The Open Microbiology Journal




ISSN: 1874-2858 ― Volume 14, 2020
RESEARCH ARTICLE

Antimicrobial Resistance Profiling of Coagulase-Negative Staphylococci in a Referral Center in South Italy: A Surveillance Study



Daria Nicolosi1, Diana Cinà2, Concettina Di Naso2, Floriana D’Angeli3, Mario Salmeri1, Carlo Genovese1, *
1 Department of Biomedical and Biotechnological Sciences, Microbiology Section, University of Catania, Catania, Italy
2 Clinical Pathology, Garibaldi Hospital, Catania, Italy
3 Department of Biomedical and Biotechnological Sciences, Biochemistry section, University of Catania, Catania, Italy

Abstract

Background:

CoNS are part of the normal flora of the skin, upper respiratory tract and human intestine. CoNS are able to colonize host tissues or inert materials such as prosthetics, heart valves, pacemakers, and urinary and venous catheters. They can also internalize in host cells, thus eluding immune defenses and attack by antibiotics.

Objective:

In this study, we collected the epidemiological data and determined the antibiotic susceptibility of 828 CoNS, collected in Garibaldi Hospital (Catania, Italy) between January 2016 and October 2018.

Methods:

Strains were evaluated by determining the Minimum Inhibitory Concentration (MIC) using the broth microdilution method, according to the guidelines of the Clinical and Laboratory Standards Institute. The antibiotic sensitivity pattern of CoNS against eighteen antibiotics was determined.

Results:

For all the 828 clinical isolates, varying resistance rates were observed: ampicillin (87%), penicillin (86%), amoxicillin-clavulanate (71%), oxacillin (70%), erythromycin (69%), azithromycin (68%), levofloxacin (55%), ciprofloxacin (54%), gentamycin (47%), moxifloxacin (42%), trimethoprim-sulfamethoxazole (30%), clindamycin (28%), tetracycline (24%), rifampicin (20%), quinupristin-dalfopristin (synercid) (4%). No strains investigated demonstrated resistance to teicoplanin, vancomycin and linezolid.

Conclusion:

Our results highlight the importance of monitoring the evolution of CoNS resistance in order to implement control measures and reduce the risk of spread in the population.

Keywords: Coagulase-negative staphylococci, Nosocomial pathogens, Epidemiological data, Antimicrobial, Resistance, Virulence factors.


Article Information


Identifiers and Pagination:

Year: 2020
Volume: 14
First Page: 91
Last Page: 97
Publisher Id: TOMICROJ-14-91
DOI: 10.2174/1874285802014010091

Article History:

Received Date: 28/01/2019
Revision Received Date: 09/04/2020
Acceptance Date: 10/04/2020
Electronic publication date: 21/05/2020
Collection year: 2020

© 2020 Nicolosi et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Department of Biomedical and Biotechnological Sciences, Microbiology Section, University of Catania, Via Santa Sofia, 97, Catania, 95123, Italy; Tel: +39 095 4781252; E-mail: gnv.carlo@gmail.com





