Melchor Riera

A Large Multicenter Study of Methicillin–Susceptible and Methicillin–Resistant Staphylococcus aureus Prosthetic Joint Infections Managed With Implant Retention

BACKGROUND Several series predicting the prognosis of staphylococcal prosthetic joint infection (PJI) managed with debridement, antibiotics, and implant retention (DAIR) have been published, but some of their conclusions are controversial. At present, little is known regarding the efficacy of the different antibiotics that are used or their ability to eliminate methicillin-resistant S. aureus (MRSA) infection. METHODS This was a retrospective, multicenter, observational study of cases of PJI by S. aureus that were managed with DAIR (2003-2010). Cases were classified as failures when infection persistence/relapse, death, need for salvage therapy, or prosthesis removal occurred. The parameters that predicted failure were analyzed with logistic and Cox regression. RESULTS Out of 345 episodes (41% men, 73 years), 81 episodes were caused by MRSA. Fifty-two were hematogenous, with poorer prognoses, and 88% were caused by methicillin-susceptible S. aureus (MSSA). Antibiotics were used for a median of 93 days, with similar use of rifampin-based combinations in MSSA- and MRSA-PJI. Failure occurred in 45% of episodes, often early after debridement. The median survival time was 1257 days. There were no overall prognostic differences between MSSA- and MRSA-PJI, but there was a higher incidence of MRSA-PJI treatment failure during the period of treatment (HR 2.34), while there was a higher incidence of MSSA-PJI treatment failure after therapy. Rifampin-based combinations exhibited an independent protective effect. Other independent predictors of outcome were polymicrobial, inflammatory, and bacteremic infections requiring more than 1 debridement, immunosuppressive therapy, and the exchange of removable components of the prosthesis. CONCLUSIONS This is the largest series of PJI by S. aureus managed with DAIR reported to date. The success rate was 55%. The use of rifampin may have contributed to homogenizing MSSA and MRSA prognoses, although the specific rifampin combinations may have had different efficacies.

Visceral leishmaniasis : another HIV-associated opportunistic infection? report of eight cases and review of the literature

Visceral leishmaniasis (VL) is considered an opportunistic infection in immunocompromised patients. We review the clinical, laboratory, and therapeutic data in 63 patients (eight new cases and 55 cases reported in the literature) with Mediterranean VL (kala azar) and HIV-1 infection to determine whether VL should be considered an opportunistic infection in HIV-infected adults. We conclude that: (1) in areas where both leishmaniasis and HIV-1 infection are endemic, VL may be more frequent among HIV-infected adults; (2) in HIV-infected patients, the clinical picture did not differ significantly from classical kala azar, although it often ran a recurrent course, with resistance to antimonial therapy. We propose the inclusion of VL in the IVC-2 subgroup of the Centers for Disease Control (CDC) clinical classification of HIV-1 infection while prospective and larger studies further define whether there are clinical presentations that could justify adding VL to the list of opportunistic infections indicative of AIDS.

Cohorte RIS de pacientes con infección por VIH sin tratamiento antirretroviral previo (CoRIS): metodología y primeros resultados

Objetivo Describir la metodologia y los resultados basales de la cohorte de pacientes con infeccion por virus de la inmunodeficiencia humana (VIH) de la Red de Investigacion de Sida (CoRIS). Metodos Cohorte abierta, prospectiva, multicentrica, de pacientes mayores de 13 anos con diagnostico de VIH sin tratamiento antirretroviral previo. La seleccion se realizo entre enero de 2004 y octubre de 2005 en 17 hospitales de 8 comunidades autonomas. Se recogieron variables sociodemograficas, epidemiologicas, clinicas y analiticas, junto con muestras biologicas iniciales y de seguimiento. Resultados Se han incluido 1.591 pacientes, 24% mujeres, mediana de edad 36 anos, el 74% diagnosticados de VIH en 2004 o 2005. El 27% provenian de otros lugares de origen, destacando Latinoamerica (16%) y Africa subsahariana (5%). El 32% tenian estudios secundarios y el 16% universitarios. La categoria de transmision mas frecuente fue la de hombres homosexuales (37%), seguida por la heterosexual (36%); y solo el 21% tenian antecedente de consumo de drogas inyectadas. Al ingreso en la cohorte la mediana de CD4 era 317 celulas/μl, la de carga viral 52.300 copias/ml y el 18% tenian diagnostico de sida. Las enfermedades diagnosticas de sida mas frecuentes fueron: neumonia por Pneumocystis jiroveci (6,1%), candidiasis esofagica (3,3%) y tuberculosis extrapulmonar (3,0%) y pulmonar (2,7%). Se registraron 35 fallecimientos (2,2%). El 33% de los pacientes han aportado muestras basales al BioBanco. Conclusiones CoRIS proporciona informacion relevante del perfil epidemiologico reciente de la infeccion por el VIH en nuestro medio, en el que predomina la transmision sexual. Se demuestra la viabilidad de esta cohorte, recogiendo datos clinicos y epidemiologicos junto con muestras biologicas, lo que abre grandes posibilidades de investigacion.

