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A continuous dosing schedule of aerosolized ribavirin has been used for respiratory syncytial virus (RSV) upper respiratory tract infection and lower respiratory tract infection (LRTI) but is associated with high cost and inconvenient administration. We conducted an adaptive randomized trial to evaluate the effectiveness of an intermittent dosing schedule of ribavirin versus that of a continuous dosing schedule of ribavirin in preventing RSV LRTIs in 50 hematopoietic stem cell transplant recipients or patients with hematologic malignancies. LRTI occurred in 3 patients (9%) receiving the intermittent schedule and in 4 (22%) receiving the continuous schedule, with a 0.889 posterior probability. Because the intermittent schedule is easy to administer and has a higher efficacy than the continuous schedule, we recommend the intermittent schedule for patients who are at risk for RSV LRTI. Clinical Trials Registration. NCT00500578.

Background Multidrug-resistant (MDR) Escherichia coli is a serious threat to cancer patients. We aimed to determine the risk factors associated with the development of MDR E coli bacteremia in cancer patients and the possibility of horizontal transmission. Methods We conducted a 1:2 case-control study of 58 patients with MDR E coli bacteremia. The patient's demographics, clinical characteristics, and antibiotic use were obtained. MDR E coli was defined as resistant strains to quinolones plus 1 of the following: piperacillin, ceftazidime, or cefepime. Repetitive sequence-based polymerase chain reaction (Rep-PCR) was used to identify DNA interstrain similarities. Results Conditional multiple logistic analysis showed that admission to the hospital within the 30 days prior to infection and chemotherapy use were risk factors for infection with MDR E coli . Rep-PCR showed that, among the MDR E coli strains recovered, 48.6% showed >95% similarity, representing a possible clonal outbreak. Infection control measures were implemented and controlled this horizontal transmission. Conclusion Prior admission to the hospital and previous chemotherapy were independent risk factors of acquiring MDR E coli . Molecular fingerprinting techniques detected a possible nosocomial clonal outbreak of MDR E coli , which was aborted through infection control measures.

The importance of neutropenia as a predisposing factor for infection in patients with haematological malignancies was not clearly appreciated until effective therapeutic agents became available. This led to the important advance of administering antibiotics promptly to neutropenic patients when they developed fever, before a diagnosis was established. Although some antibiotics available in the 1960s had activity against many pathogens in vitro, they were ineffective against infections in neutropenic patients. The development of methods to administer white blood cell transfusions along with antibiotics was beneficial to some patients. The development of new antibiotics was of critical importance, such as methicillin for treatment of Staphylococcus aureus and carbenicillin for Pseudomonas aeruginosa. Prevention of infection was attempted, using isolation rooms, air filtration and prophylactic antibiotics. All of these early efforts laid the foundations for the many important current investigations.

BACKGROUND: The clinical significance of herpes simplex virus (HSV) isolated in lower respiratory tract specimens (LRTS) of patients with solid tumors (ST) is unknown. In the current study, the authors attempted to determine the clinical relevance of this finding among ST patients. METHODS: The authors reviewed records of ST patients admitted to the study institution between April 2000 and April 2004 with clinical and radiologic evidence of pneumonia, and HSV identified in LRTS by culture alone or culture and cytology. Patients were categorized as having proven (HSV identified by culture and cytology from the LRTS), probable (HSV as the sole pathogen by culture alone), and possible (HSV along with copathogens identified by culture) HSV pneumonia. RESULTS: Forty-five ST patients with either proven (6 patients), probable (25 patients), or possible (14 patients) HSV pneumonia were identified. When compared with patients with probable or possible HSV pneumonia, more patients with proven infection were on mechanical ventilation (40% vs 50% vs 100%, respectively; P = .03), and had longer length of stay in the intensive care unit (12 days vs 13 days vs 26 days, respectively; P = .05). The overall mortality rate was 22% (10 patients). Four of 25 (16%) patients who received HSV-directed antiviral therapy died during their hospital stay versus 6 of 20 (30%) who were not treated (P = .3). None of the 6 patients with proven HSV pneumonia who were treated with acyclovir died. On univariate analysis, risk factors for mortality included underlying breast cancer, an Acute Physiology and Chronic Health Evaluation (APACHE) II score >15, admission to the intensive care unit, and use of mechanical ventilation and vasopressors (all P ≤ .05), with underlying breast cancer and APACHE II score >15 being found to be independent predictors of death by multiple logistic regression analysis (all P ≤ .05). CONCLUSIONS: Having a proven HSV pneumonia appears to be associated with high morbidity and with no increase in mortality in ST patients. This subset of patients appears to benefit from acyclovir therapy. Cancer 2009. © 2008 American Cancer Society.

Polymicrobial infections account for ~15% of infections in immunocompromised patients with cancer. However, limited information exists regarding the spectrum and microbiology of these infections, even in severely neutropenic patients. Most studies describe only monomicrobial bloodstream infections in detail, and information regarding polymicrobial infections and nonbacteremic infections is often incomplete or not provided at all. The current lack of well-established definitions for various infections in the immunocompromised host, including pneumonia, neutropenic enterocolitis, and polymicrobial infections, probably plays an important role in the paucity of published information. In this review, we briefly describe the limited information available regarding polymicrobial infections in patients with cancer and address the need for establishing consensus definitions for site-specific polymicrobial infections in neutropenic and nonneutropenic patients. We anticipate that, as factual information regarding such infections becomes available, a more comprehensive understanding of the true scope and impact of these infections will emerge, leading to appropriate modifications in the diagnostic work-up and in the therapeutic approaches used in treating these patients.

The increasing incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa is a worldwide health problem. Because no new antipseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism. We collected clinical and demographic data on 95 cancer patients diagnosed with infections caused by multidrug-resistant P. aeruginosa between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active antipseudomonal agent (a beta-lactam antibiotic or a quinolone) (control group). We compared the results obtained for both groups. Thirty-one patients had been treated with colistin and 64 had been treated with an antipseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had a lower median age (52 and 62 years, respectively; P = 0.012) but were more likely to have had nosocomial infections (87% and 64%, respectively; P = 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 ( P = 0.074). The overall clinical response rates were 52% in the colistin group and 31% in the control group ( P = 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% confidence interval, 1.1 to 7.6 times) more likely than those in the control group to experience a clinical response to therapy ( P = 0.026). Colistin therapy was at least as effective and as safe a beta-lactam antibiotic or a quinolone in the treatment of infections caused by multidrug-resistant P. aeruginosa and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.

