Effects of exogenous Strigolactone on the physiological and ecological characteristics of Pennisetum purpureum Schum. Seedlings under drought stress.

BACKGROUND: Drought is one of the main environmental factors limiting plant growth and development. Pennisetum purpureum Schum. was used to explore the mitigation effects of exogenous strigolactone (SL) on drought stress during the seedling stage. The effects of different concentrations (1, 3, 5, and 7 µmol·L- 1) of SL on the photosynthesis characteristics, growth performance, and endogenous abscisic acid (ABA) of P. purpureum under drought stress were studied. RESULTS: Exogenous SL could effectively alleviate the inhibitory effect of drought stress on P. purpureum growth. Compared with drought stress, the net photosynthesis rate, stomatal conductance, transpiration rate, and water-use efficiency of the leaves of P. purpureum after SL treatment significantly increased, thereby exerting a significant mitigation effect on the decrease in photosystem II maximum photochemical efficiency and the performance index based on light absorption caused by drought. Moreover, the exogenous application of SL can effectively increase the fresh and dry weight of the leaves and roots and the main-root length. After applying SL for 120 h, the ABA content of P. purpureum decreased significantly. The activity of key enzymes of photosynthesis significantly increased after 48 h of external application of SL to P. purpureum. CONCLUSIONS: SL treatment can improve the photosynthesis performance of P. purpureum leaves under drought conditions and increase the antioxidant capacity of the leaves, thereby reducing the adverse effects of drought, promoting the growth of P. purpureum, and effectively improving the drought resistance of P. purpureum.

Aspergillus fumigatus Induces the Release of IL-8 and MCP-1 by Activating Nuclear Transcription Through Dectin-1 and CR3 Receptors in Alveolar Epithelial Cells.

Invasive pulmonary aspergillosis induced by the pathogenic fungus Aspergillus fumigatus is one of the common fatal complications in immunocompromised patients. Lung epithelial cells play an important role in host immune defense against A. fumigatus. However, the interaction between lung epithelial cells and A. fumigatus conidia is not fully understood. In this study, we used the swollen conidia of A. fumigatus to stimulate the type II lung epithelial A549 cells. Results showed that swollen conidia could significantly increase RNA transcription and protein expression of interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1), but not TNF-α in A549 cells in a time-dependent manner. Moreover, serum opsonization was able to improve the release of inflammatory factors induced by swollen conidia. Blocking of the dectin-1 or CR3 receptors, or both simultaneously, in the A549 cells could decrease the release of IL-8 and MCP-1. Additionally, blocking dectin-1 or CR3 could inhibit the transcription of nuclear factor NF-κB that was activated by swollen conidia. Here we reported for the first time that dectin-1 and CR3 receptors in A549 cells mediate the release of pro-inflammatory factors IL-8 and MCP-1 induced by A. fumigatus.

Identification and Characterization of Key Charged Residues in the Cofilin Protein Involved in Azole Susceptibility, Apoptosis, and Virulence of Aspergillus fumigatus.

Through some specific amino acid residues, cofilin, a ubiquitous actin depolymerization factor, can significantly affect mitochondrial function related to drug resistance and apoptosis in Saccharomyces cerevisiae; however, this modulation in a major fungal pathogen, Aspergillus fumigatus, was still unclear. Hereby, it was found, first, that mutations on several charged residues in cofilin to alanine, D19A-R21A, E48A, and K36A, increased the formation of reactive oxygen species and induced apoptosis along with typical hallmarks, including mitochondrial membrane potential depolarization, cytochrome c release, upregulation of metacaspases, and DNA cleavage, in A. fumigatus Two of these mutations (D19A-R21A and K36A) increased acetyl coenzyme A and ATP concentrations by triggering fatty acid ß-oxidation. The upregulated acetyl coenzyme A affected the ergosterol biosynthetic pathway, leading to overexpression of cyp51A and -B, while excess ATP fueled ATP-binding cassette transporters. Besides, both of these mutations reduced the susceptibility of A. fumigatus to azole drugs and enhanced the virulence of A. fumigatus in a Galleria mellonella infection model. Taken together, novel and key charged residues in cofilin were identified to be essential modules regulating the mitochondrial function involved in azole susceptibility, apoptosis, and virulence of A. fumigatus.

