Impact of pre-hospital antibiotic therapy on mortality in invasive meningococcal disease: a propensity score study.

The role of pre-hospital antibiotic therapy in invasive meningococcal diseases remains unclear with contradictory data. The aim was to determine this role in the outcome of invasive meningococcal disease. Observational cohort study of patients with/without pre-hospital antibiotic therapy in invasive meningococcal disease attended at the Hospital Universitari de Bellvitge (Barcelona) during the period 1977-2013. Univariate and multivariate analyses of mortality, corrected by propensity score used as a covariate to adjust for potential confounding, were performed. Patients with pre-hospital antibiotic therapy were also analyzed according to whether they had received oral (group A) or parenteral antibiotics (early therapy) (group B). Five hundred twenty-seven cases of invasive meningococcal disease were recorded and 125 (24%) of them received pre-hospital antibiotic therapy. Shock and age were the risk factors independently related to mortality. Mortality differed between patients with/without pre-hospital antibiotic therapy (0.8% vs. 8%, p = 0.003). Pre-hospital antibiotic therapy seemed to be a protective factor in the multivariate analysis of mortality (p = 0.038; OR, 0.188; 95% CI, 0.013-0.882). However, it was no longer protective when the propensity score was included in the analysis (p = 0.103; OR, 0.173; 95% CI, 0.021-1.423). Analysis of the oral and parenteral pre-hospital antibiotic groups revealed that there were no deaths in early therapy group. Patients able to receive oral antibiotics had less severe symptoms than those who did not receive pre-hospital antibiotics. Age and shock were the factors independently related to mortality. Early parenteral therapy was not associated with death. Oral antibiotic therapy in patients able to take it was associated with a beneficial effect in the prognosis of invasive meningococcal disease.

Serotypes and genotypes of Streptococcus pneumoniae causing pneumonia and acute exacerbations in patients with chronic obstructive pulmonary disease.

OBJECTIVES: This study aimed to compare the antibiotic susceptibilities, serotypes and genotypes of pneumococci causing pneumonia or acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in patients with COPD. METHODS: A total of 611 pneumococci collected from 487 COPD patients with pneumonia (n = 255, 94 bacteraemic pneumonia) or AECOPD episodes (n = 356), from 2001 to 2008, were analysed. Antibiotic susceptibility was studied by microdilution. Serotypes (PCR or Quellung) and genotypes (PFGE and multilocus sequence typing) were determined. RESULTS: Pneumococci isolated from AECOPD episodes were significantly more resistant to co-trimoxazole and chloramphenicol than those isolated from pneumonia episodes (39.0% versus 29.7% and 13.8% versus 8.2%, respectively, P < 0.05). Comparing serotypes of isolates causing bacteraemic pneumonia, non-bacteraemic pneumonia and AECOPD, serotypes 4, 5 and 8 were associated with bacteraemic pneumonia (P < 0.05), serotypes 1 and 3 were associated with bacteraemic and non-bacteraemic pneumonia (P < 0.05) and serotypes 16F and 11A and non-typeable pneumococci were associated with AECOPD episodes (P < 0.05). The genotypes related to serotypes 3 (Netherlands(3)-ST180 and ST260(3)), 1 (Sweden(1)-ST306), 5 (Colombia(5)-ST289) and 8 (Netherlands(8)-ST53) were isolated more frequently in pneumonia episodes (P < 0.05), whereas genotype ST30(16F) (serotype 16F) was more frequently recovered from AECOPD episodes. CONCLUSIONS: In our experience, serotype 3 pneumococci (Netherlands(3)-ST180 and ST260(3) genotypes) commonly cause pneumonia and acute exacerbations in COPD patients. Pneumococci of serotypes 1 (Sweden(1)-ST306), 4 (ST247(4)), 5 (Colombia(5)-ST289) and 8 (Netherlands(8)-ST53) were more often associated with pneumonia. Non-typeable pneumococci may play an important role in acute exacerbations.

Epidemiology, clinical features and outcomes of pneumonia in patients with chronic kidney disease.

