大肠埃希菌耐药与抗菌药物使用量的相关性研究

目的探讨大肠埃希菌的耐药率与多种抗菌药物使用量之间的相关关系。方法计算主要抗菌药物每百床日的用药频度（DDDs）,以及温州医学院附属第一医院院内感染大肠埃希菌的耐药率,并采用多元线性回归的方法进行分析。结果大肠埃希菌对头孢他啶的耐药率与头孢哌酮和头孢克罗的用量呈负相关,与头孢他啶的用量呈正相关;对庆大霉素的耐药率与头孢他啶、哌拉西林的用量里负相关;对亚胺培南的耐药率与哌拉西林用量呈正相关,与季度呈负相关;对复方新诺明的耐药率与阿米卡星用量呈正相关;对呋喃妥因的耐药率与头孢他啶、去甲万古霉素用量呈负相关。结论在大肠埃希菌耐药水平和抗菌药物使用量之间存在相关关系。     

Imbalance of Pro- vs. Anti-Coagulation Factors in Chinese Patients with Budd-Chiari Syndrome and Non-Cirrhotic Portal Vein Thrombosis

Background and Aim

The coagulation abnormalities in non-cirrhotic Budd-Chiari syndrome (NC-BCS) and non-cirrhotic portal vein thrombosis (NC-PVT) are unclear. We conducted this case-control study to investigate the coagulation profile of NC-BCS and NC-PVT in Chinese patients.

Methods

We measured the levels of factors II, V, VII, VIII, IX, X, XI, XII, protein C (PC), protein S (PS) and antithrombin (AT) in blood samples from 37 NC-BCS patients, 74 NC-PVT patients, and 100 healthy controls. The levels and ratios of pro- and anti-coagulation factors were compared between patients with NC-BCS and healthy controls, between different types of NC-BCS and between NC-PVT and healthy controls.

Results

In patients with NC-BCS, factor VIII (P<0.001) was significantly elevated; factor V (P<0.001), VII (P<0.001), IX (P = 0.003), X (P<0.001), XI (P<0.001), XII (P<0.001), PC (P<0.001) and AT (P<0.001) were significantly decreased; and no difference was observed for factor II (P = 0.088) and PS (P = 0.199) compared with healthy controls. Factor VIII-to-PC (P = 0.008), factor VIII-to-PS (P = 0.037) and factor VIII-to-AT (P = 0.001) were significantly increased; other ratios were significantly reduced or did not show any difference. No differences were observed between different types of NC-BCS for individual pro- and anti-coagulation factors or the ratios between them. Among patients with NC-PVT, factor VIII (P<0.001) was significantly elevated and other factors were significantly decreased. Factor II-to-PC (P<0.001), factor VIII-to-PC (P<0.001), factor IX-to-PC (P<0.001), factor VIII-to-PS (P<0.001), factor II-to-AT (P<0.001), factor VIII-to-AT (P<0.001) and factor IX-to-AT (P<0.001) were significantly increased; all other ratios for NC-PVT were significantly reduced or did not show any significant difference.

Conclusions

NC-BCS and NC-PVT are associated with elevated levels of factor VIII and the decreased levels of PC and AT were probably the most significant features of coagulation imbalance. Additionally, NC-PVT was associated with decreased levels of PS.     

Analysis of multiple bacterial species and antibiotic classes reveals large variation in the association between seasonal antibiotic use and resistance

Understanding how antibiotic use drives resistance is crucial for guiding effective strategies to limit the spread of resistance, but the use–resistance relationship across pathogens and antibiotics remains unclear. We applied sinusoidal models to evaluate the seasonal use–resistance relationship across 3 species (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) and 5 antibiotic classes (penicillins, macrolides, quinolones, tetracyclines, and nitrofurans) in Boston, Massachusetts. Outpatient use of all 5 classes and resistance in inpatient and outpatient isolates in 9 of 15 species–antibiotic combinations showed statistically significant amplitudes of seasonality (false discovery rate (FDR) < 0.05). While seasonal peaks in use varied by class, resistance in all 9 species–antibiotic combinations peaked in the winter and spring. The correlations between seasonal use and resistance thus varied widely, with resistance to all antibiotic classes being most positively correlated with use of the winter peaking classes (penicillins and macrolides). These findings challenge the simple model of antibiotic use independently selecting for resistance and suggest that stewardship strategies will not be equally effective across all species and antibiotics. Rather, seasonal selection for resistance across multiple antibiotic classes may be dominated by use of the most highly prescribed antibiotic classes, penicillins and macrolides.

