Phage Activity Against Planktonic and Biofilm Staphylococcus aureus Periprosthetic Joint Infection Isolates

2021 ◽  
Author(s):  
Katherine M. Caflisch ◽  
Robin Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Successful Treatment ◽  
Periprosthetic Joint Infection ◽  
Joint Infection ◽  
Bacterial Isolates ◽  
Small Colony Variant ◽  
Small Colony ◽  
Planktonic State ◽  
Phage Activity

We recently reported the successful treatment of a case of periprosthetic joint infection (PJI) with phage. Phage activity against bacteria causing PJI has not been systematically evaluated. Here we examined the in vitro activity of seven lytic phages against 122 clinical isolates of Staphylococcus aureus recovered between April 1999 and February 2018 from subjects with PJI. Phages were assessed against planktonic and biofilm phenotypes. Activity of individual phages was demonstrated against up to 73% of bacterial isolates in the planktonic state and up to 100% of biofilms formed by isolates that were planktonically phage-susceptible. Susceptibility to phage was not correlated with small colony variant status. These results demonstrate that phages can infect S. aureus causing PJI in both planktonic and biofilm phenotypes, and thus are worthy of investigation as an alternative or addition to antibiotics in this setting.

Antibiofilm and intraosteoblastic activities of rifamycins against Staphylococcus aureus: promising in vitro profile of rifabutin

2020 ◽  
Vol 75 (6) ◽  
pp. 1466-1473 ◽  
Author(s):  
Lélia Abad ◽  
Jérôme Josse ◽  
Jason Tasse ◽  
Sébastien Lustig ◽  
Tristan Ferry ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Therapeutic Potential ◽  
Joint Infection ◽  
Small Colony Variant ◽  
Resistance Selection ◽  
Low Concentrations ◽  
Infection Models ◽  
Small Colony

Abstract Background Targeting biofilm-embedded and intraosteoblastic Staphylococcus aureus, rifampicin gained a pivotal role in bone and joint infection (BJI) treatment. Two other rifamycins, rifabutin and rifapentine, may represent better-tolerated alternatives, but their activity against bacterial reservoirs associated with BJI chronicity has never been evaluated. Objectives To evaluate the activities of rifampicin, rifabutin and rifapentine in osteoblast infection models. Methods Using three S. aureus isolates, rifamycins were compared regarding: (i) their intracellular activity in ‘acute’ (24 h) and ‘chronic’ (7 days) osteoblast infection models at 0.1× MIC, 1× MIC, 10× MIC and 100× MIC, while impacting infection-induced cytotoxicity (MTT assay), intracellular phenol-soluble modulin (PSM) secretion (RT–PCR), resistance selection and small colony variant (SCV) emergence; and (ii) their minimal biofilm eradication concentration (MBEC) and their MIC to prevent biofilm formation (bMIC). Results At 0.1× MIC, only rifabutin significantly reduced intracellular inoculum and PSM secretion. All rifamycins allowed a 50% reduction of intraosteoblastic inoculum at higher concentrations, with no difference between acute and chronic infection models, while reducing infection-induced cytotoxicity and PSM secretion. Dose-dependent emergence of intracellular SCVs was observed for all molecules. No intracellular emergence of resistance was detected. bMICs were equivalent for all molecules, but MBEC90s of rifapentine and rifabutin were 10- to 100-fold lower than those of rifampicin, respectively. Conclusions All rifamycins are efficient in reducing the S. aureus intraosteoblastic reservoir while limiting infection-induced cytotoxicity, with a higher activity of rifabutin at low concentrations. All molecules prevent biofilm formation, but only rifapentine and rifabutin consistently reduce formed biofilm-embedded bacteria for all isolates. The activity of rifabutin at lower doses highlights its therapeutic potential.

scholarly journals Attenuated Vancomycin Bactericidal Activity against Staphylococcus aureus hemB Mutants Expressing the Small-Colony-Variant Phenotype

