nature publishing group The CYP3A4*18 Genotype in the Cytochrome P450 3A4 Gene, a Rapid Metabolizer of Sex Steroids, Is Associated With Low Bone Mineral DensityYS Kang1, SY Park1, CH Yim1, HS Kwak1, P Gajendrarao2, N Krishnamoorthy2, S-C Yun3, KW Lee2 and KO Han1 Osteoporosis is influenced by genetic factors. The interindividual variability in the activity of CYP3A, the metabolic enzyme of sex hormones, may result from genetic polymorphisms. In a study of 2,178 women of ages 40–79 years, the presence of the CYP3A4*18 variant was found to be significantly associated with low bone mass. In vitro functional analyses indicate that CYP3A4*18 is a gain-of-function mutation in sex steroid metabolism, resulting in rapid oxidation of estrogens and testosterone; in vivo pharmacokinetics using midazolam (MDZ) verify the altered activity of the CYP3A4*18, showing lower metabolic turnover in the mutant than in the wild type. Molecular modeling reveals the structural changes in the substrate recognition sites of CYP3A4*18 that can cause changes in enzymatic activity and that potentially account for the difference between the catalytic activities of estrogen and MDZ, depending on the genotype. The results indicate that a genetic variation in the CYP3A4 gene—as a gain-of-function mutation in the metabolism of certain CYP3A substrates, including sex steroids—may predispose individuals to osteoporosis.
Current research in microbiology and biotechnology
Current Research in Microbiology and Biotechnology Vol. 3, No. 4 (2015): 690-693 Research Article Open Access ISSN: 2320-2246
Prevalence and antibiotics sensitivity of
Staphylococcus aureus skin infection in children in
Salwa A. Aboud1, Abdallah El-yamani1, Mohamed A. Hussain1,* and Aimun AE. Ahmed2,3 1 Department of pharmaceutical Microbiology, International University of Africa, Sudan. 2 Department of Pharmacology, Faculty of Pharmacy, Omdurman Islamic University, Sudan. 3 Department of Pharmacology, Faculty of Pharmacy, International University of Africa, Sudan. * Corresponding author: Mohamed A. Hussain; e-mail Received: 02 July 2015 Accepted: 23 July 2015 Online: 30 July 2015 ABSTRACT
Staphylococcus aureus has been reported to cause severe community-associated infections of skin and soft tissues that are especially prevalent in children. Recently S. aureus is increasingly becoming resistant to majority of the available antibiotics in use and subsequently have developed into a challenging public health problem. The aim of this study was to investigate the prevalence and antibiotic sensitivity of S. aureus skin infections in children. Clinical samples (n=212) of Pus and skin swabs were collected from patients enrolled from the out-patient department (OPD) of Khartoum dermatology and venereal teaching hospital over a period of 6 months. The samples were cultured on bacteriological media for the isolation of S. aureus using standard methods of isolation and identification of bacteria. Antibiotics sensitivity test was carried out using Kirby-Bauer Disk Diffusion Technique in accordance with Clinical and Laboratory Standard Institute (CLSI). 198 (93%) of the total samples showed abundant growth. Of these 150 isolates were identified as S. aureus. The most commonly diagnosed skin infection was impetigo accounting for 61 (30.8%) of the samples of which 48 (78.7%) isolates were S. aureus. Sex differences in the prevalence of S. aureus were not significant whilst age differences were significant. The most effective antimicrobial agent was gentamicin (97.3%) efficacy, then fusidic acid (78%) efficacy. The sensitivity of the rest antimicrobial agents were erythromycin (50%), amoxy-clav (21.3%) and
bacitracin (12.7%). The present study demonstrated that Staphylococcus aureus are important pathogens in the
context of skin infections. In addition, S. aureus is the main pathogen isolated from Impetigo. S. aureus isolates
showed a very low degree of sensitivity to B-lactam antibiotic and bacitracin indicating the ineffectiveness of
these antibiotics and need to re-assess the policies on antibiotic usage in hospital environment.
Keywords: prevalence, S. aureus, skin infection in children, antibiotic sensitivity, Sudan.
