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Biomedical subjects

C C Kibbler

Publications and source records attributed to C C Kibbler.

At least 37 records · Page 2Linked to original sources

Infrequency of pulmonary microbial colonisation prior to respiratory disease in HIV-infected individuals.

To determine whether organisms are present in the HIV-infected lung prior to clinical respiratory disease, a cross-sectional bronchoscopic comparative analysis of 39 asymptomatic HIV-positive subjects and 31 healthy controls with 2-year prospective bronchoscopic monitoring of the HIV study group was performed. Pathological examination of bronchoalveolar lavage (BAL) fluid using standard microbiological techniques was undertaken. Organisms were recovered from similar numbers of HIV-positive and control subjects (7 of 39 and 3 of 31) and comprised predominantly scanty growths of bacteria. Five subjects developed respiratory disease during follow-up. Repeat BAL was performed in 11 asymptomatic HIV-positive patients; no relationship was found between the organisms isolated at the two procedures. The findings suggest that the asymptomatic HIV-positive lung is not a frequent site of either microbial colonisation or subclinical infection. This has implications for the understanding of the pathogenesis of HIV-related pulmonary disease.

Adult↗

Fatal invasive cerebral Absidia corymbifera infection following bone marrow transplantation.

A 56-year-old dairy farmer received a fully HLA matched unrelated donor marrow transplant for high risk CML in chronic phase. His early post-transplant course was complicated by a series of massive intracerebral bleeds and by sepsis related to a malignant otitis externa. The microbial pathogen isolated from ear swabs was found to be Absidia corymbifera, but CT scan at the time showed no intracerebral extension. Despite neutrophil engraftment and aggressive antifungal management he succumbed. Autopsy revealed invasion of Absidia into the brain from the ear. We speculate that colonisation by Absidia resulted from occupational exposure.

Absidia↗

Antifungal prophylaxis with itraconazole oral solution in neutropenic patients.

The role of itraconazole in anti-fungal prophylaxis has been limited by the low bioavailability of the capsule formulation but the bioavailability of the oral solution is much improved. Three multi-centre studies using itraconazole solution (5 mg/kg/day) have recently been completed. The UK trial compared itraconazole solution with fluconazole suspension (100 mg/day). No invasive aspergillosis occurred in the itraconazole arm and there were more fungal deaths due to proven/suspected infection in the fluconazole group than in the itraconazole group (0 versus 7, p = 0.024). An Italian study compared itraconazole solution with placebo. Proven, suspected and superficial fungal infections were fewer in the itraconazole arm compared with placebo, with significant differences in proven and suspected systemic fungal infections (itraconazole 24% versus placebo 33%, p = 0.035). The third study compared itraconazole with amphotericin B capsules (2 g/day). There were more invasive fungal infections, Aspergillus infections and fungal deaths in the amphotericin B arm than with itraconazole but none of these differences were statistically significant. Azole prophylaxis in neutropenic patients may reduce the incidence of Candida infections, empirical amphotericin B usage, and the incidence of proven fungal infections. Itraconazole may be more effective than fluconazole in preventing invasive aspergillosis. All of these effects are more pronounced in high risk patients.

Administration, Oral↗

Cytokine release and mitogenic activity in the viridans streptococcal shock syndrome.

Viridans streptococci are a heterogeneous group of Gram-positive bacteria that are normal inhabitants of the mouth, upper gastrointestinal tract and oropharynx. These organisms are typically thought of as of low virulence, classically as the cause of infective endocarditis, although recently they have been implicated in serious infections in other settings. In particular, viridans group streptococci have been described as responsible for the alpha-streptococcal shock syndrome in neutropenic patients. The mechanism by which viridans streptococci cause bacteraemia associated with adult respiratory distress syndrome (ARDS) in these patients has not been elucidated. Using enzyme-linked immunosorbent assays, we compared the ability of cell-free bacterial supernatants derived from commensal and clinical strains of viridans streptococci to induce the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha), tumour necrosis factor beta (TNF-beta) and interleukin 8 (IL-8) from human peripheral blood mononuclear cells (PBMC) in vitro. Supernatants of clinical isolates induced significantly more TNF-beta (P < 0.002) and IL-8 (P < 0.001) than did supernatants from commensal strains. The increased production of IL-8 by the clinical strains may be of importance in view of the role of IL-8 in the pathogenesis of the acute respiratory distress syndrome (ARDS), one of the principal clinical features of the alpha-streptococcal shock syndrome.

Adult↗

The effect of increased bed numbers on MRSA transmission in acute medical wards.

An 18-month prospective survey was performed to examine the effect of adding a fifth bed to four-bedded bays in three acute medical wards on colonization by methicillin-resistant Staphylococcus aureus (MRSA). Screening procedures were in accordance with the UK national guidelines. All patients newly colonized with MRSA were visited, and their bed location determined. Data from the five-bedded bays were compared with those from four-bedded bays in similar wards. Potential routes of transmission were investigated by observational surveys. The relative risk of colonization in five-bedded medium dependency bays was 3.15 compared with that of similar four-bedded bays (P < 0.005), and in five-bedded low dependency bays was 3.16 (P < 0.005). Increasing the number of beds in a fixed area heightens the risk of cross-infection with MRSA.

Acute Disease↗

The epidemiology and prevention of invasive aspergillosis.

