Effects of Ciprofloxacin on the Dynamics of Biofilm Formation by Staphylococcus Epidermidis Strains Isolated from Implant-Associated Infection

  • Authors: Babushkina I.V.1, Mamonova I.A.2, Ulyanov V.Y.2, Shpinyak S.P.3, Bondarenko A.S.4
  • Affiliations:
    1.  Research Institute of Traumatology, Orthopedics and Neuosurgery of Razumovsky Saratov State Medical University, Russia.
    2. Scientific Research Institute of Traumatology, Orthopedics and Neurosurgery of Saratov State Medical University n.a. V. I. Razumovsky
    3. Research Institute of Traumatology, Orthopedics and Neuosurgery of Razumovsky Saratov State Medical University, Russia.
    4. Saratov State Medical University n.a. V. I. Razumovsky
  • Issue: Vol 13, No 3 (2020)
  • Pages: 241-247
  • Section: Original articles
  • URL: https://vestnik-surgery.com/index.php/journal/article/view/1412
  • DOI: https://doi.org/10.18499/2070-478X-2020-13-3-241-247
  • Cite item

Abstract


Introduction. The formation of a microbial biofilm in implant-associated infection after arthroplasty of large joints reduces the informative value of traditional microbiological diagnostic methods and limits the range of effective antimicrobial drugs. When prescribing etiotropic therapy for periprosthetic joint infection, it is necessary to take into account not only the antibacterial effect of the drug, but also its effect on biofilm formation. Ciprofloxacin therapy may be a risk factor for the development of biofilm periprosthetic infection caused by multidrug-resistant staphylococcal strains.
The aim of research was to study the effect of sub-inhibiting and therapeutic doses of ciprofloxacin on biofilm formation by Staphylococcus epidermidis strains isolated from implant-associated infection.
Materials and methods. The authors studied the effect of various concentrations of ciprofloxacin on 15 strains of St. epidermidis isolated from 83 patients with deep periprosthetic joint infection after primary knee arthroplasty, treated at NIITON SSMU in 2018-2019. The effect of the calculated concentrations of ciprofloxacin on the planktonic culture, forming and preformed biofilms was investigated. Biofilm simulation was performed according to the method described by G.D. Christensen under in vitro conditions with determination of the optical density of alcohol eluates of gentian violet in polystyrene microplates.
Results. It was demonstrated that ciprofloxacin in a dose 0.01 μg/ml inhibits the growth of planktonic forms by 50% and statistically significantly (p = 0.001) stimulates formation of microbial biofilms as compared to the control without antibiotic addition. Concentration of ciprofloxacin equal 0.03 μg/ml inhibits the growth of planktonic forms by 90%, statistically significantly (p = 0.001) stimulates formation of biofilms and activates further increase in the mass of pre-formed microbial biofilms. An increase in the concentration of ciprofloxacin to 0.05 μg/ml completely inhibits the growth of planktonic forms and statistically significantly stimulates further growth of preformed biofilms.
The use of ciprofloxacin at concentrations equal 1-3 μg/ml statistically significantly (p = 0.001) inhibits the formation of microbial biofilms, but does not affect the preformed biofilm.
Conclusions. Thus, there has been found a dose-dependent effect of ciprofloxacin towards clinical strains of St. epidermidis: subinhibitory and therapeutic concentrations of the drug have a stimulating effect on the formation and further increase in the mass of the preformed microbial biofilms. This fact must be taken into account when prescribing etiotropic therapy for implant-associated complications following large joint replacements.


