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Fait A, Silva SF, Abrahamsson JÅH, Ingmer H. Staphylococcus aureus response and adaptation to vancomycin. Adv Microb Physiol 2024; 85:201-258. [PMID: 39059821 DOI: 10.1016/bs.ampbs.2024.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Antibiotic resistance is an increasing challenge for the human pathogen Staphylococcus aureus. Methicillin-resistant S. aureus (MRSA) clones have spread globally, and a growing number display decreased susceptibility to vancomycin, the favoured antibiotic for treatment of MRSA infections. These vancomycin-intermediate S. aureus (VISA) or heterogeneous vancomycin-intermediate S. aureus (hVISA) strains arise from accumulation of a variety of point mutations, leading to cell wall thickening and reduced vancomycin binding to the cell wall building block, Lipid II, at the septum. They display only minor changes in vancomycin susceptibility, with varying tolerance between cells in a population, and therefore, they can be difficult to detect. In this review, we summarize current knowledge of VISA and hVISA. We discuss the role of genetic strain background or epistasis for VISA development and the possibility of strains being 'transient' VISA with gene expression changes mediated by, for example, VraTSR, GraXSR, or WalRK signal transduction systems, leading to temporary vancomycin tolerance. Additionally, we address collateral susceptibility to other antibiotics than vancomycin. Specifically, we estimate how mutations in rpoB, encoding the β-subunit of the RNA polymerase, affect overall protein structure and compare changes with rifampicin resistance. Ultimately, such in-depth analysis of VISA and hVISA strains in terms of genetic and transcriptional changes, as well as changes in protein structures, may pave the way for improved detection and guide antibiotic therapy by revealing strains at risk of VISA development. Such tools will be valuable for keeping vancomycin an asset also in the future.
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Affiliation(s)
- Anaëlle Fait
- Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark; Department of Environmental Systems Science, ETH Zürich, Zürich, Switzerland
| | - Stephanie Fulaz Silva
- Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark
| | | | - Hanne Ingmer
- Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
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2
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Fait A, Andersson DI, Ingmer H. Evolutionary history of Staphylococcus aureus influences antibiotic resistance evolution. Curr Biol 2023; 33:3389-3397.e5. [PMID: 37494936 DOI: 10.1016/j.cub.2023.06.082] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 05/05/2023] [Accepted: 06/29/2023] [Indexed: 07/28/2023]
Abstract
Antibiotic resistance often confers a fitness cost to the resistant cell and thus raises key questions of how resistance is maintained in the absence of antibiotics and, if lost, whether cells are genetically primed for re-evolving resistance. To address these questions, we have examined vancomycin-intermediate Staphylococcus aureus (VISA) strains that arise during vancomycin therapy. VISA strains harbor a broad spectrum of mutations, and they are known to be unstable both in patients and in the laboratory. Here, we show that loss of resistance in VISA strains is correlated with a fitness increase and is attributed to adaptive mutations, leaving the initial VISA-adaptive mutations intact. Importantly, upon a second exposure to vancomycin, such revertants evolve significantly faster to become VISA, and they reach higher resistance levels than vancomycin-naive cells. Further, we find that sub-lethal concentrations of vancomycin stabilize the VISA phenotype, as do the human β-defensin 3 (hBD-3) and the bacteriocin nisin that both, like vancomycin, bind to the peptidoglycan building block, lipid II. Thus, factors binding lipid II may stabilize VISA both in vivo and in vitro, and in case resistance is lost, mutations remain that predispose to resistance development. These findings may explain why VISA infections often are re-occurring and suggest that previous vancomycin adaptation should be considered a risk factor when deciding on antimicrobial chemotherapy.
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Affiliation(s)
- Anaëlle Fait
- Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark; Department of Environmental Systems Science, ETH Zürich, 8092 Zürich, Switzerland
| | - Dan I Andersson
- Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden
| | - Hanne Ingmer
- Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.
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3
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Hyodo Y, Arizono T, Inokuchi A, Hamada T, Imamura R. Prophylactic Intrawound Vancomycin Powder in Minimally Invasive Spine Stabilization May Cause an Acute Inflammatory Response. Cureus 2022; 14:e28881. [PMID: 36225472 PMCID: PMC9541380 DOI: 10.7759/cureus.28881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/07/2022] [Indexed: 11/12/2022] Open
Abstract
Introduction Surgical site infections (SSIs) with methicillin-resistant Staphylococcus aureus are serious complications of spinal instrumentation surgery. Many spine surgeons are concerned that using prophylactic vancomycin powder will lead to certain risks: the development of multidrug-resistant pathogens, anaphylactic reactions, and organ toxicity. Minimally invasive spine stabilization (MISt) is associated with shorter operation times and less blood loss and may therefore require the use of less vancomycin powder, which may reduce these risks. This retrospective comparative study of patients who underwent MISt at a single institution aimed to evaluate the complications (such as allergy, SSIs, and organ toxicity) and the local and serum levels associated with using prophylactic intrawound vancomycin powder compared with IV cefazolin alone. Methods Thirty-four patients received intrawound vancomycin powder (1 g) applied during wound closure in minimally invasive posterior lumbar interbody fusion (MIS-PLIF). This group was compared with 133 control patients who did not receive vancomycin. White blood cell counts and C-reactive protein (CRP) levels were measured for both groups on postoperative days (PODs) 1, 3, and 7 and were statistically analyzed. In the vancomycin group, serum vancomycin levels were measured on PODs 1, 3, 7, and 14; drain vancomycin levels and postoperative blood loss were determined on PODs 1 and 2. Results The CRP levels on PODs 1 and 3 were significantly higher in the vancomycin group than in the control group (P<0.001, P=0.024). In the vancomycin group, mean drain levels trended downward from 313 μg/mL (POD 1) to 155 μg/mL (POD 2). These levels correlated negatively with drain drainage volume on both days (POD 1: r=-0.48, P=0.015; POD 2: r=-0.47, P=0.019). Mean serum vancomycin levels also trended downward from 2.3 μg/mL (POD 1) to 1.7 μg/mL (POD 14). Conclusions Our results unexpectedly demonstrated that the local application of vancomycin powder causes an acute inflammatory response and the long-term detection of low serum vancomycin levels. Less than 1 g of intrawound vancomycin powder may be useful only at high risk of SSI.
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Wang S, Yao R, Li Z, Gong X, Xu J, Yang F, Yang K. Vancomycin Use in Posterior Lumbar Interbody Fusion of Deep Surgical Site Infection. Infect Drug Resist 2022; 15:3103-3109. [PMID: 35747329 PMCID: PMC9212791 DOI: 10.2147/idr.s364432] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 05/27/2022] [Indexed: 12/12/2022] Open
Abstract
Objective To retrospectively analyze if the use of topical intraoperative vancomycin powder reduces deep surgical site infection (DSSI) after posterior lumbar interbody fusion. Methods All spinal surgeries for lumbar degenerative disease and underwent posterior fixation interbody fusion between January 2013 and December 2018 were reviewed. A total of 891 patients were included, of which 527 patients (treatment group) received intraoperatively topical vancomycin powder; the others were served as control group. The primary outcomes were the overall incidence of DSSI and the effect of vancomycin on its development. The secondary outcome was risk factors for DSSI. Data on the baseline characteristics, postoperative complications, perioperative risk factors, and one-year postoperative prognoses were extracted from the medical records. Results A total of 20 patients met the diagnostic criteria for DSSI (2.24%), of which 7 patients (1.33%) in the treatment group and 13 patients (3.57%) in the control group. There was a significant difference in the incidence of DSSI between the groups (P = 0.026). Multivariate logistic regression analysis with stepwise backward elimination showed that the local use of vancomycin powder was an independent protective factor for DSSI (odds ratio (OR): 0.25, P = 0.01), whereas high body mass index (BMI) (OR: 1.21, P = 0.005), drinking (OR: 5.19, P = 0.005), urinary tract infections (OR: 4.49, P = 0.021), diabetes mellitus (OR: 4.32, P = 0.03), and blood transfusions (OR: 3.67, P = 0.03) were independent risk factors for DSSI. Conclusion The intraoperative usage of vancomycin powder could reduce effectively decreases the incidence of DSSI after posterior lumbar interbody fusion for degenerative lumbar diseases. High BMI, diabetes mellitus, drinking, and urinary tract infections were independent risk factors for DSSI, whereas the local use of vancomycin protected against these factors.
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Affiliation(s)
- Shiyong Wang
- Department of Spinal Surgery, First Affiliated Hospital of Dali University, Dali, Yunnan, People's Republic of China
| | - Rubin Yao
- Department of Spinal Surgery, First Affiliated Hospital of Dali University, Dali, Yunnan, People's Republic of China
| | - Zhongjie Li
- Department of Spinal Surgery, First Affiliated Hospital of Dali University, Dali, Yunnan, People's Republic of China
| | - Xiangdong Gong
- Department of Spinal Surgery, First Affiliated Hospital of Dali University, Dali, Yunnan, People's Republic of China
| | - Jitao Xu
- Department of Spinal Surgery, First Affiliated Hospital of Dali University, Dali, Yunnan, People's Republic of China
| | - Fajun Yang
- Department of Spinal Surgery, First Affiliated Hospital of Dali University, Dali, Yunnan, People's Republic of China
| | - Kaishun Yang
- Department of Spinal Surgery, First Affiliated Hospital of Dali University, Dali, Yunnan, People's Republic of China
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Dao TT, Williams K, de Mattos-Shipley KMJ, Song Z, Takebayashi Y, Simpson TJ, Spencer J, Bailey AM, Willis CL. Cladobotric Acids: Metabolites from Cultures of Cladobotryum sp., Semisynthetic Analogues and Antibacterial Activity. JOURNAL OF NATURAL PRODUCTS 2022; 85:572-580. [PMID: 35170975 PMCID: PMC9097583 DOI: 10.1021/acs.jnatprod.1c01063] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Indexed: 06/14/2023]
Abstract
Three new polyketide-derived natural products, cladobotric acids G-I (1-3), and six known metabolites (4, 5, 8-11) were isolated from fermentation of the fungus Cladobotryum sp. grown on rice. Their structures were elucidated by extensive spectroscopic methods. Two metabolites, cladobotric acid A (4) and pyrenulic acid A (10), were converted to a series of new products (12-20) by semisynthesis. The antibacterial activities of all these compounds were investigated against the Gram-positive pathogen Staphylococcus aureus including methicillin-susceptible (MSSA), methicillin-resistant and vancomycin-intermediate (MRSA/VISA), and heterogeneous vancomycin-intermediate (hVISA) strains. Results of these antibacterial assays revealed structural features of the unsaturated decalins important for biological activity.
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Affiliation(s)
- Trong-Tuan Dao
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, U.K.
| | - Katherine Williams
- School
of Biological Sciences, Life Sciences Building, University of Bristol, 24 Tyndall Avenue, Bristol, BS8 1TQ, U.K.
| | - Kate M. J. de Mattos-Shipley
- School
of Biological Sciences, Life Sciences Building, University of Bristol, 24 Tyndall Avenue, Bristol, BS8 1TQ, U.K.
| | - Zhongshu Song
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, U.K.
| | - Yuiko Takebayashi
- School
of Cellular and Molecular Medicine, University
of Bristol, University Walk, Bristol, BS8 1TD, U.K.
| | - Thomas J. Simpson
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, U.K.
| | - James Spencer
- School
of Cellular and Molecular Medicine, University
of Bristol, University Walk, Bristol, BS8 1TD, U.K.
| | - Andrew M. Bailey
- School
of Biological Sciences, Life Sciences Building, University of Bristol, 24 Tyndall Avenue, Bristol, BS8 1TQ, U.K.
| | - Christine L. Willis
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, U.K.
