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Introduction: The impact of remdesivir on mortality in patients with COVID-19 is still controversial. We aimed to identify clinical phenotype clusters of COVID-19 hospitalized patients with highest benefit from remdesivir use and validate these findings in an external cohort. Methods: We included consecutive patients hospitalized between February 2020 and February 2021 for COVID-19. The derivation cohort comprised subjects admitted to Hospital Clinic of Barcelona. The validation cohort included patients from Hospital Universitari Mutua de Terrassa (Terrassa) and Hospital Universitari La Fe (Valencia), all tertiary centers in Spain. We employed K-means clustering to group patients according to reverse transcription polymerase chain reaction (rRT-PCR) cycle threshold (Ct) values and lymphocyte counts at diagnosis, and pre-test symptom duration. The impact of remdesivir on 60-day mortality in each cluster was assessed. Results: A total of 1160 patients (median age 66, interquartile range (IQR) 55–78) were included. We identified five clusters, with mortality rates ranging from 0 to 36.7%. Highest mortality rate was observed in the cluster including patients with shorter pre-test symptom duration, lower lymphocyte counts, and lower Ct values at diagnosis. The absence of remdesivir administration was associated with worse outcome in the high-mortality cluster (10.5% vs. 36.7%; p< 0.001), comprising subjects with higher viral loads. These results were validated in an external multicenter cohort of 981 patients. Conclusions: Patients with COVID-19 exhibit varying mortality rates across different clinical phenotypes. K-means clustering aids in identifying patients who derive the greatest mortality benefit from remdesivir use.

Introduction: Increased mortality has been reported in the Latin American population. The objective is to compare the clinical characteristics and outcome of Latin American and Spanish populations in a cohort of patients hospitalized with COVID-19 during the first year of the pandemic. Methods: We retrospectively analysed all the Latin American patients (born in South or Central America) hospitalized in our centre from February 2020 to February 2021 and compared them with an age- and gender-matched group of Spanish subjects. Variables included were demographics, co-morbidities, clinical and analytical parameters at admission and treatment received. The primary outcomes were ICU admission and mortality at 60 days. A conditional regression analysis was performed to evaluate the independent baseline predictors of both outcomes. Results: From the 3216 patients in the whole cohort, 216 pairs of case-controls (Latin American and Spanish patients, respectively) with same age and gender were analysed. COPD was more frequent in the Spanish group, while HIV was more prevalent in the Latin American group. Other co-morbidities showed no significant difference. Both groups presented with similar numbers of days from symptom onset, but the Latin American population had a higher respiratory rate (21 vs. 20 bpm, P= 0.041), CRP (9.13 vs. 6.22 mg/dl, P= 0.001), ferritin (571 vs. 383 ng/ml, P= 0.012) and procalcitonin (0.10 vs. 0.07 ng/ml, P= 0.020) at admission and lower cycle threshold of PCR (27 vs. 28.8, P= 0.045). While ICU admission and IVM were higher in the Latin American group (17.1% vs. 13% and 9.7% vs. 5.1%, respectively), this was not statistically significant. Latin American patients received remdesivir and anti-inflammatory therapies more often, and no difference in the 60-day mortality rate was found (3.2% for both groups). Conclusion: Latin American patients with COVID-19 have more severe disease than Spanish patients, requiring ICU admission, antiviral and anti-inflammatory therapies more frequently. However, the mortality rate was similar in both groups.

Introduction: We aimed to assess risk factors for multidrug-resistant Gram-negative bacilli (MDR-GNB) from a large amount of data retrieved from electronic health records (EHRs) and determine whether machine learning (ML) may be useful in assessing the risk of MDR-GNB infection at febrile neutropenia (FN) onset. Methods: Retrospective study of almost 7 million pieces of structured data from all consecutive episodes of FN in hematological patients in a tertiary hospital in Barcelona (January 2008–December 2017). Conventional multivariate analysis and ML algorithms (random forest, gradient boosting machine, XGBoost, and GLM) were done. Results: A total of 3235 episodes of FN in 349 patients were documented; MDR-GNB caused 180 (5.6%) infections in 132 patients. The most frequent MDR-GNBs were MDR-Pseudomonas aeruginosa(53%) and extended-spectrum beta-lactamase-producing Enterobacterales (46%). According to conventional logistic regression analysis, independent factors associated with MDR-GNB infection were age older than 45 years (OR 2.07; 95% CI 1.31–3.24), prior antibiotics (2.62; 1.39–4.92), first-ever FN in this hospitalization (2.94; 1.33–6.52), prior hospitalizations for FN (1.72; 1.02–2.89); at least 15 prior hospital visits (2.65; 1.31–5.33), high-risk hematological diseases (3.62; 1.12–11.67), and hospitalization in a room formerly occupied by patients with MDR-GNB isolation (1.69; 1.20–2.38). ML algorithms achieved the following AUC and F1 score for MDR-GNB prediction: random forest, 0.79–0.9711; GMB, 0.79–0.9705; XGBoost, 0.79–0.9670; and GLM, 0.78–0.9716. Conclusion: Data generated in EHRs proved useful in assessing risk factors for MDR-GNB infections in patients with FN. The great number of analyzed variables allowed us to identify new factors related to MDR infection, as well as to train ML algorithms for infection predictions. This information may be used by clinicians to make better clinical decisions.

