ABSTRACT
Nasal decolonization has a proven effect on the prevention of severe Staphylococcus aureus infections and the control of methicillin-resistant S. aureus (MRSA). However, rising rates of resistance to antibiotics highlight the need for new substances for nasal decolonization. LTX-109 is a broad-spectrum, fast-acting bactericidal antimicrobial drug for topical treatment, which causes membrane disruption and cell lysis. This mechanism of action is not associated with cross-resistance and has a low propensity for development of resistance. In the present study, persistent nasal MRSA and methicillin-sensitive S. aureus (MSSA) carriers were treated for 3 days with vehicle or with 1%, 2%, or 5% LTX-109. A significant effect on nasal decolonization was observed already after 2 days of LTX-109 treatment in subjects treated with 2% or 5% LTX-109 compared to vehicle (P ≤ 0.0012 by Dunnett's test). No safety issues were noted during the 9-week follow-up period. Minimal reversible epithelial lesions were observed in the nasal cavity. The systemic exposure was very low, with a maximum concentration of drug in plasma (Cmax) at 1 to 2 h postdosing (3.72 to 11.7 ng/ml). One week after treatment initiation, LTX-109 was not detectable in any subject. Intranasal treatment of S. aureus with LTX-109 is safe and reduces the bacterial load already after a single day of treatment. Hence, LTX-109 has potential as a new and effective antimicrobial agent with a low propensity of resistance development that can prevent infections by MSSA/MRSA during hospitalization. (This study has been registered at ClinicalTrials.gov under registration no. NCT01158235.).
Subject(s)
Anti-Bacterial Agents/therapeutic use , Methicillin-Resistant Staphylococcus aureus/drug effects , Nasal Cavity/microbiology , Oligopeptides/therapeutic use , Staphylococcal Infections/drug therapy , Administration, Intranasal , Adolescent , Adult , Aged , Anti-Bacterial Agents/adverse effects , Bacterial Load/drug effects , Double-Blind Method , Female , Humans , Male , Middle Aged , Oligopeptides/adverse effects , Oligopeptides/pharmacokinetics , Young AdultABSTRACT
PURPOSE: To determine if anti-retroviral therapy (ART) in HIV-infected patients is associated with an increased risk for development of abdominal wall hernia. METHODS: A cohort study of 1072 HIV-infected patients in Sweden. Information was collected by questionnaires to patients and treating physicians, chart reviews by study physicians and regular blood tests for metabolic disorders. Adjusted relative risks were estimated by Cox proportional hazards models. RESULTS: Sixty-three patients (5.9%) developed abdominal wall hernia during the study period, 34 inguinal and 29 midline. Compared to the male general population, inguinal hernia was twice as common in the male study population, standardized incidence ratio (SIR) 2.0 (95% confidence interval (CI) 1.4-2.8). An increased incidence rate of abdominal wall hernia was found in patients exposed to ART, 11.3 per 1000 person-years (PY) compared with therapy naïves, 2.1 per 1000 PY. When adjusting for confounding risk-factors, ART containing protease inhibitors (PIs) during the 2nd and 3rd year of treatment was associated with the development of midline hernia with a hazard ratio (HR) of 10.7 (95%CI 1.3-85.7), and of inguinal hernia with an HR of 4.4 (95%CI 1.1-16.6). Other independent risk factors were age and diabetes/impaired fasting glucose for midline hernia, and age and a previous diagnosis of AIDS for inguinal hernia. CONCLUSIONS: We found an increased risk of developing abdominal wall hernia associated with PI-containing ART. The size of the study-population did not permit any conclusions regarding non-PI-containing ART.
Subject(s)
Anti-HIV Agents/adverse effects , HIV Infections/drug therapy , Hernia, Abdominal/chemically induced , Abdominal Fat/drug effects , Adult , Age Factors , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Body Fat Distribution , Cohort Studies , Female , Hernia, Abdominal/epidemiology , Humans , Male , Middle Aged , Pharmacoepidemiology , Proportional Hazards Models , Risk , Surveys and Questionnaires , Sweden , Time FactorsABSTRACT
In order to investigate whether previous findings of ubiquitous skin papillomavirus infection in Caucasians apply to populations from other parts of the world, skin swab samples from Bangladesh, Japan, Ethiopia and Zambia were analysed in parallel with Swedish samples. The prevalence of HPV DNA in the material from Bangladesh was 68 %, Japan 54 %, Ethiopia 52 %, Zambia 42 % and Sweden 70 %. A great multiplicity of genotypes was demonstrated by the finding of 88 HPV types or putative types in 142 HPV DNA-positive samples in total. Double or multiple genotypes were frequently found in the same sample. The most prevalent HPV type was HPV-5, with an overall prevalence of 6.5 %. This was also the only type that was found in samples from all of the countries in the study. The results presented show that commensal skin HPV infections have a worldwide distribution with a very broad spectrum of genotypes.
