It is important to know the spectrum of the microbial aetiology of prosthetic joint infections (PJIs) to guide empiric treatment and establish antimicrobial prophylaxis in joint replacements. There are no available data based on large contemporary patient cohorts. We sought to characterize the causative pathogens of PJIs and to evaluate trends in the microbial aetiology. We hypothesized that the frequency of antimicrobial-resistant organisms in PJIs has increased in the recent years. We performed a cohort study in 19 hospitals in Spain, from 2003 to 2012. For each 2-year period (2003-2004 to 2011-2012), the incidence of microorganisms causing PJIs and multidrug-resistant bacteria was assessed. Temporal trends over the study period were evaluated. We included 2524 consecutive adult patients with a diagnosis of PJI. A microbiological diagnosis was obtained for 2288 cases (90.6%). Staphylococci were the most common cause of infection (1492, 65.2%). However, a statistically significant rising linear trend was observed for the proportion of infections caused by Gram-negative bacilli, mainly due to the increase in the last 2-year period (25% in 2003-2004, 33.3% in 2011-2012; p 0.024 for trend). No particular species contributed disproportionally to this overall increase. The percentage of multidrug-resistant bacteria PJIs increased from 9.3% in 2003-2004 to 15.8% in 2011-2012 (p 0.008), mainly because of the significant rise in multidrug-resistant Gram-negative bacilli (from 5.3% in 2003-2004 to 8.2% in 2011-2012; p 0.032). The observed trends have important implications for the management of PJIs and prophylaxis in joint replacements.

There is significant intra-and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI 95 There is significant controversy regarding ritonavir-boosted protease inhibitor (PI) monotherapy as a maintenance therapeutic strategy (1-5). Notwithstanding, a considerable proportion of patients maintained an undetectable viremia on lopinavirritonavir maintenance monotherapy (mtLPVr) and could benefit from a simpler regimen without nucleoside analogues or other antiretroviral drugs. Moreover, lack of adherence has been indicated as the main reason for virological failure (VF) in different studies (6-13).Moreover, there is significant intra-and intersubject variability in LPV plasma concentrations after standard dosing, determined largely by variability in drug absorption, cytochrome P450 metabolism, plasma protein binding, and drug transporter activity, which may affect the disposition of the drug (14, 15). As LPV plasma concentrations and the genotype inhibitory quotient have been related to virological efficacy in experienced patients on LPVr-based regimens (16)(17)(18)(19), in this study, we tested whether low plasma LPV trough concentrations contribute to VF throughout the mtLPVr treatment period. The confirmation of this hypothesis would demonstrate that LPV therapeutic drug monitoring could be useful in improving the efficacy of LPV when prescribed as a monotherapy. MATERIALS AND METHODSStudy population and design. From April 2009 to April 2010, adult HIV-1-infected patients who started a regimen of mtLPVr at our outpatient clinic were consecutively included in this observational, prospective, open-label study. The LPVr dosing regimen (400 mg of LPV and 100 mg of ritonavir twice daily or 800 mg-200 mg once daily) was selected by the patients' physicians. All subjects had plasma HIV RNA levels of Ͻ50 copies/ml for at least 6 months. Patients with VF while on a PI-containing regimen were also included in the study when genotypic resistance tests showed no major or Յ3 minor resistance mutations associated with reduced...