Endocarditis is uncommon in patients with cancer. The characteristics of culture-positive (CPE) and culture-negative endocarditis (CNE) in high-risk cancer patients are not known; therefore we sought to evaluate the disease characteristics in patients with endocarditis at a comprehensive cancer center. We retrospectively reviewed the transthoracic (TTE) and transesophageal (TEE) echocardiograms obtained from 654 consecutive cancer patients in whom endocarditis was suspected between 1994 and 2004. Endocarditis was confirmed in 45 (7%) of 654 patients using modified Duke University criteria based on information obtained from hospital records and computerized data systems. In 21 (95%) of 22 cases, TEE examinations were diagnostic, and 16 (42%) of 38 patients with initially nondiagnostic TTE studies had the diagnosis confirmed by TEE study; this difference between diagnostic TEE and initial nondiagnostic TTE was significant (p < 0.0001). Among the 26 (58%) patients with CPE, Staphylococcus aureus (35%) was the most common organism isolated, followed by coagulase-negative Staphylococcus species (23%). Eighteen (78%) of 23 patients with a central venous catheter had CPE, whereas only 8 (36%) of 22 patients without a central venous catheter had CPE (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.69-23.53; p < 0.006). Vegetations were larger in patients with CPE than in patients with CNE (median +/- standard deviation, 10 +/- 8.8 vs. 8.7 +/- 3.9 mm). Fifteen patients (58%) with CPE and 10 (53%) with CNE had embolic complications. We note that cutaneous and septic pulmonary emboli were more common in patients with CPE than in patients with CNE (31% vs. 11% and 15% vs. 0%, respectively), whereas embolic cerebrovascular and fatal embolic coronary events were more common in patients with CNE than in those with CPE (37% vs. 12% and 21% vs. 0%, respectively; p = 0.026). The 4-week endocarditis-attributable death rate did not differ significantly between the groups (CPE, 15% vs. CNE, 32%; p = 0.28). On stepwise multivariate regression analysis, patients with neutropenia (OR, 22.52; 95% CI, 2.25-225.48; p < 0.008) and those with embolic cerebrovascular events (OR, 17.07; 95% CI, 1.63-178.45; p < 0.01) had an increased probability of death due to endocarditis. The clinical spectrums of CPE and CNE differed in these patients with cancer. In patients with CNE, embolic cerebrovascular and fatal myocardial infarction were relatively common.

There are two main types of fungal infections in the oncology patient: primary cutaneous fungal infections and cutaneous manifestations of fungemia. The main risk factor for all types of fungal infections in the oncology patient is prolonged and severe neutropenia; this is especially true for disseminated fungal infections. Severe neutropenia occurs most often in leukemia and lymphoma patients exposed to high-dose chemotherapy. Fungal infections in cancer patients can be further divided into five groups: (i) superficial dermatophyte infections with little potential for dissemination; (ii) superficial candidiasis; (iii) opportunistic fungal skin infections with distinct potential for dissemination; (iv) fungal sinusitis with cutaneous extension; and (v) cutaneous manifestations of disseminated fungal infections. In the oncology population, dermatophyte infections (i) and superficial candidiasis (ii) have similar presentations to those seen in the immunocompetent host. Primary cutaneous mold infections (iii) are especially caused by Aspergillus, Fusarium, Mucor, and Rhizopus spp. These infections may invade deeper tissues and cause disseminated fungal infections in the neutropenic host. Primary cutaneous mold infections are treated with systemic antifungal therapy and sometimes with debridement. The role of debridement in the severely neutropenic patient is unclear. In some patients with an invasive fungal sinusitis (iv) there may be direct extension to the overlying skin, causing a fungal cellulitis of the face. Aspergillus, Rhizopus, and Mucor spp. are the most common causes. We also describe the cutaneous manifestations of disseminated fungal infections (v). These infections usually occur in the setting of prolonged neutropenia. The most common causes are Candida, Aspergillus, and Fusarium spp. Therapy is with systemic antifungal therapy. The relative efficacies of amphotericin B, fluconazole, itraconazole, voriconazole, and caspofungin are discussed. Recovery from disseminated fungal infections is unlikely, however, unless the patient's neutropenia resolves.

Although gastrointestinal cytomegalovirus disease (GI-CMVd) is not common in cancer patients, it is associated with high morbidity and mortality. Herein, we review our 2-decade experience with GI-CMVd in such patient population at The University of Texas M.D. Anderson Cancer Center. Forty-seven patients were identified. Thirty-four patients (72%) had an underlying haematological malignancy, and 18 patients (38%) developed GI-CMVd following hematopoietic stem cell transplantation (HSCT). Nine (25%) of the 36 cancer patients with data available had AIDS. Upper-GI tract involvement was more common in patients with haematological malignancies than in those with solid tumours (P=0.02). Patients with AIDS were more likely to have colonic involvement than were those without AIDS (67% vs. 15%, P=0.006), and patients without AIDS were more likely to have gastric involvement (59% vs. 11%, P=0.01). The CMV-attributable mortality rate was 42%. Independent predictors of death by multivariate analysis included disseminated CMV and AIDS (P

