Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.

BACKGROUND: Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec). METHODS: Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders. RESULTS: Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen. CONCLUSIONS: Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.

Effects of the COVID-19 Pandemic on Incidence and Epidemiology of Catheter-Related Bacteremia, Spain.

We compared hospital-acquired catheter-related bacteremia (CRB) episodes diagnosed at acute care hospitals in Catalonia, Spain, during the COVID-19 pandemic in 2020 with those detected during 2007-2019. We compared the annual observed and predicted CRB rates by using the negative binomial regression model and calculated stratified annual root mean squared errors. A total of 10,030 episodes were diagnosed during 2007-2020. During 2020, the observed CRB incidence rate was 0.29/103 patient-days, whereas the predicted CRB rate was 0.14/103 patient-days. The root mean squared error was 0.153. Thus, a substantial increase in hospital-acquired CRB cases was observed during the COVID-19 pandemic in 2020 compared with the rate predicted from 2007-2019. The incidence rate was expected to increase by 1.07 (95% CI 1-1.15) for every 1,000 COVID-19-related hospital admissions. We recommend maintaining all CRB prevention efforts regardless of the coexistence of other challenges, such as the COVID-19 pandemic.

Air trapping in COVID-19 patients following hospital discharge: retrospective evaluation with paired inspiratory/expiratory thin-section CT.

OBJECTIVES: The study reports our experience with paired inspiration/expiration thin-section computed tomographic (CT) scans in the follow-up of COVID-19 patients with persistent respiratory symptoms. METHODS: From August 13, 2020, to May 31, 2021, 48 long-COVID patients with respiratory symptoms (27 men and 21 women; median age, 62.0 years; interquartile range: 54.0-69.0 years) underwent follow-up paired inspiration-expiration thin-section CT scans. Patient demographics, length of hospital stay, intensive care unit admission rate, and clinical and laboratory features of acute infection were also included. The scans were obtained on a median of 72.5 days after onset of symptoms (interquartile range: 58.5-86.5) and at least 30 days after hospital discharge. Thin-section CT findings included ground-glass opacity, mosaic attenuation pattern, consolidation, traction bronchiectasis, reticulation, parenchymal bands, bronchial wall thickening, and air trapping. We used a quantitative score to determine the degree of air trapping in the expiratory scans. RESULTS: Parenchymal abnormality was found in 50% (24/48) of patients and included air trapping (37/48, 77%), ground-glass opacities (19/48, 40%), reticulation (18/48, 38%), parenchymal bands (15/48, 31%), traction bronchiectasis (9/48, 19%), mosaic attenuation pattern (9/48, 19%), bronchial wall thickening (6/48, 13%), and consolidation (2/48, 4%). The absence of air trapping was observed in 11/48 (23%), mild air trapping in 20/48 (42%), moderate in 13/48 (27%), and severe in 4/48 (8%). Independent predictors of air trapping were, in decreasing order of importance, gender (p = 0.0085), and age (p = 0.0182). CONCLUSIONS: Our results, in a limited number of patients, suggest that follow-up with paired inspiratory/expiratory CT in long-COVID patients with persistent respiratory symptoms commonly displays air trapping. KEY POINTS: • Our experience indicates that paired inspiratory/expiratory CT in long-COVID patients with persistent respiratory symptoms commonly displays air trapping. • Iterative reconstruction and dose-reduction options are recommended for demonstrating air trapping in long-COVID patients.

Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift, Spain, 2007 to 2019.

BackgroundCatheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death.AimTo analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat).MethodsA cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007-2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000 patient days. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000 patient days and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported.ResultsDuring the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate: 0.20 episodes/1,000 patient days). Patients' median age was 64.1 years; 36.6% (3,403/9,290) were female. In total, 73.7% (n = 6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n = 5,822) were related to central venous catheter (CVC), 24.1% (n = 2,236) to peripheral venous catheters (PVC) and 13.3% (n = 1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR: 0.94; 95%CI: 0.93-0.96), especially in the ICU (IRR: 0.88; 95%CI: 0.87-0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR: 0.88; 95%CI: 0.87-0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC: 1.08; 95%CI: 1.05-1.11; IRR PVC: 1.03; 95% 1.00-1.05).ConclusionsOver the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards.

