Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial

Importance: The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. Objective: To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. Design, Setting, and Participants: A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. Interventions: Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. Main Outcomes and Measures: Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. Results: Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6]). Conclusions and Relevance: Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm. Trial Registration: ClinicalTrials.gov Identifier: NCT01191840

Rhodococcus Bacteremia in Cancer Patients Is Mostly Catheter Related and Associated with Biofilm Formation

Rhodococcus is an emerging cause of opportunistic infection in immunocompromised patients, most commonly causing cavitary pneumonia. It has rarely been reported as a cause of isolated bacteremia. However, the relationship between bacteremia and central venous catheter is unknown. Between 2002 and 2010, the characteristics and outcomes of seventeen cancer patients with Rhodococcus bacteremia and indwelling central venous catheters were evaluated. Rhodococcus bacteremias were for the most part (94%) central line-associated bloodstream infection (CLABSI). Most of the bacteremia isolates were Rhodococcus equi (82%). Rhodococcus isolates formed heavy microbial biofilm on the surface of polyurethane catheters, which was reduced completely or partially by antimicrobial lock solution. All CLABSI patients had successful response to catheter removal and antimicrobial therapy. Rhodococcus species should be added to the list of biofilm forming organisms in immunocompromised hosts and most of the Rhodococcus bacteremias in cancer patients are central line associated

Fusion and Binary-Decay Mechanisms in the 35^{35}Cl+24^{24}Mg System at E/A ≈\approx 8 MeV/Nucleon

Compound-nucleus fusion and binary-reaction mechanisms have been investigated for the $^{35}$Cl+$^{24}$Mg system at an incident beam energy of E$_{Lab}$= 282 MeV. Charge distributions, inclusive energy spectra, and angular distributions have been obtained for the evaporation residues and the binary fragments. Angle-integrated cross sections have been determined for evaporation residues from both the complete and incomplete fusion mechanisms. Energy spectra for binary fragment channels near to the entrance-channel mass partition are characterized by an inelastic contribution that is in addition to a fully energy damped component. The fully damped component which is observed in all the binary mass channels can be associated with decay times that are comparable to, or longer than the rotation period. The observed mass-dependent cross sections for the fully damped component are well reproduced by the fission transition-state model, suggesting a fusion followed by fission origin. The present data cannot, however, rule out the possibility that a long-lived orbiting mechanism accounts for part or all of this yield.Comment: 41 pages standard REVTeX file, 14 Figures available upon request -

Sphingomonas paucimobilis-related bone and soft-tissue infections: A systematic review

Background: Sphingomonas paucimobilis is an emerging opportunistic bacterium with a particular tropism toward bones and soft tissues. It is a gram-negative rod that can infect immunosuppressed or immunocompetent individuals in the community or hospital settings. Prognosis of infected patients is generally good, but morbidity and mortality cases have both been documented. Objectives: To present and discuss all reported Sphingomonas paucimobilis-mediated bone and soft-tissue infections, and shed light upon the relevance of this organism in orthopaedic surgery. Data sources: Pubmed and Cochrane Library. Study eligibility criteria: Studies reporting at least one human bone or soft-tissue infection due to Sphingomonas paucimobilis. Results: Ten articles describing 19 patients met the inclusion criteria. Common infections included osteomyelitis, cellulitis, and septic arthritis. Fifteen patients (78.9%) had community-acquired diseases. All patients were successfully treated with antibiotic therapy and only one (5.3%) had a residual complication. Limitations: The study included a small sample size presenting with bone or soft-tissue infections. Some cases had lacking data. Conclusion: Despite being associated with a good prognosis in most cases, Sphingomonas paucimobilis-related orthopaedic infections may exhibit some complications. Keywords: Sphingomonas paucimobilis, Bone, Soft tissue, Infection

Insights on the Role of Antimicrobial Cuffed Endotracheal Tubes in Preventing Transtracheal Transmission of VAP Pathogens from an In Vitro Model of Microaspiration and Microbial Proliferation

We developed an in vitro model to evaluate the effect of different cuffed endotracheal tubes (ETTs) on transtracheal transmission of ventilator-associated pneumonia (VAP) pathogens along external surfaces of ETTs. The model independently assessed the relative contributions of microbial proliferation to the distal tip and microaspiration of contaminated secretions past the cuff by testing in three modes: microaspiration only, microbial proliferation only, and simultaneous microaspiration and microbial proliferation. We evaluated transmission of methicillin resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PA) in the presence of a standard ETT; a soft, tapered cuff ETT with subglottic suctioning; and a novel antimicrobial gendine (combination of gentian violet and chlorhexidine) ETT in the model. In the microaspiration only mode, when leakage past the cuff occurred quickly, no ETT prevented transmission. When microaspiration was delayed, the gendine ETT was able to completely disinfect the fluid above the cuff and thereby prevent transmission of pathogens. In microbial proliferation only mode, the gendine ETT was the sole ETT that prevented transmission. With both mechanisms simultaneously available, transmission was dependent on how long microaspiration was delayed. Potent antimicrobial ETTs, such as a gendine ETT, can make unique contributions to prevent VAP when microaspiration is gradual

Optimal Antimicrobial Catheter Lock Solution, Using Different Combinations of Minocycline, EDTA, and 25-Percent Ethanol, Rapidly Eradicates Organisms Embedded in Biofilm

Antimicrobial lock solutions may be needed to salvage indwelling catheters in patients requiring continuous intravenous therapy. We determined the activity of minocycline, EDTA, and 25% ethanol, alone or in combination, against methicillin-resistant Staphylococcus aureus and Candida parapsilosis catheter-related bloodstream infection strains in two established models of biofilm colonization. Biofilm-colonized catheter segments from a modified Robbins device and a silicone disk biofilm colonization model were exposed to these antimicrobial agents for 15 or 60 min, respectively. After exposure, segments were sonicated and cultured. To determine regrowth after incubation at 37°C, following the brief exposure to the antimicrobial agents, an equal number of segments were washed, reincubated for 24 h, and then sonicated and cultured. The triple combination of minocycline-EDTA (M-EDTA) in 25% ethanol was the only antimicrobial lock solution that completely eradicated S. aureus and C. parapsilosis in biofilm of all segments tested in the two models, and it completely prevented regrowth. In addition, M-EDTA in 25% ethanol was significantly more effective in rapidly eradicating the growth or regrowth of methicillin-resistant S. aureus and C. parapsilosis biofilm colonization in the two models than the other solutions—minocycline, EDTA, M-EDTA, 25% ethanol, and EDTA in ethanol. We conclude that M-EDTA in 25% ethanol is highly effective at rapidly eradicating S. aureus and C. parapsilosis embedded in biofilm adhering to catheter segments

EDTA as an Adjunct Antifungal Agent for Invasive Pulmonary Aspergillosis in a Rodent Model

Rats immunosuppressed by the administration of cyclophosphamide and cortisone acetate and then infected with Aspergillus fumigatus were treated with an antifungal drug, EDTA, or a combination of one of the antifungal agents, amphotericin B lipid complex (ABLC; 5 mg/kg of body weight/day for 7 days), and EDTA (30 mg/kg/day for 7 days). The mortality rate was reduced, the duration of survival was increased, fewer A. fumigatus organisms were recovered from the lungs, and less-severe lung lesions were seen histopathologically in the rats receiving the combination treatment than in the rats receiving either an antifungal agent or EDTA alone. Further studies regarding the mechanisms of EDTA and its interactions with ABLC are warranted, and further studies are needed to more fully examine the safety, tolerance, and optimal dosing of EDTA in the treatment of this and other fungal infections