scholarly journals Results of a Multicenter Population Pharmacokinetic Study of Ciprofloxacin in Children with Complicated Urinary Tract Infection

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Kevin Meesters ◽  
Robin Michelet ◽  
Reiner Mauel ◽  
Ann Raes ◽  
Jan Van Bocxlaer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Body Weight ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Complicated Urinary Tract Infection ◽  
Fat Free Mass ◽  
Population Pharmacokinetic ◽  
Content Type ◽  
Tract Infections ◽  
Significant Covariates

ABSTRACTResistance rates for ciprofloxacin, which is labeled for treating complicated urinary tract infections in children, are rapidly rising. As there is limited knowledge on developmental pharmacology of ciprofloxacin, the primary aim of this study was to develop a population pharmacokinetic model for ciprofloxacin in children treated for complicated urinary tract infections. Children to whom ciprofloxacin was prescribed, intravenous (10 to 15 mg/kg body weight every 12 h) orper os(15 to 20 mg/kg every 12 h), were enrolled. One hundred eight serum and 119 urine samples were obtained during 10 intravenous and 13 oral courses of ciprofloxacin in 22 patients (age range, 0.31 to 15.51 years). A one-compartment model best described our data. Fat-free mass and glomerular filtration rate (estimated by a formula using cystatin C and creatinine), standardized for body surface area, were significant covariates for ciprofloxacin clearance. In our population, ciprofloxacin clearance is 0.16 to 0.43 liter/h/kg of body weight, volume of distribution 0.06 to 2.88 liters/kg, and bioavailability 59.6%. All of our patients had a clinical cure of their infection. Based on target attainment simulations across doses, all children reached the pharmacodynamic target forEnterobacteriaceae, but on average only 53% did forPseudomonas aeruginosaand 3% forStaphylococcus aureus, at the 15-mg/kg oral dose. For treating urinary tract infections caused byPseudomonas aeruginosa, oral doses should be at least 20 mg/kg. Furthermore, in our population, fat-free mass and kidney function should be considered, as they prove to be significant covariates for ciprofloxacin clearance and, hence, exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT02598362.)

scholarly journals Azithromycin-Ciprofloxacin-Impregnated Urinary Catheters Avert Bacterial Colonization, Biofilm Formation, and Inflammation in a Murine Model of Foreign-Body-Associated Urinary Tract Infections Caused by Pseudomonas aeruginosa

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Hina Saini ◽  
Anitha Vadekeetil ◽  
Sanjay Chhibber ◽  
Kusum Harjai
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Murine Model ◽  
Biofilm Formation ◽  
Bacterial Colonization ◽  
Silicone Implants ◽  
Urinary Catheters ◽  
Content Type ◽  
Tract Infections

ABSTRACT Pseudomonas aeruginosa is a multifaceted pathogen causing a variety of biofilm-mediated infections, including catheter-associated urinary tract infections (CAUTIs). The high prevalence of CAUTIs in hospitals, their clinical manifestations, such as urethritis, cystitis, pyelonephritis, meningitis, urosepsis, and death, and the associated economic challenges underscore the need for management of these infections. Biomaterial modification of urinary catheters with two drugs seems an interesting approach to combat CAUTIs by inhibiting biofilm. Previously, we demonstrated the in vitro efficacy of urinary catheters impregnated with azithromycin (AZM) and ciprofloxacin (CIP) against P. aeruginosa. Here, we report how these coated catheters impact the course of CAUTI induced by P. aeruginosa in a murine model. CAUTI was established in female LACA mice with uncoated or AZM-CIP-coated silicone implants in the bladder, followed by transurethral inoculation of 108 CFU/ml of biofilm cells of P. aeruginosa PAO1. AZM-CIP-coated implants (i) prevented biofilm formation on the implant's surface (P ≤ 0.01), (ii) restricted bacterial colonization in the bladder and kidney (P < 0.0001), (iii) averted bacteriuria (P < 0.0001), and (iv) exhibited no major histopathological changes for 28 days in comparison to uncoated implants, which showed persistent CAUTI. Antibiotic implants also overcame implant-mediated inflammation, as characterized by trivial levels of inflammatory markers such as malondialdehyde (P < 0.001), myeloperoxidase (P < 0.05), reactive oxygen species (P ≤ 0.001), and reactive nitrogen intermediates (P < 0.01) in comparison to those in uncoated implants. Further, AZM-CIP-coated implants showed immunomodulation by manipulating the release of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-10 to the benefit of the host. Overall, the study demonstrates long-term in vivo effectiveness of AZM-CIP-impregnated catheters, which may possibly be a key to success in preventing CAUTIs.

