The combination of oral amphotericin B with azoles prevents the emergence of resistant Candida species in neutropenic patients.

The role of antifungal prophylaxis remains controversial and concerns exist that the use of azoles may potentiate the emergence of resistant Candida species. We used a strategy of combining the latest azole/triazole with oral amphotericin B to reduce this risk. We analysed data on Candida colonization and candidaemia in neutropenic patients from four prophylaxis periods (1985/6: ketoconazole and amphotericin B suspension; 1991/2 & 1997: fluconazole and amphotericin B suspension; 1998/9: itraconazole) to look for evidence of the emergence of potentially resistant species. Overall, the percentage of patients colonized with Candida fell significantly (69.3%, 57.5%, 43.2% and 46%, respectively, P < 0.001) due to a decrease in colonization with C. albicans (49%, 23.1%, 22.2% and 25.2%, respectively, P < 0.001). However, in 1998/9, increased colonization, particularly with C. glabrata in the lower gastrointestinal tract, was noted to coincide with the omission of oral amphotericin B. Despite an increasing population of 'high risk' patients, the incidence of candidaemia has not changed significantly (2%, 1.4%, 1.2% and 2% respectively). However, species causing candidaemia have changed, with resistant organisms now predominating. Our findings support the use of azole prophylaxis although, in view of the trends noted when itraconazole was used alone, we would recommend the additional use of oral amphotericin B.

Management of invasive pulmonary aspergillosis in hematology patients: a review of 87 consecutive cases at a single institution.

Eighty-seven patients with hematologic malignancies and invasive pulmonary aspergillosis (IPA) were identified between 1982 and 1995. Of these, 39 underwent lung resection on the basis of radiological detection of at least 1 lesion with imaging suggestive of aspergillosis (LISA). IPA was confirmed histologically in 35. The presence of LISA had 90% positive predictive value for IPA. The actuarial survival at 2 years was 36% for 37 patients treated surgically, 20% for 12 patients with unresected LISA but no cultures of Aspergillus species, and 5% for 21 patients diagnosed only by isolation of Aspergillus from respiratory secretions. Analysis by proportional hazard models showed a significant independent negative association between the radiological appearance of LISA and death from all causes. Relapsed hematologic disease was independently significantly associated with death. Age, sex, surgery, previous bone marrow transplantation, or Aspergillus isolation were not independent predictors of death. IPA presenting as LISA carries a relatively good prognosis, possibly explaining the better survival of patients undergoing surgery for such lesions.

Failure to produce detectable antibodies to Legionella pneumophila by an immunocompetent adult.

A case of legionella pneumonia diagnosed by co-culture with amoebae and urinary antigen detection is described. Diagnostic antibody tests remained negative despite prolonged follow-up. Investigation showed no evidence of an under-lying immunodeficiency. The value of culture-based diagnosis and consequences of missed diagnoses are discussed.

Activity of quinolones against viridans group streptococci isolated from blood cultures of patients with haematological malignancy.

Use of fluoroquinolones for antimicrobial prophylaxis during neutropenia is often cited as a significant predisposing factor for viridans group streptococcus (VGS) bacteraemia. Newer compounds in this class are reputed to have enhanced activity against Gram-positive bacteria, and we determined the minimal inhibitory concentrations (MICs) for ciprofloxacin and three of the newer compounds: trovafloxacin, fleroxacin and clinafloxacin, against 44 isolates of VGS. On a gravimetric basis, clinafloxacin was most active (MIC90 0.19 mg/l), whereas ciprofloxacin and fleroxacin were the least active (both MIC90 16 mg/l). Clinafloxacin warrants further study as an agent of prophylaxis against bacterial infection in neutropenic patients.

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.

Disseminated infection due to Cylindrocarpon lichenicola in a patient with acute myeloid leukaemia.

We describe what is to our knowledge the first reported case of disseminated infection due to Cylindrocarpon. The presumed source was athlete's foot, a condition with which this fungus has previously been associated. Diagnosis was made by needle aspiration of a cutaneous lesion. Radiographic evidence of pulmonary involvement was present. The infection resolved following marrow regeneration and treatment with amphotericin B. Correct identification of Cylindrocarpon may be useful in guiding antifungal therapy.

