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.

Formal adult infectious disease specialist consultations in the outpatient setting at a comprehensive cancer center (1998-2008): diverse and impactful.

PURPOSE: The literature on the impact of infectious disease (ID) consulations in the outpatient treatment of cancer is scarce. METHODS: The medical records of consecutive adult patients with cancer formally evaluated by two board-certified ID specialists in an outpatient setting at our institution over a 10-year period (1998-2008) were reviewed retrospectively. The patients' demographics, referring departments, purposes for consultation, ID specialist recommendations, and overall impact of consultations on outcome were analyzed. RESULTS: We identified 598 patients who underwent ID specialist consultations. Most of them had solid tumors (53%), predominantly breast cancer, whereas non-Hodgkin's lymphoma was the most common hematologic malignancy. Almost half of the patients (45%) had active malignancies, but few of them were severely neutropenic (8%) or had been receiving high doses of corticosteroids (17%). The most frequent requests for consultation were culture or serologic test (15%), and treatment of cellulitis and/or surgical wound infections (14%). Of 337 isolated pathogens, the most prevalent were methicillin-resistant Staphylococcus aureus (13%) and Pseudomonas aeruginosa (8%), as well as atypical mycobacteria (16%) and Aspergillus species (11%). ID specialists provided alternative diagnoses in 53% of the cases, including identification of a different infection (46%), a noninfectious etiology (29%), colonization (16%), and drug-related toxic effects (9%). Overall, we deemed the contribution of the ID specialist to be significant in 62% of the consultations. CONCLUSIONS: ID specialists contribute significantly to the outpatient care of individuals with cancer.

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.

Stenotrophomonas maltophilia pneumonia in cancer patients without traditional risk factors for infection, 1997-2004.

In order to elucidate the spectrum of Stenotrophomonas maltophilia pneumonia in cancer patients without traditional risk factors, 44 cancer patients (cases) with S. maltophilia pneumonia in whom S. maltophilia pneumonia risk factors were not present were compared with two S. maltophilia pneumonia risk groups (controls) including 43 neutropenic non-intensive care unit (ICU) and 21 non-neutropenic ICU patients. The case and control patients had similar demographic and underlying clinical characteristics. Compared with case patients with S. maltophilia pneumonia, neutropenic patients had higher exposure to carbapenem antibiotics (58 vs. 41%; p < 0.03), more frequent hematologic malignancy (95 vs. 64%; p < 0.0003), and they presented with concurrent bacteremia more often (23 vs. 0%; p < 0.0005). Patients with S. maltophilia pneumonia in the ICU needed vasopressor therapy more frequently than cases (62 vs. 5%; p < 0.0001). Hospital-acquired S. maltophilia pneumonia was more common among controls than cases (98 vs. 61%; p < 0.000002). Among the cases, 15 (34%) received outpatient oral antimicrobial therapy, while 29 were hospitalized and eight (28%) were subsequently admitted to the ICU. The mean duration of ICU stay, even among these eight patients (19 +/- 40 days), was comparable to that of patients with neutropenia (23 +/- 26 days) and those who developed S. maltophilia pneumonia during their ICU stay (34 +/- 22 days; p = 0.46). The overall infection-associated mortality in the 108 patients with S. maltophilia pneumonia was 25%. Twenty percent of patients without traditional risk factors for S. maltophilia pneumonia died due to progressive infection. In a multivariate logistic regression analysis, only admission to the ICU predicted death (odds ratio 33; 95% confidence interval, 4.51-241.2; p < 0.0006). The results of this study indicate S. maltophilia pneumonia is a serious infection even in non-neutropenic, non-ICU patients with cancer.

High-dose caspofungin combination antifungal therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation.

