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Objective: We previously reported on the ability of SurgihoneyRO (SHRO), an engineered honey, to prevent biofilm formation in vitro, but data were lacking regarding the activity against preformed biofilms. This study aims to assess whether SHRO has any antibacterial activity against mature, preformed biofilms and whether there is any evidence to support the observed clinical effectiveness when SHRO has been used anecdotally on acute and chronic wounds where biofilm is most likely present. Method: We tested the in vitro antibacterial activity of SHRO against the mature biofilms of 16 clinically relevant wound pathogens, in terms of impacts on biofilm seeding and biofilm biomass. The honey was serially double diluted from 1:3 down to 1:6144, and the lowest dilution achieving a statistically significant reduction in biomass of >50%, compared with untreated controls, was recorded. Results: All 16 bacterial isolates were susceptible to SHRO, with reduced biofilm seeding observed for all, and percentage reductions ranging from 58% (ACI_C59) to 94.3% (MDR_B) for the strongest concentration of honey (1:3). Furthermore at this concentration, biofilm seeding of the test biofilm was reduced by 80-94.3% (when compared with the positive control) for 12/16 isolates. We additionally demonstrated that SHRO has antibiofilm impacts, with the 24 hour exposure resulting in disruption of the biofilm, reduced seeding and reduced biomass. Conclusion: SHRO is effective at reducing seeding of preformed biofilms of clinically important wound pathogens in vitro, and also has antibiofilm activity. This supports the anecdotal clinical data for antibiofilm efficacy, and supports the use of SHRO as a promising topical wound care agent. Declaration of interest: None to declare. This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not of the NHS, the NIHR or the Department of Health. [ABSTRACT FROM AUTHOR] more...

* Objective: Honey is recognised to be a good topical wound care agent owing to a broad-spectrum of antimicrobial activity combined with healing properties. Surgihoney RO (SH I) is a product based on honey that is engineered to produce enhanced reactive oxygen species (ROS) and has been reported to be highly antimicrobial. The objective was to investigate the ability of the engineered honey and its comparators to prevent biofilm formation in vitro. * Method: We tested the ability of three medical-grade honeys SH I, Activon manuka honey (MH) and Medihoney manuka honey (Med), alongside five antimicrobial dressings (AMDs) to prevent the formation of biofilms by 16 isolates. Honeys were serially double diluted from 1:3 down to 1:6144 and the lowest dilution achieving a statistically significant reduction in biomass of at least 50%, compared with untreated controls, was recorded. * Results: Although all the honeys were antibacterial and were able to prevent the formation of biofilms, SH I was the most potent, with efficacy at lower dilutions than the medical honeys for five isolates, and equivalent dilutions for a further six. Additionally, SH I was superior in antibacterial potency to three commercially available AMDs that contain honey. * Conclusion: SH I is effective at preventing biofilms from forming and is superior to medical honeys and AMDs in in vitro tests. [ABSTRACT FROM AUTHOR] more...

The aim of this study was to review the characteristics and outcome of 21 patients with invasive mucormycosis treated with amphotericin B colloidal dispersion (ABCD) in five phase I and phase II studies. Mucormycosis is an increasing concern in immunocompromised patients, in whom mortality exceeds 60%. The standard treatment has been amphotericin B combined with surgical debridement. Twenty-one patients with invasive mucormycosis treated with ABCD, a lipid complex of amphotericin B and cholesteryl sulfate, were identified. Patients were given ABCD on the basis of pre-existing renal insufficiency, development of nephrotoxicity during amphotericin B therapy, or fungal infection that failed to respond to amphotericin B. Response could be evaluated in 20 patients, all of whom had bone marrow or organ transplantation, haematologic malignancies, or diabetes. Infection was disseminated in six patients and localised to the sinuses, lower respiratory tract, or skin in the other patients. ABCD was given at a mean dose of 4.8 mg/kg per infusion for a mean duration of 37 days. Twelve of 20 patients responded to ABCD therapy. Response rates were similar when patients were treated with ABCD alone (4/7) and ABCD combined with surgery (8/13), with more complete response obtained in the latter group. No difference in response rate was observed in leukaemic patients (3/5) or transplant recipients (6/10) compared to diabetics (3/5). No renal or hepatic toxicity was observed. These results compare favourably with the results of standard treatment and suggest that ABCD combined with surgery may be a useful therapy in patients with mucormycosis. [ABSTRACT FROM AUTHOR] more...

