Development of echinocandin-resistant Candida albicans candidemia following brief prophylactic exposure to micafungin therapy.

Empiric antifungal coverage is indicated in patients with graft-versus-host disease (GVHD) following a stem cell transplant (SCT) who are febrile and neutropenic for extended periods of time. Empiric antifungal coverage is indicated for patients with hematologic malignancies who have persistent fever and neutropenia as well as patients who have GVHD following SCT. Although the prophylactic use of antifungals is a cornerstone of the care for such patients, the selection of the particular antifungal is at the discretion of the clinician. We report a patient case whose surveillance blood cultures obtained 14 days after the switch from voriconazole to micafungin were positive for the growth of Candida albicans. Clinicians prescribing echinocandin therapy for antifungal prophylaxis must be aware of the risks of echinocandin resistance and possible breakthrough candidemia with C. albicans.

Molecular Adsorbent Recirculating System (MARS(®)) removal of piperacillin/tazobactam in a patient with acetaminophen-induced acute liver failure.

The objective of this study was to illustrate the pharmacokinetic removal of piperacillin/tazobactam in an anuric patient on Molecular Adsorbent Recirculating System (MARS(®)). The patient was a 32-year-old woman who presented to a medical intensive care unit with acute liver failure secondary to an acetaminophen overdose. While awaiting transplant, she was started on MARS therapy as a bridge to liver transplant and empirically started on piperacillin/tazobactam therapy. MARS is an extracorporeal hemofiltration device, which incorporates a continuous venovenous hemofiltration (CVVHD) machine linked to an albumin-enriched dialysate filter to normalize excess electrolytes, metabolic waste, and protein-bound toxins. In addition to protein-bound waste, MARS removes water-soluble, low molecular-weight molecules. The patient received piperacillin/tazobactam 4.5 g infused intravenously over 3 h. A steep decline in serum levels occurred between hours 4 and 6 while MARS continued and no antibiotic was infused. The elimination rate constant (k(e)) for the removal of piperacillin in this patent was 0.453 h(-1) and the half-life (λ) was 1.53 h. The k(e) was 2.9-fold higher than with CVVHD alone and the λ was 3.7-fold shorter. Low levels of piperacillin are achieved during MARS therapy, but in the treatment of more resistant organisms, such as Pseudomonas aeruginosa, these low levels may not be adequate to achieve bactericidal activity. Drug levels following a standard infusion of 30 min would likely be even lower. Formalized pharmacokinetic studies of piperacillin/tazobactam removal in patients on MARS therapy are necessary to make clear dosing recommendations.

Association of polymorphisms in the dopamine D4 receptor gene and the activity-impulsivity endophenotype in dogs.

A variable number of tandem repeats (VNTR) polymorphism in exon 3 of the human dopamine D4 receptor gene (DRD4) has been associated with attention deficit hyperactivity disorder (ADHD). Rodents possess no analogous repeat sequence, whereas a similar tandem repeat polymorphism of the DRD4 gene was identified in dogs, horses and chimpanzees. Here, we present a genetic association study of the DRD4 VNTR and the activity-impulsivity dimension of the recently validated dog-ADHD Rating Scale. To avoid false positives arising from population stratification, a single breed of dogs (German shepherd) was studied. Two DRD4 alleles (referred to as 2 and 3a) were detected in this breed, and genotype frequencies were in Hardy-Weinberg equilibrium. For modelling distinct environmental conditions, 'pet' and 'police' German shepherds were characterized. Police German shepherds possessing at least one 3a allele showed significantly higher scores in the activity-impulsivity dimension of the dog-ADHD Rating Scale than dogs without this allele (P = 0.0180). This difference was not significant in pet German shepherds. To the best of our knowledge, this is the first report of an association between a candidate gene and a behaviour trait in dogs, and it reinforces the functional role of DRD4 exon 3 polymorphism.

Detection of temporal patterns in dog-human interaction.

