desacetylcefotaxime and Bacterial-Infections

We have prospectively studied 13 episodes of spontaneous bacterial peritonitis (SBP) in 12 patients treated with cefotaxime (CTX) 2 g intravenously every 8 h (mean duration, 5.3 days). Ascitic fluid was inoculated at the bedside. The cultures were done before, during (day 3 after CTX initiation), and 48-72 h (mean, 56 h) after the end of therapy. All SBP episodes were monomicrobial. During treatment, the concentrations of CTX and desacetyl-cefotaxime (d-CTX) in ascitic fluid were high in all 13 SBP episodes, and d-CTX was still present in 6 patients who had residual ascitic bactericidal titer (ABT) activity after the last dose of CTX. ABTs were >/=1:128 during CTX therapy in 12 episodes and were measurable in 7 patients after the last dose. All patients were cured. The present study provides scientific rationale to the clinical studies that suggest treating SBP episodes with lower doses of antibiotics and shorter treatment duration.

Topics: Adult; Aged; Aged, 80 and over; Ascitic Fluid; Bacteria; Bacterial Infections; Cefotaxime; Cephalosporins; Female; Humans; Male; Middle Aged; Peritonitis; Prospective Studies

Pharmacokinetic parameters of cefotaxime (CTX) and its metabolite desacetylcefotaxime (DCTX) were assessed on the 3rd day of treatment in 10 preterm infants (28-37 weeks gestation) aged 3-8 days and receiving 25 mg/kg CTX twice daily. Blood samples were collected from an umbilical artery catheter at 0, 0.08, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12 h after a short peripheral infusion (5 min) and were assayed by high-performance liquid chromatography. During the 12 h following the CTX infusion, serum concentrations of CTX remained above the mean bactericidal concentration for pathogens commonly isolated during the neonatal period. The mean (+/- SD) elimination half-life, volume of distribution, total body clearance and area under the serum concentration-time curve (AUC0-12 h) for CTX were: 3.68 +/- 1.48 h (range: 1.89-6.82), 431 +/- 149 ml/kg (219-636), 1.57 +/- 0.80 ml/kg/min (0.60-3.27) and 373 +/- 206 micrograms/ml/h (170-867), respectively. The AUC0-12 h for DCTX was 170 +/- 93 micrograms/ml/h (61-374). A significant inverse relationship was found between gestational age and the elimination half-life of CTX, and the AUC of both CTX and DCTX.

Topics: Bacterial Infections; Cefotaxime; Female; Gestational Age; Half-Life; Humans; Infant, Newborn; Infant, Premature; Male

The antimicrobial activity of cefotaxime and its intermediate metabolite, desacetylcefotaxime, against 320 Gram-negative bacterial strains was analysed to investigate whether combination of the 2 substances led to increased bactericidal activity. The in vitro study of the minimum inhibitory concentration (MIC) showed the combination to be more effective against Escherichia coli, Klebsiella spp., Enterobacter spp. and Proteus mirabilis, requiring less than or equal to 50% of the concentration of cefotaxime alone to inhibit 90% of strains. For other micro-organisms the MIC90 for the combination was equal to or within 1 dilution of that for cefotaxime alone.

Topics: Bacterial Infections; Cefotaxime; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enterobacter; Escherichia coli; Gram-Negative Bacteria; Humans; Pseudomonas aeruginosa

The synergistic interaction of cefotaxime and desacetylcefotaxime against 187 clinically significant anaerobic organisms was investigated. Fusobacterium nucleatum, Actinomyces odontolyticus, propionibacteria, lactobacilli, peptostreptococci, Streptococcus intermedius and Veillonella were sensitive to cefotaxime. Both Eubacterium lentum and Streptococcus morbillorum were resistant. The susceptibility of the clostridia varied from 0.125 to greater than 256 mg/L; only 20% of species demonstrated synergy between cefotaxime and desacetylcefotaxime. The minimum inhibitory concentration (MIC) of cefotaxime against members of the genus Bacteroides ranged from 0.0625 to greater than 256 mg/L. The MIC50 of cefotaxime to Bacteroides fragilis and B. vulgatus was lowered from 6 and 4 mg/L, respectively, to 2 and 1 mg/L, respectively, when 4 mg/L desacetylcefotaxime was added to the medium. Full or partial synergy was demonstrated by 50.7% of the Bacteroides species tested. While cefotaxime and desacetylcefotaxime act synergistically against many members of the genus Bacteroides, the MIC of at least 10% of strains is not affected by this combination.