BACKGROUND Candidemia is a common cause of bloodstream infections in patients with cancer, with the majority of these infections being caused by a single Candida species. Studies of multiple-species candidemia (MSC) have rarely been reported. METHODS The authors identified 33 patients with cancer who had candidemia (diagnosed between 1993 and 2000) caused by more than 1 Candida species. This group of 33 patients was compared with a control group of 66 patients with cancer who had C. albicans candidemia that arose soon before or soon after each case of MSC that was investigated in the current study. RESULTS Patients with MSC, compared with control patients, were more likely to have leukemia (33% vs. 8%; P = 0.001), to have had prolonged neutropenia before the onset of their infection (mean ± standard deviation, 10 ± 17 days vs. 3 ± 6 days; P = 0.02), and to have received chemotherapy within 1 month before their infection (42% vs. 18%; P = 0.01). Patients with MSC also had higher Acute Physiology and Chronic Health Evaluation II scores at the onset of infection (score ≥ 16, 45% vs. 26%; P = 0.05) and were more likely to have received previous antifungal prophylaxis compared with patients who had candidemia caused by C. albicans (33% vs. 11%; P = 0.006). The response of C. albicans candidemia to single-agent antifungal therapy was significantly better than that of MSC (69% vs. 35% P = 0.004). CONCLUSIONS In patients with cancer, MSC was more likely to occur as breakthrough candidemia, predominantly in those with leukemia and prolonged neutropenia, and was associated with suboptimal responses to single-agent antifungal therapy. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND. Invasive aspergillosis (IA) has emerged as a common cause of morbidity and mortality among immunocompromised patients. At The University of Texas M. D. Anderson Cancer Center (Houston, TX), Aspergillus terreus is second to A. fumigatus as the most common cause of IA. In the current study, the authors compared the risk factors and outcomes associated with IA caused by A. terreus and IA caused by A. fumigatus. METHODS. The authors retrospectively reviewed the medical records of 300 patients who received care at our institution between 1995 and 2001 and who had cultures that were positive for Aspergillus infection, including 90 patients whose cultures were positive for A. fumigatus and 70 patients whose cultures were positive for A. terreus. RESULTS. Thirty-two patients with IA caused by A. terreus and 33 patients with IA caused by A. fumigatus were evaluated. The two groups were comparable in terms of age, gender, and underlying disease. Leukemia was the most common underlying malignancy (84%). More than 40% of patients in each group had undergone bone marrow transplantation. There was a trend toward a higher frequency of neutropenia among patients with IA caused by A. terreus (P = 0.12). IA caused by A. terreus was considered to be nosocomial in origin significantly more frequently compared with IA caused by A. fumigates (P = 0.03). In vitro, A. terreus was found to be more resistant to amphotericin B (minimal inhibitory concentration [MIC 90 ], 4.0 μg/mL) than to antifungal therapy (MIC 90 , 1.0 Hg/mL) in the isolates that were tested (< 50% of all isolates). The overall rate of response to antifungal therapy was 39% for patients with A. fumigatus infection, compared with 28% for patients with A. terreus infection (P = 0.43). CONCLUSIONS. Despite the decreased in vitro susceptibility of A. terreus (relative to A. fumigatus) to amphotericin B, the two groups within the current patient population had comparably poor responses to amphotericin B preparation and somewhat improved responses to posaconazole.

BACKGROUND Infection is a significant cause of death in patients with aplastic anemia (AA). However, few recent studies have examined infectious complications in patients with AA. METHODS The authors retrospectively evaluated the type of infections, associated pathogens, and outcome of infectious episodes (IEs) in patients with AA who were treated at The University of Texas M. D. Anderson Cancer Center between July 1994 and June 2000. RESULTS Fifty-two patients with a median age of 37 years (range, 3–83 years) were identified. Overall, 104 IEs were documented in 42 patients (81%). The most common microbiologically documented infections were bacteremias (38%) followed by pneumonias (16%). Most patients (55%) had bacterial infections, mainly caused by gram-positive cocci. Multidrug-resistant, gram-negative bacilli also were not uncommon in this patient population. Five of 12 patients who died during the study period died of infection. All of these patients had invasive fungal infections, mostly due to molds. All five patients had prolonged and severe neutropenia. CONCLUSIONS Infections remain a major cause of death in patients with AA. Bacterial infections, especially those caused by gram-positive cocci, constitute the main cause of IE. Invasive mold infections, however, are the major cause of death in this patient population. Cancer 2003;98:86–93. © 2003 American Cancer Society. DOI 10.1002/cncr.11478

Objectives:To evaluate the risk factors associated with breakthrough candidemia in patients with cancer and to compare them with those of de novo candidemia in this patient population. DESIGN: Retrospective case series of 120 episodes of candidemia, 90 de novo and 30 breakthrough candidemias.Setting:University-affiliated, tertiary-care cancer center in Houston, Texas.Patients:All patients with cancer who acquired candidemia between January 1993 and December 1998 were included if they had non-catheter-related candidemia and information about quantitative blood cultures.Results:Although less frequent, breakthrough candidemia was seen more often in neutropenic patients with leukemia. The intensity of breakthrough candidemia was comparable to that of de novo candidemia. Most (70%) of the breakthrough candidemias were due toCandida glabrataorC. krusei.Conclusions:In breakthrough candidemia, the same risk factors seen in de novo candidemia were encountered, although more frequently.C. glabrataandC. kruseiare the leading causes of breakthrough candidemia in patients with cancer.

Nocardiosis (NOC) is an important cause of infection in immunocompromised patients. However, large series in patients with cancer have not been described. We review the records of patients with cancer and NOC who were evaluated at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, between 1988 and 2001, and we describe the incidence, microbiologic and clinical characteristics, treatment, and outcome of NOC in this population. Forty-two patients with a total of 43 episodes of NOC were identified (incidence of 60 cases of NOC per 100,000 admissions). Twenty-seven patients (64%) had hematologic malignancies. In 13 patients, NOC complicated bone marrow transplantation. Neutropenia was observed in 4 (10%) of 40 episodes with information available, and lymphopenia in 20 (50%) of 40 episodes. Patients had received steroids for 25 episodes (58%) and had received chemotherapy for 10 episodes (23%) within 30 days before the onset of NOC. Nine episodes of breakthrough NOC were identified in 7 (23%) of the 40 patients with information available. Pulmonary NOC was seen in 30 (70%) of 43 cases; soft-tissue NOC in 7 (16%); central venous catheter-related nocardemia in 3 (7%); and disseminated NOC, central nervous system NOC, and a perinephric abscess each in 1 (2%). Twenty-three percent of patients with pulmonary NOC had an acute presentation. complex was the most common causative species (77%). Therapy for NOC was mainly concurrent trimethoprim/ sulfamethoxazole and either a tetracycline or a beta-lactam. The median duration of treatment was 113 days (range, 10-600 d). Nine (60%) of 15 patients with outcome data died from NOC. NOC, although infrequent, is an important cause of morbidity and mortality in patients with cancer. It has pleomorphic manifestations, and it can be seen as a breakthrough infection. The present study confirms that timely diagnosis, the site of NOC, the type of, the presence of comorbidities, and cytomegalovirus coinfection influence the outcome of patients with cancer and NOC.

