Low prevalence of tissue detection of cefepime and daptomycin used as empirical treatment during revision for periprosthetic joint infections: results of a prospective multicenter study.

Data demonstrating that antibiotics administered intraoperatively in patients with surgical revision for periprosthetic joint infection achieve concentrations exceeding minimal inhibitory concentrations of the identified bacteria at the surgical site when the new implant is inserted are lacking. We prospectively included patients with periprosthetic joint infection operated with one- or two-stage replacement during which cefepime (2g)-daptomycin (10mg/kg) combination was administered intravenously as intraoperative empirical antibiotic treatment. Three biopsies (two bones and one synovial membrane) were taken from each patient just before the insertion of the new implant. Eighteen adults of median age 68 years were included. Knee was involved in 10 patients (55.6%) and surgery consisted in one-/two-stage replacement in 11/7 patients. A tourniquet was used during the intervention in the 10 patients with knee prosthesis. Among 54 tissue samples, cefepime and daptomycin were detected respectively in 35 (64.8%) and 21 (38.9%) cases (P=0.01). A total of 17 bacteria dominated by staphylococci (n=14) were identified in 10 patients; tissue inhibitory quotient calculated in 51 samples was >1 in 22 cases (43.1%) for cefepime and in 16 cases (31.4%) for daptomycin. The proportion of tissue samples with detectable antibiotic was significantly higher in hip versus knee prosthesis (P=0.03). The present study suggests that intraoperative empirical administration of cefepime-daptomycin combination during septic prosthetic joint replacement results in a high proportion of tissue samples in which at least one of the two antibiotics was not detected or at a low concentration despite satisfactory concomitant blood serum concentrations.

Chicken adaptive response to low energy diet: main role of the hypothalamic lipid metabolism revealed by a phenotypic and multi-tissue transcriptomic approach.

BACKGROUND: Production conditions of layer chicken can vary in terms of temperature or diet energy content compared to the controlled environment where pure-bred selection is undertaken. The aim of this study was to better understand the long-term effects of a 15%-energy depleted diet on egg-production, energy homeostasis and metabolism via a multi-tissue transcriptomic analysis. Study was designed to compare effects of the nutritional intervention in two layer chicken lines divergently selected for residual feed intake. RESULTS: Chicken adapted to the diet in terms of production by significantly increasing their feed intake and decreasing their body weight and body fat composition, while their egg production was unchanged. No significant interaction was observed between diet and line for the production traits. The low energy diet had no effect on adipose tissue and liver transcriptomes. By contrast, the nutritional challenge affected the blood transcriptome and, more severely, the hypothalamus transcriptome which displayed 2700 differentially expressed genes. In this tissue, the low-energy diet lead to an over-expression of genes related to endocannabinoid signaling (CN1R, NAPE-PLD) and to the complement system, a part of the immune system, both known to regulate feed intake. Both mechanisms are associated to genes related polyunsaturated fatty acids synthesis (FADS1, ELOVL5 and FADS2), like the arachidonic acid, a precursor of anandamide, a key endocannabinoid, and of prostaglandins, that mediate the regulatory effects of the complement system. A possible regulatory role of NR1H3 (alias LXRα) has been associated to these transcriptional changes. The low-energy diet further affected brain plasticity-related genes involved in the cholesterol synthesis and in the synaptic activity, revealing a link between nutrition and brain plasticity. It upregulated genes related to protein synthesis, mitochondrial oxidative phosphorylation and fatty acid oxidation in the hypothalamus, suggesting reorganization in nutrient utilization and biological synthesis in this brain area. CONCLUSIONS: We observed a complex transcriptome modulation in the hypothalamus of chicken in response to low-energy diet suggesting numerous changes in synaptic plasticity, endocannabinoid regulation, neurotransmission, lipid metabolism, mitochondrial activity and protein synthesis. This global transcriptomic reprogramming could explain the adaptive behavioral response (i.e. increase of feed intake) of the animals to the low-energy content of the diet.