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6
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Oktay K, Özsoy KM, Çetinalp NE, Erman T, Güzel A. Efficacy of prophylactic application of vancomycin powder in preventing surgical site infections after instrumented spinal surgery: A retrospective analysis of patients with high-risk conditions. ACTA ORTHOPAEDICA ET TRAUMATOLOGICA TURCICA 2021; 55:48-52. [PMID: 33650511 DOI: 10.5152/j.aott.2021.18372] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
OBJECTIVE This study aimed to determine the efficacy of prophylactic use of vancomycin powder against surgical site infections in patients with high-risk conditions who underwent posterior spinal instrumentation. METHODS Data obtained from 209 patients who underwent posterior spinal instrumentation at a single institution from 2014 to 2017 were retrospectively reviewed. Patients were then divided into two groups: control group, including 107 patients (61 females, 46 males; mean age=54 years; age range=16-85 years), and treatment group, including 102 patients (63 females, 39 males; mean age=53 years; age range=14-90 years). All patients received the same standard prophylactic antibiotic regimen. In addition to the prophylactic antibiotic, vancomycin powder was applied locally to the surgical site in the treatment group. All patients were followed up for at least 90 days postoperatively. Infections were categorized as superficial and deep infections. Subgroup analysis of high-risk patients (Syrian refugees) was also performed. RESULTS The infection rates were 1.96% (two patients) in the treatment group and 6.54% (seven patients) in the control group. A significant decrease in the infection rates was observed with local vancomycin powder application. Advanced age (>46 years) and prolonged surgical duration (>140 min) were found to be the main risk factors for surgical site infections (p=0.004 and p=0.028, respectively). The infection rates were 3.22% and 8.11% in the treatment and control groups of refugees, respectively. There were three superficial and four deep infections in the control group and one superficial and one deep infection in the treatment group. A dominance of staphylococcus infections was observed in the control group, whereas no significant dominance was observed in the treatment group. Three patients in the control group and one patient in the treatment group received implant removal. CONCLUSION Evidence from this study has revealed that local application of vancomycin powder reduces the rate of surgical site infections after instrumented spinal surgery. The benefit of vancomycin application may be most appreciated in higher risk populations or in clinics with high baseline rates of infection. LEVEL OF EVIDENCE Level III, Therapeutic Study.
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Affiliation(s)
- Kadir Oktay
- Department of Neurosurgery, Çukurova University, School of Medicine, Adana, Turkey
| | - Kerem Mazhar Özsoy
- Department of Neurosurgery, Çukurova University, School of Medicine, Adana, Turkey
| | - Nuri Eralp Çetinalp
- Department of Neurosurgery, Çukurova University, School of Medicine, Adana, Turkey
| | - Tahsin Erman
- Department of Neurosurgery, Çukurova University, School of Medicine, Adana, Turkey
| | - Aslan Güzel
- Department of Neurosurgery, Bahçeşehir University, School of Medicine, İstanbul, Turkey
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7
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Alshehri N, Ahmed AE, Yenugadhati N, Javad S, Al Sulaiman K, M Al-Dorzi H, Aljerasiy M, Badri M. Vancomycin in ICU Patients with Gram-Positive Infections: Initial Trough Levels and Mortality. Ther Clin Risk Manag 2020; 16:979-987. [PMID: 33116547 PMCID: PMC7569025 DOI: 10.2147/tcrm.s266295] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 09/06/2020] [Indexed: 12/11/2022] Open
Abstract
Background Vancomycin is one of the most common therapeutic agents for treating gram-positive infections, particularly in critically ill patients. The aim of this study was to identify factors associated with initial therapeutic vancomycin trough levels and mortality in a tertiary-care intensive care unit (ICU). Methods This retrospective study evaluated 301 adult ICU patients admitted to King Abdulaziz Medical City in Riyadh between October 1, 2017 and December 31, 2018 with confirmed gram-positive infections and received intravenous vancomycin. Vancomycin trough levels of 15–20 mg/L for severe infections and 10–15 mg/L for less severe infections were considered therapeutic. Results The patients were relatively older with a mean age of 60 (SD ±20) years. Initial vancomycin trough levels were therapeutic in 168 (55.8%). Factors associated with initial therapeutic vancomycin trough levels were female gender (adjusted odds ratio [aOR]=2.575), older age (aOR=1.024), receiving a loading dose (aOR=2.445), having bacteremia (aOR=2.061), and high platelet count (aOR=1.003). On the other hand, the increase of estimated glomerular filtration rate (eGFR) (aOR=0.993) and albumin levels (aOR=0.944) were associated with lower odds of initial therapeutic vancomycin trough levels. Factors associated with higher mortality were female gender (adjusted hazard ratio [aHR]=2.630), increased body weight (aHR=1.021), cancer (aHR=3.451), and high APACHE II score (aHR=1.068). Conclusion The study identified several factors associated with achieving initial therapeutic vancomycin trough levels (i.e. older age, female gender, receiving a loading dose, bacteremia, high platelets count, low eGFR and albumin level). These factors should be considered in the dosing of vancomycin in critically ill patients with gram-positive infections.
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Affiliation(s)
- Nadiyah Alshehri
- Pharmaceutical Care Department, Ministry of National Guard- Health Affairs, Riyadh, Saudi Arabia.,Department of Epidemiology & Biostatistics, College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Anwar E Ahmed
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
| | - Nagarajkumar Yenugadhati
- Department of Epidemiology & Biostatistics, College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.,King Abdullah International Medical Research Center, King Saud Bin-Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Sundas Javad
- Department of Epidemiology & Biostatistics, College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.,King Abdullah International Medical Research Center, King Saud Bin-Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Khalid Al Sulaiman
- Pharmaceutical Care Department, Ministry of National Guard- Health Affairs, Riyadh, Saudi Arabia
| | - Hasan M Al-Dorzi
- Intensive Care Department, College of Medicine King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Majed Aljerasiy
- King Abdullah International Medical Research Center, King Saud Bin-Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Motasim Badri
- Department of Epidemiology & Biostatistics, College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.,King Abdullah International Medical Research Center, King Saud Bin-Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
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Luzum M, Sebolt J, Chopra V. Catheter-Associated Urinary Tract Infection, Clostridioides difficile Colitis, Central Line-Associated Bloodstream Infection, and Methicillin-Resistant Staphylococcus aureus. Med Clin North Am 2020; 104:663-679. [PMID: 32505259 DOI: 10.1016/j.mcna.2020.02.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Hospital-acquired infections increase cost, morbidity, and mortality for patients across the United States and the world. Principal among these infections are central line-associated bloodstream infection, catheter-associated urinary tract infection, Clostridioides difficile, and methicillin-resistant Staphylococcus aureus colonization and infections. This article provides succinct summaries of the background, epidemiology, diagnosis, and treatment of these conditions. In addition, novel prevention strategies, including those related to recent national interventions, are reviewed.
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Affiliation(s)
- Matthew Luzum
- The Division of Hospital Medicine, Department of Medicine, University of Michigan, 2800 Plymouth Road, Building 16 #432W, Ann Arbor, MI 48109, USA
| | - Jonathan Sebolt
- The Division of Hospital Medicine, Department of Medicine, University of Michigan, 2800 Plymouth Road, Building 16 #432W, Ann Arbor, MI 48109, USA
| | - Vineet Chopra
- The Division of Hospital Medicine, Department of Medicine, University of Michigan, 2800 Plymouth Road, Building 16 #432W, Ann Arbor, MI 48109, USA.
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9
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Yang X, Liu Y, Wang L, Qian S, Yao K, Dong F, Song W, Xu H, Zhen J, Zhou W. Clonal and drug resistance dynamics of methicillin-resistant Staphylococcus aureus in pediatric populations in China. Pediatr Investig 2019; 3:72-80. [PMID: 32851295 PMCID: PMC7331318 DOI: 10.1002/ped4.12129] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 05/28/2019] [Indexed: 12/30/2022] Open
Abstract
IMPORTANCE Regional clonal replacements of methicillin-resistant Staphylococcus aureus (MRSA) are common. It is necessary to understand the clonal and drug resistance changes in specific areas. OBJECTIVE To evaluate the clonal and drug resistance dynamics of MRSA in Chinese children from 2010 to 2017. METHODS MRSA was isolated from patients in Beijing Children's Hospital from 2010 to 2013 and from 2016 to 2017. The molecular characteristics and antibiotic resistance were determined. RESULTS In total, 211 MRSA isolates were collected, and 104 isolates were classified as community-associated MRSA (CA-MRSA). ST59-SCC mec IV was the most prevalent type in both CA-MRSA (65.4%) and healthcare- associated-MRSA (HA-MRSA) (46.7%). ST239-SCC mec III accounted for 21.5% of all HA-MRSA, which were not detected in 2016, and only three isolates were detected in 2017. The pvl gene carrying rate of CA- MRSA was significantly higher than that of HA-MRSA (42.3% vs. 29.0%, P = 0.0456). Among CA-MRSA, resistance rate to all tested antibiotics excluding chloramphenicol remained stable over the periods of 2010-2013 and 2016-2017. HA-MRSA displayed an overall trend of decreased resistance to oxacillin, gentamicin, tetracycline, ciprofloxacin, and rifampin, and increased resistance to chloramphenicol, consistent with the difference of antibiotic resistance patterns between ST59-SCC mec IV and ST239-SCC mec III isolates. Vancomycin minimal inhibitory concentration (MIC) creep was found in the study period in all MRSA and ST59-SCC mec IV isolates. INTERPRETATION ST59-SCC mec IV has spread to hospitals and replaced the traditional ST239-SCC mec III clone, accompanied by changes in drug resistance. Furthermore, vancomycin MIC creep indicated that the rational use of antibiotics should be seriously considered.
