Ursula Flückiger

Epidemiology of Candidemia in Swiss Tertiary Care Hospitals: Secular Trends, 1991–2000

Candida species are among the most common bloodstream pathogens in the United States, where the emergence of azole-resistant Candida glabrata and Candida krusei are major concerns. Recent comprehensive longitudinal data from Europe are lacking. We conducted a nationwide survey of candidemia during 1991-2000 in 17 university and university-affiliated hospitals representing 79% of all tertiary care hospital beds in Switzerland. The number of transplantations and bloodstream infections increased significantly (P<.001). A total of 1137 episodes of candidemia were observed: Candida species ranked seventh among etiologic agents (2.9% of all bloodstream isolates). The incidence of candidemia was stable over a 10-year period. C. albicans remained the predominant Candida species recovered (66%), followed by C. glabrata (15%). Candida tropicalis emerged (9%), the incidence of Candida parapsilosis decreased (1%), and recovery of C. krusei remained rare (2%). Fluconazole consumption increased significantly (P<.001). Despite increasing high-risk activities, the incidence of candidemia remained unchanged, and no shift to resistant species occurred.

Throat Swabs Are Necessary to Reliably Detect Carriers of Staphylococcus aureus

The anterior nares are the most important screening site of colonization with Staphylococcus aureus. We screened 2966 individuals for S. aureus carriage with swabs of both nares and throat. A total of 37.1% of persons were nasal carriers, and 12.8% were solely throat carriers. Screening of throat swabs significantly increases the sensitivity of detection among carriers by 25.7%.

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.

Characteristics and Treatment Outcome of Cerebrospinal Fluid Shunt-Associated Infections in Adults: A Retrospective Analysis over an 11-Year Period

BACKGROUND Data on infections associated with cerebrospinal fluid (CSF) shunts among adults are limited. Therefore, we performed a retrospective study of shunt-associated infections in adults. METHODS Patients aged > or = 12 years with infections associated with CSF shunts and admitted to our institution(University Hospital Basel, Basel, Switzerland) from January 1996 through December 2006 were included retrospectively. Hospital charts were reviewed, and follow-up was performed by assessment of later hospitalizations and telephone contact with patients, their families, and general practitioners. RESULTS Seventy-eight episodes of infection associated with ventriculoperitoneal shunt (65 episodes), ventriculoatrial shunt (7), lumboperitoneal shunt (5), and central nervous system reservoir (1) were included. Median patient age was 50 years (range, 12-80 years); 49 (63%) of the patients were men. Most infections (48 [62%])manifested within 1 month after shunt surgery. Fever was present in 61 episodes (78%), neck stiffness was present in 35 (45%), and local signs of infection were present in 38 (49%). In CSF, leukocyte count was >5 x 10(6) cells/L in 80% of episodes, and lactate level was 11.9 mmol/L in 81% of episodes. Leukocyte counts were significantly higher in CSF obtained by use of lumbar puncture (median leukocyte count, 573 x 10(6) cells/L; P = .001) and valve puncture (median leukocyte count, 484 x 10(6) cells/L; P = .016) than in ventricular CSF (median leukocyte count, 8.5 x 10(6) cells/L). Overall, results of CSF cultures were positive in 66% of episodes (48 of 73 episodes for which CSF was collected), and microorganisms were isolated more often from valve puncture CSF specimens(91% of specimens) and ventricular CSF specimens (70%) than from lumbar CSF specimens (45%). The most prevalent organisms were coagulase-negative staphylococci (found in 37% of specimens), Staphylococcus aureus(18%), and Propionibacterium acnes (9%). A surgical procedure was performed to treat infection in 63 (81% of the episodes) (shunt removal in 37 episodes and shunt replacement in 26). The shunt was retained without surgery for 15 episodes (19% of episodes). Median duration of patient follow-up was 4.6 years (range, 0.1-11.1 years),with favorable treatment outcome in 75 (96%) of 78 cases. One of the 63 patients who underwent surgical treatment of shunt-associated infection experienced infection relapse; of the 15 patients who received treatment with antibiotics alone, 1 experienced infection relapse and 1 died. The 2 relapses involved rifampin-resistant coagulase-negative staphylococci. CONCLUSIONS Shunt-associated infections among adults often present with nonspecific clinical signs, and affected patients can have normal CSF leukocyte counts and lactate levels; therefore, a high index of suspicion and improved methods are required for diagnosing shunt-associated infection.

