Fungal infections: guidelines for reporting. PHLS Mycology Committee.
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Biomedical subjects
Publications and source records attributed to I D Farrell.
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In the spring of 1989 the largest outbreak of acute Q fever recorded in the United Kingdom occurred in Solihull and surrounding areas of the West Midlands. The diagnosis was confirmed in 147 people, mainly males of working age. Windborne spread from farmland to the south of the urban area was the most likely route of infection. Fever was the commonest symptom, seen in 101/102 (99%) cases, followed by weight loss reported by 83/101 (82%). Headache, often severe, was experienced by 69/101 (68%). The commonest respiratory symptom was breathlessness, 65/102 (64%), followed by cough, 52/102 (51%), and chest pain, 46/102 (45%). Neurological features, seen in 23% of cases, were more prominent in this outbreak than is commonly recognized. Persisting ill health 6 months following the acute episode not due to chronic Q fever was also a prominent feature of this largely urban outbreak.
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Of 147 patients with acute Q fever diagnosed during a major outbreak in Birmingham, England, in early summer 1989, 41 provided sets of sera which allowed us to make a detailed analysis of the primary humoral immune response. Antibody titers specific for Coxiella burnetii were measured by the complement fixation test and by an immunoglobulin M (IgM)- and IgG-specific indirect immunofluorescence test. The relative avidity of specific IgGs was determined by the indirect immunofluorescence test with and without treatment of antigen-antibody complexes with 8 M urea. The IgG subclass responses after primary infection and their avidities were also determined for a limited number of paired serum specimens. Specific IgM titers persisted for more than 6 months in the majority of cases and were therefore not a sufficient criterion for the diagnosis of recent infection. However, for serial samples the antibody titer ratios (IgG/IgM) and the ratios (IgG titer with treatment/IgG titer without treatment) that indicated relative avidity changed significantly, depending on the time postinfection. Within the IgG class, the C. burnetii-specific antibody response over time was almost exclusively represented by subclass 1 molecules, which thus showed affinity maturation.
A large outbreak of Legionnaires' disease was associated with Stafford District General Hospital. A total of 68 confirmed cases was treated in hospital and 22 of these patients died. A further 35 patients, 14 of whom were treated at home, were suspected cases of Legionnaires' disease. All these patients had visited the hospital during April 1985. Epidemiological investigations demonstrated that there had been a high risk of acquiring the disease in the out patient department (OPD), but no risk in other parts of the hospital. The epidemic strain of Legionella pneumophila, serogroup 1, subgroup Pontiac 1a was isolated from the cooling water system of one of the air conditioning plants. This plant served several departments of the hospital including the OPD. The water in the cooling tower and a chiller unit which cooled the air entering the OPD were contaminated with legionellae. Bacteriological and engineering investigations showed how the chiller unit could have been contaminated and how an aerosol containing legionellae could have been generated in the U-trap below the chiller unit. These results, together with the epidemiological evidence, suggest that the chiller unit was most likely to have been the major source of the outbreak. Nearly one third of hospital staff had legionella antibodies. These staff were likely to have worked in areas of the hospital ventilated by the contaminated air conditioning plant, but not necessarily the OPD. There was evidence that a small proportion of these staff had a mild legionellosis and that these 'influenza-like' illnesses had been spread over a 5-month period. A possible explanation of this finding is that small amounts of aerosol from cooling tower sources could have entered the air-intake and been distributed throughout the areas of the hospital served by this ventilation system. Legionellae, subsequently found to be of the epidemic strain, had been found in the cooling tower pond in November 1984 and thus it is possible that staff were exposed to low doses of contaminated aerosol over several months. Control measures are described, but it was later apparent that the outbreak had ended before these interventions were introduced. The investigations revealed faults in the design of the ventilation system.
The colonization, survival and control of Legionella pneumophila in a hospital hot-water system was examined. The organism was consistently isolated from calorifier drain-water samples at temperatures of 50 degrees C or below, despite previous chlorination of the system. When the temperature of one of two linked calorifiers was raised to 60 degrees C, by closing off the cold-water feed, the legionella count decreased from c. 10(4) c.f.u./l to an undetectable level. However, 10 min after turning on the cold-water feed which produced a fall in calorifier temperature, the count in the calorifier drain water returned to its original level. Investigations revealed that the cold-water supply was continually feeding the calorifiers with L. pneumophila. Simple modifications in the design of the system were made so that the cold-water feed no longer exceeds 20 degrees C; these measures have considerably reduced the number of L. pneumophila reaching the calorifiers.
The combinations of erythromycin with rifampicin, with ciprofloxacin or with amoxycillin, and ciprofloxacin plus rifampicin were tested by the time-kill curve method to assess their bactericidal activity against Legionella pneumophila. Rifampicin-resistant strains were found in broth cultures of the micro-organism even before exposure to the drug. In the presence of MBCs of rifampicin, the sensitive organisms were killed, allowing the resistant mutants to multiply. In broths containing both erythromycin and rifampicin, the rifampicin-resistant mutants were killed more rapidly than by erythromycin alone. In addition, erythromycin was effective in preventing the growth of amoxycillin- and ciprofloxacin-resistant organisms. Fortunately resistance to erythromycin was not detected by these time-kill studies. Thus for patients with severe forms of Legionnaires' disease, erythromycin should be combined with other more inhibitory drugs, such as rifampicin or ciprofloxacin, to enhance bactericidal activity.