Early prosthetic joint infection: outcomes with debridement and implant retention followed by antibiotic therapy

Recent expert reviews recommend a conservative surgical strategy - debridement and irrigation, antibiotics and implant retention (DAIR) - for most early post-surgical prosthetic joint infections (PJI). However, differences exist in published series regarding success rates with DAIR, and the size of most series is small. In this prospective multicenter cohort study of early PJI managed by DAIR, factors associated with failure of the DAIR were analyzed. Out of 139 early PJI, 117 cases managed with DAIR were studied For 67 patients (57.3%), infection was cured and the implant was salvaged with definite antimicrobial therapy. In 35 (29.9%) DAIR failed and removal of the prosthesis was necessary during follow-up. Finally, 15 patients (12.8%) needed chronic suppressive antimicrobial therapy due to suspected or confirmed persistent infection. Infections due to methicillin-resistant S. aureus (72.7% failed; p 0.05) and those treated at one of the hospitals (80.0% failed; p <0.05) had worse outcomes, but only this last variable was associated with treatment failure following multivariate analysis. Seventy-four per cent of patients who were successfully treated by DAIR and only 32.7% of the failures were able to walk without help or with one stick at the last follow-up visit (p <0.05). In conclusion, a substantial proportion of patients with an early PJI may be successfully treated with DAIR and definite antimicrobial therapy. In more than half of these, the infection can be cured. Since identification of factors associated with failure of DAIR is not simple, we recommend offering DAIR to most patients with early PJI.

Timing of Oseltamivir Administration and Outcomes in Hospitalized Adults With Pandemic 2009 Influenza A(H1N1) Virus Infection

BACKGROUND Data on the clinical effectiveness of oseltamivir in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) virus infection are scarce. We aimed to determine the effect of timing of oseltamivir administration on outcomes in hospitalized adults with A(H1N1). METHODS Observational analysis of a prospective cohort of adults hospitalized with laboratory-confirmed A(H1N1) was performed at 13 Spanish hospitals. Time from onset of symptoms to oseltamivir administration was the independent variable. Outcomes were duration of fever, hospital length of stay (LOS), need for mechanical ventilation, and mortality during hospitalization. Multivariate logistic regression was used to describe the association between the independent variable and the outcomes. RESULTS Five hundred thirty-eight hospitalized patients with A(H1N1) were studied. The median time from onset of symptoms to oseltamivir administration was 3 days (interquartile range [IQR], 2-5 days). With regard to outcomes, the median duration of fever was 2 days (IQR, 1-3 days), the median LOS was 5 days (IQR, 3-8 days), 49 patients (9.1%) underwent mechanical ventilation, and 11 patients (2%) died during hospitalization. In univariate analysis, prolonged duration of fever (above the median), prolonged LOS (above the median), need for mechanical ventilation, and mortality all increased with time to oseltamivir administration (χ(2) test for trend P = .001, P ≤ .001, P = .008, and P = .001, respectively). After adjustment for confounding factors, time from onset of symptoms to oseltamivir administration (+ 1-day increase) was associated with a prolonged duration of fever (OR, 1.10; 95% CI, 1.02-1.19), prolonged LOS (OR, 1.07; 95% CI, 1.00-1.15), and higher mortality (OR, 1.20; 95% CI, 1.06-1.35). CONCLUSIONS Timely oseltamivir administration has a beneficial effect on outcomes in hospitalized adults with A(H1N1), even in those who are admitted beyond 48 h after onset of symptoms.

