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T Sorrell

Publications and source records attributed to T Sorrell.

18 recordsLinked to original sources

Guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections.

ABSTRACT Treatment of invasive fungal infections is increasingly complex. Amphotericin B deoxycholate has long been the mainstay of treatment. However, there has been increasing recognition of both the propensity for nephro-toxicity in haematology, transplant and intensive care patients as well as its adverse impact on morbidity and mortality. This has coincided with the availabilty of newer, and in certain settings, more effective antifungal agents. Although the newer agents clearly cause less nephrotoxicity than amphotericin B, drug interactions, hepatic effects and unique side-effects need to be considered. The spectrum of the newer triazoles and echinocandins varies, highlighting the importance of accurate identification of the causative organism where possible. Consensus Australian guidelines have been developed to assist clinicians with treatment choices by reviewing the current evidence for the efficacy, the toxicity and the cost of these agents.

Antifungal Agents↗

Identification of Enterococcus, Streptococcus, and Staphylococcus by multivariate analysis of proton magnetic resonance spectroscopic data from plate cultures.

A new fingerprinting technique with the potential for rapid identification of bacteria was developed by combining proton magnetic resonance spectroscopy ((1)H MRS) with multivariate statistical analysis. This resulted in an objective identification strategy for common clinical isolates belonging to the bacterial species Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, and the Streptococcus milleri group. Duplicate cultures of 104 different isolates were examined one or more times using (1)H MRS. A total of 312 cultures were examined. An optimized classifier was developed using a bootstrapping process and a seven-group linear discriminant analysis to provide objective classification of the spectra. Identification of isolates was based on consistent high-probability classification of spectra from duplicate cultures and achieved 92% agreement with conventional methods of identification. Fewer than 1% of isolates were identified incorrectly. Identification of the remaining 7% of isolates was defined as indeterminate.

Culture Media↗

Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group.

A prospective population-based study was conducted in Australia and New Zealand during 1994-1997 to elucidate the epidemiology of cryptococcosis due to Cryptococcus neoformans var. neoformans (CNVN) and C. neoformans var. gattii (CNVG) and to relate clinical manifestations to host immune status and cryptococcal variety. The mean annual incidence per 10(6) population was 6.6 in Australia and 2.2 in New Zealand. Of 312 episodes, CNVN caused 265 (85%; 98% of the episodes in immunocompromised hosts) and CNVG caused 47 (15%; 44% of the episodes in immunocompetent hosts). The incidence of AIDS-associated cases in Australia declined annually (P<.001). Aborigines in rural or semirural locations (P<.001) and immunocompetent males (P<.001) were at increased risk of CNVG infection. Cryptococcomas in lung or brain were more common in immunocompetent hosts (P< or =.03) in whom there was an association only between lung cryptococcomas and CNVG. An AIDS-associated genetic profile of CNVN serotype A was confirmed by random amplification of polymorphic DNA analysis. Resistance to antifungal drugs was uncommon. The epidemiology of CNVN infection has changed substantially. Clinical manifestations of disease are influenced more strongly by host immune status than by cryptococcal variety.

AIDS-Related Opportunistic Infections↗

Eicosapentaenoic acid in cystic fibrosis: evidence of a pathogenetic role for leukotriene B4.

