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Bacterial infections are a serious complication of hematologic malignancies and the therapies used to treat them. Neutropenia can result from the malignancy itself or develop as a complication of chemotherapy and remains a major risk factor for the development of infections in these patients. In addition, the mechanical and chemotherapeutic interventions applied to patients with hematologic malignancies impose additional challenges to host defenses against bacterial invasion. The bacteria responsible for most infections in this patient population have continued to evolve as different therapeutic, preventive, and preemptive strategies are introduced into the armamentarium for leukemias, lymphomas, and myelomas. Both Gram-negative and Gram-positive pathogens have become increasingly resistant to available antimicrobial agents, in part due to the increasing use of agents, especially the fluoroquinolones, to prevent bacterial infections. This review addresses recent clinical developments in the epidemiology and prevention of bacterial infections in these unique populations of patients.

Background: Cryptococcosis occurring ≤30 days after transplantation is an unusual event, and its characteristics are not known., Methods: Patients included 175 solid-organ transplant (SOT) recipients with cryptococcosis in a multicenter cohort. Very early-onset and late-onset cryptococcosis were defined as disease occurring ≤30 days or >30 days after transplantation, respectively., Results: Very early-onset disease developed in 9 (5%) of the 175 patients at a mean of 5.7 days after transplantation. Overall, 55.6% (5 of 9) of the patients with very early-onset disease versus 25.9% (43 of 166) of the patients with late-onset disease were liver transplant recipients (P = .05). Very early cases were more likely to present with disease at unusual locations, including transplanted allograft and surgical fossa/site infections (55.6% vs 7.2%; P < .001). Two very early cases with onset on day 1 after transplantation (in a liver transplant recipient with Cryptococcus isolated from the lung and a heart transplant recipient with fungemia) likely were the result of undetected pretransplant disease. An additional 5 cases involving the allograft or surgical sites were likely the result of donor&#x2010;acquired infection., Conclusions: A subset of SOT recipients with cryptococcosis present very early after transplantation with disease that appears to occur preferentially in liver transplant recipients and involves unusual sites, such as the transplanted organ or the surgical site. These patients may have unrecognized pretransplant or donor-derived cryptococcosis.

Background: Whether there are geographic differences in clinical presentation of cryptococcosis in solid organ transplant (SOT) recipients in the United States (US) is not known., Material/methods: Patients comprised a cohort of 120 SOT recipients from US transplant centers who fulfilled the EORTC/MSG criteria for cryptococcal disease., Results: Central nervous system, pulmonary, and cutaneous cryptococcal disease were observed in 51% (61/120), 64% (77/120), and 15% (18/120) of the patients, respectively. Cutaneous disease was documented in 9% (3/32) of the patients from South Atlantic region, 19% (6/32) from Mid Atlantic, 26% (6/23) from Southern, 7% (2/29) from Midwestern, and in 1 of 4 patients from the Northwestern region of the US. When controlled for age, immunosuppressive regimen, type of transplant, and renal failure at baseline, patients from the Southern compared with other regions of the US were significantly more likely to have cutaneous cryptococcal disease (OR 3.8, 95% CI 1.1-14, P=0.045)., Conclusions: Post-transplant cryptococcosis is more likely to present with cutaneous disease in the Southern region compared with other regions in the US. This predilection for cutaneous cryptococcosis could not be explained on the basis of differences in immunosuppression or the type of transplant. Whether our findings are related to strain-related variations in characteristics of the yeast or other transplant variables remains to be determined.

Background: Infection remains the most common complication following renal transplantation (RT). Cytomegalovirus (CMV) is one of the most important pathogens in this patient population and Clostridium difficile-associated colitis (CDAC) has emerged as one of the most frequent gastrointestinal complications. Only few cases of simultaneous CMV enterocolitis and CDAC have been reported., Case Report: A 73-year-old woman who underwent RT more than 10 years earlier developed severe abdominal pain and profound bloody diarrhea. She was diagnosed with simultaneous CMV enterocolitis and CDAC and treated with ganciclovir and metronidazole. She was unable to clear the infections and underwent colonic and small bowel resection, but ultimately died from indirect complications following the two severe infections., Conclusions: Late-onset CMV disease in this patient who was CMV negative prior to transplantation and received a CMV-negative graft was an unexpected event; the simultaneous occurrence of CDAC aggravated the clinical picture ultimately leading to surgery, graft failure and death. Clinicians should be aware that opportunistic infections may develop many years post transplant and may occur simultaneously.

The posttransplant outcomes and optimal management of patients with end-stage liver disease who develop cryptococcosis prior to transplantation have not been defined. We discuss these issues in the context of successful liver transplantation and pretransplant cryptococcal disease. Our report suggests that liver transplantation may be cautiously considered under the umbrella of fluconazole therapy in patients with end-stage liver disease and pretransplant cryptococcosis, provided that disease control is achieved with adequate treatment before transplantation., ((c) 2010 AASLD.)