Elevated MIC Values of Imidazole Drugs against Aspergillus fumigatus Isolates with TR34/L98H/S297T/F495I Mutation.

The use of azole fungicides in agriculture is believed to be one of the main reasons for the emergence of azole resistance in Aspergillus fumigatus Though widely used in agriculture, imidazole fungicides have not been linked to resistance in A. fumigatus This study showed that elevated MIC values of imidazole drugs were observed against A. fumigatus isolates with TR34/L98H/S297T/F495I mutation, but not among isolates with TR34/L98H mutation. Short-tandem-repeat (STR) typing analysis of 580 A. fumigatus isolates from 20 countries suggested that the majority of TR34/L98H/S297T/F495I strains from China were genetically different from the predominant major clade comprising most of the azole-resistant strains and the strains with the same mutation from the Netherlands and Denmark. Alignments of sterol 14α-demethylase sequences suggested that F495I in A. fumigatus was orthologous to F506I in Penicillium digitatum and F489L in Pyrenophora teres, which have been reported to be associated with imidazole resistance. In vitro antifungal susceptibility testing of different recombinants with cyp51A mutations further confirmed the association of the F495I mutation with imidazole resistance. In conclusion, this study suggested that environmental use of imidazole fungicides might confer selection pressure for the emergence of azole resistance in A. fumigatus.

Role of actin depolymerizing factor cofilin in Aspergillus fumigatus oxidative stress response and pathogenesis.

Aspergillus fumigatus is a major fungal pathogen that is responsible for approximately 90% of human aspergillosis. Cofilin is an actin depolymerizing factor that plays crucial roles in multiple cellular functions in many organisms. However, the functions of cofilin in A. fumigatus are still unknown. In this study, we constructed an A. fumigatus strain overexpressing cofilin (cofilin OE). The cofilin OE strain displayed a slightly different growth phenotype, significantly increased resistance against H2O2 and diamide, and increased activation of the high osmolarity glycerol pathway compared to the wild-type strain (WT). The cofilin OE strain internalized more efficiently into lung epithelial A549 cells, and induced increased transcription of inflammatory factors (MCP-1, TNF-α and IL-8) compared to WT. Cofilin overexpression also resulted in increased polysaccharides including ß-1, 3-glucan and chitin, and increased transcription of genes related to oxidative stress responses and polysaccharide synthesis in A. fumigatus. However, the cofilin OE strain exhibited similar virulence to the wild-type strain in murine and Galleria mellonella infection models. These results demonstrated for the first time that cofilin, a regulator of actin cytoskeleton dynamics, might play a critical role in the regulation of oxidative stress responses and cell wall polysaccharide synthesis in A. fumigatus.

Role of the small GTPase Rho1 in cell wall integrity, stress response, and pathogenesis of Aspergillus fumigatus.

Aspergillus fumigatus is a major pathogen of invasive pulmonary aspergillosis. The small GTPase, Rho1, of A. fumigatus is reported to comprise a potential regulatory subunit of ß-1,3-glucan synthase and is indispensable for fungal viability; however, the role of AfRho1 on the growth, cell wall integrity, and pathogenesis of A. fumigatus is still poorly understood. We constructed A. fumigatus mutants with conditional- and overexpression of Rho1 and found that defects of AfRho1 expression led to the reduction of ß-1,3-glucan and glucosamine moieties on the cell wall, with down-regulated transcription of genes in the cell wall integrity signaling pathway and a decrease of calcofluor white (CFW)-stimulated mitogen-activated protein kinase (MpkA) phosphorylation and cytoplasmic leakage compared to those of the wild-type strain (WT). In addition, down-regulation of AfRho1 expression caused much higher sensitivity of A. fumigatus to H2O2 and alkaline pH compared to that of WT. Decrease of AfRho1 expression also attenuated the A. fumigatus pathogenicity in Galleria mellonella and inhibited conidial internalization into lung epithelial cells and inflammatory factor release. In contrast, overexpression of Rho1 did not alter A. fumigatus morphology, susceptibility to cell wall stresses, or pathogenicity relative to its parental strain. Taken together, our findings support AfRho1 as an essential regulator of the cell wall integrity, stress response, and pathogenesis of A. fumigatus.

