Mild isoniazid-induced liver injury in humans is associated with an increase in Th17 cells and T cells producing IL-10.

Isoniazid (INH) remains a mainstay for the treatment of tuberculosis despite the fact that it can cause liver failure. The mechanism of INH-induced liver injury remains controversial. It had been proposed that the mechanism involves metabolic idiosyncrasy based on the observations that liver injury is not usually associated with fever, rash, or prompt increase in alanine aminotransferase (ALT) upon rechallenge. In the present study, we found that patients who were treated with INH because of a positive tuberculosis (TB) skin test and developed a small increase in ALT had an increase in Th17 cells as well as T cells that produce interleukin (IL)-10, which suggests stimulation of an adaptive immune response. Th17 cells are considered inflammatory and could be involved in causing the liver injury. IL-10 is considered anti-inflammatory and could be the reason that more serious liver injury did not occur. These changes were not observed in patients who did not have an increase in ALT. These are the first data to show a change in the T cell profile in patients with mild INH-induced liver injury; however, it is difficult to determine whether these changes were the cause or the result of the liver injury. Nevertheless, together with other studies, the data suggest that INH-induced liver injury is immune-mediated, with mild injury resulting in immune tolerance.

Canadian Rheumatology Association recommendations for the pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs: part II safety.

OBJECTIVE: The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of rheumatoid arthritis (RA) with traditional and biologic disease-modifying antirheumatic drugs (DMARD) in 2 parts. Part II, focusing on specific safety aspects of treatment with traditional and biologic DMARD in patients with RA, is reported here. METHODS: Key questions were identified a priori based on results of a national needs-assessment survey. A systematic review of all clinical practice guidelines and consensus statements regarding treatment with traditional and biologic DMARD in patients with RA published between January 2000 and June 2010 was performed in Medline, Embase, and CINAHL databases, and was supplemented with a "grey literature" search including relevant public health guidelines. Systematic reviews of postmarketing surveillance and RA registry studies were performed to update included guideline literature reviews as appropriate. Guideline quality was independently assessed by 2 reviewers. Guideline characteristics, recommendations, and supporting evidence from observational studies and randomized trials were synthesized into evidence tables. The working group voted on recommendations using a modified Delphi technique. RESULTS: Thirteen recommendations addressing perioperative care, screening for latent tuberculosis infection prior to the initiation of biologic DMARD, optimal vaccination practices, and treatment of RA patients with active or a history of malignancy were developed for rheumatologists, other primary prescribers of RA drug therapies, and RA patients. CONCLUSION: These recommendations were developed based on a synthesis of international RA and public health guidelines, supporting evidence, and expert consensus in the context of the Canadian health system. They are intended to help promote best practices and improve healthcare delivery for persons with RA.

Determining mortality rates attributable to Clostridium difficile infection.

To determine accuracy of measures of deaths attributable to Clostridium difficile infection, we compared 3 measures for 2007-2008 in Ontario, Canada: death certificate; death within 30 days of infection; and panel review. Data on death within 30 days were more feasible than panel review and more accurate than death certificate data.

Antimicrobial properties of hemokinin-1 against strains of Pseudomonas aeruginosa.

AIMS: In this study, we examined whether hemokinin-1, the newest member of the tachykinin family and a close relative of substance P, has antimicrobial properties which have been attributed to other neuropeptides including substance P. MAIN METHODS: Top agar assays were performed to determine the antimicrobial activity of hemokinin-1 and substance P against various microorganisms. KEY FINDINGS: Here we provide evidence that hemokinin-1 peptide possesses antimicrobial properties against some strains of Pseudomonas aeruginosa, while substance P was only marginally effective. SIGNIFICANCE: Our study is the first to link hemokinin-1 to the essential role of defending the body against microbial challenges and adds hemokinin-1 to the list of potential drugs that could help in the fight against P. aeruginosa, an opportunistic human pathogen.

Healthcare-associated infections as patient safety indicators.

Healthcare-associated infections (HAIs) are a pressing and imminent patient safety concern as they cause substantial preventable morbidity and mortality. Despite this, there is a strong tendency for healthcare administrators and providers to view them as far less of a threat to patient safety than adverse events such as medication administration errors and falls. Further, validated strategies to prevent HAIs are frequently slow to be adopted. This paper reviews two HAIs of increasing visibility and importance - namely, methicillin-resistant Staphylococcus aureus and Clostridium difficile - and discusses the pivotal importance of hand hygiene and environmental cleaning in their prevention. Possible reasons why HAIs are approached differently from other patient safety issues are discussed, including the false sense of security created by the advent of antibiotics, the lack of randomized controlled trials supporting infection-control interventions and the systemic multifactorial causes of HAIs that result in a need for interventions that go far beyond traditional clinical boundaries. Suggested strategies to improve patient safety with respect to HAIs are provided, including a focus on the role of potential links to accreditation; the role of public reporting; healthcare facility design; change management strategies; visible leadership and role modelling; collaboration between facilities and with public health; reducing hospital overcrowding; and accountability and funding. Finally, the impact of the burgeoning interest of the media, the threat of legal liability and the well-being of healthcare providers are discussed.

Outbreak of multidrug-resistant Pseudomonas aeruginosa colonization and infection secondary to imperfect intensive care unit room design.

