A rapid, LC-MS/MS assay for quantification of piperacillin and tazobactam in human plasma and pleural fluid; application to a clinical pharmacokinetic study.

Piperacillin, in combination with tazobactam is a common first-line antibiotic used for the treatment of pleural infection, however its pleural pharmacokinetics and penetration has not previously been reported. The objective of this work was to develop and validate a rapid and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay for quantification of piperacillin (PIP) and tazobactam (TAZ). PIP and TAZ were extracted from both human plasma and pleural fluid samples by protein precipitation in methanol containing the internal standards (IS) piperacillin-d5 (PIP-d5) and sulbactam (SUL). Briefly, 5 µL of sample was mixed with 125 µL of methanol containing IS, vortexed and centrifuged. Supernatant (50 µL) was diluted into 500 µL of mobile phase containing 10 mM of ammonium bicarbonate in LCMS grade water and transferred to the autosampler tray. Electrospray ionization in positive mode and multiple reaction monitoring (MRM) were used for PIP and PIP-d5 at the transitions m/z 518.2 → 143.2 and m/z 523.2 → 148.2 respectively, and electrospray ionization in negative mode and MRM were used for TAZ and SUL at the transitions m/z 299.1 → 138.1 and m/z 232.4 → 140.1. The chromatographic separation was achieved using an Acquity BEH C-18 column with gradient elution of mobile phase containing 10 mmol/L ammonium bicarbonate in water and methanol. A linear range was observed over the concentration range of 0.25-352 mg/L and 0.25-50.5 mg/L for PIP and TAZ respectively. Complete method validation was performed according to US FDA guidelines for selectivity, specificity, precision and accuracy, LLOQ, matrix effects, recovery and stability, with all results within acceptable limits. This method was successfully applied to two patients with pleural infection and is suitable for further pharmacokinetic studies and therapeutic drug monitoring.

Therapeutic drug monitoring of piperacillin and tazobactam by RP-HPLC of residual blood specimens.

BACKGROUND: Sepsis is a common diagnosis in critical care with inpatient mortality rates up to 50%. Sepsis care is organized around source control, antibiotics, and supportive care. Drug disposition is deranged by changes in volume of distribution and regional blood flow, as well as multiple organ failure. Thus, assuring that each patient with sepsis attains pharmacokinetic targets is challenging. There is currently no commercially available FDA-approved assay to measure piperacillin-tazobactam, very commonly used as a beta-lactam/beta-lactamase inhibitor combination antibiotic in the intensive care unit (ICU). METHODS: Samples were prepared by ultrafiltration of plasma collected in lithium heparin Vacutainers. Separation was achieved by gradient elution on a C-18 column followed by UV detection at 214 nm. The method is validated in residual blood samples allowing investigators to exploit a waste product to develop insight into beta-lactam pharmacokinetics in the ICU. RESULTS: Accuracy and precision were within the 25% CLIA error standard for other antibiotic assays. Free piperacillin concentrations were also in good agreement with total piperacillin concentrations measured in the same plasma by an assay in clinical use outside the United States. CONCLUSION: We describe a method for measuring piperacillin and tazobactam that meets clinical validation standards. Quick turnaround time and excellent accuracy on a low-cost platform make this method more than adequate for use as a routine therapeutic drug monitoring tool.

Chromatographic Methods for Quantitative Determination of Ampicillin, Dicloxacillin and Their Impurity 6-Aminopenicillanic Acid.

Two accurate, precise and sensitive high-performance thin layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC) methods were developed for assay of ampicillin (AMP) and dicloxacillin (DX) in the presence of their impurity, 6-aminopenicillanic acid (APA). Method (A) is HPTLC method; using silica gel HPTLC F254 plates as a stationary phase with methanol: chloroform: acetic acid (1:9: 0.2, by volume) as a developing system. All the bands were scanned at 220 nm. Method (B) is reversed phase- HPLC which depended on isocratic elution using C18 column and mobile phase consisting of acetonitrile: water (60:40, v/v), pH adjusted to 4 with orthophosphoric acid, at a flow rate of 1 mL min-1 and ultraviolet detection at 240 nm. The proposed methods were validated as per ICH guidelines and their linearity was evident in the ranges of 0.5-2 µg band-1, 0.4-2 µg band-1 and 0.2-1.2 µg band-1 for method (A) and 5-40 µg mL-1, 5-40 µg mL-1 and 2-16 µg mL-1 for method (B) for AMP, DX and APA, respectively. The proposed methods were successfully used for assay of AMP and DX in pure form and in pharmaceutical formulation where no interference from the excipients was detected.

