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Infectious disease AND Urinary tract infection [keywords]
- The In Vitro and In Vivo Antibacterial Activities of Omadacycline, a Novel Aminomethylcycline. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2013 Dec 2.
Omadacycline is the first intravenous and oral 9-aminomethylcycline in clinical development for multiple infectious disease indications including Acute Bacterial Skin and Skin Structure Infections (ABSSSI), Community-Acquired Bacterial Pneumonia (CABP) and urinary tract infections (UTI). The comparative in vitro activity of omadacycline was determined against a broad panel of gram-positive clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococccus (VRE), and Lancefield Groups A and B beta-hemolytic streptococci, penicillin-resistant Streptococcus pneumoniae (PRSP), and Haemophilus influenzae (H. influenzae). The MIC90s for MRSA, VRE and beta-hemolytic streptococci were 1.0 μg/ml, 0.25 μg/ml and 0.5 μg/ml, respectively, and the MIC90s for PRSP and H. influenzae were 0.25 μg/ml and 2.0 μg/ml, respectively. Omadacycline was active against organisms demonstrating the two major mechanisms of resistance, ribosomal protection and active tetracycline efflux. In vivo efficacy of omadacycline was demonstrated using an intraperitoneal infection model in mice. A single intravenous dose of omadacycline exhibited efficacy against Streptococcus pneumoniae, Escherichia coli, and Staphylococcus aureus, including tet (M) and tet (K) efflux containing, and MRSA, strains. The ED50s for Streptococcus pneumoniae obtained ranged from 0.45 mg/kg to 3.39 mg/kg, the ED50s for Staphylococcus aureus obtained ranged from 0.30 mg/kg to 1.74 mg/kg, and the ED50 for Escherichia coli was 2.02 mg/kg. These results demonstrate potent in vivo efficacy including activity against strains containing common resistance determinants. Omadacycline demonstrated in vitro activity against a broad range of gram-positive and select gram-negative pathogens, including resistance determinant containing strains, and this activity translated to potent efficacy in vivo.
- A Review of Ten Years of the Study for Monitoring Antimicrobial Resistance Trends (SMART) from 2002 to 2011. [JOURNAL ARTICLE]
- Pharmaceuticals (Basel) 2013; 6(11):1335-1346.
Surveillance of antimicrobial agent resistance provides important information to guide microbiologists and infectious disease specialists understanding of the control and the spread of resistance mechanisms within the local environment. Continued monitoring of antimicrobial resistance patterns in the community and in local hospital environments is essential to guide effective empiric therapy. The Study for Monitoring Antimicrobial Resistance Trends (SMART) has monitored the in vitro susceptibility patterns of clinical Gram-negative bacilli to antimicrobial agents collected worldwide from intra-abdominal infections since 2002 and urinary tract infections since 2009. Resistance trends, with a particular focus on carbapenem resistance and the rate of extended-spectrum β-lactamases (ESBLs), were analyzed. Isolates from intra-abdominal infections (n = 92,086) and urinary-tract infections (n = 24,705) were collected and tested using Clinical and Laboratory Standards Institute methods. This review presents carbapenem susceptibility and ESBL rates over ten years of SMART study analysis, including key publications during this period. The SMART study has proved to be a valuable resource in determining pathogen prevalence and antibiotic susceptibility over the last ten years and continues to provide evidence for regulatory susceptibility breakpoints and clinical decision making.
- The Role of TLR4 896 A>G and 1196 C>T in Susceptibility to Infections: A Review and Meta-Analysis of Genetic Association Studies. [Journal Article]
- PLoS One 2013; 8(11):e81047.
