Inferior Outcomes on the Waiting List in Low-Volume Pediatric Heart Transplant Centers.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

Periumbilical parasitic thumbprint purpura: strongyloides hyperinfection syndrome acquired from a cadaveric renal transplant.

Periumbilical parasitic thumbprint purpura may be a presenting sign of hyperinfection strongyloidiasis in the immunocompromised host. We report a case of fatal hyperinfection strongyloidiasis acquired from a cadaveric renal allograft, diagnosed by the pathognomonic periumbilical thumbprint purpuric eruption, confirmed by skin biopsy and laboratory testing.

Treatment of Candida albicans pericarditis in a heart transplant patient.

Pericarditis due to Candida species is a rare clinical entity, associated with thoracic surgery and immunosuppression. We report here the second case of pericarditis due to Candida albicans in a heart transplant patient, which presented as tamponade approximately 3 weeks post transplant, in the absence of evidence of sternal osteomyelitis. The patient was treated with pericardiocentesis and a combination of caspofungin and fluconazole, but the patient ultimately required the explantation of retained epicardial leads and the creation of a pericardial window. This case illustrates that Candida species must be considered in the differential diagnosis in post-transplant pericarditis, and that foreign body removal is, as always, key in helping to resolve such infections. This case also demonstrates the first use of caspofungin with fluconazole to treat Candida pericarditis. We discuss the conflicting data regarding the use of caspofungin, alone or in combination therapy, in treating infections involving biofilms, such as the infected pericardium.

Resistance to Spodoptera frugiperda (Lepidoptera: Noctuidae) and Euxesta stigmatias (Diptera: Ulidiidae) in sweet corn derived from exogenous and endogenous genetic systems.

Field trials using Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) and Euxesta stigmatias Loew (Diptera: Ulidiidae) were conducted to evaluate resistance and potential damage interactions between these two primary corn, Zea mays L., pests against Lepidoptera-resistant corn varieties derived from both endogenous and exogenous sources. The endogenous source of resistance was maysin, a C-glycosyl flavone produced in high concentrations in varieties 'Zapalote Chico 2451' and 'Zapalote Chico sh2'. The exogenous resistance source was the Bacillus thuringiensis (Bt)11 gene that expresses Cry1A(b) insecticidal protein found in 'Attribute GSS-0966'. Damage by the two pests was compared among these resistant varieties and the susceptible 'Primetime'. Single-species tests determined that the Zapalote Chico varieties and GSS-0966 effectively reduced S. frugiperda larval damage compared with Primetime. E. stigmatias larval damage was less in the Zapalote Chico varieties than the other varieties in single-species tests. E. stigmatias damage was greater on S. frugiperda-infested versus S. frugiperda-excluded ears. Ears with S. frugiperda damage to husk, silk and kernels had greater E. stigmatias damage than ears with less S. frugiperda damage. Reversed phase high-performance liquid chromatography analysis of nonpollinated corn silk collected from field plots determined that isoorientin, maysin, and apimaysin plus 3'-methoxymaysin concentrations followed the order Zapalote Chico sh2 > Zapalote Chico 2451 > Attribute GSS-0966 = Primetime. Chlorogenic acid concentrations were greatest in Zapalote Chico 2451. The two high maysin Zapalote Chico varieties did as well against fall armyworm as the Bt-enhanced GSS-0966, and they outperformed GSS-0966 against E. stigmatias.

Mycobacterium avium complex infection in kidney transplant patients.

Mycobacterium avium complex (MAC) infections have been reported rarely in renal transplant patients. Consequently the clinical course and optimal treatment of these patients are not well understood. We present 3 patients with MAC infections after receiving a renal transplant (2 with generalized and 1 with localized infection). All patients were treated with combination antibiotic therapy and reduction of immunosuppression. One patient experienced clinical control of disease but a mild cellular rejection that was successfully treated with high-dose corticosteroids. One patient died of disseminated MAC infection. The patient with localized infection died of unrelated causes. In summary, MAC infection, although rare in renal transplant patients, may respond to combination antimicrobial therapy and reduction of immunosuppression.

Natural Infection of Vicia faba by Bidens mottle virus in Florida.