Purpose Candida glabrata is an increasing cause of candidemia, especially at cancer and bone marrow transplant centers where fluconazole is used for antifungal prophylaxis. This yeast is less susceptible to fluconazole in vitro than is Candida albicans . We compared the characteristics of patients who had C. glabrata and C. albicans candidemia at a large cancer center. Subjects and methods We searched the microbiological laboratory reports and identified 116 cases of C. glabrata candidemia between 1993 and 1999. The 116 cases of C. albicans candidemia that occurred most closely in time (before or after each case of C. glabrata candidemia) served as the control group. Data were collected from patients' medical records. Results When compared with patients who had C. albicans infection, patients with C. glabrata candidemia more often had an underlying hematologic malignancy (68 [59%] vs. 26 [22%], P = 0.0001), had an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥16 (55 [48%] vs. 28 [25%], P = 0.0002), and received fluconazole prophylaxis (57 [49%] vs. 8 [7%], P = 0.0001). Patients with C. albicans candidemia more often had concomitant infections (101 [87%] vs. 78 [67%], P = 0.0003) and septic thrombophlebitis (11 [10%] vs. 2 [2%], P = 0.01). Among patients treated with antifungal therapy, those with C. albicans candidemia had a significantly greater overall response to therapy (83/104 [80%] vs. 60/97 [62%], P = 0.005) and to primary therapy (74/104 [71%] vs. 45/97 [46%], P = 0.0003). Amphotericin B preparations were not more effective than fluconazole (19/45 [42%] vs. 20/38 [53%], P = 0.5) in patients with C. glabrata candidemia. Fluconazole was less effective against C. glabrata than against C. albicans (20/38 [53%] vs. 57/74 [77%], P = 0.008). Conclusion C. glabrata has emerged as an important cause of candidemia, especially among neutropenic patients who receive fluconazole prophylaxis.

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.

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

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.

Much progress has been made over the last decade in diagnosing and treating CDC, a chronic and debilitating infection that interferes with the delivery of intensive cytotoxic chemotherapy in patients with leukemia. The use of fluconazole prophylaxis in these patients has decreased the incidence of CDC dramatically. The greatest future challenges are gaining a better understanding of its pathophysiology, and the continued development of effective diagnostic and therapeutic strategies to treat this unusual manifestation of systemic candidiasis.

Twenty-four patients with cancer met predetermined criteria for a diagnosis of zygomycosis over a 10-year period at our institution. All had hematologic malignancy, and most had either neutropenia or steroid use as a risk factor. Pulmonary involvement mimicking invasive aspergillosis was the most common presentation, and dissemination was seen in 58% of patients on whom autopsies were performed. Three-fourths of the patients with pulmonary zygomycosis had pathogenic microorganisms other than zygomycetes isolated from respiratory specimens. The sensitivity of cultures in detecting zygomycetes from respiratory specimens was low. A culture positive for zygomycetes was typically a preterminal finding in the fatal, acute cases. Two-thirds of the patients died. Favorable outcome seemed to correlate with lack of pulmonary involvement, surgical debridement, neutrophil recovery, and a cumulative total amphotericin B dose of 2000 mg. Therapy with high-dose amphotericin B, combined with aggressive surgery and immune reconstitution, offers the best chance for survival of cancer patients with zygomycosis.

A total of 240 patients with suspected bacteremia/septicemia secondary to vascular access-associated gram-positive infection was enrolled in a multicenter trial in 47 centers in the United States and Canada, comparing teicoplanin (3 3 6 mg/kg 12-hourly, then 6 mg/kg 24-hourly) with vancomycin (15 mg/kg 12-hourly). Groups were well matched for all demographic variables. In all, 124 patients were evaluable for efficacy in the “per protocol” analysis (60 receiving teicoplanin and 64 receiving vancomycin). Clinical cure and improvement was achieved in 48 (80.0%) of 60 patients for teicoplanin and 51 (79.7%) of 64 patients for vancomycin. “Intent-to-treat” analysis also showed similar efficacy for the two glycopeptides. The pathogens most often isolated were coagulase-negative staphylococci (64 patients) and Staphylococcus aureus (60 patients). Eradication was achieved in 49 (81.7%) of 60 patients for teicoplanin and 55 (85.9%) of 64 patients for vancomycin. Serum level data were available for 170 episodes. Adverse events were reported by 32 (27.4%) of 117 patients receiving teicoplanin and 37 (30.6%) of 121 patients receiving vancomycin. The most often reported adverse events, other than gastrointestinal events, were hypersensitivity reactions (rash, pruritus, and fever). There were no differences between the groups for the types of events experienced. In all, 15 of 240 patients included in the safety analysis (7/118 [5.9%] receiving teicoplanin and 8/122 [6.6%] receiving vancomycin) discontinued treatment due to adverse events. It is concluded that teicoplanin and vancomycin show equivalent efficacy and tolerance in vascular access-associated bacteremia/septicemia caused by gram-positive pathogens.

BACKGROUND Imipenem-cilastatin (referred to hereafter as imipenem) is administered at different doses as monotherapy or with other agents. Limited comparisons of the alternatives exist. The authors compared the efficacy and safety of several imipenem-containing regimens (ICRs) to determine the appropriate dose and the need for combination therapy. METHODS Between 1985 and 1994, febrile neutropenic patients were given ICRs according to the same methodology on prospective trials at a referral cancer center. The ICRs were high dose imipenem (HIP), high dose imipenem and amikacin (HIPA), high dose imipenem and vancomycin (HIPV), and low dose imipenem and vancomycin (LIPV). RESULTS The overall response rates were comparable (70-77%). There was a univariate trend toward better response among patients with pneumonia and documented infections with unidentified organisms who received HIPV versus LIPV (P = 0.06), as well as a significantly better response among patients with gram positive infections who received HIPV versus HIP (P = 0.02) and HIPA (P = 0.002). HIPV was a more effective treatment for documented infections with identified organisms (P = 0.05) and bloodstream infections (P = 0.04) than HIP; there was a univariate trend toward better response among patients infected with gram negative organisms who received HIPA versus HIP (P = 0.12). Multivariate adjustment for baseline and prognostic factors did not reveal a relative advantage for any regimen. No differences in overall toxicities were observed between HIPV and LIPV. CONCLUSIONS Imipenem monotherapy is adequate treatment for most febrile neutropenic cancer patients. Low dose imipenem could be effective and safe in uncomplicated cases without pneumonia. Further studies are needed to establish the usefulness of low dose imipenem in this context. Cancer 1998;82:2449-2458. © 1998 American Cancer Society.