Potential risk factors for CMV infection and the use of quantitative CMV PCR screening to guide pre-emptive anti-CMV therapy were reviewed retrospectively in 32 allogeneic bone marrow transplant patients accrued over a 2-year period. Significant CMV PCR positivity (an indicator of CMV infection) developed in 34% of patients. When analysed by recipient CMV IgG serostatus, 69% of seropositive recipients developed significant CMV PCR positivity while none of the seronegative recipients did so (P = 0.00007). Considering only the seropositive recipients, 100% of those who received the low intensity campath-1H/fludarabine/melphalan ‘mini-allograft’ conditioning regimen developed significant CMV PCR positivity, while only 44% of those who had received cyclophosphamide/TBI did so (P = 0.0337). The mean time to first episode of significant CMV PCR positivity for those who had received campath/fludarabine/ melphalan was 25 days while for those who had received cyclophosphamide/TBI, this was 66 days (P = 0.0372). For the first episode of significant CMV PCR positivity, the mean index and peak CMV PCR counts for those who had received campath/fludarabine/melphalan were 4.54 and 5.22 log copies/ml respectively, while for cyclophosphamide/TBI, the corresponding figures were 3.85 and 4.12 log copies/ml respectively (P = 0.2986 and P = 0.0472 for index and peak values). 85% of those who had significant CMV PCR positivity with the campath/fludarabine/melphalan regimen developed more than one such episode, while 50% of those receiving cyclophosphamide/TBI regimen did so (P = 0.491). Significant CMV PCR positivity was associated with symptoms in a proportion of patients (pyrexia 45%, cough 18%, rise in AST 72%). No patient developed overt CMV disease. CMV PCR is useful for guiding pre-emptive anti-CMV therapy and for monitoring response. Bone Marrow Transplantation (2001) 27, 301–306. [ABSTRACT FROM AUTHOR] more...

The activities of cefpirome, cefotaxime, ceftazidime and ceftriaxone were compared against laboratory and clinical strains of Pseudomonas aeruginosa. Isolates with well characterised resistance mechanisms were included. Against carbenicillin-susceptible isolates cefpirome was more active than cefotaxime and ceftriaxone, but less active than ceftazidime. The activity of all four cephalosporins was impaired against isolates that had increased intrinsic (i.e. non-beta-lactamase-mediated) carbenicillin resistance. However, cefpirome and ceftazidime, unlike the other compounds, remained active at less than 16 mg/l against such strains, whereas cefotaxime and ceftriaxone largely failed to do so. Cefpirome maintained full activity against most isolates with plasmid-mediated beta-lactamases, as did the other cephalosporins. Transconjugant studies indicated that only LCR-1 and PSE-2 enzymes could protect P. aeruginosa against cefpirome. Isolates with partial or total chromosomal beta-lactamase derepression were highly resistant to cefotaxime and ceftriaxone (MIC greater than 128 mg/l) but only those with total derepression were resistant (MIC 16-32 mg/l) to cefpirome and ceftazidime, while those with partial derepression were sensitive to 4-8 mg/l of the latter antibiotics. Comparison of cefpirome MICs for totally-derepressed P. aeruginosa and their enzyme-deficient mutants indicated that chromosomal beta-lactamase gave less protection against cefpirome than against other cephalosporins tested. Cefpirome was a weak inducer of class I beta-lactamases. Overall, therefore, cefpirome behaved similarly to ceftazidime against the different P. aeruginosa resistance types. [ABSTRACT FROM AUTHOR] more...

To assess the possible role of endotoxaemia in the pathogenesis of sudden infant death syndrome (SIDS), antibodies to endotoxin core (EndoCAb), which have previously been shown to be depressed by systemic endotoxaemia, were measured. IgG and IgM EndoCAb and total serum IgG and IgM were measured in serum samples from 25 children who had died from SIDS and 164 control children under 1 year of age. Twelve (48%) of the 25 children who had died from SIDS had no detectable IgG EndoCAb compared with 28 (17%) of the 164 control children, and this difference was concentrated in children aged less than 3 months. There was no significant difference between the two groups in the percentage of children with no IgM EndoCAb, nor in the total IgG and IgM concentrations. For IgM EndoCAb, the younger children who had died from SIDS had higher concentrations than the controls. These results suggest that, in children who have died from SIDS, due to either unusually early or severe exposure to endotoxin, maternal IgG EndoCAb have been depleted and early IgM EndoCAb triggered. [ABSTRACT FROM AUTHOR] more...

