Health-related quality of life in men with localized prostate cancer treated with radiotherapy: validation of an abbreviated version of the Expanded Prostate Cancer Index Composite for Clinical Practice in Spain.

BACKGROUND: Health-related quality of life (HRQoL) is greatly affected by prostate cancer (PCa) and associated treatments. This study aimed to measure the impact of radiotherapy on HRQoL and to further validate the Spanish version of the 16-item Expanded Prostate Cancer Index Composite (EPIC-16) in routine clinical practice. METHODS: An observational, non-interventional, multicenter study was conducted in Spain with localized PCa patients initiating treatment with external beam radiotherapy (EBRT) or brachytherapy (BQT). Changes from baseline in EPIC-16, University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), and patient-perceived health status were longitudinally assessed at end of radiotherapy (V2) and 90 days thereafter (V3). Psychometric evaluations of the Spanish EPIC-16 were conducted. RESULTS: Of 516 patients enrolled, 495 were included in the analysis (EBRT, n = 361; BQT, n = 134). At baseline, mean (standard deviation [SD]) EPIC-16 global scores were 11.9 (7.5) and 10.3 (7.7) for EBRT and BQT patients, respectively; scores increased, i.e., HRQoL worsened, from baseline, by mean (SD) of 6.8 (7.6) at V2 and 2.4 (7.4) at V3 for EBRT and 4.2 (7.6) and 3.9 (8.2) for BQT patients. Changes in Spanish EPIC-16 domains correlated well with urinary, bowel, and sexual UCLA-PCI domains. EPIC-16 showed good internal consistency (Cronbach's alpha = .84), reliability, and construct validity. CONCLUSION: The Spanish EPIC-16 questionnaire demonstrated sensitivity, strong discriminative properties and reliability, and validity for use in clinical practice. EPIC-16 scores worsened after radiotherapy in different HRQoL domains; however, a strong tendency towards recovery was seen at the 3-month follow-up visit.

Epidemiology and risk factors for Clostridium difficile infection in critically ill patients in Spain: The PROCRID study.

INTRODUCTION: Our objectives were to describe the incidence, clinical characteristics, and risk factors for Clostridium difficile infection (CDI) in critically ill patients and to determine C. difficile PCR-ribotypes. METHODS: Prospective, observational study in 26 Spanish ICUs. Patients with diarrhea meeting ESCMID criteria for CDI were included. Molecular characterization of isolates was performed using PCR ribotyping. RESULTS: Of 4258 patients admitted to the ICUs, 190 (4.5%) developed diarrhea. Only 16 patients (8.4%) were diagnosed with CDI. Ribotype 078/126 (25.0%) was the most frequently identified. The mortality rate was similar in patients with ICD compared to patients with diarrhea not caused by C. difficile (p=0.115). Chronic renal insufficiency was identified as the only factor independently associated with the development of CDI (OR 5.87, 95% CI 1.24-27.83; p=0.026). CONCLUSIONS: The incidence of CDI in Spanish ICUs is low. Only chronic renal insufficiency was observed to be a risk factor for CDI development.

Ceftobiprole medocaril (BAL5788) treatment of experimental Haemophilus influenzae, Enterobacter cloacae, and Klebsiella pneumoniae murine pneumonia.

Ceftobiprole (BAL9141) is an investigational cephalosporin active against methicillin- and vancomycin-resistant staphylococci administered as a water-soluble prodrug, ceftobiprole medocaril (BAL5788). Using an immunocompetent murine pneumonia model of Haemophilus influenzae, Enterobacter cloacae, or extended-spectrum beta-lactamase (ESBL) nonproducing or producing Klebsiella pneumoniae pneumonia, we compared results of treatment with ceftobiprole medocaril (71 mg/kg, sc, qid), ceftriaxone (50 mg/kg, im, bid), or cefepime (50 mg/kg, ip, q.i.d.). Results were expressed as median and 25th to 75th percentile log10 colony forming units per gram of lung tissue. Ceftobiprole, ceftriaxone, and cefepime were each more active than was no treatment and were equally active for treatment of experimental H. influenzae, E. cloacae, or ESBL-nonproducing K. pneumoniae pneumonia. For ESBL-producing K. pneumoniae, no differences were detected between no treatment and treatment with ceftobiprole, ceftriaxone, or cefepime. Ceftobiprole is active against H. influenzae, E. cloacae, and ESBL-nonproducing K. pneumoniae in an immunocompetent experimental murine pneumonia model.