Much of the lung damage that limits the life of young adults with cystic fibrosis is due to proteases and oxygen metabolites generated by neutrophils, which are recruited into the airway by the interaction between Pseudomonas aeruginosa and pulmonary macrophages. Leukotriene B4 (LTB4) has been proposed as a local mediator of this process; its production is susceptible to specific modulation with dietary eicosapentaenoic acid (EPA). We carried out a placebo-controlled trial of EPA (2.7 g daily for 6 weeks) to assess its effects on markers of clinical state, peripheral neutrophil function, and lung inflammation in sixteen patients with cystic fibrosis colonised with P aeruginosa. EPA was well tolerated and resulted in a significant reduction in sputum volume (median change with EPA -10 mL/day, placebo 0; p = 0.015), and improvements in Schwachman score (EPA 5%, placebo 0; p = 0.034), forced expiratory volume in 1 s (EPA 0.25 L, placebo -0.1 L; p = 0.006), and vital capacity (EPA 0.6 L, placebo 0; p = 0.011). Relative chemotaxis of circulating neutrophils to LTB4 increased from a subnormal baseline of 4 (median; range 0-10) microns/30 min before treatment, to a near normal value of 11 (5-18) microns/30 min after EPA. Relative chemotaxis to LTB4 of patients taking placebo did not change: the difference in response was highly significant (p = 0.001). Specific reduction of neutrophil chemotaxis to LTB4 is a sensitive assay of chronic in-vivo exposure to LTB4. Our results suggest that LTB4 has a pathogenetic role in the lung damage of cystic fibrosis. Longer-term clinical trials of EPA are warranted in a larger number of cystic fibrosis patients.

Adolescent↗

Human immunodeficiency virus infection in pregnancy.

Human immunodeficiency virus (HIV) infection in women is an increasing problem. World wide, at least 25% of all infections occur in adolescent or adult women, most of whom are of child-bearing age. The commonest modes of acquisition of HIV infection are sexual contact with an HIV-infected male and sharing needles during injecting drug use. Vertical transmission is the major route of HIV infection in infants and children and can occur in utero, intrapartum, through exposure to infected blood or secretions, or post partum, via breast milk. HIV infection has not been demonstrated to affect fertility, or to influence the outcome of pregnancy unless there is evidence of significant immune dysfunction, with CD4 counts below 400/mm3. Though data are limited, pregnancy does not appear to affect the course of HIV infection. Low CD4 counts predispose women to the opportunistic infectious complications of HIV. Pathogens include Candida sp., Mycobacterium tuberculosis, Pneumocystis carinii, Toxoplasma gondii, Cryptococcus neoformans and Cryptosporidium. These pathogens require early recognition and diagnosis if optimal treatment and outcome are to be attained. Treatment with zidovudine and prophylaxis against Pneumocystis carinii are appropriate when CD4 counts are less than 200/mm3, though the safety of zidovudine in early pregnancy is not known. Similarly it is not known whether zidovudine treatment of the mother prevents transmission of HIV infection to her baby. Caesarean section does not prevent peripartum transmission of HIV and should be undertaken only for other appropriate indications. The utility of antenatal screening for HIV depends upon the seroprevalence in the population. Such programmes must be supported by comprehensive clinical care as well as sensitive and non-judgemental counselling.

Female↗

Empiric single agent or combination antibiotic therapy for febrile episodes in neutropenic patients: an overview.

Febrile episodes during chemotherapy-induced neutropenia are a frequent cause of morbidity and mortality in cancer patients. Empiric antibiotic therapy commencing at the onset of fever is selected according to three principles: intravenous therapy is used to rapidly achieve bactericidal serum levels, antibiotics with appropriate antibacterial spectra are required, and combinations of antibiotics have been preferred for their synergistic activity. Initial empiric monotherapy with single antibiotics such as imipenem which have a sufficiently broad antibacterial spectrum in their own right are potentially as efficacious as conventional combination therapies. Granulocytopenic periods complicated by fever are significantly longer in patients receiving chemotherapy for leukaemia than in patients undergoing treatment for lymphoma and solid tumours. However, defervescence of fever following commencement of antibiotic therapy occurs equally rapidly in these three groups. The persistent granulocytopenia leaves leukaemic patients at greatest risk of breakthrough or second infections. These patients therefore appear to be the most likely to benefit from the clinical use of haemopoietic growth factors such as granulocyte and granulocyte-macrophage colony-stimulating factor.

Agranulocytosis↗

Sepsis associated with central vein catheters in critically ill patients.

