Search PubMed⌕ Search

Biomedical subjects

S C Aronoff

Publications and source records attributed to S C Aronoff.

At least 37 records · Page 2Linked to original sources
PubMed1988

The effect of exocrine pancreatic function on chloramphenicol pharmacokinetics in patients with cystic fibrosis.

The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis. Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-amino-benzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule. In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes. The relative amounts of active chloramphenicol available in systemic circulation was CAP-base greater than CAP-S greater than CAP-P. Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation. Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable. Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens. This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement. The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency.

Administration, Oral↗
PubMed1987

Pseudomonas aeruginosa as a primary pathogen in children with bacterial peritonitis.

This prospective study compared the efficacy of sulbactam/ampicillin and clindamycin/gentamicin in the treatment of children with bacterial peritonitis. Of the 29 children enrolled, 17 were evaluable; eight received sulbactam/ampicillin/gentamicin and nine clindamycin/gentamicin. Sixteen patients were previously healthy children with appendicitis. An average of 3.6 bacterial species were recovered from the peritoneal fluid of each patient. E coli and B fragilis were the most common aerobic and anaerobic isolates, recovered from 15 and ten patients, respectively. Pseudomonas aeruginosa was recovered from seven of 17 children; the three children with P aeruginosa infections randomized to the sulbactam/ampicillin group received gentamicin in addition to the investigational agents throughout the treatment course. Although the study groups were small, there was no difference in age, sex, number of pathogens per patient, duration of hospitalization, toxicity, or treatment failures between the two treatment groups or between children infected with P aeruginosa and controls. As a result of the high prevalence of P aeruginosa in the peritoneal exudate of otherwise healthy children with appendicitis, initial antimicrobial therapy in this patient population should include agents effective against this organism.

Adolescent↗
PubMed1987

Factors that influence the evolution of beta-lactam resistance in beta-lactamase-inducible strains of Enterobacter cloacae and Pseudomonas aeruginosa.

Induction ratios were determined for beta-lactamase-inducible strains of Enterobacter cloacae and Pseudomonas aeruginosa by using 10 beta-lactam agents. For E. cloacae, pre-incubation with ceftriaxone, cefoxitin, cefamandole, cefoperazone, or imipenem produced significantly larger amounts of beta-lactamase than did pre-incubation with moxalactam, clavulanate, ceftazidime, or aztreonam. For P. aeruginosa, imipenem was the best inducer, whereas ceftriaxone, piperacillin, cefoperazone, cefamandole, clavulanate, and aztreonam were poor beta-lactamase inducers. The rate of emergence of resistance by E. cloacae p99 and P. aeruginosa ATCC 27853 did not correlate with the induction ratio of the selecting agent; however, a strong correlation was noted between the mutation rate and the ratio of the MIC to the concentration of selecting antibiotic used. Emergence of resistance is related to the MIC of the antibiotic and the concentration of antibiotic used to select for resistance and is independent of the efficacy of the beta-lactam inducer. Resistant mutants arise through both beta-lactamase-dependent and -independent mechanisms.

Anti-Bacterial Agents↗
PubMed1987

Sultamicillin in the treatment of superficial skin and soft tissue infections in children.

Fifty-two children with superficial skin and soft tissue infections were randomized to receive sultamicillin or cloxacillin for 7 days. Twenty-one children in each group finished the study. A total of 16 of 21 in the sultamicillin group and 13 of 21 in the cloxacillin group were cured. One child in the sultamicillin group and two in the cloxacillin group failed therapy. Four children who received sultamicillin and six who received cloxacillin had recurrences of lesions. Differences were not statistically significant.

Abscess↗
PubMed1986

Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate and sulbactam combined with extended-spectrum penicillins against ticarcillin-resistant Enterobacteriaceae and pseudomonads.