Introduction: We aimed to compare the clinical characteristics and outcomes of bloodstream infections (BSI) in cancer patients presenting febrile neutropenia with and without HIV infection, and analyze the prognostic factors for mortality. Methods: BSI episodes in febrile neutropenic patients following chemotherapy were prospectively collected (1997–2018). A case (HIV-infected)–control (non-HIV-infected) sub-analysis was performed (1:2 ratio), matching patients by age, gender, baseline disease, and etiological microorganism. Results: From 1755 BSI episodes in neutropenic cancer patients, 60 (3.4%) occurred in those with HIV. HIV characteristics: 51.7% were men who have sex with men; 58.3% had < 200 CD4; 51.7% had a detectable HIV-1 RNA viral load before the BSI episode; 70.0% met AIDS-defining criteria; and 93.3% were on antiretroviral therapy, with a protease inhibitor-based regimen being the most common (53.0%). HIV-infected patients were younger, more frequently male and more commonly presenting chronic liver disease (p< 0.001 for all). BSI due to Enterococcusspp. was significantly more frequent among patients with HIV (p= 0.017) with no differences in other pathogens. HIV-infected patients with cancer presented with shock more frequently (p= 0.014) and had higher mortality (31.7% vs. 18.1%, p= 0.008). In the case–control analysis, cases (HIV-infected) had chronic liver disease (p= 0.003) more frequently, whereas acute leukemia (p= 0.013) and hematopoietic stem-cell transplant (p= 0.023) were more common among controls. There was a non-significant trend for cases to have higher mortality (p= 0.084). However, in multivariate analysis, HIV infection was not associated with mortality (p= 0.196). Conclusion: HIV-infected patients with cancer developing febrile neutropenia and BSI have different epidemiological and clinical profiles, and experience higher mortality. However, HIV infection by itself was not associated with mortality.

•Characteristics and outcomes of bloodstream infection (BSI) change depending on time since hematopoietic stem cell transplantation (HSCT).•Inappropriate empiric antibiotic therapy occurred in more than one-quarter of BSIs.•Inappropriate empiric antibiotic therapy was more frequent in Pseudomonas aeruginosaand multidrug-resistant gram-negative bacilli.•BSI occurring ≥30 days after HSCT and shock were associated with increased mortality.•BSI caused by multidrug-resistant P. aeruginosaand receipt of inappropriate empiric antibiotic therapy were associated with higher mortality.

We aimed to describe epidemiology changes in bloodstream infections (BSI) episodes in hematopoietic stem cell transplant (HSCT) recipients throughout a 25-year period (1993–2017), comparing five-year time spans, and we evaluate their impact on inappropriate empirical antibiotic treatment (IEAT) and mortality. During the study period, 1164 BSI episodes were documented in patients undergoing HSCT (71.6% allogenic and 29% autologous). A significant decrease in gram-positive cocci (GPC) and increase in gram-negative bacilli (GNB) were observed (p< 0.001). Among GP, coagulase-negative staphylococci (CoNS) significantly decreased whereas rising E. faeciumBSI was documented. Among GNB, E. coli, Pseudomonas aeruginosaand K. pneumoniaerates increased. Multidrug-resistant (MDR) GNB, especially ESBL-E. coliand MDR-P. aeruginosa, emerged in 2008 and has gradually increased. IEAT against MDR-P. aeruginosa, but not in other MDR-GNB, augmented throughout the study period. Overall, 30-day and related mortality rates were 12.7% and 7.7% respectively, both increasing over time (p< 0.001 and p= 0.025). In GNB, 30-day and related mortality were 18.5% and 12.8%, respectively, increasing over time (p< 0.001 and p= 0.004). To conclude, important BSI epidemiological changes were described in a 25-year period. Concerning increase in IEAT for P. aeruginosainfections and rising 30-day mortality rate were documented.

La descripción antiguamente más frecuente de la mucormicosis era la afectación nasosinusal en pacientes con cetoacidosis diabética. Sin embargo, en los últimos años han surgido nuevos grupos de pacientes con riesgo de mucormicosis.

The study aimed to investigate whether the clinical presentations and outcomes (length of stay, ICU admission, and 30-day mortality) of pneumococcal pneumonia in virologically suppressed patients who were HIV-infected on ART with a CD4+ T-cell count > 350 cells/mm3are comparable to those seen in patients with HIV, using a case-control design.

In spite of increased awareness and the efforts taken to optimize Clostridium difficileinfection (CDI) management, with the limited number of currently available antibiotics for C. difficilethe halt of this increasing epidemic remains out of reach. There are, however, close to 80 alternative treatment methods with controversial anti-clostridial efficacy or in experimental phase today. Indeed, some of these therapies are expected to become acknowledged members of the recommended anti-CDI arsenal within the next few years. None of these alternative treatment methods can respond in itself to all the major challenges of CDI management, which are primary prophylaxis in the susceptible population, clinical cure of severe cases, prevention of recurrences, and forestallment of asymptomatic C. difficilecarriage and in-hospital spread. Yet, the greater the variety of treatment choices on hand, the better combination strategies can be developed to reach these goals in the future. The aim of this article is to provide a comprehensive summary of these experimental and currently off-label therapeutic options.

Clostridium difficileinfection (CDI) is increasingly recognized as an emerging healthcare problem of elevated importance. Prevention and treatment strategies are constantly evolving along with the apperance of new scientific evidence and novel treatment methods, which is well-reflected in the differences among consecutive international guidelines. In this article, we summarize and compare current guidelines of five international medical societies on CDI management, and discuss some of the controversial and currently unresolved aspects which should be addressed by future research.

Pseudomonas aeruginosais not a frequent pathogen in community-acquired pneumonia (CAP). However, in patients with severe CAP, P aeruginosacan be the etiology in 1.8% to 8.3% of patients, with a case-fatality rate of 50% to 100%. We describe the prevalence, clinical characteristics, outcomes, and risk factors associated with CAP resulting from multidrug-resistant (MDR) and non-MDR P aeruginosa.