A study of the relationship between antibiotic use and resistance in Boston, Massachusetts shows that antibiotic resistance in multiple pathogens peaks in the winter/spring and is most correlated with the use of penicillins and macrolides – the antibiotics with winter-peaking use.     

A Multidisciplinary Intervention to Reduce Infections of ESBL- and AmpC-Producing,Gram-Negative Bacteria at a University Hospital

In response to a considerable increase in the infections caused by ESBL/AmpC-producing Klebsiella pneumonia in 2008, a multidisciplinary intervention, with a main focus on antimicrobial stewardship, was carried out at one university hospital. Four other hospitals were used as controls. Stringent guidelines for antimicrobial treatment and prophylaxis were disseminated throughout the intervention hospital; cephalosporins were restricted for prophylaxis use only, fluoroquinolones for empiric use in septic shock only, and carbapenems were selected for penicillin-allergic patients, infections due to ESBL/AmpC-producing and other resistant bacteria, in addition to their use in severe sepsis/septic shock. Piperacillin-tazobactam ± gentamicin was recommended for empiric treatments of most febrile conditions. The intervention also included education and guidance on infection control, as well as various other surveillances. Two year follow-up data on the incidence rates of patients with selected bacterial infections, outcomes, and antibiotic consumption were assessed, employing before-and-after analysis and segmented regression analysis of interrupted time series, using the other hospitals as controls. The intervention led to a sustained change in antimicrobial consumption, and the incidence of patients infected with ESBL-producing K. pneumoniae decreased significantly (p<0.001). The incidences of other hospital-associated infections also declined (p’s<0.02), but piperacillin-tazobactam-resistant Pseudomonas aeruginosa and Enterococcus faecium infections increased (p’s<0.033). In wards with high antimicrobial consumption, the patient gut carrier rate of ESBL-producing bacteria significantly decreased (p = 0.023). The unadjusted, all-cause 30-day mortality rates of K. pneumoniae and E. coli were unchanged over the four-year period, with similar results in all five hospitals. Although not statistically significant, the 30-day mortality rate of patients with ESBL-producing K. pneumoniae decreased, from 35% in 2008–2009, to 17% in 2010–2011. The two-year follow-up data indicated that this multidisciplinary intervention led to a statistically significant decrease in the incidence of ESBL/AmpC-resistant K. pneumoniae infections, as well as in the incidences of other typical hospital-associated bacterial infections.     

Vitamin D and Exercise Performance in Professional Soccer Players

Aim

The current study had two aims. The primary purpose was to examine the association between serum vitamin D levels and the ergometric evaluation of muscle strength, aerobic capacity, and speed in professional soccer players. The secondary aim was to evaluate the effects of the soccer off-season period on serum vitamin D levels.

Methods

Sixty-seven Caucasian male soccer players (age 25.6±6.2 and height 1.81±0.08 m), members of two Greek Superleague Soccer teams and one Football-league championship team participated in this study. Exercise performance testing for the determination of squat jump (SJ), countermovement jump (CMJ), 10 (10 m) and 20 meters (20 m) sprint performance, maximal oxygen consumption (VO₂max), anthropometry, and blood sampling were performed before (pre) and after (post) the six-week off-season period.

Results

Analysis of our results showed the following: (a) a significant correlations between serum vitamin D levels and performance parameters in both pre (SJ; P<0.001, CMJ; P<0.001, VO₂max; P<0.001, 10 m; P<0.001, and 20 m; P<0.001) and post (SJ; P<0.001, CMJ; P<0.001, VO₂max; P = 0.006, 10 m; P<0.001, and 20 m; P<0.001) experimental sessions. (b) Vitamin D concentration increased significantly (P<0.001) following the six-week off-season period compared to baseline, while at the same time all measured performance parameters decreased (SJ; P<0.001, CMJ; P<0.001, 10 m; P<0.001, 20 m; P<0.001, VO₂max; P<0.001).

