Synergistic effects of pathogen and pesticide exposure on honey bee (Apis mellifera) survival and immunity.

Declines in native insect pollinator populations and substantial losses in managed honey bees have been reported on a global scale and become a widespread concern because of the importance of these insects for human food production and ecosystem stability. Several potential factors have been studied as possible causes of declining pollinator health, such as parasites and pathogens, exposure to agricultural pesticides, habitat loss and/or climate change. More recently, a combination of these factors rather than a single cause have been blamed for observed pollinator losses, but field studies of such interactions are challenging, especially in the presence of confounding environmental stressors. We therefore examined the impact of single and combined stressors on the honey bee (Apis mellifera) in a generally healthy Australian population. We exposed workers during their larval development and drones until they reached sexual maturity to the neonicotinoid pesticide Thiamethoxam, at concentrations more than 20 times lower than we initially measured in the field, the microsporidian gut pathogen Nosema apis or both stressors at the same time. We found that simultaneous exposure significantly reduced bee health. We observed a substantial increase in mortality and a reduction of immunocompetence in workers exposed to both the pathogen and the pesticide. We conclude that the exposure of generally healthy bees to multiple environmental stressors results in synergistic effects where the effects are expected to negatively impact performance and could be sufficient to trigger colony collapse. We found that the vast majority of males did not survive to sexual maturity after exposure to very low levels of Thiamethoxam. This would not only reduce the reproductive success of individual colonies, but can also impact gene flow and genetic diversity at the population level, which are both known as key components of honey bee health.

Reducing Carbapenem Exposure: Extended-Spectrum ß-Lactamase Catheter-Associated Urinary Tract Infection Management.

Catheter-associated urinary tract infections are one of the most common sources of infection, accounting for up to 40% of health care-associated infections each year in the United States. Extended-spectrum ß-lactamase-producing Enterobacteriaceae are frequent causes of urinary tract infections in health care settings. Prevalent use of carbapenems has led to the emergence of carbapenem-resistant Enterobacteriaceae infections, leaving clinicians with few treatment options. Reducing carbapenem use and investigating alternative options for low-severity extended-spectrum ß-lactamase infections is imperative to prevent more cases of carbapenem-resistant Enterobacteriaceae. Although carbapenems are the antibiotics of choice for treating extended-spectrum ß-lactamase-producing Enterobacteriaceae catheter-associated urinary tract infections, carbapenem-sparing regimens may be appropriate for treating hemodynamically stable patients with low inoculum levels. Moreover, frontline health care providers can initiate efforts to reduce the development of multidrug-resistant organisms by decresing inappropriate antibiotic use during the treatment of catheter-associated asymptomatic bacteruria, avoiding unnecessary catheterizations, and avoiding culturing urine in asymptomatic patients.

Mycobacterium bovis Cerebellar Abscess Following Treatment With Bacillus Calmette-Guérin.

Bacillus Calmette-Guérin (BCG) is a live, attenuated strain of Mycobacterium bovis that is used to treat superficial bladder cancer. Although its use is typically associated with only mild, localized side effects, rare systemic complications can occur. Disseminated mycobacterium infections after BCG therapy have been reported in over 30 cases; however, central nervous system (CNS) infections do not commonly occur. We report a 74-year-old male who developed a M. bovis cerebellar abscess after receiving intravesical BCG infusion for bladder cancer for less than 1 year. This patient was successfully treated with antituberculosis therapy and corticosteroids. This patient case demonstrates that early-onset M bovis CNS infections can occur after BCG therapy. Patients presenting with altered mental status while on BCG therapy should be evaluated for disseminated infections.

Relationship between serum carnitine, acylcarnitines, and renal function in patients with chronic renal disease.

