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BMC Infectious Diseases Sep 2023Many factors determine empirical antibiotic treatment of community-acquired pneumonia (CAP). We aimed to describe the empirical antibiotic treatment CAP patients with an...
Empirical antibiotic treatment for community-acquired pneumonia and accuracy for Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae: a descriptive cross-sectional study of adult patients in the emergency department.
BACKGROUND
Many factors determine empirical antibiotic treatment of community-acquired pneumonia (CAP). We aimed to describe the empirical antibiotic treatment CAP patients with an acute hospital visit and to determine if the current treatment algorithm provided specific and sufficient coverage against Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae (LMC).
METHODS
A descriptive cross-sectional, multicenter study of all adults with an acute hospital visit in the Region of Southern Denmark between January 2016 and March 2018 was performed. Using medical records, we retrospectively identified the empirical antibiotic treatment and the microbiological etiology for CAP patients. CAP patients who were prescribed antibiotics within 24 h of admission and with an identified bacterial pathogen were included. The prescribed empirical antibiotic treatment and its ability to provide specific and sufficient coverage against LMC pneumonia were determined.
RESULTS
Of the 19,133 patients diagnosed with CAP, 1590 (8.3%) patients were included in this study. Piperacillin-tazobactam and Beta-lactamase sensitive penicillins were the most commonly prescribed empirical treatments, 515 (32%) and 388 (24%), respectively. Our analysis showed that 42 (37%, 95% CI: 28-47%) of 113 patients with LMC pneumonia were prescribed antibiotics with LMC coverage, and 42 (12%, 95% CI: 8-15%) of 364 patients prescribed antibiotics with LMC coverage had LMC pneumonia.
CONCLUSION
Piperacillin-tazobactam, a broad-spectrum antibiotic recommended for uncertain infectious focus, was the most frequent CAP treatment and prescribed to every third patient. In addition, the current empirical antibiotic treatment accuracy was low for LMC pneumonia. Therefore, future research should focus on faster diagnostic tools for identifying the infection focus and precise microbiological testing.
Topics: Humans; Adult; Legionella pneumophila; Mycoplasma pneumoniae; Cross-Sectional Studies; Retrospective Studies; Anti-Bacterial Agents; Piperacillin, Tazobactam Drug Combination; Emergency Service, Hospital; Pneumonia; Community-Acquired Infections
PubMed: 37670282
DOI: 10.1186/s12879-023-08565-6 -
The Journal of Antimicrobial... Oct 2022The efficacy and quality of generic antibacterial drug formulations are often questioned by both healthcare specialists and patients. Therefore, the present study... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of pharmacokinetics and stability of generics of cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs: an intravenous bioequivalence study in healthy volunteers.
OBJECTIVES
The efficacy and quality of generic antibacterial drug formulations are often questioned by both healthcare specialists and patients. Therefore, the present study investigated the interchangeability of generic drugs with their originators by comparing bioequivalence parameters and stability data of generic cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs.
METHODS
In this open-label, randomized, crossover bioequivalence study, three groups of 12 healthy volunteers each received a single intravenous infusion of either 2 g of cefepime or 4.5 g of piperacillin/tazobactam and two generic formulations, or 600 mg of linezolid and one generic formulation. Plasma sampling was performed, with a 5 day washout period between study days. Stability was tested by storing reconstituted generic and originator products according to their own storage specifications and those of the comparator products. All concentrations were measured by LC-MS.
RESULTS
Similar ratios of generic/originator (90% CI) Cmax were observed for Cefepime-MIP/Maxipime [93.7 (88.4-99.4)], Cefepime Sandoz/Maxipime [95.9 (89.1-103.2)], Linezolid Kabi/Zyvoxid [104.5 (91.1-119.9)], Piperacillin Kabi/Tazobac [95.9 (90.4-101.7)], Piperacillin Aurobindo/Tazobac [99.7 (84.9-104.7)], Tazobactam Kabi/Tazobac [93.4 (87.4-99.8)] and Tazobactam Aurobindo/Tazobac [97.4 (89.7-105.8)]. Accordingly, similar ratios of AUC0-t were observed for Cefepime-MIP/Maxipime [91.1 (87.6-94.8)], Cefepime Sandoz/Maxipime [97.9 (92.5-103.5)], Linezolid Kabi/Zyvoxid [99.7 (93.3-106.6)], Piperacillin Kabi/Tazobac [92.2 (88.3-96.3)], Piperacillin Aurobindo/Tazobac [99.9 (97.0-102.8)], Tazobactam Kabi/Tazobac [91.4 (86.4-96.7)] and Tazobactam Aurobindo/Tazobac [98.8 (94.3-103.6)]. Stable and similar concentrations were measured for all contiguous substances, regardless of storage conditions.
