Bronchoalveolar Lavage Fluid Cytology in Culture-Documented Invasive Pulmonary Aspergillosis in Patients with Hematologic Diseases: Analysis of 67 Episodes.

There is a paucity of studies on the yield of Gomori-methenamine-silver (GMS) staining in bronchoalveolar lavage (BAL) fluid cytology and its comparison with fluorescent dye staining for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematologic malignancies. To that end, we analyzed the yield of direct fungal visualization in BAL fluid cytology with GMS staining, in a series of culture-positive IPA cases in 67 patients with hematologic malignancies, and we compared the results with those of direct examination with calcofluor white staining and BAL fluid galactomannan assays, when available. GMS staining in BAL fluid cytology was positive in 42% of the 67 cases and revealed coinfections in 7 cases. In contrast, only 2/67 (3.6%) BAL fluid samples were positive in direct smears stained with the fluorescent dye calcofluor white. Positive GMS staining results were significantly more frequent in IPA cases with cavitary lesions and IPA cases caused by >1 Aspergillus species, but the proportions of positive cytology results among Aspergillus species were not different.

Symptomatic BK Virus Infection Is Associated With Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients.

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline, and the Fine-Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.

Fecal colonization and infection with Pseudomonas aeruginosa in recipients of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Pseudomonas aeruginosa, especially multidrug-resistant (MDR) isolates, is an important pathogen in allogeneic hematopoietic stem cell transplant (HCT) recipients. The ability to identify patients at risk for these infections and administer appropriate empiric therapy, particularly during episodes of neutropenia, may improve outcomes and also direct infection control and antimicrobial stewardship efforts. Many transplant centers obtain routine surveillance stool cultures (SSCs) from HCT recipients to test for colonization with vancomycin-resistant enterococci, and extended-spectrum beta lactamase-producing Enterobacteriaceae. Our center initiated the performance of SSCs for P. aeruginosa, because of a perceived increase in the frequency of infection with MDR strains. The aim of this study was to determine the utility of this practice. METHODS: We conducted a 2-year (2010-2011) retrospective review of the medical records of all patients who underwent allogeneic HCT at our cancer center to (a) determine the frequency of fecal colonization with P. aeruginosa, including MDR strains; (b) to determine the overall frequency of subsequent P. aeruginosa infection, as well as the frequency of infection with MDR strains; (c) to ascertain the proportion of subsequent infections likely arising from the intestinal tract; and (d) to determine risk factors for progression from colonization to infection. RESULTS: Of 794 study patients, 58 (7.3%) had at least 1 positive SSC for P. aeruginosa; 19/58 (32.8%) developed a subsequent pseudomonal infection (11 with matching antimicrobial resistance patterns). On the other hand, 37/736 (5%) of the patients who were not colonized, developed a pseudomonal infection. The type of infection observed was pneumonia in 26 (46%) patients, bloodstream infection in 20 (36%), urinary tract infection in 8 (14%), and infections at other sites in 2 (4%). The incidence of MDR P. aeruginosa in the entire cohort was 2.2% (18 of 794): 12 had positive SSCs and 7 of these patients later developed MDR P. aeruginosa infections. Patients with acute myelogenous leukemia were more likely to be colonized and to develop subsequent infection. No infection-related deaths were observed during the first 30 days after infection. CONCLUSIONS: The incidence of P. aeruginosa colonization and subsequent infection was low. Patients who were not colonized had a low chance of developing P. aeruginosa infection. Most patients who developed infection did not have fecal colonization, suggesting a different source of infection. SSCs for P. aeruginosa provide incomplete information regarding the source of infection.

Incidence of fluoroquinolone-resistant and extended-spectrum ß-lactamase-producing Escherichia coli at a comprehensive cancer center in the United States.

