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This report describes an unusual case of primary cryptococcoma in the proximal thoracic spinal cord of an 11-year-old immunocompetent cat from a farm on which there were large numbers of pigeons. This animal was referred for examination with progressive paralysis and shown to be free from feline immunodeficiency virus, feline leukaemia virus, feline coronavirus and Toxoplasma gondii. It died 2 months later. At necropsy, the only lesion detected was a malacic area, 4cm in length, in the spinal cord. Histopathological examination of the spinal cord revealed severe granulomatous inflammation associated with large numbers of encapsulated yeast cells. In addition to the granulomatous host response, necrosis, digestion chambers, Gitter cells, spheroids and lymphocytic perivascular cuffs were features of the malacic areas. Immunohistochemistry confirmed the presence of Cryptococcus neoformans var. grubii yeast cells.

As part of a needs analysis preceding the development of an e-learning platform on infection prevention, European intensive care unit (ICU) nurses were subjected to a knowledge test on evidence-based guidelines for preventing ventilator-associated pneumonia (VAP). A validated multiple-choice questionnaire was distributed to 22 European countries between October 2006 and March 2007. Demographics included nationality, gender, ICU experience, number of ICU beds and acquisition of a specialised degree in intensive care. We collected 3329 questionnaires (response rate 69.1%). The average score was 45.1%. Fifty-five percent of respondents knew that the oral route is recommended for intubation; 35% knew that ventilator circuits should be changed for each new patient; 38% knew that heat and moisture exchangers were the recommended humidifier type, but only 21% knew that these should be changed once weekly; closed suctioning systems were recommended by 46%, and 18% knew that these must be changed for each new patient only; 51% and 57%, respectively, recognised that subglottic drainage and kinetic beds reduce VAP incidence. Most (85%) knew that semi-recumbent positioning prevents VAP. Professional seniority and number of ICU beds were shown to be independently associated with better test scores. Further research may determine whether low scores are related to a lack of knowledge, deficiencies in training, differences in what is regarded as good practice, and/or a lack of consistent policy.

Purpose of Review: The epidemiological and clinical relevance of Candida in the ICU is reviewed. Three issues were appraised. First is the prevalence of Candida. Second is the relevance of nonblood cultures positive for Candida and multisite colonization. Third is the importance of invasive candidiasis in terms of mortality., Recent Findings: The diagnosis of invasive candidiasis remains problematic in nonblood cultures. Consequently, the true prevalence of invasive candidiasis is difficult to assess. Another result of the complicated diagnosis is the risk for delayed antifungal therapy in case of systemic Candida infection. Therefore, pre-emptive therapy has become increasingly popular in high-risk patients., Summary: Candida spp. cause a minority of nosocomial bloodstream infections ( approximately 4-9%). Yet, delayed initiation of appropriate antifungal therapy results in significant attributable mortality. Given the inability to efficiently discriminate colonization from invasive candidiasis, this is a problematic issue. The presence of Candida in tracheal aspirates, urine cultures or wound swabs frequently reflects colonization. Yet, multisite colonization frequently precedes systemic invasion. As such, multisite Candida colonization is a crucial element in the decision to start pre-emptive therapy. However, the predictive value of multisite colonization in the absence of an overt risk profile for invasive candidiasis appears to be low.

A 4-year-old, male Jack Russell terrier was presented for a 6-month history of progressive right hemiparesis with episodic cervical hyperesthesia. The neurological examination showed a right-sided, upper motoneuron syndrome and partial Horner's syndrome. Two magnetic resonance imaging (MRI) examinations were performed 3 months apart and revealed a persistent cervical intramedullary hematoma. A dorsal myelotomy was performed. A subacute hematoma was confirmed histologically without underlying lesions. Eighteen months later, the dog's clinical signs were minimal. Two MRI examinations were performed 2 weeks and 5 months after surgery and revealed regressing signal abnormalities at the surgical site, consistent with a surgical scar.

Purpose of Review: Increasing interest is being directed toward possible benefits associated with continuous infusion of time-dependent antibiotics such as beta-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with continuous infusions are discussed., Recent Findings: One large retrospective cohort study has found clinical outcome benefits of administering a beta-lactam antibiotic by extended infusion compared with bolus administration. This complements a smaller randomized controlled trial comparing continuous infusion and intermittent bolus administration. For vancomycin, clinical outcome benefits have only been shown in a ventilator-associated pneumonia cohort of critically ill patients. No clinical outcome studies have been conducted for other time-dependent antibiotics., Summary: Continuous infusion of vancomycin and beta-lactam antibiotics enables faster and more consistent attainment of therapeutic levels compared with intermittent bolus dosing. Although the clinical benefits have not been conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic support for continuous infusion nevertheless exists. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearances, individualized therapy through the use of therapeutic drug monitoring is required. A definitive determination of the relative clinical efficacy of intermittent bolus and continuous administration of beta-lactams or vancomycin will only be achieved after a large-scale multicenter randomized controlled trial has been performed.

