scholarly journals Nasal Methicillin-Resistant Staphylococcus aureus (MRSA) PCR Testing Reduces the Duration of MRSA-Targeted Therapy in Patients with Suspected MRSA Pneumonia

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Nidhu Baby ◽  
Andrew C. Faust ◽  
Terri Smith ◽  
Lyndsay A. Sheperd ◽  
Laura Knoll ◽  
...  

ABSTRACT The objective of this study was to evaluate the impact of pharmacist-ordered methicillin-resistant Staphylococcus aureus (MRSA) PCR testing on the duration of empirical MRSA-targeted antibiotic therapy in patients with suspected pneumonia. This is a retrospective analysis of patients who received vancomycin or linezolid for suspected pneumonia before and after the implementation of a pharmacist-driven protocol for nasal MRSA PCR testing. Patients were included if they were adults of >18 years of age and initiated on vancomycin or linezolid for suspected MRSA pneumonia. The primary endpoint was the duration of vancomycin or linezolid therapy. After screening 368 patients, 57 patients met inclusion criteria (27 pre-PCR and 30 post-PCR). Baseline characteristics were similar between the two groups, with the majority of patients classified as having health care-associated pneumonia (68.4%). The use of the nasal MRSA PCR test reduced the mean duration of MRSA-targeted therapy by 46.6 h (74.0 ± 48.9 h versus 27.4 ± 18.7 h; 95% confidence interval [CI], 27.3 to 65.8 h; P < 0.0001). Fewer patients in the post-PCR group required vancomycin serum levels and dose adjustment (48.1% versus 16.7%; P = 0.02). There were no significant differences between the pre- and post-PCR groups regarding days to clinical improvement (1.78 ± 2.52 versus 2.27 ± 3.34; P = 0.54), length of hospital stay (11.04 ± 9.5 versus 8.2 ± 7.8; P = 0.22), or hospital mortality (14.8% versus 6.7%; P = 0.41). The use of nasal MRSA PCR testing in patients with suspected MRSA pneumonia reduced the duration of empirical MRSA-targeted therapy by approximately 2 days without increasing adverse clinical outcomes.

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Atul K. Verma ◽  
Christopher Bauer ◽  
Vijaya Kumar Yajjala ◽  
Shruti Bansal ◽  
Keer Sun

ABSTRACT Postinfluenza methicillin-resistant Staphylococcus aureus (MRSA) infection can quickly develop into severe, necrotizing pneumonia, causing over 50% mortality despite antibiotic treatments. In this study, we investigated the efficacy of antibiotic therapies and the impact of S. aureus alpha-toxin in a model of lethal influenza virus and MRSA coinfection. We demonstrate that antibiotics primarily attenuate alpha-toxin-induced acute lethality, even though both alpha-toxin-dependent and -independent mechanisms significantly contribute to animal mortality after coinfection. Furthermore, we found that the protein synthesis-suppressing antibiotic linezolid has an advantageous therapeutic effect on alpha-toxin-induced lung damage, as measured by protein leak and lactate dehydrogenase (LDH) activity. Importantly, using a Panton-Valentine leucocidin (PVL)-negative MRSA isolate from patient sputum, we show that linezolid therapy significantly improves animal survival from postinfluenza MRSA pneumonia compared with vancomycin treatment. Rather than improved viral or bacterial control, this advantageous therapeutic effect is associated with a significantly attenuated proinflammatory cytokine response and acute lung damage in linezolid-treated mice. Together, our findings not only establish a critical role of alpha-toxin in the extreme mortality of secondary MRSA pneumonia after influenza but also provide support for the possibility that linezolid could be a more effective treatment than vancomycin to improve disease outcomes.