Over the past two decades, the incidence of invasive aspergillosis (IA) has risen inexorably. This is almost certainly the consequence of the more widespread use of aggressive cancer chemotherapy regimens, the expansion of organ transplant programmes and the advent of the acquired immunodeficiency syndrome (AIDS) epidemic. Despite the development of new approaches to therapy, IA still remains a life-threatening infection in immunocompromised patients and is the most important cause of fungal death in cancer patients. It is clear that the prevention of severe fungal infection by the use of effective infection control measure should be the priority of the teams involved in managing at-risk patients. The evidence from clinical and molecular epidemiological studies is reviewed and current thinking on sources and routes of transmission of the organism are discussed. Our increasing understanding of these has led to the development of a variety of environmental and general strategies for the prevention of IA. It is anticipated that these, coupled with the use of prophylactic antifungal agents active against Aspergillus spp., will have a significant impact upon the morbidity and mortality associated with this infection.

Aspergillosis↗

The effect of an enhanced infection-control policy on the incidence of Clostridium difficile infection and methicillin-resistant Staphyloccocus aureus colonization in acute elderly medical patients.

BACKGROUND: Clostridium difficile (CD) infection and methicillin-resistant Staphylococcus aureus (MRSA) colonization are increasingly common in elderly patients, are associated with cephalosporin or prolonged aminopenicillin courses and can be transmitted by direct contact. Management is by side-room isolation. Ward closure may be required to control outbreaks. METHODS: following prolonged bed closures due to CD and MRSA in an acute age-related geriatric service, an enhanced infection control policy was introduced-emphasis on handwashing, cephalosporin restriction, 7-day time limits on antibiotics and feedback of infection rates. The effect of this policy was evaluated by investigating 2,467 consecutive admissions in the 9 months before and after its introduction. RESULTS: CD infection fell from 36/1,075 admissions (3.35 per 100) to 27/1,392 (1.94 per 100; P < 0.05). MRSA incidence fell from 3.95 per 100 to 1.94 (P < 0.01) whilst that in the rest of the hospital continued to fluctuate. Cephalosporin use fell (and aminopenicillin and trimethoprim use rose) by a factor of three. Unoccupied bed days fell from 1,164 (12.6%) to 513 (5.1%) over the winter, an increase in bed availability of 4.95 a day. CONCLUSIONS: introduction of the policy was associated with significant reductions in CD infection and unoccupied bed-days and helped maintain a lower incidence of MRSA. It is not clear which elements of the policy most influenced outcome. A multi-centre study is needed to determine whether our findings are generally applicable.

Aged↗

An evaluation of the cost-effectiveness of using CHROMagar for yeast identification in a routine microbiology laboratory.

CHROMagar, a chromogenic differential culture medium, is claimed to facilitate the isolation and presumptive identification of certain clinically important yeast species, e.g., Candida albicans. This study evaluated the cost-effectiveness and time advantage of using it in comparison with Sabouraud dextrose agar (SDA). Three possible pathways, each of which included the use of one or both media, were compared in a routine laboratory. A total of 21 yeast isolates was cultured from 298 clinical samples from neutropenic and AIDS patients. An overall sensitivity of 95.2% was observed for each medium and primary isolation on CHROMagar was found to be 100% sensitive and 100% specific for C. albicans. For identification purposes, after initial culture the use of CHROMagar provided the most economical and least time-consuming method. Direct inoculation on to CHROMagar is recommended for blood cultures when yeast cells are seen on microscopy and where early appropriate therapy is imperative.

Acquired Immunodeficiency Syndrome↗

A prospective randomized trial of ceftazidime versus netilmicin plus mezlocillin in the empirical therapy of presumed sepsis in cirrhotic patients.

Aminoglycosides are frequently used to treat sepsis in patients with liver disease. However, it has been suggested that cirrhotic patients are particularly sensitive to aminoglycoside-induced renal dysfunction. We investigated the efficacy and incidence of renal impairment with netilmicin plus mezlocillin compared with ceftazidime in 128 cirrhotic patients who required empirical treatment for sepsis. Renal impairment developed in 8 of 63 (13%) patients receiving netilmicin compared with 2 of 65 (3%) patients receiving ceftazidime (P < .05); it occurred despite regular monitoring of trough netilmicin levels. Renal impairment was present at the time of death in 1 of 13 (8%) patients treated with ceftazidime compared with 5 of 9 (56%) of the netilmicin patients (P < .05). Mortality rates were similar in the two groups (ceftazidime 20%, aminoglycoside 14%; P = NS). Renal dysfunction is significantly more frequent in cirrhotic patients treated with netilmicin but with careful attention to dosage and fluid management the clinical effect is likely to be relatively modest.

Adolescent↗

Guidelines for the investigation of invasive fungal infections in haematological malignancy and solid organ transplantation. British Society for Medical Mycology.

Invasive fungal infections are increasing in incidence and now affect as many as 50% of neutropenic/bone marrow transplant patients and 5 to 20% of solid organ transplant recipients. Unfortunately, many of the diagnostic tests available have a low sensitivity. The guidelines presented here have been produced by a working party of the British Society for Medical Mycology in an attempt to optimise the use of these tests. The yield of fungi from blood cultures can be increased by ensuring that at least 20 ml of blood are taken for aerobic culture, by using more than one method of blood culture, and by employing terminal subculture if continuous monitoring systems are used with a five-day incubation protocol. Skin lesions in febrile neutropenic patients should be biopsied and cultured for fungi. The detection of galactomannan in blood or urine is of value in diagnosing invasive aspergillosis only if tests are performed at least twice weekly in high-risk patients. Antigen detection tests for invasive candidiasis are less valuable. Computed tomography scanning is particularly valuable in diagnosing invasive pulmonary fungal infection when the chest radiograph is negative or shows only minimal changes. Bronchoalveolar lavage is most useful in patients with diffuse changes on computed tomography scan. The major advances in the diagnosis of invasive fungal infection in patients with haematological malignancy or solid organ transplantation have been in the use of imaging techniques, rather than in the development of new mycological methods in the routine laboratory.

Algorithms↗