A new time structure model and pattern detection procedures developed by (Magnusson, M.S., 1996. Hidden real-time patterns in intra- and inter-individual behaviour description and detection. Eur. J. Psychol. Assess. 12, 112-123; Magnusson, M.S., 2000. Discovering hidden time patterns in behaviour: T-patterns and their detection. Behav. Res. Methods, Instrum. Comput. 32, 93-110) enables us to detect complex temporal patterns in behaviour. This method has been used successfully in studying human and neuronal interactions (Anolli, L., Duncan, S. Magnusson, M.S., Riva G. (Eds.), 2005. The Hidden Structure of Interaction, IOS Press, Amsterdam). We assume that similarly to interactions between humans, cooperative and communicative interaction between dogs and humans also consist of patterns in time. We coded and analyzed a cooperative situation when the owner instructs the dog to help build a tower and complete the task. In this situation, a cooperative interaction developed spontaneously, and occurrences of hidden time patterns in behaviour can be expected. We have found such complex temporal patterns (T-patterns) in each pair during the task that cannot be detected by "standard" behaviour analysis. During cooperative interactions the dogs' and humans' behaviour becomes organized into interactive temporal patterns and that dog-human interaction is much more regular than yet has been thought. We have found that communicative behaviour units and action units can be detected in the same T-pattern during cooperative interactions. Comparing the T-patterns detected in the dog-human dyads, we have found a typical sequence emerging during the task, which was the outline of the successfully completed task. Such temporal patterns were conspicuously missing from the "randomized data" that gives additional support to the claim that interactive T-patterns do not occur by chance or arbitrarily but play a functional role during the task.

The organization of infection control in Italy.

This paper describes the organization of infection control in Italy with respect to regulatory requirements, the tasks and training of the infection control physician and nurse, and the function and responsibilities of the infection control committee. Moreover, the paper reports on incidence and prevalence of hospital-acquired infections (HAI), antibiotic usage and antimicrobial resistance in Italy.

Incidence, timing and site of infections among pancreas transplant recipients.

The incidence, timing and site of infections among the different categories of pancreas transplant recipients were investigated. Patients were divided into three groups: pancreas transplant alone (PTA), pancreas after kidney transplant (PAK), or simultaneous pancreas and kidney (SPK) transplants. Length of follow-up, time to death, pancreas graft survival, incidence, timing and site of bacterial infections were noted. Our study showed that at least 75% of pancreas transplant recipients experienced at least one infection (range from 77.8% in the PTA group to 86.7% in the PAK group). The SPK group presented the highest rate of infections with 35.1 infections per 1000/patient-days. Symptomatic urinary tract infections were the most common cause of infection in all patients. The incidence of infections was higher during the first month after transplantation, except for the SPK transplant group, where infections occurred over a longer time period.

Attachment behavior in dogs (Canis familiaris): a new application of Ainsworth's (1969) Strange Situation Test.

Fifty-one owner-dog pairs were observed in a modified version of M. D. S. Ainsworth's (1969) Strange Situation Test. The results demonstrate that adult dogs (Canis familiaris) show patterns of attachment behavior toward the owner. Although there was considerable variability in dogs' attachment behavior to humans, the authors did not find any effect of gender, age, living conditions, or breed on most of the behavioral variables. The human-dog relationship was described by means of a factor analysis in a 3-dimensional factor space: Anxiety, Acceptance, and Attachment. A cluster analysis revealed 5 substantially different classes of dogs, and dogs could be categorized along the secure-insecure attached dimensions of Ainsworth's original test. A dog's relationship to humans is analogous to child-parent and chimpanzee-human attachment behavior because the observed behavioral phenomena and the classification are similar to those described in mother-infant interactions.

Comprehension of human communicative signs in pet dogs (Canis familiaris).

On the basis of a study by D. J. Povinelli, D. T. Bierschwale, and C. G. Cech (1999), the performance of family dogs (Canis familiaris) was examined in a 2-way food choice task in which 4 types of directional cues were given by the experimenter: pointing and gazing, head-nodding ("at target"), head turning above the correct container ("above target"), and glancing only ("eyes only"). The results showed that the performance of the dogs resembled more closely that of the children in D. J. Povinelli et al.'s study, in contrast to the chimpanzees' performance in the same study. It seems that dogs, like children, interpret the test situation as being a form of communication. The hypothesis is that this similarity is attributable to the social experience and acquired social routines in dogs because they spend more time in close contact with humans than apes do, and as a result dogs are probably more experienced in the recognition of human gestures.

