Summary
Synopsis
Clavulanic acid enhances the antibacterial spectrum of amoxicillin by rendering most β-lactamase-producing isolates susceptible to the drug. In clinical trials amoxicillin/clavulanic acid is clinically and bacteriologically superior to amoxicillin alone and at least as effective as numerous other comparative agents, such as orally administered cephalosporins, cotrimoxazole, doxycycline and bacampicillin, in the treatment of adults and children with the most common forms of infection encountered in general practice, i.e. urinary tract infections, upper and lower respiratory tract infections, otorhinolaryngological infections, and skin and soft tissue infections. It may also provide effective treatment for uncomplicated gonorrhoea, chancroid and gynaecological infections as well as acting as a prophylactic agent against surgical infection.
Thus, in general practice environments where β-lactamase production has restricted the effectiveness of amoxicillin, the combination of clavulanic acid with amoxicillin has clearly extended the usefulness of a tried and proven first-line antibacterial agent.
Antibacterial Activity
Clavulanic acid is an irreversible ‘suicide’ inhibitor of intracellular and extracellular β-lactamases, effective against a wide variety of these enzymes including those of Richmond and Sykes classes II to V (but not class I cephalosporinases), staphylococcal β- lactamase, and β-lactamase produced by Bacteroides fragilis. Clavulanic acid, therefore, protects amoxicillin from inactivation by many β-lactamases. As a consequence the antibacterial activity of amoxicillin has been restored at a time when the spread of resistance due to β-lactamase production severely threatened its usefulness.
Clavulanic acid alone possesses only weak antibacterial activity, except against Legionella spp., and certain strains of Branhamella catarrhalis, B. fragilis and Neisseria gonorrhoeae. However, the addition of clavulanic acid to amoxicillin increases the susceptibility to amoxicillin of amoxicillin-resistant strains of Gram-negative and Gram-positive aerobic and anaerobic bacteria where resistance is caused by β-lactamase production. These include Staphylococcus aureus (but not methicillin-resistant strains), Haemophilus spp., Branhamella catarrhalis, Neisseria gonorrhoeae, Escherichia coli, Proteus spp., Klebsiella pneumoniae, Citrobacter diversus, Salmonella and Shigella spp., Campylobacter jejuni, Bacteroides spp., and Mycobacterium spp. The susceptibility of amoxicillin-sensitive strains is not generally affected by the addition of clavulanic acid.
Amoxicillin/clavulanic acid is bactericidal in vitro, usually at concentrations no more than one dilution higher than in vitro inhibitory concentrations. The in vitro synergy of clavulanic acid combined with amoxicillin has been confirmed in vivo in numerous experimental infections in animals. The combination of amoxicillin with clavulanic acid appears to suppress the development of resistance under experimental conditions.
Pharmacokinetic Properties
Combining clavulanic acid with amoxicillin causes no appreciable alteration of the pharmacokinetics of either drug compared with their separate administration. After oral administration, both components achieve maximum plasma concentrations in about 1 hour and these concentrations show a direct relationship to the dose administered. The absolute bioavailability of clavulanic acid is about 60%. Absorption is unaffected by concomitant administration of food, milk, ranitidine or pirenzepine and little affected by antacid administration, but cimetidine may increase the rate of absorption of both components. Probenecid increases the plasma concentration of amoxicillin but not clavulanic acid.
Clavulanic acid has a volume of distribution of about 25% of bodyweight and is about 22% protein bound in vitro. The tissue and body fluid distribution of both components is generally adequate to achieve antibacterial levels, although concentrations may be somewhat low in bronchial secretions and cerebrospinal fluid. Both components transfer across the placenta but only very small quantities transfer into breast milk.
Both clavulanic acid and amoxicillin possess a mean elimination half-life of about 1 hour and a mean total clearance of about 25 L/h in healthy subjects. The main route of elimination is via the urine, and 6-hour urinary recovery of intact drug after oral administration is about 60 to 80% for amoxicillin and 30 to 50% for clavulanic acid. Clavulanic acid is excreted mainly by glomerular filtration and amoxicillin by tubular secretion; thus, probenecid delays the excretion of amoxicillin but not clavulanic acid. While amoxicillin is mainly excreted unchanged, clavulanic acid is subject to hydrolysis and subsequent decarboxylation.
Gastrointestinal disease may slow the rate of absorption of amoxicillin and clavulanic acid. The pharmacokinetic profile in children administered bodyweight adjusted dosages paralleled that in adults. Renal impairment decreases the clearance of amoxicillin and less markedly clavulanic acid: dosage reductions or increasing the dose interval are thus required. Both components are removed by haemodialysis and appropriate dose supplementation is therefore necessary at the end of a haemodialysis session.
Therapeutic Trials
Amoxicillin/clavulanic acid has usually been administered empirically to patients with symptoms suggestive of bacterial infection without selection of patients according to the resistance or susceptibility of the pathogen. Dosages of amoxicillin/clavulanic acid wereusually in the range 250/125 to 875/125mg 2 or 3 times daily in adults and bodyweight adjusted dosages were administered to children.
In adult patients with complicated or uncomplicated urinary tract infection, amoxicillin/clavulanic acid was clinically and bacteriologically superior at a statistically significant level compared with amoxicillin alone and cefatrizine propylene glycol, and bacteriologically superior compared with cotrimoxazole. In addition, it was at least as effective as cefaclor, cefalexin and pivmecillinam/pivampicillin.
In adult patients with upper or lower respiratory tract infections, amoxicillin/clavulanic acid was clinically more effective than amoxicillin alone or josamycin at a statistically significant level. Clinically and bacteriologically it was at least as effective as bacampicillin, pivmecillinam/pivampicillin, doxycycline, erythromycin, cefuroxime axetil, cefixime and cefaclor.
Amoxicillin/clavulanic acid has been shown to be clinically more effective at a statistically significant level than amoxicillin alone in the treatment of acute otitis media in adults, but statistically significant differences were not identified in comparisons with amoxicillin in children with otitis media or maxillary sinusitis. Some studies have shown statistically significant superiority of amoxicillin/clavulanic acid over cefaclor or myringotomy both clinically and bacteriologically in children with acute otitis media.
In skin and soft tissue infection amoxicillin/clavulanic acid produced a statistically significant higher bacteriological response rate and a tendency towards a higher clinical response rate compared with amoxicillin in adults with wound infection and children with nonbullous impetigo. In addition, in adults with wound infection amoxicillin/clavulanic acid was equivalent to cefuroxime axetil. In adults and children with skin and soft tissue infection, amoxicillin/clavulanic acid and cefaclor achieved similar clinical and bacteriological responses.
In uncomplicated gonorrhoea, administration of 2 doses of amoxieillin/clavulanic acid 3000/125 or 3000/250mg 4 to 6 hours apart or a single dose concomitantly with probenecid 1g proved the most satisfactory and convenient regimens, with antibacterial activity extended to cover penicillinase-producing Neisseria gonorrhoeae. Amoxicillin/ clavulanic acid 500/250mg 3 times daily for 3 days appears to provide an excellent treatment for chancroid.
Amoxieillin/clavulanic acid may provide an effective and more manageable regimenthan the standard triple combination of a β-lactam/an aminoglycoside/an imidazole in the treatment of obstetric and gynaecological infections but more study is required in this area before any definitive conclusions may be drawn. Amoxieillin/clavulanic acid has shown excellent results compared with other prophylactic regimens such as cephalosporins or aminoglycosides, and was superior to metronidazole at a statistically significant level, in the prevention of postoperative infectious complications following gynaecological, abdominal and vascular surgery.
Adverse Effects
About 13% of patients report adverse effects with amoxieillin/clavulanic acid, requiring withdrawal of treatment in less than 3% of patients. The adverse effects are primarily mild gastrointestinal disturbances, including diarrhoea, nausea, vomiting and indigestion. Rash, and Candida vaginitis or stomatitis each occur in about 1 % of patients. There have been isolated reports of urticaria, anaphylaxis, behavioural changes, and laboratory test abnormalities.
Gastrointestinal adverse effects may be reduced by taking the drug with food. Their frequency may be related to the dose of clavulanic acid and they may also occur considerably more frequently in children. Compared with other antibacterial agents, amoxieillin/clavulanic acid has usually been at least as well tolerated, although some orally administered cephalosporins (e.g. cefaclor) caused fewer gastrointestinal effects.
Dosage and Administration
The usual dosage for routine oral use in adult infections is 250/125mg or 500/125mg 3 times daily, although in Italy the usual dose is 875/125mg twice or 3 times daily, depending on the severity of infection. A number of parenteral preparations are available which may be administered intravenously in cases of severe infection or as a prophylactic in patients undergoing surgery. The recommended daily dose in children is 20 to 40mg/ kg, based on the amoxicillin component. Doses towards the lower end of this range should be adequate in mild to moderate infections while higher doses may be used against more severe infections. Dosage reductions are necessary in patients with renal failure. Amoxieillin/clavulanic acid should be administered with food and is contraindicated in patients with a known history of β-lactam hypersensitivity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abbas AMA, Chandra U, Dongaonkar PP, Goel PK, Kacker P, et al. Ciprofloxacin versus amoxicillin/clavulanic acid in the treatment of urinary tract infections in general practice. Abstract 468. Proceedings of the 6th Mediterranean Congress on Chemotherapy, Taormina, 1988
Abbas AMA, Goel PK, Venkit N, Gowers E. Augmentin therapy in the treatment of urinary tract infections in general practice. British Journal of Clinical Practice 38: 49–51, 1984
Abri O, Schulz L, Lohde E, Poschel F, Kraas E. Peri-operative antibiotic prophylaxis in colon surgery: amoxycillin/clavulanic acid versus mezlocillin + metronidazole. Proceedings of the 2nd Biennial Congress of Chemotherapy, Infectious Diseases and Malignancies, Beecham Satellite Symposium, Montreux, p. 41, 1989
Adam D, De Visser I, Koeppe P. Pharmacokinetics of amoxicillin and clavulanic acid administered alone and in combination. Antimicrobial Agents and Chemotherapy 22: 353–357, 1982
Agrawal SK, Jain S, Sahai J. Clavulanic acid potentiated amoxicillin (Augmentin) in the treatment of urinary infections. Antiseptic 84: 18–21, 1987
Ahmad F, McLeod DT, Croughan MJ, Calder MA. Antimicrobial susceptibility of Branhamella catarrhalis isolates from bronchopulmonary infections. Antimicrobial Agents and Chemotherapy 26: 424–425, 1984
Aigner K, Schindl R, Mittermayer H. Augmentin in acute exacerbations of chronic bronchitis. Journal of International Medical Research 12: 321–326, 1984
Al Roomi LG, Sutton AM, Cockburn F, McAllister TA. Amoxycillin and clavulanic acid in the treatment of urinary infection. Archives of Disease in Childhood 59: 256–259, 1984
Alvarez S, Jones M, Holtsclaw-Berk S, Guarderas J, Berk S. In vitro susceptibilities and β-lactamase production of 53 clinical isolates of Branhamella catarrhalis. Antimicrobial Agents and Chemotherapy 27: 646–647, 1985
Ambrose NS, Young SDJ, Keighley MRB. The penetration of Augmentin into perianal abscesses. Abstract 179. Proceedings of the 6th Mediterranean Congress of Chemotherapy, Taormina, 22–27 May, 1988
Amendola F, Natuzzi M, De Mattia D, Schettini F. Pédiatric suspension of amoxycillin and clavulanic acid in the treatment of bacterial infections of the upper respiratory tract and ear. Minerva Pediatrica 41: 97–103, 1989
Ancill RJ, Ballard JM, Capewell MA. Urinary tract infections in geriatric inpatients: a comparative study of amoxicillin — clavulanic acid and cotrimoxazole. Current Therapeutic Research 41: 444–448, 1987
Aronoff SC, Jacobs MR, Labrozzi PH, Yamabe S. Synergy of amoxicillin combined with clavulanate and YTR 830 in experimental infections in mice. Journal of Antimicrobial Chemotherapy 18: 271–276, 1986
Ashall G, Mouchizadeh J, Ornstein MH, Pyper RJD, Glazer G. A trial of augmentin versus cephazolin and metronidazole for antibiotic prophylaxis in general surgery. Chemioterapia 4 (Suppl. 2): 776–777, 1985