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Affiliation(s)
- Xin Yang
- Pediatric Intensive Care UnitBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Yingchao Liu
- Pediatric Intensive Care UnitBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Lijuan Wang
- Pediatric Intensive Care UnitBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Suyun Qian
- Pediatric Intensive Care UnitBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Kaihu Yao
- MOE Key Laboratory of Major Diseases in ChildrenNational Key Discipline of Pediatrics (Capital Medical University)National Clinical Research Center for Respiratory DiseasesBeijing Key Laboratory of Pediatric Respiratory Infection DiseasesBeijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Fang Dong
- Bacteriology LaboratoryBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Wenqi Song
- Bacteriology LaboratoryBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Hong Xu
- Bacteriology LaboratoryBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Jinghui Zhen
- Bacteriology LaboratoryBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Wei Zhou
- Bacteriology LaboratoryBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
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10
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Usefulness of Gram stain examination of peritoneal fluid in postoperative peritonitis to guide empirical antibiotherapy. Eur J Trauma Emerg Surg 2019; 46:1335-1340. [PMID: 31143982 DOI: 10.1007/s00068-019-01161-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 05/22/2019] [Indexed: 10/26/2022]
Abstract
PURPOSE In postoperative peritonitis, Gram stain examination (GSE) of peritoneal fluid has been proposed as a guide for the prescription of glycopeptides and antifungal therapy in empirical antibiotherapy. No data support this approach for Gram-positive cocci. We aimed to evaluate the performance of GSE in predicting the results of the culture of peritoneal fluid. METHODS In this retrospective single-center study, concordance between GSE and culture of peritoneal fluid was assessed for different types of microorganisms. Factors associated with concordance of the two tests were evaluated in the subpopulation of Gram-positive cocci peritonitis. RESULTS Among the 152 episodes, the GSE was negative in 57 cases. The negative predictive value and the positive predictive value were 41% and 87% for Gram-positive cocci (GPC), 31% and 86% for Gram-negative bacilli, and 78% and 94% for fungi. GSE is not a reliable guide for the choice of empirical antibiotherapy and cannot reliably rule out the presence of GPC at culture. If we aim to achieve a high rate of adequacy, the systematic use of glycopeptide in the empirical antibiotherapy may be considered. CONCLUSION GSE shows poor performance to predict the results of culture of peritoneal fluid in postoperative peritonitis. Avoiding covering resistant GPC cannot be based on the result of GSE.
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11
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Belykh E, Carotenuto A, Kalinin AA, Akshulakov SK, Kerimbayev T, Borisov VE, Aliyev MA, Nakaji P, Preul MC, Byvaltsev VA. Surgical Protocol for Infections, Nonhealing Wound Prophylaxis, and Analgesia: Development and Implementation for Posterior Spinal Fusions. World Neurosurg 2019; 123:390-401.e2. [DOI: 10.1016/j.wneu.2018.11.135] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 11/14/2018] [Accepted: 11/16/2018] [Indexed: 12/21/2022]
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Abulfathi AA, Chirehwa M, Rosenkranz B, Decloedt EH. Evaluation of the Effectiveness of Dose Individualization to Achieve Therapeutic Vancomycin Concentrations. J Clin Pharmacol 2018; 58:1134-1139. [DOI: 10.1002/jcph.1254] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 04/08/2018] [Indexed: 11/08/2022]
Affiliation(s)
- Ahmed A. Abulfathi
- Division of Clinical Pharmacology; Department of Medicine; Faculty of Medicine and Health Sciences; University of Stellenbosch; South Africa
| | - Maxwell Chirehwa
- Biostatistics Unit; Centre for Evidence Based Health Care (CEHBC); Faculty of Medicine and Health Sciences; University of Stellenbosch; South Africa
| | - Bernd Rosenkranz
- Division of Clinical Pharmacology; Department of Medicine; Faculty of Medicine and Health Sciences; University of Stellenbosch; South Africa
| | - Eric H. Decloedt
- Division of Clinical Pharmacology; Department of Medicine; Faculty of Medicine and Health Sciences; University of Stellenbosch; South Africa
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Singh VA, Sim LH, Haseeb A, Ju CTS. Ceftaroline fosamil laden allograft: A new modality in reducing infection? J Orthop Surg (Hong Kong) 2018; 26:2309499018806671. [PMID: 30343651 DOI: 10.1177/2309499018806671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
PURPOSE Allograft infection remains the greatest challenge in orthopaedic reconstructive surgery especially methicillin-resistant Staphylococcus aureus (MRSA). This risk can be minimized with the use of antibiotic laden allograft (ALA) via iontophoresis. Ceftaroline fosamil (CF) is an advanced-generation cephalosporin, an alternative treatment for MRSA infections. Its antibacterial activity and safety profile are better than vancomycin. CF iontophoresed bone has not been used before. This study was conducted to establish the feasibility of creating a CF ALA and establish the prime conditions for its expenditure. METHOD We created an iontophoresis cell; 3% CF was inserted within medullary segment of goat bone and sealed from external saline solution. The cell operated at the following voltages 30, 60 and 90 V and at the following durations 5, 10, 15, 20, 25 and 30 min. Information regarding optimal conditions for its application was then obtained. After which, correlation between voltages and time with CF concentration in the bone was analysed. A bioavailability test was also conducted to observe the optimal rate of CF elution from the graft. RESULT The optimal condition for the impregnation process is 3% CF at 90 V for 10 min. Bone graft impregnated with CF at optimal conditions can elute above minimum inhibitory concentration of the CF against MRSA for 21 days. CONCLUSION CF iontophoresis was found feasible for allograft impregnation. The technique is simple, inexpensive and reproducible clinically. Iontophoresis offers a novel solution to reduce the rate of perioperative infection in reconstructive surgery involving use of bone graft.
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Affiliation(s)
- Vivek Ajit Singh
- 1 Department of Orthopedics, University of Malaya, Kuala Lumpur, Malaysia
| | - Lim Han Sim
- 1 Department of Orthopedics, University of Malaya, Kuala Lumpur, Malaysia
| | - Amber Haseeb
- 1 Department of Orthopedics, University of Malaya, Kuala Lumpur, Malaysia
| | - Cindy Teh Shuan Ju
- 2 Department of Microbiology, University of Malaya, Kuala Lumpur, Malaysia
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Bouiller K, Laborde C, Aho SL, Hocquet D, Pechinot A, Le Moing V, Bertrand X, Piroth L, Chirouze C. No effect of vancomycin MIC ≥ 1.5 mg/L on treatment outcome in methicillin-susceptible Staphylococcus aureus bacteraemia. Int J Antimicrob Agents 2018; 51:721-726. [DOI: 10.1016/j.ijantimicag.2017.12.028] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 12/19/2017] [Accepted: 12/28/2017] [Indexed: 10/18/2022]
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Mirzashahi B, Chehrassan M, Mortazavi SMJ. Intrawound application of vancomycin changes the responsible germ in elective spine surgery without significant effect on the rate of infection: a randomized prospective study. Musculoskelet Surg 2017; 102:35-39. [PMID: 28699136 DOI: 10.1007/s12306-017-0490-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2017] [Accepted: 07/05/2017] [Indexed: 01/02/2023]
Abstract
PURPOSE Surgical site infection (SSI) is a costly complication associated with spine surgery. The impact of intrawound vancomycin has not been strongly postulated to decrease the risk of surgical site infection. We designed study to determine whether intrawound vancomycin application reduces the risk of SSI in patients after spine surgery. METHODS A prospective randomized control trial study to evaluate the patients with elective spine surgery in a period of 15 month was designed. Patients were divided into two groups based on whether intrawound vancomycin was applied or not. The relative risk of SSI within postoperative 30 days was evaluated. RESULTS Three hundred and eighty patients were included in this study: degenerative spine pathologies and tumor 80% (304), trauma 11% (42) and deformity 9% (34). Intrawound vancomycin was used in 51% of patients. Prevalence of SSI was 2.7% in the absence of vancomycin use versus 5.2% with intrawound vancomycin. In multivariable regression model, those with higher number of levels exposed, postoperative ICU admission and obesity and use of instrumentation more than two levels had higher risk of developing SSI. In the treatment group Acinetobacter and Pseudomonas aeruginosa (20%) were the most common pathogens. In control group, Staphylococcus aureus and Acinetobacter (40%) were the most common organisms. CONCLUSIONS Intrawound application of vancomycin after elective spine surgery was not associated with reduced risk of SSI and return to OR associated with SSI in our patients. However, the use of intrawound vancomycin changed the responsible infection germ.
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Affiliation(s)
- B Mirzashahi
- Orthopedic Department of Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - S M J Mortazavi
- Orthopedic Department of Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Joint Reconstruction Research Center (JRRC), Orthopedic Department of Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Is Intraoperative Local Vancomycin Powder the Answer to Surgical Site Infections in Spine Surgery? Spine (Phila Pa 1976) 2017; 42:267-274. [PMID: 28207669 DOI: 10.1097/brs.0000000000001710] [Citation(s) in RCA: 98] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN This is a retrospective cohort comparative study of all patients who underwent instrumented spine surgery at a single institution. OBJECTIVE To compare the rate of surgical site infection (SSI) between the treatment (vancomycin) and the control group (no vancomycin) in patients undergoing instrumented spine surgery. SUMMARY OF BACKGROUND DATA SSI after spine surgery is a dreaded complication associated with increased morbidity and mortality. Prophylactic intraoperative local vancomycin powder to the wound has been recently adopted as a strategy to reduce SSI but results have been variable. METHODS In the present study, there were 117 (30%) patients in the treatment group and 272 (70%) patients in the comparison cohort. All patients received identical standard operative and postoperative care procedures based on protocolized department guidelines. The present study compared the rate of SSI with and without the use of prophylactic intraoperative local vancomycin powder in patients undergoing various instrumented spine surgery, adjusted for confounders. RESULTS The overall rate of SSI was 4.7% with a decrease in infection rate found in the treatment group (0.9% vs. 6.3%). This was statistically significant (P = 0.049) with an odds ratio of 0.13 (95% confidence interval 0.02-0.99). The treatment group had a significantly shorter onset of infection (5 vs. 16.7 days; P < 0.001) and shorter duration of infection (8.5 vs. 26.8 days; P < 0.001). The most common causative organism was Pseudomonas aeruginosa (35.2%). Patient diagnosis, surgical approach, and intraoperative blood loss were significant risk factors for SSI after multivariable analysis. CONCLUSION Prophylactic Intraoperative local vancomycin powder reduces the risk and morbidity of SSI in patients undergoing instrumented spine surgery. P. aeruginosa infection is common in the treatment arm. Future prospective randomized controlled trials in larger populations involving other spine surgeries with a long-term follow-up duration are recommended. LEVEL OF EVIDENCE 3.
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Britt NS, Patel N, Shireman TI, El Atrouni WI, Horvat RT, Steed ME. Relationship between vancomycin tolerance and clinical outcomes in Staphylococcus aureus bacteraemia. J Antimicrob Chemother 2016; 72:535-542. [PMID: 27999028 DOI: 10.1093/jac/dkw453] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 09/18/2016] [Accepted: 09/23/2016] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Previous data have demonstrated the clinical importance of vancomycin MIC values in Staphylococcus aureus bacteraemia (SAB); however, the impact of vancomycin tolerance (VT) is unknown. OBJECTIVES To compare the frequency of clinical failure between patients with VT and non-VT isolates in SAB. METHODS This was a retrospective cohort study of patients with SAB, excluding treatment <48 h or polymicrobial bacteraemia. The primary outcome was clinical failure (composite of 30 day mortality, non-resolving signs and symptoms, and 60 day recurrence). Vancomycin MIC and MBC were determined by broth microdilution. The association between VT (MBC/MIC ≥32) and clinical failure was evaluated by multivariable Poisson regression. RESULTS Of the 225 patients, 26.7% had VT isolates. VT was associated with clinical failure (48.0% overall) in unadjusted analysis [68.3% (n = 41/60) versus 40.6% (n = 67/165); P < 0.001] and this relationship persisted in multivariable analysis (adjusted risk ratio, 1.74; 95% CI, 1.36-2.24; P < 0.001). The association between VT and clinical failure was also consistent within strata of methicillin susceptibility [methicillin susceptible (n = 125, risk ratio, 1.67; 95% CI, 1.20-2.32; P = 0.002); methicillin resistant (n = 100, risk ratio, 1.69; 95% CI, 1.14-2.51; P = 0.010)]. Among methicillin-susceptible SAB cases treated with β-lactam therapy, VT remained associated with clinical failure (risk ratio, 1.77; 95% CI, 1.19-2.61; P = 0.004). CONCLUSIONS VT was associated with clinical failure in SAB, irrespective of methicillin susceptibility or definitive treatment. VT may decrease the effectiveness of cell-wall-active therapy or be a surrogate marker of some other pathogen-specific factor associated with poor outcomes. Future research should evaluate if bactericidal non-cell-wall-active agents improve outcomes in VT SAB.
