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Biomedical subjects

R G Finch

Publications and source records attributed to R G Finch.

At least 19 recordsLinked to original sources

Community-acquired pneumonia.

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.

Anti-Bacterial Agents

Effects of carbon dioxide and sub-lethal levels of antibiotics on adherence of coagulase-negative staphylococci to polystyrene and silicone rubber.

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.

Anti-Bacterial Agents

Relationship between cefpirome clearance, serum creatinine, weight and age in patients treated for infection.

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.

Adult

Variation in the expression of cell envelope proteins of coagulase-negative staphylococci cultured under iron-restricted conditions in human peritoneal dialysate.

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.

Antibodies, Bacterial

Peritonitis complicating continuous ambulatory peritoneal dialysis in Nottingham 1983-1988.

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.

Bacteria

Characterization of cell envelope proteins of Staphylococcus epidermidis cultured in human peritoneal dialysate.

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.

Bacterial Proteins

Third-generation cephalosporins in the treatment of rare infections.

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.

Bacterial Infections

The clinical evaluation of antibacterial drugs: guidelines of the British Society for Antimicrobial Chemotherapy.

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.

Anti-Infective Agents

Epidemiological features and chemotherapy of community-acquired respiratory tract infections.

The epidemiology of community-acquired respiratory tract infections (RTI) is reviewed with emphasis on acute pharyngitis, otitis media, sinusitis, epiglottitis and pneumonia. The numerical importance of upper respiratory tract infections is stressed and their economic impact discussed. Community-acquired pneumonia, although less common, is a more serious infection with a frequent requirement for hospitalization. The heterogeneous microbial aetiology of RTI is stressed, together with the impact this has on chemotherapeutic choice. The latter is likely to remain largely empirical and based on the prevalence of identified pathogens, spectrum of activity and the pharmacokinetic behaviour of the selected agents. The increasing frequency of resistance among respiratory pathogens, notably Haemophilus influenzae, and to a lesser extent Streptococcus pneumoniae, together with the high incidence of beta-lactamase production among Branhamella catarrhalis is of concern. In addition, the issue of beta-lactam inactivation by commensal bacteria suggests that chemotherapeutic strategies for the control of community-acquired respiratory tract infection might justifiably be reconsidered.

Epiglottitis

Influence of carbon dioxide on growth and antibiotic susceptibility of coagulase-negative staphylococci cultured in human peritoneal dialysate.

Used peritoneal dialysis fluid was collected from patients undergoing continuous ambulatory peritoneal dialysis, and its pH and composition were assessed after incubation in either air or air with 5% CO2. Precipitation of calcium, magnesium, phosphate, and proteins occurred in the dialysis fluid incubated in air at 37 degrees C and was associated with a mean pH increase of 1.23 U. Incubation of dialysis fluid in air with 5% CO2 prevented precipitation and maintained pCO2 and pH levels at those found physiologically. Coagulase-negative staphylococcal strains isolated from patients with peritonitis tended to grow less well in dialysis fluid incubated in air than in dialysis fluid incubated in the carbon dioxide-enriched atmosphere. MICs of cefuroxime, ciprofloxacin, and vancomycin for seven strains of coagulase-negative staphylococci in dialysis fluid were markedly affected by atmosphere type (16 of 21 MICs). Of these 16 atmosphere-dependent MICs, 14 were at least fourfold higher in air than in air with 5% CO2.

Air

Influence of carbon dioxide on the surface characteristics and adherence potential of coagulase-negative staphylococci.

Coagulase-negative staphylococci obtained from patients with continuous ambulatory peritoneal dialysis-related peritonitis were cultured in nutrient broth in an atmosphere of air containing 5% carbon dioxide (reflecting the CO2 tension found in freshly used dialysate). Significant differences were observed between the surface chemistries of cells grown in the two atmospheres, as determined by X-ray photoelectron spectroscopy and changes in the cell wall protein profile. The growth atmosphere also influenced the adherence potential toward polystyrene and silicone in a proportion of strains examined. Thus, gaseous conditions can profoundly influence the nature of the staphylococcal surface, and this should be considered in any in vitro study of in vivo behavior.

