Preclinical murine models for the testing of antimicrobials against Mycobacterium abscessus pulmonary infections: Current practices and recommendations.

Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, is increasingly recognized as an important pathogen of the human lung, disproportionally affecting people with cystic fibrosis (CF) and other susceptible individuals with non-CF bronchiectasis and compromised immune functions. M. abscessus infections are extremely difficult to treat due to intrinsic resistance to many antibiotics, including most anti-tuberculous drugs.

New drugs to treat difficult tuberculous and nontuberculous mycobacterial pulmonary disease.

Purpose Of Review: Treatment of drug-sensitive tuberculosis (TB) is effective, whereas that of multidrug-resistant and extensively drug-resistant TB as well as nontuberculous mycobacterial (NTM) disease are less so. Therapy in general requires good adherence to potentially toxic drug regimens over prolonged periods. Poor adherence is associated with resistance development and poor outcome.

Remembering the Host in Tuberculosis Drug Development.

New therapeutics to augment current approaches and shorten treatment duration are of critical importance for combating tuberculosis (TB), especially those with novel mechanisms of action to counter the emergence of drug-resistant TB. Host-directed therapy (HDT) offers a novel strategy with mechanisms that include activating immune defense mechanisms or ameliorating tissue damage. These and related concepts will be discussed along with issues that emerged from the workshop organized by the Stop TB Working Group on New Drugs, held at the Gordon Research Conference for Tuberculosis Drug Development in Lucca, Italy in June 2017, titled "Strategic Discussion on Repurposing Drugs & Host Directed Therapies for TB.

High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv.

There is an urgent need for the discovery and development of new antitubercular agents that target new biochemical pathways and treat drug resistant forms of the disease. One approach to addressing this need is through high-throughput screening of medicinally relevant libraries against the whole bacterium in order to discover a variety of new, active scaffolds that will stimulate new biological research and drug discovery. Through the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (www.

Discovery and validation of new antitubercular compounds as potential drug leads and probes.

Increasing multidrug resistance in Mycobacterium tuberculosis continues to diminish the number of effective drugs available for treatment of active tuberculosis. Although there are four new products (representing three new chemical classes) in clinical development, an active, robust pipeline of new chemical entities is critical to discovery of medicines to dramatically improve or shorten length of therapy via new mechanisms of action. In the absence of major pharmaceutical industry activity in tuberculosis drug development, the National Institute of Allergy and Infectious Diseases (NIAID) has supported the development of a high throughput screen for growth inhibitors of M.

Programs to facilitate tuberculosis drug discovery: the tuberculosis antimicrobial acquisition and coordinating facility.

There is a real need to discover new drugs that are active on drug-resistant tuberculosis (TB), and for drugs that will shorten the time of therapy. Large pharmaceutical companies have traditionally led the quest for discovering and developing new antiinfective agents but this is not the case when it comes to diseases like tuberculosis that primarily occur in resource restricted countries. Throughout the world many research groups are actively engaged in the scientific discovery of new TB drugs.

The evolution of extensively drug resistant tuberculosis (XDR-TB): history, status and issues for global control.

Tuberculosis (TB) is a devastating disease caused by Mycobacterium tuberculosis that killed an estimated 4000-5000 person each day during 2005. Although infections with drug sensitive strains can be effectively cured with a 6 to 9 month regimen of multiple antibiotics, the inability to deliver and complete appropriate courses of therapy on a global level has led to the selection of resistant strains over the past 50 years. The selection and spread of multiple drug resistant M.

New tuberculosis drugs in development.

Over the past 50 years, no new drug classes have been introduced to treat tuberculosis. Tuberculosis (TB) kills nearly two million people a year mainly in the poorest communities in the developing world. It afflicts millions more.

Experimental model for Porphyromonas gingivalis infection in animals.

A virulence model suitable for studying the dynamics of Porphyromonas gingivalis infection, including the pathogenicity of P. gingivalis in experimentally induced infections of multiple organs was developed using mouse and hamster. Virulence of P.

NIH conference. Recent advances in the management of AIDS-related opportunistic infections.

Secondary infections remain the leading cause of death in patients with the acquired immunodeficiency syndrome (AIDS). Dealing with the rapidly evolving spectrum of infectious problems seen in patients with AIDS requires knowledge of current therapeutic and prophylactic strategies. Through an extensive preclinical trials network supported by both industry and government, an increasing number of new agents are being identified and rapidly moved into clinical trials.