Discussion

Our findings suggest that vitamin D levels are associated with the ergometric evaluation of muscle strength, as expressed by SJ and CMJ, sprinting capacity, and VO₂max in professional soccer players, irrespective the levels of performance. Furthermore, our data reaffirm the importance of UVB on serum vitamin D levels. Moreover, reductions in exercise training stress may also have beneficial effects on vitamin D levels, suggesting a possible association of its levels and the training-induced stress. Our results indicate a possibly bidirectional interaction between soccer performance indices and vitamin D levels.     

Effect of H. pylori Infection on Cytokine Profiles and Oxidative Balance in Subjects with Chronic Alcohol Ingestion

Different amounts of ingested alcohol can have distinct effects on the human body. However, there is limited research on chronic alcohol consumption with Helicobacter pylori infection. We sought to investigate the relationship between the cytokine profile, oxidative balance and H. pylori infection in subjects with chronic alcohol consumption. A total of 142 subjects were divided into three groups: 59 subjects with chronic alcohol ingestion and H. pylori infection (group A); 53 subjects with chronic alcohol ingestion without H. pylori infection (group B); and 30 control subjects (group C). The serum levels of CagA, interleukin (IL)-10, E-selectin, TNF-α, malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by enzyme-linked immunosorbent assay (ELISA). We found that the ages and serum H. pylori CagA levels among the three groups, as well as both the mean drinking age and the mean daily alcohol consumption between groups A and B, were matched and comparable. Comparing the BMIs among the three groups, the BMI differences were found to be statistically significant (F=3.921, P<0.05). Compared with group C, the BMIs in groups A and B were significantly higher (P<0.001 and P<0.01, respectively); however, the BMI differences between group A and group B were not statistically significant (P>0.05). Additionally, no differences in the serum CagA levels were found in comparisons among the groups (all P>0.05). The serum IL-10 and E-selectin levels in group A were significantly lower than those in group B (serum IL-10: P<0.05; E-selectin: P<0.05). The serum IL-10 in group A was significantly higher than that in group C (P<0.01); the serum E-selectin levels in group A did not significantly differ compared with those in group C (P>0.05). Furthermore, the serum IL-10 and E-selectin levels in group B were significantly higher than those in group C (serum IL-10: P<0.001; E-selectin: P<0.05); however, the serum TNF-α levels did not differ among groups (all P>0.05). Although the serum levels of MDA and SOD in groups A and B were slightly lower than those in group C, there were no significant differences among groups (all P>0.05). In conclusion, we believe that H. pylori infection might cause a significant inhibition of certain cytokine profiles in subjects with chronic alcohol ingestion. Moreover, chronically ingested alcohol may exert an adjusted inflammatory effect, but there was no association between H. pylori infection, chronic alcohol consumption and oxidative balance.     

Metabolomic Analysis Reveals Extended Metabolic Consequences of Marginal Vitamin B-6 Deficiency in Healthy Human Subjects

Marginal deficiency of vitamin B-6 is common among segments of the population worldwide. Because pyridoxal 5′-phosphate (PLP) serves as a coenzyme in the metabolism of amino acids, carbohydrates, organic acids, and neurotransmitters, as well as in aspects of one-carbon metabolism, vitamin B-6 deficiency could have many effects. Healthy men and women (age: 20-40 y; n = 23) were fed a 2-day controlled, nutritionally adequate diet followed by a 28-day low-vitamin B-6 diet (<0.5 mg/d) to induce marginal deficiency, as reflected by a decline of plasma PLP from 52.6±14.1 (mean ± SD) to 21.5±4.6 nmol/L (P<0.0001) and increased cystathionine from 131±65 to 199±56 nmol/L (P<0.001). Fasting plasma samples obtained before and after vitamin B6 restriction were analyzed by ¹H-NMR with and without filtration and by targeted quantitative analysis by mass spectrometry (MS). Multilevel partial least squares-discriminant analysis and S-plots of NMR spectra showed that NMR is effective in classifying samples according to vitamin B-6 status and identified discriminating features. NMR spectral features of selected metabolites indicated that vitamin B-6 restriction significantly increased the ratios of glutamine/glutamate and 2-oxoglutarate/glutamate (P<0.001) and tended to increase concentrations of acetate, pyruvate, and trimethylamine-N-oxide (adjusted P<0.05). Tandem MS showed significantly greater plasma proline after vitamin B-6 restriction (adjusted P<0.05), but there were no effects on the profile of 14 other amino acids and 45 acylcarnitines. These findings demonstrate that marginal vitamin B-6 deficiency has widespread metabolic perturbations and illustrate the utility of metabolomics in evaluating complex effects of altered vitamin B-6 intake.     