Toll-like receptor 4 plays a role in pathogen recognition, and common polymorphisms may alter host susceptibility to infectious diseases.To review the association of two common polymorphisms (TLR4 896A>G and TLR4 1196C>T) with infectious diseases.We searched PubMed and EMBASE up to March 2013 for pertinent literature in English, and complemented search with references lists of eligible studies.WE INCLUDED ALL STUDIES THAT: reported an infectious outcome; had a case-control design and reported the TLR4 896A>G and/or TLR4 1196C>T genotype frequencies; 59 studies fulfilled these criteria and were analyzed.Two authors independently extracted study data.The generalized odds ratio metric (ORG) was used to quantify the impact of TLR4 variants on disease susceptibility. A meta-analysis was undertaken for outcomes reported in >1 study. Eleven of 37 distinct outcomes were significant. TLR4 896 A>G increased risk for all parasitic infections (ORG 1.59; 95%CI 1.05-2.42), malaria (1.31; 95%CI 1.04-1.66), brucellosis (2.66; 95%CI 1.66-4.27), cutaneous leishmaniasis (7.22; 95%CI 1.91-27.29), neurocysticercosis (4.39; 95%CI 2.53-7.61), Streptococcus pyogenes tonsillar disease (2.93; 95%CI 1.24-6.93) , typhoid fever (2.51; 95%CI 1.18-5.34) and adult urinary tract infections (1.98; 95%CI 1.04-3.98), but was protective for leprosy (0.36; 95%CI 0.22-0.60). TLR4 1196 C>T effects were similar to TLR4 896 A>G for brucellosis, cutaneous leishmaniasis, leprosy, typhoid fever and S. pyogenes tonsillar disease, and was protective for bacterial vaginosis in pregnancy (0.55; 95%CI 0.31-0.98) and Haemophilus influenzae tonsillar disease (0.42; 95%CI 0.17-1.00). The majority of significant associations were among predominantly Asian populations and significant associations were rare among European populations.Depending on the type of infection and population, TLR4 polymorphisms are associated with increased, decreased or no difference in infectious disease. This may be due to differential functional expression of TLR4, the co-segregation of TLR4 variants or a favorable inflammatory response.
- Critical evaluation of antimicrobial use - A Turkish university hospital example. [Journal Article]
- J Infect Dev Ctries 2013; 7(11):873-9.
Antimicrobials are being used unnecessarily for different reasons. The aims of this study were: assessment of the quality of antimicrobial use and determination of the factors related to correct use.Antimicrobial practice at Dicle University Hospital (DUH) was evaluated with a point prevalence approach. Using a standardized data collection form, the patients' data (clinic, epidemiology, laboratory and antimicrobial use) was collected. Possible influential factors on antimicrobial use were examined.In the surveillance study 1,350 inpatients were evaluated; 461 (34.1%) of them were using antimicrobials for treatment and 187 (13.9%) for prophylaxis. Antimicrobial indication was found in 355 of 461 patients (77.0%), and the number of antimicrobials was 1.8 per patient in the treatment group. The most common reason for antimicrobial use was community-acquired infection (57.9%). Pneumonia (20.4%), skin and soft tissue infections (9.11%) and urinary tract infections (7.9%) were the most common infectious diseases. Positive culture results were available for 39 patients (8.5.0%) when antimicrobial treatment started. All steps of antimicrobial use were found appropriate in 243 patients (52.7%). In multivariate analyses, clinical manifestation of infection at the beginning (p <0.001), presence of leukocyte counting (p <0.001) and prescription by an infectious disease specialist were found significantly positive factors for wholly appropriate antimicrobial use. Hospitalization with a diagnosis other than infection was found a significantly negative factor for appropriate antimicrobial use (p=0.001).The quality of antimicrobial use could be improved with better clinical and laboratory diagnosis and consultation with infectious diseases specialists.
- Update on new medicinal application of gentamicin: Evidence-based review. [JOURNAL ARTICLE]
- J Formos Med Assoc 2013 Nov 8.
Gentamicin (GM) was discovered in 1963 and was introduced into parenteral usage in 1971. Since then, GM has been widely used in medicinal applications. The Food and Drug Administration of the United States approved the routine prescription of GM to treat the following infectious disorders: infection due to Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, Citrobacter spp., Enterobacteriaceae spp., Pseudomonas spp.; Staphylococcus infectious disease; bacterial meningitis; bacterial sepsis of newborns; bacterial septicemia; infection of the eye, bone, skin and/or subcutaneous tissue; infective endocarditis; peritoneal dialysis-associated peritonitis due to Pseudomonas and other gram-negative organisms; peritonitis due to gastrointestinal tract infections; respiratory tract infections; and urinary tract infectious disease. GM is an old antibiotic and is used widely beyond its FDA-labeled indications as follows: actinomycotic infection; Staph. saprophyticus bacteremia with pyelonephritis; appendicitis; cystic fibrosis; diverticulitis; adjunct regimen for febrile neutropenia; female genital infection; uterine infection; postnatal infection; necrotizing enterocolitis in fetus or newborn; osteomyelitis; pelvic inflammatory disease; plague; gonorrhea; tularemia; prophylaxis of post-cholecystectomy infection, transrectal prostate biopsy, and post-tympanostomy-related infection; malignant otitis externa; and intratympanically or transtympanically for Ménière's disease. GM is also used in combination regimens, such as with beta-lactam antibiotics to treat mixed infection and with bacteriophage to treat Staph. aureus infections. It is also added to medical materials, such as GM-loaded cement spacers for osteomyelitis and prosthetic joint-associated infections. Overall, there are many medicinal applications for GM. To reduce the development of GM-resistant bacteria and to maintain its effectiveness, GM should be used only to treat or prevent infections that are proven or strongly suspected as being caused by susceptible bacteria. In the future, we believe that GM will be used more widely in combination therapy and applied to medical materials for clinical applications. A definitive, appropriately powered study of this antibiotic and its clinical applications is now required, especially in terms of its effectiveness, safety, and cost.
