The Use of Corticosteroids or Tocilizumab in COVID-19 Based on Inflammatory Markers.

BACKGROUND: The inflammatory cascade is the main cause of death in COVID-19 patients. Corticosteroids (CS) and tocilizumab (TCZ) are available to treat this escalation but which patients to administer it remains undefined. OBJECTIVE: We aimed to evaluate the efficacy of immunosuppressive/anti-inflammatory therapy in COVID-19, based on the degree of inflammation. DESIGN: A retrospective cohort study with data on patients collected and followed up from March 1st, 2020, to May 1st, 2021, from the nationwide Spanish SEMI-COVID-19 Registry. Patients under treatment with CS vs. those under CS plus TCZ were compared. Effectiveness was explored in 3 risk categories (low, intermediate, high) based on lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer values. PATIENTS: A total of 21,962 patients were included in the Registry by May 2021. Of these, 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). MAIN MEASURES: The primary outcome of the study was in-hospital mortality. Secondary outcomes were the composite variable of in-hospital mortality, requirement for high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), or intensive care unit (ICU) admission. KEY RESULTS: A total of 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). No significant differences were observed in either the low/intermediate-risk category (1.5% vs. 7.4%, p=0.175) or the high-risk category (23.1% vs. 20%, p=0.223) after propensity score matching. A statistically significant lower mortality was observed in the very high-risk category (31.9% vs. 23.9%, p=0.049). CONCLUSIONS: The prescription of CS alone or in combination with TCZ should be based on the degrees of inflammation and reserve the CS plus TCZ combination for patients at high and especially very high risk.

High comorbidity, measured by the Charlson Comorbidity Index, associates with higher 1-year mortality risks in elderly patients experiencing a first acute heart failure hospitalization.

BACKGROUND: Comorbidity is related to poor health results in chronic heart failure (HF). AIMS: The purpose of the study was to assess whether a high Charlson Comorbidity Index score (CCI) relates to 1 year mortality after a first hospitalization for acute HF (AHF). METHODS: We reviewed the medical records of 897 patients > 65 years of age admitted within a two-year period because of a first episode of AHF. We analyzed two groups: low (CCI ≤ 2) and high (CCI > 2) comorbidity. RESULTS: Patients' mean CCI was 2.2 ± 1.7; 344 patients (38.35%) had a CCI > 2. 1-year all-cause mortality rate in the high comorbidity group was 32.6%, worse than that among low comorbidity group patients (23.7%, p = 0.002). Cox multivariate analysis identified a CCI > 2 as an independent risk factor for 1-year mortality (p = 0.002; HR: 1.525; CI 95% 1.161-2.003), along with older age, history of arterial hypertension, and higher admission heart rate and serum potassium values. Analyzing CCI as a continuous variable, the association remained is also significant (p = 0.0001; HR 1.145; CI 95% 1.069-1.854). CONCLUSIONS: Higher global comorbidity (CCI > 2) at the time of a first hospitalization because of AHF is an independent predictor of mid-term post-discharge mortality among elderly HF patients.

Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project.

BACKGROUND: Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm) versus i.v. ferric carboxymaltose (FE arm) versus a placebo (PLACEBO arm) in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention. METHODS/DESIGN: Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU), or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients. DISCUSSION: We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. CLINICALTRIALS.GOV IDENTIFIER: NCT01154491.

Spinal cord compression of neoplastic origin: surgical experience using a common clinical language.