BACKGROUND: Although infection remains among the most common causes of morbidity and mortality in patients with chronic kidney disease (CKD), data on epidemiology, clinical features and outcomes of pneumonia in this population are scarce. METHODS: Observational analysis of a prospective cohort of hospitalized adults with pneumonia, between 13 February 1995 and 30 April 2010, in a tertiary teaching hospital. CKD patients, defined as patients with a baseline glomerular filtration rate <60 mL/min/1.73 m(2), were compared with non-CKD patients. RESULTS: During the study period, 3800 patients with pneumonia required hospitalization. Two-hundred and three (5.3%) patients had CKD, of whom 46 were on dialysis therapy. Patients with CKD were older (77 versus 70 years; P < 0.001), were more likely to have comorbidities (82.3 versus 63.3%; P < 0.001) and more commonly classified into high-risk pneumonia severity index classes (89.6 versus 57%; P < 0.001) than were the remaining patients. Streptococcus pneumoniae was the most frequent pathogen (28.1 versus 34.7%; P = 0.05). Mortality was higher in patients with CKD (15.8 versus 8.3%; P < 0.001). Among CKD patients, age [+1 year increase; adjusted odds ratio, 1.25; 95% confidence interval (CI) 1.07-1.46] and cardiac complications during hospitalization (adjusted odds ratio, 9.23; 95% CI 1.39-61.1) were found to be independent risk factors for mortality, whereas prior pneumococcal vaccination (adjusted odds ratio, 0.05; 95% CI 0.005-0.69) and leukocytosis at hospital admission (adjusted odds ratio, 0.10; 95% CI 0.01-0.64) were protective factors. CONCLUSIONS: Pneumonia is a serious complication in CKD patients. Independent factors for mortality are older age and cardiac complications, whereas prior pneumococcal vaccination and leucokytosis at hospital admission are protective factors. These findings should encourage physicians to increase pneumococcal vaccine coverage among CKD patients.

Invasive Meningococcal Disease: What We Should Know, Before It Comes Back.

BACKGROUND: Invasive meningococcal disease (IMD), sepsis and/or meningitis continues to be a public health problem, with mortality rates ranging from 5% to 16%. The aim of our study was to further knowledge about IMD with a large series of cases occurring over a long period of time, in a cohort with a high percentage of adult patients. METHODS: Observational cohort study of patients with IMD between 1977 hand 2013 at our hospital, comparing patients with only sepsis and those with meningitis and several degrees of sepsis. The impact of dexamethasone and prophylactic phenytoin was determined, and an analysis of cutaneous and neurological sequelae was performed. RESULTS: A total of 527 episodes of IMD were recorded, comprising 57 cases of sepsis (11%) and 470 of meningitis with or without sepsis (89%). The number of episodes of IMD decreased from 352 of 527 (67%) in the first to 20 of 527 (4%) in the last quarter (P < .001). Thirty-three patients died (6%): 8 with sepsis (14%) and 25 with meningitis (5%) (P = .02). Cutaneous and neurological sequelae were present in 3% and 5% of survivors of sepsis and meningitis, respectively. The use of dexamethasone was safe and resulted in less arthritis, and patients given prophylactic phenytoin avoided seizures. CONCLUSIONS: The frequency of IMD has decreased sharply since 1977. Patients with sepsis only have the highest mortality and complication rates, dexamethasone use is safe and can prevent some arthritis episodes, and prophylactic phenytoin might be useful in a selected population. A rapid response and antibiotic therapy may help improve the prognosis.

Health care-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes.

BACKGROUND: Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. However, limited data exist to validate this entity. We aimed to ascertain the epidemiology, causative organisms, antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for HCAP requiring hospitalization. METHODS: Observational analysis of a prospective cohort of nonseverely immunosuppressed hospitalized adults with pneumonia. Patients who had recent contact with the health care system through nursing homes, home health care programs, hemodialysis clinics, or prior hospitalization were considered to have HCAP. RESULTS: Of 727 cases of pneumonia, 126 (17.3%) were HCAP and 601 (82.7%) were community acquired. Compared with patients with community-acquired pneumonia, patients with HCAP were older (mean age, 69.5 vs 63.7 years; P < .001), had greater comorbidity (95.2% vs 74.7%; P < .001), and were more commonly classified into high-risk pneumonia severity index classes (67.5% vs 48.8%; P < .001). The most common causative organism was Streptococcus pneumoniae in both groups (27.8% vs 33.9%). Drug-resistant pneumococci were more frequently encountered in cases of HCAP. Legionella pneumophila was less common in patients with HCAP (2.4% vs 8.8%; P = .01). Aspiration pneumonia (20.6% vs 3.0%; P < .001), Haemophilus influenzae (11.9% vs 6.0%; P = .02), Staphylococcus aureus (2.4% vs 0%; P = .005), and gram-negative bacilli (4.0% vs 1.0%; P = .03) were more frequent in HCAP. Patients with HCAP more frequently received an initial inappropriate empirical antibiotic therapy (5.6% vs 2.0%; P = .03). The overall case-fatality rate (< 30 days) was higher in patients with HCAP (10.3% vs 4.3%; P = .007). CONCLUSIONS: At present, a substantial number of patients initially seen with pneumonia in the emergency department have HCAP. These patients require a targeted approach when selecting empirical antibiotic therapy.

