Comparative efficacy and safety of four-day cefuroxime axetil and ten-day penicillin treatment of group A beta-hemolytic streptococcal pharyngitis in children.

In a prospective randomized multicenter study, 308 children, ages 2 to 15 years, were randomized to receive either cefuroxime axetil suspension (N = 152; 20 mg/kg/day twice daily) for 4 days, penicillin suspension (N = 156; 45 mg/kg/day divided three times daily) for 10 days, of whom 97 and 103, respectively, had culture-proved group A beta-hemolytic Streptococcus infection. Two to 4 days after completion of the treatment, group A beta-hemolytic Streptococcus were eradicated from 85 of 97 (87.6%) children taking cefuroxime and from 90 of 103 (87.4%) taking penicillin; respective clinical cure rates were 94.8% and 96.1%. Clinical signs and symptoms resolved significantly more rapidly with cefuroxime (P < 0.05). At 28 to 32 days posttreatment the eradication of the primary isolate was confirmed in 94.4 and 91.9% of cefuroxime axetil and penicillin-treated patients, respectively. Drug-related adverse events (mainly gastrointestinal and cutaneous reactions) were reported in 2.1 and 2.7% of the cefuroxime- and penicillin-treated patients, respectively. Results indicated that a 4-day treatment with cefuroxime axetil was as effective and well-tolerated as the conventional 10-day treatment with penicillin in children with acute group A beta-hemolytic Streptococcus pharyngitis.

Is there a rationale for the continuous infusion of cefepime? A multidisciplinary approach.

This review is the fruit of multidisciplinary discussions concerning the continuous administration of beta-lactams, with a special focus on cefepime. Pooling of the analyses and viewpoints of all members of the group, based on a review of the literature on this subject, has made it possible to test the hypothesis concerning the applicability of this method of administering cefepime. Cefepime is a cephalosporin for injection which exhibits a broader spectrum of activity than that of older, third-generation cephalosporins for injection (cefotaxime, ceftriaxone, ceftazidime). The specific activity of cefepime is based on its more rapid penetration (probably due to its zwitterionic structure, this molecule being both positively and negatively charged) through the outer membrane of Gram-negative bacteria, its greater affinity for penicillin-binding proteins, its weak affinity for beta-lactamases, and its stability versus certain beta-lactamases, particularly derepressed cephalosporinases. The stability of cefepime in various solutions intended for parenteral administration has been studied, and the results obtained demonstrated the good compatibility of cefepime with these different solutions. These results thus permit the administration of cefepime in a continuous infusion over a 24-h period, using two consecutive syringes.

Pulmonary edema and shock after high-dose aracytine-C for lymphoma; possible role of TNF-alpha and PAF.

Four out of 23 consecutive patients treated with high-dose Ara-C for lymphomas in our institution developed a strikingly similar syndrome during the perfusion. It was characterized by the onset of fever, diarrhea, shock, pulmonary edema, acute renal failure, metabolic acidosis, weight gain and leukocytosis. Thorough bacteriological screening failed to provide evidence of infection. Sequential biological assays of IL-1, IL-2, TNF and PAF were performed during Ara-C infusion to ten patients, including the four who developed the syndrome. TNF and PAF activity was found in the serum of respectively two and four of the cases, but not in the six controls. As TNF and PAF are thought to be involved in the development of septic shock and adult respiratory distress syndrome, we hypothesize that high-dose Ara-C may be associated with cytokine release.

Pharmacokinetics and pharmacodynamics of two oral forms of cefuroxime axetil.

Cefuroxime axetil is a cefuroxime ester that can be administered by mouth. Two dosage forms (tablets and granules) have been developed for oral administration. We evaluated the pharmacokinetics and pharmacodynamics of these forms in an open cross-over study involving 12 healthy volunteers receiving single doses of 250 mg. The bioavailability of the two forms was different, the observed peak concentration and time-concentration curve values of the tablet form being, respectively, 39 and 27% higher than those of the granule form. However, ex vivo studies of serum bactericidal activity against Streptococcus pneumoniae showed no significant differences between the two formulations. This is in keeping with the fact that the bactericidal activity of samples from only six subjects gave evaluable data for Haemophilus influenzae; although small differences were found between the two formulations, further investigations are required. The pharmacodynamic approach is becoming an essential element in determining the equivalence of antibiotic dosage forms.

Penetration of ceftazidime into middle ear fluid in children with otitis media with effusion.

