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.

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.

Adenoviral infections in adult allogeneic hematopoietic SCT recipients: a single center experience.

Disseminated adenoviral infection (AI) is associated with profound immunosuppression and poor outcome after allogeneic hematopoietic SCT (allo-HSCT). A better understanding of AI in allo-HSCT recipients can serve as a basis to develop more effective management strategies. We evaluated all adult patients who received allo-HSCT at MD Anderson Cancer Center between 1999 and 2008. Among the 2879 allo-HSCT patients, 73 (2.5%) were diagnosed with AI. Enteritis (26%) and pneumonia (24%) were the most common clinical manifestations; pneumonia was the most common cause of adenovirus-associated death. A multivariable Bayesian logistic regression showed that when the joint effects of all covariates were accounted for, cord blood transplant, absolute lymphocyte count (ALC) ≤ 200/mm(3) and male gender were associated with a higher probability of disseminated AI. The OS was significantly worse for patients with AI that was disseminated rather than localized (median of 5 months vs median of 28 months, P<0.001) and for patients with ALC ≤ 200/mm(3) (P<0.001). Disseminated AI, in patients who received allo-HSCT, is a significant cause of morbidity and mortality. Strategies for early diagnosis and intervention are essential, especially for high-risk patients.

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.

Changing trends in etiology of bacteremia in patients with cancer.

The present study was conducted to determine trends in the quantitative bacterial load patterns of bacterial bloodstream infections (BSI) caused by various bacteria in patients receiving care at a comprehensive cancer center. Bacterial loads of all consecutive quantitative blood cultures performed during 1998 and 2004 were graded quantitatively. Gram-positive bacteria (GPB) were responsible for the majority of BSI episodes in both years studied: 740 of 1,055 (73%) in 1998 and 820 of 1,025 (82%) in 2004. Compared with GPB infections, a significant proportion of infections caused by Gram-negative bacteria was associated with a high bacterial load (HBL) (11 vs 28% in 1998 and 10 vs 30% in 2004; p<0.001). In 2004, BSI episodes due to non-Pseudomonas non-fermentative GNB (Stenotrophomonas maltophilia and Acinetobacter spp) were significantly associated with a HBL compared to BSI due to Pseudomonas aeruginosa (47 vs 23%; p<0.05); this was not the case in 1998. Conversely, the HBLs commonly associated with BSI due to Staphylococcus aureus (50%) and Streptococcus spp (35%) versus coagulase-negative staphylococci (13%; p<0.0001) during 1998 were not noted during 2004 (22% Staphylococcus aureus, 20% Streptococcus spp, 21% coagulase-negative staphylococci; p>0.5). The spectrum of BSI continues to change and its prognostic implications in cancer patients needs further study.

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.

Infections by the yeast Kodomaea (Pichia) ohmeri: two cases and literature review.

A 14-year-old boy who was neutropenic following chemotherapy for leukemia developed fungemia caused by the yeast Kodomaea ohmeri ( Pichia ohmeri). The infection was cured by catheter removal and the use of fluconazole. A 74-year-old man who had undergone surgeries for a subcutaneous tumor developed polymicrobic cellulitis involving Kodomaea ohmeri. Despite surgical debridement and antibiotic therapy, the patient died of complications. Including these 2 cases, there have been 10 Kodomaea ohmeri infections reported thus far, all occurring in patients with pre-existing conditions. There have been seven cases of fungemia and one case each of peritonitis, funguria, and cellulitis. The treatment employed varied depending on the site/source of infection. Seven patients recovered and three died. The microbiological data available suggest that Kodomaea ohmeri can be identified definitively by biochemical tests and is susceptible to amphotericin B and either susceptible to or dose dependently susceptible to itraconazole and fluconazole.

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.

Non-albicans Candida is the most common cause of candidemia in pediatric cancer patients.

GOALS: Candidemia is a serious infection that can severely complicate the care of children with cancer. We sought to determine the spectrum of Candida species in children with cancer, since effective therapy may depend on the species involved. PATIENTS AND METHODS: A retrospective review of candidemia episodes in our pediatric oncology patients over a 9-year period was conducted. During this period azole prophylaxis was not routine in this group. RESULTS: 38 episodes of candidemia were identified: C. albicans 29%, C. tropicalis 26%, C. parapsilosis 24%, C. krusei 8%, C. glabrata 8%, and C. lusitaniae 5%. Non-albicans Candida was common in patients not receiving azole prophylaxis. Species typically susceptible to azoles were common among patients not using azoles. Death attributed to the fungal infection occurred in 21% of episodes, with nearly all the deaths occurring in patients with C. albicans and C. tropicalis. CONCLUSIONS: C. albicans is not the predominant species in pediatric oncology patients experiencing candidemia, even in azole-naive patients.