Invasive meningococcal disease: Impact of short course therapy. A DOOR/RADAR study.

BACKGROUND: Invasive meningococcal disease is a severe infection. The appropriate duration of antibiotic therapy is not well established. METHODS: Two hundred and sixty-three consecutive patients with invasive meningococcal disease treated with 4 days' antibiotic therapy were compared with 264 consecutive patients treated previously at the same center with 7 days' antibiotic therapy. A Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) study was also performed. RESULTS: No relapses were recorded in any patient. Patients on the 4-day course were 63% female, with a median age of 23 years old (IQR 16-54) and patients on the 7-day course were 61% female, with a median age of 17 years old (IQR 12-43). Case fatality rate was 7% in the 4-d patients and 6% in the 7-d patients (p = 0.582). Neurological sequelae were recorded in 6% of the 4-d group and in 7% of the 7-d group ((p = 0.509) and cutaneous sequelae in 3% in both groups. There were no statistical significant differences between the groups in terms of clinical characteristics, laboratory findings or complications. The probability that a patient had a randomly chosen DOOR better with the 4-day regimen than with the 7-day regimen was 80.4% [95% CI 80.1-80.7%]. CONCLUSION: Invasive meningococcal disease may be successfully treated with a four-day course of antibiotic therapy without relapses.

Outpatient care compared with hospitalization for community-acquired pneumonia: a randomized trial in low-risk patients.

BACKGROUND: The Pneumonia Severity Index (PSI) has been advocated as an objective measure of risk stratification to help determine the initial site of treatment for patients with community-acquired pneumonia. OBJECTIVE: To determine whether outpatient care of PSI-defined low-risk patients with community-acquired pneumonia is as safe and effective as hospitalization. DESIGN: Unblinded, randomized, controlled trial. SETTING: 2 tertiary care hospitals. PATIENTS: 224 immunocompetent adults in risk class II or III (PSI scores

Factors Associated with Long-Term Sickness Absence Due to Mental Disorders: A Cohort Study of 7.112 Patients during the Spanish Economic Crisis.

BACKGROUND: Mental health problems are very common and often lead to prolonged sickness absence, having serious economic repercussions for most European countries. Periods of economic crisis are important social phenomena that are assumed to increase sickness absence due to mental disorders, although research on this topic remains scarce. The aim of this study was to gather data on long-term sickness absence (and relapse) due to mental disorders in Spain during a period of considerable socio-economic crisis. METHODS: Relationships were analyzed (using chi-squared tests and multivariate modelling via binary logistic regression) between clinical, social/employment-related and demographic factors associated and long-term sickness absence (>60 consecutive days) due to mental disorders in a cohort of 7112 Spanish patients during the period 2008-2012. RESULTS: Older age, severe mental disorders, being self-employed, having a non-permanent contract, and working in the real estate and construction sector were associated with an increased probability of long-term sickness absence (gender had a mediating role with respect to some of these variables). Relapses were associated with short-term sick leave (return to work due to 'improvement') and with working in the transport sector and public administration. CONCLUSIONS: Aside from medical factors, other social/employment-related and demographic factors have a significant influence on the duration of sickness absence due to mental disorders.

Clinical outcomes for hospitalized patients with Legionella pneumonia in the antigenuria era: the influence of levofloxacin therapy.