1. INTRODUCTION

Staphylococci are non-spore-forming bacteria that are widespread in nature. Various species of Staphylococcus constitute the normal microbiota of humans and animals: they are found on the skin, on the mucous membranes of the upper respiratory tract and in the intestinal tract. The skin is frequently colonized by staphylococci, especially in humid areas: navel, armpits, groin, perineum, face, hands and scalp. The skin, either intact (through hair follicles or sweat ducts) or interrupted by lesions, represents a frequent entrance for staphylococci. Historically, Coagulase-Negative Staphylococci (CoNS) had been considered to be less pathogenic compared to coagulase-positive ones. However, numerous studies have reported that even coagulase-negative species are equally pathogenic [1Méric G, Mageiros L, Pensar J, et al. Disease-associated genotypes of the commensal skin bacterium Staphylococcus epidermidis. Nat Commun 2018; 9(1): 5034.
[http://dx.doi.org/10.1038/s41467-018-07368-7] [PMID: 30487573]
, 2Kini GD, Patel K, Parris AR, Tang JS. An unusual presentation of endocarditis caused by Staphylococcus warneri. Open Microbiol J 2010; 4: 103-5.
[http://dx.doi.org/10.2174/1874285801004010103] [PMID: 21258573]
]. CoNS, as opportunists, are responsible for severe nosocomial and health-care related infections. They are capable of colonizing and infecting humans through different mechanisms, such as adherence, invasion, persistence and evasion of innate and adaptive immunity [3Le KY, Park MD, Otto M. Immune Evasion Mechanisms of Staphylococcus epidermidis Biofilm Infection. Front Microbiol 2018; 9: 359.
[http://dx.doi.org/10.3389/fmicb.2018.00359] [PMID: 29541068]
]. S. epidermidis is the most commonly isolated CoNS [4Kleinschmidt S, Huygens F, Faoagali J, Rathnayake IU, Hafner LM. Staphylococcus epidermidis as a cause of bacteremia. Future Microbiol 2015; 10(11): 1859-79.
[http://dx.doi.org/10.2217/fmb.15.98] [PMID: 26517189]
-7Sabaté Brescó M, Harris LG, Thompson K, et al. Pathogenic Mechanisms and Host Interactions in Staphylococcus epidermidis Device-Related Infection. Front Microbiol 2017; 8: 1401.
[http://dx.doi.org/10.3389/fmicb.2017.01401] [PMID: 28824556]
], followed by S. hominis [8Mendoza-Olazarán S, Morfin-Otero R, Rodríguez-Noriega E, et al. Microbiological and molecular characterization of Staphylococcus hominis isolates from blood. PLoS One 2013; 8(4)e61161
[http://dx.doi.org/10.1371/journal.pone.0061161] [PMID: 23585877]
-10Szczuka E, Krzymińska S, Kaznowski A. Clonality, virulence and the occurrence of genes encoding antibiotic resistance among Staphylococcus warneri isolates from bloodstream infections. J Med Microbiol 2016; 65(8): 828-36.
[http://dx.doi.org/10.1099/jmm.0.000287] [PMID: 27226348]
], S. haemolyticus [11Czekaj T, Ciszewski M, Szewczyk EM. Staphylococcus haemolyticus - an emerging threat in the twilight of the antibiotics age. Microbiology 2015; 161(11): 2061-8.
[http://dx.doi.org/10.1099/mic.0.000178] [PMID: 26363644]
, 12Parashar S. Staphylococcus haemolyticus; A Nosocomial Pathogen Showing Higher Antimicobial Resistance. Med Sci 2014; 3: 381-2.
[http://dx.doi.org/10.1537/2249555x]
] and S. capitis [13Yamamoto K, Ohmagari N. Infective Endarteritis due to Staphylococcus capitis. Intern Med 2018; 57(8): 1185.
[http://dx.doi.org/10.2169/internalmedicine.0070-17] [PMID: 29279472]
-15Shahandeh Z, Shafi H, Sadighian F. Association of staphylococcus cohnii subspecies urealyticum infection with recurrence of renal staghorn stone. Caspian J Intern Med 2015; 6(1): 40-2.
[PMID: 26221496]
]. S. lugdunensis and S. saprophyticus are often responsible for septic arthritis [16Gaglani B, Dahdouh M, Shah K. Septic arthritis of native hip joint by Staphylococcus lugdunensis: A case report. Rev Soc Bras Med Trop 2018; 51(4): 554-6.
[http://dx.doi.org/10.1590/0037-8682-0169-2017] [PMID: 30133645]
-19Carter GP, Ussher JE, Da Silva AG, et al. Genomic analysis of multi-resistant Staphylococcus capitis associated with neonatal sepsis. Antimicrob Agents Chemother 2018; 62(11): e00898-18.
[http://dx.doi.org/10.1128/AAC.00898-18] [PMID: 30150477]
] and uncomplicated urinary tract infections [20Genovese C, Davinelli S, Mangano K, et al. Effects of a new combination of plant extracts plus d-mannose for the management of uncomplicated recurrent urinary tract infections. J Chemother 2018; 30(2): 107-14.
[http://dx.doi.org/10.1080/1120009X.2017.1393587] [PMID: 29078739]
], respectively. The role of CoNS as pathogens has been demonstrated in human infections, particularly in patients with implanted devices, immunocompromised subjects and preterm infants. Virulence factors of these microorganisms are poorly defined and it is very difficult to determine the pathogenicity of clinical isolates [1Méric G, Mageiros L, Pensar J, et al. Disease-associated genotypes of the commensal skin bacterium Staphylococcus epidermidis. Nat Commun 2018; 9(1): 5034.
[http://dx.doi.org/10.1038/s41467-018-07368-7] [PMID: 30487573]
]. Furthermore, several CoNS have shown resistance to different antibiotics and the treatment of infections has become very difficult [21Diekema DJ, Pfaller MA, Schmitz FJ, et al. SENTRY Partcipants Group. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis 2001; 32(Suppl. 2): S114-32.
[http://dx.doi.org/10.1086/320184] [PMID: 11320452]
-23Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH. Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol 2003; 41(10): 4740-4.
[http://dx.doi.org/10.1128/JCM.41.10.4740-4744.2003] [PMID: 14532213]
]. Among CoNS, S. lugdunensis is the only species susceptible to a wide range of antimicrobials [24McHardy IH, Veltman J, Hindler J, Bruxvoort K, Carvalho MM, Humphries RM. Clinical and microbiological aspects of β-lactam resistance in Staphylococcus lugdunensis. J Clin Microbiol 2017; 55(2): 585-95.
[http://dx.doi.org/10.1128/JCM.02092-16] [PMID: 27927926]
]. In addition, there are few recent data in the literature [25De Vecchi E, George DA, Romanò CL, Pregliasco FE, Mattina R, Drago L. Antibiotic sensitivities of coagulase-negative staphylococci and Staphylococcus aureus in hip and knee periprosthetic joint infections: does this differ if patients meet the International Consensus Meeting Criteria? Infect Drug Resist 2018; 11: 539-46.
[http://dx.doi.org/10.2147/IDR.S151271] [PMID: 29695923]
-28Stefani S, Varaldo PE. Epidemiology of methicillin-resistant staphylococci in Europe. Clin Microbiol Infect 2003; 9(12): 1179-86.
[http://dx.doi.org/10.1111/j.1469-0691.2003.00698.x] [PMID: 14686982]
]. Accordingly, the aim of the present study was to investigate the etiology and the antibiotic-resistance profiles of CoNS isolated from hospital environments in South Italy.

2. MATERIALS AND METHODS

2.1. Study Design

The retrospective study was conducted in the National Reference and Specialization Hospitals “Garibaldi” (Catania, Italy) between January 2016 and October 2018. Patient epidemiological data were collected and the identification of bacterial strains provided by the hospital laboratory was confirmed at the Department of Biomedical and Biotechnological Sciences, University of Catania.