scholarly journals Antimicrobial Activities of Ceftazidime-Avibactam and Comparator Agents against Gram-Negative Organisms Isolated from Patients with Urinary Tract Infections in U.S. Medical Centers, 2012 to 2014

2016 ◽  
Vol 60 (7) ◽  
pp. 4355-4360 ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Antimicrobial Activities ◽  
Broth Microdilution ◽  
Gram Negative ◽  
Content Type ◽  
Medical Centers ◽  
Gram Negative Organisms ◽  
Tract Infections

ABSTRACTA total of 7,272 unique patient clinical isolates were collected from 71 U.S. medical centers from patients with urinary tract infections in 2012 to 2014 and tested for susceptibility to ceftazidime-avibactam and comparators by broth microdilution methods. Ceftazidime-avibactam inhibited >99.9% of allEnterobacteriaceaeat the susceptible breakpoint of ≤8 μg/ml (there were only three nonsusceptible strains). Ceftazidime-avibactam was also active againstPseudomonas aeruginosaisolates (MIC50, 2 μg/ml; MIC90, 4 μg/ml; 97.7% susceptible), including many isolates not susceptible to meropenem, ceftazidime, and/or piperacillin-tazobactam.

Detection of tox A gene in Pseudomonas aeruginosa that isolates from different clinical cases by using PCR.

2018 ◽  
pp. 26
Author(s):  
Rana M. Abdullah Al-Shwaikh ◽  
Abbas Falih Alornaaouti
Keyword(s):  
Molecular Weight ◽  
Pseudomonas Aeruginosa ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Otitis Media ◽  
Urinary Tract Infections ◽  
Gel Electrophoresis ◽  
Wound Infections ◽  
Tract Infections

       Current study obtained (75) isolate of Pseudomonas aeruginosa collected from different cases included : 28 isolates from otitis media, 23 isolates from burn infections, 10 isolates from wound infections, 8 isolates from urinary tract infections and 6 isolates from blood, during the period between 1/9/2014 to 1/11/2014        The result revealed that the tox A gene was present in 54 isolates (72%) of Pseudomonas aeruginosa. The gel electrophoresis showed that the molecular weight of tox A gene was 352 bp. The result shows 17 isolates (60.71%) from otitis media has tox A gene, 18 isolates (78.26%) from burn followed by 8 isolate (80%) from wound infection and 5 isolates (62.5%) from urinary tract infection , finally 6 isolates (100%) from blood have this gene.

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

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
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.

The Clinical Features of Complicated Urinary Tract Infections by Pseudomonas aeruginosa

2008 ◽  
Vol 49 (12) ◽  
pp. 1149
Author(s):  
Jung Woo Lee ◽  
Kyung Jae Oh ◽  
Seung Chol Park ◽  
Joung Sik Rim
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Clinical Features ◽  
Urinary Tract Infections ◽  
Tract Infections

Genotypic and phenotypic characterization of Pseudomonas aeruginosa isolates from urinary tract infections

2011 ◽  
Vol 301 (4) ◽  
pp. 282-292 ◽  
Author(s):  
Petra Tielen ◽  
Maike Narten ◽  
Nathalie Rosin ◽  
Ilona Biegler ◽  
Isam Haddad ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Phenotypic Characterization ◽  
Tract Infections

scholarly journals The Extracellular Domain of the β2Integrin β Subunit (CD18) Is Sufficient forEscherichia coliHemolysin andAggregatibacter actinomycetemcomitansLeukotoxin Cytotoxic Activity

