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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.
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The authors summarized 514 questionner on dental patient medication, and established that, the dentists use an average in Hungary 29 box antibiotics per months. The most frequently prescribed medicine (Dalacin C, Rulid, Augmentin, Semicillin, Maripen, Doxycycline) take the 75% of the total number. The 52% of dentists use antibiotics for prophylactic aims, 94.6% for the treatment of inflammatory diseases. The examination gave data for creating the picture of the use of antibiotics in Hungarian dental practice in 1995.
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By the 1960s and 1970s, problems in the antibacterial treatment of infections had begun to emerge. Previously active antibacterials were being compromised by the development of resistance. Beta-lactamase production was identified in isolates of staphylococci, and, amongst others, in Escherichia coli, Proteus mirabilis, Haemophilus influenzae and Moraxella catarrhalis. The discovery of the potent beta-lactamase inhibitor clavulanic acid, and its protective effect on amoxicillin, a semi-synthetic penicillin with good oral absorption and potent broad-spectrum antimicrobial activity, was thus of great importance in the treatment of bacterial disease. Following preliminary clinical studies in bronchitis and urinary tract infections, amoxicillin/clavulanate therapy was investigated in a wide range of infections and proved to demonstrate a high level of clinical efficacy. These results supported the launch of amoxicillin/clavulanate (Augmentin) in 1981 for use in upper and lower respiratory tract infections, urinary tract infections, skin and soft tissue infections and obstetric, gynaecological and intra-abdominal infections.
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Fundamental and clinical studies on BRL 25000 granules were carried out in the pediatric field. BRL 25000 is a formulation comprising 1 part of clavulanic acid (CVA) and 2 parts of amoxicillin (AMPC). The MICs of BRL 25000 and AMPC were assessed against 24 clinically isolated strains of S. aureus (including 23 beta-lactamase producing strains), 22 S. pyogenes, 20 E. coli (8 beta-lactamase producing strains), 24 K. pneumoniae (24 beta-lactamase producing strains), 20 H. influenzae (6 beta-lactamase producing strains). BRL 25000 showed MIC80 (cumulatively 80% of strains were inhibited) at 6.25 micrograms/ml against S. aureus, less than or equal to 0.10 micrograms/ml against inst S. pyogenes, 12.5 micrograms/ml against E. coli, 6.25 micrograms/ml against K. pneumoniae and 0.39 micrograms/ml against H. influenzae. BRL 25000 showed no improvement in MIC terms against beta-lactamase nonproducing strains compared with AMPC. However, BRL 25000 was markedly more effective against beta-lactamase producing strains. Thus BRL 25000 was up to 8 fold more active against S. aureus, 2 to 64 fold against E. coli, 4 to 128 fold against K. pneumoniae, 4 to 16 fold against H. influenzae than AMPC. Following oral administration of BRL 25000 granules (at a dose level of 12.5 mg/kg) to 2 children aged 9 and 11 years, the mean peak serum concentrations of AMPC and CVA were 8.33 +/- 2.43 micrograms/ml and 4.44 +/- 1.65 micrograms/ml respectively 1 hour after dosing. The half-lives of AMPC and CVA were 1.35 +/- 0.42 hours and 0.91 +/- 0.05 hour, respectively. The urinary excretion was 48.21 +/- 3.83% for AMPC and 16.90 +/- 7.06% for CVA in the first 6 hours after administration. In clinical studies, 23 pediatric patients aged 2 months to 12 years with bacterial infections were treated with BRL 25000 granules and the clinical effectiveness, bacteriological response and side effects were evaluated. The clinical response was assessed in 23 cases, 3 with acute rhinitis, 6 with acute purulent tonsillitis, 5 with acute bronchitis, 4 with acute pneumonia, 3 with impetigo, 1 with furunculosis and 1 with periproctal abscess. Results were excellent in 13 cases, good in 7, fair in 3 and hence the efficacy rate (excellent and good cases) was 87.0% (20/23). In particular the clinical response in 9 cases with infections due to beta-lactamase producing organisms was excellent in 6, good in 2, fair in 1 and the efficacy rate was 88.9% (8/9).(ABSTRACT TRUNCATED AT 400 WORDS)
