Intensive care antibiotic consumption and resistance patterns: a cross-correlation analysis

Background

Over recent decades, a dramatic increase in infections caused by multidrug-resistant pathogens has been observed worldwide. The aim of the present study was to investigate the relationship between local resistance bacterial patterns and antibiotic consumption in an intensive care unit in a Romanian university hospital.

Methods

A prospective study was conducted between 1st January 2012 and 31st December 2013. Data covering the consumption of antibacterial drugs and the incidence density for the main resistance phenotypes was collected on a monthly basis, and this data was aggregated quarterly. The relationship between the antibiotic consumption and resistance was investigated using cross-correlation, and four regression models were constructed, using the SPSS version 20.0 (IBM, Chicago, IL) and the R version 3.2.3 packages.

Results

During the period studied, the incidence of combined-resistant and carbapenem-resistant P. aeruginosa strains increased significantly [(gradient = 0.78, R² = 0.707, p = 0.009) (gradient = 0.74, R² = 0.666, p = 0.013) respectively], mirroring the increase in consumption of β-lactam antibiotics with β-lactamase inhibitors (piperacillin/tazobactam) and carbapenems (meropenem) [(gradient = 10.91, R² = 0.698, p = 0.010) and (gradient = 14.63, R² = 0.753, p = 0.005) respectively]. The highest cross-correlation coefficients for zero time lags were found between combined-resistant vs. penicillins consumption and carbapenem-resistant P. aeruginosa strains vs. carbapenems consumption (0.876 and 0.928, respectively). The best model describing the relation between combined-resistant P. aeruginosa strains and penicillins consumption during a given quarter incorporates both the consumption and the incidence of combined-resistant strains in the hospital department during the previous quarter (multiple R² = 0.953, p = 0.017). The best model for explaining the carbapenem resistance of P. aeruginosa strains based on meropenem consumption during a given quarter proved to be the adjusted model which takes into consideration both previous consumption and incidence density of strains during the previous quarter (Multiple R² = 0.921, p = 0.037).

Conclusions

The cross-correlation coefficients and the fitted regression models provide additional evidence that resistance during the a given quarter depends not only on the consumption of antibacterial chemotherapeutic drugs in both that quarter and the previous one, but also on the incidence of resistant strains circulating during the previous quarter.

     

Parasitism of Aganaspis daci against Ceratitis capitata under Mediterranean climate conditions

The effect of environmental factors is essential to the success of parasitoids as biological control agents, as it determines their foraging activity, development, and survival. The larval‐pupal parasitoid wasp Aganaspis daci (Weld) (Hymenoptera: Figitidae) is known to have a very low fertility (i.e., offspring production) in the field in certain Mediterranean areas, probably due to its inability to efficiently oviposit under such climatic conditions. In this study, the percentage of parasitism and induced mortality (mortality of host pupae attributed to parasitoids, from which adults do not emerge) caused by this wasp to the Mediterranean fruit fly (medfly), Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), was assessed under field conditions across 1 year, using medfly‐infested apples and parasitoid‐confined release in a lemon orchard of southeastern Spain. As A. daci is known to have very few emergences in the field, fertility was assessed in the laboratory from parasitized pupae recovered from the field. We found average parasitism rates of 27% and high induced mortality rates of 66% under field conditions. Consequently, medfly population reduction (total mortality of C. capitata caused by A. daci, i.e., induced mortality + % parasitism) was, on average, 87%. Parasitism and induced mortality varied throughout the year, depending on the average temperature and relative humidity. The interaction of these factors resulted in the highest parasitism rates at low mean temperature and humidity values; likewise, the highest percentages of induced mortality were obtained with a combination of high mean temperature and low mean humidity values. In conclusion, A. daci may exert a strong impact on medfly populations, being a good candidate for inundative field releases for the management of C. capitata in the Mediterranean Basin.     

Association between line per se and testcross performance for eight agronomic and quality traits in winter rye

Key message

We investigated associations between line per se and testcross performance in rye and suggested that selection for per se performance is valuable for several traits in multi-stage selection programs.