Effectiveness and safety of intravenous tocilizumab to treat COVID-19-associated hyperinflammatory syndrome: Covizumab-6 observational cohort.

Although the starting event in COVID-19 is a viral infection some patients present with an over-exuberant inflammatory response, leading to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS). Since IL-6 plays a critical role in the inflammatory response, we assessed the efficacy and safety of tocilizumab (TCZ) in this single-centre, observational study in all Covid-19 in-patient with a proven SARS-CoV-2 rapidly progressing infection to prevent ALI and ARDS. 104 patients with COVID-19 treated with TCZ had a lower mortality rate (5·8%) compared with the regional mortality rate (11%), hospitalized patient's mortality (10%), and slightly lower than hospitalized patients treated with our standard of care alone (6%). We found that TCZ rapidly decreased acute phase reactants, ferritin and liver release of proteins. D-Dimer decreased slowly. We did not observe specific safety concerns. Early administration of IL6-R antagonists in COVID-19 patients with impending hyperinflammatory response, may be safe and effective treatment to prevent, ICU admission and further complications.

Whole-genome analysis to describe a human adenovirus D8 conjunctivitis outbreak in a tertiary hospital.

Conjunctivitis is a frequent ocular disorder caused by human adenoviruses (HAdVs). Only a few of the 45 HAdV-D species are associated with epidemic keratoconjunctivitis, including HAdV-D8. Nosocomial outbreaks due to HAdV-D8 have been rarely described, because keratoconjunctivitis cases are clinically diagnosed and treated without having to characterize the causative agent. Moreover, molecular typing is tedious when using classical techniques. In this study, a hospital outbreak of conjunctivitis caused by HAdV-D8 was characterized using the recently developed whole-genome sequencing (WGS) method. Of the 363 patients attending the Ophthalmology Department between July 13 and August 13, 2018, 36 may have acquired intrahospital conjunctivitis. Also, 11 of 22 samples sent to the Virology section were selected for WGS analysis. The WGS results revealed that 10 out of 11 HAdV-D8 strains were closely related. The remaining strain (Case 28) was more similar to a strain from an outbreak in Germany obtained from a public sequence database. WGS results showed that outbreak HAdV-D8 strains had a minimum percentage of identity of 94.3%. WGS is useful in a clinical setting, because it avoids carrying out viral culture or specific polymerase chain reaction sequencing. The public availability of sequence reads makes it easier to compare clusters in circulation. In conclusion, WGS can play an important role in standard routines to describe viral outbreaks.

Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: a position paper.

Chimeric antigen receptor (CAR) T-cell therapy is one of the most promising emerging treatments for B-cell malignancies. Recently, two CAR T-cell products (axicabtagene ciloleucel and tisagenlecleucel) have been approved for patients with aggressive B-cell lymphoma and acute lymphoblastic leukemia; many other CAR-T constructs are in research for both hematological and non-hematological diseases. Most of the patients receiving CAR-T therapy will develop fever at some point after infusion, mainly due to cytokine release syndrome (CRS). The onset of CRS is often indistinguishable from an infection, which makes management of these patients challenging. In addition to the lymphodepleting chemotherapy and CAR T cells, the treatment of complications with corticosteroids and/or tocilizumab increases the risk of infection in these patients. Data regarding incidence, risk factors and prevention of infections in patients receiving CAR-T cell therapy are scarce. To assist in patient care, a multidisciplinary team from hospitals designated by the Spanish Ministry of Health to perform CAR-T therapy prepared these recommendations. We reviewed the literature on the incidence, risk factors, and management of infections in adult and pediatric patients receiving CAR-T cell treatment. Recommendations cover different areas: monitoring and treatment of hypogammaglobulinemia, prevention, prophylaxis, and management of bacterial, viral, and fungal infections as well as vaccination prior and after CAR-T cell therapy.