The challenge of Pneumocystis carinii culture.

Published and unpublished data on the cultivation of P. carinii were reviewed by a panel of investigators convened by the National Institutes of Health. Although several cell culture systems allow propagation of P.

Alcohol-impregnated wipes as an alternative in hand hygiene.

The antimicrobial effectiveness of four hand-wash products for health care personnel included three liquid soaps that contained 4% chlorhexidine gluconate, 1% triclosan, or no antiseptic ingredient, respectively, and a 30% w/w ethyl alcohol-impregnated hand wipe. These products were evaluated for reduction in bacterial counts on hands after extended use of 15 handwashes per day for 5 consecutive days. The order of greatest to least log reduction among products at the end of the 5-day test period was chlorhexidine gluconate (2.

Postantibiotic colonization with Clostridium difficile in nursing home patients.

Clostridium difficile causes pseudomembranous colitis and is responsible for 20% to 25% of cases of postantibiotic diarrhea. In an earlier study, nursing-home patients with C. difficile infection were noted to have a high mortality rate.

Leakage of virus through used vinyl and latex examination gloves.

A total of 480 examination gloves (240 vinyl and 240 latex) were stressed by using manipulations designed to mimic patient care. At the highest use level, 38 (63%) of 60 vinyl gloves leaked bacteriophage phi X174 compared with 4 (7%) of 60 latex gloves. At lower use levels, there was no statistically significant difference in leakage.

Alcohol for surgical scrubbing?

To test the effects of four surgical scrub products on colonizing hand flora, 60 healthy adult volunteers were assigned by block randomization (12 subjects per group) to use one of the following formulations: 70% ethyl alcohol with 0.5% chlorhexidine gluconate (ALC); a liquid detergent base containing 1% triclosan (TRI); a liquid detergent base containing 4% chlorhexidine gluconate (CHG); a liquid detergent base containing 7.5% povidone-iodine (PI); or a nonantimicrobial liquid soap (control).

Prevalence of acute enteric viral pathogens in acquired immunodeficiency syndrome patients with diarrhea.

Diarrhea due to enteric pathogens is an important complication of advanced human immunodeficiency virus infection. Whereas numerous bacterial and parasitic agents have been implicated, the role of pathogenic enteric viruses is less clear. Stools from 153 human immunodeficiency virus seropositive men were tested by electrophoresis, enzyme-linked immunosorbent assay, and immune electron microscopy for the presence of rotaviruses (group A and non-group A), adenoviruses, and Norwalk agent.

Protein-losing enteropathy associated with Clostridium difficile infection.

A commercially available radial immunodiffusion assay was used to measure serum alpha-1-antitrypsin levels in stool samples from subjects aged over 60 years as a marker of protein-losing enteropathy. alpha 1-antitrypsin was found in all of 12 patients with colonoscopy-confirmed pseudomembranous colitis, 6 of 14 (43%) patients with Clostridium difficile diarrhoea without pseudomembranes, 6 of 12 (50%) nursing-home patients culture-positive for Cl difficile but negative for its cytotoxin, and none of 15 healthy control subjects. It is concluded that serum protein loss into the gastrointestinal tract can occur as a result of Cl difficile infection, that its presence correlates with the severity of disease, and that it may occur even in the absence of diarrhoea.

Evaluation of a latex agglutination test for Clostridium difficile in two nursing home outbreaks.

The Culturette Brand Clostridium difficile test (CDT; Marion Laboratories, Inc., Kansas City, Mo.) is a latex agglutination test for C.

Integrity of vinyl and latex procedure gloves.

In a series of experiments the integrity of vinyl and latex procedure gloves were tested under in-use conditions. Both types of gloves were tested by three methods: watertight (645 samples), bacterial penetration (50), and dye exclusion (90). Results of the watertight test demonstrated visible defects in 4.

Influence of two handwashing frequencies on reduction in colonizing flora with three handwashing products used by health care personnel.

Four handwashing products (containing either 2% chlorhexidine gluconate, 0.6% parachlorometaxylenol, 0.3% triclosan, or a nonantimicrobial control) at two handwashing frequencies (6 or 18 times/day) were compared with regard to their effectiveness in reducing colonizing hand flora.