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Biomedical subjects

H C Standiford

Publications and source records attributed to H C Standiford.

9 recordsLinked to original sources

Gentamicin and ticarcillin serum levels.

Ticarcillin disodium and gentamicin sulfate serum levels were measured one and five hours after intravenous administration. Patients receiving ticarcillin plus gentamicin had a significantly lower mean gentamicin level one and five hours after antibiotic administration than patients receiving cephalothin sodium plus gentamicin. The serum ticarcillin levels were significantly lower five hours after administration in patients receiving ticarcillin plus gentamicin than in those receiving ticarcillin plus cephalothin. Low antibiotic serum levels in patients with serious infections treated with these antibiotic combinations are of potential clinical significance; therefore, to ensure an optimal antimicrobial therapy, it is advisable to determine the drug serum concentrations (especially aminoglycoside) even in patients with normal renal function when treating with combinations of antimicrobials.

Bacterial Infections

Randomized trial of empiric antibiotic therapy with ticarcillin in combination with gentamicin, amikacin or netilmicin in febrile patients with granulocytopenia and cancer.

A randomized trial of ticarcillin plus gentamicin (group 1), ticarcillin plus amikacin (group 2) and ticarcillin plus netilmicin (group 3) as empiric antibiotic therapy in patients with granulocytopenia and cancer was carried out at the Baltimore Cancer Research Center. The response rate for all infections was 97 per cent in group 1, 91 per cent in group 2 and 95 per cent in group 3. Patients with bacteremias showed improvement in 93 per cent (group 1), 78 per cent (group 2) and 82 per cent (group 3) of cases. All failures were among patients with gram-negative bacteremias. Both antibiotic susceptibility of the bacteremic organism and granulocyte recovery correlated with patient improvement. Nephrotoxicity and ototoxicity were rare and were not significantly different in three groups of patients. Therefore, ticarcillin plus gentamicin, ticarcillin plus amikacin and ticarcillin plus netilmicin appear to be equally efficacious and minimally toxic in this patient population. Excellent over-all results can be expected with these combinations provided the etiologic agent is susceptible.

Adolescent

Comparison of serum bactericidal activity among three antimicrobial combinations.

Three antimicrobial combinations, ticarcillin plus cephalothin (T+C), ticarcillin plus gentamicin (T+G), and cephalothin plus gentamicin (C+G), were administered to 105 febrile granulocytopenic cancer patients at the Baltimore Cancer Research Center as part of a multi-institutional prospective randomized antibiotic trial. The sera from 32 of these patients (T+C-10 patients, T+G-10 patients, and C+G-12 patients) obtained 1 h post-antibiotic administration were examined for bactericidal activity against 11 strains each of the most common pathogens infecting the granulocytopenic host: Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. Each of the three antibiotic regimens produced a high degree of bactericidal activity in these sera against S. aureus and E. coli. P. aeruginosa was equally, although poorly, killed by sera containing ticarcillin (T+G, T+C), whereas C+G produced no measurable serocidal activity (P < 0.05). Sera with C+G killed K. pneumoniae more effectively than T+G; T+C produced the least killing effect of the three regimens against this organism (P < 0.05). The bactericidal activity of the serum from these 32 patients supplements the overall clinical results of the multi-institutional antibiotic trial and suggests that T+G is a useful initial regimen for empiric therapy of febrile episodes in granulocytopenic cancer patients.

Anti-Bacterial Agents

Anaerobic bacteriuria in a male urologic outpatient population.

We screened 517 urine samples from male outpatients, many of whom had underlying urinary tract pathology, for anaerobic and aerobic bacteriuria. Of the 153 specimens containing greater than 10(5) bacteria per ml. 20% yielded anaerobes only and an additional 6% revealed mixed anaerobic and aerobic growth. Pyuria was found more frequently in samples containing anaerobic bacteriuria than in those containing no growth but not as frequently as when aerobic bacteria were present. The high counts of anaerobic bacteria in first-voided specimens compared to midstream and post-prostatic massage aliquots suggested a urethral source for most bacteria. However, suprapubic aspiration of bladder urine demonstrated the organism in 2 of 10 patients with high numbers of anaerobes and pyuria in voided samples.

Aerobiosis

Pirbenicillin: comparison with carbenicillin and BL-P1654, alone and with gentamicin, against Pseudomonas aeruginosa.

Minimum inhibitory concentrations (MIC) of pirbenicillin against 135 clinical isolates of Pseudomonas aeruginosa were one-fourth of those required for carbenicillin but two times higher than those for BL-P1654. Increasing the inoculum size produced an adverse effect on the bactericidal activity for all three antibiotics. This was more apparent for pirbenicillin than for carbenicillin, but less than the effect on BL-P1654. When concentrations of antibiotics likely to be achieved clinically were used, gentamicin increased the inhibitory and bactericidal effects of all three semisynthetic penicillins for the majority of isolates. Strains highly resistant to the aminoglycoside antibiotic, however, were inhibited no more by the penicillin-gentamicin combinations than by the most effective of the antibiotics alone.

