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Biomedical subjects

J Unowsky

Publications and source records attributed to J Unowsky.

17 recordsLinked to original sources
PubMed1999

Sparfloxacin versus clarithromycin in the treatment of community-acquired pneumonia.

Community-acquired pneumonia remains a significant health concern despite the availability of effective antibiotics. This randomized, double-masked, double-dummy, multicenter comparative trial was undertaken to compare the efficacy and safety of sparfloxacin with those of clarithromycin in the treatment of community-acquired pneumonia. In 54 centers throughout the United States, 342 patients aged > or = 18 years with community-acquired pneumonia were enrolled in this trial. A total of 167 patients, 98 males and 69 females with a mean age of 51.0 years (range, 18-87), received a 400-mg loading dose of sparfloxacin on the first day, followed by 200 mg once daily for a total of 10 days. A total of 175 patients, 85 males and 90 females with a mean age of 51.3 years (range, 18-91), received clarithromycin 250 mg twice daily for 10 days. In the intent-to-treat population, 133 (79.6%) patients in the sparfloxacin group and 145 (82.9%) in the clarithromycin group were cured or improved (the 95% confidence interval [CI] for the differences in success rate between sparfloxacin and clarithromycin was -11.5% to 5.1%). Success rates for the per-protocol patients were 88.7% (133/150) in the sparfloxacin group and 88.9% (144/162) in the clarithromycin groups (95% CI, -7.2% to 6.8%). There were no significant differences in success rate between treatment groups based on age > or = 65 years. The overall bacteriologic response rates in the bacteriologically assessable population were 97.0% (64/66 isolates) in the sparfloxacin group and 91.4% (74/81 isolates) in the clarithromycin group. Recurrence occurred in 6.0% of per-protocol patients in the sparfloxacin group and 6.3% of patients in the clarithromycin group. The overall frequency of adverse events was 56.3% in the sparfloxacin group and 65.1% in the clarithromycin group. Gastrointestinal disturbances were the most common adverse event in both groups. Abnormal taste related to study drug was reported by 17 patients (9.7%) treated with clarithromycin, versus 3 patients (1.8%) treated with sparfloxacin (P = 0.002). Photosensitivity reactions were reported in 10 patients (6.0%) treated with sparfloxacin, versus 1 patient (0.6%) treated with clarithromycin (P = 0.002). QT-interval prolongation was documented in 4 patients (2.4%) in the sparfloxacin group and no patients in the clarithromycin group. Thus sparfloxacin was as well tolerated and as effective as clarithromycin in the treatment of community-acquired pneumonia.

Adult↗
PubMed1999

Treating acute bacterial exacerbations of chronic bronchitis in patients unresponsive to previous therapy: sparfloxacin versus clarithromycin.

The optimal antibiotic therapy for patients with acute bacterial exacerbations of chronic bronchitis (ABECB) who have failed to respond to previous oral antimicrobial therapy is not known; however, newer macrolide and fluoroquinolone antibiotics may be appropriate. This multicenter, randomized, double-masked, double-dummy study was undertaken to compare the efficacy and tolerability of sparfloxacin with those of clarithromycin in the treatment of ABECB. In 43 centers in the United States, 298 patients (52% male; age range, 19 to 92 years) were randomly allocated to receive a 400-mg loading dose of sparfloxacin, followed by 200 mg once daily, or clarithromycin 500 mg twice daily, for a total of 10 days. Signs and symptoms of ABECB were assessed at each of 4 visits, including a follow-up visit approximately 1 month after the completion of therapy. Efficacy was determined on the basis of the clinical and bacteriologic response rates in the clinically assessable population. Tolerability was assessed on the basis of patient reports, clinical evaluations, and laboratory tests. Of the 266 clinically assessable patients, 109 (85.2%) of 128 patients receiving sparfloxacin and 115 (83.3%) of 138 patients receiving clarithromycin had a clinically successful outcome (cure or improvement). The bacteriologic success rate (eradication of pathogen) was 88.9% (64 of 72 isolates) in the sparfloxacin group and 84.7% (83 of 98 isolates) in the clarithromycin group. Adverse events possibly or probably related to study drug included photosensitivity in 12 (8.3%) and rash in 6 (4.1%) of 145 patients in the sparfloxacin group, and diarrhea in 10 (6.5%), taste perversion in 9 (5.9%), and nausea in 8 (5.2%) of 153 patients in the clarithromycin group. Thus sparfloxacin was as well tolerated and as effective as clarithromycin in the treatment of patients with ABECB unresponsive to previous oral antimicrobial therapy. The overall rate of adverse events was comparable for the 2 study drugs, but the types of events differed.

