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International Journal of Antimicrobial... Nov 2023Knowledge on the tissue penetration of piperacillin-tazobactam in children with sepsis is lacking. In this study, the feasibility and performance of microdialysis...
OBJECTIVES
Knowledge on the tissue penetration of piperacillin-tazobactam in children with sepsis is lacking. In this study, the feasibility and performance of microdialysis experiments were explored in septic piglets and children as part of a translational research project.
METHODS
Multiple-day microdialysis investigations were performed in muscle tissue of 22 piglets (of which 11 were septic) and 6 children with sepsis. An in vitro experiment preceded the (pre)clinical trials to derive optimal experimental settings and calibration technique. Linear mixed-effects models quantified the impact of sepsis on relative recovery (RR) and intercatheter, interindividual, interoccasion, and residual variability.
RESULTS
In vivo microdialysis was well tolerated in piglets and children, with no significant adverse events reported. Using identical experimental settings, lower RR values were recorded in healthy and septic piglets (range: piperacillin, 17.2-29.1% and tazobactam, 23.5-29.1%) compared with the in vitro experiment (piperacillin, 43.3% and tazobactam, 55.3%), and there were unacceptably low values in children with sepsis (<10%). As a result, methodological changes were made in the pediatric trial. Realistic tissue concentration-time curves were derived in piglets and children. In piglets, sepsis reduced the RR. The greatest contributors to RR variability were residual (>40%) and interoccasion (>30%) variability. The internal standard method was the preferred calibration technique in both piglets and children.
CONCLUSIONS
Microdialysis is a safe and applicable method for the measurement of tissue drug concentrations in piglets and children. This study demonstrated the impact of experimental settings, sepsis, and target population on individual RR.
Topics: Humans; Child; Animals; Swine; Anti-Bacterial Agents; Microdialysis; Piperacillin, Tazobactam Drug Combination; Piperacillin; Tazobactam; Sepsis; Penicillanic Acid
PubMed: 37716576
DOI: 10.1016/j.ijantimicag.2023.106970 -
Paediatric Drugs Jul 2021The antibiotic combination of vancomycin (VAN) and piperacillin-tazobactam (PTZ) has been associated with an increased risk of acute kidney injury (AKI) in both adult... (Review)
Review
The antibiotic combination of vancomycin (VAN) and piperacillin-tazobactam (PTZ) has been associated with an increased risk of acute kidney injury (AKI) in both adult and pediatric patients. In this review, we highlight some of the limitations of existing pediatric studies evaluating the combination of VAN/PTZ, focusing on AKI risk in specific pediatric patient populations. We also review the variability in defining AKI in children and provide guidance to clinicians for use of prospective surveillance and stewardship in mitigating the risk of AKI in pediatric patients treated with combination of VAN/PTZ. Based on review of available pediatric studies, if the combination of VAN/PTZ is selected as an empirical antibiotic combination, it should be used in those at low risk for AKI and should be used with extreme caution in patients with additional nephrotoxic risks. Systems should be in place to monitor the use of VAN/PTZ and associated renal function in those receiving this antibiotic combination.
Topics: Acute Kidney Injury; Anti-Bacterial Agents; Child; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Retrospective Studies; Risk Factors; Vancomycin
PubMed: 34235634
DOI: 10.1007/s40272-021-00458-y -
Pediatric Pulmonology Nov 2022Antibiotic allergy is a big problem that may affect the treatment and life quality of patients with cystic fibrosis (CF).
UNLABELLED
Antibiotic allergy is a big problem that may affect the treatment and life quality of patients with cystic fibrosis (CF).
AIM
To evaluate predictive factors for confirmed antibiotic hypersensitivity in children with CF.
METHODS
In this case-controlled study, we examined 15 patients with CF who had been confirmed with antibiotic allergy. Additionally, we included a control group of age- and gender-matched 45 CF patients with no antibiotic allergy. The diagnosis of antibiotic allergy was confirmed in the presence of a compatible history and a positive response in the drug skin test or provocation test. Multiple drug hypersensitivity was classified according to the temporal relationship of antibiotics: (i) distant, (ii) simultaneous, and (iii) sequential. The data were analyzed by conditional logistic regression.
