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.

[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.

[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.

Clinical pharmacokinetics of vinorelbine.

Vinorelbine (5'-noranhydrovinblastine) is a recently developed semisynthetic anticancer drug which belongs to the Catharanthus alkaloid family. Its mechanism of action is only partially known but it is assumed that it acts, like vinblastine and vincristine, as an antimicrotubule agent arresting cell division in mitosis. Clinically, vinorelbine has mainly shown activity in the treatment of advanced non-small-cell lung cancer and the treatment of metastatic breast cancer. Early pharmacokinetic data were obtained with radioactive assays (radio-immunoassay or 3H-labelled vinorelbine), then with more selective high performance liquid chromatographic techniques. Vinorelbine is usually administered intravenously but there has also been some experimentation with an oral formulation. The bioavailability of a liquid filled gelatin capsule ranges between 12 and 59% with a mean value of 27% [standard deviation (SD) 12%]. Vinorelbine is rapidly absorbed with peak serum concentration reached within 2 hours. In vitro, vinorelbine is mainly distributed into the blood cells, especially platelets (78%) and lymphocytes (4.8%) The unbound blood fraction is around 2%. In lung tissue vinorelbine concentrations are much higher than in serum, by up to 300-fold 3 hours after administration. Little is known about the biotransformation of vinorelbine. Desacetylvinorelbine is considered to be a minor metabolite and is only found in urine fractions, representing 0.25% of the injected dose. Urinary excretion of vinorelbine is low, accounting for less than 20% of the dose. Faecal elimination has been demonstrated in 2 patients who were administered 3H-labelled vinorelbine; the amount of radioactivity recovered in the faeces was 33.9 and 58.4% for the 2 patients, respectively. The pharmacokinetic profile of vinorelbine is often described as a 3-compartment model characterised by a long terminal half-life (t1/2) that varies between 20 and 40 hours and a large apparent volume of distribution (Vd) of around 70 L/kg. Systemic clearance ranges between 72.54 and 89.46 L/h (1209 and 1491 ml/min) when determined by high performance liquid chromatography and is higher than that reported by radioimmunoassay [46.2 L/h (770 ml/min)]. This could be due to the greater specificity of the chromatographic method. Vinorelbine has been administered by continuous intravenous infusion over 4 days. Steady-state was reached and the concentrations obtained were above the in vitro IC50 (concentration of drug causing 50% inhibition). The effect of liver disease on vinorelbine pharmacokinetics has been studied in patients with breast cancer. Patients with massive secondary liver disease had a lower systemic clearance than those who have no liver disease or a lesser invasion. In children, vinorelbine seems to display a shorter t1/2 (14.7 hours) than that found in adults. In addition, the systemic clearance is highly variable [from 12 to 93.96 L/h/m2 (200 to 1566 ml/min/m2)]. Vinorelbine is often co-administered with cisplatin in the treatment of advanced non-small-cell lung cancer. The disposition of the alkaloid is not altered by concurrent administration of cisplatin.

Ocular penetration kinetics of fosfomycin administered as a one-hour infusion.

The penetration of fosfomycin in aqueous humour was studied in 21 patients who were to undergo cataract surgery. All patients received 4 grams of fosfomycin as an infusion lasting one hour. Concentrations of the drug in aqueous humour were measured 1, 2, 4, 6 and 12 hours after the start of infusion. Drug concentrations in aqueous humour and serum were measured by HPCE (High Performance Capillary Electrophoresis). The aqueous humour concentration at one hour was 11.46 mg/l +/- 2.12. Peak concentration was 14.63 mg/l +/- 5.54, reached two hours after the infusion. Concentrations were high until 6 hours and remained significant at 12 hours. These results confirm the excellent diffusion of fosfomycin in aqueous humour, with high levels at 12 hours. They justify its use in intraocular infections, by infusions repeated every eight hours, to maintain concentrations above the MIC 90 for organisms usually susceptible to the drug.

[Pharmacology of Catharanthus alkaloids]. / Pharmacologie des Catharanthus alcaloïdes.

Catharanthus alkaloids are antitumoral drugs widely used in the treatment of malignant diseases. This review summarizes different aspects of their pharmacology (mechanism of action, resistance, clinical pharmacokinetics) as well as information on their uses in the clinical setting.

P-glycoprotein and pharmacokinetics.

P-glycoprotein (P-gp) is a transmembrane protein associated with a phenotype of cross resistance to certain anticancer agents. P-gp is thought to act as an energy dependent pump that expels the anticancer drug out of the tumoral cell, reducing its accumulation and hence its activity. P-gp has been detected in vivo and in vitro in numerous tumor cell types but also in normal tissues and particularly in organs involved in the pharmacokinetic behaviour of xenobiotics. The physiologic functions of P-gp remain unclear but a growing amount of information suggests that it can play an important role at the different steps of pharmacokinetics (i.e., absorption, distribution, elimination). This review gives an update on what is known about the impact of P-gp on the disposition of drugs.

