Clinical outcomes in cystic fibrosis patients with Trichosporon respiratory infection.

BACKGROUND: Relationships between clinical outcomes and novel respiratory pathogens such as Trichosporon are not well understood. METHODS: Respiratory cultures from CF patients were screened for novel pathogens Trichosporon and Chryseobacterium as well as other pathogens over 28months. Relationships between microbiologic and clinical data were assessed using univariate and multivariate methods. RESULTS: Of 4934 respiratory cultures from 474 CF patients, 37 cultures from 10 patients were Trichosporon positive. Patients with positive Trichosproron cultures had a greater decline in FEV1 over time (-3.9%/year vs. -1.3%/year, p<0.05), whereas Chryseobacterium did not influence lung function. These findings were confirmed in multivariate analyses that included age, gender, and other common pathogens as confounders. Treatment of Trichosporon infected patients was associated with improved lung function. CONCLUSIONS: Trichosporon can be recovered from a small but clinically meaningful fraction of CF patients. The presence of Trichosporon, but not Chryseobacterium, is associated with greater declines in lung function.

Ventricular Function Before and After Surgery for Isolated and Combined Regurgitation in the Young.

BACKGROUND: Chronic mitral and aortic regurgitation (MR and AR) are associated with progressive contractile dysfunction. In the young, the risk of left ventricle (LV) dysfunction after operation for isolated and combined AR and MR is poorly defined. We aimed to compare LV mechanics in children and young adults with isolated and combined AR and MR, and identify risk factors for LV dysfunction after valve surgery. METHODS: Echocardiograms from children and young adults undergoing surgery for isolated severe AR (group I, n = 14), MR (group II, n = 21), or combined AR and MR (group III, n = 13), before and up to 18 months after surgery were compared with a normal population (n = 89). Normalized measures of LV geometry and mechanics were expressed as z scores. RESULTS: Before surgery all groups had LV dilatation, while groups I and III had afterload elevation and LV dysfunction. After operation LV dysfunction was more common in group III than in groups I and II (11 [84.5%] vs 5 [35.7%] vs 12 [57.1%], p = 0.04). The preoperative end-systolic volume z score predicted LV dysfunction after surgery in group I and II patients (p = 0.047, area under the curve = 0.75) but not in group III, where moderate LV dysfunction was related to the preoperative stress velocity index (-2.6 with vs -1.1 without, p = 0.04). CONCLUSIONS: Left ventricular mechanics in combined AR and MR closely resemble those of AR. End-systolic volume predicts postoperative LV dysfunction in patients with isolated valve regurgitation, while those with combined disease were at high risk of postoperative LV dysfunction.

Cost Savings Realized by Implementation of Routine Microbiological Identification by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) is an emerging technology for rapid identification of bacterial and fungal isolates. In comparison to conventional methods, this technology is much less labor intensive and can provide accurate and reliable results in minutes from a single isolated colony. We compared the cost of performing the bioMérieux Vitek MALDI-TOF MS with conventional microbiological methods to determine the amount saved by the laboratory by converting to the new technology. Identification costs for 21,930 isolates collected between April 1, 2013, and March 31, 2014, were directly compared for MALDI-TOF MS and conventional methodologies. These isolates were composed of commonly isolated organisms, including commonly encountered aerobic and facultative bacteria and yeast but excluding anaerobes and filamentous fungi. Mycobacterium tuberculosis complex and rapidly growing mycobacteria were also evaluated for a 5-month period during the study. Reagent costs and a total cost analysis that included technologist time in addition to reagent expenses and maintenance service agreement costs were analyzed as part of this study. The use of MALDI-TOF MS equated to a net savings of $69,108.61, or 87.8%, in reagent costs annually compared to traditional methods. When total costs are calculated to include technologist time and maintenance costs, traditional identification would have cost $142,532.69, versus $68,886.51 with the MALDI-TOF MS method, resulting in a laboratory savings of $73,646.18, or 51.7%, annually by adopting the new technology. The initial cost of the instrument at our usage level would be offset in about 3 years. MALDI-TOF MS not only represents an innovative technology for the rapid and accurate identification of bacterial and fungal isolates, it also provides a significant cost savings for the laboratory.

