scholarly journals Association of mprF mutations with cross-resistance to daptomycin and vancomycin in methicillin-resistant Staphylococcus aureus (MRSA)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kanate Thitiananpakorn ◽  
Yoshifumi Aiba ◽  
Xin-Ee Tan ◽  
Shinya Watanabe ◽  
Kotaro Kiga ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cross Resistance ◽  
Surface Charges ◽  
Genetic Determinants ◽  
Methicillin Resistant ◽  
Bacterial Surface ◽  
The Cross ◽  
Altered Gene ◽  
The Impact

Abstract We first reported a phenomenon of cross-resistance to vancomycin (VCM) and daptomycin (DAP) in methicillin-resistant Staphylococcus aureus (MRSA) in 2006, but mechanisms underlying the cross-resistance remain incompletely understood. Here, we present a follow-up study aimed to investigate genetic determinants associated with the cross-resistance. Using 12 sets of paired DAP susceptible (DAPS) and DAP non-susceptible (DAPR) MRSA isolates from 12 patients who had DAP therapy, we (i) assessed susceptibility to DAP and VCM, (ii) compared whole-genome sequences, (iii) identified mutations associated with cross-resistance to DAP and VCM, and (iv) investigated the impact of altered gene expression and metabolic pathway relevant to the cross-resistance. We found that all 12 DAPR strains exhibiting cross-resistance to DAP and VCM carried mutations in mprF, while one DAPR strain with reduced susceptibility to only DAP carried a lacF mutation. On the other hand, among the 32 vancomycin-intermediate S. aureus (VISA) strains isolated from patients treated with VCM, five out of the 18 strains showing cross-resistance to DAP and VCM carried a mprF mutation, while 14 strains resistant to only VCM had no mprF mutation. Moreover, substitution of mprF in a DAPS strain with mutated mprF resulted in cross-resistance and vice versa. The elevated lysyl-phosphatidylglycerol (L-PG) production, increased positive bacterial surface charges and activated cell wall (CW) synthetic pathways were commonly found in both clinical isolates and laboratory-developed mutants that carry mprF mutations. We conclude that mprF mutation is responsible for the cross-resistance of MRSA to DAP and VCM, and treatment with DAP is more likely to select for mprF-mediated cross-resistance than is with VCM.

Risk Factors for Methicillin-Resistant Staphylococcus aureus (MRSA) Acquisition in Roommate Contacts of Patients Colonized or Infected With MRSA in an Acute-Care Hospital

2008 ◽  
Vol 29 (7) ◽  
pp. 600-606 ◽  
Author(s):  
Christine Moore ◽  
Jastej Dhaliwal ◽  
Agnes Tong ◽  
Sarah Eden ◽  
Cindi Wigston ◽  
...  
Keyword(s):  
Risk Factors ◽  
Staphylococcus Aureus ◽  
Acute Care ◽  
Significant Risk ◽  
Acute Care Hospital ◽  
Skin Lesions ◽  
Care Hospital ◽  
Methicillin Resistant ◽  
The Impact

Objective.To identify risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in patients exposed to an MRSA-colonized roommate.Design.Retrospective cohort study.Setting.A 472-bed acute-care teaching hospital in Toronto, Canada.Patients.Inpatients who shared a room between 1996 and 2004 with a patient who had unrecognized MRSA colonization.Methods.Exposed roommates were identified from infection-control logs and from results of screening for MRSA in the microbiology database. Completed follow-up was defined as completion of at least 2 sets of screening cultures (swab samples from the nares, the rectum, and skin lesions), with at least 1 set of samples obtained 7–10 days after the last exposure. Chart reviews were performed to compare those who did and did not become colonized with MRSA.Results.Of 326 roommates, 198 (61.7%) had completed follow-up, and 25 (12.6%) acquired MRSA by day 7–10 after exposure was recognized, all with strains indistinguishable by pulsed-field gel electrophoresis from those of their roommate. Two (2%) of 101 patients were not colonized at day 7–10 but, with subsequent testing, were identified as being colonized with the same strain as their roommate (one at day 16 and one at day 18 after exposure). A history of alcohol abuse (odds ratio [OR], 9.8 [95% confidence limits {CLs}, 1.8, 53]), exposure to a patient with nosocomially acquired MRSA (OR, 20 [95% CLs, 2.4,171]), increasing care dependency (OR per activity of daily living, 1.7 [95% CLs, 1.1, 2.7]), and having received levofloxacin (OR, 3.6 [95% CLs, 1.1,12]) were associated with MRSA acquisition.Conclusions.Roommates of patients with MRSA are at significant risk for becoming colonized. Further study is needed of the impact of hospital antimicrobial formulary decisions on the risk of acquisition of MRSA.