Objective: To assess prediction of multidrug resistant (MDR) pathogens in ventilator-associated pneumonia (VAP) by systematic surveillance cultures (SC) and to assess the contribution of SC to initial antibiotic therapy., Design: Prospective cohort study of patients with microbiologically confirmed VAP. Comparison of actual early antibiotic coverage with three hypothetical empirical schemes., Setting: A 50-bed university hospital ICU. SC consisted of oral, nasal, urinary and rectal samples upon admission, 3-weekly urinary and 1-weekly oral, nasal, and rectal samples in all patients, 3-weekly tracheal aspirates in intubated patients., Results: MDR pathogens were found in 86 of 199 VAP episodes. Sensitivity of SC to predict MDR pathogens was 69% (tracheal SC) and 82% (all SC); specificity was 96% (tracheal) and 91% (all), respectively. Appropriate antibiotic coverage within 24 h and 48 h following MDR VAP was 77% and 89%, respectively. A carbapenem-based empirical scheme would have been equally appropriate (83% vs. 77% at 24 h; 83% vs. 89% at 48 h), but a beta-lactam-fluoroquinolone empirical therapy would have been less (59% vs. 77% at 24 h; 59% vs. 89% at 48 h) as would have been beta-lactam-aminoglycoside therapy (68% vs. 77% at 24 h; 68% vs. 89% at 48 h). Empirical comparators would have resulted in significantly more prescription of broad-spectrum antibiotics within the first 48 h., Conclusions: With MDR pathogens highly prevalent, systematic SC predicted MDR pathogens causing VAP in 69% to 82% and may have contributed to high rates of early appropriate antibiotic therapy with limited use of broad-spectrum antimicrobials.

Objective: Patients receiving mechanical ventilation through an endotracheal tube are at increased risk for pneumonia. Because microaspiration of contaminated supraglottic secretions past the endotracheal tube cuff is considered to be central in the pathogenesis of ventilator-associated and postoperative pneumonia, better sealing of the upper trachea by the endotracheal tube cuff could possibly reduce this risk. We therefore postulated that use of a polyurethane cuffed tube would prevent early postoperative pneumonia through this mechanism in a population of cardiac surgical patients., Methods: In a prospective, single-blind, randomized study, patients scheduled for cardiac surgery were allocated to intubation with a polyurethane cuffed endotracheal tube or the routinely used polyvinyl chloride cuffed endotracheal tube. Patients were scheduled for routine or emergency cardiac surgery and admitted to an 8-bed cardiac surgical intensive care unit of a tertiary care hospital., Results: A total of 134 patients were available for analysis (67 in each group). Whereas mortality was not different between the groups, the incidence of early postoperative pneumonia and empirical prescription of antibiotic therapy were significantly lower in the polyurethane group than in the polyvinyl chloride group (23% vs 42%, P < .03). Intensive care unit and hospital stays were not significantly different between the two study subsets (3 +/- 5 days vs 3 +/- 4 days and 16 +/- 9 vs 17+/-11 days, respectively). In a multivariate regression analysis, preoperative serum creatinine levels (odds ratio 1.85, confidence interval 1.02-3.37, P = .04) and perioperative transfusion (odds ratio 1.50, confidence interval 1.08-3.37, P = .015) were independently associated with increased risk of early postoperative pneumonia, whereas use of a polyurethane endotracheal tube was protective (odds ratio 0.31, confidence interval 0.13-0.77, P = .01)., Conclusion: Polyurethane cuffed endotracheal tubes can reduce the frequency of early postoperative pneumonia in cardiac surgical patients.

Severe nosocomial infections and multidrug resistance (MDR) are associated with a poor prognosis for patients in intensive care units. This is partly because most of these patients suffer from high disease severity and acute illness before the onset of infection. Nevertheless, the mortality attributed directly to infection can also be devastating. However, the attributable mortality can be limited by taking account of a number of key points. General infection prevention measures, prevention of cross-transmission and a policy of restricted antimicrobial use are all important because of their positive influence on the rates of infection and MDR. In turn, this will increase the odds for successful empirical coverage of the causative microorganism. Once infection occurs, benefits are to be expected from early recognition of the septic episode and prompt initiation of empirical antimicrobial therapy. The choice of empirical therapy should be based on the local bacterial ecology and patterns of resistance, the presence of risk-factors for MDR, and the colonisation status of the patient. Attention should also be given to adequate doses of antimicrobial agents and, if possible, elimination of the sources of infection, e.g., contaminated devices or intra-abdominal collections or leakages. In the latter case, timely surgical intervention is essential. In addition, haemodynamic stabilisation and optimisation of tissue oxygenation can save lives.

Ventilator-associated pneumonia (VAP) continues to be an important cause of morbidity and mortality in ventilated patients. Evidence-based guidelines have been issued since 2001 by the European Task Force on ventilator-associated pneumonia, the Centers for Disease Control and Prevention, the Canadian Critical Care Society, and also by the American Thoracic Society and Infectious Diseases Society of America, which have produced a joint set of recommendations. The present review article is based on a comparison of these guidelines, together with an update of further publications in the literature. The 100,000 Lives campaign, endorsed by leading US agencies and societies, states that all ventilated patients should receive a ventilator bundle to reduce the incidence of VAP. The present review article is useful for identifying evidence-based processes that can be modified to improve patients' safety.

Purpose of Review: The review examines potential confounders hampering measurement of the impact of multidrug resistance in nosocomial infections. Methodological techniques dealing with the problem of confounding are discussed and current findings in how multidrug resistance affects outcome in patients with nosocomial infection are highlighted., Recent Findings: Outcome comparisons between patients infected with multidrug-resistant pathogens and patients infected with susceptible microorganisms are hampered by confounders such as differences in disease severity, prolonged hospitalization prior to onset of infection (exposure time), the causative pathogen, the type of infection, and the rate of appropriate empirical antimicrobial therapy. The confounding effect can be countered by means of either multivariable regression techniques or matched cohort studies, or a combination of both. Recent literature on the impact of multidrug resistance (methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase producing Enterobacteriaceae, etc) is conflicting and highly dependable on the way disturbing variables are accounted for., Summary: Recent data underscore that the impact of multidrug resistance on the outcome of nosocomial infection might differ depending on the study population, type of infection, type of pathogen and appropriateness of therapy, and hence, that any conclusion drawn prior to accurate accounting for imbalanced confounders is premature and potentially false.

