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Evaluation of the clinical efficacy of Qingqiao capsule in treating patients with secretory otitis media.

OBJECTIVE: To observe the clinical efficacy of Qingqiao Capsule (QQC) in treating patients with secretory otitis media (SOM). METHODS: A total of 90 patients were randomly assigned into the treated group (n = 45) and the control group (n = 45). Patients in the treated group were administrated with QQC, 5 capsules each time, 3 times a day for totally 10-14 days, and those in the control group were given per os cefaclor capsules 0.5 g each time for adult, 3 times a day, or 20 mg/(kg.d) for children, for 10-14 days. The therapeutic efficacy of treatment on the patients was observed and compared after treatment and followed up for 3-6 months. RESULTS: (1) The clinical efficacy in the treated group was superior to that in the control group with significant statistical difference (P < 0.01); (2) Comparison of the efficacies in patients of three different TCM syndrome types (the external pathogenic wind invasion caused auditory orifice stuffiness type, the Gan-Dan damp-heat steaming up auditory orifice type and the Pi-deficiency dysfunction induced dirty dampness blocking ear type) showed no statistically significant difference (P > 0.05); (3) The vanishing rate and time needed of the main symptoms and signs in the treated group were superior to those in the control group on ear muffle, tinnitus, hearing impairment, hydrotypanum, pure tone threshold and abnormal tongue figure, and the difference was statistically significant (P < 0.05 or P < 0.01), only those of earache, otopiesis and abnormal pulse figure were insignificantly different between the two groups (P > 0.05). CONCLUSION: QQC is an effective Chinese composite medicine on patients with SOM, and shows no obvious adverse reaction.

Adolescent↗

Beta-lactam resistance in Streptococcus mitis isolated from saliva of healthy subjects.

The purpose of this study was to examine the percentage of Beta-lactam-resistant streptococcal carriers in healthy adults, and to investigate the relationships among minimum inhibitory concentrations (MICs) of Beta-lactams, alterations in the penicillin-binding protein genes ( pbp genes), and the affinity of penicillin-binding proteins (PBPs) for ampicillin (ABPC) in Streptococcus mitis. We also compared numbers of surviving bacteria at various ABPC concentrations in both ABPC-susceptible and -resistant S. mitis strains. The percentages of subjects carrying ABPC- and cefaclor (CCL)-resistant streptococci were 52% (27 of 52 subjects) and 100%, respectively. S. mitis, including both antibiotic-susceptible and -resistant strains, were classified into five groups according to the pbp gene mutations that resulted in alterations of the deduced amino-acid sequence in the homology boxes of PBPs. All ABPC-resistant strains showed alterations in PBP1A, 2X, and 2B, while no or only PBP2X alterations were detected in the susceptible strains. These results suggest that the accumulation of pbp gene mutations is strongly related to the MIC of ABPC for S. mitis. In the resistant strains, the affinity of PBPs for ABPC was reduced in comparison with that in the susceptible strains, and the bactericidal effect of ABPC was also reduced. Therefore, we should be aware of conditions such as infective endocarditis that are caused by Beta-lactam-nonsusceptible streptococci in the normal oral flora.

Adult↗

Detection of penicillin-binding protein 2b gene alteration in Streptococcus mitis by polymerase chain reaction.

Three isolates of beta-lactam-resistant streptococci from the saliva of healthy adults were identified as Streptococcus mitis. Minimum inhibitory concentrations (MICs) were 2 to 4 micro g/ml for ampicillin (ABPC) and 64 to more than 128 micro g/ml for cefaclor (CCL). To determine the position of base alterations of the penicillin-binding protein 2b ( pbp2b) gene, upstream primers containing possible mutation points were designed, and used for polymerase chain reaction (PCR), together with a downstream primer. Alterations adjacent to the conserved motifs of the pbp2b gene were apparent. DNA sequencing data indicated replacements in deduced amino acid sequences in all resistant isolates: from threonine to alanine just after the serine-serine-asparagine (SSN) motif, and from alanine to glycine two residues downstream of the lysine-threonine-glycine (KTG) motif. These changes were the same as those in penicillin-resistant Streptococcus pneumoniae (PRSP), suggesting importance for the enzymatic activity of the protein. Thus, Beta-lactam susceptibility of S. mitis may be partially predicted by PCR using our primer set for pbp2b.