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Affiliation(s)
- Nicholas S Britt
- Department of Pharmacy Practice, University of Kansas School of Pharmacy, 2010 Becker Drive, Lawrence, KS, USA.,Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA
| | - Nimish Patel
- Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY, USA
| | - Theresa I Shireman
- Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA
| | - Wissam I El Atrouni
- Department of Medicine, Division of Infectious Diseases, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA
| | - Rebecca T Horvat
- Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA
| | - Molly E Steed
- Department of Pharmacy Practice, University of Kansas School of Pharmacy, 2010 Becker Drive, Lawrence, KS, USA
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Impact of Time to Appropriate Therapy on Mortality in Patients with Vancomycin-Intermediate Staphylococcus aureus Infection. Antimicrob Agents Chemother 2016; 60:5546-53. [PMID: 27401565 DOI: 10.1128/aac.00925-16] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Accepted: 07/01/2016] [Indexed: 12/29/2022] Open
Abstract
Despite the increasing incidence of vancomycin-intermediate Staphylococcus aureus (VISA) infections, few studies have examined the impact of delay in receipt of appropriate antimicrobial therapy on outcomes in VISA patients. We examined the effects of timing of appropriate antimicrobial therapy in a cohort of patients with sterile-site methicillin-resistant S. aureus (MRSA) and VISA infections. In this single-center, retrospective cohort study, we identified all patients with MRSA or VISA sterile-site infections from June 2009 to February 2015. Clinical outcomes were compared according to MRSA/VISA classification, demographics, comorbidities, and antimicrobial treatment. Thirty-day all-cause mortality was modeled with Kaplan-Meier curves. Multivariate logistic regression analysis (MVLRA) was used to determine odds ratios for mortality. We identified 354 patients with MRSA (n = 267) or VISA (n = 87) sterile-site infection. Fifty-five patients (15.5%) were nonsurvivors. Factors associated with mortality in MVLRA included pneumonia, unknown source of infection, acute physiology and chronic health evaluation (APACHE) II score, solid-organ malignancy, and admission from skilled care facilities. Time to appropriate antimicrobial therapy was not significantly associated with outcome. Presence of a VISA infection compared to that of a non-VISA S. aureus infection did not result in excess mortality. Linezolid use was a risk for mortality in patients with APACHE II scores of ≥14. Our results suggest that empirical vancomycin use in patients with VISA infections does not result in excess mortality. Future studies should (i) include larger numbers of patients with VISA infections to confirm the findings presented here and (ii) determine the optimal antibiotic therapy for critically ill patients with MRSA and VISA infections.
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Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia. Antimicrob Agents Chemother 2016; 60:3070-5. [PMID: 26953202 DOI: 10.1128/aac.02714-15] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 03/03/2016] [Indexed: 12/13/2022] Open
Abstract
While previous studies have examined the association between vancomycin (VAN) exposure and MIC with regard to outcomes in methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B), none have explored if a relationship exists with the VAN minimum bactericidal concentration (MBC). The objective of this study was to evaluate the VAN 24-h area under the curve (AUC24)/MBC ratio as a pharmacodynamic predictor of mortality. This retrospective cohort study included patients treated with VAN for MRSA-B with the primary outcome of 30-day all-cause mortality. Data collected included patient demographics, comorbidities, antimicrobial treatment data, therapeutic drug levels, and laboratory and microbiological data. Vancomycin MICs and MBCs were determined by Etest (MIC only) and broth microdilution (BMD). The vancomycin AUC24 was determined by pharmacokinetic maximum a posteriori probability Bayesian (MAP-Bayesian) analysis. The most significant breakpoint for 30-day mortality was determined by classification and regression tree (CART) analysis. The association between pharmacodynamic parameters (VAN AUC24/MICBMD, VAN AUC24/MICEtest, and AUC24/MBCBMD) and mortality were determined by χ(2) and multivariable Poisson regression. Overall mortality in this cohort (n = 53) was 20.8% (n = 11/53), and all corresponding MRSA blood isolates were VAN susceptible (MIC range, 0.5 to 2 μg/ml; MIC50, 1 μg/ml; MIC90, 1 μg/ml). The CART-derived breakpoints for mortality were 176 (VAN AUC24/MBC) and 334 (VAN AUC24/MICBMD). In multivariable analysis, the association between a VAN AUC24/MBC of ≥176 and survival persisted, but VAN AUC24/MICBMD values (≥334 or ≥400) were not associated with improved mortality. In conclusion, VAN AUC24/MBC was a more important predictor of 30-day mortality than VAN AUC24/MIC for MRSA-B.
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Cuervo G, Camoez M, Shaw E, Dominguez MÁ, Gasch O, Padilla B, Pintado V, Almirante B, Molina J, López-Medrano F, Ruiz de Gopegui E, Martinez JA, Bereciartua E, Rodriguez-Lopez F, Fernandez-Mazarrasa C, Goenaga MÁ, Benito N, Rodriguez-Baño J, Espejo E, Pujol M. Methicillin-resistant Staphylococcus aureus (MRSA) catheter-related bacteraemia in haemodialysis patients. BMC Infect Dis 2015; 15:484. [PMID: 26518487 PMCID: PMC4628295 DOI: 10.1186/s12879-015-1227-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 10/19/2015] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The aim of the study was to determine clinical and microbiological differences between patients with methicillin-resistant Staphylococcus aureus (MRSA) catheter-related bacteraemia (CRB) undergoing or not undergoing haemodialysis, and to compare outcomes. METHODS Prospective multicentre study conducted at 21 Spanish hospitals of patients with MRSA bacteraemia diagnosed between June 2008 and December 2009. Patients with MRSA-CRB were selected. Data of patients on haemodialysis (HD-CRB) and those not on haemodialysis (non-HD-CRB) were compared. RESULTS Among 579 episodes of MRSA bacteraemia, 218 (37.7%) were CRB. Thirty-four (15.6%) were HD-CRB and 184 (84.4%) non-HD-CRB. All HD-CRB patients acquired the infection at dialysis centres, while in 85.3% of the non-HD-CRB group the infection was nosocomial (p < .001). There were no differences in age, gender or severity of bacteraemia (Pitt score); comorbidities (Charlson score ≥ 4) were higher in the HD-CRB group than in the non-HD-CRB group (73.5% vs. 46.2%, p = .003). Although there were no differences in VAN-MIC ≥ 1.5 mg/L according to microdilution, using the E-test a higher rate of VAN-MIC ≥ 1.5 mg/L was observed in HD-CRB than in non-HD-CRB patients (63.3% vs. 44.1%, p = .051). Vancomycin was more frequently administered in the HD-CRB group than in the non-HD-CRB group (82.3% vs. 42.4%, p = <.001) and therefore the appropriate empirical therapy was significantly higher in HD-CRB group (91.2% vs. 73.9%, p = .029). There were no differences with regard to catheter removal (79.4% vs. 84.2%, p = .555, respectively). No significant differences in mortality rate were observed between both groups (Overall mortality: 11.8% vs. 27.2%, p = .081, respectively), but there was a trend towards a higher recurrence rate in HD-CRB group (8.8% vs. 2.2%, p = .076). CONCLUSIONS In our multicentre study, ambulatory patients in chronic haemodialysis represented a significant proportion of cases of MRSA catheter-related bacteraemia. Although haemodialysis patients with MRSA catheter-related bacteraemia had significantly more comorbidities and higher proportion of strains with reduced vancomycin susceptibility than non-haemodialysis patients, overall mortality between both groups was similar.
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Affiliation(s)
- Guillermo Cuervo
- Department of Infectious Diseases, Hospital Universitari de Bellvitge; Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.
| | - Mariana Camoez
- Department of Microbiology, H. Bellvitge, Barcelona, Spain.
| | - Evelyn Shaw
- Department of Infectious Diseases, Hospital Universitari de Bellvitge; Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.
| | | | - Oriol Gasch
- Department of Infectious Diseases, H. Parc Taulí, Sabadell, Spain.
| | - Belén Padilla
- Department of Infectious Diseases, H. Gregorio Marañón, Madrid, Spain.
| | - Vicente Pintado
- Department of Infectious Diseases, H. Ramón y Cajal, Madrid, Spain.
| | - Benito Almirante
- Department of Infectious Diseases, H. Vall d'Hebrón, Barcelona, Spain.
| | - José Molina
- Department of Infectious Diseases, H. Virgen del Rocío, Sevilla, Spain.
| | | | | | - José A Martinez
- Department of Infectious Diseases, H. Clìnic, Barcelona, Spain.
| | | | | | | | | | - Natividad Benito
- Department of Infectious Diseases, H. de la Santa Creu i Sant Pau, Barcelona, Spain.
| | | | - Elena Espejo
- Department of Infectious Diseases, H. Terrassa, Terrassa, Spain.
| | - Miquel Pujol
- Department of Infectious Diseases, Hospital Universitari de Bellvitge; Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.
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Duration of prior vancomycin therapy and subsequent daptomycin treatment outcomes in methicillin-resistant Staphylococcus aureus bacteremia. Diagn Microbiol Infect Dis 2015; 83:193-7. [DOI: 10.1016/j.diagmicrobio.2015.06.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Revised: 04/24/2015] [Accepted: 06/06/2015] [Indexed: 11/24/2022]
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Revest M, Camou F, Senneville E, Caillon J, Laurent F, Calvet B, Feugier P, Batt M, Chidiac C. Medical treatment of prosthetic vascular graft infections: Review of the literature and proposals of a Working Group. Int J Antimicrob Agents 2015; 46:254-65. [PMID: 26163735 DOI: 10.1016/j.ijantimicag.2015.04.014] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Revised: 04/07/2015] [Accepted: 04/21/2015] [Indexed: 02/07/2023]
Abstract
More than 400000 vascular grafts are inserted annually in the USA. Graft insertion is complicated by infection in 0.5-4% of cases. Vascular graft infections (VGIs) are becoming one of the most frequent prosthesis-related infections and are associated with considerable mortality, ranging from 10 to 25% within 30 days following the diagnosis. Treatment of VGI is based on urgent surgical removal of the infected graft followed by prolonged antibiotherapy. Data regarding the best antibiotherapy to use are lacking since no well designed trial to study antimicrobial treatment of VGI exists. Moreover, since VGIs demonstrate very specific pathophysiology, guidelines on other material-related infections or infective endocarditis treatment cannot be entirely applied to VGI. A French multidisciplinary group gathering infectious diseases specialists, anaesthesiologists, intensivists, microbiologists, radiologists and vascular surgeons was created to review the literature dealing with VGI and to make some proposals regarding empirical and documented antibiotic therapy for these infections. This article reveals these proposals.