Spinal epidural empyema (SEE) represents a severe pyogenic infection of the epidural space. Clinical signs of the disease are non-specific--increased body temperature, intense neck pain, neurological signs of a transverse myelopathy--and can lead to severe and permanent neurological deficits. This report describes the diagnosis and successful surgical treatment of cervical SEE secondary to grass awn migration in a cat. Although it is uncommon, this disease should be suspected in cats with progressive myelopathy. Early diagnosis and emergency surgery combined with antibiotic therapy are required to allow a complete recovery.

The Golden Retriever Muscular Dystrophy dog lacks dystrophin. Disease progression in this model shares many similarities with the Duchenne muscular dystrophy, both from anatomico pathological and clinical standpoints. The model is increasingly used in pre-clinical trials but needs to be further investigated, particularly with reference to the evaluation of therapies. The aim of this study was to identify quantitative indices that would help characterize the dystrophic dog non-invasively using NMR imaging. Two-month-old dystrophic dogs and healthy control animals were scanned at 4T. Standard T2- and T1-weighted images, fat-saturated T1-weighted images pre- and post-gadolinium chelate injection were acquired and kinetics of muscle enhancement were studied over a 2-h period. Several indices were found to be abnormally high in dystrophic dogs: the T2-weighted/T1-weighted signal ratio, T2-weighted image heterogeneity and maximal signal enhancement post-gadolinium. These may be proposed to evaluate muscle structural alterations non-invasively in this disease.

Objective: To explore the type and frequency of oral care practices in European ICUs and the attitudes, beliefs, and knowledge of health care workers., Design: An anonymous questionnaire was distributed to representatives of European ICUs. Results were obtained from 59 ICUs (one questionnaire per ICU) in seven countries 91% of respondents were registered nurses., Measurements and Results: Of the respondents 77% reported that they had received adequate training on providing oral care; most (93%) also expressed the desire to learn more about oral care. Oral care was perceived to be high priority in mechanically ventilated patients (88%). Cleaning the oral cavity was considered difficult by 68%, and unpleasant as well as difficult by 32%. In 37% of cases respondents felt that despite their efforts oral health worsens over time in intubated patients. Oral care practices are carried out once daily (20%), twice (31%) or three times (37%). Oral care consists principally of mouth washes (88%), mostly performed with chlorhexidine (61%). Foam swabs (22%) and moisture agents (42%) are used less frequently as well as manual toothbrushes (41%) although the literature indicates that these are more effective for thorough cleaning of the oral cavity. Electric toothbrushes were never used., Conclusions: In European ICUs oral care is considered very important. It is experienced as a task that is difficult to perform, and that does not necessarily succeed in ensuring oral health in patients with prolonged intubation. Oral care consists primarily of mouth washes. The use of toothbrushes should be given more attention.

Introduction: Intra-abdominal hypertension (IAH) and subsequent abdominal compartment syndrome (ACS) in burned patients is common. This sequence of events typically occurs in patients with larger burns receiving high volume fluid resuscitation., Methods: A review of the literature was performed. The National Library of Medicine (PUBMED) was queried for "Burn" and "Abdominal Compartment Syndrome". Twenty-nine articles were retained for study., Results: Abdominal pressure monitoring is appropriate in all patients with burns that require significant volume resuscitation (>30% total burned surface area-TBSA). Prevention of ACS in burns includes limiting fluid resuscitation, burn escharotomy, and percutaneous drainage when abdominal pressures are reaching perilous levels. Treatment includes all of the above and in addition, decompressive laparotomy when needed. However, despite decompressive laparotomy, mortality rates among burn victims with ACS remain unacceptably high., Conclusion: Increasing amounts of volume delivery are associated with an increased risk of IAH. Therefore, intra-abdominal pressure should be monitored in all burn patients requiring massive fluid resuscitation. Escharotomy, paracentesis, and decompressive laparotomy may all be needed to counter the side effects of appropriate fluid resuscitation in the severely burned patient. Nevertheless, the prognosis in burn patients developing ACS is grim.

Introduction: Intra-abdominal hypertension (IAH) and subsequent abdominal compartment syndrome (ACS) in burned patients is common. This sequence of events typically occurs in patients with larger burns receiving high volume fluid resuscitation., Methods: A review of the literature was performed. The National Library of Medicine (PUBMED) was queried for "Burn" and "Abdominal Compartment Syndrome". Twenty-nine articles were retained for study., Results: Abdominal pressure monitoring is appropriate in all patients with burns that require significant volume resuscitation (>30% total burned surface area- TBSA). Prevention of ACS in burns includes limiting fluid resuscitation, burn escharotomy, and percutaneous drainage when abdominal pressures are reaching perilous levels. Treatment includes all of the above and in addition, decompressive laparotomy when needed. However, despite decompressive laparotomy, mortality rates among burn victims with ACS remain unacceptably high., Conclusion: Increasing amounts of volume delivery are associated with an increased risk of IAH. Therefore, intra-abdominal pressure should be monitored in all burn patients requiring massive fluid resuscitation. Escharotomy, paracentesis, and decompressive laparotomy may all be needed to counter the side effects of appropriate fluid resuscitation in the severely burned patient. Nevertheless, the prognosis in burn patients developing ACS is grim.