This is the first in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline. The targeted providers are internists, pediatricians, and family practitioners. The targeted patients and setting for the fever and neutropenia guideline are hospitalized individuals with neutropenia secondary to cancer chemotherapy. Panel members represented experts in adult and pediatric infectious diseases and oncology. The guidelines are evidence-based. A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary, algorithms, and tables highlight the major recommendations. The guideline will be listed on the IDSA home page at http://www.idsociety.org.

BACKGROUND Chemotherapy-induced neutropenia and associated fever and infection are the most common complications of systemic chemotherapy. In this retrospective analysis, the authors evaluated the incidence of neutropenic fever, infection, and mortality in relation to the level of neutropenia, performance status, course number of chemotherapy, bone marrow metastasis, and age among patients with metastatic breast carcinoma receiving salvage chemotherapy. METHODS A total of 174 patients with previously treated metastatic breast carcinoma enrolled on 4 consecutive Phase II protocols were evaluated. RESULTS Twenty-three percent of the patients had an episode of neutropenic fever (41 episodes among 40 patients). The incidence of neutropenic fever did not increase until the absolute neutrophil count (ANC) had decreased to less than 500/μL, and then fever incidence had a linear relationship with decreasing ANC (linear trend, P < 0.01). A source of infection was documented in 59% of the neutropenic fever episodes. The incidence of infection did not increase significantly until the ANC had decreased to less than 250/μL (P < 0.01). The risk of neutropenic fever and infection was also significantly higher when patients had poor performance status or were undergoing the initial courses of chemotherapy. Patients with bone marrow metastases also had a higher frequency of fever, infection, and death, but these differences were not statistically significant. CONCLUSIONS For patients with metastatic breast carcinoma receiving salvage chemotherapy, the risk of fever increases with decreasing ANC, but the risk of infection does not increase significantly until ANC decreases to less than 250/μL. Poor performance status, initial courses of chemotherapy, and bone marrow metastases further increase the risk of fever, infection, and death. Cancer 1997; 79:1150-7. © 1997 American Cancer Society.

Clinicians first became interested in infectious complications in immunocompromised hosts in the late 1950s and early 1960s. Three major medical advances stimulated this interest: successes in renal transplantation, effective chemotherapeutic regimens with curative potential against a few malignant diseases, and the availability of antimicrobial agents with activity against gram-negative bacilli. Bacterial infections were the major cause of mortality in those early years, so much attention centered on management of these infections. Fungal infections were also recognized as a complication in some immunocompromised hosts, such as those with acute leukemia. Most of these infections occurred in leukemia patients who were not responding to chemotherapy, and progress in this area was thwarted by difficulties in diagnosis and limited therapeutic options.

Autopsy studies remain an essential tool for understanding the patterns of fungal disease not detected ante mortem with current diagnostic approaches. We collected data concerning the microbiological trends, patient clinical characteristics and sites of involvement for invasive fungal infections (IFIs) identified at autopsy in a single large cancer treatment centre over a 20-year period (1989-2008). The autopsy rate and IFI prevalence both declined significantly during the study period. The prevalence of Aspergillus spp. decreased significantly from the first 15 years of the study (from 0.12 to 0.14 cases per 100 autopsies to 0.07 in 2004-2008; P = 0.04), with only Mucorales accounting for a greater proportion of IFIs over the duration of the study period (0.06 to 0.2 cases per 100 autopsies, P = 0.04). After 2003, moulds accounted for the majority of infections identified at autopsy in the spleen, kidney, heart and gastrointestinal tract. Despite a trend of decreasing prevalence from 1989 to 2004, invasive candidiasis increased in prevalence during later periods 2004-2008 (0.02-0.05 per 100 autopsies) with decreasing kidney, heart and spleen involvement. Despite a declining autopsy rate, these data suggest a decreasing prevalence overall of IFIs with changing patterns of dissemination in patients with haematological malignancies.

We reviewed the frequency and clinical course of parainfluenza virus (PIV) infections in 1,173 adult bone marrow transplant (BMT) recipients cared for at The University of Texas M.D. Anderson Cancer Center (Houston). Between January 1991 and September 1994, PIV was isolated from the respiratory secretions of 61 (5.2%) of these patients. Thirty-four (56%) of the 61 patients had uncomplicated upper respiratory tract illnesses and survived. The remaining 27 patients (44%) developed pneumonia, and the associated mortality was 37% (10 of 27 patients). Twenty-three (85%) of the patients with pneumonia had had preceding upper respiratory illnesses. Of the 10 patients who died, nine died within 100 days after transplantation. Histopathologic examination of lung tissue from seven patients revealed intracytoplasmic viral inclusions in six, a finding consistent with invasive PIV pneumonia, and viral changes in the seventh patient. Seven of the 10 patients who died had other serious concurrent infections. Of 42 patients who developed PIV infection early after transplantation (i.e., < 100 days), the frequency of pneumonia was higher among the 18 allogeneic BMT recipients (61%) than among the 24 autologous BMT recipients (42%), and the associated mortality was also higher (55% vs. 30%, respectively). PIVs are an important cause of life-threatening pneumonia in adult BMT recipients, particularly patients who have recently undergone allogeneic bone marrow transplantation.

We conducted a prospective, randomized, multicenter study comparing fluconazole and amphotericin B in the treatment of candidal infections. One hundred and sixty-four patients (60 of whom were neutropenic) with documented or presumed invasive candidiasis were assigned to treatment with either fluconazole (400 mg daily) or amphotericin B (25-50 mg daily; 0.67 mg/kg daily for neutropenic patients). Clinical response and survival rates were assessed at 48 hours, after 5 days, and at the end of therapy. Overall response rates to fluconazole and amphotericin B were similar (66% and 64%, respectively). There were no differences in response as related to site of infection, pathogen, time to defervescence, relapse, or survival rates between the groups. Adverse effects were more frequent with amphotericin B (35%) than with fluconazole (5%; P < .0001). The results of this study confirm that fluconazole is as effective as but better tolerated than amphotericin B in the treatment of candidal infections.