[Comparative study of Vitek-2™ AIX versus Vitek-2™ PC: phenotypic resistance of enterobacteriaceae to ß-lactams]. / Comparaison du Vitek-2™ AIX versus Vitek-2™ PC par l'étude des phénotypes de résistance des entérobactéries aux ß-lactamines.

AIM OF THE STUDY: Vitek-2™ AIX versus Vitek-2™ PC have different rules for phenotypic interpretation. The aim of this study is to ensure that the raw results determined by these two versions of Vitek-2™ allow biologists to conclude to the same resistance phenotype, but also to evaluate their own phenotypic interpretation system (advanced expert system). MATERIAL AND METHODS: A total of 251 strains of Enterobacteriaceae of different groups and phenotypes was tested. Each strain was studied simultaneously on both types of Vitek-2™ from the same calibrated inoculum. We then compared their resistance phenotype to beta-lactams. RESULTS: For strains not producing ESBL or CHN, the biologist concluded in 99.3% of cases to the same resistance phenotype by interpreting the raw results of Vitek-2™ AIX versus PC. The phenotypic interpretation of biologist is different from the Vitek-2™ in respectively 40% versus 43% of cases for AIX and PC versions. For multi-resistant strains, the biologist concluded in 100% of cases to the same resistance phenotype by interpreting the raw results of Vitek-2™ AIX versus PC. In 51.5% of cases the biologist use the disk diffusion method (DD). The results of this technique put forward 29% discrepancy with the two types of Vitek-2™. Finally, when Vitek-2™ claims the presence of an ESBL alone, this result is routinely confirmed by DD. CONCLUSION: The switch from Vitek-2™ AIX to Vitek-2™ PC does not alter the results of the phenotypic interpretation of biologist.

[Advantages of corticosteroids in managing acute bacterial postoperative endophthalmitis]. / Intérêt des corticoïdes dans la prise en charge de l'endophtalmie postopératoire aiguë bactérienne.

Most studies show a trend toward a beneficial or at least neutral effect of associating corticosteroids and antibiotics. However, caution must be taken, with various factors considered: the type, virulence, and size of the inoculum, and the treatment chosen. Early intravitreal administration of 400 microg of dexamethasone seems to be beneficial in treating postoperative Staphylococcus epidermidis-related endophthalmitis. However, a large-scale prospective, randomized, controlled study is mandatory to gain evidence supporting steroid therapy in postoperative endophthalmitis.

[Evolution of antibiotic resistance of Streptococcus pneumoniae: results of Alsace observatory in 2005]. / Evolution de la sensibilité de Streptococcus pneumoniae aux antibiotiques: résultats de l'observatoire du pneumocoque Alsace (année 2005).

OBJECTIVES: Between 1st January 2005 and 31st December 2005, 232 strains of Streptococcus pneumoniae were collected in the Alsace county from participating laboratories (one from university hospital, 7 from general hospitals and 12 private laboratories) to assess their susceptibility to penicillin and evaluated serogroups of strains. METHOD: The coordinating centre performed MICs by the reference agar dilution test, interpreted according to CA-SFM breakpoints. Others antibiotics (erythromycin, cotrimoxazole, tetracycline...) were tested by agar diffusion, ATB-PNEUMO gallery or VITEK gallery (BioMérieux, France) by each participating laboratory. Data were processed, using 4th dimension software. RESULTS: Strains were collected from 151 blood samples, 38 ear pus, 11 cerebrospinal fluids, 8 pleural liquids and 24 representative pulmonary samples. The prevalence of pneumococci with decreased susceptibility to penicillin G (PDSP) is 35.1% (pulmonary samples excluded). The rate of PNSP decreases for all types of samples compared with other years of surveillance 2003 (44.0%). The rate of blood samples decreases for first time between the creation of Pneumococcal Observatory. The high-level resistance tend to decrease and began low. The PDSP are rather resistant to erythromycin, cotrimoxazole and fosfomycin. Among the PDSP, the most prevalent serotypes were 14, 19, 6 and 9. CONCLUSION: Among pneumococcal strains, the rate of PDSP tend however to decrease in 2005 compared with 2003. The rate stays inferior to the observed rates in other French counties where the same decreasing is described.

