Hybrid immunity protection against SARS-CoV-2 and severe COVID-19 in kidney transplantation: A retrospective, comparative cohort study.

Hybrid immunity, resulting from a combination of SARS-CoV-2 infection and vaccination, offers robust protection against COVID-19 in the general population. However, its impact on immunocompromised patients remains unexplored. We investigated the effect of hybrid immunity against the Omicron variant in a population of kidney transplant recipients receiving the fourth dose mRNA monovalent vaccination. By extracting data from the clinical records and performing individual interviews, participants were categorized into the hybrid cohort (previously infected and vaccinated individuals) and the vaccine cohort (vaccinated-only individuals). The study comprised 1114 participants, 442 in the hybrid and 672 in the vaccine cohorts. From April 2022 to August 2023, 286 infections, 38 hospitalizations and 9 deaths were reported. The cumulative incidence of infection was 12.1% (95% confidence interval [CI], 9.03-16.03) for the hybrid cohort and 36.54% (95% CI, 32.81-40.54) for the vaccine cohort after 300 days of follow-up. Hybrid immunity was associated to a 72% lower risk of infection (adjusted hazard ratio, 0.28; 95% CI, 0.21-0.38) and a 96% lower risk of hospitalization (adjusted hazard ratio, 0.04; 95% CI, 0.01-0.32). No deaths occurred in the hybrid cohort. Hybrid immunity was associated with a lower incidence of SARS-CoV-2 infection and severe COVID-19, underscoring its importance for risk stratification in this vulnerable patient population.

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial.

BACKGROUND: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. METHODS: A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. RESULTS: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). CONCLUSIONS: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338.

The Alere BinaxNOW Pneumococcal Urinary Antigen Test: Diagnostic Sensitivity for Adult Pneumococcal Pneumonia and Relationship to Specific Serotypes.

Little is known about the sensitivity of the BinaxNOW pneumococcal urinary antigen (PUA) test for adult pneumococcal pneumonia caused by different serotypes. In this study, we aimed to analyze the trends in the sensitivity of the PUA test over a 15-year period (2001 to 2015) and to analyze its sensitivity for pneumococcal pneumonia caused by different serotypes. In total, we analyzed 1,096 pneumococcal isolates from adults with pneumococcal pneumonia who had a PUA test performed at the onset of the episode. Three periods were analyzed: 2001 to 2005 (early use of the seven-valent pneumococcal conjugate vaccine [early PCV7]), 2006 to 2010 (late PCV7), and 2011 to 2015 (early PCV13). The sensitivity of the PUA test varied from 76.4% (95% confidence interval [CI], 70.5% to 82.4%) in the period from 2001 to 2005 to 77.9% in 2006 to 2010 (95% CI, 74.4% to 81.4%) and decreased to 60.5% (95% CI, 55.4% to 65.6%) in 2011 to 2015. This decrease was observed in 560 proven (83.2% in 2001 to 2005, 86.5% in 2006 to 2010, and 78.1%) and 536 probable (70.0% in 2001 to 2005, 68.7% in 2006 to 2010, and 41.5% in 2011 to 2015) episodes of pneumococcal pneumonia. Differences were observed in the sensitivity of the PUA test for diagnosing pneumonia caused by certain serotypes, being highest for the 9V (90.6%), 14 (86.8%), 18C (100%), and 20 (100%) serotypes and lowest for the 8 (55.2%), 9L/N (39.1%), 11A (48.8%), 23B (33.3%), and nontypeable (47.8%) serotypes. Comparing 2001 to 2005, 2006 to 2010, and 2011 to 2015, the prevalence of serotypes 9V (3.1%, 3.7%, and 1.7%, respectively) and 14 (7.2%, 5.1%, and 3.1%, respectively) decreased, while the prevalence of serotypes 23B (0%, 0.7%, and 1.4%, respectively), 9L/N (1.0%, 1.6%, and 3.4%, respectively), 11A (2.6%, 4.2%, and 3.7%, respectively), and 8 (1.5%, 1.5%, and 5.1%, respectively) increased. The PUA test sensitivity varied by pneumococcal pneumonia serotype, and these differences and the changes in serotype distribution were associated with an overall decrease in the sensitivity of the PUA test.

High vancomycin MICs predict the development of infective endocarditis in patients with catheter-related bacteraemia due to methicillin-resistant Staphylococcus aureus.