PURPOSE: To assess the value of a common clinical language in a multidisciplinary tumour board for spinal metastasis, using both the Rades score and the Spinal Instability Neoplastic Score (SINS) for multidisciplinary decision-making. METHODS: Retrospective study of 60 consecutive patients treated surgically for MSCC. The indication for surgery was done in a multidisciplinary board, basically according to SINS and RADES scores. Three prognostic groups were defined according to the Rades score: poor (Rades 1: 20-30 points), intermediate (Rades 2: 31-35), and good (Rades 3: 36-45). RESULTS: The 2-year overall survival (OS) rate was 50%, with median survival of 19 months. By Rades prognostic group (1, 2, 3), median OS was 6 months, 15 months, and not reached, respectively. OS rates at 6 months (Rades 1, 2, 3) were 51, 69, and 74.1%, respectively. Within the Rades 1 group, 6-month survival in patients with new-onset cancer was 68 vs. 40% in those with a known primary. The overall complication rate ≥ grade 3 was 23.3% (n = 14). In patients who underwent urgent surgery (< 48 h), the complication rate was 45.5% (5/11) versus 18.3% (9/49) in the planned surgeries. CONCLUSIONS: Our findings supports the utility of using a common language in multidisciplinary tumour board for spinal metastasis. The 2-year OS rate in this series was 50%, which is the highest OS reported to date in this population. In the poor prognosis subgroup (Rades 1), OS at 6 months was higher in patients with new-onset cancer versus those with a known primary (68 vs. 40%). These findings suggest that surgery should be the first treatment option in patients with MSCC as first symptom of cancer although a predicted poor prognosis.

High-Dose Methylprednisolone Pulses for 3 Days vs. Low-Dose Dexamethasone for 10 Days in Severe, Non-Critical COVID-19: A Retrospective Propensity Score Matched Analysis.

Corticosteroids are largely recommended in patients with severe COVID-19. However, evidence to support high-dose methylprednisolone (MP) pulses is not as robust as that demonstrated for low-dose dexamethasone (DXM) in the RECOVERY trial. This is a retrospective cohort study on severe, non-critically ill patients with COVID-19, comparing 3-day MP pulses ≥ 100 mg/day vs. DXM 6 mg/day for 10 days. The primary outcome was in-hospital mortality, and the secondary outcomes were need of intensive care unit (ICU) admission or invasive mechanical ventilation (IMV). Propensity-score matching (PSM) analysis was applied. From March 2020 to April 2021, a total of 2,284 patients were admitted to our hospital due to severe, non-critically ill COVID-19, and of these, 189 (8.3%) were treated with MP, and 493 (21.6%) with DXM. The results showed that patients receiving MP showed higher in-hospital mortality (31.2% vs. 17.8%, p < 0.001), need of ICU admission (29.1% vs. 20.5%, p = 0.017), need of IMV (25.9% vs. 13.8, p < 0.001), and median hospital length of stay (14 days vs. 11 days, p < 0.001). Our results suggest that treatment with low-dose DXM for 10 days is superior to 3 days of high-dose MP pulses in preventing in-hospital mortality and need for ICU admission or IMV in severe, non-critically ill patients with COVID-19.

Beneficial and harmful outcomes of tocilizumab in severe COVID-19: A systematic review and meta-analysis.

INTRODUCTION: The results of studies of tocilizumab (TCZ) in COVID-19 are contradictory. Our study aims to update medical evidence from controlled observational studies and randomized clinical trials (RCTs) on the use of TCZ in hospitalized patients with COVID-19. METHODS: We searched the following databases from January 1, 2020 to April 13, 2021 (date of the last search): MEDLINE database through the PubMed search engine and Scopus, using the terms ("COVID-19" [Supplementary Concept]) AND "tocilizumab" [Supplementary Concept]). RESULTS: Sixty four studies were included in the present study: 54 were controlled observational studies (50 retrospective and 4 prospective) and 10 were RCTs. The overall results provided data from 20,616 hospitalized patients with COVID-19: 7668 patients received TCZ in addition to standard of care (SOC) (including 1915 patients admitted to intensive care units (ICU) with reported mortality) and 12,948 patients only receiving SOC (including 4410 patients admitted to the ICU with reported mortality). After applying the random-effects model, the hospital-wide (including ICU) pooled mortality odds ratio (OR) of patients with COVID-19 treated with TCZ was 0.73 (95% confidence interval (CI) = 0.56-0.93). The pooled hospital-wide mortality OR was 1.25 (95% CI = 0.74-2.18) in patients admitted at conventional wards versus 0.66 (95% CI = 0.59-0.76) in patients admitted to the ICU. The pooled OR of hospital-wide mortality (including ICU) of COVID-19 patients treated with TCZ plus corticosteroids (CS) was 0.67 (95% CI = 0.54-0.84). The pooled in-hospital mortality OR was 0.71 (95% CI = 0.35-1.42) when TCZ was early administered (≤10 days from symptom onset) versus 0.83 (95% CI 0.48-1.45) for late administration (>10 days from symptom onset). The meta-analysis did not find significantly higher risk for secondary infections in COVID-19 patients treated with TCZ. CONCLUSIONS: TCZ prevented mortality in patients hospitalized for COVID-19. This benefit was seen to a greater extent in patients receiving concomitant CS and when TCZ administration occurred within the first 10 days after symptom onset.