The in-vitro synergistic activity of YTR 830, a new beta-lactamase inhibitor, combined with four extended-spectrum penicillins (ticarcillin, piperacillin, mezlocillin and apalcillin) against ticarcillin-resistant clinical isolates of Gram-negative enteric bacilli was compared with that of clavulanate and sulbactam. Synergy testing was performed with fixed concentrations of beta-lactamase inhibitors (8 mg/l) combined with doubling dilutions of beta-lactams in microdilution trays. Synergy was defined as a four-fold or greater decrease of beta-lactam MIC in the combination compared with the beta-lactam alone. For 79 ticarcillin-resistant Enterobacteriaceae, ticarcillin-YTR 830 and ticarcillin-clavulanate were synergistic against 90% of strains; for ticarcillin-sulbactam, 70% showed synergy. The synergistic activity of all three inhibitors was similar against strains resistant only to ticarcillin; for strains resistant to all four extended-spectrum penicillins, the activity of ticarcillin with YTR 830 and clavulanate was similar (synergy against 79% of strains) and superior to ticarcillin-sulbactam (synergy against 39% of strains). YTR 830 was more active than clavulanate against Serratia, Citrobacter, Proteus and Providencia spp. Piperacillin, mezlocillin and apalcillin susceptible strains, with MICs of 8-16 mg/l, showed synergy with inhibitors against 37-87% of strains. Amongst pseudomonads, no synergy was demonstrated against Pseudomonas aeruginosa; ticarcillin produced synergy with the inhibitors against Ps. maltophilia, while piperacillin-YTR 830 and apalcillin-YTR 830 were synergistic against Ps. cepacia. YTR 830 appears to have comparable in-vitro activity to that of clavulanate, and further development of this compound is warranted.

Ampicillin↗
PubMed1986

Synergy of amoxycillin combined with clavulanate and YTR 830 in experimental infections in mice.

YTR 830, a new beta-lactamase inhibitor, is synergistic with amoxycillin in vitro against a number of beta-lactamase-producing organisms. The combination of amoxycillin-YTR 830 was compared to amoxycillin-clavulanate in the treatment of experimental Staphylococcus aureus, Citrobacter freundii and Proteus mirabilis infections in mice. Both combinations were synergistic with amoxycillin against all three test organisms. The amoxycillin-clavulanate combination was superior against S. aureus and C. freundii while amoxycillin-YTR 830 was more effective against P. mirabilis. The difference in efficacy between the two drug combinations appears to relate to the degree of protection afforded the animals by the beta-lactamase inhibitor alone. YTR 830 is a promising new agent and should undergo further investigation.

Amoxicillin↗
PubMed1986

Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam combined with ampicillin and broad-spectrum penicillins against defined beta-lactamase-producing aerobic gram-negative bacilli.

The in vitro synergistic activities of the beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam, combined with ampicillin, ticarcillin, mezlocillin, azlocillin, piperacillin, and apalcillin, were determined against 34 strains of members of the Enterobacteriaceae family, Pseudomonas aeruginosa, Aeromonas hydrophila, and Haemophilus influenzae with characterized plasmid or chromosomal beta-lactamases or both. Strains were tested against fixed concentrations of beta-lactamase inhibitors (8 micrograms/ml) combined with doubling dilutions of beta-lactams. Synergy was defined as a fourfold or greater decrease in the MIC of the beta-lactam. Against Enterobacteriaceae producing Richmond and Sykes class III and V plasmid-mediated beta-lactamases, synergy was obtained against most strains with YTR 830- and clavulanate-beta-lactam combinations, with sulbactam being less effective. Against Enterobacteriaceae producing class I chromosomal beta-lactamases, combinations containing YTR 830 or sulbactam were more synergistic than combinations containing clavulanate. Against strains producing class V PSE enzymes, all three inhibitors were synergistic with piperacillin and apalcillin against strains producing PSE-1, -3, and -4 enzymes, while the PSE-2-producing strain was resistant to all inhibitors. YTR 830-beta-lactam combinations were also synergistic against strains producing the novel beta-lactamases OHIO-1, TLE-1, AER-1, and ROB-1. Overall, YTR 830 with piperacillin or apalcillin was the most effective combination.

