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Biomedical subjects

H H Gadebusch

Publications and source records attributed to H H Gadebusch.

At least 37 records · Page 2Linked to original sources
PubMed1983

Tentative interpretive standards for disk diffusion susceptibility testing with norfloxacin (MK-0366, AM-715).

Norfloxacin is a new orally absorbed quinoline derivative structurally related to nalidixic acid but showing an expanded antibacterial spectrum which includes Enterobacteriaceae, Pseudomonas aeruginosa, Streptococcus faecalis, and staphylococci, among other susceptible bacterial species. The application of the regression line and error rate-bounded methods of analysis to the minimal inhibitory concentration and zone size data collected on 413 clinical isolates favored the selection of a 10-micrograms disk content and the adoption of the following interpretive zone size breakpoints for antimicrobial susceptibility testing with norfloxacin: greater than or equal to 17 mm for susceptible, 13 to 16 mm for intermediate, and less than or equal to 12 mm for resistant categories. It is proposed that isolates with minimal inhibitory concentrations of less than or equal to 16 and greater than or equal to 32 micrograms/ml be considered susceptible and resistant to norfloxacin, respectively. Differences in the antibiotic disk contents and in vitro antibacterial spectra and pharmacokinetic properties, together with the much lower rates of cross-resistance reported between norfloxacin and related drugs, strongly argue against the use of the "class disk" concept in this instance and suggest that the 10-micrograms norfloxacin susceptibility disk should be tested separately.

Anti-Bacterial Agents↗
PubMed1983

Multicenter evaluation of the proposed quality control limits and interpretive zone standards for in vitro susceptibility testing with norfloxacin.

A seven-center collaborative study was carried out to evaluate the in vitro performance of the 10 micrograms norfloxacin disks on the basis of previously proposed interpretive susceptibility zone standards and quality control parameters. Of 7,858 clinical isolates tested, 93.2, 4.9, and 1.9% fell into the susceptible, moderately susceptible, and resistant groups, respectively. The quality control data based on a total of 1,368 zone diameter measurements compared quite favorably with the proposed performance limits as follows: Escherichia coli ATCC 25922, 28 to 35 mm versus 28 to 36 mm; Staphylococcus aureus ATCC 25923, 21 to 29 mm versus 17 to 29 mm; and Pseudomonas aeruginosa ATCC 27853, 23 to 27 mm versus 22 to 29 mm.

Anti-Infective Agents↗
PubMed1983

Quaternary heterocyclylamino beta-lactams. II. The in vitro antibacterial properties of L-640,876, a new type of beta-lactam antibiotic.

A new semisynthetic cephalosporin antibiotic designated 7-beta-(1-benzylpyridinium-4-yl)-amino-3-[( (1-methyl-1H-tetrazol-5-yl) thio]methyl)ceph-3-em-4-carboxylate (L-640,876) was compared for antibacterial activity in vitro with mecillinam, cefoxitin and cefotaxime. The antibacterial spectrum of L-640,876 and the effect of culture medium composition and inoculum size on activity are most similar to those of mecillinam. In some cases the inoculum effect on MICs correlated with instability of the compound to certain beta-lactamases and in others to the presence of ionized compounds such as sodium chloride in the medium. On balance, L-640,876 was superior to mecillinam in potency and breadth of spectrum.

Amdinocillin↗
PubMed1983

Quaternary heterocyclylamino beta-lactams. III. The mode of action of L-640,876 and the effect of NaCl on membrane permeability and binding.

L-640,876, 7-beta(1-benzylpyridinium-4-yl)amino-3-[( (1-methyl-1 H-tetrazol-5-yl)thio]methyl)-ceph-3-em-4-carboxylate, is a potent representative of a new family of beta-lactam antibiotics which are similar in some respects to mecillinam. When L-640,876 and mecillinam were compared for effects on growth and morphology of Escherichia coli, it was observed that both drugs caused the formation of lemon-shaped cells during the first 30 minutes of exposure and during this period the culture turbidity increased without an appreciable change in culture viability. Unlike mecillinam, after 60 minutes of exposure to L-640,876 the majority of the lemon-shaped cells transformed into spindle-shaped cells and in the continuing presence of the drug formed osmotically fragile spheroplasts. Membrane binding studies indicated that, like mecillinam, L-640,876 was bound to the PBP-2 of E. coli and Proteus morganii; however, some binding of L-640,876 to the PBP-3 of E. coli was detected. In Staphylococcus aureus binding differences were more evident as L-640,876 was more rapidly bound to PBP-1 and 2 whereas mecillinam was rapidly bound to PBP-3. The reversal of inhibition of certain strains of Gram-negative bacteria by high ionic strength media could not be directly attributed to a reversal of antibiotic binding to the PBPs. Permeability studies indicated that the superior potency of L-640,876 in E. coli was partly due to its higher concentration in the periplasm which was unaffected by the simultaneous addition of drug and NaCl, however, in cells cultured in high ionic strength medium there was a marked reduction in penetration rate of all beta-lactams tested.