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We conducted a prospective multicenter study in Spain to characterize the mechanisms of resistance to amoxicillin-clavulanate (AMC) in Escherichia coli. Up to 44 AMC-resistant E. coli isolates (MIC ≥ 32/16 μg/ml) were collected at each of the seven participant hospitals. Resistance mechanisms were characterized by PCR and sequencing. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and by multilocus sequence typing. Overall AMC resistance was 9.3%. The resistance mechanisms detected in the 257 AMC-resistant isolates were OXA-1 production (26.1%), hyperproduction of penicillinase (22.6%), production of plasmidic AmpC (19.5%), hyperproduction of chromosomic AmpC (18.3%), and production of inhibitor-resistant TEM (IRT) (17.5%). The IRTs identified were TEM-40 (33.3%), TEM-30 (28.9%), TEM-33 (11.1%), TEM-32 (4.4%), TEM-34 (4.4%), TEM-35 (2.2%), TEM-54 (2.2%), TEM-76 (2.2%), TEM-79 (2.2%), and the new TEM-185 (8.8%). By PFGE, a high degree of genetic diversity was observed although two well-defined clusters were detected in the OXA-1-producing isolates: the C1 cluster consisting of 19 phylogroup A/sequence type 88 [ST88] isolates and the C2 cluster consisting of 19 phylogroup B2/ST131 isolates (16 of them producing CTX-M-15). Each of the clusters was detected in six different hospitals. In total, 21.8% of the isolates were serotype O25b/phylogroup B2 (O25b/B2). AMC resistance in E. coli is widespread in Spain at the hospital and community levels. A high prevalence of OXA-1 was found. Although resistant isolates were genetically diverse, clonality was linked to OXA-1-producing isolates of the STs 88 and 131. Dissemination of IRTs was frequent, and the epidemic O25b/B2/ST131 clone carried many different mechanisms of AMC resistance.
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During an outbreak of infection with ampicillin-resistant, TEM-1 beta-lactamase-producing Escherichia coli serotype O15, some strains were noted to differ from the majority in that they showed reduced susceptibility to amoxycillin/clavulanic acid (Augmentin), ureidopenicillins and first generation cephalosporins and produced increased amounts of beta-lactamase. The plasmid from one such isolate was compared with that from an isolate that produced normal amounts of beta-lactamase. Restriction analysis with EcoRI revealed extra fragments in the plasmid from the beta-lactamase hyperproducer and use of DNA-DNA hybridisation with a biotinylated TEM-1 probe showed genetic rearrangement in the beta-lactamase hyperproducer so that the TEM gene appeared to be present in larger amounts and was located on a smaller fragment than for the plasmid from the strain that produced normal amounts of beta-lactamase.
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A total of 137 children with acute otitis media with effusion were randomly allocated to treatment with cefprozil (30 mg/kg/day divided into two equal doses), an investigational cephalosporin or amoxicillin clavulanate potassium (40 mg/kg/day divided into three equal doses) for 10 days. The most common pathogens obtained from middle ear cavities by tympanocentesis were Streptococcus pneumoniae (33%), Haemophilus influenzae (19.6%) and Moraxella catarrhalis (8.3%). Patients were scheduled for follow-up visits at midtreatment, at end of therapy and at 30 days. Of the 137 children 122 were evaluable. Five of 60 patients (8.3%) treated with cefprozil and 14 of 62 patients (22.5%) treated with amoxicillin clavulanate potassium were considered therapeutic failures because of persistence of symptoms and/or isolation of the original pathogen or superinfection (P = 0.05). Rates of relapse, reinfection and persistent middle ear effusion as documented by tympanogram were comparable in both groups. When persistent middle ear effusion was analyzed by pneumatic otoscopy, 64 of 103 affected ears (62.1%) treated with cefprozil and 80 of 105 affected ears (76.1%) treated with amoxicillin clavulanate potassium were abnormal (P = 0.04). Loose stools were more common in children treated with amoxicillin clavulanate potassium than in children treated with cefprozil (P = 0.0004). Based on the efficacy results from this study, the lower gastrointestinal side effects and the convenience of twice-a-day dosing, we believe that cefprozil in a dosage of 30 mg/kg/day divided every 12 hours represents a potential alternative for the treatment of acute otitis media with effusion in children.
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There is excessive use of antimicrobial drugs in acute respiratory infections, and the majority are used for viral infections. There is indiscriminate use of broad spectrum antibiotics, which are valid in some infections but clearly inappropriate in others. Similarly, there are important differences in the choice of antibiotics and their degree of appropriateness among hospitals.
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Fecal Enterobacteriaceae were enumerated onto EMB agar containing amoxicillin (AMX). A total of 173 CF isolates and 41 sibling isolates were grouped into seven Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) clusters and identified through 16S rRNA and rpoB sequence analysis.
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The rapid increase in CIPNS E. coli causing bacteraemia was closely related to the increase in resistance to amoxicillin/clavulanic acid, production of ESBLs and resistance to aminoglycosides. Community use of fluoroquinolones (mainly moxifloxacin and levofloxacin) and of amoxicillin/clavulanic acid represents a significant driver in the progression of fluoroquinolone resistance in bacteraemic E. coli.
