Telavancin for hospital-acquired pneumonia: Clinical response and 28-day survival

U.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality. The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in a post hoc analysis. ATS/IDSA criteria were applied in a blind fashion to the original all-treated (AT) group. Clinical cure rates at final follow-up were determined in the refined AT and clinically evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively). The exploratory endpoint of 28-day survival was evaluated for the ATS/IDSA-AT group. Noninferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%) and ATS/IDSA-CE (83% versus 80%) groups. Cure rates favored telavancin in ATS/IDSA-CE patients where Staphylococcus aureus was the sole pathogen (86% versus 75%). Overall, 28-day survival rates were similar in the telavancin (76%) and vancomycin (77%) groups but lower in telavancin-treated patients with preexisting moderate-to-severe renal impairment (creatinine clearance [CL(CR)] of <50 ml/min). Telavancin should be administered to patients with moderate-to-severe renal impairment only if treatment benefit outweighs the risk or if no suitable alternatives are available

Pattern and Outcome of Chest Injuries at Bugando Medical Centre in Northwestern Tanzania.

Chest injuries constitute a continuing challenge to the trauma or general surgeon practicing in developing countries. This study was conducted to outline the etiological spectrum, injury patterns and short term outcome of these injuries in our setting. This was a prospective study involving chest injury patients admitted to Bugando Medical Centre over a six-month period from November 2009 to April 2010 inclusive. A total of 150 chest injury patients were studied. Males outnumbered females by a ratio of 3.8:1. Their ages ranged from 1 to 80 years (mean = 32.17 years). The majority of patients (72.7%) sustained blunt injuries. Road traffic crush was the most common cause of injuries affecting 50.7% of patients. Chest wall wounds, hemothorax and rib fractures were the most common type of injuries accounting for 30.0%, 21.3% and 20.7% respectively. Associated injuries were noted in 56.0% of patients and head/neck (33.3%) and musculoskeletal regions (26.7%) were commonly affected. The majority of patients (55.3%) were treated successfully with non-operative approach. Underwater seal drainage was performed in 39 patients (19.3%). One patient (0.7%) underwent thoracotomy due to hemopericardium. Thirty nine patients (26.0%) had complications of which wound sepsis (14.7%) and complications of long bone fractures (12.0%) were the most common complications. The mean LOS was 13.17 days and mortality rate was 3.3%. Using multivariate logistic regression analysis, associated injuries, the type of injury, trauma scores (ISS, RTS and PTS) were found to be significant predictors of the LOS (P < 0.001), whereas mortality was significantly associated with pre-morbid illness, associated injuries, trauma scores (ISS, RTS and PTS), the need for ICU admission and the presence of complications (P < 0.001). Chest injuries resulting from RTCs remain a major public health problem in this part of Tanzania. Urgent preventive measures targeting at reducing the occurrence of RTCs is necessary to reduce the incidence of chest injuries in this region

Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: A retrospective cohort study

INTRODUCTION: The impact of in vitro resistance on initially appropriate antibiotic therapy (IAAT) remains unclear. We elucidated the relationship between non-IAAT and mortality, and between IAAT and multi-drug resistance (MDR) in sepsis due to Gram-negative bacteremia (GNS). METHODS: We conducted a single-center retrospective cohort study of adult intensive care unit patients with bacteremia and severe sepsis/septic shock caused by a gram-negative (GN) organism. We identified the following MDR pathogens: MDR P. aeruginosa, extended spectrum beta-lactamase and carbapenemase-producing organisms. IAAT was defined as exposure within 24 hours of infection onset to antibiotics active against identified pathogens based on in vitro susceptibility testing. We derived logistic regression models to examine a) predictors of hospital mortality and b) impact of MDR on non-IAAT. Proportions are presented for categorical variables, and median values with interquartile ranges (IQR) for continuous. RESULTS: Out of 1,064 patients with GNS, 351 (29.2%) did not survive hospitalization. Non-survivors were older (66.5 (55, 73.5) versus 63 (53, 72) years, P = 0.036), sicker (Acute Physiology and Chronic Health Evaluation II (19 (15, 25) versus 16 (12, 19), P <0.001), and more likely to be on pressors (odds ratio (OR) 2.79, 95% confidence interval (CI) 2.12 to 3.68), mechanically ventilated (OR 3.06, 95% CI 2.29 to 4.10) have MDR (10.0% versus 4.0%, P <0.001) and receive non-IAAT (43.4% versus 14.6%, P <0.001). In a logistic regression model, non-IAAT was an independent predictor of hospital mortality (adjusted OR 3.87, 95% CI 2.77 to 5.41). In a separate model, MDR was strongly associated with the receipt of non-IAAT (adjusted OR 13.05, 95% CI 7.00 to 24.31). CONCLUSIONS: MDR, an important determinant of non-IAAT, is associated with a three-fold increase in the risk of hospital mortality. Given the paucity of therapies to cover GN MDRs, prevention and development of new agents are critical