2.2. Specimen Collection

All specimens were collected in strict aseptic conditions, according to Guidelines of the Italian National Institute of Health – ISS [29 Available from: https://www.iss.it/]. Samples were expeditiously transported to the laboratory and processed without undue delay.

2.3. Microbiological Evaluation

Each sample was cultured into Columbia agar plates containing 5% defibrinated horse blood (bioMérieux) and incubated for 18-24 h at 37°C [30Becker K, Heilmann C, Peters G. Coagulase-negative staphylococci. Clin Microbiol Rev 2014; 27(4): 870-926.
[http://dx.doi.org/10.1128/CMR.00109-13] [PMID: 25278577]
]. For S. lugdunensis isolation, the incubation time was prolonged (48 h) to obtain visible colonies [31Sundqvist M, Bieber L, Smyth R, Kahlmeter G. Detection and identification of Staphylococcus lugdunensis are not hampered by use of defibrinated horse blood in blood agar plates. J Clin Microbiol 2010; 48(5): 1987-8.
[http://dx.doi.org/10.1128/JCM.02307-09] [PMID: 20305013]
]. Colonies in pure culture were identified by Gram staining, catalase and coagulase tests [32Ruoff KL. Algorithm for identification of aerobic gram positive cocci.Manual of Clinical Microbiology 2003; 331-3.].

2.4. Bacteria Identification and Antimicrobial Susceptibility

Strains identification was performed through the Vitek 2 compact (bioMérieux) system using a GP ID card for Gram-positive bacteria. All the procedures were carried out according to the manufacturer’s instructions. The coagulase-negative Staphylococcus species isolated during the study are reported in Table 1. Antibiotic susceptibility tests were performed by determining the MIC using the broth microdilution method, according to the guidelines of the Clinical and Laboratory Standards Institute [33CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement. CLSI Document M100-S26, Clinical and Laboratory Standards Institute 2016.].

2.5. Statistical Analysis

A Chi-square test was used to study distribution and changes in resistance patterns. Statistical significance was determined if a two-tailed p-value was <0.0001.

3. RESULTS

3.1. Distribution of Clinical Isolates

In total, 828 CoNS were isolated from patients admitted to various wards at the hospital. The 828 CoNS isolated belonged to 12 different species (Table 1), and 89.7% of these strains were isolated from urine, sperm, vaginal swabs, endovascular catheter-associated infections, bladder catheters, blood cultures and bronchial-aspirates (Table 2). The other 10.3% were isolated from other patient samples (Table 2). Data analysis showed that the most frequently detected CoNS were S. haemolyticus, S. epidermidis and S. hominis. S. haemolyticus was mainly isolated from urine (94/390, 24%), whereas S. epidermidis and S. hominis were mainly isolated from blood cultures (94/247, 38% and 40/65, 62%, respectively). All other species accounted for only a small portion of the isolates investigated (126/828, 15%) (Table 2).

3.2. Trends of Antimicrobial Resistance in Coagulase-Negative Staphylococci

The antibiotic susceptibility profiles of CoNS are reported in Table 3. Of the species investigated, S. warneri demonstrated broad antimicrobial susceptibility. The other species showed a similar susceptibility profile except for quinupristin-dalfopristin (synercid). It is noteworthy that S. epidermidis and S. haemolyticus demonstrated the broadest degree of resistance to the antimicrobials investigated. S. hominis and S. simulans showed higher resistance to trimethoprim-sulfamethoxazole. Furthermore, elevated resistance to rifampicin was found for S. simulans, with respect to the other CoNS strains. For all the tested strains, no resistance was found for linezolid, teicoplanin and vancomycin.

Table 1
Coagulase-negative staphylococci isolated during the study.


Table 2
Distribution of coagulase-negative staphylococci in clinical samples.


Table 3
Antibiotic susceptibility patterns of coagulase-negative staphylococci.