2008 ◽  
Vol 52 (4) ◽  
pp. 1533-1537 ◽  
Author(s):  
Brian T. Tsuji ◽  
Christof von Eiff ◽  
Pamela A. Kelchlin ◽  
Alan Forrest ◽  
Patrick F. Smith
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Pharmacodynamic Model ◽  
Small Colony Variant ◽  
Variant Phenotype ◽  
Small Colony ◽  
Bactericidal Activities

ABSTRACT The in vitro bactericidal activities of vancomycin against Staphylococcus aureus hemB mutants displaying the small-colony-variant phenotype and their parental strains were evaluated. Vancomycin killing activities against hemB mutants were markedly attenuated, demonstrating approximately 50% less effect, a result which was well described by a Hill-type pharmacodynamic model.

scholarly journals 1255. In Vitro Activity of Vancapticin against Methicillin-Resistant Staphylococcus aureus from Periprosthetic Joint Infection

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S645-S645
Author(s):  
Hye-Kyung Cho ◽  
Melissa J Karau ◽  
Kerryl E Greenwood-Quaintance ◽  
Karl A Hansford ◽  
Matthew A Cooper ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Periprosthetic Joint Infection ◽  
Mayo Clinic ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Research Support ◽  
Material Support

Abstract Background The vancapticins are modified vancomycin derivatives developed by adding membrane targeting motifs to the C-terminus of vancomycin. We determined the in vitro activity of a lead vancapticin candidate against periprosthetic joint infection-associated methicillin-resistant Staphylococcus aureus (MRSA) in the planktonic and biofilm states, and the effect of adding 0.002% polysorbate 80 (P-80; Sigma-Aldrich) on vancapticin susceptibility testing. Methods Thirty-seven clinical isolates of MRSA collected at Mayo Clinic (Rochester, Minnesota) were studied. Vancapticin minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institutes guidelines. Minimum biofilm bactericidal concentrations (MBBCs) were determined using a pegged lid microtiter plate assay. Vancapticin MIC and MBBC values were assessed with and without P-80. Vancapticin, vancomycin, and dalbavancin biofilm time-kill assays were performed using biofilms formed by 10 MRSA isolates on Teflon coupons. Results Vancapticin MICs with and without P-80 ranged from 0.015 to 0.12 μg/mL and 0.25 to 1 μg/mL, respectively. Vancapticin MBBCs with and without P-80 ranged from 0.25 to 4 μg/mL and 1 to 8 μg/mL, respectively. Reductions of biofilm bacterial densities on Teflon coupons after 8 and 24 hours of incubation with vancapticin, vancapticin with P-80, vancomycin, or dalbavancin with P-80 were less than 3-log10 cfu/cm2 for all isolates tested. Conclusion Vancapticin has promising in vitro activity against planktonic MRSA and MRSA in a pegged lid biofilm assay, but was not bactericidal against biofilms on Teflon coupons. P-80 decreased vancapticin MICs and MBBCs. Disclosures Mark A. Blaskovich, PhD, MAB Consulting (Consultant)The University of Queensland (Employee, Grant/Research Support, Other Financial or Material Support, Inventor on patent) Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)

scholarly journals In Vitro Activity of Vancapticin MCC5145 against Methicillin-Resistant Staphylococcus aureus from Periprosthetic Joint Infection

2021 ◽  
Author(s):  
Hye-Kyung Cho ◽  
Melissa J. Karau ◽  
Kerryl E. Greenwood-Quaintance ◽  
Karl A. Hansford ◽  
Matthew A. Cooper ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Periprosthetic Joint Infection ◽  
Biofilm Formation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Methicillin Resistant

MRSA periprosthetic 1 joint infection (PJI) can be challenging to treat due to biofilm formation, alongside sometimes limited vancomycin activity (1-3).…

scholarly journals In VitroSusceptibility of ClinicalStaphylococcus aureusSmall-Colony Variants to β-Lactam and Non-β-Lactam Antibiotics

