Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre– or post–liver transplant

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre– or post–liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6–29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre–LT and 26 post–LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre–LT and three post–LT. Overall, transplant free survival was 42.8% at 4 years and post–LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post–LT, with post–LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.     

Letermovir in lung transplant recipients with cytomegalovirus infection: A retrospective observational study

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log₁₀) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.     

Selective transperineal prostate biopsy for fluoroquinolone-resistance patients reduces sepsis and cost

Background:Urosepsis is a recognized complication of transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Pre-biopsy rectal swabs have been used to identify patients with microorganisms in the rectal flora resistant to the conventionally used empirical prophylaxis. The transperineal route of biopsy (TP-Bx) has a lower complication risk but comes at an increased cost.Materials and methods:Retrospective cohort study including patients undergoing prostate biopsies between October/2015 and April/2018. The intervention cohort, a rectal swab was performed, the result of which dictated the biopsy route; TRUS-Bx against TP-Bx. TP-Bx for patients with fluoroquinolone resistance or extended-spectrum β-lactamase. The control cohort underwent TRUS without a rectal swab receiving empirical antibiotics—oral ciprofloxacin and intravenous gentamicin.Results:Total 1000 patients were included in which 500 underwent a swab, 14 (2.8%) developed post-TRUS biopsy infective complications with 3 having positive bacteremia (0.6%); 500 had no swab, 47 (9.4%) developed post-TRUS biopsy infective complications with 22 (4.4%, p < 0.05) having positive bacteremia. Three patients (0.6%) of patients who underwent swab developed urinary tract infection symptoms whilst 12 (2.4%) had urinary tract infection in the control group. In those patients that underwent a swab, 14 required hospitalization with mean length of stay of 2.5 days versus 43 patients of the control with 3.6 days. Cost analysis concluded savings of this strategy was £18,711.Conclusions:We have demonstrated a protocol that reserves template biopsies for higher risk patients and can significantly reduce sepsis and other infectious complication rates whilst also proving to be a cost-efficient strategy. We recommend that units not utilizing rectal swabs to uncover the fluoroquinolone resistance rate by introducing them. We advocate units that already utilize rectal swabs, to introduce transperineal biopsy for their higher risk patients.     

Effects of low, subinhibitory concentrations of antibiotics on expression of a virulence gene cluster of pathogenic Escherichia coli by using a wild-type gene fusion

S fimbrial adhesins (Sfa) represent virulence factors of E. coli wild-type strains causing urinary tract infections and meningitis of the new born. In order to determine the influence of subinhibitory concentration of antibiotics on the expression of the sfa gene cluster, a wild-type strain carrying the lacZ gene, coding for the enzyme β-galactosidase fused to the sfa determinant was used. The expression of lacZ which was under the control of the sfa wild-type promoters, was now equivalent to the sfa gene expression of wild-type strain 536. With this strain the influence of subinhibitory concentrations of 28 antibiotics on the expression of the sfa determinant was studied. The expression was strongly suppressed by a treatment of the wild-type fusion strain by aztreonam, gentamicin, clindamycin and trimethoprim; the latter had a dramatic effect on sfa expression. It was further shown for clindamycin and trimethoprim that the reduction of sfa gene expression was dependent on the concentration of the antibiotics. In contrast imipinem, amphotericin B and rifampicin weakly stimulated sfa expression. We conclude that gene fusions between virulence-associated loci and indicator genes in wild-type pathogens are useful to study virulence modulation due to subinhibitory concentration of antibiotics on the genetic level.     

Experimental antitumor activity of BMY-28175 a new fermentation derived antitumor agent