CONCLUSIONS
Compared with their respective originator drugs, generic cefepime, linezolid and piperacillin/tazobactam met the predetermined bioequivalence criteria. All formulations were stable under the storage conditions of their respective comparators.
Topics: Humans; Cefepime; Linezolid; Drugs, Generic; Therapeutic Equivalency; Healthy Volunteers; Piperacillin, Tazobactam Drug Combination; Piperacillin; Tazobactam; Anti-Bacterial Agents; Penicillanic Acid
PubMed: 36039038
DOI: 10.1093/jac/dkac285 -
Orthopaedics & Traumatology, Surgery &... Dec 2022Antibiotics differ in their elution characteristics from bone cement. But no such data is available on piperacillin and tazobactam. Therefore, we performed an in vitro... (Observational Study)
Observational Study
BACKGROUND
Antibiotics differ in their elution characteristics from bone cement. But no such data is available on piperacillin and tazobactam. Therefore, we performed an in vitro observational study to examine (1) in vitro elution characteristics of piperacillin and tazobactam from bone cement, (2) their biological activity using minimum inhibitory concentration and (3) elution characteristics and biological activity when combined with gentamicin in bone cement.
HYPOTHESIS
The null hypothesis was that piperacillin and tazobactam after elution from bone cement can achieve concentrations higher than minimum inhibitory concentration.
MATERIAL AND METHODS
Forty milligrams bone cement was mixed with the following combination of antibiotics: without any antibiotic (sample A, control), 4g/0.50g piperacillin/tazobactam (sample B), 6g/0.75g piperacillin/tazobactam (sample C), 8g/1.0g piperacillin/tazobactam (sample D) and 4g/0.50g piperacillin/tazobactam and 400mg gentamicin (sample E). Samples were analysed on reverse-phase ultra-high-performance liquid chromatography. Antibacterial activity in the elute were tested against standard American Type Culture Collection (ATCC) strains.
RESULTS
Detectable drug elution for piperacillin and tazobactam was seen till 21days. Peak drug levels for all formulations were seen at 48hours (140.8 & 297.5μg/mL for samples B of piperacillin and tazobactam respectively). About 0.83-1.24% of piperacillin and 23.17-29.17% of tazobactam were released from the samples. Gentamicin improved elution of piperacillin and tazobactam: 140.8 vs. 919.9μg/mL (p=0.000) for samples B & E of piperacillin respectively and 297.5 & 1138.4μg/mL (p=0.001) for samples B & E of tazobactam respectively at 2days. Sample E showed complete inhibition of tested microorganisms, while B sample was microbiologically less active compared to E on day 5.
CONCLUSIONS
Piperacillin and tazobactam eluted successfully from bone cement and also retained antimicrobial activity after elution. Maximum elution was seen up to day 2 after which it reduced drastically. Antimicrobial action was seen up to 7days.
LEVEL OF EVIDENCE
III; comparative study.
Topics: Humans; Gentamicins; Polymethyl Methacrylate; Penicillanic Acid; Bone Cements; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 35123032
DOI: 10.1016/j.otsr.2022.103230 -
Therapeutic Drug Monitoring Feb 2022For many antibiotics, the convenient one-fits-all dosing regimen had to be abandoned. Owing to highly variable pharmacokinetics, therapeutic drug monitoring has become... (Review)
Review
BACKGROUND
For many antibiotics, the convenient one-fits-all dosing regimen had to be abandoned. Owing to highly variable pharmacokinetics, therapeutic drug monitoring has become an indispensable prerequisite. It is based on a suitable measuring method, sample materials, and standardization. Appropriate quality control including external quality assessment (EQA) is essential. For many antibiotics, EQAs have been established for many decades, whereas others have only lately been introduced. This article gives an insight into the state of the art regarding the therapeutic drug monitoring of antibiotics regarding standardization, EQAs, and reference measurement procedures (RMPs).
METHODS
An overview of the currently available international EQA schemes for antibiotics and a literature overview of available RMPs are given. EQAs including gentamicin and vancomycin have been offered by German providers for more than 25 years. The period 2000-2020 was selected for a detailed analysis. The experiences with a new EQA including linezolid, meropenem, and piperacillin are described.
