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Biomedical subjects

R C Slack

Publications and source records attributed to R C Slack.

At least 55 records · Page 3Linked to original sources

Selection of enhanced cefotaxime resistance in Enterobacter spp.

Four strains of Enterobacter spp. with different chromosomal beta-lactamase expression (inducible, constitutive or negligible) were grown in broth containing either cefoxitin or cefotaxime, then plated on to agar containing 20 mg cefotaxime per litre to quantitate the cefotaxime-resistant mutants present in the population. Spontaneous resistant mutants were initially isolated from each strain at frequencies of 10(-4) to 10(-5). These high frequencies of spontaneous mutation suggested that more than one type of mutational event could yield cefotaxime resistance. Induction of a high level of beta-lactamase in broth cultures was not in itself sufficient to confer a high level of cefotaxime resistance on the population, and increased resistance following selection of resistant mutants did not necessarily correlate with any significant increase in beta-lactamase activity.

Cefotaxime↗

Response of pharyngeal gonorrhoea to single dose penicillin treatment.

The prevalence of gonococcal infection of the pharynx in 205 women, 331 heterosexual men, and 11 homosexual men with gonorrhoea was 6.8%, 4.2%, and 27.3% respectively. In only one patient, a heterosexual man, was the pharynx the sole site of infection. Throat symptoms were found in 7% of women, 21% of heterosexual men, and none of the homosexual men. Orogenital contact was reported by 29% of women, 36% of heterosexual men, and all the homosexual men. A single intramuscular dose of 1.8 g Bicillin (procaine penicillin 1.5 g plus benzyl penicillin 300 mg) cured 90% of patients.

Adult↗

The penetration of antibiotics into the normal intervertebral disc.

The role of antibiotics in the treatment of disc-space infection is controversial. This study assessed the tissue penetration of flucloxacillin and cephradine into the normal intervertebral disc after intravenous administration of a bolus dose of antibiotic. Twenty-five discs were removed from 12 adolescent patients having anterior spinal surgery to correct scoliosis; antibiotic had been administered between 30 minutes and four hours before operation. Despite high blood levels, no antibiotic could be detected by bioassay or by high-pressure liquid chromatography (h.p.l.c.) in any of the specimens from the nucleus pulposus or the annulus fibrosus.

Absorption↗

Effect of changing selection pressures on trimethoprim resistance in Enterobacteriaceae.

The incidence of trimethoprim resistance was correlated with changes in prescription behaviour in the Nottingham area from 1978-1985. The prevalence of trimethoprim resistance among Enterobacteriaceae isolated from patients with urinary tract infection rose from 5% to 15% of total strains examined. Strains resistant to trimethoprim but susceptible to sulfamethoxazole appeared from 1980 onward and represented 35% of the total trimethoprim-resistant strains examined in 1985. Co-trimoxazole (trimethoprim + sulfamethoxazole) has been generally available for prescription in the United Kingdom since 1969, whereas trimethoprim alone was released in October 1979. By 1983, prescriptions in the form of trimethoprim alone accounted for approximately 50% (in hospitals) and 15% (in the community) of total trimethoprim usage in the Nottingham area. Although the introduction of trimethoprim alone seems to have had only a minor effect on overall resistance levels, it has greatly increased the proportion of trimethoprim-resistant strains which are susceptible to sulfamethoxazole. This was particularly evident in strains of Proteus spp., in which 52% of the total trimethoprim-resistant strains were sulfamethoxazole-susceptible in 1985.

Drug Combinations↗

Randomised observer blind comparative trial of ceftriaxone and penicillin in treating uncomplicated gonorrhoea in men and women.

Ceftriaxone is a third generation cephalosporin with a prolonged half life. It was used in doses of 500 mg intramuscularly in 27 men (group 1) and 23 women (group 2) and 250 mg in 48 men (group 3) and 45 women (group 4) with uncomplicated urogenital gonorrhoea. Similar numbers of patients in each group were treated with 2 MIU intramuscular Bicillin (procaine penicillin 1.5 g plus benzylpenicillin 300 mg (Brocades, Weybridge, Surrey, England). Success of treatment was measured as one or two negative cultures after three or more days. The success rate for ceftriaxone was 100% in 19 evaluable men and 19 women treated with 500 mg and in 38 men and 31 women treated with 250 mg, including one infection due to penicillinase producing Neisseria gonorrhoeae (PPNG). Success rates for Bicillin were 90% (19/21) evaluable patients cured in group 1, 100% (19/19) in group 2, 95% (37/39) in group 3, and 92% (33/36) in group 4. Both drugs were well tolerated. Each isolate of N gonorrhoeae isolated was sensitive to 0.05 mg/l or less of ceftriaxone.

