Cefazolin in the treatment of gonorrhea.
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Biomedical subjects
Publications and source records attributed to M Turck.
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Amoxicillin (alpha-amino-p-hydroxybenzyl penicillin, BRL 2333) is a new semisynthetic penicillin which is structurally similar to ampicillin, but which is better absorbed and yields higher concentrations in serum and urine. The in vitro susceptibility of 145 strains of Enterobacteriaceae and 30 isolates of Pseudomonas aeruginosa was determined against various concentrations of amoxicillin and ampicillin in agar. In addition, inhibitory zones around discs containing 10 mug of amoxicillin were measured and compared with results of agar dilution studies. The drug also was evaluated in the treatment of 38 patients with bacteriuria, who received doses of either 750 mg or 1 g/day for 10 days. In vitro, amoxicillin was comparable in activity to ampicillin; most isolates of Escherichia coli and Proteus mirabilis were inhibited by 10 mug or less/ml, whereas the majority of strains of Enterobacter, Klebsiella, indole-positive Proteus species, and Pseudomonas grew in concentrations greater than 50 mug/ml. Clinically, amoxicillin was effective in eradicating bacteriuria due to susceptible organisms and was very well tolerated. For practical purposes, however, amoxicillin performed no better than a host of other drugs presently available for the treatment of acute, uncomplicated bacteriuria.
The in vitro susceptibility of 163 strains of Enterobacteriaceae and 23 isolates of Pseudomonas aeruginosa to various concentrations of gentamicin, kanamycin, spectinomycin, tobramycin, and BB-K8, a new semisynthetic aminoglycoside antibiotic, was determined. Studies were performed in Mueller-Hinton agar and broth, and two different sizes of bacterial inocula were used. On a weight basis, gentamicin and tobramycin demonstrated comparable activity in vitro and were the most active of the five drugs tested against Escherichia coli, Klebsiella, Enterobacter, and Proteus species. All of these organisms were inhibited by gentamicin or tobramycin at concentrations of 5.0 mug or less/ml in agar with both inocula of bacterial cells. In addition, tobramycin was the most active drug against isolates of P. aeruginosa and gentamicin was the most active against Salmonella and Shigella species. Although kanamycin and BB-K8 demonstrated a high degree of activity against most Enterobacteriaceae, they were not the most active agents tested for any genus. Spectinomycin was the least active compound, and many isolates grew in concentrations higher than those readily attainable in serum.
Cefazolin sodium was tested in vitro against 308 isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aureus, and enterococcus. Broth and agar dilution and disk diffusion techniques were used with at least two sizes of inocula of organisms. Cefazolin was also studied in the treatment of 85 hospitalized patients with a variety of serious infections. In concentations of 5 mug or less/ml, cefazolin inhibited and killed more than 90% of isolates of Enterobacteriaceae with the exception of indole-positive Proteus and Enterobacter species. No isolate of P. aeruginosa and only a few of Enterobacter and enterococci were killed by 25 mug of cefazolin/ml, a concentration readily attainable in serum with a 500-mg dose given intramuscularly. Penicillin-susceptible as well as penicillin-resistant isolates of S. aureus were killed by 1 mug or less of cefazolin per ml; however, 25 mug/ml was required to kill 100% of the strains when the inoculum size was increased 100-fold. Cefazolin treatment appeared effective in 82 of 85 patients, including four with endocarditis. Pain was minimal after intramuscular injection, and thrombophlebitis was not observed in those treated intravenously. No patient developed a positive Coombs test, and no evidence of renal toxicity was apparent in clinical studies.
Analysis of 111 rough strains of Escherichia coli from known urinary infections revealed for the first time that galactose-deficient rough mutants are not exclusively a laboratory phenomenon. They exist naturally with or without an epimerase deficiency and represent natural examples of the key role of galactose in the attachment of "O" side chains to the core of bacterial lipopolysaccharides.
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Cephapirin sodium, a parenterally administered derivative of cephalosporanic acid, was tested in vitro against 150 stock cultures of Enterobacteriaceae and 30 stock cultures each of Pseudomonas aeruginosa and Staphylococcus aureus. Both broth- and agar-dilution techniques were employed with two sizes of inocula of organisms. At a concentration of 7.5 mug or less/ml, cephapirin inhibited and killed 100% of strains of Escherichia coli and Proteus mirabilis and more than 80% of Klebsiella species when tested against an inoculum of 10(5) bacterial cells/ml. However, even at 100 mug/ml, only a few isolates of other Enterobacteriaceae and Pseudomonas were inhibited. A 100-fold increase in the inoculum resulted in decreased susceptibility of organisms. All penicillin-susceptible as well as penicillin-resistant S. aureus isolates were inhibited and killed by 5 mug or less of cephapirin/ml when tested with an inoculum of either 10(4) or 10(6) organisms/ml. The drug also was studied in various doses in the treatment of 77 patients with diverse infections. Cephapirin was effective in the treatment of 27 of 32 patients with pulmonary infection, as well as in 6 of 7 patients with staphylococcal or streptococcal soft tissue infection. Of 25 patients with urinary-tract infections, 19 developed a negative culture during therapy. A single 4-g intramuscular dose of cephapirin was effective in only 2 of 11 patients with gonococcal urethritis or endocervicitis. Two patients with gonococcal urethritis treated with multiple injections were cured. The drug was well tolerated except for pain at the site of injection in 14 patients and phlebitis in 4 patients. No abnormalities in renal or hepatic function could be attributed to cephapirin. In addition, no abnormalities were found in the renal tubules of rabbits challenged with 500 mg of cephapirin/kg. If further studies document that cephapirin is well tolerated by the parenteral route, it may have advantages over cephalothin or cephaloridine.
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The differentiation of renal from bladder bacteriuria is difficult on clinical grounds alone. To evaluate the correlation between site of infection and urinary beta-glucuronidase activity, 46 patients with well documented recurrent bacteriuria were studied by bilateral ureteral catheterization. Urinary beta-glucuronidase activity was also determined in 46 control subjects. In general, asymptomatic patients with renal bacteriuria, either unilateral or bilateral, had levels of enzyme activity in their urine comparable to patients with infection confined to the bladder and to normals. Only 4 of 25 patients with renal bacteriuria had significant elevations of urinary beta-glucuronidase. After localization of infection, 9 of 10 patients treated with kanamycin, a potentially nephrotoxic drug, developed significant elevations of urinary beta-glucuronidase. The results of these studies indicate that determination of beta-glucuronidase activity in urine is not useful in predicting the site of infection in patients with bacteriuria but may find a role in screening for early nephrotoxicity.
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