BACKGROUND: Although the reduction in case-fatality rate recently observed among patients with Legionella pneumonia has been largely attributed to the progressive utilization of urine antigen testing, other factors, such as changes in empirical antibiotic therapy, may also have contributed. We have analyzed more-recent outcomes of Legionella pneumonia in an institution where urine antigen testing was reflexly performed in cases of community-acquired pneumonia without an etiological diagnosis. METHODS: From a prospective series of 1934 consecutive cases of community-acquired pneumonia in nonimmunocompromised adults, 139 cases of Legionella pneumophila pneumonia were selected for observational review. Legionella cases were analyzed for outcome with respect to antibiotic treatment, mortality, complications, length of stay, time to defervescence, and stability. RESULTS: The early case-fatality rate was 2.9% (4 of 139 patients), and the overall case-fatality rate was 5% (7 of 139 patients). One hundred twenty patients (86.3%) received an appropriate initial therapy, which included macrolides (i.e., erythromycin or clarithromycin) in 80 patients and levofloxacin in 40. Levofloxacin progressively replaced macrolides as the initial therapy during the study period. Compared with patients who received macrolides, patients who received levofloxacin had a faster time to defervescence (2.0 vs. 4.5 days; P<.001) and to clinical stability (3 vs. 5 days; P=.002). No differences were found regarding the development of complications (25% vs. 25%; P=.906) and case-fatality rate (2.5% vs. 5%; P=.518). The median length of hospital stay was 8 days in patients treated with levofloxacin and 10 days in those who received macrolides (P=.014). CONCLUSIONS: Legionella pneumonia is still associated with significant complications in hospitalized patients, but recent mortality is substantially lower than that found in earlier series. Levofloxacin may produce a faster clinical response than older macrolides, allowing for shorter hospital stay.

Contribution of a urinary antigen assay (Binax NOW) to the early diagnosis of pneumococcal pneumonia.

We evaluated the usefulness of a rapid urinary antigen test (Binax NOW; Binax) to detect Streptococcus pneumoniae for the early diagnosis of community-acquired pneumococcal pneumonia (PP) in 220 nonseverely immunosuppressed adults. We compared results of this test with those of sputum Gram staining. The rapid urinary antigen test showed limited sensitivity (65.9%; 95% confidence interval [CI], 51.4-80.4) but high specificity (100%; 95% CI, 99.7-100) for diagnosing PP. The test was more sensitive for patients with versus those without high-risk pneumonia (94% vs. 63%; P<.001) and for patients without versus those with demonstrative results of a sputum Gram stain (97% vs. 55%; P<.001), and it tended to be more sensitive for patients with versus those without bacteremic PP (92% vs. 74%; P=NS). Rapid urinary antigen testing permitted early diagnosis of PP in 26% more patients than did Gram staining but missed 22% of the rapid diagnoses initially identified by Gram staining. On the basis of our results, a sequential approach is proposed, with reservation of urinary antigen testing for high-risk patients for whom demonstrative results of a sputum Gram stain are unavailable.

Community-acquired pneumonia in very elderly patients: causative organisms, clinical characteristics, and outcomes.

We performed an observational analysis of prospectively collected data on 1,474 adult patients who were hospitalized for community-acquired pneumonia; 1,169 patients were under 80 years of age and 305 (21%) patients were over 80 years ("very elderly"). Mean patient ages were 60 years in the former group and 85 years in the latter group. Severely immunosuppressed patients and nursing-home residents were not included. Comorbidities significantly associated with older age were chronic obstructive pulmonary disease, chronic heart disease, and dementia. The most common causative organism was Streptococcus pneumoniae (23% in both groups). Aspiration pneumonia was more frequent in the very elderly (5% in younger patients versus 10% in the very elderly); Legionella pneumophila (8% in younger patients versus 1% in the very elderly) and atypical agents (7% in younger patients versus 1% in the very elderly) were rarely recorded in the very elderly. While very elderly patients complained less frequently of pleuritic chest pain, headache, and myalgias, they were more likely to have absence of fever and altered mental status on admission. No significant differences were observed between groups as regards incidence of classic bacterial pneumonia syndrome (60% versus 59%) in 343 patients with pneumococcal pneumonia. The development of inhospital complications (26% in younger versus 32% in very elderly patients) as well as early mortality (2% in younger versus 7% in very elderly patients) and overall mortality (6% in younger versus 15% very elderly patients) were significantly higher in very elderly patients. Acute respiratory failure and shock/multiorgan failure were the most frequent causes of death, especially of early mortality. Factors independently associated with 30-day mortality in the very elderly were altered mental status on admission (odds ratio, 3.69), shock (odds ratio, 10.69), respiratory failure (odds ratio, 3.50), renal insufficiency (odds ratio, 5.83), and Gram-negative pneumonia (odds ratio, 20.27).