Twenty-five children with otitis media with effusion received ceftazidime 50 mg/kg intravenously before bilateral myringotomy with insertion of tympanostomy tubes. Concentrations of ceftazidime measured in serum and middle ear fluid exceeded 4 mg/L (i.e., largely above the minimal inhibitory concentrations for the gram-negative pathogens commonly recovered from children with otitis media) for at least 4 hours. Mean peak concentrations occurred 30 to 90 minutes after the injection and reached 11 to 14 mg/L. These results are in keeping with the clinical efficacy of ceftazidime in the treatment of chronic middle ear infections in children.

[Severe bladder dysfunction in the child abuse victim. Hinman syndrome]. / Dysfonctionnements vésicaux graves chez l'enfant victime de maltraitance. Le syndrome de Hinman.

Severe bladder dysfunction with possible consequence on the upper urinary tract caused by psychological trauma were recently identified. Hinman in 1973 was the first to report a series of 14 patients with severe abnormal bladder and bowels behaviour with organic cause. He described the most common symptoms met in this group of patients and their management using a non surgical approach based on bladder reeducation and hypnosis. Other authors such as Allen in 1977 reported a similar experience and found severe detrusor-sphincter dyssynergia. In 1995, Ellsworth reported a relation between these abnormal bladder behaviour and a medical history of sexual aggression. We report here in a series of 7 patients with Hinman syndrome associated with aggression. Diagnosis and management by a multidisciplinary team involving paediatricians, paediatric urologists, physiotherapists, paediatric psychologists are detailed [corrected].

[Antibiotic therapy protocol using ceftazidime 3g/day alone or in combination with vancomycin or amikacin. In febrile episodes in neutropenic patients]. / Protocole d'antibiothérapie utilisant la ceftazidime à la dose de 3 g/jour seule ou en association avec la vancomycine ou l'amikacine. Lors des épisodes fébriles chez le neutropénique.

In a preliminary study of 21 febrile episodes in neutropenic patients ceftazidime used as empirical treatment in doses of 3 grams per day succeeded in controlling fever in 74 per cent of the cases. Laboratory studies performed in patients with Gram-negative septicaemia showed clinically effective plasma concentrations of the antibiotic. A trial of ceftazidime (3 g/day) administered alone or combined with amikacin or vancomycin is currently in progress in two medical centres. No statistically significant conclusions could be reached from an intermediate study.

[Ambulatory treatment with cefuroxime-axetil of infectious bronchitis in patients sixty years of age or older: comparative study of the combination of amoxicillin and clavulanic acid]. / Traitement ambulatoire par le céfuroxime-axetil des bronchites infectieuses du sujet de soixante ans ou plus: étude comparative avec l'association d'amoxicilline et d'acide clavulanique.

The aim of this multicenter, prospective randomized trial was to compare the efficacy and safety of cefuroxime-axetil and amoxycillin/clavulanic acid for the treatment of infectious bronchitis in the elderly patient. Between January and April 1989, 157 out patients aged 60 years or more and presenting with infectious bronchitis were treated with either cefuroxime-axetil (250 mg bid), or the association amoxycillin/clavulanic acid (500 mg/125 mg bid). The two treatment groups were comparable at the time of inclusion; the mean age was 70 years, 82% of the patients were febrile, 75% presented purulent expectoration, 24% had a history of chronic bronchitis and 19% received symptomatic treatment was NSAIDs. The mean duration of treatment was 9 days. Clinical efficacy was assessed by the investigators. While fever and cough resolved similarly in the two groups, statistically fewer patients presented persistent purulent expectoration in the cefuroxime-axetil treatment group than in the group receiving amoxycillin/clavulanic acid (2% and 13%, respectively, p = 0.03). The proportion of patients who reported at least one side-effect was 3.6% in the cefuroxime-axetil treatment group against 21.6% of those who received the association (p = 0.006).

[Efficacy of the combination of ceftazidime/vancomycin in the first line treatment of infection in neutropenic children]. / Efficacité de l'association ceftazidime/vancomycine dans le traitement de première intention des infections des enfants neutropéniques.