4. DISCUSSION

In the last few years, CoNS have emerged as important nosocomial pathogens and are exhibiting increasing virulence and resistance to many antibiotics [34Acquaviva R, D’Angeli F, Malfa GA, et al. Antibacterial and anti-biofilm activities of walnut pellicle extract (Juglans regia L.) against coagulase-negative staphylococci. Nat Prod Res 2019; 1-6.
[http://dx.doi.org/10.1080/14786419.2019.1650352] [PMID: 31397177]
, 35Nicolosi D, Cupri S, Genovese C, Tempera G, Mattina R, Pignatello R. Nanotechnology approaches for antibacterial drug delivery: Preparation and microbiological evaluation of fusogenic liposomes carrying fusidic acid. Int J Antimicrob Agents 2015; 45(6): 622-6.
[http://dx.doi.org/10.1016/j.ijantimicag.2015.01.016] [PMID: 25816979]
]. In this study, the antibiotic-resistance profiles of CoNS isolated from a hospital environment in South Italy were evaluated. Staphylococcus haemolyticus and Staphylococcus epidermidis were the most prevalent CoNS isolated from clinical samples. In addition, among the CoNS that were found, we observed differences in antimicrobial resistance. The strains did not exhibit any resistance to linezolid, an oxazolidinone antibacterial agent that inhibits protein synthesis [36Tian Y, Li T, Zhu Y, Wang B, Zou X, Li M. Mechanisms of linezolid resistance in staphylococci and enterococci isolated from two teaching hospitals in Shanghai, China. BMC Microbiol 2014; 14: 292.
[http://dx.doi.org/10.1186/s12866-014-0292-5] [PMID: 25420718]
]. However, in Italy, plasmidic cfr-mediated linezolid resistance has been reported for S. epidermidis [37Brenciani A, Morroni G, Mingoia M, Varaldo PE, Giovanetti E. Stability of the cargo regions of the cfr-carrying, multiresistance plasmid pSP01 from Staphylococcus epidermidis. Int J Med Microbiol 2016; 306(8): 717-21.
[http://dx.doi.org/10.1016/j.ijmm.2016.08.002] [PMID: 27554790]
]. No clinical isolate was resistant to the glycopeptides vancomycin and teicoplanin. The high susceptibility rate against these antibiotics could be due to the preferential use of linezolid by hospital clinicians [38Biavasco F, Vignaroli C, Varaldo PE. Glycopeptide resistance in coagulase-negative staphylococci. Eur J Clin Microbiol Infect Dis 2000; 19(6): 403-17.
[http://dx.doi.org/10.1007/s100960000299] [PMID: 10947214]
]. The first two cases of glycopeptide-resistant CoNS strains were reported by Wilson et al. and Schwalbe et al. [39Wilson APR, O’Hare MD, Felmingham D, Grüneberg RN. Teicoplanin-resistant coagulase-negative staphylococcus. Lancet 1986; 2(8513): 973.
[http://dx.doi.org/10.1016/S0140-6736(86)90622-7] [PMID: 2877149]
, 40Schwalbe RS, Stapleton JT, Gilligan PH. Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med 1987; 316(15): 927-31.
[http://dx.doi.org/10.1056/NEJM198704093161507] [PMID: 3821839]
]. In a one-year prospective control study conducted in an Italian University Hospital, Tacconelli et al. isolated nineteen strains resistant to teicoplanin and one strain resistant to both teicoplanin and vancomycin from 535 subjects with bacteremia. They verified that previous exposure to beta-lactams and glycopeptides, multiple hospitalizations and the concomitant presence of pneumonia were connected with the development of resistance to these antibiotics [41Tacconelli E, Tumbarello M, Donati KG, et al. Glycopeptide resistance among coagulase-negative staphylococci that cause bacteremia: epidemiological and clinical findings from a case-control study. Clin Infect Dis 2001; 33(10): 1628-35.
[http://dx.doi.org/10.1086/323676] [PMID: 11595984]
]. In recent years, a worldwide increase in the number of glycopeptide-resistant CoNS has been reported [42Mehri H, Jahanbakhsh R, Shakeri F, et al. Investigation of glycopeptide susceptibility of coagulase-negative staphylococci (CoNS) from a tertiary care hospital in Gorgan, northern Iran. Arch Pediatr Infect Dis 2017; 5e37264
[http://dx.doi.org/10.5812/pedinfect.37264]
]. Sgarabotto et al. suggested the association synercid/vancomycin against multidrug-resistant CoNS. The combination of the two antibiotics avoids any side effects [43Venkatesh MP, Placencia F, Weisman LE. Coagulase-negative staphylococcal infections in the neonate and child: an update. Semin Pediatr Infect Dis 2006; 17(3): 120-7.
[http://dx.doi.org/10.1053/j.spid.2006.06.005] [PMID: 16934706]
, 44Sgarabotto D, Cusinato R, Narne E, et al. Synercid plus vancomycin for the treatment of severe methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci infections: evaluation of 5 cases. Scand J Infect Dis 2002; 34(2): 122-6.
[http://dx.doi.org/10.1080/00365540110077245] [PMID: 11928842]
]. Among the β-lactams, the highest resistance rates were observed for ampicillin and penicillin, followed by amoxicillin-clavulanate, and oxacillin. In Italy, Arciola et al. determined the resistance patterns of 15 different species of CoNS isolated from orthopedic implants. The most prevalent species were S. hominis, S. haemolyticus, S. capitis, S. warneri and S. cohnii, with a resistance rate to penicillin between 51% and 66%. S. haemolyticus exhibited high resistance to oxacillin [45Arciola CR, Campoccia D, Baldassarri L, et al. Detection of biofilm formation in Staphylococcus epidermidis from implant infections. Comparison of a PCR-method that recognizes the presence of ica genes with two classic phenotypic methods. J Biomed Mater Res A 2006; 76(2): 425-30.
[http://dx.doi.org/10.1002/jbm.a.30552] [PMID: 16270350]
]. For the macrolides group, S. haemolyticus, S. epidermidis and S. hominis showed a high rate of erythromycin-resistance [26Gherardi G, De Florio L, Lorino G, Fico L, Dicuonzo G. Macrolide resistance genotypes and phenotypes among erythromycin-resistant clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci, Italy. FEMS Immunol Med Microbiol 2009; 55(1): 62-7.
[http://dx.doi.org/10.1111/j.1574-695X.2008.00499.x] [PMID: 19076222]
]. Within the quinolones, resistance to levofloxacin, ciprofloxacin and ofloxacin was found in about 50% of the clinical isolates. Ligozzi et al. demonstrated that norA-like genes played an important role in the resistance of CoNS to fluoroquinolones [46Marco L, Liliana G, Anna B, Annarita M. Intrinsic role of coagulase negative staphylococci norA-like efflux system in fluoroquinolones resistance. AIMS Microbiol 2017; 3(4): 908-14.
[http://dx.doi.org/10.3934/microbiol.2017.4.908] [PMID: 31294197]
]. Resistance mechanisms to quinolones include mutations of DNA gyrase and topoisomerase IV [47Talukdar A, Therese KL, Ali HN. Mutations within the Quinolone Resistance Determining Region in fluoroquinolone-resistant Staphylococcus epidermidis recovered from different ocular isolates. Int J Curr Microbiol Appl Sci 2018; 7: 1301-11.
[http://dx.doi.org/10.20546/ijcmas.2018.709.155]
]. Rifampicin is one of the antibiotics of choice for the treatment of joint and bone infections, due to its ability to penetrate staphylococcal biofilm. The use of this antibiotic has been associated with the development of resistant mutants. Therefore, it is usually administered in association with other antibacterial agents [48Szczuka E, Jabłońska L, Kaznowski A. Coagulase-negative staphylococci: pathogenesis, occurrence of antibiotic resistance genes and in vitro effects of antimicrobial agents on biofilm-growing bacteria. J Med Microbiol 2016; 65(12): 1405-13.
[http://dx.doi.org/10.1099/jmm.0.000372] [PMID: 27902368]
]. Trimethoprim-sulfamethoxazole exerts a bacteriostatic effect against staphylococci and susceptibility to this antibiotic combination is highly variable [49Osman K, Alvarez-Ordóñez A, Ruiz L, et al. Antimicrobial resistance and virulence characterization of Staphylococcus aureus and coagulase-negative staphylococci from imported beef meat. Ann Clin Microbiol Antimicrob 2017; 16(1): 35.
[http://dx.doi.org/10.1186/s12941-017-0210-4] [PMID: 28486995]
]. Regarding tetracycline, in our study, 24% of the strains exhibited resistance. The aminoglycoside gentamycin was tested against CoNS, with a resistance rate of 47%. For the lincosamides class, CoNS showed 28% resistance against clindamycin. Our data are consistent with a recent study by De Vecchi et al. [25De Vecchi E, George DA, Romanò CL, Pregliasco FE, Mattina R, Drago L. Antibiotic sensitivities of coagulase-negative staphylococci and Staphylococcus aureus in hip and knee periprosthetic joint infections: does this differ if patients meet the International Consensus Meeting Criteria? Infect Drug Resist 2018; 11: 539-46.
[http://dx.doi.org/10.2147/IDR.S151271] [PMID: 29695923]
], where there was a greater antibiotic resistance in S. haemolyticus than in S. capitis and S. warneri. However, it was not possible to compare our results with others obtained in the same geographical area, since any data regarding the frequency of isolation and antibiotic-resistance of coagulase-negative staphylococci in South Italy are available. From our results concerning CoNS resistance, it is possible to state that the antibiotics rifampicin, tetracycline, trimethoprim-sulfamethoxazole and, to a lesser extent, clindamycin could be used with a good success rate. The antibiotics synercid, linezolid, teicoplanin and vancomycin should be used only in cases where the other antimicrobial agents are not effective.