Debridement and prosthesis retention, combined with a prolonged antibiotic regimen including rifampicin, is an accepted therapeutic approach when the duration of symptoms is less than 4 weeks and there are no radiological signs of loosening. The outcome of patients managed with this strategy has been previously assessed in several articles with success rates of 60–90%. This study aims to review the clinical experience with linezolid in 3 different hospitals from Spain and France in patients with prosthetic joint infection (PJI) managed with debridement, retention of the implant and treated with linezolid with or without rifampicin. Patients with an acute PJI who underwent open debridement with implant retention treated with linezolid for more than 7 days in 3 hospitals from Barcelona, Tours and Lille between 2005 and 2011 were retrospectively reviewed. Relevant information about demographics, co-morbidity, type of implant, surgical treatment, microorganism isolated, antimicrobial therapy, adverse events (AEs) and outcomes were recorded from patients. A total of 39 patients were retrospectively reviewed. The mean age (SD) was 70.5 (8.8) years and 9 patients had diabetes mellitus (23%). There were 25 (64%) knee prostheses, 13 (33%) hips and 1 shoulder (3%). The median interquartile range (IQR) days from arthroplasty to infection diagnosis was 17 (19–48) and 33 (85%) cases were diagnosed within the first 60 days. The median (IQR) duration of antibiotic treatment was 70.5 (34–96) days and the median (IQR) number of days on linezolid treatment was 44.5 (30–81). AEs were observed in 15 patients (38%), with gastrointestinal complaints in 8 cases and anemia in 5 being the most frequent. After a median (IQR) follow-up of 2.5 (1.8–3.6) years, there were 11 failures (28%) (8 relapses and 3 new infections). The failure rate was higher in the rifampicin group (36% vs. 18%) mainly due to a higher relapse rate (27% vs. 12%) although differences were not statistically significant. Management of acute PJIs with debridement and retention of the implant linezolid, with or without rifampicin, is associated with a high remission rate and it is an alternative treatment for infections due to fluoroquinolone and/or rifampicin-resistant staphylococci.

ABSTRACTThe aim of this study was to compare the prosthetic joint infection (PJI) rate after total joint arthroplasty in two consecutive periods of treatment with different antibiotic prophylaxes: cefuroxime versus cefuroxime plus teicoplanin. We retrospectively reviewed 1,896 patients who underwent total hip arthroplasty or total knee arthroplasty between March 2010 and February 2013. From March 2010 to August 2011, patients received 1.5 g of cefuroxime during induction of anesthesia and another 1.5 g 2 h later (the C group). From September 2011, 800 mg of teicoplanin was added to cefuroxime (the CT group). Throughout the period studied, there were no variations in pre- or postoperative protocols. Univariate and multivariate analyses were performed to evaluate independent predictors of PJI. There were 995 (55.7%) patients in the C group and 791 (44.3%) in the CT group. Patients in the CT group had a significantly lower PJI rate than patients in the C group (1.26% versus 3.51%, P= 0.002). There were no infections due to Staphylococcus aureusin the CT group (0% versus 1.6% in the C group, P< 0.001). A stepwise forward Cox regression model identified male sex (hazard ratio [HR], 3.85; 95% confidence interval [CI], 2.09 to 7.18), a body mass index of ≥35 kg/m2(HR, 2.93; 95% CI, 1.37 to 6.27), the presence of lung disease (HR, 2.46; 95% CI, 1.17 to 5.15), and red blood cell transfusion (HR, 3.70; 95% CI, 1.89 to 7.23) to be independent variables associated with a higher risk of PJI. The addition of teicoplanin was associated with a lower risk of infection (HR, 0.35; 95% CI, 0.17 to 0.74). In conclusion, the addition of teicoplanin to cefuroxime during primary arthroplasty was associated with a significant reduction in the global PJI rate due to a reduction of infections caused by Gram-positive bacteria.

ABSTRACTThe role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patients with Gram-negative bacteremia in the Hospital Clinic of Barcelona from 2000 to 2012 were included in this study. In order to compare the mortality rates between patients who received linezolid or glycopeptides, the propensity scores on baseline variables were used to balance the treatment groups, and both propensity score matching and propensity-adjusted logistic regression were used to compare the 30-day mortality rates between the groups. The overall 30-day mortality rate was 16.0% during the study period. Sixty-eight patients received empirical treatment with linezolid, and 1,058 received glycopeptides. The propensity score matching included 64 patients in each treatment group. After matching, the mortality rates were 14.1% (9/64) in patients who received glycopeptides and 21.9% (14/64) in those who received linezolid, and a nonsignificant association between empirical linezolid treatment and mortality rate (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.69 to 3.82; P= 0.275, McNemar's test) was found. This association remained nonsignificant when variables that remained unbalanced after matching were included in a conditional logistic regression model. Further, the stratified propensity score analysis did not show any significant relationship between empirical linezolid treatment and the mortality rate after adjustment by propensity score quintiles or other variables potentially associated with mortality. In conclusion, the propensity score analysis showed that empirical treatment with linezolid compared with that with glycopeptides was not associated with 30-day mortality rates in patients with Gram-negative bacteremia.

ABSTRACTMortality and morbidity are significantly higher among patients with dialysis catheters, which has been associated with chronic activation of the immune system. We hypothesized that bacteria colonizing the catheter lumen trigger an inflammatory response. We aimed to evaluate the inflammatory profile of hemodialysis patients before and after locking catheters with an antimicrobial lock solution. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha (TNF-α) were measured in serum, and levels of mRNA gene expression of IL-6, IL-10, and TNF-α were analyzed in peripheral blood mononuclear cells (PBMC). Samples were obtained at baseline and again after 3 months' use of taurolidine-citrate-heparin lock solution (TCHLS) in 31 hemodialysis patients. The rate of catheter-related bloodstream infections (CRBSI) was 1.08 per 1,000 catheter-days in the heparin period and 0.04 in the TCHLS period (P= 0.023). Compared with the baseline data, serum levels of hs-CRP and IL-6 showed median percent reductions of 18.1% and 25.2%, respectively (P< 0.01), without significant changes in TNF-α or IL-10 levels. Regarding cytokine gene expression in PBMC, the median mRNA expression levels of TNF-α and IL-6 decreased by 20% (P< 0.05) and 19.7% (P= 0.01), respectively, without changes in IL-10 expression levels. The use of TCHLS to maintain the catheter lumen sterility significantly reduces the incidence of CRBSI and improves the inflammatory profile in hemodialysis patients with tunneled catheters. Further studies are needed to evaluate the potential beneficial effects on clinical outcomes.

Prolonged life expectancy has currently increased the proportion of the very elderly among patients with community-acquired pneumonia (CAP). The aim of this study was to determine the influence of age and comorbidity on microbial patterns in patients over 65 years of age with CAP.

