Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients.

Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad-spectrum antibiotics and a complex interplay of preparative regimen and GvHD-induced gut mucosal damage. Our study evaluated risk factors (RF) for recurrent CDI in HSCT recipients given the ubiquity of traditional RF for CDI in this population. Of the 499 allogeneic HSCT recipients transplanted between 2005 and 2012, 61 (12%) developed CDI within 6 months before transplant or 2 years after transplant and were included in the analysis. Recurrent CDI occurred in 20 (33%) patients. One year incidence of CDI recurrence was 31%. Multivariable analyses identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (hazard ratio 1.96, 95% confidence interval 1.09-3.52, P=0.025). Most recurrences occurred within 6 months of the first CDI, and the recurrence of CDI was associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI.

Improvement in the outcome of invasive fusariosis in the last decade.

Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade.

Epidemiology and risk factors for infections in myelodysplastic syndromes.

We conducted a case-control study to describe the epidemiology and risk factors for infections requiring hospitalization in patients with myelodysplastic syndromes (MDS). Of 497 patients identified, 103 patients developed 201 episodes of infection. The probability of acquiring an infection 1 year from date of MDS diagnosis was 15% (95% confidence interval [CI] 12-18%). Patients developing infections had decreased survival compared to those who did not (P = 0.007). Significant risk factors for infection were higher risk MDS (hazard ratio [HR] = 2.7, 95% CI = 1.7-4.1, P < 0.0001), nadir absolute neutrophil count <500/mL (HR = 1.8, 95% CI = 1.2-2.7, P < 0.007), chronic obstructive pulmonary disease (HR = 2.6, 95% CI = 1.4-4.9, P < 0.003), history of other malignancy (HR 2.0, 95% CI = 1.3-3.1, P < 0.003), and autoimmune disease (HR 2.9, 95% CI = 1.4-6.0, P < 0.005). Age, nadir platelet count <20,000/mL, diabetes mellitus, and MDS treatment were not significant risk factors. Pneumonia was the most common infection, and bacteria the predominant pathogens.

Fatal human metapneumovirus and influenza B virus coinfection in an allogeneic hematopoietic stem cell transplant recipient.

Human metapneumovirus (hMPV) infection can occur in all age groups with significant morbidity and mortality. Coinfection with influenza virus occurs mainly with influenza type A and all reported cases recovered completely. We report the case of a 61-year-old man who had hematopoietic stem cell transplant for myelodysplastic syndrome. He was admitted to hospital for septic shock and neutropenia, and blood culture was positive for Pseudomonas aeruginosa. He rapidly developed respiratory failure and required ventilator support. His respiratory culture grew P. aeruginosa and hMPV. His course was complicated by persistent shock requiring vasopressor support, and repeat nasopharyngeal swab was positive for influenza type B and hMPV. His condition rapidly deteriorated, his family elected comfort care, and the patient died shortly thereafter. Coinfection with hMPV and influenza virus type B may have a poor outcome and can be fatal, especially in immunocompromised patients.

Influenza A/H1N1 2009 pneumonia in kidney transplant recipients: characteristics and outcomes following high-dose oseltamivir exposure.

We report 2 cases of severe pneumonia due to the novel pandemic influenza A/H1N1 2009 in kidney transplant recipients. Our patients initially experienced influenza-like illness that rapidly progressed to severe pneumonia within 48 h. The patients became hypoxic and required non-invasive ventilation. The novel influenza A/H1N1 2009 was identified from their nasal swabs. These cases were treated successfully with a relatively high dose of oseltamivir, adjusted for their renal function. Clinical improvement was documented only after a week of antiviral therapy. Despite early antiviral treatment, we showed that morbidity following novel pandemic influenza A/H1N1 2009 infection is high among kidney transplant recipients.

Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined.

Effect of zincum gluconicum nasal gel on the duration and symptom severity of the common cold in otherwise healthy adults.

