Microbiology insights最新文献

Development of new antibiotics is always needed in the fight against growing threat from multiple drug-resistant bacteria, such as resistant Gram-negative (G-) Escherichia coli and Klebsiella pneumoniae. While the development of broad-spectrum antibiotics has attracted great attention, careful administration of these antibiotics is important to avoid adverse effects, like Clostridium difficile infection (CDI). The use of broad-spectrum antibiotics, for example, quinolones, can increase the risk of CDI by eradicating the protective bacteria in intestine and encouraging C difficile spore germination. Many common intestine bacteria are G- or anaerobic, including Enterococcus faecalis, Bacteroides fragilis, and E coli. Hence, it may be advantageous in certain therapeutic practices to employ selective antimicrobials. For instance, Gram-positive (G+) methicillin-resistant Staphylococcus aureus (MRSA) that can cause life-threatening sepsis can be controlled with the use of selective antibiotic, vancomycin. Nevertheless, its effectiveness has been limited with the emerging of vancomycin-resistant Staphylococcus aureus (VRSA). A recent report on antimicrobial cationic anthraquinone analogs (CAAs) that show tunable activity and selectivity may provide new hope in the search for selective antimicrobials. In particular, the lead CAA displays prominent activity against MRSA while manifesting low activity against E coli and low cytotoxicity toward normal mammalian cells.

Widespread antimalarial drug resistance has prompted the need for new therapeutics and greater understanding of malaria parasite biology. To this end, the isoprenoid biosynthesis inhibitor fosmidomycin has been used to probe the metabolic regulation in the malaria parasite, Plasmodium falciparum. Genetic changes in the haloacid dehalogenase (HAD) superfamily member HAD2 conferred resistance to fosmidomycin, at the cost of decreased fitness. In the absence of fosmidomycin, parasites gained mutations to phosphofructokinase that restored growth and fosmidomycin sensitivity, thus revealing an intriguing example of plasticity in a core glycolytic process. Moreover, this study marks a second report of a HAD superfamily protein-modulating metabolic homeostasis in P falciparum parasites. Haloacid dehalogenase enzymes are distributed across all domains of life and have increasingly been found to influence central carbon metabolism and drug sensitivity in P falciparum. Investigating the mechanisms by which HAD superfamily members modulate metabolism may shed light on how metabolic networks are connected in apicomplexan parasites and other organisms and may guide future therapeutic endeavors.

Objective: To provide insight into the practical implications of the use of ceftazidime/avibactam and meropenem/vaborbactam for the management of carbapenem-resistant Enterobacteriaceae (CRE) and to identify strategies for overcoming barriers to the use of these agents in clinical practice.

Data sources: A literature search of PubMed was conducted using the following search terms: ceftazidime/avibactam, meropenem/vaborbactam, carbapenem-resistant Enterobacteriaceae, antimicrobial stewardship, and clinical laboratory standards institute. Abstracts from infectious diseases conferences, article bibliographies, and relevant drug monographs were also reviewed.

Study selection/data extraction: Relevant English-language studies were considered.

Data synthesis: Studies demonstrating the clinical utility of ceftazidime/avibactam and meropenem/vaborbactam over older agents for CRE were summarized. Laboratory challenges, including lack of widespread technology and delays in usable information, and formulary considerations were discussed. Insight was provided into overcoming these challenges and minimizing barriers using infectious diseases pharmacists, antimicrobial stewardship teams, and infection control teams.

Relevance to patient care and clinical practice: This review informs clinicians of the potential difficulties of the use of ceftazidime/avibactam and meropenem/vaborbactam in clinical practice and provides tools to overcome these difficulties, thus allowing clinicians to stay at the forefront of CRE treatment.

Conclusions: Clinicians treating patients with CRE infections need to be aware of challenges they may face when using ceftazidime/avibactam and meropenem/vaborbactam. Infectious disease (ID) pharmacists and antimicrobial stewardship teams play an important role in minimizing barriers and ensuring appropriate use of these antibiotics.