UNLABELLED: Infection is the first reason of mortality in children with bone marrow aplasia. It justifies the immediate treatment initiation before bacteriological cultures results. First line probabilistic treatment must have a bactericidal activity on the pathogens and must be atoxic. The empirical therapy consisted of ceftazidime 100 mg/k/d and vancomycine 40 mg/k/d three times a day. We treated 41 patients, ranged from 0.5 to 17 years (mean 9.5 years). 27 lymphoblastic leukaemias, 10 myeloblastic leukaemias, 4 lymphomas, presenting post therapeutic prolonged aplasia: PMN less than 500/mm3. 23 strains were isolated from 15 patients. 12 Gram+: 7 ceftazidime sensitive, 12 vancomycine sensitive and 11 Gram-: 10 ceftazidime sensitive. Only one is resistant to ceftazidime + vancomycine. Apyrexia was obtained in less than 48 hours in 36 patients. Mean treatment duration was 16 days. Hyperthermia relapsed 17 times and was susceptible to ampho B ten times, although no candida was isolated. When ceftazidime + vancomycine combination failed, other antibiotic treatment was ineffective. There were 4 superinfections (2 in blood, 1 enteric, 1 pharyngeal) and 2 germs were ceftazidime resistant. IN CONCLUSION: ceftazidime + vancomycine combination is a very effective treatment of infection in the neutropenic children: 88% success. 95% of the germs are sensitive to, at least, one of the 2 antibiotics. There are very few superinfections. Tolerance is excellent.

[Binding of cefuroxime to macromolecules from bronchitic sputum in patients with chronic bronchitis]. / Liaison de la céfuroxime aux macromolécules du mucus bronchique de malades atteints de bronchite chronique.

Cefuroxime binding to soluble bronchial macromolecules has been performed in vitro with preparations obtained from ten patients. Cefuroxime at various concentrations have been added to soluble macromolecules (10 g/l). Free cefuroxime has been obtained by equilibrium dialysis and measured by HPLC. Results show that cefuroxime binding is about 30% of total antibiotic.

Behavior of morphometric indices in pancreatic elastase-induced emphysema in rats.

Two morphometric indices, the destructive index (DI), a measure of alveolar wall destruction, and the proportion of destroyed alveolar attachments to the airways (AA), have been proposed as measures of early lung destruction in human smokers. The aim of this study was to compare DI and AA to the usual measure of airspace enlargement--the mean linear intercept (Lm)--in experimental emphysema. Porcine pancreatic elastase was administered intratracheally to 2 groups of Brown Norway rats (high-dose, n = 8, 1 IU/g body weight; low-dose, n = 4, 0.7 IU/g; control, n = 7). Total lung capacity (TLC), functional residual capacity (FRC) and pressure-volume curves were measured 3 weeks after administration of elastase. Lung elasticity was assessed by chord compliance (Cst). Administration of high-dose, but not low-dose, elastase led to significant increases in FRC and TLC. Cst significantly increased after high-dose elastase compared to controls (p less than 0.01). Lm increased after both low-dose and high-dose elastase compared to controls (p less than 0.01); DI and AA were increased only after high-dose elastase. Significant correlations were found between each morphometric index and Cst; the highest correlation was with AA. Behavior of the morphometric indices in this model differed from that reported in human smokers: Lm was a more sensitive measure of destruction than DI, reflecting a process marked by predominance of airspace enlargement over alveolar septal breaks. These differences from human smokers may result from a differing underlying pathogenesis of lung destruction.

[Susceptibility of Pseudomonas aeruginosa to antibiotics isolated from patients of intensive care units in France in 1998. Resistant phenotypes to beta-lactams]. / Sensibilité de Pseudomonas aeruginosa aux antibiotiques, isolés chez des malades de soins intensifs français en 1998. Phénotypes de résistance aux beta-lactamines. Etude ESCRIME.

Pseudomonas aeruginosa is responsible for nosocomial infections and demonstrates many types of resistance mechanisms to antibiotics. Thus, in vitro susceptibility survey are frequently required. In this study, susceptibility has been assessed on 105 non redundant consecutive strains isolated from ICU's in 18 general hospitals, from 01.02.98 to 30.06.98. Only clinically significant samples have been considered. MICs have been measured for nine beta-lactams, three aminoglycosides, one fluoroquinolone and colistine. For ticarcilline resistant strains, phenotype has been assessed on Mueller-Hinton medium supplemented with beta-lactamases inhibitor. Transferable beta-lactamases has been identified using pl and PCR. MIC 50 and MIC 90 (mg/L) for beta-lactams are the following (MIC 50-->90): ticarcilline (16-->512), ticarcilline + clavulanic acid (16-->512), piperacilline (4-->512), pipéracilline + tazobactam (4-->64), aztreonam (4-->16), cefsulodine (4-->32), ceftazidime (2-->16), cefepime (4-->16), imipeneme (1-->8). For aminoglycosides: gentamicine (2-->32), tobramycine (1-->32), amikacine (4-->16). For ciprofloxacine (0.25-->32) and colistine (0.5-->2). According to CA-SFM break points recommendations, 50% of isolated strains are resistant to gentamicine, one out of three for ticarcilline + clavulanic acid (29%), one out of four for tobramycine (25%) and ciprofloxacine (25%), one out of ten for amikacine (9%), tazocilline (8%) and imipeneme (9%). Resistance to ceftazidime and aztreonam is uncommon (respectively 2%-1%) and never observed for cefepim. For ticarcilline resistant strains, (38% of total isolates) the following phenotypes have been detected: 6.7% non enzymatic resistance, 15.2% transferable beta-lactamase (TEM 4.8%, CARB 4.8%, TEM + CARB 4.8% and OXA-10 and derivated 0.9%) and 16.2% high level cephalosporinase. Extended-spectrum beta-lactamase has never been detected. TEM beta-lactamase is associated with resistance to amikacine and ciprofloxacine.