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Among the patients who did not deviate from the protocol (clinical per-protocol population), clinical success at day 21-28 post-therapy (test of cure; primary efficacy endpoint) was 92.4% (266/288) for amoxicillin/clavulanate 2000/125 mg and 91.2% (135/148) for amoxicillin/clavulanate 875/125 mg (treatment difference, 1.1; 95% confidence interval, -4.4, 6.6). Bacteriological success at test of cure in the bacteriology per-protocol population was 90.8% (79/87) with amoxicillin/clavulanate 2000/125 mg and 86.0% (43/50) with amoxicillin/clavulanate 875/125 mg (treatment difference 4.8; 95% confidence interval, -6.6, 16.2). At test of cure, amoxicillin/clavulanate 2000/125 mg was clinically and bacteriologically effective against 7/7 penicillin-resistant Streptococcus pneumoniae (MIC > or = 2 mg/L) isolates (including three amoxicillin non-susceptible strains) and amoxicillin/clavulanate 875/125 mg against 5/5 isolates (including one amoxicillin non-susceptible strain).
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Our data suggest that there has been an increasing resistance trend to the first-line antibiotics like trimethoprim and Augmentin against E coli. In accordance with NICE (National Institute for Health and Clinical Excellence) guidance, each region should monitor resistance patterns to urinary pathogens on a regular basis and use antibiotics with a low resistance pattern. Further studies are required from other centres in the UK to look at similar data.
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Amoxicillin/clavulanic acid is a widely used antibiotic. Hepatic dysfunction is a rare adverse reaction associated with this combination antibiotic. We report the case of a 40-yr-old woman with a somewhat unusual presentation of amoxicillin/clavulanate-related cholestatic hepatotoxicity and multiple duodenal erosions whose diagnosis was delayed until inadvertent rechallenge with the antibiotic combination. The relevant literature is also reviewed and discussed. The diagnosis may be missed because the onset of signs/symptoms may occur several weeks after the cessation of therapy. The hepatic dysfunction, which may be severe and is more prevalent in elderly patients, is usually reversible, although chronic liver disease and deaths have been reported. Immunological hypersensitivity is considered to be the most likely mechanism resulting in liver injury. Amoxicillin/clavulanate should be used with caution in patients with underlying liver disease and in the elderly.
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At the test-of-cure visit (7-14 days after the end of therapy), the clinical success rate in the moxifloxacin group was 93.4% similar to that in the amoxicillin/clavulanate group (92.7%). Documented bacteriological eradication plus presumed eradication rates in the moxifloxacin (96.5%) and the amoxicillin/clavulanate (96.7%) groups were also similar. Drug-related adverse events were recorded in 32.2% of patients in the moxifloxacin group and 29.7% in the amoxicillin/clavulanate group. Patient discontinuation in the trial due to adverse events occurred for 10 patients in the moxifloxacin group and 6 in the amoxicillin/clavulanate group.
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All four cocultures showed lower susceptibilities to azithromycin and minocycline than to pure cultures. The coculture Aa-Co showed a lower susceptibility to moxifloxacin as did the coculture Aa-Pm to benzylpenicillin G; the coculture Co-Pm showed a lower susceptibility to amoxicillin, amoxicillin/clavulanic acid, metronidazole, and benzylpenicillin G. However, the coculture Co-Pm showed a higher susceptibility to ampicillin, linezolid and moxifloxacin as did Aa-Pm and Aa-Co-Pm to linezolid.
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Melioidosis is a tropical disease caused by infection with the bacterium Burkholderia pseudomallei. Most cases present as an acute febrile illness with severe pneumonia and sepsis. Sub-acute and late onset disease can also occur Melioidosis has been diagnosed among travellers who contracted the disease while staying in endemic areas during the rainy season. We report a case of travel-associated B. pseudomallei cutaneous infection in a febrile 90-year-old woman with diabetes mellitus, with early stage manifestations of an isolated inoculation lesion. A 32 weeks' treatment with oral amoxicillin-clavulanate and doxycycline combination regimen led to resolution of the lesion and lack of relapse over fifteen months of follow-up. Melioidosis should be considered in the differential diagnosis of unusual subacute cutaneous lesions in a febrile patients returning from endemic areas, as successful management largely depends on early diagnosis and specific long-term suppressive antimicrobial therapy at an early stage of the course of the disease.
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To investigate whether an interaction exists between amoxicillin/clavulanic acid (amoxiclav) and warfarin in patients treated with stable oral anticoagulant therapy.
