Observed antagonistic effect of linezolid on daptomycin or vancomycin activity against biofilm-forming methicillin-resistant Staphylococcus aureus in an in vitro pharmacodynamic model

Pharmacodynamic activity in antibiotic combinations of daptomycin, vancomycin and linezolid was investigated in a 48h in vitro pharmacodynamic model. Using free human-simulated concentrations, activity against clinical biofilm-forming methicillin-resistant Staphylococcus aureus isolates was evaluated. Linezolid antagonized vancomycin activity at 24 and 48h. Linezolid antagonized daptomycin at 24 and 48h depending on dose and strain. Adding daptomycin increased vancomycin activity at 48h (P \u3c 0.03). These results may be strain dependent and require further clinical investigation

Overconsumption of Antibiotics

We applaud Thomas Van Boeckel and colleagues1 for their large analysis of antibiotic consumption in 71 countries. A 36% increase in use of antibiotics worldwide, 76% of which was in Brazil, Russia, India, China, and South Africa, is a concerning finding. In Europe and the USA, practitioners are increasingly aware of the importance of infection control and antimicrobial stewardship. However, 50% of antimicrobials, irrespective of setting, are used inappropriately.2,3 We agree that most increases in global antibiotic consumption are probably caused by inappropriate use and that coordinated efforts to improve antimicrobial use internationally are desperately needed

In Vitro Activities of Telavancin and Vancomycin against Biofilm-Producing Staphylococcus aureus, S. epidermidis, and Enterococcus faecalis Strains

We investigated the activities of telavancin and vancomycin against biofilm-producing Staphylococcus and Enterococcus strains. At clinically attainable concentrations, telavancin was active against bacteria embedded in biofilm (minimal biofilm eradication concentration [MBEC], 0.125 to 2 μg/ml) and inhibited biofilm formation at concentrations below the MIC. Vancomycin did not demonstrate the same activity (MBEC, ≥512 μg/ml) against Staphylococcus aureus and Enterococcus faecalis. Telavancin may have a unique role in biofilm-associated infections

470. Concomitant Antibiotic Use and Death Among a National Cohort of Veterans With Clostridium difficile Infection (CDI)

Background: Antibiotic use is a well-known risk factor for development of CDI, and there is preliminary evidence suggesting concomitant antibiotic use may result in poor outcomes, including death. This work investigated the effect of concomitant antibiotic exposure during CDI treatment on mortality among patients with CDI. Methods: We conducted a national retrospective study of Veterans with a first CDI between 2010 and 2014, defined as a positive C. difficile toxin(s) and no episode in the year prior. Those treated with guideline recommended CDI treatment were included (10–14 days of PO or IV metronidazole, PO or PR vancomycin, or fidaxomicin). The exposure of interest was any non-CDI antibiotic use during CDI treatment; and the outcome was all cause death within 30 days of the end of CDI treatment. Inverse probability of treatment weighted Cox proportional hazards models were used to estimate the effect of concomitant antibiotic use on time to mortality. Weights were derived from propensity score modeling of the probability of exposure to antibiotics during CDI treatment as a function of potential confounders. Sensitivity analyses by antibiotic class were conducted. Results: Of the 9,517 patients included in the study cohort, mean age was 65.3 years (±SD 14.6), 92.5% (n = 8,802) were male, and 75.03% (n = 7,141) were white. Half were exposed to non-CDI antibiotics during CDI treatment (51.8%, n = 4,925) and 8.9% (n = 849) died. In unadjusted and adjusted analyses, concomitant antibiotic use was associated with death (HR 5.74, 95% CI 4.75–6.93; aHR 2.39, 95% CI 2.07–2.75). Advanced generation cephalosporin (aHR 2.36, 95% CI 2.05–2.71), β-lactam/β-lactamase inhibitor combinations (aHR 1.45, 95% CI 1.16–1.82), and clindamycin (aHR 1.95, 95% CI 1.26–3.02) were associated with death, while fluoroquinolone use was not (aHR 0.97, 95% CI 0.84–1.12) Conclusion: Among our national cohort, concomitant antibiotic use was common during CDI treatment. Any concomitant antibiotic use increased the risk of death; however, results suggest risk might vary by antibiotic class. Results support continued efforts in the reduction of unnecessary antibiotic use during CDI treatment, and future studies into which antibiotics may have the least risk of death when treatment is necessary

Clinical Implications of Vancomycin Heteroresistant and Intermediately Susceptible Staphylococcus aureus

Staphylococcus aureus (S. aureus) has proven to be a major pathogen with the emergence of methicillin-resistant S. aureus (MRSA) infections and recently with heteroresistant vancomycin-intermediate S. aureus (hVISA) and vancomycin-intermediate S. aureus (VISA) infections. Although vancomycin is traditionally a first-line and relatively effective antibiotic, its continued use is under question because reports of heteroresistance in S. aureus isolates are increasing. Both hVISA and VISA infections are associated with complicated clinical courses and treatment failures. The prevalence, mechanism of resistance, clinical significance, and laboratory detection of hVISA and VISA infections are not conclusive, making it difficult to apply research findings to clinical situations. We provide an evidence-based review of S. aureus isolates expressing heterogenic and reduced susceptibility to vancomycin