[Diabetes mellitus and risk of hip fracture. A systematic review]. / Diabetes mellitus y riesgo de fractura de cadera. Revisión sistemática.

BACKGROUND AND OBJECTIVES: It has been reported that the risk of fracture is increased in patients with diabetes mellitus (DM). The aim of this study was to investigate the possible relationship between DM and hip fracture, as well as any associated risk factors, by means of a systemic review of the literature. METHODS: PubMed and SCOPUS databases were used to search for relevant studies published from January 2001 to August 2018. Retrospective and prospective cohort studies were selected in which the estimated risk of hip fracture was demonstrated by comparing groups of diabetic patients with non-diabetics. A search was also made for risk factors independent from the association between DM and hip fracture. RESULTS: A total of 27 articles that fulfilled the inclusion criteria were included. A clear association was observed in diabetic patients (women and men) compared to non-diabetics patients. Among the risk factors, the most important ones were the fact that diabetes was type 1, probably associated with greater risk to a longer duration of DM, and being a female. CONCLUSIONS: There is an increased risk of hip fracture in patients diagnosed with DM. This association is more significant in diabetes type 1 and women.

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

OBJECTIVES: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). METHODS: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. RESULTS: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. CONCLUSIONS: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.

Association between diabetes and mortality in elderly patients admitted for a first episode of acute heart failure.

AIM: To examine whether the presence of a prior diagnosis of diabetes mellitus (DM) influences mortality risk in elderly patients experiencing a first episode of heart failure (HF) hospitalization. METHODS: A total of 677 consecutive patients aged ≥75 years admitted for a first episode of acute decompensated heart failure were evaluated according to the presence or not of DM, and in-hospital and 1-year mortality rates were evaluated. RESULTS: A total of 240 patients (35.4%) had a diagnosis of DM. Overall, 42 patients (6.2%) died during admission; and 205 patients (30.3%) died after 1 year; however, no differences were observed in mortality rates between both groups. Cox univariate analysis did not identify prior DM diagnosis as a risk factor for 1-year mortality (HR 0.767, P < 0.082). Multivariate analysis identified older age (HR 1.101, P < 0.0001), lower preadmission Barthel Index (HR 0.987, P = 0.002), higher heart rate (HR 1.013, P = 0.02), higher admission serum potassium (HR 1.471, P = 0.016) and non-prescription of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists (HR 1.597, P = 0.018) as independent risk factors for 1-year mortality. CONCLUSIONS: More than one-third of elderly patients experiencing a first admission because of acute heart failure decompensation had a prior diagnosis of DM. However, DM did not seem to be associated to a significant 1-year mortality risk. Geriatr Gerontol Int 2018; 18: 554-560.

Evidence of functional declining and global comorbidity measured at baseline proved to be the strongest predictors for long-term death in elderly community residents aged 85 years: a 5-year follow-up evaluation, the OCTABAIX study.