There are over 26 species currently recognized in the S. aureus skin infections were classified as primary or genus staphylococci . Staphylococcus aureus is by far secondary . Primary infections were those occurring the most important and virulent pathogen among the on apparently normal skin and mainly comprises of staphylococci [2-3]. S. aureus has been reported to impetigo, folliculitis, cellulitis and ecthyma. Secondary cause severe community-associated infections of skin infections were those arising in damaged skin and soft tissues  that are especially prevalent in (traumatized skin, or a preexisting skin disease) [8-9]. children . Behavioral factors of children (e.g. the tendency of children to put hands and objects in their Impetigo is a common cutaneous infection that is mouths) as well as their physiologic factors (e.g. especially prevalent in children. Historically, impetigo immature immune systems) contribute to the success is caused by either group A β-hemolytic streptococci or of pathogen transmission . Salwa A. Aboud et al. / Curr Res Microbiol Biotechnol. 2015, 3(4): 690-693 Staphylococcus aureus. Currently, the most frequently 3. RESULTS AND DISCUSSION
isolated pathogen from impetigo is S. aureus . Out of 212 skin specimens that were collected from infected children 198 (93%) showed abundant growth Topical antibiotics are the treatment of choice since (population pattern is shown in table 1). Of these 150 oral antibiotics have more side effects . Mupirocin were identified to be S. aureus. Colonial morphology, and fusidic acid are the first choice options. The gram stain and biochemical reactions (tube coagulase, combination of neomycin and bacitracin does not lead tube catalase and DNAse) were found to be similar to to bacterial eradication  because Bacitracin became those described by Cheesebrough et al . ineffective. The rise of resistant strains of Staphylococcal infection has been well documented According to the report of Pereira (2014), S. aureus is  and clinicians should be cautious not to contribute the most frequently isolated pathogen from impetigo to this problem. As Heng et al (2013) concluded in their . Similarly, Alsterholm (2012), proved that S. aureus work on antimicrobial resistance, physicians should was by far the most common bacteria found in cultures ‘prescribe topical fusidic acid discerningly'. If from skin lesions in impetigo . In this study, the possible, topical antiseptic preparations should be used prevalence of impetigo (the commonest diagnosis) was to treat skin infection. If action is not taken now, the found to be 78%. This result is in aggreement with future use of fusidic acid will be compromised .' Alsterholm's report that noted a prevalence of 76-88% Recent study has lent a voice to the already existing body of knowledge that S. aureus are increasingly There were no significant differences in the prevalence becoming resistant to majority of the available of S. aureus in males and females (df = 1, P = 0.939) as antibiotics in use and subsequently have developed shown in figure 1. Similarly there were no significant into a challenging public health problem [14-15]. sex differences noted by Farajzadeh et al. at 2008  Moreover, geographic variation has been found in the and Alenizi at 2013 . In addition, Hill et al. (2011) antimicrobial susceptibility patterns of S. aureus . proved that there was no statistical difference between Hence, continuous local surveillance on antimicrobial males and females regarding the rate of S. aureus susceptibility of S. aureus is essential. colonization . The aim of this study was to determine the prevalence Age differences in the prevalence of S. aureus was and antibiotic sensitivity of S. aureus skin infection in significant (df = 2, P = 0.020) see figure 2. Noting a higher prevalence in adolescents and infants compared to children. It is believed that the infants immunity is not properly developed at this stage to cope up with 2. MATERIALS AND METHODS
bacterial infections hence they are vulnerable and Clinical samples (n=212) of Pus and skin swabs were easily infected by ubiquitous bacteria such as S. aureus. collected from patients enrolled from the outpatient However in this study, it is not clearly understood why department (OPD) of Khartoum dermatology and S. aureus prevalence in adolescents was higher than in venereal teaching hospital over a period of 6 months. children. This may be probably due to a significantly Nutrient agar, Blood agar, Mannitol salt agar, Dnase smaller sample size in adolescents compared to agar and Mueller-Hinton agar were prepared according to manufacturer's instruction (HiMedia Ltd, India), then used for the isolation of S. aureus using standard In the present study, antibiotic sensitivity to Fusidic methods of isolation and identification of the bacteria Acid was found to be 78%. This result is consistent with . Antibiotics susceptibility testing was performed that of Mir et al. (2015) where antibiotic sensitivity to by Kirby-Bauer disc diffusion method and the Fusidic Acid was noted to be 79.8% . In this study, susceptibility to antibiotics was assessed based on the the antibiotic sensitivity to Erythromycin was found to Clinical Laboratory Standards Institute (CLSI 2013) be 50%. This result compares favourably with the guidelines . The antibiotics tested were Fusidic published articles from Kenya at 2006, Pakistan at Acid (10μg), Erythromycin (15μg), Gentamicin (10μg), 2007 and Nigeria at 2011 that reported erythromycin Amoxiclav (30μg) and Bacitracin (10 units). All sensitivity of 44.7%, 55.6% and 52.4%, respectively antibiotic discs were procured from Himedia [15, 25-26]. However higher percentages of 71.43% Laboratories Pvt. Ltd. The data was analyzed using a and 60.6% were reported by two recent published personal computer and statistical package for social articles [24, 27] and also lower percentages of 17.2% sciences (SPSS). Statistical analysis was performed with , 33.3% , and 25.64%  were noted. This chi-square test. Significance level was set to be less than 0.05%, throughout the study analysis. The microorganisms varies from time to time and from children were classified according to US FDA  into place to place. In the present study, the antibiotic four major categories: Neonates: birth to 1 month, sensitivity to Gentamicin was 97.3%. Although this Infant: 1 month to 2 years, Children: 2 to 12 years and result is higher than those of Kaup et al. (2014)  Adolescent: 12 years to <16 years. and Mir et al. (2015)  where Gentamicin sensitivity was found to be 80.95% and 76.6%, respectively, it was found to be similar to the report of Onbuwiko et al. Salwa A. Aboud et al. / Curr Res Microbiol Biotechnol. 2015, 3(4): 690-693 (2011)  that noted 92.4% sensitivity. In the present sensitivity to Amoxyclav was noted to be 21.3% in this study, the antibiotic sensitivity to Bacitracin was study. This result was found to be lower than that from 12.7%. This was lower than that of Bashir et al. at 2007 that reported a 25.0% sensitivity . The antibiotic Figure 1: Bar chart illustrating Sex differences in the prevalence of S. aureus
Figure 2: Differences in the prevalence of S. aureus from different age groups.
Table 1: Population pattern of n=198 by Age, Sex and Diagnosis.
Salwa A. Aboud et al. / Curr Res Microbiol Biotechnol. 2015, 3(4): 690-693
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