scholarly journals Clinical Pharmacodynamics of Cefepime in Patients Infected with Pseudomonas aeruginosa

2009 ◽  
Vol 54 (3) ◽  
pp. 1111-1116 ◽  
Author(s):  
Jared L. Crandon ◽  
Catharine C. Bulik ◽  
Joseph L. Kuti ◽  
David P. Nicolau
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Confidence Interval ◽  
Free Drug ◽  
Classification And Regression Tree ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Minimum Concentration ◽  
Skin Structure ◽  
Tract Infections

ABSTRACT We evaluated cefepime exposures in patients infected with Pseudomonas aeruginosa to identify the pharmacodynamic relationship predictive of microbiological response. Patients with non-urinary tract P. aeruginosa infections and treated with cefepime were included. Free cefepime exposures were estimated by using a validated population pharmacokinetic model. P. aeruginosa MICs were determined by Etest and pharmacodynamic indices (the percentage of the dosing interval that the free drug concentration remains above the MIC of the infecting organism [f T > MIC], the ratio of the minimum concentration of free drug to the MIC [f C min/MIC], and the ratio of the area under the concentration-time curve for free drug to the MIC [fAUC/MIC]) were calculated for each patient. Classification and regression tree analysis was used to partition the pharmacodynamic parameters for prediction of the microbiological response. Monte Carlo simulation was utilized to determine the optimal dosing regimens needed to achieve the pharmacodynamic target. Fifty-six patients with pneumonia (66.1%), skin and skin structure infections (SSSIs) (25%), and bacteremia (8.9%) were included. Twenty-four (42.9%) patients failed cefepime therapy. The MICs ranged from 0.75 to 96 μg/ml, resulting in median f T > MIC, f C m in/MIC, and fAUC/MIC exposures of 100% (range, 0.8 to 100%), 4.3 (range, 0.1 to 27.3), and 206.2 (range, 4.2 to 1,028.7), respectively. Microbiological failure was associated with an f T > MIC of ≤60% (77.8% failed cefepime therapy when f T > MIC was ≤60%, whereas 36.2% failed cefepime therapy when f T > MIC was >60%; P = 0.013). A similar f T > MIC target of ≤63.9% (P = 0.009) was identified when skin and skin structure infections were excluded. While controlling for the SSSI source (odds ratio [OR], 0.18 [95% confidence interval, 0.03 to 1.19]; P = 0.07) and combination therapy (OR, 2.15 [95% confidence interval, 0.59 to 7.88]; P = 0.25), patients with f T > MIC values of ≤60% were 8.1 times (95% confidence interval, 1.2 to 55.6 times) more likely to experience a poor microbiological response. Cefepime doses of at least 2 g every 8 h are required to achieve this target against CLSI-defined susceptible P. aeruginosa organisms in patients with normal renal function. In patients with non-urinary tract infections caused by P. aeruginosa, achievement of cefepime exposures of >60% f T > MIC will minimize the possibility of a poor microbiological response.

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 Pharmacodynamics of Fluoroquinolones againstStreptococcus pneumoniae in Patients with Community-Acquired Respiratory Tract Infections

2001 ◽  
Vol 45 (10) ◽  
pp. 2793-2797 ◽  
Author(s):  
Paul G. Ambrose ◽  
Dennis M. Grasela ◽  
Thaddeus H. Grasela ◽  
Julie Passarell ◽  
Howard B. Mayer ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Drug Exposure ◽  
Free Drug ◽  
Classification And Regression Tree ◽  
Phase Iii ◽  
Population Pharmacokinetic ◽  
In Vitro Susceptibility ◽  
Fluoroquinolone Antibiotics ◽  
Tract Infections

