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Infectious disease AND Urinary tract infection [keywords]
- Vaccines for the elderly need to be introduced into the immunization program in India. [Journal Article]
- Hum Vaccin Immunother 2014 Aug; 10(8):2468-70.
The population in India over age 60 years has tripled in the past 50 years and will relentlessly increase in the near future. According to census 2011, elderly people were 8.1% of the total population, and the projections for population over 60 years over the next 4 censuses are 133 million (2021) expanding to 301 million (2051). In developing countries, the elderly have suffered from both communicable and non-communicable diseases. Moreover, advancing age is associated with decreased immunity along with physiological changes, and poor health leads to increased risk of infectious diseases. Infections such as pneumococcal, influenza, tetanus, and zoster are more common among elderly population. These infections are major causes of morbidity and mortality among the elderly and are responsible for a large number of deaths and hospitalizations. Communicable diseases like influenza and pneumonia are the fifth leading cause of death among elderly persons. A study reported the incidence of nosocomial infections in geriatric patients in India to be ~20%. Pseudomonas aeruginosa was the most common microbe associated with Urinary Tract Infection, while Staphylococcus aureus was frequently observed in cases of pneumonia among hospitalized elderly population. In India, because of many reasons, preventive care for elderly persons is often neglected. Among the many infections to which the elderly are prone, some can be prevented by administration of appropriate vaccines. Vaccination of the elderly is one of the most effective means of preventing disease, disability, and death from infectious diseases.
- Reactogenicity and safety of the human rotavirus vaccine, Rotarix™ in The Philippines, Sri Lanka, and India: A post-marketing surveillance study. [Journal Article]
- Hum Vaccin Immunother 2014 Aug; 10(8):2276-83.
Regulatory bodies in The Philippines, Sri Lanka, and India require post-marketing surveillance to provide additional safety data on Rotarix™ in real-life settings. In such studies conducted in The Philippines (November 2006 to July 2012; NCT00353366), Sri Lanka (November 2008 to August 2009; NCT00779779), and India (August 2009 to April 2010; NCT00938327), 2 doses of Rotarix™ were administered according to the local prescribing information (PI). The occurrence of at least Grade "2"/"3" solicited adverse event (AE) (fever, vomiting, or diarrhea), within 15 days in The Philippines or 8 days in Sri Lanka and India; unsolicited AEs within 31 days and serious adverse events (SAEs) throughout the study were recorded. Of the 1494, 522, and 332 infants enrolled in The Philippines, Sri Lanka, and India, 14.7% 14.9% and 12.7% infants, respectively recorded at least Grade "2"/"3" solicited AEs. The most commonly reported solicited AEs were irritability in The Philippines (32.2% post-Dose-1; 23.5% post-Dose-2) and India (23.0% post-Dose-1; 13.2% post-Dose-2), and fever (18.0% post-Dose-1; 20.2% post-Dose-2) in Sri Lanka. Unsolicited AEs were recorded in 24.5% (The Philippines), 4.8% (Sri Lanka), and 6.9% (India) of infants. Forty-one SAEs were recorded in the Philippines of which 6 (decreased oral intake with increased sleeping time and constipation; pneumonia, urinary tract infection, and intussusception) were considered by the investigators as causally related to vaccination. One vaccine-unrelated SAE occurred in a Sri Lankan infant. All SAEs resolved and the infants recovered. Two doses of Rotarix™, administered to healthy infants according to local PI, were well tolerated in The Philippines, Sri Lanka, and India.
- A protocol to identify non-classical risk factors for preterm births: the Brazilian Ribeirão Preto and São Luís prenatal cohort (BRISA). [Journal Article]
- Reprod Health 2014; 11(1):79.
Preterm birth is the main cause of morbidity and mortality during the perinatal period. Classical risk factors are held responsible for only 1/3 of preterm births and no current intervention has produced an appreciable reduction of this event. It is necessary to explore new hypotheses and mechanisms of causality by using an integrated approach, collaboration among research groups and less fragmented theoretical-methodological approaches in order to detect new risk factors and to formulate more effective intervention strategies.The study will be conducted on a convenience cohort of Brazilian pregnant women recruited at public and private prenatal health services. A total of 1500 pregnant women in São Luís, and 1500 in Ribeirão Preto, will be invited for an interview and for the collection of biological specimens from the 22nd to the 25th week of gestational age (GA). At the time of delivery they will be reinterviewed. GA will be determined using an algorithm based on two criteria: date of last menstruation (DLM) and obstetric ultrasound (OUS) performed at less than 20 weeks of GA. Illicit drug consumption during pregnancy will be determined using a self-applied questionnaire and the following instruments will be used: perceived stress scale, Beck anxiety scale, screening for depression of the Center of Epidemiological Studies (CES-D), experiences of racial discrimination, social network and social support scale of the Medical Outcomes Study and violence (Abuse Assessment Screening and violence questionnaire of the WHO). Bacterial vaginosis, urinary tract infection and periodontal disease will also be identified. Neuroendocrine, immunoinflammatory and medical intervention hypotheses will be tested. The occurrence of elective cesarean section in the absence of labor will be used as a marker of medical intervention.Psychosocial, genetic and infectious mechanisms will be selected, since there are indications that they influence preterm birth (PTB). The studies will be conducted in two Brazilian cities with discrepant socioeconomic conditions. The expectation is to identify risk factors for PTB having a greater predictive power than classically studied factors. The final objective is to propose more effective interventions for the reduction of PTB, which, after being tested, might subsidize health policies.