Four consecutive patients with relapsing peritonitis due to coagulase-negative staphylococci have been successfully treated by the addition of urokinase to their treatment regime, having failed to respond to appropriate antibiotic therapy alone. The organisms isolated from each episode of peritonitis in an individual patient were shown to be identical by antibiotic sensitivity, phage typing, slime production and immunoblot analysis. The action of urokinase is unknown but it may act by fibrinolysis, allowing antibiotics access to a source of infection previously protected by fibrin. The technique described is a simple, safe and effective treatment of relapsing peritonitis due to coagulase-negative staphylococci, and its use can markedly reduce the morbidity associated with this infection. [ABSTRACT FROM PUBLISHER] more...

The twin register of the Maudsley Hospital was used to select a series of monozygotic (MZ) and same-sexed dizygotic (DZ) twins who had been given an ICD8 diagnosis related to alcoholism. They and their co-twins were traced. Medical and drinking histories were compiled (from records and by interview) for 56 twin-pairs, to permit current and retrospective diagnosis of any neurotic disorders. RDC diagnoses of panic disorder, generalised anxiety disorder, obsessive-compulsive disorder and phobias were more common in the alcoholic probands and the co-twins who were also alcoholics than in the normal-drinking co-twins. The Eysenck Personality Questionnaire (EPQ) and the Severity of Alcohol Dependence Questionnaire (SADQ) were completed by 54 individuals. Neuroticism scores were significantly higher for both male and female alcoholics than for their normal-drinking co-twins; and intra-pair differences in neuroticism were significantly correlated with intra-pair differences in severity of dependence. These results suggest that both clinically diagnosed neurotic illness and high neuroticism scores are more often a consequence than a cause of alcoholism. [ABSTRACT FROM AUTHOR] more...

The effect of L-deprenyl in combination with L-Dopa was studied in 22 Parkinsonian patients, with various forms of 'on-off' phenomena. L-deprenyl is a selective, irreversible inhibitor of monoamine oxidase type B, without tyramine potentiating property. The results were very encouraging with regard to amelioration of 'on-off effect'. More than 80% of the patients with nocturnal akinesia, early morning akinesia, end-of-dose akinesia and non-dose-dependent akinesia, showed improvement. In 9 out of 22 patients, the 'off' period disappeared. The platelet monoamine oxidase activity, which is of type B and similar to the brain enzyme, was fully inhibited by the daily dose of L-deprenyl. There was no significant change in serum prolactin level during the duration of 6 weeks' treatment with L-deprenyl. [ABSTRACT FROM AUTHOR] more...

1 Enhancement of platelet aggregation response (PAR) to 5- hydroxytryptamine (5-HT) in some schizophrenic patients receiving chlorpromazine (CPZ) may provide a biological index for the efficacy of this drug. 2 In a double-blind study 33 schizophrenic patients hospitalized following their first psychotic breakdown were followed up clinically with concurrent assessment of their PAR to 5-HT. The patients followed a standardized treatment schedule with (CPZ) as the sole antipsychotic medication. 3 Twelve patients (Group A) developed an enhanced biphasic 5-HT PAR, within 2-3 weeks and improved clinically by the sixth week. In most cases, the appearance of the enhanced biphasic PAR preceded clinical improvement. Twenty-one patients (Group B) did not have enhanced biphasic PAR to 5-HT by the sixteenth week of treatment. However, twelve subjects from this group showed clinical response to CPZ by the end of this period, while the remaining patients did not improve. 4 The enhanced PAR to 5-HT in Group A discriminated best between good and bad outcome cases when Feighner's research diagnostic criteria were used. We could not confirm the previous reports of platelet aggregation response to dopamine in pre- or post- chlorpromazine treatment. [ABSTRACT FROM AUTHOR] more...