Antimicrobial Stewardship Program Prompts Increased and Earlier Infectious Diseases Consultation

A recent analysis demonstrated that infectious diseases (ID) specialty intervention was associated with decreased mortality and hospital readmission. These benefits were greatest if involvement occurred within two days of hospital admission. Antimicrobial stewardship programs should augment the services of an ID specialist team and promote formal consultation. Implementation of an antimicrobial stewardship program at the Providence Veterans Affairs Medical Center was associated with an increased number of consults (increase of 72.2%) and decreased time to consult (3.5 days sooner), which might also dramatically improve patient outcomes, including mortality and readmission rates

Activity of tobramycin and polymyxin-E against Pseudomonas aeruginosa biofilm coated medical grade endotracheal tubes.

Indwelling medical devices have become a major source of nosocomial infections; especially Pseudomonas aeruginosa (P. aeruginosa) infection, which remain the most common cause of ventilator associated pneumonia (VAP) in neonates and children. Using medical grade polyvinyl chloride endotracheal tubes (ETTs), the activity of tobramycin and polymyxin-E was quantified in a simulated prevention and treatment static time kill model using biofilm forming P. aeruginosa. The model simulated three clinical conditions: 1) planktonic bacteria in the presence of antibiotics, tobramycin and polymyxin-E, without ETTs, 2) planktonic bacteria grown in the presence of P. aeruginosa, antibiotic and ETTs (simulating prevention) and 3) a 24h formed P. aeruginosa biofilm on ETTs prior to antibiotic exposure (simulating treatment). In the model simulating prevention (conditions 1 and 2 above), tobramycin alone or in combination with polymyxin-E was more bactericidal than polymyxin-E alone at 24 hours using a concentration greater than 2 times the minimum inhibitory concentration (MIC). However, after a 24h old biofilm was allowed to form on the ETTs, neither monotherapy nor combination therapy over 24 hours exhibited bactericidal or bacteriostatic effects. Against the same pathogens, tobramycin and polymyxin-E, both alone or in combination exhibited bactericidal activity prior to biofilm attachment to the ETTs, however no activity was observed once biofilm formed on ETTs. These findings support surveillance culturing to identify pathogens for a rapid and targeted approach to therapy, especially when P. aeruginosa is a potential pathogen

What is the role for metronidazole in the treatment of Clostridium difficile infection? Results from a national cohort study of Veterans with initial mild disease

Background: Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data is limited to guide clinicians in identifying these patients. Methods: Our two-stage study included a national cohort of Veterans with a first episode of mild CDI (2010–2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30-days post-treatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristic/s predictive of success identified in the first-stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. Results: Among 3,656 patients treated with metronidazole, we identified 3,282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI] 1.29 – 2.06) than age \u3e65 years. Among 115 propensity-score matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR] 0.29, 95% CI 0.06–1.38), CDI recurrence (HR 0.62, 95% CI 0.26–1.49), or failure (HR 0.50, 95% CI 0.23–1.07). Conclusion: Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger

Comparison of Telavancin and Vancomycin Antibiotic Lock Solutions in the Eradication of Biofilm-Producing Staphylococci and Enterococci from Central Venous Catheters

Purpose: Results of a study of the activity of antibiotic lock solutions of vancomycin and telavancin against biofilm-forming strains of Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus are reported. Methods: An established in vitro central venous catheter model was used to evaluate lock solutions containing vancomycin (5 mg/mL) or telavancin (5 mg/mL), with and without preservative-containing heparin sodium (with 0.45% benzyl alcohol) 2500 units/mL, heparin, and 0.9% sodium chloride solution. Lock solutions were introduced after 24-hour bacterial growth in catheters incubated at 35 °C. After 72 hours of exposure to the lock solutions, catheters were drained, flushed, and cut into segments for quantification of colony-forming units. Results: Against S. epidermidis, vancomycin and telavancin (with or without heparin) had similar activity. Against E. faecalis, vancomycin alone was more active than telavancin alone (p \u3c 0.01). Against S. aureus, vancomycin plus heparin had activity than telavancin (p \u3c 0.02). The addition of heparin was associated with reduced activity of the vancomycin lock solution against S. epidermidis and E. faecalis (p \u3c 0.01). Telavancin activity was not significantly changed with the addition of heparin. Conclusion: In a central venous catheter model, vancomycin and telavancin activity was similar in reducing biofilm-producing S. epidermidis. However, vancomycin was more active than telavancin against E. faecalis and S. aureus. None of the tested agents eradicated biofilm-forming strains. The addition of preservative-containing heparin sodium 2500 units/mL to vancomycin was associated with reduced activity against S. epidermidis and E. faecalis

Risk Factors Associated with Mupirocin Resistance in Methicillin-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) 8–128 mg/L; 23 cases, 202 controls; OR: 6.32; 95% CI: 1.58–25.33] and high-level (MIC ≥256 mg/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