RESULTS
EQAs for gentamicin and vancomycin are provided in many countries. Those for linezolid, meropenem, and piperacillin do not seem to be very common. Most of the antibiotics monitored for decades are measured by commercially available assays. EQAs for linezolid, meropenem, and piperacillin introduced in 2018 were rapidly accepted in Germany. Methods reported in this study were HPLC based either with UV or mass spectrometric detection. The number of participants succeeding was comparable between UV and mass spectrometry. Candidate RMPs for gentamicin, vancomycin, and linezolid based on isotope dilution mass spectrometry were published.
CONCLUSIONS
EQAs are offered regularly for many antibiotics worldwide. The results of EQAs in Germany generally compare well, but there is potential for improvement. Both immunoassays and HPLC-based methods work properly in EQAs evaluated in Germany. From a quality control perspective, fast and inexpensive methods may be selected without endangering the patient's health based on clinical needs.
Topics: Anti-Bacterial Agents; Humans; Linezolid; Meropenem; Piperacillin; Reference Standards
PubMed: 34923543
DOI: 10.1097/FTD.0000000000000953 -
International Journal of Antimicrobial... Nov 2023Guidelines recommend 5-7 days of antibiotic treatment in patients with surgical infection and adequate source control. This nationwide stewardship intervention aimed to...
Reducing the duration of antibiotic therapy in surgical patients through a specific nationwide antimicrobial stewardship program. A prospective, interventional cohort study.
BACKGROUND
Guidelines recommend 5-7 days of antibiotic treatment in patients with surgical infection and adequate source control. This nationwide stewardship intervention aimed to reduce the duration of treatments in surgical patients to <7 days.
METHODS
Prospective cohort study evaluating surgical patients receiving antibiotics ≥7 days in 32 hospitals. Indication for treatment, quality of source control, type of recommendations issued, and adherence to the recommendations were analysed. Temporal trends in the percentages of patients with treatment >7 days were evaluated using a linear regression model and Pearson's correlation coefficients.
RESULTS
A total of 32 499 patients were included. Of these, 13.7% had treatments ≥7 days. In all, 3912 stewardship interventions were performed, primarily in general surgery (90.7%) and urology (8.1%). The main types of infection were intra-abdominal (73.4%), skin/soft tissues (9.8%) and urinary (9.2%). The septic focus was considered controlled in 59.9% of cases. Out of 5458 antibiotic prescriptions, the most frequently analysed drugs were piperacillin/tazobactam (21.7%), metronidazole (11.2%), amoxicillin/clavulanate (10.3%), meropenem (10.7%), ceftriaxone (9.3%) and ciprofloxacin (6.7%). The main recommendations issued were: treatment discontinuation (35.0%), maintenance (40.0%) or de-escalation (15.5%), and the overall adherence rate was 91.5%. With adequate source control, the most frequent recommendation was to terminate treatment (51.2%). Throughout the study period, a significant decrease in the percentage of prolonged treatments was observed (Pc=-0.69;P < 0.001).
CONCLUSIONS
This stewardship programme reduced the duration of treatments in surgical departments. Preference was given to general surgery services, intra-abdominal infection, and beta-lactam antibiotics, including carbapenems. Adherence to the issued recommendations was high.
Topics: Humans; Prospective Studies; Cohort Studies; Antimicrobial Stewardship; Anti-Bacterial Agents; Piperacillin, Tazobactam Drug Combination
PubMed: 37541529
DOI: 10.1016/j.ijantimicag.2023.106943 -
European Journal of Clinical... Jun 2022Estimated glomerular filtration rate (eGFR) equations reflect kidney function imprecisely. We aimed to describe whether iohexol-based GFR or eGFRs predict clearance of...
PURPOSE
Estimated glomerular filtration rate (eGFR) equations reflect kidney function imprecisely. We aimed to describe whether iohexol-based GFR or eGFRs predict clearance of cefepime, piperacillin, and tazobactam in pharmacokinetic (PK) models in this population and its clinical significance.
METHODS
Hospitalized patients (0.5-25 years) with haemato-oncological disease and infection receiving cefepime or piperacillin/tazobactam were included. PK samples were collected at a steady state concomitantly with samples for iohexol-based GFR. PK models were developed in NONMEM. Weight, postmenstrual age, iohexol-based GFR, different eGFR equations (Schwartz updated, Lund-Malmö revised, CKD-EPI, Bouvet, Schwartz cystatin C-based) were tested as covariates. Probabilities of neurotoxic/therapeutic concentrations were assessed by simulations.