Table 1. Optical density of gentian violet extracts obtained at biofilm formation by St. epidermidis strains

Group

 

Concentration, µg/mL

 

Biofilm formation

 

Preliminary-formed biofilm

 

1

Control without antibiotic

 

0,281

(0,230; 0,427)

p1-3=0,000261

p1-4=0,000192

0,479

(0,419; 0,543)

p1-2=0,000527

 

2

0,01

0,607

(0,456; 0,729)

p2-6=0,005683

p2-7=0,000012

0,854

(0,711; 0,978)

p*=0,017842

 

3

0,03

0,789

(0,679; 0,930)

p3-5=0,039910

p3-6=0,000006

p3-7=0,000001

0,911

(0,825; 0,978)

p3-1=0,000021

 

 

4

0,05

0,803

(0,712; 0,985)

p4-5=0,031869

p4-6=0,000004

p4-7=0,000001

0,897

(0,856; 1,134)

p4-1=0,000010

р4-6=0,000043

5

0,1

0,428

(0,342; 562)

p5-7=0,014042

0,759

(0,562; 0,834)

 

6

1

0,219

(0,156; 0,278)

 

0,485

(0,345; 0,567)

p6-2=0,001775

7

3

0,145

(0,089; 0,205)

0,456

(0,389; 0,589)

           p7-2-=0,00026

p7-3-=0,000009

p7-4-=0,000004

 

Note: the table shows median and quartile values (25 %; 75 %); p – confidence index for various groups when using various ciprofloxacin concentrations; p*– statistical difference between the effect of 0.01 µg/mL ciprofloxacin concentration on biofilm formation and preliminary-formed biofilm

Irina V. Babushkina

 Research Institute of Traumatology, Orthopedics and Neuosurgery of Razumovsky Saratov State Medical University, Russia.

Author for correspondence.
Email: 10051968@mail.ru
ORCID iD: 0000-0001-6740-1050
SPIN-code: 8777-6795

Russian Federation, 148, Chernyshevskogo Str., Saratov, 410002, Russia

Cand.Med. Sci., Senior Research Assistant in the Department of Fundamental, Clinical and Experimental Studies, Research Institute of Traumatology, Orthopedics and Neurosurgery of Razumovsky Saratov State Medical University

Irina A. Mamonova

Scientific Research Institute of Traumatology, Orthopedics and Neurosurgery of Saratov State Medical University n.a. V. I. Razumovsky

Email: sarniito@yandex.ru
ORCID iD: 0000-0003-3941-4334
SPIN-code: 7957-2955
Scopus Author ID: https://orcid.org/0000-0003-3941-4334

Russian Federation, Russian Federation, Saratov, 410002, 148 Chernyshevskogo str.

Cand. Biol. Sci., Junior Research Assistant of the Fundamental, Clinical and Experimental Research Department

Vladimir Yu. Ulyanov

Scientific Research Institute of Traumatology, Orthopedics and Neurosurgery of Saratov State Medical University n.a. V. I. Razumovsky

Email: sartiito@yandex.ru
ORCID iD: 0000-0002-9466-8348
SPIN-code: 8280-3339
Scopus Author ID: 0000-0002-9466-8348

Russian Federation, Russian Federation, Saratov, 410002, 148 Chernyshevskogo str.

Dr. Med. Sci, deputy director for Science and Innovations

Sergey P. Shpinyak

Research Institute of Traumatology, Orthopedics and Neuosurgery of Razumovsky Saratov State Medical University, Russia.

Email: 10051968@mail.ru
ORCID iD: 0000-0002-0345-6287
SPIN-code: 6540-1764

Russian Federation, 148, Chernyshevskogo Str., Saratov, 410002, Russia.

Cand.Med. Sci., Junior Research Assistant in the Department of Traumatological and Orthopedic Innovations of Research Institute of Traumatology, Othopedics and Neurosurgery of Razumovsky Saratov State Medical University.

Aleksandr S. Bondarenko

Saratov State Medical University n.a. V. I. Razumovsky

Email: sarniito@yandex.ru
ORCID iD: 0000-0001-6345-1851
SPIN-code: 6719-4520

Russian Federation,  Russian Federation, Saratov, 410012, Bolshaya Kazachya str., 112.  

Vice-Dean of General Medicine Department and Clinical Psychology Department

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