Biofilm Formation, icaADBC Transcription, and Polysaccharide Intercellular Adhesin Synthesis by Staphylococci in a Device-Related Infection Model

ABSTRACT Biofilm formation of Staphylococcus epidermidis and S. aureus is mediated by the polysaccharide intercellular adhesin (PIA) encoded by the ica operon. We used a device-related animal model to investigate biofilm formation, PIA expression (immunofluorescence), and ica transcription (quantitative transcript analysis) throughout the course of infection by using two prototypic S. aureus strains and one S. epidermidis strain as well as corresponding ica mutants. During infection, the ica mutants were growth attenuated when inoculated in competition with the corresponding wild-type strains but not when grown singly. A typical biofilm was observed at the late course of infection. Only in S. aureus RN6390, not in S. aureus Newman, were PIA and ica-specific transcripts detectable after anaerobic growth in vitro. However, both S. aureus strains were PIA positive in vivo by day 8 of infection. ica transcription preceded PIA expression and biofilm formation in vivo. In S. epidermidis, both PIA and ica expression levels were elevated compared to those in the S. aureus strains in vitro as well as in vivo and were detectable throughout the course of infection. In conclusion, in S. aureus, PIA expression is dependent on the genetic background of the strain as well as on strong inducing conditions, such as those dominating in vivo. In S. epidermidis, PIA expression is elevated and less vulnerable to environmental conditions.

β-Glucan Antigenemia Anticipates Diagnosis of Blood Culture–Negative Intraabdominal Candidiasis

RATIONALE Life-threatening intraabdominal candidiasis (IAC) occurs in 30 to 40% of high-risk surgical intensive care unit (ICU) patients. Although early IAC diagnosis is crucial, blood cultures are negative, and the role of Candida score/colonization indexes is not established. OBJECTIVES The aim of this prospective Fungal Infection Network of Switzerland (FUNGINOS) cohort study was to assess accuracy of 1,3-β-d-glucan (BG) antigenemia for diagnosis of IAC. METHODS Four hundred thirty-four consecutive adults with abdominal surgery or acute pancreatitis and ICU stay 72 hours or longer were screened: 89 (20.5%) at high risk for IAC were studied (68 recurrent gastrointestinal tract perforation, 21 acute necrotizing pancreatitis). Diagnostic accuracy of serum BG (Fungitell), Candida score, and colonization indexes was compared. MEASUREMENTS AND MAIN RESULTS Fifty-eight of 89 (65%) patients were colonized by Candida; 29 of 89 (33%) presented IAC (27 of 29 with negative blood cultures). Nine hundred twenty-one sera were analyzed (9/patient): median BG was 253 pg/ml (46-9,557) in IAC versus 99 pg/ml (8-440) in colonization (P < 0.01). Sensitivity and specificity of two consecutive BG measurements greater than or equal to 80 pg/ml were 65 and 78%, respectively. In recurrent gastrointestinal tract perforation it was 75 and 77% versus 90 and 38% (Candida score ≥ 3), 79 and 34% (colonization index ≥ 0.5), and 54 and 63% (corrected colonization index ≥ 0.4), respectively. BG positivity anticipated IAC diagnosis (5 d) and antifungal therapy (6 d). Severe sepsis/septic shock and death occurred in 10 of 11 (91%) and 4 of 11 (36%) patients with BG 400 pg/ml or more versus 5 of 18 (28%, P = 0.002) and 1 of 18 (6%, P = 0.05) with BG measurement less than 400 pg/ml. β-Glucan decreased in IAC responding to therapy and increased in nonresponse. CONCLUSIONS BG antigenemia is superior to Candida score and colonization indexes and anticipates diagnosis of blood culture-negative IAC. This proof-of-concept observation in strictly selected high-risk surgical ICU patients deserves investigation of BG-driven preemptive therapy.