Simultaneous determination of clavulanic acid and tazobactam in bovine milk by HPLC.

A rapid and specific high-performance liquid chromatographic method was developed and validated for the simultaneous determination of the ß-lactamase inhibitors clavulanic acid and tazobactam in bovine milk. The HPLC system was equipped with ultraviolet absorption detection using a C18 column with a detection wavelength of 215 nm. The mobile phase (pH 4) was 0.02% phosphoric acid and methanol in the ratio of 90:10 v/v. The retention times were 5.67 min for clavulanic acid and 7.22 min for tazobactam. The method exhibited good linearity for clavulanic acid and tazobactam, with R2 > 0.9988. Recovery ranged from 81.953% to 87.688% for clavulanic acid and from 85.007% to 92.991% for tazobactam. The precision expressed as RSD ranged from 0.975% to 1.248% for clavulanic acid and from 0.872% to 1.650% for tazobactam. A simple and precise HPLC method was developed for the determination of clavulanic acid and tazobactam in bovine milk. This method is intended for use in surveys of milk adulteration by the relevant inspection departments.

A simple and rapid RP-HPLC method for the simultaneous determination of piperacillin and tazobactam in human plasma.

A rapid and sensitive reverse phase HPLC (RP-HPLC) method for the simultaneous quantitation of piperacillin and tazobactam in human plasma has been developed and validated. The method utilizes a novel, simple and rapid solid phase extraction step, which results in an improved extraction yield of analytes from human plasma, as well as significantly reduced interference from serum components at low UV wavelength detection compared to previously published liquid-liquid extraction methods. Chromatographic separation was carried out on a Hypersil ODS C18, 3µm column using an acetonitrile-trifluoroacetic acid-water gradient elution with dual wavelength quantitation at 254nm for piperacillin and 218nm for tazobactam. Linear relationships between peak area and drug concentration were obtained in the range of 1.0-200µg/mL for piperacillin and 0.78-50µg/mL for tazobactam, with r2=0.9997 and 0.9994 respectively. The assay proved to be sensitive (with a lower limit of quantitation of 1µg/mL for piperacillin and 0.78µg/mL for tazobactam), specific (no interference from plasma components at either 218nm or 254nm), and reproducible (both intra- and inter- day coefficients of variation were ≤6%). With a total process/assay time of less than 30min, the method provides a simple, precise and reproducible assay for monitoring piperacillin and tazobactam plasma levels that can be readily adapted for routine clinical use.

Partial Least-Squares and Linear Support Vector Regression Chemometric Methods for Simultaneous Determination of Amoxicillin Trihydrate and Dicloxacillin Sodium in the Presence of Their Common Impurity.

Two multivariate chemometric models, namely, partial least-squares regression (PLSR) and linear support vector regression (SVR), are presented for the analysis of amoxicillin trihydrate and dicloxacillin sodium in the presence of their common impurity (6-aminopenicillanic acid) in raw materials and in pharmaceutical dosage form via handling UV spectral data and making a modest comparison between the two models, highlighting the advantages and limitations of each. For optimum analysis, a three-factor, four-level experimental design was established, resulting in a training set of 16 mixtures containing different ratios of interfering species. To validate the prediction ability of the suggested models, an independent test set consisting of eight mixtures was used. The presented results show the ability of the two proposed models to determine the two drugs simultaneously in the presence of small levels of the common impurity with high accuracy and selectivity. The analysis results of the dosage form were statistically compared to a reported HPLC method, with no significant difference regarding accuracy and precision, indicating the ability of the suggested multivariate calibration models to be reliable and suitable for routine analysis of the drug product. Compared to the PLSR model, the SVR model gives more accurate results with a lower prediction error, as well as high generalization ability; however, the PLSR model is easy to handle and fast to optimize.