Background: It has been suggested that there is an increased risk of treatment failure in episodes of MRSA bloodstream infection (BSI) caused by strains with high vancomycin MICs. However, it is unknown if this phenomenon may also act as a risk factor for the development of infective endocarditis (IE). Methods: We analysed 207 episodes of catheter-related (CR)-BSI recruited from June 2008 to December 2009 within a prospective study on MRSA BSI in 21 Spanish hospitals. Vancomycin susceptibility was centrally tested. The impact of high vancomycin MIC values (≥1.5 mg/L by Etest) on the subsequent development of IE was investigated by Cox regression. Results: High vancomycin MIC values were observed in 46.9% of the isolates. Initial therapy consisted of vancomycin [99 episodes (44.7%)], daptomycin [25 (12.1%)], linezolid [18 (8.7%)] and other antistaphylococcal agents [16 (7.7%)]. Haematogenous complications occurred in 41 patients (19.8%), including 10 episodes complicated by IE. Early (48 h) and late (30 day) all-cause mortality were 3.4% and 25.1%, respectively. High vancomycin MIC isolates were more common among patients that developed IE compared with those free from this complication [90.9% (9/10) versus 44.7% (88/197); P = 0.007]. This association remained significant after adjusting for multiple confounders (including initial antibiotic therapy and catheter removal) in different models (minimum hazard ratio: 9.18; 95% CI: 1.16-72.78; P = 0.036). There were no differences in mortality according to vancomycin MIC values. Conclusions: Decreased susceptibility to vancomycin acted as a predictor of the development of IE complicating MRSA CR-BSI.

Deciphering the Resistome of the Widespread Pseudomonas aeruginosa Sequence Type 175 International High-Risk Clone through Whole-Genome Sequencing.

Whole-genome sequencing (WGS) was used for the characterization of the frequently extensively drug resistant (XDR) Pseudomonas aeruginosa sequence type 175 (ST175) high-risk clone. A total of 18 ST175 isolates recovered from 8 different Spanish hospitals were analyzed; 4 isolates from 4 different French hospitals were included for comparison. The typical resistance profile of ST175 included penicillins, cephalosporins, monobactams, carbapenems, aminoglycosides, and fluoroquinolones. In the phylogenetic analysis, the four French isolates clustered together with two isolates from one of the Spanish regions. Sequence variation was analyzed for 146 chromosomal genes related to antimicrobial resistance, and horizontally acquired genes were explored using online databases. The resistome of ST175 was determined mainly by mutational events; resistance traits common to all or nearly all of the strains included specific ampR mutations leading to ampC overexpression, specific mutations in oprD conferring carbapenem resistance, or a mexZ mutation leading to MexXY overexpression. All isolates additionally harbored an aadB gene conferring gentamicin and tobramycin resistance. Several other resistance traits were specific to certain geographic areas, such as a streptomycin resistance gene, aadA13, detected in all four isolates from France and in the two isolates from the Cantabria region and a glpT mutation conferring fosfomycin resistance, detected in all but these six isolates. Finally, several unique resistance mutations were detected in single isolates; particularly interesting were those in genes encoding penicillin-binding proteins (PBP1A, PBP3, and PBP4). Thus, these results provide information valuable for understanding the genetic basis of resistance and the dynamics of the dissemination and evolution of high-risk clones.

Methicillin-resistant Staphylococcus aureus (MRSA) catheter-related bacteraemia in haemodialysis patients.