[Role of pharmacokinetics in anticancer chemotherapy]. / Place de la pharmacocinétique en chimiothérapie anticancéreuse.

This review presents different aspects of oncological pharmacokinetics and emphasizes the clinical applications. Pharmacodynamics, pharmacokinetics in phase I trials, search for kinetic interactions are approached.

Pharmacokinetic profile of vinorelbine, a new semi-synthetic vinca alkaloid, determined by high-performance liquid chromatography.

1. Vinorelbine (NVB), a new semi-synthetic vinca alkaloid, is currently used in the treatment of advanced non-small-cell lung cancer (NSCLC) and advanced breast cancer. The pharmacokinetic profile of NVB has been redefined with a specific h.p.l.c. method which measures NVB and desacetyl-NVB. 2. In man, the pharmacokinetics of NVB are best characterized by a three-compartment model with a terminal half-life of 42 h and a large volume of distribution (75 l/kg). The total clearance was 1.26 lh-1 kg-1 and about 11% of the dose was eliminated by the kidneys. Desacetyl-NVB was a minor urinary metabolite. 3. Human pulmonary distribution study showed higher levels of NVB in lung tissue than in serum during the first 3 h after NVB injection; the tumour concentrations were lower than those determined in healthy parenchyma. 4. In the micropig, the 0-48 h biliary excretion of unchanged drug accounted for 25% dose with 21.5% being eliminated during the first 8 h. Desacetyl-NVB concentrations were low and inconsistent. 5. Preliminary results show a better response rate with the combination of cisplatin and NVB than that obtained with NVB alone in the treatment of advanced NSCLC. This increased activity is not the result of a pharmacokinetic interaction since it was shown that cisplatin did not alter the kinetic profile of NVB. 6. This is the first pharmacokinetic investigation of unlabelled vinca alkaloids by a h.p.l.c. procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary distribution of vinorelbine in patients with non-small-cell lung cancer.

Vinorelbine (Navelbine, NVB) is a new semi-synthetic vinca alkaloid that is currently used in the treatment of advanced breast cancer and advanced non-small-cell lung cancer (NSCLC). In this study we investigated the tumoral and healthy pulmonary tissue concentrations of NVB in previously untreated NSCLC patients undergoing surgery. A total of 13 patients (mean age, 60 years; range, 42-70 years) were included and received NVB (20 mg/m2) at 1 h (mean, 1.1 h; SD, 0.2 h; n = 6 patients) and 3 h (mean, 3.0 h; SD, 0.6 h; n = 7 patients) before tumor resection. A tumoral and adjacent healthy lung-tissue specimen as well as simultaneously sampled serum were analyzed for NVB by high-performance liquid chromatography (HPLC). NVB levels were much higher in tissue than in serum (up to 300-fold). The tissue/serum ratio increased between the 1-h sampling time (range, 0.1-100) and the 3-h time point (range, 10-300). In all patients but two, NVB concentrations were lower in tumors than in healthy lung tissue. The tumor/healthy tissue ratio ranged from 0.06 to 1.3 (median, 0.09) at 1 h and from 0.18 to 1.1 (median, 0.55) at 3 h. This ratio increased between the 1-h sampling time and the 3-h time point as a consequence of increasing tumor levels (median, 50.4 ng/g at 1 h and 278 ng/g at 3 h). In four patients, concentrations could be measured in necrotic and peripheral tumor zones, showing lower values in necrotic areas. Thus, these data indicate that NVB is highly distributed in lung tissue, with the disposition rate being slower in tumor tissue than in healthy parenchyma during the first 3 h.

Biliary elimination and pharmacokinetics of vinorelbine in micropigs.

The biliary elimination and pharmacokinetics of vinorelbine (NVB) were investigated in five conscious micropigs provided with a double-terminal choledocal fistula allowing the collection and reinstillation of bile. After the i.v. administration of NVB (0.5 mg/kg), serum and bile samples were collected over a 48-h period. The concentrations of NVB were measured by high-performance liquid chromatography. The serum concentrations decreased rapidly from a maximal value of 208.6 ng/ml (SD, 111.7 ng/ml). The mean half-life was 10.9 h (SD, 8.6 h) and the mean AUC0-48 h was 292.8 ng ml-1 h (SD, 79.4 ng ml-1 h). The bile concentrations were high, amounting to 16.0 micrograms/ml (range, 5.4-27.7 micrograms/ml). The 0- to 48-h biliary excretion of unchanged NVB accounted for 25.8% (SD, 5.7%) of the injected dose, with 21.5% (SD, 4.0%) being eliminated during the 0- to 8-h period. Desacetyl-NVB was found in an inconstant manner and in very low amounts in bile samples. In addition, no glucuronide of NVB could be detected. Thus, in the micropig, biliary excretion represents an important route of elimination for NVB.