Development of an HPLC Method for the Determination of Ceftolozane/Tazobactam in Biological and Aqueous Matrixes.

Herein, we report the development and validation of an HPLC method to analyze ceftolozane and tazobactam simultaneously in human plasma, human serum, swine serum and saline matrixes. A reversed-phase column was used with a UV detector set at 260 nm and switched to 218 nm. The mobile phase consisted of methanol and sodium phosphate buffer at a flow rate of 1.1 mL/min. Cefepime was used as the internal standard. The standard curves were linear over a range of 0.4-50 µg/mL. This methodology represents a simple, reproducible approach to the determination of drug concentrations with sufficient accuracy and precision for pharmacokinetic studies undertaken with this recently FDA-approved antimicrobial therapy.

Degradation Kinetics and Mechanism of a ß-Lactam Antibiotic Intermediate, 6-Aminopenicillanic Acid, in a New Integrated Production Process.

In an effort to promote sustainability and to reduce manufacturing costs, the traditional production process for 6-aminopenicillanic acid (6-APA) has been modified to include less processing units. The objectives of this study are to investigate the degradation kinetics of 6-APA, to propose a reasonable degradation mechanism, and to optimize the manufacturing conditions within this new process. A series of degradation kinetic studies were conducted in the presence of impurities, as well as at various chemical and physical conditions. The concentrations of 6-APA were determined by high-performance liquid chromatography. An Arrhenius-type kinetic model was established to give a more accurate prediction on the degradation rates of 6-APA. A hydrolysis degradation mechanism is shown to be the major pathway for 6-APA. The degradation mechanisms and the kinetic models for 6-APA in the new system enable the design of a good manufacturing process with optimized parameters.

Label-free surface-enhanced Raman scattering strategy for rapid detection of penicilloic acid in milk products.

A label-free surface-enhanced Raman scattering (SERS) strategy based on silver-coated gold nanoparticles (Au@Ag NPs) was developed for rapid detection of penicilloic acid (PA) in milk products. It has been demonstrated that core size and shell thickness of Au@Ag NPs are two critical variants affecting enhancement of Raman signals by coupling of two plasma resonance absorption. The Au@Ag NPs with 26-nm core and 9-nm Ag shell exhibit excellent Raman enhancement, in particular, upon the formation of hot spots through NPs aggregation induced by interaction between target molecules and Au@Ag NPs. Compared to the early studies limited to laboratory settings, our analytical approach is simple (without sample pretreatment), less time-consuming (within ∼3 min) and inexpensive. The limit of detection of PA is 3.00 ppm, 3.00 ppm and 4.00 ppm in liquid milk, yogurt and milk powder, respectively. The label-free SERS technique offers a potential for the on-site monitoring of chemical contaminants in milk products.

Ligand Replacement Approach to Raman-Responded Molecularly Imprinted Monolayer for Rapid Determination of Penicilloic Acid in Penicillin.

Penicilloic acid (PA) is a degraded byproduct of penicillin and often causes fatal allergies to humans, but its rapid detection in penicillin drugs remains a challenge due to its similarity to the mother structure of penicillin. Here, we reported a ligand-replaced molecularly imprinted monolayer strategy on a surface-enhanced Raman scattering (SERS) substrate for the specific recognition and rapid detection of Raman-inactive PA in penicillin. The bis(phenylenediamine)-Cu(2+)-PA complex was first synthesized and stabilized onto the surface of silver nanoparticle film that was fabricated by a bromide ion-added silver mirror reaction. A molecularly imprinted monolayer was formed by the further modification of alkanethiol around the stabilized complex on the Ag film substrate, and the imprinted recognition site was then created by the replacement of the complex template with Raman-active probe molecule p-aminothiophenol. When PA rebound into the imprinted site in the alkanethiol monolayer, the SERS signal of p-aminothiophenol exhibited remarkable enhancement with a detection limit of 0.10 nM. The imprinted monolayer can efficiently exclude the interference of penicillin and thus provides a selective determination of 0.10‰ (w/w) PA in penicillin, which is about 1 order of magnitude lower than the prescribed residual amount of 1.0‰. The strategy reported here is simple, rapid and inexpensive compared to the traditional chromatography-based methods.

