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S C Schimpff

Publications and source records attributed to S C Schimpff.

154 records · Page 9Linked to original sources
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Moxalactam and piperacillin: a study of in vitro characteristics and pharmacokinetics in cancer patients.

We evaluated the microbiologic characteristics including MIC determinations, synergy plate assays and serum bactericidal activity for two regimens being examined as empiric antibiotic therapy for febrile granulocytopenic cancer patients. The regimens consisted of moxalactam (4 g.i.v. q12h) plus piperacillin (75 mg/kg i.v. q6h) or moxalactam (as above) plus amikacin (levels adjusted to one hour post-infusion levels of 25 mg/l and troughs of 6-8 mg/l). Detailed pharmacokinetics were ascertained for the beta lactams. All drugs were active against a panel of 11 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. The pharmacokinetic profile showed serum levels sufficient to provide good antimicrobial activity throughout the dosing interval. Both regimens displayed synergistic or partially synergistic activity in the main for the test organisms; moxalactam plus piperacillin produced good results against S. aureus and P. aeruginosa. In the serum bactericidal assays, the moxalactam-piperacillin combination produced significantly higher mean titers at both peak and trough when compared to the moxalactam-amikacin regimen. This may be because moxalactam acts as a beta lactamase inhibitor for both staphylococcal beta lactamase, as well as the Sabath-Abraham Id type beta lactamase carried by P. aeruginosa (among others). Moxalactam-piperacillin deserves extensive evaluation as empiric therapy for the febrile neutropenic cancer patients.

Amikacin↗
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Comparative pharmacokinetics of moxalactam, cefoperazone, and cefotaxime in normal volunteers.

The pharmacokinetic parameters of moxalactam were compared with those of cefoperazone and cefotaxime in normal volunteers in a crossover manner. Following 30-min intravenous infusions of 2 g of each of the three antibiotics, serum levels at 1 hr were slightly lower for moxalactam (88 micrograms/ml) than for cefoperazone (112 micrograms/ml) but more than three times those obtained for cefotaxime (29 micrograms/ml). By 8 hr, levels of moxalactam (9.2 micrograms/ml) were slightly higher than those of cefoperazone (6.5 micrograms/ml), and levels of cefotaxime in serum were unmeasurable (less than 1 micrograms/ml). These values reflect differences in half lives of the three agents. Peak serum levels following intramuscular injection and serum levels during constant intravenous infusion were similar for moxalactam and cefoperazone because of counterbalancing differences in the apparent volume of distribution and rates of elimination of the two antibiotics. Serum levels of cefotaxime were much lower than those of the other two antibiotics primarily because of the rapid elimination of cefotaxime from the body. The kidney was the major route of excretion of moxalactam, whereas extrarenal mechanisms were more important for elimination of cefoperazone. These differences in pharmacokinetics may have significant implications for the clinical use of these new antibiotics.

Adolescent↗
PubMedDate not supplied

The acylampicillins: mezlocillin, piperacillin, and azlocillin.

The new acylampicillin derivatives azlocillin, mezlocillin, and piperacillin have an increased activity against many gram-negative bacilli, especially Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa, when compared with the carboxypenicillins carbenicillin and ticarcillin. The new penicillins show synergistic activity in combination with aminoglycosides but, when combined with other beta-lactams, may be synergistic (piperacillin and moxalactam; mezlocillin and cefoperazone), indifferent, or antagonistic (azlocillin, mezlocillin, or piperacillin and cefoxitin or cefamandole). The in vitro activity of these agents, either alone or in combination, appears to correlate with in vivo efficacy in animal models. The new penicillins are clinically effective for a very broad range of infections, including life-threatening nosocomial infections. Adverse effects with these, as with other semisynthetic penicillins, are minimal. Attention must be paid to the potential for infection by naturally resistant, gram-negative bacilli such as beta-lactamase-producing Escherichia coli and for the emergence of resistance during therapy. The granulocytopenic patient should receive these agents only in conjunction with another agent, such as an aminoglycoside; this combination will often result in a synergistic effect when tested in vitro. The carboxypenicillins and the newer penicillins have substantial similarities, and prospective, comparative studies have so far failed to demonstrate significant clinical superiority. However, the increased activity of the acylampicillins may be advantageous for the treatment of infections due to K. pneumoniae and P. aeruginosa.

Agranulocytosis↗
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Integration of selected pharmacologic and microbiologic properties of three new beta-lactam antibiotics: a hypothesis for rational comparison.

To enable the comparison of antibiotics in a standardized, meaningful manner, a system that integrates the pharmacologic and microbiologic properties of beta-lactam antibiotics has been developed. The system compares the duration of time that concentrations of both total and free drug exceed the 90% minimal inhibitory concentration ( MIC90 ) of various pathogens as well as the area under the concentration-time curve for both total and free drug, the latter measurement being an indication of potential for antibiotic diffusion to the periphery. Of the three cephalosporin(-like) compounds evaluated, moxalactam produced the longest duration of free drug above the MIC90 for the Enterobacteriaceae as well as the largest free-drug area under the concentration-time curve following a standardized 2-g intravenous infusion. Both the duration of time cefotaxime was above the MIC90 for the Enterobacteriaceae and the area under the concentration-time curve were significantly less because of its short elimination half-life, results indicating the need for more frequent dosing with cefotaxime than with moxalactam. Cefoperazone, because of its high degree of protein binding and higher MIC90 , develops the least duration of time above the MIC90 for most pathogens. None of these new agents provides free-drug concentrations above the MIC90 for Pseudomonas aeruginosa for longer than 0.6 hr, which suggests that they may be inadequate as single-agent therapy for many serious infections due to this pathogen. Because promotion of comparisons by this method relies on in vitro data for analysis, the conclusions relating to expected clinical efficacy are proffered and should be interpreted with caution.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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Overview of empiric antibiotic therapy for the febrile neutropenic patient.

