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Fundamental and clinical studies on BRL 25000 granules, containing 2 parts amoxicillin (AMPC) and 1 part clavulanic acid (CVA) (a beta-lactamase inhibitor) were carried out in the pediatric field. Serum concentrations and urinary excretion rates were determined after oral administration of BRL 25000 granules at a dose of 20 mg/kg to 2 children. The mean peak serum concentrations of AMPC and CVA were 4.89 and 2.85 micrograms/ml at 1 hour after administration, with serum half-lives (T 1/2) of 1.15 and 0.89 hours respectively. Mean cumulative urinary excretion rates of AMPC and CVA in the 6 hours after administration were 24.91% and 10.19%, respectively. BRL 25000 granules were also administered at daily doses of 25.1-60.4 mg/kg in 3 divided doses, to 20 pediatric patients with bacterial infections (4 acute tonsillitis, 2 acute pharyngitis, 3 suspected scarlet fever, 3 acute bronchitis, 8 urinary tract infection). The efficacy rate was 100% clinically and 70% bacteriologically. No adverse reactions were observed, however, abnormal laboratory findings were observed in 4 cases (slight elevation of GOT in 2, GPT in 1, eosinophilia in 1).
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To evaluate the safety and efficacy of an abbreviated course of antibiotic therapy in postpartum endomyometritis, 109 patients with endomyometritis were randomized to three study groups. All were treated with clindamycin and tobramycin until afebrility and clinical signs of disease were absent. Patients in group I received antibiotics for greater than or equal to 24 hours, group II received therapy for greater than or equal to 48 hours, and group III received antibiotic therapy for greater than or equal to 48 hours that preceded a 7-day course of oral Augmentin. The groups were similar in size and in demographic and clinical parameters. Two patients from each group required a third antibiotic, and no patient required rehospitalization. Group III required more days of antibiotic therapy than did group I, 2.9 versus 2.1 days (p less than 0.01), and cost $412.00 more per patient. This data strongly suggest that a short course of antibiotic therapy is efficacious and safe and would result in substantial monetary savings.
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Understandable concerns about the development of hospital-acquired infection led to a new protocol for antibiotic prophylaxis which in turn led to a number of patients being put at increased risk of potentially serious infective complications. Antibiotic prophylaxis must reflect tissue penetration, the organisms encountered and their susceptibilities, as well as being based on objective evidence.
There were two significant findings from the study. First, HLA-DRB1*15 was increased in patients (53%) versus both treated (33%: OR=2.29: 95% CI: 1.00-5.26) and population controls (30%: OR=2.59:95% CI: 1.44-4.68: p=0.002). Second, DRB1*07 was found to be reduced in patients (9.8%) compared to both treated (35%: OR=0.18: 95% CI: 0.06-0.52: p=0.0011, pc=0.0154) and population controls (29%: OR=0.266: 95% CI: 0.11-0.65: p=0.0019, pc=0.0266).
Two clinical strains of Klebsiella pneumoniae, TP 01 and TP 02, presented resistance to amoxicillin-clavulanate and were fully susceptible to cephalothin. These strains produced two beta-lactamases, SHV-1 and a TEM enzyme with a pI of 5.2. The previously described changes Arg-244-->Cys and Arg-244-->Ser in IRT-1 and IRT-2 (A. Belaaouaj, C. Lapoumeroulie, M. M. Caniça, G. Vedel, P. Nevot, R. Krishnamoorthy, and G. Paul, FEMS Microbiol. Lett. 120:75-80, 1994) were found in TEM enzymes from the TP 01 and TP 02 strains, respectively. This is the first report of inhibitor-resistant TEM (IRT) in species other than Escherichia coli from the family Enterobacteriaceae.
Although chronic Helicobacter pylori infection is associated with gastric cancer, the effect of H pylori treatment on prevention of gastric cancer development in chronic carriers is unknown.
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Over a six-month period in 1993, 2972 non-duplicated isolates of Escherichia coli causing urinary tract infections were collected in a French teaching hospital (n = 785) and in three private laboratories (n = 2187). The resistance rate to amoxycillin-clavulanate combination (MIC > 16 mg/l) was 25.0% in the hospital isolates and 10.0% in the community isolates. Respectively, 27.5% and 45.0% of hospital and community isolates resistant to amoxycillin-clavulanate exhibited an unusual beta-lactam resistance pattern, suggesting inhibitor-resistant TEM (IRT) beta-lactamase production. These isolates were highly resistant to amoxycillin-clavulanate (MIC90 > 1024 mg/L), but were susceptible to cephalosporins (MIC < 32 mg/L). Enzyme extracts of these IRT-producing strains focused at pI 5.2 (n = 100) or 5.4 (n = 53). DNA-DNA hybridization confirmed that the beta-lactamases involved in this resistance mechanism were TEM-1 derived and contained variations in the altered positions described in IRT enzymes. This study shows a total frequency of 4.9% of IRT-producing isolates among E. coli isolated from urine specimens.
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Autoinoculation and dissemination (or Kaposi's varicelliform eruption or eczema herpeticum) of herpetic lesions are two forms of viral spread, and it is essential to differentiate between the two. Presented are typical examples of the two forms of viral spread.
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While modern cephalosporins developed for broad spectrum antibacterial activities have never been pursued for tuberculosis (TB) therapy, we identified first generation cephalosporins having clinically relevant inhibitory concentrations, both alone and in synergistic drug combinations. Common chemical patterns required for activity against Mycobacterium tuberculosis were identified using structure-activity relationships (SAR) studies. Numerous cephalosporins were synergistic with rifampicin, the cornerstone drug for TB therapy, and ethambutol, a first-line anti-TB drug. Synergy was observed even under intracellular growth conditions where beta-lactams typically have limited activities. Cephalosporins and rifampicin were 4- to 64-fold more active in combination than either drug alone; however, limited synergy was observed with rifapentine or rifabutin. Clavulanate was a key synergistic partner in triple combinations. Cephalosporins (and other beta-lactams) together with clavulanate rescued the activity of rifampicin against a rifampicin resistant strain. Synergy was not due exclusively to increased rifampicin accumulation within the mycobacterial cells. Cephalosporins were also synergistic with new anti-TB drugs such as bedaquiline and delamanid. Studies will be needed to validate their in vivo activities. However, the fact that cephalosporins are orally bioavailable with good safety profiles, together with their anti-mycobacterial activities reported here, suggest that they could be repurposed within new combinatorial TB therapies.