Efficacy of Ceftolozane-Tazobactam in Combination with Colistin against Extensively Drug-Resistant Pseudomonas aeruginosa, Including High-Risk Clones, in an In Vitro Pharmacodynamic Model.

Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Colistin has been the only treatment available for these infections for many years, but its results are suboptimal. Ceftolozane-tazobactam (C/T) is a newly available therapeutic option that has shown good antipseudomonal activity, even against a number of XDR P. aeruginosa strains. However, data about combinations containing C/T are scarce. The aim of this study was to analyze the activity of C/T and colistin alone and in combination against a collection of XDR P. aeruginosa strains containing 24 representative clinical isolates from a multicentre Spanish study. Twenty-four time-kill experiments performed over 24 h were conducted in duplicate to determine the effects of colistin and C/T alone and combined. An in vitro pharmacodynamic chemostat model then was used to validate this combination against three selected XDR P. aeruginosa ST175 isolates with different susceptibility levels to C/T. Static time-kill assays demonstrated superior synergistic or additive effect for C/T plus colistin against 21 of the 24 isolates studied. In the in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, the C/T regimen of 2/1 g every 8 h with a steady-state concentration of 2 mg/liter colistin effectively suppressed the bacterial growth at 24 h. Additive or synergistic interactions were observed for C/T plus colistin against XDR P. aeruginosa strains and particularly against C/T-resistant strains. C/T plus colistin may be a useful treatment for XDR P. aeruginosa infections, including those caused by high risk-clones resistant to C/T.

Characteristics and outcome of spontaneous bacterial meningitis in patients with diabetes mellitus.

BACKGROUND: Studies on bacterial meningitis in diabetics patients versus non-diabetics are scarce. In patients with diabetes, bacterial meningitis may have a different presentation, etiology and course. We analyzed and compared the characteristics and outcome of spontaneous BM in adult patients with and without diabetes mellitus (DM). METHODS: We performed a single-center, prospective observational cohort study, conducted between 1982 and 2017, in a tertiary university hospital in Barcelona (Spain). The primary outcome measure was in-hospital mortality. RESULTS: We evaluated 715 episodes of bacterial meningitis; 106 patients (15%) had diabetes mellitus. Patients with diabetes were older (median 67 [IQR 17] vs 49 [IQR 40] years, p <  0.001) and more often had a Charlson comorbidity score of ≥3 (40% vs 15%, p <  0.001). Neck stiffness (56% vs 75%, p <  0.001), headache (41% vs 78%) p <  0.001), nausea and/or vomiting (32% vs 56% p < 0.001), and rash (12% vs 26%, p = 0.007) were less frequent in diabetics, whereas altered mental status was more common. Streptococcus pneumoniae and Listeria meningitis were the most common etiologic agents (24 and 18%, respectively). Listeria was more frequent (18% vs. 10%, p = 0.033), whereas meningococcal meningitis was less frequent (10% vs 32%, p < 0.001). Overall mortality was higher in patients with diabetes (26% vs 16%, p = 0.025) concerning non-diabetics. CONCLUSIONS: Patients with bacterial meningitis and diabetes mellitus are older, have more comorbidities, and higher mortality. S. pneumoniae and L. monocytogenes are the predominant pathogens, Listeria being more common, whereas Neisseria meningitidis is significantly less frequent than in non-diabetics.

Influence of virulence genotype and resistance profile in the mortality of Pseudomonas aeruginosa bloodstream infections.

