Clostridium difficile-associated diarrhoea (CDAD) is the most common hospital-acquired diarrhoea, and is a major type of gastroenteritis infection in nursing homes and facilities for the elderly. In this study the antimicrobial activity of the two-component lantibiotic, lacticin 3147, against a range of genetically distinct C. difficile isolates was studied. The bacteriocin exhibited an MIC50 of 3.6 μg ml−1 for 10 genetically distinct C. difficile strains isolated from healthy subjects, inflammatory bowel disease patients and culture collection strains. In time-kill studies, 106 c.f.u. ml−1
C. difficile ATCC 42593 and CDAD isolate DPC 6220 were killed within 120 or 20 min incubation, respectively, at a concentration of 6 μg lacticin ml−1. Interestingly, addition of lacticin 3147 to exponentially growing cells of C. difficile ATCC 43593 caused rapid lysis of the cells after an initial lag phase, as measured by the concomitant release of the intracellular enzyme, acetate kinase. The addition of a food-grade, milk-based lacticin containing powder to faecal fermentation demonstrated that lacticin is effective in completely eliminating 106 c.f.u. C. difficile ml−1 from a model faecal environment within 30 min when present at concentrations as low as 18 μg ml−1. While other culturable microflora such as total anaerobes, bacteroides, total non-spore-forming anaerobes and total Gram-negative anaerobes were unaffected, populations of lactobacilli and bifidobacteria were reduced by 3 log cycles at bacteriocin levels sufficient to eliminate over 106
C. difficile. In light of these findings, the potential of lacticin 3147 for treatment of CDAD is discussed.

Antimicrobial activity of lacticin 3147 against clinical Clostridium difficile strains

The emergence of drug-resistant pathogens such as staphylococci and enterococci in the hospital setting has long being recognized as a serious clinical problem. Staphylococcus aureus is the causative agent of many nosocomial infections from minor skin abscesses to serious, potentially life threatening diseases such as bone and soft tissue intra-surgical infections, sepsis and invasive endocarditis, while enterococci are responsible for nosocomial bacteraemia, surgical wound infections and endocarditis. The most infamous drug-resistant forms of these include MRSA (methicillin resistant S. aureus), VISA (vancomycin insensitive S. aureus), hVISA (heterogenous vancomycin insensitive S. aureus) and VRE (vancomycin resistant S. aureus). While enhanced hygiene awareness is essential to any solution, the identification of effective novel antimicrobial compounds remains a major goal in eradicating these and other infections caused by multi-drug resistant pathogens. In recent years a class of antimicrobial peptides, the Lantibiotics, have been the focus of an ever increasing level of attention. This interest has been prompted by an enhanced appreciation of the mode of action of these peptides (including, in many cases, the ability to bind lipid II) and their frequently high levels of antimicrobial activity. Here we review lantibiotic-related issues in drug discovery, outline the strategies that have been employed to identify these peptides and summarize the use of bioengineering to generate enhanced forms of these peptides as well as the application of the associated biological machinery to generate novel forms of existing pharmaceutical compounds. In so doing we highlight how some, or all, of these approaches have the potential to result in the development of clinically important drugs.

Discovery of Medically Significant Lantibiotics

Objective We examined whether having a psychiatric disorder among HIV-infected individuals is associated with differential rates of discontinuation of HAART and whether the number of mental health visits impact these rates. Design This longitudinal study (fiscal year: 2000-2005) used discrete time survival analysis to evaluate time to discontinuation of HAART. The predictor variable was presence of a psychiatric diagnosis (serious mental illness versus depressive disorders versus none). Setting Five United States outpatient HIV sites affiliated with the HIV Research Network. Patients The sample consisted of 4989 patients. The majority was nonwhite (74.0%) and men (71.3%); 24.8% were diagnosed with a depressive disorder, and 9% were diagnosed with serious mental illness. Main outcome measures Time to discontinuation of HAART adjusting for demographic factors, injection drug use history, and nadir CD4 cell count. Results Relative to those with no psychiatric disorders, the hazard probability for discontinuation of HAART was significantly lower in the first and second years among those with SMI [adjusted odds ratio: first year, 0.57 (0.47-0.69); second year, 0.68 (0.52-0.89)] and in the first year among those with depressive disorders [adjusted odds ratio: first year, 0.61 (0.54-0.69)]. The hazard probabilities did not significantly differ among diagnostic groups in subsequent years. Among those with psychiatric diagnoses, those with six or more mental health visits in a year were significantly less likely to discontinue HAART compared with patients with no mental health visits. Conclusion Individuals with psychiatric disorders were significantly less likely to discontinue HAART in the first and second years of treatment. Mental health visits are associated with decreased risk of discontinuing HAART.