Aminoacyltransferases↗

Reversed-phase high-performance liquid chromatography of amphoteric beta-lactam antibiotics: effects of columns, ion-pairing reagents and mobile phase pH on their retention times.

The separation of five amino beta-lactam antibiotics by reversed-phase high-performance liquid chromatography was studied as an insight into their retention behaviour. These five amphoteric compounds are cephradine, cephalexine, cefaclor, ampicillin and amoxicillin. Both octadecylsilane-bonded silica (C18) columns and phenyl-bonded silica (phenyl) columns were used, with mobile phase pH values between 2.5 and 7.4. In the absence of ion-pairing reagents the retention times for all the five compounds were the shortest at pH 4-6. The phenyl column was found to improve the separation between cephradine and ampicillin at pH values lower than 3, when these two compounds appeared as fused peaks on the C18 on C18 columns, with mobile phases both with and without ion-pairing reagents, were compared. The addition of 0.005 or 0.02 M tetraethylammonium acetate to the mobile phase did not result in significant ion-pair formation, except at pH values higher than 5.5. A strong ion-pairing effect was obtained at pH values higher than 6 with 0.005 or 0.02 M tetrabutylammonium phosphate, and the retention was decreased at pH values lower than 4. On the other hand, 0.005 M heptanesulphonic acid exhibited an ion-pair retention effect at pH values lower than 5. The molecular structures and pK(a) values were used to account for the retention behaviour of these antibiotics in the various mobile phases.

Amoxicillin↗

Antimicrobial activity of U-76,252 (CS-807), a new orally administered cephalosporin ester, including recommendations for MIC quality control.

U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807), was tested against 4,742 fresh clinical isolates from four large medical centers. U-76,253A was very active against nearly all species of Enterobacteriaceae (87.7% inhibited at less than or equal to 4.0 micrograms/ml). Staphylococcus spp., and the streptococci. The U-76,253A spectrum was superior to the comparison orally administered cephalosporins (cephalexin, cephradine, cefaclor). Pseudomonas spp., Acinetobacter spp., and the enterococci were resistant to U-76,253A and the other tested drugs. Broth microdilution MIC quality control (QC) limits were established for U-76,253A in a multilaboratory investigation using a minimum of 125 MIC determinations per organism. The following MIC QC ranges were recommended; Escherichia coli (ATCC 25922) = 0.25-1.0 micrograms/ml, Staphylococcus aureus (ATCC 29213) = 2.0-4.0 micrograms/ml and Pseudomonas aeruginosa (ATCC 27853) = greater than 32 micrograms/ml.

Administration, Oral↗

Cefdinir (FK482), an orally administered cephalosporin in vitro activity comparison against recent clinical isolates from five medical centers and determination of MIC quality control guidelines.

Cefdinir, a new oral cephalosporin, was compared to cefaclor, cefadroxil, cefixime, and cefuroxime against greater than 5000 recent aerobic clinical isolates. This multicenter study revealed broad-spectrum cefdinir activity against all Enterobacteriaceae (MIC50s, 0.06-2 micrograms/ml) except Enterobacter cloacae, Morganella morganii, Proteus vulgaris, and Serratia marcescens (MIC50s, greater than or equal to 4 micrograms/ml). Oxacillin-susceptible staphylococci (MIC90s, 0.5-2 micrograms/ml), beta-hemolytic Streptococcus group B (MIC90, 0.06 micrograms/ml), and Acinetobacter lwoffii were also susceptible to cefdinir. The activity of cefdinir was similar to that of cefixime and cefuroxime against Gram-negative organisms and superior to all tested oral cephems when tested against Gram-positive cocci. None of the cephalosporins were active against oxacillin-resistant Staphylococcus spp., enterococci, Pseudomonas spp., or Xanthomonas maltophilia. MIC quality control range guidelines were established for the strains recommended by the National Committee for Clinical Laboratory Standards documents.