In the present study, the frequency of isolation and the antibiotic-resistance of coagulase-negative staphylococci from the hospital environment were investigated; not a correlation with the different types of infections. Indeed, since CoNS are commonly present in the human skin and mucous membranes, in some cases, they could contaminate clinical specimens [50Asaad AM, Ansar Qureshi M, Mujeeb Hasan S. Clinical significance of coagulase-negative staphylococci isolates from nosocomial bloodstream infections. Infect Dis (Lond) 2016; 48(5): 356-60.
[http://dx.doi.org/10.3109/23744235.2015.1122833] [PMID: 26666168]
, 51Morioka S, Ichikawa M, Mori K, Kurai H. Coagulase-negative staphylococcal bacteraemia in cancer patients. Time to positive culture can distinguish bacteraemia from contamination. Infect Dis (Lond) 2018; 50(9): 660-5.
[http://dx.doi.org/10.1080/23744235.2018.1451917] [PMID: 29544362]
]. It is well known that the differentiation between a pathogen and a contaminant is based on several clinical and microbiological factors. Accordingly, in the last few years, different clinical studies have provided guidelines to distinguish pathogenic strains from contaminants, to date, clear, definitive guidelines are still lacking [52Fowler ML, Zhu C, Byrne K, et al. Pathogen or contaminant? Distinguishing true infection from synovial fluid culture contamination in patients with suspected septic arthritis. Infection 2017; 45(6): 825-30.
[http://dx.doi.org/10.1007/s15010-017-1051-y] [PMID: 28766274]
]. Although the contamination of specimens is clinically relevant, in this context, we focused on the antibiotic-resistance of coagulase-negative staphylococci isolated from hospital samples. Therefore, we found that, among CoNS, S. haemolyticus and S. epidermidis are the most frequently isolated bacteria from clinical specimens in a single center in South Italy.

CONCLUSION

The comparative analysis of antibiotic resistance patterns of different CoNS revealed high resistance levels of these strains to the most common antibiotics used in clinical practice. Furthermore, the role of CoNS in the pathogenesis of infection should be assessed for each patient. Different antibiotics, including penicillins, cephalosporins, macrolides, tetracycline and aminoglycosides, have proven to be ineffective against several CoNS species. Hence, there is a need to find new effective antimicrobial drugs. In conclusion, our study could be viewed as the first step of a wider investigation that significantly contributes to the evaluation of the clinical importance of coagulase-negative staphylococci, in a small area of the South of Italy.

LIST OF ABBREVIATIONS

CoNS Coagulase-negative Staphylococci;
MIC Minimum Inhibitory Concentration.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

Not applicable.

