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Biomedical subjects

M A Cooper

Publications and source records attributed to M A Cooper.

At least 19 recordsLinked to original sources

In-vitro activity of PD 131628, a new quinolone antimicrobial agent.

The in-vitro activity of PD 131628, the active metabolite of the prodrug PD 131112, was compared with that of ciprofloxacin and members of other groups of antimicrobial agents against 701 recent clinical isolates and strains with known mechanisms of resistance. The MIC90s of PD 131628 against the Enterobacteriaceae were between 0.008 and 0.5 mg/L; PD 131628 was one- to four-fold more active than ciprofloxacin against these strains and was four-fold more active than ciprofloxacin against Pseudomonas aeruginosa. Against the Gram-positive species tested, PD 131628 was two- to four-fold more active than ciprofloxacin, inhibiting all strains of Staphylococcus aureus and Streptococcus pneumoniae with 0.5 mg/L or less. PD 131628 was very active against Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis, with MIC90s ranging from 0.004 to 0.008 mg/L. Organisms with decreased susceptibility to other quinolones had decreased susceptibility to PD 131628, but there was no cross-resistance between this class of antimicrobial and other classes. The protein binding of PD 131628 was at most 25% across a broad range of concentrations. The addition of 70% human serum had little effect on the MICs, but caused a two- to eight-fold increase in MBCs.

Anti-Infective Agents

In-vitro activity of tosufloxacin, a new quinolone antibacterial agent.

The in-vitro activity of tosufloxacin (A-61827) was compared with that of temafloxacin, ciprofloxacin and selected members of other groups of antimicrobial agents, against 684 recent distinct clinical isolates and strains with known mechanisms of resistance. Against members of the Enterobacteriaceae, ciprofloxacin was slightly more active than tosufloxacin, which was more active than temafloxacin. The MIC90 of tosufloxacin for all species of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. was less than or equal to 1 mg/L. Tosufloxacin was slightly more active than temafloxacin, and four to eight fold more active than ciprofloxacin, against the Gram-positive species tested. The MIC90 of tosufloxacin for Staphylococcus aureus was 0.12 mg/L, and for Streptococcus pneumoniae was 0.5 mg/L. All strains of Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis were inhibited by tosufloxacin at a concentration of less than or equal to 0.12 mg/L. Tosufloxacin was the most active quinolone against the anaerobic organisms tested. Cross resistance between quinolones was seen, but not between quinolones and other groups of antimicrobials. The protein binding of tosufloxacin across a range of concentrations averaged 60%. Human serum at a concentration of 70% decreased the bactericidal activity of tosufloxacin by about four-fold.

4-Quinolones

Pharmacokinetics and inflammatory fluid penetration of sparfloxacin.

A single 400-mg oral dose of sparfloxacin was given to each of six healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 52 h. The mean peak concentration in plasma of 1.6 micrograms/ml was attained at a mean time of 2.7 h postdose. The mean peak concentration in inflammatory fluid of 1.3 micrograms/ml was attained at a mean time of 5 h postdose. The mean elimination half-life in plasma was 17.6 h, and that in inflammatory fluid was 19.7 h. The overall penetration into inflammatory fluid was 117%. Urinary recovery within the first 52 h postdose was 8.8% of the administered dose. Our results indicate that a once-daily dosage of sparfloxacin should be adequate to treat systemic infections caused by most common bacterial pathogens.

Administration, Oral

In-vitro activity and beta-lactamase stability of SR 44337, a new long acting cephalosporin.

The in-vitro activity of SR 44337 was compared with that of other broad-spectrum parenteral cephalosporins, plus imipenem and co-amoxiclav. SR 44337 showed good activity against the Enterobacteriaceae, with MIC90s of less than 0.5 mg/L against all species tested, with the exception of Citrobacter spp. (MIC90 2 mg/L) and Serratia spp. (MIC90 4 mg/L). Of the agents tested, only ceftriaxone showed consistently greater activity against this family of organisms. SR 44337 had higher activity than ceftriaxone against Acinetobacter spp. and Pseudomonas aeruginosa, and was the most active agent tested against Neisseria meningitidis (MIC90 0.004 mg/L). All strains of N. gonorrhoeae, Haemophilus influenzae and the streptococci (excluding the enterococci) were susceptible to less than or equal to 0.25 mg/L of SR 44337, which was also the most active cephalosporin tested against Staphylococcus aureus. SR 44337 was stable to hydrolysis by the TEM-1, SHV-1 and P99 beta-lactamases, and was more stable than ceftriaxone to the K-1 beta-lactamase.

