scholarly journals Fosfomycin susceptibility among ESBL producing gram negative bacilli causing urinary tract infections

2021 ◽  
Vol 8 (2) ◽  
pp. 142-145
Author(s):  
Rajeshwari K G

Urinary tract infection is one of the common infection encountered in day to day practice. Due to emergence of drug resitance among uropathogens treatment options have become limited. Fosfomycin being a safe oral antibiotic is being used widely to treat multidrug resistant uropathogens. In the present study 831 (48.45%) samples that yielded significant growth were processed out of 1715 sample for ESBL detection by double disc synergy and phenotypic confirmatory method. E.coli constituted the predominant isolate (60.4%) followed by K.pneumoniae. 256 (30.80%) samples yielding growth were from out patients and 575 from inpatients. Over all 44% of isolates in the present study were ESBL producers. 50% of Ecoli were ESBL producers. 70.64% of ESBL isolates were susceptible to fosfomycin in vitro. Present study finding suggest that resistance to fosfomysin is on rise even though majority of ESBLs were sensitive to it. The current study recommends to use fosfomycin only after testing susceptibility among uropathogens.

2012 ◽  
Vol 56 (11) ◽  
pp. 5744-5748 ◽  
Author(s):  
Elizabeth A. Neuner ◽  
Jennifer Sekeres ◽  
Gerri S. Hall ◽  
David van Duin

ABSTRACTFosfomycin has shown promisingin vitroactivity against multidrug-resistant (MDR) urinary pathogens; however, clinical data are lacking. We conducted a retrospective chart review to describe the microbiological and clinical outcomes of urinary tract infections (UTIs) with MDR pathogens treated with fosfomycin tromethamine. Charts for 41 hospitalized patients with a urine culture for an MDR pathogen who received fosfomycin tromethamine from 2006 to 2010 were reviewed. Forty-one patients had 44 urinary pathogens, including 13 carbapenem-resistantKlebsiella pneumoniae(CR-Kp), 8Pseudomonas aeruginosa, and 7 vancomycin-resistantEnterococcus faecium(VRE) isolates, 7 extended-spectrum beta-lactamase (ESBL) producers, and 9 others.In vitrofosfomycin susceptibility was 86% (median MIC, 16 μg/ml; range, 0.25 to 1,024 μg/ml). Patients received an average of 2.9 fosfomycin doses per treatment course. The overall microbiological cure was 59%; failure was due to either relapse (24%) or reinfection UTI (17%). Microbiological cure rates by pathogen were 46% for CR-Kp, 38% forP. aeruginosa, 71% for VRE, 57% for ESBL producers, and 100% for others. Microbiological cure (n= 24) was compared to microbiological failure (n= 17). There were significantly more solid organ transplant recipients in the microbiological failure group (59% versus 21%;P= 0.02). None of the patients in the microbiological cure group had a ureteral stent, compared to 24% of patients within the microbiological failure group (P= 0.02). Fosfomycin demonstratedin vitroactivity against UTIs due to MDR pathogens. For CR-KP, there was a divergence betweenin vitrosusceptibility (92%) and microbiological cure (46%). Multiple confounding factors may have contributed to microbiological failures, and further data regarding the use of fosfomycin for UTIs due to MDR pathogens are needed.


Chemotherapy ◽  
2016 ◽  
Vol 62 (2) ◽  
pp. 100-104 ◽  
Author(s):  
Stephanie E. Giancola ◽  
Monica V. Mahoney ◽  
Michael D. Hogan ◽  
Brian R. Raux ◽  
Christopher McCoy ◽  
...  

Background: Bacterial resistance among uropathogens is on the rise and has led to a decreased effectiveness of oral therapies. Fosfomycin tromethamine (fosfomycin) is indicated for uncomplicated urinary tract infections (UTIs) and displays in vitro activity against multidrug-resistant (MDR) isolates; however, clinical data assessing fosfomycin for the treatment of complicated or MDR UTIs are limited. Methods: We conducted a retrospective evaluation of patients who received ≥1 dose of fosfomycin between January 2009 and September 2015 for treatment of a UTI. Patients were included if they had a positive urine culture and documented signs/symptoms of a UTI. Results: Fifty-seven patients were included; 44 (77.2%) had complicated UTIs, 36 (63.2%) had MDR UTIs, and a total of 23 (40.4%) patients had a UTI that was both complicated and MDR. The majority of patients were female (66.7%) and elderly (median age, 79 years). Overall, the most common pathogens isolated were Escherichia coli (n = 28), Enterococcus spp. (n = 22), and Pseudomonas aeruginosa (n = 8). Twenty-eight patients (49.1%) were clinically evaluable; the preponderance achieved clinical success (96.4%). Fifteen out of 20 (75%) patients with repeat urine cultures had a microbiological cure. Conclusions: This retrospective study adds to the limited literature exploring alternative therapies for complicated and MDR UTIs with results providing additional evidence that fosfomycin may be an effective oral option.