Topics: Bacteria, Anaerobic; Bacterial Infections; Bacteroides; Bacteroides Infections; Cefotaxime; Clostridium; Dose-Response Relationship, Drug; Drug Synergism; Eubacterium; Humans; Streptococcus

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Bone and Bones; Cefotaxime; Half-Life; Humans; Injections, Intravenous; Male; Middle Aged

Cefotaxime (CTX) was intravenously administered in an amount of 2.0 g to each of 34 adult patients before the surgery mainly of the hip joint. Samples of the blood from the bone marrow around the trochanter were taken at the time of the operation. At the same time blood samples were taken from peripheral veins. The sample was centrifuged and the supernatant was analyzed for CTX and desacetyl-CTX. The concentration of CTX in the marrow blood was 150.9 micrograms/ml and that in the blood was 182.5 micrograms/ml in the earliest samples taken at 20 minutes after injection. In the 44 pairs of samples, the concentration of CTX in the marrow blood was lower than that in the peripheral blood in all the cases except 4. The concentration of desacetyl-CTX (Des-CTX), however, in the marrow blood was higher than in the peripheral blood in 33 of the 44 pairs of specimens. Since the degradation of the drug progresses with time, the ratio of Des-CTX to CTX increased with time. This trend was particularly marked in the bone marrow blood and can be expressed as Y = 113.0 + 0.32 t, when Y is the ratio percentage (Des-CTX/CTX) and t is time after the injection of the drug in minute. Thus, CTX transferred into the bone marrow tends to remain there and transformed into the desacetyl form.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Bone Marrow; Cefotaxime; Female; Hip Joint; Humans; Male; Middle Aged; Surgical Wound Infection

Seventy-five children with bacterial meningitis were included in a multicentre trial for evaluation of cerebrospinal fluid (CSF) pharmacokinetics and clinical efficacy of cefotaxime. Mean age of patients was 4 years. Causative pathogens were Haemophilus influenzae in 28 patients (37%), Neisseria meningitidis in 27 patients (36%), Streptococcus pneumoniae in 10 patients (13%), group B streptococcus in 2 patients (2%) and unknown in 8 patients. All isolated pathogens were susceptible to cefotaxime. Seven ampicillin-resistant H. influenzae (9.4%) were found. Cefotaxime was 50 mg/kg intravenously, 4 times daily. The duration of treatment ranged from 5 to 22 days (mean: 13.8). Blood and CSF concentrations of cefotaxime were performed in 50 patients 3 h after infusion at day one and seven cefotaxime levels were determinated both by microbiological assay procedure and high pressure liquid chromatography. On day 1, CSF levels ranged from 0.39 to 2.0 mg/l by microbiological assay procedure (median 3.6) and from 0.0 to 17.4 mg/l (median 2.2) for cefotaxime and from 0.0 to 11.5 mg/l (median 2.2) for desacetyl-cefotaxime by HPLC. We observed a decrease in CSF levels of cefotaxime on day 7. They ranged from 0.3 to 7.0 mg/l (median 1.1) by microbiological assay and from 0.0 to 3.3 mg/l (median 0.8) for cefotaxime and from 0.0 to 6.0 mg/l (median 1.0) for desacetyl-cefotaxime by HPLC. On day 1 and day 7, CSF levels determined by microbiological assay and HPLC were correlated as follows: day 1:r = 0.59 (P less than 0.001). All children (100%) were cured and efficacy of cefotaxime was excellent in 72 cases (96%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Bacterial Infections; Cefotaxime; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Kinetics; Male; Meningitis

On the occasion of clinically indicated lumbar of cisternal punctures in 19 newborn and premature babies treated with Cefotaxime 33 CSF-levels of Cefotaxime (CTX) and it's metabolite Desacetyl-Cefotaxime (D-CTX) were measured by means of HPLC. 6 of the 19 infants suffered from meningitis. The highest CTX-levels were found 2 to 4 hours after the last infusion of CTX (50 or 100 mg/kg within 20 min, each 12 hours). Patients with meningitis showed CTX-levels between 20 mg/l and less than 0.5 mg/l (limit of detection), those without meningitis between 11 mg/l and less than 0.5 mg/l. Because of the widely scattered CTX-levels any dependence from CTX-dosage or from degree of meningeal inflammation is not to be shown. With two exceptions D-CTX-levels ranged from 2 to 20 mg/l. Up to 9 1/2 hours after the last CTX-dose no clear decrease of the D-CTX-concentration in CSF may be seen. On the other hand, D-CTX-levels are also widely scattered. Nevertheless D-CTX apparently stays significantly longer in the CSF than CTX does. An influence of meningeal inflammation on the D-CTX-levels can not be observed. In E. coli- and in Klebsiella-spp. The geometrical means of MIC are found to range below 0.5 mg/l for CTX and below 2 mg/l for D-CTX. Therefore CTX might be recommended for treatment of meningitis caused by these germs. This recommendation may be supported by some reports about good clinical results, from our unit and from the literature as well.

Topics: Bacterial Infections; Cefotaxime; Chromatography, High Pressure Liquid; Humans; Infant, Newborn; Infant, Premature, Diseases; Meningitis