A 30-year perspective of low-dose dexamethasone, a single dose of mannitol and antiseizures prophylaxis on the prognosis of pneumococcal meningitis.

OBJECTIVES: This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis. METHODS: Data have been prospectively collected for the period1977-2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5-1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin. RESULTS: In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone (p = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone (p = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone (p = 0.000). CONCLUSIONS: A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients.

Penicillin- and Cephalosporin-Resistant Pneumococcal Meningitis: Treatment in the Real World and in Guidelines.

To report on the therapy used for penicillin- and cephalosporin-resistant pneumococcal meningitis, we conducted an observational cohort study of patients admitted to our hospital with pneumococcal meningitis between 1977 and 2018. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations, we defined pneumococci as susceptible and resistant to penicillin with MIC values of ≤0.06 mg/L and > 0.06 mg/L, respectively; the corresponding values for cefotaxime (CTX) were ≤0.5 mg/L and >0.5 mg/L. We treated 363 episodes of pneumococcal meningitis during the study period. Of these, 24 had no viable strain, leaving 339 episodes with a known MIC for inclusion. Penicillin-susceptible strains accounted for 246 episodes (73%), penicillin-resistant strains for 93 (27%), CTX susceptible for 58, and CTX resistant for 35. Nine patients failed or relapsed and 69 died (20%), of whom 22% were among susceptible cases and 17% were among resistant cases. During the dexamethasone period, mortality was equal (12%) in both susceptible and resistant cases. High-dose CTX (300 mg/Kg/day) helped to treat failed or relapsed cases and protected against failure when used as empirical therapy (P = 0.02), even in CTX-resistant cases. High-dose CTX is a good empirical therapy option for pneumococcal meningitis in the presence of a high prevalence of penicillin and cephalosporin resistance, effectively treating pneumococcal strains with MICs up to 2 mg/L for either penicillin or CTX.

Impact of a training program on the surveillance of Clostridioides difficile infection.

A high degree of vigilance and appropriate diagnostic methods are required to detect Clostridioides difficile infection (CDI). We studied the effectiveness of a multimodal training program for improving CDI surveillance and prevention. Between 2011 and 2016, this program was made available to healthcare staff of acute care hospitals in Catalonia. The program included an online course, two face-to-face workshops and dissemination of recommendations on prevention and diagnosis. Adherence to the recommendations was evaluated through surveys administered to the infection control teams at the 38 participating hospitals. The incidence of CDI increased from 2.20 cases/10 000 patient-days in 2011 to 3.41 in 2016 (P < 0.001). The number of hospitals that applied an optimal diagnostic algorithm rose from 32.0% to 71.1% (P = 0.002). Hospitals that applied an optimal diagnostic algorithm reported a higher overall incidence of CDI (3.62 vs. 1.92, P < 0.001), and hospitals that were more active in searching for cases reported higher rates of hospital-acquired CDI (1.76 vs. 0.84, P < 0.001). The results suggest that the application of a multimodal training strategy was associated with a significant rise in the reporting of CDI, as well as with an increase in the application of the optimal diagnostic algorithm.

Preoperative oral antibiotic prophylaxis reduces Pseudomonas aeruginosa surgical site infections after elective colorectal surgery: a multicenter prospective cohort study.