HUMAN AND ANIMAL RIGHTS

Not applicable.

CONSENT FOR PUBLICATION

Not applicable.

AVAILABILITY OF DATA AND MATERIALS

The datasets generated during the current study are available from the corresponding author on a reasonable request.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

We wish to thank the Scientific Bureau of the University of Catania for language support.

REFERENCES

[1] Méric G, Mageiros L, Pensar J, et al. Disease-associated genotypes of the commensal skin bacterium Staphylococcus epidermidis. Nat Commun 2018; 9(1): 5034.
[http://dx.doi.org/10.1038/s41467-018-07368-7] [PMID: 30487573]
[2] Kini GD, Patel K, Parris AR, Tang JS. An unusual presentation of endocarditis caused by Staphylococcus warneri. Open Microbiol J 2010; 4: 103-5.
[http://dx.doi.org/10.2174/1874285801004010103] [PMID: 21258573]
[3] Le KY, Park MD, Otto M. Immune Evasion Mechanisms of Staphylococcus epidermidis Biofilm Infection. Front Microbiol 2018; 9: 359.
[http://dx.doi.org/10.3389/fmicb.2018.00359] [PMID: 29541068]
[4] Kleinschmidt S, Huygens F, Faoagali J, Rathnayake IU, Hafner LM. Staphylococcus epidermidis as a cause of bacteremia. Future Microbiol 2015; 10(11): 1859-79.
[http://dx.doi.org/10.2217/fmb.15.98] [PMID: 26517189]
[5] Cherifi S, Byl B, Deplano A, et al. Genetic characteristics and antimicrobial resistance of Staphylococcus epidermidis isolates from patients with catheter-related bloodstream infections and from colonized healthcare workers in a Belgian hospital. Ann Clin Microbiol Antimicrob 2014; 13: 20.
[http://dx.doi.org/10.1186/1476-0711-13-20] [PMID: 24899534]
[6] Sani NA, Sapri HF, Neoh HM, Hussin S. First report on the molecular epidemiology of Malaysian Staphylococcus epidermidis isolated from a university teaching hospital. BMC Res Notes 2014; 7: 597.
[http://dx.doi.org/10.1186/1756-0500-7-597] [PMID: 25186825]
[7] Sabaté Brescó M, Harris LG, Thompson K, et al. Pathogenic Mechanisms and Host Interactions in Staphylococcus epidermidis Device-Related Infection. Front Microbiol 2017; 8: 1401.
[http://dx.doi.org/10.3389/fmicb.2017.01401] [PMID: 28824556]
[8] Mendoza-Olazarán S, Morfin-Otero R, Rodríguez-Noriega E, et al. Microbiological and molecular characterization of Staphylococcus hominis isolates from blood. PLoS One 2013; 8(4)e61161
[http://dx.doi.org/10.1371/journal.pone.0061161] [PMID: 23585877]
[9] Frickmann H, Hahn A, Skusa R, et al. Comparison of the etiological relevance of Staphylococcus haemolyticus and Staphylococcus hominis. Eur J Clin Microbiol Infect Dis 2018; 37(8): 1539-45.
[http://dx.doi.org/10.1007/s10096-018-3282-y] [PMID: 29777490]
[10] Szczuka E, Krzymińska S, Kaznowski A. Clonality, virulence and the occurrence of genes encoding antibiotic resistance among Staphylococcus warneri isolates from bloodstream infections. J Med Microbiol 2016; 65(8): 828-36.
[http://dx.doi.org/10.1099/jmm.0.000287] [PMID: 27226348]
[11] Czekaj T, Ciszewski M, Szewczyk EM. Staphylococcus haemolyticus - an emerging threat in the twilight of the antibiotics age. Microbiology 2015; 161(11): 2061-8.
[http://dx.doi.org/10.1099/mic.0.000178] [PMID: 26363644]
[12] Parashar S. Staphylococcus haemolyticus; A Nosocomial Pathogen Showing Higher Antimicobial Resistance. Med Sci 2014; 3: 381-2.
[http://dx.doi.org/10.1537/2249555x]
[13] Yamamoto K, Ohmagari N. Infective Endarteritis due to Staphylococcus capitis. Intern Med 2018; 57(8): 1185.
[http://dx.doi.org/10.2169/internalmedicine.0070-17] [PMID: 29279472]
[14] Ehlersson G, Hellmark B, Svartström O, Stenmark B, Söderquist B. Phenotypic characterisation of coagulase-negative staphylococci isolated from blood cultures in newborn infants, with a special focus on Staphylococcus capitis. Acta Paediatr 2017; 106(10): 1576-82.
[http://dx.doi.org/10.1111/apa.13950] [PMID: 28631328]
[15] Shahandeh Z, Shafi H, Sadighian F. Association of staphylococcus cohnii subspecies urealyticum infection with recurrence of renal staghorn stone. Caspian J Intern Med 2015; 6(1): 40-2.
[PMID: 26221496]
[16] Gaglani B, Dahdouh M, Shah K. Septic arthritis of native hip joint by Staphylococcus lugdunensis: A case report. Rev Soc Bras Med Trop 2018; 51(4): 554-6.
[http://dx.doi.org/10.1590/0037-8682-0169-2017] [PMID: 30133645]
[17] Zaaroura H, Geffen Y, Bergman R, Avitan-Hersh E. Clinical and microbiological properties of Staphylococcus lugdunensis skin infections. J Dermatol 2018; 45(8): 994-9.
[http://dx.doi.org/10.1111/1346-8138.14496] [PMID: 29897142]