BACKGROUND: The type III secretion system (TTSS) is a major virulence determinant of Pseudomonas aeruginosa. The objective of this study was to determine whether the TTSS genotype is a useful prognostic marker of P. aeruginosa bacteremia mortality. We also studied the potential association between TTSS genotypes and multidrug-resistant (MDR) profiles, and how this interaction impacts the outcome of bloodstream infections. METHODS: We performed a post hoc analysis of a published prospective multicenter cohort of P. aeruginosa bloodstream infections. The impact in mortality of TTSS genotypes (exoS, exoT, exoU, and exoY genes) and resistance profiles was investigated. Cox regression analysis was used to control for confounding variables. RESULTS: Among 590 patients, the 30-day mortality rate was 30% (175 patients), and 53% of them died in the first 5 days (early mortality). The unadjusted probabilities of survival until 5 days was 31.4% (95% confidence interval [CI], 17.4%-49.4%) for the patients with exoU-positive isolates and 53.2% (95% CI, 44.6%-61.5%) for exoU-negative isolates (log rank P = .005). After adjustment for confounders, exoU genotype (adjusted hazard ratio [aHR], 1.90 [95% CI, 1.15-3.14]; P = .01) showed association with early mortality. In contrast, late (30-day) mortality was not influenced by TTSS genotype but was independently associated with MDR profiles (aHR,1.40 [95% CI, 1.01-1.94]; P = .04). Moreover, the exoU genotype (21% of all isolates) was significantly less frequent (13%) among MDR strains (particularly among extensively drug-resistant isolates, 5%), but was positively linked to moderately resistant (1-2 antipseudomonals) phenotypes (34%). CONCLUSIONS: Our results indicate that the exoU genotype, which is associated with specific susceptibility profiles, is a relevant independent marker of early mortality in P. aeruginosa bacteremia.

Anti-tumour necrosis factor-induced visceral and cutaneous leishmaniasis: case report and review of the literature.

BACKGROUND: Leishmaniasis is a chronic protozoan disease in which organisms are found within phagolysosomes of the mononuclear phagocyte system. There are three major forms: cutaneous, mucocutaneous and visceral. We report the first case of visceral leishmaniasis with cutaneous involvement in a patient with rheumatoid arthritis treated with the anti-tumour necrosis factor (anti-TNF) adalimumab. OBJECTIVE: To highlight cutaneous leishmaniasis as the first indicator of a kala-azar disease in a patient treated with anti-TNF and to review the literature on leishmaniasis in the context of anti-TNF therapy. CASE REPORT: A 59-year-old woman presented with a crusted plaque on the right elbow 34 months after the initiation of adalimumab. A cutaneous biopsy showed intracellular amastigotes. No Leishmania parasites were observed in a bone marrow aspirate, but laboratory tests showed anaemia and impaired liver function, abdominal ultrasonography showed hepatomegaly, and ELISA serology was strongly positive for Leishmania antibodies in serum and urine. Adalimumab was withdrawn and treatment combining intralesional pentavalent antimonials and liposomal amphotericin was started. Eight weeks later, the leishmaniasis had resolved. CONCLUSION: A skin biopsy disclosing leishmaniasis should prompt tests to rule out visceral leishmaniasis, especially in an area such as the Mediterranean where the prevalence of latent Leishmania infection is high.

Evolving trends in neuropsychological profiles of post COVID-19 condition: A 1-year follow-up in individuals with cognitive complaints.

