scholarly journals Multicenter Study of High-Dose Daptomycin for Treatment of Enterococcal Infections

2013 ◽  
Vol 57 (9) ◽  
pp. 4190-4196 ◽  
Author(s):  
Anthony M. Casapao ◽  
Ravina Kullar ◽  
Susan L. Davis ◽  
Donald P. Levine ◽  
Jing J. Zhao ◽  
...  
Keyword(s):  
Clinical Success ◽  
Clinical Success Rate ◽  
High Dose ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Median Dosage ◽  
All Cause Mortality ◽  
Vancomycin Resistant ◽  
Hospital Acquired ◽  
Enterococcal Infections

ABSTRACTEnterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated.Enterococcus faeciumwas identified in 175 (71%), followed byEnterococcus faecalisin 49 (20%) andEnterococcusspp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.

scholarly journals Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci

2016 ◽  
Vol 60 (4) ◽  
pp. 2209-2221 ◽  
Author(s):  
Pooja Bhardwaj ◽  
Elizabeth Ziegler ◽  
Kelli L. Palmer
Keyword(s):  
Resistance Genes ◽  
Venous Catheter ◽  
Vancomycin Resistance ◽  
Chlorhexidine Gluconate ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Chlorhexidine Bathing ◽  
Vancomycin Resistant ◽  
Species Specific ◽  
Hospital Acquired

ABSTRACTChlorhexidine is a bisbiguanide antiseptic used for infection control. Vancomycin-resistantE. faecium(VREfm) is among the leading causes of hospital-acquired infections. VREfm may be exposed to chlorhexidine at supra- and subinhibitory concentrations as a result of chlorhexidine bathing and chlorhexidine-impregnated central venous catheter use. We used RNA sequencing to investigate how VREfm responds to chlorhexidine gluconate exposure. Among the 35 genes upregulated ≥10-fold after 15 min of exposure to the MIC of chlorhexidine gluconate were those encoding VanA-type vancomycin resistance (vanHAX) and those associated with reduced daptomycin susceptibility (liaXYZ). We confirmed thatvanAupregulation was not strain or species specific by querying other VanA-type VRE. VanB-type genes were not induced. ThevanHpromoter was found to be responsive to subinhibitory chlorhexidine gluconate in VREfm, as was production of the VanX protein. UsingvanHreporter experiments withBacillus subtilisand deletion analysis in VREfm, we found that this phenomenon is VanR dependent. Deletion ofvanRdid not result in increased chlorhexidine susceptibility, demonstrating thatvanHAXinduction is not protective against chlorhexidine. As expected, VanA-type VRE is more susceptible to ceftriaxone in the presence of sub-MIC chlorhexidine. Unexpectedly, VREfm is also more susceptible to vancomycin in the presence of subinhibitory chlorhexidine, suggesting that chlorhexidine-induced gene expression changes lead to additional alterations in cell wall synthesis. We conclude that chlorhexidine induces expression of VanA-type vancomycin resistance genes and genes associated with daptomycin nonsusceptibility. Overall, our results indicate that the impacts of subinhibitory chlorhexidine exposure on hospital-associated pathogens should be further investigated in laboratory studies.

scholarly journals Reciprocal Regulation of Cephalosporin Resistance in Enterococcus faecalis

mBio ◽  
2011 ◽  
Vol 2 (6) ◽  
Author(s):  
Christopher J. Kristich ◽  
Jaime L. Little ◽  
Cherisse L. Hall ◽  
Jessica S. Hoff
Keyword(s):  
Public Health ◽  
Molecular Basis ◽  
Public Health Problem ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Cephalosporin Resistance ◽  
Cephalosporin Antibiotics ◽  
Hospital Acquired ◽  
Enterococcal Infections

