Prevalence, mechanisms, and risk factors of carbapenem resistance in bloodstream isolates of Pseudomonas aeruginosa

We examined the prevalence of various carbapenem resistance mechanisms in Pseudomonas aeruginosa bloodstream isolates from a university-affiliated hospital. Isolates obtained in 2003 and 2004 were screened for meropenem/imipenem resistance, and clonality was assessed by repetitive-element-based polymerase chain reaction. The presence of carbapenemase and AmpC overexpression was ascertained by spectrophotometric assays. Outer membrane protein profiles were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and efflux pump overexpression was confirmed by Western blotting. We examined 129 nonrepeat isolates; 21 isolates (from 13 distinct clones) were resistant to meropenem or imipenem (prevalence rate = 16.3%). Nineteen (90.5%) carbapenem-resistant isolates had reduced OprD expression, and 6 (28.6%) isolates had overexpression of MexB. Increased length of hospital stay was identified as a significant risk factor for bacteremia due to carbapenem-resistant P. aeruginosa. Understanding the prevalence and mechanism of carbapenem resistance in P. aeruginosa may guide empiric therapy for nosocomial infections in our hospital.     

Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda.

Uroporphyrinogen decarboxylase (URO-D) is a cytosolic heme-biosynthetic enzyme that converts uroporphyrinogen to coproporphyrinogen. Defects at the uroporphyrinogen decarboxylase locus cause the human genetic disease familial porphyria cutanea tarda. A splice site mutation has been found in a pedigree with familial porphyria cutanea tarda that causes exon 6 to be deleted from the mRNA. The intron/exon junctions on either side of exon 6 fall between codons, so the resulting protein is shorter than the normal protein, missing only the amino acids coded by exon 6. The shortened protein lacks catalytic activity, is rapidly degraded when exposed to human lymphocyte lysates, and is not detectable by Western blot analysis in lymphocyte lysates derived from affected individuals. The mutation was detected in five of 22 unrelated familial porphyria cutanea tarda pedigrees tested, so it appears to be common. This is the first splice site mutation to be found at the URO-D locus, and the first mutation that causes familial porphyria cutanea tarda to be found in more than one pedigree.     

Association of fluconazole area under the concentration-time curve/MIC and dose/MIC ratios with mortality in nonneutropenic patients with candidemia

The present study tested in vitro susceptibility of Candida bloodstream isolates to fluconazole to determine if the ratio of the fluconazole area under the concentration-time curve (AUC) or weight-normalized daily dose (dose(wn)) to MIC correlated with mortality. Fluconazole susceptibility and outcome data were determined for 77 patients with a positive Candida blood culture between 2002 and 2005. The most commonly isolated Candida species were C. albicans (64%), C. glabrata (14%), C. parapsilosis (8%), C. tropicalis (6%), and C. lusitaniae (4%). Only two isolates were classified as fluconazole resistant by the CLSI M27-A2 method. Fluconazole MICs were highest against C. glabrata relative to other Candida species. Overall the crude mortality assessed at hospital discharge was 19.4% (n = 15). Mortality rates by species were as follows: C. albicans, 16.3%; C. glabrata, 36.4%; C. parapsilosis, 0%; C. tropicalis, 0%; C. lusitaniae, 33.3%. A mortality rate of 50% was noted among patients infected with nonsusceptible isolates (MIC > or = 16 microg/ml) compared to 18% for patients infected with susceptible (MIC < or = 8 microg/ml) isolates (P = 0.17). The fluconazole dose(wn)/MIC (24-h) values were significantly higher for the 62 survivors (13.3 +/- 10.5 [mean +/- standard deviation]) compared to the 15 nonsurvivors (7.0 +/- 8.0) (P = 0.03). The fluconazole AUC/MIC (24 h) values also trended higher for survivors (775 +/- 739) compared to nonsurvivors (589 +/- 715) (P = 0.09). These data support the dose-dependent properties of fluconazole. Underdosing fluconazole against less-susceptible Candida isolates has the potential to increase the risk of mortality associated with candidemia.     

Quality of life assessment between laparoscopic appendectomy at presentation and interval appendectomy for perforated appendicitis with abscess: analysis of a prospective randomized trial

Purpose

The current study examined the impact of immediate laparoscopic surgery vs nonoperative initial management followed by interval appendectomy for appendicitis with abscess on child and family psychosocial well-being.

Methods

After obtaining Internal Review Board approval, 40 patients presenting with a perforated appendicitis and a well-formed abscess were randomized to surgical condition. Parents were asked to complete child quality of life and parenting stress ratings at presentation, at 2 weeks postadmission, and at approximately 12 weeks postadmission (2 weeks postoperation for the interval appendectomy group).

