blaVIM-2 and blaVIM-7 carbapenemase-producing Pseudomonas aeruginosa isolates detected in a tertiary care medical center in the United States: report from the MYSTIC program.

Two Pseudomonas aeruginosa strains resistant to beta-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and carbapenems and susceptible only to polymyxin B (MIC

The significance of blood cultures positive for emerging saprophytic moulds in cancer patients.

The significance of blood cultures positive for emerging saprophytic moulds (e.g., Scedosporium apiospermum, Scedosporium prolificans, Paecilomyces spp.) was evaluated in 30 cancer patients (1996-2002). Diagnostic criteria proposed previously for evaluation of aspergillaemia were used. Blood cultures positive for emerging saprophytic moulds represented 1% of all positive fungal cultures. One case of catheter-related fungaemia was excluded. The remaining 29 cases consisted of true (n = 5), probable (n = 1), indeterminate (n = 7) fungaemia, and contamination (n = 16). True fungaemia was seen only in leukaemia patients and allogeneic bone marrow transplant recipients. S. apiospermum and S. prolificans were the commonest causes of true fungaemia.

Outcome determinants of fusariosis in a tertiary care cancer center: the impact of neutrophil recovery.

Factors associated with failure of antifungal therapy were examined in 42 cancer patients with fusariosis (1987-1997). Thirty-six patients (86%) had leukemia and 39 (93%) were neutropenic. Disseminated infection was the most common presentation. The majority (83%) received amphotericin B-based therapy. Thirty patients (71%) failed therapy. No patient with persistent neutropenia responded.

Protothecosis in patients with cancer: case series and literature review.

OBJECTIVE: To review our recent experience with protothecosis in patients with cancer at The University of Texas MD Anderson Cancer Center, and compare these cases with others reported in the literature. METHODS: We report on three patients with protothecosis and cancer who were seen at The University of Texas MD Anderson Cancer Center from January 1979 to May 2002, and reviewed all cases of protothecosis in patients with cancer reported in the literature since 1966. RESULTS: Overall, 13 cases of protothecosis complicating cancer were evaluated. The median age of the patients was 41 years (range, 7-73 years). Seven patients (54%) had an underlying hematologic malignancy, and one infection occurred after bone marrow transplantation. Neutropenia was uncommon in these patients (14%). Prototheca wickerhamii was the most common Prototheca species identified as the causative agent of infection. Skin infection was the most common presentation of protothecosis, occurring in five patients (38%), followed by disseminated disease in three patients (23%), algaemia in three patients (23%), pulmonary infection in one patient (8%), and olecranon bursitis in one patient (8%). Information on the use of antifungal therapy was available for ten patients. Seven of the ten patients received amphotericin B, while three received triazoles (fluconazole in two, itraconazole in one). Breakthrough protothecosis occurred during the administration of systemic antifungal therapy with itraconazole in one patient. All seven patients who received amphotericin B showed a response, as did one of the three patients given triazoles. Seven (58%) of the patients died during the study period, only one (17%) of protothecosis. CONCLUSIONS: Protothecosis is an uncommon infection in cancer patients, implying that Prototheca spp. have a low pathogenic potential in this population. Pulmonary involvement in particular is uncommon in these patients. Amphotericin B appears to be the most effective antifungal agent; the role of triazoles in treating protothecosis is uncertain, but they may be less effective.

Respiratory disease due to parainfluenza virus in adult leukemia patients.

Reports of human parainfluenza viruses (HPIV) in patients with leukemia have been limited to a few cases or as a portion of general surveys. In order to expand the knowledge of these infections in this patient group, the frequency and clinical course of HPIV infections was determined among 1,787 patients with leukemia treated at The University of Texas M.D. Anderson Cancer Center between July 1994 and December 1997. HPIV was isolated from 47 (6.2%) of the 770 patients who were cultured for respiratory viruses. HPIV type 3 accounted for 39 of the 47 HPIV infections. Twenty-six patients developed pneumonia, and the associated mortality was 27%. Multivariate analysis revealed that a low absolute lymphocyte count and pneumonia were associated with increased mortality. Concurrent respiratory and other infections were associated with an increased frequency of pneumonia. Only five patients with pneumonia received antiviral therapy and four of them survived the infection. HPIV infection in leukemic patients is frequently associated with pneumonia and the mortality rate from pneumonia is substantial among lymphopenic patients.

Invasive aspergillosis in 2002: an update.

Despite significant advances in the management of immunosuppressed patients, invasive aspergillosis remains an important life-threatening complication. In the past two decades, the incidence of invasive aspergillosis in this population has continued to increase. Factors that predispose patients to develop invasive aspergillosis include prolonged granulocytopenia, the development of graft-versus-host disease, immunosuppressive therapy, the use of adrenal corticosteroids, and the prolonged impairment of host defenses associated with diseases such as chronic granulomatous disease. Environmental factors also play a key part in the pathogenesis of this infection, and therefore, infection control measures play a critical role in reducing exposure of patients to Aspergillus. New exciting developments in the early diagnosis of invasive aspergillosis and the acceleration of antifungal drug discovery offer promise for the future.