Introduction:Inhaled antibiotics are probably the safest and most effective therapy for Pseudomonas aeruginosachronic lung infection in cystic fibrosis (CF) patients.Areas covered:To summarise the available evidence, a systematic review of the three currently available inhaled antibiotics (aztreonam lysine (AZLI), colistin (COL) and tobramycin (TOB)) was performed. The three AZLI placebo-controlled studies showed that the improvements in FEV1and mean sputum P. aeruginosadensity were statistically significant better than with placebo. The two COL placebo-controlled studies involved few patients but showed that COL was better than placebo in terms of maintenance of some pulmonary function parameters. The tobramycin inhalation solution (TIS) and tobramycin inhalation powder studies showed that the efficacy of both formulations was similar but significantly better than placebo. In the comparative studies, TIS showed more efficacy than COL solution, colistin inhalation powder showed non-inferiority to TIS and AZLI was superior to TIS.Expert opinion:Placebo-controlled and comparative clinical trials have shown that clinical evidence of inhaled antibiotics is very different. The choice of treatment for each individual CF patient must be based on the features of the drug (clinical evidence on efficacy and safety), the inhalation system and the patient characteristics. Development of new inhaled antibiotics will allow new end points of efficacy and therapy regimens to be assessed.

Thrombocytosis, often considered a marker of normal inflammatory reaction of infections, has been recently associated with increased mortality in hospitalized patients with community-acquired pneumonia (CAP). We assessed the characteristics and outcomes of patients with CAP and thrombocytosis (platelet count ≥ 4 × 105/mm3) compared with thrombocytopenia (platelet count < 105/mm3) and normal platelet count.

ABSTRACTLinezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (Cmin) and to determine factors associated with a Cmin< 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with a Cmindetermination at the steady state and within the first 10 days of treatment were retrospectively reviewed. Concentrations were measured using high-pressure liquid chromatography. Univariate and multivariate analysis were performed to identify risk factors of low Cmin. A total of 29.5% of patients had a Cmin< 2 mg/liter. The percentage was significantly higher in patients with an estimated glomerular filtration (eGF) > 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of Cmin< 2 mg/liter were an eGF > 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P= 0.001) and infection due to S. aureus(OR, 5.906; 95% CI, 1.651 to 21.126; P= 0.006). A linezolid Cminof <2 mg/liter was found in 29.5% of cases, and the risk was significantly higher among those with an eGF > 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy.

Purposes To evaluate the long-term outcome (at least 4 years) of patients who underwent a surgical debridement due to an acute prosthetic joint infection (PJI) and to compare them with a control group that did not have an acute septic complication.Methods From January 1999 to December 2007, 61 patients with an acute PJI in remission after 2 years of follow-up (cases) were retrospectively reviewed and compared with a control group (2:1) without an acute PJI matched by age, year of arthroplasty, and type of prosthesis. Septic and aseptic complications of each group were gathered and compared using a chi-square test. A two-tailed p value <0.05 was considered statistically significant.Results Out of 183 patients, 4 cases and 2 controls were excluded due to death or lost to follow up; 113 (63.8%) were females and 109 (61.5%) had a knee replacement. The mean age and time of followup were 68.3 and 6.4 years, respectively. There were no statistically significant differences between cases and controls in the percentage of late septic or aseptic loosening. However, the late relapse rate in patients with acute PJI caused by S. aureus, was 12.5% (2 out of 16) and there was a trend towards significance when compared with the rest of the cohort (3.3%, p = 0.09). Aseptic late complications were more frequent in GN-cases (10.7%) than in the other groups (3.4% in GP-cases and 5% in controls) but this difference was not statistically significant (p = 0.19).Conclusions In conclusion, although analyzing all late complications together, patients with an acute PJI have a similar long-term outcome in comparison with controls; patients with an acute PJI due to S. aureus had a higher late relapse rate; and GN-cases developed an aseptic loosening more frequently. In the future, it is necessary to evaluate larger series to confirm our results.

Purposes To evaluate the specific characteristics, outcome, and predictors of failure of prosthetic joint infections (PJI) due to S. aureus and coagulase-negative staphylococci (CNS) treated with open debridement and retention of the implant.Methods PJI due to S. aureus or CNS prospectively registered in a database from 1999 to 2009 were retrospectively reviewed. During the study period, 106 patients met the inclusion criteria. The mean follow-up period was 3.8 years and for at least 2 years in all patients. The failure rate was 23.6% (25 out of 106). The only variable significantly associated with failure in the global cohort was polymicrobial infection (38.7% vs. 17.3%, p = 0.024). Fifty-seven (53.8%) patients had an infection due to S. aureus and 49 (46.2%) due to CNS. Among S. aureus infections, 95% corresponded to primary arthroplasties while 98% of PJIs due to CNS were after revision arthroplasties (p<0.001). C-reactive protein was significantly higher in PJI due to S. aureus (9.5 mg/dl vs. 4.9 mg/dl, p = 0.007). The rate of methicillin-resistance (8.8% vs. 59.2%, p<0.001) and fluoroquinolone-resistance (15.8% vs. 34.7%, p = 0.005) was significantly higher in CNS infections. The global failure rate was higher in S. aureus infections (28% vs. 18.3. p = 0.26). In S. aureus infections, patients diagnosed within the first 15 days after joint arthroplasty (p = 0.031) and with bacteremia (p = 0.046) had poor prognosis. In CNS infections only the location of the prosthesis (knee 27.6% vs. hip 5%, p = 0.045) was associated with failure.Conclusions PJIs due to S. aureus were mainly in primary arthroplasties; they had a higher inflammatory response; and the strains were more susceptible to fluoroquinolones and methicillin than CNS infections. S. aureus infections had a higher failure rate than CNS infections, however, the difference was not statistically significant. There were few factors associated with failure and they were different in S. aureus and CNS infections.