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Affiliation(s)
- M Revest
- Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France; CIC Inserm 1414, Rennes 1 University, Rennes, France
| | - F Camou
- Intensive Care Unit, Saint-André University Hospital, Bordeaux, France
| | - E Senneville
- Infectious Diseases Department, Gustave Dron Hospital, Tourcoing, Lille 2 University, France
| | - J Caillon
- Bacteriology Department, EA 3826 Nantes University, Hôtel Dieu University Hospital, Nantes, France
| | - F Laurent
- Bacteriology Department, International Center for Infectiology Research (CIRI) - INSERM U1111, CNRS UMR5308, Lyon 1 University, ENS de Lyon, Hospices Civils de Lyon, Lyon, France
| | - B Calvet
- Anesthesiology Department, Beziers, France
| | - P Feugier
- Department of Vascular Surgery, University Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon, France
| | - M Batt
- Department of Vascular Surgery, University of Nice-Sophia Antipolis, Nice, France
| | - C Chidiac
- Infectious Diseases Department, University Claude Bernard Lyon 1, Hospices Civils de Lyon, Inserm U1111, Lyon 1 University, Lyon, France.
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Morales-Cartagena A, Lalueza A, López-Medrano F, Juan RS, Aguado JM. Treatment of methicillin-resistant Staphylococcus aureus infections: Importance of high vancomycin minumum inhibitory concentrations. World J Clin Infect Dis 2015; 5:14-29. [DOI: 10.5495/wjcid.v5.i2.14] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Revised: 10/30/2014] [Accepted: 03/09/2015] [Indexed: 02/06/2023] Open
Abstract
Staphylococcus aureus (SA) infections remain a major cause of morbidity and mortality despite the availability of numerous effective anti-staphylococcal antibiotics. This organism is responsible for both nosocomial and community-acquired infections ranging from relatively minor skin and soft tissue infections to life-threatening systemic infections. The increasing incidence of methicillin-resistant strains has granted an increasing use of vancomycin causing a covert progressive increase of its minimum inhibitory concentration (MIC) (dubbed the MIC “creep”). In this way, the emergence of vancomycin-intermediate SA (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant SA. These strains show different mechanisms of resistance but have similar problems in terms of therapeutic approach. Ultimately, various debate issues have arisen regarding the emergence of SA strains with a minimum inhibitory concentration sitting on the superior limit of the sensitivity range (i.e., MIC = 2 μg/mL). These strains have shown certain resilience to vancomycin and a different clinical behaviour regardless of vancomycin use, both in methicillin-resistant SA and in methicillin-sensitive SA. The aim of this text is to revise the clinical impact and consequences of the emergence of reduced vancomycin susceptibility SA strains, and the different optimal treatment options known.
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Chang W, Ma X, Gao P, Lv X, Lu H, Chen F. Vancomycin MIC creep in methicillin-resistant Staphylococcus aureus (MRSA) isolates from 2006 to 2010 in a hospital in China. Indian J Med Microbiol 2015; 33:262-6. [DOI: 10.4103/0255-0857.148837] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Mueller K, McCammon C, Skrupky L, Fuller BM. Vancomycin Use in Patients Discharged From the Emergency Department: A Retrospective Observational Cohort Study. J Emerg Med 2015; 49:50-7. [PMID: 25802166 DOI: 10.1016/j.jemermed.2015.01.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Revised: 12/23/2014] [Accepted: 01/05/2015] [Indexed: 12/01/2022]
Abstract
BACKGROUND Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are associated with significant morbidity and mortality and are typically treated with intravenous vancomycin. Given vancomycin's time-dependent mechanism of action, it is unlikely that vancomycin administration in the emergency department (ED) prior to disposition home could be beneficial. STUDY OBJECTIVES To characterize the indications, dosing, and appropriateness of vancomycin use in patients discharged from the ED. METHODS This is a single-center retrospective observational cohort study of patients who received vancomycin in an urban, academic, tertiary care ED. The subjects were consecutive adult patients administered intravenous vancomycin in the ED and then discharged home over an 18-month period. Outcomes were measured 1) to characterize patients receiving vancomycin prior to discharge home from the ED; and 2) to identify patients that did not meet indications for appropriate use based on the 2011 Infectious Diseases Society of America guidelines for treating MRSA infections. RESULTS There were 526 patients that received vancomycin in the ED prior to discharge during the study period. In this cohort, 368 (70%) patients were diagnosed with skin and soft tissue infections. A MRSA risk factor was present in 396 (75%) patients. Prior to discharge, one dose of vancomycin was administered to 357 (68%) patients. Underdosing of vancomycin occurred in 239 (73%) patients. CONCLUSIONS Vancomycin was given frequently to patients discharged home from the ED, most commonly for conditions where vancomycin was not indicated, such as skin and soft tissue infections. The majority of these patients received a vancomycin dosing strategy that is not only unlikely to lead to clinical improvement, but also has the potential to contribute adversely to the development of antibiotic resistance. Further investigation is needed into the impact of vancomycin use, the emergence of vancomycin resistance, and the role of ED-based antibiotic stewardship.
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Affiliation(s)
- Kristen Mueller
- Division of Emergency Medicine, Washington University School of Medicine and Barnes Jewish Hospital, Saint Louis, Missouri
| | - Craig McCammon
- Department of Pharmacy, Barnes Jewish Hospital, Saint Louis, Missouri
| | - Lee Skrupky
- Department of Pharmacy, Barnes Jewish Hospital, Saint Louis, Missouri
| | - Brian M Fuller
- Division of Emergency Medicine, Department of Anesthesiology, Division of Critical Care, Washington University School of Medicine, Saint Louis, Missouri
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Chen SY, Hsueh PR, Chiang WC, Huang EPC, Lin CF, Chang CH, Chen SC, Chen WJ, Chang SC, Lai MS, Chie WC. Predicting high vancomycin minimum inhibitory concentration isolate infection among patients with community-onset methicillin-resistant Staphylococcus aureus bacteraemia. J Infect 2014; 69:259-65. [DOI: 10.1016/j.jinf.2014.04.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2013] [Revised: 04/24/2014] [Accepted: 04/27/2014] [Indexed: 10/25/2022]
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Tsukimori A, Nakamura I, Okamura S, Sato A, Fukushima S, Mizuno Y, Yamaguchi T, Matsumoto T. First case report of vancomycin-intermediate sequence type 72 Staphylococcus aureus with nonsusceptibility to daptomycin. BMC Infect Dis 2014; 14:459. [PMID: 25149872 PMCID: PMC4150982 DOI: 10.1186/1471-2334-14-459] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2014] [Accepted: 08/18/2014] [Indexed: 11/10/2022] Open
Abstract
Background Sequence type 72 methicillin-resistant Staphylococcus aureus (MRSA) SCCmec type IV (ST72-MRSA-IV) is the most common community-acquired MRSA clone in Korea. Resistance to daptomycin or vancomycin among community-acquired MRSA clones is not well described in the literature. We herein report the first case of vancomycin-intermediate, daptomycin-nonsusceptible ST72-MRSA-IV. Case presentation A 45-year-old Japanese man underwent aortic arch prosthesis implantation for treatment of a dissecting aortic aneurysm. Fourteen months later, he developed a prosthetic graft infection of the aortic arch and an anterior mediastinal abscess caused by ST72-MRSA-IV. First-line treatment with vancomycin and rifampicin failed, and daptomycin was thus administered. After several days, the treatment was changed to linezolid because of the re-emergence of fever. The patient’s condition resolved and no recurrence or other problems were seen for 1 year post-treatment. The infectious agent was definitively identified as vancomycin-intermediate, daptomycin-nonsusceptible, rifampicin-resistant ST72-MRSA-IV based on culture results and minimum inhibitory concentration testing. Conclusion This case report illustrates the importance of fully understanding the changing epidemiology of infectious agents and the risk factors for the development of antibiotic resistance. Such information will help to minimize the emergence and spread of antibiotic-resistant strains. This report concerns one particular bacterial strain; however, the basic concepts involved in this case translate to all infectious disease fields. Electronic supplementary material The online version of this article (doi:10.1186/1471-2334-14-459) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | - Itaru Nakamura
- Department of Infection Control and Prevention, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
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Hill BW, Emohare O, Song B, Davis R, Kang MM. The use of vancomycin powder reduces surgical reoperation in posterior instrumented and noninstrumented spinal surgery. Acta Neurochir (Wien) 2014; 156:749-54. [PMID: 24570187 DOI: 10.1007/s00701-014-2022-z] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Accepted: 01/30/2014] [Indexed: 12/19/2022]
Abstract
BACKGROUND Surgical site infections can complicate posterior spine surgery. Multiple hospital admissions may be required to adequately treat a surgical site infection, which is associated with increased costs and lower patient satisfaction. The objective of this study was to evaluate the efficacy of prophylactic intra-wound vancomycin powder in reducing the incidence of repeat surgery for infections after posterior instrumented and noninstrumented spine surgery. METHODS A series of consecutive patients who underwent instrumented or noninstrumented posterior spine surgery for any indication by two surgeons from July 2010 to July 2012 were reviewed. The preoperative antibiotic regimens of both surgeons were identical, except that one surgeon applied 1 g vancomycin powder directly to the surgical bed before wound closure, while the other did not. Patient demographics, operative details, and rates of reoperation for wound infection in the control and the treatment groups were compared. RESULTS Both the control group and treatment group consisted of 150 patients; mean ages were 58.33 and 54.14 years, respectively. Both groups had low rates of deep infection requiring surgical intervention. The treatment group had a significantly lower rate of infection requiring reoperation or surgical debridement (0 %; 95 % CI: 0 %-2.4 %) compared with the control group (4 %; 95 % CI: 1.5 %-8.5 %) (P = 0.0297). The six infections identified in the control group resulted in 12 repeat operative debridement procedures. Gram-positive organisms were identified in 66.7 % of infections. No complications were related to the application of vancomycin powder. CONCLUSIONS The results of this study demonstrate that adjunctive vancomycin powder applied directly to the surgical bed before closure seems effective in preventing deep infections that require operative debridement following posterior spine surgery.
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Abstract
Daptomycin is a lipopeptide antimicrobial with in vitro bactericidal activity against Gram-positive bacteria that was first approved for clinical use in 2004 in the United States. Since this time, significant data have emerged regarding the use of daptomycin for the treatment of serious infections, such as bacteremia and endocarditis, caused by Gram-positive pathogens. However, there are also increasing reports of daptomycin nonsusceptibility, in Staphylococcus aureus and, in particular, Enterococcus faecium and Enterococcus faecalis. Such nonsusceptibility is largely in the context of prolonged treatment courses and infections with high bacterial burdens, but it may occur in the absence of prior daptomycin exposure. Nonsusceptibility in both S. aureus and Enterococcus is mediated by adaptations to cell wall homeostasis and membrane phospholipid metabolism. This review summarizes the data on daptomycin, including daptomycin's unique mode of action and spectrum of activity and mechanisms for nonsusceptibility in key pathogens, including S. aureus, E. faecium, and E. faecalis. The challenges faced by the clinical laboratory in obtaining accurate susceptibility results and reporting daptomycin MICs are also discussed.