Ceftriaxone↗

The effect of an antibiotic policy on bacterial resistance in patients in geriatric medical wards.

In an effort to reduce levels of trimethoprim resistance amongst urinary isolates and faecal organisms two antibiotic policies (policy 1, erythromycin, nitrofurantoin substituted for trimethoprim and ampicillin; policy 2, Augmentin (ampicillin + clavulinic acid) substituted for trimethoprim and ampicillin) were used for 50 weeks on two geriatric acute/rehabilitation wards. The policies were evaluated by comparison with the pre-policy period and between policies. The policies were applied successfully and both were associated with a fall in the proportion of trimethoprim-resistant faecal coliforms and urinary isolates. Policy 1 appeared to affect plasmid-mediated resistance to a greater extent than policy 2. There were no differences in outcome for patients during policy periods. Control of antibiotic usage by formal policies is a viable means of controlling bacterial resistance in geriatric wards. The mode of action of such policies requires further elucidation.

Aged↗

Bacteriology and ultrastructure of the bladder in patients with urinary tract infections.

Tissue obtained by biopsy of the bladder from 33 patients with various urinary tract symptoms was studied by conventional bacteriological techniques and by scanning electron microscopy (SEM). All the patients had recurrent urinary tract symptoms which had not completely responded to antibiotic therapy. Eleven of the patients had greater than or equal to 10(8) colony-forming units (CFU) of bacteria/1 urine; six had between 10(6) and 10(7) CFU/1, and 16 were abacteruric. Bacteria were isolated, however, from the tissue obtained by biopsy from eight of the 16 patients with sterile urine and bacteria were seen on the uro-epithelium in 14 of these patients. By comparison, in all samples of tissue obtained from the 11 patients with greater than or equal to 10(8) CFU/1 of urine bacteria were seen on the uro-epithelium and from nine of these, bacteria were subsequently grown. Fastidious organisms were not isolated from any of the patients. The uro-epithelium of all those studied was also shown to be grossly disrupted with increased disturbance and loss of the epithelial cells when compared with tissue obtained from uninfected patients. The degree of uro-epithelial disturbance was greatest in patients with histories of urinary tract infections lasting more than 4 months. The findings suggest that bacteriological examination of the urine does not always reflect bacterial infection on the bladder surface nor disruption of the uro-epithelium. The changes on the bladder surface may explain the patients' symptoms. In view of the results, a scheme is proposed that explains the development of symptoms in patients with urinary tract and bladder infections.

Adult↗

Trimethoprim resistance plasmids in Escherichia coli isolated from cases of diarrhoea in cattle, pigs and sheep.

A total of 1572 isolates of Escherichia coli obtained from the faeces of young farm animals with diarrhoea over the period 1980-1983 were screened for resistance to trimethoprim (Tp). Resistance to Tp was detected in 263/954 (28%) of bovine isolates, 59/441 (13%) of porcine isolates and 15/177 (9%) of ovine isolates. Seventy-five resistant isolates from separate outbreaks of infection on farms within a 25 mile radius of Nottingham were examined in detail. Sixty-eight (91%) of the 75 isolates were resistant to greater than 1024 mg Tp/l and 34 (50%) of these 'highly resistant' isolates (45% of total resistant isolates) transferred their Tp resistance to E. coli K12. A further 13 (17%) isolates were demonstrated to carry non-self-transferable plasmids which were capable of being mobilized to E. coli K12 by the broad host range plasmid RP4. Thirty-one self-transferable Tp R plasmids were divided between the following incompatibility groups: IncB (14 plasmids), IncFII (4 plasmids), IncH2 (1 plasmid), IncI alpha (10 plasmids), IncI delta (1 plasmid) and IncP (1 plasmid). In terms of antibiotic resistance patterns and incompatibility properties, many of these plasmids closely resembled those isolated from human patients in the same area, suggesting that there may be a common pool of Tp R plasmids.