Cognitive difficulties are reported as lasting sequelae within post COVID-19 condition. However, the chronicity of these difficulties and related factors of fatigue, mood, and perceived health have yet to be fully determined. To address this, the current longitudinal study aimed to clarify the trends of cognitive test performance and cognitive domain impairment following COVID-19 onset, and whether hospitalization influences outcomes. 57 participants who reported subjective cognitive difficulties after confirmed COVID-19 infection were assessed at baseline (~6 months post COVID-19) and follow-up (~15 months later) visits. Assessments included measures across multiple cognitive domains and self-report questionnaires of fatigue, mood, and overall health. Analyses were conducted in three stages: at the test score level (raw and adjusted scores), at the cognitive domain level, and stratified by hospitalization status during infection. Results at the test-score level indicate that cognitive performance remains relatively stable across assessments at the group level, with no significant improvements in any adjusted test scores at follow-up. Cognitive domain analyses indicate significant reductions in attention and executive functioning impairment, while memory impairment is slower to resolve. On self-report measures, there was a significant improvement in overall health ratings at follow-up. Finally, those hospitalized during infection performed worse on timed cognitive measures across visits and accounted for a larger proportion of cases with short-term and working memory impairment at follow-up. Overall, our findings indicate that cognitive difficulties persist both at test score and cognitive domain levels in many cases of post COVID-19 condition, but evidence suggests some improvement in global measures of attention, executive functioning and overall self-rated health. Furthermore, an effect of hospitalization on cognitive symptoms post COVID-19 may be more discernible over time.

Effect of adequate single-drug vs combination antimicrobial therapy on mortality in Pseudomonas aeruginosa bloodstream infections: a post Hoc analysis of a prospective cohort.

BACKGROUND: Empirical combination therapy is recommended for patients with known or suspected Pseudomonas aeruginosa (PA) infection as a means to decrease the likelihood of administering inadequate antimicrobial treatment, to prevent the emergence of resistance, and to achieve a possible additive or even synergistic effect. METHODS: We performed a post hoc analysis of patients with PA bloodstream infections from a published prospective cohort. Mortality was compared in patients treated with adequate empirical and definitive combination therapy (AECT, ADCT), and adequate empirical and definitive single-drug therapy (AESD, ADSD). Confounding was controlled by Cox regression analysis, and a propensity score for receiving AECT or ADCT was also used. RESULTS: The final cohort comprised 593 patients with a single episode of PA bacteremia. The 30-day mortality was 30% (176 patients); 76 patients (13%) died during the first 48 hours. The unadjusted probabilities of survival until day 30 were 69.4% (95% confidence interval [CI], 59.1-81.6) for the patients receiving AECT, 73.5% (95% CI, 68.4%-79.0%) for the AESD group, and 66.7% (95% CI, 61.2%-72.7%) for patients who received inadequate empirical therapy (P = .17, log-rank test). After adjustment for confounders, the AESD group (adjusted hazard ratio [AHR], 1.17; 95% CI, .70-1.96; P = .54) and patients who received ADSD (AHR, 1.34; 95% CI, .73-2.47; P = .35) showed no association with 30-day mortality compared with the AECT and ADCT groups, respectively. CONCLUSIONS: These results suggests that treatment with combination antimicrobial therapy did not reduce the mortality risk compared with single-drug therapy in PA bloodstream infections.

Epidemiology of Clostridium difficile infection and risk factors for unfavorable clinical outcomes: results of a hospital-based study in Barcelona, Spain.

Prospective hospital-based surveillance for Clostridium difficile-associated disease (CDAD) was conducted in Barcelona (Spain) to describe the epidemiology of this condition and investigate the risk factors for an unfavorable outcome. All patients diagnosed with CDAD during 2009 were included. Using logistic regression modeling, we analyzed the potential risk factors associated with recurrent and complicated CDAD, defined as a need for colectomy or death within 30 days. There were 365 episodes of CDAD, yielding an incidence of 22.5 cases/10(5) person-years, 1.22 cases/10(3) hospital discharges, and 1.93 cases/10(4) patient-days. The main PCR ribotypes identified were 241 (26%), 126 (18%), 078 (7%), and 020 (5%). PCR ribotype 027 was not detected. Among the 348 cases analyzed, 232 (67%) patients were cured, 63 (18%) had a recurrence of CDAD, and 53 (15%) developed complicated CDAD. Predictors of complicated CDAD were continued use of antibiotics following CDAD diagnosis (odds ratio [OR], 2.009; 95% confidence interval [CI], 1.012 to 3.988; P = 0.046), Charlson comorbidity index score (OR, 1.265; 95% CI, 1.105 to 1.449; P = 0.001), and age (OR, 1.028; 95% CI, 1.005 to 1.053; P = 0.019). A leukocyte count of >15 × 10(3) cells/ml (OR, 2.277; 95% CI, 1.189 to 4.362; P = 0.013), continuation of proton pump inhibitor (PPI) use after CDAD diagnosis (OR, 2.168; 95% CI, 1.081 to 4.347; P = 0.029), and age (OR, 1.021; 95% CI, 1.001 to 1.041; P = 0.036) were independently associated with higher odds of recurrence. The incidence of CDAD in Barcelona during 2009 was on the lower end of the previously described range for all of Europe. Our analysis suggests that the continuation of non-C. difficile antibiotics and use of PPIs in patients diagnosed with CDAD are associated with unfavorable clinical outcomes.