[18] Heldt Manica LA, Cohen PR. Cutaneous Staphylococcus lugdunensis infection: an emerging bacterial pathogen. Dermatol Online J 2018; 24 ` : 13030/qt4sv3z6gk.
[19] Carter GP, Ussher JE, Da Silva AG, et al. Genomic analysis of multi-resistant Staphylococcus capitis associated with neonatal sepsis. Antimicrob Agents Chemother 2018; 62(11): e00898-18.
[http://dx.doi.org/10.1128/AAC.00898-18] [PMID: 30150477]
[20] Genovese C, Davinelli S, Mangano K, et al. Effects of a new combination of plant extracts plus d-mannose for the management of uncomplicated recurrent urinary tract infections. J Chemother 2018; 30(2): 107-14.
[http://dx.doi.org/10.1080/1120009X.2017.1393587] [PMID: 29078739]
[21] Diekema DJ, Pfaller MA, Schmitz FJ, et al. SENTRY Partcipants Group. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis 2001; 32(Suppl. 2): S114-32.
[http://dx.doi.org/10.1086/320184] [PMID: 11320452]
[22] Bouchami O, Ben Hassen A, de Lencastre H, Miragaia M. Molecular epidemiology of methicillin-resistant Staphylococcus hominis (MRSHo): low clonality and reservoirs of SCCmec structural elements. PLoS One 2011; 6(7)e21940
[http://dx.doi.org/10.1371/journal.pone.0021940] [PMID: 21760926]
[23] Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH. Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol 2003; 41(10): 4740-4.
[http://dx.doi.org/10.1128/JCM.41.10.4740-4744.2003] [PMID: 14532213]
[24] McHardy IH, Veltman J, Hindler J, Bruxvoort K, Carvalho MM, Humphries RM. Clinical and microbiological aspects of β-lactam resistance in Staphylococcus lugdunensis. J Clin Microbiol 2017; 55(2): 585-95.
[http://dx.doi.org/10.1128/JCM.02092-16] [PMID: 27927926]
[25] De Vecchi E, George DA, Romanò CL, Pregliasco FE, Mattina R, Drago L. Antibiotic sensitivities of coagulase-negative staphylococci and Staphylococcus aureus in hip and knee periprosthetic joint infections: does this differ if patients meet the International Consensus Meeting Criteria? Infect Drug Resist 2018; 11: 539-46.
[http://dx.doi.org/10.2147/IDR.S151271] [PMID: 29695923]
[26] Gherardi G, De Florio L, Lorino G, Fico L, Dicuonzo G. Macrolide resistance genotypes and phenotypes among erythromycin-resistant clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci, Italy. FEMS Immunol Med Microbiol 2009; 55(1): 62-7.
[http://dx.doi.org/10.1111/j.1574-695X.2008.00499.x] [PMID: 19076222]
[27] Carretto E, Barbarini D, Couto I, et al. Identification of coagulase-negative staphylococci other than Staphylococcus epidermidis by automated ribotyping. Clin Microbiol Infect 2005; 11(3): 177-84.
[http://dx.doi.org/10.1111/j.1469-0691.2004.01052.x] [PMID: 15715714]
[28] Stefani S, Varaldo PE. Epidemiology of methicillin-resistant staphylococci in Europe. Clin Microbiol Infect 2003; 9(12): 1179-86.
[http://dx.doi.org/10.1111/j.1469-0691.2003.00698.x] [PMID: 14686982]
[29] Available from: https://www.iss.it/
[30] Becker K, Heilmann C, Peters G. Coagulase-negative staphylococci. Clin Microbiol Rev 2014; 27(4): 870-926.
[http://dx.doi.org/10.1128/CMR.00109-13] [PMID: 25278577]
[31] Sundqvist M, Bieber L, Smyth R, Kahlmeter G. Detection and identification of Staphylococcus lugdunensis are not hampered by use of defibrinated horse blood in blood agar plates. J Clin Microbiol 2010; 48(5): 1987-8.
[http://dx.doi.org/10.1128/JCM.02307-09] [PMID: 20305013]
[32] Ruoff KL. Algorithm for identification of aerobic gram positive cocci.Manual of Clinical Microbiology 2003; 331-3.
[33] CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement. CLSI Document M100-S26, Clinical and Laboratory Standards Institute 2016.
[34] Acquaviva R, D’Angeli F, Malfa GA, et al. Antibacterial and anti-biofilm activities of walnut pellicle extract (Juglans regia L.) against coagulase-negative staphylococci. Nat Prod Res 2019; 1-6.
[http://dx.doi.org/10.1080/14786419.2019.1650352] [PMID: 31397177]
[35] Nicolosi D, Cupri S, Genovese C, Tempera G, Mattina R, Pignatello R. Nanotechnology approaches for antibacterial drug delivery: Preparation and microbiological evaluation of fusogenic liposomes carrying fusidic acid. Int J Antimicrob Agents 2015; 45(6): 622-6.
[http://dx.doi.org/10.1016/j.ijantimicag.2015.01.016] [PMID: 25816979]
[36] Tian Y, Li T, Zhu Y, Wang B, Zou X, Li M. Mechanisms of linezolid resistance in staphylococci and enterococci isolated from two teaching hospitals in Shanghai, China. BMC Microbiol 2014; 14: 292.
[http://dx.doi.org/10.1186/s12866-014-0292-5] [PMID: 25420718]