Amdinocillin↗
PubMed1983

Quaternary heterocyclylamino beta-lactams. IV. Comparison of the in vivo antibacterial activities of L-640,876, mecillinam, cefoxitin and cefotaxime.

The novel beta-lactam, L-640,876, exhibited excellent therapeutic activity when administered parenterally but not orally to mice infected with a variety of pathogenic bacteria. In this respect, the compound was as potent as cefotaxime against representative Gram-positive and Gram-negative organisms, in most cases, equal to or more potent than cefoxitin, and more effective than mecillinam. When administered subcutaneously to normal mice at dose levels ranging from 10 to 50 mg/kg, L-640,876 provided an adequate dose response, recovery of ca. 45% of biological activity in the urine, and excellent distribution at the highest dose level into liver, lung, kidney, heart muscle, but not brain.

Amdinocillin↗
PubMed1983

Quaternary heterocyclylamino beta-lactams. V. L-640,876 treatment of induced enterotoxigenic colibacillosis (scours) in calves and piglets.

A new semisynthetic cephalosporin antibiotic designated L-640,876, 7-beta-(1-benzylpyridinium-4-yl)amino-3-[( (1-methyl-1H-tetrazol-5-yl)thio] methyl)ceph-3-em-4-carboxylate, was highly active in vitro against 110 enteropathogenic strains of Escherichia coli and Salmonella species of animal origin. The MIC90 was 0.125 microgram/ml for the E. coli strains, 2 micrograms/ml for the S. choleraesuis strains and 4 micrograms/ml for the S. typhimurium strains. In colostrum-fed calves infected with E. coli strain B44, L-640,876 administered by gavage at 30 mg/calf (0.67 mg/kg) twice a day for 3 days, starting at 20-hour post-inoculation, eliminated the diarrhea and reduced the mortality from 82% in the infected, nonmedicated calves to 11% in the infected, medicated calves (P less than 0.05). In colostrum-fed piglets infected with E. coli strain P155, L-640,876 administered by gavage at 12.5 or 20 mg/piglet (10 or 16 mg/kg) twice a day for 3 days, starting at 6-hour post-inoculation, eliminated the diarrhea and reduced the mortality from 79% in the infected, nonmedicated to 25% in the infected, medicated piglets (P less than 0.05). Thus, L-640,876 was highly effective in restoring the calves and piglets to good health by eliminating diarrhea and reducing mortality.

Animals↗
PubMed1983

Ethanol-cephalosporin antibiotic interactions: an animal model for the detection of disulfiram (Antabuse)-like effects.

Disulfiram (Antabuse)-like reactions occurring in patients undergoing antibacterial therapy with certain cephalosporin antibiotics, and after ingestion of ethanol, are well documented. A murine model is described which may prove useful in the detection of compounds likely to produce this effect. Eight cephem compounds (moxalactam, cefamandole, cefmetazole, cefonicid, cefmenoxime, cefoperazone, cefotiam, ceforanide) each carrying an N-methyltetrazolethiol substituent in the 3-position of the dihydrothiazine ring of the parent antibiotic were capable of inducing a disulfiram-like reaction in the test animals. Evidence is presented which strongly suggests a direct relationship between N-methyltetrazolethiol and related heterocyclic thiols and the ability to induce this reaction.

Animals↗
PubMed1982

Comparison of the antibacterial activity of norfloxacin (MK 0366, AM 715), a new organic acid, with that of other orally absorbed chemotherapeutic agents.