Activities of potential therapeutic and prophylactic antibiotics against blood culture isolates of viridans group streptococci from neutropenic patients receiving ciprofloxacin.

All 47 sequential blood culture isolates of viridans group streptococci obtained from febrile neutropenic patients receiving quinolone prophylaxis were susceptible to vancomycin, teicoplanin, and imipenem. Resistance to benzylpenicillin (MIC for 50% of isolates [MIC50], 0.125 microgram/ml) and ceftazidime (MIC50, 4 micrograms/ml) was common. Most isolates were susceptible to amoxicillin, co-amoxiclav (amoxicillin-clavulanic acid at a 2:1 ratio by weight), azlocillin, clarithromycin, and erythromycin, with azithromycin showing comparable activity. The MIC90 of sparfloxacin was 1 microgram/ml; those for ciprofloxacin and ofloxacin were > 16 and 16 micrograms/ml, respectively.

Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years' experience.

Over 13 years, we have seen 16 cases of proven invasive aspergillosis in 446 bone marrow transplant recipients, an incidence of 3.6%. The incidence of infection is low in patients with uncomplicated allogeneic or autologous bone-marrow transplants (< 2% and 0, respectively). Of the 16 episodes following transplantation, 10 occurred in patients with late transplant complications who were no longer in protective isolation. In patients who had focal pulmonary lesions (as diagnosed by computed tomographic scanning), culture of bronchoalveolar lavage (BAL) fluid was not an effective diagnostic procedure. In diffuse pulmonary disease due to Aspergillus, culture of BAL fluid had a sensitivity of 100%. Aspergillus species were isolated from an additional six patients who had no evidence of invasive aspergillosis. Graft rejection was a significant predisposing factor for the development of invasive aspergillosis (P < .001, log-rank test), and in our hospital, these patients now receive intravenous amphotericin B as prophylaxis. None of the six patients whose chest roentgenograms showed abnormalities before transplantation and who underwent surgical resection as part of the treatment for invasive aspergillosis developed recurrent infection.

Species of alpha-hemolytic streptococci possessing a C-polysaccharide phosphorylcholine-containing antigen.

An enzyme-linked immunosorbent assay technique was used to detect and quantify C-polysaccharide-like antigen in strains of alpha-hemolytic streptococci classified into species by following the latest taxonomic recommendations. C-polysaccharide-like antigen is found only in Streptococcus oralis, S. mitis, and S. pneumoniae, which are genetically closely related.

Infection caused by Mycobacterium chelonae: a diagnostic and therapeutic problem in the neutropenic patient.

Mycobacterium chelonae, a rapidly growing species, is a significant cause of fever in neutropenic patients. We describe three febrile neutropenic patients at the Royal Free Hospital from whom this organism was isolated on several occasions. The condition of the first patient improved as the neutrophil count recovered. The second patient developed pulmonary disease and required surgical resection of a pulmonary lesion. The third patient, who had rapidly progressive, diffuse pulmonary disease, responded to an antibiotic regimen including erythromycin and ciprofloxacin. Both our findings and reports in the literature suggest that neutropenia may be a major risk factor for disseminated infection due to M. chelonae and that treatment is effective only after the recovery of the neutrophil count.

Stomatococcus mucilaginosus: an emerging pathogen in neutropenic patients.

Stomatococcus mucilaginosus was isolated from eight neutropenic patients during nine febrile episodes over a 13-month period. Five of these isolates were from definite infections, including one case of fatal meningitis. This slime-producing, catalase-variable, gram-positive coccus is a component of the normal oral flora of humans. Its biochemical profile may result in misidentification; however, unlike most micrococci, it characteristically fails to grow on media containing 5% NaCl. All but one of our isolates were sensitive to benzylpenicillin, and all were sensitive to vancomycin. S. mucilaginosus may prove to be an important pathogen in severely immunocompromised patients.