Effect of clavulanic acid and beta-lactamase on phagocytosis of Staphylococcus aureus.
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Three paraplegic patients with urinary tract infections caused by a beta-lactamase-producing Klebsiella pneumoniae were treated with a combination of amoxycillin and clavulanic acid (A-CA) (Augmentin; Beecham), after initial and unsuccessful therapy with amoxycillin alone. The administration of A-CA resulted in a rapid decrease in the urinary bacterial cell count, coupled with a dramatic increase in urinary amoxycillin concentrations.
In a large multinational study, the clinical and bacteriological efficacy of intravenous cefuroxime 750 mg t.i.d. followed by oral cefuroxime axetil 500 mg b.i.d. was compared to that of amoxicillin plus clavulanic acid (CA) administered as 1.2 g intravenously t.i.d. followed by 625 mg orally t.i.d. in the treatment of lower respiratory tract infections in hospitalised patients. A total of 512 patients were entered (256 in each treatment group). All were suffering from pneumonia or acute exacerbations of chronic bronchitis or bronchiectasis and required initial parenteral antibiotic therapy. Parenteral therapy lasted 48 to 72 h and was followed by five days of oral therapy. The clinical responses in the two treatment groups were very similar: 223 of 256 (87.1%) patients were cured or improved with cefuroxime/cefuroxime axetil compared to 220 of 256 (85.9%) with amoxicillin/CA. Positive pre-treatment sputum samples were obtained from 44% of the patients. Clearance rates obtained were again similar: 72.8% with cefuroxime/cefuroxime axetil and 70% with amoxicillin/CA. Ten percent of the isolates were beta-lactamase producers, similar numbers of which were cleared in both groups. Both regimens were generally well tolerated, with only 5% of patients treated with the cefuroxime regimen and 4.3% of patients treated with amoxicillin/CA experiencing drug-related adverse events. Cefuroxime/cefuroxime axetil "follow-on" therapy produces clinical and bacteriological efficacy equivalent to that of amoxicillin/CA, with the advantage of twice daily oral administration.
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Burkholderia pseudomallei, the causative agent of melioidosis, is inherently resistant to a variety of antibiotics including aminoglycosides, macrolides, polymyxins, and beta-lactam antibiotics. Despite resistance to many beta-lactams, ceftazidime and beta-lactamase inhibitor-beta-lactam combinations are commonly used for treatment of melioidosis. Here, we examine the enzyme kinetics of beta-lactamase isolated from mutants resistant to ceftazidime and clavulanic acid inhibition and describe specific mutations within conserved motifs of the beta-lactamase enzyme which account for these resistance patterns. Sequence analysis of regions flanking the B. pseudomallei penA gene revealed a putative regulator gene located downstream of penA. We have cloned and sequenced the penA gene from B. mallei and found it to be identical to penA from B. pseudomallei.
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Increase of acute liver injury in patients taking amoxicillin-clavulanic acid (co-amoxiclav) as compared to those taking amoxicillin has been suggested. To further investigate the potential hepatotoxicity of the two drugs a historical cohort study was conducted in the Italian region of Friuli-Venezia Giulia. One hundred and eighteen potential cases of acute liver injury were identified through the regional hospital information system and medical records were reviewed for all of them. Overall, 12 cases of acute liver injury were identified: 3 cases occurred in the amoxicillin exposure category, 2 among co-amoxiclav group, and 7 in the non-use category. The adjusted estimate of the rate ratio was 5.7 (CI 95% 1.5-22.1) among users of amoxicillin alone and 6.2 (CI 95% 1.3-29.7) among users of co-amoxiclav.
We undertook a prospective double-blind controlled study to compare the efficacy of a drug that usually has no antistaphylococcal activity (amoxicillin trihydrate) with the efficacy of the same drug with an addition of a beta-lactamase inhibitor (amoxicillin plus clavulanic acid [Augmentin]) in the treatment of nonbullous impetigo. Fifty-one culture-positive patients, aged 6 months to 9 years, were included, 26 in the amoxicillin group and 25 in the Augmentin group. The study groups were clinically and bacteriologically comparable at the start of the study. Staphylococcus aureus was isolated from all patients and beta-hemolytic streptococcus from 14 (29%). All staphylococci were sensitive to Augmentin but resistant to amoxicillin. Forty-nine patients completed the study. The clinical response was significantly better among the Augmentin recipients (marked improvement in 71% and 95% of patients after 2 and 5 days, respectively; no new lesions during the treatment course) than among the amoxicillin recipients (marked improvement in 44% and 68% of patients after 2 and 5 days, respectively; new lesions appeared in 20% of patients). Recurrence within 3 weeks occurred in 12 (26%) of 49 patients, and no difference was observed between the two groups. We conclude that S aureus is common in nonbullous impetigo, and that at least in some cases it plays an important role in the course of the disease that can be altered by specific therapy.
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