Community-acquired Legionella pneumophila pneumonia: a single-center experience with 214 hospitalized sporadic cases over 15 years.

Legionella pneumophila has been increasingly recognized as a cause of community-acquired pneumonia (CAP) and an important public health problem worldwide. We conducted the present study to assess trends in epidemiology, diagnosis, clinical features, treatment, and outcomes of sporadic community-acquired L. pneumophila pneumonia requiring hospitalization at a university hospital over a 15-year period (1995-2010). Among 3934 nonimmunosuppressed hospitalized patients with CAP, 214 (5.4%) had L. pneumophila pneumonia (16 cases were categorized as travel-associated pneumonia, and 21 were part of small clusters). Since the introduction of the urinary antigen test, the diagnosis of L. pneumophila using this method remained stable over the years (p = 0.42); however, diagnosis by means of seroconversion and culture decreased (p < 0.001 and p = 0.001, respectively). The median age of patients with L. pneumophila pneumonia was 58.2 years (SD 13.8), and 76.4% were male. At least 1 comorbid condition was present in 119 (55.6%) patients with L. pneumophila pneumonia, mainly chronic heart disease, diabetes mellitus, and chronic pulmonary disease. The frequency of older patients (aged >65 yr) and comorbidities among patients with L. pneumophila pneumonia increased over the years (p = 0.06 and p = 0.02, respectively). In addition, 100 (46.9%) patients were classified into high-risk classes according to the Pneumonia Severity Index (groups IV-V). Twenty-four (11.2%) patients with L. pneumophila pneumonia received inappropriate empirical antibiotic therapy at hospital admission. Compared with patients who received appropriate empirical antibiotic, patients who received inappropriate therapy more frequently had acute onset of illness (p = 0.004), pleuritic chest pain (p = 0.03), and pleural effusion (p = 0.05). The number of patients who received macrolides decreased over the study period (p < 0.001), whereas the number of patients who received levofloxacin increased (p < 0.001). No significant difference was found in the outcomes between patients who received erythromycin and clarithromycin. However, compared with macrolide use during hospital admission, levofloxacin therapy was associated with a trend toward a shorter time to reach clinical stability (median, 3 vs. 5 d; p = 0.09) and a shorter length of hospital stay (median, 7 vs. 10 d; p < 0.001). Regarding outcomes, 38 (17.8%) patients required intensive care unit (ICU) admission, and the inhospital case-fatality rate was 6.1% (13 of 214 patients). The frequency of ICU admission (p = 0.34) and the need for mechanical ventilation (p = 0.57) remained stable over the study period, but the inhospital case-fatality rate decreased (p = 0.04). In the logistic regression analysis, independent factors associated with severe disease (ICU admission and death) were current/former smoker (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.01-8.62), macrolide use (OR, 2.40; 95% CI, 1.03-5.56), initial inappropriate therapy (OR, 2.97; 95% CI, 1.01-8.74), and high-risk Pneumonia Severity Index classes (OR, 9.1; 95% CI, 3.52-23.4). In conclusion, L. pneumophila is a relatively frequent causative pathogen among hospitalized patients with CAP and is associated with high morbidity. The annual number of L. pneumophila cases remained stable over the study period. In recent years, there have been significant changes in diagnosis and treatment, and the inhospital case-fatality rate of L. pneumophila pneumonia has decreased.

Effect of a 3-step critical pathway to reduce duration of intravenous antibiotic therapy and length of stay in community-acquired pneumonia: a randomized controlled trial.

