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Comparative activities of ampicillin and teicoplanin against Enterococcus faecalis isolates



Enterococcus faecalis remains one of the most common pathogens causing infection in surgical patients. Our goal was to evaluate the antibiotic resistance of E. faecalis, causing infections in a surgical clinic, against two antibacterial drugs, ampicillin and teicoplanin. One commonly administered in the past for such infections, ampicillin, and another newer, teicoplanin, which demonstrated exceptionally good efficacy.


Data from 1882 isolates were retrieved from the microbiology department database during two 5-year periods. Standard biochemical methods were employed for the identification of the isolates. The prevalence of E. faecalis among patients with clinical evidence of infection in a surgical oncology ward was assessed. Confidence interval (CI) as well as standard error (SE) were calculated. Moreover, the annual incidence of E. faecalis infections in this surgical ward was recorded. The susceptibility of E. faecalis to ampicillin and teicoplanin was studied and compared using Fisher’s exact test.

Results and conclusion

Results showed that the incidence of E. faecalis infections in the surgical clinic was increasing. Ampicillin, in the later year period, was not statistically different from teicoplanin in treating E. faecalis infections. Consequently, ampicillin seems currently to be an effective antibiotic against such infections that could be used as empiric therapy.

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Surgical infection represents one of the most serious complications that patients face during their healing process. It is associated with a higher death rate, longer hospitalization, and more intense post-discharge care [1]. Enterococci are one of the most common bacteria isolated from infections in surgical patients. Phylogenetically, the genus Enterococcus belongs to the branch of Gram-positive bacteria. The genus Enterococcus consists of several species that occur in human and animal gastrointestinal (GI) tracts, as well as in the guts of insects, traditional fermented food, and dairy products, and in various environments including plants, soil, and water [1,2,3,4,5]. Enterococcus is also a nosocomial pathogen with opportunistic behavior. It is responsible for a variety of infections such as wounds, intra-abdominal, urinary tract, catheter-associated infections, suppurative thrombophlebitis, endocarditis as well as pneumonia [6]. During the past few decades, enterococci have emerged as important healthcare-associated pathogens [7,8,9,10,11,12]. Moreover, antibiotics-resistant Enterococcus that are isolated from nosocomial infections is difficult to treat, making the bacterium a challenging issue for clinicians in the twenty-first century [12,13,14].

As there is a paucity of data regarding the incidence of E. faecalis infections and their antimicrobial resistance to ampicillin and teicoplanin in tertiary hospitals in South Greece, the aim of this study was to describe the epidemiological features of E. faecalis infections in surgical patients at Heraklion University Hospital in Heraklion, Crete, by outlining their antimicrobial resistance against two commonly used drugs, ampicillin, and teicoplanin. All methods were carried out in accordance with relevant guidelines and regulations.

Materials and methods

A total of 1882 isolates from wound, blood, and urine cultures were collected over two 5-year periods from patients hospitalized in the department of surgical oncology at the university hospital of Heraklion, Crete. Five hundred eighty-six isolates were collected from 2010 to 2014 and 1296 isolates from 2017 to 2021. All data were retrieved from the Microbiology department database.

Isolates were identified at the genus level by standard biochemical assays (esculin hydrolysis, growth in 6.5% salt broth), and at the species level by the Vitek 2 system (Vitek 2, GP panel; BioMérieux, Marcy l’ Etoile, France), and was confirmed by the matrix-assisted laser desorption time of flight mass spectrometry (MALDI-TOF MS) (version 3.2) (BioMérieux). Susceptibility to antimicrobials was determined using the automated system Vitek2 (BioMérieux) [15, 16]. Results were interpreted according to the Clinical and Laboratory Standards Institute criteria (CLSI) [17].

During the 2010–2014 period, the susceptibility to ampicillin was tested in 67 out of 78 Enterococcus isolates while the susceptibility to teicoplanin was in 76 out of 78. In each 5-year period, the percentage of E. faecalis infections out of total infections (Figs. 1 and 2), the confidence interval (CI) as well as standard error (SE) were calculated. Moreover, the number of infections with E. faecalis per year was recorded. (Figs. 3 and 4) The susceptibility of E. faecalis to ampicillin and teicoplanin per year in both periods was calculated (Figs. 5 and 6). Fisher’s exact test was used to compare this susceptibility in these two periods. (Table 1).