[Microbial description of bacteriuria in long-term care facilities: a prospective study in the French Teaching Hospital of Strasbourg]. / Description de la flore bactérienne responsable des bactériuries symptomatiques en unité de soins de longue durée: étude prospective au CHRU de Strasbourg.

OBJECTIVE: The authors had for aim to assess, the incidence of symptomatic bacteriuria and the level of antibiotic resistance in bacteria identified in long-term care facilities (LTC). DESIGN: Symptomatic bacteriuria cases were prospectively collected, during 9 months in the two LTC of the Strasbourg French Teaching Hospital (196 beds). RESULTS: One hundred and eleven bacteriuria cases were included. They concerned 67 of the 274 residents (cumulative incidence: 2.07/1,000 patients-day). A gram-negative bacillus was identified in 85% of the symptomatic bacteriuria cases, and Escherichia coli in 40%. Sixty percent of the identified bacterial strain was resistant to amoxicillin (Amx-R) and 42% to the clavulanic acid combination (AmC-R). Third generation cephalosporins (3GC) were effective in 90% of Urinary tract infections (UTIs) and fluoroquinolones in 65% (Fq). Four bacterias with broad beta-lactamase spectrum were identified (0.04%) including 3 Enterobacter aerogenes. No yeast infection was diagnosed. E. coli strains were 65% Amx-R and 50% AmC-R. Concerning the Fq-R strains (15%), 50% were cotrimoxazole resistant (Stx-R) and 70% Amx-R; 3GC remained effective (82%). CONCLUSION: In LTC, multi-drug resistance bacteria are rare and 3GCs seem to be the best first line treatment. Nevertheless, Fq-R is increasing (15 vs 8%), and attention must be paid to the antibiotic therapy used.

[Use of linezolid for the treatment of lung infections in adults with cystic fibrosis]. / Utilisation du linézolide dans le traitement des infections broncho-pulmonaires du patient adulte atteint par la mucoviscidose.

INTRODUCTION: Linezolid, a new antistaphylococcal agent for oral or intravenous administration is active against Staphylococcus aureus with limited sensitivity to glycopeptides. The purpose of the present work was to compare data in the literature with practical clinical experience with the use of linezolid for lung infections in adult cystic fibrosis patients with the objective of developing local guidelines for use. MATERIAL AND METHODS: This retrospective clinical study was conducted in the adult pneumology department of a university hospital. RESULTS: The main clinical signs leading to prescription of linezolid were aggravating cough, bronchial obstruction, and exercise-induced fatigue. Among 42 cystic fibrosis patients, six aged 24+/-3 years were given 22 treatments of linezolid. Two patients were given the drug once and the others 2, 4, 5, and 9 times, 600 mg b.i.d. Mean duration of treatment with linezolid was 16+/-5 days. Among the six patients, two presented meti-R S. aureus infection. For twelve cases, clinical improvement was observed; and in two others the situation worsened leading to interruption of linezolid. CONCLUSIONS: There are few reports in the literature on use of linezolid in cystic fibrosis patients. Writing internal guidelines for our department has enabled standardized use: 600 mg b.i.d. p.o. for 14 days as second-line treatment for bronchial exacerbation of S. aureus infection.

[Sinusal penetration of amoxicillin-clavulanic acid. Formulation 1 g./125 mg., twice daily versus formulation 500 mg./125 mg., three times daily]. / Pénétration sinusienne de l'amoxicilline-acide clavulanique. Formulation 1 g/125 mg, 2 fois/jour, versus formulation 500 mg/125 mg, 3 fois/jour.