Surveillance and Correlation of Antimicrobial Usage and Resistance of Pseudomonas aeruginosa: A Hospital Population-Based Study

This retrospective study evaluated trends and association between resistance of Pseudomonas aeruginosa isolated from patients with hospital-acquired infections (HAIs) and hospital antimicrobial usage from 2003 through 2011 in a tertiary care hospital in northeast China. HAI was defined as occurrence of infection after hospital admission, without evidence that infection was present or incubating (≦48 h) on admission. In vitro susceptibilities were determined by disk diffusion test and susceptibility profiles were determined using zone diameter interpretive criteria, as recommended by Clinical and Laboratory Standards Institute (CLSI). Data on usage of various antimicrobial agents, expressed as defined daily dose (DDD) per 1,000 patients-days developed by WHO Anatomical Therapeutical Chemical (ATC)/DDD index 2011, were collected from hospital pharmacy computer database. Most of 747 strains of P. aeruginosa were collected from respiratory samples (201 isolates, 26.9%), blood (179, 24.0%), secretions and pus (145, 19.4%) over the years. Time series analysis demonstrated a significant increase in resistance rates of P. aeruginosa to ticarcillin/clavulanic acid, piperacillin/tazobactam, cefoperazone/sulbactam, piperacillin, imipenem, meropenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin except aminoglycosides over time in the hospital (P<0.001). The rates of carbapenem-resistant P. aeruginosa (CRPA) isolated from patients with HAIs were 14.3%, 17.1%, 21.1%, 24.6%, 37.0%, 48.8%, 56.4%, 51.2%, and 54.1% over time. A significant increase in usage of anti-pseudomonal carbapenems (P<0.001) was seen. ARIMA models demonstrated that anti-pseudomonal carbapenems usage was strongly correlated with the prevalence of imipenem and meropenem-resistant P. aeruginosa (P<0.001). Increasing of quarterly CRPA was strongly correlated at one time lag with quarterly use of anti-pseudomonal carbapenems (P<0.001). Our data demonstrated positive correlation between anti-pseudomonal antimicrobial usage and P. aeruginosa resistance to several classes of antibiotics, but not all antimicrobial agents in the hospital.     

The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors—A Nationwide Study

Objective

The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.

Methods

The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.

Results

The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000–2007 to 8.3% in 2008–2010 and 13.4% in 2011–2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.

Conclusions

The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.     

Obesity and Risk of Hip Fracture in Adults: A Meta-Analysis of Prospective Cohort Studies

Background

Many observational studies assessed the association between obesity and risk of hip fracture in adults, but reported controversial results. Our goal was to evaluate the association between obesity and risk of hip fracture in adults by conducting a meta-analysis of prospective cohort studies.

Methods

Three databases, PubMed, Embase and Web of Science, were searched through May 2012 to identify eligible cohort studies. Either a fixed- or a random-effects model was used to calculate the pooled relative risk (RR) with its 95% confidence interval (95%CI).

Results

Fifteen prospective cohort studies involving a total 3,126,313 participants were finally included into this meta-analysis. Overall, adults with obesity compared with the normal weight group had a significantly decreased risk of hip fracture (RR: 0.66, 95% CI 0.57 to 0.77, P<0.001). Meta-analyses by the adjusted status of RRs also suggested adults with obesity compared with the reference group had a significantly decreased risk of hip fracture (adjusted RR: 0.48, 95% CI 0.39 to 0.58, P<0.001; unadjusted RR: 0.66, 95% CI 0.56 to 0.78, P<0.001). Subgroup analyses by gender suggested individuals with obesity had a significantly decreased risk for developing hip fracture compared with the reference group in both men (RR 0.54, 95% CI 0.48 to 0.60, P<0.001) and women (RR 0.70, 95% CI 0.58 to 0.84, P<0.001). No evidence of publication bias was observed in this meta-analysis.

Conclusions

This meta-analysis of prospective cohort studies suggests that obesity significantly decreases the risk of hip fracture in adults, and obesity is probably a protective factor of hip fracture in adults.     