BACKGROUND: Healthcare-associated infections caused by Pseudomonas aeruginosa are associated with poor outcomes. However, the role of P. aeruginosa in surgical site infections after colorectal surgery has not been evaluated. The aim of this study was to determine the predictive factors and outcomes of surgical site infections caused by P. aeruginosa after colorectal surgery, with special emphasis on the role of preoperative oral antibiotic prophylaxis. METHODS: We conducted an observational, multicenter, prospective cohort study of all patients undergoing elective colorectal surgery at 10 Spanish hospitals (2011-2014). A logistic regression model was used to identify predictive factors for P. aeruginosa surgical site infections. RESULTS: Out of 3701 patients, 669 (18.1%) developed surgical site infections, and 62 (9.3%) of these were due to P. aeruginosa. The following factors were found to differentiate between P. aeruginosa surgical site infections and those caused by other microorganisms: American Society of Anesthesiologists' score III-IV (67.7% vs 45.5%, p = 0.001, odds ratio (OR) 2.5, 95% confidence interval (95% CI) 1.44-4.39), National Nosocomial Infections Surveillance risk index 1-2 (74.2% vs 44.2%, p < 0.001, OR 3.6, 95% CI 2.01-6.56), duration of surgery ≥75thpercentile (61.3% vs 41.4%, p = 0.003, OR 2.2, 95% CI 1.31-3.83) and oral antibiotic prophylaxis (17.7% vs 33.6%, p = 0.01, OR 0.4, 95% CI 0.21-0.83). Patients with P. aeruginosa surgical site infections were administered antibiotic treatment for a longer duration (median 17 days [interquartile range (IQR) 10-24] vs 13d [IQR 8-20], p = 0.015, OR 1.1, 95% CI 1.00-1.12), had a higher treatment failure rate (30.6% vs 20.8%, p = 0.07, OR 1.7, 95% CI 0.96-2.99), and longer hospitalization (median 22 days [IQR 15-42] vs 19d [IQR 12-28], p = 0.02, OR 1.1, 95% CI 1.00-1.17) than those with surgical site infections due to other microorganisms. Independent predictive factors associated with P. aeruginosa surgical site infections were the National Nosocomial Infections Surveillance risk index 1-2 (OR 2.3, 95% CI 1.03-5.40) and the use of oral antibiotic prophylaxis (OR 0.4, 95% CI 0.23-0.90). CONCLUSIONS: We observed that surgical site infections due to P. aeruginosa are associated with a higher National Nosocomial Infections Surveillance risk index, poor outcomes, and lack of preoperative oral antibiotic prophylaxis. These findings can aid in establishing specific preventive measures and appropriate empirical antibiotic treatment.

Multistate modelling to estimate excess length of stay and risk of death associated with organ/space infection after elective colorectal surgery.

BACKGROUND: Accounting for time-dependency and competing events are strongly recommended to estimate excess length of stay (LOS) and risk of death associated with healthcare-associated infections. AIM: To assess the effect of organ/space (OS) surgical site infection (SSI) on excess LOS and in-hospital mortality in patients undergoing elective colorectal surgery (ECS). METHODS: A multicentre prospective adult cohort undergoing ECS, January 2012 to December 2014, at 10 Spanish hospitals was used. SSI was considered the time-varying exposure and defined as incisional (superficial and deep) or OS. Discharge alive and death were the study endpoints. The mean excess LOS was estimated using a multistate model which provided a weighted average based on the states patients passed through. Multivariate Cox regression models were used to assess the effect of OS-SSI on risk of discharge alive or in-hospital mortality. FINDINGS: Of 2778 patients, 343 (12.3%) developed SSI: 194 (7%) OS-SSI and 149 (5.3%) incisional SSI. Compared to incisional SSI or no infection, OS-SSI prolonged LOS by 4.2 days (95% confidence interval (CI): 4.1-4.3) and 9 days (8.9-9.1), respectively, reduced the risk of discharge alive (adjusted hazard ratio (aHR): 0.36 (95% CI: 0.28-0.47) and aHR: 0.17 (0.14-0.21), respectively), and increased the risk of in-hospital mortality (aHR: 8.02 (1.03-62.9) and aHR: 10.7 (3.7-30.9), respectively). CONCLUSION: OS-SSI substantially extended LOS and increased risk of death in patients undergoing ECS. These results reinforce OS-SSI as the SSI with the highest health burden in ECS.

Predictive factors for early- and late-onset surgical site infections in patients undergoing elective colorectal surgery. A multicentre, prospective, cohort study.