BACKGROUND: Serum free carnitine is decreased and serum acylcarnitines are increased in maintenance hemodialysis (MHD) patients, and the causes for these abnormalities are not known. This study examined the role of renal failure in the occurrence of low serum carnitine and increased acylcarnitines in patients with advanced chronic kidney disease (CKD) by assessing the relationship between these compounds and renal function in normal individuals and patients with CKD. If these compounds decrease as glomerular filtration rate (GFR) decreases, this suggests that decreased intake or impaired synthesis in kidneys explain the low serum values. If serum compounds increase as GFR decreases, this suggests that impaired excretion may predispose to these values. METHODS: The study, conducted in Lyon, France (part A), and Los Angeles, California (part B), compared serum free carnitine and acylcarnitines to renal function in 20 normal patients, 65 CKD patients, and 29 MHD patients. GFR was measured using inulin (A) and iothalamate (B) clearances. Carnitine compounds were measured by tandem mass spectrometry (A) and electron spray mass spectrometry (B). RESULTS: There was no relationship between serum total carnitine or free carnitine and GFR in the normal subjects and CKD patients. In contrast, serum acylcarnitines were inversely correlated with GFR in these 2 groups. Serum free carnitine was significantly lower in MHD patients than in CKD patients and normal controls in study B, whereas acylcarnitines were significantly greater than controls in studies A and B and than in CKD patients in study A. CONCLUSIONS: Serum free carnitine is not reduced in CKD and decreases in MHD patients. Serum acylcarnitines increase in CKD and MHD patients primarily because of impaired excretory function in the failing kidney.

Treating Central Catheter-Associated Bacteremia Due to Methicillin-Resistant Staphylococcus aureus: Beyond Vancomycin.

Methicillin-resistant Staphylococcus aureus is a frequent cause of hospital-associated infections, including central catheter-associated bacteremia. Vancomycin has been the drug of choice for treating this type of bacteremia for decades in patients who have no contraindications to the antibiotic. However, resistance to vancomycin is an emerging problem. Newer antibiotics approved by the Food and Drug Administration have activity against methicillin-resistant S aureus Some of the antibiotics also have activity against strains of S aureus that are intermediately susceptible or resistant to vancomycin. This article uses a case study to highlight the clinical signs of vancomycin failure and describes the indications for and appropriate use of alternative antimicrobials such as ceftaroline, daptomycin, linezolid, tigecycline, and telavancin. (Critical Care Nurse 2016;36[4]:46-57).

Activation of descending pain-facilitatory pathways from the rostral ventromedial medulla by cholecystokinin elicits release of prostaglandin-E2 in the spinal cord.

Cholecystokinin (CCK) has been suggested to be both pro-nociceptive and "anti-opioid" by actions on pain-modulatory cells within the rostral ventromedial medulla (RVM). One consequence of activation of RVM CCK2 receptors may be enhanced spinal nociceptive transmission; but how this might occur, especially in states of pathological pain, is unknown. Here, in vivo microdialysis was used to demonstrate that levels of RVM CCK increased by approximately 2-fold after ligation of L5/L6 spinal nerves (SNL). Microinjection of CCK into the RVM of naïve rats elicited hypersensitivity to tactile stimulation of the hindpaw. In addition, RVM CCK elicited a time-related increase in (prostaglandin-E2) PGE2 measured in cerebrospinal fluid from the lumbar spinal cord. The peak increase in spinal PGE2 was approximately 5-fold and was observed at approximately 80 minutes post-RVM CCK, a time coincident with maximal RVM CCK-induced mechanical hypersensitivity. Spinal administration of naproxen, a nonselective COX-inhibitor, significantly attenuated RVM CCK-induced hindpaw tactile hypersensitivity. RVM-CCK also resulted in a 2-fold increase in spinal 5-hydroxyindoleacetic acid (5-HIAA), a 5-hydoxytryptophan (5-HT) metabolite, as compared with controls, and mechanical hypersensitivity that was attenuated by spinal application of ondansetron, a 5-HT3 antagonist. The present studies suggest that chronic nerve injury can result in activation of descending facilitatory mechanisms that may promote hyperalgesia via ultimate release of PGE2 and 5-HT in the spinal cord.

Echinocandins: addressing outstanding questions surrounding treatment of invasive fungal infections.