抗生素的使用情况调查及细菌耐药性分析

目的:分析我院的抗生素的使用频率以及细菌耐药率的变化,为规范临床用药提供参考资料。方法:采用回顾性分析的方法对我院2009年3月-2013年3月收治的8000例住院患者的抗生素使用情况进行调查,并对我院临床上常见革兰阴性菌和阳性菌的耐药率变化进行比较,分析抗生素的使用频率与细菌耐药率变化之间的关系。结果:临床上抗生素的使用频率最大的是β-内酰胺酶抑制剂以及头孢菌素类。金葡菌对环丙沙星的耐药率与青霉素类抗生素的DDDs呈正相关,大肠埃希菌对亚胺培南的耐药率与头孢菌素类抗生素的DDDs呈负相关。结论:抗生素的用药频率与病原菌对抗生素的耐药率有相关性,并且,单一的抗生素并不能引起病原菌的耐药性,而会同时影响其他类型的抗生素的耐药情况。     

Improvement of Insulin Sensitivity by Isoenergy High Carbohydrate Traditional Asian Diet: A Randomized Controlled Pilot Feasibility Study

The prevalence of diabetes is rising dramatically among Asians, with increased consumption of the typical Western diet as one possible cause. We explored the metabolic responses in East Asian Americans (AA) and Caucasian Americans (CA) when transitioning from a traditional Asian diet (TAD) to a typical Western diet (TWD), which has not been reported before. This 16-week randomized control pilot feasibility study, included 28AA and 22CA who were at risk of developing type 2 diabetes. Eight weeks of TAD were provided to all participants, followed by 8 weeks of isoenergy TWD (intervention) or TAD (control). Anthropometric measures, lipid profile, insulin resistance and inflammatory markers were assessed. While on TAD, both AA and CA improved in insulin AUC (−960.2 µU/mL×h, P = 0.001) and reduced in weight (−1.6 kg; P<0.001), body fat (−1.7%, P<0.001) and trunk fat (−2.2%, P<0.001). Comparing changes from TAD to TWD, AA had a smaller weight gain (−1.8 to 0.3 kg, P<0.001) than CA (−1.4 to 0.9 kg, P = 0.001), but a greater increase in insulin AUC (AA: −1402.4 to 606.2 µU/mL×h, P = 0.015 vs CA: −466.0 to 223.5 µU/mL×h, P = 0.034) and homeostatic static model assessment-insulin resistance (HOMA-IR) (AA: −0.3 to 0.2, P = 0.042 vs CA: −0.1 to 0.0, P = 0.221). Despite efforts to maintain isoenergy state and consumption of similar energy, TAD induced weight loss and improved insulin sensitivity in both groups, while TWD worsened the metabolic profile. Trial Registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00379548","term_id":"NCT00379548"}}NCT00379548     

Measuring Motivation for Appetitive Behaviour: Food-Restricted Broiler Breeder Chickens Cross a Water Barrier to Forage in an Area of Wood Shavings without Food

Broiler breeders (parents of meat chickens) are selected for fast growth and become obese if fed ad libitum. To avoid this and maintain good health and reproductive ability, they are feed restricted to about 1/3 of what they would eat ad libitum. As a result, they experience chronic hunger and exhibit abnormal behaviour patterns that may indicate stress and frustration. One approach to measuring hunger is to observe how much birds will work, such as pecking a key, for access to more or different types of food. However, the sight, smell, and feedback from consumption of the feed reward changes the context and may artificially raise feeding motivation. To avoid this, we tested broiler breeders in an apparatus in which they could work for access to a wooden platform covered in wood shavings by crossing a water runway which increased in length and depth in 8 successive tests. In the wood shavings area, they could perform exploratory and foraging behaviour (the appetitive phase of feeding) but were never rewarded with feed. Sixty birds were divided into three feed quantity treatments: commercial restriction (R), and twice (2R) or three times (3R) this amount. Overall, birds fed R worked harder to reach the wood shavings area (reached it in a larger number of tests) than 2R and 3R birds (P<0.001). More restricted birds took less time to reach the area (P<0.001, R<2R<3R) and spent more time foraging while there (P<0.001, R>2R>3R). This indicates that restricted-fed birds were hungry and willing to work for the opportunity to forage even though food was never provided, suggesting that their motivation to perform the appetitive component of feeding behaviour (foraging/food searching) was sufficient to sustain their response. Thus food restriction in broiler breeders is a welfare concern. However these methods could be used to test alternative feeding regimes to attempt to find ways of alleviating hunger while still maintaining healthy growth and reproduction in these birds.     