Background: Cerebrospinal fluid (CSF) analysis is often deferred in patients with cryptococcal disease, particularly in the absence of neurologic manifestations. We sought to determine whether a subset of solid organ transplant (SOT) recipients with high likelihood of central nervous system (CNS) disease could be identified in whom CSF analysis must be performed., Methods: Patients comprised a multicenter cohort of SOT recipients with cryptococcosis., Results: Of 129 (88%) of 146 SOT recipients with cryptococcosis who underwent CSF analysis, 80 (62%) had CNS disease. In the overall study population, abnormal mental status, time to onset of cryptococcosis more than 24 months posttransplantation (late-onset disease), serum cryptococcal antigen titer more than 1:64, and fungemia were independently associated with an increased risk of CNS disease. Of patients with abnormal mental status, 95% had CNS cryptococcosis. When only patients with normal mental status were considered, three predictors (serum antigen titer >1:64, fungemia, and late-onset disease) independently identified patients with CNS cryptococcosis; the risk of CNS disease was 14% if none, 39% if one, and 94% if two of the aforementioned predictors existed (chi for trend P<0.001)., Conclusions: CSF analysis should be strongly considered in SOT recipients with cryptococcosis who have late-onset disease, fungemia, or serum cryptococcal antigen titer more than 1:64 even in the presence of normal mental status.

Background: Leuconostoc spp. are vancomycin resistant Gram positive lactobacilli. Little is known about their significance in transplant recipients., Case Report: A 64-year-old female liver transplant recipient developed Leuconostoc sepsis originating from a bile leak after extended exposure to vancomycin. The infection was readily controlled clindamycin, however, the patient died later on unrelated to the infection. Five articles on Leuconostoc infections in transplant patients were found in PubMed including two liver recipients with intraabdominal infection due to biliary complications and four stem cell recipients with sepsis., Conclusions: Leuconostoc spp. should be considered pathogens in transplant recipients who are exposed to vancomycin.

Background: Whether outcome of central nervous system (CNS) cryptococcosis in solid organ transplant recipients treated with lipid formulations of amphotericin B is different from the outcome of the condition treated with amphotericin B deoxycholate (AmBd) is not known., Methods: We performed a multicenter study involving a cohort comprising consecutive solid organ transplant recipients with CNS cryptococcosis., Results: Of 75 patients treated with polyenes as induction regimens, 55 (73.3%) received lipid formulations of amphotericin B and 20 (26.7%) received AmBd. Similar proportions of patients in both groups had renal failure at baseline (P = .94 ). Overall, mortality at 90 days was 10.9% in the group that received lipid formulations of amphotericin B and 40.0% in the group that received AmBd. In univariate analysis, nonreceipt of calcineurin inhibitors (P = .034), renal failure at baseline (P = .016), and fungemia (P = .003) were significantly associated with mortality. Compared with AmBd, lipid formulations of amphotericin B were associated with a lower mortality (P = .007). Mortality did not differ between patients receiving lipid formulations of amphotericin B with or without flucytosine (P = .349). In stepwise logistic regression analysis, renal failure at baseline (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.02-20.80; P = .047) and fungemia (OR, 10.66; 95% CI, 2.08-54.55; P = .004 ) were associated with an increased mortality, whereas lipid formulations of amphotericin B were associated with a lower mortality (OR, 0.11; 95% CI, 0.02-0.57; P = .008)., Conclusions: Lipid formulations of amphotericin B were independently associated with better outcome and may be considered as the first-line treatment for CNS cryptococcosis in these patients.

The nematode Caenorhabditis elegans is emerging as a facile and economical model host for the study of evolutionarily conserved mechanisms of microbial pathogenesis and innate immunity. A rapidly growing number of human and animal microbial pathogens have been shown to injure and kill nematodes. In many cases, microbial genes known to be important for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity in nematodes. C. elegans has been used in mutation-based screening systems to identify novel virulence-related microbial genes and immune-related host genes, many of which have been validated in mammalian models of disease. C. elegans-based pathogenesis systems hold the potential to simultaneously explore the molecular genetic determinants of both pathogen virulence and host defense.

Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against Pneumocystis jiroveci pneumonia. Alternative agents are used in treating patients who do not tolerate this medication. We report 2 cases of prophylaxis failure in patients receiving low-dose atovaquone. We discuss the use of atovaquone as an alternative agent for prophylaxis in transplant recipients.

Pseudomonas aeruginosa is an opportunistic pathogen that may cause severe infections in humans and other vertebrates. In addition, a human clinical isolate of P. aeruginosa, strain PA14, also causes disease in a variety of nonvertebrate hosts, including plants, Caenorhabditis elegans, and the greater wax moth, Galleria mellonella. This has led to the development of a multihost pathogenesis system in which plants, nematodes, and insects have been used as adjuncts to animal models for the identification of P. aeruginosa virulence factors. Another approach to identifying virulence genes in bacteria is to take advantage of the natural differences in pathogenicity between isolates of the same species and to use a subtractive hybridization technique to recover relevant genomic differences. The sequenced strain of P. aeruginosa, strain PAO1, has substantial differences in virulence from strain PA14 in several of the multihost models of pathogenicity, and we have utilized the technique of representational difference analysis (RDA) to directly identify genomic differences between P. aeruginosa strains PA14 and PAO1. We have found that the pilC, pilA, and uvrD genes in strain PA14 differ substantially from their counterparts in strain PAO1. In addition, we have recovered a gene homologous to the ybtQ gene from Yersinia, which is specifically present in strain PA14 but absent in strain PAO1. Mutation of the ybtQ homolog in P. aeruginosa strain PA14 significantly attenuates the virulence of this strain in both G. mellonella and a burned mouse model of sepsis to levels comparable to those seen with PAO1. This suggests that the increased virulence of P. aeruginosa strain PA14 compared to PAO1 may relate to specific genomic differences identifiable by RDA.