Maricela Valerio

Campylobacter bacteremia: clinical characteristics, incidence, and outcome over 23 years.

Campylobacter is a very rare cause of bloodstream infection, although it has been found relatively frequently in patients infected with human immunodeficiency virus (HIV). The impact of highly active antiretroviral therapy (HAART) and new forms of immunosuppression on the incidence of Campylobacter bacteremia has not been sufficiently assessed. In this study we analyzed the incidence and microbiologic and clinical characteristics of Campylobacter bacteremia over 23 years. We reviewed the clinical records of all patients who had Campylobacter bacteremia from 1985 to 2007. Available strains were reidentified using universal polymerase chain reaction (PCR). During the study period, there were 71 episodes of Campylobacter bacteremia in 63 patients (0.24% of all bloodstream infections), and the incidence remained stable (mean, 0.06/1000 admissions per year and 0.47/100,000 inhabitants per year). Median age was 52 years (interquartile range, 31.25-72.5 yr), and 82% of patients were male. The underlying conditions included liver disease (21/64, 32.8%), HIV infection (15/64, 23.4%), malignancy (7/64, 10.9%), solid organ transplantation (2/64, 3%), hypogammaglobulinemia (10/64, 15.6%), and other (18/64, 31.2%). Twelve patients shared more than 1 underlying condition. Campylobacter bacteremia was community acquired in 81% of the episodes. The origin of the bloodstream infection was abdominal (43.5%), primary (26%), or extraintestinal (31%: respiratory 15%, cellulitis 4.8%, urinary 8%, other 3%). C jejuni was recovered in 66% of cases, C fetus in 19%, and C coli in 12%. Universal PCR was performed on 14 available strains. Molecular and conventional identification matched in 8 isolates. In contrast, molecular methods classified as C fetus (n = 2) and C jejuni (n = 1) 3 strains formerly identified only to genus level as Campylobacter species. In another 3 isolates, molecular identification was not consistent with the phenotypic identification (C fetus identified as C jejuni). Complications appeared in 23.9% of patients. Quinolone resistance was observed in 50% of the isolates. Only 37.8% of patients received appropriate empirical therapy. Mortality was 16.4%, although it was higher in HIV-infected patients than uninfected patients (33% vs. 10%; p = 0.04), in cases of hospital-acquired Campylobacter bacteremia compared with community-acquired cases (38.5% vs. 9.4%; p = 0.02), and in the presence of complications compared with patients without complications (100% vs. 0%; p < 0.001). The incidence of recurrence was 5% (3 patients with humoral immunodeficiency). There was a higher proportion of HIV-infected patients among patients with Campylobacter bacteremia in the pre-HAART era (1985-1996) than in the HAART era (1997-2007)-27.5% (11/40) vs. 14.3% (4/28)-although the difference was not statistically significant. Debilitating diseases such as chronic obstructive pulmonary disease emerged as predisposing conditions in the HAART era (0% before HAART era vs. 14.3% in HAART era; p = 0.032). Campylobacter bacteremia is no longer a significant disease of HIV-positive patients on HAART, but often affects other immunocompromised patients as well. Campylobacter bacteremia has an extraintestinal origin in as many as 31% of cases, and humoral immunodeficiency must be sought in patients with recurrent episodes. Quinolones should not be considered for empirical therapy. Abbreviations: AIDS = acquired immunodeficiency syndrome, ARIMA = autoregressive integrated moving average test, BSI = bloodstream infection, COPD = chronic obstructive pulmonary disease, HAART = highly active antiretroviral therapy, HIV = human immunodeficiency virus, IQR = interquartile range, PCR = polymerase chain reaction, rRNA = ribosomal ribonucleic acid.