ABSTRACT Fluoroquinolone antibiotic agents have demonstrated efficacy in the treatment of respiratory tract infections. This analysis was designed to examine the relationship between drug exposure, as measured by the free-drug area under the concentration-time curve at 24 h (AUC24)/MIC ratio, and clinical and microbiological responses in patients with community-acquired respiratory tract infections involving Streptococcus pneumoniae. The study population included 58 adult patients (34 males, 24 females) who were enrolled in either of two phase III, randomized, multicenter, double-blind studies of levofloxacin versus gatifloxacin for the treatment of community-acquired pneumonia or acute exacerbation of chronic bronchitis. Clearance equations from previously published population pharmacokinetic models were used in conjunction with dose and adjusted for protein binding to estimate individual patient free-drug AUC24s. In vitro susceptibility was determined in a central laboratory by broth microdilution in accordance with NCCLS guidelines. Pharmacodynamic analyses were performed on data from all evaluable patients with documented S. pneumoniaeinfection using univariate and multivariable logistic regression; pharmacodynamic breakpoints were estimated using Classification and Regression Tree analysis. A statistically significant (P = 0.013) relationship between microbiological response and the free-drug AUC24/MIC ratio was detected. At a free-drug AUC24/MIC ratio of <33.7, the probability of a microbiological response was 64%, and at a free-drug AUC24/MIC ratio of >33.7, it was 100% (P < 0.01). These findings may provide a minimum target free-drug AUC24/MIC ratio for the treatment of infections involving S. pneumoniae with fluoroquinolone antibiotics and provide a paradigm for the selection of fluoroquinolones to be brought forward from drug discovery into clinical development and dose selection for clinical trials. Further, when target free-drug AUC24/MIC ratios are used in conjunction with stochastic modeling techniques, these findings may be used to support susceptibility breakpoints for fluoroquinolone antibiotics and S. pneumoniae.

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.

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 Pharmacodynamic Analysis of Daptomycin-treated Enterococcal Bacteremia: It Is Time to Change the Breakpoint

2018 ◽  
Vol 68 (10) ◽  
pp. 1650-1657 ◽  
Author(s):  
Lindsay M Avery ◽  
Joseph L Kuti ◽  
Maja Weisser ◽  
Adrian Egli ◽  
Michael J Rybak ◽  
...  
Keyword(s):  
Regression Tree ◽  
Classification And Regression Tree ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Regression Tree Analysis ◽  
Lactam Antibiotic ◽  
Infection Source ◽  
High Doses ◽  
Susceptibility Breakpoint ◽  
Enterococcal Bacteremia

Abstract Background Currently, there is debate over whether the daptomycin susceptibility breakpoint for enterococci (ie, minimum inhibitory concentration [MIC] ≤4 mg/L) is appropriate. In bacteremia, observational data support prescription of high doses (&gt;8 mg/kg). However, pharmacodynamic targets associated with positive patient outcomes are undefined. Methods Data were pooled from observational studies that assessed outcomes in daptomycin-treated enterococcal bacteremia. Patients who received an additional antienterococcal antibiotic and/or a β-lactam antibiotic at any time during treatment were excluded. Daptomycin exposures were calculated using a published population pharmacokinetic model. The free drug area under the concentration-time curve to MIC ratio (fAUC/MIC) threshold predictive of survival at 30 days was identified by classification and regression tree analysis and confirmed with multivariable logistic regression. Monte Carlo simulations determined the probability of target attainment (PTA) at clinically relevant MICs. Results Of 114 patients who received daptomycin monotherapy, 67 (58.8%) were alive at 30 days. A fAUC/MIC &gt;27.43 was associated with survival in low-acuity (n = 77) patients (68.9 vs 37.5%, P = .006), which remained significant after adjusting for infection source and immunosuppression (P = .026). The PTA for a 6-mg/kg/day (every 24 hours) dose was 1.5%–5.5% when the MIC was 4 mg/L (ie, daptomycin-susceptible) and 91.0%–97.9% when the MIC was 1 mg/L. Conclusions For enterococcal bacteremia, a daptomycin fAUC/MIC &gt;27.43 was associated with 30-day survival among low-acuity patients. As pharmacodynamics for the approved dose are optimized only when MIC ≤1 mg/L, these data continue to stress the importance of reevaluation of the susceptibility breakpoint.

scholarly journals Prevalence of antibiotic resistance and blaIMP-1 gene among Pseudomonas aeruginosa strains isolated from burn and urinary tract infections in Isfahan, central Iran

