Ciprofloxacin and CAPD peritonitis.
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Biomedical subjects
Publications and source records attributed to R G Finch.
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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.
A patient with pneumococcal septicaemia and serological evidence of infection with human immunodeficiency virus (HIV) presented with a peripheral T-cell lymphoma. As far as we are aware this association has not been reported previously.
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.
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.
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.
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.
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.
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.
Solutions of vancomycin in phosphate-buffered saline, peritoneal dialysis effluent fluid and human serum were incubated at 37 degrees C for ten days and sampled at daily intervals. The samples were assayed for vancomycin content by a microbiological assay, HPLC and polarisation fluoroimmunoassay (Abbott TDX). The results obtained by HPLC and microbiological assay agreed well and indicated approximately 50% loss over ten days in serum and buffered saline and over 70% loss in dialysate. TDX results indicated losses of only 20% and 40%, respectively. Degradation products were prepared from vancomycin by acid hydrolysis and purified by HPLC. These purified products were shown to cross-react in the TDX assay. It is suggested that the TDX assay becomes non-specific in the presence of vancomycin breakdown products and thus overestimates true vancomycin concentrations.
A prospective one-year study of community pneumonia was conducted in Nottingham. 236 of 251 episodes of pneumonia (defined as an acute lower respiratory tract infection, for which antibiotics were prescribed, associated with new focal signs on examination of the chest) were investigated. Acute radiographic changes were present in 93 (39%). A pathogen was identified in 129 (55%) episodes, with Streptococcus pneumoniae, Haemophilus influenzae, and influenza viruses those most frequently identified. Mycoplasma pneumoniae was uncommon and infection with Legionella pneumophila was found in only 1 episode. Hospital admission was required in 52 (22%) episodes. 7 patients died (3%), all but one of the deaths occurring in patients who had been admitted to hospital. Pneumonia in the community is common but few people die of it. Initial antibiotic therapy should always cover S pneumoniae and H influenzae.
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Five episodes of pseudomonas peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD) which were not cured by intraperitoneal antibiotics were studied to assess causes for treatment failure. The activity of gentamicin and ceftazidime against these strains was decreased in the presence of sterile used dialysate compared with nutrient broth. Likewise, kinetic studies showed that in dialysate therapeutically used concentrations of antibiotics failed to kill the isolates over 24 h. All five pseudomonas strains were adherent to silicone rubber Tenckoff catheter segments. An in vitro model of CAPD peritonitis demonstrated that persistence of viable adherent bacteria, after exposure to therapeutic concentrations of gentamicin and ceftazidime, contributes to the failure of antibiotics to cure pseudomonas CAPD peritonitis.
The pharmacokinetics of single dose intravenous vancomycin (25 mg/kg) were studied in six patients with peritonitis complicating continuous ambulatory peritoneal dialysis. The volume of distribution after equilibration was 1.1 +/- 0.1 l/kg (mean +/- standard error) with a serum elimination half-life of 115 +/- 6 h. The peritoneal clearance was 1.4 +/- 0.5 ml/min and the serum clearance was 7.2 +/- 0.3 ml/min. Mean peak serum levels of 56.8 +/- 4.7 mg/l were detected. Initial mean overnight dialysate level was 12.3 +/- 0.8 mg/l. Vancomycin dialysate levels of 8 mg/l were achieved for a mean of 3.0 days and levels of 4 mg/l for a mean of 6.2 days. Single dose intravenous vancomycin may, therefore, have therapeutic value in selected patients.
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This study compared the static and kinetic activities of six antifungal agents, in broth and used dialysate, against six yeast strains known to have caused peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). Minimum inhibitory concentrations (MIC) and IC50 results show a trend towards greater activity by amphotericin B, 5-fluorocytosine, tioconazole and itraconazole in comparison to miconazole and ketoconazole although there was some strain variability. Minimum fungicidal concentrations (MFCs) of amphotericin B were less than or equal to 1mg/l, while 5-fluorocytosine and the azoles showed large discrepancies between MIC and MFC values. In kinetic studies amphotericin B was the most potent fungicidal agent. 5-fluorocytosine showed modest activity and failed to achieve total killing. The azoles demonstrated variable degrees of inhibition of C. glabrata and showed minimal activity with C. albicans. Itraconazole showed good activity against C. parapsilosis in broth. All agents, with the exception of 5-fluorocytosine, showed reduced activity in used dialysate in comparison to broth.
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