Anti-Bacterial Agents↗

In vitro investigation of the indirect pathogenicity of beta-lactamase-producing microorganisms in the nasopharyngeal microflora.

OBJECTIVE: Nasopharyngeal microflora contains some beta-lactamase-producing microorganisms. In this study, we investigated in vitro on the indirect pathogenicities of Haemophilus parainfluenzae (H. parainfluenzae) and Moraxella catarrhalis (M. catarrhalis) against the antipneumococcul activities of some beta-lactams. METHODS: We compared the antimicrobial and bactericidal activities of beta-lactams against penicillin-susceptible Streptococcus pneumoniae (PSSP) with or without presence of the enzymes of two species of beta-lactamase-producing microorganisms, H. parainfluenzae and M. catarrhalis. RESULTS: When adding the enzymes extracted from these two beta-lactamase-producing microorganisms in equivalent amounts of 10(7) CFU/spot, the minimum inhibitory concentrations of amoxicillin (AMPC) and cefaclor (CCL) increased to >64 microg/mL. Even third-generation cephalosporins, such as cefditren (CDTR) and ceftriaxone (CTRX) showed marked increases with the enzyme of M. catarrhalis. In time-kill kinetics, same phenomenon was observed in mixed culture indicating the indirect pathogenicities of distinct bacteria, not extracted enzymes, on the cidal activities of beta-lactams against PSSP. Clavulanic acid (CVA)/AMPC, faropenem (FRPM), and imipenem (IPM) were not affected by these beta-lactamase-producing strains with respect to their activities against PSSP. However, these two beta-lactamase-producing strains and their enzymes did not show any significant influence on the antipneumococcul activities of beta-lactams, until the number of bacterial cells reached >10(8) CFU/mL. CONCLUSION: Our results suggest that these two species of beta-lactamase-producing microorganisms in the nasopharyngeal microflora may act as indirect pathogens on the antipneumococcul activities of beta-lactams with reflecting their substrate profiles, but this is dependent on sufficient amounts of enzyme for their influence as indirect pathogens.

Amoxicillin↗

Carrier-mediated uptake of cephalexin in human intestinal cells.

A transport carrier for cephalexin, a cephalosporin antibiotic, was identified in a human intestinal cell line, HT-29. Uptake via the carrier was inhibited by dipeptides, phe-gly, gly-pro, carnosine, and cefaclor, a close drug analog. Uptake was unaffected by the presence of amino acids. The pH optimum for uptake was 6.2. Drug uptake was not dependent on the presence of sodium and was insensitive to metabolic inhibitors. The efflux of cephalexin was stimulated by extracellular carnosine, indicating counter-transport. Taken together, drug uptake is mediated by a dipeptide transport carrier and not by an amino acid transport carrier. This is the first demonstration of the carrier in an established cell line.

Carnosine↗

Bactericidal eradication from carious lesions of prepared abutments by an antibacterial temporary cement.

PURPOSE: The aim of this study was to observe the antibacterial potential of polycarboxylate temporary cement containing a mixture of metronidazole, ciprofloxacin, and cefaclor on carious lesions of prepared abutments that were designed to leave caries on the abutments. MATERIAL AND METHODS: Antibacterial efficacy was estimated in vitro and in vivo by measuring bacterial recovery from the lesions. Bacteria counts ranged from 10(4) to 10(7) both in vitro (nine samples) and in vivo (five samples) in time-zero samples, just before the application of the antibacterial cement. RESULTS: No bacteria were recovered from carious lesions in vitro (six samples) or in vivo (four samples) after the lesions were covered by the antibacterial temporary cement. For the remaining samples, some bacteria (5 to 80 counts per sample) were recovered, with one notable exception in which marginal leakage provided a bacteria count of 10(3). Bacteria counts ranging from 10(3) to 10(5) occurred in carious lesions covered by temporary cement without antibacterial agents, which indicated that temporary cement alone was not a potent disinfectant. CONCLUSIONS: The results of this study indicated that the antibacterial temporary cement can be useful for eradicating bacteria from carious lesions of prepared abutments.