BACKGROUND: The aim of the study was to determine clinical and microbiological differences between patients with methicillin-resistant Staphylococcus aureus (MRSA) catheter-related bacteraemia (CRB) undergoing or not undergoing haemodialysis, and to compare outcomes. METHODS: Prospective multicentre study conducted at 21 Spanish hospitals of patients with MRSA bacteraemia diagnosed between June 2008 and December 2009. Patients with MRSA-CRB were selected. Data of patients on haemodialysis (HD-CRB) and those not on haemodialysis (non-HD-CRB) were compared. RESULTS: Among 579 episodes of MRSA bacteraemia, 218 (37.7%) were CRB. Thirty-four (15.6%) were HD-CRB and 184 (84.4%) non-HD-CRB. All HD-CRB patients acquired the infection at dialysis centres, while in 85.3% of the non-HD-CRB group the infection was nosocomial (p < .001). There were no differences in age, gender or severity of bacteraemia (Pitt score); comorbidities (Charlson score ≥ 4) were higher in the HD-CRB group than in the non-HD-CRB group (73.5% vs. 46.2%, p = .003). Although there were no differences in VAN-MIC ≥ 1.5 mg/L according to microdilution, using the E-test a higher rate of VAN-MIC ≥ 1.5 mg/L was observed in HD-CRB than in non-HD-CRB patients (63.3% vs. 44.1%, p = .051). Vancomycin was more frequently administered in the HD-CRB group than in the non-HD-CRB group (82.3% vs. 42.4%, p = <.001) and therefore the appropriate empirical therapy was significantly higher in HD-CRB group (91.2% vs. 73.9%, p = .029). There were no differences with regard to catheter removal (79.4% vs. 84.2%, p = .555, respectively). No significant differences in mortality rate were observed between both groups (Overall mortality: 11.8% vs. 27.2%, p = .081, respectively), but there was a trend towards a higher recurrence rate in HD-CRB group (8.8% vs. 2.2%, p = .076). CONCLUSIONS: In our multicentre study, ambulatory patients in chronic haemodialysis represented a significant proportion of cases of MRSA catheter-related bacteraemia. Although haemodialysis patients with MRSA catheter-related bacteraemia had significantly more comorbidities and higher proportion of strains with reduced vancomycin susceptibility than non-haemodialysis patients, overall mortality between both groups was similar.

A New Integrative and Mobilizable Element Is a Major Contributor to Tetracycline Resistance in Streptococcus dysgalactiae subsp. equisimilis.

Tetracycline resistance in streptococci is mainly due to ribosomal protection mediated by the tet(M) gene that is usually located in the integrative and conjugative elements (ICEs) of the Tn916-family. In this study, we analyzed the genes involved in tetracycline resistance and the associated mobile genetic elements (MGEs) in Streptococcus dysgalactiae subsp. equisimilis (SDSE) causing invasive disease. SDSE resistant to tetracycline collected from 2012 to 2019 in a single hospital and from 2018 in three other hospitals were analyzed by whole genome sequencing. Out of a total of 84 SDSE isolates, 24 (28.5%) were resistant to tetracycline due to the presence of tet(M) (n = 22), tet(W) (n = 1), or tet(L) plus tet(W) (n = 1). The tet(M) genes were found in the ICEs of the Tn916-family (n = 10) and in a new integrative and mobilizable element (IME; n = 12). Phylogenetic analysis showed a higher genetic diversity among the strains carrying Tn916 than those having the new IME, which were closely related, and all belonged to CC15. In conclusion, tetracycline resistance in SDSE is mostly due to the tet(M) gene associated with ICEs belonging to the Tn916-family and a new IME. This new IME is a major cause of tetracycline resistance in invasive Streptococcus dysgalactiae subsp. equisimilis in our settings.

COVID-19 among workers of a comprehensive cancer centre between first and second epidemic waves (2020): a seroprevalence study in Catalonia, Spain.

OBJECTIVES: Patients with cancer are at higher risk for severe COVID-19 infection. COVID-19 surveillance of workers in oncological centres is crucial to assess infection burden and prevent transmission. We estimate the SARS-CoV-2 seroprevalence among healthcare workers (HCWs) of a comprehensive cancer centre in Catalonia, Spain, and analyse its association with sociodemographic characteristics, exposure factors and behaviours. DESIGN: Cross-sectional study (21 May 2020-26 June 2020). SETTING: A comprehensive cancer centre (Institut Català d'Oncologia) in Catalonia, Spain. PARTICIPANTS: All HCWs (N=1969) were invited to complete an online self-administered epidemiological survey and provide a blood sample for SARS-CoV-2 antibodies detection. PRIMARY OUTCOME MEASURE: Prevalence (%) and 95% CIs of seropositivity together with adjusted prevalence ratios (aPR) and 95% CI were estimated. RESULTS: A total of 1266 HCWs filled the survey (participation rate: 64.0%) and 1238 underwent serological testing (97.8%). The median age was 43.7 years (p25-p75: 34.8-51.0 years), 76.0% were female, 52.0% were nursing or medical staff and 79.0% worked on-site during the pandemic period. SARS-CoV-2 seroprevalence was 8.9% (95% CI 7.44% to 10.63%), with no differences by age and sex. No significant differences in terms of seroprevalence were observed between onsite workers and teleworkers. Seropositivity was associated with living with a person with COVID-19 (aPR 3.86, 95% CI 2.49 to 5.98). Among on-site workers, seropositive participants were twofold more likely to be nursing or medical staff. Nursing and medical staff working in a COVID-19 area showed a higher seroprevalence than other staff (aPR 2.45, 95% CI 1.08 to 5.52). CONCLUSIONS: At the end of the first wave of the pandemic in Spain, SARS-CoV-2 seroprevalence among Institut Català d'Oncologia HCW was lower than the reported in other Spanish hospitals. The main risk factors were sharing household with infected people and contact with COVID-19 patients and colleagues. Strengthening preventive measures and health education among HCW is fundamental.