Impact of a Methicillin-Resistant Staphylococcus Aureus Active Surveillance Culture Protocol on Mupirocin Prescribing

2009 ◽  
Vol 44 (9) ◽  
pp. 781-784
Author(s):  
Marisel Segarra-Newnham ◽  
Kristin St. John
Keyword(s):  
Staphylococcus Aureus ◽  
Active Surveillance ◽  
Nasal Swab ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inpatient Setting ◽  
Surveillance Culture ◽  
Methicillin Resistant ◽  
The Impact ◽  
Active Surveillance Culture

Background To identify patients colonized with methicillin-resistant Staphylococcus aureus (MRSA), an active surveillance culture (ASC) protocol has been in place since March 2007. Decolonization with mupirocin ointment is not recommended but may be attempted after a positive MRSA screen. Objective Assess the impact of an inpatient ASC protocol on prescribing of mupirocin nasal ointment for decolonization before and after protocol implementation. Methods A retrospective review of mupirocin inpatient prescribing and outpatient clinic requests from March 2006 through February 2007 (1 year before ASC implementation) and from March 2007 through February 2008 (1 year after ASC implementation) was conducted. Cultures for MRSA after decolonization were evaluated. Results During the 24 months reviewed, 38 inpatients received mupirocin (18 before and 20 after ASC). Only 14 patients (37%) had a follow-up nasal swab (5 before and 9 after ASC). Of these patients, 5 (36%) had a positive nasal swab after the initial decolonization attempt. Ten patients (26%) had at least 1 clinical culture positive for MRSA after the initial decolonization (7 before and 3 after ASC). Outpatient requests for mupirocin increased 2.5-fold after ASC implementation. Sixty percent of the requests were not appropriate. Conclusion After implementation of the ASC protocol, there was no change in mupirocin prescribing for decolonization in the inpatient setting. However, outpatient requests—most of which were not indicated—increased. Success of decolonization cannot be assessed because follow-up nasal screening was not universally performed.

scholarly journals LTX-109 Is a Novel Agent for Nasal Decolonization of Methicillin-Resistant and -Sensitive Staphylococcus aureus

2014 ◽  
Vol 59 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Anna C. Nilsson ◽  
Håkan Janson ◽  
Hedda Wold ◽  
Anders Fugelli ◽  
Karin Andersson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Load ◽  
Systemic Exposure ◽  
Cross Resistance ◽  
Methicillin Resistant ◽  
Content Type ◽  
Safety Issues ◽  
Development Of Resistance ◽  
Epithelial Lesions

ABSTRACTNasal decolonization has a proven effect on the prevention of severeStaphylococcus aureusinfections and the control of methicillin-resistantS. aureus(MRSA). However, rising rates of resistance to antibiotics highlight the need for new substances for nasal decolonization. LTX-109 is a broad-spectrum, fast-acting bactericidal antimicrobial drug for topical treatment, which causes membrane disruption and cell lysis. This mechanism of action is not associated with cross-resistance and has a low propensity for development of resistance. In the present study, persistent nasal MRSA and methicillin-sensitiveS. aureus(MSSA) carriers were treated for 3 days with vehicle or with 1%, 2%, or 5% LTX-109. A significant effect on nasal decolonization was observed already after 2 days of LTX-109 treatment in subjects treated with 2% or 5% LTX-109 compared to vehicle (P≤ 0.0012 by Dunnett′s test). No safety issues were noted during the 9-week follow-up period. Minimal reversible epithelial lesions were observed in the nasal cavity. The systemic exposure was very low, with a maximum concentration of drug in plasma (Cmax) at 1 to 2 h postdosing (3.72 to 11.7 ng/ml). One week after treatment initiation, LTX-109 was not detectable in any subject. Intranasal treatment ofS. aureuswith LTX-109 is safe and reduces the bacterial load already after a single day of treatment. Hence, LTX-109 has potential as a new and effective antimicrobial agent with a low propensity of resistance development that can prevent infections by MSSA/MRSA during hospitalization. (This study has been registered atClinicalTrials.govunder registration no. NCT01158235.)