Animals↗

Enzyme amplified immunoassay: a novel technique applied to direct detection of Chlamydia trachomatis in clinical specimens.

Endocervical swabs from 212 women and urethral swabs from 100 men were tested by the routine methods for McCoy cell culture and simultaneously by a novel enzyme amplified immunoassay test to detect chlamydia antigen. Overall correlation of the amplified test with culture was 96.5%. The test proved to be a suitable screening procedure for genital chlamydial infection, particularly for large numbers of specimens or in cases in which culture was not available.

Antigens, Bacterial↗

The use of injectable antibiotics in two general hospitals.

Injectable antibiotic use in Nottingham has shown a change in the past 3 years: the quantity of cefotaxime and cefuroxime prescribed by the end of 1983 was double that of aminoglycosides. The majority (69%) of use of the newer cephalosporins is for prophylaxis. This significant increase in use of cephalosporins has not been accompanied by an increase in bacterial resistance to cefuroxime or cefotaxime. However, these two agents cause the majority of toxin-positive antibiotic-associated diarrhoea in Nottingham hospitals.

Anti-Bacterial Agents↗

Scanning electron microscopy of human bladder mucosa in acute and chronic urinary tract infection.

The morphological response of the bladder surface to acute and chronic urinary tract infection (UTI) was investigated using both scanning and transmission electron microscopy of bladder biopsies taken during routine cystoscopy. Acute bacterial infection only minimally altered bladder epithelium, whereas in chronic infections the surface layers showed gross changes which included loss of the outer layers of epithelial cells and alteration of the bladder contour. In addition, more erythrocytes and polymorphonucleocytes were present in chronic infection. In both acute and chronic urinary infection, bacteria were confined to a limited number of sites on the bladder surface and appeared to be arranged in microcolonies, but more bacteria were attached to bladder surfaces in chronic than in acute UTI. These findings were confirmed by studying epithelial cells shed from patients with proven urinary infections. A few patients who had been treated with antibiotics before cystoscopy and biopsy were also studied. These antibiotics included cephalosporins which had been previously shown to produce bacterial morphological variations in vitro. Some of these changes were subsequently observed in the biopsies and the results suggest mechanisms whereby bacteria involved in urinary tract infection can survive exposure to antibiotics.

Acute Disease↗

Acrosoxacin in the treatment of uncomplicated gonorrhoea.

Acrosoxacin was given as a single 300 mg oral dose to 105 patients with acute gonorrhoea. Of the 100 patients followed completely there was a 93% cure rate and 33% of men developed postgonococcal urethritis (PGU). This compared with a 97% cure and 30% PGU with 2 megaunits penicillin. The in vitro activity of acrosoxacin in Nottingham against strains of Neisseria gonorrhoeae showed that it was a highly active agent with 90% of strains inhibited by a concentration of 0.03 mg/l.

4-Quinolones↗

The antibacterial activity of hexamine (methenamine), hexamine hippurate and hexamine mandelate.

The antibacterial activity of hexamine and two of its organic acid salts was compared by continuous turbidimetric monitoring of static cultures exposed to the drugs and in an in vitro model of the treatment of bacterial cystitis. At pH 5.5, concentrations of 32 to 125 mg hexamine per 1 caused some inhibition of bacterial growth, but 250 to 500 mg/l were needed to suppress growth overnight. Hexamine hippurate was found to be less active than hexamine itself, whereas hexamine mandelate was as active as the parent compound. The antibacterial effect was not inoculum dependent over the range 10(6) to 10(8) bacteria per ml, but the activity observed in pooled urine was rather less than that found in broth at the same pH. When a dense bacterial culture was exposed to changing concentrations of hexamine compounds in the bladder model, a 1 g dose infused over a 12-hour period suppressed bacterial growth for 16 to 20 hours. No systematic difference was found in the activity of the three hexamine compounds, but a similar effect was achieved by a very much lower concentration of ampicillin.

Ampicillin↗