ABSTRACT Antibiotic-resistant enterococci are major causes of hospital-acquired infections and therefore represent a serious public health problem. One well-known risk factor for the acquisition of hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporin antibiotics. Enterococci can proliferate in patients undergoing cephalosporin therapy due to intrinsic cephalosporin resistance, a characteristic of the genus Enterococcus. However, the molecular basis for cephalosporin resistance in E. faecalis has yet to be adequately elucidated. Previously we determined that a putative Ser/Thr kinase, IreK (formerly PrkC), is required for intrinsic cephalosporin resistance in E. faecalis. Here we show that kinase activity is required for cephalosporin resistance and, further, that resistance in E. faecalis is reciprocally regulated by IreK and IreP, a PP2C-type protein phosphatase encoded immediately upstream of IreK. Mutants of two divergent lineages of E. faecalis lacking IreP exhibit remarkable hyperresistance to cephalosporins but not to antibiotics targeting other cellular processes. Further genetic analyses indicate that hyperresistance of the IreP mutant is mediated by the IreK kinase. Additionally, competition experiments reveal that hyperresistant ΔireP mutants exhibit a substantial fitness defect in the absence of antibiotics, providing an evolutionary rationale for the use of a complex signaling system to control intrinsic cephalosporin resistance. These results support a model in which IreK and IreP act antagonistically via protein phosphorylation and dephosphorylation as part of a signal transduction circuit to regulate cellular adaptation to cephalosporin-induced stress. IMPORTANCE As a major cause of hospital-acquired infections, antibiotic-resistant enterococci represent a serious public health problem. Enterococci are well-known to exhibit intrinsic resistance to broad-spectrum cephalosporin antibiotics, a trait that enables them to proliferate in patients undergoing cephalosporin therapy, thereby predisposing these patients to acquisition of an enterococcal infection. Thus, inhibition of enterococcal cephalosporin resistance could represent an effective new strategy to prevent the emergence of hospital-acquired enterococcal infections. At this time, however, the molecular basis for cephalosporin resistance in E. faecalis is poorly understood. Our results begin to unravel the details of a new phosphorylation-dependent signal transduction system that controls cephalosporin resistance in enterococci. Deeper understanding of the mechanism underlying cephalosporin resistance in E. faecalis may enable the development of new therapeutics designed to reduce the incidence of hospital-acquired enterococcal infections.

Clinical effectiveness of high dose versus standard dose of meropenem in ventilator-associated pneumonia caused by multidrug-resistant bacteria: a randomized single-blind clinical trial

2020 ◽  
Vol 20 ◽  
Author(s):  
Mahila Monajati ◽  
Shahram Ala ◽  
Masoud Aliyali ◽  
Roya Ghasemian ◽  
Fatemeh Heidari ◽  
...  
Keyword(s):  
Success Rate ◽  
Sofa Score ◽  
Dose Group ◽  
Clinical Success ◽  
Standard Dose ◽  
Clinical Success Rate ◽  
High Dose Group ◽  
Resistant Bacteria ◽  
High Dose ◽  
Ventilator Associated Pneumonia

Background: Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP). Methods: 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard dose group, 13 patients) as a 3h infusion. Primary outcome was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. A sputum culture was taken before intervention. Results: Clinical success rate was not significantly different between the high and standard dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in reduction of clinical pulmonary infection score (CPIS) compared to high dose with standard group (P=0.038). SOFA score declined significantly in high dose group through the study (P=0.006). A shorter duration of VAP treatment was recorded in high dose group (P=0.061). We did not observe any significant adverse event related to meropenem. Acinetobacter spp. (34.8%), Klebsiella spp. (32.6%) and, Pseudomonas aeruginosa (19.5%) isolated more frequently from sputum cultures. Conclusion: Treatment with high dose of meropenem seems to be safe. However, it did not provide significantly higher clinical success rate in comparison with the standard dose, but could be considered as an appropriate empirical treatment in patients with severe infection due to reducing in SOFA and CPIS.

scholarly journals 1306. Comparison of the Use of Extended and Intermittent Infusion Cefepime and Piperacillin/tazobactam in Non-critically Ill, Obese Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S667-S667
Author(s):  
Carolyn Marg ◽  
Zach DeLanoit ◽  
Kimberly D Boeser
Keyword(s):  
Clinical Success ◽  
Small Sample Size ◽  
Clinical Success Rate ◽  
Intermittent Infusion ◽  
Volume Of Distribution ◽  
Small Sample ◽  
Hospital Length Of Stay ◽  
Obese Patients ◽  
Target Time ◽  
All Cause Mortality