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Inhaled corticosteroids have been shown to reduce rates of hospitalization and emergency department use compared with leukotriene receptor antagonists.
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Departments of internal medicine at six German hospitals.
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Premature birth carries substantial neonatal morbidity and mortality. Subclinical infection is associated with preterm rupture of membranes (PROM). Prophylactic maternal antibiotic therapy might lessen infectious morbidity and delay labour, but could suppress labour without treating underlying infection.
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The results suggest that every asthmatic patient needs to carefully evaluate to determine whether the patient has concomitant sinusitis. Respiratory infections that meet criteria for sinusitis, even if they do not exacerbate asthma, should be treated. It is suggested that sinusitis should always be kept in mind as a possible inducible factor for BHR, and that aggressive treatment of chronic sinusitis is indicated when dealing with an asthmatic patient who shows an unpredictable response to appropriate treatment. Moreover, the findings of this study provide more evidence for an association between sinusitis and asthma with respect to BHR.
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The cumulative complete response rate at 6 months was 48.65%. Serum bone-specific alkaline phosphatase (BSAP) level >10 μg/L, lesion depth ≦ 10 mm, and lesions in anterior regions denoted a better chance of healing within 6 months and the adjusted hazard ratios were 2.48 (95% confidence interval [CI], 1.41-4.37), 2.71 (95% CI, 1.57-4.70), and 3.94 (95% CI, 1.87-8.30), respectively.
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A 20% reduction of the duration of clinical symptoms of exacerbation is expected. To this end, 520 patients are planned to be included in 15 centers in a 2-year period. Secondary end-points are the incidence of documented infection (lower respiratory tract or other sites), antibiotic use, the proportion of patients having infection with resistant bacteria, the incidence of endotracheal intubation, the duration of stay and mortality in the ICU and the hospital.
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An 8-year-old, male neutered Siamese cat was presented with Horner syndrome and right head tilt. A soft tissue mass was observed in the right tympanic cavity, and bulla osteotomy was performed. Tissue samples retrieved from the tympanic cavity were sent for histology, and a middle ear fluid swab was sent for bacterial culture and sensitivity. Histologic diagnosis was of otitis media associated with cholesterol granuloma (CG). Bacterial culture yielded Pasteurella multocida and Leifsonia (Corynebacterium) aquaticum. Middle ear CG is frequently seen in human beings and is associated with a variety of middle ear diseases including otitis media. Cholesterol granuloma of the middle ear has been experimentally induced in cats. The clinical and pathological findings of a spontaneous case of CG in the tympanic cavity of a cat with otitis media are described herein.
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The aim of our study was to compare three search strategies using a computerized administrative database to identify cases of idiosyncratic drug-induced liver injury (DILI) due to amoxicillin/clavulanic acid, phenytoin, valproic acid, and isoniazid.
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Melioidosis is an infectious disease endemic to northern Australia and Southeast Asia. In response to clinical confusion regarding the appropriate dose of amoxicillin-clavulanate, we have developed guidelines for the appropriate dosing of this second-line agent. For eradication therapy for melioidosis, we recommend 20/5 mg/kg orally, three times daily.
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Of 143 subjects enrolled in the study, the final analysis was performed among 67 subjects in the prophylaxis group and 64 in the control group. The frequency of postbronchoscopy fever did not differ between the groups (25.4% for the prophylaxis group vs. 26.6% for controls, P > 0.05). Pneumonia developed in 1.5% of the prophylaxis group and 4.7% of the controls. There was no bacteraemia in either group. Serum pyrogenic cytokines did not differ between the groups.
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The aerobic and anaerobic flora from gingival pockets of 49 dogs with severe gingivitis and periodontitis were cultured. The susceptibility of each isolate to four antimicrobial agents currently approved for veterinary use in the USA (amoxicillin-clavulanic acid; clindamycin; cefadroxil; and enrofloxacin) was determined. Amoxicillin-clavulanic acid (Clavamox Pfizer Animal Health) had the highest in-vitro susceptibility against all isolates (96%), all aerobes (94%) and all anaerobes (100%) tested. For gram-negative aerobes, enrofloxacin (Baytril, Bayer Corp.) had the highest in-vitro susceptibility activity. For bacteria associated with treatment of gingivitis, which typically are mixed aerobic/anaerobic and gram-positive/gram-negative organisms, the antimicrobial of choice for clinical use based on these susceptibility tests is amoxicillin-clavulanic acid.
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Randomised and quasi-randomised controlled trials, which compared azithromycin to amoxycillin or amoxycillin/clavulanic acid in patients with clinical evidence of acute LRTI: acute bronchitis, pneumonia, and acute exacerbation of chronic bronchitis were studied.