Purposes To review patients with a hematogenous and early post-surgical prosthetic joint infection (PJI) due to S. aureus treated with debridement and retention of the implant and to compare their clinical characteristics and outcome.Methods From January 2000 all patients with a prosthetic joint infection treated in a single-center were prospectively registered and followed-up. All potentially variables associated with outcome were recorded. For the present study, cases with a hematogenous or early post-surgical PJI due to S. aureus treated with debridement and at least 2 years of follow-up were reviewed. Cox regression model to identify factors associated with outcome were applied.Results 12 hematogenous and 53 early post-surgical PJI due to S. aureus were included. Number of patients presenting with fever, leucocyte count, C-reactive protein concentration, and the number of bacteremic patients were significantly higher in hematogenous infections while the number of polymicrobial infections was lower in hematogenous than in early post-surgical infections. The global failure rate in hematogenous and early post-surgical PJI was 58.7% and 24.5%, respectively (p=0.02). The Cox regression model identified hematogenous infections (OR: 2.57, CI95%: 1.02–6.51, p=0.04) and the need of a second debridement (OR: 4.61, CI95%: 1.86–11.4, p=0.001) as independent predictors of failure.Conclusion Hematogenous infections were monomicrobial and had more severe symptoms and signs of infection than early post-surgical PJI. Hematogenous PJI due to S. aureus, using debridement with implant retention, had a worse outcome than early post-surgical infections.

Purpose To evaluate the relationship between intraoperative cultures during hip arthroplasty, the different patient characteristics, and the risk of developing a prosthetic joint infection (PJI).Methods A prospective observational study was performed. Patients who underwent elective THA from March 2007 to March of 2011 were included. Three samples were taken just after arthrotomy: synovial fluid inoculated into blood culture flasks (SF), a tissue sample (TS), and a swab of periprosthetic tissue (S). Patients received standard antibiotic prophylaxis. The PJI rate within the first 3 months after arthroplasty was recorded.Results 402 prostheses were included in the study. Contamination rate of synovial fluid was 10.2%. The most frequent isolated microorganism was coagulase-negative staphylococci (CoNS) (32 out of 41). Body mass index (BMI) was the only host characteristic associated with positive intraoperative culture (p=0.009). The PJI rate was 3.7%. Variables associated with PJI in the univariate and multivariate analysis were: age ≥67 years (p=0.012 OR: 5.35 (1.45–19.81); CI95%) and a BMI ≥35 (p=0.002, OR: 7.7 (2.12–27.85) CI95%). PJI rate among patients with BMI<35 with negative and positive intraoperative cultures was 3% and 2.7%, respectively, however, the rate among patients with BMI ≥ 35 was 15% and 25%, respectively.Conclusion A BMI ≥35 was associated with a higher risk of positive intraoperative culture during hip arthroplasty. In addition, a BMI ≥35 was independently associated with a high risk of PJI and the highest rate was documented among obese patients with positive intraoperative cultures.

The objective of our study was to study which is the most accurate specimen for histological diagnosis of prosthetic joint infections (pseudocapsule or interface membrane). This is a prospective study including hip revision arthroplasties performed from January 2007 to June 2009. Specimens from pseudocapsule and from interface membrane were obtained from each patient. The histology was considered positive for infection when ≥5 neutrophils per high-power field ( × 40) were found. Definitive diagnosis of infection was considered when ≥2 cultures were positive for the same microorganism. According to the definition of infection, patients were classified in two groups: (A) patients with aseptic loosening in whom cultures obtained during surgery were negative and (B) patients with prosthetic joint infection. A total of 69 revisions were included in the study; 57 were classified in group A and 12 in group B. In group B, the percentage of positive interface membrane histology was significantly higher than the percentage of positive pseudocapsule histology (83 vs 42%, P=0.04, Fisher's exact test). The results suggest that periprosthetic interface membrane is the best specimen for the histological diagnosis of prosthetic joint infection.

To evaluate the usefulness of 99mTc-ciprofloxacin scintigraphy (CFS) in patients with hip or knee arthroplasty and suspected infection.

ABSTRACTThe aim of our study was to evaluate the outcome of acute prosthetic joint infections (PJIs) due to gram-negative bacilli (GNB) treated without implant removal. Patients with an acute PJI due to GNB diagnosed from 2000 to 2007 were prospectively registered. Demographics, comorbidity, type of implant, microbiology data, surgical treatment, antimicrobial therapy, and outcome were recorded. Classification and regression tree analysis, the Kaplan-Meier survival method, and the Cox regression model were applied. Forty-seven patients were included. The mean age was 70.7 years, and there were 15 hip prostheses and 32 knee prostheses. The median number of days from the time of arthroplasty was 20. The most frequent pathogens were members of the Enterobacteriaceaefamily in 41 cases and Pseudomonasspp. in 20 cases. Among the Enterobacteriaceae, 14 were resistant to ciprofloxacin, while all Pseudomonas aeruginosaisolates were susceptible to ciprofloxacin. The median durations of intravenous and oral antibiotic treatment were 14 and 64 days, respectively. A total of 35 (74.5%) patients were in remission after a median follow-up of 463 days (interquartile range, 344 to 704) days. By use of the Kaplan-Meier survival curve, a C-reactive protein (CRP) concentration of ≤15 mg/dl (P= 0.03) and receipt of a fluoroquinolone, when all GNB isolated were susceptible (P= 0.0009), were associated with a better outcome. By use of a Cox regression model, a CRP concentration of ≤15 mg/dl (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.05 to 12.5; P= 0.043) and receipt of a fluoroquinolone (OR, 9.09; 95% CI, 1.96 to 50; P= 0.005) were independently associated with better outcomes. Open debridement without removal of the implant had a success rate of 74.5%, and the factors associated with good prognosis were a CRP concentration at the time of diagnosis ≤15 mg/dl and treatment with a fluoroquinolone.

Some deficient genetic polymorphisms of the innate immune system have been correlated to a higher susceptibility to different infections, especially in immunocompromised patients. The possible association between an increased incidence of pneumococcal bacteremia in HIV-infected patients, and deficient polymorphisms of the mannose-binding lectin (MBL), MBL-associated serine protease 2 (MASP-2), and toll-like receptors (TLR) 2 and 4 is analyzed by means of a case-control study. Cases: HIV-infected patients with pneumococcal bacteremia. Controls: HIV-infected patients without previous pneumococcal bacteremia matched with cases by sex and CD4 count in a 2:1 ratio. Fifty-seven cases and 114 controls were studied. Demographics, HIV infection status, antiretroviral therapy, risk factors for pneumococcal disease, and genotypes of MBL2, MASP2, TLR2 and TLR4 were analyzed. The prevalence of the MBL2, MASP2, TLR2 and TLR4 gene polymorphisms was similar in both groups. No statistical significance was found (OR 0.77, IC95 0.27 - 2.13) when analyzing the possible association of MBL2 deficient polymorphisms with pneumococcal bacteremia. In HIV infected patients, no association between the presence of deficient polymorphisms of MBL2, MASP2, TLR2 and TLR4 and the incidence of pneumococcal bacteremia was found.