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Laura C. Ristow ◽  
Vy Tran ◽  
Kevin J. Schwartz ◽  
Lillie Pankratz ◽  
Andrew Mehle ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Integrin Signaling ◽  
Β Subunit ◽  
Wild Type ◽  
Α Subunit ◽  
Content Type ◽  
Animal Pathogens ◽  
Tract Infections

ABSTRACTTheEscherichia colihemolysin (HlyA) is a pore-forming exotoxin associated with severe complications of human urinary tract infections. HlyA is the prototype of the repeats-in-toxin (RTX) family, which includes LtxA fromAggregatibacter actinomycetemcomitans, a periodontal pathogen. The existence and requirement for a host cell receptor for these toxins are controversial. We performed an unbiased forward genetic selection in a mutant library of human monocytic cells, U-937, for host factors involved in HlyA cytotoxicity. The top candidate was the β2integrin β subunit. Δβ2cell lines are approximately 100-fold more resistant than wild-type U-937 cells to HlyA, but remain sensitive to HlyA at high concentrations. Similarly, Δβ2cells are more resistant than wild-type U-937 cells to LtxA, as Δβ2cells remain LtxA resistant even at >1,000-fold-higher concentrations of the toxin. Loss of any single β2integrin α subunit, or even all four α subunits together, does not confer resistance to HlyA. HlyA and LtxA bind to the β2subunit, but not to αL, αM, or αXin far-Western blots. Genetic complementation of Δβ2cells with either β2or β2with a cytoplasmic tail deletion restores HlyA and LtxA sensitivity, suggesting that β2integrin signaling is not required for cytotoxicity. Finally, β2mutations do not alter sensitivity to unrelated pore-forming toxins, as wild-type or Δβ2cells are equally sensitive toStaphylococcus aureusα-toxin andProteus mirabilisHpmA. Our studies show two RTX toxins use the β2integrin β subunit alone to facilitate cytotoxicity, but downstream integrin signaling is dispensable.IMPORTANCEUrinary tract infections are one of the most common bacterial infections worldwide. UropathogenicEscherichia colistrains are responsible for more than 80% of community-acquired urinary tract infections. Although we have known for nearly a century that severe infections stemming from urinary tract infections, including kidney or bloodstream infections are associated with expression of a toxin, hemolysin, from uropathogenicEscherichia coli, how hemolysin functions to enhance virulence is unknown. Our research defines the interaction of hemolysin with the β2integrin, a human white cell adhesion molecule, as a potential therapeutic target during urinary tract infections. TheE. colihemolysin is the prototype for a toxin family (RTX family) produced by a wide array of human and animal pathogens. Our work extends to the identification and characterization of the receptor for an additional member of the RTX family, suggesting that this interaction may be broadly conserved throughout the RTX toxin family.

scholarly journals Ceftolozane-Tazobactam Activity against Phylogenetically Diverse Clostridium difficile Strains

2015 ◽  
Vol 59 (11) ◽  
pp. 7084-7085 ◽  
Author(s):  
Mark D. Gonzalez ◽  
Meghan A. Wallace ◽  
Tiffany Hink ◽  
Erik R. Dubberke ◽  
Carey-Ann D. Burnham
Keyword(s):  
Urinary Tract ◽  
Clostridium Difficile ◽  
Urinary Tract Infections ◽  
Anaerobic Bacteria ◽  
Content Type ◽  
Tract Infections ◽  
High Mics

ABSTRACTCeftolozane-tazobactam (C/T) is approved for the treatment of complicated intra-abdominal and urinary tract infections and has varied activity against anaerobic bacteria. Here, we evaluate the activity of C/T against a phylogenetically diverse collection ofClostridium difficileisolates and report uniformly high MICs (≥256 μg/ml) to C/T.

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