[Pulmonary and bronchial kinetics of cefuroxime after a single 500 mg intramuscular injection]. / Cinétique pulmonaire et bronchique de la céfuroxime après dose unique de 500 mg par voie intramusculaire.

Thirty-two patients (28 males; mean age 56 +/- 10 years) who were undergoing bronchopulmonary exeresis surgery were included in this study of the pulmonary (pulm), bronchial (br), and plasma (pl) kinetics of cefuroxime after a single 500 mg intramuscular injection. Twenty-nine bronchial specimens and 38 pulmonary and plasma specimens were taken on average at the following times after the cefuroxime injection: 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 10 h. Cefuroxime was assayed using HPLC on ground tissues, with a correction for contamination by blood. Peak concentrations (C) were found after one hour (Cpl = 11.6 +/- 0.8 micrograms/ml; Cpulm = 7.3 +/- 3.3 micrograms/g; Cbr = 3.7 +/- 1.5 micrograms/g) with the following residual values after 8 hours: Cpl = 0.94 +/- 1.04 micrograms/ml, Cpulm = 0.49 +/- 0.45 micrograms/g, Cbr = 0.15 +/- 0.07 micrograms/g (means +/- 1 SD). Elimination kinetics were monoexponential and similar in plasma, lung tissue and bronchial tissue (elimination half-lives: 1.74 h, 1.66 h, and 1.56 h, respectively), suggesting that all three elements belong to the same pharmacokinetic compartment. Mean intrapolated area-under-the-curve values (AUC) were 33.58 micrograms.ml-1.h (plasma), 20.08 micrograms.g-1.h (lung), and 10.22 micrograms/g-1.h (bronchus). The AUCpulm/AUCpl and AUCbr/AUCpl ratios were 0.60 and 0.30, respectively, in agreement with mean values of tissue level/simultaneous plasma level ratios (lung: 0.59; bronchus: 0.33).

Should vancomycin be used empirically in febrile patients with prolonged and profound neutropenia? Results of a randomized trial.

OBJECTIVES: We conducted a randomized trial with ceftazidine alone or associated with amikacin or vancomycin to investigate the efficacy of the daily 3 g dosage of ceftazidime and the efficacy of monotherapy with ceftazidime and to determine if vancomycin should be added empirically. METHODS: Patient inclusion criteria were: age over 10 years, therapeutically-induced neutropenia and fever for at least three hours above 38.5 degrees C in absence of a clear non-infectious aetiology. Patients were randomized into three groups: group C, ceftazidime alone 3 g/day; group CA, ceftazidime 3 g/day plus amikacin 15 mg/kg/day; or group C, ceftazidime 3 g/day plus vancomycin 1.5 g/day. RESULTS: Results from one hundred and two episodes of fever were analyzed. The underlying diseases were haematological malignancies (89 patients) and solid tumours (13 patients). The median duration of neutropenia (< 0.5 x 10(9) PMN/L) was 18 days and the minimum duration of 7 days. The main criterion for the analysis of efficacy was the onset of a major infectious event, i.e. death related to documented or suspected infection and any infectious event considered life-threatening or hindering future treatment of the underlying disease. Eight (22%) patients in group C developed major infectious events compared with four (13%) in group CA and none in group CV (p < 0.01). Major infectious events were mainly due to Gram-positive organisms, particularly Streptococcus species. CONCLUSION: We conclude that: 1) ceftazidime alone and in association with amikacin is effective in preventing Gram-negative major infectious events; and 2) vancomycin should not be added only when a Gram-positive infection is documented, but used empirically.