PRACA ORYGINALNA

ORIGINAL ARTICLE

Antimicrobial Resistance of Staphylococcus aureus Causing of Surgical Site Infections in Ear, Nose and Throat Surgery

ANTYBIOTYKOOPORNOŚĆ STAPHYLOCOCCUS AUREUS STANOWIĄCEGO CZYNIK ETIOLOGICZNY ZAKAŻEŃ POLA OPERACYJNEGO W PRZYPADKU OPERACJI USZU, NOSA I GARDŁA

Aidyn G. Salmanov, Volodymyr O. Shkorbotun, Yaroslav V. Shkorbotun

Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine

ABSTRACT

Introduction: Staphylococcus aureus is one of the major pathogens that causes of surgical site infection (SSI). Scant information is available on the occurrence and antimicrobial susceptibility of S. aureus in patients with SSI in Ear, Nose and Throat (ENT) surgery.

The aim: To assess the activity of antimicrobials against S.aureus, isolated from patients with SSI by the ENT departments of Kyiv hospitals.

Materials and methods: A total of 516 S. aureus isolates from of patients with SSI in ENT surgery. Antimicrobial susceptibility of S. aureus were determined, using automated microbiology analyzer. Some antimicrobial susceptibility test used Kirby – Bauer antibiotic testing. Interpretative criteria were those suggested by the Clinical and Laboratory Standards Institute (CLSI).

Results: The most active antibiotics found in the study were linezolid and tigecycline, showing growth inhibition of 100% strains tested. Susceptibility to the other antimicrobials was also on a high level: 98,4% of strains were found susceptible to nitrofurantoin, 98.1% – to trimethoprim/sulphamethoxazole, 97.6% – to fusidic acid, 97.1% – to mupirocin, 95.9% – to teicoplanin, 94.7% – to vancomycin and fosfomicin, 90.6% – to moxifloxacin, 89.1% – to tobramycin, 87.3% – to gentamycin. Susceptibility to rifampicin (85.5%), cefoxitin (84.6%), levofloxacin (84.3%), erythromycin (82.6%), tetracycline (76.3%), and clindamycin (75.4%) was observed to be some lower. Resistance to oxacyllin S.aureus (MRSA) came up to 21.1%.

Conclusions: S. aureus in ENT departments to be a serious therapeutic and epidemiologic problem. The constant monitoring of antimicrobials resistance in every hospital is required. Antibiotics application tactics should be determined in accordance with the local data of resistance to them.

KEY WORDS: ENT, SSI, S.aureus, MRSA, antimicrobial resistance

Wiad Lek 2019, 72, 2, 154-158

Introduction

Despite major advances in infection control interventions, healthcare-associated infections remain a major public health problem and patient safety threat worldwide [1, 2]. Surgical site infections (SSI) are the most common type of nosocomial infection among surgical patients. [3-7].

Staphylococcus aureus is a major pathogen that causes of surgical site infection [5, 6, 8-10]. Worldwide, the increasing resistance of this pathogen to various antibiotics complicates treatment of S aureus infections [8-10]. S. aureus has been recognized as an epidemiologically important pathogen [9]. Despite anti -biotic therapy, staphylococcal infections occur frequently in hospitalized patients and have severe consequences [9, 10]. About 35-40 % of patients undergoing surgery acquire at least one nosocomial S. aureus infection [5], leading to increased morbidity, mortality, hospital stay, and costs [11]. Development of resistance to commonly used antimicrobials limited treatment options against infections due to this pathogen [5, 9].

S. aureus is both a commensal bacterium and a human pathogen. Approximately 30% of the human population is colonized with S. aureus [12]. Nasal carriage of S. aureus among hospital personnel is a common cause of hospital acquired infections [12, 13]. It is estimated that 20 -30 % of individuals are persistent carriers of S. aureus, around 30 % are intermittent carriers, and 40-50 % are non carriers [14].