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HIV patients with psychiatric disorders are less likely to discontinue HAART

Clostridium difficile infection (CDI) has become a significant threat to public health. Although broad-spectrum antibiotic therapy is the primary treatment option for CDI, its use has evident limitations. Probiotics have been proved to be effective in the treatment of CDI and are a promising therapeutic option for CDI. In this study, 4 strains of lactic acid bacteria (LAB), namely, Lactobacillus rhamnosus (LR5), Lactococcuslactis (SL3), Bifidobacterium breve (BR3), and Bifidobacterium lactis (BL3) were evaluated for their anti-C. difficile activity. Co-culture incubation of C. difficile (106 and 1010 CFU/ml) with each strain of LAB indicated that SL3 possessed the highest antimicrobial activity over a 24-hr period. The cell-free supernatants of the 4 LAB strains exhibited MIC50 values between 0.424 mg/ml (SL3) and 1.318 (BR3) mg/ml. These results may provide a basis for alternative therapies for the treatment of C. difficile-associated gut disorders.

/pdf/in-vitro-evaluation-of-antimicrobial-activity-of-lactic-acid-35wp4aki0b.pdf

In Vitro Evaluation of Antimicrobial Activity of Lactic Acid Bacteria against Clostridium difficile

This study examines the association of sexual identity and gender among older clients with HIV at an AIDS service organization using the Andersen Model. Data confirm those aging with HIV exhibit high rates of age-associated illnesses 10 to 20 years before expected. They have fragile social networks that cannot supply the informal supports needed. This aging population will need to increasingly access community-based services. Sexual identity and gender were weak covariates of service utilization. Although heterosexual men used more services, utilization was largely predicted by service needs and the use of case management. Implications for service delivery and policy are discussed.

Service Utilization Among Older Adults With HIV: The Joint Association of Sexual Identity and Gender

Objective: Many persons with HIV do not receive needed behavioral health services. This study examined the impact of medical clinic characteristics on access to mental health and substance abuse care for persons with HIV. Methods: This was a longitudinal survey of patients and clinic directors participating in the HIV Cost and Services Utilization Study, a national probability sample of persons in care for HIV between 1996 and 1998 (N=2,031). Primary outcomes were receipt of outpatient mental health specialist care, outpatient substance abuse care, and abstinence from substance use in the past 30 days. Results: After adjustment for patient characteristics, the likelihood of care by a mental health specialist was higher for patients in HIV specialty clinics (odds ratio [OR]=2.1, 95% confidence interval [CI]=1.2–3.5) and clinics with a combination of on-site case management and affiliated mental health care (OR=2.3, CI 1.3–4.4, for off-site affiliated care; OR=2.1, CI=1.2– 3.7, for on-site care). Outpatient substance abuse care also was more likely for patients in clinics with on-site case management and affiliated substance abuse care (OR=4.3, CI=1.5–12.2, for off-site affiliated care; OR=3.2, CI=1.3–8.0, for on-site care). In a subgroup of persons reporting active substance use, care in clinics with on-site case management predicted 30-day abstinence from substances at follow-up (OR=1.7, CI=1.1–2.5). Conclusions: The organizational structure of medical clinics can have an important effect on use of mental health and substance abuse specialist care. (Psychiatric Services 59:400–407, 2008)

https://ps.psychiatryonline.org/doi/pdf/10.1176/ps.2008.59.4.400

M.S.P.H. Michael E. Ohl

Papers

Medical clinic characteristics and access to behavioral health services for persons with HIV.

Clinical inquiries. What are effective therapies for Clostridium difficile-associated diarrhea?

3-year interval between Pap smears adequate for women with prior negative results.