Gliotoxin destructs the pulmonary epithelium barrier function by reducing cofilin oligomer formation to promote the dissolution of actin stress fibers.

The destruction of pulmonary epithelium is a major feature of lung diseases caused by the fungal pathogen Aspergillus fumigatus (A. fumigatus). Gliotoxin, a major mycotoxin of A. fumigatus, is widely postulated to be associated with the tissue invasion. However, the mechanism is unclear. In this study, we first discovered that cofilin, a regulator of actin dynamics in the pulmonary epithelial cells, existed mainly in the form of oligomer, which kept it unable to depolymerize actin filaments. Gliotoxin could reduce the formation of cofilin oligomer and promote the release of active cofilin monomer by regulating cofilin phosphorylation balance. Then, the active cofilin induced the dissolution of actin stress fibers to result in the disruption of pulmonary epithelium barrier function. Collectively, our study revealed a novel mechanism of gliotoxin destructing lung epithelium barrier function and for the first time indicated the role of cofilin oligomer in this process.

High prevalence and clonal dissemination of OXA-72-producing Acinetobacter baumannii in a Chinese hospital: a cross sectional study.

BACKGROUND: Carbapenem resistance in Acinetobacter baumannii in China was mainly mediated by OXA-23-like carbapenemases, while OXA-24/40-like carbapenemases were rarely identified. OXA-72 is one variant of OXA-24/40-like carbapenemases. This study aimed to demonstrate the epidemiology and characterizations of OXA-72-producing A. baumannii in a Chinese hospital. METHODS: A total of 107 clinical A. calcoaceticus-A. baumannii (Acb) complex isolates were collected in a Chinese hospital during between 2014 and 2016. These isolates were identified using Vitek 2 system and gyrB multiplex PCR. Vitek 2 system was used for antibiotic susceptibility testing. Genes encoding for major classes of carbapenemases were investigated by PCR. Rep-PCR was used for genotyping of all the A. baumannii isolates. The risk factors for carriage of OXA-72-producing or OXA-23-producing A. baumannii were analyzed through univariate and multivariate logistic regression. RESULTS: Of the 107 Acb isolates collected, 101 isolates (94.4%) and 6 isolates (5.6%) were identified as A. baumannii and A. pittii, respectively. 78 A. baumannii isolates (77.2%) were carbapenem resistant and mainly cultured from intensive care unit (ICU). blaOXA-72 and blaOXA-23 genes were identified in 45(57.7%) and 33(42.3%) carbapenem-resistant A. baumannii (CRAB), respectively. Multivariate risk factor analyses showed that prior carbapenem usage and nasogastric intubation were significantly associated with carriage of OXA-72-producing A. baumannii or OXA-23-producing A. baumannii. Rep-PCR analysis showed that 9 and 22 Rep-PCR types were assigned to 78 CRAB isolates and 23 carbapenem-susceptible A. baumannii (CSAB) isolates, respectively. A higher diverstiy of Rep-PCR patterns was observed among OXA-72-producing A. baumannii isolates than OXA-23-producing A. baumannii isolates, but all of them belonged to the same clone complex. MLST analysis suggested that the OXA-72 isolates from this study correspond to CC92/CC2 clone complex. CONCLUSIONS: This study demonstrates high prevalence and potential clonal spread of closely related genotypes of OXA-72-producing A. baumannii within a Chinese hospital. Continuous surveillance is necessary to monitor the dissemination of these strains in other healthcare settings to guide infection control policies in order to curb the spread of this bacterium.