2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Iain J. Abbott ◽  
Elke van Gorp ◽  
Aart van der Meijden ◽  
Rixt A. Wijma ◽  
Joseph Meletiadis ◽  
...  

ABSTRACT There are limited treatment options for enterococcal urinary tract infections, especially vancomycin-resistant Enterococcus (VRE). Oral fosfomycin is a potential option, although limited data are available guiding dosing and susceptibility. We undertook pharmacodynamic profiling of fosfomycin against E. faecalis and E. faecium isolates using a dynamic in vitro bladder infection model. Eighty-four isolates underwent fosfomycin agar dilution susceptibility testing (E. faecalis MIC50/90 32/64 μg/ml; E. faecium MIC50/90 64/128 μg/ml). Sixteen isolates (including E. faecalis ATCC 29212 and E. faecium ATCC 35667) were chosen to reflect the MIC range and tested in the bladder infection model with synthetic human urine (SHU). Under drug-free conditions, E. faecium demonstrated greater growth restriction in SHU compared to E. faecalis (E. faecium maximal growth 5.8 ± 0.6 log10 CFU/ml; E. faecalis 8.0 ± 1.0 log10 CFU/ml). Isolates were exposed to high and low fosfomycin urinary concentrations after a single dose, and after two doses given over two days with low urinary concentration exposure. Simulated concentrations closely matched the target (bias 2.3%). E. faecalis isolates required greater fosfomycin exposure for 3 log10 kill from the starting inoculum compared with E. faecium. The ƒAUC0-72/MIC and ƒ%T > MIC0-72 for E. faecalis were 672 and 70%, compared to 216 and 51% for E. faecium, respectively. There was no rise in fosfomycin MIC postexposure. Two doses of fosfomycin with low urinary concentrations resulted in equivalent growth inhibition to a single dose with high urinary concentrations. With this urinary exposure, fosfomycin was effective in promoting suppression of regrowth (>3 log10 kill) in the majority of isolates.


2017 ◽  
Vol 11 (9) ◽  
pp. E350-4 ◽  
Author(s):  
Lindsey Cox ◽  
Chang He ◽  
Jack Bevins ◽  
J. Quentin Clemens ◽  
John T. Stoffel ◽  
...  

Introduction: This study aimed to determine if gentamicin bladder instillations reduce the rate of symptomatic urinary tract infection (UTI) in neurogenic bladder (NGB) patients on intermittent self-catheterization (ISC) who have recurrent UTIs. Secondary aims were to examine the effects of intravesical gentamicin on the organism resistance patterns.Methods: We retrospectively reviewed our prospective NGB database. Inclusion criteria were NGB patients performing ISC exclusively for bladder drainage with clinical data available for six months before and six months after initiating prophylactic intravesical gentamicin instillations. Symptomatic UTIs were defined as symptoms consistent with UTI plus the need for antibiotic treatment.Results: Twenty-two patients met inclusion criteria; etiology of NGB was 63.6% spinal cord injury, 13.6% multiple sclerosis. Median time since injury/diagnosis was 14 years and 6/22 (27.3%) hadundergone urological reconstruction. Patients had fewer symptomatic UTI’s (median 4 vs. 1 episodes; p<0.004) and underwent fewer courses of oral antibiotics after initiating gentamicin (median 3.5 vs. 1; p<0.01). Days of oral antibiotic therapy decreased from 15 before to five after gentamicin, but this did not reach significance. There were fewer telephone encounters for UTI concerns per patient (median 3 vs. 0; p=0.03). The proportion of multidrug-resistant organisms in urine cultures decreased from 58.3%to 47.1% (p=0.04) and the rate of gentamicin resistance did not increase. Adverse events were mild and rare.Conclusions: Gentamicin bladder instillations decrease symptomatic UTI episodes and reduce oral antibiotics in patients with NGB on ISC who were suffering from recurrent UTIs. Antibiotic resistancedecreased while on gentamicin instillations.


Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 181
Author(s):  
Soo Tein Ngoi ◽  
Cindy Shuan Ju Teh ◽  
Chun Wie Chong ◽  
Kartini Abdul Jabar ◽  
Shiang Chiet Tan ◽  
...  

The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has greatly affected the clinical efficacy of β-lactam antibiotics in the management of urinary tract infections (UTIs). The limited treatment options have resulted in the increased use of carbapenem. However, flomoxef could be a potential carbapenem-sparing strategy for UTIs caused by ESBL-producers. Here, we compared the in vitro susceptibility of UTI-associated ESBL-producers to flomoxef and established β-lactam antibiotics. Fifty Escherichia coli and Klebsiella pneumoniae strains isolated from urine samples were subjected to broth microdilution assay, and the presence of ESBL genes was detected by polymerase chain reactions. High rates of resistance to amoxicillin-clavulanate (76–80%), ticarcillin-clavulanate (58–76%), and piperacillin-tazobactam (48–50%) were observed, indicated by high minimum inhibitory concentration (MIC) values (32 µg/mL to 128 µg/mL) for both species. The ESBL genes blaCTX-M and blaTEM were detected in both E. coli (58% and 54%, respectively) and K. pneumoniae (88% and 74%, respectively), whereas blaSHV was found only in K. pneumoniae (94%). Carbapenems remained as the most effective antibiotics against ESBL-producing E. coli and K. pneumoniae associated with UTIs, followed by flomoxef and cephamycins. In conclusion, flomoxef may be a potential alternative to carbapenem for UTIs caused by ESBL-producers in Malaysia.


2020 ◽  
Vol 75 (9) ◽  
pp. 2384-2393 ◽  
Author(s):  
Adam G Stewart ◽  
Patrick N A Harris ◽  
Andrew Henderson ◽  
Mark A Schembri ◽  
David L Paterson

Abstract ESBL-producing Enterobacteriaceae as uropathogens have given rise to a sizeable amount of global morbidity. Community and hospital surveillance studies continue to report increasing proportions of these organisms as causes of urinary tract infection (UTI). Due to limited treatment options and the presence of cross-resistance amongst oral antibiotics of different classes, patients often require IV therapy, thereby increasing healthcare costs and reducing the effectiveness of delivering healthcare. Oral cephalosporin antibiotics are well known for their ability to achieve high urinary concentrations, in addition to achieving clinical success for treatment of uncomplicated UTI with a drug-susceptible pathogen. Novel cephalosporin/β-lactamase inhibitor combinations have been developed and demonstrate good in vitro activity against ESBL-producing isolates. A pooled analysis of in vitro activity of existing oral cephalosporin/clavulanate combinations in ESBL-producing Enterobacteriaceae has shown MIC50s of 0.5–1, 0.125–1 and 0.25 mg/L for cefpodoxime, ceftibuten and cefixime, respectively. A novel cyclic boronic acid β-lactamase inhibitor, QPX7728, was able to produce MIC50 values of 0.5 and ≤0.06 mg/L when paired with cefpodoxime and ceftibuten, respectively. Other novel combinations, cefpodoxime/ETX0282 and ceftibuten/VNRX7145, have also demonstrated excellent activity against ESBL producers. Clinical trials are now awaited.