Enterococcus (Streptococcus) faecalis expresses three species-specific surface protein antigens of molecular weights 73,000, 40,000, and 37,000. On Western blotting (immunoblotting), they were detected strongly by immunoglobulin G (IgG) in sera from patients with E. faecalis endocarditis, but not in sera from patients with other E. faecalis infections or with endocarditis due to other streptococci. We developed an enzyme-linked immunosorbent assay system to measure IgG, IgM, and IgA levels to these antigens and evaluated its potential as a serodiagnostic test for E. faecalis endocarditis. The test correctly diagnosed E. faecalis endocarditis in 15 of 16 cases. Of 10 cases of endocarditis due to other streptococci and 10 E. faecalis infections other than endocarditis, 9 and 8, respectively, gave negative results. The test should prove particularly useful in culture-negative cases, for which choice of appropriate antibiotic therapy for E. faecalis endocarditis is vital.
Three patients with pyogenic liver abscesses had actinomycetes cultured from aspirated pus, although it is unusual for hepatic actinomycosis to present in this way. The spectrum of bacteria found in liver abscesses appears to be changing, with the increased isolation of anaerobes partly due to improved techniques. It is important to recognise the presence of actinomycetes so that appropriate chemotherapy can be given.
A point source outbreak of haemorrhagic colitis due to Escherichia coli O 157.H7 producing verocytotoxin (VT), took place following a christening party in Birmingham in June 1987. Twenty-six people were affected, six were admitted to hospital and one developed haemolytic uraemic syndrome: there were no deaths. VT + E. coli O 157.H7 was isolated from 13 (57%) of 23 faecal specimens from affected people and from 3 (9%) of 33 specimens from asymptomatic people. Free VT was detected in the faeces of one further asymptomatic person. Illness was associated with eating turkey-roll sandwiches (P less than 0.001) suggesting that cold meats might be an important source of infection.
Aztreonam, the first available monobactam, was used to treat 38 episodes of serious infection presumed or proven to be due to aerobic Gram-negative bacteria. On 15 occasions it was used empirically in combination with other antibiotics and on 23 occasions as therapy specifically directed against Gram-negative pathogens. Thirty-six Gram-negative infections were documented (including 23 septicaemias) and 35 of them were clinically cured by aztreonam. Likewise 35 of the 36 aerobic Gram-negative pathogens were eradicated. Both of the failures (one clinical and one microbiological were Salmonella infections). No major toxicity was seen but there were five superinfections (four due to Streptococcus faecalis). The results indicate that aztreonam is a useful alternative to the aminoglycosides or the broad-spectrum beta-lactam antibiotics for the treatment of severe Gram-negative infections.
Forty-six episodes of fever in 34 patients with neutropenia and haematological malignancy were treated empirically with a combination of ciprofloxacin and vancomycin. Improvement or temporary improvement was seen in 86% of evaluable episodes, and 75% of bacteraemias improved. There was no difference in the response rate between infections due to Gram-negative and those due to Gram-positive organisms, despite the fact that MICs for ciprofloxacin for Gram-negative organisms were generally much lower. Pharmacokinetic data were obtained from five patients while receiving iv ciprofloxacin and after conversion to the oral form of the drug. The mean plasma half life on 200 mg iv was 5.7 +/- 1.7 h and mean plasma clearance 389 ml/min. The peak serum level after 750 mg orally was 3.6 +/- 2.2 mg/l and occurred between 1 and 3 h.
We describe a method for the serodiagnosis of Streptococcus faecalis in infective endocarditis which could be of value in culture-negative cases. Serum-grown cells of S. faecalis produced three major characteristic protein antigens (73,000, 40,000, and 37,000 molecular weight) which were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of solubilized whole cells. After electrophoretic transfer to a nitrocellulose membrane, these antigens were visualized by probing with serum from patients with endocarditis caused by S. faecalis. Serum from patients with endocarditis caused by other organisms did not react with the S. faecalis-specific antigens. This procedure should facilitate positive early diagnosis of S. faecalis endocarditis or establish its absence in culture-negative cases.
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Twenty-four episodes of fever in neutropenic patients with haematological malignancy were treated with ciprofloxacin. In 13 episodes ciprofloxacin was used after failure of first-line antibiotic therapy, and in 11 episodes because of a history of allergy to the proposed first line antibiotics. Improvement or temporary improvement was seen in 64% of patients with evaluable infection. Fifty per cent of patients with bacteraemia improved. Resistance to ciprofloxacin developed in strains of staphylococci and streptococci, but Gram-negative organisms were generally extremely sensitive to the antibiotic. One patient developed a severe photosensitivity rash but there were no other adverse reactions. Preliminary pharmacokinetic data were obtained following intravenous infusion of 400 mg of ciprofloxacin in five patients. The mean plasma half-life was 3.6 +/- 1.0 h and the mean plasma clearance was 8.42 +/- 2.5 ml/min/kg.
The antigenic composition of an endocarditis-associated isolate of Streptococcus faecalis was studied by immunoblotting of whole cells and cell walls from sodium-dodecyl sulphate polyacrylamide gels on to nitrocellulose and detection with serum from patients and hyperimmune rabbit serum. A major envelope protein antigen of mol. wt 53 X 10(3) detected with patient's serum was also present in three urinary strains of Str. faecalis and a laboratory strain of Str. faecalis ss. zymogenes but not in Staphylococcus aureus. Other common antigens of Str. faecalis were of mol. wt (10(3)) 65, 63, 56, 49.5, 30 and 21. Two other protein antigens (43 and 37 X 10(3) mol. wt) reacted strongly with asparagus pea lectin-peroxidase conjugate indicating the presence of fucosyl residues. Other lectin-peroxidase conjugates were used to demonstrate the presence of various glycosyl residues on envelope proteins. Growth of Str. faecalis in serum to mimic in-vivo growth conditions in endocarditis infections dramatically altered the antigenic patterns. Only two major antigens of mol. wt (10(3)) 56 and 53 reacted with sera from endocarditis patients. These antigens may, therefore, be of diagnostic or protective potential.