BACKGROUND: Surgical site infections (SSIs) are the leading cause of healthcare-associated infections in acute care hospitals in Europe. However, the risk factors for the development of early-onset (EO) and late-onset (LO) SSI have not been elucidated. AIM: This study investigated the predictive factors for EO-SSI and LO-SSI in a large cohort of patients undergoing colorectal surgery. METHODS: We prospectively followed-up adult patients undergoing elective colorectal surgery in 10 hospitals (2011-2014). Patients were divided into three groups: EO-SSI, LO-SSI, or no infection (no-SSI). The cut-off defining EO-SSI and LO-SSI was seven days (median time to SSI development). Different predictive factors for EO-SSI and LO-SSI were analysed, comparing each group with the no-SSI patients. FINDINGS: Of 3701 patients, 320 (8.6%) and 349 (9.4%) developed EO-SSI and LO-SSI, respectively. The rest had no-SSI. Patients with EO-SSI were mostly males, had colon surgery and developed organ-space SSI whereas LO-SSI patients frequently received chemotherapy or radiotherapy and had incisional SSI. Male sex (odds ratio (OR): 1.92; P < 0.001), American Society of Anesthesiologists' physical status >2 (OR: 1.51; P = 0.01), administration of mechanical bowel preparation (OR: 0.7; P = 0.03) and stoma creation (OR: 1.95; P < 0.001) predicted EO-SSI whereas rectal surgery (OR: 1.43; P = 0.03), prolonged surgery (OR: 1.4; P = 0.03) and previous chemotherapy (OR: 1.8; P = 0.03) predicted LO-SSI. CONCLUSION: We found distinctive predictive factors for the development of SSI before and after seven days following elective colorectal surgery. These factors could help establish specific preventive measures in each group.

Declining mortality among hospitalized patients with community-acquired pneumonia.

Little information is available on the changes over time in community-acquired pneumonia (CAP) management and their impact on 30-day mortality in hospitalized patients. We performed a prospective, observational study of non-severely immunosuppressed hospitalized adults with CAP from 1995 to 2014. A total of 4558 patients were included. Thirty-day mortality decreased from 9.6% in the first study period (1995-99) to 4.1% in the last period (2010-14); with a progressive downward trend (-0.2% death/year; p for trend = 0.003). Over time, patients were older (p 0.02), had more co-morbidities (p 0.037), more frequently presented severe illness according to the Pneumonia Severity Index (p <0.001) and septic shock (p <0.001), and more often required intensive care unit admission (p <0.001). Combination antibiotic therapy (p <0.001) and fluoroquinolone use (p <0.001) increased. Factors independently associated with 30-day mortality were increasing age (OR 1.04; 95% CI 1.03-1.05), co-morbidities (OR 1.48; 95% CI 1.04-2.11), shock at admission (OR 4.95; 95% CI 3.49-7.00), respiratory failure (OR 1.89; 95% CI 1.42-2.52), bacteraemia (OR 2.16; 95% CI 1.58-2.96), Gram-negative bacilli aetiology (OR 4.79; 95% CI 2.52-9.10) and fluoroquinolone use (OR 0.45; 95% CI 0.29-0.71). When we adjusted for a propensity score to receive fluoroquinolones, the protective effect of fluoroquinolone use was not confirmed. In conclusion, 30-day mortality decreased significantly over time in hospitalized patients with CAP in spite of an upward trend in patient age and other factors associated with poor outcomes. Several changes in the management of CAP and a general improvement in global care over time may have caused the observed outcomes.

Post-discharge surgical site infections after uncomplicated elective colorectal surgery: impact and risk factors. The experience of the VINCat Program.

BACKGROUND: Surgical site infection (SSI) after colorectal procedures represents a measurable quality indicator of a healthcare system. There is an increasing interest in comparing SSI rates between different hospitals and countries: however, the variability of the data regarding the incidence of SSI makes this comparison difficult. For the purposes of evaluation, data collection must be standardized and must include reliable post-discharge surveillance (PDS). AIM: To determine impact and risk factors for PDS SSI after elective colorectal surgery. METHODS: VINCat is a nosocomial infection surveillance programme in Catalonia, Spain. Between 2007 and 2011, 52 hospitals joined the programme. Hospitals performed active, prospective, standardized surveillance of elective colorectal resection. PDS was implemented by a multimodal approach and was mandatory within the first 30 days after surgery. FINDINGS: During the study period, 13,661 elective colorectal procedures were included. SSI was diagnosed in 2826 (20.7%) patients, of whom 22.5% during PDS; of these, 52% required readmission. Patients with PDS SSI were younger (odds ratio: 1.57; 95% confidence interval: 1.29-1.91), predominantly female (1.40; 1.16-1.69), had more frequently undergone endoscopic procedures (1.56; 1.30-1.88) and had more incisional SSI (1.88; 1.54-2.28) than patients with in-hospital SSI. CONCLUSION: SSI rates in elective colorectal procedures at VINCat hospitals were inside the higher range of those reported by other national programmes. PDS SSI increased the overall rate of SSI, had a significant clinical impact, and accounted for almost a quarter of SSI. Younger age and laparoscopic procedures were the most relevant risk factors. Standardized multimodal PDS should be implemented for hospitals performing surveillance of colorectal surgery.

