Pseudomonas aeruginosa biofilm hampers murine central wound healing by suppression of vascular epithelial growth factor

Biofilm‐infected wounds are clinically challenging. Vascular endothelial growth factor and host defence S100A8/A9 are crucial for wound healing but may be suppressed by biofilms. The natural course of Pseudomonas aeruginosa biofilm infection was compared in central and peripheral zones of burn‐wounded, infection‐susceptible BALB/c mice, which display delayed wound closure compared to C3H/HeN mice. Wounds were evaluated histopathologically 4, 7 or 10 days post‐infection. Photoplanimetry evaluated necrotic areas. P. aeruginosa biofilm suppressed vascular endothelial growth factor levels centrally in BALB/c wounds but increased peripheral levels 4–7 days post‐infection. Central zones of the burn wound displayed lower levels of central vascular endothelial growth factor as observed 4 and 7 days post‐infection in BALB/c mice compared to their C3H/HeN counterparts. Biofilm suppressed early, centrally located S100A8/A9 in BALB/c and centrally and peripherally later on in C3H/HeN wounds as compared to uninfected mice. Peripheral polymorphonuclear‐dominated inflammation and larger necrosis were observed in BALB/c wounds. In conclusion, P. aeruginosa biofilm modulates wounds by suppressing central, but inducing peripheral, vascular endothelial growth factor levels and reducing host response in wounds of BALB/c mice. This suppression is detrimental to the resolution of biofilm‐infected necrosis.     

The changing pattern of antimicrobial resistance within 42,033 Escherichia coli isolates from nosocomial, community and urology patient-specific urinary tract infections, Dublin, 1999-2009

Study Type – Therapy (practice patterns cohort) Level of Evidence not applicable What's known on the subject? and What does the study add? Epidemiological and resistance patterns of bacterial pathogens in urinary tract infections show large inter‐regional variability, and rates of bacterial resistance are continually changing due to different regional antibiotic treatment regime. In Ireland and the UK, trimethoprim or nitrofurantoin is usually recommended for empirical treatment of uncomplicated cystitis in the community whilst parenteral cephalosporins, aminoglycosides, quinolones and co‐amoxyclav are reserved for complicated UTIs. Neither penicillins nor trimethoprim represent suitable empirical antimicrobial agents for UTI in this study population. The high rate of ciprofloxacin resistance in encountered is suggestive of an over‐reliance on this agent in this population and with resistance rates approaching 30%, empirical use of quinolones for urology patients is inadvisable. E. coli UTIs have remained extremely sensitive to nitrofurantoin across all three patient sample groups in this population and the resistance rate has not changed significantly over the eleven‐year study period.

OBJECTIVE

• ? To investigate the changing pattern of antimicrobial resistance in Escherichia coli urinary tract infection over an eleven year period, and to determine whether E. coli antibiotic resistance rates vary depending on whether the UTI represents a nosocomial, community acquired or urology patient specific infection.

PATIENT AND METHODS

• ? A retrospective analysis of the 42 033 E. coli urine isolates from the 11‐year period 1999–2009 in a single Dublin teaching hospital was performed.
• ? WHONET^TM software was used to analyse the changing pattern of sensitivity and resistance of E. coli to commonly used antibiotics over the study period.
• ? The origins of the urine samples were stratified into three groups: inpatients with nosocomial UTIs; urine originating from the emergency department and general practice (community UTIs); and UTIs in urology patients.

RESULTS

• ? Urinary tract infections in the urology patient population demonstrate higher antibiotic resistance rates than nosocomial or community UTIs.
• ? There were significant trends of increasing resistance over the 11‐year period for ampicillin, trimethoprim, gentamicin and ciprofloxacin, and significant differences in co‐amoxyclav, gentamicin, nitrofurantion and ciprofloxacin resistance rates depending on the sample origin.
• ? Ampicillin and trimethoprim were the least active agents against E. coli, with total 11‐year resistance rates of 58.3 and 33.8%, respectively.
• ? The overall gentamicin resistance rate was 3.4% and is climbing at a rate of 0.7% per year (P < 0.001). Within the urology patient population the resistance rate was 6.4%.
• ? Ciprofloxacin resistance approaches 20% in the nosocomial UTI population and approaches 30% in the urology population; however, it remains a reasonable empirical antibiotic choice in this community, with an 11‐year resistance rate of 10.6%.

CONCLUSIONS

• ? E. coli remains the commonest infecting uropathogen in the community and hospital setting with its incidence climbing from 50 to 60% of UTIs over the 11‐year period.
• ? Neither penicillins nor trimethoprim represent suitable empirical antimicrobials for UTI and ciprofloxacin resistance in this Dublin‐based study renders it unsuitable empirical therapy for nosocomial UTIs and UTIs in the urology population.
• ? The dramatic 11‐year rate increase in gentamicin resistance is of paramount concern.