ABSTRACTHematological disturbances that develop during linezolid treatment are a major concern when linezolid is administered for prolonged periods of time. The aim of this study was to evaluate the influences of pyridoxine, rifampin, and renal function on hematological adverse events. From January 2002 to April 2006, 52 patients received a long-term course of linezolid. Blood cell counts were monitored weekly. Thrombocytopenia was defined as a decrease to <75% of the baseline platelet count, and anemia was defined when the hemoglobin concentration decreased by ≥2 g/liter from the baseline value. Twenty-four patients received linezolid alone, and 28 patients received linezolid plus 200 mg of pyridoxine. The Kaplan-Meier survival method, followed by the log-rank test, was used to estimate the cumulative probability of adverse events, and Cox regression analysis was performed to evaluate the independent predictors of toxicity. The baseline characteristics of the patients in both groups were similar. The cumulative probability of thrombocytopenia and anemia in patients who received pyridoxine was not different from that in patients who did not receive it. Hematological adverse events were less frequent in patients taking rifampin and were more frequent in patients with renal failure. However; the Cox regression analysis showed that rifampin was the only independent predictor associated with a lower risk of thrombocytopenia (hazard ratio, 0.37; 95% confidence interval, 0.14 to 0.98; P= 0.045). In conclusion, pyridoxine did not prevent linezolid-related hematological adverse events, and the coadministration of rifampin was associated with a lower risk of thrombocytopenia.

ABSTRACTThe objective of the present study was to determine the mitochondrial toxicity mechanisms of linezolid-related hyperlactatemia. Five patients on a long-term schedule of linezolid treatment were studied during the acute phase of hyperlactatemia and after clinical recovery and lactate normalization following linezolid withdrawal. Mitochondrial studies were performed with peripheral blood mononuclear cells and consisted of measurement of mitochondrial mass, mitochondrial protein synthesis homeostasis (cytochrome coxidase [COX] activity, COX-II subunit expression, COX-II mRNA abundance, and mitochondrial DNA [mtDNA] content), and overall mitochondrial function (mitochondrial membrane potential and intact-cell oxidative capacity). During linezolid-induced hyperlactatemia, we found extremely reduced protein expression (16% of the remaining content compared to control values [100%], P< 0.001) for the mitochondrially coded, transcribed, and translated COX-II subunit. Accordingly, COX activity was also found to be decreased (51% of the remaining activity, P< 0.05). These reductions were observed despite the numbers of COX-II mitochondrial RNA transcripts being abnormally increased (297%, P= 0.10 [not significant]) and the mitochondrial DNA content remaining stable. These abnormalities persisted even after the correction for mitochondrial mass, which was mildly decreased during the hyperlactatemic phase. Most of the mitochondrial abnormalities returned to control ranges after linezolid withdrawal, lactate normalization, and clinical recovery. Linezolid inhibits mitochondrial protein synthesis, leading to decreased mitochondrial enzymatic activity, which causes linezolid-related hyperlactatemia, which resolves upon discontinuation of linezolid treatment.

We describe an outbreak of multidrug-resistant Serratia marcescensinfection and colonization involving adults admitted to a surgical intensive care unit. Examination of the outbreak revealed epidemiological evidence that consumption of tap water from a contaminated faucet during receipt of oral medication was the mechanism of S. marcescensacquisition.

ABSTRACTIn patients with Escherichia colibacteremia, data on the relationship of phylogenetic background, biofilm production, and degree of bacteremia with clinical variables and prognosis are scarce. During a 1-year period, all adults with bacteremia due to Escherichia colidiagnosed at a university center were enrolled. Determination of phylogenetic background, biofilm production, and genotyping was performed with all strains, and the time to positivity of blood culture vials was recorded. A total of 185 episodes of diverse-source E. colibacteremia was analyzed. Strains of phylogroup D were predominant (52%). Phylogroup A isolates were associated with pneumonia and prior antibiotic intake, B1 with an abdominal source of infection, B2 with the absence of urological abnormalities, and D with urological abnormalities and age below 65 years. Resistance to antibiotics and no biofilm production were concentrated in phylogroup A strains. Biofilm production was not associated with any clinical variable. An immunocompromising condition (odds ratio [OR] = 5.01, 95% confidence interval [CI] = 1.4 to 17.9), peritonitis (OR = 17, 95% CI = 3.32 to 87), pneumonia (OR = 9.97, 95% CI = 1.96 to 50.6), and =7 h to bacteremia detection (OR = 4.37, 95% CI = 1.38 to 13.8) were the best predictors of a fatal outcome. Results from this study suggest that the distribution of phylogenetic backgrounds among E. colistrains involved in diverse-source bacteremia may be subject to geographical variation and that, in afflicted individuals, some high-risk sources, the patient's underlying condition, and the degree of bacteremia are more important than microbial factors in determining the outcome. Time to positivity of blood culture vials may be a variable of potential clinical impact.

In patients with Escherichia coli bacteremia, data on the relationship of phylogenetic background, biofilm production, and degree of bacteremia with clinical variables and prognosis are scarce. During a 1-year period, all adults with bacteremia due to Escherichia coli diagnosed at a university center were enrolled. Determination of phylogenetic background, biofilm production, and genotyping was performed with all strains, and the time to positivity of blood culture vials was recorded. A total of 185 episodes of diverse-source E. coli bacteremia was analyzed. Strains of phylogroup D were predominant (52%). Phylogroup A isolates were associated with pneumonia and prior antibiotic intake, B1 with an abdominal source of infection, B2 with the absence of urological abnormalities, and D with urological abnormalities and age below 65 years. Resistance to antibiotics and no biofilm production were concentrated in phylogroup A strains. Biofilm production was not associated with any clinical variable. An immunocompromising condition (odds ratio [OR] = 5.01, 95% confidence interval [CI] = 1.4 to 17.9), peritonitis (OR = 17, 95% CI = 3.32 to 87), pneumonia (OR = 9.97, 95% CI = 1.96 to 50.6), and ≤7 h to bacteremia detection (OR = 4.37, 95% CI = 1.38 to 13.8) were the best predictors of a fatal outcome. Results from this study suggest that the distribution of phylogenetic backgrounds among E. coli strains involved in diverse-source bacteremia may be subject to geographical variation and that, in afflicted individuals, some high-risk sources, the patient's underlying condition, and the degree of bacteremia are more important than microbial factors in determining the outcome. Time to positivity of blood culture vials may be a variable of potential clinical impact.

