Browsing by Subject "Vancomycin"
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Item Open Access A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study.(BMC Infect Dis, 2014-05-23) Stryjewski, Martin E; Lentnek, Arnold; O'Riordan, William; Pullman, John; Tambyah, Paul Anantharajah; Miró, Jose M; Fowler, Vance G; Barriere, Steven L; Kitt, Michael M; Corey, G RalphBACKGROUND: Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality. Telavancin is a bactericidal lipoglycopeptide active against Gram-positive pathogens, including methicillin-resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2 trial in patients with uncomplicated S. aureus bacteremia. METHODS: Patients were randomized to either telavancin or standard therapy (vancomycin or anti-staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid complicated S. aureus bacteremia. The primary end point was clinical cure at 84 days. RESULTS: In total, 60 patients were randomized and 58 received ≥1 study medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy 16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar proportion of CE patients were cured in the telavancin (88%) and standard therapy (89%) groups. All patients with MRSA bacteremia were cured and one patient with MSSA bacteremia failed study treatment in each group. Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms. Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%). CONCLUSIONS: This study suggests that telavancin may have utility for treatment of uncomplicated S. aureus bacteremia; additional studies are warranted. (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia (ASSURE); NCT00062647).Item Open Access Antistaphylococcal β-Lactams versus Vancomycin for Treatment of Infective Endocarditis Due to Methicillin-Susceptible Coagulase-Negative Staphylococci: a Prospective Cohort Study from the International Collaboration on Endocarditis.(Antimicrobial agents and chemotherapy, 2016-10) Carugati, M; Petti, CA; Arnold, C; Miro, JM; Pericàs, JM; Garcia de la Maria, C; Kanafani, Z; Durante-Mangoni, E; Baddley, J; Wray, D; Klein, JL; Delahaye, F; Fernandez-Hidalgo, N; Hannan, MM; Murdoch, D; Bayer, A; Chu, VHThe phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal β-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%; P = 0.27), 6-month mortality (31.6% versus 25.9%; P = 0.58), and survival time after discharge (P = 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7; P = 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE.Item Open Access CAMERA2 - combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection: study protocol for a randomised controlled trial.(Trials, 2016-03-31) Tong, Steven YC; Nelson, Jane; Paterson, David L; Fowler, Vance G; Howden, Benjamin P; Cheng, Allen C; Chatfield, Mark; Lipman, Jeffrey; Van Hal, Sebastian; O'Sullivan, Matthew; Robinson, James O; Yahav, Dafna; Lye, David; Davis, Joshua S; CAMERA2 study group and the Australasian Society for Infectious Diseases Clinical Research NetworkBACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a serious infection resulting in 20-50 % 90-day mortality. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. Surprisingly, there has been consistent in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or daptomycin and an anti-staphylococcal β-lactam antibiotic. There is also growing clinical data to support such combinations, including a recent pilot randomised controlled trial (RCT) that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone. Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia. METHODS/DESIGN: We will perform an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older) with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion. Participants will be randomised to vancomycin or daptomycin (standard therapy) given intravenously or to standard therapy plus 7 days of an anti-staphylococcal β-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4) microbiological treatment failure. The recruitment target of 440 patients is based on an expected failure rate for the primary outcome of 30 % in the control arm and the ability to detect a clinically meaningful absolute decrease of 12.5 %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients will not be evaluable for the primary endpoint. DISCUSSION: Key potential advantages of adding anti-staphylococcal β-lactams to standard therapy for MRSA bacteraemia include their safety profile, low cost, and wide availability. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02365493 . Registered 24 February 2015.Item Open Access Controlled Release of Vancomycin and Tigecycline from an Orthopaedic Implant Coating Prevents Staphylococcus aureus Infection in an Open Fracture Animal Model.