RESULTS
β-lactam allergy was confirmed in eight patients (ceftazidime n = 5, piperacillin-tazobactam n = 3) and non-β-lactam allergy was confirmed in two patients (ciprofloxacin n = 1, azithromycin n = 1). Additionally, multiple drug hypersensitivity in five patients (distant n = 4, sequential n = 1), among whom two patients showed hypersensitivity against ceftazidime/piperacillin-tazobactam+ ciprofloxacin/levofloxacin, two patients showed hypersensitivity against ceftazidime+ ciprofloxacin n = 2, and one patient showed hypersensitivity against piperacillin-tazobactam+ amikacin+ trimethoprim-sulfamethoxazole. All patients (n = 13) with confirmed β-lactam allergy were meropenem tolerant. Multivariate analysis indicated that immediate reactions (, p < 0.001) and allergic evaluation in the first six months after the reaction (p = 0.036) were significant risk factors for the prediction of antibiotic hypersensitivity.
CONCLUSION
Beta-lactam antibiotic allergy is the most commonly confirmed drug allergy in children with CF. However, unlike normal children, ceftazidime and piperacillin-tazobactam account for the majority.
Topics: Amikacin; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Ceftazidime; Child; Ciprofloxacin; Cystic Fibrosis; Drug Hypersensitivity; Humans; Levofloxacin; Meropenem; Piperacillin; Retrospective Studies; Tazobactam; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 35833362
DOI: 10.1002/ppul.26073 -
Clinical Laboratory Sep 2019Therapeutic drug monitoring (TDM) of beta-lactam antibiotics has become a valuable tool to guide dosing in critically ill patients. The main goal of the study was to... (Comparative Study)
Comparative Study
BACKGROUND
Therapeutic drug monitoring (TDM) of beta-lactam antibiotics has become a valuable tool to guide dosing in critically ill patients. The main goal of the study was to compare two routinely used techniques for beta-lactam TDM in intensive care unit (ICU) patient samples, namely isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) and high-performance liquid chromatography combined with ultra-violet detection (HPLC-UV).
METHODS
A set of 80 sera/plasma samples from ICU patients receiving therapeutic meropenem or piperacillin dosage was investigated. Sample duplicates and quality assessment samples were assayed in parallel with an in-house LC-MS/MS and a commercially available IVD HPLC-UV kit. A pharmacokinetic and pharmacodynamic (PK/PD) target with ≥ 22.5 mg/L for piperacillin and ≥ 8.0 mg/L for meropenem was used for medical assessment of trough sample (n = 40) antibiotic concentrations.
RESULTS
There was no difference between serum and Li-heparin plasmas. Concentration deviations were found for 4% of meropenem and 17% of piperacillin samples. Eliminating the influence of the systemic bias of approximately 10% for piperacillin, measurement discrepancies ≥ 25% between LC-MS/MS and HPLC-UV analyses were only observed for ≈ 4 - 6% of all samples. In the same way, identical PK/PD target attainment rates of 50 - 60% could be obtained.
CONCLUSIONS
After correction of the analytical bias for piperacillin measurements, both methods showed comparable results, also with respect to clinical decision limits. HPLC-UV analysis is an adequate TDM methodology for testing of beta-lactam antibiotics in centers where no special knowledge in LC-MS/MS based TDM is present. However, potential matrix effects, interferences, and calibration issues for both methods must be taken into account.
Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Chromatography, Liquid; Critical Care; Critical Illness; Drug Monitoring; Humans; Meropenem; Piperacillin; Reproducibility of Results; Tandem Mass Spectrometry; Ultraviolet Rays
PubMed: 31532096
DOI: 10.7754/Clin.Lab.2019.190210 -
Surgical Infections Jun 2022Although abdominal foci are the second most common source of sepsis, only few studies focus on the optimal length of post-operative antibiotic therapy in critically ill... (Review)
Review
Although abdominal foci are the second most common source of sepsis, only few studies focus on the optimal length of post-operative antibiotic therapy in critically ill patients with abdominal sepsis. The aim of this study was to compare the outcomes of short versus long antibiotic therapy as well as broad-spectrum penicillin versus carbapenem in patients with abdominal sepsis. We performed a single center retrospective study in patients with abdominal sepsis who underwent emergency surgery. The study was conducted in a tertiary hospital in Germany during 2016-2018. We reviewed the duration of post-operative antibiotic therapy and the initially used agent, comparing patients treated shorter or longer than seven days with or without source control. Depending on the empirically given antibiotic, a subgroup analysis was conducted comparing patients treated with piperacillin-tazobactam versus carbapenems. Longer duration of post-operative antibacterial treatment (>7 days) was not substantially advantageous. The group with a longer course of antibiotic therapy had more severe post-operative complications (82.4% [n = 61] vs. 62.5% [n = 20]; p = 0.01) requiring longer critical care support (18 days vs. 11 days; p = 0.027), prolonging the length of stay (28 days vs. 20 days; p = 0.044). Surgical re-interventions were more frequent in the long-course arm (70.3% vs. 40.6%; p = 0.004). The subgroup analysis comparing piperacillin-tazobactam versus carbapenems confirmed more severe complications (86.3% vs. 67.5%; p = 0.04) for the carbapenem arm. Post-surgical continuation of antibiotic agents beyond seven days was observed with more post-operative complications and delayed recovery. Piperacillin-tazobactam seems to be a potent alternative for patients with abdominal sepsis.
Topics: Anti-Bacterial Agents; Carbapenems; Humans; Intraabdominal Infections; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis
PubMed: 35532964
DOI: 10.1089/sur.2021.344 -
International Journal of Antimicrobial... Mar 2024Piperacillin/tazobactam (PTZ) is a broad-spectrum antibiotic, typically dosed every six hours (q6h). Guidelines recommend dosing PTZ every 2 hours (q2h)...
Piperacillin/tazobactam (PTZ) is a broad-spectrum antibiotic, typically dosed every six hours (q6h). Guidelines recommend dosing PTZ every 2 hours (q2h) intra-operatively for complex abdominal surgery, including liver transplant. The data supporting the guidelines for intra-operative dosing are sparse and the pharmacokinetics/pharmacodynamics (PK/PD) of q2h dosing has not been studied by simulation or in humans. In this study, PK/PD parameters of high-frequency intra-operative dosing and q6h post-operative dosing were compared in critically ill children. Paediatric patients who received PTZ during complex abdominal surgery or transplant and who had intra-operative and post-operative opportunistic samples were included. Using a published PK model and observed concentrations, individual piperacillin PK/PD parameters were estimated using Bayesian estimation. Alternative post-operative dosing strategies were simulated using the patients with the highest and lowest estimated piperacillin clearance. Thirteen patients were included (median age: 3.1 years, 85% liver transplant recipients). PK parameters in the intra-operative and post-operative phases were not significantly different (clearance: 15.8 ± 7.2 vs. 12.6 ± 6.3 L/h/70 kg, P=0.070; central volume: 13.4 [13.1, 13.8] vs. 15.2 [12.2, 16.0] L/70 kg, P=0.22). At an individual level, intra-operative clearance values were -35% to 139% of the post-operative values, whereas central volume intra-operative values were -40% to 77% of the post-operative values. Intra-operative piperacillin exposure was higher during high-frequency dosing compared with the post-operative period (AUC/h: 109 [93.4, 127] vs. 62.8 [41.6, 78.3] mg/L, P=0.002). Simulations showed great variation in optimal dosing strategies that would minimise toxicity and maximise efficacy, indicating a role for individualised dosing in paediatric surgical populations.