Amoxicillin

Bactericidal activity of sparfloxacin and ciprofloxacin under anaerobic conditions.

The kill kinetics of sparfloxacin and ciprofloxacin have been investigated under anaerobic conditions against Bacteroides fragilis and Escherichia coli. The results for E. coli were compared with those obtained under aerobic conditions. It was found that the quinolones were bactericidal under anaerobic conditions. This bactericidal activity is inhibited by the presence of chloramphenicol, a known protein synthesis inhibitor. Filamentation was seen with B. fragilis after 2 h exposure to either agent.

Anaerobiosis

In-vitro susceptibility of Chlamydia pneumoniae (TWAR) to seven antibiotics.

A modification of an immunofluorescence method previously used to study the in-vitro antimicrobial susceptibilities of Chlamydia trachomatis was used to investigate the activity of seven antimicrobials against a strain of C. pneumoniae. Our results differed from those obtained by other workers, so we modified our original method and repeated the study. Adding antimicrobial to pre-infected cells gave higher MICs and MLCs than when cells were infected in the presence of the antimicrobials, and this difference in methodology could account for the discrepancy between our results and those of others. Of the antimicrobials studied, clarithromycin and its 14-hydroxy metabolite were the most active agents; sparfloxacin was more active than ciprofloxacin, but no more active than more conventional antichlamydial agents.

Anti-Bacterial Agents

Congestive hepatomegaly--typical features on computed tomography, ultrasound and nuclear medicine.

The features of hepatic congestion on computed tomography, ultrasound and nuclear medicine sulphur colloid scans have been reviewed. Hepatic congestion may not be appreciated clinically, especially in the elderly, but the features described should be sufficiently characteristic to establish the diagnosis. The CT appearance may be confused with neoplastic infiltration, so that recognition of the condition may avoid further unnecessary investigations.

Aged

Immediate exposed skin grafting in children's burns.

The technique of immediate exposed skin grafting following early tangential excision of burns in children overcomes the difficulties of applying dressings with the attendant risk of graft loss from shearing forces. We report on 36 patients treated by this method. Wound healing was achieved in all patients without the need for further surgery.

Burns

The multiple Y-V plasty in linear burn scar contracture release.

The technique of the multiple Y-V plasty is described. The records of all 129 patients who underwent surgery to release burn scar contractures over a 5-year period are reviewed. Halfway through this study period the multiple Y-V plasty was introduced, resulting in a marked reduction in the number of Z-plasty and skin grafting procedures carried out. There was an associated fall in the number of wound complications seen and the length of hospital stay required.

Adolescent

In-vitro comparison of the post-antibiotic effect of vancomycin and teicoplanin.

The post-antibiotic effect (PAE) of teicoplanin was compared with that of vancomycin for five selected Gram-positive cocci. Two concentrations of each antibiotic were investigated, with the test organisms being exposed to each for both 1 and 2 h. At a concentration of 25 mg/l, teicoplanin had a greater PAE than vancomycin for the methicillin resistant staphylococci and Enterococcus faecalis strains tested. At a concentration of 5 mg/l, teicoplanin gave equal effects to those of vancomycin except for the strain of methicillin-resistant Staphylococcus aureus (MRSA) tested. The variation in the antibiotic exposure time gave only small changes in the PAE, except for the MRSA tested.

Enterococcus faecalis

The pharmacokinetics and inflammatory fluid penetration of orally administered azithromycin.

The pharmacokinetics of azithromycin were determined during a 24 h period following oral administration of a single 500-mg dose to each of six male volunteers. Concentrations in serum, urine and cantharides-induced inflammatory fluid were determined by microbiological assay. The mean peak serum concentration of 0.45 mg/l was obtained at a mean time of 2.6 h post-administration. The elimination half-life from serum was seen to increase with time post-dose; the mean elimination half-life at 16 h post-dose was 9.6 h. Inflammatory fluid was penetrated rapidly, with the mean peak concentration of 0.13 mg/l achieved at a mean time of 3.25 h post-dose. After this peak, levels initially decreased, but after 8 h from drug administration until the end of the trial period, inflammatory fluid concentrations remained relatively constant. The mean inflammatory fluid penetration up to the end of the study period was 74%. The mean urinary recovery of azithromycin, during the initial 24 h post-dose, was 6%.