2006 ◽  
Vol 27 (10) ◽  
pp. 1018-1024 ◽  
Author(s):  
Kwan Kew Lai ◽  
Sally Fontecchio ◽  
Zita Melvin ◽  
Stephen P. Baker

Objective:Colonized and infected inpatients are major reservoirs for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), and transient carriage of these pathogens on the hands of healthcare workers remains the most common mechanism of patient-to-patient transmission. We hypothesized that use of alcohol-based, waterless hand antiseptic would lower the incidence of colonization and/or infection with MRSA and VRE.Methods.On June 19, 2001, alcohol hand antiseptic was introduced at the University campus and not the nearby Memorial campus of the University of Massachusetts Medical School (Worcester, MA), allowing us to evaluate the impact of this antiseptic on the incidence of MRSA and VRE colonization and infection. From January 1 through December 31, 2001, the incidence of MRSA colonization or infection was compared between the 2 campuses before and after the hand antiseptic was introduced. Its effect on VRE colonization and infection was only studied in the medical intensive care unit at the University campus.Results.At the University campus, the incidence of MRSA colonization or infection decreased from 1.26 cases/1,000 patient-days before the intervention to 0.75 cases/1,000 patient-days after the intervention, for a 1.46-fold decrease (95% confidence interval, 1.04-2.58; P = .037). At the Memorial campus, the incidence of MRSA colonization or infection remained virtually unchanged, from 0.34 cases/1,000 patient-days to 0.49 cases/1,000 patient-days during the same period. However, a separate analysis of the University campus data that controlled for proximity to prevalent cases did not show a significant improvement in the rates of infection or colonization. The incidence of nosocomial VRE colonization or infection before and after the hand antiseptic decreased from 12.0 cases/1,000 patient-days to 3.0 cases/1,000 patient-days, a 2.25-fold decrease (P = .018). Compliance with rectal surveillance for detection of VRE was 86% before and 84% after implementation of the hand antiseptic intervention. The prevalences of VRE cases during these 2 periods were 25% and 29%, respectively (P = .017).Conclusions.Alcohol hand antiseptic appears to be effective in controlling the transmission of VRE. However, after controlling for proximity to prevalent cases (ie, for clustering), it does not appear to be more effective than standard methods for controlling MRSA. Further controlled studies are needed to evaluate its effectiveness.


2013 ◽  
Vol 58 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Thomas J. Dilworth ◽  
Omar Ibrahim ◽  
Pamela Hall ◽  
Jora Sliwinski ◽  
Carla Walraven ◽  
...  

ABSTRACTVancomycin (VAN) is often used to treat methicillin-resistantStaphylococcus aureus(MRSA) bacteremia despite a high incidence of microbiological failure. Recentin vitroanalyses of β-lactams in combination with VAN demonstrated synergistic activity against MRSA. The goal of this study was to examine the impact of combination therapy with VAN and a β-lactam (Combo) on the microbiological eradication of MRSA bacteremia compared to VAN alone. This was a retrospective cohort study of patients with MRSA bacteremia who received Combo therapy or VAN alone. Microbiological eradication of MRSA, defined as a negative blood culture obtained after initiation of therapy, was used to evaluate the efficacy of each regimen. A total of 80 patients were included: 50 patients in the Combo group and 30 patients in the VAN-alone group. Microbiological eradication was achieved in 48 patients (96%) in the Combo group compared to 24 patients (80%) in the VAN-alone group (P= 0.021). In a multivariable model, the Combo treatment had a higher likelihood of achieving microbiological eradication (adjusted odds ratio, 11.24; 95% confidence interval, 1.7 to 144.3;P= 0.01). In patients with infective endocarditis (n= 22), 11/11 (100%) who received Combo therapy achieved microbiological eradication compared to 9/11 (81.8%) treated with VAN alone, but the difference was not statistically significant (P= 0.20). Patients with MRSA bacteremia who received Combo therapy were more likely to experience microbiological eradication of MRSA than patients who received VAN alone.