Results

Children in the interval arm experienced trends toward poorer quality of life at 2 and 12 weeks postadmission. However, no group differences in parenting stress were observed at 2 weeks postoperation. At 12 weeks postadmission, participants in the interval condition demonstrated significant impairment in both frequency and difficulty of problems contributing to parenting distress.

Conclusion

Families experience significant parenting distress related to the child's functioning and disruption in the child's quality of life that may be because of the delay in fully resolving the child's medical condition. In addition, parents experience negative consequences to their own stress as a result of the delay before the child's appendectomy.     

Outcomes of perforated appendicitis in obese and nonobese children

Introduction

Despite abundant data on the impact of obesity in adults, little data exist that examine the impact of obesity on surgical outcomes in children. Therefore, we analyzed the impact of obesity on children with perforated appendicitis.

Methods

We analyzed data from 3 prospective trials on perforated appendicitis between 2005 and 2009. Perforation was defined as a hole in the appendix or fecalith in the abdomen. There was no difference in abscess rate in the 6 arms of these trials. Body mass index (BMI) was calculated, and BMI percentile was identified according to sex and age. The obese group was defined as BMI greater than 95th percentile. Data were compared between nonobese and obese patients.

Results

There were 220 patients, of which 37 patients were obese. The obese group was older with no other differences in presentation. Mean length of stay was 7.9 days in the obese patients compared with 5.8 days for the nonobese (P < .001). Mean operative time was 55.2 minutes in obese patients compared with 43.6 for nonobese (P = .003). Abscess rate was 35% in obese patients compared with 15% for nonobese (P = .01).

Conclusions

Obese children undergoing laparoscopic appendectomy for perforated appendicitis experience longer operative times and suffer worse outcomes.     

Length of stay and hospital costs among patients admitted to hospital by family physicians

Objective

To compare length of stay and total hospital costs among patients admitted to hospital under the care of family physicians who were their usual health care providers in the community (group A) and patients admitted to the same inpatient service under the care of family physicians who were not their usual health care providers (group B).

Design

Retrospective observational study.

Setting

A large urban hospital in Vancouver, BC.

Participants

All adult admissions to the family practice inpatient service between April 1, 2006, and June 30, 2008.

Main outcome measures

Ratio of length of stay to expected length of stay and total hospital costs per resource intensity weight unit. Multivariate linear regression was performed to determine the effect of admitting group (group A vs group B) on the natural logarithm transformations of the outcomes.

Results

The median acute length of stay was 8.0 days (interquartile range [IQR] 4.0 to 13.0 days) for group A admissions and 8.0 days (IQR 4.0 to 15.0 days) for group B admissions. The median (IQR) total hospital costs were $6498 ($4035 to $11 313) for group A admissions and $6798 ($4040 to $12 713) for group B admissions. After adjustment for patient characteristics, patients admitted to hospital under the care of their own family physicians did not significantly differ in terms of acute length of stay to expected length of stay ratio (percent change 0.6%, P = .942) or total hospital costs per resource intensity weight unit (percent change −2.0%, P = .722) compared with patients admitted under the care of other family physicians.

Conclusion

These findings suggest that having networks of family physicians involved in hospital care for patients is not less efficient than having family physicians provide care for their own patients.     

Decreased numerical density of kainate receptor-positive neurons in the orbitofrontal cortex of chronic schizophrenics

We utilised postmortem brain tissue to quantify sections of left and right orbitofrontal cortex (area 11) from nine schizophrenic and eight control patients from the Charing Cross Prospective Schizophrenia Study immunostained for the presence of the kainate receptor (GluR5/6/7). The numerical density of neurons immunopositive for kainate receptor was measured. Other sections from the same blocks were stained with cresyl violet to determine the total neuronal numerical density. All measurements were made blind: diagnoses were only revealed by a third party after measurements were completed. There was a significant reduction (21%) in numerical density of kainate receptor-positive neurons in both cortices in the schizophrenic group (488 cells/mm²) compared to that in the control group (618 cells/mm²) (P=0.033). Nissl-stained tissue showed no significant difference in total neuronal numerical density between control and schizophrenic groups. These observations suggest that there are actually fewer kainate receptor-positive neurons in schizophrenic orbitofrontal cortex. There was no correlation of reduced kainate receptor-positive cell number with age at death, postmortem interval, or other possibly confounding neuropathology. Our results support the concept of there being reduced glutamatergic activity in frontal cortex in schizophrenia.