BACKGROUND: Previous studies suggest that zinc salts may be effective in treating the common cold. Since rhinovirus infections occur primarily in the nasal cavity, an attempt to arrest the infection at the portal of entry seems logical. AIM: To assess the ability of zinc nasal gel to shorten the duration and reduce the severity of the common cold in healthy adults. STUDY DESIGN: Randomized, double blind, placebo-controlled study. METHODS: Of 1087 patients screened by telephone, 80 patients were enrolled, all presenting within 24-48 h of the onset of illness. They received one dose per nostril of a nasal gel spray containing either 33 mmol/l zincum gluconicum, or an identical placebo four times daily until their symptoms resolved, for a maximum of 10 days. RESULTS: Median duration of cold symptoms in the zinc group was significantly shorter than in the placebo group (median [IQR] 4.3 days [2.5-5.5] vs. 6 days [5-8.5], p=0.002). Nasal drainage, nasal congestion, hoarseness, and sore throat were the symptoms most affected. Significant reduction of total symptom scores started from the second day of the study. Adverse effects (mainly nasal stinging) were similar in both groups. DISCUSSION: Zincum gluconicum nasal gel shortens duration and reduces symptom severity of the common cold in healthy adults, when started within 24-48 h of the onset of illness.

The efficacy of prophylactic outpatient antibiotics for the prevention of neutropenic fever associated with high-dose etoposide (VP-16) for stem cell mobilization.

High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia is common. The infectious complications associated with high-dose etoposide have not been previously described. After noting a high incidence of hospitalizations for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for patients receiving high-dose etoposide plus G-CSF, attempting to reduce infectious complications. Ninety-eight patients underwent etoposide mobilization between December 1997 and June 2000. Three chronological patient groups received: (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not receiving antibiotic prophylaxis had a 68% incidence of hospitalization for neutropenic fever. In the patients receiving prophylaxis, the incidence was reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001 for comparison between prophylaxed and unprophylaxed groups). We conclude that etoposide mobilization is associated with a significant incidence of neutropenic fever, which can be substantially reduced by a vigorous antimicrobial prophylactic program.

Clinical characteristics of 13 solid organ transplant recipients with ganciclovir-resistant cytomegalovirus infection.

BACKGROUND: Ganciclovir-resistant (GCV-R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients. OBJECTIVE: To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV-R CMV seen between 1990 and 2000 at a single center. METHODS: Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV-R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data. RESULTS: Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R-), and 11/13 (85%) had tissue-invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV-based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3 x/week) IV ganciclovir for prophylaxis. CONCLUSIONS: GCV-R CMV is associated with CMV D+/R- status, tissue-invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV-R CMV.

Infectious complications within the first year after nonmyeloablative allogeneic peripheral blood stem cell transplantation.

Nonmyeloablative peripheral blood stem cell transplantation (PBSCT) is a novel therapeutic strategy for patients with malignant and non-malignant hematologic diseases. Infectious complications of this procedure have not been previously well described. Data on 12 patients transplanted at a tertiary care center were collected prospectively and verified retrospectively. Neutropenia developed in a third of patients, lasting for a median of 5 days. All patients developed some degree of graft-versus-host disease, as intended. Most patients achieved full chimerism by week 5. Bacterial infections occurred in two patients (17%). Cytomegalovirus (CMV) viremia occurred in five patients (42%) at a median of 80 days; none had received CMV prophylaxis. Viremia was associated with fever and fatigue in three patients, possible gastrointestinal involvement in one patient and was asymptomatic in one patient. All viremic patients responded to intravenous ganciclovir therapy. No fungal infections were documented. No patients died as a result of infection. The incidence of CMV viremia in our patients was high, but the incidence of invasive disease due to CMV was low. The best strategy to prevent CMV in patients undergoing nonmyeloablative PBSCT remains to be determined, but strategies employed in traditional allogeneic bone marrow transplantation should be considered in these patients.

Influenza in the older adult. Indications for the use of vaccine and antiviral therapy.

Each year, the influenza virus is responsible for 20,000 to 40,000 deaths and up to 300,000 hospitalizations in the United States. Although children and younger adults experience more cases of influenza, older individuals who are infected with the virus experience greater morbidity and mortality. The most effective means of influenza prevention for older adults is the influenza vaccine. Antivirals are used as adjuvant therapy, but they are not intended as primary prevention except for at-risk patients who are allergic to the vaccine. The neuroaminidase inhibitors may cause fewer side effects than the older antivirals and therefore may be a useful alternative in the treatment of influenza symptoms in older adults.