Duchenne muscular dystrophy remains an untreatable genetic disease that severely limits motility and life expectancy in affected children. The only animal model specifically reproducing the alterations in the dystrophin gene and the full spectrum of human pathology is the golden retriever dog model. Affected animals present a single mutation in intron 6, resulting in complete absence of the dystrophin protein, and early and severe muscle degeneration with nearly complete loss of motility and walking ability. Death usually occurs at about 1 year of age as a result of failure of respiratory muscles. Here we report that intra-arterial delivery of wild-type canine mesoangioblasts (vessel-associated stem cells) results in an extensive recovery of dystrophin expression, normal muscle morphology and function (confirmed by measurement of contraction force on single fibres). The outcome is a remarkable clinical amelioration and preservation of active motility. These data qualify mesoangioblasts as candidates for future stem cell therapy for Duchenne patients.

Objective: To assess whether pathogen prediction in bacteremia associated with nosocomial pneumonia (NP) by tracheal surveillance cultures improves adequacy of early antibiotic therapy and impacts mortality., Design and Setting: A retrospective observational study of a prospectively gathered cohort. This cohort included all adult patients admitted to the ICU of a tertiary care hospital from 1992 through 2001 and who developed bacteremia associated with NP., Measurements and Main Results: 128 episodes of bacteremia associated with NP were identified. In 110 episodes a tracheal surveillance culture 48-96h prior to bacteremia was available: this culture predicted the pathogen in 67 episodes (61%). Overall rates of appropriate empiric antibiotic therapy within 24 and 48h were 62 and 87%, respectively. Pathogen prediction was associated with a significantly higher rate of appropriate antibiotic therapy within 24h (71 vs 45%; p=0.01), but not within 48h (91 vs 82%; p=0.15). Crude in-hospital mortality was 50%. Pathogen prediction was associated with increased survival in univariate (OR 0.43; CI 0.19-0.93; p=0.04) and multivariate analysis (OR 0.32; CI 0.12-0.82; p=0.02). Multivariate analysis further identified age (OR 1.04; CI 1.01-1.07; p=0.02), increasing APACHEII score (OR 1.08; CI 1.02-1.15; p=0.01), and methicillin-resistant Staphylococcus aureus (OR 5.90; CI 1.36-25.36; p=0.01) and Pseudomonas aeruginosa (OR 3.30; CI 1.04-10.4; p=0.04) as independent risk factors for mortality., Conclusion: Pathogen prediction in bacteremia associated with NP by tracheal surveillance cultures is associated with a higher rate of adequate empiric antibiotic therapy within 24[Symbol: see text]h and with increased survival.

Cultures of myoblasts isolated from cricopharyngeal muscles from patients with oculopharyngeal muscular dystrophy (OPMD) have been performed to study the effect of the expanded (GCG)8-13 repeat, located on the poly(A) binding protein nuclear-1 (PABPN1), on satellite cell phenotype. Cell cultures exhibited a reduced myogenicity, as well as a rapid decrease in proliferative lifespan, as compared to controls. The incorporation of BrdU decreased during the proliferative lifespan, due to a progressive accumulation of non-dividing cells. A lower fusion index was also observed, but myoblasts were able to form large myotubes when OPMD cultures were purified, although a rapid loss of myogenicity during successive passages was also observed. Myoblasts isolated from unaffected muscles did not show the defects observed in cricopharyngeal muscle cultures. The PABPN1 was predominantly located in nuclei of myoblasts and in both the nuclei and cytoplasm of myotubes in OPMD cultures. In vivo analysis of OPMD muscles showed that the number of satellite cells was slightly higher than that observed in age matched controls. Mutation of the PABPN1 in OPMD provokes premature senescence in dividing myoblasts, that may be due to intranuclear toxic aggregates. These results suggest that myoblast autografts, isolated from unaffected muscles, and injected into the dystrophic pharyngeal muscles, may be a useful therapeutic strategy to restore muscular function. Its tolerance and feasibility has been preclinically demonstrated in the dog.

Background: Fluconazole is an antifungal agent that is widely used for the treatment of Candida infection. Because of its favourable safety profile it is extensively used for prophylaxis in patient populations with a substantial risk for Candida infection. At the individual patient level, exposure to fluconazole selects for Candida non-albicans strains such as Candida glabrata and Candida krusei, with reduced susceptibility or intrinsic resistance to fluconazole. The effect of the volume of consumption of fluconazole on candidal ecology, however, is poorly investigated., Objectives: The long-term effect of fluconazole consumption on distribution of species causing candidaemia was investigated in a university hospital during an 11 year period (1994-2004)., Methods: In a historical cohort the incidence of nosocomial candidaemia (expressed per 100,000 patient days) was linked with volume consumption of fluconazole [expressed as defined daily doses (DDDs) per 100,000 patient days] and evaluated over time., Results: During the study period 308 episodes of candidaemia occurred (63.3% caused by Candida albicans). The incidence of candidaemia varied from 6.0 to 13.8 per 100,000 patient days. The percentage candidaemia caused by Candida non-albicans spp. varied between 21% and 50%. No trends in the number of candidaemias or in the proportion of C. albicans versus Candida non-albicans spp. were observed. Fluconazole consumption was high but stable ranging from 5013 to 6807 DDDs per 100,000 patient days. No relationship could be demonstrated between volume of fluconazole consumption and Candida spp. distribution (Pearson's correlation coefficient: -0.083; P=0.808)., Conclusions: Despite long-term exposure to fluconazole, no change in candidal ecology was observed.