Baba S, Murai K, Kinoshita H, Iwasawa T, Sugimori H, et al. Evaluation of BRL25000 (clavulanic acid — amoxicillin) in acute purulent otitis media and acute exacerbation of chronic purulent otitis media: a comparative double blind study with amoxicillin. Chemotherapy (Tokyo) 31 (Suppl 2): 97–112, 1983
Bailey RR, Bishop V, Peddie B, Chambers PFM, Davies PR, et al. Comparison of Augmentin with co-trimoxazole for treatment of uncomplicated urinary tract infections. New Zealand Medical Journal 96: 970–972, 1983
Bakken JS, Bruun JN, Gaustad P, Tasker TCG. Penetration of amoxicillin and potassium clavulanate into the cerebrospinal fluid of patients with inflamed meninges. Antimicrobial Agents and Chemotherapy 30: 481–484, 1986
Ball AP, Davey PG, Geddes AM, Farrell ID, Brookes GR. Clavulanic acid and amoxycillin: a clinical, bacteriological, and pharmacological study. Lancet 1: 620–623, 1980
Barry AL, Jones RN, Packer RR. In-vitro susceptibility of the Bacteroides fragilis group to cefoperazone, ampicillin, ticarcillin and amoxicillin combined with β-lactamase inhibitors. Journal of Antimicrobial Chemotherapy 17: 125–127, 1986
Beale AS, Gisby J, Sutherland R. Efficacy of Augmentin (amoxicillin/clavulanic acid) in experimental Bacteroides fragilis/ Escherichia coli mixed infections. Journal of Drug Development 2 (Suppl. 1): 59–62, 1989
Beale AS, Sutherland R. Antibiotic sensitivity of urinary isolates in Great Britain during 1983–1985. A multicentre study. Journal of Drug Development 2 (Suppl. 1): 11–14, 1989
Bee LH, Phang T. Treatment of uncomplicated gonococcal urethritis in males with two doses of Augmentin, six hours apart. Singapore Medical Journal 26: 147–149, 1985
Beeuwkes H, Rutgers VH. A combination of amoxicillin and clavulanic acid in the treatment of respiratory tract infections caused by amoxicillin-resistant Haemophilus influenzae. Infection 9: 244–248, 1981
Bégué P, Astruc J, Barthe P, Boulesteix J, Bourrillon A, et al. Amoxycillin-clavulanic acid formulation versus amoxicillin and netilmicin in acute pyelonephritis in infants and children. Abstract 453. Proceedings of the 27th International Congress on Antimicrobial Agents and Chemotherapy, New York, 1987
Bégué P, Quiniou F, Nocquet N, Gaillard C, Safron C. Pharmacokinetics of Augmentin in children. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Benard Y, Lemenager J, Morel C. A comparative study of amoxicillin and Augmentin in the treatment of bronchopulmonary infections. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Bennett S, Wise R, Weston D, et al. Pharmacokinetics and tissue penetration of ticarcillin combined with clavulanic acid. Antimicrobial Agents and Chemotherapy 23: 831–834, 1983
Bernard E, Bertrand JC, Dellamonica P. Prophylactic antibiotic treatment in colo-rectal surgery — a randomised single-blind study of amoxycillin-clavulanic acid versus cefoxitin. Proceedings of the 2nd Biennial Congress of Chemotherapy, Infectious Diseases and Malignancies, Beecham Satellite Symposium, Montreux, p. 42, 1989
Beumer HM. Cefixime versus amoxicillin/clavulanic acid in lower respiratory tract infections. International Journal of Clinical Pharmacology, Therapy and Toxicology 27: 30–33, 1989
Beumer HM, Sips AP. Miraxid versus Augmentin in exacerbations of chronic bronchitis. Drugs under Experimental and Clinical Research 10: 351–356, 1984
Beytout J, Ferrier C, Lointier P, Chipponi J, Boutin-Tranchant ME, et al. Antibiotherapie prophylactique en chirurgie digestive: resultat d’unre etude randomisee comparant amoxicilline — a. clavulanique a gentalline + ornidazole. Abstract 134/p7. Proceedings of the Reunion Interdisciplinaire de Chimiotherapie Antiinfectieuse, Paris, 3 December, 1987
Bille J, Malinverni R, Glauser P. In vitro sensitivity of 65 Listeria monocytogenes isolates to new and old antibiotics. Chemioterapia 6 (Suppl. 2): 52–53, 1987
Bingen E, Lambert-Zechovsky N, Guihaire E, Mariani P, Coache M, et al. Interêt de l’etude du temps minimal bactercide du serum dans le choix, du traitement optimal des septicemies neonatales. Pathologie Biologie 35: 599–602, 1987
Bisetti A, Grassi L, Romano V, Scacciavillani E. Terapia di infezioni batteriche polmonari con amoxicillina ed acido clavulanico: esperienza clinica. Archivio Monaldi 42: 505–517, 1987
Bonsignore G, Bellia V, Ferrara G, Genovese G, Nicotra R, et al. Amoxicillina ed acido clavulanico nel trattamento di infezioni batteriche di pertinenza respiratoria. Medicina Toracica 11: 63–69, 1989
Boon RG, Masters PJ, Sutherland R. Bactericidal effect of amoxicillin arid clavulanic acid in an vitro model simulating pharmacokinetics in man. Abstract 301. Proceedings of the 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, 1982b
Boon RJ, Beale AS, Comber KR, Pierce CV, Sutherland R. Distribution of amoxicillin and clavulanic acid in infected animals and efficacy against experimental infections. Antimicrobial Agents and Chemotherapy 22: 369–375, 1982a
Borderon JC, Rastegar A, Rolland JC, Laugier J. Effet de l’association amoxicilline — acide clavulanique sur la flore fecale aérobie de l’enfant. Pathologie Biologie 33: 569–572, 1985
Borgo M, Caramia G, Castello D, Cremonesi D, Gaburro I, et al. Efficacia e tollerabilita di amoxicillina-acido clavulanico nelle infezioni in eta pediatrica: studio policentrico su 225 pazienti. Congresso nazionale Delia Societa Italiana per lo studio delie malattie infecttive e parassitarie, Rome, Oct 10–14, 1989. Conference report: pp 30–31, 1989.
Borgo M, Caramia G, Castello D, Cremonesi G, Gaburro I, et al. Efficacia e tollerabilità di amoxicillina-acido clavulanico nelle infezioni in età pediatrica: studio policentrico SU 225 pazienti. XXV Congresso Nazionale Delia Società Italiana per lo Studio Delle Malattie Infettive e Parassitarie, Rome, Oct 10–14, 1989. Conference Report pp. 30–31, 1989
Boston PF, Gowers E, Rose AJ. Augmentin compared with oxytetracycline for chest infections in general practice. British Journal of Diseases of the Chest 80: 148–156, 1986
Bourgault A-M, Lamothe F. In-vitro activity of amoxicillin and ticarcillin in combination with clavulanic acid compared with that of new β-lactam agents against species of the Bacteroides fragilis group. Journal of Antimicrobial Chemotherapy 17: 593–603, 1986
Bowie WR. In vitro activity of clavulanic acid, amoxicillin, and ticarcillin against Chlamydia trachomatis. Antimicrobial Agents and Chemotherapy 29: 713–715, 1986
Brackenbury PH, Adams J. A comparative double blind study of amoxycillin/clavulanate vs placebo in the prevention of infection after animal bites. Archives of Emergency Medicine 6: 251–256, 1989
Brazier JS, Levett PN, Stannard AJ, Phillips KD, Willis AT. Antibiotic susceptibilities of clinical isolates of clostridia. Journal of Antimicrobial Chemotherapy 15: 181–185, 1985
Brereton RJ, Ward HC, Valente A, Ghandour K, Price E, Dale P. A prospective trial of augmentin (amoxycillin/clavulanic acid) prophylaxis in paediatric abdominal surgery. Journal of Drug Development 2 (Suppl. 1): 95–104, 1989
Brogden RN, Carmine A, Heel RC, Morley PA, Speight TM, et al. Amoxycillin/clavulanic acid: a review of its antibacterial activity, pharmacokinetics and therapeutic use. Drugs 22: 337–362, 1981
Brown EM, Depares J, Robertson AA, Jones S, Hughes AB, et al. Amoxycillin-clavulanic acid (Augmentin) versus metronidazole as prophylaxis in hysterectomy: a prospective, randomized clinical trial. British Journal of Obstetrics and Gynaecology 95: 286–293, 1988
Brown EM, Ribeiro CD. Media factors affecting Augmentin disc sensitivity testing results. Journal of Antimicrobial Chemotherapy 16: 75–77, 1982
Brown EM. The in-vitro susceptibility of the Bacteroides fragilis group to amoxicillin-clavulanic acid. Journal of Antimicrobial Chemotherapy 14: 367–372, 1984
Brumfitt W, Franklin I, Grady D, Hamilton-Miller JMT. Effect of amoxicillin-clavulanate and cephradine on the fecal flora of healthy volunteers not exposed to a hospital environment. Antimicrobial Agents and Chemotherapy 30: 335–337, 1986
Brumfitt W, Hamilton-Miller JMT. Amoxicillin plus clavulanic acid in the treatment of recurrent urinary tract infections. Antimicrobial Agents and Chemotherapy 25: 276–278, 1984
Brumfitt W, Hamilton-Miller JMT. Changing role of co-trimoxazole in the treatment of recurrent urinary infections: a comparison with Augmentin. British Journal of Clinical Practice 39: 346–351, 1985
Bruna S, Bagnasco G, Gamna F, Denaro R, Orlandi O. Trattamento di infezioni batteriche dell’apparato respiratorio con l’associazione amoxicillina-acido clavulanico. Minerva Pneumologica 28: 17–22, 1989
Burnat C, Breuil J, Dublanchet A, Patey O. The beta lactams sensitivity of the bacteroides fragilis group in France: a multicenter survey study. Proceedings of the 4th European Congress of Clinical Microbiology, Nice, 1989. Abstract 315/PP20, p. 127, 1989
Campoli-Richards DM, Brogden RN. Sulbactam/ampicillin: a review of its antibacterial activity, pharmacokinetic properties, and therapeutic use. Drugs 33: 577–609, 1987
Cantoni L, Wenger A, Glauser MP, Bille J. Comparative efficacy of amoxicillin-clavulanate, cloxacillin, and vancomycin against methicillin-sensitive and methicillin-resistant Staphylococcus aureus endocarditis in rats. Journal of Infectious Diseases 159: 989–993, 1989
Casal M, Rodriguez F, Benavente M, Luna M. In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium fortuitum and Mycobacterium chelonei to Augmentin. European Journal of Clinical Microbiology 5: 453–454, 1986
Casey PA, Walther M. Comparison of amoxicillin/clindamycin (AMX/CLN) with Augmentin (AUG) in treatment of non-puerperal breast abscesses in women. Abstract 850. Proceedings of the 23rd International Congress on Antimicrobial Agents and Chemotherapy, Las Vegas, 24–26 Oct, 1983
Catalano GB, Serra A, La Mantia I. L’impiego dell’associazione amoxicillina ed acido clavulanico nelle infezioni del distretto otorinolaringoiatrico. Rivista Italiana di Otorinolaringologia, Audiologia e Foniatria 8: 359–365, 1988
Catherall EJ, Irwin RG, Mizen LW. Comparative efficacy of amoxicillin/clavulanic acid (Augmentin), flucloxacillin and vancomycin against Staphylococcus aureus endocarditis in the rat. Journal of Drug Development 2 (Suppl. 1): 62–65, 1989
Catherall EJ, Mizen L. Protection of amoxicillin and ticarcillin with clavulanic acid from inactivation by β-lactamases in an experimental localized infection. Drugs under Experimental and Clinical Research 10: 697–702, 1984
Chan KH, Mandel EM, Rockette HE, Bluestone CD, Bass LW, et al. A comparative study of amoxicillin-clavulanate and amoxicillin. Archives of Otolaryngology — Head and Neck Surgery 14: 142–146, 1988
Chau PY, Ng WS, Leung YK, Lolekha S. In vitro susceptibility of strains of Pseudomonas pseudomellei isolated in Thailand and Hong Kong to some newer β-lactam antibiotics and quinolone derivatives. Journal of Infectious Diseases 153: 167–170, 1986
Cho N, Fukunaga K, Kunii K. Fundamental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) in the field of obstetrics and gynecology. Japanese Journal of Antibiotics 36: 481–486, 1983
Ciraru-Vigneron N, Barrier J, Becue J, Chartier M, Giraud JR, et al. Amoxycillin/clavulanic acid (‘Augmentin’) compared with a combination of aminopenicillin, aminoglycoside and metronidazole in the treatment of pelvic inflammatory disease. Pharmatherapeutica 5: 312–319, 1989
Cohen R, Lebeaut A, Narcy Ph. Traitement des otites moyennes aiguës du jeune enfant par la formulation amoxicilline-acide clavulanique(*). Annales de Pédiatrie 36: 49–54, 1989
Comber KR, Horton R, Layte SJ, White AR, Sutherland R. Augmentin: antibacterial activity in vitro and in vivo. In Robinson and Watson (Eds) Proceedings of the First Symposium on Augmentin: clavulanate-potentiated amoxicillin, 3–4 Jun, p. 19, Excerpta Medica; Amsterdam, 1980
Cox AL, Meewis JMJM, Horton R. Penetration of amoxycillin and clavulanate into lung tissue after intravenous dosage of amoxycillin/clavulanate. Journal of Antimicrobial Chemotherapy 24 (Suppl. B): 87–92, 1989
Crokaert F, Van der Linden MP, Yourassowsky E. Activities of amoxicillin and clavulanic acid combinations against urinary tract infections. Antimicrobial Agents and Chemotherapy 22: 346–349, 1982
Croydon EAP, Jackson D, Staniforth DH. Pharmacokinetics of parenteral ‘Augmentin’. Abstract. Presented at the 12th International Congress of Chemotherapy, Florence, Jul 1981
Croydon EA, Sutherland A. Alpha-amino-p-hydroxybenzyl penicilln (BRL 2333), a new semisynthetic penicillin: absorption and excretion in man. Antimicrobial Agents and Chemotherapy 10: 427–433, 1970
Croydon P. A worldwide survey of clinical experience with Augmentin. Journal of Drug Development 2 (Suppl. 1): 67–69, 1989
Cullmann W, Dick W. A sensitive enzymatic assay for determination of cefoperazone and clavulanic acid concentrations in body fluids. Abstract B/31. Journal of Clinical Chemistry and Clinical Biochemistry 23: 614, 1985
Cynamon MH, Palmer GS. In vitro activity of amoxicillin in combination with clavulanic acid against Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy 24: 429–431, 1983
Dagan R, Bar-David Y. Comparison of Amoxicillin and Clavulanic Acid (Augmentin) for the Treatment of Nonbullous Impetigo. American Journal of Diseases of Children, 143: 916–918, 1989.
