Pharmacotherapy of Complicated Urinary Tract and Intra-abdominal Infections with Doripenem

2009 ◽  
Vol 1 ◽  
pp. CMT.S2062
Author(s):  
Anthony M. Nicasio ◽  
Joseph L. Kuti ◽  
David P. Nicolau
Keyword(s):  
Urinary Tract ◽  
Broad Spectrum ◽  
Drug Dose ◽  
Resistant Bacteria ◽  
Drug Resistant Bacteria ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections ◽  
Abdominal Infections

Due to the growing rate of multi-drug resistant bacteria in complicated infections, the need for new broad-spectrum antimicrobials is paramount. Doripenem, a new addition to the intravenous carbapenem class, has recently been approved for the treatment of complicated lower urinary tract infections and/or pyelonephritis (cUTI) and complicated intra-abdominal infections (cIAI) in adult patients. Doripenem exhibits potent in vitro and in vivo bactericidal activity against an assortment of Gram-positive and Gram-negative aerobic and anaerobic organisms, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae that produce extended spectrum beta-lactamases (ESBL). Relative to other available carbapenems, doripenem typically displays MICs that are 1-2 dilutions lower than meropenem and 2-4 dilutions lower than imipenem against P. aeruginosa. Since the kidneys primarily excrete doripenem as whole drug, dose adjustments are needed in patients with renal impairment. Doripenem 500 mg q8 h demonstrated non-inferiority to levofloxacin 250 mg q24 h in clinical trials of patients with cUTI; it was non-inferior to meropenem 1000 mg q8 h in patients with cIAI. Doripenem's broad spectrum of activity, in vitro potency against particularly difficult to treat organisms, and desirable safety profile make it an attractive option in the treatment of cUTI and cIAI.

scholarly journals Biological Cost of Single and Multiple Norfloxacin Resistance Mutations in Escherichia coli Implicated in Urinary Tract Infections

2005 ◽  
Vol 49 (6) ◽  
pp. 2343-2351 ◽  
Author(s):  
Patricia Komp Lindgren ◽  
Linda L. Marcusson ◽  
Dorthe Sandvang ◽  
Niels Frimodt-Møller ◽  
Diarmaid Hughes
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Infection Model ◽  
Resistance Mutations ◽  
Topoisomerase Iv ◽  
E Coli ◽  
Tract Infections ◽  
Subsequent Selection

ABSTRACT Resistance to fluoroquinolones in urinary tract infection (UTIs) caused by Escherichia coli is associated with multiple mutations, typically those that alter DNA gyrase and DNA topoisomerase IV and those that regulate AcrAB-TolC-mediated efflux. We asked whether a fitness cost is associated with the accumulation of these multiple mutations. Mutants of the susceptible E. coli UTI isolate Nu14 were selected through three to five successive steps with norfloxacin. Each selection was performed with the MIC of the selected strain. After each selection the MIC was measured; and the regions of gyrA, gyrB, parC, and parE, previously associated with resistance mutations, and all of marOR and acrR were sequenced. The first selection step yielded mutations in gyrA, gyrB, and marOR. Subsequent selection steps yielded mutations in gyrA, parE, and marOR but not in gyrB, parC, or acrR. Resistance-associated mutations were identified in almost all isolates after selection steps 1 and 2 but in less than 50% of isolates after subsequent selection steps. Selected strains were competed in vitro, in urine, and in a mouse UTI infection model against the starting strain, Nu14. First-step mutations were not associated with significant fitness costs. However, the accumulation of three or more resistance-associated mutations was usually associated with a large reduction in biological fitness, both in vitro and in vivo. Interestingly, in some lineages a partial restoration of fitness was associated with the accumulation of additional mutations in late selection steps. We suggest that the relative biological costs of multiple mutations may influence the evolution of E. coli strains that develop resistance to fluoroquinolones.