Impact of a multimodal intervention to reduce bloodstream infections related to vascular catheters in non-ICU wards: a multicentre study.

To determine the impact of a multimodal intervention designed to reduce the incidence of catheter-related bloodstream infections (CRBSIs) outside the ICU, we conducted a prospective, quasi-experimental, before-after intervention study in 11 hospitals participating in the VINCat programme in Catalonia, Spain. The intervention consists of: (i) an evidence-based bundle of practices relating to catheter insertion and maintenance; (ii) a training programme for healthcare workers; (iii) four point-prevalence surveys to track the status of the catheters; and (iv) feedback reports to the staff involved. The study included both central (CVC) and peripheral venous catheters (PVCs). Rates of CRBSI per 1000 patient-days were prospectively measured in 2009 (pre-intervention period) and 2010 (post-intervention period). The analysis included 1 191 843 patient-days in 2009 and 1 173 672 patient-days in 2010. The overall incidence of CRBSI decreased from 0.19 to 0.15 (p 0.04) and the incidence of CRBSI associated with a CVC decreased from 0.14 to 0.10 (p 0.004) after the intervention. The incidence in PVCs remained unchanged. There was a statistically significant improvement in the adequate maintenance of both CVCs and PVCs. Among the CRBSIs originating in PVCs, 61.8% appeared more than 72 h every insertion. There was a lower infection rate in the hospitals with a higher adherence to the recommendation to replace PVCs after 72 h. Our findings suggest that the implementation of intervention programmes similar to ours could have a major impact on patient safety by reducing the incidence of CRBSIs, and that routine replacement of PVCs might additionally prevent a significant number of bloodstream infections.

Laboratory-based surveillance of hospital-acquired catheter-related bloodstream infections in Catalonia. Results of the VINCat Program (2007-2010).

The VINCat Program is an institutional surveillance program for hospital-acquired infections developed in the healthcare institutions of Catalonia, Spain. The program includes the monitoring of various components of hospital-acquired infection, among which is catheter-related bloodstream infection (CRBSI). The aim of this study was to describe the frequency of CRBSI in hospitals participating in the VINCat Program over a period of 4 years (2007-2010). The monitoring of the CRBSI component is carried out continuously in all inpatient units by performing a daily assessment of all blood culture results issued by the Microbiology Laboratories. Precise definitions are used for CRBSI, and adjusted rates are expressed per 1,000 days of hospitalization, hospital size and type of catheter. The rates of CRBSI in catheters used for parenteral nutrition are adjusted and expressed per 1,000 days of device use. The aggregate data of the total period are shown in percentiles (10%, 25%, 50% or median, 75%, and 90%). From 2007 to 2010, a total of 2977 episodes of CRBSI were reported in 40 hospitals participating in the VINCat Program. The cumulative incidence of CRBSI has been 0.26 episodes per 1,000 days of hospitalization (CI95% 0.2 to 0.3). The overall incidence varied depending on hospital size: 0.36 ‰ for hospitals in Group I (>500 beds), 0.17 ‰ for Group II (200-500 beds), and 0.09 ‰ for Group III (<200 beds). 76% of the episodes were associated with central venous catheters (CVC), 19% of the episodes with peripheral venous catheters (PVC), and the remaining 5% with peripherally inserted CVCs (PICC). The most common organisms causing CRBSI were staphylococci, the group Klebsiella, Serratia and Enterobacter, Candida spp., and Pseudomonas aeruginosa. There are important differences in the etiology of CRBSI in relation to these variables. During the reporting period, a significant reduction (38.1%, CI95%, 29.0-46.0%) of CRBSI rates have been observed in Group I hospitals. CRBSI surveillance is an important element of the VINCat Program, offering to us the possibility of establishing standard values for this component and implementing intervention strategies for its reduction.

Timing of antibiotic administration and outcomes of hospitalized patients with community-acquired and healthcare-associated pneumonia.

