Early switch to oral antibiotic therapy in patients with low-risk neutropenic sepsis (EASI-SWITCH): a randomized non-inferiority trial.

OBJECTIVES: To determine whether early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications is non-inferior to switching later. METHODS: This non-inferiority, parallel-group, randomized, open-label clinical trial enrolled UK adults hospitalized with neutropenic sepsis. Participants were randomly assigned to either switch to oral ciprofloxacin plus co-amoxiclav within 12-24 hours or to continue intravenous treatment for at least 48 hours. The primary outcome was a composite measure of treatment failure, 14 days after randomization. The non-inferiority margin was 15%. RESULTS: There were 129 participants from 16 centres and 125 were assessed for the primary outcome. Of these, 113 patients completed protocolized treatment and comprised the per-protocol population. In total, 9 (14.1%) of 64 patients in the standard care arm met the primary end point, compared with 15 (24.6%) of 61 in the early switch arm, giving a risk difference of 10.5% (1-sided 95% CI, -∞% to 22%; p 0.14). In the per-protocol population, 8 (13.3%) of the 60 patients in the standard care arm met the primary end point, compared with 9 (17%) of 53 in the intervention arm giving a risk difference of 3.7% (one-sided 95% CI, -∞% to 14.8%; p 0.59). Duration of hospital stay was shorter in the intervention arm (median 2 [inter-quartile range (IQR) 2-3] vs. 3 days [IQR 2-4]; p 0.002). DISCUSSION: Although non-inferiority of early oral switch was found in the per-protocol population, the intervention was not non-inferior in the intent-to-treat population.

Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis (the EASI-SWITCH trial): study protocol for a randomised controlled trial.

BACKGROUND: Neutropenic sepsis remains a common treatment complication for patients receiving systemic anti-cancer treatment. The UK National Institute for Health and Care Excellence have not recommended switching from empirical intravenous antibiotics to oral antibiotics within 48 h for patients assessed as low risk for septic complications because of uncertainty about whether this would achieve comparable outcomes to using intravenous antibiotics for longer. The UK National Institute for Health Research funded the EASI-SWITCH trial to tackle this uncertainty. METHODS: The trial is a pragmatic, randomised, non-inferiority trial that aims to establish the clinical and cost-effectiveness of early switching from intravenous to oral antibiotics in cancer patients with low-risk neutropenic sepsis. Patients ≥ 16 years, receiving systemic anti-cancer treatment (acute leukaemics/stem cell transplants excluded), with a temperature of > 38 °C, neutrophil count ≤ 1.0 × 109/L, MASCC (Multinational Association of Supportive Care in Cancer) score ≥ 21 and receiving IV piperacillin/tazobactam or meropenem for less than 24 h are eligible to participate. Patients are randomised 1:1 either (i) to switch to oral ciprofloxacin and co-amoxiclav within 12-24 h of commencing intravenous antibiotics, completing at least 5 days total antibiotics (intervention), or (ii) to continue intravenous antibiotics for at least 48 h, with ongoing antibiotics being continued at the physician's discretion (control). Patients are discharged home when their physician deems it appropriate. The primary outcome measure is a composite of treatment failures as assessed at day 14. The criteria for treatment failure include fever persistence or recurrence 72 h after starting intravenous antibiotics, escalation from protocolised antibiotics, hospital readmission related to infection/antibiotics, critical care support or death. Based on a 15% treatment failure rate in the control group and a 15% non-inferiority margin, the recruitment target is 230 patients. DISCUSSION: If the trial demonstrates non-inferiority of early switching to oral antibiotics, with potential benefits for patient quality of life and resource savings, this finding will have significant implications for the routine clinical management of those with low-risk neutropenic sepsis. TRIAL REGISTRATION: ISRCTN: 84288963. Registered on the 1 July 2015. https://doi.org/10.1186/ISRCTN84288963. EudraCT: 2015-002830-35.

Tea tree oil (5%) body wash versus standard care (Johnson's Baby Softwash) to prevent colonization with methicillin-resistant Staphylococcus aureus in critically ill adults: a randomized controlled trial.

OBJECTIVES: To determine whether the daily use of 5% tea tree oil (TTO) body wash (Novabac 5% Skin Wash) compared with standard care [Johnson's Baby Softwash (JBS)] had a lower incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization. PATIENTS: The study setting was two intensive care units (ICUs; mixed medical, surgical and trauma) in Northern Ireland between October 2007 and July 2009. The study population comprised 391 patients who were randomized to JBS or TTO body wash. METHODS: This was a Phase 2/3, prospective, open-label, randomized, controlled trial. TRIAL REGISTRATION: ISRCTN65190967. The primary outcome was new MRSA colonization during ICU stay. Secondary outcomes included the incidence of MRSA bacteraemia and maximum increase in sequential organ failure assessment score. RESULTS: A total of 445 patients were randomized to the study. After randomization, 54 patients were withdrawn; 30 because of a positive MRSA screen at study entry, 11 due to lack of consent, 11 were inappropriately randomized and 2 had adverse reactions. Thirty-nine (10%) patients developed new MRSA colonization (JBS n = 22, 11.2%; TTO body wash n = 17, 8.7%). The difference in percentage colonized (2.5%, 95% CI - 8.95 to 3.94; P = 0.50) was not significant. The mean maximum increase in sequential organ failure assessment score was not significant (JBS 1.44, SD 1.92; TTO body wash 1.28, SD 1.79; P = 0.85) and no study patients developed MRSA bacteraemia. CONCLUSIONS: Compared with JBS, TTO body wash cannot be recommended as an effective means of reducing MRSA colonization.

