Epidemiology and outcomes associated with enterococcal blood stream infection among liver and kidney transplant recipients.

Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus accounts for up to 20% of BSIs in this population, with vancomycin-resistant enterococcus (VRE) posing a particular risk. This is a retrospective, case-control study of adult liver and kidney transplant recipients between 01/01/2016 and 06/30/2021 that characterizes the epidemiology and outcomes of enterococcal BSIs in liver and kidney transplantations at a single institution. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n = 54; 10.3%). Cases were mostly liver transplant recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14-43); controls included 14 KT recipients (50%). Groups differed significantly (all p < .05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p < .0001). There were no differences in 1-year mortality between the groups. Enterococcus faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. In our liver and kidney transplants, enterococcal BSIs occurred early among liver transplant recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period.

Perioperative antimicrobial prophylaxis and prevention of hepatobiliary surgical site infections.

OBJECTIVE: To characterize the microbiology of hepatobiliary surgical site infections (SSIs) and to explore the relationship between specific antimicrobial prophylaxis regimens and the development of SSIs. DESIGN: Retrospective matched case-control study comparing patient, procedure, and antimicrobial prophylaxis characteristics among patients undergoing a hepatobiliary surgical procedure with and without an SSI. SETTING: A tertiary referral acute-care facility. METHODS: Patients undergoing procedures defined as "BILI" (bile duct, liver, or pancreas surgery) using National Healthcare Safety Network (NHSN) definitions, excluding those undergoing concomitant liver transplantation, from January 2013 through June 2016 were included in the study population. The SSIs were identified through routine infection control surveillance using NHSN definitions. All patients who developed an SSI were considered cases. Controls were selected randomly matched 2:1 with cases based on fiscal quarter of the procedure. Logistic regression modeling was performed to explore variables associated with SSI, including antimicrobial prophylaxis received. RESULTS: Among 975 procedures, 80 (8.2%) resulted in an SSI. Most cases involved an organism nonsusceptible to standard prophylaxis regimens, including cefazolin (68.8%), cefazolin plus metronidazole (61.3%), and ampicillin-sulbactam (52.5%). In a multivariate model, antimicrobial coverage against Enterococcus spp (aOR, 0.58; 95% confidence interval [CI], 0.17-2.04; P=.40) and against Pseudomonas spp (aOR, 2.40; 95% CI, 0.56-10.29; P=.24) were not protective against the development of an SSI. The presence of a documented ß-lactam allergy was significantly associated with the development of an SSI (aOR, 3.54; 95% CI, 1.36-9.19; P=.009). CONCLUSIONS: Although SSIs at the study institution were associated with pathogens nonsusceptible to the most commonly used prophylaxis regimens, broader-spectrum coverage was not associated with a reduction in SSIs.

Regardless of genotype, offspring of VIP-deficient female mice exhibit developmental delays and deficits in social behavior.

Pharmacological studies indicate that vasoactive intestinal peptide (VIP) may be necessary for normal embryonic development in the mouse. For example, VIP antagonist treatment before embryonic day 11 resulted in developmental delays, growth restriction, modified adult brain chemistry and reduced social behavior. Here, developmental milestones, growth, and social behaviors of neonates of VIP-deficient mothers (VIP +/-) mated to VIP +/- males were compared with the offspring of wild type mothers (VIP +/+) mated to VIP +/+ and +/- males, to assess the contributions of both maternal and offspring VIP genotype. Regardless of their own genotype, all offsprings of VIP-deficient mothers exhibited developmental delays. No delays were seen in the offspring of wild type mothers, regardless of their own genotype. Body weights were significantly reduced in offspring of VIP-deficient mothers, with VIP null (-/-) the most affected. Regardless of genotype, all offspring of VIP-deficient mothers expressed reduced maternal affiliation compared with wild type offspring of wild type mothers; +/- offspring of wild type mothers did not differ in maternal affiliation from their wild type littermates. Play behavior was significantly reduced in all offsprings of VIP-deficient mothers. Maternal behavior did not differ between wild type and VIP-deficient mothers, and cross-fostering of litters did not change offspring development, indicating that offspring deficits were induced prenatally. This study illustrated that the VIP status of a pregnant mouse had a greater influence on the growth, development and behavior of her offspring than the VIP genotype of the offspring themselves. Deficiencies were apparent in +/+, +/- and -/- offspring born to VIP-deficient mothers; no deficiencies were apparent in +/- offspring born to normal mothers. These results underscore the significant contribution of the uterine environment to normal development and indicate a potential usefulness of the VIP knockout mouse in furthering the understanding of neurodevelopmental disorders with social behavior deficits such as autism.

Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice.

Blockage of vasoactive intestinal peptide (VIP) receptors during early embryogenesis in the mouse has been shown to result in developmental delays in neonates, and social behavior deficits selectively in adult male offspring. Offspring of VIP deficient mothers (VIP +/-) also exhibited developmental delays, and reductions in maternal affiliation and play behavior. In the current study, comparisons among the offspring of VIP deficient mothers (VIP +/-) mated to VIP +/- males with the offspring of wild type (WT) mothers mated to VIP +/- males allowed assessment of the contributions of both maternal and offspring VIP genotype to general health measures, social behavior, fear conditioning, and spatial learning and memory in the water maze. These comparisons revealed few differences in general health among offspring of WT and VIP deficient mothers, and all offspring exhibited normal responses in fear conditioning and in the acquisition phase of spatial discrimination in the water maze. WT mothers produced offspring that were normal in all tests; the reduced VIP in their VIP +/- offspring apparently did not contribute to any defects in the measures under study. However, regardless of their own VIP genotype, all male offspring of VIP deficient mothers exhibited severe deficits in social approach behavior and reversal learning. The deficits in these behaviors in the female offspring of VIP deficient mothers were less severe than in their male littermates, and the extent of their impairment was related to their own VIP genotype. This study has shown that intrauterine conditions had a greater influence on behavioral outcome than did genetic inheritance. In addition, the greater prevalence of deficits in social behavior and the resistance to change seen in reversal learning in the male offspring of VIP deficient mothers indicate a potential usefulness of the VIP knockout mouse in furthering the understanding of neurodevelopmental disorders such as autism.

Vasoactive intestinal peptide (VIP) regulates activity-dependent neuroprotective protein (ADNP) expression in vivo.

Vasoactive intestinal peptide (VIP) is an important mediator of development during the neural tube closure period of embryogenesis and may regulate, in part, the expression of activity-dependent neuroprotective protein (ADNP), which is essential for neural tube closure and embryogenesis. To evaluate the impact of VIP expression in vivo on ADNP and the related protein ADNP2 the current study examined gene expression in adult wild-type (VIP +/+) and VIP null (VIP -/-) offspring of VIP deficient mothers (VIP+/-) comparing them to wild-type offspring of wild-type mothers. Quantitative real time polymerase chain reaction (PCR), using an ABI Prisma cycler revealed regionally specific reductions of ADNP mRNA in the brains of VIP null mice compared with the brains of wild-type offspring of a wild-type mother. ADNP was significantly reduced in the cortex and hypothalamus of VIP null mice, but not in the hippocampus or thalamus. ADNP2 exhibited a similar pattern but reached a statistically significant reduction only in the hypothalamus. The mRNA for ADNP and ADNP2 also tended to be reduced in the cortex and hippocampus of the wild-type littermates of the VIP null mice, indicating that the VIP genotype of the mother may have had an impact on the ADNP expression of her offspring, regardless of their own VIP genotype. These results showed that VIP regulated brain ADNP expression in a regionally specific manner and indicated that both maternal and offspring VIP genotype may influence ADNP expression in the brain.

Cholinergic modulation in the olfactory bulb influences spontaneous olfactory discrimination in adult rats.

Cholinergic neuromodulation in the olfactory bulb has been hypothesized to regulate mitral cell molecular receptive ranges and the behavioral discrimination of similar odorants. We tested the effects of cholinergic modulation in the olfactory bulb of cannulated rats by bilaterally infusing cholinergic agents into the olfactory bulbs and measuring the rats' performances on separate spontaneous and motivated odor-discrimination tasks. Specifically, 6 microL/bulb infusions of vehicle (0.9% saline), the muscarinic antagonist scopolamine (7.6 mM and 38 mM), the nicotinic antagonist mecamylamine hydrochloride (3.8 mM and 19 mM), a combination of both antagonists, or the acetylcholinesterase inhibitor neostigmine (8.7 mM) were made 20 min prior to testing on an olfactory cross-habituation task or a rewarded, forced-choice odor-discrimination task. Spontaneous discrimination between chemically related odorants was abolished when nicotinic receptors were blocked in the olfactory bulb, and enhanced when the efficacy of cholinergic inputs was increased with neostigmine. Blocking muscarinic receptors reduced but did not abolish odor discrimination. Interestingly, no behavioral effects of modulating either nicotinic or muscarinic receptors were observed when rats were trained on a reward-motivated odor-discrimination task. Computational modeling of glomerular circuitry demonstrates that known nicotinic cholinergic effects on bulbar neurons suffice to explain these results.