INTRODUCTION: In order to meet the evolution of pneumococcus resistance to beta-lactam antibiotics, a new formulation of amoxicillin (AMX) and clavulanic acid (CA), with twice as much AMX (1 g/125 mg vs. 500 mg/125 mg) was developed for the treatment of acute pneumonia in patients at risk. This formulation can also be used in the treatment of acute maxillary sinusitis using a 1 g/125 mg regimen twice-daily. OBJECTIVES: Compare the sinusal penetration of AMX and CA (1 g/125 mg twice-daily vs. 500 mg/125 mg three times a day) when administered at both regimens to demonstrate equivalent pharmacokinetic and pharmacodynamic behaviour of the former when compared to the latter. METHODS: Concentrations of AMX and CA were measured in the anterior ethmoid, maxillary, posterior ethmoid sinus and in the middle nasa concha in 62 patients undergoing surgery for nasosinusal polyps. Patients randomised in two groups corresponding to 2 oral regimens, received either 1 g/125 mg twice a day or 500 mg/125 mg three times a day for 4 days. The last dose in both groups was administered 1 h 30, 3, 5 or 8 hrs prior to surgery. Serum samples were taken simultaneously to tissue samples. AMX and CA were measured by high performance liquid chromatography. Exogenous and above all endogenous blood contamination were taken into account with the hematocrit as well as blood and tissue haemoglobin concentrations. Comparisons of tissue concentrations were made for each sampling time, according to values obtained for a specific tissue with both doses on one hand, and on the other to values obtained with a specific dose in different tissues. The calculated pharmacodynamic parameters, which are considered to be predictive for bacteriological and clinical efficacy, result directly from tissue concentrations of AMX. tissue inhibitory quotients (IQtissue = Tissue concentration/MIC). time above MICs for serum and tissue concentrations (T > MIC). RESULTS: As regards AMX, whatever the dose, at 1 h 30 and at 3 hrs, tissue concentrations did not differ significantly whatever the tissue studied (from 1.1 to 2.5 micrograms/g). Conversely, at 5 and 8 hrs, they were greater than after the 1 g/125 mg regimen given twice-daily (0.06-0.7 vs. 0.7-1.8 micrograms/g). If we consider a given dose, the comparison between the various tissues showed identical concentrations in the four tissues studied at each sampling time, except in two cases with the dose of 500 mg/125 mg 3 times a day. T > MIC for serum and tissue showed higher values than those required for AMX/pneumococcus association (40-50%) with, nevertheless, greater tissue values for the 1 g/125 mg dose given twice-daily when MIC was of 1 microgram/ml (40-52% vs. 50-66%). The maximum tissue inhibitory quotients were also greater with the twice-daily 1 g/125 mg dose, when calculated with MIC 50 or 90 of S. Pneumoniae, H. influenzae, M. catarrhalis or S. pyogenes. As for CA, concentrations were equivalent for both doses at each sampling time and greater than those required in vitro during respectively 4 and 5 hours for beta-lactamases H. influenzae and M. catarrhalis. DISCUSSION-CONCLUSION: A least an equivalence between both dose regimens was observed, with occasionally a superiority of the twice-daily 1 g/125 mg dose, in terms of pharmacokinetics, tissue penetration and pharmacodynamics for both AMX and CA. This new regimen therefore appears more appropriate for the treatment of acute maxillary sinusitis in adults.

[Urinary tract infections due to wide spectrum beta lactamase producing enterobacteriaceae]. / Infections urinaires à entérobactéries productrices de bêta-lactamases à spectre étendu. Prévalence dans un service de médecine interne gériatrique.

OBJECTIVES: The aim of this study was to specify the characteristics of enterobacterial urinary infections producing wide spectrum beta-lactamase (WSBL) and the management strategies for these patients infected in geriatric wards. METHODS: The prevalence, bacteriological characteristics and treatment regimens of enterobacterial urinary infections producing WSBL, diagnosed in a geriatric department of internal medicine from May 1977 to April 2001, were studied retrospectively. RESULTS: Sixty-six enterobacterial urinary infections producing WSBL were diagnosed, with 53 (80%) of them acquired in the ward. They represented 1.6% of admissions and concerned 24 men and 42 women (sex ratio: 0.57), with a mean age of 87 years. Their prevalence was of 20 in the 1st year, 11 in the 2nd, 9 in the third and 26 in the 4th year. The mean duration of hospitalization of infected patients was 4.5-fold longer (90 vs. 20 days) and the mortality rate 2-fold higher (32 vs. 14%). Enterobacter aerogenes were responsible for half (46%) of the WSBL urinary infections. The skin was invaded by enterobacteria in 67% and the feces in 57% of cases. More than one third of the urinary infections treated relapsed, and digestive decontamination was only efficient in half of the patients treated. CONCLUSION: This 4-year study emphasizes the limits of antibiotherapy in eradicating WSBL-producing enterobacteria and the fact that only the strict respect of hygiene by all caregivers (isolation of patients exhibiting WSBL and washing-disinfection of the hands between each patient) limits the incidence of such infections.