RESULTS
Fifteen patients receiving cefepime and 17 piperacillin/tazobactam were included (median (range) age 16.2 (1.9-26.0) and 10.5 (0.8-25.6) years, iohexol-based GFR 102 (68-140) and 116 (74-137) mL/min/1.73 m, respectively). Two-compartment model provided the best fit for all drugs. Weight was covariate for central and peripheral compartment, clearance and intercompartmental clearance (only tazobactam), and postmenstrual age for clearance (excluding cefepime). Iohexol-based GFR was the best predictor of clearance. The model of cefepime without vs with iohexol-based GFR underestimated the probability of neurotoxic concentrations (28.3-28.6% vs 52.1-69.3%) and overestimated the probability of therapeutic concentrations (> 90% vs 81.9-87.1%) in the case of iohexol-based GFR 70-80 and 130-140 mL/min/1.73 m, respectively.
CONCLUSION
Iohexol-based GFR can predict better than eGFRs the clearance of cefepime, piperacillin, and tazobactam in children and young adults with haemato-oncological disease and infection, warranting further investigation as an indicator of renal function to improve targeting of therapeutic window.
TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION
EudraCT 2015-000,631-32, EudraCT 2016-003,374-40 (24.10.2016).
Topics: Adolescent; Cefepime; Child; Creatinine; Glomerular Filtration Rate; Humans; Iohexol; Kidney Function Tests; Piperacillin; Tazobactam; Young Adult
PubMed: 35275224
DOI: 10.1007/s00228-022-03307-0 -
Therapeutic Drug Monitoring Apr 2023The use of regional citrate anticoagulation during continuous venovenous hemodiafiltration (CVVHDF) has increased worldwide. However, data on its effect on the...
BACKGROUND
The use of regional citrate anticoagulation during continuous venovenous hemodiafiltration (CVVHDF) has increased worldwide. However, data on its effect on the pharmacokinetics of antibiotics are limited. In this study, the authors aimed to measure the clearance of piperacillin-tazobactam and vancomycin in patients receiving CVVHDF with regional citrate anticoagulation.
METHODS
This study measured piperacillin-tazobactam and vancomycin concentrations in patients receiving CVVHDF with regional citrate anticoagulation. Dosing regimens were independently selected by intensivists. Arterial blood and effluent fluid samples were obtained over a single dosing interval and analyzed using ultra-high-performance liquid chromatography with tandem mass spectrometry.
RESULTS
Seventeen sampling intervals in 15 patients (9 receiving piperacillin-tazobactam only, 4 receiving vancomycin only, and 2 receiving both) were used. The median overall clearance for piperacillin was 35.2 mL/min [interquartile range (IQR): 32.2-38.6], 70 mL/min (IQR: 62.7-76.2) for tazobactam, and 29.5 mL/min (IQR: 26.2-32) for vancomycin.
CONCLUSIONS
This is the first study to quantify the pharmacokinetics of vancomycin and piperacillin-tazobactam in patients receiving CVVHDF with regional citrate anticoagulation. These results indicate high clearance and provide key information to guide optimal dosing.
Topics: Humans; Vancomycin; Citric Acid; Anti-Bacterial Agents; Piperacillin, Tazobactam Drug Combination; Piperacillin; Tazobactam; Citrates; Anticoagulants; Critical Illness; Acute Kidney Injury
PubMed: 35994070
DOI: 10.1097/FTD.0000000000001028 -
Journal of Critical Care Feb 2022Beta-lactam dosing is challenging in critically ill patients with slow extended daily dialysis (SLEDD). This prospective observational study aimed to investigate... (Observational Study)
Observational Study
Trough concentrations of meropenem and piperacillin during slow extended dialysis in critically ill patients with intermittent and continuous infusion: A prospective observational study.
Beta-lactam dosing is challenging in critically ill patients with slow extended daily dialysis (SLEDD). This prospective observational study aimed to investigate meropenem and piperacillin concentrations and half-lives during SLEDD and in SLEDD-free intervals. Critically ill patients with SLEDD-therapy and meropenem or piperacillin therapy were included. Breakpoints of target attainment were defined as 2 and 20.8 mg/L for meropenem and piperacillin, respectively. Daily TDM was performed and therapies were adapted based on the measured concentrations. Elimination rate constants were determined by using nonlinear regression analysis. Seventeen patients were included (48 SLEDD intervals; median SLEDD-duration: 7.25 h). The median antibiotic trough concentrations and half-lives were significantly (p < 0.001) lower during and after the SLEDD-therapy compared to SLEDD-free intervals (median meropenem: 22.3 (IQR: 12.8, 25.6) vs. 28.3 mg/L (IQR: 16.9, 37.4); median piperacillin: 55.8 (IQR: 45.1, 84.9) vs. 130 mg/L (IQR: 91.5, 154.5); relative change: -48.0% each, IQR meropenem: -33.3, -58.5%; IQR piperacillin: -36.3, -52.1%). However, none of the measured trough concentrations were subtherapeutic during SLEDD. SLEDD leads to a reduction in meropenem and piperacillin concentrations of approximately 50% independently of the initial concentration. If the concentration is twice as high as the breakpoint of target attainment before SLEDD-therapy, subtherapeutic levels can be avoided.