Background: Tuberculosis (TB) incidence remains low in health departments of Castellon and La Plana-Vila-real, but TB elimination is challenging. The objective of this study was to estimate associated factors of pulmonary tuberculosis (PTB) compared with extrapulmonary tuberculosis (ETB) and investigate epidemiological characteristics of these pathologies to orient control and prevention actions.

Materials and methods: A prospective case-case study was implemented by comparing PTB and ETB incidences during 2013-2016 from notification reports, epidemiological surveillance, and microbiological results of hospitals' laboratories Hospital General Castellon and La Plana-Vila-Real in the province of Castellon of Valencia region in Spain. In this design, cases were patients with PTB and controls were patients with ETB. Directed acyclic graph approach was used for selection of potential risk and confounding factors. Adjusted odds ratios (AORs) were estimated by logistic regression models.

Results: The study included 136 patients with PTB and 57 patients with ETB, with microbiological confirmation of 93.4% and 52.6%, and the annual median of incidence rates were 7.5 and 3.1 per 100 000 inhabitants, respectively. In general, patients with PTB were younger with higher male proportion than patients with ETB. Risk factors of PTB were smoking tobacco (AOR = 3.98; 95% confidence interval [CI] = 1.66-9.56), social problems (social marginalization, homeless, residence in shelters for the poor, or stay in prison) (AOR = 3.39; 95% CI = 1.05-10.94), and contact with patients with TB (AOR = 2.51; 95% CI = 1.06-5.95). No-smoking tobacco and no-drug abuse interaction decrease PTB risk (AOR = 0.27; 95% CI = 0.12-0.64). From these results, specific measures of health promotion and prevention can be addressed.

Conclusions: The estimated associated factors of PTB may be prevented, and it was demonstrated that the case-case design is useful in the study of TB.

The biocontrol potential of four wild yeast strains (Meyerozyma guilliermondii - strain YS-1, Meyerozyma caribbica - strain YS-3, Cryptococcus albidus - strain YS-4, and Cryptococcus sp. - strain YS-5) against Penicillium expansum was studied in vivo (on Golden Delicious apples). The test yeasts were applied to the fruits alone as well as in combination with 2% CaCl₂. Treated apples were stored at room temperature (~21°C) for up to 2 weeks or under refrigeration (3°C) for up to 2 months. Candida oleophila was used as positive biocontrol agent. Biocontrol activities were expressed as percentages of lesion size reduction caused by the test yeasts or by test yeasts + CaCl₂ as compared with decays on apples treated with P. expansum alone. All strains tested during this study showed some degree of biocontrol activity against P. expansum. When the test yeasts were applied alone, they effected moderate pathogen inhibition reducing the decay size by 28% to 52% at day 7 and 11% to 27% at day 14 of incubation at room temperature. When the treated apples were stored at 3°C, lesion size reduction was between 48% and 63% after 1 month and 24% to 41% after 2 months of incubation. Addition of CaCl₂ to yeast suspensions facilitated much higher pathogen inhibition. At room temperature, lesion size reduction ranged between 74% and 77% during the first week. After 2 weeks of incubation, decays on yeast + CaCl₂-treated apples were still substantially smaller (49%-73% lower) than those on apples treated with P. expansum alone. At refrigeration, lesion size reduction ranged between 76% and 92% in the first month of storage and between 75% and 87% after 2 months of incubation. Decay incidence was 75% to 100% in apples stored at room temperature and 30% to 85% in those kept under refrigeration. The inhibitory activities of the wild yeast strains were similar to those exhibited by C. oleophila for the most part. These strains, when combined with CaCl₂, showed high potential as biocontrol agents against P. expansum on stored apples.

Objectives: The purpose of this study was to describe and explore potential driving factors of trends in reported chlamydia infections over time in Manitoba, Canada.

Methods: Surveillance and laboratory testing data from Manitoba Health, Seniors and Active Living were analysed using SAS v9.4. Kaplan-Meier plots of time from the first to second chlamydia infection were constructed, and Cox proportional hazards regression was used to estimate the risk of second repeat chlamydia infections in males and females.