Prophylactic and symptomatic treatment of influenza. Current and developing options.

The influenza vaccine is the primary method for the prevention and control of influenza. Anti-influenza drugs also have been shown to be useful prophylactically and to shorten the duration of illness by 1 or 2 days when started within 48 hours of symptom onset. In this article, Dr Mossad discusses indications for the vaccine and compares the relative advantages and disadvantages of each of the anti-influenza drugs.

Management of an epidural abscess after continuous epidural catheter infusion.

OBJECTIVE: To increase awareness of the possibility of epidural infection after continuous epidural infusion. Outline the salient diagnostic features of epidural infection. Outline a strategy to manage epidural infection and minimize morbidity. SETTING: Academic multidisciplinary pain clinic. PATIENT: A patient with a left knee meniscal tear with a history of Chronic Regional Pain Syndrome Type I (CRPS I) of the left foot. INTERVENTIONS: Attempted control of CRPS I symptoms with a tunnelled epidural catheter infusion. RESULTS AND CONCLUSIONS: The patient developed an epidural abscess diagnosed on the 11th postoperative day. The catheter was removed and the patient was treated successfully with intravenous antibiotics.

The humoral immune response to influenza vaccination in lung transplant patients.

The purpose of this study was to evaluate the humoral immune response to influenza vaccination in lung transplant recipients. Antibody levels to the three viral antigens included in the 1999-2000 trivalent influenza vaccine (A/Sydney/5/97-like (H3N2), A/Beijing262/95-like (H1N1), and B/Yamanashi/16/ 98) were measured before and 4 weeks postvaccination in 43 lung transplant recipients and 21 healthy adult controls. The ability to develop protective antibody levels, a serological response, and the magnitude of change in levels were assessed. The humoral immune response to influenza vaccination was significantly lower in the transplant group for all three viral antigens. To A/Sydney, 95% of the control group and 40% of the transplant group developed protective levels (p=0.0009); to A/Beijing, 71% of the control group and 30% of the transplant group developed protective levels (p=0.004); and to B/Yamanashi, 48% of the control group and 19% of the transplant group developed protective levels (p=0.02). Those receiving cyclosporine had lower antibody responses when compared to those receiving tacrolimus (r=-0.3056, p=0.0463). The humoral immune response to influenza vaccination in lung transplant recipients is poor. Lung transplant recipients receiving cyclosporine may have a lower antibody response than those receiving tacrolimus. Alternative prevention strategies may be needed.

Mycobacterium fortuitum osteomyelitis in a peripheral blood stem cell transplant recipient.

Mycobacterium fortuitum is an uncommon, but well-recognized, pathogen in immunocompromised hosts, with special predilection for bone and soft tissue infections in solid organ transplant recipients. We describe a case of osteomyelitis due to this pathogen in a peripheral blood stem cell transplant recipient.

Isolated primary hepatic lymphoma in a patient with acquired immunodeficiency syndrome.

Non-Hodgkin lymphoma (NHL) of the B-cell type is the second most common neoplasm in patients with human immunodeficiency virus (HIV) infection after Kaposi sarcoma (KS). The majority of cases of NHL in patients with acquired immunodeficiency syndrome (AIDS) involve extranodal sites; most frequently the gastrointestinal tract (GIT) and the central nervous system (CNS). Hepatic NHL in patients with AIDS was first described by Reichert et al in 1983 in an autopsy series. It usually presents with multiple large hepatic masses and involvement of other abdominal organs or lymph nodes. The authors present a case of primary hepatic NHL in a patient with AIDS, presenting with innumerable small intrahepatic masses without the involvement of any other organs.

Antiviral agents for treating influenza.

The new neuraminidase inhibitors zanamivir and oseltamivir are important additions to the treatment of influenza, being the first class of agents active against both influenza A and influenza B. The decision to use these agents rather than amantadine or rimantadine, which are effective only against influenza A, should be based on the age of the patient, antiviral activity, side effect profile, ease of administration, drug interactions, and cost. All of these agents are effective only when started within 24 to 48 hours of onset of symptoms. To avoid inappropriate use of these agents, treatment should be continued only in patients with a confirmed diagnosis of influenza. Although effective in decreasing symptoms, none of these agents prevent pneumonia or hospitalization secondary to influenza.