In a study to evaluate the potential of Vicia faba (faba bean) as a cover and forage crop for Florida, 60 accessions of faba bean with diverse genetic backgrounds and geographic origins were acquired from the USDA Germplasm Repository in Pullman, WA. The beans were grown south of Lake Okeechobee in Belle Glade, FL, from December 2000 to April 2001. Reddish-brown elliptical lesions first appeared on the leaflets of two of the faba bean plants 10 to 12 weeks after planting. Within 2 weeks of initial symptoms, a mosaic pattern was expressed on the newly emergent leaves of the same plants. After disease expression, new pods aborted, while developing pods became stunted, distorted, and blistered. Potyvirus cylindrical inclusions (CI) were found in leaf strips (1) of the original plants. Viral symptoms were expressed in manually inoculated plants of Chenopodium amaraticolor, C. quinoa, Lactuca sativa, Nicotiana benthamiana, Petunia × hybrida, Verbena × hybrida, Vicia faba, and Zinnia elegans. Inoculated species of Phaseolus and Pisum were not infected. The virus causing the disease was identified as Bidens mottle virus (2) based on host range, characteristic CI in Z. elegans, and homologous lines of precipitation in SDS-immunodiffusion using antiserum to Bidens mottle and a known antigen. Both the primary host of this virus Bidens mottle virus and its aphid vectors are ubiquitous throughout Florida. To our knowledge, this is the first report of Bidens mottle virus infecting a member of the Leguminosae. References: (1) R. G. Christie and J. R. Edwardson. Light and Electron Microscopy of Plant Virus. Monogr. 9, IFAS, University of Florida, 1994. (2) D. E. Purcifull et al. Bidens mottle virus. Descriptions of Plant Viruses. No. 161. CMI/AAB, Surrey, England, 1976.

Infections during left ventricular assist device support do not affect posttransplant outcomes.

BACKGROUND: Although infections acquired during ventricular assist device support may increase the risk of infection and have an impact on transplant survival, their true posttransplant consequences remain to be determined. This study evaluates the impact of an outpatient program, newer devices, and an updated infection management protocol on infection-related patient outcomes after transplant. METHODS AND RESULTS: Eighty-six patients received a left ventricular assist device (LVAD) between June 1996 and June 1999. Fifty patients transplanted during the same period, without prior device support, were used as controls; they were matched to transplanted LVAD recipients by age, sex, diagnosis, and transplant date. The nature of and actuarial freedom from peritransplant and posttransplant infections were compared at 6 months after transplant; actuarial patient survival was compared at 3 years. Infection was defined as leukocytosis or leukopenia, with a positive culture requiring either medical or surgical intervention. Forty-four patients (51%) were successfully discharged home on LVAD support, and 61 (71%) were transplanted. A high incidence of infection during device support did not have an impact on pretransplant or posttransplant mortality, posttransplant infectious rate, or overall patient survival. Active infections at transplant also did not significantly influence 6-month mortality. In comparison, LVAD recipients had a lower freedom from infection than did controls (P:<0.05); however, 3-year survival did not differ: 79% and 87% for the LVAD and control groups, respectively. CONCLUSIONS: Although LVADs increase the risk of infection in the early posttransplant period, this appears not to have an impact on transplantability or patient survival and likely reflects effective infection control in both inpatient and outpatient settings.

An outbreak of Legionella micdadei pneumonia in transplant patients: evaluation, molecular epidemiology, and control.

PURPOSE: To describe a nosocomial outbreak of Legionella micdadei pneumonia in transplant patients and to characterize the source of the outbreak and the control measures utilized. SUBJECTS AND METHODS: We performed retrospective Legionella micdadei serologic testing to enhance case finding in transplant patients with pneumonia that lacked a documented microbial etiology, as well as prospective environmental surveillance of water sites and testing for Legionella in clinical specimens. RESULTS: During a 3-month period, 12 cases of Legionella micdadei pneumonia were identified either by culture or serologic testing among 38 renal and cardiac transplant patients. Legionella micdadei isolates from hot water sources were found by pulsed-field gel electrophoresis to have a DNA banding pattern that was identical to the isolates from the first 3 culture-positive cases and from 2 cases that occurred 16 months later. CONCLUSIONS: Hospitals caring for organ transplant recipients and other immunosuppressed patients must be aware of the possibility of environmental sources of outbreaks of Legionella infection. A first-line screen with the Legionella urine antigen test will identify Legionella pneumophila serogroup 1. However, specific cultures in outbreak situations should be considered to identify other Legionella pneumophila serotypes and the nonpneumophila Legionella species.

The influence of infection on survival and successful transplantation in patients with left ventricular assist devices.