- [Complications of pediatric renal transplantation]. [English Abstract, Journal Article]
- Acta Med Port 2013 Sep-Oct; 26(5):517-22.
Background:Renal transplantation is the treatment of choice for children with end stage renal disease with positive impact on survival and quality of life. However, some complications affect morbidity and mortality. This study examines the renal transplantation complications profile in pediatric patients (<18 y). Material and
Methods:Retrospective analysis of clinical files from renal transplantation patients followed in Pediatric Nephrology Unit from September 1995 to August 2010. Collection of data regarding: demography, end stage renal disease etiology, previous renal replacement therapy, graft loss and death, complications: surgical, infectious and non-infectious (acute and chronic rejection, primary disease recurrence, metabolic and cardiovascular risk factors). Descriptive statistical analysis was performed.
Results:78 children (male: 48.7%), mean age at renal transplantation: 11.7 4.1 years. Previous peritoneal dialysis in 49 (62.6%). Five patients (6.4%) with preemptive renal transplantation. Median follow up: 37.5 months (1-169). Main end stage renal disease etiologies were urologic conditions in 41% and glomerular disease in 28.2%. Infectious complications occurred in 74%: viral: 56.4% (cytomegalovirus in 39.7%); bacterial in 53.8% (mainly urinary tract infections). Non-infectious complications were: 1) cardiovascular risk factors: hypertension in 85.9%, hyperlipidemia in 16.7% and new onset diabetes post transplantation in 7.7%; 2) acute graft dysfunction in 32.1%; graft chronic nephropathy 17.9%; 3) surgical complications 16.7%. In the first month after renal transplantation, surgical complications (11.5%) and bacterial infections were the most prevalent complications. Between the 1st and the 6th month there were more bacterial (34.6% patients) and viral (17.9% patients) infections. From 6th month on, cardiovascular risk factors (89.7% patients) became the more prevalent. There was one death.
Conclusions:The most frequent infections were viral, mainly CMV. Acute graft dysfunction was frequent after the 6th month, probably associated with poor compliance. New morbidities, namely cardiovascular risk factors, are emerging with the evolution of new diagnostic, prophylactic and therapeutic strategies for renal transplantation.
- [Risk factors of prematurity. A case control study]. [English Abstract, Journal Article]
- Ginecol Obstet Mex 2013 Sep; 81(9):499-503.
Prematurity is the most frequent cause of perinatal morbidity and mortality, and is responsible with 75% of neonantal deaths not related to congenital defects.The aim of this study was to know risk factors that influence premature delivery in a third level attention in a Gyneco-Obstetric Unit.In a case-control study, was conducted an interview with 300 mothers who had their delivery at 28 and 36 gestational weeks in group of cases and 600 mothers from 37 to 41 weeks in controls, who assisted for attention from April to September 2011.The factors associated eighth higher risk for prematurity were: maternal age above 35 years was more frequent in cases (14.6%), previous placenta occurred more frequent in cases (9.3%), Infectious disease were highly present in cases such as: urinary tract infection (46%). But association of 2 or more factors such as premature rupture of membranes and cervicovaginitis, were more frequent significantly in study group (76%).The prematurity risk factor more freqeunt were: infectouse disease in study group. A deficient prenatal attention can be increased in order to prevent premature delivery. When 2 or more factors associated in a gestation the risk also increase, and should increase the following and medical attention to reduce premature risk.
- Epidemiology, antibiotic therapy and outcomes of bacteremia caused by drug-resistant ESKAPE pathogens in cancer patients. [JOURNAL ARTICLE]
- Support Care Cancer 2013 Oct 30.