Acute Disease↗
PubMed1992

Dual-action penems and carbapenems.

Two new series of dual-action antibacterial agents were synthesized in which penems and carbapenems were linked at the 2'-position to quinolones through either an ester or a carbamate moiety. Potent, broad-spectrum antibacterial activity was observed for both classes of compounds, indicative of a dual-mode of action.

Anti-Bacterial Agents↗
PubMed1989

Stimulation of hematopoiesis and antibacterial resistance by interleukin-1.

The beneficial effects of IL-1 and other cytokines on hematopoiesis and on resistance to infection are profound. IL-1 stimulates proliferation of bone marrow cells in normal mice and potentiates the recovery of peripheral blood neutrophils in mice with drug-induced neutropenia. Prophylactic cytokine administration provides an elevated level of natural resistance to infections which is correlated with increased numbers of phagocytic leukocytes. These studies suggest that IL-1 has potential clinical application as a therapy to limit bone marrow dysfunction and immunosuppression and to augment hematopoiesis and natural immunity. Further research will continue to elucidate the mechanisms whereby interleukins and colony-stimulating factors act, and interact, to promote restoration of leukocyte production and to enhance host resistance.

Animals↗
PubMed1989

In vitro activities of a dual-action antibacterial agent, Ro 23-9424, and comparative agents.

The in vitro activity of the dual-action antibacterial agent Ro 23-9424 was compared with those of cefotaxime, ceftazidime, ciprofloxacin, fleroxacin, imipenem, and amikacin against 358 aerobes and anaerobes. The MIC ranges, MICs for 50 and 90% of the strains (MIC50s and MIC90s), and percentage of strains susceptible for each agent at the recommended susceptible MIC breakpoint were determined for each genus. The MIC90s (micrograms per milliliter) of the agents against members of the family Enterobacteriaceae were as follows: ciprofloxacin, 0.063; Ro 23-9424, fleroxacin, and imipenem, 0.5; ceftazidime, 2; amikacin, 4; and cefotaxime, 16. The MIC90s (micrograms per milliliter) against Pseudomonas and Acinetobacter spp. were as follows: ciprofloxacin, 2; ceftazidime and imipenem, 8; Ro 23-9424, 16; fleroxacin, 32; amikacin, 64; and cefotaxime, 128. Against gram-positive bacteria, excluding the enterococci, the MIC90s (micrograms per milliliter) were as follows: ciprofloxacin, 1; imipenem, 4; Ro 23-9424 and fleroxacin, 8; amikacin, 64; and ceftazidime and cefotaxime, greater than 128. Against gram-positive bacteria, including the enterococci, the MIC90s changed only for the following agents: Ro 23-9424, 16 micrograms/ml; and amikacin, 128 micrograms/ml. Strains of Branhamella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae were 100% susceptible to Ro 23-9424, cefotaxime, ciprofloxacin, and fleroxacin, while the other three agents showed somewhat less activity only against N. gonorrhoeae. Against anaerobes, imipenem was the most effective agent, while the activities of the other six agents were variable.

Anti-Bacterial Agents↗
PubMed1989

Enhancement of antibacterial resistance of neutropenic, bone marrow-suppressed mice by interleukin-1 alpha.

The effect of recombinant human interleukin-1 alpha (IL-1) on the resistance of normal and bone marrow-suppressed mice against bacterial infection was evaluated. IL-1 induced neutrophilia and enhanced the resistance of normal mice against acute, systemic intraperitoneal infection with Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus. Mice with cyclophosphamide-induced bone marrow suppression were neutropenic and exhibited increased susceptibility to infection. Treatment of neutropenic C57BL/6 and C3H/HeJ mice with IL-1 before infection accelerated recovery of peripheral neutrophil counts and stimulated resistance against infection. Increases in neutrophils and enhancement of resistance induced by IL-1 were both dose and time dependent. Both neutrophilia and augmented resistance to infection were eliminated by a second dose of cyclophosphamide administered during the IL-1 treatments. Bone marrow-suppressed mice treated with IL-1 showed, at 4 h postinfection, greater increases in peripheral blood neutrophils and in numbers of peritoneal exudate neutrophils than suppressed mice treated with vehicle. The data suggest that the IL-1-stimulated recovery of myelopoiesis is an important factor in the enhancement of antibacterial resistance in bone marrow-suppressed, neutropenic mice. These findings indicate that IL-1 may be efficacious in limiting the duration of the neutropenia and of the increased risk for the development of bacterial infection associated with bone marrow suppression.