Nasal carriage of S. aureus among hospital personnel is a common cause of hospital acquired infections [12-14]. Approximately 5 % of colonised healthcare workers (HCWs) develop clinical infections [15] and symptomatic methicillin – resistant S. aureus (MRSA) infections among HCWs have been described in several case reports [16]. Emergence of drug resistant strains especially MRSA is a serious problem in hospital environment. Nasal carriage among HCWs is the main source for the transmission of MRSA and most S. aureus among patients within and between wards [13].

It has been shown that overall epidemiology and clinical manifestations of S. aureus vary significantly among different countries [10] and different regions of the same country [5, 8]. In Ukraine, the potential public health threat due to antimicrobial resistance is high because of the fact that antimicrobial agents can easily be purchased without prescription, lack of coordinated routine surveillance of antimicrobial resistance, poor laboratory capacity, and poor infection control mechanisms by health facilities contributing to the emergence and spread of antimicrobial resistance.

Knowledge on the antimicrobial susceptibility status of circulating pathogens in a given health facility is important for better management of infectious pathogens particularly where routine culture and sensitivity testing is not practiced. Recent study at 12 Ukrainian hospitals, showed isolation rate of S. aureus from 27.6% of clinical specimens, of which over 29.1% of the isolates were MRSA [6]. Scant information is available on the occurrence and antimicrobial susceptibility of S. aureus in patients with surgical site infection in ENT departments in Ukraine.

THE AIM

The objective of the current study was to assess the activity of antimicrobials of S. aureus among patients with SSI in ENT departments in Kyiv hospitals, Ukraine.

MATERIALS AND METHODS

Study population

Over a 36 month period (January 2014 to December 2016), this retrospective study was performed in ENT departments of 3 Kyiv hospitals that are similar in terms of medical equipment, laboratory facilities and number of surgeries performed. The patients’ age ranged from 19 to 74. All patients undergoing ENT surgery with SSI were included in the database.

Ethics

According to Ukrainian law, as this retrospective study did not modify the laboratory or clinical practices of the physicians, no informed consent and no approval of an Ethics Committee were required.

Data collection

In order to determine of SSIs cases in the participating hospitals, passive search (through records from medical officers) and active identification (through epidemiological diagnostics) were used. In each hospital, the microbiologist and the attending physician collected the data in an electronic case report form. Case identification was triggered by the microbiologist after a positive culture S.aureus. After verification, microbiological and clinical data were recorded on the case report form. Information from the other types of medical documents was also considered. The information was collected using tables for the standard criteria of SSIs diagnostics that were developed by the Centers for Disease Control and Prevention (Atlanta, USA) [17] and adopted for use in Ukraine.

Antimicrobial susceptibility testing

The intraoperative specimens were collected in sterile containers using all aseptic precautions. The identification and antimicrobial susceptibility of the S.aureus were determined, using automated microbiology analyzer Vitek 2 Compact (BioMerieux, France). Some antimicrobial susceptibility test used Kirby – Bauer antibiotic testing. In general, susceptibility of staphylococci strains to the following antibiotics was analyzed: benzylpenicillin, oxacyllin, cefoxitin, gentamycin, tobramycin, levofloxacin, moxifloxacin, erythromycin, clindamycin, linezolid, teicoplanin, vancomycin, tetracycline, tigecycline, fosfomicin, nitrofurantoin, fusidic acid, mupirocin, rifampicin, and trimethoprim/sulphamethoxazole. Interpretative criteria were those suggested by the Clinical and Laboratory Standards Institute (CLSI) [18].

Definitions

The investigation was based on the standard definition of an SSIs as purulent discharge from a surgical wound and the identification of microorganisms in the liquid at the surgical site. SSI was defined as an infection absent upon admission that became evident 48 h or more after admission in patients hospitalized for a reason other than SSI [17]. Only patients with post-operative infections were considered as SSI cases.