Infection due to the six ESKAPE pathogens has recently been identified as a serious emerging problem. However, there is still a lack of information on bacteremia caused by these organisms in cancer patients. We aimed to assess the epidemiology, antibiotic therapy and outcomes of bacteremia due to drug-resistant ESKAPE pathogens (rESKAPE) in patients with cancer.All episodes of bacteremia prospectively documented in hospitalized adults with cancer from 2006 to 2011 were analyzed.Of 1,148 episodes of bacteremia, 392 (34 %) were caused by ESKAPE pathogens. Fifty-four episodes (4.7 %) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium 0, methicillin-resistant Staphylococcus aureus (MRSA) 13, extended-spectrum beta-lactamase (ESLB)-producing Klebsiella pneumoniae 7, carbapenem-resistant Acinetobacter baumannii 4, carbapenem- and quinolone-resistant Pseudomonas aeruginosa 18 and derepression chromosomic ß-lactam and ESBL-producing Enterobacter species 12. Risk factors independently associated with rESKAPE bacteremia were comorbidities, prior antibiotic therapy, urinary catheter and urinary tract source. Inappropriate empirical antibiotic therapy was more frequent in patients with rESKAPE bacteremia than in the other cases (55.6 % vs. 21.5 %, p < 0.001). Persistence of bacteremia (25 % vs. 9.7 %), septic metastasis (8 % vs. 4 %) and early case-fatality rate (23 % vs. 11 %) were more frequent in patients with rESKAPE bacteremia than in patients with other etiologies (p < 0.05).Bacteremia due to rESKAPE pathogens in cancer patients occurs mainly among those with comorbidities who have received prior antibiotic therapy and have a urinary tract source. These patients often receive inappropriate empirical antibiotic therapy and have a poor outcome.
- The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli clone. [Journal Article, Research Support, Non-U.S. Gov't]
- PLoS Genet 2013 Oct; 9(10):e1003834.
Escherichia coli ST131 is a globally disseminated, multidrug resistant clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with antibiotic resistance; however, this phenotype alone is unlikely to explain its dominance amongst multidrug resistant uropathogens circulating worldwide in hospitals and the community. Thus, a greater understanding of the molecular mechanisms that underpin the fitness of E. coli ST131 is required. In this study, we employed hyper-saturated transposon mutagenesis in combination with multiplexed transposon directed insertion-site sequencing to define the essential genes required for in vitro growth and the serum resistome (i.e. genes required for resistance to human serum) of E. coli EC958, a representative of the predominant E. coli ST131 clonal lineage. We identified 315 essential genes in E. coli EC958, 231 (73%) of which were also essential in E. coli K-12. The serum resistome comprised 56 genes, the majority of which encode membrane proteins or factors involved in lipopolysaccharide (LPS) biosynthesis. Targeted mutagenesis confirmed a role in serum resistance for 46 (82%) of these genes. The murein lipoprotein Lpp, along with two lipid A-core biosynthesis enzymes WaaP and WaaG, were most strongly associated with serum resistance. While LPS was the main resistance mechanism defined for E. coli EC958 in serum, the enterobacterial common antigen and colanic acid also impacted on this phenotype. Our analysis also identified a novel function for two genes, hyxA and hyxR, as minor regulators of O-antigen chain length. This study offers novel insight into the genetic make-up of E. coli ST131, and provides a framework for future research on E. coli and other Gram-negative pathogens to define their essential gene repertoire and to dissect the molecular mechanisms that enable them to survive in the bloodstream and cause disease.
- Greater saphenous venous access as an alternative in children. [JOURNAL ARTICLE]
- Pediatr Radiol 2013 Oct 6.
In the pediatric population, obtaining venous access in high-risk neonates, severely ill children with cardiac anomalies or very young children (<10 kg) can be very challenging. In the literature to date, the greater saphenous vein has not been primarily used by interventional radiologists as an entry site for venous access in children.To demonstrate the utility and effectiveness of using the greater saphenous vein as a venous access site for the placement of peripherally inserted central catheters in children.This is a retrospective study from a large tertiary care children's hospital from November 2010 to August 2012. Peripheral insertion of central venous catheters (PICC) using the greater saphenous vein was attempted in 86 children ranging in age from 3 days to 17 years (mean: 1.8 years). Indications included congenital heart disease, urinary tract infection, intravenous access, pneumonia, meningitis, total parenteral nutrition, sepsis and other infections. All procedures were performed by interventional radiologists. No insertion-related complications were identified. There was no follow-up planning, but no mechanical or infectious complications were brought to our attention.Of the 86 patients in whom PICC placement was attempted, placement was successful in 67 (78%). Forty-two PICCs were placed in the greater saphenous vein at the thigh level using US guidance and 25 at the ankle level using anatomical landmarks. The mean weight of the 67 patients who underwent successful placement was 9.98 kg, with 51 (76%) weighing <10 kg. The mean vessel diameter in placement failures was 1.35 mm compared to 1.83 mm in successful placement. Inability to obtain venous access was the cause of failure in all thigh access sites while inability to advance the catheter centrally was the cause of failure for all ankle access sites. A total of 1,060 catheter days (with a maximum dwell time of 97 days in one patient) were reviewed without complication.In children, the greater saphenous vein provides a safe, suitable alternative for venous access, particularly in very young children (<10 kg) and in a select group of older children who are not mobile. In the lower extremities, greater saphenous venous puncture and access may be a preferred initial access site in small children to preserve future venous access.