The Analysis of the Impact of a Mild, Low-iodine, Lotion Soap on the Reduction of Nosocomial Methicillin-Resistant Staphylococcus aureus: A New Opportunity for Surveillance by Objectives

1987 ◽  
Vol 8 (7) ◽  
pp. 284-288 ◽  
Author(s):  
Kim M. Onesko ◽  
Eugene C. Wienke
Keyword(s):  
Staphylococcus Aureus ◽  
Nosocomial Infections ◽  
Control Measures ◽  
Methicillin Resistant ◽  
Care Community ◽  
Infection Control Measures ◽  
Medical Division ◽  
Tract Infections ◽  
The Impact ◽  
Community Teaching

AbstractA significant unremitting increase in the incidence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infections in a 500-bed acute care community teaching hospital prompted reevaluation of the efficacy of the infection control measures used. A well-accepted, low-iodine, antimicrobial soap was used to replace a liquid natural handsoap in two areas with the highest incidence of MRSA—the intensive care unit, and a medical division.Over a two-year period, an analysis was made of the effect of soap replacement on nosocomial infections and pathogens. Soap changeover occurred at the midpoint of the two-year period. From year to year, the nosocomial MRSA rate decreased 80% (t test, P=0.005). Other pathogens that demonstrated a dramatic decrease included methicillin-sensitive Staphylococcus aureus (MSSA), infections where no pathogens were isolated, and various gram-negative infections. Categories of nosocomial infections that decreased included surgical wound infections, primary bacteremias, and respiratory tract infections. The overall nosocomial infection rate of the two combined areas decreased 21.5%, representing a year-to-year savings of $109,500. As a result, the decision was made to install the low-iodine hand-soap permanently at all sinks within the hospital.

scholarly journals Ceftaroline Desensitization Procedure in a Pregnant Patient With Multiple Drug Allergies

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
James L. Kuhlen ◽  
Kimberly G. Blumenthal ◽  
Caroline L. Sokol ◽  
Diana S. Balekian ◽  
Ana A. Weil ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Skin Testing ◽  
Pregnant Patient ◽  
Cross Reactivity ◽  
Multiple Drug ◽  
Methicillin Resistant ◽  
The Cross ◽  
Staphylococcus Aureus Pneumonia

Abstract Validated skin testing is lacking for many drugs, including ceftaroline. The cross-reactivity between ceftaroline and other β-lactam antibiotics is unknown. We report a case of a pregnant patient with cystic fibrosis and multiple drug allergies who required ceftaroline for methicillin-resistant Staphylococcus aureus pneumonia and underwent an uncomplicated empiric desensitization procedure.

scholarly journals Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Atul K. Verma ◽  
Christopher Bauer ◽  
Vijaya Kumar Yajjala ◽  
Shruti Bansal ◽  
Keer Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Therapeutic Effect ◽  
Critical Role ◽  
Lung Damage ◽  
Alpha Toxin ◽  
Methicillin Resistant ◽  
Content Type ◽  
Linezolid Therapy ◽  
Staphylococcus Aureus Pneumonia ◽  
The Impact

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

scholarly journals Introduction of the mec Element (Methicillin Resistance) into Staphylococcus aureus Alters In Vitro Functional Activities of Fibrinogen and Fibronectin Adhesins

1998 ◽  
Vol 42 (3) ◽  
pp. 564-570 ◽  
Author(s):  
Pierre E. Vaudaux ◽  
Vincenza Monzillo ◽  
Patrice Francois ◽  
Daniel P. Lew ◽  
Tim J. Foster ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Bacterial Colonization ◽  
Protein A ◽  
Methicillin Resistant ◽  
Functional Activities ◽  
Extracellular Matrix Components ◽  
Resistant Strains ◽  
The Impact