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Lee WS, Chen YC, Chen HP, Chen TH, Cheng CY. Vertebral osteomyelitis caused by vancomycin-tolerant methicillin-resistant Staphylococcus aureus bacteremia: Experience with teicoplanin plus fosfomycin combination therapy. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2013; 49:600-3. [PMID: 24269007 DOI: 10.1016/j.jmii.2013.09.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2012] [Revised: 08/30/2013] [Accepted: 09/03/2013] [Indexed: 11/25/2022]
Abstract
An 85-year-old female presented with fever and consciousness disturbance for 3 days. The patient's blood culture subsequently revealed persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia despite the administration of vancomycin or teicoplanin monotherapy. Gallium inflammation scan and magnetic resonance image of the spine disclosed osteomyelitis and discitis at the level of L4-5. Surgical debridement was not feasible in this debilitated patient. Because of the creeping minimal inhibitory concentration of vancomycin of the causative isolate (1.5 μg/mL) and clinical failure with glycopeptide monotherapy, we changed the antibiotic therapy to a fosfomycin and teicoplanin combination therapy. The patient showed improved clinical response in terms of her enhanced consciousness as well as subsidence of persisted bacteremia. Despite the potential side effects of fosfomycin (such as diarrhea and hypernatremia), it combined with a glycopeptide may be an alternative therapy for invasive refractory MRSA infections.
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Affiliation(s)
- Wen-Sen Lee
- Section of Infectious Disease, Department of Internal Medicine, Wan Fang Medical Center, Taipei Medical University, Taiwan.
| | - Yen-Chuo Chen
- Section of Nephrology, Department of Internal Medicine, Wan Fang Medical Center, Taipei Medical University, Taiwan
| | - Hung-Ping Chen
- Section of Nephrology, Department of Internal Medicine, Wan Fang Medical Center, Taipei Medical University, Taiwan
| | - Tso-Hsiao Chen
- Section of Nephrology, Department of Internal Medicine, Wan Fang Medical Center, Taipei Medical University, Taiwan
| | - Chung-Yi Cheng
- Section of Nephrology, Department of Internal Medicine, Wan Fang Medical Center, Taipei Medical University, Taiwan.
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Alexander EL, Satlin MJ, Gamaletsou MN, Sipsas NV, Walsh TJ. Worldwide challenges of multidrug-resistant bacteria in patients with hematologic malignancies. Int J Hematol Oncol 2013. [DOI: 10.2217/ijh.13.46] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
SUMMARY The emergence of infections due to multidrug-resistant (MDR) bacteria poses a major public health threat to all patients, but patients with hematologic malignancies are especially at risk. A common thread across all classes of bacteria is that increased reliance on and usage of broad-spectrum antibacterial agents, combined with the intrinsic ability of bacteria to develop and transmit resistance-conferring mutations, has led to the widespread dissemination of MDR organisms. In this article, we summarize the most worrisome MDR bacteria, assess their clinical impact on patients with hematologic malignancies and outline measures that are required to mitigate this impact.
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Affiliation(s)
| | - Michael J Satlin
- Division of Infectious Diseases, Weill Cornell Medical Center, New York, NY, USA
- Transplantation–Oncology Infectious Diseases Program, Department of Medicine, Weill Cornell Medical Center, New York, NY, USA
| | - Maria N Gamaletsou
- University of Athens School of Medicine & Laikon Hospital, Athens, Greece
| | - Nikolaos V Sipsas
- University of Athens School of Medicine & Laikon Hospital, Athens, Greece
| | - Thomas J Walsh
- Department of Pediatrics, Weill Cornell Medical Center, New York, NY, USA
- Department of Microbiology & Immunology, Weill Cornell Medical Center, New York, NY, USA
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Kim HS, Lee SG, Kim WK, Park CW, Son S. Prophylactic intrawound application of vancomycin powder in instrumented spinal fusion surgery. KOREAN JOURNAL OF SPINE 2013; 10:121-5. [PMID: 24757472 PMCID: PMC3941757 DOI: 10.14245/kjs.2013.10.3.121] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Revised: 07/27/2013] [Accepted: 07/29/2013] [Indexed: 01/22/2023]
Abstract
Objective We evaluated the effect of intrawound application of vancomycin powder for infection prophylaxis in wounds caused by instrumented spinal surgery. Methods From July 2012 to December 2012, 74 instrumented spinal fusion procedures were performed by 1 neurosurgeon at a single institute. We divided the patients into 2 groups, depending on the use of local application of vancomycin powder: Group A (intrawound application of vancomycin powder with perioperative intravenous cefazolin) and Group B (perioperative intravenous cefazolin alone). A retrospective cohort comparative study was conducted between the 2 groups. The age, sex, comorbidities, smoking, surgical procedure, and surgical site infection (SSI) of consecutive patients were analyzed. Results Among the 74 patients, 34 patients were assigned to group A and 40 patients to group B. No wound infections were found in group A. However, in group B, 5 cases of SSI (12.5%) were found. A statistically significant reduction in SSI incidence was observed in group A (p<0.033). The 5 cases of SSI in group B consisted of 3 cases of deep wound infection and 2 cases of superficial wound infection. All SSIs were found in cases of posterior approach surgery and tended to be more frequent in older patients. Conclusion Adjunctive intrawound local application of vancomycin powder is a simple uncomplicated procedure and can result in a significant reduction of SSI in instrumented spinal fusions. Furthermore, culture of the drainage tip is very important for confirmation of deep wound infection.
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Affiliation(s)
- Hyun Su Kim
- Department of Neurosurgery, Gachon University Gil Medical Center, Incheon, Korea
| | - Sang Gu Lee
- Department of Neurosurgery, Gachon University Gil Medical Center, Incheon, Korea
| | - Woo Kyung Kim
- Department of Neurosurgery, Gachon University Gil Medical Center, Incheon, Korea
| | - Chan Woo Park
- Department of Neurosurgery, Gachon University Gil Medical Center, Incheon, Korea
| | - Seong Son
- Department of Neurosurgery, Gachon University Gil Medical Center, Incheon, Korea
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Akinosoglou K, Apostolakis E, Marangos M, Pasvol G. Native valve right sided infective endocarditis. Eur J Intern Med 2013; 24:510-9. [PMID: 23369408 DOI: 10.1016/j.ejim.2013.01.010] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2012] [Revised: 12/23/2012] [Accepted: 01/04/2013] [Indexed: 11/25/2022]
Abstract
Right-sided infective endocarditis (RSIE) accounts for 5-10% of all cases of infective endocarditis (IE), and is predominantly encountered in the injecting drug user (IDU) population, where HIV and HCV coinfections often coexist. Staphylococcus aureus is the most common pathogen. The pathogenesis of RSIE is still not well understood. RSIE usually presents as a persistent fever with respiratory symptoms whilst signs of systemic embolisation as seen in left-sided IE are notably absent. The prompt diagnosis of RSIE thus requires a high index of suspicion. Transthoracic echocardiography (TTE) can detect the majority of RSIE, whilst transoesophageal echocardiography (TOE) can increase sensitivity. Virulence of the causative organism and vegetation size are the major determinants of prognosis. Most cases of RSIE resolve with appropriate antibiotic administration.
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Affiliation(s)
- Karolina Akinosoglou
- Department of Internal Medicine and Infectious Diseases, University Hospital of Patras, 26504, Rio, Greece.
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Pastagia M, Kleinman LC, Lacerda de la Cruz EG, Jenkins SG. Predicting risk for death from MRSA bacteremia. Emerg Infect Dis 2012; 18:1072-80. [PMID: 22709685 PMCID: PMC3376787 DOI: 10.3201/eid1807.101371] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is often fatal. To determine predictors of risk for death, we conducted a retrospective cohort study. We examined 699 episodes of MRSA bacteremia involving 603 patients admitted to an academic medical center in New York City during 2002-2007. Data came from chart reviews, hospital databases, and recultured frozen MRSA specimens. Among the 699 episodes, 55 were caused by vancomycin-intermediate resistant S. aureus strains, 55 by heteroresistant vancomycin-intermediate S. aureus strains, and 589 by non-vancomycin-resistant strains; 190 (31.5%) patients died. We used regression risk analysis to quantify the association between clinical correlates and death. We found that older age, residence in a nursing home, severe bacteremia, and organ impairment were independently associated with increased risk for death; consultation with an infectious disease specialist was associated with lower risk for death; and MRSA strain types were not associated with risk for death.
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Affiliation(s)
- Mina Pastagia
- The Rockefeller University, New York, New York 10065, USA.
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Mavros MN, Tansarli GS, Vardakas KZ, Rafailidis PI, Karageorgopoulos DE, Falagas ME. Impact of vancomycin minimum inhibitory concentration on clinical outcomes of patients with vancomycin-susceptible Staphylococcus aureus infections: a meta-analysis and meta-regression. Int J Antimicrob Agents 2012; 40:496-509. [PMID: 23068600 DOI: 10.1016/j.ijantimicag.2012.07.023] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2012] [Revised: 07/24/2012] [Accepted: 07/27/2012] [Indexed: 12/29/2022]
Abstract
Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ≤2 mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure) of patients with S. aureus infections by 'high-VMIC' (conventionally defined as VMIC >1 mg/L but ≤2 mg/L) and 'low-VMIC' (VMIC≤1 mg/L) isolates were compared by performing a systematic review and meta-analysis. The effect of potential confounders was assessed by univariate meta-regression analyses. In total, 33 studies (6210 patients) were included. Most studies were retrospective (28/33), used the Etest (22/33) and referred to meticillin-resistant S. aureus (MRSA) infections (26/33) and bacteraemia (23/33). Irrespective of VMIC testing method, meticillin resistance and site of infection, the high-VMIC group had higher mortality [relative risk (RR)=1.21 (95% confidence interval 1.03-1.43); 4612 patients] and more treatment failures [RR=1.67 (1.26-2.21); 2049 patients] than the low-VMIC group. The results were not affected by the potential confounders and were reproduced in the subset of patients with MRSA infections [mortality, RR=1.19 (1.02-1.40), 2956 patients; treatment failure, RR=1.69 (1.26-2.25), 1793 patients]. In conclusion, infection by vancomycin-susceptible S. aureus with VMIC>1mg/L appears to be associated with higher mortality than VMIC≤1mg/L. Further research is warranted to verify these results and to assess the impact of VMIC on meticillin-susceptible S. aureus infections. Evaluation of alternative antimicrobial agents also appears justified.
