Long-term management after splenectomy. ... and may be ineffective.
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Biomedical subjects
Publications and source records attributed to R G Finch.
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Resistant peritonitis in continuous ambulatory peritoneal dialysis (CAPD) is an indication for catheter removal, followed by interim haemodialysis and subsequent catheter replacement. This involves two surgical procedures using general anaesthetic and the availability of adequate hospital haemodialysis facilities. Urokinase is an alternative therapy but evidence of its effect is anecdotal and it has not been studied in a double-blind manner. Patients with resistant peritonitis (either no resolution of peritonitis within 4 days of appropriate antibiotic therapy or a third episode of peritonitis within 6 months) were randomized to receive intraperitoneal urokinase or placebo (saline) followed by 14 days of antibiotics in this double-blind prospective study. Treatment success was resolution of peritonitis within 4 days of giving urokinase/placebo (persistent infection) and no recurrence with the same organism for 6 months (recurrent infection). Twelve patients received urokinase and 12 placebo. Treatment was successful in 8/12 in the urokinase group and 1/12 in the placebo group (Fisher's exact test; P = 0.0047). Urokinase was successful in 8/12 patients with resistant peritonitis and significantly better than placebo. Urokinase is an effective and simple treatment that may avoid the need for catheter removal and interim haemodialysis in patients with resistant CAPD peritonitis.
The course of primary Giarda muris infections was studied in H-2 congenic strains of mice on the BALB and C57BL/10 (B10) genetic backgrounds. Infection was curtailed more rapidly in B10 strains, compared with BALB strains, and unaffected by H-2 haplotype. On the other hand the duration of infection in BALB strains did vary with H-2 haplotype with BALB/B(H-2b) mice taking significantly longer to clear infection than BALB/c(H-2d) and BALB/K(H-2k) mice. These experiments demonstrate that both MHC and non-MHC genes influence the outcome of primary G.muris infections.
The presence of pneumococcal capsular antigen (PCA) in the oropharynx was sought in subjects without respiratory tract infection. Saliva specimens from 239 subjects were analysed by counter-current immunoelectrophoresis using 'Omniserum'. 15.5% gave positive reactions but only 24% of positive samples were typable and therefore due to pneumococcal or pneumococcal-like antigens. Given that oropharyngeal production of antigens occurs we investigated whether PCA in expectorated sputum arose from oropharyngeal contamination. Sixteen patients with pneumococcal pneumonia, and with sputum positive for PCA, were investigated in detail. On the basis of serotyping and concentration the PCA in sputum was thought to arise from the lower respiratory tract in all cases. This was confirmed by a simple, novel approach involving the comparison of concentrations in concomitant samples of saliva and sputum. Thus while oropharyngeal production of antigens poses a potential diagnostic problem the latter approach can be used to exclude contamination.
The clinical and bacteriological efficacy and safety of the antibiotics ceftazidime or imipenem/cilastatin in seriously ill patients with nosocomial infections were compared in a prospective, open, evaluator-blind, multicentre comparative trial. The study was performed in 26 European centres, the majority being intensive care units. Subjects were randomized to receive either ceftazidime 2 g bid or imipenem cilastatin 0.5 g qid given for at least five days after stratification for pneumonia, septicaemia or urinary tract infection (UTI). Three hundred and ninety-three patients with serious nosocomial infections (254 with pneumonia; 91 with septicaemia and 48 UTI were treated between February 1988 and January 1990 and their clinical and bacteriological response to antibiotic treatment assessed. There were no significant differences between ceftazidime and imipenem/cilastatin in clinical efficacy. The failure rates in evaluable patients were 22 and 26% in pneumonia, 23 and 19% in septicaemia and 0 and 5% respectively in those with UTI. Overall there was no significant difference between the two antibiotics for bacteriological response in the three infection strata. However, in patients with pneumonia ceftazidime was significantly more effective than imipenem/cilastatin in clearing patients of Pseudomonas spp.: 3/17 and 11/19 patients respectively had persistent growth of Pseudomonas spp. post-treatment (P = 0.004), and in one ceftazidime failure resistance emerged compared to six imipenem/cilastatin failures in which resistance emerged. Few drug-related adverse events were recorded in either treatment group. Monotherapy with either ceftazidime (2 g bid) or imipenem/cilastatin (0.5 g qid) is safe and effective and could be considered as an alternative to combination therapy for the treatment of serious hospital-acquired infections.