To compare the efficacy and toxicity of fluconazole and amphotericin B in the treatment of hematogenous candidiasis in cancer patients.A matched cohort study of cancer patients with hematogenous candidiasis was conducted. Forty-five patients with hematogenous candidiasis who received fluconazole (200 to 600 mg/day) in an open-label trial at the University of Texas M. D. Anderson Cancer Center, Houston, Texas, between February 1990 and June 1992 were matched to 45 patients treated with amphotericin B (0.3 to 1.2 mg/kg/day) for the same diagnosis. Criteria for matching included the following prognostic variables at the initiation of therapy: pneumonia, neutropenia (1,000 cells/mm3), number of positive blood cultures before therapy, infecting Candida species, underlying disease, and the simplified acute physiology score. Response and survival at 48 hours, after 5 days of therapy, and at the end of therapy, as well as toxicity rates were obtained. Other post hoc analyses were performed. Differences in outcomes were assessed by the McNemar, the sign, and the log rank tests.Patients were similar with respect to the matching criteria, age, sex, status of underlying disease, use of antibiotics and growth factors, duration of treatment, presence and removal of central venous catheters, disseminated disease, and concomitant infections. Response rates at 48 hours and 5 days were similar between the two study groups. Overall response rates at the end of therapy were 73% for patients treated with fluconazole and 71% for patients treated with amphotericin B (P = 0.78). There were no differences in survival rates or causes of death. Toxicity was observed in 9% of patients treated with fluconazole and in 67% of patients treated with amphotericin B (P0.0001). Toxic effects of amphotericin B included nephrotoxicity, hypokaliemia, and fever and chills.Fluconazole is effective and better tolerated than amphotericin B for the treatment of hematogenous candidiasis in cancer patients.

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.

BACKGROUND The improved efficacy of imipenem over other beta-lactam antibiotics in the treatment of febrile neutropenic patients has been attributed to its broad spectrum of activity. METHODS A prospective, randomized, clinical trial was performed comparing vancomycin 1 g every 12 hours plus imipenem/cilastatin 500 mg every 6 hours and the same dose of vancomycin plus aztreonam 2 g every 6 hours for empiric treatment of febrile episodes in neutropenic patients with cancer. RESULTS The imipenem regimen cured 76% of the 148 evaluable episodes compared with a 67% cure rate for the 152 episodes treated with the aztreonam regimen (P = 0.1). Most of the polymicrobial infections (77% or 10/13) treated with the imipenem responded, whereas only 38% (5/13) of these infections responded to the aztreonam regimen. Although the cost of the imipenem regimen was less than the cost of the aztreonam regimen, it was associated significantly more with skin rashes (12/194 vs. 3/189, P = 0.02). In a multivariate analysis, a poor outcome was independently associated in both instances with the persistence of neutropenia and the presence of pneumonia (P < 0.001). CONCLUSIONS Overall, in a multifactorial analysis that included efficacy, toxicity, and cost, the imipenem and aztreonam regimens were comparable. Cancer 1996;77:1386-94.

We identified 91 cases of bacteremia due to Stenotrophomonas (Xanthomonas) maltophilia in a prospective, multicenter observational study. The patients were highly compromised; the majority had an underlying malignancy, had received immunosuppressive therapy, and had indwelling venous catheters. Although 94% of patients received an antimicrobial agent to which the blood isolate was susceptible, the mortality among these patients 14 days after the onset of bacteremia was 21%. Mortality was significantly correlated with the presence of a hematologic malignancy or neutropenia or transplantation, immunosuppressive therapy, and a severity-of-illness score of > 4. S. maltophilia infection is associated with substantial morbidity and mortality among highly compromised patients. The organism is typically resistant to expanded spectrum beta-lactam agents and aminoglycoside antibiotics. Trimethoprim-sulfamethoxazole should be administered if the isolate is susceptible to this combination; addition of another agent to which the isolate is susceptible should be considered in treating patients who are neutropenic, immunocompromised, or critically ill.

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

Respiratory syncytial virus (RSV) has been demonstrated to be an important cause of life-threatening pneumonia in adult bone marrow transplant recipients; however, its role in other immunocompromised adults has not been defined. We prospectively studied all adult patients with leukemia who were hospitalized at M. D. Anderson Cancer Center (Houston) during a 1-year period (November 1993 through October 1994). During a 19-week period when RSV was prevalent in the community, it was isolated from 9 (10%) of 87 patients with leukemia who developed an acute respiratory illness. In 6 (75%) of 8 patients with profound chemotherapy-induced myelosuppression, the RSV infection was complicated by pneumonia, with an 83% mortality rate. RSV appears to be an important cause of severe and often fatal pneumonia in myelosuppressed patients with leukemia.

A trial of the antifungal triazole fluconazole was conducted in cancer patients with presumed or proven mold infection. Groups of patients received fluconazole at four dosages (800, 1200, 1600, or 2000 mg/day). Adverse events, plasma levels, and clinical response were examined. Thirty-nine patients were enrolled. The 28 evaluable patients had presumed (13 patients) or proven (15) mold infection with Aspergillus (4) and Fusarium (3) species, Zygomycetes organisms (1), or nonspeciated mold (7). Adverse effects included elevated liver function test results (8 patients), nausea and vomiting (2), and erythema multiforme (1). Neurologic toxicity occurred in 3 patients receiving 2000 mg/day. Average steady-state peak plasma concentrations were 51.8, 74.4, and 91.8 mg/L for dosages 1200, 1600, and 2000 mg/day, respectively. Seven of 28 evaluable patients responded. Response did not appear to be related to dose. Fluconazole is well tolerated at total daily doses up to 1600 mg. The data suggest a linear plasma concentration-dose relationship. The activity of fluconazole in refractory mold infections seems to be limited.