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Evgeny A. Idelevich ◽  
André Kriegeskorte ◽  
Nina Schleimer ◽  
Georg Peters ◽  
Christof von Eiff ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Prolonged Incubation ◽  
Content Type ◽  
Small Colony Variant ◽  
Normal Phenotype ◽  
Gradient Diffusion ◽  
Small Colony ◽  
Inhibition Zones

ABSTRACTTheStaphylococcus aureussmall-colony variant (SCV) phenotype has been associated with relapsing and antibiotic-refractory infections. However, little is known about the activities of antibiotics on clinical SCVs. Here, we demonstrated that SCVs without detectable auxotrophies were at least as susceptible to most β-lactam and non-β-lactam antibioticsin vitroas their corresponding clonally identical strains with a normal phenotype. After prolonged incubation, a regrowth phenomenon has been observed in gradient diffusion inhibition zones irrespective of the strains' phenotype.

scholarly journals Involvement of Small Colony Variant-Related Heme Biosynthesis Genes in Staphylococcus aureus Persister Formation in vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuyang Wang ◽  
Weizheng Li ◽  
Wenjie Wang ◽  
Shiyong Wang ◽  
Tao Xu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Acid Stress ◽  
Heme Biosynthesis ◽  
Rna Seq ◽  
Small Colony Variant ◽  
Persistent Infections ◽  
Allelic Replacement ◽  
Small Colony ◽  
The Relationship

Background: Persisters are important reasons for persistent infections, and they can lead to antibiotic treatment failure in patients and consequently chronic infection. Staphylococcus aureus small colony variants (SCVs) have been shown to be related to persistent infection. Mutations in the genes of the heme biosynthesis pathway lead to the formation of SCVs. However, the relationship between heme production genes and persister has not been tested.Methods:HemA and hemB were knocked out by allelic replacement from S. aureus strain USA500 separately, and then, the heme deficiency was complemented by overexpression of related genes and the addition of hemin. The stress-related persister assay was conducted. RNA-sequencing was performed to find genes and pathways involved in heme-related persister formation, and relative genes and operons were further knocked out and overexpressed to confirm their role in each process.Results: We found that heme biosynthesis deficiency can lead to decreased persister. After complementing the corresponding genes or hemin, the persister levels could be restored. RNA-seq on knockout strains showed that various metabolic pathways were influenced, such as energy metabolism, amino acid metabolism, carbohydrate metabolism, and membrane transport. Overexpression of epiF and operon asp23 could restore USA500∆hemA persister formation under acid stress. Knocking out operon arc in USA500∆hemA could further reduce USA500∆hemA persister formation under acid and oxidative stress.Conclusion: Heme synthesis has a role in S. aureus persister formation.

scholarly journals In Vitro Activity of the Bacteriophage Endolysin HY-133 against Staphylococcus aureus Small-Colony Variants and Their Corresponding Wild Types

2019 ◽  
Vol 20 (3) ◽  
pp. 716 ◽  
Author(s):  
Nina Schleimer ◽  
Ursula Kaspar ◽  
Dennis Knaack ◽  
Christof von Eiff ◽  
Sonja Molinaro ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Options ◽  
Nasal Carriage ◽  
Resistance Mechanisms ◽  
Resistance Pattern ◽  
Small Colony Variant ◽  
Small Colony ◽  
Time Kill ◽  
Bacteriophage Endolysin