Ex vivo 12 h bactericidal activity of oral co-amoxiclav (1.125 g) against beta-lactamase-producing Haemophilus influenzae.

The aim of the study was to evaluate the in vitro/ex vivo bactericidal activity of a new coamoxiclav single-dose sachet formulation (1 g amoxicillin + 0.125 g clavulanic acid) against a beta-lactamase-producing strain of Haemophilus influenzae. The evaluation covered the 12 h period after antibiotic administration. Serum specimens from the 12 healthy volunteers included in the pharmacokinetic study were pooled by time point and in equal volumes. Eight of 12 pharmacokinetic sampling time points were included in the study. At time points 0.5, 0.75, 1, 1.5, 2.5, 5, 8 and 12 h post-dosing, the kinetics of bactericidal activity were determined for each of the serial dilutions. Each specimen was serially diluted from 1:2 to 1:256. The index of surviving bacteria (ISB) was subsequently determined for each pharmacokinetic time point. For all the serum samples, bactericidal activity was fast (3-6 h), marked (3-6 log(10) reduction in the initial inoculum) and sustained over the 12 h between-dosing interval. The results obtained also confirmed that the potency of the amoxicillin plus clavulanic acid combination was time dependent against the species under study and that the time interval over which the concentrations were greater than the MIC (t > MIC) was 100% for the strain under study. The data thus generated constitute an interesting prerequisite with a view to using co-amoxiclav 1.125 g in a bd oral regimen.

[Chronic experimental bacteremia in Yucatan micropigs]. / Bactériémie chronique expérimentale du microporc Yucatan.

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.

Evidence for a true post-beta-lactamase-inhibitor effect of clavulanic acid against Klebsiella pneumoniae and Haemophilus influenzae.

OBJECTIVE: The purpose of this study was to investigate and characterize in vitro the post-beta-lactamase inhibitor effect (PLIE) of clavulanic acid against two beta-lactamase-producing species of bacteria. METHODS: The PLIE was investigated against one strain of Klebsiella pneumoniae and one strain of Haemophilus influenzae. A stationary-phase inoculum of about 107 colony-forming units per mL of each bacterium was pre-exposed for 2 h to clavulanic acid, either alone or in combination with amoxicillin at various concentrations. After pre-exposure, the dilution required to remove the beta-lactamase inhibitor was 1:100 or 1:1000 according to the bacterial species and their susceptibilities to clavulanic acid. Bacteria were counted hourly after drug removal, on solid agar medium. RESULTS: Control cultures exposed to amoxicillin alone after dilution, showed a delay in growth, which may be inherent to the time required to synthesize sufficient beta-lactamase after the dilution steps. Control experiments clearly distinguished the post-antibiotic effect and the growth delay from the PLIE. CONCLUSION: The PLIE could be one of several factors explaining why beta-lactam/beta-lactamase inhibitor combinations remain effective throughout the dosing interval, even if a few hours after in vivo administration, serum concentrations of beta-lactamase inhibitor fall below levels that are active in vitro.

[Bacterial growth delay in E. coli: demonstration and evaluation of the beta-lactamase post-inhibitor effect on 6 strains with different resistance phenotypes]. / Retard de recroissance bactérienne chez E. coli: mise en évidence et évaluation d'un effet postinhibiteur de beta-lactamases sur six souches de phénotypes de résistance différents.