Epidemiology and Molecular Characterizations of Azole Resistance in Clinical and Environmental Aspergillus fumigatus Isolates from China.

Azole resistance in Aspergillus fumigatus has emerged as a worldwide public health problem. We sought here to demonstrate the occurrence and characteristics of azole resistance in A. fumigatus from different parts of China. A total of 317 clinical and 144 environmental A. fumigatus isolates from 12 provinces were collected and subjected to screening for azole resistance. Antifungal susceptibility, cyp51A gene sequencing, and genotyping were carried out for all suspected azole-resistant isolates and a subset of azole-susceptible isolates. As a result, 8 (2.5%) clinical and 2 (1.4%) environmental A. fumigatus isolates were identified as azole resistant. Five azole-resistant strains exhibit the TR34/L98H mutation, whereas four carry the TR34/L98H/S297T/F495I mutation in the cyp51A gene. Genetic typing and phylogenetic analysis showed that there was a worldwide clonal expansion of the TR34/L98H isolates, while the TR34/L98H/S297T/F495I isolates from China harbored a distinct genetic background with resistant isolates from other countries. High polymorphisms existed in the cyp51A gene that produced amino acid changes among azole-susceptible A. fumigatus isolates, with N248K being the most common mutation. These data suggest that the wide distribution of azole-resistant A. fumigatus might be attributed to the environmental resistance mechanisms in China.

Occurrence of oral Candida colonization and its risk factors among patients with malignancies in China.

OBJECTIVES: Oral colonization of Candida could lead to later development of oropharyngeal candidiasis or candidemia among the immunocompromised patients. This study aims to describe the occurrence and risk factors of oral Candida colonization in patients with malignancies. MATERIALS AND METHODS: From October 2012 to March 2013, 78 patients with pulmonary cancer (group I), 101 patients with gastrointestinal tract tumor (group II), 79 patients with hematopoietic system malignant tumor (group III), and 101 healthy controls were consecutively recruited in a hospital in Beijing, China. The oral rinse samples were taken and Candida species were identified; the enzymes activities were tested. RESULTS: In total, 110 and 27 Candida strains were isolated from 91 patients and 26 controls, respectively. The oral colonization rate with Candida albicans in group III (12.7 %) was significant lower than that in group I (30.8 %), group II (33.7 %), and control group (25.7 %). The oral colonization rates with non-albicans Candida species in group I, group II, and group III were 15.4, 10.9, and 12.7 %, respectively, while only one non-albicans Candida strain was identified in control group. The non-albicans Candida species exhibited a lower virulence than C. albicans. Age was an independent risk factor for Candida colonization in patients with pulmonary cancer and digestive tract malignant tumor, "Teeth brush <1 time/day" was an independent risk factor for Candida colonization in patients with hematopoietic system tumor. CONCLUSIONS: The differences of risk factors for oral Candida colonization in patients with different cancers require different strategies for the prevention and control of Candida infection. CLINICAL RELEVANCE: Old aged patients with pulmonary cancer and digestive tract malignant tumor are high-risk population for Candida colonization. Increasing frequency of teeth brush might be helpful for preventing Candida colonization.

Evidence for the involvement of cofilin in Aspergillus fumigatus internalization into type II alveolar epithelial cells.