Initial Use of Echinocandins Does Not Negatively Influence Outcome in Candida parapsilosis Bloodstream Infection: A Propensity Score Analysis

BACKGROUND Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis bloodstream infection (BSI) in view of its reduced susceptibility to echinocandins. METHODS The Prospective Population Study on Candidemia in Spain (CANDIPOP) is a prospective multicenter, population-based surveillance program on Candida BSI conducted through a 12-month period in 29 Spanish hospitals. Clinical isolates were identified by DNA sequencing, and antifungal susceptibility testing was performed by the European Committee on Antimicrobial Susceptibility Testing methodology. Predictors for clinical failure (all-cause mortality between days 3 to 30, or persistent candidemia for ≥72 hours after initiation of therapy) in episodes of C. parapsilosis species complex BSI were assessed by logistic regression analysis. We further analyzed the impact of echinocandin-based regimen as the initial antifungal therapy (within the first 72 hours) by using a propensity score approach. RESULTS Among 752 episodes of Candida BSI identified, 200 (26.6%) were due to C. parapsilosis species complex. We finally analyzed 194 episodes occurring in 190 patients. Clinical failure occurred in 58 of 177 (32.8%) of evaluable episodes. Orotracheal intubation (adjusted odds ratio [AOR], 2.81; P = .018) and septic shock (AOR, 2.91; P = .081) emerged as risk factors for clinical failure, whereas early central venous catheter removal was protective (AOR, 0.43; P = .040). Neither univariate nor multivariate analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of clinical failure. Incorporation of the propensity score into the model did not change this finding. CONCLUSIONS The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.

Evaluation of antifungal use in a tertiary care institution: antifungal stewardship urgently needed

OBJECTIVES To assess the quality of antifungal use, to propose a point score for this evaluation and to estimate the potential economic savings of an antifungal stewardship programme. METHODS From December 2010 to January 2011, we identified 100 adult inpatients receiving systemic antifungals. Antifungal use was evaluated by means of a predefined score that considered indication, drug selection, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. Total antifungal prescriptions [in defined daily doses (DDDs) and days of therapy (DOTs)] and potential cost savings were calculated. RESULTS Overall, 43% of prescriptions came from medical departments, 25% from haematology/oncology and 17% from intensive care units. The main reasons for starting antifungals were empirical (42%), pre-emptive (20%) and targeted treatment (20%). Antifungals were unnecessary in 16% of cases. Inadequacies in other aspects of antifungal prescription were: drug selection, 31%; dosing, 16%; no switch from intravenous to oral administration, 20%; no adjustment after microbiological results, 35%; and length of therapy, 27%. The number of antifungal DDDs per 1000 patient-days was 65.1. The total number of DOTs was 1556, which added a direct cost of €219 364. Only 51.3% of DOTs were considered optimal. The potential estimated savings would be €50 536. CONCLUSIONS Major efforts should be made to improve the selection and duration of antifungal therapy. Our study demonstrated the potential cost savings that could be achieved by optimizing antifungal therapy. A stewardship programme should include an instrument to objectively evaluate the adequacy of antifungal use.

Outbreak of invasive aspergillosis after major heart surgery caused by spores in the air of the intensive care unit.

BACKGROUND Outbreaks of invasive aspergillosis (IA) are believed to be caused by airborne Aspergillus conidia. Few studies have established a correlation between high levels of Aspergillus fumigatus conidia and the appearance of new cases of IA or have demonstrated matching genotypes between clinical isolates and those from the environment. METHODS We detected an outbreak of IA (December 2006 through April 2008) in the major heart surgery intensive care unit (MHS-ICU) of our institution. Our local surveillance program consists of monthly environmental air sampling in operating rooms and ICUs for quantitative and qualitative identification of filamentous fungi. During the study period, we obtained 508 environmental samples from 3 different periods: 6 months before the outbreak, during it, and 6 months after it. Available environmental and clinical strains were genotyped according to the short tandem repeats assay. RESULTS Seven patients developed proven or probable IA (5 with lung infection, 1 with mediastinitis, and 1 with lung infection and mediastinitis). A. fumigatus was involved in 6 cases. The underlying conditions of the patients were heart transplantation (n = 3), corticosteroid-dependent conditions (n = 2), and diabetes mellitus (n = 2). The mortality rate was 85.7%. Before and after the outbreak (±6 months), the median airborne A. fumigatus conidia levels were 0 colony-forming units (CFUs) per cubic meter, and no cases of IA occurred during these periods. However, during the outbreak period, the occurrence of the 6 cases of IA caused by A. fumigatus was linked to peaks of abnormally high A. fumigatus airborne conidia levels (175, 50, 25, 20, 160, and 400 CFUs/m(3)) in the MHS-ICU, whereas counts in the air of both operating rooms remained negative. Matches between A. fumigatus genotypes collected from the air of the MHS-ICU and from representative clinical samples were found in 3 of the 6 patients. The outbreak abated when high-efficiency particulate air filters were installed in the affected areas. CONCLUSIONS Our study revealed that abnormally high levels of airborne A. fumigatus conidia correlated with new cases of IA, even in patients who were not severely immunocompromised. The demonstration of matches between air and clinical genotypes reinforces the role of environmental air in the acquisition of IA during the period following MHS. Environmental monitoring of Aspergillus spores in the air of postoperative units is mandatory, even when these units receive nonimmunocompromised patients undergoing major surgery.