Case Description: A 2-year-old Griffon Vendéen was examined because of a 1-month history of right hind limb lameness after a traumatic injury., Clinical Findings: Neurologic examination revealed monoplegia and anesthesia of the right hind limb distal to the stifle (femorotibial) joint except for the area supplied by the cutaneous saphenous nerve. Results of electromyographic testing were consistent with a severe lesion of the tibial and peroneal nerves at the level of the stifle joint., Treatment and Outcome: Exploratory surgery revealed an 80-mm-long gap in both the peroneal and tibial branches of the right sciatic nerve. A section of the left cutaneous saphenous nerve was interposed to graft the nerve defects. The dog received joint mechanotherapy and electrophysiologic therapy during the reinnervation process. Ten months after surgery, the dog had recovered almost completely. Neurologic examination revealed diminished flexion of the tarsal and digital joints. Repeat electromyographic testing revealed no abnormal spontaneous electrical activity in the right hind limb musculature, and small compound muscle action potentials were recorded in the right interosseous and cranial tibial muscles., Clinical Relevance: Without surgical treatment, neurotmesis injury results in poor recovery of motor and sensory functions and may result in amputation. If a nerve defect exists, nerve grafting should be considered, even if the procedure is delayed until well after the injury. The sensory portion of the cutaneous saphenous nerve is a potential source of peripheral nerve for grafting in dogs. Reinnervation is a long-term process and physiologic support and owner involvement are necessary, but nearly complete functional recovery is possible.

Objectives: To collect reliable, comparable and publicly available data on hospital use of antibiotics in Europe aggregated at the national level (1997-2002)., Methods: Consumption data of systemic antibiotics in Anatomical Therapeutic Chemical (ATC) class J01 were collected and expressed in defined daily doses (DDD) per 1000 inhabitants per day. Valid data for 2002 were available for 15 countries, and 6 year trends for 10 countries. Comparison with ambulatory care (AC) consumption data was possible in 14 countries., Results: In 2002, median national hospital antibiotic consumption in Europe was 2.1 DDD/1000 inhabitants/day in Europe, ranging from 3.9 in Finland and France to 1.3 in Norway and Sweden. Hospital care (HC) consumption as a proportion of total antibiotic consumption ranged from 17.8% to 6.4%. The consumption of hospital-specific antibiotics ranged from 0.43 DDD/1000 inhabitants/day in Greece and 0.08 in Sweden. Six-year trends in consumption were stable, except for rising co-amoxiclav exposure and more rapid market penetration of new antibiotics (e.g. levofloxacin) in some countries. There was a strong, positive correlation between the extent of antibiotic use in AC and in HC (Spearman coefficient 0.745; P = 0.002), both for overall use and for use of five main classes (not macrolides and 'others'). In contrast to AC consumption no substantial seasonal variation in consumption was observed., Conclusions: It was cumbersome but feasible to collect ecological data on hospital antibiotic consumption in a set of 15 European countries on a retrospective basis, illustrating substantial cross-national variations in the extent and distribution of exposure to antibiotics in hospital care.

Purpose of Review: This review highlights recent advances in the aetiology of nosocomial pneumonia, and in strategies to increase accuracy of diagnosis and antibiotic prescription while limiting unnecessary antibiotic consumption., Recent Findings: Bacterial pathogens still cause the bulk of nosocomial pneumonia and are of concern because of ever-rising antimicrobial resistance. Yet, the pathogenic role of fungal and viral organisms is increasingly recognized. Since early appropriate antimicrobial therapy is the cornerstone of an effective treatment, further studies have been conducted to improve appropriateness of early antibiotic therapy. De-escalation strategies combine initial broad-spectrum antibiotics to maximize early antibiotic coverage with a subsequent focusing of the antibiotic spectrum when the cause is identified. Invasive techniques probably do not alter the immediate outcome but have the potential to reduce unnecessary antibiotic exposure. Decisions to stop or change antibiotic therapy are hampered due to a lack of reliable parameters to assess the resolution of pneumonia., Summary: Increasing antimicrobial resistance in nosocomial pneumonia both challenges treatment and mandates limitation of selection pressure by reducing antibiotic burden. Treating physicians should be both aggressive in initiating antimicrobials when suspecting nosocomial pneumonia but willing to discontinue antimicrobials when diagnostic results point to an alternative diagnosis. Efforts should be made to limit duration of antibiotic therapy when possible.

Diagnosis of feline hypertrophic cardiomyopathy currently is based on the presence of myocardial hypertrophy detected using conventional echocardiography. The accuracy of tissue Doppler imaging (TDI) for earlier detection of the disease has never been described. The objective of this sudy was to quantify left ventricular free wall (LVFW) velocities in cats with hypertrophic muscular dystrophy (HFMD) during preclinical cardiomyopathy using TDI. The study animals included 22 healthy controls and 7 cats belonging to a family of cats with HFMD (2 affected adult males, 2 heterozygous adult females, one 2.5-month-old affected male kitten, and 2 phenotypically normal female kittens from the same litter). All cats were examined via conventional echocardiography and 2-dimensional color TDI. No LVFW hypertrophy was detected in the 2 carriers or in the affected kitten when using conventional echocardiography and histologic examination, respectively. The LVFW also was normal for 1 affected male and at the upper limit of normal for the 2nd male. Conversely, LVFW dysfunction was detected in all affected and carrier cats with HFMD when using TDI. TDI consistently detects LVFW dysfunction in cats with HFMD despite the absence of myocardial hypertrophy. Therefore, TDI appears more sensitive than conventional echocardiography in detecting regional myocardial abnormalities.