Liposomal amphotericin (AmBisome) 2 mg/kg three times weekly was compared with placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation (BMT) for haematological malignancies. Prophylaxis began on day 1 of chemotherapy and continued until neutrophils regenerated or infection was suspected. Of 161 evaluable patients, 74 received AmBisome and 87 received placebo. Proven fungal infections developed in no patients on AmBisome and in three on placebo (3.4%) (P = NS). Suspected fungal infections requiring intervention with systemic antifungal therapy (usually amphotericin B) occurred in 31 patients on AmBisome (42%) and in 40 on placebo (46%) (P = NS). Suspected deep-seated infections developed in 21 (28.3%) and 31 (35.6%) patients, respectively (P = NS). Time to develop a suspected or proven deep-seated infection showed a trend in favour of AmBisome (P = 0.11). Fifty patients had fungal colonisation (48 with Candida spp, two with Aspergillus spp) of at least one body site during prophylaxis; 15 patients while receiving AmBisome (20%) and 35 while on placebo (40%) (P < 0.01). time to colonisation was significantly delayed in the group receiving ambisome (P < 0.05). treatment-related toxicity was modest and no additional toxicity was observed in patients receiving ambisome. ambisome 2 mg/kg three times weekly is safe and reduces fungal colonisation in patients receiving intensive chemotherapy or bmt. however, despite encouraging trends, prophylactic ambisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy. [ABSTRACT FROM AUTHOR] more...

AIMS: To develop techniques for the characterisation of toxins elaborated by a strain of Escherichia coli associated with sudden infant death syndrome (SIDS). METHODS: E coli SIDS 04, isolated from the nasopharynx of a case of SIDS, was studied. Cell-free toxin preparations were standardised, their protein measured, and analytical separation of proteins achieved using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Acetone precipitation of proteins was required prior to Coomassie blue staining of bands. Preparative separation was achieved on an anion exchange column using a programmed concentration gradient of NaCl in TRIS buffer. Fractions were tested individually or pooled for presence of lethal toxin including endotoxin. Lethal toxin was detected with the chick embryo test system. Endotoxin was measured using a chromogenic modification of the Limulus amoebocyte assay. RESULTS: Twenty one peaks were detected by chromatography. Ten individual, or pooled, fractions were assayed for endotoxin which ranged from 27-33 pg/ml. Much greater variation was found when the same fractions were assayed in chick embryos. E coli fractions varied considerably in lethal toxicity, from 0/10 to 10/10 chick embryos killed/tested. Certain E coli fractions tested individually (lethality four out of 10 to eight out of 10) proved more lethal (10 out of 10) if pooled prior to testing. CONCLUSIONS: In E coli infection associated with SIDS relatively low concentrations of extracellular protein are lethally toxigenic for the chick embryo model of SIDS. These proteins can be separated analytically by SDS-PAGE and preparatively by anion exchange chromatography. Toxicity of individual fractions is not correlated with endotoxin concentrations in samples tested. [ABSTRACT FROM PUBLISHER] more...

AIM: To test the hypothesis that sudden infant death syndrome (SIDS) may be caused by toxins of commonly occurring bacteria in infants lacking developed immunity. METHODS: Nasopharyngeal microbial isolates from 22 pairs of SIDS cases and healthy infants matched for age (by month), sex, and sampling time (by month) were compared for lethal toxigenicity. Crude toxin preparations were made from isolates cultured on dialysis membrane overlaid on agar, and these preparations were then tested for lethality by intravenous injection into 11 day old chick embryos. RESULTS: Fifteen (68%) of the SIDS cases were each found to have at least one lethally toxigenic organism in their nasopharyngeal flora; only eight (36%) of the flora of normal infants included a lethally toxigenic species. CONCLUSION: Infants who have died of SIDS have a significantly higher (p less than 0.05) probability than matched healthy infants of having a lethally toxigenic bacterial species in their nasopharyngeal flora. [ABSTRACT FROM PUBLISHER] more...

The hypothesis that the prone sleeping position is associated with accumulation of upper airways secretions and increased bacterial growth was investigated in adults. Ten subjects with upper respiratory tract infection lay prone for one hour and then supine for one hour. Nasal swabs after the prone period yielded higher bacterial counts than swabs obtained after the supine period. This result could be relevant to sudden infant death syndrome (SIDS), as infants who sleep in the prone position are at increased risk of SIDS and one theory is that death is caused by toxins produced by bacterial overgrowth in the upper respiratory tract following a viral infection. [ABSTRACT FROM PUBLISHER] more...