Epidemiology and risk factors for Clostridium difficile infection in critically ill patients in Spain: The PROCRID study / Epidemiología y factores de riesgo para la infección por Clostridium difficile en pacientes críticos en España: Estudio PROCRID

INTRODUCTION: Our objectives were to describe the incidence, clinical characteristics, and risk factors for Clostridium difficile infection (CDI) in critically ill patients and to determine C. difficile PCR-ribotypes. METHODS: Prospective, observational study in 26 Spanish ICUs. Patients with diarrhea meeting ESCMID criteria for CDI were included. Molecular characterization of isolates was performed using PCR ribotyping. RESULTS: Of 4258 patients admitted to the ICUs, 190 (4.5%) developed diarrhea. Only 16 patients (8.4%) were diagnosed with CDI. Ribotype 078/126 (25.0%) was the most frequently identified. The mortality rate was similar in patients with ICD compared to patients with diarrhea not caused by C. difficile (p = 0.115). Chronic renal insufficiency was identified as the only factor independently associated with the development of CDI (OR 5.87, 95% CI 1.24-27.83; p = 0.026). CONCLUSIONS: The incidence of CDI in Spanish ICUs is low. Only chronic renal insufficiency was observed to be a risk factor for CDI development

INTRODUCCIÓN: Pretendemos describir la incidencia, las características clínicas y los factores de riesgo de la infección por Clostridium difficile (ICD) en pacientes ingresados en unidades de cuidados intensivos, así como los ribotipos identificados. MÉTODOS: Estudio observacional, prospectivo, realizado en 26 unidades de cuidados intensivos de España. Se incluyeron pacientes con diarrea y criterios clínicos de la ESCMID por sospecha de ICD. La caracterización molecular se realizó mediante PCR. RESULTADOS: De 4.258 pacientes ingresados, 190 (4,5%) presentaron diarrea; en 16 causada por ICD. El ribotipo más frecuentemente aislado fue 078/126 (25%). La tasa de mortalidad cruda fue similar en pacientes con ICD y en pacientes con diarrea no causada por Clostridium difficile (p = 0,115). La insuficiencia renal crónica fue identificada como factor independientemente asociado a desarrollo de ICD (OR: 5,87; IC 95%: 1,24-27,83; p = 0,026). CONCLUSIONES: La incidencia de ICD en las unidades de cuidados intensivos españolas es baja. La insuficiencia renal crónica es el único factor identificado para desarrollo de ICD

RNAIII-inhibiting-peptide-loaded polymethylmethacrylate prevents in vivo Staphylococcus aureus biofilm formation.

Staphylococci, common orthopedic pathogens, form antibiotic-resistant biofilms. Polymethylmethacrylate (PMMA) beads loaded with the quorum-sensing inhibitor RNAIII-inhibiting peptide (RIP) were implanted in rats and shown to prevent methicillin-resistant Staphylococcus aureus infection. RIP release was bimodal, typical of previously-tested antibiotics. These results suggest that RIP-PMMA warrants further evaluation for management of orthopedic infections caused by staphylococci.

Garenoxacin treatment of experimental endocarditis caused by viridans group streptococci.