Carbenicillin

Amikacin and cephalothin: empiric regimen for granulocytopenic cancer patients.

Amikacin (15 mg/kg per day) was used in combination with cephalothin (7 g/m(2) per day) as an empiric regimen for de novo febrile (>101 degrees F [38.3 degrees C]) episodes in 93 granulocytopenic (<1,000/mm(3)) cancer patients. Both drugs were given intravenously in four equal doses every 6 h. The response rate for all documented infections was 83%, including 11 of 17 (65%) bacteremias. Escherichia coli (14 cases) was the most common pathogen, whereas Pseudomonas aeruginosa (2 cases) caused fewer infections. Mean amikacin serum levels were 8.7 mug/ml at 1 h and 2.2 mug/ml at 5 h. Failure of bone marrow recovery in association with a bacteremia was a bad prognostic sign (only two of eight improving). Ototoxicity occurred in two (2%) patients, whereas presumed antibiotic-induced nephrotoxicity developed in six (7%) patients. Surveillance cultures (nose, gums axilla, and rectum) of all hospitalized patients revealed no significant change in the incidence of amikacin resistance. The combination of amikacin and cephalothin in this dose and schedule was safe and efficacious in these granulocytopenic patients.

Adult

Ticarcillin in combination with cephalothin or gentamicin as empiric antibiotic therapy in granulocytopenic cancer patients.

Ticarcillin was used in combination with either cephalothin or gentamicin as initial empiric antibiotic therapy for 127 patient trials of suspected infection in granulocytopenic cancer patients. Bacteremia was present in 20%, nonbacteremic microbiologically documented infections in 21%, clinically documented infections in 23%, and possible infections in 5%; infection was doubtful in 31%. Although Staphylococcus aureus was the most common single organism isolated (23%), gram-negative bacilli accounted for 54% of all pathogens. Both antibiotic regimens were highly efficacious, with complete resolution in 46% of bacteremias, 88% of nonbacteremic microbiologically documented infections, and 95% of clinically documented infections. Among bacteremias, 8 of 9 caused by S. aureus but only 4 of 15 (27%) caused by gram-negative bacilli were completely resolved with these antibiotic combinations. Reasons for nonresponse in bacteremias were persistent granulocytopenia, mixed infection and, in two patients, antibiotic-resistant organisms. Toxicities other than hypokalemia were minimal. Although the rate of further infections was high overall (18/127), only one occurred among the 39 patients with <4 days of antibiotic therapy. Ticarcillin in combination with either cephalothin or gentamicin was effective as initial empiric therapy of suspected infection in granulocytopenic cancer patients.

Adult

BL-P1654, ticarcillin, and carbenicillin: in vitro comparison alone and in combination with gentamicin against Pseudomonas aeruginosa.

Minimum inhibitory concentrations of carbenicillin, ticarcillin, and BL-P1654 were determined for 89 clinical isolates of Pseudomonas aeruginosa. Ticarcillin was generally twice as active and BL-P1654 eight to 16 times as active as carbenicillin. Usually carbenicillin and ticarcillin killed at the same concentration or twice the concentration needed to inhibit, whereas 400 mug of BL-P1654 per ml was not bactericidal for the majority of isolates tested. The inhibitory effect of all three drugs varied markedly with the size of bacterial inoculum. When therapeutically achievable concentrations were used, adding gentamicin enhanced the inhibitory and bactericidal activity of all three penicillin derivatives for the majority of isolates. However, inhibition of isolates highly resistant to gentamicin was not improved by combining the semisynthetic penicillins with gentamicin.

Carbenicillin

Parenteral prophylaxis against enterococcal endocarditis.

Three commonly used antibiotic regimens for the prevention of enterococcal endocarditis were administered parenterally to six healthy men in a crossover manner. The regimens included 1 gm of streptomycin intramuscularly (IM) in combination with (1) procaine penicillin 600,000 units plus aqueous penicillin G 200,000 units IM; or (2) ampicillin 25 mg/kg intravenously (IV); or (3) ampicillin 1 gm IM. The combinations containing ampicillin IM or IV with streptomycin produced bactericidal activity at dilutions of 1:2 or greater for the majority of the strains, whereas the penicillin-streptomycin regimen did not. All regimens were poorly bactericidal against three strains of enterococci which were highly resistant to streptomycin. These data suggest that ampicillin plus streptomycin is the preferred regimen for prophylaxis.

Ampicillin