Distinguishing logic from association in the solution of an invisible displacement task by children (Homo sapiens) and dogs (Canis familiaris): using negation of disjunction.

Prior research on the ability to solve the Piagetian invisible displacement task has focused on prerequisite representational capacity. This study examines the additional prerequisite of deduction. As in other tasks (e.g., conservation and transitivity), it is difficult to distinguish between behavior that reflects logical inference from behavior that reflects associative generalization. Using the role of negation in logic whereby negative feedback about one belief increases the certainty of another (e.g., a disjunctive syllogism), task-naive dogs (Canis familiaris; n=19) and 4- to 6-year-old children (Homo sapiens; n=24) were given a task wherein a desirable object was shown to have disappeared from a container after it had passed behind 3 separate screens. As predicted, children (as per logic of negated disjunction) tended to increase their speed of checking the 3rd screen after failing to find the object behind the first 2 screens, whereas dogs (as per associative extinction) tended to significantly decrease their speed of checking the 3rd screen after failing to find the object behind the first 2 screens.

Is the testing of TFT strategy during predator inspections possible by use of mirror image? A review and some controls of recent studies.

In order to answer some of the questions concerning the "inadequacies" of mirror-images in experiments examining co-operative behaviour during predator inspection, several control experiments were carried out. The average positions (distance from predator's tank) of guppies was influenced by the presence of a preadator, but the effect of previous experience with a predator was manifestated only in the presence of predator. The average position of guppies also depended on the mirror-treatment (changing the length and position) but it was influenced only by the length but not the angle of mirror. The relative independence of the position of the mirror observed in the guppies' behaviour challenges the basic assumption (i.e. closer to the predator by long parallel than short angled mirror) is indeed the result of TFT as interpreted earlier. Instead, the effect of mirror treatment appears superpositioned on the predator inspection as an independent variable. In light of these results we discuss the usefulness of mirror systems in testing predator inspection as TFT-like behaviour.

A nonverbal test of knowledge attribution: a comparative study on dogs and children.

The sensitivity of eleven pet dogs and eleven 2.5-year-old children to others' past perceptual access was tested for object-specificity in a playful, nonverbal task in which a human Helper's knowledge state regarding the whereabouts of a hidden toy and a stick (a tool necessary for getting the out-of-reach toy) was systematically manipulated. In the four experimental conditions the Helper either participated or was absent during hiding of the toy and the stick and therefore she knew the place(s) of (1) both the toy and the stick, (2) only the toy, (3) only the stick or (4) neither of them. The subjects observed the hiding processes, but they could not reach the objects, so they had to involve the Helper to retrieve the toy. The dogs were more inclined to signal the place of the toy in each condition and indicated the location of the stick only sporadically. However the children signalled both the location of the toy and that of the stick in those situations when the Helper had similar knowledge regarding the whereabouts of them (i.e. knew or ignored both of them), and in those conditions in which the Helper was ignorant of the whereabouts of only one object the children indicated the place of this object more often than that of the known one. At the same time however, both dogs and children signalled the place of the toy more frequently if the Helper had been absent during toy-hiding compared to those conditions when she had participated in the hiding. Although this behaviour appears to correspond with the Helper's knowledge state, even the subtle distinction made by the children can be interpreted without a casual understanding of knowledge-formation in others.

Development of open-field and social behavior of the paradise fish (Macropodus opercularis L.).

In a series of experiments, we examined the development of some characteristic behavior elements in the paradise fish. It was shown that the behavior in the open field was dependent on the age of the fish. The attraction of fries of paradise fish toward conspecifics undergo some changes between 12 and 25 days of age: Larger groups become more attractive. Social orientation toward individual conspecifics develops by 24 days of age.

Use of experimenter-given cues in dogs.