BACKGROUND: Quinolones are used extensively for prophylaxis in high-risk cancer patients; however, increasing quinolone resistance is being reported. Extended-spectrum ß-lactamase (ESBL)-producing E. coli may be associated with increased morbidity and mortality particularly in neutropenic cancer patients. METHODS: We conducted a retrospective study of consecutive E. coli isolates from January 2009 to August 2009 at our institution. Data on antimicrobial susceptibility of E. coli isolates to commonly used antimicrobial agents and the frequency of ESBL production and fluoroquinolone resistance were gathered based on CLSI guidelines. RESULTS: There were 443 isolates of E. coli recovered. The majority were from urine cultures (308 isolates, 69.5%). Forty-one (9.2%) isolates were ESBL producing. Nine (18.3%) of the 49 isolates recovered from blood stream infections were ESBL producing. Quinolone resistance was present in 204 isolates (46%). Carbapenems and aminoglycosides retained excellent activity. E. coli resistance to quinolones increased from 13 to 46% in a period of 13 years (p = 0.001). CONCLUSION: The incidence of resistance to quinolones at our center may be increasing as a consequence of widespread use of quinolones as prophylaxis for neutropenic patients. ESBL-producing E. coli are frequent at our center and are associated with blood stream infections.

Effects of chronic hepatitis C infection on the treatment of breast cancer patients.

BACKGROUND: Although hepatitis C (HCV) is the most common blood-borne infection in the United States, little information exists about treatment of breast cancer in the setting of chronic HCV. PATIENTS AND METHODS: The databases of the University of Texas M.D. Anderson Cancer Center (MDACC) Tumor Registry, Department of Breast Medical Oncology, and Department of Laboratory Medicine were cross-referenced for patients with breast cancer, who were also identified as having HCV. Eligible patients had a diagnosis of invasive breast cancer, breast cancer treatment at MDACC, and a diagnosis of HCV. RESULTS: During chemotherapy, 25% of patients experienced elevations in aminotransferases and 44% of patients required dose reductions/delays in chemotherapy. More than 60% of the patients who received chemotherapy demonstrated a grade 2 or greater complication. However, 92% of patients were able to complete the number of cycles specified in the initial chemotherapy plan. CONCLUSIONS: As the majority of these breast cancer patients completed the initial chemotherapy plan, this study indicates that breast cancer patients with HCV can be treated with cytotoxic therapy. Comparison with historical controls showed similar rates of hepatic toxicity in the presence (or absence) of HCV, indicating that incidence of transaminitis may not be significantly affected by HCV.

Severe parainfluenza virus type 2 supraglottitis in an immunocompetent adult host: an unusual cause of a paramyxoviridae viral infection.

Parainfluenza virus is a major cause of respiratory illness in humans, manifesting from mild upper respiratory tract infection to bronchiolitis and pneumonia, especially in children. We report - to our knowledge - the first case of a nonimmunocompromised adult patient with human parainfluenza type 2 supraglottitis immediately after returning from China.

Microbial contamination of hematopoietic progenitor cell products: clinical outcome.

We reviewed the results of routine microbiological assays of 3078 infused hematopoietic progenitor cell (HPC) products for autologous and allogeneic transplantation between January 2001 and December 2005. Thirty-seven (1.2%) contaminated products were found. All patients receiving contaminated infusions received empirical antibiotic prophylaxis according to the assay result. None of these patients developed a positive blood culture with the same agent, developed infections that could be attributable to the contaminated product or experienced any clinical sequelae. Coagulase-negative Staphylococcus was found in 32 (86.5%) products. Admission lengths and time to engraftment were within the expected time frame for autologous and allogeneic transplants. Microbial contamination of HPC products occurs at a low frequency; prophylactic use of antibiotics based on the microbiological assay appears to be effective in preventing clinical complications.

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.

Early initiation of appropriate treatment is associated with increased survival in cancer patients with Candida glabrata fungaemia: a potential benefit from infectious disease consultation.