Fig. 1
figure 1

Bacterial ratio of surgical infections in the 2017–2021 period

Fig. 2
figure 2

Bacterial ratio of surgical infections in the 2010–2014 period

Fig. 3
figure 3

The annual incidence of Enterococcus faecalis infections in the surgical clinic 2017–2021 represented also in a line bar diagram

Fig. 4
figure 4

The annual incidence of Enterococcus faecalis causing infections in the surgical clinic 2010–2014 represented in a line bar diagram

Fig. 5
figure 5

Annual resistance of Enterococcus faecalis isolates against ampicillin and teicoplanin 2017–2021

Fig. 6
figure 6

Annual resistance of Enterococcus faecalis isolates against ampicillin and teicoplanin 2010–2014

Table 1 Comparison of the effectiveness of Ampicillin-Teicoplanin against Enterococcus faecalis between 2010 and 2014 and 2017–2021


A higher number of enterococcal infections was recorded in the period 2017–2021(143) (Fig. 5) compared to 2010–2014 (78) (Fig. 6). Nevertheless, the percentage of enterococcal infections among all infections remained roughly the same between 2017 and 2021 11.03% [95% CI = 0.1103 + − 1.96*0.0087 = (0.0932,0.1274)] and 2010–2014 (13.31%) [95%CI = 0.1331 + − 1.96*0.0140 = (0.1056,0.1606)] (Figs. 1 and 2).

A decrease in the percentage of resistant Enterococcus strains to ampicillin was observed from 21.8% (17 out of 67) in the period 2010–2014 to 0.7% (1 out of 143) in the period 2017–2021. (Table 1).

In the period 2010–2014 teicoplanin was effective against all strains of E. faecalis but ampicillin was not (Fig. 6), making the former preferable to administer against E. faecalis. (P < 0.000001) (Table 1). After 3 years, during the 2017–2021 period, ampicillin was not statistically different from teicoplanin in treating E. faecalis infections. (P = 0.5) (Table 1).


In our study, a clear increase in E. faecalis infections were reported between the two 5-year periods. However, the overall prevalence of E. faecalis remained almost stable ranging from 13.31% in the 2010–2014 to 11.03% during the 2017–2021 period. These data were higher than that of the 4-year summary from 2011 to 2014 reported to the national healthcare safety network at the Centers for Disease Control and Prevention of the USA, which was 7.4% [18]. This could be explained by the study participants as the American study included patients from all the departments, various hospitals as well as rehabilitation facilities. The methods employed for the detection of E. faecalis could also attribute to the different results. In another study, E. faecalis was isolated in 24 of 200 (12%) surgical wound samples and in 2 of 100 (2%) blood cultures [19]. All isolates were resistant to ampicillin and 19.2% were resistant to teicoplanin [19]. The results of our study are in accordance with a recent publication from China that reported that resistance rates to ampicillin decreased gradually but to teicoplanin increased for E. faecalis [20].

Ampicillin is a penicillin beta-lactam antibiotic, with effectiveness against most infectious organisms like E. coli, S. pneumoniae, and H. influenzae [21, 22]. Teicoplanin is a glycopeptide antibiotic that was isolated more than 40 years ago as a product of Actionplanes teicomyceticus [23]. It has potent bactericidal activity against a wide variety of aerobic and anaerobic gram-positive bacteria. Its adverse effects include ototoxicity, nephrotoxicity, skin rash, eosinophilia, neutropenia, and transient elevation of serum aminotransferases [24]. It has been shown that serum levels of teicoplanin may not be predictable when administered to seriously ill patients, making cautious use in such cases mandatory [25].

Presently, the treatment of enterococcal infections represents one of the most arduous problems that physicians are dealing with. An increased prevalence of strains that are resistant to almost all antibiotics with in vitro bactericidal activity against enterococci has been observed, reflecting a perturbing tendency. The enterococci are intrinsically resistant to many commonly used antimicrobial agents, namely cephalosporins, aminoglycosides, clindamycin, quinupristin/dalfopristin, and trimethoprim-sulfamethoxazole [26]. All enterococci exhibit decreased susceptibility to penicillin and ampicillin, as well as high-level resistance to most all semi-synthetic penicillins [27]. Nonetheless, for many isolates, despite their level of resistance to ampicillin, its clinical use is not prohibited. Actually, ampicillin remains the treatment of choice for enterococcal infections that lack other mechanisms for high-level resistance [27]. Our data are in concordance with this therapeutic trend indicating that, currently, ampicillin could be effective against E. faecalis isolates. In the second 5-year period both ampicillin and teicoplanin remained highly active against E. faecalis isolates.

