Search PubMed⌕ Search

Biomedical subjects

D J Hardy

Publications and source records attributed to D J Hardy.

At least 37 records · Page 2Linked to original sources
PubMed1993

Neonatal Trichosporon beigelii infection: report of a cluster of cases in a neonatal intensive care unit.

Trichosporon beigelii, a ubiquitous yeast found in soil, causes superficial dermatologic infections in normal hosts and rare cases of disseminated disease among immunocompromised patients. Neonatal cases are exceptionally rare. We report a cluster of cases of T. beigelii infections in a tertiary care hospital in Rochester, NY, during May to July, 1991. Three cases occurred in very low birth weight premature infants (23 to 25 weeks of gestation), two of whom died. The organism was isolated from urine alone in one case, skin and blood in one case and blood, tracheal aspirate and central venous catheter tip in one case. In a fourth, full term infant with respiratory distress syndrome T. beigelii was grown only from a femoral central venous catheter tip with no clinical evidence of infection. An epidemiologic investigation was performed and the mode of transmission in this outbreak was not identified, although cross-infection was suspected in the initial two cases. Our isolates were inhibited but not killed by usually achievable concentrations of amphotericin B. T. beigelii may cause outbreaks of serious infection in neonatal intensive care units, especially among premature infants.

Antifungal Agents↗
PubMed1992

Preparation and in vitro and in vivo evaluation of quinolones with selective activity against gram-positive organisms.

A series of quinolones were prepared which contained oximes or substituted oximes as replacements for the amine substituents normally found on the pyrrolidine or piperidine fragments of quinolone antibacterial agents. These substituents led to compounds that had selective activity against Gram-positive organisms. These compounds showed in vivo activity against Staphylococcus aureus. Only compound 29 had in vivo activity against Streptococcus pneumoniae.

4-Quinolones↗
PubMed1992

Error rates in cefoperazone and cefoperazone-sulbactam disk tests with Enterobacteriaceae and Pseudomonas aeruginosa.

In a collaborative study involving five medical centers, 6% of 2,440 consecutive isolates of Enterobacteriaceae were resistant to cefoperazone; resistance to cefoperazone was reduced to < 1% by the addition of sulbactam. Susceptibility to cefoperazone and cefoperazone-sulbactam was accurately predicted by disk diffusion tests. Resistance to cefoperazone, however, was not as reliably detected by disk tests and results of dilution tests were not always consistent. The prevalence of resistance to cefoperazone and/or the ability to detect resistance had a significant influence on very major error rates for individual laboratories.

Agar↗
PubMed1992

Comparison of fixed concentration and fixed ratio options for testing susceptibility of gram-negative bacilli to piperacillin and piperacillin/tazobactam.

Piperacillin combined with tazobactam was tested at both a fixed ratio (8:1) and fixed tazobactam concentration (4 micrograms/ml) against 2,685 consecutively isolated gram-negative bacilli and 56 highly piperacillin-resistant isolates. Tazobactam significantly enhanced the spectrum of piperacillin activity. Overall, at a concentration of 16 micrograms/ml piperacillin alone inhibited 78.8% of the Enterobacteriaceae isolates compared to inhibition of 92.7% and 95.5% by the 8:1 ratio and fixed (4 micrograms/ml) tazobactam combinations, respectively. In MIC tests the two combination options performed comparably against both routine and highly piperacillin-resistant isolates. Synergistic inhibition was observed for comparable numbers of isolates with the two combination options, the most marked effect being seen in the more highly piperacillin-resistant isolates. Both testing options are supported by the available human pharmacokinetic data; however the 8:1 ratio of piperacillin to tazobactam may be preferable given that the clinical formulation contains the two compounds in an 8:1 ratio and this ratio is maintained in vivo.

Drug Synergism↗
PubMed1992

Clarithromycin, a unique macrolide. A pharmacokinetic, microbiological, and clinical overview.