[Determination of 7 penicilins and penicilloic acids in milk products by high performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: A high performance liquid chromatography-tandem mass spectrometric method was established for determination of 7 penicilins (cloxacillin, nafcillin, oxacillin, penicillin V, amoxicillin, penicillin G, ampicillin) and their penicilloic acids (cloxacilloic acid, nafcilloic acid, oxacilloic acid, penicilloic acid V, amoxicilloic acid, penicilloic acid G and ampicilloic acid) in milk products. And the 7 penicilins and penicilloic acids in milk products were surveyed. METHODS: The 7 penicilins and penicilloic acids in milk products were extracted by water in super-sonic instrument , precipitated proteins by acetonitrile and degreased fat by n-hexane with liquid-liquid extraction, then the purified solution was concentrated by nitrogen, dissolved with acetonitrile-water (10 + 90, V/V) and cleaned by 0.22 µm millipore filter. The filtrate was detected by high performance liquid chromatography-tandem mass spectrometry, identified by electrospray ionization (ESI) in positive mode using multiple reaction monitoring, and quantified with external standards. RESULTS: The calibration curves of 7 penicilins and penicilloic acids showed good linearity in the range of 1.0-200 µg/kg with correlation coefficients were above 0.9992. The detection limits of the method were from 0.03 µg/kg to 0.15 µg/kg. The recoveries of three spiking levels ranged from 80.0% to 110.0%, and RSDs of 7.06% or less were obtained. CONCLUSION: The method for determination of 7 penicilins and penicilloic acids in milk products by HPLC-MS/MS was of operation convenience, less interference from impurities and good accuracy, which could meet the requirements for the determination of 7 penicilins and penicilloic acids residues in milk products.

Utility of surface enhanced Raman spectroscopy (SERS) for elucidation and simultaneous determination of some penicillins and penicilloic acid using hydroxylamine silver nanoparticles.

Elucidation and quantitative determination of some of commonly used penicillins (ampicillin, penicillin G and carbenicillin) in the presence of their main degradation product (penicilloic acid) were developed. Forced acidic and basic degradation processes were applied at different time intervals. The formed degradation products were elucidated and quantified using surface enhanced Raman spectroscopy (SERS). Silver nanoparticles (AgNPs) prepared by reduction of silver nitrate using hydroxylamine-HCl in alkaline medium were used as SERS substrate. The results obtained in SERS were confirmed by the application of LC/MS method. The concentration range was 100-600 ng/ml in case of the studied penicillins and 100-700 ng/ml in case of penicilloic acid. An excellent correlation coefficient was found in case of ampicillin (r=0.9993) and in the case of penicilloic acid (r=0.9997). Validation procedures were carried out including precision, robustness and accuracy by comparing F- and t-values of both the proposed and reported methods.

Molecularly imprinted polymer cartridges coupled to liquid chromatography for simple and selective analysis of penicilloic acid and penilloic acid in milk by matrix solid-phase dispersion.

A simple, fast and sensitive method for determination of the degradation products of penicillin (penicilloic acid and penilloic acid) in milk samples has been developed by combining selective surface molecularly imprinted matrix solid-phase dispersion and high performance liquid chromatography (SMIPs-MSPD-HPLC). The selected dispersant SMIPs had high affinity for penicilloic acid and penilloic acid in milk matrix and the obtained extract was sufficiently clean for direct injection for HPLC analysis without any interference from the matrix. The proposed SMIPs-MSPD-HPLC method was validated for linearity, precision, accuracy, limit of detection and limit of quantitation. Linearity ranged from 0.04 to 4 µg g(-1) (correlation coefficient r(2) > 0.999). Recoveries of penicilloic acid from milk samples at different spiked levels were between 79.8 and 90.3%, with RSD values within 5.2-7.4%, and the limit of detection and limit of quantitation values were 0.04 and 0.13 µg g(-1), respectively. Recoveries of penilloic acid from milk samples at different spiked levels were between 77.4 and 86.2%, with RSD values within 3.1-6.4%, and the limit of detection and limit of quantitation values were 0.05 and 0.17 µg g(-1), respectively. The developed SMIPs-MSPD-HPLC method was successfully applied to direct determination of penicilloic acid and penilloic acid in milk samples.