Nasal carriage of methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) represents both a source and a risk factor for subsequent infections. However, existing MRSA decolonization strategies and antibiotic treatment options are hampered by the duration of administration and particularly by the emergence of resistance. Moreover, beyond classical resistance mechanisms, functional resistance as the formation of the small-colony variant (SCV) phenotype may also impair the course and treatment of S. aureus infections. For the recombinant bacteriophage endolysin HY-133, rapid bactericidal and highly selective in vitro activities against MSSA and MRSA has been shown. In order to assess the in vitro efficacy of HY-133 against the SCV phenotype, minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) were evaluated on clinical SCVs, their isogenic wild types, as well as on genetically derived and gentamicin-selected SCVs. For all strains and growth phases, HY-133 MIC and MBC ranged between 0.12 and 1 mg/L. Time-kill studies revealed a fast-acting bactericidal activity of HY-133 resulting in a ≥3 − log10 decrease in CFU/mL within 1 h compared to oxacillin, which required 4–24 h. Since the mode of action of HY-133 was independent of growth phase, resistance pattern, and phenotype, it is a promising candidate for future S. aureus decolonization strategies comprising rapid activity against phenotypic variants exhibiting functional resistance.

scholarly journals Comparative In Vitro Activity of Ceftobiprole against Staphylococci Displaying Normal and Small-Colony Variant Phenotypes

2005 ◽  
Vol 49 (10) ◽  
pp. 4372-4374 ◽  
Author(s):  
Christof von Eiff ◽  
Alexander W. Friedrich ◽  
Karsten Becker ◽  
Georg Peters
Keyword(s):  
Staphylococcus Aureus ◽  
Vitro Activity ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
In Vitro Activity ◽  
Small Colony Variant ◽  
Antistaphylococcal Activity ◽  
Agar Dilution ◽  
Small Colony

ABSTRACT The antistaphylococcal activity of ceftobiprole was compared with those of cefuroxime, linezolid, and moxifloxacin by using the agar dilution method. Apart from three strains with small-colony variant phenotypes, all Staphylococcus aureus isolates tested were inhibited by ≤2 μg/ml of ceftobiprole. This compound exhibited an excellent antistaphylococcal activity, comparable to that of linezolid.

scholarly journals The bactericidal effect of vancomycin is not altered by tranexamic acid, adrenalin, dexamethasone, or lidocaine in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christiane Schwerdt ◽  
Eric Röhner ◽  
Sabrina Böhle ◽  
Benjamin Jacob ◽  
Georg Matziolis
Keyword(s):  
Staphylococcus Aureus ◽  
Tranexamic Acid ◽  
Total Joint Arthroplasty ◽  
Staphylococcus Epidermidis ◽  
Joint Infection ◽  
Bactericidal Effect ◽  
Joint Arthroplasty ◽  
Zone Of Inhibition ◽  
Agar Diffusion Test

AbstractOne of the most challenging complications of total knee arthroplasty (TKA) is periprosthetic joint infection (PJI). There is growing evidence of a good anti-infective effect of intrawound vancomycin powder in total joint arthroplasty. At the same time, various different locally applied substances have become popular in total joint arthroplasty. The objective of this study was therefore to investigate a possible inhibition of the bactericidal effect of vancomycin by tranexamic acid, adrenalin, lidocaine, or dexamethasone. The bactericidal effect of vancomycin was quantified using the established method of the agar diffusion test. The plates were incubated with Staphylococcus aureus or Staphylococcus epidermidis and four wells were stamped out. The wells were filled with vancomycin alone, the tested substance alone or a mixture of the two. The fourth well remained empty as a control. The plates were incubated overnight at 37 °C and the zone of inhibition in each field was measured on the next day. All tests were run three times for each pathogen and mean values and standard deviations of the measurements were calculated. Differences between the substances were tested using the t-test at a level of significance of 0.05. The bacterial growth was homogeneous on all plates. The baseline value for the zone of inhibition of vancomycin was on average 6.2 ± 0.4 mm for Staphylococcus aureus and 12 ± 0.3 mm for Staphylococcus epidermidis. In all other substances, no inhibition was detected around the well. The combination of vancomycin and each other substance did not show any different result compared to vancomycin alone. The bactericidal effect of vancomycin on staphylococci is not altered by tranexamic acid, adrenalin, dexamethasone, or lidocaine in vitro.

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