Dalet F, Cabrera E, Donate T, Del Rio G. Inhibidores de beta-lactamases. II. Farmacocinetica de la asociación amoxicilina + ácido clavulánico en la insuficiencia renal y durante la hemodialisis. Revista Clinica Espanola 172: 159–163, 1984
Dalet F, Del Rio G. Inhibidores de betalactamases. I. Evaluacion ‘in vivo’ de la asociacion amoxicilina + acido clavulanico en el tratamiento de infecciones urinarias. Revista Clinica Española 172: 153–157, 1984
Davies BE, Boon R, Horton R, Reubi FC, Descoeudres CE. Pharmacokinetics of amoxicillin and clavulanic acid in haemodialysis patients following intravenous administration of Augmentin. British Journal of Clinical Pharmacology 26: 385–390, 1988
Davies BE. Displacement of bilirubin from cord serum by sulphadimethoxine, amoxicillin, clavulanic acid in combination with either amoxicillin or ticarcillin, temocillin and cloxacillin. British Journal of Clinical Pharmacology 20: 345–348, 1985
Davies JG, Rose AJ, Walker GD. A comparison of Augmentin and co-trimoxazole in the treatment of adult infections in general practice. British Journal of Clinical Practice 36: 387–393, 1982
De Moüy D, Armengaud M, Lefevre M, Discamps G, Pagnon M, et al. Fréquence d’isolement des germes d’infection urinaire en pratique de ville; leur sensibilité à sept antibiotiques dont l’association amoxicilline-acide clavulanique. Pathologie Biologie 37: 402–405, 1989
De Silva AH, Bashi SAQ, Basu Roy R. Treatment of uncomplicated anogenital gonorrhoea with a single oral dose of 3g amoxicillin combined with 250mg clavulanic acid. British Journal of Venereal Diseases 60: 132–134, 1984
Decazes JM, Bure A, Wolff M, Kitzis MD, Pangon B, et al. Bactericidal activity against Haemophilus influenzae of cerebrospinal fluid of patients given amoxicillin-clavulanic acid. Antimicrobial Agents and Chemotherapy 31: 2018–2019, 1987
Deforges L, Soussy CJ, Duval J. Activite in vitro de l’association amoxicilline-acide clavulanique sur les bacteries anaerobies. Pathologie Biologie 32: 540–543, 1984
Deppermann KM, Lode H, Hoffken G, Tschink G, Kalz C, et al. Influence of pirenzepine, ranitidine and antacids on the bio-availability of different beta-lactam antibiotics. Abstract 274. Proceedings of the 6th Mediterranean Congress on Chemotherapy, Taormina, 22–27 May, 1988
Derluyn J. Clinical experience with 3 dosage regimens of oral Augmentin in patients with urinary tract infections. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Derriennic M, Reynaud A, Lauray C, Courtieu AL. Activite comparee de neuf betalactamines, de la clindamycine et du metro nidazole sur les bacteries anaerobies strictes. Pathologie Biologie 35: 572–576, 1987
Desgrandchamps D, Schnyder C. Severe neutropenia in prolonged treatment with orally administered Augmentin (amoxicillin/clavulanic acid). Infection 15: 260–261, 1987
Desplaces N, Gutmann L, Kitzis MD, Mamoudy P, Leonard P, et al. Efficacy and safety of amoxycillin-clavulanic acid (A-CA) alone or in combination with other antibiotics as long-term treatment of chronic bone and joint infections (CBJI). Proceedings of the 4th European Congress of Clinical Microbiology, Nice, 1989. Abstract 1203/PP60, p. 506, 1989
Dickie AS, Lang SDR. Pilot study of single dose of Augmentin for acute bacterial cystitis. New Zealand Medical Journal 99: 600, 1986
Dieterich HJ, Behringer K, Lauterjung L, Peter K. Prophylactic activity of Augmentin (amoxicillin/clavulanic acid) and cefoxitin in vascular surgery — a randomised clinical study. Journal of Drug Development 2 (Suppl. 1): 105–106, 1989
Dombrovicz N, Foidart JM. Use of augmentin as antibiopro-phylaxis in hysterectomy: a comparative study. Abstract 238. Proceedings of the 6th Mediterranean Congress on Chemotherapy, Taormina, 22–27 May, 1988
Drumm J, Donovan IA, Wise R, Lowe P. Metronidazole and augmentin in the prevention of sepsis after appendicectomy. British Journal of Surgery 72: 571–573, 1985
Dubs MMA. Beta-lactam-induced neutropenia. Pediatric Infectious Disease 4: 705–706, 1985
D’Adda D, Maruzzi MM, Pravettoni G, Raiteri D, Carotenuto E. Studio sull’ efficacia terapeutica di una nuova formulazione costituita da amoxicillina e acido clavulanico nel trattamento dei processi batterici broncopolmonari. Giornale Italiano Malattie del Torace 43: 33–36, 1989
Düben W, Schmitt MM, Student A. Bone levels of the components of parenteral amoxicillin/clavulanic acid. Fortschritte der Antimikrobiellen und Antineoplasticschen Chemotherapie 5: 41–45, 1986
Earnshaw JJ, Slack RCB, Makin GS, Hopkinson BR. Tissue and serum concentrations of amoxicillin and clavulanic acid in patients having reconstructive vascular surgery. Journal of International Medical Research 15: 205–211, 1987
El Mufti MB, Glessa A. Single-dose clavulanate-potentiated amoxicillin versus three-dose cefotaxime in the prevention of wound infection following elective cholecystectomy: a prospective randomized study. Journal of International Medical Research 16: 92–97, 1988
Ellis-Pegler RB, Lang SDR, Downey DJ, Anderson SDR. Augmentin treatment of bacterial infections in hospitalized patients. New Zealand Medical Journal 95: 542–545, 1982
El-Mufti M, Rakas FS, Glessa A, Abdulhadi A, Ekgam S, et al. Ceftriaxone versus clavulanate-potentiated amoxycillin for prophylaxis against post-operative sepsis in biliary surgery: a prospective randomized study in 200 patients. Current Medical Research and Opinion 11: 354–359, 1989
Engelhard D, Strauss N, Jorczak-Sarni L, Cohen D, Sacks TG, et al. Randomised study of myringotomy, amoxycillin/clavulanate, or both for acute otitis media in infants. Lancet 2: 141–143, 1989
English AR, Retsema JA, Girard AE, et al. CP-45,899, a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactams: initial bacteriological characterization. Antimicrobial Agents and Chemotherapy 14: 414–419, 1978
Eshelman FN, Spyker DA. Pharmacokinetics of amoxicillin and ampicillin: crossover study of the effect of food. Antimicrobial Agents and Chemotherapy 14: 539–543, 1978
Esposito S, Noviello S, D’Errico G, Montanaro C. Congresso Nazionale della societa italiana per lo studio delle malattie. Infettive e parassitarie, Rome, Oct 10–14, 1989. Conference Report: pp 6–7, 1989.