Abstract

Genotypic correlation between line per se and testcross performance is an important quantitative-genetic parameter for optimizing hybrid breeding programs. The main goal of this survey was to study the association of line per se and testcross performance at the phenotypic level. We used experimental data from the line per se and testcross performance of two segregating winter rye populations (A, B) with each of 220 progenies tested in six environments for eight agronomic and quality traits. Genotypic variances were considerably larger for per se than for testcross performance of all investigated traits resulting in higher heritabilities of the former in most instances. Genotypic correlations (r _g) between testcross and line per se performance decreased with increasing complexity of the trait as shown by the respective heritabilities. They were highest (r _g ≥ 0.7) for plant height and test weight in population B, and thousand-kernel weight, falling number and starch content in both populations. A selection of these traits for line per se performance in early generations will save field plots in further testing testcross performance and increase efficiency of hybrid breeding.     

Recurrent dominant mutations affecting two adjacent residues in the motor domain of the monomeric kinesin KIF22 result in skeletal dysplasia and joint laxity

Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto-SEMDJL, aka SEMDJL, Hall type), is an autosomal dominant skeletal disorder that, in spite of being relatively common among skeletal dysplasias, has eluded molecular elucidation so far. We used whole-exome sequencing of five unrelated individuals with lepto-SEMDJL to identify mutations in KIF22 as the cause of this skeletal condition. Missense mutations affecting one of two adjacent amino acids in the motor domain of KIF22 were present in 20 familial cases from eight families and in 12 other sporadic cases. The skeletal and connective tissue phenotype produced by these specific mutations point to functions of KIF22 beyond those previously ascribed functions involving chromosome segregation. Although we have found Kif22 to be strongly upregulated at the growth plate, the precise pathogenetic mechanisms remain to be elucidated.     

Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion

Autosomal-recessive exfoliative ichthyosis presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of nonerythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Using whole-genome homozygosity mapping, candidate-gene analysis and deep sequencing, we have identified loss-of-function mutations in the gene for protease inhibitor cystatin A (CSTA) as the underlying genetic cause of exfoliative ichthyosis. We found two homozygous mutations, a splice-site and a nonsense mutation, in two consanguineous families of Bedouin and Turkish origin. Electron microscopy of skin biopsies from affected individuals revealed that the level of detachment occurs in the basal and lower suprabasal layers. In addition, in vitro modeling suggests that in the absence of cystatin A protein, there is a cell-cell adhesion defect in human keratinocytes that is particularly prominent when cells are subject to mechanical stress. We show here evidence of a key role for a protease inhibitor in epidermal adhesion within the lower layers of the human epidermis.     

Effect of the tyrosine kinase inhibitor lapatinib on CUB-domain containing protein (CDCP1)-mediated breast cancer cell survival and migration

The surface receptor CUB domain-containing protein 1 (CDCP1) is highly expressed in several adenocarcinomas and speculated to participate in anchorage-independent cell survival and cell motility. Tyrosine kinase phosphorylation seems to be crucial for intracellular signaling of CDCP1. Lapatinib, a tyrosine kinase inhibitor (TKI), is approved for treatment of HER-2/neu overexpressing metastatic breast cancer and functions by preventing autophosphorylation following HER-2/neu receptor activation. This study aimed to investigate the effect of CDCP1 expression on anchorage-independent growth and cell motility of breast cancer cells. Moreover, studies were performed to examine if lapatinib provided any beneficial effect on HER-2/neu^(+)/−/CDCP1⁺ breast cancer cell lines. In our studies, we affirmed that CDCP1 prevents cells from undergoing apoptosis when cultured in the absence of cell–substratum anchorage and that migratory and invasive properties of these cells were decreased when CDCP1 was down-regulated. However, only HER-2/neu⁺, but not HER-2/neu^(+)/− cells showed decreased proliferation and invasion and an enhanced level of apoptosis towards loss of anchorage when treated with lapatinib. Therefore, we conclude that CDCP1 might be involved in regulating adhesion and motility of breast cancer cells but that lapatinib has no effect on tyrosine kinases regulating CDCP1. Nonetheless, other TKIs might offer therapeutic approaches for CDCP1-targeted breast cancer therapy and should be studied considering this aspect.