Candida tropicalis fungaemia: incidence, risk factors and mortality in a general hospital

The risk factors and clinical features of patients with Candida tropicalis fungaemia have not been fully defined. We performed a case-control study comparing 59 cases of C. tropicalis fungaemia with 177 episodes of fungaemia caused by other species of Candida in our hospital over a 24-year period (January 1985 to December 2008). Patients with C. tropicalis fungaemia were more likely to be older (median age, 67 vs. 56 years; p 0.01), to have cancer (45.5% vs. 31.6%, p 0.04), and to have the abdomen as the portal of entry (32.2% vs. 11.9%, p 0.001), and had a higher in-hospital mortality rate (61% vs. 44%, p 0.03). Multivariate analysis showed that the independent risk factors for C. tropicalis fungaemia were cancer (OR 4.5; 95% CI 1.05-3.83; p 0.03) and the abdomen as the portal of entry (OR 13.6; 95% CI 1.9-8.2; p <0.001). When survivors were compared with non-survivors, the risk factors associated with a poor outcome were neutropenia (19.4% vs. 0; p 0.03), corticosteroid treatment (36% vs. 13%; p 0.07), and septic shock (50% vs. 17.4%; p 0.01). The independent risk factors for mortality in the multivariate analysis were corticosteroid treatment (OR 8.2; 95% CI 0.9-27.7; p 0.04) and septic shock (OR 14.6; 95% CI 2.4-90.2; p 0.004), whereas urinary tract infection (OR 0.07; 95% CI 0.01-0.8; p 0.03) and catheter removal (OR 0.06; 95% CI 0.01-0.4; p 0.002) were protective factors. C. tropicalis is the fourth most common cause of fungaemia in our hospital. It is associated with underlying malignancy, the abdomen as the portal of entry, and poor outcome.

Invasive aspergillosis caused by cryptic Aspergillus species: a report of two consecutive episodes in a patient with leukaemia.

We report a case of two consecutive episodes of invasive aspergillosis caused by cryptic Aspergillus species in a patient with leukaemia. A first episode of pulmonary infection was caused by Aspergillus calidoustus and Aspergillus novofumigatus, and the second episode by A. novofumigatus and Aspergillus viridinutans. Fungal isolates were identified to species level using traditional and sequencing-based molecular methods.

Heart Valves Should Not Be Routinely Cultured

ABSTRACT Heart valve (HV) culture is one of the major Duke criteria for the diagnosis of definite infectious endocarditis (IE). However, previous series suggest that heart valve culture does not have good sensitivity (7.8 to 17.6%) and may be contaminated during manipulation. Our goal was to establish the value of routine cultures of heart valves in patients with and without IE. From 2004 to 2006, resected heart valves were systematically cultured according to standard procedures. The definition and etiology of IE were based on the Duke criteria and on valve PCR of specimens from blood culture-negative patients. Bacterial and fungal broad-range PCR was performed. A total of 1,101 heart valves were studied: 1,030 (93.6%) from patients without IE and 71 (6.4%) from patients with IE (42 patients). Overall, 321 (29.2%) cultures were positive (28/71 [39.4%] IE cases and 293/1,030 [28.4%] non-IE). All IE patients with negative heart valve cultures had received antimicrobial therapy. The yield of culture of heart valves for IE diagnosis was as follows: sensitivity, 25.4%; specificity, 71.6%; positive predictive value (PPV), 5.8%; and negative predictive value, 93.3%. Because of its poor sensitivity and PPV, valve cultures should not be performed for patients without a clinical suspicion of IE. For patients with confirmed IE, heart valve cultures should be interpreted with caution.