BACKGROUND: The length of hospital stay (LOS) for community-acquired pneumonia (CAP) varies considerably, even though this factor has a major impact on the cost of care. We aimed to determine whether the use of a 3-step critical pathway is safe and effective in reducing duration of intravenous antibiotic therapy and length of stay in hospitalized patients with CAP. METHODS: We randomly assigned 401 adults who required hospitalization for CAP to follow a 3-step critical pathway including early mobilization and use of objective criteria for switching to oral antibiotic therapy and for deciding on hospital discharge or usual care. The primary end point was LOS. Secondary end points were the duration of intravenous antibiotic therapy, adverse drug reactions, need for readmission, overall case-fatality rate, and patients' satisfaction. RESULTS: Median LOS was 3.9 days in the 3-step group and 6.0 days in the usual care group (difference, -2.1 days; 95% CI, -2.7 to -1.7; P < .001). Median duration of intravenous antibiotic therapy was 2.0 days in the 3-step group and 4.0 days in the usual care group (difference, -2.0 days; 95% CI, -2.0 to -1.0; P < .001). More patients assigned to usual care experienced adverse drug reactions (4.5% vs 15.9% [difference, -11.4 percentage points; 95% CI, -17.2 to -5.6 percentage points; P < .001]). No significant differences were observed regarding subsequent readmissions, case fatality rate, and patients' satisfaction with care. CONCLUSIONS: The use of a 3-step critical pathway was safe and effective in reducing the duration of intravenous antibiotic therapy and LOS for CAP and did not adversely affect patient outcomes. Such a strategy will help optimize the process of care of hospitalized patients with CAP, and hospital costs would be reduced. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN17875607.

Bacteremia related with arterial catheter in critically ill patients.

OBJECTIVE: Catheter-related bloodstream infections (CR-BSI) are an increasing problem in the management of critically ill patients. Our objective was to analyze the incidence and epidemiology of CR-BSI in arterial catheters (AC) in a population of critically ill patients. METHODS: We conducted a two-year, prospective, non-randomized study of patients admitted for > 24 h in a 24-bed medical-surgical major teaching ICU. We analyzed the arterial catheters and differentiated between femoral and radial locations. Difference testing between groups was performed using the two-tailed t-test and chi-square test as appropriate. Multivariate logistic regression analyses were conducted to identify independent predictors of CR-BSI occurrence and type of micro-organism responsible. RESULTS: The study included 1456 patients requiring AC placement for ≥ 24 h. A total of 1543 AC were inserted for 14,437 catheter days. The incidence of AC-related bloodstream infections (ACR-BSI) was 3.53 episodes per 1000 catheter days. In the same period the incidence of central venous catheter (CVC)-related bloodstream infections was 4.98 episodes per 1000 catheter days. Logistic regression analysis showed that days of insertion (OR: 1.118 95% confidence interval (CI) 1.026-1.219) and length of ICU stay (OR: 1.052 95% CI: 1.025-1.079) were associated with a higher risk of ACR-BSI. Comparing 705 arterial catheters in femoral location with 838 in radial location, no significant differences in infection rates were found, although there was a trend toward a higher rate among femoral catheters (4.13 vs. 3.36 episodes per 1000 catheter days) (p = 0.72). Among patients with ACR-BSI, Gram-negative bacteria were isolated in 16 episodes (61.5%) in the femoral location and seven (28%) in radial location (OR: 2.586; 95% CI: 1.051-6.363). CONCLUSIONS: We concluded that as has been reported for venous catheters ACR-BSI plays an important role in critically ill patients. Days of insertion and length of ICU stay increase the risk of ACR-BSI. The femoral site increases the risk for Gram-negative infection.

Changing trends in the epidemiology of pyogenic vertebral osteomyelitis: the impact of cases with no microbiologic diagnosis.