2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Naeimeh Sadat Hashemi ◽  
Meysam Mojiri ◽  
Parivash Yazdani Kachouyi ◽  
Shiva Eskandari ◽  
Mehrsa Mohammadian ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Resistance Pattern ◽  
Public Health Issue ◽  
High Prevalence ◽  
Tract Infections

Pseudomonas aeruginosa is one of the most important opportunistic pathogens responsible for various types of hospital infections. High prevalence of antibiotic resistance in P. aeruginosa strains of human clinical samples cause more severe diseases for a longer period of time. The current research was done in order to study the distribution of blaIMP-1 gene among the imipenem-resistant P. aeruginosa strains isolated from burn and urinary tract infections of hospitalized patients. Two-hundred and forty-three P. aeruginosa isolates recovered from the cases of burn and urinary tract infections of inpatients and outpatients were analysis for antibiotic resistance pattern using the disk diffusion method. Then, imipenem-resistant isolates were further analyzed for distribution of blaIMP-1 gene using the PCR. Of 243 P. aeruginosa isolates, 146 strains (60.08%) were taken from outpatients and 97 strains (39.91%) were taken from inpatients. P. aeruginosa isolates harbored the highest levels of resistance against streptomycin (100%), nalidixic acid (100%), aztreonam (100%), cotrimoxazole (95.47%), ciprofloxacin (88.47%), cefotaxime (84.36%) and gentamycin (83.95%). Inpatients had a relatively higher levels of antibiotic resistance. One-hundred and twenty-one out of 126 (96.03%) imipenem-resistant P. aeruginosa isolates harbored the blaIMP-1 gene. Inpatients also had a relatively higher prevalence of blaIMP-1 gene. High prevalence of blaIMP-1 gene and also imipenemresistant P. aeruginosa are important public health issue. Clinical laboratories should consider the detection of the blaIMP-1 gene among the P. aeruginosa isolates of clinical samples.

scholarly journals In Vivo Bioluminescent Monitoring of Therapeutic Efficacy and Pharmacodynamic Target Assessment of Antofloxacin against Escherichia coli in a Neutropenic Murine Thigh Infection Model

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Yu-Feng Zhou ◽  
Meng-Ting Tao ◽  
Yu-Zhang He ◽  
Jian Sun ◽  
Ya-Hong Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Subcutaneous Administration ◽  
Free Drug ◽  
Infection Model ◽  
Bioluminescent Imaging ◽  
Time Curve ◽  
Content Type ◽  
E Coli ◽  
Tract Infections

ABSTRACT Antimicrobial resistance among uropathogens has increased the rates of infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli, such as Escherichia coli. This study monitored the in vivo efficacy of antofloxacin using bioluminescent imaging and determined pharmacokinetic (PK)/pharmacodynamic (PD) targets against E. coli isolates in a neutropenic murine thigh infection model. The PK properties were determined after subcutaneous administration of antofloxacin at 2.5, 10, 40, and 160 mg/kg of body weight. Following thigh infection, the mice were treated with 2-fold-increasing doses of antofloxacin from 2.5 to 80 mg/kg administered every 12 h. Efficacy was assessed by quantitative determination of the bacterial burdens in thigh homogenates and was compared with the bioluminescent density. Antofloxacin demonstrated both static and killing endpoints in relation to the initial burden against all study strains. The PK/PD index area under the concentration-time curve (AUC)/MIC correlated well with efficacy (R 2 = 0.92), and the dose-response relationship was relatively steep, as observed with escalating doses of antofloxacin. The mean free drug AUC/MIC targets necessary to produce net bacterial stasis and 1-log10 and 2-log10 kill for each isolate were 38.7, 66.1, and 147.0 h, respectively. In vivo bioluminescent imaging showed a rapid decrease in the bioluminescent density at free drug AUC/MIC exposures that exceeded the stasis targets. The integration of these PD targets combined with the results of PK studies with humans will be useful in setting optimal dosing regimens for the treatment of urinary tract infections due to E. coli.

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