A green capillary zone electrophoresis method for the simultaneous determination of piperacillin, tazobactam and cefepime in pharmaceutical formulations and human plasma.

A green, novel, rapid, accurate and reliable capillary zone electrophoresis method was developed and validated for the simultaneous determination of piperacillin, tazobactam and cefepime in pharmaceutical preparations. Separation was carried out using fused silica capillary (50 µm i.d. × 48.6 cm and 40.2 cm detection length) and applied potential of 20 kV (positive polarity) and a running buffer containing 15 m m sodium borate buffer adjusted to pH 9.3 with UV detection at 215 nm. Amoxicillin was used as an internal standard. The method was suitably validated according to International Conference on Harmonization guidelines. The method showed good linearity in the ranges of 10-100, 20-400 and 10-400 µg/mL with limits of quantitation of 1.87, 3.17 and 6.97 µg/mL and limits of detection of 0.56, 0.95 and 2.09 µg/mL for tazobactam, piperacillin and cefepime, respectively. The proposed method was successfully applied for the analysis of these drugs in their synthetic mixtures and co-formulated injection vials. The method was extended to the in vitro determination of the two drugs in spiked human plasma. It is considered a 'green' method as it consumes no organic solvents.

Highly sensitive bacterial susceptibility test against penicillin using parylene-matrix chip.

This work presented a highly sensitive bacterial antibiotic susceptibility test through ß-lactamase assay using Parylene-matrix chip. ß-lactamases (EC 3.5.2.6) are an important family of enzymes that confer resistance to ß-lactam antibiotics by catalyzing the hydrolysis of these antibiotics. Here we present a highly sensitive assay to quantitate ß-lactamase-mediated hydrolysis of penicillin into penicilloic acid. Typically, MALDI-TOF mass spectrometry has been used to quantitate low molecular weight analytes and to discriminate them from noise peaks of matrix fragments that occur at low m/z ratios (m/z<500). The ß-lactamase assay for the Escherichia coli antibiotic susceptibility test was carried out using Parylene-matrix chip and MALDI-TOF mass spectrometry. The Parylene-matrix chip was successfully used to quantitate penicillin (m/z: [PEN+H](+)=335.1 and [PEN+Na](+)=357.8) and penicilloic acid (m/z: [PA+H](+)=353.1) in a ß-lactamase assay with minimal interference of low molecular weight noise peaks. The ß-lactamase assay was carried out with an antibiotic-resistant E. coli strain and an antibiotic-susceptible E. coli strain, revealing that the minimum number of E. coli cells required to screen for antibiotic resistance was 1000 cells for the MALDI-TOF mass spectrometry/Parylene-matrix chip assay.

Prejuízos nutricionais e distúrbios no padrão de sono de trabalhadores da Enfermagem / Nutritional damages and disturbances in the sleep pattern of nursing workers / Prejuicios nutricionales y alteraciones en los patrones de sueño de los trabajadores de Enfermería

Este artigo apresenta uma revisão integrativa das publicações científicas da última década, que investigaram os hábitos de sono, a ingestão alimentar e o estado nutricional de profissionais de enfermagem. Foram analisados artigos publicados em periódicos nacionais e internacionais no período de 2002 a 2014, disponibilizados na base de dados PubMed/MEDLINE (USA National Library of Medicine), Lilacs / SciELO (Scientific Eletronic Library Online) e Google Acadêmico. Trinta e um artigos preencheram os critérios estabelecidos. Na análise destes estudos foi identificada elevada prevalência de sobrepeso e obesidade, além de uma modificação negativa nos hábitos alimentares, bem como prejuízos na dinâmica do sono dos profissionais da área de enfermagem.