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial.

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. METHODS: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

[Community-onset and nosocomial bacteremia due to methicillin-resistant Staphylococcus aureus in Spanish hospitals]. / Bacteriemias de presentación comunitaria y nosocomial por Staphylococcus aureus resistente a meticilina en hospitales españoles.

INTRODUCTION: Community-onset infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are increasing. However, there is little information about community-onset bacteremia (CB) due to MRSA in Spain. The objectives of this study were to evaluate the prevalence, clinical and molecular epidemiology, clinical features, and prognosis of CB due to MRSA in comparison with nosocomial bacteremia (NB). METHODS: Prospective multicenter cohort study; all new cases of bacteremia due to MRSA occurring during June 2003 in 59 Spanish hospitals were included. Episodes diagnosed during the first 48 hours of admission were considered CB, and otherwise, NB. Isolates were typed by pulsed field electrophoresis and multilocus sequence typing. Staphylococcal cassete chromosome mec types and Panton-Valentine leukocidin genes were studied by polymerase chain reaction. RESULTS: Sixty-four cases were included; 21 (33%) were classified as CB. In all CB cases, a relation was found with health care, or the isolate proved to be clonally related to nosocomial isolates. There were no significant differences between the groups in terms of demographic data, underlying conditions, prognosis, or characteristics of the isolates. Regarding the source of bacteremia, catheter-related cases were more frequent in NB than CB (39.5% vs 5%, P=0.005), whereas a urinary source was more frequent in CB than NB (25% vs 0%, P=0.001). Most isolates belonged to 2 clones related to the pandemic "pediatric" clone. CONCLUSION: MRSA should be considered in empiric treatment for certain infectious syndromes in patients with healthcare-associated community-onset sepsis.

Recommendations of the Spanish Antibiogram Committee (COESANT) for selecting antimicrobial agents and concentrations for in vitro susceptibility studies using automated systems.

Automated antimicrobial susceptibility testing devices are widely implemented in clinical microbiology laboratories in Spain, mainly using EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoints. In 2007, a group of experts published recommendations for including antimicrobial agents and selecting concentrations in these systems. Under the patronage of the Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) and the Study Group on Mechanisms of Action and Resistance to Antimicrobial Agents (GEMARA) from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), and aligned with the Spanish National Plan against Antimicrobial Resistance (PRAN), a group of experts have updated this document. The main modifications from the previous version comprise the inclusion of new antimicrobial agents, adaptation of the ranges of concentrations to cover the EUCAST breakpoints and epidemiological cut-off values (ECOFFs), and the inference of new resistance mechanisms. This proposal should be considered by different manufacturers and users when designing new panels or cards. In addition, recommendations for selective reporting are also included. With this approach, the implementation of EUCAST breakpoints will be easier, increasing the quality of antimicrobial susceptibility testing data and their microbiological interpretation. It will also benefit epidemiological surveillance studies as well as the clinical use of antimicrobials aligned with antimicrobial stewardship programs.

Epidemiology of invasive pneumococcal disease among adult patients in barcelona before and after pediatric 7-valent pneumococcal conjugate vaccine introduction, 1997-2007.