OBJECTIVE: To investigate the predictive value of functional impairment, chronic conditions, and laboratory biomarkers of aging for predicting 5-year mortality in the elderly aged 85 years. METHODS: Predictive value for mortality of different geriatric assessments carried out during the OCTABAIX study was evaluated after 5 years of follow-up in 328 subjects aged 85 years. Measurements included assessment of functional status comorbidity, along with laboratory tests on vitamin D, cholesterol, CD4/CD8 ratio, hemoglobin, and serum thyrotropin. RESULTS: Overall, the mortality rate after 5 years of follow-up was 42.07%. Bivariate analysis showed that patients who survived were predominantly female (P=0.02), and they showed a significantly better baseline functional status for both basic (P<0.001) and instrumental (P<0.001) activities of daily living (Barthel and Lawton index), better cognitive performance (Spanish version of the Mini-Mental State Examination) (P<0.001), lower comorbidity conditions (Charlson) (P<0.001), lower nutritional risk (Mini Nutritional Assessment) (P<0.001), lower risk of falls (Tinetti gait scale) (P<0.001), less percentage of heart failure (P=0.03) and chronic obstructive pulmonary disease (P=0.03), and took less chronic prescription drugs (P=0.002) than nonsurvivors. Multivariate Cox regression analysis identified a decreased score in the Lawton index (hazard ratio 0.86, 95% confidence interval: 0.78-0.91) and higher comorbidity conditions (hazard ratio 1.20, 95% confidence interval: 1.08-1.33) as independent predictors of mortality at 5 years in the studied population. CONCLUSION: The ability to perform instrumental activities of daily living and the global comorbidity assessed at baseline were the predictors of death, identified in our 85-year-old community-dwelling subjects after 5 years of follow-up.

Characteristics of falls producing hip fracture in patients on oral anticoagulants.

OBJECTIVE: To analyze the demographic and clinical characteristics of patients on chronic anticoagulant therapy (CAT) admitted because of a hip fracture secondary to a fall, and to compare with patients not receiving CAT. METHODS: A prospective, observational study realized in six hospitals in the Barcelona area. Demographic and clinical characteristics of patients were collected. The index fall characteristics - cause, height, location, and time of occurrence - were evaluated. RESULTS: Of the 1225 patients included, 99 (8%) patients were on CAT. When we compare with the rest logistic regression analysis showed that patients receiving CAT were more likely to be male (odds ratio 3.7), not institutionalized (odds ratio 3.5), to take more number of drugs (odds ratio 1.3), to have dementia (odds ratio 2.1) and stroke (odds ratio 1.7). Results revealed a higher prevalence of combined factors as the cause of the index fall in the group of patients on anticoagulants. CONCLUSIONS: Characteristics of falls were very similar when comparing the group of patients receiving CAT with those who did not. A prior history of falls should lead physicians to take actions for preventing falls causing hip fracture, in all patients and particularly in these on CAT.

[Profile and prognosis of patients over 85 years old with anemia living in the community. Octabaix Study]. / Perfil y pronóstico del paciente con anemia mayor de 85 años que vive en la comunidad. Estudio Octabaix.

OBJECTIVES: To analyze the prevalence of anemia in a sample of patients over 85 years old. To explore possible differentiating features in the groups of people with and without anemia, and to evaluate the relationship of anemia with mortality after a follow-up of 3 years. MATERIAL AND METHODS: An observational multicenter study was conducted on a cohort of people born in 1924 and who lived in the community. Socio-demographic variables, comorbidity, functionality, cognitive status, social risk, perceived quality of life, nutritional status, drug consumption and laboratory parameters were collected. Multivariate logistic regression analysis was performed. RESULTS: A total of 328 inhabitants were included, of whom 61.6% were women. The prevalence of anemia was 24%. Statistically significant differences in the Charlson index were found, showing higher values in anemic patients (P=0001) and in the Barthel index (BI) and in the Lawton index (LI), with lower levels in anemic patients (P=002 for both). Patients with anemia had a poorer perception of their quality of life (P=015). The presence of anemia was associated with more dependence according the BI values (OR 0.985; 95% CI: 0973-0997) and with higher comorbidity according the Charlson index (OR 1.314; 95% CI: 1124-1536). Mortality was higher in the group of patients with anemia, reaching statistically significant differences in the third year P=005). CONCLUSIONS: In our cohort anemia is a fairly prevalent feature in the population over 85 years old, and is associated with higher mortality at three years of follow up. Patients with anemia had worse physical functioning and greater comorbidity.