- Efficacy and safety of biapenem in treatment of infectious disease: a meta-analysis of randomized controlled trials. [JOURNAL ARTICLE]
- J Chemother 2014 Nov 19.:1973947814Y0000000226.
Background: Biapenem is a parenteral carbapenem antibiotic that has powerful antibacterial activity. The aim of this study is to evaluate the efficacy and safety of biapenem for the treatment of infection diseases. Methods: We performed a meta-analysis of published randomized-controlled trials (RCTs) identified in Embase, PubMed, and Cochrane library that compared the efficacy and safety of biapenem with other antibiotic regimes for the treatment of patients with infections. Results: Eight RCTs were included in the meta-analysis, involving totally 1685 patients with lower respiratory tract infections (LRTIs), complicated urinary tract infections (cUTIs), and complicated intra-abdominal infections (cIAIs). There was no difference found between the patients with LRTIs, cUTIs, or cIAIs treated with biapenem and comparators, regarding treatment success and adverse events. Conclusion: This meta-analysis provides evidence that biapenem can be used as effectively and safely as imipenem-cilstatin or meropenem, for the treatment of patients with LRTIs, cUTIs, and cIAIs. It may be a considerable option for the treatment of these infections.
- Carbapenem-Resistant Klebsiella pneumoniae Urinary Tract Infection following Solid Organ Transplantation. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Nov 10.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging pathogen with devastating impact on organ transplant recipients (OTR). Data describing urinary tract infection (UTI) due to CRKP compared to extended-spectrum β-lactamase (ESBL) and susceptible K. pneumoniae are lacking. We conducted a retrospective cohort study comparing OTR with a first episode of UTI due to CRKP, ESBL, or susceptible K. pneumoniae. We identified 108 individuals: 22 (20%) had UTI due to CRKP, 22 (20%) ESBL, and 64 (60%) susceptible. Compared to susceptible K. pneumoniae (27%), patients with UTI due to CRKP or ESBL were more likely to have a ≥24-hour stay in the ICU before or after development of the UTI (64 and 77%, respectively; p<0.001). Among 105/108 (97%) hospitalized patients, median length of stay (LOS) prior to UTI with CRKP or ESBL (7 and 8 days, respectively) was significantly longer than susceptible K. pneumoniae (1 day; p<0.001). Clinical failure was observed in 8 (36%) patients with CRKP, 4 (18%) ESBL, and 9 (14%) susceptible (p=0.073). Microbiological failure was seen in 10 (45%) patients with CRKP compared with 2 (9%) ESBL and 2 (3%) susceptible (p<0.001). In multivariable logistic regression analyses, CRKP was associated with higher odds of microbiologic failure (vs. ESBL, OR 9.36, 95% CI 1.94-72.1; vs. susceptible, OR 31.4, 95% CI 5.91-264). In conclusion, CRKP is associated with the ICU, long LOS, and microbiologic failure among OTR with UTI. Greater numbers are needed to determine risk factors for infection and differences in meaningful endpoints associated with carbapenem resistance.
- [Recurrent urinary tract infection]. [English Abstract, Journal Article]
- Rev Prat 2014 Sep; 64(7):969-71.
Recurrent urinary tract infection involves mainly women and exhibits an ecological as well as economical risk. 4% of all urinary tract infection are recurrent and usually secondary to general or local abnormalities. A multidisciplinary medical and surgical team (urology, nephrology, bacteriology, infectious disease) best performs diagnosis and treatment as well as rules out reversible etiology. Treatment relies on behavioral changes before offering cranberry products and/or antibioprophylaxis if necessary.
- Rapid identification of major Escherichia coli sequence types causing urinary tract and bloodstream infections. [JOURNAL ARTICLE]
- J Clin Microbiol 2014 Oct 29.