The spectrum of acute bacterial meningitis in elderly patients.

BACKGROUND: We conducted a prospective, observational study in Barcelona to determine the epidemiology, clinical features, and outcome of elderly patients with acute bacterial meningitis (ABM) compared with younger adults. METHODS: During 1982-2010, all patients with ABM were prospectively evaluated. There were two groups: I (15-64 years) and II (≥ 65 years). All patients underwent clinical examination on admission and at discharge following a predefined protocol. RESULTS: We evaluated 635 episodes of ABM. The incidence was 4.03/100,000 (Group I) and 7.40 /100,000 inhabitants/year (Group II) (RR = 1.84; 95%CI: 1.56-2.17, P < 0.0001). Elderly patients had co-morbid conditions more frequently (P < 0.0001) and more frequently lacked fever (P = 0.0625), neck stiffness (P < 0.0001) and skin rash (P < 0.0001), but had an altered level of consciousness more often (P < 0.0001). The interval admission-start of antibiotic therapy was longer for elderly patients (P < 0.0001). Meningococcal meningitis was less frequent in elderly patients (P < 0.0001), whereas listerial (P = 0.0196), gram-negative bacillary (P = 0.0065), and meningitis of unknown origin (P = 0.0076) were more frequent. Elderly patients had a higher number of neurologic (P = 0.0009) and extra-neurologic complications (P < 0.0001). The overall mortality ratio was higher in elderly patients (P < 0.0001). CONCLUSIONS: Elderly people are at higher risk of having ABM than younger adults. ABM in the elderly presents with co-morbid conditions, is clinically subtler, has a longer interval admission-antibiotic therapy, and has non-meningococcal etiology. It is associated with an earlier and higher mortality rate than in younger patients.

Spontaneous gram-negative bacillary meningitis in adult patients: characteristics and outcome.

BACKGROUND: Spontaneous meningitis caused by gram-negative bacilli in adult patients is uncommon and poorly characterized. Our objective is to describe and compare the characteristics and the outcome of adult patients with spontaneous gram-negative bacilli meningitis (GNBM) and spontaneous meningitis due to other pathogens. METHODS: Prospective single hospital-based observational cohort study conducted between 1982 and 2006 in a university tertiary hospital in Barcelona (Spain). The Main Outcome Measure: In-hospital mortality. RESULTS: Gram-negative bacilli meningitis was diagnosed in 40 (7%) of 544 episodes of spontaneous acute bacterial meningitis. The most common pathogens were Escherichia coli and Pseudomonas species. On admission, characteristics associated with spontaneous gram-negative bacilli meningitis by multivariate modeling were advanced age, history of cancer, nosocomial acquisition of infection, urinary tract infection as distant focus of infection, absence of rash, hypotension, and a high cerebrospinal fluid white-cell count. Nine (23%) episodes were acquired in the hospital and they were most commonly caused by Pseudomonas. The in-hospital mortality rate was 53%. The mortality rate was higher among patients with Gram-negative bacillary meningitis than among those with other bacterial meningitis and their risk of death was twenty times higher than among patients infected with Neisseria meningitidis (odds ratio 20.47; 95% confidence interval 4.03-103.93; p<0.001). CONCLUSIONS: Gram-negative bacilli cause 9% of spontaneous bacterial meningitis of known etiology in adults. Characteristics associated with GNBM include advanced age, history of cancer, nosocomial acquisition, and urinary tract infection as distant focus of infection. The mortality rate is higher among patients with gram-negative bacillary meningitis than among those with other bacterial meningitides.

