Low pH reduces the activity of ceftolozane/tazobactam in human urine, but confirms current breakpoints for urinary tract infections

Abstract Background Acidic pH has been shown to impact the antibiotic activity of non-β-lactams in urine. Objectives To investigate the in vitro activity of ceftolozane/tazobactam compared with meropenem at different pH settings in urine. Methods We determined the MICs for 30 clinical isolates of Escherichia coli, 25 clinical isolates of Klebsiella pneumoniae and 24 clinical isolates of Proteus mirabilis in pooled human urine and standard growth medium at pH 5 and 7. Time–kill curves were produced for one representative clinical isolate of tested bacterial strains in urine at pH 5, 6 and 7 for both antibiotics at concentrations above and below the MIC. HPLC analysis of the stability of ceftolozane/tazobactam and meropenem was performed at different pH values. Results The median MICs of both antibiotics were up to 8-fold higher at pH 5 than at pH 7. Bacterial growth of E. coli was not impacted by pH, while for K. pneumoniae and P. mirabilis low pH slightly reduced growth. Compared with pH 7, pH 5 resulted in a significant decrease in antibiotic activity with a delta of up to 3 log10 bacterial counts after 24 h. Impact of acidic pH was lowest for P. mirabilis; however, this strain metabolically increased the pH during experiments. Stability was not impacted by low pH. Conclusions Acidic pH had a significant negative impact on the activity of ceftolozane/tazobactam and meropenem in urine. Considering concentrations achieved in urine, our results confirm existing breakpoints and do not advocate increasing ceftolozane/tazobactam breakpoints for urinary tract infections.

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In Vitro Coliform Resistance to Bioactive Compounds in Urinary Infection, Assessed in a Lab Catheterization Model

Applied Sciences ◽

10.3390/app11094315 ◽

2021 ◽

Vol 11 (9) ◽

pp. 4315

Author(s):

Emanuel Vamanu ◽

Laura Dorina Dinu ◽

Cristina Mihaela Luntraru ◽

Alexandru Suciu

Keyword(s):

Urinary Tract ◽

Bioactive Compounds ◽

Urinary Tract Infections ◽

Antimicrobial Effect ◽

Biologically Active ◽

Bacterial Strains ◽

E Coli ◽

Functional Product ◽

Tract Infections

Bioactive compounds and phenolic compounds are viable alternatives to antibiotics in recurrent urinary tract infections. This study aimed to use a natural functional product, based on the bioactive compounds’ composition, to inhibit the uropathogenic strains of Escherichia coli. E. coli ATCC 25922 was used to characterize the IVCM (new in vitro catheterization model). As support for reducing bacterial proliferation, the cytotoxicity against a strain of Candida albicans was also determined (over 75% at 1 mg/mL). The results were correlated with the analysis of the distribution of biologically active compounds (trans-ferulic acid-268.44 ± 0.001 mg/100 g extract and an equal quantity of Trans-p-coumaric acid and rosmarinic acid). A pronounced inhibitory effect against the uropathogenic strain E. coli 317 (4 log copy no./mL after 72 h) was determined. The results showed a targeted response to the product for tested bacterial strains. The importance of research resulted from the easy and fast characterization of the functional product with antimicrobial effect against uropathogenic strains of E. coli. This study demonstrated that the proposed in vitro model was a valuable tool for assessing urinary tract infections with E. coli.

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Effect of Hydrolysable Tannins and Anthocyanins on Recurrent Urinary Tract Infections in Nephropathic Patients: Preliminary Data

Nutrients ◽

10.3390/nu13020591 ◽

2021 ◽

Vol 13 (2) ◽

pp. 591 ◽

Cited By ~ 1

Author(s):

Annalisa Noce ◽

Francesca Di Daniele ◽

Margherita Campo ◽

Manuela Di Lauro ◽

Anna Pietroboni Zaitseva ◽

...

Keyword(s):

Urinary Tract ◽

Urinary Tract Infections ◽

Bacterial Flora ◽

Bioactive Compound ◽

In Vitro Tests ◽

Bacterial Strains ◽

Quercetin Derivatives ◽

Hydrolysable Tannins ◽

Tract Infections

Urinary tract infections (UTIs) are caused by uropathogenic microorganism colonization. UTIs often require an antibiotic therapy that can cause the selection of antibiotic-resistant bacterial strains. A natural bioactive compound may represent a valid therapeutic adjuvant approach, in combination with drug therapy. In this paper, we present a pilot study, based on the administration of an oral food supplement (OFS), containing chestnut tannins and anthocyanins, to nephropathic patients suffering from recurrent UTIs (16 treated patients with 1 cp/day and 10 untreated patients). We performed laboratory tests and quality of life and body composition assessments, at T0 (baseline) and T1 (after 6 weeks OFS assumption). The analysis of OFS was performed by HPLC-DAD-MS for its content in polyphenols and by in vitro tests for its antioxidative and anti-free radical activities. In each capsule, polyphenol content was 6.21 mg (4.57 mg hydrolysable tannins, 0.94 mg anthocyanosides, 0.51 mg proanthocyanidins, 0.18 mg quercetin derivatives). A significant reduction of erythrocyte sedimentation rate was observed only in male patients. Urinalysis showed a significant reduction of leukocytes in both genders, whereas urinary bacterial flora at T1 significantly decreased only in male subjects. Tannins seem to exert an antimicrobial action according to gender, useful to counteract the recurrence of UTIs.