Cryotherapy is a safe and effective way of treating haemangiomas of the oval cavity and lips without complications in adults in a reported series. Two cases of serious group A streptococcal infection after cryotherapy in two children are reported. In conclusion it is likely that these children were undiagnosed carriers for the organism. Pre-operative nasopharyngeal swabs would have identified this and prevented the complications which occurred.
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The aetiology of community-acquired pneumonia is reviewed, and the identification of the most likely pathogens, based on clinical presentation, is discussed. By far the major pathogen in community-acquired pneumonia is Streptococcus pneumoniae; the relative frequency of other pathogens, and particularly the atypical pneumonias caused by Mycoplasma and Legionella spp., will depend on local epidemiological factors. The diagnostic tests to confirm diagnosis and subsequent treatment of these infections are reviewed.
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Fifty coagulase-negative staphylococci (CNS) strains were investigated for adherence to both silicone rubber and polystyrene using a microtitre tray system. Culture in an atmosphere containing a physiological level of carbon dioxide (5% CO2) profoundly affected adherent growth to both surfaces. Most strains adhered less well in this atmosphere compared to in air alone, with mean reductions in adherence of 84% and 86% to silicone rubber and polystyrene respectively. Occasional strains adhered better in 5% CO2. The effects of antibiotic concentrations equivalent to 1/4 MIC of cefuroxime, ciprofloxacin, vancomycin and teicoplanin on the adherence of 10 CNS strains were also studied. Vancomycin and teicoplanin frequently increased adherence to silicone rubber and polystyrene compared to controls. The effects of antibiotics on adherence were not only strain dependent but also sometimes atmosphere or surface specific. Antibiotic-induced changes in adherence did not appear to correlate with changes in strain protein profiles or surface hydrophobicities.
Cefpirome serum concentrations were measured by microbiological assay in 30 patients after five to nine days of treatment with 1 or 2 g bd for moderate to severe infection of presumed bacterial origin. Patients with serum creatinine (SCr) greater than 220 mumol/L were excluded. The age of patients ranged from 34-86 years. Creatinine clearance (Clcr) was calculated from age, sex, weight and SCr. The range of SCr was 63-220 mumol/L and the range of Clcr was 18-169 mL/min. The correlation coefficient with cefpirome clearance was 0.464 for SCr and 0.747 for Clcr. More than half of the patients with Clcr less than 50 mL/min had SCr within the normal range of 70-150 mumol/L. Mean cefpirome clearance in patients with Clcr 18-50 mL/min was 42.7 mL/min, which is very similar to the figure of 43.5 mL/min reported in a single dose volunteer study in patients with renal failure. Mean cefpirome clearance in patients with Clcr greater than 80 mL/min was 107.6 mL/min. In conclusion, these data on cefpirome clearance obtained after multiple dose treatment of patients with presumed bacterial infection are consistent with data previously obtained from single dose volunteer studies and support the currently recommended dose regimens. Clinicians should take account of age, weight and sex when estimating renal function from SCr.
Strains of coagulase-negative staphylococci (CNS), including Staphylococcus epidermidis, S. hominis, S. warnerii, S. simulans, S. capitis, S. haemolyticus and S. saprophyticus, were isolated from patients with continuous-ambulatory-peritoneal-dialysis-related peritonitis. The cell wall and cytoplasmic membrane protein profiles of CNS strains cultured in either nutrient broth (NB) or pooled human peritoneal dialysate (HPD) were compared. Some interspecies variation in both the wall and membrane protein profiles was noted. However, the cell wall protein profiles of HPD-grown CNS strains differed markedly from those cultured in NB. Growth in HPD resulted in a marked reduction in the total number of cell-wall-associated proteins but up to three antigenically related proteins in the 40-56 kDa range, depending on the species, predominated. Growth in HPD also resulted in the induction of two iron-repressible cytoplasmic membrane proteins (IRMPs) of 32 and 36 kDa in S. epidermidis. Other CNS strains only appeared to express a single IRMP, which varied in molecular mass from 32 to 36 kDa. Whilst the IRMP in these CNS strains showed considerable antigenic homology with the 32 kDa IRMP, the S. warneri IRMP showed cross-reactivity with both the 32 and 36 kDa IRMPs of S. epidermidis. Immunoblotting experiments revealed that whilst the CNS cell wall proteins were poorly immunogenic, the IRMPs were the immunodominant CNS protein antigens, reacting strongly with antibodies present in HPD. This finding provides evidence to suggest that the IRMPs are expressed in vivo during infection.