Abstract Background Obesity rates have dramatically increased over the last several decades, however, there is limited data to guide how antibiotics should be adjusted in obese patients. Physiologic differences including an increased volume of distribution and increased renal clearance may alter their pharmacokinetics and pharmacodynamics and subsequently, their efficacy. For beta-lactams like piperacillin/tazobactam (pip/tazo) and cefepime, extended infusion (EI) maximizes the time above the minimum inhibitory concentration (MIC) for optimal bactericidal activity. This dosing strategy may help decrease variability in achieving the target time above MIC in this patient population and lead to more favorable outcomes. Methods This single-center, retrospective, pre-/post- analysis included patients with a body mass index (BMI) > 30 that received EI (infused over 4 hours) or intermittent infusion (II) (infused over 30 minutes) pip/tazo or cefepime between 2/1/2020-4/30/2020 and 2/1/2019-4/30/2019, respectively. The primary outcome was in-hospital, all-cause mortality. Secondary outcomes included clinical success rate and hospital length of stay (LOS). Results During the evaluation periods, 98 patients met inclusion criteria (EI, N=53; II, N=45). Mean BMI was not statistically different between groups (EI, 36.0 kg/m2 [30.1-46.3]; II, 36.5 kg/m2 [30-48]). There were no cases of mortality in either group. The mean LOS in the II group was 13 days compared to 11.5 days in the EI group [95% CI -4.14-7.04; p=0.606]. After excluding one outlier of 104 days in the EI group, the average LOS was 9.5 days [95% CI: -0.87-7.33; p=0.121]. Markers of clinical success including time to resolution of fever (II: 47 hours; EI: 34 hours; p=0.216) and time to resolution of leukocytosis (II: 2 days; EI: 3.8 days; p=0.089) were not significantly different between groups. Conclusion The use of EI pip/tazo and cefepime was not associated with any differences in in-hospital, all-cause mortality, hospital LOS, or clinical success when compared to the use of II pip/tazo and cefepime. The lack of significant differences between groups may be attributable to the small sample size limiting the ability to detect a difference, especially regarding hospital LOS. Disclosures All Authors: No reported disclosures

scholarly journals Lon Protease Has Multifaceted Biological Functions inAcinetobacter baumannii

2018 ◽  
Vol 201 (2) ◽  
Author(s):  
Carly Ching ◽  
Brendan Yang ◽  
Chineme Onwubueke ◽  
David Lazinski ◽  
Andrew Camilli ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Developmental Process ◽  
Cell Envelope ◽  
Opportunistic Pathogen ◽  
Lon Protease ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Biofilm Development ◽  
Hospital Acquired

ABSTRACTAcinetobacter baumanniiis a Gram-negative opportunistic pathogen that is known to survive harsh environmental conditions and is a leading cause of hospital-acquired infections. Specifically, multicellular communities (known as biofilms) ofA. baumanniican withstand desiccation and survive on hospital surfaces and equipment. Biofilms are bacteria embedded in a self-produced extracellular matrix composed of proteins, sugars, and/or DNA. Bacteria in a biofilm are protected from environmental stresses, including antibiotics, which provides the bacteria with selective advantage for survival. Although some gene products are known to play roles in this developmental process inA. baumannii, mechanisms and signaling remain mostly unknown. Here, we find that Lon protease inA. baumanniiaffects biofilm development and has other important physiological roles, including motility and the cell envelope. Lon proteases are found in all domains of life, participating in regulatory processes and maintaining cellular homeostasis. These data reveal the importance of Lon protease in influencing keyA. baumanniiprocesses to survive stress and to maintain viability.IMPORTANCEAcinetobacter baumanniiis an opportunistic pathogen and is a leading cause of hospital-acquired infections.A. baumanniiis difficult to eradicate and to manage, because this bacterium is known to robustly survive desiccation and to quickly gain antibiotic resistance. We sought to investigate biofilm formation inA. baumannii, since much remains unknown about biofilm formation in this bacterium. Biofilms, which are multicellular communities of bacteria, are surface attached and difficult to eliminate from hospital equipment and implanted devices. Our research identifies multifaceted physiological roles for the conserved bacterial protease Lon inA. baumannii. These roles include biofilm formation, motility, and viability. This work broadly affects and expands understanding of the biology ofA. baumannii, which will permit us to find effective ways to eliminate the bacterium.

scholarly journals Novel Drivers of Virulence in Clostridioides difficile Identified via Context-Specific Metabolic Network Analysis

mSystems ◽  
2021 ◽  
Author(s):  
Matthew L. Jenior ◽  
Jhansi L. Leslie ◽  
Deborah A. Powers ◽  
Elizabeth M. Garrett ◽  
Kimberly A. Walker ◽  
...  
Keyword(s):  
Network Analysis ◽  
Metabolic Network ◽  
Virulence Factors ◽  
Metabolic Pathways ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Metabolic Network Analysis ◽  
Clostridioides Difficile ◽  
Context Specific ◽  
Hospital Acquired

Clostridioides difficile has become the leading single cause of hospital-acquired infections. Numerous studies have demonstrated the importance of specific metabolic pathways in aspects of C. difficile pathophysiology, from initial colonization to regulation of virulence factors.

scholarly journals Complete Genome Sequence of Klebsiella pneumoniae Phage Sweeny