The activity of garenoxacin was compared to that of levofloxacin or penicillin in a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 microg/ml) and Streptococcus sanguinis group (penicillin MIC, 0.25 microg/ml) endocarditis. Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 microg/ml, respectively, for both study isolates. Rabbits with catheter-induced aortic valve endocarditis were given no treatment, penicillin at 1.2x10(6) IU/8 h intramuscularly, garenoxacin at 20 mg/kg of body weight/12 h intravenously, or levofloxacin at 40 mg/kg/12 h intravenously. For both isolates tested, garenoxacin area under the curve (AUC)/MIC and maximum concentration of drug in serum (Cmax)/MIC ratios were 368 and 91, respectively. Rabbits were sacrificed after 3 days of treatment; cardiac valve vegetations were aseptically removed and quantitatively cultured. For S. mitis group experimental endocarditis, all studied antimicrobial agents were more active than no treatment (P<0.001), whereas for S. sanguinis group endocarditis, no studied antimicrobial agents were more active than no treatment. We conclude that AUC/MIC and Cmax/MIC ratios may not predict activity of some quinolones in experimental viridans group endocarditis and that garenoxacin and levofloxacin may not be ideal choices for serious infections caused by some quinolone-susceptible viridans group streptococci.

Comparative study of antimicrobial release kinetics from polymethylmethacrylate.

Polymethylmethacrylate loaded with antimicrobial agents (most commonly vancomycin and/or aminoglycosides) is used for treatment and prevention of orthopaedic infections. Emergence of organisms resistant to vancomycin or aminoglycosides or both has been reported. Therefore, we studied in vitro release from polymethylmethacrylate beads of antimicrobials with suitable spectra for orthopaedic infections, including cefazolin, ciprofloxacin, gatifloxacin, levofloxacin, linezolid, and rifampin (2.5%, 7.5%, and 15%). Beads were placed in a continuous flow chamber, and antimicrobial concentrations in chamber outflow were determined by bioassay at timed intervals thereafter. Release profiles were bimodal with initial rapid release of high concentrations followed by sustained, slow release. Antimicrobial agents studied showed varied release profiles, indicating that elution from polymethylmethacrylate is unique to individual antimicrobial agents. Increasing antimicrobial concentration in polymethylmethacrylate increased peak concentrations and area under the curve. Cefazolin, ciprofloxacin, gatifloxacin, levofloxacin, linezolid, and rifampin may be suitable for incorporation into polymethylmethacrylate for management of orthopaedic infections.

Prosthetic joint infection.

Infection is the second most common cause of prosthetic joint failure. Signs and symptoms associated with prosthetic joint infection may develop weeks or even years following arthroplasty. While some patients with prosthetic joint infection present with findings consistent with acute septic arthritis, many present with pain alone. Morbidity and cost associated with repeat surgery, prolonged medical treatment and joint immobilization render importance to the accurate and timely diagnosis, and appropriate treatment of prosthetic joint infection. No consensus exists, however, in terms of the most cost-effective diagnostic methods or the ideal medical and/or surgical interventions. This review describes diagnostic tests and available treatment for prosthetic joint infection and gives a practical approach to this challenging clinical entity.

High rate of aminoglycoside resistance among staphylococci causing prosthetic joint infection.

Gentamicin and tobramycin are two aminoglycosides commonly impregnated into polymethylmethacrylate for treatment and prevention of prosthetic joint infection. Susceptibilities of staphylococci to aminoglycosides are not reported routinely in the United States. The gentamicin and tobramycin minimum inhibitory value of 93 staphylococci from patients with PJI were determined. Forty-one and 66% of the isolates were resistant to gentamicin and tobramycin, respectively. Methicillin-resistant Staphylococcus aureus isolates were more likely to be resistant to gentamicin or tobramycin than were their methicillin susceptible counterparts. The findings suggest that consideration should be given to the further study of agents other than aminoglycosides for incorporation into polymethylmethacrylate for the treatment and prevention of prosthetic joint infection.

Molecular Methods in the Diagnosis of Endocarditis.

Advances in molecular microbiologic diagnostics have yielded new tools to diagnose infective endocarditis. These tools can detect microorganisms that are difficult to grow or are uncultivable, because of prior antimicrobial therapy or because of innate characteristics of the microorganisms. This paper reviews molecular microbiologic diagnostic techniques and their role in the diagnosis of infective endocarditis.