(BioMed research international, 2019-01) Stavrakis, AI; Zhu, S; Loftin, AH; Weixian, X; Niska, J; Hegde, V; Segura, T; Bernthal, NMIntroduction:Treatment of open fractures routinely involves multiple surgeries and delayed definitive fracture fixation because of concern for infection. If implants were made less susceptible to infection, a one-stage procedure with intramedullary nailing would be more feasible, which would reduce morbidity and improve outcomes. Methods:In this study, a novel open fracture mouse model was developed using Staphylococcus aureus (S. aureus) and single-stage intramedullary fixation. The model was used to evaluate whether implants coated with a novel "smart" polymer coating containing vancomycin or tigecycline would be colonized by bacteria in an open fracture model infected with S. aureus. In vivo bioluminescence, ex vivo CFUs, and X-ray images were evaluated over a 42-day postoperative period. Results:We found evidence of a markedly decreased bacterial burden with the local release of vancomycin and tigecycline from the PEG-PPS polymer compared to polymer alone. Vancomycin was released in a controlled fashion and maintained local drug concentrations above the minimum inhibition concentration for S. aureus for greater than 7 days postoperatively. Bacteria were reduced 139-fold from implants containing vancomycin and undetected from the bone and soft tissue. Tigecycline coatings led to a 5991-fold reduction in bacteria isolated from bone and soft tissue and 15-fold reduction on the implants compared to polymer alone. Antibiotic coatings also prevented osteomyelitis and implant loosening as observed on X-ray. Conclusion:Vancomycin and tigecycline can be encapsulated in a polymer coating and released over time to maintain therapeutic levels during the perioperative period. Our results suggest that antibiotic coatings can be used to prevent implant infection and osteomyelitis in the setting of open fracture. This novel open fracture mouse model can be used as a powerful in vivo preclinical tool to evaluate and optimize the treatment of open fractures before further studies in humans.Item Open Access Experience with intrawound vancomycin powder for spinal deformity surgery.(Spine, 2014-01) Martin, Joel R; Adogwa, Owoicho; Brown, Christopher R; Bagley, Carlos A; Richardson, William J; Lad, Shivanand P; Kuchibhatla, Maragatha; Gottfried, Oren NStudy design
Retrospective cohort study.Objective
To evaluate the ability of local vancomycin powder to prevent deep wound infection after thoracolumbar and lumbar spinal fusion for open deformity cases.Summary of background data
Recent studies report that local delivery of vancomycin powder is associated with a decrease in spinal surgical site infection (SSI). This study compares deformity fusion cases before and after the routine application of spinal vancomycin powder.Methods
Posterior spinal deformity surgical procedures by a single institution were reviewed from January 2011 to April 2013. Routine application of vancomycin powder started in April 2012. Inclusion criteria included adult patients who underwent posterior fusion for deformity pathologies, including spondylolisthesis, kyphosis, sagittal imbalance, and scoliosis. Each cohort's baseline characteristics including infection risk factors, operative data, and rates of wound infection were compared. Associations between infection and vancomycin powder, with and without propensity score adjustment for risk factors were determined using logistic regression.Results
A total of 306 patients were included in the study. All measured baseline and operative variables were statistically similar between untreated (n = 150) and those who received vancomycin powder (n = 156). No significant change in deep wound infection rate was seen between the control (5.3%) and intervention group (5.1%, P = 0.936). Logistic regression with and without propensity score adjusted for risk factors demonstrated that the use of vancomycin powder did not impact the development of SSI (odds ratio [95% confidence interval]: 1.01 [0.36-2.79], P = 0.9910) and (odds ratio [95% confidence interval]: 0.87 [0.31-2.42], P = 0.7876), respectively.Conclusion
The local application of powdered vancomycin was not associated with a significant difference in the rate of deep SSI after spinal deformity surgery, and other treatment modalities are necessary to limit infection for this high-risk group. This study is in contrary to prior studies, which have reported a decrease in SSI with vancomycin powder.Level of evidence