Randomized trial evaluating serial protein C levels in severe sepsis patients treated with variable doses of drotrecogin alfa (activated)

International audienceINTRODUCTION: Serial alterations in protein C levels appear to correlate with disease severity in patients with severe sepsis, and it may be possible to tailor severe sepsis therapy with the use of this biomarker. The purpose of this study was to evaluate the dose and duration of drotrecogin alfa (activated) treatment using serial measurements of protein C compared to standard therapy in patients with severe sepsis. METHODS: This was a phase 2 multicenter, randomized, double-blind, controlled study. Adult patients with two or more sepsis-induced organ dysfunctions were enrolled. Protein C deficient patients were randomized to standard therapy (24 μg/kg/hr infusion for 96 hours) or alternative therapy (higher dose and/or variable duration; 24/30/36 μg/kg/hr for 48 to 168 hours). The primary outcome was a change in protein C level in the alternative therapy group, between study Day 1 and Day 7, compared to standard therapy. RESULTS: Of 557 patients enrolled, 433 patients received randomized therapy; 206 alternative, and 227 standard. Baseline characteristics of the groups were largely similar. The difference in absolute change in protein C from Day 1 to Day 7 between the two therapy groups was 7% (P = 0.011). Higher doses and longer infusions were associated with a more pronounced increase in protein C level, with no serious bleeding events. The same doses and longer infusions were associated with a larger increase in protein C level; higher rates of serious bleeding when groups received the same treatment; but no clear increased risk of bleeding during the longer infusion. This group also experienced a higher mortality rate; however, there was no clear link to infusion duration. CONCLUSIONS: The study met its primary objective of increased protein C levels in patients receiving alternative therapy demonstrating that variable doses and/or duration of drotrecogin alfa (activated) can improve protein C levels, and also provides valuable information for incorporation into potential future studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00386425

Antimicrobial use and microbiological testing in district general hospital ICUs of the Veneto region of north-east Italy

International - predominantly American - studies undertaken in the ICUs of teaching centres show that inadequate antibiotic therapy increases mortality and length of stay. We sought to ascertain whether this also pertains to smaller ICUs in the Veneto region of north-east Italy. To the best of our knowledge, this is the first such survey in the Veneto area or in Italy as a whole. A retrospective, observational study was performed across five general-hospital ICUs to examine appropriateness of microbiological sampling, empirical antibiotic adequacy, and outcomes. Among 911 patients (mean age, 65.8 years ± 16.2 SD; median ICU stay, 17.0 days [IQR, 8.0–29.0]), 757 (83.1 %) were given empirical antibiotics. Treatment adequacy could be fully assessed in only 212 patients (28.0 %), who received empirical treatment and who had a relevant clinical sample collected at the initiation of this antibiotic (T0). Many other patients only had delayed microbiological investigation of their infections between day 1 and day 10 of therapy. Mortality was significantly higher among the 34.9 % of patients receiving inadequate treatment (48.6 % vs 18.80 %; p < 0.001). Only 32.5 % of combination regimens comprised a broad-spectrum Gram-negative β-lactam plus an anti-MRSA agent, and many combinations were irrational. Inadequate treatment was frequent and was strongly associated with mortality; moreover, there was delayed microbiological investigation of many infections, precluding appropriate treatment modification and de-escalation. Improvements in these aspects and in antibiotic stewardship are being sought

An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: Impact of multidrug resistance