OBJECTIVES: The observed higher incidence of pyogenic vertebral osteomyelitis (PVO) may entail an increasing number of patients with no microbiologic diagnosis. The true incidence of these cases, how exhaustive the etiologic diagnostic efforts must be, and the usefulness of an empirical antibiotic therapy are not well defined. METHODS: Retrospective analysis of all cases of vertebral osteomyelitis in our center (1991-2009) and retrospective analysis of cases of PVO (2005-2009). Clinical data, diagnostic procedures, treatment, and outcome were reviewed. A comparative analysis between microbiologically confirmed PVO (MCPVO) and probable PVO (PPVO) was performed. RESULTS: Increasing incidence of PVO (+0.047 episodes/100,000 inhabitants-year). During the last decade, there was an increase of PPVO (+0.059 episodes/100,000 inhabitants-year) with stable incidence of MCPVO. During 2005-2009, there were 72 patients [47 (65%) MCPVO and 25 (35%) PPVO]. 60% men; mean age was 66 years. Bacteremia was found in 59%. Computed tomographic guided vertebral biopsy, positive in 7/36 (19%), was more successful among patients with bacteremia. Among MCPVO, there was an increasing proportion of less virulent bacteria. Cases of MCPVO presented more frequently with sepsis, fever, and high acute-phase reactants, and PPVO cases were mostly treated with oral fluoroquinolones plus rifampin. No differences were found between both groups in outcome (93% success, 22% sequelae). CONCLUSIONS: An epidemiologic change of PVO is suggested by a higher incidence of PPVO and the isolation of less virulent microorganisms among MCPVO. In this setting, the availability of an oral and effective empirical antibiotic therapy may challenge an exhaustive prosecution of the etiology.

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-acquired pneumonia in patients with liver cirrhosis: clinical features, outcomes, and usefulness of severity scores.

We performed an observational analysis of a prospective cohort of nonimmunocompromised hospitalized adults with community-acquired pneumonia (CAP) to determine the epidemiology, clinical features, and outcomes of patients with liver cirrhosis. We also analyzed the prognostic value of several severity scores. Of 3420 CAP episodes, 90 occurred in patients with liver cirrhosis. The median value of the Model for End-Stage Liver Disease (MELD) was 14 (range, 6-36). On the Child-Pugh (CP) score, 56% of patients were defined as grade B and 22% as grade C. Patients with liver cirrhosis were younger (61.8 vs. 66.8 yr; p = 0.001) than patients without cirrhosis, more frequently presented impaired consciousness at admission (33% vs. 14%; p < 0.001) and septic shock (13% vs. 6%; p = 0.011), and were more commonly classified in high-risk Pneumonia Severity Index (PSI) classes (classes IV-V) (74% vs. 58%; p = 0.002). Streptococcus pneumoniae (47% vs. 33%; p = 0.009) and Pseudomonas aeruginosa (4.4% vs. 0.9%; p = 0.001) were more frequently documented in patients with cirrhosis. Bacteremia was also more common in these patients (22% vs. 13%; p = 0.023). Areas under the curve (AUCs) from disease-specific scores (MELD, CP, PSI, and CURB-65 [confusion, urea, respiratory rate, blood pressure, and age ≥65 yr]) were comparable in predicting severe disease (30-d mortality and intensive care unit [ICU] admission). A new score based on MELD, multilobar pneumonia, and septic shock at admission (MELD-CAP) had an AUC of 0.945 (95% confidence interval [CI], 0.872-0.983) for predicting severe disease and was significantly different from other scores. Early (5.6% vs. 2.1%; p = 0.048) and overall (14.4% vs. 7.4%; p < 0.024) mortality rates were higher in cirrhotic patients than in patients without cirrhosis. Factors associated with mortality were impaired consciousness, multilobar pneumonia, ascites, acute renal failure, bacteremia, ICU admission, and MELD score. Among the severity scores, MELD-CAP was the only score associated with severe disease (odds ratio [OR], 1.33; 95% CI, 1.09-1.52) and mortality (OR, 1.21; 95% CI, 1.03-1.42). In conclusion, CAP in patients with liver cirrhosis presents a distinctive clinical picture and is associated with higher mortality than is found in patients without cirrhosis. The severity of hepatic dysfunction plays an important role in the development of adverse events. Cirrhosis-specific scores may be useful for predicting and stratifying cirrhotic patients with CAP who have a high risk of severe disease.

High doses of levofloxacin vs moxifloxacin against staphylococcal experimental foreign-body infection: the effect of higher MIC-related pharmacokinetic parameters on efficacy.