Pulmonary granuloma caused by Pseudomonas andersonii sp nov.

Pulmonary granuloma is a common lesion for which gram-negative bacteria are rarely implicated as a cause. Hence, most physicians are unaware of this etiology. We isolated a gram-negative bacterium from a surgically resected pulmonary granuloma in a 42-year-old, nonimmunocompromised woman. Within the necrotizing granuloma, numerous organisms also were demonstrated by Gram stain, suggesting a cause-disease relationship. Characterization of the bacterium by sequence analysis of the 16S ribosomal gene, cellular fatty acid profiling, and microbiologic studies revealed a novel bacterium with a close relationship to Pseudomonas. We propose a new species for the bacterium, Pseudomonas andersonii. These results suggest that the differential diagnosis of a lung granuloma also should include this gram-negative bacterium as a potential causative agent, in addition to the more common infections caused by acid-fast bacilli and fungi. This bacterium was shown to be susceptible to most antibiotics that are active against gram-negative bacteria.

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.

Community respiratory virus infections among hospitalized adult bone marrow transplant recipients.

From 1 November 1992 through 1 May 1993 and from 1 November 1993 through 1 May 1994, we conducted a prospective surveillance study at the University of Texas M.D. Anderson Cancer Center (Houston) to evaluate the role of community respiratory virus infections in hospitalized adult bone marrow transplant (BMT) recipients, Respiratory secretions were obtained from all adult BMT recipients with acute respiratory illnesses. During these two winters, a community respiratory virus was isolated from 37 (36%) of 102 patients and 30 (26%) of 115 patients, respectively. Approximately half (49%) of these infections were due to respiratory syncytial virus (RSV); the remainder were due to influenza virus (18%), picornaviruses (18%), parainfluenza virus (9%), or adenovirus (6%). Fifty-eight percent of these infections were complicated by pneumonia, with an associated mortality of 51%. The pneumonias that complicated RSV infection were almost exclusively viral in origin and were associated with a mortality of 100% if not treated promptly with antiviral agents. In contrast, many of the pneumonias that complicated the other viral infections, such as influenza, appeared to be either self-limited viral pneumonias or secondary bacterial or fungal pneumonias. Community respiratory viruses are frequent causes of acute respiratory illnesses in adult BMT recipients hospitalized during the winter and are associated with substantial morbidity and mortality.

In vitro activities of free and liposomal drugs against Mycobacterium avium-M. intracellulare complex and M. tuberculosis.

We compared MICs and MBCs of various free- and liposome-incorporated antimicrobial agents against several patient isolates of Mycobacterium avium-M. intracellulare complex and certain American Type Culture Collection strains of M. avium, M. intracellulare, and Mycobacterium tuberculosis. Seven of 19 agents were selected for incorporation into liposomes. The MICs of these agents for 50 and 90% of isolates tested (MIC50s and MIC90s, respectively) ranged from 0.5 to 62 micrograms/ml. Members of the M. avium-M. intracellulare complex were resistant to killing by most of the other agents tested in the free form. However, clofazimine, resorcinomycin A, and PD 117558 showed complete killing of bacteria at concentrations ranging from 8 to 31 micrograms/ml, represented as MBC90s. Among the liposome-incorporated agents, clofazimine and resorcinomycin A had the highest killing effects (MBC90s, 8 and 16 micrograms/ml, respectively). Furthermore, both free and liposome-incorporated clofazimine had equivalent growth-inhibitory and killing effects on all American Type Culture Collection strains of M. avium, M. intracellulare, and M. tuberculosis tested. These results show that the antibacterial activities of certain drugs, particularly those of clofazimine and resorcinomycin, were maintained after the drugs were incorporated into liposomes.

Evaluation of a rapid enzyme-linked immunoassay for the diagnosis of herpes simplex virus in cancer patients with oral lesions.

Oral herpes simplex virus infection in immunocompromised cancer patients can have a variety of different clinical appearances, which makes diagnosis difficult, and it can be associated with significant morbidity. Prompt diagnosis is important so that therapy can be started as soon as possible. The standard by which the diagnosis of herpes simplex virus is made is a culture that can take up to 10 days to produce results. In an effort to test a possibly better method, we evaluated a 12-minute, enzyme-linked immunoassay and found the sensitivity, specificity, positive predictive value, and negative predictive value to be 75.9%, 90.0%, 84.6%, and 83.7%, respectively. This test is easy, inexpensive, and can be done in a clinical setting, thus providing a prompt, accurate result so that treatment can be started without delay. This promptness is especially important in the immunocompromised cancer patient.