Introduction: Pseudomonas aeruginosa nosocomial pneumonia (Pa-NP) is associated with considerable morbidity, prolonged hospitalization, increased costs, and mortality. Methods: We conducted a retrospective cohort study of adult patients with Pa-NP to determine 1) risk factors for multidrug-resistant (MDR) strains and 2) whether MDR increases the risk for hospital death. Twelve hospitals in 5 countries (United States, n = 3; France, n = 2; Germany, n = 2; Italy, n = 2; and Spain, n = 3) participated. We compared characteristics of patients who had MDR strains to those who did not and derived regression models to identify predictors of MDR and hospital mortality. Results: Of 740 patients with Pa-NP, 226 patients (30.5%) were infected with MDR strains. In multivariable analyses, independent predictors of multidrug-resistance included decreasing age (adjusted odds ratio [AOR] 0.91, 95% confidence interval [CI] 0.96-0.98), diabetes mellitus (AOR 1.90, 95% CI 1.21-3.00) and ICU admission (AOR 1.73, 95% CI 1.06-2.81). Multidrug-resistance, heart failure, increasing age, mechanical ventilation, and bacteremia were independently associated with in-hospital mortality in the Cox Proportional Hazards Model analysis. Conclusions: Among patients with Pa-NP the presence of infection with a MDR strain is associated with increased in-hospital mortality. Identification of patients at risk of MDR Pa-NP could facilitate appropriate empiric antibiotic decisions that in turn could lead to improved hospital survival

Younger adult type 2 diabetic patients have poorer glycaemic control: A cross-sectional study in a primary care setting in Singapore

10.1186/1472-6823-13-18BMC Endocrine Disorders13-BEDM

Insights into Candida tropicalis nosocomial infections and virulence factors

Candida tropicalis is considered the first or the second non-Candida albicans Candida (NCAC) species most frequently isolated from candidosis, mainly in patients admitted in intensive care units (ICUs), especially with cancer, requiring prolonged catheterization, or receiving broad-spectrum antibiotics. The proportion of candiduria and candidemia caused by C. tropicalis varies widely with geographical area and patient group. Actually, in certain countries, C. tropicalis is more prevalent, even compared with C. albicans or other NCAC species. Although prophylactic treatments with fluconazole cause a decrease in the frequency of candidosis caused by C. tropicalis, it is increasingly showing a moderate level of fluconazole resistance. The propensity of C. tropicalis for dissemination and the high mortality associated with its infections might be strongly related to the potential of virulence factors exhibited by this species, such as adhesion to different host surfaces, biofilm formation, infection and dissemination, and enzymes secretion. Therefore, the aim of this review is to outline the present knowledge on all the above-mentioned C. tropicalis virulence traits.The authors acknowledge Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil, for supporting Melyssa Negri (BEX 4642/06-6) and Fundacao para a Ciencia e Tecnologia (FCT), Portugal, for supporting Sonia Silva (SFRH/BPD/71076/2010), and European Community fund FEDER, trough Program COMPETE under the Project FCOMP-01-0124-FEDER-007025 (PTDC/AMB/68393/2006) is gratefully acknowledged

A risk score for identifying methicillin-resistant Staphylococcus aureus in patients presenting to the hospital with pneumonia.

Background Methicillin-resistant Staphylococcus aureus (MRSA) represents an important pathogen in healthcare-associated pneumonia (HCAP). The concept of HCAP, though, may not perform well as a screening test for MRSA and can lead to overuse of antibiotics. We developed a risk score to identify patients presenting to the hospital with pneumonia unlikely to have MRSA. Methods We identified patients admitted with pneumonia (Apr 2005 – Mar 2009) at 62 hospitals in the US. We only included patients with lab evidence of bacterial infection (e.g., positive respiratory secretions, blood, or pleural cultures or urinary antigen testing). We determined variables independently associated with the presence of MRSA based on logistic regression (two-thirds of cohort) and developed a risk prediction model based on these factors. We validated the model in the remaining population. Results The cohort included 5975 patients and MRSA was identified in 14%. The final risk score consisted of eight variables and a potential total score of 10. Points were assigned as follows: two for recent hospitalization or ICU admission; one each for age \u3c 30 or \u3e 79 years, prior IV antibiotic exposure, dementia, cerebrovascular disease, female with diabetes, or recent exposure to a nursing home/long term acute care facility/skilled nursing facility. This study shows how the prevalence of MRSA rose with increasing score after stratifying the scores into Low (0 to 1 points), Medium (2 to 5 points) and High (6 or more points) risk. When the score was 0 or 1, the prevalence of MRSA was \u3c 10% while the prevalence of MRSA climbed to \u3e 30% when the score was 6 or greater. Conclusions MRSA represents a cause of pneumonia presenting to the hospital. This simple risk score identifies patients at low risk for MRSA and in whom anti-MRSA therapy might be withheld