BACKGROUND: The internalization of Aspergillus fumigatus into alveolar epithelial cells (AECs) is tightly controlled by host cellular actin dynamics, which require close modulation of the ADF (actin depolymerizing factor)/cofilin family. However, the role of cofilin in A. fumigatus internalization into AECs remains unclear. RESULTS: Here, we demonstrated that germinated A. fumigatus conidia were able to induce phosphorylation of cofilin in A549 cells during the early stage of internalization. The modulation of cofilin activity by overexpression, knockdown, or mutation of the cofilin gene in A549 cells decreased the efficacy of A. fumigatus internalization. Reducing the phosphorylation status of cofilin with BMS-5 (LIM kinase inhibitor) or overexpression of the slingshot phosphatases also impeded A. fumigatus internalization. Both the C. botulimun C3 transferase (a specific RhoA inhibitor) and Y27632 (a specific ROCK inhibitor) reduced the internalization of A. fumigatus and the level of phosphorylated cofilin. ß-1,3-glucan (the major component of the conidial cell wall) and its host cell receptor dectin-1 did not seem to be associated with cofilin phosphorylation during A. fumigatus infection. CONCLUSION: These results indicated that cofilin might be involved in the modulation of A. fumigatus internalization into type II alveolar epithelial cells through the RhoA-ROCK-LIM kinase pathway.

Disruption of the phospholipase D gene attenuates the virulence of Aspergillus fumigatus.

Aspergillus fumigatus is the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases on A. fumigatus virulence is rather limited. In this study, disruption of the pld gene encoding phospholipase D (PLD), an important member of the phospholipase protein family in A. fumigatus, was confirmed to significantly decrease both intracellular and extracellular PLD activity of A. fumigatus. The pld gene disruption did not alter conidial morphological characteristics, germination, growth, and biofilm formation but significantly suppressed the internalization of A. fumigatus into A549 epithelial cells without affecting conidial adhesion to epithelial cells. Importantly, the suppressed internalization was fully rescued in the presence of 100 µM phosphatidic acid, the PLD product. Indeed, complementation of pld restored the PLD activity and internalization capacity of A. fumigatus. Phagocytosis of A. fumigatus conidia by J774 macrophages was not affected by the absence of the pld gene. Pretreatment of conidia with 1-butanol and a specific PLD inhibitor decreased the internalization of A. fumigatus into A549 epithelial cells but had no effect on phagocytosis by J774 macrophages. Finally, loss of the pld gene attenuated the virulence of A. fumigatus in mice immunosuppressed with hydrocortisone acetate but not with cyclophosphamide. These data suggest that PLD of A. fumigatus regulates its internalization into lung epithelial cells and may represent an important virulence factor for A. fumigatus infection.

InlB-mediated Listeria monocytogenes internalization requires a balanced phospholipase D activity maintained through phospho-cofilin.

Internalization of Listeria monocytogenes into non-phagocytic cells is tightly controlled by host cell actin dynamics and cell membrane alterations. However, knowledge about the impact of phosphatidylcholine cleavage driven by host cell phospholipase D (PLD) on Listeria internalization into epithelial cells is limited. Here, we report that L. monocytogenes activates PLD in Vero cells during the internalization. With immunostaining it was shown that both PLD1 and PLD2 surrounded partially or completely the phagocytic cup of most L. monocytogenes. Either up- or down-regulation of PLD expression (activity) diminished Listeria internalization. Both PLD1 and PLD2 in Vero cells were required for efficient Listeria internalization, and could substitute for each other in the regulation of Listeria internalization. Further, exogenous InlB activated host cell PLD1 and PLD2 via the Met receptor, and restored host PLD activation by InlB-deficient L. monocytogenes. InlB-induced PLD activation and Listeria internalization were tightly controlled by phospho-cycling of cofilin. PLD1, but not PLD2, was involved in cofilin-mediated PLD activation and Listeria internalization. These data indicate that cofilin-dependent PLD activation induced by InlB may represent a novel regulation mechanism for efficient Listeria internalization into epithelial cells.

A bronchofiberoscopy-associated outbreak of multidrug-resistant Acinetobacter baumannii in an intensive care unit in Beijing, China.