Respiratory viruses are associated with common respiratory pathogens in cystic fibrosis.

OBJECTIVES: Test the hypothesis that the link between respiratory viruses and pulmonary exacerbation in cystic fibrosis (CF) reflects increased frequency or severity of lower airways infection. STUDY DESIGN: Molecular respiratory viral panels (RVPs), cell counts, and quantitative bacterial cultures were assessed in 235 bronchoalveolar lavage fluid (BALF) samples from 138 children with CF. Relationships among the data were analyzed using multivariate methods. RESULTS: RVPs were positive in 67 (28.5%) BALF samples from 52 (37.7%) patients, with rhinovirus/enterovirus most common (82.4% of RVP+). RVP+ patients were younger (5.4 years, IQR 3.0-9.7 vs. 8.0 years, IQR 3.5-12.9; P < 0.01), more likely to have respiratory symptoms (74.6% vs. 55.2%, P < 0.01), and had higher BALF percent neutrophils (70.5%, IQR 46-85% vs. 59.3%, IQR 34-77%; P < 0.05). Percent predicted FEV1 at bronchoscopy was diminished from baseline in both groups, but recovered in the RVP- (90.2 ± 22.2% vs. 89.6 ± 19.7%, P = 0.62) but not the RVP+ subjects (95.7 ± 21.1% vs. 89.1 ± 18.0%, P < 0.05). RVP status did not alter recovery rates of typical CF respiratory pathogens including Staphylococcus aureus (44.8% vs. 42.9%) and Pseudomonas aeruginosa (25.4% vs. 25.6%). However, common respiratory pathogens (Haemophilus species, Moraxella species, and Streptococcus pneumoniae) were recovered more frequently from RVP+ samples independent of age (OR 3.6, 95% CI 1.8-7.5, P < 0.001). CONCLUSIONS: Respiratory viruses were frequently detected in BALF from CF patients and associated with markers of disease severity. Respiratory viruses did not impact frequency or severity of infection with typical CF pathogens, but rates of infection with common respiratory pathogens were increased. This finding may have treatment implications.

Arterial switch operation: early and late outcome for intramural coronary arteries.

BACKGROUND: Intramural coronary artery course (IMCA) is associated with an increased risk of coronary event and mortality after the arterial switch operation (ASO). We describe early and late outcomes at our institution from 1996 to 2006. METHODS: Operation notes for all patients who underwent ASO within 60 days of birth were reviewed, and those with IMCA were identified. Mortality and morbidity were obtained from discharge summary, predischarge electrocardiogram, and echocardiogram. Follow-up included clinical review, electrocardiogram, echocardiography, dobutamine stress echocardiography, and angiography. RESULTS: Eighteen patients of 215 in the cohort (8.4%) had IMCA. Intramural coronary artery course was more common in patients from French Polynesia (6 of 17; 35.3% versus 12 of 198; 6.1%; p=0.001). Early mortality for patients with IMCA was 1 of 18 (5.6%) compared with 6 of 197 (3%) for those without IMCA (p=0.46). One IMCA patient was lost to follow-up. The remaining 16 are alive and asymptomatic. Of the 13 who underwent angiography, 2 had minor coronary artery stenoses at initial nonselective aortic root angiography. Both stenoses resolved at subsequent selective coronary angiography. None of the 11 who underwent dobutamine stress echocardiography had inducible ischemia. CONCLUSIONS: We report a high prevalence of IMCA in an ASO population, particularly among patients referred from French Polynesia. Intramural coronary artery course was not a risk factor for mortality after ASO. Angiography demonstrated excellent short-term and long-term structural outcome for IMCA.

Evolution of testing algorithms at a university hospital for detection of Clostridium difficile infections.