The effects of antibiotic timing on outcomes of patients with community-acquired pneumonia (CAP) are controversial. Moreover, no information is available regarding this issue in healthcare-associated pneumonia (HCAP). We aimed to determine the impact of antibiotic timing on 30-day mortality of patients with CAP and HCAP. Non-immunocompromised adults admitted to hospital through the emergency department (ED) with community-onset pneumonia were prospectively observed from 2001 to 2009. Patients who received prior antibiotics were excluded. Of 1593 patients with pneumonia who were analyzed, 1274 had CAP and 319 HCAP. The mean time from patient arrival at the ED until antibiotic administration was 5.8 h (standard deviation (SD) 3.5) in CAP and 6.1 h (SD 3.8) in HCAP (p 0.30). Mortality was higher in patients with HCAP (5.5% vs. 13.5%; p <0.001). After adjusting for confounding factors in a logistic regression analysis, the antibiotic administration ≤4 h was not associated with decreased 30-day mortality in patients with CAP (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.57-2.21) and in patients with HCAP (OR 0.59, 95% CI 0.19-1.83). Similarly, antibiotic administration ≤8 h was not associated with decreased 30-day mortality in CAP (OR 1.58, 95% CI 0.64-3.88) and HCAP patients (OR 0.59, 95% CI 0.19-1.83). In conclusion, antibiotic administration within 4 or 8 h of arrival at the ED did not improve 30-day survival in hospitalized adults for CAP or HCAP.

Predictive factors, microbiology and outcome of patients with parapneumonic effusion.

We aimed to determine the incidence, clinical consequences and microbiological findings related to the presence of pleural effusion in community-acquired pneumonia, and to identify predictive factors for empyema/complicated parapneumonic effusion. We analysed 4,715 consecutive patients with community-acquired pneumonia from two acute care hospitals. Patients were classified into three groups: no pleural effusion, uncomplicated parapneumonic effusion and empyema/complicated parapneumonic effusion. A total of 882 (19%) patients had radiological evidence of pleural fluid, of whom 261 (30%) met criteria for empyema/complicated parapneumonic effusion. The most important event related to the presence of uncomplicated parapneumonic effusion was a longer hospital stay. Relevant clinical and microbiological consequences were associated with empyema/complicated parapneumonic effusion. Five independent baseline characteristics could predict the development of empyema/complicated parapneumonic effusion: age < 60 yrs (p = 0.012), alcoholism (p = 0.002), pleuritic pain (p = 0.002), tachycardia >100 beats·min⁻¹ (p = 0.006) and leukocytosis >15,000 mm⁻³ (p < 0.001). A higher incidence of anaerobes and Gram-positive cocci was found in this subgroup of patients. We conclude that only the development of empyema/complicated parapneumonic effusion carried relevant consequences; this condition should be suspected in the presence of some baseline characteristics and managed by using antimicrobials active against Gram-positive cocci and anaerobes.

Low incidence of multidrug-resistant organisms in patients with healthcare-associated pneumonia requiring hospitalization.

Healthcare-associated pneumonia (HCAP) includes a broad spectrum of patients who acquire pneumonia through outpatient contact with the health system. Although limited prospective data exist, it has been suggested that all patients with HCAP should receive empirical therapy with a multidrug regimen directed against drug-resistant organisms. We aimed to determine the differences in aetiology and outcomes between HCAP groups and a community-acquired pneumonia (CAP) group, and to assess the presence of antibiotic-resistant bacteria. All consecutive non-immunocompromised adults hospitalized with pneumonia were prospectively included from 2001 to 2009. Patients who had had recent contact with the health system through nursing homes, home healthcare programmes, haemodialysis clinics or prior hospitalization were considered to have HCAP. A total of 2245 patients with pneumonia were hospitalized through the emergency room, of whom 577 (25.7%) had HCAP. Significant differences in causative pathogens were found between groups. Antibiotic-resistant organisms, including methicillin-resistant Staphylococcus aureus, resistant strains of Pseudomonas aeruginosa, and extended-spectrum ß-lactamase-producing Enterobacteriaceae, were scarce in all groups. In contrast, aspiration pneumonia was particularly frequent. No differences were found regarding inappropriate initial empirical antibiotic therapy between groups. Overall mortality was higher in patients who attended a hospital or haemodialysis clinic or received intravenous chemotherapy in the 30 days before pneumonia, and among patients who resided in a nursing home or long-term-care facility. In conclusion, most HCAP patients could be treated in the same way as patients with CAP, after carefully ruling out the presence of aspiration pneumonia.

