Anna Conen

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.

Association of Alcohol Consumption and HIV Surrogate Markers in Participants of the Swiss HIV Cohort Study

Background:Alcohol consumption may affect the course of HIV infection and/or antiretroviral therapy (ART). The authors investigated the association between self-reported alcohol consumption and HIV surrogate markers in both treated and untreated individuals. Design:Prospective cohort study. Methods:Over a 7-year period, the authors analyzed 2 groups of individuals in the Swiss HIV Cohort Study: (1) ART-naïve individuals remaining off ART and (2) individuals initiating first ART. For individuals initiating first ART, time-dependent Cox proportional hazards models were used to assess the association between alcohol consumption, virological failure, and ART interruption. For both groups, trajectories of log-transformed CD4 cell counts were analyzed using linear mixed models with repeated measures. Results:The authors included 2982 individuals initiating first ART and 2085 ART naives. In individuals initiating first ART, 241 (8%) experienced virological failure. Alcohol consumption was not associated with virological failure. ART interruption was noted in 449 (15%) individuals and was more prevalent in severe compared with none/light health risk drinkers [hazard ratio: 2.24, 95% confidence interval: 1.42 to 3.52]. The association remained significant even after adjusting for nonadherence. The authors did not find an association between alcohol consumption and change in CD4 cell count over time in either group. Conclusions:No effect of alcohol consumption on either virological failure or CD4 cell count in both groups of ART-initiating and ART-naive individuals was found. However, severe drinkers were more likely to interrupt ART. Efforts on ART continuation should be especially implemented in individuals reporting high alcohol consumption.

Characteristics of infections associated with external ventricular drains of cerebrospinal fluid

OBJECTIVES Manifestations of external ventricular drain (EVD) - associated infections overlap with those of the underlying neurosurgical conditions. We analyzed characteristics of EVD-associated infections. METHODS We included patients aged ≥18 years with EVD-associated infections from 1997 to 2008, using modified CDC criteria for nosocomial infections. Hospital charts were reviewed retrospectively and the in-hospital outcome was evaluated. RESULTS Forty-eight patients with EVD-associated infections were included (median age, 52 years, range 20-74 years). The median EVD-indwelling time was 7 days (range, 1-39 days) and EVD-associated infection occurred 6 days after insertion (range, 1-17 days). In 23% of patients, meningitis occurred 1-10 days after EVD removal. Fever >38 °C was present in 79% of patients, but Glasgow Coma Scale (GCS) scores were reduced in only 29%, and headache, vomiting and/or neck stiffness were present in only 31%. The median cerebrospinal fluid (CSF) leukocyte count was higher at onset of EVD-associated infection than at EVD insertion (175 × 10(6)/l versus 46 × 10(6)/l, p = 0.021), but other CSF parameters did not differ significantly. The most commonly implicated organisms were coagulase-negative staphylococci (63%) and Propionibacterium acnes (15%). CONCLUSIONS Fever and increased CSF leukocytes should raise the suspicion of EVD-associated infection, which may occur up to 10 days after removal of EVD.

Hormographiella aspergillata: an emerging mould in acute leukaemia patients?

We describe three invasive mould infections due to Hormographiella aspergillata occurring within 1 year in patients undergoing treatment for acute leukaemia. All patients presented with pulmonary infiltrates; one patient additionally had cerebral and ocular involvement. Diagnostic procedures included bronchoalveolar lavage in all, and video-assisted thoracoscopic surgery in two patients. Susceptibility testing was performed by E-test and detected low minimal inhibitory concentrations for voriconazole and amphotericin B. All patients received systemic antifungal therapy; however, all of them died. Despite this cluster of three cases of an unusual mould infection, no hospital source was detected.

Comparison of infectious complications during induction/consolidation chemotherapy versus allogeneic hematopoietic stem cell transplantation

Induction/consolidation chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies are associated with treatment-related risks such as infections. The predominant types of infections are blood stream infections (BSIs) and respiratory tract infections. We prospectively compared infectious complications after induction/consolidation chemotherapy versus allogeneic HSCT in a directly comparable setting with both groups being hospitalized on the same ward. From July 2003 until June 2008, 492 hospitalizations of 321 patients took place; 237 chemotherapies and 255 HSCTs were performed. We observed 49 (20.7%) BSIs, 70 (29.5%) pneumonias and 11 (4.6%) probable or proven invasive mould infections in the chemotherapy group. In the HSCT group we detected 70 (27.5%) BSIs, 71 (27.8%) pneumonias and 14 (5.4%) probable or proven invasive mould infections. There was a trend toward more transfers to the intensive care unit (OR 1.61; 95%CI 0.95–2.72; P=0.074) and BSIs (OR 1.45; 95%CI 0.95–2.22; P=0.079) after HSCT; 44 (13.7%) patients died. In-hospital mortality was significantly higher in the HSCT group (OR 2.39; 95%CI 1.22–4.68; P=0.010). We conclude that the risk of pneumonia and invasive mould infection is comparable after induction/consolidation chemotherapy and allogeneic HSCT. However, there was a trend for more BSIs and intensive care unit stays and a higher mortality in the latter.

The J-Curve in HIV: Low and Moderate Alcohol Intake Predicts Mortality but Not the Occurrence of Major Cardiovascular Events.