Limited information is available regarding the pathogenesis and clinical manifestations of infection with Cunninghamella bertholletiae. In this report, we describe the clinical courses of three patients with leukemia and fatal C. bertholletiae infection and review the literature. In all patients, the infection developed in the setting of severe neutropenia following high doses of cytotoxic chemotherapy. Clinical presentation always consisted of fever and pneumonia and could be associated with dissemination to numerous organs. The course of infection was very rapid, and the diagnosis was made around or after the time of death. The most important risk factors for C. bertholletiae infection described in the literature include corticosteroid administration and prolonged severe granulocytopenia. Four infectious syndromes due to Zygomycetes have been described: rhinocerebral, pulmonary, cutaneous and soft tissue, and disseminated. The outcome of disseminated infection with C. bertholletiae has been almost uniformly fatal. Most previously described patients, however, did not receive aggressive treatment consisting of amphotericin B administration, resection of infected tissues, and, most importantly, control of the underlying disease.

Background. Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new anti-fungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as anti-fungal prophylaxis. Methods. Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Tri-methoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity. Results. Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02). Conclusions. At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia.

Patients with neoplastic disease are often highly susceptible to severe infections. The following factors influence the types, severity, and response to therapy of these infections: (1) Changing epidemiology of infections; (2) cancer- and/or treatment-associated neutropenia; (3) acquired immune deficiency states such as cellular immune defect; (4) recent development of new-generation diagnostic tools including widely available DNA amplification tests; (5) effective intervention for infection prevention; (6) empiric or presumptive therapy during high-risk periods; (7) availability of new classes of highly active antimicrobial drugs; (8) strategies to promote hosts’ immune response; and (9) future measures. This introductory chapter intended for the reader to become familiar with the important historical milestones in the understanding and development in the field of infectious diseases in immunosuppressed patients with an underlying neoplasms and patients undergoing hematopoietic stem cell trans­plantation.

Neutrophils provide protection against a wide variety of common and opportunistic bacterial and fungal pathogens. Consequently, the frequency and severity of infections caused by these organisms is increased in patients with neutropenia. At most cancer treatment centers, Gram-positive organisms are isolated more frequently from neutropenic patients with documented bacterial infections than Gram-negative bacilli, although institutional and regional differences occur as do periodic shifts in the spectrum of bacterial infections. Candida spp. and Aspergillus spp. remain the most common fungal pathogens in this setting, although a number of opportunistic fungal pathogens have emerged. The prompt administration of empiric, broad-spectrum, parenteral antibiotics in the hospital when a neutropenic patient becomes febrile is the standard of care. Over the past decade, it has become possible to reliably identify “low-risk” neutropenic patients both in adult and pediatric patient populations. Infection prevention (prophylaxis), infection control, and antimicrobial stewardship are important aspects in the overall management of the febrile neutropenic patient.

Background. Hospitalization and intravenous (IV) broad-spectrum antibiotics are the standard of care for all febrile neutropenic patients with cancer. Recent work suggests that a low-risk population exists who might benefit from an alternate approach. Methods. A prospective randomized clinical trial was performed comparing oral ciprofloxacin 750 mg plus clindamycin 600 mg every 8 hours with IV aztreonam 2 g plus clindamycin 600 mg every 8 hours for the empiric outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer. Results. The oral regimen cured 35 of 40 episodes (88% response rate), whereas the IV regimen cured 41 of 43 episodes (95% response rate, P = 0.19). Although the cost of the oral regimen was significantly less than that of the IV regimen (P < 0.0001), it was associated with significant renal toxicity (P < 0.05), which led to early termination of the study. Overall, combining its safety and efficacy, the IV regimen was superior (P = 0.03). Conclusions. This prospective study suggested that outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients with cancer is safe and effective. Better oral regimens are needed.

We reviewed the experience over 20 years with primary Candida pneumonia among fatal cancer cases at our hospital. Unequivocal evidence of primary Candida pneumonia has been reported in only 55 cases. We report here 31 such cases. Unlike patients with disseminated candidiasis, and contrary to previous studies concentrating on cancer patients, only 9 of our 31 patients had severe neutropenia. In this report, the lack of organ involvement other than the lungs at complete autopsy examination, the exclusion of patients with candidemia, the very high percentage of intrabronchial and intra-alveolar fungal involvement without vascular invasion, and the concomitant presence of candidal esophagitis in some patients suggest that the mechanism of entry of the infectious particles may have been aspiration of oropharyngeal contents. The major clinical manifestations of primary Candida pneumonia are fever and tachypnea. Radiologically, nonspecific patchy infiltrates can be seen. Histopathologically, there is prevalence of bronchopneumonia, hemorrhage, and necrosis. The only accepted criterion for the definitive diagnosis of Candida pneumonia is histologic demonstration of the fungus in lung tissue. In contrast to previous reports, we demonstrated that primary Candida pneumonia can be life-threatening in patients with cancer since it directly contributed to the death of 84% of the patients in the present series. Very little data are available on the therapy and outcome of patients with Candida pneumonia. However, primary Candida pneumonia in the compromised host should be treated as a life-threatening infection with systemic antifungal therapy.

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

We studied the in vivo antifungal activity of azoles in humans and in a murine model of disseminated trichosporonosis. Eight patients infected with Trichosporon species were treated with fluconazole, SCH 39304, or miconazole for 2-26 weeks. Four patients had fungemia, two patients had disseminated trichosporonosis, and one patient each had soft-tissue infection and cystitis. Response of trichosporonosis to azoles was seen in all eight patients, although one patient died with disseminated aspergillosis while still receiving SCH 39304. A literature review indicated that responses to ketoconazole or miconazole were noted in four patients with trichosporonosis. In the experimental infection, amphotericin B, SCH 39304, and fluconazole were effective in prolonging survival and reducing fungal counts in the kidneys of mice infected with a clinical strain of Trichosporon beigelii. Fluconazole but not amphotericin B prolonged survival of mice infected with a clinical strain of Trichosporon capitatum. We conclude that azoles represent effective therapy for infection with Trichosporon species.