Summary BMY-28175 is a novel antitumor antibiotic produced in fermentation by Actinomadura verrucosospora. The cytotoxic effects of BMY-28175 were determined using murine and human tumor cell lines in vitro. Following 72 hour exposure, the drug had IC50 values 1.5 to 13.5 ng/ml in a microtiter assay. BMY-28175 was evaluated for antitumor activity against several experimental murine and human tumor models. The drug administered ip was active against ip implanted P388 leukemia, L1210 leukemia, B16 melanoma, M109 lung carcinoma, C26 colon carcinoma, M5076 sarcoma and Lewis lung carcinoma. In addition, BMY-28175 administered iv was active against iv implanted P388 and L1210 leukemias. BMY-28175 was active against sc implanted B16 melanoma (increased lifespan and/or inhibition of primary tumor growth) in about 60% of the tests. The growth of sc implanted M109 was inhibited by BMY-28175 in a single experiment. BMY-28175 was also active against the MX-1 human mammary xenograft implanted in the subrenal capsule of nude mice. The optimal dose for BMY-28175 in these various studies ranged from 0.16 g/kg per injection with consecutive daily (qd1-9) administration, to 51.2 g/kg with single dose administration. The results of these studies indicate that BMY-28175 is one of the most potent antitumor agents yet observed, with a broad spectrum of activity against tumors of murine and human origin and activity against tumors located distal to the site of drug administration.     

注射用阿奇霉素治疗细菌性感染临床观察

目的 :评价国产注射用阿奇霉素治疗细菌性感染的临床疗效和安全性。方法 :采用随机对照方法 ,将 43例下呼吸道感染和 33例泌尿道感染分验证组和对照组。 43例验证组给予注射用阿奇霉素 0 .2 5 g静脉滴注 ,每天 1次 ;33例对照组给予注射用头孢呋辛 1.5g静脉滴注 ,每天 2次 ,两组疗程均为 5天。结果 :验证组有效率为 83.7% ,细菌清除率为 72 .5 % ,药物敏感率为 80 .8% ;对照组有效率为 81.8% ,细菌清除率为 77.4% ,药物敏感率为 82 .2 % ,两组差异均无显著性 (P >0 .0 5 )。两组不良反应轻微。结论 :注射用阿奇霉素是一种有效、安全的治疗细菌性感染的抗生素     

全自动细菌分析系统检测耐甲氧西林葡萄球菌的初步评价

采用琼脂筛选法、纸片扩散法和仪器法平行进行葡萄球菌苯唑西林敏感性的测定 ,同时进行微生物敏感性试验。结果显示 :MRS的分离率为 5 4.4% ,琼脂筛选法和仪器法两法对MRS检测的符合率为 96 .7%。MRS对万古霉素最敏感 ,敏感率 10 0 % ;呋喃妥因次之 (耐药率 0 .0 2 4% )。VITEK32型细菌分析系统可准确检测MRS。认为MRS以万古霉素治疗效果最佳 ,其次为呋喃妥因     

下呼吸道感染痰标本细菌学检查和耐药菌株的观察

目的：为合理使用抗生素治疗下呼吸道感染提供细菌学指标。方法：采集痰标本１１２４份,其中经涂片染色镜检确定为下呼吸道感染痰标本３４６份,占总标本数的３１,采用细菌培养法对３４６份痰标本进行病原学鉴定并做药敏试验。结果：经鉴定的标本中,涂片镜检２１３份找到细菌,２０６份培养出细菌,鉴定出菌株２８８株,其中２２份标本分离出两种以上细菌,鉴定出的Ｇ＾＋菌对头孢菌素类、喹诺酮类敏感,对青霉素耐药;Ｇ＾－菌对     

15种抗菌药物对大肠埃希氏菌抗生素后效应（PAE）的研究

本采用光密度法测定15种抗菌药物对医院感染主要致病菌——大肠埃希氏菌的抗生素后效应(PAE),结果表明在亚抑菌浓度时,青霉素类和头孢菌素类对大肠埃希氏菌的PAE很短甚至为负值,氨基糖甙类和磷霉素的PAE较短,碳青霉烯和氟喹诺酮类PAE很明显,随浓度的增加,PAE显延长;在4倍MIC时．青霉素类和头孢菌素类PAE有一定延长,磷霉素、碳青霉烯类、氨基糖甙类及氟睦诺酮类PAE显延长,其中氟喹诺酮类药物在4倍MIC时PAE可达4．5h左右。青霉素类和头孢菌素类对大肠埃希氏菌PAE较短．呈部分浓度依赖性;磷霉素、碳青霉烯类、氨基糖甙类及氟喹诺酮类PAE很明显,且显示出显的浓度依赖性,各类药物PAE的不同可能与其产生机制不同有关。