BACKGROUND: A dramatic decrease in the incidence of invasive pneumococcal disease (IPD) was observed among children and adults in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Little is known about the incidence of IPD after PCV7 licensure in Europe. The objective of this study was to examine changes in the prevalence of IPD among adults in the PCV7 era. METHODS: We undertook a prospective study involving adults with IPD who required hospital admission in the southern area of Barcelona, Spain. Three periods were studied: the pre-PCV7 period (1997-2001), the early PCV7 period (2002-2004), and the late PCV7 period (2005-2007). RESULTS: A total of 1007 episodes of IPD were observed. Rates of IPD among adults increased from 13.9 to 14.6 episodes per 100,000 population between the pre-PCV7 period and the early PCV7 period (P = .6) and then to 19.55 episodes per 100,000 population in the late PCV7 period (P < .001). The rates of IPD among adults due to non-PCV7 serotypes increased from 8.4 to 9.7 episodes per 100,000 population between the pre-PCV7 period and the early PCV7 period (P = .15) and then to 15.3 episodes per 100,000 population in the late PCV7 period (P < .001); IPD due to PCV7 serotypes decreased from 5.6 to 4.9 episodes per 100,000 population between the pre-PCV7 period and the early PCV7 period (P = .3), then to 4.3 episodes per 100,000 population in the late PCV7 period (P = .056). Among people aged > or = 65 years, IPD due to PCV7 serotypes decreased from 19.5 to 14.6 episodes per 100,000 population between the pre-PCV7 period and the early PCV7 period (P = .13), then to 12.3 episodes per 100,000 population in the late PCV7 period (P = .02). A decrease in the prevalence of antibioticresistant pneumococci in the late PCV7 period was associated with a decrease in the prevalence of multidrugresistant PCV7 clones (Spain(23F)-ST81, Spain(6B)-ST90, and ST88(19F)) and an increase in the prevalence of non-PCV7 antibiotic-susceptible clones (ST306(1), ST191(7F), ST989(12F), and ST433(22F)). CONCLUSIONS: Rates of IPD among adults increased in Barcelona in the late PCV7 period, coinciding with a clonal expansion of non-PCV7 serotypes. In contrast, rates of IPD caused by PCV7 serotypes decreased among people aged > or = 65 years, which suggests the development of a herd immunity.

Understanding the acute inflammatory response to Pseudomonas aeruginosa infection: differences between susceptible and multidrug-resistant strains in a mouse peritonitis model.

The increasing emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa strains is associated with the spread of a few international epidemic clones called high-risk clones. The existence of a fitness cost associated with multidrug resistance remains unclear, and little is known about the host inflammatory response in acute P. aeruginosa infections. This study aimed to investigate how the inflammatory response occurs in the most relevant high-risk clones and to compare the process with that recorded in clinical susceptible isolates. Nine P. aeruginosa strains were studied, including the most relevant MDR high-risk clones (ST111, ST175 and ST235) circulating worldwide. The inflammatory response in terms of the release of interleukins in serum was investigated in a mouse peritonitis-sepsis model at three time points (4, 8 and 12 h). TNFα and interleukin-10 (IL-10) levels were significantly higher at all time points in mice inoculated with clinical susceptible strains compared with those inoculated with MDR strains. IL-6 levels were significantly higher in the clinical susceptible strain group at 8 h and 12 h (P = 0.036 and P = 0.007, respectively). Bacterial counts (log CFU/mL) in peritoneal fluid were higher in the clinical susceptible strain group compared with the MDR strain group at 8 h [6.00 (4.30-6.90) vs. 4.46 (3.30-5.34); P = 0.005] and 12 h [7.75 (4.00-7.97) vs. 4.04 (2.58-4.94); P = 0.003]. MDR P. aeruginosa strains elicited a weaker inflammatory response than susceptible strains in an experimental mouse model, suggesting the existence of a fitness cost associated with multidrug resistance.

Acute Inflammatory Response of Patients with Pseudomonas aeruginosa Infections: A Prospective Study.