Ampicillin↗
PubMed1986

Decreased baseline beta-lactamase production and inducibility associated with increased piperacillin susceptibility of Pseudomonas cepacia isolated from children with cystic fibrosis.

The incidence of pulmonary infections in children with cystic fibrosis caused by Pseudomonas cepacia, an organism which may possess an inducible beta-lactamase, has increased since 1978. Seven of 13 sputum isolates of P. cepacia from children with cystic fibrosis were classified as inducible by quantitative enzyme production following preincubation with 100, 200, or 400 micrograms/ml of cefoxitin. The recovery of inducible strains tended to be associated with recent ceftazidime therapy. Susceptibility to aztreonam, ceftazidime, and piperacillin alone or combined with the beta-lactamase inhibitors. YTR 830 or sulbactam, and isoelectric focusing for beta-lactamase were performed. Inducible isolates produced significantly more beta-lactamase than noninducible strains with or without the addition of cefoxitin. Noninducible isolates were more susceptible than inducible isolates to 8 micrograms/ml of piperacillin, a difference that was eliminated with the addition of either beta-lactamase inhibitor. Twelve of 13 strains produced a beta-lactamase band in the pH range of 7.9-8.1; no differences in satellite patterns were noted between the two groups of organisms. Increased production of beta-lactamase in the absence of an inducer may account for piperacillin resistance in P. cepacia in children with cystic fibrosis.

Analysis of Variance↗
PubMed1985

Comparison of cefpiramide (HR-810) and four anti-pseudomonal beta-lactam agents against pseudomonas isolates from children with cystic fibrosis.

Cefpiramide (HR-810), ceftazidime, piperacillin, ticarcillin, and aztreonam were tested against tobramycin-sensitive and -resistant strains of Pseudomonas aeruginosa and tobramycin/amikacin-resistant isolates of Ps. cepacia recovered from the sputum of patients with cystic fibrosis. Against Ps. aeruginosa, none of the drugs inhibited 90% of the test strains at levels of less than 128 mg/l. Median minimal, inhibitory concentrations (MIC50) for all of the beta-lactam agents were lower for tobramycin-sensitive versus tobramycin-resistant isolates of Ps. aeruginosa. Ceftazidime was the most effective agent against Ps. cepacia. Aminoglycoside-resistance appears to be associated with significant beta-lactam resistance in Ps. aeruginosa isolated from the sputum of patients with cystic fibrosis.

Anti-Bacterial Agents↗
PubMed1985

In-vitro activity of ciprofloxacin and other antibacterial agents against Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients.

The in-vitro activities of ciprofloxacin, a new oxyquinoline derivative, norfloxacin and six anti-pseudomal beta-lactam antibiotics were tested against pulmonary isolates of smooth and mucoid colony forms of Pseudomonas aeruginosa, and Ps. cepacia from children with cystic fibrosis. Ciprofloxacin was the most effective of the agents tested against either species. Minimal inhibitory concentrations of ciprofloxacin were 0.5, and 16 mg/l, for 90% of the Ps. aeruginosa and Ps. cepacia strains tested, respectively. No effect of inoculum size or discordance between inhibitory or bactericidal concentrations was observed. Ciprofloxacin is a potentially useful agent for the treatment of acute pseudomonal pulmonary exacerbations in children with cystic fibrosis.

Anti-Bacterial Agents↗
PubMed1985

Hemophilus influenzae type f meningitis in an adolescent.

A 17-year-old male with Hemophilus influenzae type f meningitis is reported. Recent studies which suggest that the incidence of H. influenzae meningitis in older individuals is increasing are reviewed. Therefore, we recommend that antimicrobial therapy directed against H. influenzae be included in the initial management of older children, adolescents, and adults with acute bacterial meningitis.