2.Item Open Access Host gene expression profiling and in vivo cytokine studies to characterize the role of linezolid and vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) murine sepsis model.(PLoS One, 2013) Sharma-Kuinkel, Batu K; Zhang, Yurong; Yan, Qin; Ahn, Sun Hee; Fowler, Vance GLinezolid (L), a potent antibiotic for Methicillin Resistant Staphylococcus aureus (MRSA), inhibits bacterial protein synthesis. By contrast, vancomycin (V) is a cell wall active agent. Here, we used a murine sepsis model to test the hypothesis that L treatment is associated with differences in bacterial and host characteristics as compared to V. Mice were injected with S. aureus USA300, and then intravenously treated with 25 mg/kg of either L or V at 2 hours post infection (hpi). In vivo alpha-hemolysin production was reduced in both L and V-treated mice compared to untreated mice but the reduction did not reach the statistical significance [P = 0.12 for L; P = 0.70 for V). PVL was significantly reduced in L-treated mice compared to untreated mice (P = 0.02). However the reduction of in vivo PVL did not reach the statistical significance in V- treated mice compared to untreated mice (P = 0.27). Both antibiotics significantly reduced IL-1β production [P = 0.001 for L; P = 0.006 for V]. IL-6 was significantly reduced with L but not V antibiotic treatment [P<0.001 for L; P = 0.11 for V]. Neither treatment significantly reduced production of TNF-α. Whole-blood gene expression profiling showed no significant effect of L and V on uninfected mice. In S. aureus-infected mice, L altered the expression of a greater number of genes than V (95 vs. 42; P = 0.001). Pathway analysis for the differentially expressed genes identified toll-like receptor signaling pathway to be common to each S. aureus-infected comparison. Expression of immunomodulatory genes like Cxcl9, Cxcl10, Il1r2, Cd14 and Nfkbia was different among the treatment groups. Glycerolipid metabolism pathway was uniquely associated with L treatment in S. aureus infection. This study demonstrates that, as compared to V, treatment with L is associated with reduced levels of toxin production, differences in host inflammatory response, and distinct host gene expression characteristics in MRSA sepsis.Item Open Access Influence of vancomycin minimum inhibitory concentration on the outcome of methicillin-susceptible Staphylococcus aureus left-sided infective endocarditis treated with antistaphylococcal β-lactam antibiotics: a prospective cohort study by the International Collaboration on Endocarditis.(Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2017-08) Pericàs, JM; Messina, JA; Garcia-de-la-Mària, C; Park, L; Sharma-Kuinkel, BK; Marco, F; Wray, D; Kanafani, ZA; Carugati, M; Durante-Mangoni, E; Tattevin, P; Chu, VH; Moreno, A; Fowler, VG; Miró, JM; International Collaboration on Endocarditis Microbiology InvestigatorsObjectives
Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype.Methods
All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal β-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype.Results
Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively).Conclusions
In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal β-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire.Item Open Access Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection.(Clin Infect Dis, 2010-09-15) Corey, G Ralph; Wilcox, Mark; Talbot, George H; Friedland, H David; Baculik, Tanya; Witherell, Gary W; Critchley, Ian; Das, Anita F; Thye, DirkBACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated skin and skin-structure infection (cSSSI). Increasing antimicrobial resistance in cSSSI has led to a need for new safe and effective therapies. Ceftaroline was evaluated as treatment for cSSSI in 2 identical phase 3 clinical trials, the pooled analysis of which is presented here. The primary objective of each trial was to determine the noninferiority of the clinical cure rate achieved with ceftaroline monotherapy, compared with that achieved with vancomycin plus aztreonam combination therapy, in the clinically evaluable (CE) and modified intent-to-treat (MITT) patient populations. METHODS: Adult patients with cSSSI requiring intravenous therapy received ceftaroline (600 mg every 12 h) or vancomycin plus aztreonam (1 g each every 12 h) for 5-14 days. RESULTS: Of 1378 patients enrolled in both trials, 693 received ceftaroline and 685 received vancomycin plus aztreonam. Baseline characteristics of the treatment groups were comparable. Clinical cure rates were similar for ceftaroline and vancomycin plus aztreonam in the CE (91.6% vs 92.7%) and MITT (85.9% vs 85.5%) populations, respectively, as well as in patients infected with MRSA (93.4% vs 94.3%). The rates of adverse events, discontinuations because of an adverse event, serious adverse events, and death also were similar between treatment groups. CONCLUSIONS: Ceftaroline achieved high clinical cure rates, was efficacious against cSSSI caused by MRSA and other common cSSSI pathogens, and was well tolerated, with a safety profile consistent with the cephalosporin class. Ceftaroline has the potential to provide a monotherapy alternative for the treatment of cSSSI. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00424190 for CANVAS 1 and NCT00423657 for CANVAS 2.Item Open Access Intrawound Vancomycin Decreases the Risk of Surgical Site Infection After Posterior Spine Surgery: A Multicenter Analysis.(Spine, 2018-01) Devin, Clinton J; Chotai, Silky; McGirt, Matthew J; Vaccaro, Alexander R; Youssef, Jim A; Orndorff, Douglas G; Arnold, Paul M; Frempong-Boadu, Anthony K; Lieberman, Isador H; Branch, Charles; Hedayat, Hirad S; Liu, Ann; Wang, Jeffrey C; Isaacs, Robert E; Radcliff, Kris E; Patt, Joshua C; Archer, Kristin RStudy design
Secondary analysis of data from a prospective multicenter observational study.Objective
The aim of this study was to evaluate the occurrence of surgical site infection (SSI) in patients with and without intrawound vancomycin application controlling for confounding factors associated with higher SSI after elective spine surgery.Summary of background data
SSI is a morbid and expensive complication associated with spine surgery. The application of intrawound vancomycin is rapidly emerging as a solution to reduce SSI following spine surgery. The impact of intrawound vancomycin has not been systematically studied in a well-designed multicenter study.Methods
Patients undergoing elective spine surgery over a period of 4 years at seven spine surgery centers across the United States were included in the study. Patients were dichotomized on the basis of whether intrawound vancomycin was applied. Outcomes were occurrence of SSI within postoperative 30 days and SSI that required return to the operating room (OR). Multivariable random-effect log-binomial regression analyses were conducted to determine the relative risk of having an SSI and an SSI with return to OR.Results
.: A total of 2056 patients were included in the analysis. Intrawound vancomycin was utilized in 47% (n = 966) of patients. The prevalence of SSI was higher in patients with no vancomycin use (5.1%) than those with use of intrawound vancomycin (2.2%). The risk of SSI was higher in patients in whom intrawound vancomycin was not used (relative risk (RR) -2.5, P < 0.001), increased number of levels exposed (RR -1.1, P = 0.01), and those admitted postoperatively to intensive care unit (ICU) (RR -2.1, P = 0.005). Patients in whom intrawound vancomycin was not used (RR -5.9, P < 0.001), increased number of levels were exposed (RR-1.1, P = 0.001), and postoperative ICU admission (RR -3.3, P < 0.001) were significant risk factors for SSI requiring a return to the OR.Conclusion
The intrawound application of vancomycin after posterior approach spine surgery was associated with a reduced risk of SSI and return to OR associated with SSI.Level of evidence
2.Item Open Access New Approaches To Studying Non-Covalent Molecular Interactions In Nano-Confined Environments(2010) Carlson, David AndrewThe goal of this work is to develop novel molecular systems, functionalization techniques, and data collection routines with which to study the binding of immobilized cognate binding partners. Our ultimate goal is the routine evaluation of thermodynamic parameters for immobilized systems through interpretation of the variation of the binary probability of binding as a function of soluble ligand concentration. The development of both data collection routines that minimize non-specific binding and functionalization techniques that produce stable ordered molecular systems on surfaces are of paramount importance towards achievement of this goal. Methodologies developed here will be applied to investigating the thermodynamics of multivalent systems.
In the first part of this work, the effect of contact force on molecular recognition force microscopy experiments was investigated. Increased contact forces (>250 pN) resulted in increased probabilities of binding and decreased blocking efficiencies for the cognate ligand-receptor pair lactose-G3. Increased contact force applied to two control systems with no known affinity, mannose-G3 and lactose-KDPG aldolase resulted in non-specific ruptures that were indistinguishable from those of specific lactose-G3 interactions. Thus, it is essential to design data collections routines that minimize contact forces to ensure that ruptures originate from specific, blockable interactions.