Six E. coli, whose phenotypes of resistance were different, were tested in vitro in order to evaluate a regrowth delay, the post beta-lactamases inhibitor effect (PLIE). This PLIE was investigated after a brief incubation in contact with clavulanic acid (CA) alone or associated with amoxicillin (AMX). After removal of the drugs used during the pre-exposure phase, the bacteria were incubated with AMX at different concentrations. The PLIE was shown not to be in association with any other regrowth delay (post-antibiotic effect or effect inherent to the technical procedures used). A PLIE was evaluated on the five intermediary or high-level beta-lactamases-producing strains. Generally, the duration of the PLIE was prolonged after the CA alone pre-exposure phase and could reach values up to 22 hours. The concentrations of AMX added in cultures previously exposed to sufficient CA concentrations were related to an extended PLIE.

[Comparative diffusion of fusidic acid, oxacillin, and pristinamycin in dermal interstitial fluid after repeated oral administration]. / Diffusions comparées de l'acide fusidique, de l'oxacilline et de la pristinamycine dans le liquide interstitiel dermique après administration orale répétée.

OBJECTIVE: The aim of this study was to use the suction bullae technique to compare skin diffusion of 3 antibiotics commonly used for skin infections (fusidic acid, oxacillin, pristinamycin) and to estimate their potential activity at the site of skin infections. SUBJECTS AND METHODS: This comparative open study was conducted in 12 healthy volunteers using a repeated latin square experimental scheme. Antibiotic concentrations in serum and suction bullae fluid were measured by high performance liquid chromatography after 5.5 days of repeated oral administration of fusidic acid (1 g/d), oxacillin (2 g/d), and pristinamycin (2 g/d). RESULTS: Mean antibiotic concentrations in serum and interstitial fluid (suction bullae fluid) were highest for fusidic acid with a Cmax at 91.3 +/- 23.0 mg/l and 45.5 +/- 18.0 mg/l respectively (interstitial fluid/serum ratio=49 +/- 10 p. 100). For oxacillin, Cmax was 8.3 +/- 3.6 mg/l and 0.98 +/- 0.49 mg/l (ratio 13 +/- 5 p. 100). Pristinamycin concentrations were low with a Cmax at 0.51 +/- 0.40 and 0.26 +/- 0.15 mg/l (ratio 73 +/- 57 p. 100). Comparing the area under the interstitial fluid and the serum concentration-time curves showed that the best diffusion was obtained with pristinamycin (114 +/- 61 p. 100), followed by fusidic acid (57 +/- 13 p. 100) and oxacillin (48 +/- 25 p. 100). DISCUSSION: These data were used to calculate indicators of potential efficacy in the interstitial dermal fluid: inhibitor quotient (Cmax/MIC) and AUIC (ASC/MIC), indicator of the time antibiotic concentrations are maintained above the minimal inhibitor concentration (MIC). This showed that fusidic acid was potentially more active against all staphylococci. For streptococci, the observed interstitial concentrations of pristinamycin and of fusidic acid should theoretically inhibit streptococci A growth, but oxacillin was the most adapted antibiotic.

[Biliary diffusion of tazocillin in man]. / Etude de la diffusion biliaire de la tazocilline chez l'homme.

The objective of this study was to determine the extent of biliary excretion of tazocillin, a combination of piperacillin and tazobactam administered as an intravenous infusion in a dose of 4 g of piperacillin and 0.5 g of tazobactam. In 10 patients, piperacillin and tazobactam levels were determined in serum, main bile duct bile, gallbladder bile, and gallbladder wall specimens harvested during a cholecystectomy procedure 1 h after completion of a tazocillin infusion. In five other patients, piperacillin and tazobactam levels were determined in bile collected from a main bile duct T-tube during 12 h following a tazocillin infusion given seven days after cholecystectomy. HPLC was used to assay both compounds. Piperacillin and tazobactam levels in the intraoperative specimens were as follows: 69.1 +/- 13.8 and 9.9 +/- 1.7 micrograms/ml, respectively, in the serum; 630 +/- 133 and 11.9 +/- 2.2 micrograms/ml, respectively, in the main bile duct bile; 342 +/- 114 and 7.7 +/- 2.3 micrograms/ml, respectively, in the gallbladder bile; and 49.3 +/- 20.2 and 2.9 +/- 0.6 micrograms/g, respectively, in the gallbladder wall. In the T-tube bile specimens, peak piperacillin and tazobactam levels were 358 +/- 281 and 9.9 +/- 3.3 micrograms/ml, respectively, after 1 h; total biliary excretion over 12 hours was 28.3 +/- 18.0 mg and 1.0 +/- 0.5 mg, i.e., 0.7 +/- 0.4% and 0.2 +/- 0.1% of the dose, respectively. The levels of piperacillin and tazobactam found in bile and gallbladder wall specimens in this study suggest that tazocillin may prove valuable for the prevention and treatment of biliary infections.