Topics: Humans; Child; Child, Preschool; Piperacillin; Bayes Theorem; Piperacillin, Tazobactam Drug Combination; Anti-Bacterial Agents; Computer Simulation
PubMed: 38161045
DOI: 10.1016/j.ijantimicag.2023.107079 -
The Journal of Allergy and Clinical... Jun 2021
Topics: Humans; Hypersensitivity, Delayed; Piperacillin; Piperacillin, Tazobactam Drug Combination
PubMed: 34112492
DOI: 10.1016/j.jaip.2021.03.025 -
Anaerobe Dec 2023Infections from anaerobic microorganisms result from breached mucosal barriers, posing a significant mortality risk. A retrospective study at Hospital Universitario La...
Infections from anaerobic microorganisms result from breached mucosal barriers, posing a significant mortality risk. A retrospective study at Hospital Universitario La Paz (Madrid) from 2010 to 2022 analyzed 491 (6.17 %) anaerobic bacteremia cases out of 7956 significant bacteremia cases among 171,833 blood culture requests. Bacteroides fragilis was the most frequently isolated species (28.3 %), followed by Clostridium perfringens (13.6 %). B. fragilis showed good susceptibility to amoxicillin/ clavulanic acid (86 %), piperacillin/tazobactam (86 %), and metronidazole (87.7 %). In general, non-fragilis Bacteroides species showed low susceptibility to penicillin (7 %), amoxicillin (17.5 %), and clindamycin (64.9 %). Of our 13 non-perfringens Clostridium isolates, four exhibited resistance to penicillin and four showed resistance to clindamycin. Lactobacillus species were highly susceptible to antibiotics tested. Prevotella spp. showed low susceptibility to penicillin (20 %), amoxicillin (20 %), and clindamycin (40 %). The study contributes valuable data for monitoring and improving anaerobic bacteremia treatment.
Topics: Humans; Bacteria, Anaerobic; Clindamycin; Retrospective Studies; Tertiary Care Centers; Microbial Sensitivity Tests; Anti-Bacterial Agents; Bacteremia; Piperacillin, Tazobactam Drug Combination; Bacteroides fragilis; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Clostridium perfringens
PubMed: 37984560
DOI: 10.1016/j.anaerobe.2023.102803 -
Assessing Rates of Co-Resistance and Patient Outcomes in Multidrug-Resistant Pseudomonas aeruginosa.Microbiology Spectrum Oct 2022Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with poor patient outcomes due to complex co-resistance patterns. We described common...
Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with poor patient outcomes due to complex co-resistance patterns. We described common co-resistance patterns, clinical characteristics, and associated outcomes in patients admitted with an MDR P. aeruginosa. This national, multicenter, retrospective cohort study within the Veterans Affairs included adults hospitalized with a MDR P. aeruginosa infection (January 2015-December 2020) per Centers for Disease Control definition. Clinical outcomes were compared among those with differing MDR P. aeruginosa co-resistance: resistant to carbapenems and extended-spectrum cephalosporins and piperacillin-tazobactam (CARB/ESC/PT) versus without CARB/ESC/PT resistance; resistant to carbapenems and extended-spectrum cephalosporins and fluoroquinolone (CARB/ESC/FQ) versus without CARB/ESC/FQ resistance. We included 3,763 hospitalized patients. Co-resistance to CARB/ESC/PT was observed in 42.7%, and to CARB/ESC/FQ in 40.7%. The lowest co-resistance rates were observed with ceftolozane-tazobactam (6.2%, = 6/97; 12.5%, = 10/80, respectively) and ceftazidime-avibactam (5.2%, = 5/97; 12.5%, = 10/80, respectively). Overall, 14.2% of patients died during hospitalization, 59.7% had an extended length of stay, and 14.9% had reinfection with hospitalization. Outcomes were similar between patients with MDR P. aeruginosa strains with and without co-resistance to CARB/ESC/PT and CARB/ESC/FQ. Among a national cohort of patients hospitalized with MDR P. aeruginosa infections, co-resistance to three classes of standard of care antibiotics, such as carbapenem, extended-spectrum cephalosporins, and piperacillin-tazobactam or fluoroquinolones, exceeded 40% in our study population, posing great concerns for selecting appropriate empirical therapy. Clinical outcomes were poor for all patients, regardless of different co-resistance patterns. New treatment options are needed for hospitalized patients with suspected or confirmed MDR P. aeruginosa infections. We studied antibiotic co-resistance patterns in a national group of hospitalized patients with infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa, a type of bacteria that resists treatment to at least three classes of antibiotics. Co-resistance to antibiotic classes most typically used for treatment was common, which makes selecting appropriate antibiotics to successfully treat the infections difficult. Outcomes, including death, were poor for all patients in our study, regardless of the different patterns of co-resistance to common antibiotic classes. New antibiotics are needed to help treat hospitalized patients with MDR P. aeruginosa infections.