In patients with malignancies, Candida glabrata is one of the most frequent non-albicans Candida clinical isolates. As antifungal resistance in C. glabrata is common, we investigated the relationship between early appropriate antifungal treatment, infectious disease (ID) consultation and mortality in a contemporary cohort of cancer patients with C. glabrata fungaemia. We included patients with at least one C. glabrata-positive blood culture and symptoms or signs of infection seen at the MD Anderson Cancer Center between March 2005 and September 2013. In vitro susceptibility to antifungals was defined according to the 2010 CLSI clinical breakpoints. One-hundred and forty-six episodes of candidaemia were studied. Thirty isolates (20.5%) had fluconazole MIC ≥ 64 mg/L and 15 (10.3%) were caspofungin-resistant. Early (within 48 h after blood culture collection) initiation of appropriate antifungal treatment (hazard ratio 0.374, p 0.003) and early ID consultation (hazard ratio 0.421, p 0.004) were associated with decreased mortality, after adjustment for significant confounders. Thirty-two of 58 patients (55.2%) followed by ID were on appropriate antifungals within 48 h, compared with 16/88 patients (18.2%) who were not followed by ID an ID specialist (p <0.001). The median time-to-reporting of blood culture positivity for yeast was 71 h. Delayed time-to-reporting was associated with increased 28-day all-cause mortality (log-rank p 0.023). The benefits from early initiation of appropriate antifungal treatment and ID consultation were more prominent in patients with non-catheter-related candidaemia. In conclusion, in cancer patients with C. glabrata fungaemia, early ID consultation may lead to timely initiation of appropriate treatment and improved clinical outcomes.

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.

Transfusion support using filtered unscreened blood products for cytomegalovirus-negative allogeneic marrow transplant recipients.

It has been suggested that leukoreduced unscreened blood products can be used as an alternative to components from cytomegalovirus (CMV)-seronegative donors in order to prevent transmission of CMV from transfusions for CMV-seronegative marrow transplant recipients with CMV-seronegative donors, but confirmatory data are lacking. A retrospective chart review was undertaken for patients undergoing allogeneic transplantation over a 4-year period during which blood products were filtered for CMV-seronegative patients with CMV-seronegative donors when CMV-seronegative components were not available. Forty-five CMV-seronegative patient-donor pairs were identified. Only one patient developed CMV disease (pneumonia) and no other patients developed an infection. In this group of patients, the rate of CMV infection was 2.7% (95% CI, 0-8%) by life-table analysis. We conclude that filtered unscreened blood products as partial transfusion support for CMV-seronegative marrow transplant recipients were associated with a low incidence of CMV infection, justifying further evaluation of filtered blood products as total transfusion support for this patient population. However, since CMV infections still occur, continued surveillance by periodic culture or other techniques is warranted.

Ganciclovir prophylaxis for cytomegalovirus infection in pediatric allogeneic bone marrow transplant recipients.

Twenty-nine pediatric allogeneic bone marrow transplant (BMT) recipients, ages 2-17 years, were followed prospectively for cytomegalovirus (CMV) infection. Patients at risk received ganciclovir (GCV) prophylactically at a dose of 5 mg/kg/day i.v., 3 to 5 days per week, until day 100. Surveillance blood and urines were obtained weekly. Twelve patients developed DMV infection: one patient died with CMV interstitial pneumonitis on day 19 post-transplant prior to initiating GCV prophylaxis; 10 patients developed CMV viremia (n = 9) or viruria (n = 1) between day 30 and day 95 (median day 50) while receiving GCV prophylaxis; and one patient developed asymptomatic CMV viruria on day 130, 1 month after completing GCV prophylaxis. Patients with breakthrough infections on prophylaxis were treated with intensified GCV and i.v. immunoglobulin. No patient developed visceral involvement, although five patients had recurrent viremia. Six of the seven long-term survivors continued to excrete CMV in the urine intermittently for 6 to 28 months post-transplant. GCV was well tolerated with transient, mild neutropenia in five patients and thrombocytopenia in four patients. No extramedullary toxicity was encountered. GCV prophylaxis at a dose of 15-25 mg/kg/week is not adequate to prevent CMV reactivation in children receiving marrow transplants from unrelated donors and/or T cell-depleted grafts.

Comparison of cytomegalovirus antigenemia and shell vial culture in allogeneic marrow transplantation recipients receiving ganciclovir prophylaxis.