The in vitro and in vivo spectrum of antibacterial activity of clarithromycin is summarized and related to its human pharmacokinetics. In vitro studies by several investigators have documented clarithromycin's activity against bacterial agents of respiratory tract infections, skin and soft tissue infections, and sexually transmitted diseases. Clinical cure rates of 52%-83% (pneumonia), 79%-96% (bronchitis), 82%-96% (pharyngitis), 58% (sinusitis), and 78% (skin/skin-structure infections) have been reported in patients receiving clarithromycin in comparative trials. Respective bacteriologic eradication rates in clarithromycin recipients have been reported as 57%-89%, 79%-96%, 88%-100%, 89%, and 90%. In vitro and in vivo studies suggest that clarithromycin, when combined with its major human metabolite, 14-hydroxyclarithromycin, is also effective against Haemophilus influenzae. A New Drug Application claiming efficacy in the treatment of lower respiratory tract infection, sinusitis, pharyngitis, and skin and skin-structure infections caused by susceptible pathogens has been filed with the Food and Drug Administration (FDA). This review summarizes relevant pharmacokinetic, microbiological, and clinical data for clarithromycin.

Clarithromycin↗
PubMed1992

Ticarcillin and ticarcillin-clavulanic acid susceptibility tests: error rates for disk tests with consecutively isolated members of the family Enterobacteriaceae.

A five-laboratory coordinated study was undertaken to determine whether ticarcillin and ticarcillin-clavulanic acid disk susceptibility tests could accurately detect resistance among enteric bacilli. Each facility performed disk tests and broth microdilution susceptibility tests with reagents distributed from a common source, and appropriate controls were included in order to ensure methodologic uniformity. Each institution tested 500 consecutively isolated enteric bacilli against ticarcillin and ticarcillin-clavulanic acid. The prevalence of discrepancies between disk tests and dilution tests with 2,435 unselected enteric bacilli provided a valid estimate of the true error rate for tests with the two disks. The current interpretive criteria for susceptibility tests with ticarcillin and ticarcillin-clavulanic acid disks were found to be reliable; i.e., there were major or very major discrepancies between MIC categories and disk test results for less than 1% of all strains and minor discrepancies for only 5 to 10%. Even lower error rates would occur if the zone size-interpretive criteria were modified, but at this time it is difficult to determine whether the practical problems created by making such changes can be justified by the magnitude of the problem that is being resolved.

Clavulanic Acids↗
PubMed1992

Time to detection of positive BacT/Alert blood cultures and lack of need for routine subculture of 5- to 7-day negative cultures.

Consecutive BacT/Alert blood cultures which were instrument negative following a 7-day incubation were subcultured. Eighteen (0.2%) of 11,476 bottles had growth on subculture. Eleven of these eighteen isolates were considered contaminants on the basis of the identity of the organism and lack of other positive blood cultures from the same patient. In addition, analysis of time to instrument detection for approximately 2,900 positive blood cultures indicates that 5 or 6 days of incubation is sufficient for the routine detection of clinically significant organisms from BacT/Alert blood cultures. These data indicate that subculture of 5- to 7-day instrument-negative BacT/Alert blood culture bottles is not necessary.

Bacteria↗
PubMed1992

Interpretive criteria and quality control parameters for testing susceptibility of Haemophilus influenzae to enoxacin, ofloxacin, and temafloxacin.

Haemophilus influenzae isolates were uniformly susceptible to enoxacin, ofloxacin, and temafloxacin. Zone diameter and MIC interpretive criteria were proposed to define susceptible populations so that mutants with diminished susceptibility might be detected when and if they appear in clinical specimens. Additional collaborative quality control studies defined MIC and zone size limits for tests with H. influenzae ATCC 49247.

Anti-Infective Agents↗
PubMed1992

Haemophilus influenzae ATCC 49766, an alternative quality control strain for monitoring broth microdilution susceptibility tests with selected beta-lactams.

A beta-lactamase-negative, ampicillin-resistant strain of Haemophilus influenzae is currently used for quality control of broth microdilution tests performed with Haemophilus test medium (HTM). Studies with eight lots of HTM broth documented the fact that MIC limits for some antimicrobial agents are unrealistically stringent; i.e., only three of eight lots of HTM broth were satisfactory for testing cefaclor. An alternative, ampicillin-susceptible strain of H. influenzae (ATCC 49766) was found to provide much more reproducible results with five problematic drugs (cefaclor, cefuroxime, cefamandole, loracarbef, and cefonicid). Multilaboratory studies defined MIC control limits for both control strains tested against 12 antimicrobial agents.

Ampicillin↗
PubMed1992

Total parenteral nutrition-induced changes in gut mucosal function: atrophy alone is not the issue.