Disseminated adiaspiromycosis: case report of a liver transplant patient with human immunodeficiency infection, and literature review.

Disseminated adiaspiromycosis is a rare infection that is sometimes associated with immunocompromised situations. We report the case of a patient, infected with human immunodeficiency virus and receiving highly active antiretroviral therapy, who had a liver transplant for hepatocellular carcinoma. The patient presented skin and pulmonary lesions due to adiaspiromycosis during immunosuppressive therapy. A review of >60 cases in the literature shows that adiaspiromycosis is a rare infection and Emmonsia is a dimorphic fungus that is difficult to grow. It should be considered a possible diagnosis in case of fungal infection and pulmonary granulomatosis. We should be aware of emerging adiaspiromycosis in patients with risk factors of immunosuppression, particularly transplant recipients. In these patients in particular, liposomal amphotericin B therapy should be considered.

Risk factors for, and clinical relevance of, faecal extended-spectrum ß-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic patients with haematological malignancies.

The purpose of this study was to assess the risk factors for, and the clinical relevance of, faecal carriage by extended-spectrum ß-lactamase producing Escherichia coli (ESBL-EC) in neutropenic cancer patients (NCP). An observational prospective multicentre cohort study was conducted over 2 years at two teaching hospitals. Patients with acute leukaemia or undergoing stem cell transplantation were included during neutropenia episodes. Rectal swabs were obtained at hospital admission and weekly thereafter until discharge or death. ESBL-EC colonized episodes were compared with non-colonized episodes. ESBL-EC strains were studied by PCR and isoelectric focusing, and molecular typing was performed by pulsed field gel electrophoresis (PFGE). Among 217 episodes of neutropenia, the prevalence of ESBL-EC faecal carriage was 29% (14% at hospital admission). Multivariate analysis identified previous antibiotics as the only independent risk factor for ESBL-EC faecal colonization (OR 5.38; 95% CI 2.79-10.39). Analysis of ESBL-EC isolates revealed a polyclonal distribution with CTX-M predominance (81.3%). E. coli bacteraemia was mainly caused by non-ESBL producing strains and its rate was similar in both groups (13% vs. 11%). We found no association between ESBL-EC carriage and an increased risk of ESBL-EC bacteremia or a negative influence on other clinical outcomes, including length of hospitalisation, early and overall mortality rates. ESBL-EC faecal colonization is frequent in NCP but difficult to identify by epidemiological or clinical features on presentation. Prior antibiotic therapy is the major associated risk factor. In this setting colonization does not appear to have a significant clinical relevance. Thus, routine testing for ESBL-EC faecal carriage does not seem to be beneficial.

Efficacy of fosfomycin and its combination with linezolid, vancomycin and imipenem in an experimental peritonitis model caused by a Staphylococcus aureus strain with reduced susceptibility to vancomycin.

The objective of this study was to evaluate the in vitro and in vivo efficacies of therapies including fosfomycin against clinical Staphylococcus aureus isolates with reduced susceptibility to vancomycin (hGISA). Time-kill curves were performed over 24 h. Peritonitis in C57BL/6 mice was induced by intraperitoneal inoculation of 10(8) CFU/ml. Four hours later (0 h), therapy was started and the treatment groups were: control (not treated), fosfomycin (100 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h), fosfomycin plus linezolid, fosfomycin plus vancomycin and fosfomycin plus imipenem, receiving subcutaneous therapy over 25 h. Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were determined. In vitro, fosfomycin showed a synergistic effect when combined with the other antimicrobials tested. In the animal model, fosfomycin combinations were effective and significantly reduced the bacteraemia rates achieved in the control, imipenem and vancomycin groups (p < 0.05). The best combination in vivo was fosfomycin plus imipenem. Also, fosfomycin plus linezolid was significantly better than vancomycin alone, reducing the bacterial concentration in the peritoneal fluid. In conclusion, in vitro and in vivo, fosfomycin in combination with linezolid, vancomycin or imipenem exerted a good activity. Fosfomycin plus imipenem was the most active combination, decreasing 3 log CFU/ml, and appears to be a promising combination for clinical practice.