BACKGROUND: Bronchofiberscopy, a widely used procedure for the diagnosis of various pulmonary diseases within intensive care units, has a history of association with nosocomial infections. Between September and November 2009, an outbreak caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) was observed in the intensive care unit of a tertiary care hospital in Beijing, China. This study is aimed to describe the course and control of this outbreak and investigate the related risk factors. METHODS: Clinical and environmental sampling, genotyping with repetitive extragenic palindromic polymerase chain reaction (REP-PCR), and case-control risk factor analysis were performed in the current study. RESULTS: During the epidemic period, 12 patients were infected or colonized with MDR-Ab. Sixteen (72.7%) of twenty-two MDR-Ab isolates from the 12 patients and 22 (84.6%) of 26 MDR-Ab isolates from the bronchofiberscope and the healthcare-associated environment were clustered significantly into a major clone (outbreak MDR-Ab strain) by REP-PCR typing. Seven patients carrying the outbreak MDR-Ab strain were defined as the cases. Six of the seven cases (83%) received bronchofiberscopy versus four of the 19 controls (21%) (odds ratio, 22.5; 95% confidence interval, 2.07-244.84; P = 0.005). Several potential administrative and technical problems existed in bronchofiberscope reprocessing. CONCLUSIONS: Bronchofiberscopy was associated with this MDR-Ab outbreak. Infection control precautions including appropriate bronchofiberscope reprocessing and environmental decontamination should be strengthened.

Complement receptor 3 mediates Aspergillus fumigatus internalization into alveolar epithelial cells with the increase of intracellular phosphatidic acid by activating FAK.

Complement receptor 3 (CD11b/CD18) is an important receptor that mediates adhesion, phagocytosis and chemotaxis in various immunocytes. The conidia of the medically-important pathogenic fungus, Aspergillus fumigatus can be internalized into alveolar epithelial cells to disseminate its infection in immunocompromised host; however, the role of CR3 in this process is poorly understood. In the present study, we investigated the potential role of CR3 on A. fumigatus internalization into type II alveolar epithelial cells and its effect on host intracellular PA content induced by A. fumigatus. We found that CR3 is expressed in alveolar epithelial cells and that human serum and bronchoalveolar lavage fluid (BALF) could improve A. fumigatus conidial internalization into A549 type II alveolar epithelial cell line and mouse primary alveolar epithelial cells, which were significantly inhibited by the complement C3 quencher and CD11b-blocking antibody. Serum-opsonization of swollen conidia, but not resting conidia led to the increase of cellular phosphatidic acid (PA) in A549 cells during infection. Moreover, both conidial internalization and induced PA production were interfered by CD11b-blocking antibody and dependent on FAK activity, but not Syk in alveolar epithelial cells. Overall, our results revealed that CR3 is a critical modulator of Aspergillus fumigatus internalization into alveolar epithelial cells.

Gliotoxin Induces Cofilin Phosphorylation to Promote Actin Cytoskeleton Dynamics and Internalization of Aspergillus fumigatus Into Type II Human Pneumocyte Cells.

Aspergillus fumigatus is able to internalize into lung epithelial cells to escape from immune attack for further dissemination. We previously reported that gliotoxin, a major mycotoxin of A. fumigatus, promotes this internalization; however, the mechanism remained unclear. Here, we report that gliotoxin is able to induce cofilin phosphorylation in A549 type II human pneumocytes. Either too high or too low a level of cofilin phosphorylation blocked the gliotoxin-induced actin cytoskeleton rearrangement and A. fumigatus internalization. LIM domain kinase 1 (LIMK1) and its upstream small GTPases (Cdc42 and RhoA, but not Rac1) predominantly mediated the gliotoxin-induced cofilin phosphorylation and A. fumigatus internalization. Simultaneously, gliotoxin significantly stimulated an increase in cAMP; however, adding an antagonist of PKA did not block gliotoxin-induced A. fumigatus internalization. In vivo, exogenous gliotoxin helped gliotoxin synthesis deficient strain gliPΔ invade into the lung tissue and the lung fungal burden increased markedly in immunosuppressed mice. In conclusion, these data revealed a novel role of gliotoxin in inducing cofilin phosphorylation mostly through the Cdc42/RhoA-LIMK1 signaling pathway to promote actin cytoskeleton rearrangement and internalization of A. fumigatus into type II human pneumocytes.