BACKGROUND: Mechanical cardiac assistance has recently emerged as a tenable option in the treatment of end-stage heart failure. In spite of recent technical improvements that have reduced the incidence of life-threatening complications, the reported frequency of infections in these patients has remained high. METHODS: Over a 5-year period, 60 patients underwent insertion of a left ventricular assist device (LVAD) at our institution. Detailed medical records were kept prospectively for all patients, and a variety of endpoints were analyzed, including the incidence, nature, and sequelae of infections before and after LVAD implantation and after transplantation. RESULTS: Twenty-nine of 60 patients (48%) undergoing LVAD insertion subsequently had development of infections. The most frequent sites of infection were blood, LVAD drivelines, and central venous catheters, representing 61% of all infections. At the time of LVAD implantation, 13 of 60 patients (22%) had culture-proven infections. In spite of an increased incidence of subsequent infection (77% vs 40%), there were no differences in rates of mortality (31% vs 26%), LVAD endocarditis, (23% vs 11%) and eventual transplantation (62% vs 57%) between these patients and those without periimplantation infections. Although the overall mortality rate was not influenced by infections during LVAD support (28% vs 26%), the development of LVAD endocarditis was associated with a high mortality rate. Finally, although patients with infections during LVAD support had significantly longer median support times than those who remained infection free (101 vs 49 days, respectively), there was no difference in the rate of successful transplantation (59% vs 58%) or in the rate of infection after transplantation (35% vs 28%). CONCLUSIONS: Infections are common in patients undergoing LVAD support, but they do not adversely affect survival, the rate of successful transplantation, or the incidence of posttransplantation infection. Periimplantation infections may increase the risk of subsequent infections, but they also do not influence survival or transplantability. Patients with development of LVAD endocarditis are at increased risk for morbidity and death and require early and aggressive therapy, potentially including device explantation.

Pulmonary tuberculosis after lung transplantation.

During a 5-year study period, we diagnosed pulmonary tuberculosis in two (2%) of 94 lung and heart-lung transplant recipients. Each infection occurred 3 months after bilateral lung transplantation in the presence of evidence implicating donor-to-recipient transmission of the pathogen. The radiographic patterns of pulmonary tuberculosis were subtle: narrowing of the middle lobe bronchus of the right lung caused by an endobronchial granulomatous mass (n = 1) and a focal cluster of small nodules in the upper lobe of the left lung and small bilateral pleural effusions (n = 1). Each patient achieved complete clinical and radiographic response after antituberculous therapy. We conclude that Mycobacterium tuberculosis may be transmitted directly by a donor lung and may involve bronchial mucosa, pulmonary parenchyma, and pleura.

Elimination of Staphylococcus aureus nasal carriage in health care workers: analysis of six clinical trials with calcium mupirocin ointment. The Mupirocin Collaborative Study Group.

Six double-blind, independently randomized studies evaluated the efficacy and safety of calcium mupirocin ointment in eliminating nasal carriage of Staphylococcus aureus among health care workers. Healthy volunteers with stable nasal carriage of S. aureus (n = 339) received either calcium mupirocin ointment (n = 170) or an identical placebo ointment (n = 169) intranasally for 5 days. Nasal carriage was eliminated 48-96 hours after completion of treatment in 130 (91%) of 143 evaluable volunteers receiving mupirocin but in only 8 (6%) of 142 evaluable volunteers receiving placebo. The 85% crude difference represents a 90% pooled (adjusted) estimate of the risk difference (95% confidence interval, 0.86-0.95) and a risk ratio of 16 (P < .0001). This effect of treatment with mupirocin was observed consistently (risk ratio, 8-32) in all six centers. In addition, 96 of the 130 mupirocin-treated volunteers and 1 of the 8 placebo-treated volunteers who were culture-negative at the end of therapy remained free of S. aureus 4 weeks after treatment. Adverse events in each treatment arm were mild and equally frequent. These data, consistent across six institutions, demonstrate that calcium mupirocin ointment administered intranasally for 5 days is safe and effective in eliminating stable nasal carriage of S. aureus.

A parsimonious statistical design and breeding procedure for evaluating and selecting desirable characteristics over environments.

The concept of stability as described in the literature does not meet all of the desirable criteria required by growers of cultivars. Various types of possible responses are discussed, and these are divided into those desirable from a grower's viewpoint and those not. Measures of stability appearing in the literature are based on variances, linear regression slopes, and/or deviations from regression. The most desirable response type would be denoted as unstable by current concepts of stability. It is shown how to simulate environments that exceed the ranges found in practice. A statistical design is described which is the height of parsimony and has the advantage that the conditions varied are known. The experimental results can then be interpreted in light of the known conditions. The design is optimally cost effective in terms of funds, material, and personnel. A breeding procedure is presented for such characteristics as desired response, stability under current definitions, tolerance (to pests, cold, drought, etc.), protein, quality, fiber, etc.