Prophylaxis of cytomegalovirus infection with ganciclovir in allogeneic marrow transplantation.

Cytomegalovirus (CMV) infection is one of the most common causes of morbidity and mortality after allogeneic marrow transplantation. We studied 14 consecutive CMV-seropositive patients adding ganciclovir (2.5 mg/kg i.v. every 8 hours for 7 days prior to transplant and 6 mg/kg three times a week after neutrophils became greater than 0.5 x 10(9)/l and the patients were platelet transfusion-independent until d 70) to our previous prophylaxis regimen which consisted of intravenous immunoglobulin and acyclovir. The result was compared with 30 consecutive patients whom we studied with our previous regimen. The addition of ganciclovir did not cause any extra toxicities. The incidence of interstitial pneumonitis and cumulative probability of CMV excretion in the first 100 d post-transplantation was significantly reduced (p = 0.038 and p = 0.035 respectively). The result shows that addition of ganciclovir significantly decreased the incidence of CMV infection in the early post-transplantation period.

Clinical comparison of the resin-containing BACTEC 26 Plus and the Isolator 10 blood culturing systems.

The new resin-containing BACTEC 26 Plus blood culturing system (Becton Dickinson Diagnostic Instrument Systems, Towson, Md.) was compared with the Isolator 10 system (Wampole Laboratories, Cranbury, N.J.). Blood samples were drawn by syringe, and equal 10-ml volumes were evaluated in each blood culture system by the recommended methods. Both systems were incubated aerobically with 5% CO2. Of 11,506 acceptable study specimens, 1,788 aerobic isolates were recovered. Overall, recoveries was similar for the two systems, with 626 bacteria or fungi recovered in the BACTEC 26 Plus system only, 499 recovered in the Isolator system only, and 663 recovered in both systems. Of 345 gram-negative rods, 62 grew in the BACTEC system only and 109 grew in the Isolator system only (P less than 0.001). Thirty-three of these Isolator-only gram-negative organisms were Acinetobacter spp. Of 209 yeasts, 38 grew in BACTEC only and 81 grew in Isolator only (P less than 0.001). Of 200 streptococci and enterococci, 98 were recovered in BACTEC only and 26 grew in Isolator only (P less than 0.001). Two hundred twenty-eight independent episodes of gram-negative rod bacteremia occurred. Isolator was the first system positive in 59 of 197 episodes, compared with 45 of 197 for BACTEC when Acinetobacter episodes were excluded. Times to detection were similar for the two systems. High colony counts correlated with repeat positive blood cultures. Isolator and BACTEC had similar overall recoveries, with individual merits and deficiencies for both systems. The additional quantitative information derived from Isolator had utility in our institution.

Lack of IgG4 antibody response to carbohydrate antigens in patients with lymphatic filariasis.

It has been suggested that humans are genetically restricted from making IgG4 antibody responses to carbohydrate antigens. To test this hypothesis we examined sera from 35 patients with bancroftian filariasis (an infection known to induce very high levels of IgG4 antibodies to the parasite and known to be associated with repeated streptococcal infections) as well as from 15 normal individuals for their IgG and IgG subclass responses to streptococcal protein [streptolysin-O (SO), deoxyribonuclease B (DB)] and carbohydrate [group A carbohydrate (GAC)] antigens. Levels of IgG antibodies to all three antigens were found to be significantly higher in the filariasis patients compared to normals (P less than 0.01), and the subclass composition of these antibodies proved heterogenous. Although responses to all three antigens included IgG1, IgG2 and IgG3 antibodies and although IgG4 responses to the proteins SO and DB were significantly higher in the filariasis patients than in normals (P less than 0.001), more importantly there were no detectable anti-GAC IgG4 antibodies in either study group. These observations, coupled with our earlier finding of the absence of IgG4 responses to phosphocholine (PC) in patients with lymphatic filariasis, suggest that even the chronic antigenic stimulation of filarial helminth infection, which leads to very prominent IgG4 responses to protein antigens, cannot overcome the genetic restriction in humans for making IgG4 antibodies to carbohydrate antigens, whether of parasite or non-parasite origin.

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.