Factors associated with severe disease in hospitalized adults with pandemic (H1N1) 2009 in Spain.

The risk factors for complications in patients with influenza A (H1N1)v virus infection have not been fully elucidated. We performed an observational analysis of a prospective cohort of hospitalized adults with confirmed pandemic influenza A (H1N1)v virus infection at 13 hospitals in Spain, between June 12 and November 10, 2009, to identify factors associated with severe disease. Severe disease was defined as the composite outcome of intensive-care unit (ICU) admission or in-hospital mortality. During the study period, 585 adult patients (median age 40 years) required hospitalization because of pandemic (H1N1) 2009. At least one comorbid condition was present in 318 (54.4%) patients. Pneumonia was diagnosed in 234 (43.2%) patients and bacterial co-infection in 45 (7.6%). Severe disease occurred in 75 (12.8%) patients, of whom 71 required ICU admission and 13 (2.2%) died. Independent factors for severe disease were age <50 years (OR, 2.39; 95% CI, 1.05-5.47), chronic comorbid conditions (OR, 2.93; 95% CI, 1.41-6.09), morbid obesity (OR, 6.7; 95% CI, 2.25-20.19), concomitant and secondary bacterial co-infection (OR, 2.78; 95% CI, 1.11-7) and early oseltamivir therapy (OR, 0.32; 95% CI 0.16-0.63). In conclusion, although adults hospitalized for pandemic (H1N1) 2009 suffer from significant morbidity, mortality is lower than that reported in the earliest studies. Younger age, chronic comorbid conditions, morbid obesity and bacterial co-infection are independent risk factors for severe disease, whereas early oseltamivir therapy is a protective factor.

In vitro and in vivo activities of linezolid alone and combined with vancomycin and imipenem against Staphylococcus aureus with reduced susceptibility to glycopeptides.

The objective of this study was to evaluate the in vitro and in vivo efficacies of linezolid (35 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h), linezolid+imipenem, linezolid+vancomycin and vancomycin+imipenem against two clinical Staphylococcus aureus isolates with reduced susceptibility to glycopeptides using time-kill curves and the murine peritonitis model. Time-kill curves were performed over 24 h. For the murine peritonitis model, peritonitis was induced by the intraperitoneal inoculation of 10(8) CFU/ml of each bacterial strain. Four hours later (0 h), the mice were randomly assigned to a control group or to therapeutic groups receiving subcutaneous treatment for 25 h. Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were determined. The time-kill curves showed that the addition of linezolid to imipenem yielded synergistic results after 24 h. The addition of linezolid decreased vancomycin activity. In the animal model, vancomycin and linezolid monotherapies produced comparable bacterial decreases in mice infected with each strain but linezolid achieved higher rates of blood sterilisation. Linezolid tested either in monotherapy or in combination showed similar efficacy against both strains in terms of bacterial killing, number of negative blood cultures and survival. Linezolid and vancomycin were moderately bactericidal and similar in efficacy against glycopeptide-intermediate or -resistant S. aureus. Linezolid combinations, as effective as linezolid tested alone, could be considered as alternative options for the treatment of glycopeptide-intermediate S. aureus (GISA) infections.

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia.

The aim of this study was to compare the evolution of systemic cytokine levels over time in patients with pneumococal pneumonia treated either with ß-lactam monotherapy or with combination therapy (ß-lactam plus fluoroquinolone). Prospective observational study of hospitalized non-immunocompromised adults with PP. Concentrations of IL-6, IL-8, IL-10, and TNF-α were determined on days 0, 1, 2, 3, 5, and 7. Patients on ß-lactam monotherapy were compared with those receiving combination therapy. Fifty-two patients were enrolled in the study. Concentrations of IL-6, IL-8, and IL-10 decreased rapidly in the first days after admission, in accordance with the mean time to defervescence. High levels of IL-6 were found in patients with the worst outcomes, measured by the need for intensive care unit admission and mortality. No major differences in demographic or clinical characteristics or severity of disease were found between patients treated with ß-lactam monotherapy and those treated with combination therapy. IL-6 levels fell more rapidly in patients with combination therapy in the first 48 h (p = 0.016). Our data suggest that systemic expression of IL-6 production in patients with PP correlates with prognosis. Initial combination antibiotic therapy produces a faster decrease in this cytokine in the first 48 h.