Effects of Synthetic Retinoids on the Growth of Bacteria and Their Susceptibility to Antibiotics

Summary

In patients treated with oral retinoids the recovery of Propionibacterium acnes and other anaerobic bacteria in the skin is markedly reduced, whereas an increased colonization of the skin and a significant rise in the incidence of cutaneous staphylococcal infections are observed. Since very little is known about the effects of retinoids on bacteria, in the present study we investigated the influence of 4 retinoids (isotretinoin, etretinate, arotinoid ethyl ester, arotinoid sultane) in 15 different concentrations on the growth of 10 Gram-positive and Gram-negative bacteria in vitro and on their susceptibility to 10 antibiotics.

It was found that all retinoids were not capable of affecting either the growth of bacteria or their susceptibility to antibiotics. It seems reasonable, therefore, to assume that the retinoid-induced changes in cutaneous bacterial flora in vivo are due to mechanisms other than to the direct action of these compounds on bacteria.     

23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G

The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 2057-2611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects susceptibility to ketolides but does not influence susceptibility to other macrolide antibiotics. In addition, we provide evidence that the 2057-2611 polymorphism determines the fitness cost of the 23S rRNA A2058G resistance mutation. Supported by structural analysis, our results indicate that polymorphic nucleotides mediate the disparate phenotype of genotypically identical resistance mutations and provide an explanation for the large species differences in the epidemiology of defined drug resistance mutations.     

糖尿病患者腹股沟疝无张力修补术围手术期抗生素的临床应用

目的探讨糖尿病患者腹股沟疝无张力修补术是否需要常规预防性应用抗生素。方法回顾性分析近年收治合并糖尿病的腹股沟疝手术患者96例,其中预防性使用抗生素患者36例(A组);未使用抗生素患者60例(B组)。比较和评价两组患者术后体温、血液检查、切口的愈合情况。结果两组患者切口均愈合良好,手术前后外周血象白细胞计数,中性粒细胞比例及体温的变化差异均无统计学意义(P>0.05);结论糖尿病患者行腹股沟疝无张力修补术,只要在围手术期控制好血糖水平,勿需常规性使用抗生素。     

抗菌药物使用的多变量监控

目的 建立基于多变量数据分析(multivariate data analysis,MVA)的抗菌药物监控模型,为规范临床抗菌药物的合理使用提供依据。方法 提取浙江省立同德医院住院患者2011—2013年共12个季度81种抗菌药物的用药频度(defined daily doses,DDDs)数据,建立主成分分析(principal component analysis,PCA)模型。通过构建得分图和X区块模型距离(distance to model X block,DModX)控制图,结合变量贡献图,对不同季度的抗菌药物进行监控,评价季度一致性,分析导致异常的原因。结果 2011年第4季度和2012年、2013年4个季度抗菌药物DDDs的一致性较好。2011年第1~3季度的DModX统计值超出了控制限,主要原因为3种特殊使用级抗菌药物(头孢噻利、夫西地酸、去甲万古霉素)、8种限制使用级抗菌药物(头孢米诺、哌拉西林/舒巴坦、阿莫西林/舒巴坦、呋苄西林、头孢丙烯、头孢唑肟、异帕米星、奥硝唑)和4种非限制使用级抗菌药物(氯唑西林、头孢氨苄、头孢羟氨苄、头孢噻肟)的DDDs偏高。结论 本研究证明了MVA在抗菌药物监控中的有效性,为临床抗菌药物监控提供新的方法。     

Plazomicin: an investigational therapy for the treatment of urinary tract infections

Introduction: Living in the ever-expanding era of multidrug-resistant (MDR), extensively drug-resistant (XDR), and even pandrug-resistant Gram-negative microorganisms, the medical community is facing the approaching fear of the “End of Antibiotics.” Plazomicin is a next-generation aminoglycoside designed to evade all clinically relevant aminoglycoside-modifying enzymes, the main mechanism of aminoglycoside resistance. A newer aminoglycoside active against several MDR-XDR microorganisms is herein presented and discussed.

Areas covered: Herein, the authors present the currently available information on plazomicin. This includes the current knowledge concerning plazomicin’s: mechanisms of action, in vitro activity and interactions, its pharmacokinetics, its clinical efficacy in complicated urinary tract infections (cUTIs) and acute pyelonephritis, and its toxicity issues.

Expert opinion: Plazomicin was developed to evade all clinically relevant aminoglycoside-modifying enzymes. Unfortunately, ribosomal enzymatic modification by ribosomal 16S-rRNA methyltransferases confers broad-spectrum high-level aminoglycoside resistance. Still, plazomicin demonstrates high activity against the Enterobacteriaceae including extended spectrum beta lactamase and most carbapenemase producers, as well as several of the non-fermenters. When compared to levofloxacin, the in vivo activity of plazomicin in complicated urinary tract infections (cUTIs) and in acute pyelonephritis in humans was very promising. Furthermore, regarding safety, no clinically significant effects on renal, vestibular, or cochlear function have been observed both at Phase I and II studies in humans, with mild to moderate adverse events being dose related. However, the authors believe that the real position of plazomicin in the MDR-XDR world will be revealed once pending Phase III studies are completed.     