Statistical analysis

The analysis of statistical data was performed using Microsoft Excel for Windows. The primary end point was the epidemiology of the S.aureus isolated in SSI samples and their resistance to antibiotics. Values of p < 0.05 were considered statistically significant.

Results

Over the studied period, 586 patients (52.8% female, 56 ± 20 years, range 19–74 years) with microbiologically proven SSI were included. There was no statistically significant difference in occurrence of S. aureus among different age group and sex. As a result of studying of staphylococci tested strains susceptibility to antibiotics it was established, that based on antimicrobial susceptibility analysis, the most active antibiotics found in the study were linezolid and tigecycline, showing growth inhibition of 100% strains tested (Table I).

Susceptibility to the other antimicrobials was also on a high level: 98,4% of strains were found susceptible to nitrofurantoin, 98.1% – to trimethoprim/sulphamethoxazole, 97.6% – to fusidic acid, 97.1% – to mupirocin, 95.9% – to teicoplanin, 94.7% – to vancomycin and fosfomicin, 90.6% – to moxifloxacin. Susceptibility to tobramycin (89.1%), gentamycin (87.3%), rifampicin (85.5%), cefoxitin (84.6%), levofloxacin (84.3%), erythromycin (82.6%), tetracycline (76.3%), and clindamycin (75.4%) was observed to be some lower. Resistance to oxacyllin S.aureus (MRSA) came up to 21.1%.

Analysis of the profiles for strains resistant to 6 and more classes of antibiotics demonstrated, that all the S. aureus strains were resistant to oxacyllin (MRSA), suggesting previously shown evidences on multiple antimicrobial resistance among staphylococci, resistant to oxacyllin. Oxacyllin-resistant strains were found not to have identical susceptibility to cefoxitin, and therefore, different mechanisms of resistance to oxacyllin were presumed. Thus, oxacyllin-resistant strains were also resistant to cefoxitin.

Research of MRSA prevalence in ENT departments shown, that 11% of staphylococci strains, isolated from patients having SSI, had multiple resistance to antibiotics. Further, 35.7% of MRSA strains were resistant only to the group of beta-lactamic antibiotics, while the rest – also to the other classes of antibiotics.

It should be highlighted, that when isolating MRSA, particular attention should be paid to the choice of antibiotic, prescribed for treatment. Having analyzed MRSA resistance levels to antibiotics, our data allowed us to determine the antibiotics, that can be chosen for treatment of staphylococcal infections (Table II).

MRSA resistance levels, in comparison with resistance of all analyzed S.aureus strains in general, were higher, and therefore, the list of antibiotics to be effective used for MRSA treatment, had more limitations. Except of linezolid and tigecycline, that no strain demonstrated resistance to, MRSA indicated quite high levels of susceptibility to mupirocin (97.1%), nitrofurantoin and trimethoprim/sulphamethoxazole (both 94,7%), fusidic acid (89,4%). These antibiotics could be the preparations of choice for the treatment of MRSA-caused infections.

It is important to specifically note low levels of MRSA susceptibility to glycopeptide antibiotics, vancomycin and teicoplanin (vancomycin – 15,8%, and teicoplanin – 10,5 %), that no strain quite recently demonstrated resistance to, and that were typically chosen for treatment of infections, caused by MRSA. Isolation of such strains suggested, that staphylococci have acquired resistance to vancomycin, and that it is greatly important to find new antibiotics, active against MRSA.

DISCUSSION

In this study presents the first data on the activity of antimicrobials against S.aureus, isolated from patients with SSI in ENT departments in Ukraine. The current study revealed high rate of resistance to most of the antimicrobials by strains of S. aureus isolated from patients with SSI in ENT departments. Interestingly, benzylpenicillin, which is currently not used for treatment of staphylococcal infections anymore, was shown to be ineffective in 75.4% of strains, which still suggests the usefulness of this antibiotic for patient treatment, based on the individual antibiogram data.