This article presents an integrative review of national and international scientific publications that investigate the sleep habits, the feed intake and nutritional status of nursing professionals. It was analyzed articles published in national and international journals in the period 2002 to 2014 and made available in the database PubMed / MEDLINE (USA National Library of Medicine), Lilacs / SciELO (Scientific Eletronic Library Online) and Google Scholar. Thirty one articles met the criteria. In the analysis of these studies it has been found a high prevalence of overweight and obesity, a negative change in the eating habits, as well as losses in the sleep patterns of nursing professionals.

En este artículo se presenta una revisión integradora de las publicaciones científicas nacionales e internacionales que investigan los hábitos de sueño, el consumo de alimento y el estado nutricional de los profesionales de enfermería. Se analizaron los artículos publicados en revistas nacionales e internacionales en el período de 2002 a 2014, disponibles en la base de datos PubMed / MEDLINE (USA Biblioteca Nacional de Medicina), Lilacs / SciELO (Scientific Eletronic Library Online) y Google Scholar. Treinta y uno artículos cumplieron con los criterios de inclusión. En el análisis de estos estudios se encontró una alta prevalencia de sobrepeso y obesidad, un cambio negativo en los hábitos alimenticios, así como prejuicios en la dinámica del sueño de los profesionales de enfermería.

Structure-selective hot-spot Raman enhancement for direct identification and detection of trace penicilloic acid allergen in penicillin.

Trace penicilloic acid allergen frequently leads to various fatal immune responses to many patients, but it is still a challenge to directly discriminate and detect its residue in penicillin by a chemosensing way. Here, we report that silver-coated gold nanoparticles (Au@Ag NPs) exhibit a structure-selective hot-spot Raman enhancement capability for direct identification and detection of trace penicilloic acid in penicillin. It has been demonstrated that penicilloic acid can very easily link Au@Ag NPs together by its two carboxyl groups, locating itself spontaneously at the interparticle of Au@Ag NPs to form strong Raman hot-spot. At the critical concentration inducing the nanoparticle aggregation, Raman-enhanced effect of penicilloic acid is ~60,000 folds higher than that of penicillin. In particular, the selective Raman enhancement to the two carboxyl groups makes the peak of carboxyl group at C6 of penicilloic acid appear as a new Raman signal due to the opening of ß-lactam ring of penicillin. The surface-enhanced Raman scattering (SERS) nanoparticle sensor reaches a sensitive limit lower than the prescribed 1.0‰ penicilloic acid residue in penicillin. The novel strategy to examine allergen is more rapid, convenient and inexpensive than the conventional separation-based assay methods.

[Experimental study on concentrations and pharmacokinetics of antibiotics in bile and evaluation of their microbicidal potential].

