Characteristics, risk factors and outcomes of adult cancer patients with extensively drug-resistant Pseudomonas aeruginosa infections.

OBJECTIVE: To evaluate the characteristics and outcomes of cancer patients with extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. METHODS: This was a retrospective cohort of P. aeruginosa infections in cancer patients in Crete, Greece. Patients were followed until discharge. Mortality, predictors of mortality and risk factors for XDR P. aeruginosa infection were studied. RESULTS: Ninety seven episodes (89 patients) of P. aeruginosa infections (52 with bacteremia) were included in the study. In 22 cases, the infection was due to XDR isolates. All XDR isolates were susceptible to colistin and variably resistant to almost all other antibiotics. The multivariate analysis showed that the independent risk factors for XDR P. aeruginosa infection were hematologic malignancy (OR 40.7, 95 % CI 4.5-367.6) and prior fluoroquinolone use (OR 11.0, 95 % CI 2.0-60.5); lymphopenia was inversely associated with XDR infections (OR 0.16, 95 % CI 0.03-0.92). Mortality was 43 %; infection-related mortality was 24 %. Bacteremia (OR 8.47, 95 % CI 2.38-30.15), infection due to XDR isolates (OR 5.11, 95 % CI 1.15-22.62) and age (OR 1.05, 95 % CI 1.00-1.09) were independently associated with mortality. CONCLUSION: Mortality in cancer patients with P. aeruginosa infections was high. Infection due to XDR isolates was independently associated with mortality.

Sources and outcome of bloodstream infections in cancer patients: the role of central venous catheters.

Simultaneously drawn quantitative blood cultures are used to diagnose catheter-related bloodstream infections. We conducted this study to determine the frequency with which central venous catheters were the source of bloodstream infections detected through paired positive blood cultures drawn from cancer patients and the potential for quantitative blood cultures to help predict outcome in neutropenic and non-neutropenic patients. From September 1999 to November 2000, we identified 169 patients with bloodstream infections. Of all bloodstream infections, 56% were catheter-related bloodstream infections. Gram-positive bacteremia was found to be catheter-related in 55% and 69% of patients with hematologic malignancy and solid tumors, respectively, whereas gram-negative bacteremia was catheter-related in only 19% of patients with underlying hematologic malignancy and in 60% of patients with solid tumor (P = 0.01). By multivariate analysis, poor response was associated with critical illness and persistent neutropenia (P < 0.01). In neutropenic patients with catheter-related bloodstream infections, peripheral quantitative blood cultures of >or=100 CFU/mL was also associated with poor response (P = 0.05). Central venous catheters were the major source of bloodstream infection, particularly in patients with solid tumors. In addition to critical illness and persistent neutropenia, quantitative blood cultures might be useful in predicting outcomes for neutropenic patients with catheter-related bloodstream infections.

Prospective evaluation of the impact of amoxicillin, clarithromycin and their combination on human gastrointestinal colonization by Candida species.

BACKGROUND: Amoxicillin and clarithromycin have been used extensively for the eradication of Helicobacter pylori. However, no study has examined the impact of their combination on the Candida albicans concentration of the gastrointestinal (GI) tract. This is the first study examining and comparing directly the effect of amoxicillin, clarithromycin and their combination on the C. albicans concentration of the human GI tract. METHODS: Thirty-three adult patients (11 in each antibiotic group) were studied prospectively. Quantitative stool cultures for Candida were conducted at the beginning, the end and 1 week after the discontinuation of antibiotic treatment. RESULTS: All three regimens increased the GI colonization in patients by Candida. The combination of amoxicillin with clarithromycin caused the highest increase; however, this was not statistically significant. CONCLUSION: Amoxicillin and clarithromycin used either alone or in combination cause a small to moderate increase in GI colonization by Candida. Hence, these drugs could be safely used in patients at risk for candidiasis originating from the GI tract.

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.

Recent experience with Pseudomonas aeruginosa bacteremia in patients with cancer: Retrospective analysis of 245 episodes.

BACKGROUND: Pseudomonas aeruginosa bacteremia is a serious and possibly fatal condition in patients with cancer. OBJECTIVES: To ascertain the frequency, demographics, and predisposing factors for P. aeruginosa bacteremia in patients with cancer and to determine the efficacy of various therapeutic regimens. SUBJECTS AND METHODS: Patient records of the Clinical Microbiology Laboratory, The University of Texas, M. D. Anderson Cancer Center, Houston, were reviewed. From January 1, 1991, through December 31, 1995, 245 eligible cases of P. aeruginosa bacteremia were identified. We examined the patient records for the underlying malignant neoplasm and its management, symptoms and signs of infection, culture results of appropriate specimens, antibiotic therapy, and outcome. We also compared our present experience with a previous analysis from this institution covering the period from January 1, 1972, to December 31, 1981. RESULTS: The incidence of P. aeruginosa bacteremia has decreased compared with the previous study (2.8 vs 4.7 cases per 1000 admissions). It was most common in patients with acute leukemia (55 of 1000 registrations), and the frequency in this disease has not changed. Half of the patients were not in the hospital when they developed their infection. The overall cure rate was 80%, which was a significant (P<.001) increase compared with the 62% cure rate in the previous study. In this study, no significant difference in the cure rates was observed between monotherapy with a beta-lactam and combination therapy overall (P = .72), and in patients with shock (P = 1.0) and those with pneumonia (P = .60). The patients' initial neutrophil counts were not of prognostic value; however, the cure rate depended on subsequent changes in neutrophil count during therapy. CONCLUSIONS: The frequency rate of P. aeruginosa bacteremia has decreased in patients with solid tumors but has remained unchanged in patients with acute leukemia. Antibiotic regimens for empirical therapy of neutropenic patients and especially patients with acute leukemia should still provide coverage against P. aeruginosa.