Topics: Anti-Bacterial Agents; Critical Illness; Humans; Meropenem; Piperacillin; Renal Dialysis
PubMed: 34628123
DOI: 10.1016/j.jcrc.2021.09.011 -
Journal of Infection and Chemotherapy :... Jul 2022Microorganisms can evolve and become resistant to antimicrobials, and this is known as antimicrobial resistance (AMR). Inappropriate use of antibiotics contributes to...
INTRODUCTION
Microorganisms can evolve and become resistant to antimicrobials, and this is known as antimicrobial resistance (AMR). Inappropriate use of antibiotics contributes to AMR, and antimicrobial stewardship programs have been developed to mitigate AMR. The Appropriate Use of Carbapenems Program was implemented in March 2019 in a university hospital and its effect was evaluated.
METHODS
We conducted a prospective audit and feedback on carbapenems at the time of prescription daily. Additionally, we compared a monthly survey of the total days of therapy (DOTs) per 1000 patient-days for carbapenems, piperacillin/tazobactam, and fluoroquinolones. The susceptibility of Pseudomonas aeruginosa to meropenem, piperacillin/tazobactam, and levofloxacin was tested before (January 2018 to February 2019) and after (March 2019 to December 2020) the intervention.
RESULTS
The monthly median DOTs of carbapenem usage decreased after the intervention; carbapenem use immediately declined during the intervention period. The monthly median DOTs of piperacillin/tazobactam and fluoroquinolones also decreased and continued to decline significantly after the intervention. Susceptibility of P. aeruginosa to meropenem, piperacillin/tazobactam, and levofloxacin did not change significantly during the study.
CONCLUSION
The implementation of the Appropriate Use of Carbapenems Program was effective in reducing the use of broad-spectrum antibiotics and maintaining the antibiotic susceptibility of P. aeruginosa.
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Carbapenems; Fluoroquinolones; Hospitals; Humans; Japan; Levofloxacin; Meropenem; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa
PubMed: 35331613
DOI: 10.1016/j.jiac.2022.03.006 -
Clinica Chimica Acta; International... Dec 2021Therapeutic drug monitoring (TDM) of β-lactam antibiotics may be used to optimize dosing for patients in the intensive care unit (ICU). A noninvasive matrix such as...
BACKGROUND
Therapeutic drug monitoring (TDM) of β-lactam antibiotics may be used to optimize dosing for patients in the intensive care unit (ICU). A noninvasive matrix such as oral fluid may be interesting in selected patient groups. We compared the oral fluid concentrations of piperacillin and meropenem with the respective unbound and total concentrations in plasma. A secondary objective was to evaluate feasibility of the collection of oral fluid samples in this specific patient population.
METHODS
The study included 20 non-intubated ICU patients, age 22 to 77 y, receiving piperacillin or meropenem via continuous intravenous infusion. The standard protocol consisted of collecting a paired plasma-oral fluid sample for 3 consecutive days. Oral fluid was obtained from the patients using a standardized procedure by spitting in a plastic container after 2 min of gathering oral fluid in the mouth.
RESULTS
Antibiotic concentrations of piperacillin and meropenem are measurable, albeit very low, in unstimulated oral fluid of ICU patients. For piperacillin, a poor correlation was found between oral fluid and both total and unbound plasma concentrations (Spearman's correlation coefficients (Rs) 0.46 and 0.48 respectively). For meropenem this correlation was better (Rs for oral fluid versus total and unbound plasma meropenem concentration 0.92 and 0.93 respectively). Dispersion of antibiotic concentrations was greater in oral fluid than in blood. Collecting oral fluid samples was difficult in non-intubated ICU patients.
CONCLUSIONS
Oral fluid from non-intubated ICU patients, obtained through a standardized procedure, cannot be recommended as an alternative matrix for quantitative meropenem or piperacillin TDM.
Topics: Adult; Aged; Anti-Bacterial Agents; Critical Illness; Humans; Intensive Care Units; Meropenem; Middle Aged; Pilot Projects; Piperacillin; Young Adult
PubMed: 34508687
DOI: 10.1016/j.cca.2021.09.005