Role of Downregulation and Phosphorylation of Cofilin in Polarized Growth, MpkA Activation and Stress Response of Aspergillus fumigatus.

Aspergillus fumigatus causes most of aspergillosis in clinic and comprehensive function analysis of its key protein would promote anti-aspergillosis. In a previous study, we speculated actin depolymerizing factor cofilin might be essential for A. fumigatus viability and found its overexpression upregulated oxidative response and cell wall polysaccharide synthesis of this pathogen. Here, we constructed a conditional cofilin mutant to determine the essential role of cofilin. And the role of cofilin downregulation and phosphorylation in A. fumigatus was further analyzed. Cofilin was required for the polarized growth and heat sensitivity of A. fumigatus. Downregulation of cofilin caused hyphal cytoplasmic leakage, increased the sensitivity of A. fumigatus to sodium dodecyl sulfonate but not to calcofluor white and Congo Red and farnesol, and enhanced the basal phosphorylation level of MpkA, suggesting that cofilin affected the cell wall integrity (CWI) signaling. Downregulation of cofilin also increased the sensitivity of A. fumigatus to alkaline pH and H2O2. Repressing cofilin expression in A. fumigatus lead to attenuated virulence, which manifested as lower adherence and internalization rates, weaker host inflammatory response and shorter survival rate in a Galleria mellonella model. Expression of non-phosphorylated cofilin with a mutation of S5A had little impacts on A. fumigatus, whereas expression of a mimic-phosphorylated cofilin with a mutation of S5E resulted in inhibited growth, increased phospho-MpkA level, and decreased pathogenicity. In conclusion, cofilin is crucial to modulating the polarized growth, stress response, CWI and virulence of A. fumigatus.

Predicting nosocomial lower respiratory tract infections by a risk index based system.

Although belonging to one of the most common type of nosocomial infection, there was currently no simple prediction model for lower respiratory tract infections (LRTIs). This study aims to develop a risk index based system for predicting nosocomial LRTIs based on data from a large point-prevalence survey. Among the 49328 patients included, the prevalence of nosocomial LRTIs was 1.70% (95% confidence interval [CI], 1.64% to 1.76%). The areas under the receiver operating characteristic (ROC) curve for logistic regression and fisher discriminant analysis were 0.907 (95% CI, 0.897 to 0.917) and 0.902 (95% CI, 0.892 to 0.912), respectively. The constructed risk index based system also displayed excellent discrimination (area under the ROC curve: 0.905 [95% CI, 0.895 to 0.915]) to identify LRTI in internal validation. Six risk levels were generated according to the risk score distribution of study population, ranging from 0 to 5, the corresponding prevalence of nosocomial LRTIs were 0.00%, 0.39%, 3.86%, 12.38%, 28.79% and 44.83%, respectively. The sensitivity and specificity of prediction were 0.87 and 0.79, respectively, when the best cut-off point of risk score was set to 14. Our study suggested that this newly constructed risk index based system might be applied to boost more rational infection control programs in clinical settings.

Assessing antibiotic therapy effectiveness against the major bacterial pathogens in a hospital using an integrated index.

AIM: To assess the effectiveness of antibiotic therapy against five indicator bacteria in a Chinese hospital using an index-based approach. METHODS: The study population comprises 1031 patients who had one clinically significant bacterial isolate in 2008, 2010 and 2013. Drug resistance index (DRI) based on pathogens was calculated. RESULTS: The adaptive DRIs for Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus decreased, while both adaptive and fixed DRIs for Acinetobacter spp. increased from 2008 to 2013. The adaptive DRIs for Escherichia coli increased from 2008 to 2013, while the fixed DRIs exhibited a decreasing trend. CONCLUSION: DRI could be used to demonstrate the changes of antimicrobial resistance and prescribing over time as a result of evolutionary processes and governmental regulatory interference.