The febrile neutropenic patient with cancer requires the prompt administration of empirically chosen antibiotic therapy. For many years the choice has usually been an aminoglycoside plus either a cephalosporin or an antipseudomonal penicillin; the exact combination was dependent on local patterns of infection and especially on local patterns of microbial resistance. In the absence of resistance problems, one normally would choose the least expensive aminoglycoside and, probably, the least expensive antipseudomonal penicillin. A new approach to be considered is the use of single agents with very broad spectra such as ceftazidime or imipenem. However, such an approach is fraught with danger--that of leaving a resistant pathogen "uncovered" and of eliminating the possible benefits of synergistic activity against bacteremia due to gram-negative organisms in the profoundly neutropenic patient. Combinations of two beta-lactam agents have the advantage of not being nephro- or ototoxic, although with a few such combinations antagonism has been demonstrated. A final approach is the use of regimens that include aztreonam, ceftazidime, or imipenem, which have little or no suppressive effect on stool anaerobes. Presumably, with these agents colonization resistance will be preserved and the opportunities for secondary infection with a resistant organism will be reduced.

Agranulocytosis↗
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Hospital hotel services as risk factors for infection among immunocompromised patients.

Much is known about the association of urinary catheters, respiratory-assist devices, intravenous catheters and infusions, and other clinically related equipment with a risk of infection. The compromised host tends to develop infection with organisms that are frequently encountered in the normal flora. However, the results of surveillance cultures suggest that these organisms have indeed been acquired during hospitalization. This report suggests that many of these pathogens are acquired not as a result of clinically related activities but, rather, in conjunction with the "hotel services" of the hospital, such as the supply of food, water, and air. Tentative recommendations to hospitals for reducing the risk of infection from these services include proper design and maintenance of air-ventilating systems, regular monitoring of the water system, and preparation of foods low in microbial content for granulocytopenic patients.

Air Microbiology↗
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Well differentiated thyroid carcinoma: epidemiology, etiology and treatment.

The well differentiated thyroid carcinomas are uncommon but are increasing in frequency. This increase may be related to the recognition that even low doses of irradiation to the thyroid may be carcinogenic with a latency period of 10, 20 or more years to clinical tumor expression. Although unproven for human cancers, elevated TSH levels will enhance irradiation-associated tumor development in animal models. Currently, a large portion of the population is at an increased risk of developing thyroid cancer because of head and neck irradiation received from 1920 to 1950 for various benign conditions or more recently for the treatment of lymphoma or carcinoma. Whether these individuals should receive thyroid hormone suppression of TSH is not known but careful yearly evaluation is essential followed by open surgical biopsy chould a nodule develop. Treatment of the well differentiated thyroid carcinoma is controversial due to a lack of adequate long-term, controlled trials. Based on current data, it is the author's opinion that surgery should in most cases be followed with radioactive iodine ablation of all remaining tissue which can concentrate iodine followed by lifelong thyroid hormone replacement sufficient to correct hypothyroidism and suppress thyroid stimulating hormone. All patients require close follow-up with examination and, possibly, imaging for 20 or more years.

Adenocarcinoma↗
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Ototoxicity and pharmacokinetically determined dosages of amikacin in granulocytopenic cancer patients.

Pharmacokinetic principles were used to determine amikacin doses for granulocytopenic cancer patients on empirical antibiotic regimens, and audiometry was used to determine the effect of this treatment on auditory acuity. Patients received ticarcillin 300 mg/kg/day plus amikacin, or moxalactam 8 g/day plus amikacin, in a blinded study. Amikacin doses were calculated to achieve a peak serum concentration (one hour after infusion) of approximately 25 micrograms/ml and a trough concentration of approximately 8 micrograms/ml. Baseline audiometry was conducted, and follow-up audiometry was done on completion of the antibiotic therapy. A decrease of greater than or equal to 20 db at any frequency in one or both ears was considered indicative of ototoxicity. Of 201 patients on the empirical antibiotic protocol, 55 had courses of treatment that could be evaluated. Ototoxicity not attributable to any other drug or disease process occurred in 10 patients. There were no significant differences related to age, weight, daily dose, or total dose between patients who developed ototoxicity and those who did not. Peak and trough amikacin concentrations were not significantly different between groups. More women than men developed ototoxicity. Duration of therapy for the ototoxic group was longer, and there was a trend for those with abnormal initial audiograms to develop further evidence of impairment. The significant risk factor for auditory toxicity was the combination of duration of aminoglycoside therapy and total dose per kilogram. Pharmacokinetically calculated doses of amikacin did not result in a higher incidence of auditory toxicity than reported in previous studies.

Adolescent↗