Inhibition of Adhesion and Invasion of \u3cem\u3ePseudomonas aeruginosa\u3c/em\u3e to Lung Epithelial Cells: A Model of Cystic Fibrosis Infection

Over their life time, CF patients experience multiple infections by various pneumoniacausing bacteria [6]. With more patients surviving to adulthood, chronic infections with Pseudomonas aeruginosa are coming to the forefront as a leading cause of death [7]. Problems presented by infected CF lung are multi-dimensional; the electrolyte balance and pH of the fluids are abnormal. The mucus is thick and of an alternative composition compared to normal lung and may contribute to colonization with Pseudomonas aeruginosa [2, 3, 5]. As such, research is multi-pronged and includes gene therapy to correct the defective protein, amelioration of inflammatory response and thinning of alveolar surface fluids [8, 9]. Significantly, Pseudomonas bacteria colonize the CF lung far easier than normal lung. Normal lung tissue has several naturally occurring defenses that work in concert with commonly prescribed antibiotics for recovery from lung infections [4, 10]. The CF patient appears to lack these natural defenses [1, 7].https://digitalcommons.chapman.edu/pharmacy_books/1009/thumbnail.jp

Ciprofioxacin in experimental Pseudomonas aeruginosa meningitis in rabbits

The potential of ciprofloxacin for the therapy of Pseudomonas aeruginosa meningitis was evaluated in an animal model by determining the penetration of the drug into CSF, its concentration-dependent killing characteristics in vivo, and its relative efficacy compared with ceftazidime and tobramycin. Meningitis was produced in 40 rabbits by intracisternal injection of 3 x 10 7 organisms. The drugs were administered intravenously over seven hours, and simultaneous serum and CSF samples were taken at 0, 1, 3, 5, and 7 h for determination of drug concentration and CSF bacterial counts. The percentage penetration of ciprofloxacin (18-4± 12'3; mean±standard deviation) in infected rabbits was substantially increased over that found in uninfected rabbits (4'1 ± 1· 3). The rate of bacterial killing for animals treated with ceftazidime (100 mg/kg/h) and high doses of tobramycin (2·5 mg/kg/h) was -0·51 ±0·13 (lOglO cfu/ml/h). This was similar to the rate of killing (-0-48±0·2) found when ciprofloxacin was infused at 5 mg/kg/h, a dose that produced a mean serum level of 6·7 ± 4·6 mg/I, which corresponds to concentrations achievable in humans. As dosages were increased (15 and 30 mg/kg/h), the rate of bacterial killing also increased (-0'70 ±O'I and -0·89±0·4 respectively; r = 0·7407; P<O·OI). The drug shows promise in the treatment of pseudomonas meningitis

Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1

Consensus recommendation for meningococcal disease prevention in children and adolescents in the Middle East region

Facing the availability of the new generation of quadrivalent meningococcal conjugate vaccines (Menveo®, Menactra® and others pending for license) and their recent implementation in Saudi Arabia, experts from 11 countries of the Middle East region met at a “Meningococcal Leadership Forum” (MLF), which took place in May 2010 in Dubai. The participants of the conference discussed the importance of introducing the concept of conjugate vaccines – especially for children and adolescents – and elaborated a consensus recommendation to support healthcare professionals and decision makers with their expertise. In experts’ opinion, conjugate vaccines are the best choice for the prevention of meningococcal disease caused by serogroups A, C, W-135 and Y. As quadrivalent meningococcal conjugate vaccines are registered and available in the Middle East region, they should replace plain polysaccharide vaccines and be integrated in pediatric and adolescent vaccination schedules, including infant vaccination concomitantly with basic EPI vaccines when licensed

Fecal Colonization with Extended-Spectrum Beta-Lactamase and AmpC-Producing Escherichia coli

Background. Extended-spectrum -lactamases (ES Ls) and AmpC -lactamases cause -lactam resistance in Escherichia coli. Fecal colonization by ES L-and/or AmpC-positive E. coli is a source of nosocomial infections. Methods. In order to investigate inpatient fecal colonization by ES Ls and AmpC, antibiotic sensitivity tests were conducted and minimum inhibitory concentrations (MICs) were determined using the disk diffusion method and E-test, respectively. Characterization of ES L and AmpC was performed using E-test strips, and a set of PCRs and DNA sequence analyses were used to characterize the ES L and AmpC genes. Results. The whole collection of E. coli isolates ( = 50) was sensitive to imipenem, tigecycline, colistin, and fosfomycin, while 26% of the isolates showed reduced susceptibility to ceftazidime (MIC ≥ 4 g/mL). ES L was phenotypically identified in 26% (13/50) of cases, while AmpC activity was detected in two ES L-producing E. coli isolates. All ES L-producing E. coli were positive for the CTX-M gene, eleven isolates carried , and two isolates carried CTX-M-14 gene. Two CTX-M-positive E. coli isolates carried CMY-2 . Conclusions. The alimentary tract is a significant reservoir for ES L-and/or AmpC-producing E. coli, which may lead to nosocomial infection

