Conflicts of interest and industry professional relationships in psychiatric neurosurgery: a comparative literature review.

OBJECTIVE The research required to establish that psychiatric treatments are effective often depends on collaboration between academic clinical researchers and industry. Some of the goals of clinical practice and those of commercial developers of psychiatric therapies overlap, such as developing safe and effective treatments. However, there might also be incompatible goals; physicians aim to provide the best care they can to their patients, whereas the medical industry ultimately aims to develop therapies that are commercially successful. In some cases, however, clinical research may be aiming both at improved patient care and commercial success. It is in these cases that a conflict of interest (COI) arises. The goal of this study was to identify differences and commonalities regarding COIs between 2 kinds of somatic psychiatric interventions: pharmacological and neurosurgical. METHODS The authors conducted a study focused on professional concerns regarding pharmacological and neurosurgical psychiatric interventions. They used medical and bioethics journal articles as an indicator of professionals' concerns and carried out a thematic content analysis of peer-reviewed articles published between 1960 and 2015, using PubMed and Google Scholar. RESULTS One hundred thirty-seven relevant articles were identified, of which 86 papers focused primarily on psychopharmacology and 51 on neurosurgery. The intervention most discussed in the psychiatric neurosurgery data set was deep brain stimulation (n = 42). While there were no significant differences at the level of categories, pharmacological and neurosurgical interventions differ in the underlying themes discussed. Two issues widely discussed in the articles on pharmaceutical interventions, but largely neglected in the neurosurgery articles, were medical professional issues and industry involvement. CONCLUSIONS COIs are a neglected issue in the discussion of ethics concerns regarding medical devices in psychiatry. Yet as these interventions become more common, it is important to address them in part through learning from the discussion regarding COIs in the pharmaceutical industry and by developing approaches to address those aspects of COIs that are unique to the medical device industry.

Flocked nylon swabs versus RODAC plates for detection of multidrug-resistant organisms on environmental surfaces in intensive care units.

To compare two culture methods [nylon fiber flocked swabs with broth enrichment versus RODAC ('replicate organism detection and counting') plates] for recovery of multidrug-resistant organisms, 780 environmental surfaces in 63 rooms of patients on contact precautions in four intensive care units at one hospital were examined. Among sites that had at least one positive culture, swab culture with broth enrichment detected the target organisms more frequently than RODAC plates (37.5% vs 26.0%, P = 0.06). There was moderate agreement between the two methods (κ = 0.44) with agreement better for small or flat surfaces compared to large or irregular surfaces.

Post-flood measurement of fungal bio-aerosol in a resource-limited hospital: can the settle plate method be used?

The performance of the settle plate method (SPM) compared with the microbiological air sampler method (MAS) for post-flood fungal bio-aerosol (FB) measurement was evaluated in a Thai hospital. Compared with closed-ventilation units, open-ventilation units had significantly higher median FB level by SPM on days 3 and 5 of incubation (270 vs 90 colony-forming units (cfu)/m(3) and 420 vs 180 cfu/m(3), respectively). Strong correlations between SPM and MAS results on day 3 (r = 1.60, P < 0.001) and day 5 (r = 1.49, P = 0.002) of incubation suggested the utility of SPM for post-flood FB measurement in open-ventilation units in resource-limited situations.

Interventional evaluation of environmental contamination by vancomycin-resistant enterococci: failure of personnel, product, or procedure?

It is not clear whether improvement in environmental decontamination is more efficiently achieved through changes in cleaning products, cleaning procedures, or performance of cleaning personnel. To assess the impact of cleaning performance on environmental contamination with vancomycin-resistant enterococci (VRE), we conducted a sequential trial in which a multifaceted environmental cleaning improvement intervention was introduced in a medical intensive care unit and respiratory step-down unit. The intervention included educational lectures for housekeepers and an observational programme of their activities without changes in cleaning products or written procedures. Following these interventions, the proportion of environmental sites cleaned improved from 49% to 85% (P<0.001); contamination of environmental sites declined from 21% to 8% (P<0.0001) before cleaning and from 13% to 8% (P<0.0001) after cleaning. The improved cleaning and contamination rates persisted in a washout period. In a multivariate model, cleaning thoroughness strongly influenced the degree of environmental contamination, with a 6% decline in VRE prevalence with every 10% increase in percentage of sites cleaned. These findings suggest that surface contamination with VRE is due to a failure to clean rather than to a faulty cleaning procedure or product.

Nosocomial acquisition of Pseudomonas aeruginosa resistant to both ciprofloxacin and imipenem: a risk factor and laboratory analysis.

In vitro, ciprofloxacin can select for dual resistance to fluoroquinolones and imipenem in Pseudomonas aeruginosa via a mutation in the regulatory gene, mexT, which downregulates OprD and upregulates MexEF-OprN. We performed a nested case-control study of patients in two medical intensive care units participating in an observational cohort study. Patients colonized or infected with P. aeruginosa resistant to both ciprofloxacin and imipenem (cases) were compared to controls. The presence of OprD and OprN from cases was evaluated by Western blot. In total, 44 cases were compared to 132 controls. Imipenem exposure [adjusted odds ratio (AOR) = 11.4, p = 0.044] was significantly associated with case status, but fluoroquinolone use was not (AOR = 1.0, p = 0.998). Neither OprD nor OprN were detected in any isolate. Fluoroquinolone use was not a risk factor for acquisitions of dually resistant P. aeruginosa. The absence of OprN in these isolates suggests that dual resistance is not due to mexT mutations.

Comparison of multiple-locus variable-number tandem repeat analysis and pulsed-field gel electrophoresis in a setting of polyclonal endemicity of vancomycin-resistant Enterococcus faecium.

In order to assess whether multiple-locus-variable number tandem repeat analysis (MLVA) could replace pulsed-field gel electrophoresis (PFGE) for genotyping vancomycin-resistant isolates of Enterococcus faecium (VREF), this study compared the typeability, discriminatory power, concordance and costs of these methods for VREF isolates obtained from patients, environmental samples and the hands of healthcare workers (HCWs) in a medical intensive care unit (ICU) where VREF was endemic. Over a 58-day period, 393 VREF isolates (373 vanA, one vanA/B, 19 vanB) were cultured from patient rectal swabs (n = 76), the environment (n = 270) and the hands of HCWs (n = 47). PFGE was able to divide 358 (91.1%) isolates into 19 PFGE types (>six bands different) and 24 subtypes (one to three bands different). MLVA was able to type 391 (99.5%) isolates into 11 genotypes. The discriminatory power of PFGE subtypes was 83%, as compared to 68% for MLVA. Concordance between the two methods, based on matched or mismatched MLVA types and PFGE types or subtypes, was 67.5% and 82.8%, respectively. Using PFGE, 13 isolates could be genotyped in 3 days; MLVA genotyped 94 isolates in 2 days. For both methods, the estimated costs were Euro 7 ($10)/isolate. PFGE and MLVA produced highly concordant results when assigning genotypes to nosocomial VREF isolates. MLVA was faster, but PFGE subtyping was more discriminatory.

Epidemiology and outcomes of community-associated methicillin-resistant Staphylococcus aureus infection.

Over a 2-year period (2003 to 2005) patients with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-acquired methicillin-susceptible Staphylococcus aureus (CA-MSSA) infections were prospectively identified. Patients infected with CA-MRSA (n = 102 patients) and CA-MSSA (n = 102 patients) had median ages of 46 and 53 years, respectively; the most common sites of infection in the two groups were skin/soft tissue (80 and 93%, respectively), respiratory tract (13 and 6%, respectively), and blood (4 and 1%, respectively). Fourteen percent of patients with CA-MRSA infections and 3% of patients with CA-MSSA infections had household contacts with similar infections (P < 0.01). Among the CA-MRSA isolates, the pulsed-field gel electrophoresis (PFGE) groups detected were USA300 (49%) and USA100 (13%), with 27 PFGE groups overall; 71% of the isolates were staphylococcal chromosome cassette mec (SCCmec) type IV, 29% were SCCmec type II, and 54% had the Panton-Valentine leucocidin (PVL) gene. Among the CA-MSSA isolates there were 33 PFGE groups, with isolates of the USA200 group comprising 11%, isolates of the USA600 group comprising 11%, isolates of the USA100 group comprising 10%, and isolates of the PVL type comprising 10%. Forty-six and 18% of the patients infected with CA-MRSA and CA-MSSA, respectively, were hospitalized (P < 0.001). Fifty percent of the patients received antibiotic therapy alone, 5% received surgery alone, 30% received antibiotics and surgery, 3% received other therapy, and 12% received no treatment. The median durations of antibiotic therapy were 12 and 10 days in the CA-MRSA- and CA-MSSA-infected patients, respectively; 48 and 56% of the patients in the two groups received adequate antimicrobial therapy, respectively (P < 0.001). The clinical success rates of the initial therapy in the two groups were 61 and 84%, respectively (P < 0.001); recurrences were more common in the CA-MRSA group (recurrences were detected in 18 and 6% of the patients in the two groups, respectively [P < 0.001]). CA-MRSA was an independent predictor of clinical failure in multivariate analysis (odds ratio, 3.4; 95% confidence interval, 1.7 to 6.9). In the community setting, the molecular characteristics of the S. aureus strains were heterogeneous. CA-MRSA infections were associated with a more adverse impact on outcome than CA-MSSA infections.

Herpes simplex virus hepatitis: expanding the spectrum of disease.

We describe 2 transplant patients with herpes simplex virus (HSV) hepatitis who were minimally symptomatic throughout their illness. The spectrum of disease caused by HSV hepatitis is more variable than previously reported in this population. HSV hepatitis should be considered in immunocompromised hosts with elevated transaminases without evidence of fulminant hepatic necrosis.

Development of Daptomycin resistance in vivo in methicillin-resistant Staphylococcus aureus.

Daptomycin is a new lipopeptide antibiotic that is rapidly bactericidal against Staphylococcus aureus. We report daptomycin resistance and treatment failure in 2 patients with osteomyelitis due to methicillin-resistant S. aureus. Disk diffusion susceptibility testing failed to detect resistance. Daptomycin at high concentration retained bactericidal activity against resistant isolates.

Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. a prospective multicenter study.

BACKGROUND: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. DESIGN: Prospective observational study. SETTING: Four academic medical centers and a community hospital. PATIENTS: All patients with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.

Effectiveness of gloves in the prevention of hand carriage of vancomycin-resistant enterococcus species by health care workers after patient care.

Gloving reduces acquisition of vancomycin-resistant Enterococcus species (VRE) on the hands, and it should be considered for routine inpatient care, even for contact with the intact skin of patients who may be colonized with VRE. However, gloving does not completely prevent contamination of the hands, and hand washing is necessary after glove removal.

Insights into the epidemiology and control of infection with vancomycin-resistant enterococci.

Despite control efforts, the incidence of nosocomial infections due to vancomycin-resistant enterococci (VRE) continues to increase in the United States. VRE are thought to spread primarily by cross-contamination. Recent molecular epidemiologic studies have refined our understanding of this phenomenon. If VRE are not controlled soon after introduction into a hospital, sporadic cases may evolve into a monoclonal outbreak, which may then evolve to polyclonal endemicity. An intervention that is effective in containing VRE in one setting may be ineffective in another. Control of VRE where they are endemic is particularly challenging. Although eradication of endemic VRE may not be possible, aggressive, multifaceted programs have been successful in diminishing the problem. A mathematical model of transmission of VRE and the effect of infection control measures in settings where they are endemic has been reported. The use of such a model may allow more precise determination of the impact of control strategies in the future.

The changing molecular epidemiology and establishment of endemicity of vancomycin resistance in enterococci at one hospital over a 6-year period.

The contributions of clonal spread, transfer of genetic elements, and introduction of new strains to the establishment of endemicity of vancomycin-resistant enterococci (VRE) were determined. The study took place at one hospital between 1990, when VRE were first detected, and 1996, when endemicity had become established. Isolates from 183 patients were categorized into 24 strain types by pulsed-field gel electrophoresis; the resistance genotype was determined by polymerase chain reaction. Between 1990 and 1993, 69% of patients were infected with the same vanB Enterococcus faecium strain. VanA resistance was not detected until 1993, but in 1996, the ratio of vanA to vanB was 2.2:1. Over time, 8 vanA strains were detected; a 35- or 40-kb conjugative vanA plasmid was found in 4 of the 8 strains. Clonal spread was a major factor in the establishment of endemicity. Transfer of genetic elements and introduction of new strain types were detected less often. However, these events may have been equally important evolutionarily.

The role of "colonization pressure" in the spread of vancomycin-resistant enterococci: an important infection control variable.