Leukocytosis and Enhanced Susceptibility to Endotoxemia but Not Atherosclerosis in Adrenalectomized APOE Knockout Mice

Hyperlipidemic apolipoprotein E (APOE) knockout mice show an enhanced level of adrenal-derived anti-inflammatory glucocorticoids. Here we determined in APOE knockout mice the impact of total removal of adrenal function through adrenalectomy (ADX) on two inflammation-associated pathologies, endotoxemia and atherosclerosis. ADX mice exhibited 91% decreased corticosterone levels (P<0.001), leukocytosis (WBC count: 10.0 ± 0.4 x 10E9/L vs 6.5 ± 0.5 x 10E9/L; P<0.001) and an increased spleen weight (P<0.01). FACS analysis on blood leukocytes revealed increased B-lymphocyte numbers (55 ± 2% vs 46 ± 1%; P<0.01). T-cell populations in blood appeared to be more immature (CD62L+: 26 ± 2% vs 19 ± 1% for CD4+ T-cells, P<0.001 and 58 ± 7% vs 47 ± 4% for CD8+ T-cells, P<0.05), which coincided with immature CD4/CD8 double positive thymocyte enrichment. Exposure to lipopolysaccharide failed to increase corticosterone levels in ADX mice and was associated with a 3-fold higher (P<0.05) TNF-alpha response. In contrast, the development of initial fatty streak lesions and progression to advanced collagen-containing atherosclerotic lesions was unaffected. Plasma cholesterol levels were decreased by 35% (P<0.001) in ADX mice. This could be attributed to a decrease in pro-atherogenic very-low-density lipoproteins (VLDL) as a result of a diminished hepatic VLDL secretion rate (-24%; P<0.05). In conclusion, our studies show that adrenalectomy induces leukocytosis and enhances the susceptibility for endotoxemia in APOE knockout mice. The adrenalectomy-associated rise in white blood cells, however, does not alter atherosclerotic lesion development probably due to the parallel decrease in plasma levels of pro-atherogenic lipoproteins.     

Voluntary Exercise Prevents Cisplatin-Induced Muscle Wasting during Chemotherapy in Mice

Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P<0.001), lean body mass (20.6%, P = 0.001), as well as anorexia, impaired muscle strength (22.5% decrease, P<0.001) and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P<0.001), maintained lean body mass (P<0.001) and muscle strength (P<0.001), reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival.     

Microbiological Surveillance of Peritoneal Dialysis Associated Peritonitis: Antimicrobial Susceptibility Profiles of a Referral Center in GERMANY over 32 Years

Objectives

Peritonitis is one of the most important causes of treatment failure in peritoneal dialysis (PD) patients. This study describes changes in characteristics of causative organisms in PD-related peritonitis and antimicrobial susceptibility.

Methods

In this single center study we analyzed retrospective 487 susceptibility profiles of the peritoneal fluid cultures of 351 adult patients with peritonitis from 1979 to 2014 (divided into three time periods, P1-P3).

Results

Staphylococcus aureus decreased from P1 compared to P2 and P3 (P<0.05 and P<0.01, respectively). Methicillin-resistant S. aureus (MRSA) occurred only in P3. Methicillin-resistant Staphylococcus epidermidis (MRSE) increased in P3 over P1 and P2 (P <0.0001, respectively). In P2 and P3, vancomycin resistant enterococci were detected. The percentage of gram-negative organisms remained unchanged. Third generation cephalosporin resistant gram-negative rods (3GCR-GN) were found exclusively in P3. Cefazolin-susceptible gram-positive organisms decreased over the three decades (93% in P1, 75% in P2 and 58% in P3, P<0.01, P<0.05 and P<0.0001, respectively). Vancomycin susceptibility decreased and gentamicin susceptibility in gram-negatives was 94% in P1, 82% in P2 and 90% in P3. Ceftazidim susceptibility was 84% in P2 and 93% in P3.

Conclusions

Peritonitis caused by MSSA decreased, but peritonitis caused by MRSE increased. MRSA peritonitis is still rare. Peritonitis caused by 3GCR-GN is increasing. An initial antibiotic treatment protocol should be adopted for PD patients to provide continuous surveillance.