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Kan LP, Lin JC, Chiu SK, Yeh YC, Lin TY, Yang YS, Wang YC, Wang NC, Yeh KM, Chang FY. Methicillin-resistant Staphylococcus aureus bacteremia in hemodialysis and nondialysis patients. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2012; 47:15-22. [PMID: 23040238 DOI: 10.1016/j.jmii.2012.08.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2012] [Revised: 07/31/2012] [Accepted: 08/15/2012] [Indexed: 10/27/2022]
Abstract
BACKGROUND/PURPOSE Increased mortality has been reported in patients treated with vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with high minimum inhibitory concentration (MIC) values within the susceptibility range. However, this finding has not been verified in hemodialysis patients, who have much higher invasive MRSA infection rates than nondialysis patients. We aimed at comparing vancomycin MICs between hemodialysis and nondialysis patients, and identifying predictors of high vancomycin MICs and infection-related mortality in hemodialysis patients with MRSA bacteremia. METHODS Patients with MRSA bacteremia from January 2008 through December 2009 were enrolled. Vancomycin MIC was determined for each first isolate using the Etest method. Clinical characteristics and vancomycin MICs were compared between hemodialysis and nondialysis patients. Factors associated with high vancomycin MIC (2 μg/mL) and infection-related mortality in hemodialysis patients were analyzed. RESULTS A total of 162 MRSA bacteremia episodes were identified. Forty-four (27.0%) isolates were obtained from hemodialysis patients and 118 (73.0%) from nondialysis patients. Diabetes (63.3% vs. 39.8%, p = 0.007) and prior vancomycin exposure in 30 days (31.8% vs. 12.7%, p = 0.005) were more prevalent in hemodialysis group than in nondialysis group. A higher prevalence of vancomycin MIC of 2 μg/mL was observed in hemodialysis group in comparison with nondialysis group (11.4% vs. 1.7%, p = 0.016). In following analyses of hemodialysis group, patients with initial presentation of septic shock had a higher risk of vancomycin MIC of 2 μg/mL than nonseptic shock patients (100.0% vs. 38.5% p = 0.014). Infection-related mortality was associated with age, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score >15, presence of septic shock, receipt of mechanical ventilation, and failure to remove source of bacteremia in univariate analysis. CONCLUSION Hemodialysis patients with MRSA bacteremia are more likely to have a high vancomycin MIC (2 μg/mL) compared with nondialysis patients. Infection-related mortality is associated with the patient's clinical manifestations, including age, APACHE-II score >15, presence of septic shock, receipt of mechanical ventilation, and failure to remove source of bacteremia. Treatment selection should be tailored according to the patient's clinical condition.
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Affiliation(s)
- Li-Ping Kan
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Jung-Chung Lin
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Sheng-Kang Chiu
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yen-Cheng Yeh
- Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Te-Yu Lin
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Ya-Sung Yang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yung-Chih Wang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Ning-Chi Wang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Kuo-Ming Yeh
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
| | - Feng-Yee Chang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Centers for Disease Control, Department of Health, Taipei, Taiwan
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Teng SO, Lee WS, Ou TY, Yu FL, Chen FL, Liu YH. Combination Therapy of Daptomycin and Fosfomycin for Vancomycin Tolerant Methicillin-Resistant Staphylococcus aureus Endocarditis Complicating Metastatic Osteomyelitis. ACTA ACUST UNITED AC 2012. [DOI: 10.1016/j.jecm.2012.09.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Mishra NN, Bayer AS, Moise PA, Yeaman MR, Sakoulas G. Reduced susceptibility to host-defense cationic peptides and daptomycin coemerge in methicillin-resistant Staphylococcus aureus from daptomycin-naive bacteremic patients. J Infect Dis 2012; 206:1160-7. [PMID: 22904338 DOI: 10.1093/infdis/jis482] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND We hypothesized that, for methicillin-resistant Staphylococcus aureus (MRSA), in vitro daptomycin susceptibility could be influenced by exposures to endogenous host defense peptides (HDPs) prior to clinical exposure to daptomycin. METHODS Two endovascular HDPs were used: thrombin-induced platelet microbicidal protein (tPMP) and human neutrophil defensin-1 (hNP-1) from neutrophils. Forty-seven unique MRSA isolates obtained from bacteremic patients in multicenter prospective clinical trials were studied. Clinical characteristics, microbiologic parameters, prior vancomycin therapy, and susceptibilities to tPMP, hNP-1, and daptomycin were compared using univariate and multivariate analyses. RESULTS All strains were daptomycin susceptible. Daptomycin minimum inhibitory concentrations (MICs) were inversely related to in vitro tPMP (but not hNP-1) killing. Strains with a daptomycin MIC of 1 mg/L exhibited significantly less killing by tPMP, compared with strains with an MIC of ≤ 0.5 mg/L. Prior vancomycin therapy did not influence this relationship. Regression tree modeling confirmed that reduced tPMP-induced killing in vitro was the strongest predictor of higher daptomycin MICs within the daptomycin-susceptible range. CONCLUSIONS Among daptomycin-susceptible MRSA isolates from patients who had never received daptomycin, higher daptomycin MICs tracked with increased resistance to killing by platelet-derived but not neutrophil-derived HDPs. These findings support the notion that endogenous exposure of MRSA to specific HDPs may play a role in selecting strains with an intrinsically higher daptomycin MIC phenotype.
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Han JH, Edelstein PH, Lautenbach E. Reduced vancomycin susceptibility and staphylococcal cassette chromosome mec (SCCmec) type distribution in methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother 2012; 67:2346-9. [PMID: 22761330 DOI: 10.1093/jac/dks255] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVES Recent epidemiological evidence suggests that genotypic and phenotypic characteristics that have typically distinguished community-associated methicillin-resistant Staphylococcus aureus (MRSA) and healthcare-associated MRSA strains may be evolving. The objective of this study was to examine the association between reduced vancomycin susceptibility (RVS) and staphylococcal cassette chromosome mec (SCCmec) type in MRSA bloodstream isolates. METHODS A cohort study of patients who were hospitalized from 2007 to 2009 with S. aureus bacteraemia was conducted within a university health system. Bivariable analyses were conducted to determine the association between RVS and SCCmec type, as well as other microbiological characteristics including Panton-Valentine leucocidin, accessory gene regulator (agr) dysfunction and vancomycin heteroresistance. RESULTS A total of 188 patients with MRSA bacteraemia were identified: 116 (61.7%) and 72 (38.3%) patients had infections due to healthcare-associated MRSA and community-associated MRSA, respectively. As defined by a vancomycin Etest MIC > 1.0 mg/L, the prevalence of RVS was 40.4%. Isolates with RVS were significantly more likely to be associated with SCCmec II compared with isolates without RVS (74.7% and 47.3%, respectively, P < 0.001), but not with Panton-Valentine leucocidin (P = 0.10), agr dysfunction (P = 0.19) or healthcare-associated infection (P = 0.36). CONCLUSIONS The results of our study demonstrate important microbiological characteristics among MRSA isolates characterized by RVS, including a significant association between SCCmec II and elevated vancomycin MIC. It is clear that the clinical and molecular epidemiology of MRSA is evolving, and further understanding of factors determining virulence will be important for the elucidation of optimal treatment approaches for associated infections.
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Affiliation(s)
- Jennifer H Han
- Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
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Mahajan SN, Shah JN, Hachem R, Tverdek F, Adachi JA, Mulanovich V, Rolston KV, Raad II, Chemaly RF. Characteristics and outcomes of methicillin-resistant staphylococcus aureus bloodstream infections in patients with cancer treated with vancomycin: 9-year experience at a comprehensive cancer center. Oncologist 2012; 17:1329-36. [PMID: 22707509 DOI: 10.1634/theoncologist.2012-0029] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) can cause significant morbidity and mortality in patients with cancer. However, data on outcomes of patients treated with vancomycin are lacking. METHODS We identified 223 patients with cancer who developed MRSA BSIs between January 2001 and June 2009 and were treated with vancomycin. Treatment failure was defined as death within 60 days of infection, persistent bacteremia ≥5 days, fever ≥4 days, recurrence or relapse, and secondary MRSA infection. RESULTS The treatment failure rate was 52% (116 of 223 patients). These patients were more likely to have been hospitalized, been treated with steroids within the previous 3 months, developed acute respiratory distress syndrome, required mechanical ventilation, required intensive care unit care, and community-onset infections (all p < .05). Risk factors for MRSA-associated mortality (27 of 223 patients; 12%) included hematologic malignancy and hematopoietic stem cell transplantation, community-onset infection, secondary BSI, MRSA with minimum inhibitory concentration (MIC) ≥2.0 μg/mL, mechanical ventilation, and a late switch to an alternative therapy (≥4 days after treatment failure; all p < .05). On multivariate analysis, mechanical ventilation and recent hospitalization were identified as independent predictors of vancomycin failure, and community-onset infection, secondary BSIs, and MIC ≥2 μg/mL were identified as significant predictors of MRSA-associated mortality. CONCLUSIONS We found a high treatment failure rate for vancomycin in patients with cancer and MRSA BSIs, as well as a higher mortality. A vancomycin MIC ≥2 μg/mL was an independent predictor of MRSA-associated mortality. An early switch to an alternative therapy at the earliest sign of failure may improve outcome.
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Affiliation(s)
- Sminil N Mahajan
- Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA
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Zelenitsky SA, Ariano RE, McCrae ML, Vercaigne LM. Initial Vancomycin Dosing Protocol to Achieve Therapeutic Serum Concentrations in Patients Undergoing Hemodialysis. Clin Infect Dis 2012; 55:527-33. [DOI: 10.1093/cid/cis458] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
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Park KH, Kim ES, Kim HS, Park SJ, Bang KM, Park HJ, Park SY, Moon SM, Chong YP, Kim SH, Lee SO, Choi SH, Jeong JY, Kim MN, Woo JH, Kim YS. Comparison of the clinical features, bacterial genotypes and outcomes of patients with bacteraemia due to heteroresistant vancomycin-intermediate Staphylococcus aureus and vancomycin-susceptible S. aureus. J Antimicrob Chemother 2012; 67:1843-9. [DOI: 10.1093/jac/dks131] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Dhand A, Sakoulas G. Reduced vancomycin susceptibility among clinical Staphylococcus aureus isolates ('the MIC Creep'): implications for therapy. F1000 MEDICINE REPORTS 2012; 4:4. [PMID: 22312414 PMCID: PMC3270590 DOI: 10.3410/m4-4] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Methicillin-resistant S. aureus (MRSA) has emerged as the most common hospital-acquired pathogen and is associated with increased morbidity and mortality compared with other strains. Vancomycin has been the cornerstone of treatment of patients with serious MRSA infections for some decades and while more than 99% of clinical S. aureus isolates remain susceptible to vancomycin, we are beginning to see strains of MRSA with reduced susceptibility. This review discusses this phenomenon, the predictors of infection with such forms of MRSA, and current and future management options.
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Affiliation(s)
- Abhay Dhand
- Department of MedicineNew York Medical College, Valhalla, NY 10595 USA
| | - George Sakoulas
- Department of MedicineNew York Medical College, Valhalla, NY 10595 USA
- Department of Pediatrics, University of California San Diego School of MedicineLa Jolla, CA 92093 USA
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Tratamiento con daptomicina en pacientes con bacteriemia. Enferm Infecc Microbiol Clin 2012; 30 Suppl 1:17-25. [DOI: 10.1016/s0213-005x(12)70067-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Jean SS, Hsueh PR. Current review of antimicrobial treatment of nosocomial pneumonia caused by multidrug-resistant pathogens. Expert Opin Pharmacother 2012; 12:2145-8. [PMID: 21895553 DOI: 10.1517/14656566.2011.599320] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Nosocomial pneumonia (including ventilator-associated pneumonia; VAP), a consistently difficult-to-treat entity, is frequently caused by multidrug-resistant (MDR) or pandrug-resistant (PDR) bacteria. Given the high mortality rates caused by drug-resistant bacteria and the difficulty of developing new potent antibiotics to target the problematic pathogens, combination regimens are under ardent evaluation as new strategies to overcome increasing drug resistance. Adjustment of the administration method of certain β-lactams (meropenem, or imipenem/cilastatin), or combination of tigecycline with some agents, may show promise with regard to successful management of MDR or PDR Acinetobacter baumannii pneumonia. Additionally, vancomycin plus rifampicin is an effective regimen against nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) responding poorly to vancomycin monotherapy. The clinical appropriateness of parenteral colistin against pneumonia caused by MDR A. baumannii has been established in a clinical trial. Facing the decline of clinical vancomycin efficacy after initial use, linezolid might be the drug of choice with regard to the treatment of MRSA-VAP. The role of tigecycline monotherapy for the management of nosocomial pneumonia caused by MRSA and extended-spectrum β-lactamase-producing Enterobacteriaceae needs to be cautiously evaluated.