Results: Overall, the number of reported infections found mirrored the number of tests conducted. From 2008 to 2014, the number of first infections found among females decreased as the number of first tests conducted among females also decreased. Between 2008 and 2012, the number of repeat tests among females increased and was accompanied by an increase in the number of repeat positive results from 2009 to 2013. From 2008 to 2016, the number of repeat tests and repeat positive results increased steadily among males.

Conclusions: Chlamydia infection rates consistently included a subset composed of repeat infections. The number of cases identified appears to mirror testing volumes, drawing into question incidence calculations that do not include testing volumes.

Summary box: 1) What is the current understanding of this subject? Chlamydia incidence is high in Manitoba, particularly among young women and in northern Manitoba.2) What does this report add to the literature? This report suggests that incidence calculated using case-based surveillance data alone does not provide an accurate estimate of chlamydia incidence in Manitoba and is heavily influenced by testing patterns.3) What are the implications for public health practice? In general, improving testing rates in clinical practices as well as through the provision of rapid services in non-clinical venues could result in higher screening and treatment rates. In turn, this could lead to a better understanding of true disease occurrence.

Pathogenic sepsis is not a monolithic condition. Three major types of sepsis exist within this category: bacterial, viral, and fungal, each with its own mechanism of action. While similar in symptoms, the etiologies and immune mechanisms of these types differ enough that a discrete patient base can be recognized for each one. Non-specific treatment, such as broad-spectrum antibiotics, without determination of sepsis origins may worsen sepsis symptoms and leads to increased morbidity and mortality in patients. However, recognition of current and historical patterns in likely patients for each sepsis type may aid in differentiation between pathogens prior to definitive blood testing. Clinicians may ultimately be able to diagnose and treat bacterial, viral, and fungal sepsis using analysis of previous patient patterns and circumstances in addition to standard care. This method is likely to decrease incidence of multidrug-resistant organisms, organ failure due to ineffective treatment, and turnaround time to the correct treatment for each sepsis patient. Ultimately, we aim to provide classification information on these patient populations and to suggest epidemiology-based screening methods that can be integrated into critical care medicine, specifically triage and treatment of sepsis.

A cascade of events leads to the development of microbial biofilm communities that are thought to be responsible for over 80% of infections in humans. However, not all surface-growing bacteria reside in a stationary biofilm state. Here, we have employed confocal Raman microscopy to analyze and compare variations in the alkyl quinolone (AQ) family of molecules during the transition between surface-attached motile-swarming and stationary biofilm communities. The AQs have been established previously as important to Pseudomonas aeruginosa biofilms, interspecies competition, and virulence. The AQ Pseudomonas quinolone signal (PQS) is also a known quorum-sensing signal. We detail spatial identification of AQ, PQS, and 2-alkyl-4-hydroxyquinoline N-oxide (AQNO) metabolites in both swarm and biofilm communities. We find that AQNO metabolites are abundant signatures in active swarming communities.

Plasmodium parasites, the causative agent of malaria infections, rapidly evolve drug resistance and escape detection by the human immune response via the incredible mutability of its genome. Understanding the genetic mechanisms by which Plasmodium parasites develop antimalarial resistance is essential to understanding why most drugs fail in the clinic and designing the next generation of therapies. A systematic genomic analysis of 262 Plasmodium falciparum clones with stable in vitro resistance to 37 diverse compounds with potent antimalarial activity was undertaken with the main goal of identifying new drug targets. Despite several challenges inherent to this method of in vitro drug resistance generation followed by whole genome sequencing, the study was able to identify a likely drug target or resistance gene for every compound for which resistant parasites could be generated. Known and novel P falciparum resistance mediators were discovered along with several new promising antimalarial drug targets. Surprisingly, gene amplification events contributed to one-third of the drug resistance acquisition events. The study can serve as a model for drug discovery and resistance analyses in other similar microbial pathogens amenable to in vitro culture.