Ciprofloxacin use and susceptibility of Gram-negative organisms to quinolone and non-quinolone antibiotics.

OBJECTIVES: A Trust strategy to reduce ciprofloxacin use was implemented at a University hospital. This study aimed to investigate whether the susceptibility of Gram-negative organisms (GNO) to alternative antimicrobials (co-amoxiclav, doxycycline, aztreonam, piperacillin/tazobactam, meropenem and gentamicin) changed, and whether there was any relationship between GNO susceptibility to these antimicrobials and ciprofloxacin usage. METHODS: The first isolate of each GNO from blood cultures, sputum and urine of hospitalized adults, between January 2008 and August 2009, was included. Antibiotic usage and GNO susceptibility were investigated using linear regression. The association between defined daily dose/1000 occupied bed days (DDD/1000 OBD) and susceptibility was assessed using Pearson correlation and linear regression. RESULTS: Ciprofloxacin use decreased significantly by 4.37 DDD/1000 OBD per month [95% confidence interval (CI) 2.99, 5.75; P < 0.001], while aztreonam and gentamicin use increased significantly (aztreonam: 0.22 DDD/1000 OBD increase per month; 95% CI 0.10, 0.34; P = 0.001; gentamicin: 0.46 DDD/1000 OBD increase per month; 95% CI 0.12, 0.79; P = 0.01). There was no change in meropenem, co-amoxiclav, doxycycline or piperacillin/tazobactam use. When DDD/1000 OBD for all non-quinolone antimicrobials were pooled, use increased significantly by 3.33 DDD/1000 OBD per month (95% CI 0.79, 5.87; P = 0.013). There were 5410 GNO isolates. A significant increase was recorded in the proportion of GNO susceptible to ciprofloxacin (0.55% increase in susceptibility per month; 95% CI 0.38, 0.72; P < 0.001), aztreonam (1.87% susceptibility increase per month; 95% CI 1.18, 2.55; P < 0.001), piperacillin/tazobactam (0.18% susceptibility increase per month; 95% CI 0.03, 0.33; P = 0.021), meropenem (0.27% susceptibility increase per month; 95% CI 0.08, 0.47; P = 0.009) and gentamicin (0.17% susceptibility increase per month; 95% CI 0.04, 0.29; P = 0.011). An inverse association between ciprofloxacin use and susceptibility to ciprofloxacin (P < 0.001), piperacillin/tazobactam (P = 0.12), aztreonam (P= 0.002), meropenem (P = 0.015) and gentamicin (P = 0.034) is suggested. CONCLUSIONS: These data demonstrate reduced ciprofloxacin usage and concomitant increasing GNO susceptibility to ß-lactams. While definitive evidence of a causal relationship is beyond the capability of a single-centre study, the results suggest that reducing quinolone exposure may exert a favourable effect on the quinolone, ß-lactam and gentamicin susceptibility of GNO.

A randomized controlled trial of tea tree oil (5%) body wash versus standard body wash to prevent colonization with methicillin-resistant Staphylococcus aureus (MRSA) in critically ill adults: research protocol.

BACKGROUND: Over the past ten years MRSA has become endemic in hospitals and is associated with increased healthcare costs. Critically ill patients are most at risk, in part because of the number of invasive therapies that they require in the intensive care unit (ICU). Washing with 5% tea tree oil (TTO) has been shown to be effective in removing MRSA on the skin. However, to date, no trials have evaluated the potential of TTO body wash to prevent MRSA colonization or infection. In addition, detecting MRSA by usual culture methods is slow. A faster method using a PCR assay has been developed in the laboratory, but requires evaluation in a large number of patients. METHODS/DESIGN: This study protocol describes the design of a multicentre, phase II/III prospective open-label randomized controlled clinical trial to evaluate whether a concentration of 5% TTO is effective in preventing MRSA colonization in comparison with a standard body wash (Johnsons Baby Softwash) in the ICU. In addition we will evaluate the cost-effectiveness of TTO body wash and assess the effectiveness of the PCR assay in detecting MRSA in critically ill patients. On admission to intensive care, swabs from the nose and groin will be taken to screen for MRSA as per current practice. Patients will be randomly assigned to be washed with the standard body wash or TTO body wash. On discharge from the unit, swabs will be taken again to identify whether there is a difference in MRSA colonization between the two groups. DISCUSSION: If TTO body wash is found to be effective, widespread implementation of such a simple colonization prevention tool has the potential to impact on patient outcomes, healthcare resource use and patient confidence both nationally and internationally.