PURPOSE: Recent in vitro and clinical data addressing outstanding issues regarding the selection, dosing, and monitoring of echinocandins for the treatment of invasive fungal infections (IFIs) are reviewed. SUMMARY: The echinocandins (caspofungin, micafungin, and anidulafungin) are attractive treatment options for the treatment of select IFIs, most notably invasive candidiasis and treatment-refractory invasive aspergillosis. A literature review of English-language articles published between January 2007 and May 2010 was performed using the terms caspofungin, micafungin, anidulafungin, and echinocandin. In vitro, in vivo, and both pediatric and adult clinical studies and case reports were included. The challenges to establish meaningful interpretive criteria for in vitro testing of yeasts continue to persist, as do the establishment of the clinical relevancy of both the reduced in vitro susceptibilities to Candida parapsilosis and the paradoxical growth of Candida species at higher dosages. Despite increasing use of these agents and reports of breakthrough infections, echinocandins have continued to maintain potency against a broad spectrum of Candida and Aspergillus species. Recent in vitro studies also support the excellent activity of echinocandins against Candida biofilms. While recent published studies have better defined dosing in special populations (such as pediatric patients and those with organ dysfunction), attempts to increase efficacy by dosage intensification have been unsuccessful. Several pharmacoeconomic studies have been performed in attempts to justify the high acquisition costs of these drugs. In general, these studies found that echinocandins may be cost-effective for such indications. CONCLUSION: Available in vitro data, animal studies, and clinical studies do not clearly differentiate agents in the echinocandin class. Clinical data continue to support the use of echinocandins as a safe and well-tolerated treatment option for candidemia and invasive aspergillosis.

Therapeutic hypothermia protocol in a community emergency department.

OBJECTIVES: Therapeutic hypothermia (TH) has been shown to improve survival and neurological outcome in patients resuscitated after out of hospital cardiac arrest (OHCA) from ventricular fibrillation/ventricular tachycardia (VF/VT). We evaluated the effects of using a TH protocol in a large community hospital emergency department (ED) for all patients with neurological impairment after resuscitated OHCA regardless of presenting rhythm. We hypothesized improved mortality and neurological outcomes without increased complication rates. METHODS: Our TH protocol entails cooling to 33°C for 24 hours with an endovascular catheter. We studied patients treated with this protocol from November 2006 to November 2008. All non-pregnant, unresponsive adult patients resuscitated from any initial rhythm were included. Exclusion criteria were initial hypotension or temperature less than 30°C, trauma, primary intracranial event, and coagulopathy. Control patients treated during the 12 months before the institution of our TH protocol met the same inclusion and exclusion criteria. We recorded survival to hospital discharge, neurological status at discharge, and rates of bleeding, sepsis, pneumonia, renal failure, and dysrhythmias in the first 72 hours of treatment. RESULTS: Mortality rates were 71.1% (95% CI, 56-86%) for 38 patients treated with TH and 72.3% (95% CI 59-86%) for 47 controls. In the TH group, 8% of patients (95% CI, 0-17%) had a good neurological outcome on discharge, compared to 0 (95% CI 0-8%) in the control group. In 17 patients with VF/VT treated with TH, mortality was 47% (95% CI 21-74%) and 18% (95% CI 0-38%) had good neurological outcome; in 9 control patients with VF/VT, mortality was 67% (95% CI 28-100%), and 0% (95% CI 0-30%) had good neurological outcome. The groups were well-matched with respect to sex and age. Complication rates were similar or favored the TH group. CONCLUSION: Instituting a TH protocol for OHCA patients with any presenting rhythm appears safe in a community hospital ED. A trend towards improved neurological outcome in TH patients was seen, but did not reach significance. Patients with VF appeared to derive more benefit from TH than patients with other rhythms.

Inhibition of Escherichia coli RecA by rationally redesigned N-terminal helix.

Bacterial RecA promotes the development and transmission of antibiotic resistance genes by self-assembling into an ATP-hydrolyzing filamentous homopolymer on single-stranded DNA. We report the design of a 29mer peptide based on the RecA N-terminal domain involved in intermonomer contact that inhibits RecA filament assembly with an IC50 of 3 microM.