Maja Weisser

Respiratory Syncytial Virus Infection in Patients with Hematological Diseases: Single-Center Study and Review of the Literature

BACKGROUND Respiratory syncytial virus (RSV) causes significant mortality in patients with hematological diseases, but diagnosis and treatment are uncertain. METHODS We retrospectively identified RSV-infected patients with upper or lower respiratory tract infection (RTI) by culture, antigen testing, and polymerase chain reaction from November 2002 through April 2007. Patients with severe immunodeficiency (SID; defined as transplantation in the previous 6 months, T or B cell depletion in the previous 3 months, graft-versus-host disease [grade, >or=2], leukopenia, lymphopenia, or hypogammaglobulinemia) preferentially received oral ribavirin, intravenous immunoglobulin, and palivizumab. The remaining patients with moderate immunodeficiency (MID) preferentially received ribavirin and intravenous immunoglobulin. RESULTS We identified 34 patients, 22 of whom had upper RTI (10 patients with MID and 12 with SID) and 12 of whom had lower RTI (2 with MID and 10 with SID). Thirty-one patients were tested by polymerase chain reaction (100% of these patients had positive results; median RSV load, 5.46 log(10) copies/mL), 30 were tested by culture (57% had positive results), and 25 were tested by antigen testing (40% had positive results). RSV-attributed mortality was 18% (6 patients died) and was associated with having >or=2 SID factors (P=.04), lower RTI (P=.01), and preengraftment (P=.012). Among 12 patients with MID (7 of whom received treatment), no progression or death occurred. Nine patients with SID and upper RTI received treatment (7 patients received ribavirin, intravenous immunoglobulin, and palivizumab); infection progressed to the lower respiratory tract in 2 patients, and 1 patient died. Ten patients with SID and lower RTI were treated, 5 of whom died, including 4 of 6 patients who received ribavirin, intravenous immunoglobulin, and palivizumab. The duration of RSV shedding correlated with the duration of symptoms in patients with SID but exceeded symptom duration in patients with MID (P<.05). CONCLUSIONS Lower RTI, >or=2 SID criteria, and preengraftment are risk factors for RSV-attributed mortality. Polymerase chain reaction may optimize diagnosis and monitoring. Oral ribavirin therapy seems safe, but trials are needed to demonstrate its efficacy.

Bacterial Colonization and Infection of Electrophysiological Cardiac Devices Detected With Sonication and Swab Culture

Background— Electrophysiological cardiac devices are increasingly used. The frequency of subclinical infection is unknown. We investigated all explanted devices using sonication, a method for detection of microbial biofilms on foreign bodies. Methods and Results— Consecutive patients in whom cardiac pacemakers and implantable cardioverter/defibrillators were removed at our institution between October 2007 and December 2008 were prospectively included. Devices (generator and/or leads) were aseptically removed and sonicated, and the resulting sonication fluid was cultured. In parallel, conventional swabs of the generator pouch were performed. A total of 121 removed devices (68 pacemakers, 53 implantable cardioverter/defibrillators) were included. The reasons for removal were insufficient battery charge (n=102), device upgrading (n=9), device dysfunction (n=4), or infection (n=6). In 115 episodes (95%) without clinical evidence of infection, 44 (38%) grew bacteria in sonication fluid, including Propionibacterium acnes (n=27), coagulase-negative staphylococci (n=11), Gram-positive anaerobe cocci (n=3), Gram-positive anaerobe rods (n=1), Gram-negative rods (n=1), and mixed bacteria (n=1). In 21 of 44 sonication-positive episodes, bacterial counts were significant (≥10 colony-forming units/mL of sonication fluid). In 26 sterilized controls, sonication cultures remained negative in 25 cases (96%). In 112 cases without clinical infection, conventional swab cultures were performed: 30 cultures (27%) were positive, and 18 (60%) were concordant with sonication fluid cultures. Six devices and leads were removed because of infection, growing Staphylococcus aureus, Streptococcus mitis, and coagulase-negative staphylococci in 6 sonication fluid cultures and 4 conventional swab cultures. Conclusions— Bacteria can colonize cardiac electrophysiological devices without clinical signs of infection.