Clinical pharmacokinetics of vinorelbine alone and combined with cisplatin.

Vinorelbine (NVB) is a new anticancer drug belonging to the vinca alkaloid family that shows activity as a single-agent treatment in advanced non-small cell lung cancer (NSCLC). Preliminary results show a better response rate with a combination of cisplatin (CDDP) and NVB than with NVB alone. To assess whether this increased activity is secondary to a pharmacokinetic interaction, the authors compared the pharmacokinetic profiles of NVB alone and combined with CDDP in previously untreated inoperable NSCLC patients. Five patients received NVB (30 mg/m2) by short intravenous infusion, and four patients received CDDP (80 mg/m2) 1 hour after the NVB infusion (30 mg/m2). Serum NVB was assayed using a specific high-performance liquid chromatography method. The mean serum concentrations in both groups were similar. In addition, the areas under the curve calculated from 1 hour (beginning of CDDP administration) to 72 hours were 414 ng.hour/mL (standard deviation [SD]: 94) (group NVB alone) and 407.1 ng.hour/mL (SD: 32.9) (group NVB + CDDP). In conclusion, the increased activity observed with the combination NVB + CDDP is not the result of a pharmacokinetic interaction.

Penetration of ofloxacin into heart valves, myocardium, mediastinal fat, and sternal bone marrow in humans.

Ofloxacin penetration into heart tissue (valve and myocardium), mediastinal fat, and sternal bone marrow was the object of a prospective nonrandomized study. Thirty-six patients undergoing mitral and/or aortic valve replacement were included. Patients were divided into two groups of 18 patients each. Group 1 patients were administered a single 400-mg intravenous dose of ofloxacin over a 30-min period upon anesthesia (n = 6) or at 1 h (n = 6) or 6 h (n = 6) prior to surgery. Group 2 patients received a 200-mg oral dose of ofloxacin every 12 h during the 48 h preceding surgery. In this group, the final dose of ofloxacin was administered 3 h (n = 9) or 8 h (n = 9) before anesthesia. Plasma and tissue ofloxacin concentrations were assayed by high-pressure liquid chromatography. In group 1 patients, the peak level in plasma was 15.9 +/- 2.5 micrograms/ml. Peak ofloxacin levels in tissue were reached by hour 1 and were 8.89 +/- 2.16 micrograms/g in myocardium and 5 +/- 0.75 micrograms/g in heart valves. A significant decrease in ofloxacin levels in heart valve tissue and sternal bone marrow was observed after hour 3. Nevertheless, ofloxacin myocardial, heart valve, and sternal bone marrow levels remained higher than the MICs for the usually susceptible pathogens for at least 3 h. In group 2 patients, myocardial levels were long lasting (6.46 +/- 1.92 micrograms/g [4 to 8 h] and 5.92 +/- 0.95 micrograms/g [8 to 12 h]) and remained higher than those observed in the other tissues over the entire study period. A progressive but insignificant decrease in ofloxacin heart valve levels was observed (from 2.46 +/- 0.40 micrograms/g [4 to 8 h] to 1.57 +/- 0.22 micrograms/g [8 to 12 h]). In both groups, concentration in mediastinal fat were lower and tended to decrease with time. These were 1.83 +/- 0.61 micrograms/g with the first hour and 0.85 +/- 0.43 micrograms/g between hours 8 and 12 in group 1 and 1.74 +/- 0.52 micrograms/g between hours 4 and 8 and 0.67 +/- 0.11 micrograms/g between hours 8 and 12 in group 2. In conclusion, satisfactory diffusion of ofloxacin into heart tissue seems to favor use of the drug in the treatment of bacterial endocarditis due to susceptible pathogens. Furthermore, the progressively decreasing concentrations observed in heart valve and sternal bone marrow and the poor levels achieved in mediastinal fat suggest the need for renewing injection 3 h following initial infusion if the drug is used as an antibiotic prophylactic agent during cardiovascular surgery.

Assessment of the biotransformation of the cardiotonic agent piroximone by high-performance liquid chromatography and gas chromatography-mass spectrometry.