Stability and compatibility of teicoplanin in parenteral nutrition solutions used in pediatrics.

AIMS: To investigate teicoplanin added to pediatric parenteral nutrition solutions in terms of its stability, its compatibility with parenteral nutrition solution components, and its diffusion through an antibacterial filter material. METHODS: Three binary solutions with and without teicoplanin were studied. Different solution compositions and teicoplanin concentrations were used: A (98.3 +/- 8.2 mg/l), B (116.3 +/- 12.4 mg/l), and C (162.7 +/- 16.2 mg/l). Concentrations of teicoplanin and of solution components, osmolality, and pH of each solution were measured at H0, after 24 h at room temperature, after 24 h at +4 degrees C followed by 24 h at room temperature, and after 144 h at +4 degrees C followed by 24 h at room temperature (H168). Teicoplanin concentrations were also measured before and after passage of each solution through a 0.22 micro filter. RESULTS: Teicoplanin concentrations remained unchanged from H0 to H168 in solutions A (99.6 +/- 8.3 mg/l), B (116.9 +/- 12. 3 mg/l), and C (162.4+12.9 mg/l). During the H0-H168 interval, iron and methionine were the only components that showed significant decreases, which were similar in solutions without teicoplanin [iron, -6.1% (A), -6.8% (B), and -4.5% (C); methionine, -7.3% (A) and -8. 7% (B)] and in those with teicoplanin [iron, -6.2% (A), -7.1% (B), and -4.0% (C, nonsignificant); methionine, -10.5% (A) and -10.7% (B)], indicating that they were not dependent on the presence of teicoplanin. Teicoplanin levels after filtration were identical to prefiltration values in solutions A (86.4 +/- 5.0 vs 89.8 +/- 3.4 mg/l) and B (112.6 +/- 4.3 vs 115.3 +/- 9.0 mg/l) but were 10.0% lower in solution C (161.6 +/- 3.9 vs 145.4 +/- 4.0; P << 0.001). CONCLUSIONS: Teicoplanin can be added to pediatric parenteral nutrition solutions to treat central venous catheter-related infections due to teicoplanin-susceptible organisms since its concentrations and those of solution components remain stable over time.

Gastric penetration of amoxicillin in a human Helicobacter pylori-infected xenograft model.

The delivery of antibiotics into Helicobacter pylori-infected human stomachs is still poorly understood. Human embryonic gastric xenografts in nude mice have recently been proposed as a new model for the study of H. pylori infection. Using this model, we compared the penetration of amoxicillin, after intraperitoneal administration of a dose of 20 mg/kg of body weight, into the gastric mucosae of infected and uninfected xenografts. The concentrations of this drug in serum and superficial gastric mucosae were determined at 20 min and 1 and 3 h after injection. Ten mice with H. pylori-infected grafts (n = 5) or uninfected grafts (n = 5) were studied. Mucosal samples were obtained by cryomicrotomy. The concentrations in serum were similar to those obtained in the serum of humans after oral administration of 1 g of amoxicillin. The mean area under the tissue concentration-versus-time curve from 0 to 3 h obtained for mice with infected grafts was significantly higher than that obtained for the animals with uninfected grafts (P = 0.01). These results suggest that the penetration of amoxicillin into the superficial gastric mucosa may be substantially increased in the case of H. pylori infection. Thus, human xenografts in nude mice represent a new, well-standardized model for investigation of systemic delivery of drugs into H. pylori-infected gastric mucosa.