Topics: Adult; Humans; Pseudomonas aeruginosa; Retrospective Studies; Cephalosporins; Tazobactam; Anti-Bacterial Agents; Carbapenems; Piperacillin, Tazobactam Drug Combination; Fluoroquinolones; Pseudomonas Infections; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial
PubMed: 36005836
DOI: 10.1128/spectrum.02336-22 -
Frontiers in Cellular and Infection... 2023The colonization of the oral cavity by potentially pathogenic antimicrobial-resistant bacteria in adolescents and its consequences is very poorly understood. The present...
INTRODUCTION
The colonization of the oral cavity by potentially pathogenic antimicrobial-resistant bacteria in adolescents and its consequences is very poorly understood. The present study focused on the occurrence of oral colonization by Gram-negative bacilli (GNB) and their multidrug resistance, including the production of extended-spectrum β-lactamases (ESBLs) and carbapenemases, among healthy adolescents and risk factors associated with GNB colonization.
MATERIALS AND METHODS
This study was conducted as part of "A program for the early detection of risk factors for lifestyle diseases SOPKARD-Junior" (SOPKARD-Junior). Oral samples were collected from 182 adolescents from four public elementary schools in Sopot, Poland, aged 13-14 years. Bacterial strains were identified by the MALDI-TOF MS method. Screening of antimicrobial resistance was performed using a disk diffusion method. The NG-Test CARBA-5 was used to detect and differentiate the five most widely distributed carbapenemases. Demographic and clinical data were collected and statistical analysis of risk factors was performed.
RESULTS
A total of 68 out of 182 (37.4%) healthy adolescents was documented oral colonization with Gram-negative bacilli, including 50/182 (27.5%) multidrug resistant (MDR-GNB) strains. Over 60% of oral carriage concerned three main genera spp., spp., and spp., which were detected in 22.1%, 19.1%, and 19.1% of participants, respectively. spp., , spp., spp., spp., spp., and spp. were also isolated. The antimicrobial resistance to ampicillin (100%), ceftazidime (69.1%), meropenem (60.3%), gentamycin (60.3%), piperacillin/tazobactam (52.9%), and piperacillin (45.6%) were the most common. Among 73.5% GNB strains multidrug resistance was observed, including all spp. strains. Among MDR-GNB, 30.4% were resistant to four groups of antibiotics, half of the MDR spp. strains were resistant to 10 groups of antibiotics. Extended-spectrum β-lactamases were produced by , spp., and spp. (7.4%). Colonization by ESBLs-positive GNB strains was significantly associated with recurrent respiratory infections, nasal congestion, and bronchitis (p<0.05).
CONCLUSION
Our study revealed high oral carriage of multi-drug resistant Gram-negative bacilli in healthy adolescents and the association of ESBL-producing strains with respiratory infections. Further studies on oral colonization with GNB are necessary due to the possibility of distinct infections and the acquisition of antibiotic resistance by resident microbiota.
Topics: Adolescent; Humans; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Gram-Negative Bacteria; beta-Lactamases; Piperacillin; Respiratory Tract Infections; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests
PubMed: 38035342
DOI: 10.3389/fcimb.2023.1265777