Acute haematogenous prosthetic joint infection: prospective evaluation of medical and surgical management

The optimum treatment for prosthetic joint infections has not been clearly defined. We report our experience of the management of acute haematogenous prosthetic joint infection (AHPJI) in patients during a 3-year prospective study in nine Spanish hospitals. Fifty patients, of whom 30 (60%) were female, with a median age of 76 years, were diagnosed with AHPJI. The median infection-free period following joint replacement was 4.9 years. Symptoms were acute in all cases. A distant previous infection and/or bacteraemia were identified in 48%. The aetiology was as follows: Staphylococcus aureus, 19; Streptococcus spp., 14; Gram-negative bacilli, 12; anaerobes, two; and mixed infections, three. Thirty-four (68%) patients were treated with a conservative surgical approach (CSA) with implant retention, and 16 had prosthesis removal. At 2-year follow-up, 24 (48%) were cured, seven (14%) had relapsed, seven (14%) had died, five (10%) had persistent infection, five had re-infection, and two had an unknown evolution. Overall, the treatment failure rates were 57.8% in staphylococcal infections and 14.3% in streptococcal infections. There were no failures in patients with Gram-negative bacillary. By multivariate analysis, CSA was the only factor independently associated with treatment failure (OR 11.6; 95% CI 1.29-104.8). We were unable to identify any factors predicting treatment failure in CSA patients, although a Gram-negative bacillary aetiology was a protective factor. These data suggest that although conservative surgery was the only factor independently associated with treatment failure, it could be the first therapeutic choice for the management of Gram-negative bacillary and streptococcal AHPJI, and for some cases with acute S. aureus infections.

Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality

The incidence of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected patients has decreased thanks to sulfa prophylaxis and combined antiretroviral therapy. The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain. This prospective multicenter study enrolled 207 HIV-infected patients with PCP from 2000 to 2004. Molecular genotyping was performed on stored specimens. Risk factors for intensive care unit (ICU) admission and mortality were identified using a logistic regression model. Seven patients (3.7%; 95% confidence interval [CI], 1.5-7.5%) had DHPS mutations. Overall mortality was 15% (95% CI, 10-21%), rising to 80% (95% CI, 61-92%) in patients requiring mechanical ventilation. None of the patients with DHPS mutants died, nor did they need ICU admission or mechanical ventilation. PaO(2) <60 mm Hg at admission was a predictor of ICU admission (P = 0.01), and previous antiretroviral therapy predicted non-ICU admission (P = 0.009). PaO(2) <60 mm Hg at admission and ICU admission during the 1st week were predictors of mortality (P = 0.03 and P < 0.001, respectively). The prevalence of DHPS mutants in Spain is low and is not associated with a worse outcome. Severe respiratory failure at admission is the strongest predictor of PCP outcome.

Características clinicoepidemiológicas y tendencias en el tratamiento antirretroviral de una cohorte de pacientes con infección por el virus de la inmunodeficiencia humana. Cohorte PISCIS

Fundamento y objetivo: Los objetivos de este estudio fueron describir el proceso de implementacion de la cohorte PISCIS y las caracteristicas clinicoepidemiologicas y las tendencias en el tratamiento antirretroviral (TARV) de los pacientes con infeccion por el virus de la inmunodeficiencia humana (VIH) incluidos desde 1998 hasta 2003. Pacientes y metodo: Estudio de cohorte prospectivo de pacientes con infeccion por el VIH de 16 anos de edad o mayores atendidos en primera visita en 10 hospitales de Cataluna y uno de las Baleares. El analisis estadistico de las tendencias se realizo mediante el test de la *2 de Mantel. Resultados: Se incluyo a un total de 5.968 pacientes (edad media: 39,5 anos; 75% varones) con un tiempo medio de seguimiento de 26,4 meses (13.130 personas-ano). Del total, 2.763 fueron nuevos diagnosticos, en los que la via de transmision mas frecuente fue la heterosexual (43%), seguida de la homosexual (31%). Se observo una tendencia significativamente creciente en la proporcion de sujetos de edad inferior a 35 anos e inmigrantes. Un 43% tenian una cifra de linfocitos CD4 inferior a 200 celulas/µl en la determinacion mas cercana al diagnostico de la infeccion por el VIH. Del total, un 87% estaban en TARV en el ano 2003. Entre los pacientes no tratados previamente que iniciaron pautas de TARV con 3 o mas farmacos, se observo una disminucion de las pautas que incluian inhibidores de la proteasa (del 85% en 1998 al 25% en 2003; p < 0,001), mientras que aumentaron otras que contenian inhibidores de la transcriptasa inversa no analogos y analogos de los nucleosidos. Conclusiones: Las cohortes de pacientes con infeccion por el VIH son viables en nuestro medio y tienen gran utilidad clinica y en salud publica. La via de transmision mas frecuente entre los nuevos diagnosticos es la heterosexual, el retraso en el diagnostico es elevado y las pautas de TARV han ido cambiando para adaptarse a las recomendadas por las guias.