Adult↗

Antimicrobial susceptibilities of Haemophilus species in Hong Kong.

Altogether 403 Haemophilus spp. were isolated in seven hospital laboratories in Hong Kong during June 1986, mostly from sputum. Of these 73% were Haemophilus influenzae and 27% Haemophilus parainfluenzae. All the isolates of H. influenzae were non-capsulated; Haemophilus spp. were not isolated from blood or cerebrospinal fluid (CSF) during the period of the study. Antimicrobial resistance, including multiple resistance, was common. Of all the strains of H. influenzae, 20% were resistant to 1 mg/l ampicillin, (all except one by production of TEM-1 beta-lactamase), 65% were resistant to 0.5 mg/l erythromycin, 25% to 1 mg/l tetracycline, 14% to 1 mg/l chloramphenicol (mediated by the production of a chloramphenicol-destroying enzyme) and less than 1% to 8 mg/l cefaclor and 0.5 mg/l trimethoprim. All isolates were susceptible to cephamandole and cefuroxime. Haemophilus parainfluenzae showed similar susceptibilities, except that a greater proportion of strains was sensitive to erythromycin and chloramphenicol. Only 50% of the ampicillin-resistant strains of H. influenzae and H. parainfluenzae contained detectable plasmids of 2-55 Mdal arranged in six to nine different plasmid profiles. Resistance to ampicillin and chloramphenicol has increased markedly in isolates of H. influenzae in Hong Kong over the last 5 years. This resistance may be associated with transposable genes.

Ampicillin↗

A comparative investigation of the restorative effects of roxithromycin on neutrophil activities.

The effects of roxithromycin, a macrolide antibiotic, on neutrophil activities were investigated in six seriously handicapped patients with severe mental retardation. Neutrophil activities were evaluated by flow cytometry using a heparinized blood analysis method. All six patients showed decreased levels of neutrophil phagocytosis, intracellular killing, and CD11b expression. Treatment with roxithromycin in vitro selectively restored the decreased phagocytic and bactericidal activities of neutrophils in these patients. There was no significant restorative effect with cefaclor, ofloxacin, or aztreonam. These results suggest the need to consider therapeutic effects of antibiotics on neutrophil functions in patients at increased risk for bacterial infections due to decreased neutrophil activities.

Adolescent↗

[Urinary antimicrobial prophylaxis].

Antibiotics are usually used to prevent childhood recurrent urinary tract infections: cystitis or pyelonephritis. The mechanism of action of these antibiotics, although imperfectly known, seems to be double: the antibiotic acts by its bactericidal effect, but also probably for minimal concentrations by reducing adhesion capability of bacteria to the urothelium. The most commonly used molecules are cotrimoxazole, trimethoprime, pivmecillinam, cefaclor and nalidixic acid. However all have not been studied rigorously as for their prophylactic capacity, and in particular very little is known for patients presenting with vesico-ureteral reflux.

Amdinocillin Pivoxil↗

Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis.

Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v. antibiotic therapy) vs. an abbreviated (2-day i.v. antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP). We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement. Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v. every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v. every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days). No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups. The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs. 95%, respectively) were similar in both groups. Patients who received early oral therapy had shorter hospital stays (7.3 vs. 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs. $5002, P < 0.05). It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy. Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome.

Administration, Oral↗

In vitro activity of cefixime and six other agents against nosocomial pathogens of the Enterobacteriaceae family.

Cefixime, a broad-spectrum, orally active cephalosporin, was more active in vitro than ampicillin, cefaclor, cephalothin, and trimethoprim/sulfamethoxazole against 194 nosocomial pathogens of the family Enterobacteriaceae. Activity was especially good against Klebsiella spp, Proteus spp, Serratia spp, and Providencia stuartii. Although gentamicin had equivalent or better activity against Citrobacter spp, Enterobacter spp, Escherichia coli, and Morganella morganii, all 23 of the gentamicin-resistant strains studied were susceptible to cefixime. Isolates tested were from urinary tract infections, abdominal infections, wounds, vascular infections, and respiratory infections; they were sequentially collected nosocomial pathogens from a single institution. This orally active cephalosporin should be considered for therapy of a variety of nosocomial infections involving gram-negative bacillary pathogens.