14C-labelled piroximone was administered to rats at a dose of 10 mg/kg body weight. Of the total radioactivity administered, 74.9 +/- 7.9% (n = 4) and 87.8 +/- 1.7 (n = 3) were recovered in the 8-h urine collection after oral and intravenous administration, respectively. Two major metabolites, M1 and M2, were detected in methanol extracts and accounted for 7.1 +/- 1.2% (n = 4) (M1) and 4.3 +/- 0.4% (n = 4) (M2) in response to oral administration and 5.7 +/- 0.8% (n = 3) (M1) and 6.7 +/- 2.0% (n = 3) (M2) in response to intravenous administration. In addition, three minor metabolites were detected; M3 and M4 in the 8-h urine collection and M5 in the 12-h urine collection. Separation of piroximone and metabolites was achieved by high-performance liquid chromatography on a C18 column by gradient elution with 0.05 M ammonium acetate (pH 7) using 0-60% methanol over 20 min at a flow-rate of 1 ml/min, followed by isocratic elution with 60% methanol for 10 min. M1 and M2 were isolated by fraction collection following the addition of 1 mM tetrabutylammonium acetate in the mobile phase. Between each injection a column re-equilibration time of 45 min was necessary to achieve optimum collection of M1 and M2 fractions. Gas chromatography-mass spectrometry of M1 provided evidence for a molecular structure consistent with isonicotinic acid methyl ester. Corroborative evidence for this identification was obtained by comparison with a synthetic standard. Isonicotinic acid is assumed to be the actual metabolite while esterification with methanol had occurred as a result of the work-up procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic and preliminary metabolic fate of navelbine in humans as determined by high performance liquid chromatography.

The pharmacokinetics and metabolism of Navelbine (NVB) were investigated in 20 patients by a specific high performance liquid chromatographic methodology allowing the monitoring of NVB, deacetyl-NVB, and N-oxide NVB. After the i.v. (15 min) administration of 30 mg/m2 of drug, blood and urine samples were collected for, respectively, 144 and 48 h. NVB is characterized by a three compartmental kinetics, with a Cmax of 1130 +/- 139 (SEM) ng/ml. The total body clearance and apparent volume of distribution, as defined by high performance liquid chromatography, are 1.26 +/- 0.09 liter/h/kg (48.6 +/- 4.1 liters/h/m2) and 75.6 +/- 9.2 liters/kg (2918.4 +/- 307.2 liters/m2). No metabolite could be detected in serum; the urinary excretion of NVB represented 11% of the administered dose. Deacetyl-NVB could be identified as a minor urinary metabolite when no N-oxide NVB appeared in the urine samples. Two additional peaks appeared in most of urinary chromatograms as trace amounts. Thus, the major pathway of NVB, as for other Vinca alkaloids, should be hepatic clearance, as biliary elimination and/or hepatic biotransformation.

Piperacillin and netilmicin combination therapy for febrile episodes in neutropenic patients.

We assessed the efficacy of a piperacillin (3 x 4 g/d) and netilmicin (5 mg/kg/d) combination therapy for infections in febrile neutropenic patients. The study was conducted over a 30-month period and 203 patients were included. Bone marrow transplant recipients were not included in this study. Origin of infection was documented in 101 (50%) episodes: 33 fungal, viral or parasitic infections and 68 bacterial infections mainly composed of septicemia. Of the 169 evaluable patients with proved bacterial infections or non-documented infections, 129 (76%) recovered with the piperacillin and netilmicin combination treatment. All gram-positive bacterial infections failing first line therapy were cured after the addition of vancomycin. Piperacillin and netilmicin appeared very effective in this large monocentric prospective study. It does not seem necessary to include vancomycin in first line therapy of infections of the neutropenic patients in our institution; however, vancomycin must be added early in the case of suspected or documented staphylococcal infection failing empiric treatment.

Urinary tract infections with tissue penetration in children: cefotaxime compared with amoxycillin/clavulanate.

In children, the site of urinary tract infection (acute pyelonephritis or cystitis) cannot usually be accurately determined from the clinical presentation. The severity of the urinary tract infection (risk of renal scars) is best correlated with its estimated degree of tissue penetration clinically (fever, general condition) and on laboratory tests (sedimentation rate, C-reactive protein). The duration of parenteral antibiotic therapy, especially in children (taking account of difficult venous access and the cost of hospitalization) needs to be specified beyond the initial period required for sterilization of the urine (usually less than 48 h). We conducted a study in children older than one year to compare the efficacy and tolerance of two treatment regimens for urinary tract infection with tissue penetration: cefotaxime 100 mg/kg/d in four divided iv doses for 14 days (group I) and amoxycillin/clavulanate 100 mg/kg/d in four divided iv doses for seven days with conversion to the oral route at a dosage of 50 mg/kg/d for seven days (group II). The randomised protocol included ten patients in each group, comparable with respect to sex, age and history. Clinical efficacy (time until the patient became afebrile), bacteriological efficacy (sterilization of the urine), and biological efficacy (time to normalization of the indices of the acute inflammatory response) were identical for both groups regardless of the duration of iv antibiotic treatment (seven days for amoxycillin/clavulanate; 14 days for cefotaxime). The only side effect was diarrhoea, which affected three patients and did not require modification of the oral treatment regimen.(ABSTRACT TRUNCATED AT 250 WORDS)