Escherichia coli sequence types (ST) 69, 73, 95 and 131 are collectively responsible for a large proportion of E. coli urinary tract and bloodstream infections, and differ markedly in their antibiotic susceptibility. We describe a novel PCR method to detect and distinguish these lineages rapidly. Three hundred and eighteen published E. coli genomes were compared, to identify signature sequences unique to each of the four major STs. The specificity of these sequences was assessed in silico by seeking them in an additional 98 genomes. A PCR assay was designed to amplify size-distinguishable fragments unique to the four lineages, and was validated using 515 E. coli isolates of known ST. Genome comparisons identified 22 regions, ranging in size from 335 bp to 26.5 kb, unique to one or other of the four predominant E. coli STs, with two to ten specific regions per ST. These regions predominantly harbored genes encoding hypothetical proteins and were within or adjacent to prophage sequences. Most (13/22) were highly conserved (>96.5% identity) in genomes of the respective ST. The new assay identified correctly all of 142 representatives of the four major STs in the validation set (n=515), with only two ST12 isolates misidentified as ST95. Compared with MLST, the assay thus had 100% sensitivity and 99.5% specificity. Rapid identification of major extra-intestinal E. coli STs will benefit future epidemiological studies and could be developed to tailor antibiotic therapy to the different susceptibilities of these dominant lineages.
- Pilicide ec240 Disrupts Virulence Circuits in Uropathogenic Escherichia coli. [Journal Article]
- MBio 2014; 5(6)
Chaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show that pilicide ec240 decreased the levels of type 1, P, and S piliation. Transcriptomic and proteomic analyses using the cystitis isolate UTI89 revealed that ec240 dysregulated CUP pili and decreased motility. Paradoxically, the transcript levels of P and S pilus genes were increased during growth in ec240, even though the level of P and S piliation decreased. In contrast, the most downregulated transcripts after growth in ec240 were from the type 1 pilus genes. Type 1 pilus expression is controlled by inversion of the fimS promoter element, which can oscillate between phase on and phase off orientations. ec240 induced the fimS phase off orientation, and this effect was necessary for the majority of ec240's inhibition of type 1 piliation. ec240 increased levels of the transcriptional regulators SfaB and PapB, which were shown to induce the fimS promoter phase off orientation. Furthermore, the effect of ec240 on motility was abolished in the absence of the SfaB, PapB, SfaX, and PapX regulators. In contrast to the effects of ec240, deletion of the type 1 pilus operon led to increased S and P piliation and motility. Thus, ec240 dysregulated several uropathogenic Escherichia coli (UPEC) virulence factors through different mechanisms and independent of its effects on type 1 pilus biogenesis and may have potential as an antivirulence compound.CUP pili and flagella play active roles in the pathogenesis of a variety of Gram-negative bacterial infections, including urinary tract infections mediated by UPEC. These are extremely common infections that are often recurrent and increasingly caused by antibiotic-resistant organisms. Preventing piliation and motility through altered regulation and assembly of these important virulence factors could aid in the development of novel therapeutics. This study increases our understanding of the regulation of these virulence factors, providing new avenues by which to target their expression.
- Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Oct 27.
GSK2251052, a novel leucyl-tRNA synthetase (LeuRS) inhibitor, was in development for the treatment of infections caused by multi-drug resistant Gram-negative pathogens. In a Phase II study (LRS114688) evaluating the efficacy of GSK2251052 in complicated urinary tract infections, resistance developed very rapidly in 3 of 14 subjects enrolled, with ≥32-fold increases in the GSK2251052 MIC of the infecting pathogen. A fourth subject did not exhibit development of resistance in the baseline pathogen, but did present with a different pathogen, resistant to GSK2251052, post-therapy. Whole genome DNA sequencing from E. coli isolates collected longitudinally from two LRS114688 subjects confirms that GSK2251052 resistance is due to specific mutations, selected on the first day of therapy, in the LeuRS editing domain. Phylogenetic analysis strongly suggests that resistant Escherichia coli isolates resulted from clonal expansion of baseline susceptible strains. This resistance development likely resulted from the confluence of multiple factors, of which only some can be assessed pre-clinically. Our study shows the challenges of developing antibiotics and the importance of clinical studies to evaluate their effect on disease pathogenesis.
- Draft Genome Assemblies of Proteus mirabilis ATCC 7002 and Proteus vulgaris ATCC 49132. [Journal Article]
- Genome Announc 2014; 2(5)
The pleomorphic swarming bacilli of the genus Proteus are common human gut commensal organisms but also the causative agents of recurrent urinary tract infections and bacteremia. We sequenced and assembled the 3.99-Mbp genome of Proteus mirabilis ATCC 7002 (accession no. JOVJ00000000) and the 3.97-Mbp genome of Proteus vulgaris ATCC 49132 (accession no. JPIX00000000), both of which are commonly used reference strains.