Fecal Colonization with Extended-Spectrum Beta-Lactamase and AmpC-Producing Escherichia coli

Background. Extended-spectrum β-lactamases (ESβLs) and AmpC β-lactamases cause β-lactam resistance in Escherichia coli. Fecal colonization by ESβL- and/or AmpC-positive E. coli is a source of nosocomial infections. Methods. In order to investigate inpatient fecal colonization by ESβLs and AmpC, antibiotic sensitivity tests were conducted and minimum inhibitory concentrations (MICs) were determined using the disk diffusion method and E-test, respectively. Characterization of ESβL and AmpC was performed using E-test strips, and a set of PCRs and DNA sequence analyses were used to characterize the ESβL and AmpC genes. Results. The whole collection of E. coli isolates (n=50) was sensitive to imipenem, tigecycline, colistin, and fosfomycin, while 26% of the isolates showed reduced susceptibility to ceftazidime (MIC ≥ 4 μg/mL). ESβL was phenotypically identified in 26% (13/50) of cases, while AmpC activity was detected in two ESβL-producing E. coli isolates. All ESβL-producing E. coli were positive for the CTX-M gene, eleven isolates carried blaCTX-M-15, and two isolates carried blaCTX-M-14 gene. Two CTX-M-positive E. coli isolates carried blaCMY-2. Conclusions. The alimentary tract is a significant reservoir for ESβL- and/or AmpC-producing E. coli, which may lead to nosocomial infection

Characterization of carbapenemases, ESBLs, and plasmid-mediated quinolone determinants in carbapenem-insensitive Escherichia coli and Klebsiella pneumoniae in Riyadh hospitals

The main objective of this work was to characterize carbapenemases, extended-spectrum β-lactamases (ESBLs), and plasmid-mediated quinolone resistance (PMQR) among carbapenem-insensitive Klebsiella pneumoniae and Escherichia coli clinical isolates which were isolated from three hospitals in Riyadh. Thirty-one carbapenem-insensitive isolates (21 K. pneumoniae and 10 E. coli) were recovered from March 2014 to May 2014. Susceptibility testing and phenotypic detection tests were used to characterize the classes of β-lactamases. PCR assays were performed for the detection of the genes encoding ESBL (blaCTX-M, blaTEM, blaSHV, and blaOXA-1), carbapenemase (blaKPC, blaGES, blaVIM, blaIMP, blaNDM, and blaOXA-48), and PMQR (qnrA, qnrB, qnrS, aac(6)-Ib-cr, qepA, oqxA, and oqxB) genes. All carbapenem-insensitive isolates were carbapenemase producers, with 41.9% and 58.1% being class B carbapenemases class D OXA-48, respectively. While the prevalence of ESBL producers was 80.6%. The following resistance genes were detected; OXA-48-like (58.1%), NDM-type (41.9%), CTX-M-1-like (77.4%), CTX-M-9-like (9.6%), TEM-1 (74.2%), OXA-1 (54.8%), SHV-1 (4.4%), qnrS (58.1%), qnrB (3.2%), and aac(6)-Ib-cr (51.6%). The predominant carbapenemases in the isolates that had carbapenem MIC ≤ 4 μg/ml and MIC ≥ 12 μg/ml were blaOXA-48-type and blaNDM-type respectively. CTX-M-1-like and qnrS were the dominant ESBL and PMQR genes, respectively. This is the first report in which qnrS was described in the isolates from Saudi Arabia. Keywords: OXA-48, NDM, Carbapenem resistance, Saudi Arabi

The epidemiology of pneumococcal, meningococcal, and Haemophilus disease in the Middle East and North Africa (MENA) Region—Current status and needs

Information about the burden and epidemiological characteristics of meningitis and other invasive disease caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis is of great value to healthcare decision makers to prioritize public health interventions. A group of regional experts in the Eastern Mediterranean and North African regions formed the MENA Vaccine-Preventable Diseases Regional Advisory Group to collate and discuss such information on an annual basis. This paper provides an up-to-date summary of the available epidemiological data regarding these pathogens in these regions. In doing so, it highlights the need for additional surveillance studies to better measure the burden of these diseases, as well as the potential impact of introduction of new vaccines against these pathogens