OBJECTIVE: To study the concentrations and pharmacokinetics of 6 different kinds of antibiotics in rabbit bile, and evaluate their microbicidal potential. METHODS: Thirty-six health rabbits were randomly divided into 6 groups, and each group was 6 rabbits. After anaesthesia, the common bile duct of rabbit was isolated and cumulated with a silicone tube. The rabbits were administered intravenously with the equal-effect dose of antibiotics. Bile (1.5 ml) was collected at different time points after administration, and the concentration of antibiotics of bile was assayed by high performance liquid chromatography. The bile drug concentration-time data were processed by software to figure out the pharmacokinetic parameters such as maximum concentration (C(max)), peak time (T(max)), half-life time (T(1/2)), clearance (CL) and apparent volume of distribution (VD). The bile antibiotics concentration contrasted to the minimum inhibitory concentration (MIC), and attained the bactericidal index (C(max)/MIC) and the time when the drug concentration exceeded the MIC (T(>MIC)). RESULTS: The C(max) and T1/2 of each antibiotic were as the followings: piperacillin (7 950 ± 3 023) mg/L and (1.97 ± 1.23) h, ceftriaxone (1 104 ± 248) mg/L and (3.14 ± 0.57) h, cefoperazone (5 215 ± 2 225) mg/L and (0.89 ± 0.13) h, meropenem (31.97 ± 12.44) mg/L and (0.36 ± 0.11) h, levofloxacin (66.3 ± 36.9) mg/L and (3.32 ± 2.57) h, metronidazole (28.2 ± 10.2) mg/L and (0.81 ± 0.33) h, respectively. Piperacillin/tazobactam and cefoperazone/sulbactam had the largest bactericidal index and the longest T(>MIC), and their bactericidal indexes were (62.1 ± 23.6) - (993.8 ± 377.9) and (164.8 ± 69.0) - (659.3 ± 275.9), their T(>MIC) were (6.00 ± 2.53) - (8.00 ± 0.00) h and (6.33 ± 1.97) - (8.00 ± 0.00) h. The bactericidal index and T(>MIC) of levofloxacin were the smallest, which were (2.1 ± 1.2) - (8.3 ± 4.6) and (0.54 ± 0.25) - (2.67 ± 1.03) h . Ceftriaxone and meropenem were as the medium, and their bactericidal indexes and T(>MIC) were (4.3 ± 1.0) - (69.2 ± 15.5) , (1.42 ± 0.65) - (8.00 ± 0.00) h and (2.0 ± 0.8) - (1 031.3 ± 401.4) , (0.29 ± 0.10) - (1.83 ± 0.26) h. The bactericidal index of metronidazole to anaerobic ranged from 7.4 to 294.9, and the T(>MIC) ranged from 1.88 to 5.00 h. CONCLUSIONS: The bile concentrations of six antibiotics all exceed their effective bactericidal concentrations. The concentration-time curves of piperacillin, cefoperazone, meropenem and metronidazole conformed to one-compartment model, and ceftriaxone and levofloxacin are conformed to two-compartment model. Piperacillin/tazobactam and cefoperazone/sulbactam have the largest bactericidal index and the longest T(>MIC), so they can be chosen as the first choice for the therapy of hepatobiliary infection.For the anaerobic, the microbicidal potential of metronidazole is high.

Drastic reduction of piperacillin-tazobactam concentrations in an in-vitro model of continuous venovenous hemofiltration: proposal of an innovative modality of administration to maintain them at constant concentration.

BACKGROUND/AIMS: Critically-ill patients often undergo continuous renal replacement therapy (CRRT) and need antimicrobial therapy. Piperacillin and tazobactam (Pip-Tzb) are cleared by CRRT. Our aim is to evaluate Pip-Tzb removal in an in-vitro-single-pool-model of continuous-veno-venous-hemofiltration (CVVH); we test a new method of Pip-Tzb administration during CRRT assuring constant levels of concentrations above the minimum inhibitory concentration (MIC). METHODS: In an in-vitro-single-pool-model of CVVH, two solutions (Protein-Free-Solution, PFS and Fresh-Frozen- Plasma, FFP) added with Pip-Tzb were tested for Pip-Tzb removal and adsorption. Then, to keep concentrations constantly above the MIC during CVVH, we add Pip-Tzb in the reinfusion bags. RESULTS: Pip-Tzb rapidly decreased than the MIC during CVVH. The adsorption was irrelevant in the test with FPS. Adding Pip-Tzb in the reinfusion bags of the CVVH system, we observed constant concentrations of Pip-Tzb over time. CONCLUSION: The association of Pip-Tzb is rapidly cleared with a real risk of inadequate dosages in patients undergoing CRRT. Adding Pip-Tzb in the reinfusion bags above the MIC, we obtained stability of concentrations during CVVH.

More potency assay results for generic non-USA lots of piperacillin/tazobactam and initial reports for generic meropenem compounds marketed in the USA.

An ongoing program of international generic antimicrobial potency assays for piperacillin/tazobactam has been summarized here through December 2010, and the initial results for meropenem generic lots from the United States are also presented. Fifteen additional piperacillin/tazobactam generic lots revealed an average of -10% activity (range, +3 to -23%) compared to the branded product (Zosyn®; Wyeth-Pfizer), a finding consistent with prior reports (46 lots) of -16%. In contrast, meropenem branded and generic products had equivalent assay results (5 generic lots from 2 manufacturers [Hospira and Sandoz]). In conclusion, potencies for generic lots of parenteral broad-spectrum ß-lactams can vary widely when directly compared to branded products, requiring documentation by chemical, in vitro activity (potency assays as measured here), and purity testing before considering their addition to a hospital formulary.