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Susceptibility of Pathogenic Bacteria to Amoxicillin/Clavulanic Acid (Augmentin) at a Referral Hospital

1989; King Faisal Specialist Hospital and Research Centre; Volume: 9; Issue: 5 Linguagem: Inglês

10.5144/0256-4947.1989.448

0975-4466

S. M. Hussain Qadri, Yoshio Ueno,

Bacterial Identification and Susceptibility Testing

Original ArticlesSusceptibility of Pathogenic Bacteria to Amoxicillin/Clavulanic Acid (Augmentin) at a Referral Hospital S. M. Hussain Qadri and PhD, Diplomate ABMM, FAAM, SM(AAM) Yoshio UenoRT(CSLT) S. M. Hussain Qadri Address reprint requests and correspondence to Dr. Qadri: Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia. From the Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh Search for more papers by this author and Yoshio Ueno From the Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh Search for more papers by this author Published Online:1 Sep 1989https://doi.org/10.5144/0256-4947.1989.448SectionsPDFCite ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutABSTRACTABSTRACTA total of 957 strains of bacteria isolated from clinical specimens were tested in vitro to determine the efficacy of amoxicillin/clavulanic acid (Augmentin). Sixty-seven percent of the 538 strains of Enterobacteriaceae, 93% of 174 Staphylococcus aureus, and all the 48 isolates of enterococci were inhibited by Augmentin. All the 156 strains of Pseudomonas aeruginosa, P. fluorescens, Enterobacter, Citrobacter, Serratia, and Shigella flexneri were resistant to Augmentin. Augmentin showed considerably increased activity against Escherichia coli, Klebsiella pneumoniae, Proteus species, and staphylococci when compared with ampicillin.IntroductionBacteria acquire resistance to penicillin by several different mechanisms. These include alteration of autolysins, transition to L-forms, development of impermeability, and production of enzymes that inactivate the drug.1–4 Synthesis of beta-lactamase is the principal mechanism of penicillin resistance in bacteria. Until recently, use of many penicillins was precluded for the treatment of infections caused by beta-lactamase producers. About a decade ago, Reading and Cole5 reported that clavulanic acid, produced by the fermentation of Streptomyces clavuligerus, had the ability to inactivate irreversibly a wide variety of beta-lac-tamases. This led to the development of Augmentin, which contains two parts of amoxicillin trihydrate to one part of clavulanate potassium (the potassium salt of clavulanic acid). (Sensitivity discs and formulary tablets of amoxicillin and clavulanate are prepared in a 2:1 ratio, but oral suspensions have a ratio of 4:1, respectively.)In vitro studies in the United States and Europe have shown Augmentin to possess increased activity against Enterobacteriaceae, staphylococci, and enterococci.6–14 Although the drug has been available in other countries for some time, it was introduced in Saudi Arabia only recently. In this paper we report the activity of Augmentin against pathogenic bacteria that have been isolated from clinical specimens in a tertiary care referral center in Saudi Arabia where the bacterial isolates are more resistant to commonly used antimicrobial agents than in the United States.MATERIALS AND METHODSAntimicrobial AgentsAgar diffusion tests were performed using commercially prepared antibotic disks. The antibiotic content of the disks was 10 μgfor ampicillin, colistin, gentamicin, and tobramycin; 15 μgfor erythromycin; 30 μgfor Augmentin, amikacin, cephalothin, chloramphenicol, tetracycline, and vancomycin; 1.25 μg/23.75 μgfor trimethoprim-sulfamethoxazole; 10 units for penicillin G; 100 μg for carbenicillin; and 1 μgfor oxacillin. The disk contents used are those recommended by the National Committee for Clinical Laboratory Standards15 for which interpretive data have been established.BacteriaClinical specimens were tested over a 6-month period at the King Faisal Specialist Hospital and Research Centre, a 470-bed referral medical and surgical hospital in Riyadh. Microorganisms were identified by conventional methods described in the Manual of Clinical Microbiology.16 These bacteria consisted of strains of Enterobacteriaceae, strains of Pseudomonas aeruginosa, strains of Staphylococcus aureus and Streptococcus species. The isolates were obtained from cultures of blood, respiratory secretions, urine, wounds, and miscellaneous sources.Susceptibility TestingAntibiotic disk susceptibility testing was performed according to the procedure described by the National Committee for Clinical LaboratoryStandards.15 Microorganisms were considered susceptible to Augmentin if the zone size was equal to or greater than 20 mm for Staphylococcus and 18 mm for all other gram-positive and gram-negative bacteria. Quality control organisms included in daily testing were Escherichia coli ATCC 25922, S. aureus ATCC 25923, and P. aeruginosa ATCC 27853. Mueller-Hinton agar with a pH between 7.2 and 7.4 was used in the tests. The susceptibility plates were incubated for 18 to 24 hours at 35°C.RESULTSA total of 957 isolates from clinical specimens were tested in vitro by the disk diffusion test to determine the susceptibility of these bacteria to Augmentin and other routinely used antimicrobial agents. Of these bacteria, 354 (37%) were isolated from urine, 134 (14%) from the respiratory tract, 77 (8%) from the genitalia, 57 (6%) from blood, and