Nghiên cứu sự kháng kháng sinh của các chủng vi khuẩn gây nhiễm khuẩn đường tiết niệu phân lập được tại Bệnh viện Hữu nghị Đa khoa Nghệ An

2021 ◽  
Author(s):  
Trâm Quế Anh
Keyword(s):  
Urinary Tract ◽  
General Hospital ◽  
Urinary Tract Infections ◽  
Resistant Bacteria ◽  
Antibiotics Resistance ◽  
Bacterial Strains ◽  
E Coli ◽  
Linezolid Resistance ◽  
Drug Resistant Bacteria ◽  
Tract Infections

TÓM TẮT Đặt vấn đề: Xác định đúng căn nguyên gây NKĐTN và mức độ kháng kháng sinh của các vi khuẩn sẽ giúp cho việc điều trị có hiệu quả, giảm được chi phí điều trị, hạn chế sự gia tăng vi khuẩn đề kháng kháng sinh. Đối tượng và phương pháp nghiên cứu: Các chủng VK gây nhiễm khuẩn đương tiết niệu phân lập được tại bệnh viện Hữu nghị Đa khoa Nghệ An từ 1/2020 đến 12/2020. Thiết kế nghiên cứu: Cắt ngang mô tả. Kết quả: Phân lập được 473 chủng vi khuẩn gây NKĐTN, trong đó, E. coli 38,48%; P. aeruginosa 14,15; Enterococcus sp 10,57; K. pneumoniae 13,32%. E. coli: kháng các kháng sinh Cephalosporine, Quinolones từ 56,7 - 63,8%, Carbapenem 4,5 - 6,2%, sinh ESBL 49,4%. P. aeruginosa: đã kháng các kháng sinh thử nghiệm từ 59,1 - 69,2%. Enterococcus sp: kháng với các kháng sinh nhóm Quinolone 73,5%, kháng Vancomycin 8,3%; Chưa ghi nhận đề kháng Linezolid. K. pneumoniae: kháng nhóm Cephalosporin, Quinolone từ 66,7 - 74,6%, đề kháng với Carbapenem từ 46,0 - 50,8%. Kết luận: Các vi khuẩn gây nhiễm khuẩn tiết niệu thường gặp là: E. coli, P. aeruginosa, Enterococcus sp. K. pneumoniae. Các vi khuẩn phân lập được đã đề kháng với nhiều kháng sinh thường dùng với các mức độ khác nhau. Xuất hiện các chủng vi khuẩn Gram âm kháng Carbapenem, Gram dương kháng Vancomycin. Từ khóa: Nhiễm khuẩn tiết niệu, E.coli, Klebsiella, P.aeruginosa, Enterococcus sp ABSTRACT RESEARCH OF ANTIBIOTICS RESISTANCE OF BACTERIA STRAINS CAUSING URINARY TRACT INFECTIONS ISOLATED AT NGHEAN FRIENDSHIP GENERAL HOSPITAL Background: The good identification of UTI microorganism and their antimicrobial susceptibility would promote the effective treatment, reduce the cost as well as the emergence of drug resistant bacteria. Methods: Bacterial strains causing urinary tract infections were isolated at Nghe An Friendship General Hospital from 1/2020 to 12/2020. Study design: Descriptive cross section. Results: 473 bacterial strains causing UTIs were isolated, in which, E. coli 38.48%; P. aeruginosa 14.15; Enterococcus sp 10.57; K. pneumoniae 13.32%. E. coli: resistant to Cephalosporin antibiotics, Quinolones from 56.7 - 63.8%, Carbapenem 4.5 - 6.2%, producing ESBL 49.4%. P. aeruginosa: was resistant to the tested antibiotics from 59.1 - 69.2%. Enterococcus sp: resistant to Quinolone antibiotics 73.5%, resistant to Vancomycin 8.3%; Linezolid resistance has not been recorded. K. pneumoniae: resistant to Cephalosporin, Quinolone from 66.7 - 74.6%, resistant to Carbapenem from 46.0 - 50.8%. Conclusion: Common bacteria causing urinary tract infections are: E. coli, P. aeruginosa, Enterococcus sp. K. pneumoniae. The isolates were resistant to many commonly used antibiotics to varying degrees. Occurrence of strains of Gram - negative bacteria resistant to Carbapenem, Gram - positive resistant to Vancomycin. Keywords: Urinary Tract infections, E. coli, Klebsiella, P. aeruginosa, Enterococcus sp.