[37] Brenciani A, Morroni G, Mingoia M, Varaldo PE, Giovanetti E. Stability of the cargo regions of the cfr-carrying, multiresistance plasmid pSP01 from Staphylococcus epidermidis. Int J Med Microbiol 2016; 306(8): 717-21.
[http://dx.doi.org/10.1016/j.ijmm.2016.08.002] [PMID: 27554790]
[38] Biavasco F, Vignaroli C, Varaldo PE. Glycopeptide resistance in coagulase-negative staphylococci. Eur J Clin Microbiol Infect Dis 2000; 19(6): 403-17.
[http://dx.doi.org/10.1007/s100960000299] [PMID: 10947214]
[39] Wilson APR, O’Hare MD, Felmingham D, Grüneberg RN. Teicoplanin-resistant coagulase-negative staphylococcus. Lancet 1986; 2(8513): 973.
[http://dx.doi.org/10.1016/S0140-6736(86)90622-7] [PMID: 2877149]
[40] Schwalbe RS, Stapleton JT, Gilligan PH. Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med 1987; 316(15): 927-31.
[http://dx.doi.org/10.1056/NEJM198704093161507] [PMID: 3821839]
[41] Tacconelli E, Tumbarello M, Donati KG, et al. Glycopeptide resistance among coagulase-negative staphylococci that cause bacteremia: epidemiological and clinical findings from a case-control study. Clin Infect Dis 2001; 33(10): 1628-35.
[http://dx.doi.org/10.1086/323676] [PMID: 11595984]
[42] Mehri H, Jahanbakhsh R, Shakeri F, et al. Investigation of glycopeptide susceptibility of coagulase-negative staphylococci (CoNS) from a tertiary care hospital in Gorgan, northern Iran. Arch Pediatr Infect Dis 2017; 5e37264
[http://dx.doi.org/10.5812/pedinfect.37264]
[43] Venkatesh MP, Placencia F, Weisman LE. Coagulase-negative staphylococcal infections in the neonate and child: an update. Semin Pediatr Infect Dis 2006; 17(3): 120-7.
[http://dx.doi.org/10.1053/j.spid.2006.06.005] [PMID: 16934706]
[44] Sgarabotto D, Cusinato R, Narne E, et al. Synercid plus vancomycin for the treatment of severe methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci infections: evaluation of 5 cases. Scand J Infect Dis 2002; 34(2): 122-6.
[http://dx.doi.org/10.1080/00365540110077245] [PMID: 11928842]
[45] Arciola CR, Campoccia D, Baldassarri L, et al. Detection of biofilm formation in Staphylococcus epidermidis from implant infections. Comparison of a PCR-method that recognizes the presence of ica genes with two classic phenotypic methods. J Biomed Mater Res A 2006; 76(2): 425-30.
[http://dx.doi.org/10.1002/jbm.a.30552] [PMID: 16270350]
[46] Marco L, Liliana G, Anna B, Annarita M. Intrinsic role of coagulase negative staphylococci norA-like efflux system in fluoroquinolones resistance. AIMS Microbiol 2017; 3(4): 908-14.
[http://dx.doi.org/10.3934/microbiol.2017.4.908] [PMID: 31294197]
[47] Talukdar A, Therese KL, Ali HN. Mutations within the Quinolone Resistance Determining Region in fluoroquinolone-resistant Staphylococcus epidermidis recovered from different ocular isolates. Int J Curr Microbiol Appl Sci 2018; 7: 1301-11.
[http://dx.doi.org/10.20546/ijcmas.2018.709.155]
[48] Szczuka E, Jabłońska L, Kaznowski A. Coagulase-negative staphylococci: pathogenesis, occurrence of antibiotic resistance genes and in vitro effects of antimicrobial agents on biofilm-growing bacteria. J Med Microbiol 2016; 65(12): 1405-13.
[http://dx.doi.org/10.1099/jmm.0.000372] [PMID: 27902368]
[49] Osman K, Alvarez-Ordóñez A, Ruiz L, et al. Antimicrobial resistance and virulence characterization of Staphylococcus aureus and coagulase-negative staphylococci from imported beef meat. Ann Clin Microbiol Antimicrob 2017; 16(1): 35.
[http://dx.doi.org/10.1186/s12941-017-0210-4] [PMID: 28486995]
[50] Asaad AM, Ansar Qureshi M, Mujeeb Hasan S. Clinical significance of coagulase-negative staphylococci isolates from nosocomial bloodstream infections. Infect Dis (Lond) 2016; 48(5): 356-60.
[http://dx.doi.org/10.3109/23744235.2015.1122833] [PMID: 26666168]
[51] Morioka S, Ichikawa M, Mori K, Kurai H. Coagulase-negative staphylococcal bacteraemia in cancer patients. Time to positive culture can distinguish bacteraemia from contamination. Infect Dis (Lond) 2018; 50(9): 660-5.
[http://dx.doi.org/10.1080/23744235.2018.1451917] [PMID: 29544362]
[52] Fowler ML, Zhu C, Byrne K, et al. Pathogen or contaminant? Distinguishing true infection from synovial fluid culture contamination in patients with suspected septic arthritis. Infection 2017; 45(6): 825-30.
[http://dx.doi.org/10.1007/s15010-017-1051-y] [PMID: 28766274]
Track Your Manuscript:


Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


Browse Contents




Webmaster Contact: info@benthamopen.net
Copyright © 2020 Bentham Open