OBJECTIVES: Since levofloxacin at high doses was the best therapy in staphylococcal tissue-cage model of foreign-body infection, we hypothesized that moxifloxacin with higher ratio of area under the concentration-time curve to the MIC (AUC/MIC) would provide better results. METHODS: MICs, MBCs, MPCs (mutant prevention concentration) and 24h kill-curves were determined in the log and stationary phases. Using the aforementioned model, we tested the efficacy of levofloxacin 100mg/kg/d, moxifloxacin 40mg/kg/d and moxifloxacin 80mg/kg/d; they were equivalent to human levels for 1000mg/d, 400mg/d and 800mg/d, respectively. We screened for the appearance of resistant strains. RESULTS: MICs and MBCs in logarithmic and stationary phases and MPCs of levofloxacin were 0.5, 1 and 4, 0.8microg/ml, respectively, and those of moxifloxacin 0.12, 0.25 and 2, 0.25microg/ml. AUC/MIC were 234 (levofloxacin), 431 (moxifloxacin 40) and 568 (moxifloxacin 80). Bacterial counts decreases in tissue-cage fluids (means of logCFU/ml) were -1.81 (n=25), -1.31 (23), and -1.46 (20), respectively; for controls it was 0.24 (22). All groups were better than controls (p<0.05); no differences between them existed. CONCLUSIONS: Moxifloxacin with higher AUC/MIC ratio did not improve the efficacy of high doses of levofloxacin.

[Factors associated with prolonged hospital stay in community-acquired pneumonia]. / Factores relacionados con una estancia media hospitalaria prolongada en la neumonía adquirida en la comunidad.

INTRODUCTION: The length of hospital stay in patients with community-acquired pneumonia (CAP) varies considerably, even though this factor has a great impact on the cost of care for this condition. The objective of this study was to identify factors associated with prolonged hospitalization in these patients (>8 days). METHODS: Observational analysis of a prospective cohort of nonimmunosuppressed adults with CAP requiring hospitalization from 1995 through 2006. RESULTS: We documented a total of 2688 consecutive episodes of CAP. Patients who required intensive care unit admission from the emergency room (n=107), those who died during hospitalization (n=200), and patients hospitalized for more than 30 days (n=60) were excluded from the analysis. The median duration of hospital stay was 8 days (IQR, 6-11). Factors independently associated with prolonged hospital stay by stepwise multiple logistic regression analysis were advanced age (OR=1.58; 95% CI, 1.002-2.503), alcohol abuse (OR=2.07; 95% CI, 1.341-3.199), high-risk Pneumonia Severity Index class (OR=1.72; 95% CI, 1.094-2.703), aspiration pneumonia (OR=4.57; 95% CI, 1.085-19.285), pleural empyema (OR=3.73; 95% CI, 1.978-7.04), and time to clinical stability (OR=1.13; 95% CI, 1.065-1.196). CONCLUSIONS: Several factors that were independently associated with longer hospital stay in adult patients with CAP. These factors should be considered when evaluating the adequacy of the duration of hospitalization in a specific center and when designing future studies investigating new strategies to reduce the length of hospital stay.

Community-acquired bacterial meningitis in elderly patients: experience over 30 years.

Clinical characteristics, etiologies, evolution, and prognostic factors of community-acquired bacterial meningitis in elderly patients are not well known. To improve this knowledge, all episodes of community-acquired bacterial meningitis were prospectively recorded and cases occurring in patients >or=65 years old were selected. During the period 1977-2006, 675 episodes in adults (aged >or=18 yr) were recorded, with 185 (27%) in patients aged >or=65 years old; 76 were male and 109 were female, with a mean age of 73 +/- 6 years (range, 65-93 yr). Causative microorganisms were Streptococcus pneumoniae 74, Neisseria meningitidis 49, Listeria monocytogenes 17, other streptococcal 9, Escherichia coli 6, Haemophilus influenzae 4, Klebsiella pneumoniae and Staphylococcus aureus 2 each, Capnocytophaga canimorsus and Enterococcus faecalis 1 each, and unknown in 20. On admission 91% had had fever, 32% were in a coma (Glasgow Coma Scale or=65 yr), who showed a higher frequency of diabetes and malignancy as underlying disease; pneumonia, otitis, and pericranial fistula as predisposing factors; and S. pneumoniae and L. monocytogenes as etiology. There were also differences in clinical presentation, complications, sequelae, and mortality. Factors independently related with mortality were age, pneumonia as a predisposing factor, coma on admission, and heart failure and seizures after therapy. Dexamethasone therapy was a protective factor. In conclusion, bacterial meningitis in elderly patients is associated with greater diagnostic difficulties and neurologic severity and more complications, as well as with increased mortality. Antiseizure prophylaxis might be useful in these patients.