Exclusive Staphylococcus aureus Throat Carriage: At-Risk Populations

BACKGROUND Approximately 25% of Staphylococcus aureus carriers have exclusive throat carriage. We aimed to identify the populations at risk for exclusive throat carriage to improve sensitivity to detect carriers. METHODS Four groups underwent nasal and throat screening for S. aureus. Three groups of individuals in the community (n = 2632) with different estimated levels of exposure to the health care system (HCS) were screened, including 1500 healthy blood donors, 498 patients from a school of dental medicine, and 634 health care workers (HCWs) at a trade fair. The fourth group comprised in-hospital patients and HCWs (n = 832) and was considered the group with the highest estimated exposure to the HCS. As a primary outcome, we analyzed risk factors for exclusive throat carriage in exclusive throat carriers vs all nasal carriers. RESULTS Of 3464 individuals screened, 428 (12.4%) had exclusive throat carriage, and 1260 (36.4%) had carriage in the nares only or in the nares and the throat. The most important independent risk factor for exclusive throat carriage was age 30 years or younger (odds ratio, 1.66; P < .001). Exposure to the HCS was a significant protective factor for exclusive throat carriage (odds ratio, 0.67; P = .001). Healthy blood donors were almost twice as likely to have exclusive throat carriage than in-hospital patients and HCWs (30.2% vs 18.4% of all carriers, P < .001). CONCLUSIONS Absence of exposure to the HCS and younger age predicted exclusive throat carriers, a population at high risk for community-onset methicillin-resistant S. aureus. Screening for S. aureus should include swabs from the anterior nares and from the throat to improve the likelihood of detecting carriers.

Role of Staphylococcus aureus Global Regulators sae and σB in Virulence Gene Expression during Device-Related Infection

ABSTRACT The ability of Staphylococcus aureus to adapt to different environments is due to a regulatory network comprising several loci. Here we present a detailed study of the interaction between the two global regulators sae and σB of S. aureus and their influence on virulence gene expression in vitro, as well as during device-related infection. The expression of sae, asp23, hla, clfA, coa, and fnbA was determined in strain Newman and its isogenic saeS/R and sigB mutants by Northern analysis and LightCycler reverse transcription-PCR. There was no indication of direct cross talk between the two regulators. sae had a dominant effect on target gene expression during device-related infection. σB seemed to be less active throughout the infection than under induced conditions in vitro.

Extensive phage dynamics in Staphylococcus aureus contributes to adaptation to the human host during infection

Bacteriophages serve as a driving force in microbial evolution, adaptation to new environments and the pathogenesis of human bacterial infections. In Staphylococcus aureus phages encoding immune evasion molecules (SAK, SCIN, CHIPS), which integrate specifically into the β‐haemolysin (Hlb) gene, are widely distributed. When comparing S. aureus strain collections from infectious and colonizing situations we could detect a translocation of sak‐encoding phages to atypical genomic integration sites in the bacterium only in the disease‐related isolates. Additionally, significantly more Hlb producing strains were detected in the infectious strain collection. Extensive phage dynamics (intragenomic translocation, duplication, transfer between hosts, recombination events) during infection was shown by analysing cocolonizing and consecutive isolates of patients. This activity leads to the splitting of the strain population into various subfractions exhibiting different virulence potentials (Hlb‐production and/or production of immune evasion molecules). Thus, phage‐inducing conditions and strong selection for survival of the bacterial host after phage movement are typical for the infectious situation. Further in vitro characterization of phages revealed that: (i) SAK is encoded not only on serogroup F phages showing a conserved tropism for hlb but also on serogroup B phages which always integrate in a distinct intergenic region, (ii) the level of sak transcription correlates to phage inducibility but is independent of the phage localization in the chromosome, and (iii) phages can be stabilized extra‐chromosomally during their life cycle.

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.