Neomycin blood agar is commonly used as a selective medium for the isolation of vancomycin resistant enterococci from faeces; however, not all isolates are recovered using this medium, perhaps because the neomycin concentrations are too high. To test this hypothesis, the neomycin minimum inhibitory concentration (MIC) was determined for 27 vancomycin resistant Enterococcus faecium isolates, 14 from patients with leukaemia and 13 from patients on the renal unit. A further eight isolates that had been recovered from the faeces of patients on the renal unit on neomycin agar were also studied. Eleven of the 14 isolates from the patients with leukaemia showed equal recovery on neomycin agar and blood agar and had MICs > 64 mg/l. In three other isolates there was a 4log10 reduction in recovery on neomycin agar and the MIC was 8 mg/l. Two of the non-selected isolates from the renal unit were recovered equally on the two media, the other 11 isolates showed a 4-5 log10 reduction in recovery. All eight faecal isolates recovered from patients on the renal unit on neomycin agar were highly resistant to neomycin (MIC > 64 mg/l). Comparative studies of screening media are urgently needed as vancomycin resistant enterococci become more prevalent nosocomial pathogens. [ABSTRACT FROM PUBLISHER] more...

This audit of 408 synovial fluid samples, analysed for cell counts and crystals, revealed that crystals were present in only 25 samples (6.1%). Of these, in only three patients was the diagnosis uncertain and therefore the analysis helpful. Cell counts and types generally reflected known underlying diagnoses of inflammatory arthritis or osteoarthritis. Routine synovial fluid analysis does not contribute to diagnosis or management in established rheumatic disorders and should be performed only when the underlying cause is uncertain or in newly presenting patients. Major savings can be made by abandoning routine synovial fluid analysis. [ABSTRACT FROM AUTHOR] more...

We report a case of septicaemia and muscle abscesses due to Aeromonas hydrophila. The patient was immunosuppressed due to Hodgkin's disease and treatment with cytotoxic chemotherapy. The abscesses resolved after prolonged antibiotic therapy. Organisms that were once considered rarely pathogenic are emerging as increasingly important in causing potentially lethal infections in immunosuppressed patients. [ABSTRACT FROM PUBLISHER] more...

An estimated third of rheumatologists send aspirated synovial fluid samples for culture routinely during the course of management of their patients irrespective of the underlying diagnosis. This is done apparently even when sepsis is not suspected. This audit of 507 synovial fluid culture requests revealed that positive bacterial growth was rare even when sepsis was queried on the request forms but none was positive in any of the routine samples. Our findings throw doubt on the value of routine synovial fluid culture. We recommend that such cultures are undertaken when infection is a possibility and in immuno-compromised patients. An average health district would save pounds 3000 per annum if such a policy was adopted, but across the National Health Service as a whole the total expenditure saved on this unnecessary investigation would be considerable. [ABSTRACT FROM PUBLISHER] more...

The AromaScan system was used to analyse vaginal swabs from 68 women attending a genitourinary clinic. Using clinical criteria, subjects were assessed for bacterial vaginosis. After training the AromaScan system to recognise patterns generated from four patients with and four patients without bacterial vaginosis, 16 of the 17 (94%) remaining subjects were correctly identified as having the condition. The positive predictive value of the test was 61.5%. These results indicate that the AromaScan technology may be of value as a screening test for bacterial vaginosis. [ABSTRACT FROM PUBLISHER] more...

The potential antimicrobial activity of cyclophosphamide, vincristine, and adriamycin against Gram positive and negative bacteria and Candida albicans was examined. The time taken for different microbial inocula to turn a simulated blood culture positive in the presence of different concentrations of these drugs was measured. Doxorubicin retarded the growth of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus sanguis in a concentration dependent manner. Cyclophosphamide and vincristine showed minimal antimicrobial activity. Escherichia coli and Pseudomonas aeruginosa were unaffected by any of the drugs. An inoculum dependent effect was seen with some combinations of microbial inocula and cytotoxic drug concentrations. [ABSTRACT FROM PUBLISHER] more...