2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Anubhav Kanwar ◽  
Jennifer L. Cadnum ◽  
Annette L. Jencson ◽  
Curtis J. Donskey

ABSTRACT We examined the impact of systemic antibiotics on the burden of nasal Staphylococcus aureus in hospitalized patients. Of 1,482 patients, 237 (16%) had nasal methicillin-susceptible S. aureus (MSSA) and 92 (6%) had nasal methicillin-resistant S. aureus (MRSA) on admission. Treatment regimens that included agents with inhibitory activity against MRSA or MSSA significantly reduced the burden of carriage, whereas regimens lacking anti-MRSA activity, including fluoroquinolones, promoted MRSA overgrowth.


2016 ◽  
Vol 60 (4) ◽  
pp. 2311-2317 ◽  
Author(s):  
Sandra Aedo ◽  
Alexander Tomasz

ABSTRACTResistance to beta-lactam antibiotics in methicillin-resistantStaphylococcus aureus(MRSA) requires the presence of an acquired genetic determinant,mecAormecC, which encode penicillin-binding protein PBP2A or PBP2A′, respectively. Although all MRSA strains share a mechanism of resistance, the phenotypic expression of beta-lactam resistance shows considerable strain-to-strain variation. The stringent stress response, a stress response that results from nutrient limitation, was shown to play a key role in determining the resistance level of an MRSA strain. In the present study, we validated the impact of the stringent stress response on transcription and translation ofmecAin the MRSA clinical isolate strain N315, which also carries known regulatory genes (mecI/mecR1/mecR2andblaI/blaR1) formecAtranscription. We showed that the impact of the stringent stress response on the resistance level may be restricted to beta-lactam resistance based on a “foreign” determinant such asmecA, as opposed to resistance based on mutations in the nativeS. aureusdeterminantpbpB(encoding PBP2). Our observations demonstrate that high-level resistance mediated by the stringent stress response follows the current model of beta-lactam resistance in which the native PBP2 protein is also essential for expression of the resistance phenotype. We also show that theStaphylococcus sciuri pbpDgene (also calledmecAI), the putative evolutionary precursor ofmecA, confers oxacillin resistance in anS. aureusstrain, generating a heterogeneous phenotype that can be converted to high and homogenous resistance by induction of the stringent stress response in the bacteria.


mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Sarah L. Baines ◽  
Kathryn E. Holt ◽  
Mark B. Schultz ◽  
Torsten Seemann ◽  
Brian O. Howden ◽  
...  

ABSTRACTInfections caused by highly successful clones of hospital-associated methicillin-resistantStaphylococcus aureus(HA-MRSA) are a major public health burden. The globally dominant sequence type 239 (ST239) HA-MRSA clone has persisted in the health care setting for decades, but the basis of its success has not been identified. Taking a collection of 123 ST239 isolates spanning 32 years, we have used population-based functional genomics to investigate the evolution of this highly persistent and successful clone. Phylogenetic reconstruction and population modeling uncovered a previously unrecognized distinct clade of ST239 that was introduced into Australia from Asia and has perpetuated the epidemic in this region. Functional analysis demonstrated attenuated virulence and enhanced resistance to last-line antimicrobials, the result of two different phenomena, adaptive evolution within the original Australian ST239 clade and the introduction of a new clade displaying shifts in both phenotypes. The genetic diversity between the clades allowed us to employ genome-wide association testing and identify mutations in other essential regulatory systems, includingwalKR, that significantly associate with and may explain these key phenotypes. The phenotypic convergence of two independently evolving ST239 clades highlights the very strong selective pressures acting on HA-MRSA, showing that hospital environments have favored the accumulation of mutations in essential MRSA genes that increase resistance to antimicrobials, attenuate virulence, and promote persistence in the health care environment. Combinations of comparative genomics and careful phenotypic measurements of longitudinal collections of clinical isolates are giving us the knowledge to intelligently address the impact of current and future antibiotic usage policies and practices on hospital pathogens globally.IMPORTANCEMethicillin-resistantStaphylococcus aureus(MRSA) is responsible for innumerable drug-resistant health care-associated infections globally. This study, the first to investigate the evolutionary response of hospital-associated MRSA (HA-MRSA) over many decades, demonstrates how MRSA can persist in a region through the reintroduction of a previously unrecognized distinct clade. This study also demonstrates the crucial adaptive responses of HA-MRSA to the highly selective environment of the health care system, the evolution of MRSA isolates to even higher levels of antibiotic resistance at the cost of attenuated virulence. However,in vivopersistence is maintained, resulting in a clone of HA-MRSA able to resist almost all antimicrobial agents and still cause invasive disease in the heavily compromised hosts found in modern health care settings.