BK virus in liver transplant recipients: a prospective study.

BACKGROUND BK virus (BKV) is a polyomavirus that is associated with nephropathy and graft loss among kidney transplant recipients. The role of BK virus in nonrenal solid organ transplant recipients has not been clearly established; only anecdotal case reports have been published. METHODS From August 2005 to September 2007, all liver transplant (OLT) recipients who gave their consent were enrolled in this prospective longitudinal study. BK viral load was measured using real-time quantitative polymerase chain reaction assays of urine and plasma, using samples collected at week 1 and months 1, 3, 6, 9, 12, 15, 18, 21, and 24 posttransplantation. We also collected demographic and clinical data, including serum creatinine and immunosuppressive therapy. RESULTS The mean age of the 62 patients was 51.4 years including 14 (22.5%) women. Hepatitis C infection was present in 24 patients (38.7%). BK viruria was detected in 14.5% of 290 samples, corresponding to 13 patients (21%). BK viremia was detected in 5.1% of 317 samples, corresponding to 11 patients (18%). Almost all cases of BK viremia (91%) occurred in the first 3 months after OLT. BKV viremia was more common among patients experiencing a rejection episode (10.6 vs 40%, P = .01). We did not observe a relationship between single episodes of BKV replication and renal function: median plasma creatinine 1.1 mg/dL in patients without versus 1.2 mg/dL with BKV viremia. The three patients with persistent viremia displayed renal insufficiency; one of them died due to multiorgan failure of unknown origin. CONCLUSIONS BKV is frequently detected in OLT recipients (viruria 21% and viremia 18%) early after transplantation. It is more common among patients with rejection episodes. Persistent BKV viremia may be related to renal dysfunction in OLT patients.

Antifungal stewardship in daily practice and health economic implications.

During recent years, inappropriate antifungal use has contributed to the global increase in antifungal resistance and has played a role in the shift in the aetiology of invasive fungal infections. Moreover, overuse of antifungals may also lead to higher toxicity associated with unnecessary medication exposure and to increased healthcare costs. Antifungal stewardship (AFS) programmes consist of multidisciplinary interventions, led by specialists in infectious disease, microbiology and pharmacy that cooperate and communicate with the major prescribing departments in order to optimise antifungal therapies evaluating the indication, dose, streamlining and duration. Herein, we review the available evidence for the use of AFS and their impact on health economics. We also describe our AFS program, the successive steps we followed and the main difficulties we found.

Invasive aspergillosis among heart transplant recipients: A 24-year perspective

BACKGROUND Invasive aspergillosis is a well-known complication in severely immunosuppressed patients, including heart transplant recipients, and associated mortality is high. Despite the severity of the disease in this population, few recent series with secular trends have addressed the problem. METHODS We performed a descriptive study of 479 consecutive heart transplant recipients from 1988 to 2011 in a single institution. RESULTS Overall invasive aspergillosis incidence in heart transplant recipients was 6.5% (31 of 479). Incidence decreased from 8.7% (24 of 277) in the period 1988 to 2000 (historical cohort) to 3.5% (7 of 202) afterward (p = 0.02); 4 of the 7 cases were in the context of an outbreak. The most common presentation was lung infection, but episodes occurring >3 months after transplantation (late aspergillosis) showed a higher frequency of disseminated disease and involvement of the central nervous system and of atypical sites compared with early (first 3 months) episodes. Related mortality was 36%, with a significant decrease between the historical cohort and the present cohort: 46% vs 0% (p = 0.04) and a trend toward lower related death in early vs late cases (26% vs 63%, p = 0.09). CONCLUSIONS In our series, both incidence and mortality associated with invasive aspergillosis in heart transplant recipients showed a decrease in recent years. Careful environmental management and targeted anti-fungal prophylaxis may minimize the incidence of invasive aspergillosis in this setting.