Between 1972 and 1989, the incidence of viridans streptococcal bacteremia at the University of Texas M. D. Anderson Cancer Center in Houston increased from one case per 10,000 admissions to 47 cases per 10,000 admissions (P less than .0001). A shock syndrome characterized by hypotension, rash, palmar desquamation, adult respiratory distress syndrome, and occasionally death developed in 26% of cases of streptococcal septicemia but in only 4% of cases of septicemia involving other gram-positive bacteria (P = .0005). The risk of streptococcal infection increased with the prophylactic administration of trimethoprim-sulfamethoxazole or a fluoroquinolone (P less than .0001) and with profound neutropenia (P less than .0001). Treatment of chemotherapy-induced gastritis with antacids or with histamine type 2 (H2) antagonists was associated with a sevenfold increase in risk (P less than .001), while sucralfate therapy did not increase risk (P = .65). Streptococcal infection may result from gastric overgrowth of organisms resistant to trimethoprim-sulfamethoxazole in an antacid- or H2 antagonist-induced alkaline environment, with the gastrointestinal tract ulceration caused by antineoplastic therapy providing a convenient portal of entry. In patients receiving chemotherapy, replacement of antacids or H2 antagonists by an acid-sparing regimen should be considered to preserve the natural acidic barrier to infection.

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.

The discovery of the antifungal activity of azole compounds represented an important therapeutic advance. Miconazole, ketoconazole, and fluconazole are currently commercially available, and itraconazole has undergone extensive clinical evaluation. Because of its limited activity and toxicity, miconazole has been replaced by newer agents. Ketoconazole has proven useful in therapy for superficial infections and invasive infections caused by the pathogenic fungi. Among its disadvantages are limited absorption in the absence of gastric acid and its potential for drug-drug interactions. Fluconazole is the only azole available as oral and intravenous preparations. Unlike other azoles, it is only minimally metabolized in the liver and largely excreted in the urine as active drug. It is more effective than ketoconazole against superficial candidal infections and is the drug of choice for maintenance therapy for cryptococcal meningitis in patients infected with human immunodeficiency virus. An advantage of itraconazole is its activity against aspergillosis. It is also active against many infections caused by pathogenic fungi. Other azole compounds are at varying stages of preclinical and clinical investigation.

Pseudomonas aeruginosa is an important cause of infection in immunosuppressed patients, particularly those with cancer. However, it is being recognized with greater frequency in patients who appear to be immunocompetent. Changes in modern lifestyles have led to the appearance of some new manifestations of pseudomonas infection including corneal ulceration and keratitis associated with contact lenses, and hot-tub- or whirlpool-associated folliculitis. These represent additional hazards to patients with cancer. Many studies, both in animals and humans, have contributed to our knowledge of the pathogenesis, immunology, treatment, and prevention of pseudomonas infections. Although the aminoglycosides represented a significant step forward in the treatment of these infections, of greater importance was the discovery of the antipseudomonal penicillins. These antibiotics are more effective than the aminoglycosides in neutropenic patients, who are especially susceptible to pseudomonal infections. The older antipseudomonal penicillins (carbenicillin, tircarcillin) have largely been replaced by newer ones (mezlocillin, azlocillin, pipercillin) which are more potent in vitro against P. aeruginosa. Although the accepted therapeutic practice has been to utilize a penicillin in combination with an aminoglycoside, the introduction of newer beta lactam agents and fluoroquinolones with antipseudomonal properties offers the possibility of other approaches to combination therapy. These include the combination of a penicillin or a cephalosporin or the combination of a quinolone with an aminoglycoside or a betalactam antibiotic. However, the development of newer antimicrobial agents is not likely to be a lasting solution to the problem of pseudomonas infections. Since pseudomonas infection often progresses rapidly, optimal results will always depend upon the prompt initiation of appropriate therapy in febrile patients, particularly those who are at high risk. The use of granulocyte transfusions has proved to be of limited benefit. Early data with the use of monoclonal antibodies is promising, and the results of large-scale trials are eagerly awaited. It is hoped that continuing investigation of pseudomonas vaccines will lead to the discovery of effective prophylaxis for highly susceptible patients. It is also hoped that with the availability of GM-CSF it will become possible to reduce the period of risk for serious infections. Finally, a reduction in the frequency of microbiologically proven P. aeruginosa infections in cancer patients should not lead to the assumption that these organisms do not constitute a problem in such patients anymore. The use of prophylactic antibiotics and prompt empiric antibiotic coverage for therapy has resulted in this decline. Cultures are therefore unlikely to be positive with the same frequency as they were before antimicrobial prophylaxis and empiric antibiotic therapy became standard practice.(ABSTRACT TRUNCATED AT 400 WORDS)

The pathogenicity of two clinical strains of Fusarium solani was studied in normal and transiently neutropenic outbred CF1 and CD1 male mice. Three inocula (5 x 10(5), 1 x 10(6), and 5 x 10(6) spores/animal) were tested. Groups of 10 mice each were injected with a single intravenous dose of one inoculum. Mortality correlated with the dose of inoculum, as survival was significantly shorter in mice injected with 5 x 10(6) cfu/mouse than in mice that received 1 x 10(6) or 5 x 10(5) cfu/mouse (P less than .001). Necrotizing abscesses with acute branching septate hyphae, neutrophil and macrophage infiltration, and hemorrhage were observed. The median survival of neutropenic mice was shorter than that of normal mice (P less than .001). Neutropenic mice did not show evidence of an inflammatory cellular reaction and exhibited significantly higher numbers of fungi per gram of infected tissue (P less than .001). Intact host defenses in normal mice were able to confine the infection to the kidneys after initial dissemination. In contrast, disseminated infection persisted in most organs in immunosuppressed animals.

Over 12 years, 136 episodes of bacteremia caused by clostridial species were documented. Eighty-three were monomicrobial, and 53 were polymicrobial. Gastrointestinal, genitourinary carcinomas, and acute leukemia were the most common underlying malignancies. Septic shock occurred in 29% of monomicrobial bacteremias and 45% of polymicrobial bacteremias and was associated with a high mortality rate. Acute hemolysis, gas gangrene, and diffuse spreading cellulitis occurred infrequently but were associated with a 100% fatality rate. Many infections caused by Clostridium perfringens and C. septicum were associated with abdominal disease. The most commonly isolated organism was C. perfringens, followed by C. septicum and C. sporogenes. Overall survival was 58%, but it was 66% for monomicrobial episodes and 45% for polymicrobial infections. All of the patients with bacteremia due to an aerobic gram-negative bacillus in addition to the clostridial species died of their infection. The most effective antibiotics were clindamycin, penicillin, metronidazole, and moxalactam. Surgical drainage of abscesses was an important component of therapy.