2021 ◽  
Vol 10 (7) ◽  
pp. 414-418
Author(s):  
Greeshma Hareendranath

BACKGROUND Escherichia coli is one of the most important causes of urinary tract infections (UTIs). Increased antibiotic resistance may limit the therapeutic options for the treatment of these infections. Fosfomycin trometamol is a phosphonic acid derivative, which acts primarily by interfering with bacterial peptidoglycan synthesis with broad spectrum of activity against agents causing urinary tract infection with good antibiofilm activity and limited reports of resistance and hence is increasingly called upon for the treatment of multi drug resistant (MDR) organisms causing UTI. There are limited studies from India regarding the efficacy of this drug; so, the study was conducted to determine the in vitro efficacy of fosfomycin against uropathogenic MDR E. coli. METHODS This was a prospective study done in the Department of Microbiology, Government T.D. Medical College, Alappuzha, over a period of 1 year from April 2018 to March 2019. A total of 150 MDR urine samples were processed by routine microbiological methods and after identification of E. coli urinary isolates, antibiotic susceptibility testing was performed and results were interpreted following the Clinical and Laboratory Standards Institute guidelines (CLSI). Fosfomycin sensitivity was tested by the Kirby-Bauer disc diffusion method. RESULTS Among the 150 MDR urinary E. coli isolates, 148 (98 %) were sensitive to fosfomycin in our study. The susceptibility rate of fosfomycin was clearly higher than other commonly used drugs for UTI. All extended-spectrum beta-lactamases (ESBL) producing E. coli were sensitive to this drug. The susceptibility for nitrofurantoin was fair, whereas for ampicillin, norfloxacin, cefotaxime and trimethoprim / sulphamethoxazole was found poor. Relatively better rates of resistance were observed for parenteral antibiotics. CONCLUSIONS With an enormous increase in the bacterial pathogens resistant to first-line antibiotics, there has been a revival in the use of fosfomycin. The convenience of a single dose regimen, a good activity proven invitro, and minimal propensity for development of resistance pathogens makes fosfomycin an attractive regimen for the treatment of uncomplicated community and hospital acquired UTIs. In this regard, with the existing limited options for treating MDR organisms, fosfomycin finds its utility acting as an effective and promising option in the treatment of UTIs due to MDR pathogens in the future.


2018 ◽  
Vol 12 (1) ◽  
pp. 248-253 ◽  
Author(s):  
Reza Ranjbar ◽  
Sajjad S. Tolon ◽  
Mehrdad Sami ◽  
Reza Golmohammadi

Background:Escherichia coliis one of the most important bacterial agents to cause urinary tract infections. Inappropriate and unnecessary administration of antibiotics has led to an increase in the appearance of multidrug-resistantE. coliisolates, limiting treatment options. The increase in a number of resistant strains of bacteria is a major concern of health authorities worldwide.Objective:The purpose of this study was to determine the presence of theqnrgenes amongE. coliisolated from UTIs of patients in Baqiyatallah hospital in Tehran province, Iran.Method:Clinical urine samples of patients with suspected urinary tract infection were collected by standard methods in sterile disposable containers. After analysis of urine, microscopic observations and culture analysis, the bacterial genome was extracted by boiling method. PCR for detection ofqnrgenes includingqnrA,qnrBandqnrSwas done by specific primers, then PCR products were run using gel electrophoresis and visualized by gel documentation system.Results:In the present study among the 95 isolates, 60 strains were resistant to nalidixic acid. PCR showed that 92 strains were positive forqnrS. TheqnrAandqnrBgenes were not found among the clinical isolates.Conclusion:Our finding indicates a high level of resistance against nalidixic acid amongE. coliisolates recovered from the patients with UTI. Also, the high frequency ofqnrSimposes the importance of survey of molecular and genetic analysis of mechanisms of quinolone resistance inE. colistrains.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 645
Author(s):  
Ulrich Dobrindt ◽  
Haleluya T. Wami ◽  
Torsten Schmidt-Wieland ◽  
Daniela Bertsch ◽  
Klaus Oberdorfer ◽  
...  

The resistance of uropathogens to various antibiotics is increasing, but nitroxoline remains active in vitro against some relevant multidrug resistant uropathogenic bacteria. E. coli strains, which are among the most common uropathogens, are unanimously susceptible. Thus, nitroxoline is an option for the therapy of urinary tract infections caused by multiresistant bacteria. Since nitroxoline is active against bacteria in biofilms, it will also be effective in patients with indwelling catheters or foreign bodies in the urinary tract. Cotrimoxazole, on the other hand, which, in principle, can also act on bacteria in biofilms, is frequently inactive against multiresistant uropathogens. Based on phenotypic resistance data from a large number of urine isolates, structural characterisation of an MDR plasmid of a recent ST131 uropathogenic E. coli isolate, and publicly available genomic data of resistant enterobacteria, we show that nitroxoline could be used instead of cotrimoxazole for intervention against MDR uropathogens. Particularly in uropathogenic E. coli, but also in other enterobacterial uropathogens, the frequent parallel resistance to different antibiotics due to the accumulation of multiple antibiotic resistance determinants on mobile genetic elements argues for greater consideration of nitroxoline in the treatment of uncomplicated urinary tract infections.


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