Clinical evidence of diabetes mellitus end-organ damage as risk factor for falls complicated by hip fracture: A multi-center study of 1225 patients.

AIMS: To identify the differential characteristics of patients with type 2 diabetes mellitus (T2DM) complicated by end-organ damage who experience a fall-related hip fracture. METHODS: We analyzed the socio-demographic data and index fall clinical characteristics of a group of patients with nephropathy, neuropathy or retinopathy related to T2DM consecutively admitted to six hospitals in Barcelona, Spain because of a fall-related hip fracture. RESULTS: Out of 1225 patients admitted because of a fall-related hip fracture, 107 (8.7%) had clinical evidence of end-organ damage related to T2DM. Among this cohort the mean number of falls during the year prior to the index admission was 2.6±3.2; and 29 of them (27.1%) had already experienced three or more falls. Most falls leading to the index admission took place at the patients' home, from a standing position, and during daylight time. An intrinsic cause of falling was identified in all but one of these patients. Multiple stepwise logistic regression analysis showed that, compared to patients without this diagnosis, patients with complicated T2DM were younger (odds ratio 0.762), had less prevalence of dementia (odds ratio 0.078), but had experienced a higher number of falls in the previous year (odds 1.183). CONCLUSIONS: A significant amount of patients with clinical evidence of end-organ damage due to T2DM who experience a fall-related hip fracture have a history of recurrent falling in the previous year. These patients should be identified and offered preventive actions aimed at reducing their risk of falling.

A mouse peritonitis model for the study of glycopeptide efficacy in GISA infections.

In recent years, the emergence of Staphylococcus aureus strains with reduced susceptibility to glycopeptides has raised considerable concern. We studied the efficacy of vancomycin and teicoplanin, as well as cloxacillin and cefotaxime, against the infection caused by four S. aureus strains with different glycopeptide and beta-lactam susceptibilities (strains A, B, C, and D; MICs for vancomycin of 1, 2, 4, and 8 microg/ml respectively), using a modified model of mouse peritonitis. This optimized model appeared to be straightforward and reproducible, and was able to detect low differences in bacterial killing between antibiotics and also between different S. aureus strains. Bactericidal activities in peritoneal fluid for vancomycin, teicoplanin, cloxacillin, and cefotaxime decreased from -2.98, -2.36, -3.22, and -3.57 log(10) cfu/ml, respectively, in infection by strain A (MICs for vancomycin and cloxacillin of 1 and 0.38 microg/ml, respectively) to -1.22, -0.65, -1.04, and +0.24 in peritonitis due to strain D (MICs for vancomycin and cloxacillin of 8 and 1,024 microg/ml). Our data confirm the superiority of beta-lactams against methicillin-susceptible S. aureus and show that bactericidal activity of glycopeptides decreases significantly with slight increases in MICs; this finding suggests a reduced efficacy of glycopeptides in the treatment of serious glycopeptide-intermediate S. aureus infections.

Recurrent sarcoidosis: a study of 17 patients with 24 episodes of recurrence.