Objective: The objective was to determine the minimum volume of instillation fluid for intra-abdominal pressure (IAP) measurement, and to evaluate the effect of instillation volume on transvesically measured IAP., Design: Prospective cohort study, Setting: Twenty-two-bed surgical ICU of the Ghent University Hospital., Patients and Participants: Twenty patients at risk of intra-abdominal hypertension (IAH)., Interventions: Transvesical IAP measurement using volumes from 10 to 100 ml. Minimal volume at which an IAP was measured was recorded (IAP(min)), as well as IAP at 50 and 100 ml of instillation volume (IAP(50) and IAP(100)). The percentage difference for IAP(50) and IAP(100) was calculated., Measurements and Results: The minimal volume for IAP measurement was 10 ml in all patients. Mean IAP(min) was 12.8 mmHg (+/- 4.9), mean IAP(50 )15 mmHg (+/- 4.5) and mean IAP(100) 17.1mmHg (+/- 4.7). The mean percentage difference for IAP(50) was 21% (+/- 17%), and 40% (+/-29%) for IAP(100.) Twelve patients were categorised as suffering from IAH when 10 ml of saline was used for IAP measurement, increasing to 15 and 17 patients respectively when using 50 and 100 ml. In patients with IAH, there was a significant correlation between the duration of bladder drainage and percentage difference for IAP(100) (Pearson correlation coefficient 0.60, p = 0.03)., Conclusions: Using 50 or 100 ml of saline for IAP measurement in critically ill patients results in higher IAP values compared with the use of 10 ml, and possibly, in overestimation of the incidence of intra-abdominal hypertension.

Background: Bacterial vaginosis (BV) is the single most common vaginal infection in women of childbearing age and associated with a sizeable infectious disease burden among both non-pregnant and pregnant women, including a significantly elevated risk of adverse pregnancy outcome. Overall, little progress has been made in identifying causal factors involved in BV acquisition and persistence. We sought to evaluate maternal iron status in early pregnancy as a putative risk factor for BV, considering that micronutrients, and iron deficiency in particular, affect the host response against bacterial colonization, even in the setting of mild micronutrient deficiencies., Methods: In a nested case-control study, we compared maternal iron status at entry to prenatal care (mean gestational age 9.2 +/- 2.6 weeks) between eighty women with healthy vaginal microflora and eighteen women with vaginosis-like microflora. Vaginal microflora status was assessed by assigning a modified Nugent score to a Gram-stained vaginal smear. Maternal iron status was assayed by an array of conventional erythrocyte and serum indicators for iron status assessment, but also by more sensitive and more specific indicators of iron deficiency, including soluble transferrin receptors (sTfR) as an accurate measure of cellular and tissue iron deficiency and the iron deficiency log10[sTfR/ferritin] index as the presently most accurate measure of body storage iron available., Results: We found no statistically significant correlation between vaginal microflora status and routinely assessed iron parameters. In contrast, a highly significant difference between the healthy and vaginosis-like microflora groups of women was shown in mean values of sTfR concentrations (1.15 +/- 0.30 mg/L versus 1.37 +/- 0.38 mg/L, p = 0.008) and in mean iron deficiency log10[sTfR/ferritin] index values (1.57 +/- 0.30 versus 1.08 +/- 0.56, p = 0.003), indicating a strong association between iron deficiency and vaginosis-like microflora. An sTfR concentration > 1.45 mg/L was associated with a 3-fold increased risk (95%CI: 1.4-6.7) of vaginosis-like microflora and after controlling for maternal age, gestational length, body mass, parity, and smoking habits with an adjusted odds ratio of 4.5 (95%CI: 1.4-14.2)., Conclusion: We conclude that subclinical iron deficiency, presumably resulting from inadequate preconceptional iron supplies, is strongly and independently associated with vaginosis-like microflora during early pregnancy.

Object: The immediate transfer of the right lateral thoracic nerve (LTN) and the thoracodorsal nerve (TDN) to the transected left musculocutaneous nerve (MCN), leading to nerve cross-neurotization, was performed in cats to evaluate reinnervation of the biceps brachii muscle (BBM)., Methods: Surgery to produce cross-neurotization of the MCN was performed in 12 cats (treatment group). Transection of the MCN was performed without attempts at neurotization in three cats (control group). Reinnervation of the BBM was assessed by performing electromyography (EMG) 6 months (14 cats) and 26 months (one cat) postsurgery. True Blue retrograde axonal tracing studies, tensile force measurements (muscle extensometry), and histopathological analyses were performed. All cats in the treatment group recovered voluntary contraction of the BBM and regained elbow flexion. Electromyography revealed no abnormal spontaneous activity in the BBM. Muscle evoked potentials were recorded in that muscle after right C-8 ventral branch stimulation. The muscle contraction strength in the left BBM varied from 108 to 557 g. The BBMs regained their normal appearances. The region of the MCN distal to the anastomosis displayed a normal histological appearance. Fluorescence was detected in the ventral horn of the spinal cord in the right C-8 and T-1 segments. In contrast, in all cats in the control group there was atrophy of the BBM, no EMG signal, and no clinical sign of recovery. There was no contraction of the BBM, no labeled neuron in the spinal cord, and the MCN displayed major degenerative changes., Conclusions: These findings demonstrate that the LTN and TDN can be used to neurotize injured contralateral brachial plexus nerves and obtain successful reinnervation in cats.