2019 ◽  
Vol 8 (39) ◽  
Author(s):  
Nicholas Martinez ◽  
Eric Williams ◽  
Heather Newkirk ◽  
Mei Liu ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Complete Genome Sequence ◽  
Protein Level ◽  
Multidrug Resistant ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Multidrug Resistant Bacterium ◽  
Protein Encoding ◽  
Hospital Acquired ◽  
Encoding Genes

Klebsiella pneumoniae is a multidrug-resistant bacterium causing many severe hospital-acquired infections. Here, we describe siphophage Sweeny that infects K. pneumoniae. Of its 78 predicted protein-encoding genes, a functional assignment was given to 36 of them. Sweeny is most closely related to T1-like phages at the protein level.

scholarly journals Resistance Mechanisms, Epidemiology, and Approaches to Screening for Vancomycin-Resistant Enterococcus in the Health Care Setting

2016 ◽  
Vol 54 (10) ◽  
pp. 2436-2447 ◽  
Author(s):  
Matthew L. Faron ◽  
Nathan A. Ledeboer ◽  
Blake W. Buchan
Keyword(s):  
Health Care ◽  
Infection Control ◽  
Control Strategies ◽  
Resistance Mechanisms ◽  
Clinical Microbiology Laboratory ◽  
Laboratory Methods ◽  
Content Type ◽  
Important Health ◽  
Vancomycin Resistant ◽  
Hospital Acquired

Infections attributable to vancomycin-resistantEnterococcus(VRE) strains have become increasingly prevalent over the past decade. Prompt identification of colonized patients combined with effective multifaceted infection control practices can reduce the transmission of VRE and aid in the prevention of hospital-acquired infections (HAIs). Increasingly, the clinical microbiology laboratory is being asked to support infection control efforts through the early identification of potential patient or environmental reservoirs. This review discusses the factors that contribute to the rise of VRE as an important health care-associated pathogen, the utility of laboratory screening and various infection control strategies, and the available laboratory methods to identify VRE in clinical specimens.

scholarly journals In Vitro Antifungal Combination of Flucytosine with Amphotericin B, Voriconazole, or Micafungin against Candida auris Shows No Antagonism

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
A. L. Bidaud ◽  
F. Botterel ◽  
A. Chowdhary ◽  
E. Dannaoui
Keyword(s):  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Resistant Mutants ◽  
Hospital Acquired

ABSTRACT Candida auris is an emerging, multidrug-resistant pathogen responsible for invasive hospital-acquired infections. Flucytosine is an effective anti-Candida species drug, but which cannot be used as a monotherapy because of the risk of development of resistant mutants during treatment. It is, therefore, noteworthy to test possible combinations with flucytosine that may have a synergistic interaction. In this study, we determined the in vitro interaction between flucytosine and amphotericin B, micafungin, or voriconazole. These combinations have been tested against 15 C. auris isolates. The MIC ranges (geometric mean [Gmean]) of flucytosine, amphotericin B, micafungin, and voriconazole were 0.125 to 1 μg/ml (0.42 μg/ml), 0.25 to 1 μg/ml (0.66 μg/ml), 0.125 to 0.5 μg/ml (0.3 μg/ml), and 0.03 to 4 μg/ml (1.05 μg/ml), respectively. When tested in combination, indifferent interactions were mostly observed with fractional inhibitory concentration index values from 0.5 to 1, 0.31 to 1.01, and 0.5 to 1.06 for the combinations of flucytosine with amphotericin B, micafungin, and voriconazole, respectively. A synergy was observed for the strain CBS 10913 from Japan. No antagonism was observed for any combination. The combination of flucytosine with amphotericin B or micafungin may be relevant for the treatment of C. auris infections.

scholarly journals High-Quality Complete Genome Sequences of Three Pseudomonas aeruginosa Isolates Retrieved from Patients Hospitalized in Intensive Care Units

2019 ◽  
Vol 8 (9) ◽  
Author(s):  
Bárbara Magalhães ◽  
Laurence Senn ◽  
Dominique S. Blanc
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Intensive Care ◽  
Intensive Care Units ◽  
Genome Sequences ◽  
High Quality ◽  
Gram Negative ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Hospital Acquired ◽  
High Quality Genome

Pseudomonas aeruginosa is one of the major Gram-negative pathogens responsible for hospital-acquired infections. Here, we present high-quality genome sequences of isolates from three P. aeruginosa genotypes retrieved from patients hospitalized in intensive care units.

Sign in / Sign up

Export Citation Format

Share Document