In 440 critically ill patients, the association between different central vein catheter insertion sites, the duration of catheter insertion and catheter-associated sepsis was examined. Of 780 catheter tips studied, 19% were colonized by microorganisms. The incidence of colonization varied with the different insertion sites. The lowest percentage of colonized catheters occurred with catheters inserted via the subclavian vein (15%) and the highest, at the femoral vein insertion site (34%, p less than 0.01). The percentage of catheters colonized increased as the duration of insertion increased, at all insertion sites studied. Catheter colonization was closely related to the development of bacteraemia and was associated with approximately 10% of colonized catheters. Our results suggest that the subclavian site is associated with the lowest infective complication rate. To minimize catheter associated sepsis, catheters at all insertion sites should be used with parsimony and only kept in place for the minimum amount of time that their continuing use is necessary.

Catheterization, Central Venous↗

Are anaerobic bacteria involved in peripheral vein catheter associated thrombophlebitis?

While thrombophlebitis is a common complication of intravenous therapy, infection has been shown to be a cause of this problem in only a minority of cases. However, the methodology employed in the past would not have detected the anaerobes as a cause of this problem. As anaerobes are associated with thrombophlebitis in situations such as septic pelvic thrombophlebitis, we undertook a study to see if they might also be involved in thrombophlebitis associated with peripheral vein catheters. We prospectively studied 26 episodes of peripheral intravenous catheter associated thrombophlebitis. These catheters were all cultured under aerobic conditions by the semiquantitative technique on blood agar plates. In addition, they were promptly processed and cultured under optimal anaerobic conditions. In none of the episodes of thrombophlebitis were the catheters positive on semiquantitative culture. In addition, we did not show the presence of anaerobes on any of these catheters. We conclude that there is no evidence that anaerobes are associated with peripheral vein thrombophlebitis.

Bacteria, Anaerobic↗

Aspiration drainage of splenic abscesses.

The successful use of guided percutaneous needle aspiration in the management of four patients with solitary splenic abscess is described. Two patients had needle aspiration alone and two patients, with large splenic abscesses, had drainage tubes inserted. The procedures were well tolerated and allowed rapid microbiological diagnosis with selection of appropriate antibiotic therapy. The techniques were useful in patients felt to be poor anaesthetic risks, and the complications of splenectomy were avoided.

Abscess↗

Ophthalmological complications of cryptococcal meningitis.

Two patients with cryptococcal meningitis associated with ophthalmological complications are described. One patient developed a cryptococcal fundal lesion which disappeared during chemotherapy. Chronically raised intracranial pressure was associated with a visual field defect. This resolved with repeated lumbar punctures. The second patient developed visual deficits secondary to papilloedema and responded to optic nerve decompression. In both cases CT scanning demonstrated swelling of the optic nerves. In the second patient this regressed after decompression. A review of the variety of the ophthalmological complications of cryptococcal meningitis and their prevalence is presented. The risk of developing severe visual disability is assessed.

Adult↗

Fungicidal activity of rabbit alveolar and peritoneal macrophages against Candida albicans.

We tested the ability of rabbit macrophages to kill Candida albicans in vitro. Resident (unstimulated) alveolar macrophages killed 28.1 +/- 1.9% of ingested organisms in 4 h, whereas resident peritoneal macrophages killed only 15.2 +/- 1.3% (mean +/- standard error of the mean, P < 0.01). Peritoneal macrophages obtained from rabbits treated 3 weeks earlier with complete Freund adjuvant showed enhanced candidacidal activity relative to normally resident peritoneal cells (28.2 +/- 3.1%, P < 0.01). Candidacidal activity by alveolar macrophages recovered from such treated animals was slightly enhanced relative to untreated alveolar macrophages (32.9 +/- 2.3%). Candidacidal activity by peritoneal and alveolar macrophages was not decreased by several agents (cyanide, azide, sulfadiazine, and phenylbutazone) that inhibit the ability of human blood monocytes to kill C. albicans. In contrast, candidacidal activity by alveolar macrophages was greatly diminished by iodoacetate, an ineffective inhibitor of this function in human monocytes. We conclude that rabbit macrophages kill C. albicans by a fungicidal mechanism distinct from the peroxidase-H2O2 mechanism of human granulocytes and monocytes, and that the fungicidal properties of peritoneal and alveolar macrophage populations are enhanced after nonspecific stimulation with complete Freund adjuvant.

Animals↗