Objectives:In HIV-negative populations, light-to-moderate alcohol consumption is associated with a lower cardiovascular morbidity and mortality than alcohol abstention. Whether the same holds true for HIV-infected individuals has not been evaluated in detail. Design:Cohort study. Methods:Adults on antiretroviral therapy in the Swiss HIV Cohort Study with follow-up after August 2005 were included. We categorized alcohol consumption into: abstention or very low (<1 g/d), low (1–9 g/d), moderate (10–29 g/d in women and 10–39 g/d in men), and high alcohol intake. Cox proportional hazards models were used to describe the association between alcohol consumption and cardiovascular disease-free survival (combined endpoint), cardiovascular disease events (CADE) and overall survival. Baseline and time-updated risk factors for CADE were included in the models. Results:Among 9741 individuals included, there were 788 events of major CADE or death during 46,719 patient-years of follow-up, corresponding to an incidence of 1.69 events/100 person-years. Follow-up according to alcohol consumption level was 51% no or very low, 20% low, 23% moderate, and 6% high intake. As compared with no or very low alcohol intake, low (hazard ratio 0.79, 95% confidence interval 0.63 to 0.98) and moderate alcohol intakes (0.78, 0.64 to 0.95) were associated with a lower incidence of the combined endpoint. There was no significant association between alcohol consumption and CADE. Conclusions:Compared with no or very low alcohol consumption, low and moderate intake associated with a better CADE-free survival. However, this result was mainly driven by mortality and the specific impact of drinking patterns and type of alcoholic beverage on this outcome remains to be determined.

Virosomal influenza-vaccine induced immunity in HIV-infected individuals with high versus low CD4+ T-cell counts : clues towards a rational vaccination strategy

In a prospective influenza-vaccination trial we show that HIV-infected individuals with CD4+ T-cell counts less than 350 μl were distinct from HIV-infected individuals with more than 350 CD4+ T-cell counts/μl, and from HIV-negative individuals, in that an influenza-specific immunoglobulin M-response was absent and expansion of interferon-γ-secreting CD4+ T cells was impaired. By contrast, immunoglobulin G-responses were induced in all study groups. These data suggest that establishing broad influenza-specific (immunoglobulin G) B-cell memory prior to severe immunodeficiency is important.

Management of infections associated with neurosurgical implanted devices

ABSTRACT Introduction: Neurosurgical devices are increasingly used. With it, neurosurgical device-related infections gain relevance. As biofilms are involved in implant-associated infections the diagnosis and treatment is challenging and requires specific anti-biofilm concepts and management algorithms. Areas covered: The literature concerning the management of neurosurgical device-associated infections is scarce and heterogeneous treatment concepts are discussed, but no standardized diagnostic and treatment procedures exist. Therefore, we emphasize extrapolating management strategies predominantly from orthopedic device-associated infections, where the concept is better established and clinically validated. This review covers infections associated with craniotomy fixation devices, cranioplasties, external ventricular and lumbar drainages, internal shunts and neurostimulators. Expert commentary: Sonication of the removed implants significantly improves microbiological diagnosis. A combined surgical and antimicrobial management is crucial for successful treatment: appropriate surgical intervention is combined with prolonged anti-biofilm therapy of usually 12 weeks. In selected patients, new treatment algorithms enable cure of neurosurgical device-associated infections without implant removal or with a one-stage implant exchange, considerably improving the quality of patient lives.

Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection

Vaccines dramatically reduce infection-related morbidity and mortality. Determining factors that modulate the host response is key to rational vaccine design and demands unsupervised analysis. To longitudinally resolve influenza-specific humoral immune response dynamics we constructed vaccine response profiles of influenza A- and B-specific IgM and IgG levels from 42 healthy and 31 HIV infected influenza-vaccinated individuals. Pre-vaccination antibody levels and levels at 3 predefined time points after vaccination were included in each profile. We performed hierarchical clustering on these profiles to study the extent to which HIV infection associated immune dysfunction, adaptive immune factors (pre-existing influenza-specific antibodies, T cell responses), an innate immune factor (Mannose Binding Lectin, MBL), demographic characteristics (gender, age), or the vaccine preparation (split vs. virosomal) impacted the immune response to influenza vaccination. Hierarchical clustering associated vaccine preparation and pre-existing IgG levels with the profiles of healthy individuals. In contrast to previous in vitro and animal data, MBL levels had no impact on the adaptive vaccine response. Importantly, while HIV infected subjects with low CD4 T cell counts showed a reduced magnitude of their vaccine response, their response profiles were indistinguishable from those of healthy controls, suggesting quantitative but not qualitative deficits. Unsupervised profile-based analysis ranks factors impacting the vaccine-response by relative importance, with substantial implications for comparing, designing and improving vaccine preparations and strategies. Profile similarity between HIV infected and HIV negative individuals suggests merely quantitative differences in the vaccine response in these individuals, offering a rationale for boosting strategies in the HIV infected population.

Severe primary cytomegalovirus infection in the immunocompetent adult patient: A case series

Abstract Primary cytomegalovirus (CMV) infection is rare in immunocompetent adults, even rarer in elderly patients. Little is known about the severity of symptoms and the clinical course in this patient group. In children and younger adults, CMV mostly presents as an asymptomatic disease or a self-limiting mild mononucleosis-like syndrome. We describe the clinical course of an unusually severe primary CMV infection in a 69-y-old otherwise healthy man, as well as 6 other severe cases in immunocompetent adults at our institution, and compare them to adult cases from the literature. CMV primary infection and antiviral treatment should be considered in immunocompetent elderly persons presenting with a severe mononucleosis-like syndrome.