scholarly journals Quinolones for the Treatment ofNeisseria GonorrhoeaeandChlamydia Trachomatis

1993 ◽  
Vol 1 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Sebastian Faro
Keyword(s):  
Urinary Tract ◽  
Soft Tissue ◽  
Chlamydia Trachomatis ◽  
Urinary Tract Infections ◽  
Single Agent ◽  
Moderate Activity ◽  
Sexually Transmitted ◽  
Tract Infections

The most commonly sexually transmitted bacteria areNeisseria gonorrhoeaeandChlamydia trachomatis.The quinolones ofloxacin and ciprofloxacin have been shown to have activity against both of these bacteria in vitro and in vivo. Ofloxacin is particularly well suited for the treatment ofN. gonorrhoeaeandC. trachomatiscervical infection, which can be considered the earliest manifestation of pelvic inflammatory disease (PID). Not only can ofloxacin be effectively used as a single agent, it is also useful in treating urinary tract infections caused by Enterobacteriaceae. Although it has moderate activity against anaerobes in general, ofloxacin does have activity against the anaerobes commonly isolated from female patients with soft tissue pelvic infections. Thus, ofloxacin has the potential for being utilized to treat early salpingitis.

scholarly journals Nanoparticles Enable Efficient Delivery of Antimicrobial Peptides for the Treatment of Deep Infections

2021 ◽  
Author(s):  
Yingxue Deng ◽  
Rui Huang ◽  
Songyin Huang ◽  
Menghua Xiong
Keyword(s):  
Antimicrobial Peptides ◽  
Broad Spectrum ◽  
Antimicrobial Properties ◽  
Therapeutic Index ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Efficient Delivery ◽  
Delivery Vehicles

Antimicrobial peptides (AMPs) have emerged as promising alternatives of traditional antibiotics against drug-resistant bacteria owing to their broad-spectrum antimicrobial properties and low tendency to drugresistance. However, their therapeutic efficacy in vivo, especially for infections in deep organs, is limited owing to their systemic toxicity and low bioavailability. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Herein, we will discuss the current progress of using nanoparticles as delivery vehicles for AMPs for the treatment of deep infections.

FimH Antagonists for the Oral Treatment of Urinary Tract Infections: From Design and Synthesis to in Vitro and in Vivo Evaluation

2010 ◽  
Vol 53 (24) ◽  
pp. 8627-8641 ◽  
Author(s):  
Tobias Klein ◽  
Daniela Abgottspon ◽  
Matthias Wittwer ◽  
Said Rabbani ◽  
Janno Herold ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Oral Treatment ◽  
In Vivo Evaluation ◽  
Design And Synthesis ◽  
Tract Infections

scholarly journals Peptidoglycan Sensing Prevents Quiescence and Promotes Quorum-Independent Colony Growth of Uropathogenic Escherichia coli

2020 ◽  
Vol 202 (20) ◽  
Author(s):  
Eric C. DiBiasio ◽  
Hilary J. Ranson ◽  
James R. Johnson ◽  
David C. Rowley ◽  
Paul S. Cohen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Recurrent Infection ◽  
Colony Growth ◽  
Quiescent State ◽  
Content Type ◽  
Tract Infections

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the leading cause of human urinary tract infections (UTIs), and many patients experience recurrent infection after successful antibiotic treatment. The source of recurrent infections may be persistent bacterial reservoirs in vivo that are in a quiescent state and thus are not susceptible to antibiotics. Here, we show that multiple UPEC strains require a quorum to proliferate in vitro with glucose as the carbon source. At low cell density, the bacteria remain viable but enter a quiescent, nonproliferative state. Of the clinical UPEC isolates tested to date, 35% (51/145) enter this quiescent state, including isolates from the recently emerged, multidrug-resistant pandemic lineage ST131 (i.e., strain JJ1886) and isolates from the classic endemic lineage ST73 (i.e., strain CFT073). Moreover, quorum-dependent UPEC quiescence is prevented and reversed by small-molecule proliferants that stimulate colony formation. These proliferation cues include d-amino acid-containing peptidoglycan (PG) tetra- and pentapeptides, as well as high local concentrations of l-lysine and l-methionine. Peptidoglycan fragments originate from the peptidoglycan layer that supports the bacterial cell wall but are released as bacteria grow. These fragments are detected by a variety of organisms, including human cells, other diverse bacteria, and, as we show here for the first time, UPEC. Together, these results show that for UPEC, (i) sensing of PG stem peptide and uptake of l-lysine modulate the quorum-regulated decision to proliferate and (ii) quiescence can be prevented by both intra- and interspecies PG peptide signaling. IMPORTANCE Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs). During pathogenesis, UPEC cells adhere to and infiltrate bladder epithelial cells, where they may form intracellular bacterial communities (IBCs) or enter a nongrowing or slowly growing quiescent state. Here, we show in vitro that UPEC strains at low population density enter a reversible, quiescent state by halting division. Quiescent cells resume proliferation in response to sensing a quorum and detecting external signals, or cues, including peptidoglycan tetra- and pentapeptides.

