[Evaluation of antimicrobial therapy by the measurement of blood bactericidal activity].
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Biomedical subjects
Publications and source records attributed to J Klastersky.
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The anti-pseudomonas activities of azlocillin and mezlocillin were compared with that of ticarcillin. We measured the minimal inhibitory and minimal bactericidal concentrations of the three drugs against 20 different strains of Pseudomonas aeruginosa and found significantly lower values for azlocillin than for the other two drugs. We then infused 5 g of each drug into 10 volunteers on three consecutive days and determined the serum levels of the three antibiotics at 1-h intervals from 1 to 6 h after injection. The levels of azlocillin were significantly higher than those of mezlocillin and ticarcillin (at 1 h: 236.55 mug/ml +/- 12.9 for azlocillin, 192.45 mug/ml +/- 28.8 for mezlocillin, and 131.5 mug/ml +/- 10.9 for ticarcillin). The inhibitory and bactericidal activities of the sera obtained 1 and 6 h after the injection against the same 20 strains of P. aeruginosa demonstrated a significantly greater anti-pseudomonas activity of azlocillin when compared with mezlocillin and ticarcillin; mezlocillin and ticarcillin had approximately the same activity. The mean values for bactericidal activity against the strains tested were 1/32 for azlocillin, 1/8 for mezlocillin, and 1/8 for ticarcillin. Azlocillin thus appears to be a promising anti-pseudomonas drug and should be tested in clinical trials.
Clindamycin and cefoxitin with or without gentamicin were administered to cancer patients having localized infections presumably caused by anaerobic pathogens. The rates of favorable response were 89% in patients receiving clindamycine alone and 78% in patients receiving cefoxitin alone. When the total experience is considered (clindamycin or cefoxitin with and without gentamicin), 20 of 24 patients (83%) responded to clindamycin and 18 of 22 (82%) responded to cefoxitin. Both therapies were well tolerated. Clindamycin was found to be more effective than cefoxitin in eradicating the offending anaerobic pathogens from the site of infection. Aerobic pathogens were frequently isolated along with anaerobes from the infectious sites in this series; their susceptibility or resistance to clindamycin or cefoxitin did not influence the therapeutic response.
Sisomicin or a placebo was administered endotracheally to two groups of 18 and 20 unconscious patients, respectively, who had tracheostomies or endotracheal tubes in place and developed a severe gram-negative broncho-pneumonia. In addition, the patients received systemically a combination of sisomicin and carbenicillin. A favorable clinical response was obtained in 14 (77 percent) of the 18 patients who were treated with sisomicin and in nine (45 percent) of the 20 patients who received the placebo (P less than 0.05). Endotracheal therapy with sisomicin was well tolerated and resulted in high levels of sisomicin and in elevated bactericidal activity within the bronchial secretions. Endotracheally administered amino-glycosides might be an important adjunct to systemically administered antibiotics in the management of severe gram-negative bronchopneumonia.
A series of 24 patients with severe neutropenia, most of whom had acute myeloblastic leukemia, were treated in an isolation unit with oral nonabsorbable antibiotics and were compared to 21 similar patients receiving oral antibiotics alone. The frequency of bacterial infections was lower in the patients receiving both isolation and oral antibiotics compared to the patients who received only oral antibiotics. The responses to chemotherapy in terms of remission rates were identical for the two groups.
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Rational antimicrobial therapy in neutropenic patients includes early empiric therapy with combinations of antibiotics active in vitro against the causal pathogen. The duration of therapy is to be adapted to the clinical response. In patients who do not respond to antimicrobial therapy, transfusion of granulocytes and empiric use of antifungal drugs should be considered.
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The bactericidal activity of clindamycin, chloramphenicol, and gentamicin alone and of gentamicin plus clindamycin and gentamicin plus chloramphenicol was studied on 8 strains of Escherichia coli and 10 strains of Bacteroides fragilis isolated from clinical material. Gentamicin did not interfere with the activity of clindamycin or chloramphenicol against B. fragilis. The activity of gentamicin against E. coli was not influenced by clindamycin, but chloramphenicol suppressed the rapid bactericidal activity of gentamicin in seven out of eight strains of E. coli examined.
A preliminary study was conducted with netilmicin, a new aminoglycoside antibiotic. Its effectiveness was evaluated in vitro against 546 strains of Enterobacteriaceae and Pseudomonas aeruginosa isolated from clinical material. Its effectiveness against gentamicin-susceptible strains was roughly similar to that of gentamicin and other newer aminoglycoside antibiotics. Cross-resistance to netilmicin was found in 9 of 44 gentamicin-resistant strains. A favorable clinical response was observed in 70% of the patients treated with a dose of netilmicin ranging from 4.5 to 7.5 mg/kg. However, the appearance of granular casts was seen in 7 of 10 patients receiving the higher dosage of netilmicin (7.5 mg/kg) and a rise in blood urea nitrogen or serum creatinine levels was observed in 5 of these patients.
Clindamycin, tinidazole (a parent compound to metronidazole), and doxycycline were compared in vitro against 376 anaerobic bacteria isolated from clinical specimens. Bacteriostatic tests indicated that clindamycin was the most active drug, on a weight basis, against these strains except for Clostridium species. The three drugs were compared as therapies for anaerobic wound infections in cancer patients. In a randomized double-blind study, no statistically significant differences between clindamycin and tinidazole could be documented. Doxycycline was less active presumably because of the lack of clinical response in three out of four patients infected with doxycycline-resistant strains. No major untoward effects were observed. The bactericidal dilution of the serum was predictive of the clinical outcome.
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In order to protect granulopenic patients against infections by pathogens from their own digestive tract, large amounts of lactobacilli were given to 5 patients whose intestinal flora had been suppressed by oral antibiotics. In all these cases, lactobacilli failed to prevent spontaneous recolonization of the gastrointestinal tract by enteric bacteria. Six attempts of colonization were made; in spite of the importance of the inoculum administered orally, large numbers of lactobacilli were recovered from stools in only two cases.
Single equimolar oral doses of bacampicillin and ampicillin were given to 9 healthy subjects on a crossover randomized basis. Data were interpreted in terms of a 3-compartment pharmacokinetic open model. Intestinal absorption of bacampicillin was found to be faster and more complete than that of ampicillin, yielding an increase in bioavailability of 30% to 40% as measured by the area under serum levels curve, the urinary excretion and absorption rate constants. After the administration of bacampicillin, much higher and sharper peaks were achieved in the serum and in the "tissue" water than after the administration of ampicillin. The maximum bactericidal dilution (MBD) of the serum samples taken 1 hr after the administration of the antibiotics against 10 strains of Diplococcus pneumoniae was higher following bacampicillin (p less than 0.01), as was the MBD of the 0 to 2 hr urine specimens against 10 strains of Escherichia coli. Further clinical trials are required to accurately assess the possible greater therapeutic effectiveness of bacampicillin than of ampicillin.