BACKGROUND AND AIM: Recurrence of sarcoidosis following complete remission and after a prolonged time of inactivity is considered a very unusual clinical event. The aim of this study was to investigate the clinical characteristics of a series of patients diagnosed as having recurrent sarcoidosis. METHODS: Recurrent sarcoidosis was defined as reappearance of the disease following complete spontaneous clinical, radiographic and other markers of activity resolution or following resolution after corticosteroid treatment and maintained for at least during 3 years without therapy. The clinical records of patients diagnosed as having episodes of recurrent sarcoidosis during a period of 28 years at the university hospital of Bellvitge in Barcelona, Spain, were reviewed. RESULTS: Seventeen patients suffering from 24 recurrences were identified. All but one patient were women. The mean follow-up time was 143 +/- 80 months (range: 52 to 282 months). Two patients had 3 recurrences, 3 had 2 and 12 had 1. The disease-free interval without treatment between the time when the disease became inactive after the initial presentation until the first recurrence varied from 10 months to more than 17 years, and the time of inactive disease without therapy between recurrences fluctuated from 23 months to more than 12 years. All the cases but one at onset and 17 at recurrence presented as Löfgren syndrome. At the time of the last control, 14 patients showed complete remission of the disease, one of them under corticosteroid therapy, 2 still had activity because of a recent recurrence, and 1 developed into chronic sarcoidosis. CONCLUSIONS: Acute sarcoidosis, and particularly Löfgren's syndrome, may recur many years after complete remission and, in general, still has a good outcome. In consequence, a long-term follow-up is recommended even in patients with inactive disease. This clinical observation strongly suggests that a re-exposure to or reinfection by an extrinsic antigen triggers the new flare-ups of the disease.

Utility of geriatric assessment to predict mortality in the oldest old: the Octabaix study 3-year follow-up.

OBJECTIVE: Few studies have prospectively evaluated the utility of geriatric assessment tools as predictors of mortality in the oldest population. We investigated predictors of death in an oldest-old cohort after 3 years of follow-up. METHODS: The Octabaix study is a prospective, community-based study with a follow-up period of 3 years involving 328 subjects aged 85 at baseline. Data were collected on functional and cognitive status, co-morbidity, nutritional and falls risk, quality of life, social risk, and long-term drug prescription. Vital status for the total cohort was evaluated after 3 years of follow-up. RESULTS: Mortality after 3 years was 17.3%. Patients who did not survive had significantly poorer baseline functional status for basic and instrumental activities of daily living (Barthel and Lawton Index), higher co-morbidity (Charlson), higher nutritional risk (Mini Nutritional Assessment), higher risk of falls (Tinetti Gait Scale), poor quality of life (visual analog scale of the Quality of Life Test), and higher number of chronic drugs prescribed. Cox regression analysis identified the Lawton Index (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73-0.89) and the number of chronic drugs prescribed (HR 1.09, 95% CI 1.01-1.18) as independent predictors of mortality at 3 years. CONCLUSIONS: Among the variables studied, the ability to perform instrumental activities of daily living and using few drugs on a chronic basis at baseline are the best predictors of which oldest-old community-dwelling subjects survive after a 3-year follow-up period.

Rifampicin/imipenem combination in the treatment of carbapenem-resistant Acinetobacter baumannii infections.

BACKGROUND: In the setting of a large endemic of Acinetobacter baumannii infections, treatment of those due to carbapenem-resistant strains, susceptible only to colistin, has become a major problem in our hospital during the past years. Successful results have been reported using colistin, but clinical experience with this antibiotic is limited. In our experimental studies using these strains in a mouse pneumonia model, the best results were observed with a combination of rifampicin and imipenem. METHODS: From July 2000 to September 2001, we performed a pilot study with patients suffering from serious infections due to carbapenem-resistant A. baumannii. Patients were treated with a rifampicin/imipenem combination and followed up prospectively. Cultures were repeated during and after treatment, and in vitro activity of rifampicin was monitored. Genotyping of these strains was performed by means of PFGE. RESULTS: Ten patients were selected: four with ventilator-associated pneumonia, and six with other infections (one catheter-related bacteraemia, five surgical infections). Three patients died, two of whom were considered therapeutic failures. In five of the seven patients who were cured, other procedures were also performed such as surgical drainage or catheter removal. In vitro development of high resistance to rifampicin was shown in seven (70%). PFGE demonstrated that initial isolates and high-resistant strains belonged to the same clones. CONCLUSIONS: The results of our study argue against the use of a rifampicin/imipenem combination for the treatment of carbapenem-resistant A. baumannii infections. However, combinations of rifampicin with other antibiotics merit further studies.