scholarly journals Thermo-responsive triple-function nanotransporter for efficient chemo-photothermal therapy of multidrug-resistant bacterial infection

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Guangchao Qing ◽  
Xianxian Zhao ◽  
Ningqiang Gong ◽  
Jing Chen ◽  
Xianlei Li ◽  
...  
Keyword(s):  
Near Infrared ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Limited Effect ◽  
Bacterial Membranes ◽  
Change Mechanism ◽  
Drug Resistant Bacteria ◽  
New Strategies

Abstract New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus, whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria.

Cephazolin Sodium—An In Vivo and In Vitro Evaluation of 100 Patients with Urinary Tract Infections

1975 ◽  
Vol 20 (5) ◽  
pp. 259-260
Author(s):  
Diana M. D. Rimmer
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
General Hospital ◽  
Urinary Tract Infections ◽  
Antimicrobial Agents ◽  
Random Group ◽  
Tract Infections

A random group of 100 patients in a general hospital were treated with cephazolin sodium for proven urinary tract infections. Sixty-six per cent had conditions predisposing to urinary tract infection. Under these somewhat difficult conditions the original infecting organism remained absent from the urine of 75 per cent of the 70 patients followed in the 3rd to 6th week period. This compares very favourably with response to other antimicrobial agents currently used in urinary tract infections.

scholarly journals Uropathogenic Escherichia coli Flagella Aid in Efficient Urinary Tract Colonization

2005 ◽  
Vol 73 (11) ◽  
pp. 7657-7668 ◽  
Author(s):  
Kelly J. Wright ◽  
Patrick C. Seed ◽  
Scott J. Hultgren
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Class I ◽  
Class Iii ◽  
Epithelial Surface ◽  
Fitness Advantage ◽  
Regulatory Cascade ◽  
Tract Infections

ABSTRACT In the murine model of urinary tract infections (UTI), cystitis by uropathogenic Escherichia coli (UPEC) occurs through an intimate relationship with the bladder superficial umbrella cell entailing cycles of adherence, invasion, intracellular bacterial community (IBC) formation, and dispersal (fluxing) from the intracellular environment. IBC dispersal is a key step that results in the spread of bacteria over the epithelial surface to initiate additional rounds of IBC formation. We investigated the role of flagella in mediating adherence and motility during UTI, hypothesizing that the dispersion of the IBC would be incomplete in the absence of motility, thus interrupting the IBC pathway and attenuating the infection. Using gfp reporter fusions, the expression of the flagellar class I flhDC and class III fliC genes was monitored to track key points of regulation throughout the pathogenic cascade. In vitro, growth under conditions promoting motility resulted in the robust expression of both fusions. In contrast, only the class I fusion produced significant expression throughout early stages of IBC development including the dispersion stage. Thus, unlike in vitro modeling of motility, the regulatory cascade appeared incomplete in vivo. Throughout IBC formation, nonmotile ΔfliC mutants achieved the same number of IBCs as the wild-type (wt) strain, demonstrating that flagella are neither essential nor required for first- or second-generation IBC formation. However, in competition experiments between wt and ΔfliC strains, the wt was shown to have a fitness advantage in persisting throughout the urinary tract for 2 weeks, demonstrating a subtle but measurable role for flagella in virulence.

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