODS: We conducted a post hoc analysis of all adult patients with SAB who were hospitalized at a Spanish university hospital between 2013 and 2018. We evaluated the compliance with 7 QIs of SAB management (i.e., Infectious Diseases consultation, follow-up blood cultures, early source control, echocardiography, early cloxacillin or cefazolin, vancomycin monitoring, and appropriate treatment duration). The QIs compliance rate was considered good if ≥75% of the QIs recommended in each patient were performed. We studied the impact of different risk factors (including QIs compliance) on 30-day all-cause mortality adjusting by multivariable modeling and propensity-matched analysis. RESULTS: We included 441 patients with SAB. The QIs compliance rate was ≥75% in 361 patients (81.9%). A total of 95 patients (21.5%) died within 30 days after the index blood culture. In the multivariable model, the variables associated with 30-day mortality were: age (OR, 1.1; 95% CI, 1.0-1.1), Charlson comorbidity index (OR, 1.2; 95% CI, 1.1-1.4), persistent bacteraemia >72 h (OR, 6.0; 95% CI, 3.2-11.5), infective endocarditis (OR, 2.8; 95% CI, 1.2-6.7), and SAB of unknown source (OR, 3.3; 95% CI, 1.5-7.1). We did not find an association between a global QIs compliance rate of ≥75% or any individual QI with 30-day mortality. CONCLUSIONS: SAB 30-day mortality remains high despite good adherence to previously published QIs for the management of SAB. Future research should focus on additional factors to further improve SAB-related mortality.

Screening for asymptomatic STIs in HIV-infected men who have sex with men.

We aimed to study the prevalence, characteristics and risk factors of asymptomatic sexually transmitted infections (STIs) in HIV-infected men who have sex with men (MSM). We conducted a prospective cross-sectional study, including asymptomatic HIV-infected MSM attending regular visits between December 2014 and December 2017. Of the 301 patients included, 60 patients (19.9%) presented at least one STI. The most common STI was syphilis (33 of 69 STIs), followed by chlamydia (19 of 69), gonorrhoea (10 of 69), hepatitis C virus (4 of 69) and lymphogranuloma venereum (3 of 69). Illicit drug use during sex was the only variable significantly associated with the presence of an STI on multivariate analysis (OR 2.13; 95% CI 1.17-3.89). We were unable to identify a subgroup of patients where we could potentially avoid STI screening. Our findings support current guidelines that recommend routine screening for all HIV-infected MSM regardless of their self-reported sexual history.

Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab.

The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4+) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.

Early Oral Switch to Linezolid for Low-risk Patients With Staphylococcus aureus Bloodstream Infections: A Propensity-matched Cohort Study.

BACKGROUND: Oral switch to linezolid is a promising alternative to standard parenteral therapy (SPT) in Staphylococcus aureus bacteremia (SAB). METHODS: We conducted a prospective cohort study of all adult cases of SAB between 2013 and 2017 in a Spanish university hospital. We compared the efficacy, safety, and length of hospital stay of patients receiving SPT and those where SPT was switched to oral linezolid between days 3 and 9 of treatment until completion. We excluded complicated SAB and osteoarticular infections. A k-nearest neighbor algorithm was used for propensity score matching with a 2:1 ratio. RESULTS: After propensity score matching, we included 45 patients from the linezolid group and 90 patients from the SPT group. Leading SAB sources were catheter related (49.6%), unknown origin (20.0%), and skin and soft tissue (17.0%). We observed no difference in 90-day relapse between the linezolid group and the SPT group (2.2% vs 4.4% respectively; P = .87). No statistically significant difference was observed in 30-day all-cause mortality between the linezolid group and the SPT group (2.2% vs 13.3%; P = .08). The median length of hospital stay after onset was 8 days in the linezolid group and 19 days in the SPT group (P < .01). No drug-related events leading to discontinuation were noted in the linezolid group. CONCLUSIONS: Treatment of SAB in selected low-risk patients with an oral switch to linezolid between days 3 and 9 of treatment until completion yielded similar clinical outcomes as SPT, allowing earlier discharge from the hospital.