Background The role of viruses in community-acquired pneumonia may have been previously underestimated. We aimed to study the incidence and clinical characteristics of community-acquired pneumonia (CAP) due to respiratory viruses in adults adding PCR to routine conventional laboratory tests.Methods Consecutive adult patients diagnosed of CAP from January 2003 to March 2004 were included. Conventional tests including cultures of blood, sputum, urine antigen detection of Streptococcus pneumoniaeand Legionella pneumophila, and paired serologies were routinely performed. Nasopharyngeal swabs were processed for study of respiratory viruses through antigen detection by indirect immunofluorescence assay, isolation of viruses in cell culture and detection of nucleic acids by two independent multiplex RT-PCR assays. According to the aetiology, patients were categorized in 4 groups: group 1, only virus detected; group 2, only bacteria detected; group 3, viral and bacterial; and group 4, unkown aetiology.Results Of 340 patients diagnosed with CAP, 198 had nasopharyngeal swabs available and were included in this study. Aetiology was established in 112 (57%) patients: group 1, n=26 (13%); group 2, n=66 (33%); group 3, n=20(10%). The most common aetiological agent was S. neumoniae(58 patients, 29%), followed by respiratory viruses (46 patients, 23%). Forty-eight respiratory viruses were identified: influenza virus A (n=16), respiratory syncytial virus A (n=5), adenovirus (n=8), parainfluenza viruses (n=5), enteroviruses (n=1), rhinoviruses (n=8) and coronavirus (n=5). There were two patients coinfected by two respiratory viruses. Serology detected 6 viruses, immunofluorescence 8, viral culture 12, and PCR 45. For the viruses that could be diagnosed with conventional methods, the sensitivity and specificity of RT-PCR was 85% and 92%, respectively. The only clinical characteristic that significantly distinguished viral from bacterial aetiology was a lower number of leukocytes (P=0.004).Conclusion PCR revealed that viruses represent a common aetiology of CAP. There is an urgent need to reconsider routine laboratory tests for an adequate diagnosis of respiratory viruses, as clinical characteristics are unable to reliably distinguish viral from bacterial aetiology.

Infection is the most severe complication of arthroplasty and in the majority of cases is due to contamination during surgery. The rate is about 1–3% or even higher in revision arthroplasties. The pathogenesis of these infections is related to microorganisms that reach the prosthesis directly during surgery or after surgery by the haematogenous route. The microorganisms grow on the implant surface forming biofilms that make the diagnosis and treatment of these infections difficult. There are two types of prosthetic joint infection according to the duration of symptoms acute and chronic. The diagnosis of an acute infection is based on clinical manifestations and the treatment consists of open debridement without removal of the implant. A chronic infection is difficult to distinguish from aseptic failure, often presenting only with pain and early radiological signs of loosening. A combination of preoperative and intraoperative tests is usually required for diagnosis. The most successful treatment in these cases is the removal of all inert material, including cement, prosthesis and necrotic tissue. In general, the adequate surgical procedure for each type of infection should be combined with long-term antimicrobial therapy including an active agent against microorganisms growing in biofilms. Since the main characteristic of these microorganisms is their slow growth, the best antibiotics are those with activity against stationary phase bacteria. In this article, pathogenesis, clinical presentation, epidemiology, diagnosis and treatment of prosthetic joint infections are reviewed.

Invasive aspergillosis (IA) has become the leading infectious cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This is partially because of the lack of a sensitive, specific, and noninvasive diagnostic test. New diagnostic tests for IA, such as the detection of Aspergillusgalactomannan antigen (AGA) by sandwich enzyme-linked immunoabsorbent assay (ELISA), have recently been described. This study validates the usefulness of this diagnostic tool in the allo-HSCT setting.

ABSTRACTThe evolution and the relationship between inflammatory and renal-injury markers in women with acute uncomplicated pyelonephritis under antimicrobial therapy were investigated in a prospective study. Markers were measured before and 6 and 24 h after the intravenous administration of 1 g of ceftriaxone. Before treatment, the median levels of all markers except the serum creatinine levels were high. Twenty-four hours after the onset of antibiotic treatment, the C-reactive protein (CRP) level continued to be high, while the serum interleukin-6 (IL-6) levels and the urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased significantly. In contrast, serum creatinine and tumor necrosis factor alpha levels and urine N-acetyl-ß-glucosaminidase, a1-microglobulin, and ß2-microglobulin levels did not change over time. There was a significant correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine albumin and IgG levels are glomerular and urinary tract-injury markers) as well as between serum CRP levels and the levels of the tubular-injury markers. In women with acute pyelonephritis, appropriate antibiotic treatment rapidly decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well with urine albumin and IgG levels.

ABSTRACTDifferences in the presence of nine urovirulence factors among clinical isolates of Escherichia colicausing cystitis and pyelonephritis in women and prostatitis in men have been studied. Hemolysin and necrotizing factor type 1 occur significantly more frequently among isolates causing prostatitis than among those causing cystitis (P< 0.0001) or pyelonephritis (P< 0.005). Moreover, the papGIIIgene occurred more frequently in E. coliisolates associated with prostatitis (27%) than in those associated with pyelonephritis (9%) (P< 0.05). Genes encoding aerobactin and PapC occurred significantly less frequently in isolates causing cystitis than in those causing prostatitis (P< 0.01 and P< 0.0001, respectively) and pyelonephritis (P< 0.01 and P< 0.0001, respectively). No differences in the presence of Sat or type 1 fimbriae were found. Finally, AAFII and Bfp fimbriae are no longer considered uropathogenic virulence factors since they were not found in any of the strains analyzed. Overall, the results showed that clinical isolates producing prostatitis need greater virulence than isolates producing pyelonephritis in women or, in particular, cystitis in women (P< 0.05). Overall, the results suggest that clinical isolates producing prostatitis are more virulent that those producing pyelonephritis or cystitis in women.