We present the evolution of testing algorithms at our institution in which the C. Diff Quik Chek Complete immunochromatographic cartridge assay determines the presence of both glutamate dehydrogenase and Clostridium difficile toxins A and B as a primary screen for C. difficile infection and indeterminate results (glutamate dehydrogenase positive, toxin A and B negative) are confirmed by the GeneXpert C. difficile PCR assay. This two-step algorithm is a cost-effective method for highly sensitive detection of toxigenic C. difficile.

Detection of rapidly growing mycobacteria in routine cultures of samples from patients with cystic fibrosis.

Rapidly growing mycobacteria (RGM) are respiratory pathogens in patients with cystic fibrosis (CF), but detection generally requires specialized cultures for acid-fast bacilli (AFB; AFB cultures). We determined that RGM could be recovered from routine cultures of samples from patients with CF by extending incubation of the Burkholderia cepacia selective agar (BCSA) from 5 to 14 days. To explore the impact of this modification, we compared results from routine and AFB cultures of samples from CF patients for 2 years before (4,212 samples by routine culture, 1,810 samples by AFB culture, 670 patients) and 2 years after (4,720 samples by routine culture, 2,179 samples by AFB culture, 695 patients) the change. Clinical relevance was assessed with samples from a subgroup of 340 patients followed regularly throughout both periods. Extending incubation of BCSA enhanced RGM recovery from routine cultures (0.7% before, 2.8% after; P < 0.001); recovery from AFB cultures was unchanged (5.5% before, 5.7% after). Estimates of RGM detection sensitivity by culture or patient-based methods ranged from ∼65 to 75% for routine cultures (nonsignificantly lower than the ∼80 to 85% for AFB cultures) and were adversely affected by coculture with mold or nonpseudomonal, nonfermenting Gram-negative rods. In the after period, 16 CF patients met the criteria for RGM infection by routine culture, including 4 who did not meet the criteria for RGM infection by AFB culture. We conclude that a simple methodological change enhanced recovery of RGM from routine cultures. The modified culture method could be utilized to improve screening for RGM in CF patients or as a simpler method to follow patients with known RGM infection. However, this method should be used cautiously in patients with certain coinfections.

Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis.

BACKGROUND: Although nontuberculous mycobacteria (NTM) are recognized pathogens in cystic fibrosis (CF), associations with clinical outcomes remain unclear. METHODS: Microbiological data was obtained from 1216 CF patients over 8years (481+/-55patients/year). Relationships to clinical outcomes were examined in the subset (n=271, 203+/-23 patients/year) with longitudinal data. RESULTS: Five hundred thirty-six of 4862 (11%) acid-fast bacilli (AFB) cultures grew NTM, with Mycobacterium abscessus (n=298, 55.6%) and Mycobacterium avium complex (n=190, 35.4%) most common. Associated bacterial cultures grew Stenotrophomonas or Aspergillus species more often when NTM were isolated (18.2% vs. 8.4% and 13.9% vs. 7.2%, respectively, p<0.01). After controlling for confounders, patients with chronic M. abscessus infection had greater rates of lung function decline than those with no NTM infection (-2.52 vs. -1.64% predicted FEV(1)/year, p<0.05). CONCLUSIONS: NTM infection is common in CF and associated with particular pathogens. Chronic M. abscessus infection is associated with increased lung function decline.

Prevalence of community-associated methicillin-resistant Staphylococcus aureus in patients with cystic fibrosis.

We prospectively determined the prevalence of community-associated Staphylococcus aureus in a large cystic fibrosis (CF) center between October 2005 and October 2007. We found that 2.7% (19/707) of the CF patients who had cultures during the study period were infected with this organism, representing 14% of the total methicillin-resistant Staphylococcus aureus strains (n = 140) recovered from the patient population during the study period.

Steroid receptor and growth factor receptor expression in human nonsmall cell lung cancers using cells procured by laser-capture microdissection.