The effect of linkage on sample size determination for multiple trait selection.

Sufficient sample sizes are needed in breeding programs to be confident, with a specified probability α, of obtaining a specified number of plants of a desired genotype in segregating populations. We develop a method of determining the minimum sample size needed to produce, with specified probability α, at least m individuals of a desired genotype. This method takes into consideration factors affecting differential selection of gametes, segregation at a single locus, and linkage among the loci of interest. We first consider the effects in the gametophyte (haploid level) of fitness and linkage on the frequencies of alleles at two linked loci, then at three or more linked loci. The probability of obtaining at least m successes, or occurrences of the desired allele, among n gametes is given by a formula based on the binomial distribution. This probability is affected by fitness and linkage through their impact on the probability that a single randomly chosen gamete is of the desired type. Using an extension of this approach, we examine the effects of the altered allelic frequencies on the likelihood of obtaining the desired genotype from a randomly chosen pair of gametes in the sporophyte (diploid level). A table and a figure show the sample size required to produce, with probability 0.95, m individuals of the desired g enotype or phenotype, as a function of m and the probability that a randomly selected individual is of the desired type.

Mupirocin treatment of nasal staphylococcal colonization.

The effectiveness and safety of mupirocin calcium ointment applied to the anterior part of the nares for 5 days in the eradication of nasal carriage of Staphylococcus aureus was investigated in a placebo-controlled, double-blind study. Subjects were healthy medical center staff who had two positive cultures of the anterior nares for S aureus. Antimicrobial susceptibility, phage typing, and restriction endonuclease analysis of plasmid DNA were used to monitor the identity of relapsing and persisting strains. Mupirocin eliminated 74% of S aureus at early follow-up and 91% of original strains. At 4 weeks, 78% of the original strains were eradicated, whereas all of the placebo group remained colonized. Recolonization with mupirocin-resistant strains occurred in six patients, but these were of different phage and plasmid types from the original isolates. None of the subjects had serious adverse effects. Applied intranasally for 5 days, a calcium preparation of mupirocin in a paraffin base is effective in eliminating S aureus nasal carriage and is well tolerated.

Home intravenous antibiotic therapy.

Intravenous therapy for a variety of infections can be performed in the home setting; the therapy is safe and relatively cost effective. Close monitoring of the patient to ensure good care is essential. In the coming years, the variety of infections treatable at home will increase.

Bactericidal activity of clarithromycin and its 14-hydroxy metabolite against Haemophilus influenzae and streptococcal pathogens.

The serum bactericidal activity of clarithromycin in six normal human volunteers was determined after oral doses of 500 mg. The mean plasma levels of clarithromycin plus 14-hydroxy clarithromycin were 2.11 micrograms/mL after the second dose and 4.36 micrograms/mL after the sixth dose. The mean serum bactericidal titer against Haemophilus influenzae after the second dose was 1:8 and after the sixth dose 1:16 when unheated serum was used. Similar values were obtained when serum to which clarithromycin and 14-hydroxy clarithromycin was added was tested. Mean serum bactericidal titers against H. influenzae determined in Haemophilus test broth or heated serum were 1:2 and 1:4, respectively. Against Streptococcus pneumoniae and Streptococcus pyogenes, there was greater than 1:16 serum bactericidal levels at 12 hours after the sixth dose of clarithromycin.

Oral ofloxacin therapy of infections due to multiply-resistant bacteria.

We determined the efficacy and safety of orally administered ofloxacin, 400 mg twice daily, in the treatment of infections due to multiply-resistant bacteria. Patients (n = 99) were treated for 84 infections in 82 patients evaluable for efficacy with a bacteriologic response of 71%. Organisms treated included Pseudomonas aeruginosa (39), Staphylococcus aureus (11), Serratia marcescens (9), Enterobacter species (7), five each of Escherichia coli, Citrobacter, Salmonella, Klebsiella, and other organisms. The overall clinical responses was 89%: 28 (90%) of 16 osteomyelitis, 10 (83%) of 12 urinary tract infections, and three of three bacteremias. Insomnia occurred in 27% and responded to dose reduction. Resistance of P. aeruginosa to ofloxacin developed in 15% of isolates. No hepatic, renal, or hematologic toxicity developed in spite of long therapy, 283 days. Ofloxacin was an effective therapy for lower respiratory, urinary, bone, and soft tissue infections due to multiply-resistant Gram-negative bacteria and is effective for selected Staphylococcus aureus infections.