Objective: Timely initiation of antibiotic therapy is crucial for severe infection. Appropriate antibiotic therapy is often delayed for nosocomial infections caused by antibiotic-resistant bacteria. The relationship between knowledge of colonization caused by antibiotic-resistant gram-negative bacteria (ABR-GNB) and rate of appropriate initial antibiotic therapy for subsequent bacteremia was evaluated., Design: Retrospective cohort study., Setting: Fifty-four-bed intensive care unit (ICU) of a university hospital. In this unit, colonization surveillance is performed through routine site-specific surveillance cultures (urine, mouth, trachea, and anus). Additional cultures are performed when presumed clinically relevant., Patients: ICU patients with nosocomial bacteremia caused by ABR-GNB., Results: Infectious and microbiological characteristics and rates of appropriate antibiotic therapy were compared between patients with and without colonization prior to bacteremia. Prior colonization was defined as the presence (detected > or = 2 days before the onset of bacteremia) of the same ABR-GNB in colonization and subsequent blood cultures. During the study period, 157 episodes of bacteremia caused by ABR-GNB were suitable for evaluation. One hundred seventeen episodes of bacteremia (74.5%) were preceded by colonization. Appropriate empiric antibiotic therapy (started within 24 hours) was administered for 74.4% of these episodes versus 55.0% of the episodes that occurred without prior colonization. Appropriate therapy was administered within 48 hours for all episodes preceded by colonization versus 90.0% of episodes without prior colonization., Conclusion: Knowledge of colonization status prior to infection is associated with higher rates of appropriate therapy for patients with bacteremia caused by ABR-GNB.

Human centronuclear and myotubular myopathies belong to a genetically heterogeneous nosological group with clinical variability ranging from fatal disorder to mild weakness. The severe X-linked form is attributed to more than 200 different mutations in the myotubularin encoding gene (MTM1). In contrast, there are no reports regarding the molecular etiology or linkage studies on the autosomal forms of the disease. Labrador retrievers affected by spontaneous centronuclear myopathy (cnm) have clinical and histological features of the human disorder and represent the first model of recessive autosomal centronuclear myopathy. We previously mapped the cnm locus to the centromeric region of canine chromosome 2. No gene of the MTM1 family maps to the human homologous chromosomal region. Described herein is a disease-associated insertion within PTPLA exon 2, found in both alleles of all affected Labradors and in a single allele in obligate carriers. The inserted tRNA-derived short interspersed repeat element (SINE) has a striking effect on the maturation of PTPLA mRNA, whereby it can be spliced out, partially exonized or involved in multiple exon-skipping. As a result, the amount of wild-type transcripts falls to 1% in affected muscles. This example therefore recapitulates cumulative SINE-associated transcriptional defects that have been previously described as exclusive consequences of independent mutations. Although the function of PTPLA in metazoa remains unknown, the characterization of a hypomorphic mutation in Labradors with centronuclear myopathy provides new clues about the molecular complexity of skeletal myofiber homeostasis. These results also suggest that impaired PTPLA signaling might be implicated in human myopathies.

Objective: To investigate the incidence, risk factors and mortality of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients., Design: Prospective, observational, population-based study., Setting: The medical (14-bed) and surgical ICU (26-bed) of the Ghent University Hospital., Methods: All 1295 patients admitted to the ICU during 4 three-month periods between 1996 and 1998 were included. A set of demographic and clinical variables were collected at the day of admission and during the ICU course., Results: The incidence of VAP among ICU patients ventilated at least 48 hours was 23.1%. The mean time to the development of VAP was 9.6 days with a median of 6 days. In the population of patients ventilated for at least 48 hours, a comparison was made between patients with (n = 89) and without VAP (n = 296). Patients with VAP had a significant longer ICU stay, with a longer ventilation dependency. Logistic regression analysis identified admission diagnosis other than trauma (OR: 0.51, 95% CI: 0.29-0.89; p = 0.02) and the length of ICU stay (OR: 1.05, 95% CI: 1.03-1.07; p < 0.001) to be independently associated with the acquisiton of VAP. In comparison with the total study population, patients with VAP had a higher ICU mortality (20.2% vs. 12.0%; p = 0.04), but not in the cohort group of patients at risk for VAP (ventilated > 48 hours)(20.2% vs. 31.3%; p = 0.03). The factors independently associated with death were higher SAPS II scores (OR 1.02, 95% CI: 1.003-1.032; p = 0.02), an admission diagnosis other than trauma (OR 0.36, 95% CI: 0.17-0.75; p = 0.006) and length of ICU stay (OR 0.97, 95% CI: 0.946-0.995; p = 0.02). This model did not recognize VAP as an independent predictor of death (OR 0.79, 95% CI: 0.41-1.53; p = 0.492)., Conclusions: The incidence of VAP in our ICU is 23.1%. Length of ICU stay and an admission diagnosis other than trauma are major risk factors for the development of this nosocomial infection. VAP is associated with a high fatality rate. However, after adjustment for disease severity and length of ICU stay, VAP was not identified as an independent predictor of death.

Objective: To evaluate the influence of matching on exposure time on estimates of attributable mortality of nosocomial bacteremia as assessed by matched cohort studies., Design: Two retrospective, pairwise-matched (1:2) cohort studies., Setting: A 54-bed intensive care unit (ICU) in a university hospital., Patients: Patients with nosocomial Escherichia coli bacteremia (n = 68) and control-patients without nosocomial bacteremia (n = 136 for each matched cohort study)., Intervention: In both matched cohort studies, the same set of bacteremic patients was matched with control-patients using the APACHE II system. In the first study, control-patients were required to have an ICU stay at least as long as the respective bacteremic patient prior to onset of bacteremia (matching on exposure time). In the second study, control-patients were required to have an ICU stay shorter than the stay prior to the development of bacteremia in the respective bacteremic patient (no matching on exposure time)., Results: For bacteremic patients, the mean ICU stay before onset of the bacteremia was 9 days (median, 6 days). In the first matched cohort study, hospital mortality was not different between bacteremic patients and control-patients (44.1% vs 43.4%; P = .999). In the second study, mortality of bacteremic patients and control-patients was also not different (44.1% vs 47.8%; P = .657). Mortality rates between control groups were not different (43.4% vs 47.8%; P = .543)., Conclusion: Matching or not matching on exposure time did not alter the estimate of attributable mortality for ICU patients with E. coli bacteremia.