BACKGROUND: Pseudomonas aeruginosa has been increasingly recognized for its ability to cause significant hospital-associated outbreaks, particularly since the emergence of multidrug-resistant strains. Biofilm formation allows the pathogen to persist in environmental reservoirs. Thus, multiple hospital room design elements, including sink placement and design, can impact nosocomial transmission of P. aeruginosa and other pathogens. METHODS: From December 2004 through March 2006, 36 patients exposed to the intensive care unit or transplant units of a tertiary care hospital were infected with a multidrug-resistant strain of P. aeruginosa. All phenotypically similar isolates were examined for genetic relatedness by means of pulsed-field gel electrophoresis. Clinical characteristics of the affected patients were collected, and a detailed epidemiological and environmental investigation of potential sources was carried out. RESULTS: Seventeen of the infected patients died within 3 months; for 12 (71%) of these patients, infection with the outbreak organism contributed to or directly caused death. The source of the outbreak was traced to hand hygiene sink drains, where biofilms containing viable organisms were found. Testing by use of a commercial fluorescent marker demonstrated that when the sink was used for handwashing, drain contents splashed at least 1 meter from the sink. Various attempts were made to disinfect the drains, but it was only when the sinks were renovated to prevent splashing onto surrounding areas that the outbreak was terminated. CONCLUSION: This report highlights the importance of biofilms and of sink and patient room design in the propagation of an outbreak and suggests some strategies to reduce the risks associated with hospital sinks.

The financial impact of controlling a respiratory virus outbreak in a teaching hospital: lessons learned from SARS.

BACKGROUND: Outbreaks of Severe Acute Respiratory Syndrome (SARS) in 2003 and renewed concerns regarding pandemic influenza have resulted in widespread planning for future respiratory disease outbreaks. Such planning should include accurate cost estimates for any proposed disease control strategies. From the acute care hospital perspective, such estimates typically take into account the cost of supplies and equipment, but rarely consider indirect costs such as lost revenue due to the scaling down of programs. METHODS: Retrospective cost analysis. Costs and savings were calculated from the hospital perspective using financial records. Costs were categorized to determine the major areas of expenditure and savings. RESULTS: We report that controlling a SARS outbreak in a teaching hospital over an 8-week period cost dollar12 million Canadian. Lost revenue and labour accounted for two thirds of the costs incurred while excess spending on services, materials, supplies and renovation of existing space accounted for the remaining one third. CONCLUSIONS: Cost estimates that consider only excess expenditures may considerably underestimate the true cost of infection control strategies.

Contamination of bone marrow products with an actinomycete resembling Microbacterium species and reinfusion into autologous stem cell and bone marrow transplant recipients.

Bacterial contamination of bone marrow or peripheral blood stem cell transplant products typically occurs with skin flora or, rarely, gram-negative organisms. We describe a clonal outbreak of contamination in transplant products caused by contamination with an aerobic actinomycete that occurred at our institution during the summer of 2001. From 1 July through 12 September 2001, 73 peripheral blood or bone marrow stem cell products were obtained from 39 patients, and 34 products were found to be contaminated with the outbreak strain. Fourteen patients were reinfused with contaminated cells, and the outbreak strain was isolated from the blood cultures for one patient. Investigation revealed multiple potential sources for contamination during the product cryopreservation process. The outbreak of contamination was aborted upon modification of the cryopreservation process.

Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management.

Cases of active tuberculosis have been reported worldwide with the use of therapeutic agents that inhibit tumour necrosis factor (TNF) alpha. TNFalpha has a central role in mycobacterial infection and disease. Accordingly, progression of recently acquired tuberculosis infection or reactivation of remotely acquired infection should be expected with the use of anti-TNF agents. The available in-vitro and epidemiological evidence for the two currently approved agents, infliximab and etanercept, shows that the risk of development of active tuberculosis is greater with infliximab. Tuberculin skin testing (TST) should be undertaken before any significant immunosuppressive therapy including these agents, though the possibility of false-negative reactions in immunocompromised populations must be borne in mind. A positive TST should be followed by medical assessment and chest radiography, as well as by other tests judged appropriate by the physician to identify active disease. Active tuberculosis must be treated appropriately before initiation of treatment with an anti-TNF agent. Treatment of latent tuberculosis can be considered on an individual basis for TST-negative patients receiving anti-TNF agents when significant risk factors for infection are present.

Is surveillance for multidrug-resistant enterobacteriaceae an effective infection control strategy in the absence of an outbreak?

Multidrug-resistant enterobacteriaceae (MDRE) are an important cause of nosocomial infections. The effectiveness of screening for MDRE in the nonoutbreak setting in an attempt to prevent transmission is unknown. Patients admitted for new organ transplantation were screened for MDRE colonization. Prospective clinical data were collected, and pulsed-field gel electrophoresis and plasmid and integron analysis of isolates were performed. Colonized patients were not isolated except when required by standard precautions. Of the 287 patients, 69 (24%) were colonized, and 6 (9%) of the 69 developed clinical infections. Most colonizing isolates (66/69) were unique. No clinical infections resulted from patient-to-patient transmission. Analysis of clinical isolates from nonstudy patients demonstrated no evidence of transmission leading to clinical disease. The annual cost of a surveillance program was calculated at Canadian $1,130,184.44. Thus, the routine and costly use of MDRE surveillance and isolation precautions are not warranted in the absence of a clonal outbreak in this population.