Twenty years of measurement of polycyclic aromatic hydrocarbons (PAHs) in UK ambient air by nationwide air quality networks.

The impact of human activities on the health of the population and of the wider environment has prompted action to monitor the presence of toxic compounds in the atmosphere. Toxic organic micropollutants (TOMPs) are some of the most insidious and persistent of these pollutants. Since 1991 the United Kingdom has operated nationwide air quality networks to assess the presence of TOMPs, including polycyclic aromatic hydrocarbons (PAHs), in ambient air. The data produced in 2010 marked 20 years of nationwide PAH monitoring. This paper marks this milestone by providing a novel and critical review of the data produced since nationwide monitoring began up to the end of 2011 (the latest year for which published data is available), discussing how the networks performing this monitoring has evolved, and elucidating trends in the concentrations of the PAHs measured. The current challenges in the area and a forward look to the future of air quality monitoring for PAHs are also discussed briefly.

Safety of daptomycin in patients receiving hemodialysis.

STUDY OBJECTIVE: To determine the safety of daptomycin administered using a variety of doses and dosing frequencies in patients receiving intermittent hemodialysis who had probable or confirmed gram-positive infections. DESIGN: Analysis of data from the Cubicin Outcomes Registry and Experience (CORE), a multicenter, retrospective, observational registry. SETTING: Fifty-four study sites, mostly (46%) large teaching hospitals. PATIENTS: Three hundred ninety-three adults in the CORE registry who received intermittent hemodialysis between 2005 and 2008. MEASUREMENTS AND MAIN RESULTS: The CORE registry is noninterventional and collects standard-of-care data on daptomycin treatment from health care institutions. Of the 393 patients, 370 (94%) could be categorized by daptomycin dosing frequency: every 48 hours (251 patients [64%]), 3 times/week (87 [22%]), and every 24 hours (32 [8%]); the remaining 23 (6%) had unreported dosing frequencies or received a single dose of daptomycin. Three hundred eighty-four patients (98%) received part of their daptomycin therapy as an inpatient and 129 patients (33%) received part of their daptomycin therapy in an intensive care setting. The primary infection type was bacteremia (224 patients [57%]), and the most common pathogen was Staphylococcus aureus (155 patients [39%]). Thirty-eight adverse events possibly related to daptomycin occurred in 28 patients (7%); increased blood creatine kinase level (7 patients [1.8%]) was the most common adverse event. Adverse-event rates were similar across all dosing regimens. CONCLUSION: In these patients undergoing hemodialysis, daptomycin was a well-tolerated treatment for gram-positive infections across several doses and dosing frequencies. Further study in prospective trials is warranted.

Daptomycin for the treatment of surgical site infections.

BACKGROUND: The increasing frequency of methicillin-resistant Staphylococcus aureus (MRSA) as a cause of surgical site infections, and decreased susceptibility to vancomycin, highlight the need for alternative therapies. METHODS: All patients with a surgical site infection enrolled in the Cubicin Outcomes Registry and Experience (CORE 2007 retrospective multicenter registry were studied. Outcome was assessed at the end of daptomycin therapy using protocol-defined criteria. Success was defined as cured or improved. Non-evaluable patients were excluded from the efficacy analysis but were included in the safety analysis. RESULTS: Of 962 patients in the CORE registry in 2007, 104 (11%) had a surgical infection and met the criteria for the efficacy analysis. The overall success rate was 91% (95/104). The distribution of surgical site infections by depth was 36% (38/104) superficial incisional, 36% (38/104) deep incisional, and 27% (28/104) organ/space. Success rates by infection depth were 92% for superficial incisional, 92% deep incisional, and 89% organ/space (P = .9). Success in patients with and without surgery was 89% (49/55) and 94% (46/49) (P = .5). The median final daptomycin dose was 5.5 mg/kg. The median duration of daptomycin therapy was 14 days. Prior antibiotic therapy was given to 79% of patients; 35% failed. Prior vancomycin was used in 45% of patients; 24% failed. Among vancomycin failures, the daptomycin success rate was 91% (10/11). Of those with a positive culture, common pathogens were S. aureus (68%; MRSA 61%) and enterococci (26%; vancomycin-resistant 36%). There were 9 possible treatment-related adverse events (AEs) in 8 of 118 (7%) patients; 2 serious AEs were reported in 1 patient. CONCLUSION: Success rates for patients with a surgical site infection treated with daptomycin were high and did not differ based on the need for surgical intervention. High success rates were achieved in patients with infection caused by MRSA as well as in patients who had failed to respond to previous antibiotic therapies, including vancomycin, regardless of the depth of the infection.

Effect of omeprazole on the plasma concentrations of indinavir when administered alone and in combination with ritonavir.