Adjuvants, Immunologic↗
PubMed1989

Potencies of ceftriaxone and cefotaxime in a single chamber pharmacokinetic system simulating their in vivo half-lives.

Ceftriaxone and cefotaxime are third-generation cephalosporins with similar in vitro potencies and spectra. However, previous studies have shown that ceftriaxone had superior in vivo activity (mouse PD50 values greater than or equal to 2-fold lower) compared to cefotaxime in 23 of 46 tested enterobacteriaceae. This superior activity was thought to be due to ceftriaxone's 5- to 8-fold longer half-life. The relationship between half-life (ceftriax-one 6 h, cefotaxime 1 h) and potency was examined by following bacterial kill curves in a single chamber, open-ended perfusion model over an 8-hour period. Both antibiotics were compared for efficacy at both half-lives against four gram-negative bacteria. For two of the bacterial strains antibiotic potency differences in the perfusion model were determined largely by pharmacokinetics. For the other two strains intrinsic bacterial and antibiotic properties were of prime importance.

Animals↗
PubMed1988

Enteral, oral, and rectal absorption of ceftriaxone using glyceride enhancers.

In vivo models in rodents and primates were used to investigate ways of overcoming the poor oral and rectal absorption of ceftriaxone. The sodium salt of ceftriaxone at 20 mg/kg was formulated in C8-C10 chain length, mono- and diglyceride extracts of coconut oil (Capmul) and administered intraduodenally to adult rats. Peak plasma levels of 17-52 micrograms/ml and bioavailability averaging 38% were attained. Significant plasma levels (42-45 micrograms/ml) were also demonstrated in squirrel monkeys with doses of 20 mg/kg ceftriaxone formulated in Capmul and given by the enteral route. Enteric-coated capsules containing this formulation were also orally administered to squirrel monkeys and gave high plasma levels (10-31 micrograms/ml) between 1 and 6 h following dosing. In rectal absorption studies, ceftriaxone formulated in Capmul as a suspension gave peak blood levels of 62-84 micrograms/ml (average bioavailability 42%) in the rabbit. In the baboon, rectal administration of ceftriaxone formulated with Capmul in a Witepsol H15 suppository gave Cmax levels ranging from 9 to 48 micrograms/ml, depending on the dose of the antibiotic and the drug/enhancer ratio.

Administration, Oral↗
PubMed1988

Effect of medium chain glycerides on enteral and rectal absorption of beta-lactam and aminoglycoside antibiotics.

The rat enteral and rabbit rectal models were utilized to study the effect of Capmul (medium chain glycerides) on the absorption of a selection of beta-lactam and aminoglycoside antibiotics. All tested non-orally available beta-lactam antibiotics (cefamandole, cefotaxime, moxalactam, cefoxitin, mezlocillin, carumonam, penicillin G and amdinocillin) showed increased absorption enterally in rats and rectally in rabbits when formulated with Capmul. The orally available beta-lactam antibiotics, cephalexin and cephradine, were not enhanced in their enteral or rectal absorption by Capmul in the two model systems. Ampicillin absorption was enhanced rectally and enterally by Capmul. Rectal absorption of the aminoglycoside antibiotics, tobramycin and gentamycin, was enhanced by Capmul while enteral absorption was not.

Aminoglycosides↗
PubMed1986

In vitro and in vivo activity of coumermycin and other antibacterial agents against methicillin-resistant strains of Staphylococcus aureus.