Background and Aims: Temperature measurement is a routine task of patient care, with considerable clinical impact, especially in the ICU. This study was conducted to evaluate the accuracy and variability of the Temporal Artery Thermometer (TAT) in ICU-patients. Therefore, a convenience sample of 57 adult patients, with indwelling pulmonary artery catheters (PAC) in a 40-bed intensive care unit in a university teaching hospital was used., Methods: The study design was a prospective, descriptive comparative analysis. Body temperature was thereby measured simultaneously with the TAT and the Axillary Thermometer (AT), and was compared with the temperature recording of the PAC. The use of vasoactive medication was recorded., Results and Conclusions: Mean temperature of all measurements was: PAC: 37.1 degrees C (SD: 0.87), TAT 37.0 degrees C (SD: 0.68) and axillary thermometer: 36.6 degrees C (SD: 0.94). The measurements of the TAT and the PAC were not significantly different (man differnce: 0.14 degrees C; SD: 0.51; p = 0.33); whereas the measurements of the PAC and the AT differed significantly (mean difference: 0.46 degerees C; SD: 0.39; p < 0.001). Mean diference in PAC versus TAT analyses, between patients with vasopressor therapy (0.12 degrees C; SD: 0.55), and without vasopressor therapy (0.19 degrees C; SD: 0.48) was not statistically significant (p = 0.47)., Conclusion: We can conclude that the temporal scanner has a relatively good reliability with an acceptable accuracy and variability in patients with normothermia. The results are comparable to those of the AT, but they do not seem to be sufficient to prove any substantial benefit compared to rectal, oral or bladder thermometry.

Intra-abdominal infections differ from other infections through the broad variety in causes and severity of the infection, the aetiology of which is often polymicrobial, the microbiological results that are difficult to interpret and the essential role of surgical intervention. From a clinical viewpoint, two major types of intra-abdominal infections can be distinguished: uncomplicated and complicated. In uncomplicated intra-abdominal infection, the infectious process only involves a single organ and no anatomical disruption is present. Generally, patients with such infections can be managed with surgical resection alone and no antimicrobial therapy besides perioperative prophylaxis is necessary. In complicated intra-abdominal infections, the infectious process proceeds beyond the organ that is the source of the infection, and causes either localised peritonitis, also referred to as abdominal abscess, or diffuse peritonitis, depending on the ability of the host to contain the process within a part of the abdominal cavity. In particular, complicated intra-abdominal infections are an important cause of morbidity and are more frequently associated with a poor prognosis. However, an early clinical diagnosis, followed by adequate source control to stop ongoing contamination and restore anatomical structures and physiological function, as well as prompt initiation of appropriate empirical therapy, can limit the associated mortality. The biggest challenge with complicated intra-abdominal infections is early recognition of the problem. Antimicrobial management is generally standardised and many regimens, either with monotherapy or combination therapy, have proven their efficacy. Routine coverage against enterococci is not recommended, but can be useful in particular clinical conditions such as the presence of septic shock in patients previously receiving prolonged treatment with cephalosporins, immunosuppressed patients at risk for bacteraemia, the presence of prosthetic heart valves and recurrent intra-abdominal infection accompanied by severe sepsis. In patients with prolonged hospital stay and antibacterial therapy, the likelihood of involvement of antibacterial-resistant pathogens must be taken into account. Antimicrobial coverage of Candida spp. is recommended when there is evidence of candidal involvement or in patients with specific risk factors for invasive candidiasis such as immunodeficiency and prolonged antibacterial exposure. In general, antimicrobial therapy should be continued for 5-7 days. If sepsis is still present after 1 week, a diagnostic work up should be performed, and if necessary a surgical reintervention should be considered.

Background: Overall, the use of antibiotics in the treatment of patients with severe acute pancreatitis has increased owing to the use of antibiotic prophylaxis., Hypothesis: The incidence of antibiotic-resistant (AB-R) bacteria in infected pancreatitis is related to prolonged antibiotic treatment and may affect outcome., Design: Case series., Setting: Fifty-six-bed intensive care unit of a tertiary care center., Patients: Forty-six consecutive patients with infected pancreatic necrosis., Main Outcome Measures: Occurrence rate of AB-R organisms in pancreatic infection, overall duration of antibiotic treatment prior to infection, and mortality, defined as inhospital mortality., Results: Infection with AB-R microorganisms was found in 24 (52%) of 46 patients. Primary infection was present in 7 patients; in 21 patients, nosocomial surinfection with AB-R organisms occurred. Patients with AB-R infections were treated with antibiotics for a longer period (24 vs 15 days, P<.05), while disease severity and the incidence of organ failure were not statistically significantly different. The intensive care unit stay was significantly longer in patients with AB-R infections (23 vs 31 days, P = .02). Mortality was not statistically significantly different in patients with AB-R infections (37% vs 28%, P = .23)., Conclusions: The occurrence rate of infections with AB-R organisms in our patients with severe acute pancreatitis was high and was associated with a longer intensive care unit stay, but no increased mortality could be demonstrated. The duration of antibiotic treatment was increased in patients in whom AB-R infections developed.