Esposito S, Noviello S, D’Errico G, Montanaro C. Amoxicillina/ acido clavulanico nel trattamento delle infezioni di pertinenza ORL. XXV Congresso Nazionale Delia Società Italiana per lo Studio Delle Malattie Infettive e Parassitarie, Rome, Oct 10–14, 1989. Conference Report pp. 6–7, 1989
Evans CM, Purohit S, Colbert JW, Lear PA, Makin T, Scobie DJ, et al. Amoxycillin-clavulanic acid (Augmentin) antibiotic prophylaxis against wound infections in renal failure patients. Journal of Antimicrobial Chemotherapy 22: 363–369, 1988
Farrell ID, Ball AP, Brookes G, Davey PG, Muscroft TJ, et al. The absorption of amoxicillin after gastric surgery. Journal of Antimicrobial Chemotherapy 7: 110–111, 1981
Fast MV, D’Costa LJ, Karasira P, Nsanze H, Plummer FA, et al. Treatment of chancroid by clavulanic acid with amoxycillin in patients with β-lactamase-positive Haemophilus ducreyi infection. Lancet 2: 509–511, 1982
Fernández-Roblas R, Jiménez Arriero M, Rodriguez-Tudela JL, Soriano F. In-vitro activity of amoxycillin/clavulanic acid and five other oral antibiotics against clinical isolates of Haemophilus influenzae and Branhamella catarrhalis. Journal of Antimicrobial Chemotherapy 22: 867–872, 1988
Fink M, Swoboda W. A trial of orally administered Augmentin in the treatment of urinary tract infection and lower respiratory tract infection in a children’s hospital. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Fior R, Zocconi E, Tamburini P, Veljak C. L’associazione amoxicillina acido clavulanico nelle infezioni batteriche dell’orecchio medio e delle cavità paranasali in età pediatrica. Rivista Italiana di Otorinolaringologia, Audiologia e Foniatria 9: 84–87, 1989
Flavell Matts SG, Fancourt GJ, Mitchell CJ, Gowers E, Boston PF. Further data on Augmentin and co-trimoxazole in the treatment of urinary tract infection. British Journal of Clinical Practice 39: 179–184, 1985
Fleisher GR, Wilmott CM, Campos JM. Amoxicillin combined with clavulanic acid for the treatment of soft tissue infections in children. Antimicrobial Agents and Chemotherapy 24: 679–681, 1983
Focht J, Klietmann W, Nösner K, Robinson GN, Johnsen J. Sensitivity of clinical isolates from German hospitals to amoxicillin/clavulanic acid (Augmentin) compared with other antibiotics. Chemotherapy (Basel) 34: 332–340, 1988
Foulstone M, Reading C. Assay of amoxicillin and clavulanic acid, the components of Augmentin, in biological fluids with high-performance liquid chromatography. Antimicrobial Agents and Chemotherapy 22: 753–762, 1982
French G, Ling T. Amoxycillin/clavulanate resistant Escherichia coli. Lancet 1: 704, 1988
Friese S, Willems FTC, Loriaux SM, Meewis JMJM. Prophylaxis in gynaecological surgery: a prospective randomised comparison between single dose prophylaxis with amoxycillin/clavulanate and the combination of cefuroxime and metronidazole. Journal of Antimicrobial Chemotherapy 24 (Suppl. B): 213–216, 1989
Fuchs PC, Barry AL, Thornsberry C, Gavan TL, Jones RN. In vitro evaluation of Augmentin by both microdilution and disk diffusion susceptibility testing: regression analysis, tentative interpretive criteria, and quality control limits. Antimicrobial Agents and Chemotherapy 24: 31–38, 1983
Gaillat J, Jacquet JF, Janin A, Micoud M. Surinfection bronchique essai clinique acide clavulanique-amoxiciline versus josamycine. Pathologie Biologie 35: 634–637, 1987
Gallacher G, Erwin L, Scott PJW, Sleigh JD. Augmentin (amoxicillin-clavulanic acid) compared with amoxicillin alone in the treatment of urinary tract infections in the elderly. Journal of Infection 12: 229–233, 1986
Galleri C, Gunella G, Fabiani A. Amoxicillina e acido clavulanico in combinazione nel trattamento delle flogosi broncopolmonari acute e croniche riacutizzate. Medicina Toracica 10: 419–426, 1988
García-Rodríguez JA, García-Sánchez JE, Muñoz JL, Trujillano I. Kinetics of antimicrobial activity of Augmentin (amoxicillin/clavulanic acid) against the Bacteroides fragilis group. Journal of Drug Development 2 (Suppl.1): 33–36, 1989
Garrel JP, Sonneck JM, Thabaut A, Leauté JB. Augmentin in the treatment of skin infections: Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Gasser TC, Larsen EH, Madsen PO. Amoxicillin/clavulanate in urinary tract infection. Urology 29: 111–114, 1987
Gaudreau CL, Lariviere LA, Lauzer JC, Turgeon FF. Effect of clavulanic acid on susceptibility of Campylobacter jejuni. Antimicrobial Agents and Chemotherapy 31: 940–942, 1987
Gehanno P, Simonet M. Use of a new paediatric oral suspension of amoxycillin-clavulanic acid (AM-CA) in acute otitis media in young children. Proceedings of 2nd Biennial Congress of Chemotherapy, Infectious Diseases and Malignancies, Bee-cham Satellite Symposium, Montreux, p. 51, 1989
Gerlach K, Schaal KP, Walz Chr, Pape H-D. Clinical efficacy of augmentin (amoxycillin/clavulanic acid) in severe odontogenic infections extending to face and neck. Journal of Drug Development 2 (Suppl. 1): 91–93, 1989
Girouard YC, Maclean IW, Ronald AR, Albritton WL. Synergistic antibacterial activity of clavulanic acid and amoxicillin against β-lactamase-producing strains of Haemophilus ducreyi. Antimicrobial Agents and Chemotherapy 20: 144–145, 1981
Goh BT, Rodin P, Johnston NA, Wong HHY. Penicillinase-producing Neisseria gonorrhoeae: epidemiology, antimicrobial susceptibility and plasmid types. Journal of Infection 11: 63–69, 1985
Goldstein EJC, Citron DM. Comparative in vitro activities of amoxicillin-clavulanic acid and imipenem against anaerobic bacteria isolated from community hospitals. Antimicrobial Agents and Chemotherapy 29: 158–160, 1986
Goldstein EJC, Reinhardt JF, Murray PM, Finegold SM. Outpatient therapy of bite wounds: demographic data, bacteriology, and a prospective, randomized trial of amoxicillin/clavulanic acid versus penicillin I dicloxacillin. International Journal of Dermatology 26: 123–127, 1987b
Goldstein FW, Hautefort B, Acar JF. Amikacin-containing regimens for treatment of Nocardiosis in immunocompromized patients. European Journal of Clinical Microbiology 6: 198–200, 1987a
Goldstein FW, Kitzis MD, Acar JF. Effect of clavulanic acid and amoxicillin formulation against β-lactamase producing Gramnegative bacteria in urinary tract infections. Journal of Antimicrobial Chemotherapy 5: 705–709, 1979
Gomez-Lus R, Gomez-Lus ML, Garcia C, Ortiz de Zarate C, Gil J, et al. Anti - Legionella pneumophila activity of amoxicillin, potassium clavulanate, and their combination compared to erythromycin and rifampin. Proceedings of the 15th International Congress of Chemotherapy, Istanbul, 1987
Gooch WM, Congeni BL, Swenson E, Snellman LW. Effectiveness and safety of Augmentin in the management of pneumonia of infants and children. Current Therapeutic Research 37: 178–183, 1985
Gordon RC, Ragamey C, Kirby WMM. Comparative clinical pharmacology of amoxicillin and ampicillin administered orally. Antimicrobial Agents and Chemotherapy 1: 504–507, 1972
Gould IM, Reid TMS, Legge JS. Amoxycillin/clavulanic acid levels in lower respiratory secretions. Journal of Antimicrobial Chemotherapy 22: 88–90, 1988
Grange JD, Gouyette A, Gutmann L, Amiot X, Kitzis MD, et al. Pharmacokinetics of amoxycillin/clavulanic acid in serum and ascitic fluid in cirrhotic patients. Journal of Antimicrobial Chemotherapy 23: 605–611, 1989
Green-Thompson RW, van der Ende J, Vawda V, Kritzinger NA. A comparison of the bacteriological efficacy of Augmentin orally and triple therapy with ampicillin, kanamycin and metronidazole parenterally in gynaecological infections. Abstract no. 182. Proceedings of the 6th Mediterranean Congress of Chemotherapy, Taormina, 22-27 May, 1988
Griffin KE, Cooper CE, Slocombe B. Comparative activities in vitro of augmentin (amoxycillin/clavulanic acid) and oral cephalosporins. Journal of Drug Development 2 (Suppl. 1): 19–24, 1989
Grimer RJ, Karpinski MRK, Andrews JM, Wise R. Penetration of amoxicillin and clavulanic acid into bone. Chemotherapy (Basel) 32: 185–191, 1986
Gurwith MJ, Stein GE, Gurwith D. Prospective comparison of amoxicillin-clavulanic acid and cefaclor in treatment of uncomplicated urinary tract infections. Antimicrobial Agents and Chemotherapy 24: 716–719, 1983
Haginaka J, Nagakawa T, Nishino T, Uno T. High performance liquid Chromatographic determination of clavulanic acid in human urine. Journal of Antibiotics 34: 1189–1194, 1981b
Haginaka J, Nakagawa T, Hoshino T, Yamaoka K, Uno T. Pharmacokinetic studies of the urinary excretion of clavulanic acid in man. Chemical and Pharmaceutical Bulletin 29: 3342–3349, 1981a
Haginaka J, Yasuda H, Uno T. High-performance liquid Chromatographic assay of clavulanate in human plasma and urine by fluorimetric detection. Journal of Chromatography 377: 269–277, 1986
Hall C, Curran F, Burdon DW, Keighley MR. A randomized trial to compare (Augmentin) amoxycillin/clavulanate with metronidazole and gentamicin in prophylaxis in elective colorectal surgery. Journal of Antimicrobial Chemotherapy 24 (Suppl. B): 195–202, 1989
Hart CA, Desmond AD, Percival A. Treatment of gentamicin-resistant Klebsiella urinary tract infections with cephradine, Augmentin, cefuroxime and amikacin. Journal of Antimicrobial Chemotherapy 8: 231–237, 1981
Haruta T, Kuroki S, Okura K-E, Kobayashi Y. Bacteriological and clinical evaluation of BRL 25000 (clavulanic acid-amoxicillin) granules in the pediatrie field. Japanese Journal of Antibiotics 38: 359–372, 1985
Hatano T, Baba S, Wada K, Murai K, Kinoshita H, et al. Laboratory and clinical studies with BRL25000 (clavulanic acid-amoxicillin) in the field of otorhinolaryngology. Chemotherapy (Tokyo) 30 (Suppl. 2): 626–632, 1982
Havard CWH, Fernando A, Brumfitt W, Hamilton-Miller JMT. A pilot study of ‘Augmentin’ in lower respiratory infections: pharmacokinetic and clinical results. British Journal of Diseases of the Chest 76: 255–260, 1982
Hebblethwaite EM, Brown GW, Cox DM. A comparison of the efficacy and safety of cefuroxime axetil and Augmentin in the treatment of upper respiratory tract infections. Drugs under Experimental and Clinical Research 13: 91–94, 1987
Henry-Suchet J, Douyeb B. Traitement des salpingites aiguës par une association Augmentin et titracycline de synthèse ou par Augmentin seul. Revue Francaise de Gynécologie et de Obstetrique 82: 281–284, 1987
Höffken G, Witkowski G, Lode H, Koeppe P. Comparative pharmacokinetics of amoxycillin, clavulanic acid and their combination. Proceedings of the 12th International Congress of Chemotherapy, Florence, 1981
Hoffler D, Dalhoff A. Pharmacokinetics of clavulanic acid in patients with normal and impaired renal function. In Nelson & Grassi (Eds) Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference of Antimicrobial Agents and Chemotherapy on Current Chemotherapy and Infectious Diseases, 1–5 Oct, 1979, pp. 322–323, American Society for Microbiology, Washington, 1980
Holl J, Konradt J. Use of Augmentin (amoxicillin/clavulanic acid) for prophylaxis in colon surgery. Abstract 273. Proceedings of the 6th Mediterranean Congress on Chemotherapy, Taormina, 22—27 May, 1988
Horber FF, Frey FJ, Descoeudres C, Murray AT, Reubi FC. Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin. Antimicrobial Agents and Chemotherapy 29: 614–619, 1986