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Antibiotic Resistance of Bacterial Strains Isolated from Patients with Community-Acquired Urinary Tract Infections: An Exploratory Study in Palestine

Current Clinical Pharmacology ◽

10.2174/157488411798375930 ◽

2011 ◽

Vol 6 (4) ◽

pp. 304-307 ◽

Cited By ~ 3

Author(s):

Adham S. Abu Taha ◽

Waleed M. Sweileh

Keyword(s):

Antibiotic Resistance ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Exploratory Study ◽

Bacterial Strains ◽

Tract Infections

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Single Clinical Isolates from Acute Uncomplicated Urinary Tract Infections Are Representative of Dominant In Situ Populations

mBio ◽

10.1128/mbio.01064-13 ◽

2014 ◽

Vol 5 (2) ◽

Cited By ~ 18

Author(s):

Dana Willner ◽

Serene Low ◽

Jason A. Steen ◽

Narelle George ◽

Graeme R. Nimmo ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Clinical Isolates ◽

Content Type ◽

E Coli ◽

Strain Diversity ◽

Amplicon Pyrosequencing ◽

Culture Independent ◽

Tract Infections

ABSTRACTUrinary tract infections (UTIs) are one of the most commonly acquired bacterial infections in humans, and uropathogenicEscherichia colistrains are responsible for over 80% of all cases. The standard method for identification of uropathogens in clinical laboratories is cultivation, primarily using solid growth media under aerobic conditions, coupled with morphological and biochemical tests of typically a single isolate colony. However, these methods detect only culturable microorganisms, and characterization is phenotypic in nature. Here, we explored the genotypic identity of communities in acute uncomplicated UTIs from 50 individuals by using culture-independent amplicon pyrosequencing and whole-genome and metagenomic shotgun sequencing. Genus-level characterization of the UTI communities was achieved using the 16S rRNA gene (V8 region). Overall UTI community richness was very low in comparison to other human microbiomes. We strain-typedEscherichia-dominated UTIs using amplicon pyrosequencing of the fimbrial adhesin gene,fimH. There were nine highly abundantfimHtypes, and each UTI sample was dominated by a single type. Molecular analysis of the corresponding clinical isolates revealed that in the majority of cases the isolate was representative of the dominant taxon in the community at both the genus and the strain level. Shotgun sequencing was performed on a subset of eightE. coliurine UTI and isolate pairs. The majority of UTI microbial metagenomic sequences mapped to isolate genomes, confirming the results obtained using phylogenetic markers. We conclude that for the majority of acute uncomplicatedE. coli-mediated UTIs, single cultured isolates are diagnostic of the infection.IMPORTANCEIn clinical practice, the diagnosis and treatment of acute uncomplicated urinary tract infection (UTI) are based on analysis of a single bacterial isolate cultured from urine, and it is assumed that this isolate represents the dominant UTI pathogen. However, these methods detect only culturable bacteria, and the existence of multiple pathogens as well as strain diversity within a single infection is not examined. Here, we explored bacteria present in acute uncomplicated UTIs using culture-independent sequence-based methods.Escherichia coliwas the most common organism identified, and analysis ofE. colidominant UTI samples and their paired clinical isolates revealed that in the majority of infections the cultured isolate was representative of the dominant taxon at both the genus and the strain level. Our data demonstrate that in most cases single cultured isolates are diagnostic of UTI and are consistent with the notion of bottlenecks that limit strain diversity during UTI pathogenesis.

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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

Journal of Clinical Medicine- Hue Central Hospital ◽

10.38103/jcmhch.2021.71.14 ◽

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.

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Human urine alters methicillin-resistant Staphylococcus aureus virulence and transcriptome

Applied and Environmental Microbiology ◽

10.1128/aem.00744-21 ◽

2021 ◽

Author(s):

Santosh Paudel ◽

Kamal Bagale ◽

Swapnil Patel ◽

Nicholas J. Kooyers ◽

Ritwij Kulkarni

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Human Urine ◽

Molecular Mechanisms ◽

Methicillin Resistant ◽

Life Threatening ◽

Tract Infections

Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections (UTI), especially in catheterized individuals. Despite being rare, MRSA UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. To delineate the molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus clinical isolates, including two MRSA strains to human urine for 2h and analyzed virulence characteristics and changes in gene expression. The in vitro virulence assays showed that human urine rapidly alters adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep RBCs, and surface hydrophobicity in a staphylococcal strain-specific manner. In addition, RNA-Seq analysis of uropathogenic strain MRSA-1369 revealed that 2h-long exposure to human urine alters MRSA transcriptome, by modifying expression of genes encoding enzymes catalyzing metabolic pathways, virulence factors, and transcriptional regulators. In summary, our results provide important insights into how human urine specifically and rapidly alters MRSA physiology and facilitates MRSA survival in the nutrient-limiting and hostile urinary microenvironment. Importance: Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. In this report, we describe how exposure to human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA in acclimating to the nutrient-limiting, immunologically hostile conditions within the urinary tract leading to MRSA-UTI.

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