ABSTRACT Some methicillin-resistant strains of Staphylococcus aureus are defective in the production of major surface components such as protein A, clumping factor, or other important adhesins to extracellular matrix components which may play a role in bacterial colonization and infection. To evaluate the impact of methicillin resistance (mec) determinants on bacterial adhesion mediated by fibrinogen or fibronectin adhesins, we compared the in vitro attachment of two genetically distinct susceptible strains (NCTC8325 and Newman) to protein-coated surfaces with that of isogenic methicillin-resistant derivatives. All strains containing an intactmec element in their chromosomes were found to be defective in adhesion to fibrinogen and fibronectin immobilized on polymethylmethacrylate coverslips, regardless of the presence or absence of additional mutations in the femA,femB, or femC gene, known to decrease expression of methicillin resistance in S. aureus. Western ligand affinity blotting or immunoblotting of cell wall-associated adhesins revealed similar contents of fibrinogen- or fibronectin-binding proteins in methicillin-resistant strains compared to those of their methicillin-susceptible counterparts. In contrast to methicillin-resistant strains carrying a mec element in their genomes, methicillin-resistant strains constructed in vitro, by introducing the mecA gene on a plasmid, retained their adhesion phenotypes. In conclusion, the chromosomal insertion of themec element into genetically defined strains of S. aureus impairs the in vitro functional activities of fibrinogen or fibronectin adhesins without altering their production. This effect is unrelated to the activity of the mecA gene.

Colonization With Methicillin-Resistant Staphylococcus aureus in ICU Patients Morbidity, Mortality, and Glycopeptide Use

2001 ◽  
Vol 22 (11) ◽  
pp. 687-692 ◽  
Author(s):  
Maité Garrouste-Orgeas ◽  
Jean-Francois Timsit ◽  
Hatem Kallel ◽  
Adel Ben Ali ◽  
Marie Francoise Dumay ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Tertiary Care ◽  
Icu Mortality ◽  
Icu Patients ◽  
Methicillin Resistant ◽  
Saps Ii ◽  
Icu Stay ◽  
Mrsa Infection ◽  
The Impact ◽  
Mrsa Colonization

Abstract Objective: To determine the impact of methicillin-resis-tant Staphylococcus aureus (MRSA) colonization on the occurrence of S aureus infections (methicillin-resistant and methicillin-suscep-tible), the use of glycopeptides, and outcome among intensive care unit (ICU) patients. Design: Prospective observational cohort survey. Setting: A medical-surgical ICU with 10 single-bed rooms in a 460-bed, tertiary-care, university-affiliated hospital. Patients: A total of 1,044 ICU patients were followed for the detection of MRSA colonization from July 1, 1995, to July, 1 1998. Methods: MRSA colonization was detected using nasal samples in all patients plus wound samples in surgical patients within 48 hours of admission or within the first 48 hours of ICU stay and weekly thereafter. MRSA infections were defined using Centers for Disease Control and Prevention standard definitions, except for ventilator-associated pneumonia and catheter-related infections, which were defined by quantitative distal culture samples. Results: One thousand forty-four patients (70% medical patients) were included in the analysis. Mean age was 61±18 years; mean Simplified Acute Physiologic Score (SAPS) II was 36.4±20; and median ICU stay was 4 (range, 1-193) days. Two hundred thirty-one patients (22%) died in the ICU. Fifty-four patients (5.1%) were colonized with MRSA on admission, and 52 (4.9%) of 1,044 acquired MRSA colonization in the ICU. Thirty-five patients developed a total of 42 S aureus infections (32 MRSA, 10 methi-cillin-susceptible). After factors associated with the development of an S aureus infection were adjusted for in a multivariate Cox model (SAPS II >36: hazard ratio [HR], 1.64; P=.09; male gender: HR, 2.2; P=.05), MRSA colonization increased the risk of S aureus infection (HR, 3.84; P=.0003). MRSA colonization did not influence ICU mortality (HR, 1.01; P=.94). Glycopeptides were used in 11.4% of the patients (119/1,044) for a median duration of 5 days. For patients with no colonization, MRSA colonization on admission, and ICU-acquired MRSA colonization, respectively, glycopeptide use per 1,000 hospital days was 37.7, 235.2, and 118.3 days. MRSA colonization per se increased by 3.3-fold the use of glycopeptides in MRSA-colonized patients, even when an MRSA infection was not demonstrated, compared to non-colonized patients. Conclusions: In our unit, MRSA colonization greatly increased the risk of S aureus infection and of glycopeptide use in colonized and non-colonized patients, without influencing ICU mortality. MRSA colonization influenced glycopeptide use even if an MRSA infection was not demonstrated; thus, an MRSA control program is warranted to decrease vancomycin use and to limit glycopeptide resistance in gram-positive cocci.

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