Galactomannan Does Not Precede Major Signs on a Pulmonary Computerized Tomographic Scan Suggestive of Invasive Aspergillosis in Patients with Hematological Malignancies

BACKGROUND Detection of serum galactomannan (GM) antigen and presence of the halo sign on a pulmonary computerized tomographic (CT) scan have a high specificity but a low sensitivity to diagnose invasive aspergillosis (IA) in patients at risk for this disease. To our knowledge, the relationship between the time at which pulmonary infiltrates are detected by CT and the time at which GM antigens are detected by enzyme immunoassay (EIA) has not been studied. METHODS In a prospective study, tests for detection of GM were performed twice weekly for patients with hematological malignancies who had undergone hematopoetic stem cell transplantation (HSCT) or had received induction and/or consolidation chemotherapy. A pulmonary CT scan was performed once weekly. Infiltrates were defined as either major or minor signs. IA was classified as proven, probable, or possible, in accordance with the definition stated by the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. RESULTS We analyzed 161 episodes of infection in 107 patients (65 allogeneic HSCT recipients, 30 autologous HSCT recipients, and 66 induction and/or consolidation chemotherapy recipients). A total of 109 episodes with no IA, 32 episodes with possible IA, and 20 episodes with probable or proven IA were identified. Minor pulmonary signs were detected by CT in 70 episodes (43%), and major pulmonary signs were detected by CT in 11 episodes (7%). Univariate and multivariate analyses revealed no significant association between detection of GM by EIA and detection of abnormal pulmonary signs by CT. A significant association was found between GM levels and receipt of piperacillin-tazobactam. GM test results were not positive before major signs were seen on CT images. Only 7 (10%) of 70 patients with minor pulmonary signs had positive GM test results before detection of the greatest pathologic change by CT. CONCLUSIONS We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of GM.

Does pregnancy influence the course of HIV infection? Evidence from two large Swiss cohort studies.

The question whether the natural history of HIV infection in women is affected by pregnancy has not so far been convincingly answered. We used prospective cohort data to compare pregnant and nonpregnant HIV-infected women during follow-up within the Swiss HIV Cohort Study (SHCS) and the Swiss Collaborative HIV and Pregnancy Study (SCHPS). Pregnant women were eligible if a CD4 cell count had been made before conception had taken place. Additional inclusion criteria were a pregnancy completed to delivery during follow-up and an observation period of at least 6 months after delivery. Thirty-two women who fulfilled these criteria were compared with 416 controls, matched for age and CD4 cell count at entry, who had not been pregnant during follow-up. Mean follow-up time was 4.8 years for pregnant women and 3.6 years for controls. The rate of any AIDS-defining event was higher in pregnant women (rate ratio [RR] from Cox regression, 1.92; 95% confidence interval [CI], 0.80-4.64) but this did not reach statistical significance (p = .15). A statistically significant difference (p = .008) emerged only for one AIDS-defining event, recurrent bacterial pneumonia (RR, 7.98; 95% CI, 1.73-36.8). The rate of death was similar in the two groups (RR, 1.14; 95% CI, 0.48-2.72; p = .8). Our results thus indicate that, after taking CD4 cell counts before conception into account, acceleration of disease progression is inconsistent among HIV-infected women who become pregnant during follow-up.

Outcome of influenza infections in outpatients after allogeneic hematopoietic stem cell transplantation

Background. Influenza can cause significant morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). The diagnostic methods and antiviral treatment have scarcely been investigated.

Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients.

We assessed the impact of antiviral prophylaxis and preemptive therapy on the incidence and outcomes of cytomegalovirus (CMV) disease in a nationwide prospective cohort of solid organ transplant recipients. Risk factors associated with CMV disease and graft failure‐free survival were analyzed using Cox regression models. One thousand two hundred thirty‐nine patients transplanted from May 2008 until March 2011 were included; 466 (38%) patients received CMV prophylaxis and 522 (42%) patients were managed preemptively. Overall incidence of CMV disease was 6.05% and was linked to CMV serostatus (D+/R− vs. R+, hazard ratio [HR] 5.36 [95% CI 3.14–9.14], p < 0.001). No difference in the incidence of CMV disease was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach (HR 1.16 [95% CI 0.63–2.17], p = 0.63). CMV disease was not associated with a lower graft failure‐free survival (HR 1.27 [95% CI 0.64–2.53], p = 0.50). Nevertheless, patients followed by the preemptive approach had an inferior graft failure‐free survival after a median of 1.05 years of follow‐up (HR 1.63 [95% CI 1.01–2.64], p = 0.044). The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy used. However, patients on CMV prophylaxis were more likely to be free from graft failure.

Co-infection of Influenza B and Streptococci causing severe pneumonia and septic shock in healthy women