2003 ◽  
Vol 98 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Kanna K. Gnanalingham ◽  
Ashraf Elsaghier ◽  
Christopher Kibbler ◽  
Colin Shieff

Object. Methicillin-resistant Staphylococcus aureus (MRSA) infection is a growing problem worldwide. To investigate the severity of the problem, the authors surveyed the incidence of MRSA colonization and infection in the neurosurgical unit at their institution. Methods. Patients colonized or infected with MRSA who had been treated in the neurosurgical unit between 1993 and 1999 were retrospectively identified from laboratory records. There were 203 patients with MRSA-positive cultures, and the incidence of infection increased between 1993 (16 cases; 1.9% of admissions) and 1999 (60 cases; 6.7% of admissions). The mean duration of hospital stay was longer in patients with MRSA than in all patients treated in the unit (33.6 compared with 10.3 days, p < 0.001). Methicillin-resistant S. aureus was isolated from the nose in 89 patients, the throat in 79, the perineum in 52, surgical wounds in 16, sputum in 15, blood in 10, and from multiple sites in 69 patients. Fifty-six patients (28%) were infected with MRSA, and there were 15 deaths, of which three (20%) were likely to be due to the infection. The sources of MRSA included the neurosurgical ward in 84 patients, the intensive care unit in 28, other hospitals in 39, and the community in 17. The common strains of MRSA isolated were epidemic (E)MRSA-16 (110 cases) and EMRSA-15 (31 cases). The microorganism was eradicated in 16 cases, not eradicated in 20, and 167 patients were discharged from the hospital before eradication was achieved. All MRSA isolates were sensitive to vancomycin and teicoplanin and there was reduced sensitivity to mupirocin. Conclusions. Infection with MRSA is a growing problem in the neurosurgical population, and most cases are hospital-acquired and are associated with longer hospital stays. Asymptomatic colonization by this organism is far more common than infection of the surgical wound, although there is still morbidity due to MRSA sepsis. Most patients with MRSA are discharged before eradication of infection is achieved, thus increasing the risk that the infection will spread in the community. Strict adherence to the basic principles of infection control is the key to eradication of MRSA.


2011 ◽  
Vol 55 (5) ◽  
pp. 2018-2025 ◽  
Author(s):  
Susan Boyle-Vavra ◽  
Marcus Jones ◽  
Brett L. Gourley ◽  
Michael Holmes ◽  
Rebecca Ruf ◽  
...  

ABSTRACTWe describe here a clinical daptomycin treatment failure in a patient with recurrent methicillin-resistantStaphylococcus aureus(MRSA) bacteremia in whom daptomycin was administered after a failed empirical treatment course with vancomycin and piperacillin-tazobactam. We had the opportunity to compare the genome sequences of an isogenic pair of daptomycin-susceptible and -resistant MRSA isolates obtained before and after initiation of daptomycin therapy, respectively. The genotype of both isolates was USA800, ST5, SCCmectype IV,agrtype II. There was no increase in cell wall thickness in the daptomycin-resistant strain despite having decreased susceptibility to both vancomycin and daptomycin. By comparing the genome sequences by pyrosequencing, we identified a polymorphism (S337L) in the tenth transmembrane segment of the multiple peptide resistance factor, MprF, encoding lysyl phosphatidylglycerol transferase. This enzyme has been shown previously to promote repulsion of daptomycin at the cell surface by addition of positively charged lysine to phosphatidylglycerol. Also, thehlbopen reading frame (ORF) encoding the β-toxin was interrupted by a prophage in the daptomycin-susceptible strain; this phage was missing in the daptomycin-resistant isolate and thehlbORF was restored. Loss of the phage in the resistant isolate also resulted in loss of the virulence factor genesclpP,scn, andsak. This is the first study to use pyrosequencing to compare the genomes of a daptomycin-susceptible/resistant MRSA isolate pair obtained during failed daptomycin therapy in humans.