Clinical presentation and prognosis of the 2009 H1N1 influenza A infection in HIV-1-infected patients: a Spanish multicenter study.

Objective:The aim of the study was to describe the clinical presentation and prognosis in HIV-1-infected patients with hospital admission and pandemic influenza A 2009 (H1N1) confirmed, and compare this data with those of a general population. Design:This is a prospective study in nature. Methods:All adult patients admitted to 13 hospitals in Spain with confirmed influenza A 2009(H1N1) virus infection by real-time reverse transcriptase PCR assay or culture from June 12 to November 10, 2009 were recruited and followed up until 1 month after discharge. In the HIV group risk factors for HIV infection, AIDS criteria, last CD4 cell count and viral load, and antiretroviral therapy and pneumococcal vaccines were collected. Results:Five hundred and eighty-five patients were recruited, 26 with HIV-1 infection and 559 non-HIV. The HIV patients had a long-term well controlled infection with a median CD4 cell count 503 cells/μl and 84% with undetectable viral load, although more frequently they had chronic liver and chronic obstructive pulmonary disease. No significant differences were observed about reported symptoms and physical findings on hospital admission. About 50% of patients in both groups present radiological infiltrates and 30% present respiratory failures. Practically all the patients in both groups received influenza antiviral therapy and in each group 80% received antibacterial therapy. No differences were observed in clinical outcomes. Conclusion:In HIV patients, well controlled on HAART, the pandemic influenza virus AH1N1 had a similar clinical outcome and prognosis to that of non-HIV patients.

Pneumonia complicating pandemic (H1N1) 2009: risk factors, clinical features, and outcomes.

We performed an observational analysis of a prospective cohort of adults hospitalized for pandemic (H1N1) 2009 at 13 Spanish hospitals, from June to November 2009, to determine the risk factors, clinical features, and outcomes of pneumonia. Of 585 patients requiring hospitalization, chest radiography was obtained in 542. A total of 234 (43.1%) patients had pneumonia, of whom 210 underwent bacterial microbiologic studies. Of these patients, 174 (82.8%) had primary viral pneumonia and 36 (17.2%) had concomitant/secondary bacterial pneumonia. Bilateral pneumonia occurred in 48.3% of patients. Streptococcus pneumoniae was the most frequent pathogen among patients with bacterial pneumonia (26 of 36 patients). None of them had received pneumococcal vaccine. Compared with patients without pneumonia, those with pneumonia more frequently had shock during hospitalization (9.8% vs. 1%; p < 0.001), required intensive care unit admission (22.6% vs. 5.8%; p < 0.001), underwent mechanical ventilation (17.9% vs. 3.2%; p < 0.001), and had longer length of hospital stay (median, 7 d vs. 5 d; p < 0.001). In-hospital mortality was higher in patients with pneumonia than in the others (5.2% vs. 0%; p < 0.001). Absence of comorbid conditions (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.32-3.24) was found to be an independent risk factor for pneumonia, whereas early (≤48 h) oseltamivir therapy (OR, 0.29; 95% CI, 0.19-0.46) was a protective factor. In conclusion, pneumonia is a frequent complication among adults hospitalized for pandemic (H1N1) 2009 and causes significant morbidity. Mortality in pandemic (H1N1) 2009 is low, but occurs mainly in patients with pneumonia. Early oseltamivir therapy is a protective factor for this complication.Abbreviations: BMI = body mass index, CAP = community-acquired pneumonia, CI = confidence interval, CURB-65 = confusion, urea, respiratory rate, blood pressure, and age ≥65 years, ICU = intensive care unit, OR = odds ratio, PSI = pneumonia severity index, ROC = receiver operating characteristic, RT-PCR = reverse-transcription polymerase chain reaction.