Houang ET, Colley N, Chapman M. Penetration of sulbactamampicillin and clavulanic acid-amoxicillin into the pelvic peritoneum. Antimicrobial Agents and Chemotherapy 28: 165–166, 1985
Houang E, Colley N, Chapman M. Comparison of amoxicillin with clavulanate (Augmentin), with ampicillin and metronidazole, as the first line treatment for postoperative infections after gynaecological surgery. Journal of Obstetrics and Gynaecology 8: 156–160, 1987
Huizinga WKJ, Kritzinger NA, Bhanjee A. The value of adjuvant systemic antibiotic therapy in localised wound infections among hospital patients: a comparative study. Journal of Infection 13: 11–16,1986
Huizinga WKJ, Robbs JV, Kritzinger NA. Prevention of wound sepsis in amputations by peri-operative antibiotic cover with an amoxicillin-clavulanic acid combination. South African Medical Journal 63: 71–73, 1983
Hunter PA, Coleman K, Fisher J, Taylor D. In vitro synergistic properties of clavulanic acid, with ampicillin, amoxicillin and ticarcillin. Journal of Antimicrobial Chemotherapy 6: 455–470, 1980
Iravani A, Richard GA. Amoxicillin-clavulanic acid versus cefaclor in the treatment of urinary tract infections and their effects on the urogenital and rectal flora. Antimicrobial Agents and Chemotherapy 29: 107–111, 1986
Iravani A, Richard GA. Treatment of urinary tract infections with a combination of amoxicillin and clavulanic acid. Antimicrobial Agents and Chemotherapy 22: 672–677, 1982
Iwasawa T. Fundamental and clinical studies with BRL25000 (clavulanic acid-amoxicillin) in the otorhinolaryngolic field. Chemotherapy (Tokyo) 30 (Suppl. S-2): 612–625, 1982
Jackson D, Cooper DL, Filer CW, Langley PF. Augmentin: absorption, excretion and pharmacokinetic studies in man. Postgraduate Medicine 76 (Suppl.): 51–70, 1984
Jackson D, Cooper DL, Horton R, Langley PF, Staniforth DS, et al. Absorption, pharmacokinetic and metabolic studies with Augmentin. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun 1982
Jacobsson S, Rigner P, von Sydow C, Bondesson G. Recurrent and penicillin V-resistant otitis media — a treatment study with amoxycillin/clavulanate and cefaclor. Acta Otolaryngologica 106: 171–177, 1988
Jaffe AC, O’Brien CA, Reed MD, Blumer JL. Randomized comparative evaluation of Augmentin and cefaclor in pediatric skin and soft-tissue infections. Current Therapeutic Research 38: 160–168, 1985
Jeffries MG, Rose AJ, Williams HN. An initial assessment of Augmentin for the treatment of paediatric infections in general practice. British Journal of Clinical Practice 37: 61–66, 1983
Jensen T, Pedersen SS, Stafanger G, Hoiby N, Koch C, et al. Comparison of amoxicillin/clavulanate with amoxicillin in children and adults with chronic obstructive pulmonary disease and infection with Haemophilus influenzae. Scandinavian Journal of Infectious Diseases 20: 517–524, 1988
Jones RN, Thornsberry C. Beta-lactamase studies of eight Legionella species: antibacterial activity of Augmentin® compared to newer cephalosporins, erythromycin and rifampin. In Progress and perspectives on beta-lactamase inhibition: a review of Augmentin®. Postgraduate Medicine: Custom Communications, New York, pp. 259–262, 1984
Jorgensen JH, Doern GV, Thornsberry C, Preston DA, Redding JS, et al. Suceptibility of multiply resistant Haemophilus influenzae to newer antimicrobial agents. Diagnosis of Microbiological Infections 9: 27–32, 1988
Jorgensen JH, Redding JS, Howell AW. Comparative activities of LY 164846 and other orally administered β-lactam antibiotics against Haemophilus influenzae. Antimicrobial Agents and Chemotherapy 29: 1090–1091, 1986
Jurincic C, Klippel KF, Sietzen W, Lang A. Concentration of amoxicillin and clavulanate in the prostate tissue and in serum: a pharmacokinetic study. Proceedings of the 15th International Congress of Chemotherapy, Istanbul, 1987
Kaieida PH, Bluestone CD, Rockette HE, Bass LW, Wolfson JH, et al. Amoxicillin-clavulanate potassium compared with cefaclor for acute otitis media in infants and children. Pediatric Infectious Diseases Journal 6: 265–271, 1987
Kaplan EL, Johnson DR. Eradication of group A streptococci from the upper respiratory tract by amoxicillin with clavulanate after oral penicillin V treatment failure. Journal of Pediatrics 113: 400–403,1988
Kaprio E, Haapaniemi J, Bondesson G. Clinical efficacy of amoxycillin/clavulanic acid and cefaclor in acute otitis media. Acta Otolaryngologica 449: 45–46, 1988
Karachalios GN, Georgiopoulos AN. Treatment of acute urinary tract infections with amoxicillin and clavulanic acid combination. IRCS Medical Science 12: 1042–1043, 1984
Karachalios GN. Randomized comparative study of amoxicillinclavulanic acid and co-trimoxazole in the treatment of acute urinary tract infections in adults. Antimicrobial Agents and Chemotherapy 28: 693–694, 1985a
Karachalios GN. Treatment of respiratory tract infections with a combination of amoxicillin and clavulanic acid. International Journal of Clinical Pharmacology, Therapy and Toxicology 23: 647–649, 1985b
Kattamis C, Syriopoulou V, Hadjiminas J, Tsivitanidou-Kacourou T. Effectiveness of intravenous Augmentin in the treatment of thalassaemic patients with Yersinia enterocolitica infection. Journal of Antimicrobial Chemotherapy 14: 303–305, 1984
Kattamis C, Syriopoulou V, Papagregoriou-Theodoridou M, Mostrou-Antonellou G, Tzanetou G. Effectiveness of Augmentin in the treatment of urinary tract infections in children. Proceedings of the European Symposium on Augmentin, Scheveningen, June, 1982
Kawada Y, Karematsu M, Nishiura T, Tsuji I, Kumamoto Y, et al. Comparative studies of BRL25000 (clavulanic acid — amoxicillin) and cefatrizine in complicated urinary tract infection. Chemotherapy (Tokyo) 31 (Suppl. 2): 64–82, 1983
Kawamura S, Sugita R, Fujimaki Y, Deguchi K. Fundamental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) in the field of otorhinolaryngology. Japanese Journal of Antibiotics 36: 500–508, 1983
Kervasdoue A. Apport de l’Augmentin en pathologie infectieuse gynecologique. Abstract. Presented at the Beecham Symposium, Bordeaux, 11 Sep, 1987
Key PR, Azadian BS, Evans BA. Augmentin compared with amoxicillin in treating uncomplicated gonorrhoea. Genitourinary Medicine 61: 165–167, 1985
Kim JH, Kim SH, Hur H, Kim YT. Treatment of uncomplicated male gonococcal urethritis with clavulanate-potentiated amoxicillin. Korean Journal of Dermatology 25: 343–350, 1987
Kiosz D, Heilmann HD. Augmentin in the treatment of cystic fibrosis. Abstract 233. Proceedings of the 6th Mediterranean Congress on Chemotherapy, Taormina, 22–27 May, 1988
Kitzis MD, Kitzis MB, Yvelin C, Acar JF, Andreassian B. The penetration of Augmentin into the pleural fluid. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Knothe H, Shah PM, Schäfer V. Efficacy and safety of ofloxacin in the treatment of urinary tract infections in comparison with cotrimoxazole and amoxicillin + clavuianic acid. Proceedings of the 14th International Congress of Chemotherapy, Kyoto, 1985
Kosmidis J, Stathakis C, Kotilis D, Daikos GK. Pharmacokinetic studies with Augmentin, a combination of amoxicillin and potassium clavulanate. Proceedings of the 12th International Congress of Chemotherapy, Florence, 1981
Kumamoto Y. Basic and clinical studies on BRL 25000-Augmentin-treatment of gonorrheal infections. In Leigh & Robinson (Eds) Proceedings of an International Symposium on Augmentin (BRL25000), Montreux, 17 Jul, 1981 pp. 204–221, Excerpta Medica, Amsterdam, 1982
Kühn K. On the importance of prophylaxis against infections in surgery. Therapiewoche 36: 3559–3562, 1986
Labia R, Beguin-Billecoq R, Baron P. A prospective study of the evolution of bacterial resistance to Augmentin. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Lacroix J-M, Lamothe F, Malouin F. Role of Bacteroides bivius β-lactamase in β-lactam susceptibility. Antimicrobial Agents and Chemotherapy 26: 694–698, 1984
Lambert T, Mégraud F, Gerbaud G, Courvalin P. Suceptibility of Campylobacter pyloridis to 20 antimicrobial agents. Antimicrobial Agents and Chemotherapy 30: 510–511, 1986
Lamothe F, Auger F, Lacroix JM. Effect of clavulanic acid on the activities of ten beta-lactam agents against members of the Bacteroides fragilis group. Antimicrobial Agents and Chemotherapy 25: 662–665, 1984
Lapointe J-R, Lavallée C. Antibiotic interaction of amoxicillin and clavulanic acid against 132 β-lactamase positive Haemophilus isolates: a comparison with some other oral agents. Journal of Antimicrobial Chemotherapy 19: 49–58, 1987
Latif AS, Sithole J, Bvumbe S, Gumbo B, Kawemba M, et al. Treating gonococcal urethritis in men: oral amoxicillin potentiated by clavulanate compared with intramuscular procaine penicillin. British Journal of Venereal Diseases 60: 29–30, 1984
Lawrence AG, Shanson DC. Single dose oral amoxicillin 3g with either 125mg or 250mg clavulanic acid to treat uncomplicated anogenital gonorrhoea. Genitourinary Medicine 61: 168–171, 1985
Le Clech G, Bourdinière J. Résultats d’une étude multicentrique de l’association amoxicilline-acide clavulanique dans les sinusites de l’enfant et de l’adulte. Annales de Oto-Laryngologie 104: 147–150, 1987
Leelarasamee A, Aswapokee N, Kobwanthanakun S, Aswapokee P. In vitro susceptibility of Pseudomonas pseudomallei to the new quinolones compared with newer β-lactams. Reviews of Infectious Diseases 10 (Suppl. 1): S43, 1988
Leng B. Augmentin in the treatment of urinary tract infections due to amoxicillin-resistant bacteria. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Leng J, Barrier J, Becue J, Chartier M, Charvet F, et al. Results of a multicenter clinical trial of the efficacy and safety of Augmentin monotherapy compared with a combination of aminopenicillin, aminoglycoside and imidazole in the treatment of acute salpingitis. Abstract no. 478. Proceedings of the Mediterranean Congress of Chemotherapy, Taormina, 1988
Lim BT, Meewis JM, Sumajow CA. In vitro activity of Augmentin (amoxicillin/clavulanate) in comparison to other antimicrobial agents and a retrospective survey to determine emergence of resistance. Journal of Drug Development 2 (Suppl.2): 15–18, 1989
Lim KB, Rajan VS, Giam YC, Lui EO, Sing EH, et al. Two dose Augmentin treatment of acute gonorrhoea in men. British Journal of Venereal Diseases 60: 161–163, 1984
Lim KB, Thirumoorthy T, Lee CT, Sing EH, Tan T. Clinical experience in the use of clavulanic acid/penicillin regimens in the treatment of uncomplicated gonorrhoea. Annals of the Academy of Medicine (Singapore) 15: 258–261, 1986
Lim VKE, Bakar R, Hussin Z. Single dose oral amoxicillin and clavulanic acid in the treatment of gonococcal urethritis in males. Medical Journal of Malaysia 37: 235–238, 1982
Lindeque KP. The protective effect of clavulanic acid in a combined formulation on the concentration of amoxicillin in the urine of patients with urinary tract infections. South African Medical Journal 62: 12A-13A, 1982
Lippert D. A trial of orally administered Augmentin in the treatment of post-traumatic bone and joint infections. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Macknin ML. Behavioural changes after amoxicillin/clavulanate. Pediatric Infectious Disease Journal 6: 873, 1987