Acute Bacterial Meningitis in Healthy Adult Patients: A Prospective Cohort Study.

Spontaneous bacterial meningitis (BM) is more common among patients with underlying conditions, but its characteristics in previously healthy patients are not well described. We analyzed the time trends of BM in terms of characteristics, and outcomes in patients without comorbidities. PATIENTS AND METHODS: Single-center, prospective observational cohort study of 328 adults with BM hospitalized in a tertiary university hospital in Barcelona (Spain). We compared the features of infections diagnosed in 1982-2000 and 2001-2019. The main outcome measure was in-hospital mortality. RESULTS: The median age of the patients increased from 37 to 45 years. Meningococcal meningitis significantly diminished (56% versus 31%, p < 0.000) whereas listerial meningitis increased (1.2% versus 8%, p = 0.004). Systemic complications were more common in the second period, although mortality did not vary significantly between periods (10.4% versus 9.2%). However, after adjusting for relevant variables, infection in the second period was associated with lower risk death. CONCLUSIONS: Adult patients without underlying comorbidities that developed BM in recent years were older and more likely to have pneumococcal or listerial infections and systemic complications. In-hospital death was less likely in the second period, after adjusting for risk factors of mortality.

Randomized Clinical Trial of the Need for Antibiotic Treatment for Low-Risk Catheter-Related Bloodstream Infection Caused by Coagulase-Negative Staphylococci.

According to clinical guidelines, the management of catheter-related bloodstream infections (CRBSI) due to coagulase-negative staphylococci (CoNS) includes catheter removal and antibiotic treatment for 5 to 7 days. However, in low-risk episodes, it remains uncertain whether antibiotic therapy is necessary. This randomized clinical trial aims to determine whether the non-administration of antibiotic therapy is as safe and effective as the recommended strategy in low-risk episodes of CRBSI caused by CoNS. With this purpose, a randomized, open-label, multicenter, non-inferiority clinical trial was conducted in 14 Spanish hospitals from 1 July 2019 to 31 January 2022. Patients with low-risk CRBSI caused by CoNS were randomized 1:1 after catheter withdrawal to receive/not receive parenteral antibiotics with activity against the isolated strain. The primary endpoint was the presence of any complication related to bacteremia or to antibiotic therapy within 90 days of follow-up. The secondary endpoints were persistent bacteremia, septic embolism, time until microbiological cure, and time until the disappearance of a fever. EudraCT: 2017-003612-39 INF-BACT-2017. A total of 741 patients were assessed for eligibility. Of these, 27 were included in the study; 15 (55.6%) were randomized to the intervention arm (non-antibiotic administration) and 12 (44.4%) to the control arm (antibiotic therapy as per standard practice). The primary endpoint occurred in one of the 15 patients in the intervention group (septic thrombophlebitis) and in no patients in the control group. The median time until microbiological cure was 3 days (IQR 1-3) in the intervention arm and 1.25 days (IQR 0.5-2.62) in the control arm, while the median time until fever resolution was zero days in both arms. The study was stopped due to the insufficient number of recruited patients. These results seem to indicate that low-risk CRBSI caused by CoNS can be managed without antibiotic therapy after catheter removal; efficacy and safety are not affected.

Reversions of QuantiFERON-TB Gold Plus in tuberculosis contact investigation: A prospective multicentre cohort study.

BACKGROUND: Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments. METHODS: Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive. RESULTS: We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes. CONCLUSION: In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments.

Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections.

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities.