Eradication of Staphylococcus epidermidis within Biofilms: Comparison of Systemic versus Supratherapeutic Concentrations of Antibiotics.

Biofilm-forming bacterial infections result in clinical failure, recurring infections, and high health care costs. The antibiotic concentrations needed to eradicate biofilm require further research. We aimed to model an in vitro prosthetic joint infection (PJI) to elucidate the activity of traditional systemic concentrations versus supratherapeutic concentrations to eradicate a Staphylococcus epidermidis biofilm PJI. We evaluated S. epidermidis high-biofilm-forming (ATCC 35984) and low-biofilm-forming (ATCC 12228) isolates in an in vitro pharmacodynamic biofilm reactor model with chromium cobalt coupons to simulate prosthetic joint infection. Vancomycin, daptomycin, levofloxacin, and minocycline were used alone and combined with rifampin to evaluate the effect of biofilm eradication. We simulated three exposures: (i) humanized systemic dosing alone, (ii) supratherapeutic doses (1,000× MIC), and (iii) and dosing in combination with rifampin. Resistance development was monitored throughout the study. Simulated humanized systemic doses of a lipoglycopeptide (daptomycin), a fluoroquinolone (levofloxacin), a tetracycline (minocycline), and a glycopeptide (vancomycin) alone failed to eradicate a formed S. epidermidis biofilm. Supratherapeutic doses of vancomycin (2,000 µg/mL) and minocycline (15 µg/mL) with or without rifampin (15 µg/mL) failed to eradicate biofilms. However, a levofloxacin supratherapeutic dose (125 µg/mL) with rifampin eradicated the high-biofilm-producing isolate by 48 h. Interestingly, supratherapeutic-dose exposures of daptomycin (500 µg/mL) alone eradicated high- and low-biofilm-forming isolates in established biofilms. The concentrations needed to eradicate biofilms on foreign materials are not obtained with systemic dosing regimens. The failure of systemic dosing regimens to eradicate biofilms validates clinical findings with recurring infections. The addition of rifampin to supratherapeutic dosing regimens does not result in synergy. Supratherapeutic daptomycin dosing may be effective at the site of action to eradicate biofilms. Further studies are needed.

Treatment, clinical outcomes, and predictors of mortality among a national cohort of hospitalized patients with Stenotrophomonas maltophilia infection.

OBJECTIVES: To analyze treatment, clinical outcomes, and predictors of inpatient mortality in hospitalized patients with Stenotrophomonas maltophilia infection. STUDY DESIGN: Retrospective cohort study. METHODS: We included patients admitted to Veterans Affairs hospitals nationally with S. maltophilia cultures and treatment from 2010 to 2019. We described patient and clinical characteristics, antibiotic treatment, and clinical outcomes. Univariate and multivariable logistic regression were used to evaluate predictors of inpatient mortality. RESULTS: We identified 3891 hospitalized patients treated for an S. maltophilia infection, of which 13.7% died during admission. The most common antibiotic agents were piperacillin/tazobactam (39.7%), sulfamethoxazole/trimethoprim (23.3%), and levofloxacin (23.2%). Combination therapy was used in 16.6% of patients. Independent predictors of inpatient mortality identified in multivariable analysis included the following: presence of current acute respiratory failure (adjusted odds ratio [aOR] 4.74, 95% confidence interval [CI] 3.63-6.19), shock (aOR 3.00, 95% CI 2.31-3.90), acute renal failure (aOR 2.06, 95% CI 1.64-2.60), and septicemia (aOR 1.90, 95% CI 1.49-2.42), age 65 years and older (aOR 2.05, 95% CI 1.07-3.94, reference age 18-49 years), hospital-acquired infection (aOR 1.87, 95% CI 1.48-2.37), Black (aOR 1.58, 95% CI 1.21-2.06) and other races (aOR 1.65, 95% CI 1.41-2.41, reference White), liver disease (aOR 1.51, 95% CI 1.02-2.22), and median Charlson comorbidity score or higher (aOR 1.36, 95% CI 1.08-1.71, reference less than median). Clinical outcomes were similar between patients infected with sulfamethoxazole/trimethoprim-resistant, levofloxacin-resistant, and multidrug-resistant S. maltophilia strains compared to non-resistant strains. CONCLUSIONS: In our national cohort of hospitalized patients with S. maltophilia infection, 13.7% of patients died during admission and several predictors of inpatient mortality were identified. Predictors related to the severity of infection were among the strongest identified. It is important that in severely ill patients presenting to the hospital, S. maltophilia be considered as a cause.

Predictors of potentially suboptimal treatment of urinary tract infections in long-term care facilities.

BACKGROUND: Suboptimal antibiotic treatment of urinary tract infection (UTI) is high in long-term care facilities (LTCFs) and likely varies between facilities. Large-scale evaluations have not been conducted. AIM: To identify facility-level predictors of potentially suboptimal treatment of UTI in Veterans Affairs (VA) LTCFs and to quantify variation across facilities. METHODS: This was a retrospective cohort study of 21,938 residents in 120 VA LTCFs (2013-2018) known as Community Living Centers (CLCs). Potentially suboptimal treatment was assessed from drug choice, dose frequency, and/or treatment duration. To identify facility characteristics predictive of suboptimal UTI treatment, LTCFs with higher and lower rates of suboptimal treatment (≥median, < median) were compared using unconditional logistic regression models. Joinpoint regression models were used to quantify average percentage difference across facilities. Multilevel logistic regression models were used to quantify variation across facilities. FINDINGS: The rate of potentially suboptimal antibiotic treatment varied from 1.7 to 34.2 per 10,000 bed-days across LTCFs. The average percentage difference in rates across facilities was 2.5% (95% confidence interval (CI): 2.4-2.7). The only facility characteristic predictive of suboptimal treatment was the incident rate of UTI per 10,000 bed-days (odds ratio: 4.9; 95% CI: 2.3-10.3). Multilevel models demonstrated that 94% of the variation between facilities was unexplained after controlling for resident and CLC characteristics. The median odds ratio for the full multilevel model was 1.37. CONCLUSION: Potentially suboptimal UTI treatment was variable across VA LTCFs. However, most of the variation across LTCFs was unexplained. Future research should continue to investigate factors that are driving suboptimal antibiotic treatment in LTCFs.

Inhibition of bacterial growth and biofilm production by constituents from Hypericum spp.

Biofilm embedded bacterial pathogens such as Staphylococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii are difficult to eradicate and are major sources of bacterial infections. New drugs are needed to combat these pathogens. Hypericum is a plant genus that contains species known to have antimicrobial properties. However, the specific constituents responsible for the antimicrobial properties are not entirely known, nor have most compounds been tested as inhibitors of biofilm development. The investigation presented here tested seven secondary metabolites isolated from the species Hypericum densiflorum, Hypericum ellipticum, Hypericum prolificum, and Hypericum punctatum as inhibitors of bacterial growth and biofilm production. Assays were conducted against Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii. Five of the seven compounds demonstrated growth inhibition against the Gram-positive bacteria with minimum inhibitory concentrations (MIC) ranging from 1.95 µg/mL to 7.81 µg/mL. Four of the secondary metabolites inhibited biofilm production by certain Gram-positive strains at sub-MIC concentrations.

Changing epidemiology of methicillin-resistant Staphylococcus aureus in the Veterans Affairs Healthcare System, 2002-2009.

PURPOSE: The epidemiology of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is changing. Temporal trends and differences between healthcare settings must be described in order to better predict future risk factors associated with this dangerous bacterial infection. METHODS: A national MRSA-infected cohort was identified from 2002 to 2009 in the Veterans Affairs Healthcare System of the United States: hospital (HOS), long-term care (LTC), and outpatient (OPT). We analyzed within-setting time trends using generalized linear mixed models and between-setting differences with χ(2) and Wilcoxon rank-sum tests. RESULTS: The incidence of S. aureus, methicillin-susceptible S. aureus (MSSA), and MRSA infections increased significantly over time in all three settings based on modeled annual percentage changes (P < 0.001). MRSA incidence rates rose by 14, 10, and 37% per year in the HOS, LTC, and OPT settings, respectively. Among 56,345 MRSA-infected patients, the comorbidity burden was highest among LTC inpatients (n = 4,427) and lowest among outpatients (n = 7,250), with an average absolute difference in specific comorbidities of +2 and -7%, respectively, compared to HOS inpatients (n = 44,668). Over time, there was a significant (P ≤ 0.02) decrease in previous inpatient admissions and surgeries (all settings); diabetes with complications and surgical site infections (HOS, OPT); and median length of stay and inpatient mortality (HOS, LTC). Alternatively, obesity, chronic renal disease, and depression were more common between 2002 and 2009 (P ≤ 0.02). CONCLUSIONS: Over the past 8 years, we observed significant changes in the epidemiology of MRSA infections, including decreases in traditional MRSA risk factors, improvements in clinical outcomes, and increases in other patient characteristics that may affect risk.

Risk factors associated with mupirocin resistance in meticillin-resistant Staphylococcus aureus.

Implementation of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation programmes has been increasing and the emergence of mupirocin resistance has been reported. However, the patient-level risk factors associated with mupirocin resistance are not clear. In this study, independent predictors of mupirocin resistance in MRSA among Providence Veterans Affairs Medical Center patients with MRSA-positive culture dates between 1 July 2004 and 30 June 2008 were identified using a frequency-matched case-control study. Forty cases (mupirocin-resistant) were matched on culture date quarter and year to 270 controls (mupirocin-susceptible). The adjusted conditional logistic regression model identified three significant independent predictors associated with mupirocin resistance in MRSA: (1) exposure to mupirocin in the year prior to the culture date [odds ratio (OR): 9.84; 95% confidence interval (CI): 2.93-33.09]; (2) Pseudomonas aeruginosa infection in the year before the culture-related admission (4.85; 1.20-19.61); and (3) cefepime use in the year prior to culture (2.80; 1.03-7.58). In sensitivity analyses, previous mupirocin exposure was associated with low-level [minimum inhibitory concentration (MIC) 8-128mg/L; 23 cases, 202 controls; OR: 6.32; 95% CI: 1.58-25.33] and high-level (MIC ≥256mg/L; 17 cases, 151 controls; OR: 11.18; 95% CI: 1.89-66.30) mupirocin resistance. To our knowledge, this is the first case-control study to reveal a strong association between previous mupirocin exposure and subsequent mupirocin resistance in MRSA, with demonstrated robustness in low- and high-level mupirocin resistance. Mupirocin susceptibility monitoring is critical for facilities instituting decolonisation with mupirocin as increased use may reduce effectiveness through resistance.

Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats.

Idiopathic hypercalciuria is the most common metabolic abnormality in patients with nephrolithiasis. Through successive inbreeding, we have developed a strain of rats whose urine calcium (UCa) excretion is approximately 8-10-fold greater than that of control rats and who spontaneously form kidney stones. We have termed these rats genetic hypercalciuric stone-forming (GHS) rats. The physiology of the hypercalciuria in the GHS rats closely parallels that of man. We have recently shown that the GHS rat kidneys have an increased number of receptors for calcium (CaR) compared to Sprague-Dawley rats, the strain of rats originally bred to develop the GHS rats. Calcimimetics, such as cinacalcet (Cin), increase the sensitivity of the CaR to Ca. The effects of Cin on UCa are complex and difficult to predict. We tested the hypothesis that Cin would alter urinary (U) Ca and supersaturation with respect to calcium hydrogen phosphate (CaHPO(4)) and calcium oxalate (CaOx). GHS or control rats were fed a normal Ca diet (0.6% Ca) for 28 days with Cin (30 mg/kg/24 h) added to the diet of half of each group for the last 14 days. The protocol was then repeated while the rats were fed a low Ca (0.02% Ca) diet. We found that Cin led to a marked reduction in circulating parathyroid hormone and a modest reduction in serum Ca. Cin did not alter UCa when the GHS rats were fed the normal Ca diet but lowered UCa when they were fed the low Ca diet. However, Cin did not alter U supersaturation with respect to either CaOx or CaHPO(4) on either diet. If these findings in GHS rats can be confirmed in man, it suggests that Cin would not be an effective agent in the treatment of human idiopathic hypercalciuria and resultant stone formation.

Latex allergy in the nursing population.

This paper analyzes the major health issue "latex allergy," and risk reduction for nurses (aggregate). First, the historical significance of latex in the environment is discussed along with our rationale for choosing latex allergy as a major health issue. Identification, description and justification of the use of Neuman's systems model are evident throughout the paper. In this model, assessment is incorporated into the nursing diagnosis of the nursing process. The second category of the nursing process, planning of actual goals, is negotiated with the client/client system. Intervention strategies are implemented in the last stage of the nursing process, nursing outcomes. The last two categories are formulated into a chart for better clarification of the goals with rationale. Lastly, an evaluation of the goals is discussed.