425 randomly selected, fresh clinical isolates were tested for susceptibility to norfloxacin and other orally absorbed agents, i.e. amoxicillin, ampicillin, carbenicillin (available commercially as the indanyl ester), cefaclor, cinoxacin, erythromycin, nalidixic acid, penicillin G, tetracycline, trimethoprim and co-trimoxazole. The results have shown norfloxacin to be the most potent agent in vitro against representative members of the family Enterobacteriaceae, Staphylococcus aureus, Pseudomanas aeruginosa, Acinetobacter spp., Neisseria gonorrhoeae and Haemophilus influenzae. Ninety percent of the isolates in these groups of bacteria were inhibited by less than 1 mg/l, 2 mg/l, 8 mg/l, 32 mg/l, 0.06 mg/l and 0.25 mg/l of norfloxacin, respectively. Although norfloxacin inhibited most streptococci and Ureaplasma at a concentration of 8 mg/l or less, penicillin G proved to be the most active against Streptococcus pygenes and Streptococcus pneumoniae; trimethoprim was the most active against Streptococcus faecalis, and tetracycline the most active against Ureaplasma.

Acinetobacter↗
PubMed1980

Evaluation of chemotherapeutic agents in experimental Haemophilus influenzae bacteremia and meningitis in infant rats.

Procedures for evaluating the efficacy of chemotherapeutic agents in an infant rat model of Haemophilus influenzae meningitis were developed. The results of efficacy studies with ampicillin, chloramphenicol, cefamandole, cefoxitin, and SQ 13,426 were compared to activity in vitro. While most of the drugs tested were very active against the two strains of H. influenzae used in vitro, this activity was not in all cases translated into efficacy in vivo. Pharmacokinetic studies using ampicillin or chloramphenicol demonstrated the presence of each antibiotic at the foci of infection in concentrations found to be bactericidal in vitro.

Ampicillin↗
PubMed1978

Cephamycin derivatives: comparison of the in vitro and in vivo antibacterial activities of SQ 14,359, CS-1170, and cefoxitin.

SQ 14,359 is a new cephamycin-type (7alpha-OCH3) antibiotic belonging to a series containing a 7alpha-ureidoacetyl substituent. The compound is the most potent extended spectrum derivative of this type yet reported, surpassing CS-1170 and cefoxitin by a wide margin. This activity in vitro which extends throughout the Enterobacteriaceae is particularly prominent against Gram-negative organisms that are producers of "cephalosporinase-type" beta-lactamases such as Enterobacter, Serratia, Citrobacter and indole-positive Proteus species. Superior activity also is demonstrated in vitro against streptococci, beta-lactamase-producing staphylococci, Haemophilus influenzae, Neisseria gonorrhoeae, and many Gram-negative pathogens resistant to aminoglycoside antibiotics. Experimental chemotherapeutic studies have confirmed these observations in wound and selected systemic infections in mice as well as acute pyelonephritis and meningitis in rats. The pharmacokinetics for each drug including antibiotic bound to serum was similar in both mice and rats. The pharmacokinetic profile in blood and cerebrospinal fluid favored SQ 14,359.

Animals↗
PubMed1978

Diastereomeric 7-ureidoacetyl cephalosporins. III. Contribution of D- and L-isomers to the growth inhibiting activities of 7alpha-H and 7alpha-OCH3 derivatives for gram-positive and gram-negative bacteria.

A series of 7beta-ureidoacetyl, 7alpha-H and 7alpha-OCH3 cephalosporin antibiotics have shown broad-spectrum antibacterial activity in vitro. In the 7alpha-H but not in the 7alpha-OCH3 series, contrary to experience in the antibiotic field, the L-isomers were substantially more active than the D-isomers both in vitro and in vivo particularly, but not exclusively, against Enterobacteriaceae that produce potent chromosomal cephalosporinases. Enhanced resistance to and inhibition of beta-lactamase (s) appeared to be responsible for this effect. Studies in vitro specifically with 7beta-thienylureidoacetyl derivatives showed that D-isomers interacted with L-isomers in the 7alpha-OCH3 series in a synergistic manner against "cephalosporinase-type" enzyme producers while isomers in the 7alpha-H series did not. Examples were presented in which this favorable event resulted in improved efficacy of the racemic mixture over the pure D- or L-isomer alone in appropriate experimental infections.

Animals↗
PubMed1977

Human serum protein binding of cephalosporin antibiotics in vitro.