Ampicillin↗

Formation of isomorphic desolvates: creating a molecular vacuum.

The objective of this work was to investigate a common but poorly understood category of crystalline organic substances: isomorphic desolvates. When solvent is lost from a crystal lattice but the lattice retains its three-dimensional order, a lattice is created which is in a high-energy state relative to the original solvate structure. The desolvated lattice can reduce its internal energy by either resorbing solvent or by relaxation processes which increase the packing efficiency of the solid by reducing the unit cell volume. In the following paper, solid-state properties of isomorphic desolvates of cephalexin, cefaclor, erythromycin A, and spirapril hydrochloride hydrates are investigated. The hygroscopicity of the compounds are evaluated using a vacuum moisture balance, and structural relaxation is measured using a combination of X-ray powder diffraction and isothermal microcalorimetry. The study results are explained in terms of Kitaigorodski's close packing principle.

Absorption↗

Mass balance approaches for estimating the intestinal absorption and metabolism of peptides and analogues: theoretical development and applications.

A theoretical analysis for estimating the extent of intestinal peptide and peptide analogue absorption was developed on the basis of a mass balance approach that incorporates convection, permeability, and reaction. The macroscopic mass balance analysis (MMBA) was extended to include chemical and enzymatic degradation. A microscopic mass balance analysis, a numerical approach, was also developed and the results compared to the MMBA. The mass balance equations for the fraction of a drug absorbed and reacted in the tube were derived from the general steady state mass balance in a tube: [formula: see text] where M is mass, z is the length of the tube, R is the tube radius, Pw is the intestinal wall permeability, kr is the reaction rate constant, C is the concentration of drug in the volume element over which the mass balance is taken, VL is the volume of the tube, and vz is the axial velocity of drug. The theory was first applied to the oral absorption of two tripeptide analogues, cefaclor (CCL) and cefatrizine (CZN), which degrade and dimerize in the intestine. Simulations using the mass balance equations, the experimental absorption parameters, and the literature stability rate constants yielded a mean estimated extent of CCL (250-mg dose) and CZN (1000-mg dose) absorption of 89 and 51%, respectively, which was similar to the mean extent of absorption reported in humans (90 and 50%). It was proposed previously that 15% of the CCL dose spontaneously degraded systematically; however, our simulations suggest that significant CCL degradation occurs (8 to 17%) presystemically in the intestinal lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefaclor↗

Antimicrobial activity of LY163892, an orally administered 1-carbacephem.

LY163892 was found to be similar to cefaclor and slightly superior to cephalexin in antimicrobial activity and spectrum. Bacteria with MIC50 less than or equal to 8.0 mg/l included Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Haemophilus influenzae, Branhamella catarrhalis, pathogenic Neisseria spp., oxacillin-susceptible staphylococci, and Streptococcus spp. Strains that produced plasmid-mediated beta-lactamases generally remained susceptible to LY163892. LY163892 was found to be bactericidal in general, but its MICs for some bacterial strains were adversely affected by increased inocula.

Bacteria↗

Therapeutic effect of fleroxacin against experimental pneumonia in mice.

Fleroxacin is a newly developed quinolone derivative with marked antimicrobial activity. In this study, we have compared the therapeutic effects of fleroxacin with those of ofloxacin, norfloxacin, ciprofloxacin, pipemidic acid and cefaclor against pneumonia in mice caused by Klebsiella pneumoniae. Fleroxacin showed a high therapeutic effect against the experimental pneumonia with an ED50 of 3.4 mg/kg/day, after three times a day oral administration. It was about twice as effective as ofloxacin and ciprofloxacin and more than 15 times more active than norfloxacin. Once or twice a day administration of fleroxacin also showed outstanding therapeutic effects.

Animals↗