The severity of Pseudomonas aeruginosa (PA) infection may be determined by the interaction with the host immune system. We designed a prospective study to assess the relationship between the inflammatory response and the clinical presentation and outcome of PA infection. We also investigated whether there are differences in the inflammatory response depending on the resistance profile of PA. Interleukin-6 (IL-6), IL-10, procalcitonin (PCT), and C-reactive protein (CRP) were measured. Sixty-nine infection episodes were recorded; 40 caused by non-multidrug-resistant (non-MDR) strains [29 (73%) respiratory; 8 (20%) bacteremia], 12 by MDR non-extensively drug-resistant (MDR-non-XDR) [9 (75%) respiratory; 3 (25%) bacteremia], and 17 by XDR strains [9 (53%) respiratory; 7 (41%) bacteremia]. All inflammatory parameters were significantly higher in patients who developed acute organ dysfunction and bacteremia. PCT levels were higher in patients with early mortality [p = 0.050]. Inflammatory biomarkers were higher in patients with XDR than in those with non-MDR PA [IL-6 430 (67-951) vs. 77 (34-216), p = 0.02; IL-10 3.3 (1.5-16.3) vs. 1.3 (0-3.9), p = 0.02; and PCT 1.1 (0.6-5.2) vs. 0.3 (0.1-1.0), p = 0.008]. The intensity of inflammatory response was associated with the severity of PA infection, particularly if bacteremia occurred. Only PCT was documented useful to predict the outcome. XDR infections presented a higher inflammatory response; related in part to the larger number of bloodstream infections in this group.

Clinical characteristics, treatment and outcomes of MRSA bacteraemia in the elderly.

OBJECTIVES: To compare clinical and microbiological characteristics, treatment and outcomes of MRSA bacteraemia among elderly and younger patients. MATERIAL AND METHODS: Prospective study conducted at 21 Spanish hospitals including patients with MRSA bacteraemia diagnosed between June/2008 and December/2009. Episodes diagnosed in patients aged 75 or more years old (≥75) were compared with the rest of them (<75). RESULTS: Out of 579 episodes of MRSA bacteraemia, 231 (39.9%) occurred in patients ≥75. Comorbidity was significantly higher in older patients (Charlson score ≥4: 52.8 vs. 44%; p = .037) as was the severity of the underlying disease (McCabe ≥1: 61.9 vs. 43.4%; p < .001). In this group the acquisition was more frequently health-care related (43.3 vs. 33.9%, p = .023), mostly from long-term care centers (12.1 vs. 3.7%, p < .001). An unknown focus was more frequent among ≥75 (19.9 vs. 13.8%; p = .050) while severity at presentation was similar between groups (Pitt score ≥3: 31.2 vs. 27.6%; p = .352). The prevalence of vancomycin resistant isolates was similar between groups, as was the appropriateness of empirical antibiotic therapy. Early (EM) and overall mortality (OM) were significantly more frequent in the ≥75 group (EM: 12.1 vs. 6%; p = .010 OM: 42.9 vs. 23%; p < .001). In multivariate analysis age ≥75 was an independent risk factor for overall mortality (aOR: 2.47, CI: 1.63-3.74; p < .001). CONCLUSION: MRSA bacteraemia was frequent in patients aged ≥75 of our cohort. This group had higher comorbidity rates and the source of infection was more likely to be unknown. Although no differences were seen in severity or adequacy of empiric therapy, elderly patients showed a higher overall mortality.

Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections.

OBJECTIVES: Antibiotic-loaded spacers may improve antimicrobial efficacy in two-stage revision of prosthetic joint infections, but they may also interfere in the course of infection. This prospective study of prosthetic joint infections managed with two-stage revision and antibiotic-loaded spacers (2004-09) analyzes case outcomes and proposes a second-stage culture interpretation scheme. METHODS: Second-stage infection was diagnosed upon second-stage cultures (synovial membranes, joint fluid, spacers), as either superinfection (≥2 samples, new organism) or persistence (≥1 samples, previously isolated organism). Isolated positive antibiotic-loaded spacers cultures were considered as colonizations. RESULTS: Of 42 patients, two had two prosthetic infections (n = 44): 25 knees, 19 hips. Spacers contained gentamicin (33), vancomycin (10) and aztreonam (1). Three patients (7%) with wound healing impairment required debridement and spacer exchange. The remainder underwent second-stage surgery as planned: 34 (77%) new arthroplasties, five arthrodeses, one resection arthroplasty and one permanent spacer. Of 18 cases (44%) with ≥1 positive sample, only four (10%) were second-stage infections. Fourteen antibiotic-loaded spacers cultures (34%) were positive. Four new prostheses (9%) supervened further infections: one by the organism isolated in the spacer, three by new bacteria. CONCLUSIONS: The findings of second-stage cultures show that the surgical site is frequently non-sterile at reimplantation. Isolated positive antibiotic-loaded spacer cultures usually have no clinical consequences, but together with tissue cultures they help to diagnose second-stage infections when clinical signs are absent.

