Carles Pigrau

Invasive Pneumococcal Disease in Patients Infected with HIV: Still a Threat in the Era of Highly Active Antiretroviral Therapy

We studied all human immunodeficiency virus (HIV)-infected patients with invasive pneumococcal disease who received their diagnosis during 1996-2002 to investigate the incidence of this disease in the highly active antiretroviral therapy era and to study the influence of CD4 lymphocyte count on the clinical presentation and outcome of disease. The overall incidence of invasive pneumococcal disease was 11.3 cases per 100,000 person-years in adult patients without known HIV infection and 677 cases per 100,000 person-years in HIV-infected patients. This incidence remained stable over the study period. Clinical presentation, severity of illness, and number of recurrent episodes were similar in patients with CD4+ cell counts of >200 or < or =200 cells/ microL. Patients receiving trimethoprim-sulfamethoxazole (TMP-SMZ) were more likely to present with TMP-SMZ-resistant pneumococci than were those who were not receiving this agent (76.7% vs. 43.6%; P=.007). The mortality rate was high (21%).

Contemporary Epidemiology and Prognosis of Health Care–Associated Infective Endocarditis

BACKGROUND The aim of this study was to describe the characteristics of health care-associated infective endocarditis (HAIE) and to establish the risk factors for mortality. METHODS We conducted a prospective, observational cohort study. HAIE was defined according to the following conditions: (1) symptom onset >48 h after hospitalization or within 6 months after hospital discharge; or (2) ambulatory manipulations causing endocarditis. RESULTS Eighty-three episodes of HAIE (accounting for 28.4% of all cases of endocarditis) were diagnosed. Compared with patients with community-acquired endocarditis, patients with HAIE were older (median age +/- standard deviation, 65.3 +/- 16.4 years vs. 57.8 +/- 17.0 years; P = .001), were in poorer health before disease onset (Charlson index, 2.5 +/- 2.3 vs. 1.7 +/- 2.1; P = .006), had more staphylococcal (55.4% vs. 28.3% of cases) and enterococcal infections (22.9% vs. 7.7% of cases; P < .005), underwent fewer surgeries (22.9% vs. 45.9% of cases; P < .005), and experienced a higher rate of in-hospital (45.8% vs. 22.0%) and 1-year mortality (59.5% vs. 29.6%; P < .005). In the HAIE cohort, independent predictors of in-hospital death were stroke (odds ratio [OR], 8.95; 95% confidence interval [CI], 2.04-39.31; P = .004), congestive heart failure (OR, 5.48; 95% CI, 1.77-17.03; P = .003), surgery indicated but not performed (OR, 3.74; 95% CI, 1.22-11.45; P = .021), and enterococcal infection (OR, 0.18; 95% CI, 0.04-0.78; P = .022). Independent predictors of 1-year mortality were surgery indicated but not performed (OR, 7.81; 95% CI, 2.06-29.67; P = .003), acute renal failure (OR, 7.18; 95% CI, 1.32-39.18; P = .023), and enterococcal infection (OR, 0.18; 95% CI, 0.04-0.81; P = .026). For the series overall (292 episodes), HAIE was an independent predictor of in-hospital (OR, 2.83; 95% CI, 1.34-5.98; P = .007) and 1-year mortality (OR, 2.59; 95% CI, 1.25-5.39; P = .011). CONCLUSIONS HAIE is an important health problem associated with considerable mortality. New strategies to prevent HAIE should be assessed.

Relationship between Escherichia coli Strains Causing Acute Cystitis in Women and the Fecal E. coli Population of the Host