BACKGROUND: Total parenteral nutrition (TPN) has been implicated in gut atrophy and breakdown of barrier function leading to bacterial translocation (BT) in animals. BT during TPN, however, is not found consistently, and it has therefore been suggested that macromolecular permeability may occur independently of BT during TPN. METHODS: Male Sprague-Dawley rats were administered isocaloric standard TPN enterally, parenterally, or split equally between the two routes or allowed food ad lib. A second group of rats was administered isocaloric TPN with and without 4% lipids, and changes in gut barrier function were assessed by measuring lactulose permeability. RESULTS: Rats receiving TPN both enterally and parenterally maintained histologic intestinal structure to the same degree as rats fed enterally and those allowed food. Although parenteral feeding led to significant gut atrophy and cecal bacterial overgrowth, BT was not increased. Gut permeability to lactulose, however, was increased significantly in the TPN groups. Lipid content did not affect outcome. CONCLUSIONS: These results suggest that gut atrophy, BT, and permeability to macromolecules are not necessarily related. Gut-origin septic states during TPN or trauma may be caused by an increased escape of macromolecules from the gut, and BT may be an end result rather than a primary cause of such septic episodes.

Animals↗
PubMed1991

Activity of temafloxacin and other fluoroquinolones against typical and atypical community-acquired respiratory tract pathogens.

The microbiologic activities of temafloxacin, ciprofloxacin, and ofloxacin against community-acquired respiratory tract pathogens are reviewed. The 90% minimal inhibitory concentrations (MIC90s) of these fluoroquinolones for gram-negative pathogens were generally comparable, that is, less than 0.06 micrograms/mL. Overall, the agents were less active against gram-positive pathogens, although temafloxacin was two- to fourfold more active than the other agents against staphylococci and streptococci. For strains of Mycoplasma pneumoniae and Chlamydia pneumoniae, temafloxacin was generally inhibitory at concentrations of 0.5-2 micrograms/mL. This microbiologic activity, combined with its pharmacokinetic profile, should make temafloxacin a useful antimicrobial agent for treating community-acquired respiratory tract infections.

Anti-Infective Agents↗
PubMed1991

In vitro activity of temafloxacin against gram-negative bacteria: an overview.

The in vitro activities of temafloxacin, ciprofloxacin, and ofloxacin against gram-negative bacteria are compared. The 90% minimal inhibitory concentrations (MIC90s) of temafloxacin for respiratory pathogens such as Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, Bordetella pertussis, and Legionella pneumophila are less than or equal to 0.06 micrograms/mL. Temafloxacin is also active against bacterial agents of sexually transmitted diseases, including Neisseria gonorrhoeae (MIC90 less than or equal to 0.015 micrograms/mL) and Chlamydia trachomatis (MIC90 0.25 micrograms/mL). For strains of Enterobacteriaceae, Campylobacter, Vibrio, Aeromonas, and Acinetobacter, temafloxacin is generally inhibitory at less than or equal to 0.5 micrograms/mL. The MIC90 of temafloxacin for Pseudomonas aeruginosa is higher than that of ciprofloxacin, approximately 4 micrograms/mL versus 0.5 micrograms/mL. This activity, combined with its pharmacokinetic characteristics, should make temafloxacin an effective antimicrobial agent against infections caused by gram-negative bacteria.

Anti-Infective Agents↗
PubMed1991

Synthesis, antibacterial activities, and pharmacological properties of enantiomers of temafloxacin hydrochloride.

Temafloxacin hydrochloride [(+/-)-7-(3-methylpiperazin-1-yl)-6-fluoro-1-(2,4-difluorophenyl)- 1,4-dihydro- 4-oxoquinoline-3-carboxylic acid hydrochloride] is a potent member of the 4-pyridone-3-carboxylic acid class of antibacterial agents and is currently under clinical development as a broad-spectrum antimicrobial agent. It is a racemate having a chiral center at the C3 of the 7-piperazin-1-yl group. The two enantiomers were synthesized and tested for their antibacterial activities. Although no difference in in vitro antibacterial activities was observed, a minor difference in in vivo antibacterial activities was observed. However, they both exhibited similar pharmacological profiles.

4-Quinolones↗
PubMed1991

Synthesis and antibacterial activities of C-21 functionalized derivatives of (9R)-9-amino-9-deoxoerythromycins A and B.