Maesen FPV, Davies BI, Baur C. Amoxycillin/clavulanate in acute purulent exacerbations of chronic bronchitis. Journal of Antimicrobial Chemotherapy 19: 373–383, 1987
Marchant CD, Shurin PA, Johnson CE, Murdell-Panck D, Feinstein JC, et al. A randomized controlled trial of amoxicillin plus clavulanate compared with cefaclor for treatment of acute otitis media. Journal of Pediatrics 109: 891–896, 1986
Martinelli R, Alberto da Silva Lopes A, De Oliveira MMMG, Rocha H. Amoxicillin-clavulanic acid in treatment of urinary tract infections due to Gram-negative bacteria resistant to penicillin. Antimicrobial Agents and Chemotherapy 20: 800–802, 1981
Martinez JL, Cercenado E, Rodriguez-Creixems M, Vincente-Perez MF, Delgado-Iribarren A, et al. Resistance to beta-lactam/ clavulanate. Lancet 2: 1473, 1987
Masters PJ, Cooper CE, Griffin KE, Slocombe B, Sutherland R. Comparative activities in vitro of augmentin (amoxycillin/clavulanic acid) and ampicillin/sulbactam. Journal of Drug Development 2 (Suppl. 1): 51–54, 1989
Matos-Ferreira A, Corte Real J. Open trial with amoxicillin + clavulanic acid (Augmentin) in complicated urinary tract infections. Abstract 285. Proceedings of the 6th Mediterranean Congress of Chemotherapy, Taormina, 22–27 May, 1988
Matsuda S. Augmentin treatment in obstetrics and gynaecology. In Leigh & Robinson (Eds) Proceedings of an International Symposium on Augmentin (BRL 25000), Montreux, 17 Jul 1981, pp. 179–191, Excerpta Medica, Amsterdam, 1982
Matsuda S, Tanno M, Kashiwagura T, Seida A. Fundamental and clinical studies on BRL25000 (clavulanic acid-amoxicillin) in the field of obstetrics and gynecology. Chemotherapy (Tokyo) 30 (Suppl. S2): S38–S47, 1982
Mayer HO, Jeschek H, Kowatsch A. Augmentin in the treatment of urinary tract infection in pregnant women and pelvic inflammatory disease. Proceedings of the European Symposium on Augmentin, Scheveningen, June, 1982
Mayhew SR. A comparison of cefuroxime axetil and amoxicillin/ clavulanic acid in the treatment of lower respiratory tract infection in general practice. Royal Society of Medicine International Congress and Symposium Series 124: 45–52, 1987
McColm AA, Shelley E, Ryan DM, Acred P. Evaluation of ceftazidime in experimental Klebsiella pneumoniae pneumonia: comparison with other antibiotics and measurement of its penetration into respiratory tissues and secretions. Journal of Antimicrobial Chemotherapy 18: 599–608, 1986
McGhie D, Kerfoot P, Talbot DJ. A comparative study of Miraxid (pivmecillinam plus pivampicillin) and Augmentin (amoxicillin plus clavulanic acid) in the treatment of lower respiratory tract infections in general practice. Journal of International Medical Research 14: 254–260, 1986
Menzies D, Gilbert JM, Shepherd MJ, Rogers TR. A comparison between amoxycillin/clavulanate and mezlocillin in abdominal surgical prophylaxis. Journal of Antimicrobial Chemotherapy 24 (Suppl. B): 203–208, 1989
Micillo E, Dericoloso A, Tranchese D, Cione P. Amoxicillina protetta dall’acido clavulanico nel trattamento di patologie infettive acute e chroniche dell’apparato polmonare. Archivio Monaldi 42: 535–549, 1987
Miki F, Takamatsu K, Kohno M, Beppu K, Saito A, et al. Comparison of BRL25000 (clavulanic acid-amoxicillin) and amoxicillin in the treatment of chronic respiratory tract infections. Chemotherapy (Tokyo) 31 (Suppl. 2): 1–43, 1983
Mittermayer HW. The effect of amoxicillin and amoxicillin plus clavulanic acid on human bowel flora. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982
Morgan JR, Williams BD, Sullivan MO, Williams K. Penetration of Augmentin and Timentin into the inflammed synovial joint. Abstract Proceedings of the 7th International Symposium on Future Trends in Chemotherapy, 1986
Motohiro T, Tanaka K, Koga T, Shimada Y, Tomita N, et al. Effect of BRL25000 (clavulanic acid-amoxicillin) on bacterial flora in human feces. Japanese Journal of Antibiotics 38: 441–480, 1985c
Motohiro T, Tanaka K, Koga T, Shimada Y, Tomita N, et al. Clinical trials of BRL25000 (clavulanic acid-amoxicillin) granules on skin and soft tissue infections in the field of pediatrics. Japanese Journal of Antibiotics 38: 507–537, 1985b
Motohiro T, Tanaka K, Koga T, Shimada Y, Tomita N, et al. Basic and clinical trials of BRL25000 (clavulanic acid-amoxicillin) granules in the field of pediatrics. Japanese Journal of Antibiotics 38: 481–506, 1985a
Motta G, Cesari U, Pittiglio R, Motta Jr G. Amoxicillina ed acido clavulanico per via orale nelle infezioni otorinolaringoiatriche. Rivista Italiana di Otorinolaringologia Audiologia e Foniatria 9: 88–92, 1989
Mouzinho A, Abrantes M, Pinto F, Marques Pinto L. Treatment of respiratory tract infections caused by Haemophilus influenzae with augmentin (amoxycillin/clavulanic acid): prospective trial. Journal of Drug Development 2 (Suppl. 1): 79–82, 1989
Munday PE, Bingham JS, Ison CA, Erdman YJ, Harris JRW, et al. Treatment of gonorrhea with clavulanate-potentiated amoxicillin (Augmentin). Sexually Transmitted Diseases 12: 163–165, 1985
Mégraud F, Gavinet A. Susceptibilities of enteric pathogens to amoxicillin and clavulanate-potentiated amoxicillin. Chemioterapia 6 (Suppl. 2): 75–76, 1987
Münch R, Lüthy R, Blaser J, Siegenthaler W. Clavulanic acid: human pharmacokinetics and penetration into cerebrospinal fluid. In Nelson & Grassi (Eds) Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy on Current Chemotherapy and Infectious Disease, 1–5 Oct, 1979, pp. 345–347, American Society for Microbiology, Washington, 1980
Münch R, Lüthy R, Blaser J, Siegenthaler W. Human pharmacokinetics and CSF penetration of clavulanic acid. Journal of Antimicrobial Chemotherapy 8: 29–37, 1981
Nakagawa K, Watanabe K, Hattori N, Yokota E. Phase I study on BRL25000 (clavulanic acid-amoxicillin). Chemotherapy (Tokyo) 30 (Suppl. 2): 98–110, 1982
Nakazawa H, Hashimoto T, Nishiura T, Mitsuhashi S. Efficacy of BRL 25OOO against Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii in urinary tract infections. Antimicrobial Agents and Chemotherapy 24: 437–439, 1983
Nakazawa S, Sato H, Narita A, Matsumoto K, Nakazawa S-l, et al. Fundamental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) granules in the pediatric field. Japanese Journal of Antibiotics 38: 296–308, 1985
Ndinya-Achola JO, Nsanze H, Karasva P, Fransen L, D’Costa LJ, et al. Three day oral course of Augmentin to treat chancroid. Genitourinary Medicine 62: 202–204, 1986
Nelson JD, Kusmiesz H, Shelton S. Pharmacokinetics of potassium clavulanate in combination with amoxicillin in pediatric patients. Antimicrobial Agents and Chemotherapy 21: 681–682, 1982
Neu HC. Amoxycillin. Annals of Internal Medicine 90: 356–360, 1979
Neu HC. Beta-lactamases: a perspective on the contribution of these enzymes to bacterial resistance. Postgraduate Medicine 76 (Suppl.): 7–21, 1984
Neu HC, Fu KP. Clavulanic acid, a novel inhibitor of β-lactamases. Antimicrobial Agents and Chemotherapy 14: 650–655, 1984
Neu HC, Winshell EB. Pharmacological studies of 6[D (−) alpha-amino-p-hydroxyphenylaceamido] penicillanic acid in humans. Antimicrobial Agents and Chemotherapy 10: 423–426, 1970
Nilsson-Ehle I, Fellner H, Hedström S-A, Nilsson-Ehle P, Sjövall J. Pharmacokinetics of clavulanic acid, given in combination with amoxicillin, in volunteers. Journal of Antimicrobial Chemotherapy 16: 491–498, 1985
Nishimura T, Tabuki K, Takashima T, Takagi M. Laboratory and clinical studies of BRL 25000 (clavulanic acid–amoxicillin) granules in the pediatrie field. Japanese Journal of Antibiotics 38: 431–440, 1985
Novelli A, Reali EF, Balocchini E, Boni S, Meli E, et al. Diffusione nel liquido di vescicola cutanea da suzione di amossicillina ed acido clavulanico dopo somministrazione per via orale in dose singola o ripetuta della loro associazione precostituita ed in proporzione 7:1. Farmaci e Terapia 4: 250–257, 1987
Nunes da Costa M, Goncalves M. Multicentre study of the sensitivity to augmentin (amoxycillin/clavulanic acid) and ampicillin of bacterial strains isolated in general practice. Journal of Drug Development 2 (Suppl. 1): 5–9, 1989
Obaseiki-Ebor EE, Oyaide SM, Okpere EE. Incidence of pencillinase producing Neisseria gonorrhoeae (PPNG) strains and susceptibility of gonococcal isolates to antibiotics in Benin City, Nigeria. Genitourinary Medicine 61: 367–370, 1985
Obwegeser J, Kunz J, Wüst J, Schär G, Steiner R, et al. Clinical efficacy of amoxycillin/clavulanate in laparoscopically confirmed salpingitis. Journal of Antimicrobial Chemotherapy 24 (Suppl. B): 165–176, 1989
Odio CM, Kusmiesz H, Shelton S, Nelson JD. Comparative treatment trial of Augmentin versus cefaclor for acute otitis media with effusion. Pediatrics 75: 819–826, 1985
Ohkawa M, Nakajima T, Tokunaga S, Motoi I, Koizumi H, et al. A double blind clinical trial of BRL 25000 (clavulanic acid-amoxicillin) and amoxicillin in complicated urinary tract infections. Chemotherapy (Tokyo) 31 (Suppl. 2): 44–63, 1983
Osato K, Tsugami H, Harada K, Maruyama J. Incidence of gonorrhoea due to penicillinase producing Neisseria gonorrhoeae in Japan 1981–1983 and treatment using a new antibiotic combination, BRL 25000 (amoxicillin and clavulanic acid). Genitourinary Medicine 62: 158–162, 1986
Osoba AO, Ogunbanjo BO, Adeyemi-Doro FAB, Rotowa NA, Ochei J. Single dose therapy of gonorrhoea with Augmentin plus probenecid. Southern African Journal of Sexually Transmitted Diseases 6: 11–13, 1986
Ottaviani A, Pagano A, Sambataro G, Berto M, Lenzi A, et al. Study of efficacy of amoxicillin plus clavulanic acid in the treatment of car, nose and throat infections. Abstract 39. Proceedings of the 6th Mediterranean Congress on Chemotherapy, Taormina, 22–27 May, 1988
O’Donovan C, Rudd R, O’Neill S, Fitzgerald MX, McNicholas W, et al. Augmentin (intravenous then oral) compared with cefuroxime followed by cephalexin for chest infections in hospitalised patients. British Journal of Clinical Practice 41: 1044–1052, 1987
O’Dowd TC, Ribeiro CD, Smail JE, Menday AP, Howells CHC. A comparative trial of pivmecillinam/pivampicillin and amoxicillin/clavulanate in the therapy of urinary tract infection in a general practice population. Current Medical Research and Opinion 9: 310–315, 1984
Palermo B, Rizza S, Pistorio MP, Crimi N, Maccarrone C, et al. Terapia di patologie infettive respiratorie mediante un antibiotico beta-lattamico protetto (amoxicillina ed acido clavulanico). Archivio Monaldi 42: 519–533, 1987
Pariente R. Resultats d’une etude clinique comparative erythromycine contre l’association amoxicilline — acide clavulanique dans les poussees de sur infections bronchiques chez des insuffisants respiratoires chroniques. Semaine des Hopitaux 63: 1653–1657,1987
Parish LC, Aten EM. Treatment of skin and skin structure infections: a comparative study of Augmentin and cefaclor. Cutis 34: 567–570, 1984
Pedler SJ, Bint AJ. Comparative study of amoxicillin-clavulanic acid and cephalexin in the treatment of bacteriuria during pregnancy. Antimicrobial Agents and Chemotherapy 27: 508–510, 1985
Penketh ARL, Hodson ME, Batten JC. The effect of Augmentin on sputum β-lactamase activity in patients with cystic fibrosis. British Journal of Clinical Practice 38: 188–189, 1984