Experimental study on the efficacy of combinations of glycopeptides and beta-lactams against Staphylococcus aureus with reduced susceptibility to glycopeptides.

OBJECTIVES: The combination of glycopeptides and beta-lactams has been proposed as an alternative therapy against infections due to Staphylococcus aureus with reduced susceptibility to glycopeptides, though its role is still controversial. Our aim was to evaluate the efficacy (decrease in bacterial concentration after 24 h therapy) of these combinations both in vitro and in vivo. METHODS: Four strains of S. aureus with different glycopeptide susceptibility (MICs of vancomycin from 1 to 8 mg/L) were used. In vitro experiments were performed by means of time-kill curves while we used the mouse peritonitis model for in vivo evaluation. RESULTS: Combinations of glycopeptides and beta-lactams showed synergy in in vitro time-kill curves against the four staphylococcal strains, the highest efficacy being detected against the glycopeptide-intermediate S. aureus (GISA) strain (MIC = 8 mg/L) (Deltalog 24 h = -3.19 cfu/mL for vancomycin at 1/2 x MIC and oxacillinat 1/64 x MIC versus -0.56 cfu/mL for vancomycin alone at 1/2 x MIC). On the other hand, no significant increase in efficacy was observed in vivo in the experimental model. The efficacy of the combinations decreased in correlation to the decreasing susceptibility of the strains to glycopeptides, showing only residual activity against the GISA strain (Deltalog 24 h = -1.42 cfu/mL for vancomycin and cloxacillin versus -1.22 cfu/mL for vancomycin). CONCLUSIONS: In the in vivo setting we were unable to demonstrate the synergism between glycopeptides and beta-lactams observed in vitro; nor did combinations show antagonism against any of the strains. Though the usefulness of these combinations cannot be totally ruled out in highly specific clinical conditions, it seems unlikely that they will provide a serious therapeutic alternative in most hGISA and GISA infections in the coming years.

Antibiotic combinations for serious infections caused by carbapenem-resistant Acinetobacter baumannii in a mouse pneumonia model.

OBJECTIVES: Successful therapy of carbapenem-resistant Acinetobacter baumannii strains has been reported with colistin, but recently we argued against its use as monotherapy because of the poor results obtained in a mouse pneumonia model. Our aim was to identify antibiotic combinations that were valid therapeutic alternatives in the same model. METHODS: We used two carbapenem-resistant A. baumannii strains (D and E; MICs of imipenem, 8 and 512 mg/L, respectively). MICs of tobramycin, rifampicin and colistin for both strains were 8, 8 and 0.5 mg/L, respectively. RESULTS: In infections caused by strain D, lung bacterial counts (log(10) cfu/g, mean +/- s.d.) were: controls (10.86+/-0.25), imipenem (5.99+/-0.59, P < 0.05 versus controls), and colistin (10.43 +/- 1.09); imipenem + tobramycin was the most active combination (5.46+/-0.62, P < 0.05 versus controls). In infections caused by strain E, results were: controls (10.82+/-0.33), rifampicin (5.62+/-0.26, P < 0.05 versus controls), colistin (8.38+/-1.22, P < 0.05 versus controls), and imipenem (11.01+/-0.2); rifampicin + imipenem (3.79+/-0.99) and rifampicin + tobramycin (3.96+/-0.30) were the most active combinations (P < 0.05); results with rifampicin + colistin (5.59+/-1.17) were similar to those with rifampicin alone. CONCLUSIONS: Our data indicate that imipenem can still be the best alternative for carbapenem-resistant A. baumannii infections with moderate levels of imipenem resistance, preferably combined with aminoglycosides. For strains highly resistant to imipenem, a combination of rifampicin with imipenem, tobramycin or colistin may be useful, if resistance to rifampicin is only moderate.