the rest from body fluids (71), wounds (130), tissues (28), and abscesses (106). The results of susceptibility testing against facultative gram-negative bacteria are shown in Table 1. Of the 538 members the Enterobacteriaceae family tested, 410 (76%) were susceptible to Augmentin, whereas only 272 (51%) were inhibited by ampicillin.Table 1. Susceptibility pattern of Enterobacteriaceae to Augmentin and other antibiotics.Table 1. Susceptibility pattern of Enterobacteriaceae to Augmentin and other antibiotics.Although the susceptibility pattern of organismslikeCitrobacter, Morganella, Salmonella, and Shigella is reported in Table 1, the numbers of each of these isolates are too low for statistic significance. The same is true of organisms numbering less than 10 in Tables 2 and 3.Table 2. In vitro activity of antimicrobial agents against Pseudomonas and Acinetobacter.Table 2. In vitro activity of antimicrobial agents against Pseudomonas and Acinetobacter.Table 3. Antimicrobial activity of Augmentin and other antibiotics against gram-positive cocci.Table 3. Antimicrobial activity of Augmentin and other antibiotics against gram-positive cocci.Of the pseudomonads tested, all strains of P. aeruginosa and P. fluorescens were resistant to Augmentin. However, two (28%) isolates of P. maltophilia and four strains of P. putrefaciens (100%) were inhibited by Augmentin. Ticarcillin, piperacillin, ceftazidime, and all the aminoglycosides were more effective against the Pseudomonas species used (Table 2).Of the 174 strains of S. aureus tested, only five (3%) were susceptible to ampicillin, but 162 (93%) were susceptible to Augmentin (Table 3). Twelve of these isolates were resistant to oxacillin, and all these were the only strains that were also resistant to Augmentin. All the isolates of micrococci and enterococci were inhibited by this antibiotic. Of the other nine antibiotics tested inour laboratory against gram-positive cocci, only vancomycin was found to be superior to Augmentin.DISCUSSIONA wide variety of antibiotics are used to combat infectious diseases in hospitals as well as in the community. Although many of these drugs are effective against microorganisms, many have serious side effects. An ideal antibiotic is the one which is active against the infecting agent without any ill effects on the patient. The only groups of drugs that come close to the definition of ideal antibiotics are probably penicillins and cephalosporins in nonallergic hosts. Thus, penicillin is usually the drug of choice to treat infections caused by susceptible bacteria in nonallergic patients. However, many of these bacteria develop resistance to penicillin by producing beta-lactamase and thus making these drugs unsuitablefor use. Combining clavulanic acid with amoxicillin in Augmentin overcomes this problem. Clavulanic acid by itself has weak broad-spectrum antibiotic activity that is too limited to be therapeutically useful. However, it irreversibly inactivates many plasmid-mediated beta-lac-tamases.5 The cephalosporinase types of enzymes found in P. aeruginosa, Enterobacter, and Serratia organisms and the chromosomally mediated penicillinases of E. coli are usually not inhibited by clavulanic acid.17 We found that none of the former three species and only 18 of the 68 (26%) ampicillin-resistant E. coli were inhibited by Augmentin.Previous studies have shown that clavulanic acid not only irreversibly inactivates beta-lac-tamase but also exhibits synergism with amoxicillin against amoxicillin-resistant bacteria.7,8,18,19 The rate of amoxicillin resistance in Saudi Arabia is markedly higher than those reported in the United States and Europe.20,21 In this study we found that these same clinical strains of E. coli, Klebsiella pneumoniae, Proteus organisms, and staphylococci showed increased susceptibility to Augmentin as compared to ampicillin. Since these bacteria constitute a great majority of organisms that are implicated in clinical disease, Augmentin appears to be a valuable drug in their treatment.ARTICLE REFERENCES:1. Bell SM, Plowman D. "Mechanisms of ampicillin resistance in Haemophilus influenzae from respiratory tract" . Lancet. 1980; 1 (8163): 279–80. Google Scholar2. Rammelkamp CH, Moxon T. "Resistance of Staphylococcus aureus to the action of penicillin" . Proc Soc Biol. 1942; 51: 386. Google Scholar3. Richmond MH. "Beta-lactamases" . Int J Clin Pharmacol Biopharm. 1979; 17 (3): 135–6. Google Scholar4. Rogers HJ, Forsberg CW. "Role of autolysins in the killing of bacteria by some bactericidal antibiotics" . J Bac-teriol. 1971; 108: 1235–43. Google Scholar5. Reading C, Cole M. "Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus" . Antimicrob Agent Chemother. 1977; 11 (5): 852–7. Google Scholar6. Goldstein FW, Kitzis MP, Malhurst C, et al. 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Qadri SM, Ostrawski S, Johnson S, Flournoy DJ. "Differences in antimicrobial susceptibilities of clinical isolates in Saudi Arabia and the United States" . J Natl Med Assoc. 1987; 79 (4): 433–7. Google Scholar21. Qadri SM, Rizvi WH, Rahman SA, Flournoy DJ. Antimicrobial resistance of Escherichia, Klebsiella and Pseudomonas in Saudi Arabia and U. S. A.J Natl Med Assoc (in press). Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 9, Issue 5September 1989 Metrics History Accepted8 January 1989Published online1 September 1989 InformationCopyright © 1989, Annals of Saudi MedicinePDF download