Bacterial Adhesion

Nosocomial lower respiratory tract infections in surgical wards.

A six month prospective study of nosocomial lower respiratory tract infection was conducted in four general surgery wards and one urological surgery ward. Thirty eight cases were identified, representing 1% of the surgical admissions to these wards. Twenty eight of the infections followed abdominal surgery. Six patients died, five of whom had pre-existing cardiorespiratory disease. Potential pathogens were isolated in 21 patients, the commonest organisms being Streptococcus pneumoniae and Haemophilus influenzae.

Adult

A hospital study of community acquired pneumonia in the elderly.

Studies on community acquired pneumonia in the United States in patients over the age of 65 years have shown that Gram negative bacilli account for an appreciable proportion of cases, in addition to usual pathogens such as Streptococcus pneumoniae and Haemophilus influenzae. There have been no reports of community acquired pneumonia in the elderly in the United Kingdom. We undertook such a study to determine the clinical features, aetiology, and outcome. Seventy three patients (38 men) with ages ranging from 65 to 97 (median 79) years were studied prospectively. Pneumonia was defined as an acute lower respiratory tract infection with new, previously unrecorded shadowing on a chest radiograph. Patients with severe chronic illness in whom pneumonia was an expected terminal event were excluded. Nearly all the patients (96%) had respiratory symptoms or signs but many had features that might obscure the true diagnosis of pneumonia. Over half the patients had non-respiratory symptoms and over a third had no systemic signs of infection. A pathogen was identified in 43% of patients, most commonly Streptococcus pneumoniae, Haemophilus influenzae and influenza B virus. Gram negative bacilli were not seen. The mortality rate was high (33%). Early deaths were due to infection whereas later deaths were associated with other factors, such as stroke (two patients) and pulmonary embolism (two patients). Prognostic indicators for mortality were apyrexia, systolic hypotension, increasing hypoxaemia, and new urinary incontinence. As the range of pathogens causing pneumonia was the same in the elderly in this study as in other age groups it is suggested that initial antibiotic treatment for patients in this age group should always cover S pneumoniae and H influenzae.

Aged

Bacterial resistance to trimethoprim in geriatric medical wards.

Urinary tract infections (UTI) caused by organisms resistant to trimethoprim (TMP), as well as their faecal carriage were studied in two geriatric wards. TMP-resistant UTI was common (26 and 50% of admission and ward-acquired infections, respectively) and was associated with male sex, recurrent and transferred admissions and length of stay. There was a strong relationship between faecal carriage and isolation of TMP-resistant organisms from urine. Antimicrobial exposure was the major determinant of TMP-resistant faecal carriage.

Aged

Continuous ambulatory peritoneal dialysis (CAPD) peritonitis: the effect of antibiotic on the adherence of coagulase-negative staphylococci to silicone rubber catheter material.

Peritonitis is the major complication of continuous ambulatory peritoneal dialysis (CAPD) and is caused predominantly by coagulase-negative staphylococci (CNS). Adherence to the silicone rubber Tenckhoff catheter has been identified as one factor in the pathogenesis and persistence of these infections. We have studied the adherence of CNS from patients and controls to silicone rubber in an in vitro model to determine whether this phenomenon can be modified by antibiotics. Adherence was strong for 7/27 (26%) CAPD isolates and for 3/27 (11%) of control strains. The strongly adherent CAPD isolates, when exposed to subinhibitory concentrations of vancomycin, cefuroxime, and ciprofloxacin, showed minimal alteration in adherence with vancomycin in both broth and used dialysate, whereas cefuroxime and ciprofloxacin both significantly reduced it. These observations may have implications for drug selection and prevention of CAPD peritonitis caused by CNS.

Bacterial Adhesion