Since the observations of O. Pfungst the use of human-provided cues by animals has been well-known in the behavioural sciences ("Clever Hans effect"). It has recently been shown that rhesus monkeys (Macaca mulatta) are unable to use the direction of gazing by the experimenter as a cue for finding food, although after some training they learned to respond to pointing by hand. Direction of gaze is used by chimpanzees, however. Dogs (Canis familiaris) are believed to be sensitive to human gestural communication but their ability has never been formally tested. In three experiments we examined whether dogs can respond to cues given by humans. We found that dogs are able to utilize pointing, bowing, nodding, head-turning and glancing gestures of humans as cues for finding hidden food. Dogs were also able to generalize from one person (owner) to another familiar person (experimenter) in using the same gestures as cues. Baseline trials were run to test the possibility that odour cues alone could be responsible for the dogs' performance. During training individual performance showed limited variability, probably because some dogs already "knew" some of the cues from their earlier experiences with humans. We suggest that the phenomenon of dogs responding to cues given by humans is better analysed as a case of interspecific communication than in terms of discrimination learning.

The effect of formulary restriction in the use of antibiotics in an Italian hospital.

OBJECTIVE: To compare the expenditure and usage of antibiotics at the San Martino Teaching Hospital, a 2500-bed hospital in Genoa, Italy, before and after the implementation of an antibiotic control program that streamlined the hospital formulary and the creation of a restricted group of antibiotics requiring approval before use. METHODS: Usage and expenditure data for all antibiotics were collected from 1996 to 1998. Antibiotic usage was standardised by defined daily doses (DDDs) per 100/patient-days. Cost data were expressed in Euros. Changes in antibiotic usage was determined by comparing the mean usage during 1996 and 1997, the period before the implementation of the antibiotic control program, to 1998 when the streamlined formulary and restricted group of antibiotics, controlled by the Infectious Disease Team (IDT). were initiated. The Wilcoxon rank sign test was used to determine statistical significance of the changes in overall antibiotic use; a P value of less than 0.05 was considered significant. RESULTS: After the implementation of the antibiotic control program, overall antibiotic usage decreased by 8.5%, 28.00 DDD/100 patient-days during 1996-1997 to 25.62 DDD/100 patient-days during 1998. The control program resulted in overall savings of 342,927 Euros after the first year of implementation. The usage and expenditure in the restricted group of antibiotics decreased by 78.5% and 53.5%, respectively, (P=0.03). Restricting the use of ceftazidime and imipenem accounted for the majority of the decreased usage and savings. In the non-restricted group of antibiotics, usage increased only by 32.6% resulting in a net reduction of 46.3% in all antibiotic use. CONCLUSION: Although antibiotic control programs have been successful in other countries, this represents the first attempt at successful antibiotic control in a large Italian teaching hospital. Streamlining the formulary to control antibiotic choices and the creation of a restriction program using the expertise of infectious disease physicians resulted in significant reductions in the use of and expenditure for antibiotics.

Evaluation of biosite triage Clostridium difficile panel for rapid detection of Clostridium difficile in stool samples.

One hundred two stool samples were tested by both the rapid Triage Clostridium difficile Panel (Triage Panel) and the cytotoxin cell culture assay. Five samples positive by both the C. difficile toxin A (Tox A) and common antigen components of the Triage Panel had cytotoxin titers of > or =10,000. Twenty-three samples were Triage Panel Tox A negative but common antigen positive. Ten of these had cytotoxin titers of 10 to 1,000, but 13 were cytotoxin negative. Bacterial isolates obtained from 8 of these 13 specimens were analyzed for Tox A and B genes by PCR, and only two contained toxigenic bacteria. Thus, the majority of samples positive only for C. difficile common antigen contained nontoxigenic bacteria. A Triage Panel Tox A-positive result indicated a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 33.3, 100, 100, and 88.2%, respectively. A Triage Panel common antigen-positive result indicated a sensitivity, specificity, PPV, and NPV of 100, 82.7, 53.6, and 100%, respectively. The high NPV of the Triage Panel common antigen, together with rapid reporting of results, should prove useful in avoiding unnecessary use of contact precautions and antibiotic treatment for C. difficile-negative patients. However, with Triage Panel common antigen-positive patients, a sensitive cytotoxin assay should be used to distinguish true cytotoxin-positive patients from C. difficile carriers.