In the second part of this work we report the first example of the preparation of stable self assembled monolayers through hydrosilylation of a protected aminoalkene onto hydrogen-terminated silicon nitride AFM probes and subsequent conjugation with biomolecules for force microscopy studies. Our technique can be used as a general attachment technique for other molecular systems.
In the third part of this work we develop novel molecular systems for tethering oriented vancomycin and its cognate binding partner L-Lys-D-Ala-D-Ala to surfaces and AFM tips. Unbinding experiments demonstrated that traditional methods for forming low surface density amine layers (silanization with APTMS and etherification with ethanolamine) provided molecular constructs which displayed probabilities of binding that were too low and showed overall variability too high to use for probabilistic evaluation of thermodynamics parameters. Instability and heat-induced polymerization of APTMS layers on tips and surfaces also prohibited their utility. Formation of Alkyl SAMs on silicon provides a more reliable, stable molecular system anchored by Si-C bonds that facilitates attachment of vancomycin and is capable of withstanding prolonged exposure to heated organic and aqueous environments. It follows that covalent immobilization of KDADA to silicon nitride AFM tips via Si-C bonds using hydrosilylation chemistry will be similarly advantageous. These methods offer great promise for probabilistic evaluation of thermodynamic parameters characterizing immobilized binding partners and will permit unambiguous determination of the role of multivalency in ligand binding, using an experimental configuration in which intermolecular binding and aggregation are precluded.
Item Open Access Panton-Valentine leukocidin is not the primary determinant of outcome for Staphylococcus aureus skin infections: evaluation from the CANVAS studies.(PLoS One, 2012) Tong, Amy; Tong, Steven YC; Zhang, Yurong; Lamlertthon, Supaporn; Sharma-Kuinkel, Batu K; Rude, Thomas; Ahn, Sun Hee; Ruffin, Felicia; Llorens, Lily; Tamarana, Ganesh; Biek, Donald; Critchley, Ian; Fowler, Vance GThe impact of Panton-Valentine leukocidin (PVL) on the severity of complicated skin and skin structure infections (cSSSI) caused by Staphylococcus aureus is controversial. We evaluated potential associations between clinical outcome and PVL presence in both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolates from patients enrolled in two large, multinational phase three clinical trials assessing ceftaroline fosamil for the treatment of cSSSI (the CANVAS 1 and 2 programs). Isolates from all microbiologically evaluable patients with monomicrobial MRSA or MSSA infections (n = 473) were genotyped by PCR for pvl and underwent pulsed-field gel electrophoresis (PFGE). Genes encoding pvl were present in 266/473 (56.2%) isolates. Infections caused by pvl-positive S. aureus were associated with younger patient age, North American acquisition, and presence of major abscesses (P<0.001 for each). Cure rates of patients infected with pvl-positive and pvl-negative S. aureus were similar overall (93.6% versus 92.8%; P = 0.72), and within MRSA-infected (94.5% vs. 93.1%; P = 0.67) and MSSA-infected patients (92.2% vs. 92.7%; P = 1.00). This finding persisted after adjustment for multiple patient characteristics. Outcomes were also similar when USA300 PVL+ and non-USA300 PVL+ infections were compared. The results of this contemporary, international study suggest that pvl presence was not the primary determinant of outcome in patients with cSSSI due to either MRSA or MSSA.Item Open Access Uncovering the Harms of Treating Clostridioides difficile Colonization.(mSphere, 2021-01-13) Polage, Christopher R; Turner, Nicholas APatients with toxin-negative Clostridioides difficile-positive diarrhea are often treated with oral vancomycin with the assumption that treatment is more beneficial than harmful. However, this hypothesis has never been formally tested, and recent studies suggest that most such patients recover quickly without treatment and can be colonized rather than infected. Fishbein et al. conducted a prospective, placebo-controlled randomized trial to systematically evaluate the effects, risks, and benefits of oral vancomycin in these patients (S. R. S. Fishbein, T. Hink, K. A. Reske, C. Cass, et al., mSphere 6:e00936-20, 2020, https://doi.org/10.1128/mSphere.00936-20). Although small, the results are intriguing and suggest the adverse antibiotic-induced effects of vancomycin outweigh the clinical benefit when colonization is more likely than disease.