Few biomarkers exist for management of nonsmall cell lung cancers (NSCLC), although estrogen receptor (ERalpha and ERbeta) and EGF receptor (EGFR) expression has been related to clinical outcome. To circumvent problems of cellular heterogeneity in whole tissue, relative gene expression of ERalpha, ERbeta, EGFR, and HER-2 (c-erb-B2) was examined in pure lung carcinoma (LC) cells and normal epithelia by LCM. Cell-specific RNA was isolated and purified for RT-qPCR and microarray. Comparison of NSCLC cells to normal epithelia indicated increased levels of mRNA expression of ERbeta, ERalpha, EGFR, and HER-2 by 31%, 38%, 54%, and 62%, respectively, in LCs. The majority of NSCLC exhibiting low ERalpha and high HER-2 expression were from smokers. Although there was no correlation between ERbeta or EGFR expression and smoking history, there appeared to be an inverse relationship between levels of ERbeta and EGFR mRNAs in normal and neoplastic lung. Additionally, microarray analyses of LCM cells revealed >2,000 genes significantly altered in LC compared with normal epithelia. Herein, differences in NSCLC gene expression and normal lung cells were noted between specimens from gender and smoking groups. Microarray data revealed ERa expression was associated with alterations in <20 genes while ERbeta expression revealed >500 associated genes, suggesting a more prominent role for ERbeta in lung. HER-2 mRNA levels appeared associated with >1,000 genes, while EGFR mRNA levels were associated with far fewer genes. Collectively, results suggest quantitative genomic analyses of pure cell populations allow more accurate interpretation of LC status, which is being correlated with clinical outcome.

Cardiac outcome up to 15 years after the arterial switch operation.

AIMS: To assess the cardiac outcome and risk factors for mortality of infants following the arterial switch operation (ASO). METHODS: A single-centre retrospective review was conducted. Preoperative assessment, operative management and outcome was detailed for 244 patients undergoing the ASO at Green Lane Hospital for transposition of the great arteries (TGA) or double outlet right ventricle. RESULTS: The postoperative survival at 1, 5 and 15 years was 85%, 84% and 83%, respectively. The calendar year of ASO and the presence of a ventricular septal defect (VSD) were the primary predictors of early mortality. Late mortality was associated with a side-by-side configuration of the great arteries. Re-intervention following ASO was more common in patients with prolonged cardiopulmonary bypass time. CONCLUSIONS: Low early and late morbidity and mortality can be obtained in infants with TGA or double outlet right ventricle by definitive repair utilising the ASO.

Surgery for acute type a aortic dissection a 37-year experience in Green Lane Hospital.

PURPOSE: To review the management of patients with acute type A aortic dissection. METHODS: Between June 1967 and December 2003, 246 patients (151 males and 95 females, 20-82 years; median 59 years) underwent operation for type A dissection. Early mortality and aortic dissection-related late events (reoperation and death related to aortic dissection) were assessed and correlated with the surgical approach. RESULTS: Over 37 years, early mortality has markedly improved, 50% in 1970s, 22% in 1980s, 17% in 1990s, and 11% after 2000. However, late deaths occurred at a constant rate, overall late survival at 10 and 20 years were 59% and 9%, respectively, and this did not improve after the 1990s. Preoperative hemodynamic instability, myocardial and kidney malperfusion, smoking history, prolonged bypass and cross-clamp time, and year of surgery were found to be risk factors for early death. The main cause (21%) of late deaths was aortic dissection-related events, especially in the distal aorta. However, no intraoperative risk factors were found to be predictive of late dissection-related events. Surgical techniques including complete resection of the intimal tear or distal extent of the surgery had no impact on late distal event-free survival. CONCLUSION: Despite improvement of short-term outcome over 37 years, patients who had aortic dissection are still living with elevated risk of death. Although late events in the distal aorta were a major risk, aggressive surgical approaches did not improve these outcomes. Vigilant follow-up is necessary for these patients.

Bacteriological outcome after valve surgery for active infective endocarditis: implications for duration of treatment after surgery.