ABSTRACT Previous epidemiological assessments of the prevalence versus special-pathogenicity hypothesis for urinary tract infection (UTI) pathogenesis in women may have been confounded by underlying host population differences between women with UTI and healthy controls and have not considered the clonal complexity of the fecal Escherichia coli population of the host. In the present study, 42 women with acute uncomplicated cystitis served as their own controls for an analysis of the causative E. coli strain and the concurrent intestinal E. coli population. Clonality among the urine isolate and 30 fecal colonies per subject was assessed by repetitive-element PCR and macrorestriction analysis. Each unique clone underwent PCR-based phylotyping and virulence genotyping. Molecular analysis resolved 109 unique clones (4 urine-only, 38 urine-fecal, and 67 fecal-only clones). Urine clones exhibited a significantly higher prevalence of group B2 than fecal-only clones (69% versus 10%; P < 0.001) and higher aggregate virulence scores (mean, 6.2 versus 2.9; P < 0.001). In multilevel regression models for predicting urine clone status, significant positive predictors included group B2, 10 individual virulence traits, the aggregate virulence score, fecal dominance, relative fecal abundance, and (unique to the present study) a pauciclonal fecal sample. In summary, within the fecal E. coli populations of women with acute cystitis, pauciclonality, clonal dominance, virulence, and group B2 status are closely intertwined. Phylogenetic group B2 status and/or associated virulence factors may promote fecal abundance and pauciclonality, thereby contributing to upstream steps in UTI pathogenesis. This relationship suggests a possible reconciliation of the prevalence and special-pathogenicity hypotheses.

Antibiotic Susceptibility in Gram-Positive Chronic Joint Arthroplasty Infections: Increased Aminoglycoside Resistance Rate in Patients With Prior Aminoglycoside-Impregnated Cement Spacer Use

Two-stage revision using aminoglycoside-cement spacers (A-CSs) is widely used to manage chronic periprosthetic joint infection (PJI). However, aminoglycoside-resistance in gram-positive cocci (GPC) seems to be increasing. Moreover, the contribution of these A-CSs to select resistant mutants is a matter of concern. We study the antibiotic susceptibility profile of GPC after 113 chronic hip and knee PJIs. Aminoglycoside susceptibility-profiles were compared between cases where A-CSs had previously been used (n: 52), and cases of primary infection (n: 61). 32% of isolates were resistant to gentamicin and 40.6% to tobramycin. Gentamicin resistance after previous A-CS use was significantly higher (49.2% [30/61] vs. 19.3% [16/83]; P: 0.0001) as well as with tobramycin (52.7% [29/55] vs. 30.9% [21/66]; P: 0.014). A high rate of gentamicin-tobramycin resistance exists among the most common bacteria involved in chronic-PJI. The risk of selection for aminoglycoside-resistant mutants in cases of infection relapse is a concern following A-CS use.

Percutaneous interface biopsy in dry-aspiration cases of chronic periprosthetic joint infections: A technique for preoperative isolation of the infecting organism

PurposePreoperative identification of the infecting micro-organism is of paramount importance in the treatment protocol for chronic periprosthetic joint infections, as it enables selection of the most appropriate antibiotic treatment. Preoperative joint aspiration, the most commonly used sampling technique, has proven to have a broad range of sensitivity values and the frequency of dry aspirations has not been well assessed. In such dry-tap cases a biopsy sample could be an option. The purpose of this study was to assess the diagnostic accuracy of percutaneous interface biopsy (PIB) in isolating the infecting organism in cases of chronic Periprosthetic Joint Infection (PJI) and dry-tap event. The basic technique is to harvest and culture a sample from the periprosthetic interface membrane by a percutaneous technique in the preoperative period.MethodsA retrospective study was done involving 24 consecutive patients suspected of PJI and where no fluid was obtained from the joint. Culture results from a percutaneous interface biopsy (PIB) were compared with intraoperative tissue cultures at the time of revision surgery. In all cases, a two-stage replacement was done.ResultsThe sensitivity was 88.2%; specificity was 100%. Positive predictive value was 100%, while negative predictive value was 77.9%. Accuracy was 91.6%. No technique-related complication was observed.ConclusionWe conclude that PIB is a useful test for preoperative isolation of the infecting organism and could play a role in cases with dry-tap joint aspirations.

High doses of daptomycin (10 mg/kg/d) plus rifampin for the treatment of staphylococcal prosthetic joint infection managed with implant retention: a comparative study.