BackgroundSince the Influenza A pandemic in 1819, the association between the influenza virus and Streptococcus pneumoniae has been well described in literature. While a leading role has been so far attributed solely to Influenza A as the primary infective pathogen, Influenza B is generally considered to be less pathogenic with little impact on morbidity and mortality of otherwise healthy adults. This report documents the severe synergistic pathogenesis of Influenza B infection and bacterial pneumonia in previously healthy persons not belonging to a special risk population and outlines therapeutic options in this clinical setting.Case PresentationDuring the seasonal influenza epidemic 2007/2008, three previously healthy women presented to our hospital with influenza-like symptoms and rapid clinical deterioration. Subsequent septic shock due to severe bilateral pneumonia necessitated intensive resuscitative measures including the use of an interventional lung assist device. Microbiological analysis identified severe dual infections of Influenza B with Streptococcus pyogenes in two cases and Streptococcus pneumoniae in one case. The patients presented with no evidence of underlying disease or other known risk factors for dual infection such as age (< one year, > 65 years), pregnancy or comorbidity.ConclusionsInfluenza B infection can pose a risk for severe secondary infection in previously healthy persons. As patients admitted to hospital due to severe pneumonia are rarely tested for Influenza B, the incidence of admission due to this virus might be greatly underestimated, therefore, a more aggressive search for influenza virus and empirical treatment might be warranted. While the use of an interventional lung assist device offers a potential treatment strategy for refractory respiratory acidosis in addition to protective lung ventilation, the combined empiric use of a neuraminidase-inhibitor and antibiotics in septic patients with pulmonary manifestations during an epidemic season should be considered.

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid Organ Transplantation

BACKGROUND Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. RESULTS Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. CONCLUSIONS Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.

Actinobaculum schaalii - invasive pathogen or innocent bystander? A retrospective observational study

BackgroundActinobaculum schaalii is a Gram-positive, facultative anaerobic coccoid rod, classified as a new genus in 1997. It grows slowly and therefore is easily overgrown by other pathogens, which are often found concomitantly. Since 1999, Actinobaculum schaalii is routinely investigated at our hospital, whenever its presence is suspected due to the detection of minute grey colonies on blood agar plates and negative reactions for catalase. The objective of this study was to determine the clinical significance of Actinobaculum schaalii, identified in our microbiology laboratory over the last 11 years.MethodsAll consecutive isolates with Actinobaculum schaalii were obtained from the computerized database of the clinical microbiology laboratory and patients whose cultures from any body site yielded this pathogen were analyzed. Observation of tiny colonies of Gram-positive, catalase-negative coccoid rods triggered molecular identification based on 16S rRNA gene sequencing.Results40 isolates were obtained from 27 patients during the last 11 years. The patients median age was 81 (19-101) years, 25 (92.6%) had underlying diseases and 12 (44.4%) had a genitourinary tract pathology. Actinobaculum schaalii was isolated in 12 urine cultures, 21 blood cultures, and 7 deep tissue biopsies. Twenty-five (62.5%) specimens were monobacterial, the remaining 15 (37.5%) were polybacterial 7/7 deep tissue samples (three bloodcultures and five urine cultures). Recovery from urine was interpreted as colonization in 5 (18.6%) cases (41.6% of all urine samples). Six (22.2%) suffered from urinary tract infections, six (22.2%) from abscesses (skin, intraabdominal, genitourinary tract, and surgical site infections) and 10 (37.0%) from bacteremia.ConclusionsIn this largest case series so far, detection of Actinobaculum schaalii was associated with an infection - primarily sepsis and abscesses - in 81.5% of our patients. Since this pathogen is frequently part of polymicrobial cultures (42.5%) it is often overlooked or considered a contaminant. Detection of Actinobaculum schaalii in clinical isolates mainly reflects infection indicating that this Gram-positive rod is not an innocent bystander.

Influence of IFNL3/4 Polymorphisms on the Incidence of Cytomegalovirus Infection After Solid-Organ Transplantation

BACKGROUND Polymorphisms in IFNL3 and IFNL4, the genes encoding interferon λ3 and interferon λ4, respectively, have been associated with reduced hepatitis C virus clearance. We explored the role of such polymorphisms on the incidence of cytomegalovirus (CMV) infection in solid-organ transplant recipients. METHODS White patients participating in the Swiss Transplant Cohort Study in 2008-2011 were included. A novel functional TT/-G polymorphism (rs368234815) in the CpG region upstream of IFNL3 was investigated. RESULTS A total of 840 solid-organ transplant recipients at risk for CMV infection were included, among whom 373 (44%) received antiviral prophylaxis. The 12-month cumulative incidence of CMV replication and disease were 0.44 and 0.08 cases, respectively. Patient homozygous for the minor rs368234815 allele (-G/-G) tended to have a higher cumulative incidence of CMV replication (subdistribution hazard ratio [SHR], 1.30 [95% confidence interval {CI}, .97-1.74]; P = .07), compared with other patients (TT/TT or TT/-G). The association was significant among patients followed by a preemptive approach (SHR, 1.46 [95% CI, 1.01-2.12]; P = .047), especially in patients receiving an organ from a seropositive donor (SHR, 1.92 [95% CI, 1.30-2.85]; P = .001), but not among those who received antiviral prophylaxis (SHR, 1.13 [95% CI, .70-1.83]; P = .6). These associations remained significant in multivariate competing risk regression models. CONCLUSIONS Polymorphisms in the IFNL3/4 region influence susceptibility to CMV replication in solid-organ transplant recipients, particularly in patients not receiving antiviral prophylaxis.