At first glance, taking into account the fact, that levels of antimicrobial resistance of tested strains of S. aureus did not exceed 24.6%, it seems quite easy to choose any of the above-mentioned antibiotics (excepting benzylpenicillin) to treat staphylococcal infections. However, analysis of antimicrobial resistance profiles revealed that some strains were resistant to 9-13 antibiotics, belonging to 6-10 classes of antimicrobials. This considerably limits the choice of antibiotics useful for treatment of infections, despite of low levels of resistance among staphylococci in general.

Resistance to oxacyllin S.aureus (MRSA) came up to 21.1%. 35.7% of MRSA strains were found to be resistant only to beta-lactamic antibiotics: penicillin, cefoxitin, and oxacyllin. Such an MRSA phenotype is specific for non-nosocomial strains of S. aureus, or for strains, resistant due to modified penicillin-binded proteins (not РВР2а) [19]. Other strains, except of anti-beta-lactam resistance, were resistant to other classes of antibiotics, and such a phenotype is considered to be specific for nosocomial MRSA [20].

MRSA strains are highly prevalent in Ukrainian surgical hospitals, those strains account for approximately 50 % of all S. aureus isolates recovered from health care infections [5-7, 20, 21]. In Europe, the proportion of MRSA isolates in infected patients varied in 2015 from less than 0 % to more than 57.2 %, with a pooled mean rate of around 16.8 % [10]. In the United States, the proportion of MRSA strains approached almost 60 % in 2003, with an average rate of resistance over the period 1998—2002 of around 50 % [22]. In 2007, a Mediterranean study found that the highest proportions of MRSA were reported by Egypt (52 %), Cyprus (55 %), Algeria (45 %), Malta (50 %) and Jordan (56 %), in comparison to other Mediterranean countries such as Lebanon (12 %), Tunisia (18 %) and Morocco (19 %) [23].

According to the global experience, the implementation of infection control system is the most efficient remedy, directed on prevention of MRSA spreading in healthcare facilities. This may explain, to some extent, such a huge difference in MRSA prevalence in various countries. To combat the spreading of strains, resistant to antibiotics, one should have, first of all, reliable data about the status of this problem (antimicrobial resistance) in each region, hospital, and even in every department. Implementation of standardized methods to receive this information, as well as introduction of efficient sanitary and hygienic approaches to control and decrease the prevalence of problematic microorganisms is of great importance, and should be based on the close cooperation between experts, both microbiologists, clinicians, and epidemiologists.

Study Limitations

According to the results of our study, the prevalence of MRSA by ENT departments was 21.1%. However, the information provided may not reflect, in our opinion, the real MRSA prevalence in the country due to impact of several factors, the most important of which was small selection of strains. An antimicrobial resistance study should preferably be performed on large cohorts. The consequence of a small population size is the low probability of detecting an important effect, since the analysis is underpowered. The present surveillance was conducted only in 3 hospitals, and the results cannot be generalized to all Ukrainian hospital settings.

Conclusions

S. aureus in the ENT departments is a serious therapeutic and epidemiological problem. The constant monitoring of antimicrobials resistance in every hospital is required. Antibiotics application tactics should be determined in accordance with the local data of resistance to them.

References

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13. Salmanov AG, Verner OM, Shelkova NG, Nicolska OI, Blahodatny VM, Slepova LF. Prevalence of Nasal Carriage of Staphylococcus aureus and its Antibiotic Susceptibility among Healthcare Workers (HCWs) in Ukraine. International Journal of Antibiotics and Probiotics. 2018 Mar; 2 (1):30-41. doi: https://doi.org/10.31405/ijap.2-1.18.03.

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20. Salmanov AG, Verner OM. Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Kyiv Surgical Hospital (Ukraine). International Journal of Antibiotics and Probiotics. 2017 Dec; 1 (2): 73-83.