Pulmonary candidiasis in patients with cancer: an autopsy study.

For patients who had cancer and autopsy-proven pneumonia, we evaluated whether cultures of respiratory secretions (sputum and/or bronchoalveolar lavage) performed < or =4 weeks before autopsy were a reliable basis for the diagnosis of pulmonary candidiasis. Pulmonary candidiasis was identified at autopsy in 36 patients, but common clinical predictors were insensitive for this diagnosis. For sputum culture, the sensitivity, specificity, and the positive and negative predictive values were 85%, 60%, 42%, and 93%, respectively; for bronchoalveolar lavage culture, these values were 71%, 57%, 29%, and 89%, respectively.

Treatment of vancomycin-resistant enterococcal infections in the immunocompromised host: quinupristin-dalfopristin in combination with minocycline.

Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D-MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.

Risk Factors for Candida tropicalis fungemia in patients with cancer.

The risk factors for and presentation of Candida tropicalis fungemia, in comparison with those of Candida albicans, have been incompletely characterized. We compared 43 cases of C. tropicalis fungemia with 148 cases of C. albicans fungemia. In univariate analysis, patients with C. tropicalis fungemia were more likely to have leukemia (P=.0006), prolonged neutropenia (P=.03), and a positive blood culture for more days (P=.02). The 2 groups did not differ with regard to baseline Acute Physiology and Chronic Health Evaluation (APACHE) II score, frequency of catheter-associated fungemia, or response to antifungals. In multivariate analysis, patients with C. tropicalis fungemia were more likely to have leukemia (P=.02), previous neutropenia (P=.002), and a longer stay in the intensive care unit during the infectious episode (P=.01). Also, the response of the breakthrough C. tropicalis fungemia was lower (P=.05). In conclusion, the host determinants associated with susceptibility to C. tropicalis are leukemia and prolonged neutropenia.

Fluconazole vs. amphotericin B for the management of candidaemia in adults: a meta-analysis.

The incidence of bloodstream infections caused by Candida species is rising. Few published studies have compared the efficacy of fluconazole with that of amphotericin B. We performed a meta-analysis of the prospective studies that compared fluconazole and amphotericin B for the treatment of candidaemia in adults. Data on total mortality, candidaemia-attributable mortality, efficacy, microbiological failure, and toxicity were extracted from eligible studies. All studies appeared homogeneous with respect to the outcome measures. Most patients were at relatively low risk for death as evidenced by the low average physiologic score and the lack of intense immunosuppression. The odds ratios (OR) of treatment with amphotericin B versus fluconazole and 95% confidence intervals (CI) were as follows: total mortality (OR, 1.06; CI, 0.89-1.25), candidaemia-attributable mortality (OR, 1.0; CI, 0.70-1.45), clinical response (OR, 1.14; CI, 0.93-1.39) and microbiological failure according to all Candida species (OR, 0.99; CI, 0.78-1.26). A trend favouring amphotericin B was seen in mycological eradication of non-albicans Candida species (OR, 0.70; CI, 0.47-1.06). Finally, amphotericin B was more toxic than fluconazole (OR, 2.94; CI, 2.14-4.4). In conclusion, fluconazole is as efficacious and less toxic than amphotericin B in stable, not severely immunosuppressed candidaemic patients at low risk for death. However, fluconazole may be less effective than amphotericin B in candidaemias caused by some non-albicans Candida species.

Management of fever in neutropenic patients.

Substantial progress has been made in the management of febrile episodes in neutropenic patients, largely by the prompt administration of potent, broad-spectrum antimicrobial agents. During the past several decades, the spectrum of organisms has changed from a predominance of gram-negative pathogens to a predominance of gram-positive pathogens. In recent years, some hospitals have experienced an increase of infections caused by multi-drug-resistant pathogens. Hence, it is no longer possible to rely on standardized regimens, but antimicrobial therapy must be selected based on the predominant pathogens and antimicrobial susceptibility patterns at each institution. It is customary to initiate antifungal therapy empirically in those patients whose fever persists despite broad-spectrum antibacterial therapy. Alternatives now exist to amphotericin B, including lipid formulations of this drug, and fluconazole. It is critically important that each patient be carefully re-assessed before starting antifungal therapy, because there are many other potential causes for persistent fever, including resistant bacteria and viruses. Novel approaches to therapy include outpatient antibiotics, and use of growth factors as adjunctive therapy. There also has been a renewed interest in white blood cell transfusions. Although the prognosis for infection in neutropenic patients has improved greatly, new infectious problems have emerged that limit our successful management of these complications.

Cryptococcosis in patients with cancer.