The in vitro activity of coumermycin, fusidic acid, cotrimoxazole, and vancomycin was determined by broth microdilution assay against 33 methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates from the Detroit Receiving Hospital, Detroit, Mich. Coumermycin was the most active drug tested, while fusidic acid, vancomycin, and cotrimoxazole also had good activity. The four antimicrobials were tested in vivo against 7 strains of MRSA employing the mouse protection model. Again, coumermycin was the most active, followed by vancomycin, cotrimoxazole, and fusidic acid. Coumermycin was very active, while vancomycin and fusidic acid were inactive in neutropenic mice infected with an MRSA strain. Coumermycin retained activity when given 18 h before an MRSA infection, while vancomycin activity was lost. Coumermycin was active in a local thigh infection while vancomycin was inactive. The results indicate that coumermycin is potent against MRSA with activity equal or superior to comparable agents in various experimental mouse infections.

Aminocoumarins↗
PubMed1982

Correlation of the results of antibiotic synergy and susceptibility testing in vitro with results in experimental mouse infections.

Recent clinical isolates (approximately 150 strains) of the family Enterobacteriaceae were examined by agar diffusion, microdilution, and the Autobac automated system for their responses to beta-lactam antibiotics singly and in combination with amdinocillin (formerly called mecillinam). The ratio of ampicillin, carbenicillin, and cephalothin to amdinocillin was maintained at a 10:1 ratio in most of the evaluations. The same isolates were studied in mice challenged with 100 to 1000 LD50s and treated with graded doses of the antibiotics singly and in combination. Efficacy in vivo was based on the concentration of antibiotic in milligrams per kilograms (mg/kg) required to protect 50% of the animals (PD50). After a single administration of the antibiotics, plasma levels were determined in the critical time period (30 min to 4 hr) during which the acute, overwhelming systemic infections could be controlled by appropriate therapy. Regression curves comparing in vivo and in vitro results were used to establish cut-off points for categorizing bacterial susceptibility in each of the laboratory tests for the single agents and combinations. A high degree of synergism between amdinocillin and the beta-lactam agents was demonstrated in animals (54 to 78% of the strains examined) and to a lesser extent by laboratory methodologies. There was an excellent correlation of in vivo and in vitro responses to ampicillin, carbenicillin, and cephalothin alone and in combination with amdinocillin for those species for which the single antibiotics are generally indicated. The correlations validated the chosen cut-off points. The correlation of in vivo and in vitro responses to the single or combined antibiotics was generally poorer for those species not usually responsive to the single antibiotics. The greatest difficulty in predicting proper in vivo responses, based on the results of in vitro tests, was observed with amdinocillin.

Ampicillin↗
PubMed1978

Increased production of the antibiotic aurodox (X-5108) by aurodox-resistant mutants.

Conventional strain and media improvement techniques were of limited success in increasing yields of the antibiotic aurodox (X-5108) above 0.5 g/liter. Higher yields were obtained by reversion of a zero producer followed by the selection of mutants resistant to aurodox. Resistant strains of Streptomyces goldiniensis ATCC 21386 able to grow on 2 g/liter of aurodox produced greater than 2.5 g/liter of antibiotic. The rate of yield increase leveled off as the strains became resistant to greater than 2 g/liter of aurodox. These strains, in contrast to those sensitive to aurodox, gave a positive response to conventional mutagenic methods for further yield increases.

Aurodox↗
PubMed1966

Mechanisms of antibiotic resistance determined by resistance-transfer factors.

Unowsky, Joel (Northwestern University Medical School, Chicago, Ill.), and Martin Rachmeler. Mechanisms of antibiotic resistance determined by resistance-transfer factors. J. Bacteriol. 92:358-365. 1966.-This study was concerned with the mechanism of expression of drug resistance carried by resistance-transfer (R) factors of two types: fi(-) (negative fertility inhibition) and fi(+) (positive fertility inhibition). The levels of drug resistance determined by R factors used in this study were similar to those reported by other investigators. A new finding was that Escherichia coli carrying the fi(-) episome was resistant to 150 to 200 mug/ml of streptomycin. The growth kinetics of R factor-containing cells were similar in the presence or absence of streptomycin, chloramphenicol, and tetracycline, but a period of adaptation was necessary before cells began exponential growth in the presence of tetracycline. By use of radioactive antibiotics, it was shown that cells containing the fi(-) episome were impermeable to tetracycline and streptomycin, whereas cells containing the fi(+) episome were impermeable only to chloramphenicol. Cell-free extracts from fi(+) and fi(-) cells were sensitive to the antibiotics tested in the polyuridylic acid-stimulated incorporation of phenylalanine into protein.

Journal Article↗