21. Salmanov AG, Marievsky VF. Antibiotic resistance of nosocomial strains of Staphylococcus aureus inthe Ukraine: the results of multicenter study. NovostiKhirurgii. 2013 Jul-Aug;21(4):78-83 [In Ukrainian].

22. NNIS. National Nosocomial Infections Surveillance(NNIS) System Report, data summary from January1992 through June 2004, issued October 2004. Am J Infect Control. 2004;14:470–485.

23. Borg MA, de Kraker M, Scicluna E, van de Sande-BruinsmaN, Tiemersma E, Monen J, Grundmann H. Prevalenceof methicillin-resistant Staphylococcus aureus (MRSA) ininvasive isolates from southern and eastern Mediterranean countries. J Antimicrob Chemother. 2007 Dec;60(6):1310-5.

The work is carried out within the framework of the planned initiative research work of the Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine.

Acknowledgment: The authors wish to express their grateful acknowledgement to all the microbiologists, physicians and nurses who contributed to this study.

Authors’ contributions:

According to the order of the Authorship

Conflict of interest:

The Authors declare no conflict of interest

CORRESPONDING AUTHOR

Aidyn Salmanov

Shupyk National Medical Academy

of Postgraduate Education,

St. Dorohozhytska 9

04112, Kyiv, Ukraine

tel. +380667997631

e-mail: mozsago@gmail.com

Received: 08.11.2018

Accepted: 22.01.2019

Table I. The activity of antimicrobials against S.aureus, isolated from patients with SSI by the ENT departments of Kyiv hospitals, Ukraine (n=586).

Antibiotic

Division by susceptibility, %

S

R

R (95 % CI)

Cefoxitin

84.6

15.4

12.5 18.3

Benzylpenicillin

21.3

78.7

75.4 82.0

Oxacyllin

78.8

21.2

17.9 24.5

Gentamycin

87,3

12.7

10.0 15.4

Tobramycin

89.1

10.9

8.4 13.4

Levofloxacin

84.3

15.7

12.8 18.6

Moxifloxacin

90.6

9.4

7.0 11.8

Erythromycin

82.6

17.4

14.3 20.5

Clindamycin

75.4

24.6

21.1 28.1

Linezolid

100.0

0

0

Teicoplanin

95.9

4,1

2.5 5.7

Vancomycin

94.7

5,3

3.5 7.1

Tetracycline

76.3

23,7

20.2 27.2

Tigecycline

100.0

0

0

Fosfomicin

94.7

5,3

3.5 7.1

Nitrofurantoin

98.4

1,6

0.6 2.6

Fusidic acid

97.6

2,4

1.2 3.6

Mupirocin

97.1

2,9

1.5 4.3

Rifampicin

85.5

14,5

11.6 17.4

Trimethoprim / sulphamethoxazole

98.1

1,9

0.7 3.1

Note: S – Susceptible; R – Resistant

Table II. Susceptibility of oxacyllin-resistant S.aureus (MRSA) to antibiotics in the ENT departments of Kyiv hospitals, Ukraine (n=124)

Antibiotic

Susceptibility, %

Resistant

Moderately resistant

Susceptible

Cefoxitin

73,7

0

26,3

Gentamycin

31,6

0

68,4

Tobramycin

26,3

0

73,7

Levofloxacin

10,5

15,8

73,7

Moxifloxacin

10,5

5,3

84,2

Erythromycin

36,8

0

63,2

Clindamycin

57,9

0

42,1

Linezolid

0

0

100,0

Teicoplanin

10,5

0

89,5

Vancomycin

15,8

0

84,2

Tetracycline

36,8

0

63,2

Tigecycline

0

0

100,0

Fosfomicin

26,3

0

73,7

Nitrofurantoin

5,3

0

94,7

Fusidic acid

5,3

5,3

89,4

Mupirocin

2.9

0

97,1

Rifampicin

42,1

15,8

42,1

Trimethoprim/sulphamethoxazole

5,3

0

94,7