     

Hyperbilirubinemia and urinary tract infection: the effect of indirect hyperbilirubinemia on the in vitro growth of uropathogen Escherichia coli in newborn urine

High serum bilirubin is antioxidant and cytoprotective. We evaluated if urine samples of hyperbilirubinemic newborns impede uropathogenic Escherichia coli growth. Bag-urine samples of hyperbilirubinemic newborns (study group) were cultured at presentation and during remission. Urine sample were obtained only once from healthy newborns (control group). Escherichia coli [2?×?104?colony-forming unit (cfu)/mL] was inoculated into the sterile urine samples and colony counts were determined after 24?h. Bilirubin levels at presentation and remission were also recorded. Escherichia coli colony counts of the control versus study groups and of the presentation versus remission samples in the study group were compared. There were 13 study and 17 control cases. Escherichia coli colony counts were not different in the study group at presentation versus remission (5.4?±?0.7 vs. 5.5?±?0.8 log₁₀, respectively; p?=?0.659). Escherichia coli colony count of the control group (5.2?±?0.6 log₁₀) was also not different from the study group. In conclusion, the urine of hyperbilirubinemic newborns did not affect the growth rate of uropathogenic E. coli.     

The effect of circumcision on the frequency of urinary tract infection,growth and nutrition status in infants with antenatal hydronephrosis

Abstract

The objective of this study was to determine the effect of circumcision on the frequency of urinary tract infection (UTI), growth development, and the nutrition status in infants with antenatal hydronephrosis (AH). The data were collected prospectively between 1998 and 2010. Infants with a fetal pelvis diameter of >5?mm identified with antenatal ultrasound were followed-up. Body height and weight were expressed as HZ scores (observed height???median height/standard deviation) and WZ scores (observed weight???median weight/Standard deviation). The nutritional status was evaluated and the body weight was transformed to a weight-for-height index (WHI?=?weight/median weight for the height age?×?100). The HZ and WZ scores or WHI were calculated for each patient at the first and last visits. The chi-square and Student’s t tests were used for statistical analysis. A p value <0.05 was considered significant. The study included 178 (134 males, 44 females) patients. Of these, 29 were diagnosed by vesicoureteral reflux (VUR), 87 by obstructive uropathy, and 54 by normal. Of 134 males, 111 infants were circumcised. The mean monitoring time was 45±24.9 months and the mean age of circumcision was 14?±?16.06 months. The pre-circumcision UTI frequency (2.97?±?1.14/y) was significantly higher than post-circumcision period (0.25?±?0.67/y) (p?<?0.05). Also, pre-circumcision UTI frequency (2.97?±?1.14/y) was significantly higher than the UTI frequency observed in female cases (0.85?±?0.91/y) and in the overall study group (0.73?±?0.79/y) (p?<?0.05). In all patients, the HZ of the circumcised subjects (0.18?±?1.01) was statistically higher than uncircumcised subjects (?0.26?±?0.92) (p?<?0.05). Although statistically insignificant, the HZ of the circumcised males (0.13?±?1.24) with VUR was higher than the uncircumcised patients (0.03?±?0.55) (p?>?0.05). In obstructive uropathy groups, the HZ of the circumcised males (?0.13?±?0.54) was also found to be higher than uncircumcised males (?0.49?±?0.66) (p?<?0.05). Although nutrition scores were found to be better in circumcised males, no statistically significant effect of circumcision on the nutrition status was detected. In conclusion, postnatal early circumcision of infants with AH seems to prevent frequent UTIs and nutritional disturbances enabling normal growth.     

血管内皮生长因子D基因转移对胆汁性肝硬变大鼠肝纤维化和门静脉压力的影响

目的观察胆汁性肝硬变大鼠门静脉注射血管内皮生长因子D(hVEGF-D)后的促血管形成效应以及对肝纤维化和门静脉压力的影响。方法30只SD大鼠胆总管结扎法制作胆汁性肝硬变模型,治疗组门静脉注射PCHO／hVEGF-D 150μg／只,2周后比较肝组织纤维化程度(苏木素-伊红染色、浸银染色法)、门静脉压力、VEGF蛋白质表达、肝组织微血管密度改变。结果肝组织纤维化程度较注射前明显降低;门静脉压力治疗前为(15．45±1．97)cm H_2O(1 cmH_2O= 0．098 kPa);治疗后则变为(12．56±1．86),差异有统计学意义(P<0．05)。治疗组VEGF蛋白质表达平均染色积分为6．56±1．81,肝硬变对照组4．4±1．02,差异有统计学意义(P<0．01)。治疗组血管计数为14．33±3．24;肝硬变对照为9．2±1．48(P<0．01)。结论胆汁性肝硬变大鼠门静脉注射血管内皮生长因子D表达载体后可以一定程度上促进肝内血管形成、减缓肝纤维化程度降低门静脉压力。     

Clinical impact of culture-positive preservation fluid on solid organ transplantation: A systematic review and meta-analysis

Contamination of the preservation fluid (PF) used for donated organs is a potential source of post-transplant infection. However, the information on this issue is scarce. We therefore conducted a systematic review and meta-analysis to assess the incidence of culture-positive PF and its impact on solid organ transplant (SOT) recipients. Seventeen studies were identified and included. The overall incidence of culture-positive PF was 37% (95% CI: 27% to 49%), and the incidence of PF-related infections among SOT recipients with PF cultures that grew pathogenic microorganisms was 10% (95% CI: 7% to 15%). There were differences in the rates of infections due to pathogenic microorganisms between SOT recipients who received pre-emptive treatment and those who did not, but without statistical significance. The mortality rate among SOT recipients with PF-related infection was 35% (95% CI: 21% to 53%). In conclusion, although contamination of the PF of donated organs is frequent, the incidence of PF-related infection is relatively low. A closely clinical and microbiologic monitoring of the SOT recipient in case of culture-positive PF, regardless of the type of microorganism isolated might be do in order to establish a prompt diagnosis of PF-related infection.