Adolescent↗
PubMed1985

Pharmacokinetics and cerebrospinal fluid penetration of ceftazidime in children with meningitis.

The single dose pharmacokinetics and cerebrospinal fluid (CSF) penetration of ceftazidime were determined in 10 children with bacterial meningitis. Serum ceftazidime pharmacokinetics showed a distinct age dependence in which the clearance in children less than 1 month of age was markedly reduced. Ceftazidime concentrations in CSF, which ranged from 1.4-8.5 micrograms/ml, exceeded the minimum bactericidal concentrations for infecting pathogens throughout the 8-hour sampling period. These concentrations were found to be independent of CSF cell count, protein concentration or the day of therapy on which the study was performed. The ratio of CSF to serum ceftazidime concentration increased with time, suggesting that ceftazidime was cleared more slowly from CSF than from peripheral blood. Our data support the initiation of a study comparing the efficacy of ceftazidime to conventional therapy in children with bacterial meningitis.

Age Factors↗
PubMed1985

Clinical presentation and management of Pseudomonas osteomyelitis.

To determine the incidence and clinical characteristics of Pseudomonas aeruginosa osteomyelitis in children, the records of 144 hospitalized patients under 19 years of age were reviewed; 104 fulfilled the study criteria for the diagnosis of acute or chronic osteomyelitis. Pseudomonas aeruginosa was recovered from 10.6 percent of the children and was the second most common pathogen isolated. In comparison to children with staphylococcal infections, patients with pseudomonal osteomyelitis were significantly older, gave an antecedent history of penetrating trauma, and lacked clinical and laboratory evidence of systemic illness. The data collected in this study suggest that osteomyelitis due to Pseudomonas aeruginosa is a distinct entity with clinical features differing from those of Staphylococcus aureus. Management should be directed at adequate surgical debridement followed by 10 to 21 days of antimicrobial therapy.

Adolescent↗
PubMed1984

Comparison of the efficacy and safety of ceftriaxone to ampicillin/chloramphenicol in the treatment of childhood meningitis.

Ceftriaxone is a new cephalosporin with a broad spectrum of antibacterial activity and unique serum and CSF pharmacokinetics. The drug was compared in a randomized fashion with ampicillin and chloramphenicol in the treatment of 19 children with Haemophilus influenzae type b meningitis. Ceftriaxone was also administered non-randomly to six other patients including three children with Gram-negative meningitis. Among the children with H. influenzae meningitis, no deaths were noted and the outcomes of the study and the control groups were similar. Ninety per cent of the isolates of H. influenzae were inhibited by 0.0625, 1 and 1 mg/l of ceftriaxone, ampicillin and chloramphenicol respectively. One child with pneumococcal meningitis and two children with meningococcal meningitis recovered rapidly and without incident during ceftriaxone therapy. Three children with Gram-negative meningitis caused by multiply-drug resistant organisms were bacteriologically cured within five days of the onset of therapy. Persistent pleocytosis and neurological disabilities were noted in two at the conclusion of therapy. Ceftriaxone, as a single agent, was comparable in efficacy with traditional antimicrobial therapy usually employed in childhood meningitis.

Adolescent↗
PubMed1984

A double-blinded comparative study of sultamicillin and potassium penicillin V in the treatment of childhood streptococcal pharyngitis.

Fifty-two children with positive pharyngeal cultures for group A streptococci were randomized to receive phenoxymethyl penicillin or sultamicillin, an ester of ampicillin and sulbactam. By serological and bacteriological criteria, sultamicillin was effective in 100% of the 20 evaluable cases of infection and carriage while penicillin was effective in six out of eight (75%) and three out of eight (93%) respectively. Of the eight children with infections treated with sultamicillin, three (37.5%) became recolonized with the organism compared to none of the children in the penicillin group. These differences were not statistically significant.

Adolescent↗