Penn RL, Manocha KL, Burford JG, George RB. Comparison of Augmentin and cefaclor as oral therapy for lower respiratory infections in patients with chronic lung disease. Abstract. Clinical Research 31: 849, 1983
Pien FD. Double-blind comparative study of two dosage regimens of cefaclor and amoxicillin-clavulanic acid in the outpatient treatment of soft tissue infections. Antimicrobial Agents and Chemotherapy 24: 856–859, 1983
Playforth MJ, Smith GMR, Evans M, Pollock A. Single-dose intravenous antibiotics for the prophylaxis of abdominal surgical wound infection: a trial of amoxicillin/clavulanate against latamoxef. Surgical Research Communications 1: 173–180,1987
Pollock AV, Evans M, Smith GMR. Preincisional intraparietal Augmentin in abdominal operations. Annals of the Royal College of Surgeons of England 71: 97–100, 1989
Principi N, Viganò A, Dalla Villa A, Reali E. Therapy of urinary tract infections (UTIs) in children with amoxicillin plus clavulanic acid. Abstract 37. Proceedings of the 6th Mediterranean Congress on Chemotherapy, Taormina, 22–27 May, 1988
Rahman S. Hyperkalaemia associated with Augmentin in a patient with urinary tract infection. Saudi Medical Journal 8: 648,1987
Raine CH, Bartzokas CA, Stell PM, Gallway A, Corkill JE. Chemoprophylaxis in major head and neck surgery. Journal of the Royal Society of Medicine 77: 1006–1009, 1984
Rajender Reddy K, Brillant P, Schiff ER. Amoxicillin-clavulanate potassium-associated cholestasis. Gastroenterology 96: 1135–1141, 1989
Reading C, Cole M. Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrobial Agents and Chemotherapy 11: 852–857, 1977
Reading C, Farmer T, Cole M. The β-lactamase stability of amoxicillin with the β-lactamase inhibitor clavulanic acid. Journal of Antimicrobial Chemotherapy II: 27–32, 1983
Reading C, Farmer T. The inhibition of beta-lactamases from gram-negative bacteria by clavulanic acid. Biochemistry Journal 199: 779–787, 1981
Reddy KR, Brillant P, Schiff ER. Amoxycillin-clavulanate potassium-associated cholestasis. Gastroenterology 96: 1135–1141, 1989
Renton RL, O’Connor JCM, Westlake DM. Comparison of bacampicillin (Ambaxin) and Augmentin in the treatment of acute bronchitis in general practice. Clinical Trials Journal 21: 207–214, 1984
Risser WL, Kaplan SL, Mason EO, Listernick R, Yogev R, et al. Treatment of soft-tissue infections in children with amoxicillin-clavulanic acid combination or cefaclor. Current Therapeutic Research 37: 747–753, 1985
Robinson OPW. Hyperkalaemia associated with Augmentin therapy in a patient with urinary tract infection. Saudi Medical Journal 9: 432, 1988
Roca J, Duran M, Suris JC, Iglesias D. Amoxycillin/clavulanic acid (A/CA) in the treatment of urinary infections in pediatrics. Proceedings of the 4th European Congress of Clinical Microbiology, Nice, 1989. Abstract 1003/0548, p. 438, 1989
Rodloff AC, Görtz G, Ponnath H, Hahn H. Identification and susceptibility patterns of anaerobic bacteria isolated from clinical specimens during a one-year period. Infection 12: 395–401, 1984
Roholt I, Keiding J, In vivo efficacy and in vitro bactericidal effect of two β-lactamase antibiotic/β-lactamase inhibitor combinations, 2085Pand Augmentin. Proceedings of the 15th International Congress of Chemotherapy, Istanbul, 1987
Rolinson GN. History and mode of action of Augmentin. Postgraduate Medicine 76 (Suppl.): 25–28, 1984
Ruberto U, D’Eufemia P, Martino F, Giardini O. Amoxycillin and clavulanic acid in the treatment of urinary tract infections in children. Journal of International Medical Research 17: 168–171, 1989
Sabbour MS, Osman LM. Experience with antimicrobial combinations in urinary tract infections. Drugs under Experimental and Clinical Research 14: 45–51, 1988
Saito A. The pharmacokinetics of BRL 25000 — Augmentin in humans. Proceedings of an International Symposium on Augmentin (BRL 25000) Montreux, 17 Jul, 1981
Sakai K, Fujimoto M, Ueda T, Sasaki T, Maeda S. Clinical trials of BRL 25000 (clavulanic acid — amoxicillin) on infectious diseases of the skin and soft tissues. Chemotherapy (Tokyo) 30 (Suppl 2): 387–396, 1982
San Joaquin VH, Scribner RK, Pickett DA, Welch DF. Antimicrobial susceptibility of Aeromonas species isolated from patients with diarrhea. Antimicrobial Agents and Chemotherapy 30: 794–795, 1986
Sanson-Le Pors MJ, Casin I, Ortenberg M, Perol Y. In-vitro susceptibility of thirty strains of Haemophilus ducreyi to several antibiotics including six cephalosporins. Journal of Antimicrobial Chemotherapy 11: 271–280, 1983
Santos M, Canton E, Gobernado M, In vitro activity of beta-lactam antibiotics in combination with clavulanic acid against M.tuberculosis. Proceedings of the 15th International Congress of Chemotherapy, Istanbul, 1987
Saroglou G, Paniara-Volika O, Sima A, Paraskevopoulou E, Makris G, et al. Amoxicillin and clavulanic acid combination: clinical and laboratory evaluation in pulmonary infections. Clinical Therapeutics 4: 442–449, 1982
Sato Y, Iwata S, Akita H, Murai T, Ibara M, et al. Fundamental and clinical studies on BRL 25000 (clavulanic acid — amoxicillin) granules in the pediatric field. Japanese Journal of Antibiotics 38: 327–341, 1985
Scaglione F, Ferrara F, Cogo R, Mezzetti M, Cicchetti F, et al. Pharmacokinetics and tissue penetration of clavulanic acid and amoxicillin given in combination and in a single intake. Abstract 35. Proceedings of the 6th Mediterranean Congress of Chemotherapy, Taormina, 22–27 May, 1988
Schaad UB, Casey PA, Cooper DL. Single-dose pharmacokinetics of intravenous clavulanic acid with amoxicillin in pediatric patients. Antimicrobial Agents and Chemotherapy 23: 252–255, 1983
Schaad UB, Casey PA, Ravenscroft AT. Pharmacokinetics of a syrup formulation of amoxicillin-potassium clavulanate in children. Journal of Antimicrobial Chemotherapy 17: 341–345, 1986
Schift R, van Ulsen J, Ansink-Schipper MC, van Joost T, Michel MF. Comparison of oral treatment of uncomplicated urogenital and rectal gonorrhoea with cefuroxime axetil ester or clavulanic acid potentiated amoxicillin (Augmentin). Genitourinary Medicine 62: 313–317, 1986
Schmidt EW, Zimmermann I, Ritzerfeld W, Voss E, Ulmer WT. Controlled prospective therapeutic study of oral amoxycillin/ clavulanate vs ciprofloxacin in acute exacerbations of chronic bronchitis. Journal of Antimicrobial Chemotherapy 24 (Suppl. B): 185–194, 1989
Schmitt M, Bondonny JM, Delmas P, Galifer RB, Revillon Y, et al. Antibiotic therapy of perforated appendicitis in children: a comparison of amoxycillin/clavulanate with combination of benzylpenicillin, netilmicin and metronidazole. Journal of Antimicrobial Chemotherapy 24 (Suppl. B), 157–163, 1989
Schneider JE, Kleinman MS, Kupiec JW. Cholestatic hepatitis after therapy with amoxicillin/clavulanate potassium. New York State Journal of Medicine June: 355–356, 1989
Simon MW. Complications involving Augmentin. American Journal of Diseases in Children 139: 962, 1985
Slaughter RL, Kohli R, Brass C. Effects of hemodialysis on the pharmacokinetics of amoxicillin/clavulanic acid combination. Therapeutic Drug Monitoring 6: 424–427, 1984
Smith BR, LeFrock JL. Amoxicillin-potassium clavulanate: a novel β-lactamase inhibitor. Drug Intelligence and Clinical Pharmacy 19: 415–420, 1985
Solbiati M, Concia E, Bassetti D. The role of Augmentin in the treatment of upper and lower respiratory tract infections in children. Abstract no. 38. Proceedings of the 6th Mediterranean Congress on Chemotherapy, Taormina, 22–27 May, 1988
Soriano F, Ponte C, Santamaria M, Torres A, Fernandez-Roblas R. Susceptibility of urinary isolates of Corynebacterium group D2 to fifteen antimicrobials and acetohydroxamic acid. Journal of Antimicrobial Chemotherapy 20: 349–355, 1987
Spyker DA, Rugloski RJ, Van RL, O’Brien WM. Pharmacokinetics of amoxicillin: dose dependence after intravenous, oral, and intramuscular administration. Antimicrobial Agents and Chemotherapy 11: 132–141, 1977
Stahl JP, Pappo M. Etude comparative du cefuroxime-axetil versus l’association d’amoxicilline et d’acide clavulanique dans les infections orl et bronchiques. Semaine des Hopitaux 65: 247–251, 1989.
Staniforth DH, Clarke HL, Horton R, Jackson D, Lau D. Augmentin bioavailability following cimetidine, aluminum hydroxide and milk. International Journal of Clinical Pharmacology, Therapy and Toxicology 23: 154–157, 1985
Staniforth DH, Jackson D, Clarke HL, Horton R. Amoxycillin/ clavulanic acid: the effect of probenecid. Journal of Antimicrobial Chemotherapy 12: 273–275, 1983
Staniforth DH, Jackson D, Horton R, Davies B. Parenteral Augmentin: pharmacokinetics. International Journal of Clinical Pharmacology, Therapy and Toxicology 22: 430–434, 1984
Staniforth DH, Lillystone RJ, Jackson D. Effect of food on the bioavailability and tolerance of clavulanic acid/amoxicillin combination. Journal of Antimicrobial Chemotherapy 10: 131–139, 1982
Stein GE, Gurwith MJ. Amoxicillin-potassium clavulanate, a β-lactamase-resistant antibiotic combination. Clinical Pharmacology 3: 591–599, 1984
Stein GE, Patterson, MJ, Gurwith D, Vander Laan BA, Gurwith MJ. Amoxycillin/clavulanic acid therapy of acute urinary tract infection. Current Therapeutic Research 32: 617–623, 1982
Stokes DH, Slocombe B, Sutherland R. Bactericidal effects of amoxycillin/clavulanic acid against Legionella pneumophila. Journal of Antimicrobial Chemotherapy 23: 43–51, 1989a
Stokes DH, Wilkinson MJ, Tyler J, Slocombe B, Sutherland R. Bactericidal effects of amoxycillin/clavulanic acid against intracellular Legionella pneumophila in tissue culture studies. Journal of Antimicrobial Chemotherapy 23: 547–556, 1989b
Sunakawa K, Akita H, Iwata S, Sato Y. Clinical superinfection and its attendant changes in pediatrics. Infection 13 (Suppl. 1): S103–S111, 1985
Swenson JM, Wallace Jr RJ, Silcox VA, Thornsberry C. Antimicrobial susceptibility of five subgroups of Mycobacterium fortuitum and Mycobacterium chelonae. Antimicrobial Agents and Chemotherapy 28: 807–811, 1985
Symonds J, Biswas AK. Amoxycillin, Augmentin, and metronidazole in bacterial vaginosis associated Gardnerella vaginalis. Genitourinary Medicine 62: 136, 1986
Takase Z, Shirafuji H, Uchida M. Clinical and laboratory studies on BRL 25000 (clavulanic acid-amoxicillin) in the field of obstetrics and gynecology. Chemotherapy (Tokyo) 30 (Suppl. 2): 579–586, 1982
Tapsall JW, Phillips EA, Morris LM. Chromosomally mediated intrinsic resistance to penicillin of pencillinase producing strains of Neisseria gonorrhoeae isolated in Sydney: guide to treatment with Augmentin. Genitourinary Medicine 63: 305–308, 1987
Tehan S, Whittaker J. A multicentre double-blind prospective study comparing the efficacy and tolerability of Augmentin with the combination of cephradine plus metronidazole as surgical prophylaxis. Surgical Research Communications 6: 97–105, 1989
Thomas MG, Gillies M, Roberts S, Lang SDR. Comparison of the antistaphylococcal activity of serum from healthy subjects taking flucloxacillin or Augmentin. New Zealand Medical Journal 98: 452–453, 1985
Thomassin JM, Pech A. Interet de l’association acide clavulanique-amoxicilline dans le traitement de l’otite auguë de l’enfant. Journal de Medecine de Lyon 67: 1420, 1986