Pneumocandins have concentration-dependent antifungal activity and higher dose of caspofungin (HD-CAP) in combination with other licensed antifungal therapy (OLAT) may improve response. Thirty-four patients who received HD-CAP were compared with 63 patients who received standard dose (SD)-CAP. There were no differences between the groups in either patient or disease characteristics. Significantly more patients in the HD-CAP arm had extrapulmonary infections (29 vs 8% in SD group; P=0.0053), and non-Aspergillus species infection (21 vs 6%; P=0.05) and had received prior antifungal therapy (71 vs 33%; P=0.0004). No serious adverse reactions were noted in patients receiving HD- or SD-CAP therapy. Twelve weeks after treatment commenced 44% had a complete or partial response compared with 29% in SD-CAP group (P=0.1). Logistic regression analysis showed a significant probability of a favorable outcome at 12 weeks in patients who received HD-CAP (OR 3.066, 95% CI, 1.092-8.61; P=0.033). This may in part reflect higher number of patients in HD group had received granulocyte-macrophage colony-stimulating factor (41 vs 14% in SD group; P=0.04) and/or interferon gamma (26 vs 5% in SD group; P=0.003) immune enhancement. Further studies are needed to evaluate efficacy of HD-CAP in severely immunosuppressed cancer patients with invasive fungal infections.

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.

Influence of type of cancer and hematopoietic stem cell transplantation on clinical presentation of Pneumocystis jiroveci pneumonia in cancer patients.

Pneumocystis jiroveci pneumonia is a common infection in patients with AIDS but an infrequent cause of pneumonia in cancer patients. Little is known about the impact of cancer type and hematopoietic stem cell transplantation on the presentation and outcome of P. jiroveci pneumonia in cancer patients. A retrospective cohort study of all patients with cancer and P. jiroveci pneumonia cared for at The M.D. Anderson Cancer Center during 1990-2003 was conducted. Eighty episodes of P. jiroveci pneumonia in 79 patients were identified. In most (67%) episodes, patients had a hematologic malignancy. In 23 (29%) episodes, patients had undergone hematopoietic stem cell transplantation. Twenty-seven percent of patients with histopathologically confirmed P. jiroveci pneumonia had nodular infiltrates on the radiographic study. Pleural effusion and pneumothorax were more common in patients with hematopoietic stem cell transplantation than in those with solid tumors. Clinical suspicion of P. jiroveci pneumonia was less common in patients with nodular infiltrates than in those without such a radiographic finding (7 vs. 39%; p=0.002). Twenty-six of 76 (34%) patients with data available died of P. jiroveci pneumonia. Predictors of death by univariate analysis included older age, tachypnea, high APACHE II score, use of mechanical ventilation or vasopressors, lower arterial pH level, absence of interstitial component, pneumothorax, and comorbid conditions (all p<0.05). Multivariate analysis identified the use of mechanical ventilation as an independent predictor of death. Death attributable to P. jiroveci pneumonia appeared to be higher in patients with hematopoietic stem cell transplantation. The clinical presentation of P. jiroveci pneumonia in cancer patients may be affected by the category of cancer and the history of hematopoietic stem cell transplantation. P. jiroveci pneumonia remains a rare yet severe infection in cancer patients.

Mycobacterium tuberculosis at a comprehensive cancer centre: active disease in patients with underlying malignancy during 1990-2000.

Thirty HIV-seronegative cancer patients with active tuberculosis were evaluated. Eighteen (60%) were immigrants, 19 (63%) had haematological malignancy, and fever was the most common presentation (97%). Of 19 (63%) patients with pulmonary tuberculosis, 11 (58%) were misdiagnosed initially as suffering from cancer following radiography. Death was attributed to tuberculosis for six (21%) of 29 patients who received anti-mycobacterial therapy. All four patients who had received high-dose systemic corticosteroids within 4 weeks of diagnosis of infection died, whereas two (8%) deaths occurred in 25 individuals without corticosteroid exposure (p < 0.001; OR 8.67). At this institution, active tuberculosis was rare, and was seen mostly in immigrants. Recent high-dose corticosteroid therapy is a significant predictor of mortality in cancer patients with tuberculosis.