BACKGROUND: There has been no systematic evaluation of outcome after surgery for infective endocarditis with respect to duration of antibiotic treatment. METHODS: We performed a retrospective chart review of episodes of valve surgery for active infective endocarditis at Green Lane Hospital (Auckland, New Zealand) for 1963-1999. We recorded the duration of antibiotic treatment before and after valve surgery; the extent of infection at operation; Gram stain, culture, and histopathological testing results for valve samples; and the bacteriological outcome after surgery. The primary outcome measure was relapse, defined as endocarditis due to the same species within 1 year after surgery. RESULTS: For the 358 patients in our study, the median duration of follow-up was 4.8 years. Thirty-two patients (9%) had 36 subsequent episodes of endocarditis. Relapse occurred after 3 (0.8%) of the operations (95% CI, 0.2%-2.0%). Relapse of infection was unrelated to the duration of antibiotic treatment before or after surgery, positive valve culture results, positive Gram stain results, or perivalvular infection. Since 1994, we have reduced the duration of antibiotic treatment by approximately 7 days for those with positive valve culture results and by approximately 14 days for those with negative valve culture results, without any increase in the number of relapses. CONCLUSIONS: Relapse is an uncommon event following surgery for endocarditis. Commonly suggested indications for prolonging postoperative treatment are not associated with higher relapse rates, and their relevance is debatable. We conclude that it is unnecessary to continue treatment for patients with negative valve culture results for an arbitrary 4-6-week period after surgery. Two weeks of treatment appears to be sufficient, and, for those operated on near the end of the standard period of treatment, simply completing the planned course should suffice.

Mild supravalvular aortic stenosis with left coronary obstruction in a neonate.

A premature infant with a large patent ductus arteriosus and mild supravalvular aortic stenosis had evidence of severe myocardial ischemia after ductus ligation. Urgent reoperation was required to relieve severe obstruction of the left coronary orifice and the supravalvular stenosis was repaired. This unusual presentation early in infancy emphasizes that left coronary artery obstruction should be suspected even in the presence of mild supravalvular stenosis.

Frozen chicken nuggets and strips--a newly identified risk factor for Salmonella Heidelberg infection in British Columbia, Canada.

Salmonella enterica var. Heidelberg was isolated from an unusual food source during routine case follow-up, prompting a case control investigation of frozen chicken nuggets and strips. Most frozen nuggets and strips are raw; however, par-frying lends a cooked appearance. As such, suitable food preparation precautions might not be undertaken by consumers. Cases were confirmed in the laboratory between 1 January and 1 April 2003. Controls were generated through forward-digit dialing and individually matched by age category. Telephone interviews were conducted, and limited sampling of unopened product was performed. Eighteen matched pairs were interviewed. The odds of infection were 11 times higher in individuals who had consumed frozen processed chicken nuggets and strips (95% confidence interval, 1.42 < odds ratio < 85.20). One-third of cases and controls considered frozen nuggets and strips to be precooked, and one quarter used the microwave, an ill-advised cooking method. Consumer misconceptions contributed to the risk of infection. Clear labels identifying nuggets and strips as raw poultry are needed.

Gram stain, culture, and histopathological examination findings for heart valves removed because of infective endocarditis.

Retrospective chart review was undertaken for 480 patients who underwent a total of 506 valve replacements or repair procedures for infective endocarditis. The influence of preoperative antimicrobial treatment on culture, Gram stain, and histopathological examination findings for resected valve specimens was examined. When valves were removed before the end of treatment, organisms were seen on the Gram stain of ground valve material performed in the microbiology laboratory and on Gram-stained histopathological sections in 231 (81%) of 285 and 140 (67%) of 208 specimens, respectively (P=.0007). Gram-positive cocci were either cultured from or observed in excised valve tissue in 42 (67%) of 63 episodes involving negative preoperative blood cultures. Positive Gram stain results for microbiological specimens should be reintroduced into the definite pathological criteria for infective endocarditis. When deciding on how long to continue antimicrobial therapy after valve replacement for endocarditis, valve culture results should be the only laboratory finding taken into account, because it takes months for dead bacteria to be removed from sterile vegetations.