Records of 31 patients with cancer who did not have known human immunodeficiency virus infection and who developed culture-proven cryptococcosis during the period of 1989-1999 (incidence of 18 cases per 100,000 admissions) were retrospectively reviewed. Several presentations of cryptococcosis were seen, including pulmonary in 19 patients (13 of which were symptomatic), disseminated in 6, meningeal in 3, and other, less common manifestations in 3. Hematologic malignancy (in 20 patients [65%]) was the most common underlying disease. Lymphopenia was present in 19 patients (61%). Previous steroid use was noted in 16 patients (51%). The diagnosis of cryptococcosis was rarely suspected; lung and brain malignancy were frequent initial impressions. Cryptococcosis was diagnosed postmortem in only 2 cases (6%). In cases of both pulmonary and meningeal cryptococcosis, the yield of invasive diagnostic procedures was good. Antifungal treatment was heterogeneous, but only 18% of patients who received it had treatment failure. Fluconazole monotherapy was successful in 92% of patients. In conclusion, cryptococcosis is rare in patients with cancer and appears to have a relatively good diagnostic yield and therapeutic outcome.

Effect of ketoconazole, itraconazole and fluconazole on the gastrointestinal colonization of mice by Candida albicans.

Crl:CD1 (ICR) BR mice were colonized in the gastrointestinal (GI) tract with Candida albicans. This strain was susceptible to ketoconazole (MIC=0.25 microg/ml), itraconazole (minimum inhibitory concentration, MIC=0.25 microg/ml), and fluconazole (MIC=4 microg/ml). Subsequently the animals received monotherapy with ketoconazole by mouth (equivalent to human dose of 2.9 mg/kg/day), or itraconazole by mouth (equivalent to human dose of 2.9 mg/kg/day), or fluconazole either subcutaneously (equivalent to human dose of 2.2 mg/kg/day), or by mouth (equivalent to human dose of 2.2 mg/kg/day), for 10 days. Quantitative stool cultures at the end and one week after the end of treatment revealed that all three azoles caused a small and statistically non significant reduction of C. albicans concentration in the stools. The different route of administration of fluconazole did not produce different results. In conclusion, these azoles, used at the present doses and schedules, have minimal effect on murine GI colonization by this strain of C. albicans which is susceptible but with rather increased MICs.

Pseudomonas aeruginosa infections in cancer patients: have they gone away?

Pseudomonas aeruginosa infection continues to be a threat to cancer patients, especially if they are neutropenic. As many as 50% of infections are community acquired. Prompt, effective therapy results in cures in about 80% of patients, although the presence of shock or pneumonia indicates a poor prognosis. Antibiotic resistance is an increasing problem.

Unusual presentations of infection in neutropenic patients.

Neutropenic patients may have unusual presentations of infection because of their inability to mount an adequate inflammatory response and their susceptibility to infection caused by less virulent organisms. About 60% of febrile episodes are associated with no other signs and symptoms and no infecting organism can be identified, yet most respond to antibacterial therapy. If not treated promptly, infection in neutropenic patients can progress rapidly. Unusual sites of infection include typhlitis, perirectal infections and atypical forms of cellulitis.

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PURPOSE: To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. METHODS: The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. RESULTS: Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). CONCLUSION: Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

Candida krusei fungemia. An escalating serious infection in immunocompromised patients.

BACKGROUND: Candida krusei is inherently resistant to fluconazole and is emerging as a frequent cause of fungemia in patients with hematologic malignant neoplasms. OBJECTIVE: To determine the risk and prognostic factors associated with C krusei fungemia in comparison with Candida albicans fungemia in patients with cancer. METHODS: Retrospective study of 57 cases of C krusei fungemia occurring at the M. D. Anderson Cancer Center, Houston, Tex, from 1989 to 1996. The C krusei cases were compared with 57 cases of C albicans fungemia with respect to demographics, underlying cancer, Acute Physiology and Chronic Health Evaluation II score, immunosuppression status, chemotherapy, and the use of central venous catheters, as well as fluconazole prophylaxis. RESULTS: At our institution, C krusei accounted for 5% of fungemias during 1989 through 1992 and for 10% during 1993 through 1996. Patients with C krusei fungemia more often had leukemia than patients with C albicans (77% vs 11%; P =.02), whereas catheter-related infections were more common among patients with C albicans fungemia (42% vs 0%; P<.001). Patients with C krusei fungemia had a lower response rate (51% vs 69%; P =.05), largely because they more frequently were neutropenic and had disseminated infection. Mortality related to fungemia was 49% in the cases with C krusei vs 28% in C albicans. Multiple logistic regression analysis showed that persistent neutropenia (P =.02) and septic shock (P =.002) were predictors of poor prognosis. CONCLUSION: In neutropenic patients, C krusei fungemia is associated with high mortality. It should be suspected in patients with leukemia who are receiving fluconazole prophylaxis and should be treated aggressively with an amphotericin B regimen.