During the period 1983-1988 the incidence of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in Nottingham fell from 2.0 to 1.2 episodes/patient/year. Cefuroxime, given intraperitoneally for 10 days, as recommended in published guidelines, failed to cure 35% of episodes of peritonitis, although only 7% of the pathogens responsible for these episodes were resistant in vitro. Cefuroxime is probably no longer appropriate as first line treatment of CAPD peritonitis.
The cell envelope protein profiles of Staphylococcus epidermidis cultured in used human peritoneal dialysate (HPD) differed markedly from those of cells cultured in nutrient broth. Compared with broth-grown cells, many cell wall proteins were repressed in HPD, although three proteins of 42, 48, and 54 kDa predominated and an iron-repressible 130-kDa protein was induced. Growth in HPD also resulted in expression of two cell membrane proteins of 32 and 36 kDa which were iron repressible. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis using monospecific polyclonal antisera raised against the 32- and 36-kDa proteins revealed considerable antigenic and molecular mass homology among 12 S. epidermidis isolates from patients with continuous ambulatory peritoneal dialysis-related peritonitis. The 32-kDa antiserum also cross-reacted with a 32-kDa S. aureus cell membrane protein. Immunoblots of S. epidermidis cell walls and membranes were also probed with normal human serum and serum and HPD from continuous ambulatory peritoneal dialysis patients. While the cell wall proteins of S. epidermidis appeared to be relatively poorly immunogenic, the 32- and 36-kDa membrane proteins reacted strongly with antibodies present in each of the body fluids evaluated. These results suggest that the highly conserved 32- and 36-kDa iron-repressible proteins are expressed during growth in vivo and may be involved in iron transport, since all 12 S. epidermidis strains examined also produced iron chelators.
This article reviews the published clinical experience of the use of the third-generation cephalosporins in the treatment of rare infections. Rare infections are defined as those caused by unusual pathogens or multi-resistant organisms as well as those occurring in unusual or pharmacologically protected body sites. Examples of such infections are uncommon causes of meningitis and ventriculitis, brain abscess, rare causes of bacterial endocarditis, metastatic Salmonella infections, spontaneous bacterial peritonitis and liver abscess, late complications of Lyme borreliosis, uncommon Pseudomonas infections, and post-reconstructive surgery Aeromonas cellulitis. Although these data are largely anecdotal, they form a useful body of information, providing guidance on the management of similar problems encountered by other doctors, while suggesting areas of further investigation for the management of a variety of unusual infections with the third-generation cephalosporins.
Anti-infective agents differ in several respects from other classes of therapeutic drugs. They are aimed at the treatment or prevention of infection which can occur at several body sites and be caused by a wide range of microorganisms. The infectious process frequently modifies metabolic behaviour which in turn may affect the pharmacology of an agent. In addition, the issue of drug resistance raises concerns in individual patients, hospital units and the broader community. The difficulties in scientifically validating the clinical efficacy and safety of anti-infective drugs led to the Report on the Clinical Evaluation of Antibacterial Drugs of the British Society for Antimicrobial Chemotherapy. The report identifies general principles relevant to the study of these drugs in man and identifies the major microbiological and clinical considerations. Detailed comments on the conduct of pharmacokinetic studies and therapeutic trials are provided with particular emphasis on design, definitions, execution and analysis. Adverse event monitoring, assessment of severity and determination of causality are also reviewed. Pharmaco-economic considerations are identified as a significant issue for the future. The revision of the 1977 FDA guidelines on anti-infective drug development provides the opportunity to harmonise these issues, particularly within the major markets of North America, Europe and Japan.