Thomsen J, Sederberg-Olsen J, Balle V, Vejlsgaard R, Stangerup S-E, et al. Antibiotic treatment of children with secretory otitis media. Archives of Otolaryngology — Head and Neck Surgery 115: 447–451, 1989
Thornley PE, Aitken JM, Nichol GM, Slevin NJ. Amoxycillinclavulanic acid combination in bronchopulmonary infection due to β-lactamase-producing Branhamella catarrhalis: preliminary report. Drugs 31 (Suppl. 3): 113–114, 1986
Tison E, Marpeau L, Pigné A, Tessier F, Barrat J. Traitement des salpingites aiguës non chlamydiennes. Etude de l’efficacité et de la tolérance d’un antibiotique en monothérapie: a’Augmentin®. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction 17: 513–519, 1988
Tsuji A, Ikeda F, Kaneko Y, Goto S. In vitro antimicrobial susceptibility of pencillinase-producing Neisseria gonorrhoeae in Japan. European Journal of Clinical Microbiology 5: 51–52, 1986
Tsutou H, Nanba R, Taguchi M, Yamomoto T, Mirami Y, et al. Fundamental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) in the field of oral surgery. Chemotherapy (Tokyo) 30 (Suppl. 2): 650–661, 1982
Ulmer WT, Zimmermann I. A controlled trial of amoxicillin with clavulanic acid (BRL 25000) against doxycycline in chronic bronchitis. Journal of International Medical Research 9: 372–377, 1981
Umbach G, Lang N, Werner H. Oral Augmentin in the treatment of urinary tract infections. Proceedings of the European Symposium on Augmentin, Scheveningen, June, 1982
Umemura S, Suwaki M, Nohara N, Arata J, Takei Y, et al. Double blind comparative test for BRL 25000 (clavulanic acid-amoxicillin) vs amoxicillin in acute skin infection. Chemotherapy (Tokyo) 31 (Suppl. 2): 83–96, 1983
Uno T, Haginaka J, Nakagawa T. HPLC analysis of clavulanic acid and pharmacokinetic investigation on urinary excretion of BRL 25000 (clavulanic acid — amoxicillin) in man. Chemotherapy (Tokyo) 30 (Suppl. 2): 118–124, 1982
Usuda Y, Tajiri M, Yuasa Y, Nakaamura T, Sekine O, et al. Serum and urine levels of amoxicillin and clavulanic acid following BRL 25000 (clavulanic acid-amoxicillin) administration to patients with various degrees of renal function. Chemotherapy (Tokyo) 30 (Suppl. 2): 91–97, 1982
Van den Broek JWG, Buennemeyer BLM, Stricker BHC. Cholestatische hepatitis door de combinatie amoxicilline en clavulaanzuur (Augmentin). Nederlander Tijdschrift vor Geneeskude 132: 1495–1497, 1988
Van der Auwera P, Sconeaux B. In vitro susceptibility of Campylobacter jejuni to 27 antimicrobial agents and various combinations of β-lactams with clavulanic acid or sulbactam. Antimicrobial Agents and Chemotherapy 28: 37–40, 1985
Van der Meijden WI, Piot P, Loriaux SM, Stolz E. Amoxycillin, amoxicillin-clavulanic acid and metronidazole in the treatment of clue cell-positive discharge. Journal of Antimicrobial Chemotherapy 20: 735–742, 1987
Van Erps P, Nowé P, Denis LJ. A clinical trial of Augmentin in urinary tract infections. Proceedings of the European Symposium on Augmentin, Scheveningen, June, 1982
Van Klingeren B, Dressens-Kroon M. The influence of clavulanic acid on the susceptibility to amoxicillin of beta-lactamase producing strains of H. influenzae using differing inoculum sizes. Journal of Antimicrobial Chemotherapy 5: 322–323, 1979
Van Klingeren B, Van Wijngaarden LJ. Inhibition of β-lactamase in penicillinase producing gonococci by clavulanic acid. Journal of Antimicrobial Chemotherapy 8: 79–83, 1981
Van Nierkerk CH, Van den Ende J, Hundt HKL, Louw EA. Pharmacokinetic study of a paediatric formulation of amoxycillin and clavulanic acid in children. European Journal of Clinical Pharmacology 29: 235–239, 1985
Verbist L. Antimicrobial activity of Augmentin in vitro. Proceedings of the European Symposium on Augmentin, Scheveningen, Jun, 1982, pp 42–46, 1983
Viniaker H, Frigard B, Gaillat J, Jeanjean P, Jourdon J, et al. Clinical and bacteriological efficacy of new dosage per os of amoxycillin-clavulanic acid (A-CA) to treat urinary tract infections (UTI) in adults. Proceedings of the 16th International Congress of Chemotherapy, Jerusalem, Israel, Jun 11–16, 1989, p. 218, 1989
Vlaspolder F, de Zeeuw G, Rozenberg-Arska M, Egyedi P, Verhoef J. The influence of flucloxacillin and amoxicillin with clavulanic acid on the aerobic flora of the alimentary tract. Infection 15: 241–244, 1987
von Kobyletzki V. Pharmacokinetic data in gynecological surgery using preoperative Augmentin: Chemioterapia 6 (Suppl.): 262–264, 1987
von Kobyletzki D, Primavesi CA. Pharmacokinetic investigations in obstetrics of a β-lactamase-inhibitor combination: augmentin. Biennial Conference on Chemotherapy of Infectious Diseases and Malignancies, Munich, April 26–29, 1987, Abstract 191, 1987
Waghorn DJ, Azadian BS, Talboys C. In vitro activity of selected antimicrobial agents against penicillinase producing Neisseria gonorrhoeae (PPNG) and non-PPNG strains. Genitourinary Medicine 62: 373–376, 1986
Wald ER, Chiponis D, Ledesma-Medina J. Comparative effectiveness of amoxicillin and amoxicillin-clavulanate potassium in acute paranasal infections in children: a double-blind, placebo-controlled trial. Pediatrics 77: 795–800, 1986
Wallace Jr RJ, Nash DR, Johnson WK, Steele LC, Steingrube VA. β-Lactam resistance in Nocardia brasiliensis is mediated by β-lactamase and reversed in the presence of clavulanic acid. Journal of Infectious Diseases 156: 959–966, 1987
Wallace RJ, Steele LC, Brooks DL, Luman JI, Wilson RW, et al. Amoxicillin-clavulanic acid in the treatment of lower respiratory tract infections caused by β-lactamase-positive Haemophilus influenzae and Branhamella catarrhalis. Antimicrobial Agents and Chemotherapy 27: 912–915, 1985
Watts HF, Williams AU, Cox DM. A pilot study of cefuroxime axetil (Zinnat) and Augmentin in the treatment of skin and soft tissue infections in general practice. Clinical Trials Journal 24: 356–363, 1987
Weber DJ, Tolkoff-Rubin NE, Rubin RH. Amoxicillin and potassium clavulanate: an antibiotic combination. Mechanism of action, pharmacokinetics, antimicrobial spectrum, clinical efficacy and adverse effects. Pharmacotherapy 4: 122–136, 1984
Weismeier K, Adam D, Heilmann H-D, Koeppe P. Penetration of amoxycillin and clavulanic acid into human bone. Journal of Antimicrobial Chemotherapy 24 (Suppl. B): 93–100, 1989
White AR, Boon BJ, Cooper CH. Bacterial effects of amoxicillin and clavulanic acid in an in vitro model of the human urinary bladder. Abstract 302. Proceedings of the 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, 1982
White AR, Boon RJ, Sutherland R. Effect of culture media and supplements on the activity of amoxycillin/clavulanic acid. Proceedings of the 13th International Congress of Chemotherapy, Vienna, 1983
White AR, Stokes DH, Slocombe B, Sutherland R. Bactericidal effects of amoxicillin/clavulanic acid and ticarcillin/clavulanic acid in in-vitro kinetic models. Journal of Antimicrobial Chemotherapy 15 (Suppl. A): 227–232, 1985
Williams H, King A, Shannon K, Phillips I. Amoxycillin/clavulanate resistant Escherichia coli. Lancet 1: 304–305, 1988
Williams KJ, Hebblethwaite EM, Brown GW, Cox DM, Plested SJ. Cefuroxime axetil in the treatment of uncomplicated UTI: a comparison with cefaclor and Augmentin. Drugs under Experimental and Clinical Research 13: 95–99, 1987
Wilson JM, Hunter PA. Comparative antibacterial effects of amoxicillin/clavulanic acid and cefotaxime against Enterobacteriaceae as determined by turbidimetry, morphology and viable count. Chemotherapy (Basel) 32: 118–125, 1986
Wise R, Bennett SA, Dent J. The pharmacokinetics of orally absorbed cefuroxime compared with amoxicillin/clavulanic acid. Journal of Antimicrobial Chemotherapy 13: 603–610, 1984
Wise R, Donovan IA, Drumm J, Andrews JM, Stephenson P. The penetration of amoxicillin/clavulanic acid into peritoneal fluid. Journal of Antimicrobial Chemotherapy 11: 57–60, 1983
Wølner P, Paavonen J, Kiviat N, Landers D, Sweet RL, et al. Ambulatory treatment of suspected pelvic inflammatory disease with Augmentin, with or without doxycycline. American Journal of Obstetrics and Gynecology 158: 577–579, 1988
Wong CS, Palmer GS, Cynamon MH. In-vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium kansasii to amoxicillin and ticarcillin in combination with clavulanic acid. Journal of Antimicrobial Chemotherapy 22: 863–866, 1988
Wust J, Wilkins TD. Effect of clavulanic acid on anaerobic bacteria resistant to beta-lactam antibiotics. Antimicrobial Agents and Chemotherapy 13: 130–133, 1978
Yamaguchi K, Chang C-H, Tanaka H, Ito N, Fujita K, et al. Laboratory and clinical studies on BRL125000 (clavulanic acid — amoxicillin). Chemotherapy (Tokyo) 30 (Suppl. 2): 338–348, 1982
Yoger R, Melick C, Kabat WJ. In vitro and in vivo synergism between amoxicillin and clavulanic acid against ampicillin-resistant Haemophilus influenzae type b. Antimicrobial Agents and Chemotherapy 19: 993–996, 1981
Yokota E, Sato M, Tatebayashi K, Hattori N. Microbiological assay of amoxicillin and clavulanic acid in specimens of body fluids after BRL 25000 (clavulanic acid-amoxicillin) administration. Chemotherapy (Tokyo) 30 (Suppl, 2): 111–117, 1982
Yoshioka K, Tudor R, Young D, Keighly MRB. Chemotherapy of Digestive System Infections. Proceedings of the 15th International Congress on Chemotherapy, Istanbul, 1987
Yourassowsky E, Van der Linden MP, Lismont MJ, Crokaert F, Glupczynski Y. Mesure par turbidometrie et bactéricidie de la vitesse d’action de l’acide clavulanique, de l’arnoxicilline et de leurs associations sur Haemophilus influenzae producteur de betalactamase. Pathologie Biologie 35: 526–530, 1987
Yourassowsky E, Van der Linden MP, Lismont MJ, Crokaert F, Glupczynski Y. Rate of bactericidal activity for Branhamella catarrhalis of fleroxacin compared with that of amoxicillinclavulanic acid. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 43–47, 1988
Author information
Authors and Affiliations
Additional information
Various sections of the manuscript reviewed by: K.E. Aldridge, Louisiana State University Medical Center, New Orleans, Louisiana, USA; S.C. Aronoff, Section of Immunologic and Infectious Diseases, Rainbow Babies and Children’s Hospital, Cleveland, Ohio, USA; B.I. Davies, Streeklaboratorium voor de Volksgeszondheid, De Wever-Ziekenhuis, Heerlen, The Netherlands; V. Fainstein, Infectious Diseases Associates of Houston, Houston, Texas, USA; D. Felmingham, Department of Clinical Microbiology, University College Hospital, London, England; R. Fujii, Research Institute of Chemotherapy for Mother and Child, Tokyo, Japan; K. Ishibiki, School of Medicine, Keio University, Tokyo, Japan; R.N. Jones, The Clinical Microbiology Institute, Tualatin, Oregon, USA; J. Kumazawa, Department of Urology, Kyushu University, Fukuoka, Japan; H.C. Neu, Columbia-Presbyterian Medical Center, New York, New York, USA; D.S. Reeves, Department of Medical Microbiology, Southmead Hospital, Bristol, England; H.W. Van Landuyt, A.Z. St-Jan, Ruddershove, Brugge, Belgium; L. Weinstein, Brigham and Women’s Hospital, Boston, Massachusetts, USA.
Rights and permissions
About this article
Cite this article
Todd, P.A., Benfield, P. Amoxicillin/Clavulanic Acid. Drugs 39, 264–307 (1990). https://doi.org/10.2165/00003495-199039020-00008
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199039020-00008