The published values for serum protein binding of antibiotics vary considerably depending upon the method and experimental conditions used. A rapid, simple, and standardized ultrafiltration procedure for determination of the serum protein binding of antibiotics has been developed and used to compare the binding characteristics of four marketed cephalosporins. The human serum protein binding of cephradine, cephalexin, cephalothin, and cefazolin at 37 degrees C. and physiological pH (7.4) was found to be 13.8, 12.4, 71.2, and 89.2 per cent, respectively. These values fall within the range of published values for these antibiotics.

Blood Proteins↗
PubMed1976

Amphotericin B and amphotericin B methyl ester ascorbate. I. Chemotherapeutic activity against Candida albicans, Cryptococcus neoformans, and Blastomyces dermatitidis in mice.

Amphotericin B methyl ester (AME) has been reported to possess in vitro antifungal activity similar to that of amphotericin B and to have less intrinsic toxicity in mice and dogs. For these reasons AME has been porposed as an alternative to amphotericin B in the therapy of deep mycoses. For comparison of the therapeutic efficacy of the two polyenes in laboratory animals before initiation of studies in humans, groups of mice were infected with Candida albicans, Cryptococcus neoformans, and Blastomyces dermatitidis. Treatment consisted of two or more doses of each drug given by the intravenous route. Concurrently, studies of subacute toxicity were conducted in the same species to permit calculation of therapeutic indices. These studies have shown that AME, as the ascorbate salt, is substantially less efficacious than amphotericin B (in colloidal dispersion with sodium deoxycholate) for treatment of the fungal infections and that amphotericin B had a higher therapeutic ratio for all infections studied than did AME.

Amphotericin B↗
PubMed1974

Cephradine: absorption, excretion, and tissue distribution in animals of a new cephalosporin antibiotic.

Metabolic studies were conducted with cephradine administred by the oral, subcutaneous, intravenous, or rectal routes to mice, rats, and dogs. Peak blood levels were usually attained in 30 to 150 min after dosing, depending on the animal species studied. Based on urinary excretion, cephradine appeared to be well absorbed after oral or subcutaneous administration; after rectal doses, cephradine was absorbed poorly. In rats and dogs given oral or intravenous doses of cephradine, about 70 to 100% of the administered dose was recovered during a 24-h collection period. Cephradine was excreted unchanged. After the oral or intravenous administration of [(3)H]cephradine to rats and dogs, respectively, its plasma half-life was about 1 h. After oral administration to rats, cephradine was distributed widely throughout the body tissues, with the greatest concentrations in the kidneys and liver; at 45 min to 6 h postdose, cephradine concentrations in the kidneys and liver were about 8 and 3 times higher, respectively, than those in plasma.

Animals↗
PubMed1974

New antimicrobial nitrofuran, trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-delta2-1,2,4-oxadiazole: antibacterial, antifungal, and antiprotozoal activities in vitro.

trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-Delta(2) -1,2,4-oxadiazole, a new antimicrobial nitrofuran, has shown microbial activity in vitro against a wide range of bacteria and fungi, and against several protozoa. The antimicrobial activity of the nitrofuran is not significantly diminished in vitro in the presence of 50% human serum. The compound is not cross-resistant with a number of common antibiotics or synthetic antimicrobial agents; some cross-resistance with furazolidone is encountered. The development of resistance to the compound in vitro, when it occurs, is mixed, but is unrelated to increase in pathogenicity of the test organism.

5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazol↗
PubMed1974

New antimicrobial nitrofuran, trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-delta2-1,2,4-oxadiazole: antimicrobial efficacy in mice, rats, and guinea pigs.

A new antimicrobial nitrofuran designated SQ 18,506 showed some therapeutic activity when administered orally to mice infected with Escherichia coli, Salmonella schottmuelleri, Shigella flexneri, or Klebsiella pneumoniae. Animals infected parenterally with Streptococcus pyogenes, Proteus mirabilis, Mycobacterium tuberculosis, and Candida albicans, or topically with Trichophyton mentagrophytes, did not respond to therapy with the drug at the dosage levels used. The compound was as effective as metronidazole in the topical treatment of experimental trichomonal infections in mice and in guinea pigs and as effective as nystatin, candicidin, or a sulfanilamide-aminacrine hydrochloride cream in the treatment of a candidal vaginal infection in rats. The chemotherapeutic efficacy of SQ 18,506 in experimental vaginitis caused by Escherichia coli in the rat surpassed that shown by four commercial products available for the treatment of bacterial vaginitis.

5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazol↗