Bloodstream infections in patients with solid tumors: associated factors, microbial spectrum and outcome.

BACKGROUND: Although patients with malignant diseases are at increased risk for bloodstream infections (BSIs), limited data are available for those with solid tumors. PATIENTS AND METHODS: The etiology, clinical features and outcome of BSIs were retrospectively studied in patients with solid tumors treated at the Department of Medical Oncology at the University Hospital of Heraklion, Greece, from November 1995 through June 2000. RESULTS: A total of 157 episodes of BSIs was identified among 137 patients over the study period. The majority of the episodes (128; 82%) occurred in non-neutropenic patients. 80 of 157 (51%) of the episodes were healthcare-associated, 35% (55 of 157) were nosocomial and 14% (22 of 157) were community acquired. A single pathogen was isolated in 86% of the episodes. A total of 184 pathogens was isolated (51% gram-negative rods, 44% gram-positive cocci, 3% anaerobes and 3% fungi), while the portal of entry was identified in 104 of 157 (66%) of the episodes. The site of the primary tumor or the metastases were the source of BSI in 39 of 104 (37.5%) of the episodes with an identified source. The overall infectious mortality was 20% and was significantly higher when the initial empirical antibiotic therapy was inappropriate (39%; p < 0.001) and in the presence of shock (63%; p < 0.001). CONCLUSION: BSIs in patients with solid tumors are frequently healthcare associated and in a large percentage the portal of entry can be identified. Neutropenia is not as common as in patients with hematologic malignancies. Inappropriate initial empirical antibiotic therapy and shock are clinical factors associated with worse outcomes.

High-dose fluconazole therapy for cancer patients with solid tumors and candidemia: an observational, noncomparative retrospective study.

BACKGROUND: Response rates for candidemia treated with standard-dose fluconazole (400 mg/day) are approximately 70%. Higher doses of fluconazole have been recommended for susceptible dose-dependent Candida isolates. Herein, we describe the outcome of 20 patients with solid tumors and candidemia treated with high-dose fluconazole (HDF) at The University of Texas M.D. Anderson Cancer Center (1998-2002). PATIENTS AND METHODS: Patients were identified either by searching the microbiology laboratory database or through direct referral from primary oncology services to the Infectious Diseases Consultative Services. A retrospective review of cases was performed. HDF was defined as > or =600 mg/day. RESULTS: Five patients were treated with 600 mg/day, whereas 15 patients received 800 mg/day. Only one patient was neutropenic. The median APACHE II score at the onset of candidemia was 12 (range 6-24). The most common species identified were Candida albicans (eight patients, 40%) and Candida parapsilosis (seven patients, 35%). Of 19 patients whose quantitative data were available, eight (42%) had high-grade candidemia [> or =200 colony forming units (CFU)/ml]. Fifteen (83%) of 18 isolates were fluconazole susceptible, and two (both Candida glabrata) were fluconazole resistant (MIC 64 each) in vitro. Nineteen patients (95%) responded to HDF therapy. The only HDF failure occurred in a patient with C. glabrata (MIC 64.0) infection. The other patient with C. glabrata (MIC 64.0) infection responded to HDF. Central venous catheters were removed from all patients with > or =10 CFU/ml candidemias. All patients with high-grade candidemias responded to HDF. The median duration of HDF therapy was 16 (range 6-42) days. No significant toxicity occurred. CONCLUSIONS: Although our data are limited, HDF appears to be well tolerated and may be associated with higher response rates than standard-dose fluconazole in a selected group of patients with solid tumors and candidemia caused by species that are susceptible to this triazole.

Listeria monocytogenes infection in patients with cancer.