Selective protection of (9R)-9-amino-9-deoxoerythromycin A allowed for elimination of the 12-hydroxyl group to afford a versatile 12,21-olefin intermediate. Further modifications of the intermediate led to the syntheses of (9R)-9-deoxo-9-(N,N-dimethylamino)-12,21-epoxyerythromycin B, (9R)-9-deoxo-9-(N,N-dimethylamino)-21-hydroxyerythromycin A, and (9R)-9-deoxo-9-(N,N-dimethylamino)-21-hydroxyerythromycin B. All three compounds retained antibacterial activity against several organisms normally susceptible to (9R)-9-deoxo-9-(N,N-dimethylamino)erythromycin A. However, the 21-hydroxylated erythromycin A analogue was weaker in potency than the corresponding erythromycin B congener and much weaker than the epoxy derivative. This suggests that while substitution of a polar functionality at C-21 does not abolish antibacterial activity, introduction of vicinal polar groups at both C-12 and C-21 may lead to reduction in potency. Nevertheless, these 21-functionalized derivatives of (9R)-erythromycylamine provide an entry into novel analogues of the important macrolide antibiotic erythromycin.

Bacteria↗
PubMed1991

Antipneumococcal activity of ciprofloxacin, ofloxacin, and temafloxacin in an experimental mouse pneumonia model at various stages of the disease.

The efficacy of temafloxacin against Streptococcus pneumoniae in an experimental murine pneumonia model was compared with that of ofloxacin and ciprofloxacin. Erythromycin and amoxicillin were used as reference agents. Subcutaneous administration of antibiotics every 12 h for 3 days was initiated at various times after infection. The cumulative survival rates of mice treated with temafloxacin at 50 mg/kg were 100%, 92%, 81%, and 50% with treatment beginning 18, 48, 72, and 96 h after infection, respectively. The activity of temafloxacin at 50 mg/kg was not significantly different from that of erythromycin and amoxicillin but was superior to that of ofloxacin and ciprofloxacin. The maximum cumulative survival rates of mice treated with ofloxacin and ciprofloxacin at 100 mg/kg were 67% and 50%, respectively, with treatment beginning 18 h after infection. Treatment with ofloxacin and ciprofloxacin at 50 mg/kg 18 h after infection did not significantly increase survival rates compared with those of untreated controls.

Amoxicillin↗
PubMed1991

Reproducibility of disc susceptibility tests with Haemophilus influenzae.

Triplicate susceptibility tests were performed in each of three laboratories with 45 strains of Haemophilus influenzae and a single lot of Haemophilus test medium (HTM) agar plates. Using clarithromycin, erythromycin and chloramphenicol discs. zone sizes varied over ranges averaging only 4.3-5.8 mm. Ampicillin zone sizes were more variable, especially when beta-lactamase-producing strains were being tested, but the latter strains were consistently categorized as being resistant. A 94% interpretive consistency was observed with the two macrolides.

Ampicillin↗
PubMed1991

Activity of temafloxacin against respiratory pathogens.

The activity of the quinolone temafloxacin against respiratory pathogens was compared with those of ciprofloxacin and ofloxacin. MICs for 90% of strains tested indicated that temafloxacin was at least two- to fourfold more potent than the other two quinolones against Staphylococcus aureus, Streptococcus pneumoniae, and Legionella pneumophila. Temafloxacin had potency equal to that of ciprofloxacin and was twofold more active than ofloxacin against Streptococcus pyogenes. Moraxella catarrhalis, and Bordetella pertussis. Against Haemophilus influenzae and Klebsiella pneumoniae, temafloxacin was four- and twofold less potent than ciprofloxacin, respectively. When administered orally in mouse protection tests against S. aureus, S. pneumoniae, and S. pyogenes, temafloxacin was at least eight times more potent than ciprofloxacin and was two to four times more active than ofloxacin. Against H. influenzae, temafloxacin was as active as ofloxacin and was two times less active than ciprofloxacin following oral administration in mice. In treating L. pneumophila in guinea pigs and H. influenzae otitis media in gerbils, temafloxacin and ofloxacin were more effective than ciprofloxacin. Against S. pneumoniae otitis media in gerbils, temafloxacin and ciprofloxacin were more active than ofloxacin. Following subcutaneous administration in mice, temafloxacin achieved higher lung levels than ciprofloxacin or ofloxacin did.

Animals↗