Dr File discloses that he has received recent research funding from Cerexa, Ortho-McNeil, Protez, Rib-X, and Pfizer and Boehringer Ingelheim, Gilead, and Tibotec and is a consultant for Cerexa/Forest, Ortho-McNeil, Protez, Merck, Nabriva, and Pfizer.
RETRACTION OF STUDY RESULTS EVALUATING SURGICAL MASKS VERSUS N95 FOR PREVENTION OF INFLUENZA
MacIntyre et al Interscience Conference on Antimicrobial Agents and Chemotherapy Abstract K-1918b: The first randomized controlled clinical trial of surgical masks compared with fit-tested and non-fit-tested N95 masks in the prevention of respiratory virus infection in hospital health care workers in Beijing, China.
At the Interscience Conference on Antimicrobial Agents and Chemotherapy, Macintyre et al (Abstract K 1918b) presented the results of a cluster randomization study of 24 hospitals (involving 1930 health care providers) in Beijing, comparing continuous use (during the entire work day) of surgical masks versus N95 respirators during the influenza season of 2008. The authors claimed that the use of the N95 respirators reduced respiratory tract infection by 60% and documented influenza by 90% (odds ratio, 0.1; 0.02-0.44). However, in a startling reversal, the authors at the time of the annual Infectious Diseases Society of America meeting in October 2009 announced a retraction of these results and indicated that there was no benefit of N95s over surgical masks.
This has sparked a concern that the recent Institute of Medicine recommendation that health care workers caring for flu patients should use the N95 respirators may in part be due to inaccurate data. Certainly, this reinforces the policy of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America to recommend surgical masks for most patient contacts and reserve N95s for high-risk procedures (eg, intubation or bronchoscopy).
CEFTAROLINE FOUND TO BE BETTER THAN CEFTRIAXONE IN COMMUNITY-ACQUIRED PNEUMONIA
Eckberg et al Interscience Conference on Antimicrobial Agents and Chemotherapy Abstract L1-345a. Focuses 1 and 2: Randomized, double-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline (CPT) versus ceftriaxone (CRO) in community-acquired pneumonia (CAP).
Eckberg et al presented the results of the combined data from 2 phase 3 double-blind randomized controlled trials comparing CPT (600 mg every 12 hours) versus CRO (1 g every 24 hours) for CAP. One study allowed for 2 doses of clarithromycin on day 1 of therapy. The combined number of patients in each group of the clinically evaluable population was 459 in the CPT arm and 449 in the CRO arm. Only pneumonia severity index class III and IV patients were evaluated (this is higher severity than that in most prior randomized controlled trials for CAP and is consistent with the recent new guidance for CAP trials issued by the Food and Drug Administration). The clinical cure rate in the clinically evaluable population was 84.3% for the CPT group compared with 77.7% for the CRO group (95% CI, 1.6-11.8). Although superiority evaluation was not preplanned for these studies, the 95% CI around the treatment difference was completely above zero. In addition, in the microbiologically evaluable patient population, cure rates were higher in the CPT group for Streptococcus pneumoniae. Of interest, all 4 patients with multidrug-resistant S. pneumoniae infection in the CPT group were successfully treated, whereas the treatment in 7 of 9 patients in the CRO group failed.
It is unusual to find studies such as this that show a difference in outcome. Further analysis of the data is needed to determine a possible explanation of these results. However, CPT is more active in vitro against some MDR S. pneumoniae strains, most notably the 19A strains.
Of course, a significant advantage of CPT and the other new cephalosporin under late-stage development is the in vitro activity against methicillin-resistant Staphylococcus aureus. This study, however, did not evaluate cases of methicillin-resistant S. aureus pneumonia.
FIDOXAMIN NOT BETTER THAN VANCOMYCIN FOR RECURRENCE OF NAP1 Clostridium difficile
Gerding et al Interscience Conference on Antimicrobial Agents and Chemotherapy Abstract L1-1642: Restriction endonuclease analysis typing of Clostridium difficile in a phase 3 treatment trial of fidaxomicin versus vancomycin: decreased cure rate for epidemic BI/NAP1/027 strain.
Gerding et al reported the results of a restriction endonuclease analysis typing of C. difficile in a phase 3 treatment trial of fidaxomicin versus vancomycin: decreased cure rate for epidemic BI/NAP1/027 strain. The overall cure rate for fidaxomicin and vancomycin was 92.1% (244/265) and 89.9% (254/283), respectively. However, the cure of the NAP1 strain was less for each arm: fidaxomicin, 86% and vancomycin, 85%. Although the recurrences overall were less in the fidaxomin arm, 13%, compared with those in the vancomycin arm, 24% (P = 0.004), the recurrences in the NAP1 strains were not different, 24% for each arm.
We had hoped that this agent would provide a significant advantage over available therapies especially for the more serious cases due to NAP1. Thus, it is a somewhat disappointing finding that the recurrence rate for NAP1 with fidaxomicin therapy was not better than vancomycin.
THE BURDEN OF Streptococcus pneumoniae INFECTIONS IN ADULTS
Several papers addressed the issue of the burden of Streptococcus pneumoniae infections in adults at the annual Infectious Diseases Society of America (IDSA) meeting. Two are reviewed here. Weyker et al IDSA Abstract 879: Clinical and economic burden of pneumococcal disease in US adults aged 50 years and older.
Huang et al IDSA Abstract: Health care use and cost of pneumococcal disease in the United States.
Weyker et al evaluated a model based on rates and costs of disease and US population estimates and projected that among 91.6 million US adults aged 50 years or older, the annual burden of pneumococcal disease includes 29,500 cases of invasive disease (including 27,700 bacteremias and 1800 cases of meningitis), 502,600 cases of nonbacteremic pneumococcal pneumonia (inpatients, 198,600; outpatient, 304,000), 25,400 deaths, $3.7 billion in direct costs, and $1.8 billion in indirect costs. Huang et al constructed a decision tree model using several data sources including the National Ambulatory Medical Care Survey, the National Hospital Discharge Survey, the Centers for Disease Control and Prevention Active Bacterial Core data, The Federal Register, and the literature review to assess health care use and the cost of pneumococcal disease in the United States. Conclusions: There are 4 million infections, 500,000 hospitalizations, and 22,000 deaths at a cost of $3.7 billion annually. Adult disease is the major driver of costs (83% of medical costs), with nearly half incurred by those older than 65 years. Pneumonia accounts for 69% of all costs.
Despite effective vaccines in children and adults, the burden of pneumococcal disease in adults remains high. It is hoped that the development of potentially better conjugate vaccines for adults may reduce the substantial morbidity and mortality among adults.
© 2010 Lippincott Williams & Wilkins, Inc.