Intravascular catheter-related infections: a preventable challenge in the critically ill.

In modem medicine, central venous catheters (CVCs) have a pivotal role in the management of critically ill patients. The most serious complication of effective CVC placement is catheter-related bloodstream infection (CRBSI). Microbial colonization and CRBSI are the byproducts of the interaction of 4 factors: (1) microbial factors (hydrophobicity and exopolysaccharide production), (2) host factors (such protein adhesins as fibrin and fibronectin that attach to the catheter surface), (3) catheter material (hydrophobicity, surface charges, thrombogenicity), and (4) iatrogenic factors (total parenteral nutrition, interleukin-2). The organisms most frequently associated with CRBSI are Staphylococcus epidermidis, Staphylococcus aureus, and Candida spp. CRBSIs were traditionally diagnosed through semiquantitative or quantitative cultures of the catheter tip. However, the diagnosis can be achieved without catheter removal through cultures of blood specimens collected simultaneously though the CVC and a peripheral vein. Currently, the most effective method of preventing a CRBSI is the use of a CVC coated with antimicrobial agents. Intravenous administration of vancomycin for 7 days is adequate for an uncomplicated CRBSI caused by coagulase-negative staphylococci, and at least 10 days of therapy with beta-lactams is required for an uncomplicated infection caused by methicillin-sensitive S. aureus. CRBSI caused by Candida albicans or Candida parapsilosis can be treated with at least 14 days of therapy with fluconazole or amphotericin B. In the case of Candida krusei, only amphotericin B is effective.

Ceftriaxone and dexamethasone affecting yeast gut flora in experimental mice.

Crl:CD1 (ICR) BR mice were fed regular food or food containing Candida albicans to induce gastrointestinal (GI) colonization by the yeast. Groups of colonized mice were subsequently treated with either ceftriaxone for 10 days or dexamethasone for 10 or 21 days. Another group of colonized mice was treated with the combination of ceftriaxone, given for 10 days, and dexamethasone given for 21 days. Other colonized mice received normal saline, and non-colonized mice received the same drugs or saline, serving as controls. Candida-colonized mice, treated either with ceftriaxone or with dexamethasone alone, had significantly increased levels of GI colonization by the yeast. Colonized mice treated with the combination of the antibiotic with dexamethasone had stool concentrations of Candida similar to those of mice treated with the antibiotic alone. Saline did not affect Candida stool concentration. Yeasts were not found in the stools of non-colonized mice treated with the study drugs or saline. There was no evidence of Candida dissemination to internal organs in any group.

Effects of cefepime, cefixime and ceftibuten on murine gut colonization by Candida albicans.

Crl:CD1(ICR) BR mice were fed chow containing Candida albicans or regular chow. Both groups were subsequently given either antibiotics or normal saline. Stool cultures were performed before, at the end of treatment and 1 week after treatment, to determine the effect on the stool yeast concentration. Candida-colonized mice treated with cefepime, cefixime or ceftibuten had higher (however not significantly) counts of the yeast in their stools than control Candida-fed mice treated with saline. A group of Candida-fed mice were treated with ceftriaxone, which is known to increase the yeast stool concentration significantly and served as positive control. Mice fed regular chow and treated with the study drugs or saline did not have any yeasts in their stools. Dissemination of Candida did not occur.

Oropharyngeal candidiasis as a marker for esophageal candidiasis in patients with cancer.

The present study was designed to determine the frequency of candidal esophagitis in cancer patients with oral thrush. Patients with clinically and microbiologically diagnosed oral candidiasis were evaluated by endoscopy for concurrent esophageal candidiasis. Esophageal involvement was documented by mucosal lesions, microbiological findings of candidal infection in smears of brushing material, positive cultures of brushing material, and histological evidence of mucosal invasion by the yeast. For 21 of the 22 patients studied, there were endoscopic and microbiological findings of candidal esophagitis. Cultures of the brushing material from all 22 patients were positive, while histological evidence was found for 14 patients. Only 10 of the patients had mild esophageal symptoms. It is concluded that oral thrush represents a reliable marker for esophageal candidiasis in patients with cancer. Routine endoscopy is not necessary to confirm the diagnosis; this procedure should be reserved for patients with persistent thrush and symptoms despite antifungal therapy.

Gut colonization of mice by yeast: effects of methylprednisolone and antibiotics.

BACKGROUND/AIMS: This study evaluated the effects of broad spectrum antibiotics and methylprednisolone on the gut colonization of mice by C. albicans. METHODOLOGY: Male Crl:CD1 (ICR) BR mice, 3 months of age, were fed chow containing Candida albicans, while similar mice were fed regular chow. The gut of the Candida-fed mice was colonized by yeast. Groups of mice were subsequently treated for 10 days, with either ceftriaxone, ticarcillin-clavulanic acid, or methylprednisolone, each alone or with the combination of methylprednisolone and each antibiotic. Other Candida-colonized mice received normal saline, and non-colonized mice, serving as controls, received the same drugs and drug combinations or saline. RESULTS: Candida-colonized mice treated with each antibiotic alone had significantly higher yeast counts in their stool, while those treated with methylprednisolone alone did not. Colonized mice treated with the combination of each antibiotic with methylprednisolone had similar stool concentrations of Candida as mice treated with each antibiotic alone. Saline did not change Candida in the stool concentration. Yeast was not found in the stool of non-colonized mice treated with the drugs under investigation or saline. Dissemination of Candida did not occur in any mouse. CONCLUSIONS: Ceftriaxone and ticarcillin-clavulanic acid significantly increase gut colonization of mice by yeast, while methylprednisolone, either alone or in combination with these antibiotics, does not.