Immune reconstitution inflammatory syndrome in HIV-infected patients with Pneumocystis jirovecii pneumonia / Síndrome inflamatorio de reconstitución inmune en pacientes con infección por VIH y neumonía por Pneumocystis jirovecii

INTRODUCTION: The incidence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients after an episode of Pneumocystis jirovecii pneumonia (PJP) seems to be lower than with other opportunistic infections. We conducted an observational study in order to determine the incidence, clinical characteristics and outcome of patients diagnosed with PJP-related IRIS. METHODS: We conducted an observational study of HIV patients diagnosed with PJP-related IRIS from January 2000 to November 2015. We analyzed epidemiological and clinical characteristics as well as laboratory findings. We also carried out a systematic review of published cases. RESULTS: Six cases of IRIS out of 123 (4.9%) HIV-infected patients with PJP who started ART were diagnosed. All six cases were men with a median age of 34 (IQR: 8) years. The six patients developed paradoxical IRIS. Subjects younger than 40 years old (p = 0.084) and with an HIV-RNA viral load >100000 copies/ml (p = 0.081) at diagnosis showed a tendency to develop IRIS. Thirty-seven published cases of PJP-related IRIS were identified. Although 51% of cases involved respiratory failure, no deaths were reported. CONCLUSIONS: PJP-related IRIS is rare condition compared to other opportunistic infections. It can lead to a severe respiratory failure in a significant proportion of cases, although no deaths have been reported

INTRODUCCIÓN: La incidencia del síndrome inflamatorio de reconstitución inmune (SIRI) en pacientes infectados por el virus de la inmunodeficiencia humana (VIH) después de un episodio de neumonía por Pneumocystis jirovecii (PJP) parece ser menor que con otras infecciones oportunistas. Hemos realizado un estudio observacional con el objetivo de conocer la incidencia, las características clínicas y la evolución de los pacientes diagnosticados de SIRI asociado con la PJP. MÉTODOS: Se ha realizado un estudio observacional de pacientes con VIH diagnosticados de SIRI asociado a PJP desde enero del 2000 hasta noviembre de 2015. Fueron analizadas características epidemiológicas y clínicas, así como hallazgos de laboratorio. Asimismo, se ha llevado a cabo una revisión sistemática de los casos publicados previamente. RESULTADOS: Se identificaron 6 casos de SIRI en 123 pacientes con VIH (4,9%) con PJP que comenzaron TAR. Los 6 casos eran varones con una edad media de 34 (IQR :8) años. En los 6 casos se trató de una SIRI paradójico. Los sujetos menores de 40 años (p = 0,084) y con VIH-ARN al diagnóstico mayor de 100.000 copias/ml (p = 0,081) mostraron una tendencia a desarrollar SIRI. Se identificaron 37 casos publicados de SIRI relacionado con PJP en la literatura. Aunque el 51% de los casos presentaron insuficiencia respiratoria, no se reportaron muertes. CONCLUSIONES: El SIRI asociado con PJP es una entidad infrecuente comparada con el relacionado con otras infecciones oportunistas. Puede provocar insuficiencia respiratoria grave en un porcentaje importante de casos, si bien no se han reportado muertes

Immune reconstitution inflammatory syndrome in HIV-infected patients with Pneumocystis jirovecii pneumonia.

INTRODUCTION: The incidence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients after an episode of Pneumocystis jirovecii pneumonia (PJP) seems to be lower than with other opportunistic infections. We conducted an observational study in order to determine the incidence, clinical characteristics and outcome of patients diagnosed with PJP-related IRIS. METHODS: We conducted an observational study of HIV patients diagnosed with PJP-related IRIS from January 2000 to November 2015. We analyzed epidemiological and clinical characteristics as well as laboratory findings. We also carried out a systematic review of published cases. RESULTS: Six cases of IRIS out of 123 (4.9%) HIV-infected patients with PJP who started ART were diagnosed. All six cases were men with a median age of 34 (IQR: 8) years. The six patients developed paradoxical IRIS. Subjects younger than 40 years old (p=0.084) and with an HIV-RNA viral load >100000 copies/ml (p=0.081) at diagnosis showed a tendency to develop IRIS. Thirty-seven published cases of PJP-related IRIS were identified. Although 51% of cases involved respiratory failure, no deaths were reported. CONCLUSIONS: PJP-related IRIS is rare condition compared to other opportunistic infections. It can lead to a severe respiratory failure in a significant proportion of cases, although no deaths have been reported.