We prospectively monitored 61 allogeneic BMT patients for evidence of CMV infection and disease starting 7 days prior to transplant until day 110 after transplant. Patients receiving pre- and post-transplantation ganciclovir prophylaxis were followed for the incidence of infection by the CMV antigenemia assay and shell vial cultures. The median age of all patients was 32 years (range 5-54 years). Fourteen (25%) of 57 evaluable patients became CMV antigenemia or culture positive. The incidence of culture or antigenemia positivity in CMV seropositive or seronegative patients with a seropositive donor was 29% (14 of 49 patients). The antigenemia assay became positive a median of 29 days (range 12-89 days) after BMT as compared to 46 days (range 26-98 days) by shell vial assay (P < 0.001). There were no cases of CMV disease in the first 110 days after transplant. This study demonstrates that despite the use of prophylactic ganciclovir, BMT patients developed CMV infection but did not progress to disease in this study, the CMV antigenemia assay may be used to monitor for CMV infection during prophylaxis, and the current regimens for CMV prophylaxis with ganciclovir may require further evaluation to determine an optimal regimen to prevent CMV infection.

Respiratory syncytial virus infections in autologous blood and marrow transplant recipients with breast cancer: combination therapy with aerosolized ribavirin and parenteral immunoglobulins.

Scant data are available concerning the impact and response to therapy of respiratory syncytial virus (RSV) infections in patients undergoing autologous blood and marrow transplantation (BMT) for breast cancer. During eight winter seasons from 1992-1993 to 1999-2000, nine (4%) of 249 such patients were hospitalized with RSV infections. Six patients, including all five patients who were early post transplant in the pre-engraftment period, developed pneumonia and were treated with a combination of aerosolized ribavirin and IVIG. Among five patients with pneumonia in whom therapy was initiated prior to respiratory failure, one (20%) died. The sixth patient, in whom therapy was initiated after respiratory failure developed, also died. In total, two (1%) patients, both of whom were in the pre-engraftment period, died of progressive pneumonia. In conclusion, RSV is a significant cause of life-threatening pneumonia in autologous BMT recipients with breast cancer during the early post-transplant period, and accounted for a substantial portion of the overall transplant-related mortality, which in recent years has been minimal.

Cytomegalovirus pneumonia in adult autologous blood and marrow transplant recipients.

CMV pneumonia is a major cause of morbidity and mortality among allogeneic BMT recipients. To assess the frequency, timing, risk factors and response to therapy of CMV pneumonia among autologous BMT recipients, we reviewed our experience with 795 patients. Sixteen (2%) patients were diagnosed with CMV pneumonia. The frequency was higher among patients who were seropositive than those who were seronegative (3.3% vs 0%, P = 0.008). Among seropositive patients, the frequency was higher among patients with hematological malignancies than patients with solid tumors (5.0 % vs 1.0%, P = 0.019). Eleven cases occurred <30 days, and five cases occurred >100 days post transplant. The overall CMV pneumonia-related mortality rate was 31%. Seven (78%) of nine patients treated with ganciclovir and IVIG prior to respiratory failure survived; neither of two patients treated after respiratory failure survived. Four of five (80%) untreated patients survived. In conclusion, CMV is a not infrequent cause of pneumonia among autologous BMT recipients. Risk factors include CMV seropositivity and an underlying hematological malignancy. A favorable response hinges on the prompt initiation of therapy. The survival of 25% of the patients without antiviral therapy suggests that the isolation of CMV from a BAL specimen occasionally reflects oropharyngeal contamination or that CMV pneumonia may sometimes be self-limited in more immunocompetent autologous BMT recipients.

Management of an outbreak of vancomycin-resistant enterococci in the medical intensive care unit of a cancer center.

Between November 1996 and February 1997, 17 episodes of vancomycin-resistant enterococci (VRE) infection or colonization (9 infections, 8 colonizations), all with the same or a similar genomic DNA pattern, were identified in the medical intensive care unit (MICU) of a tertiary-care cancer hospital. The cases were genotypically traced to a patient who was admitted to the hospital in September 1996 and who, by December 1996, had four different admissions to the MICU. Multifaceted infection control measures, including decontamination of the environment and of nondisposable equipment, halted the nosocomial transmission of VRE in the MICU.

Impact of central venous catheter removal on the recurrence of catheter-related coagulase-negative staphylococcal bacteremia.

