Faculty Bibliography

We characterized spa types, SCCmec types, and antimicrobial resistance patterns of 516 methicillin-resistant Staphylococcus aureus (MRSA) isolates, collected between 2011 and 2014 from nares and blood cultures of United States patients. Among nares isolates, 45 spa types were observed; 29.9% were t002/SCCmec II and 30.9% were t008/SCCmec IV. Among blood isolates, 40 spa types were identified; 24.4% were t002/SCCmec II and 39.9% were type t008/SCCmec IV. Compared to data from our 2009-2010 survey, the percentage of t008/SCCmec IV isolates from nares increased significantly (20.4%-30.9%; P=0.004) while the percentage from positive blood cultures remained similar (39.2% versus 39.9%; P=0.921). There were also significant changes in the overall antimicrobial resistance patterns observed, including the decrease of the clindamycin, erythromycin, levofloxacin and moxifloxacin multidrug resistance pattern, likely the result of t002/SCCmec II strains being displaced by t008/SCCmec IV strains. Rates of high-level mupirocin resistance did not change significantly from our past study (4.1% compared to 4.7%; P=0.758) but an increase in low-level resistance, particularly among t002/SCCmec II isolates, was observed.

OBJECTIVE:An increased risk of multiple myeloma (MM) has been observed among individuals with low prediagnostic circulating levels of adiponectin, a metabolic hormone that is typically underexpressed among those with overweight or obesity. To assess whether adiponectin may influence myeloma development or progression to frank MM, circulating adiponectin levels were compared across patients with different stages of MM and its precursor, monoclonal gammopathy of undetermined significance (MGUS). METHODS:Adiponectin was measured in 213 patients with MGUS, smoldering MM, or fully developed MM. Differences in adiponectin levels across patient groups were assessed using multivariate linear regression. RESULTS:Relative to MGUS patients, adiponectin levels were statistically significantly lower among those with smoldering and fully developed MM, both overall (16%-20% decrease; P = 0.048) and among those with IgG/IgA isotypes (26%-28% decrease; P = 0.004). Among MGUS patients, adiponectin levels were significantly lower for those with the higher-risk IgM isotype compared with those who had IgG/IgA isotypes (42% decrease; P = 0.036). CONCLUSIONS:The findings of this study, the largest to investigate adiponectin levels in patients with different stages of MM and the first to evaluate associations with clinical characteristics, suggest that reduced expression of adiponectin may be associated with progression from MGUS to MM.

Approximately one in five households in the United States speaks a language other than English at home. This exploratory, descriptive study sought to examine language-concordant visit patterns in an urban home health care agency serving a diverse and multilingual population. Patient care record data combined with administrative data facilitated the exploratory work. In a 2-year period, results showed that among the 238,513 visits with 18,132 limited English proficiency patients, only 20% of visits were language concordant. The study suggests that home health care services may not be meeting the demand for language services, but more research is needed to determine the right "dose" of bilingual home care visits to optimize home care outcomes and establish a standard for care.

Receptive anal intercourse and its association with sexually transmitted infections and human papillomavirus-related anal dysplasia has been well studied in various at-risk groups including men who have sex with men. However, the relationship between receptive anal intercourse and its potential complications in patients with inflammatory bowel disease is not fully understood. This narrative review discusses sexually transmitted infections and anal dysplasia in patients with inflammatory bowel disease who engage in receptive anal intercourse and the lack of evidence-based data to guide clinical practice. It addresses the psychosocial effects of stigmatization in these patients and its consequences in the clinical encounter. We review the need for sufficient data on infection, cancer prevention, and precoital and postcoital hygienic practices with hopes that future studies establish standardized guidelines and recommendations.

: The well treated HIV population remains at risk for insulin resistance and chronic immune activation. We tested the effects of acute hyperinsulinemia on inflammation in HIV. Twenty HIV-infected and 10 non-HIV-infected individuals well matched for BMI underwent oral glucose tolerance testing to stimulate insulin secretion and assess for changes in circulating soluble CD163, soluble CD14, and monocyte chemoattract protein 1. Soluble CD14 decreased significantly after stimulation of hyperinsulinemia and no significant changes in soluble CD163 or monocyte chemoattract protein 1 were demonstrated in HIV-infected and non-HIV-infected groups.

The rapid increase of carbapenem resistance in Gram-negative bacteria has resurrected the importance of the polymyxin antibiotics. The recent discovery of plasmid-mediated polymyxin resistance (mcr-1) in carbapenem-resistant Enterobacteriaceae serves as an important indicator that the golden era of antibiotics is under serious threat. We assessed the bacterial killing of 15 different FDA-approved antibiotics alone and in combination with polymyxin B in time-killing experiments against Escherichia coli MCR1_NJ, the first reported isolate in the United States to coharbor mcr-1 and a New Delhi metallo-β-lactamase gene (bla_NDM-5). The most promising regimens were advanced to the hollow-fiber infection model (HFIM), where human pharmacokinetics for polymyxin B, aztreonam, and amikacin were simulated over 240 h. Exposure to polymyxin B monotherapy was accompanied by MCR1_NJ regrowth but not resistance amplification (polymyxin B MIC from 0 to 240 h [MIC_0h to MIC_240h] of 4 mg/liter), whereas amikacin monotherapy caused regrowth and simultaneous resistance amplification (amikacin MIC_0h of 4 mg/liter versus MIC_240h of >64 mg/liter). No MCR1_NJ colonies were observed for any of the aztreonam-containing regimens after 72 h. However, HFIM cartridges for both aztreonam monotherapy and the polymyxin B-plus-aztreonam regimen were remarkably turbid, and the presence of long, filamentous MCR1_NJ cells was evident in scanning electron microscopy, suggestive of a nonreplicating persister (NRP) phenotype. In contrast, the 3-drug combination of polymyxin B, aztreonam, and amikacin provided complete eradication (>8-log₁₀ CFU/ml reduction) with suppression of resistance and prevention of NRP formation. This is the first comprehensive pharmacokinetic/pharmacodynamic study to evaluate triple-drug combinations for polymyxin- and carbapenem-resistant E. coli coproducing MCR-1 and NDM-5 and will aid in the preparation for a so-called "postantibiotic" era.IMPORTANCE A global health crisis may be on the horizon, as the golden era of antibiotics is under serious threat. We recently reported the first case in the United States of a highly resistant, Escherichia coli so-called "superbug" (MCR1_NJ), coharboring two of the most worrying antibiotic resistance genes, encoding mobile colistin resistance (mcr-1) and a New Delhi metallo-β-lactamase (bla_NDM-5). Worryingly, the medical community is vulnerable to this emerging bacterial threat because optimal treatment strategies are undefined. Here, we report the activity of an optimized combination using simulated human doses of commercially available antibiotics against MCR1_NJ. A unique triple combination involving a cocktail of polymyxin B, aztreonam, and amikacin eradicated the MCR-1- and NDM-5-producing E. coli Each antimicrobial agent administered as monotherapy or in double combinations failed to eradicate MCR1_NJ at a high inoculum. To our knowledge, this is the first study to propose 3-drug therapeutic solutions against superbugs coharboring mcr-1 and bla_NDM, seeking to prepare clinicians for future occurrences of these pathogens.

BACKGROUND:The etiology of pre-eclampsia (PE) is not yet fully understood, though current literature indicates an upregulation of inflammatory mediators produced by the placenta as a potential causal mechanism. Vitamin D is known to have anti-inflammatory properties and there is evidence of an inverse relationship between dietary calcium intake and the incidence of PE. Evidence of the role of vitamin D status and supplementation in the etiology and prevention of PE is reviewed in this article along with identification of research gaps to inform future studies. METHODS:We conducted a structured literature search using MEDLINE electronic databases to identify published studies until February 2015. These sources were retrieved, collected, indexed, and assessed for availability of pregnancy-related data on PE and vitamin D. RESULTS:Several case-control studies and cross-sectional studies have shown an association between vitamin D status and PE, although evidence has been inconsistent. Clinical trials to date have been unable to show an independent effect of vitamin D supplementation in preventing PE. CONCLUSIONS:The included clinical trials do not show an independent effect of vitamin D supplementation in preventing PE; however, issues with dose, timing, and duration of supplementation have not been completely addressed.

We describe a case of a 36-year-old man with a history of chronic hepatitis C who presented with abdominal pain 3 days after undergoing a percutaneous ultrasound-guided liver biopsy. Initial investigations revealed a venobiliary fistula with haemobilia and obstructive jaundice with direct bilirubin peaking at 9.2 mg/dL. He underwent an endoscopic retrograde cholangiopancreatography with sphincterotomy and stent placement, bilirubin decreased to 3.7 mg/dL, and the patient was discharged. The patient returned with recurrent abdominal pain and upper gastrointestinal bleeding with haemoglobin of 8.6 g/dL, requiring multiple transfusions. He underwent transcatheter arterial embolisation but continued bleeding. Radiofrequency ablation was pursued and was able to achieve haemostasis. The patient was discharged. The patient returned again with a fever of 39.2 degrees C and was found to have a large right hepatic lobe abscess. The patient underwent abscess drainage with drain placement and was treated with antibiotics for 6 weeks. He followed up in the clinic with resolution of symptoms and infection.

Objectives:KPC-producing Klebsiella pneumoniae are an emerging public health problem around the globe. We defined the combinatorial pharmacodynamics and ability to suppress resistance of two 'old' antibiotics, fosfomycin and colistin, in time-kill experiments and hollow-fibre infection models (HFIM). Methods:Two KPC-2-producing K. pneumoniae isolates were used: one susceptible to both colistin and fosfomycin (KPC 9A: MIC colistin 0.25 mg/L and MIC fosfomycin ≤8 mg/L) and the other resistant to colistin and susceptible to fosfomycin (KPC 5A: MIC colistin 64 mg/L and MIC fosfomycin 32 mg/L). Time-kill experiments assessed an array of colistin and fosfomycin concentrations against both isolates. Colistin and fosfomycin pharmacokinetics from critically ill patients were simulated in the HFIM to define the pharmacodynamic activity of humanized regimens over 5 days against KPC 9A. Results:In time-kill experiments, synergy was demonstrated for all colistin/fosfomycin combinations containing >8 mg/L fosfomycin against the double-susceptible KPC strain, 9A. Synergy versus KPC strain 5A was only achieved at the highest concentrations of colistin (4 mg/L) and fosfomycin (512 mg/L) at 48 h. In the HFIM, colistin or fosfomycin monotherapies resulted in rapid proliferation of resistant subpopulations; KPC 9A regrew by 24 h. In contrast to the monotherapies, the colistin/fosfomycin combination resulted in a rapid 6.15 log 10  cfu/mL reduction of KPC 9A by 6 h and complete suppression of resistant subpopulations until 120 h. Conclusions:Colistin and fosfomycin may represent an important treatment option for KPC-producing K. pneumoniae otherwise resistant to traditional antibiotics.