Community associated methicillin-resistant Staphylococcus aureus in HIV-infected patients.

Until recently, methicillin-resistant Staphylococcus aureus was considered an uncommon community pathogen, almost exclusively associated with healthcare exposure. Over the last decade, however, methicillin-resistant S. aureus infection, particularly skin and soft tissue infection, has emerged in healthy individuals with no traditional risk factors for its acquisition. Several risk factors, including certain lifestyle behaviors, have been associated with community-acquired methicillin-resistant S. aureus colonization and infection. Regardless of other concurrent risk factors, HIV-infected patients have an increased risk for acquiring this pathogen. This article summarizes the current knowledge regarding associated risk factors, clinical manifestations, and management of community-acquired methicillin-resistant Staphylococcus aureus infections in HIV-infected patients.

Nosocomial outbreak due to extended-spectrum-beta-lactamase- producing Enterobacter cloacae in a cardiothoracic intensive care unit.

Enterobacter cloacae has been associated with several outbreaks, usually involving strains that overproduce chromosomal beta-lactamase or, uncommonly, strains expressing extended-spectrum beta-lactamases (ESBL). Only sporadic cases of ESBL-producing E. cloacae have been identified in our hospital in recent years. We describe the epidemiology and clinical and microbiological characteristics of an outbreak caused by ESBL-producing E. cloacae in a cardiothoracic intensive care unit (CT-ICU). Prospective surveillance of patients with infection or colonization by ESBL-producing E. cloacae among patients admitted to the CT-ICU was performed during the outbreak. Production of ESBL was determined by decreased susceptibility to expanded-spectrum cephalosporins and a positive double-disk test result. Clone relatedness was determined by pulsed-field gel electrophoresis (PFGE). From July to September 2005, seven patients in the CT-ICU with ESBL-producing E. cloacae were identified (four males; median age, 73 years; range, 45 to 76 years); six patients had cardiac surgery. Four patients developed infections; three had primary bacteremia, one had ventilator-associated pneumonia, and one had tracheobronchitis. ESBL-producing E. cloacae showed resistance to quinolones and aminoglycosides. PFGE revealed two patterns. Five isolates belonged to clone A; two carried a single ESBL (pI 8.2 and a positive PCR result for the SHV type), and three carried two ESBLs (pIs 8.1 and 8.2 and positive PCR results for the SHV and CTX-M-9 types). Isolates belonging to clone B carried a single ESBL (pI 5.4 and a positive PCR result for the TEM type). Review of antibiotic consumption showed increased use of cefepime and quinolones during June and July 2005. The outbreak was stopped by the implementation of barrier measures and cephalosporin restriction. ESBL production could be increasingly common in nosocomial pathogens other than Escherichia coli or Klebsiella pneumoniae.

Genotypic diversity of imipenem resistant isolates of Acinetobacter baumannii in Spain.

OBJECTIVES: To investigate relevant clinical and microbiological features of Acinetobacter baumannii in Spanish hospitals and to establish the genotypic diversity of imipenem resistant isolates. MATERIAL AND METHODS: Seven Spanish hospitals collected 354 consecutive isolates that were subjected to antimicrobial susceptibility testing by standard methods. Further genetic analysis was determined by PFGE in a subset of 135 isolates from three hospitals selected because each of them presented high-, medium-, and low imipenem resistance rates. RESULTS: Most isolates were from males (61.9%), age >65 years (52.3%), admitted to ICU (35.6%), and isolated from the respiratory tract (31.1%). Rates of carbapenem- and sulbactam resistance were 44.9% and 39.9%, respectively. Colistin was active against multiresistant isolates. Rates of imipenem resistance varied according to individual hospital (average: 43.8%; range: 13.5%-85.0%), medical department (more prevalent in ICU), and clinical sample (higher in isolates from the respiratory tract). Of the 135 isolates studied by PFGE (64 of them imipenem-resistant), 115 (85.1%) were distributed among 14 clusters and 20 were unrelated. Of the imipenem-resistant isolates, 45 (70.3%) belonged to six clusters that also had imipenem- susceptible isolates; 14 constituted four exclusive clusters, and five were unrelated. CONCLUSIONS: Acquisition of imipenem resistance in A. baumannii is likely due to both clonal and non-clonal dissemination; resistance rates strongly vary between different hospitals and even between different hospital departments.