OBJECTIVE: To determine the impact of catheter management on the acute and long-term outcome of catheter-related coagulase-negative staphylococcal bacteremia. DESIGN: Retrospective surveillance of catheter-related sepsis using quantitative blood and catheter cultures. SETTING: University-affiliated tertiary cancer center. PATIENTS AND METHODS: Seventy patients with catheter-related coagulase-negative staphylococcal bacteremia were studied by retrospective chart review. The clinical characteristics of the patients and the management of the bacteremias were determined. The impact of immunosuppressive risk factors, antibiotic therapy, and catheter management on the recurrence of the bacteremia was investigated. RESULTS: Acute sepsis-related morbidity and mortality were not related to catheter management. However, during a 12-week followup period, the bacteremia recurred in 20% of the patients whose catheters remained in place, compared with only 3% of those whose catheters were removed (p less than .05). By multivariate analysis, patients whose catheters remained in place were 2.9 times more likely to experience a recurrence than those whose catheters were removed (odds ratio = 2.9, 95% confidence interval = 1.2-8.8, p = .03). All other potential risk factors were equally distributed between patients, with and without a recurrence. CONCLUSIONS: Although patients with catheter-related coagulase-negative staphylococcal bacteremia could be treated successfully while the catheter remains in place with the majority remaining free of recurrence, catheter retention results in a significantly higher risk for the recurrence of the bacteremia.

Control of nosocomial Clostridium difficile transmission in bone marrow transplant patients.

This is a report of six cases of Clostridium difficile-associated diarrhea (CDAD) that occurred among cancer patients undergoing bone marrow transplantation in a tertiary-care cancer hospital. Specific infection control measures that were taken to minimize the nosocomial spread of CDAD also are discussed.

Nosocomial respiratory syncytial virus infections: prevention and control in bone marrow transplant patients.

OBJECTIVE: To assess the effectiveness of a multifaceted infection control strategy in limiting the nosocomial transmission of respiratory syncytial virus (RSV) infection to patients in a bone marrow transplant (BMT) unit. DESIGN: Before/after trial. SETTING: University-affiliated tertiary cancer center. PATIENTS: Adult BMT recipients hospitalized during two consecutive wintertime community outbreaks of RSV infection. INTERVENTIONS: An infection control strategy against nosocomial RSV infection was implemented in the BMT unit in February 1993. The strategy involved prompt identification, isolation, and cohorting of RSV-infected patients; prompt therapy with aerosolized ribavirin; use of masks and gloves by anyone entering an infected BMT patient's room; screening visitors for respiratory symptoms; restricting visitation by all children under 12 years of age and all family members and other visitors with RSV symptoms; and restricting symptomatic hospital staff from working in the BMT unit. RESULTS: After implementation of the multifaceted infection-control strategy, there were four cases of nosocomial RSV infection in 3,870 patient days (incidence density, 1.0 case/1,000 patient days) compared with 14 cases of nosocomial RSV infection in 3,152 patient days (incidence density, 4.4 cases/1,000 patient days) during the 1992-1993 RSV season (rate ratio, 4.4; 95% confidence interval [CI95]. 1.4-17.9: P < .01). This decrease in incidence occurred despite a comparable prevalence of community-acquired RSV cases between the two seasons (2.2% vs 3.2% in 1992-1993 and 1993-1994, respectively; prevalence ratio, 0.7; CI95, 0.2-2.1; P = 0.5). CONCLUSION: Institution of a multifaceted infection control strategy significantly reduced the frequency of nosocomial RSV infection in a high-risk group of adult BMT recipients.

Allergic fungal sinusitis. Report of three cases associated with dematiaceous fungi.

Most reported cases of allergic sinusitis have been attributed to Aspergillus, based on the morphologic features of the organisms in tissue sections. However, in most cases, cultures have not been done. This is a report of three cases of non-Aspergillus allergic fungal sinusitis. The patients' ages were 11, 16, and 43; two were male and one was female. Histopathologic study disclosed fungal organisms resembling Aspergillus. However, cultures of these patients' nasal secretions grew Drechslera, Exserohilum, and Bipolaris fungal organisms. The non-Aspergillus nature of these infections was further supported by positive Fontana-Masson melanin staining. The authors conclude that allergic fungal sinusitis most likely results from non- Aspergillus organisms. For definitive fungal identification, tissue culture is mandatory. When tissue is not cultured or no organisms grow, a Fontana-Masson stain can be a useful adjunct in fungal identification.