OBJECTIVE: The spread of nosocomial multiresistant microorganisms is affected by compliance with infection control measures and antibiotic use. We hypothesized that "colonization pressure" (ie, the proportion of other patients colonized) also is an important variable. We studied the effect of colonization pressure, compliance with infection control measures, antibiotic use, and other previously identified risk factors on acquisition of colonization with vancomycin-resistant enterococci (VRE). METHODS: Rectal colonization was studied daily for 19 weeks in 181 consecutive patients who were admitted to a single medical intensive care unit. A statistical model was created using a Cox proportional hazards regression model including length of stay in the medical intensive care unit until acquisition of VRE, colonization pressure, personnel compliance with infection control measures (hand washing and glove use), APACHE (Acute Physiology and Chronic Health Evaluation) 11 scores, and the proportion of days that a patient received vancomycin or third-generation cephalosporins, sucralfate, and enteral feeding. RESULTS: With survival until colonization with VRE as the end point, colonization pressure was the most important variable affecting acquisition of VRE (hazard ratio [HR], 1.032; 95% confidence interval [C1], 1.012-1.052; P=.002). In addition, enteral feeding was associated with acquisition of VRE (HR, 1.009; 95% CI, 1.000-1.017; P=.05), and there was a trend toward association of third-generation cephalosporin use with acquisition (HR, 1.007; 95% CI, 0.999-1.015; P=.11). The effects of enteral feeding and third-generation cephalosporin use were more important when colonization pressure was less than 50%. Once colonization pressure was 50% or higher, these other variables hardly affected acquisition of VRE. CONCLUSIONS: Acquisition of VRE was affected by colonization pressure, the use of antibiotics, and the use of enteral feeding. However, once colonization pressure was high, it became the major variable affecting acquisition of VRE.

Stability of vancomycin-resistant enterococcal genotypes isolated from long-term-colonized patients.

Genotypic variation and stability of isolates of vancomycin-resistant enterococci (VRE) were studied to determine genetic diversity and whether strain definition based on pulsed-field gel electrophoresis (PFGE) is applicable to an endemic setting. Twenty-two PFGE types were identified among 455 VRE isolates. One-on-one comparisons of 10 vanA Enterococcus faecium strain types all yielded > 10 band differences. Variations among vanA and vanB E. faecium isolates from individual long-term-colonized (4-160 days) patients yielded < 3 band differences for > 85% of comparisons. Comparison of all strains without grouping by vancomycin resistance types yielded two peaks of band differences: one with < 3 and one with > 10 band differences. These data show that VRE isolates were genetically closely related or very different; demonstrate that within individual patients, VRE isolates show little genetic variation; and provide empirical evidence that PFGE can be used to study the epidemiology of VRE endemicity.

External sources of vancomycin-resistant enterococci for intensive care units.

OBJECTIVE: The incidence of colonization and infection with vancomycin-resistant enterococci (VRE) has increased dramatically in the last 5 yrs, especially in intensive care units (ICUs). We studied VRE-colonization in patients on admission to a medical ICU (MICU) where VRE colonization is endemic. DESIGN: Prospective, descriptive analysis. SETTING: An MICU of a public hospital. PATIENTS: Three hundred and one consecutively admitted patients. MEASUREMENTS AND MAIN RESULTS: Rectal swabs were obtained on admission from all patients. VRE isolates from all colonized patients were genetically fingerprinted by pulsed-field gel-electrophoresis (PFGE). Forty-three (14%) of 301 patients were colonized with VRE on MICU admission. Three (7%) of these 43 patients were admitted directly from the community without prior hospital contact. Risk of colonization on admission was related to the length of stay in the hospital before MICU-admission (odds ratio 4.65 for patients with a stay of at least 3 days) and previous in-hospital use of antibiotics. Of 22 VRE PFGE strain types recognized in the MICU during the study period, four (18%) were introduced by patients admitted directly from the community and ten (45%) were introduced by patients admitted from other hospital wards. CONCLUSIONS: These results show that although ICUs are considered epicenters for antibiotic resistance, sources extraneous to our MICU (e.g., other wards) contributed the majority of VRE strain types in the unit.

Heterogeneous expression of glycopeptide resistance in enterococci associated with transfer of vanB.

In mating experiments using a clinical strain that constitutively expresses vanB-encoded glycopeptide resistance, resistance transfer was detectable at a frequency of <10(-7) transconjugants/donor. Vancomycin MICs for transconjugants were 2- to 10-fold lower than those for the donor; both inducibly and constitutively resistant transconjugants were obtained. These findings demonstrate that the transfer of vanB among enterococci can be associated with substantial alterations in the level and control of glycopeptide resistance expression.