Administration, Oral

In-vitro activity of sparfloxacin, a new quinolone antimicrobial agent.

The in-vitro activity of sparfloxacin (AT-4140), a new difluorinated quinolone, was compared with those of ciprofloxacin, temafloxacin and selected members of other groups of antimicrobial agents, against 651 recent distinct clinical isolates and strains with known mechanisms of resistance. Three strains of Chlamydia trachomatis were also studied. The MICs for 90% of the Enterobacteriaceae were between 0.06 and 1 mg/l; for Pseudomonas aeruginosa the MIC90 was 2 mg/l. Sparfloxacin was 16-fold more active against Acinetobacter spp. than ciprofloxacin. For Staphylococcus spp., Streptococcus, spp. and Enterococcus faecalis the MIC90 was between 0.25 and 1 mg/l; sparfloxacin was four-fold more active against Str. pneumoniae than ciprofloxacin. Ninety percent of strains of Haemophilus influenzae, Branhamella catarrhalis and Neisseria spp. were inhibited by less than 0.03 mg/l; for Bacteroides fragilis the MIC90 was 1 mg/l. The three strains of Chl. trachomatis were susceptible to 0.06-0.12 mg/l sparfloxacin, which was 16-fold more active than ciprofloxacin. There was cross resistance among the quinolones, but not between the quinolones and other groups of antimicrobials. The protein binding of sparfloxacin was 40% and serum had little effect on its activity.

Anti-Bacterial Agents

Complications and protocol considerations in carbon monoxide-poisoned patients who require hyperbaric oxygen therapy: report from a ten-year experience.

We conducted a study to determine the type, incidence, and timing of complications that occur in patients who have a carbon monoxide (CO) exposure serious enough to require hyperbaric oxygen therapy (HBOT). Complication data were retrospectively collected from a ten-year period for 297 consecutive CO-poisoned emergency department patients who received HBOT. HBOT was indicated for 41% of the patients because of an elevated carboxyhemoglobin (COHb) level alone. Central nervous system dysfunction, including loss of consciousness, and/or cardiovascular dysfunction, was the criteria for HBOT in 59% of patients, regardless of their COHb level. The mean peak COHb level was 38 mg%, with 88% of patients having a peak COHb level greater than 25 mg%. The mortality rate was 6% in this case series. Cardiac arrest occurred in 8% of patients; all experienced their first arrest prior to HBOT. The 3% of patients who sustained an isolated respiratory arrest and those who had a myocardial infarction did so prior to HBOT. Several complications, however, occurred for the first time or as a recurrent event during HBOT. These included emesis (6%), seizures (5%), agitation requiring restraints or sedation (2%), cardiac dysrhythmias or arrests (2%), and arterial hypotension (2%). No patient's level of consciousness deteriorated subsequent to the initial resuscitation except for those who later had a generalized seizure. The most significant complication attributable to HBOT was tension pneumothorax, noted in three patients (1%).(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Monoxide Poisoning

Split-skin grafting in the management of extensive neuropathic ulceration.

Neuropathic foot ulceration can lead to long periods of in-patient treatment, and healing time is related to the size of the skin defect. We report a case where most of the skin was lost from the plantar surface of the foot, and healing was dramatically assisted by the application of split-skin grafts, a technique seldom considered for the treatment of diabetic foot lesions.

Diabetes Mellitus, Type 1

Emergency department screening for unsuspected carbon monoxide exposure.

Carbon monoxide (CO) is the leading toxic cause of death in the United States today. Unsuspected exposure to this gas will sometimes result in clinically significant, but undiagnosed, toxicity. A high incidence of such unsuspected exposures would make screening for these worthwhile among high-risk populations. We conducted a two-part study to determine the value of screening for unsuspected CO exposure in a population of patients presenting to an emergency department. The first part of our study involved the prospective screening of ED patients using CO breath analysis, regardless of their chief complaint. In the second part, COHGB levels of all patients who underwent arterial blood gas analysis during the study period were reviewed retrospectively. Of 1,038 patients screened by this combined approach, only 29 (2.8%) had abnormal CO breath readings and/or COHGB levels. Of a condensed subgroup of 152 patients defined retrospectively by chief complaint, eight (5.3%) had abnormal values. We conclude that routine screening of ED patients for unsuspected CO exposure is not practical. Although yield increases when patients are screened in a more selective manner on the basis of chief complaint, such an increase still does not appear to justify the screening process.

Adult