The in vitro activity of clinafloxacin was studied in comparison with ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, sparfloxacin and trovafloxacin against Acinetobacter baumannii clinical isolates. Clinafloxacin showed a MIC(90) of 4 mg/L, whereas the remaining quinolones showed a MIC(90) equal to or higher than 16 mg/L. MIC(50) determination in the presence of reserpine resulted in a two-fold decrease, except for trovafloxacin, which decreased four-fold, and for moxifloxacin and nalidixic acid, which did not change. The effect of reserpine was most pronounced among strains with a low level of resistance to quinolones. The MIC of clinafloxacin for strains with no mutation in either gyrA or parC genes ranged from 0.008 to 0.25 mg/L. In strains with a single mutation at amino acid codon Ser83 of the gyrA gene, the MIC of clinafloxacin ranged from 0.12 to 1 mg/L, whereas strains with a double mutation, one in the gyrA gene and another in the parC gene, showed a range of MIC of clinafloxacin from 1 to 8 mg/L. Therefore, clinafloxacin shows good activity against strains carrying a single mutation in the gyrA gene, and hence a second mutation is required for the microorganism to express resistance.

The emergence and evolution of quinolone-resistant Escherichia coli in faeces of patients with prostatitis treated with high-dose oral ciprofloxacin for 1 month were studied. In 11 of 23 patients, from whom only quinolone-susceptible E. coli was isolated before treatment, quinolone-resistant strains, genetically distinct from the quinolone-susceptible ones, predominated during and just after therapy. Two months after treatment, these were completely displaced by quinolone-susceptible E. coli, genetically distinct from the E. coli isolated before and during therapy. Hence, during ciprofloxacin therapy, half of the patients were transiently colonized with new, quinolone-resistant strains of E. coli.

Enteric and nonfermentative Gram-negative bacilli (GNB) are recognized causes of community-acquired pneumonia (CAP). Clinical presentation is usually severe, often justifying the admission of patients to an intensive care unit. The great majority of cases occur in persons who harbor GNB in the oropharynx, as a consequence of suffering from an underlying disease or taking antibiotics. Less frequently, the disease is the result of the hematogenous seeding of the lung from a distant septic focus. Clinical manifestations and radiologic features are nonspecific. However, the concurrence of a severe clinical picture and evidence of lung necrosis in a patient with comorbidity suggest the involvement of GNB. Etiologic diagnosis is difficult without resorting to invasive procedures aimed to obtain respiratory samples free of salivary contamination. Sputum Gram’s stain and culture are devoid of specificity, even if performed on a high-quality sample. CAP due to Enterobacteriaceae can usually be treated with a single -lactam antibiotic. If signs of radiologic cavitation or shock are present, the addition of an aminoglycoside is advisable. To prevent the emergence of resistance, infections due to Pseudomonas aeruginosaor other nonfermentative GNB require the combination of a -lactam with an aminoglycoside or fluoroquinolone. Optimal duration of antibiotic therapy has not been well established, but 2 to 3 weeks are generally recommended.

AbstractObjective:Identify independent risk factors associated with the development of nosocomial bacteremia.Design:Exploratory, unmatched, case-control study.Setting:A 970-bed Spanish university hospital.Patients:All non-neutropenic adult patients with nosocomial bacteremia admitted during a 12-month period were eligible as cases. All adult non-neutropenic patients without nosocomial bacteremia were eligible as controls.Results:The incidence of bacteremia in the study population was 6.9/1000 admissions/ year. One hundred eighty cases and 180 controls were analyzed. Multivariate analysis (stepwise logistic regression techniques) identified seven risk factors independently associated with nosocomial bacteremia: age above 65 years; prior admission (within six months) to the hospital; underlying diseases that were ultimately or rapidly fatal; indwelling urethral catheter in place for more than three days; intravenous central lines or peripheral venous lines (if in place for more than four days); “high-risk surgery” (i.e., lower abdominal, cardiac or thoracic); and admission to an intensive care unit.Conclusions:Although five variables are not modifiable, the remaining two relate to the use and duration of devices. Our data give strong support for the value of testing strict guidelines for limiting vascular catheters and evaluating the need for prolonged urethral catheterization. If effective infection control measures are identified, we could target hospital-wide surveillance to patients whose risk factors are amenable to intervention.

ABSTRACTThis study shows the accuracy of exclusive or earlier growth in anaerobic vials to predict Candida glabratain a large series of candidemic patients from two European hospitals using the Bactec 9240 system. Alternatively, C. glabratacan be predicted by a time to positivity cutoff value, which should be determined for each setting.

ABSTRACTThe prevalence of 31 virulence factors was analyzed among nalidixic acid-susceptible and -resistant Escherichia colistrains from phylogenetic group B2. Hemolysin, cytotoxic necrotizing factor 1, and S and F1C fimbriae genes were less prevalent among nalidixic acid-resistant E. colistrains. Quinolone resistance may be associated with a decrease in the presence of some virulence factors.

ABSTRACTTo evaluate the incidence of vancomycin tolerance among Streptococcus pneumoniaeisolates, we performed killing curve studies with 633 isolates. The penicillin MIC was ≥0.12 mg/liter for 481 (76%) of the isolates. All strains were susceptible to vancomycin. Killing curve studies were performed with a vancomycin concentration of 2.5 mg/liter. The Tupelo strain was used for quality control. No vancomycin-tolerant strain was detected.

The aim of this study was to describe the etiology and outcome of short-term peripheral venous catheter (PVC)-related bloodstream infections (PVCRBSI) in a 25-year period (1992 to 2016) and to identify predictive factors of Gram-negative PVCRBSI. This was a prospective observational study including all episodes of PVCRBSI.