Clinical study of herbal mixture “Diding Oral Medicine” as an alternative to preventative antibiotics in perioperative hemorrhoids: A CARE-compliant article

To study the clinical effects of Diding Oral Medicine as an alternative to preventative antibiotics in perioperative hemorrhoids.From August 2017 to February 2018, a total of 214 patients who were treated with external exfoliation and internal ligation of mixed hemorrhoids in our hospital were divided into the control group and experimental group by way of stratified random (107 cases in each group). Patients in the control group were given antibiotics preventatively before operation, while patients in the experimental group took Diding Oral Medicine before operation, and the white blood cell count, neutrophil count, wound recovery, pain score, anal bulge score, and pathogen culture of wound secretions were compared between the 2 groups.There was no significant difference in white blood cell count and neutrophil count between both groups before and after operation (P > .05). The wound seepage score, wound edema score, and wound area score in the experimental group were lower than those in the control group, and the wound healing in the experimental group was shorter than that in the control group (all P < .05). The pain score and anal bulge score of the experimental group were decreased significantly compared to the control group (P < .05). In addition, the detection rate of pathogenic bacteria in the experimental group was downregulated significantly compared to the control group (P < .05).The Diding Oral Medicine has prominent bacteriostatic and antibacterial effects on patients with hemorrhoids during perioperative period, and promotes wound healing, reduces pain stress, and anal bulge.     

Pharmacological approach to acute pancreatitis

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis （AP） based on experimental animal models and clinical trials. Somatostatin （SS） and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis （PEP）. The protease inhibitor Gabexate mesilate （GM） is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin （NGL） is a nitrogen oxide （NO） donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs （NSAID） indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 （IL-10） is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha （TNF-α） have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta- lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.     

Pediatric patients who receive antibiotics for fever and neutropenia in less than 60 min have decreased intensive care needs

Background

Antibiotic delivery to patients with fever and neutropenia (F&N) in <60 min is an increasingly important quality measure for oncology centers, but several published reports indicate that a time to antibiotic delivery (TTA) of <60 min is quite difficult to achieve. Here we report a quality improvement (QI) effort that sought to decrease TTA and assess associated clinical outcomes in pediatric patients with cancer and F&N.

Procedure

We used Lean‐Methodology and a Plan‐Do‐Study‐Act approach to direct QI efforts and prospectively tracked TTA measures and associated clinical outcomes (length of stay, duration of fever, use of imaging studies to search for occult infection, bacteremia, intensive care unit (ICU) consultation or admission, and mortality). We then performed statistical analysis to determine the impact of our QI interventions on total TTA, sub‐process times, and clinical outcomes.

Results

Our QI interventions significantly improved TTA such that we are now able to deliver antibiotics in <60 min nearly 100% of the time. All TTA sub‐process times also improved. Moreover, achieving TTA <60 min significantly reduced the need for ICU consultation or admission (P = 0.003) in this population.

Conclusion

Here we describe our QI effort along with a detailed assessment of several associated clinical outcomes. These data indicate that decreasing TTA to <60 min is achievable and associated with improved outcomes in pediatric patients with cancer and F&N. Pediatr Blood Cancer 2015;62:807–815. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.     

Childhood infections and the risk of inflammatory bowel disease

Adults with inflammatory bowel disease from North Carolina were questioned during 1986 and 1987 to assess risk due to a variety of childhood infections and treatments with antibiotics. Responses were compared with those of neighbor controls. Persons with Crohn's disease were more likely to report an increased frequency of childhood infections in general (odds ratio 4.67, 95% CI 2.65–8.23) and pharyngitis specifically (odds ratio 2.14, 95% CI 1.30–3.51). This was validated by an increased frequency of tonsillectomy (odds ratio 1.53, 95% CI 1.07–2.20). Crohn's cases were more likely to report frequent treatment with antibiotics for both otitis (odds ratio 2.07, 95% CI 1.03–4.14) and pharyngitis (odds ratio 2.14, 95% CI 1.20–3.84). Although Crohn's cases were more likely to report frequent exposure to penicillin (odds ratio 1.81, 95% CI 0.98–3.31), there did not appear to be excess risk conferred by penicillin after controlling for frequency of infections. Persons with ulcerative colitis also reported an excess of infections generally (odds ratio 2.37, 95% CI 1.19–4.71), but not an excess of specific infections or treatments with antibiotics. Persons who reported an increased frequency of infections tended to have an earlier onset of Crohn's disease (P<0.0001) and ulcerative colitis (P=0.04). Finally, it was noted that urban living in childhood increased the risk for Crohn's disease. We conclude that childhood infections may be a risk factor for Crohn's disease and may presage the early onset of disease.This research was supported in part by grants from the Crohn's and Colitis Foundation of America and the National Irstitutes of Health (P30 DK34987, T32 DK07364 and RR00046).