Listeriosis (LT) is an important infection in immunocompromised patients, but no large series of LT in cancer patients have been recently described. We reviewed the records of 34 cancer patients with LT at our institution (1990-2001). Twenty patients (59%) had an underlying hematologic malignancy. In 11 patients, LT complicated bone marrow transplantation. Lymphocytopenia was observed in 62% of the patients. Twenty-six patients (76%) received prior corticosteroids. Bacteremia was the most common presentation of LT (74%) followed by meningoencephalitis (21%). The most common treatment of LT was ampicillin with or without gentamicin (68%). The median duration of treatment was 26 days (range, 8-74 days). The rate of response to antimicrobial therapy was 79%. No relapses were identified. LT contributed to death in 9 (75%) of the 12 patients who died. Meningoencephalitis had the worst prognosis (3 of 6 cases were fatal). Treatment of central nervous system LT continues to have a high failure rate.

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.

Catheter-related bacteremia caused by Agrobacterium radiobacter in a cancer patient: case report and literature review.

Agrobacteria are a group of phytopathogenic organisms widely distributed in soil; they are now recognized as rare human pathogens affecting mostly immunocompromised hosts. We report a case of catheter-related bacteremia due to Agrobacterium radiobacter in a neutropenic patient and describe the clinical presentations, treatment strategies and outcome of Agrobacterium infections based on our experience and a literature review. The antimicrobial susceptibility patterns of these organisms appear to be quite variable and collective susceptibility data derived from this and previous reports are provided.

Infections in the neutropenic patient--new views of an old problem.

Infection in the neutropenic patient has remained a major clinical challenge for over three decades. While diagnostic and therapeutic interventions have improved greatly during this period, increases in the number of patients with neutropenia, changes in the etiologic agents involved, and growing antibiotic resistance have continued to be problematic. The evolving etiology of infections in this patient population is reviewed by Dr. Donowitz. Presently accepted antibiotic regimens and practices are discussed, along with ongoing controversies. In Section II, Drs. Maki and Crnich discuss line-related infection, which is a major infectious source in the neutropenic. Defining true line-related bloodstream infection remains a challenge despite the fact that various methods to do so exist. Means of prevention of line related infection, diagnosis, and therapy are reviewed. Fungal infection continues to perplex the infectious disease clinician and hematologist/oncologist. Diagnosis is difficult, and many fungal infections will lead to increased mortality even with rapid diagnosis and therapy. In Section III, Dr. Pappas reviews the major fungal etiologies of infection in the neutropenic patient and the new anti-fungals that are available to treat them. Finally, Dr. Rolston reviews the possibility of outpatient management of neutropenic fever. Recognizing that neutropenics represent a heterogeneous group of patients, identification of who can be treated as an outpatient and with what antibiotics are discussed.

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.

The spectrum of pulmonary infections in cancer patients.

The lung is a common site of infection in patients with cancer. The spectrum of pulmonary infection depends on the underlying immunologic deficit or deficits. In neutropenic patients, gram-negative bacterial infections predominate early, whereas fungal infections (Aspergillus, Zygomycetes, Fusarium species) are common if neutropenia persists. In patients with impaired cellular immunity, viral infections (cytomegalovirus, other herpes viruses) predominate and may coexist with bacterial (Legionella, Nocardia), mycobacterial, and fungal (Aspergillus, Histoplasma, etc.) infections. Pneumocystis carinii pneumonia is also common in this setting. Infections caused by Streptococcus pneumoniae and Haemophilus influenzae are the primary bacterial infections encountered in patients with impaired humoral immunity. In patients with primary or metastatic pulmonary neoplasms, postobstructive pneumonitis, lung abscess, and occasionally empyema of mixed bacterial etiology (Staphylococcus species, gram-negative bacilli, anaerobes) are frequent. Patients with brain tumors and head and neck cancer develop aspiration pneumonitis, which is usually caused by organisms living in the oropharynx and upper airways. Several immunologic deficits might be present in the same patient, making such a patient susceptible to a wide variety of opportunistic pathogens.

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.