2013 ◽  
Vol 57 (9) ◽  
pp. 4410-4416 ◽  
Author(s):  
Lidia Kardaś-Słoma ◽  
Pierre-Yves Boëlle ◽  
Lulla Opatowski ◽  
Didier Guillemot ◽  
Laura Temime

ABSTRACTInterventions designed to reduce antibiotic consumption are under way worldwide. While overall reductions are often achieved, their impact on the selection of antibiotic-resistant selection cannot be assessed accurately from currently available data. We developed a mathematical model of methicillin-sensitive and methicillin-resistantStaphylococcus aureus(MSSA and MRSA) transmission inside and outside the hospital. A systematic simulation study was then conducted with two objectives: to assess the impact of antibiotic class-specific changes during an antibiotic reduction period and to investigate the interactions between antibiotic prescription changes in the hospital and the community. The model reproduced the overall reduction in MRSA frequency in French intensive-care units (ICUs) with antibiotic consumption in France from 2002 to 2003 as an input. However, the change in MRSA frequency depended on which antibiotic classes changed the most, with the same overall 10% reduction in antibiotic use over 1 year leading to anywhere between a 69% decrease and a 52% increase in MRSA frequency in ICUs and anywhere between a 37% decrease and a 46% increase in the community. Furthermore, some combinations of antibiotic prescription changes in the hospital and the community could act in a synergistic or antagonistic way with regard to overall MRSA selection. This study shows that class-specific changes in antibiotic use, rather than overall reductions, need to be considered in order to properly anticipate the impact of an antibiotic reduction campaign. It also highlights the fact that optimal gains will be obtained by coordinating interventions in hospitals and in the community, since the effect of an intervention in a given setting may be strongly affected by exogenous factors.


2013 ◽  
Vol 57 (11) ◽  
pp. 5536-5542 ◽  
Author(s):  
So-Youn Park ◽  
In-Hwan Oh ◽  
Hee-Joo Lee ◽  
Chun-Gyoo Ihm ◽  
Jun Seong Son ◽  
...  

ABSTRACTVancomycin has been a key antibiotic agent for the treatment of methicillin-resistantStaphylococcus aureus(MRSA) infections. However, little is known about the relationship between vancomycin MIC values at the higher end of the susceptibility range and clinical outcomes. The aim of this study was to determine the impact of MRSA bacteremia on clinical outcomes in patients with a vancomycin MIC near the upper limit of the susceptible range. Patients with MRSA bacteremia were divided into a high-vancomycin-MIC group (2 μg/ml) and a low-vancomycin-MIC group (≤1.0 μg/ml). We examined the relationship between MIC, genotype, primary source of bacteremia, and mortality. Ninety-four patients with MRSA bacteremia, including 31 with a high vancomycin MIC and 63 with a low MIC were analyzed. There was no significant difference between the presence ofagrdysfunction and SCCmectype between the two groups. A higher vancomycin MIC was not found to be associated with mortality. In contrast, high-risk bloodstream infection sources (hazard ratio [HR], 4.63; 95% confidence interval [CI] = 1.24 to 17.33) and bacterial eradication after treatment (HR, 0.06; 95% CI = 0.02 to 0.17), irrespective of vancomycin MIC, were predictors of all-cause 30-day mortality. Our study suggests that a high-risk source of bacteremia is likely to be associated with unfavorable clinical outcomes, but a high vancomycin MIC in a susceptible range, as well as genotype characteristics, are not associated with mortality.


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