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Gould IM, David MZ, Esposito S, Garau J, Lina G, Mazzei T, Peters G. New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance. Int J Antimicrob Agents 2011; 39:96-104. [PMID: 22196394 DOI: 10.1016/j.ijantimicag.2011.09.028] [Citation(s) in RCA: 205] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2011] [Accepted: 09/30/2011] [Indexed: 01/02/2023]
Abstract
Meticillin-resistant Staphylococcus aureus (MRSA) remains one of the principal multiply resistant bacterial pathogens causing serious healthcare-associated and community-onset infections. This paper reviews recent studies that have elucidated the virulence strategies employed by MRSA, key clinical trials of agents used to treat serious MRSA infections, and accumulating data regarding the implications of antibacterial resistance in MRSA for clinical success during therapy. Recent pre-clinical data support a species-specific role for Panton-Valentine leukocidin in the development of acute severe S. aureus infections and have elucidated other virulence mechanisms, including novel modes of internalisation, varying post-invasion strategies (featuring both upregulation and downregulation of virulence factors) and phenotypic switching. Recent double-blind, randomised, phase III/IV clinical trials have demonstrated the efficacy of linezolid and telavancin in hospital-acquired pneumonia (HAP) and complicated skin and skin-structure infections (cSSSIs) caused by MRSA. Tigecycline was non-inferior to imipenem/cilastatin in non-ventilator-associated HAP but was inferior in ventilator-associated pneumonia and has shown a higher rate of death than comparators on meta-analysis. Ceftaroline was clinically and microbiologically non-inferior to vancomycin/aztreonam in the treatment of MRSA cSSSI. Key resistance issues include a rise in vancomycin minimum inhibitory concentrations in MRSA, reports of clonal isolates with linezolid resistance mediated by acquisition of the chloramphenicol/florfenicol resistance gene, and case reports of daptomycin resistance resulting in clinical failure. Novel antimicrobial targets must be identified with some regularity or we will face the risk of untreatable S. aureus infections.
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Affiliation(s)
- Ian M Gould
- Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, UK.
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Mascitti KB, Edelstein PH, Fishman NO, Morales KH, Baltus AJ, Lautenbach E. Prior vancomycin use is a risk factor for reduced vancomycin susceptibility in methicillin-susceptible but not methicillin-resistant Staphylococcus aureus bacteremia. Infect Control Hosp Epidemiol 2011; 33:160-6. [PMID: 22227985 DOI: 10.1086/663708] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Staphylococcus aureus is a cause of community- and healthcare-acquired infections and is associated with substantial morbidity, mortality, and costs. Vancomycin minimum inhibitory concentrations (MICs) among S. aureus have increased, and reduced vancomycin susceptibility (RVS) may be associated with treatment failure. We aimed to identify clinical risk factors for RVS in S. aureus bacteremia. DESIGN Case-control. SETTING Academic tertiary care medical center and affiliated urban community hospital. PATIENTS Cases were patients with RVS S. aureus isolates (defined as vancomycin E-test MIC >1.0 μg/mL). Controls were patients with non-RVS S. aureus isolates. RESULTS Of 392 subjects, 134 (34.2%) had RVS. Fifty-eight of 202 patients (28.7%) with methicillin-susceptible S. aureus (MSSA) isolates had RVS, and 76 of 190 patients (40.0%) with methicillin-resistant S. aureus (MRSA) isolates had RVS (P = .02). In unadjusted analyses, prior vancomycin use was associated with RVS (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.00-4.32; P = .046). In stratified analyses, there was significant effect modification by methicillin susceptibility on the association between vancomycin use and RVS (P =.04). In multivariable analyses, after hospital of admission and prior levofloxacin use were controlled for, the association between vancomycin use and RVS was significant for patients with MSSA infection (adjusted OR, 4.02; 95% CI, 1.11-14.50) but not MRSA infection (adjusted OR, 0.87; 95% CI, 0.36-2.13). CONCLUSIONS A substantial proportion of patients with S. aureus bacteremia had RVS. The association between prior vancomycin use and RVS was significant for patients with MSSA infection but not MRSA infection, suggesting a complex relationship between the clinical and molecular epidemiology of RVS in S. aureus.
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Affiliation(s)
- Kara B Mascitti
- Division of Infectious Diseases, Department of Medicine, St. Luke's Hospital and Health Network, Bethlehem, Pennsylvania, USA.
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Intrawound application of vancomycin for prophylaxis in instrumented thoracolumbar fusions: efficacy, drug levels, and patient outcomes. Spine (Phila Pa 1976) 2011; 36:2084-8. [PMID: 21304438 DOI: 10.1097/brs.0b013e3181ff2cb1] [Citation(s) in RCA: 332] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN A retrospective cohort study from a single institution of a consecutive series of spine surgery patients. OBJECTIVE To evaluate the safety and efficacy of adjunctive local application of vancomycin for infection prophylaxis in posterior instrumented thoracic and lumbar spine wounds compared to IV cephalexin alone. SUMMARY OF BACKGROUND DATA Cephalosporin resistant strains of staphylococcus (MRSA and coagulase negative staph) have diminished the efficacy of intravenous antibiotic prophylaxis for instrumented spine fusion. Intravenous vancomycin prophylaxis has not been shown to decrease wound infection rates compared to IV cephalosporins. Adjunctive application of vancomycin powder in wounds for instrumented spinal fusion surgery may decrease infection rates. METHODS Since 2000, 1732 consecutive thoracic and lumbar posterior instrumented spinal fusions have been performed with routine 24 hours of perioperative intravenous antibiotic prophylaxis with cephalexin. Since 2006, 911 of these instrumented thoracic and lumbar cases had 2 g of vancomycin powder applied to the wound before closure in addition to intravenous antibiotics. A retrospective review for infection rates and complications was performed. Oswestry and SF-36 outcomes instruments were completed before surgery, immediately after surgery, and at latest follow-up. The average follow-up is 2.5 years, range 1 to 7 years. RESULTS Eight hundred twenty-one posterior instrumented thoracic and lumbar fusions were preformed using intravenous cephalexin prophylaxis with a total of 21 deep wound infections (2.6%). Coag negative staph was the most commonly isolated organism. Nine hundred eleven posterior instrumented thoracic and lumbar fusions have been performed with IV cephalexin plus adjunctive local vancomycin powder with two deep wound infections (0.2%). The reduction in wound infections was statistically significant (P < 0.0001). There were no adverse clinical outcomes or wound complications related to the local application of vancomycin. CONCLUSION Adjunctive local application of vancomycin powder decreases the postsurgical wound infection rate with statistical significance in posterior instrumented thoracolumbar spine fusions.
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Brown J, Brown KA, Forrest A. Outcomes and costs associated with a history of vancomycin exposure in patients with MRSA-related complicated bacteremia and infective endocarditis. Clin Ther 2011; 33:1475-82. [PMID: 21925733 DOI: 10.1016/j.clinthera.2011.08.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2011] [Indexed: 11/17/2022]
Abstract
BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is the primary cause of complicated bacteremia (CB) and infective endocarditis (IE). Studies have compared the costs of treatment with vancomycin to those of other agents, as well as the efficacy and tolerability of these treatments. However, a literature search found no published studies of the effects of vancomycin exposure on outcomes and hospital costs in patients with CB or IE due to MRSA. OBJECTIVE The aim of this study was to determine whether there is a quantitative relationship between the duration of vancomycin treatment or cumulative vancomycin exposure and outcomes or costs in patient with CB or IE due to MRSA. METHODS Electronic medical records of confirmed cases of MRSA-related CB or IE from July 1, 2006, to June 30, 2008, were retrospectively reviewed to identify patients with a history of vancomycin exposure or no vancomycin exposure. Those who received vancomycin were stratified by the amount of drug administered or the duration of treatment to determine the relationship between treatment and outcomes. Data collected included demographic information, treatment information, attributable mortality, MIC data, and hospital costs. Classification and regression tree analysis (CART) was used to determine whether a history of vancomycin exposure was associated with treatment failure, attributable mortality, or both. The Mann-Whitney U test and the Fisher exact test were used for univariate analyses, and logistic regression was used for multivariate modeling. RESULTS Data from 50 patients were evaluated (CB, 32; IE, 18). Overall rates of failure and attributable mortality were 32% and 16%, respectively. No significant differences were observed between the variables and costs. The CART break points for failure were ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years; for attributable mortality, the CART break points were ≥45 g and ≥31 days. In the final multivariate model for failure, ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years were predictors of failure (both, P = 0.002). Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.04), ≥45 g (P = 0.002), and ≥31 days of treatment (P = 0.002) in the previous 3 years were predictors of attributable mortality after adjustment for all covariates. CONCLUSIONS Using the present model, cumulative vancomycin amount and duration were associated with attributable mortality and clinical failure but not with costs.
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Affiliation(s)
- Jack Brown
- State University of New York at Buffalo School of Pharmacy and Pharmaceutical Science, Buffalo, New York, USA.
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Clemens EC, Chan JD, Lynch JB, Dellit TH. Relationships between vancomycin minimum inhibitory concentration, dosing strategies, and outcomes in methicillin-resistant Staphylococcus aureus bacteremia. Diagn Microbiol Infect Dis 2011; 71:408-14. [PMID: 21924852 DOI: 10.1016/j.diagmicrobio.2011.08.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2011] [Revised: 07/22/2011] [Accepted: 08/01/2011] [Indexed: 10/17/2022]
Abstract
Retrospective study aimed to examine outcomes of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in relationship to vancomycin minimum inhibitory concentration (VAN MIC) and serum trough concentrations among subjects who had ≥1 blood culture positive for MRSA between April 2008 and August 2009. Treatment failure occurred in 7/24 (29%) subjects with VAN MIC = 2 mg/L versus 20/94 (21%) subjects with VAN MIC ≤1.5 mg/L (adjusted OR 1.11, 95% confidence interval [CI] 0.24-5.14). Among subjects who had documented VAN serum trough concentrations, treatment failure occurred in 5/26 (19%) subjects with concentrations <15 mg/L versus 18/68 (27%) subjects with concentrations ≥15 mg/L (adjusted OR 0.91, 95% CI 0.21-3.84). In conclusion, treatment outcomes were similar regardless of VAN MIC, although there was a non-statistically significant trend towards decreased clinical efficacy among patients with VAN MIC = 2 mg/L. Optimization of VAN pharmacokinetic indices did not appear to correlate with clinical responses.
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Affiliation(s)
- Evan C Clemens
- Department of Pharmacy, Harborview Medical Center and School of Pharmacy, University of Washington, Seattle, WA 98104, USA
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