We aimed to analyze the efficacy and safety of high doses of daptomycin (10 mg/kg/d) plus rifampin (D10 + R) for prosthetic joint infection (PJI). This was an observational retrospective multicenter study (2010-2012) including all patients with acute PJI by fluoroquinolone-resistant staphylococci managed with implant retention and D10 + R. Twenty cases were included: 2 (10%) were withdrawn due to toxicity, leaving 18 cases for efficacy evaluation: 13 (72%) women, age 79 years (range 58-90). Clinical failure was observed in 9 (50%) patients: in 5 cases, staphylococci were recovered (28% of microbiological failures); no modification of daptomycin-MIC was observed. These 18 cases were compared with 44 matched historical cases: failure rate was similar, but whereas in the historical series, failure occurred fundamentally during therapy, in the present series, it was recorded after discontinuation of antibiotics. In summary, D10 + R may be the initial treatment of choice for PJI by fluoroquinolone-resistant staphylococci managed with implant retention.

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial

Introduction Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. Methods and analysis A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. Ethics and dissemination The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. Trial registration number NCT01898338.

Tratamiento de la neumonía por Legionella pneumophila. ¿Macrolidos o quinolonas?

Antecedentes Los nuevos macrolidos y las fluorquinolonas constituyen actualmente el tratamiento de eleccion de la neumonia por Legionella pneumophila (NLP). El objetivo de nuestro estudio es analizar la eficacia de claritromicina, azitromicina y levofloxacino en el tratamiento de la NLP. Metodos Estudio prospectivo observacional de todos los pacientes adultos diagnosticados de NLP en el Hospital Universitario Vall d’Hebron de Barcelona entre enero de 2001 y diciembre de 2004. Se han comparado variables clinicas evolutivas (duracion de la fiebre, duracion del ingreso hospitalario y mortalidad) entre 52 pacientes tratados con claritromicina, 43 con azitromicina y 18 con levofloxacino. Resultados No se observaron diferencias significativas en cuanto a la presencia de factores de riesgo, porcentaje de pacientes inmunodeprimidos, gravedad inicial de la neumonia o necesidad de ingreso en la unidad de cuidados intensivos entre los pacientes tratados con claritromicina, azitromicina o levofloxacino. La mortalidad hospitalaria fue del 5,3%. No encontramos diferencias significativas con respecto al tiempo que se tardo en conseguir la apirexia, la media de estancia hospitalaria y la mortalidad entre ninguno de los 3 grupos. Conclusion En nuestra experiencia, la eficacia clinica de claritromicina, azitromicina y levofloxacino es similar para el tratamiento de la NLP.

Long-Term Fosfomycin-Tromethamine Oral Therapy for Difficult-To-Treat Chronic Bacterial Prostatitis.

ABSTRACT This is a retrospective study of 15 difficult-to-treat (i.e., exhibiting previous failure, patient side effects, or resistance to ciprofloxacin and co-trimoxazole) chronic bacterial prostatitis infections (5 patients with multidrug-resistant Enterobacteriaceae [MDRE]) receiving fosfomycin-tromethamine at a dose of 3 g per 48 to 72 h for 6 weeks. After a median follow-up of 20 months, 7 patients (47%) had a clinical response, and 8 patients (53%) had persistent microbiological eradication; 4/5 patients with MDRE isolates achieved eradication. There were no side effects. Fosfomycin-tromethamine is a possible alternative therapy for chronic bacterial prostatitis.

An update on surgical and antimicrobial therapy for acute periprosthetic joint infection: new challenges for the present and the future.

Periprosthetic joint infection (PJI) is a devastating complication that can occur following any arthroplasty procedure. Approximately half of these infections develop within the first year after arthroplasty, mainly in the first 1 to 3 months. These infections are known as early PJI. It is widely accepted that many early PJIs can be successfully managed by debridement, irrigation, and prosthetic retention, followed by a course of biofilm-effective antibiotics (debridement, antibiotics, implant retention procedure), but candidate patients should meet the requirements set down in Zimmerli’s algorithm. The best antibiotic regimen for acute PJI treated without implant removal remains uncertain. Rifampin-containing regimens, when feasible, are recommended in gram-positive infections, and fluoroquinolones in gram-negative cases. The duration, dosage, and administration route of antibiotics and the use of combined therapy are matters that requires further clarification, as the current level of evidence is low and most recommendations are based on experimental data, studies in small series, and expert experience.