PURPOSE: The effects of omeprazole on indinavir when administered alone or in combination with ritonavir were evaluated. METHODS: Fourteen men and women age 18-55 years not infected with human immunodeficiency virus who met study qualifications were randomized to receive placebo, 20 mg of omeprazole, or 40 mg of omeprazole daily. After seven days, the single-dose pharmacokinetic profile of an 800-mg dose of indinavir alone or in combination with 200 mg of ritonavir was evaluated. Study participants received each of four study regimens in one of four randomly assigned orders. Blood samples were collected, and plasma indinavir and ritonavir concentrations were analyzed using high-performance liquid chromatography. RESULTS: The coadministration of 20 or 40 mg of omeprazole with indinavir significantly reduced the mean indinavir area under the concentration-versus-time curve (AUC) from 30.0 mg x hr/L (95% confidence interval [CI], 21.9-41.1 mg x hr/L) to 19.7 mg x hr/L (95% CI, 14.6-26.8 mg x hr/L) or 16.0 mg x hr/L (95% CI, 11.8-21.7 mg x hr/L), respectively (p < 0.002). The addition of 200 mg of ritonavir to 800 mg of indinavir in combination with 40 mg of omeprazole significantly increased the mean indinavir AUC from 30.0 mg x hr/L (95% CI, 21.9-41.1 mg x hr/L) to 46.6 mg x hr/L (95% CI, 34.0-63.8 mg x hr/L), but it did not significantly affect mean omeprazole concentrations (p < or = 0.02). CONCLUSION: The AUC of indinavir was substantially decreased in healthy volunteers who received omeprazole 20 or 40 mg daily for seven days before the administration of a single 800-mg dose of indinavir. Concomitant administration of ritonavir 200 mg with indinavir in participants receiving omeprazole led to a significant increase in the AUC of indinavir.

Clinical experience with daptomycin for the treatment of patients with documented gram-positive septic arthritis.

BACKGROUND: Septic arthritis is considered a rheumatologic emergency that can lead to joint destruction and long-term impairment of joint function. Daptomycin is bactericidal in vitro against Staphylococcus aureus, the primary pathogen associated with septic arthritis. OBJECTIVE: To describe the use of daptomycin in patients with septic arthritis. METHODS: Data were collected as part of the Cubicin Outcomes Registry and Experience (CORE) program, a retrospective, observational, multicenter study, to describe the clinical use of daptomycin. Efficacy at the end of daptomycin therapy was determined by each center's investigator(s) as cure, improved, failure, or nonevaluable. Patients who had a diagnosis of septic arthritis, excluding concomitant osteomyelitis, as well as a positive culture by needle aspirate or deep tissue biopsy, were selected from the combined 2005 and 2006 CORE database. RESULTS: Twenty-two patients were included in this analysis. S. aureus was the most common pathogen isolated, with the majority resistant to methicillin. All patients received an antibiotic prior to daptomycin; in 7 patients, at least one of the prior antibiotics was continued with daptomycin. Almost two-thirds of patients received an antibiotic with daptomycin; rifampin was the most common. The median final dose and duration of daptomycin therapy were 5 mg/kg (range 3-6.3) and 22 days (range 3-52), respectively. Eighty-two percent of patients received daptomycin while admitted to a hospital; however, 68% received at least part of their daptomycin therapy as an outpatient. The outcomes of cure or improved were reported in 41% and 50% of the patients, respectively. Two adverse events were reported; neither was considered to be related to daptomycin. CONCLUSIONS: Daptomycin appeared to be effective when used as part of a treatment regimen for septic arthritis. These results require verification via a prospective clinical trial.

HIV infection: point-of-care testing.

OBJECTIVE: To review the data regarding point-of-care testing for the diagnosis of HIV infection in the US. DATA SOURCES: English-language literature was identified via MEDLINE (1980-August 2003) using key words such as rapid HIV tests and HIV antibody testing. Textbooks and other pertinent resources were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles identified through the data sources above were evaluated and reviewed if pertinent to the objective. DATA SYNTHESIS: The Centers for Disease Control and Prevention (CDC) has announced an effort to expand currently recommended strategies to prevent new infections with HIV. The cornerstone of this initiative is the availability of the new rapid test for antibodies to HIV (OraQuick Rapid HIV-1 Antibody Test, OraSure Technologies, Bethlehem, PA). The effectiveness, sensitivity, and specificity of this test have been evaluated in a number of cross-sectional studies using previously or simultaneously performed HIV enzyme immunoassays with Western blot confirmation as a reference standard. Although there are several limitations to consider, results of these studies suggest that this test has comparable ability to detect HIV antibodies to other commercially available tests. CONCLUSIONS: The OraQuick test is simple enough to be performed in many settings including those that facilitate achievement of the goals outlined by the CDC. Availability of this test should have a dramatic impact on HIV detection and prevention strategies.

Treatment of tick-borne diseases.

OBJECTIVE: To review the data regarding the pharmacotherapy of Lyme disease, Rocky Mountain spotted fever (RMSF), and the human ehrlichioses. DATA SOURCES: English-language literature was identified via MEDLINE (1966-January 2002) using the keywords Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis. Textbooks and other pertinent resources were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles identified through the data sources above were evaluated and reviewed if pertinent to the objective. DATA SYNTHESIS: Tick-borne diseases are the most common vector-transmitted diseases in North America. Each disease causes significant morbidity and, in the case of RMSF, mortality if patients go untreated. If the disease syndromes are recognized early and treatment is initiated, complications are greatly reduced. Doxycycline is active against each of the causative organisms, simplifying empiric treatment. CONCLUSIONS: Effective pharmacotherapy exists to treat each of these diseases, assuming diagnosis is made quickly. The beta-lactam and tetracycline antibiotics appear to be the most effective therapy for Lyme disease. The tetracyclines, but not the beta-lactams, are effective for RMSF and the human ehrlichioses. Since Borrelia burgdorferi and the human granulocytic ehrlichiosis agent are becoming more common coinfecting pathogens, tetracycline or doxycycline should be considered the drugs of choice for patients from endemic areas where exposure to both pathogens may have occurred. Doxycycline is the preferred agent because of decreased frequency of administration and adverse effects.