Vancomycin-resistant enterococci (VRE) are a usual and difficult-to-treat reason for hospital-acquired infection [28]. VRE are distinguished from other strains of Enterococcus by a raised minimum inhibitory concentration (MIC) for vancomycin and the presence of vancomycin-resistance gene clusters such as vanA [29]. High-level resistance to vancomycin is encoded by different clusters of genes referred to as the vancomycin-resistance gene clusters (for example, vanA, B, D, and M gene clusters). VanA is the most common type of vancomycin resistance, usually mediates higher levels of resistance than other types, and causes cross-resistance to teicoplanin. The VanB phenotype, the second most common type, is less frequently encountered than VanA [30].

High-level vancomycin resistance is the most problematic resistance of enterococci because it often appears in strains already highly resistant to ampicillin. The three major phenotypes, VanA, VanB, and VanD, can sometimes be differentiated by the level of vancomycin resistance, susceptibility to the glycopeptide antibiotic teicoplanin, and whether the resistance is induced by exposure to teicoplanin [30].

Adherence to protocols for cleaning patient rooms should be monitored to decrease environmental contamination with VRE [31]. Healthcare-associated VRE is transmitted in the hands of healthcare workers; as a result, good hand hygiene is considered an essential measure for reducing the spread of this pathogen. Colonization with VRE typically precedes infection. Colonization most commonly occurs in patients with previous antimicrobial therapy and residents in long-term care facilities [32].

A multimodal strategy is required for VRE prevention and control, including general infection prevention measures including the best care of vascular and urinary catheters, accurate and quick diagnosis and management, judicious use of antibiotics, and infection transmission prevention [32,33,34].

.An infection control program is essential to surgical site infection (SSI) prevention [35]. A successful program may decrease the rate of SSIs by 40% [27,28,29,30]. The prompt administration of efficient preoperative antibiotics and careful attention to surgical technique rank as the most crucial elements in the prevention of SSI, along with maintaining a clean operating room environment. A variety of topical and local antibiotic delivery methods as well as wound-protecting barrier devices have been employed during surgery to lower the incidence of SSI [36]. .The use of antimicrobial-coated sutures may minimize the risk of SSI, although the available and high-quality data are scarce [37].


Our study suggests that ampicillin could reprise its role as a first-line treatment of enterococcal infections with teicoplanin reserved for cases in which the former cannot be used, such as due to a β-lactam allergy. Clearly, larger and more meticulous studies are necessary to confirm the role of ampicillin. What is apparent from our study is that the resistance of E. faecalis to ampicillin does not remain stable but weakens over a relatively short period of time. Thus an antibiotic that in one period may not show increased activity against this pathogen in another period of time may still be suitable and effective for the treatment of E. faecalis infections. Ampicillin may be a suitable agent for treating infections caused by E. faecalis. Further research is necessary to validate these results and establish its use as empiric therapy against such infections.

Availability of data and materials

The data that supports the findings of this study are available upon reasonable request from the corresponding author.


E. faecalis :

Enterococcus faecalis


Confidence interval


Standard error


Vancomycin-resistant enterococci


minimum inhibitory concentration


surgical site infection


  1. Ator LL, Starzyk MJ. Distribution of group D streptococci in rivers and streams. Microbios. 1976;16:91–104.

    CAS  Google Scholar 

  2. Mundt JO. Occurrence of enterococci in animals in a wild environment. Appl Microbiol. 1963;11:136–40.

    Article  CAS  Google Scholar 

  3. Martin JD, Mundt JO. Enterococci in insects. Appl Microbiol. 1972;24:575–80.

    Article  CAS  Google Scholar 

  4. Mundt JO. Enterococci. In: Bergey痴 manual of systematic bacteriology, vol. 2. Baltimore: Williams & Wilkins; 1986. p. 1063–5.

    Google Scholar 

  5. Mundt JO. Occurrence of enterococci: bud, blossom, and soil studies. Appl Microbiol. 1961;9:541–4.

    Article  CAS  Google Scholar 

  6. Barie PS, Christou NV, Dellinger EP, Rout WR, Stone HH, Waymack JP. Pathogenicity of the enterococcus in surgical infections. Ann Surg. 1990;212:155–9.

    Article  CAS  Google Scholar 

  7. Arias CA, Murray BE. The rise of the enterococcus: beyond vancomycin resistance. Nat Rev Microbiol. 2012;10:266–78.

    Article  CAS  Google Scholar 

  8. Austin DJ, Bonten MJ, Weinstein RA, Slaughter S, Anderson RM. Vancomycin-resistant enterococci in intensive-care hospital settings: transmission dynamics, persistence, and the impact of infection control programs. Proc Natl Acad Sci U S A. 1999;96:6908–13.

    Article  CAS  Google Scholar 

  9. Benenson S, Cohen MJ, Block C, Stern S, Weiss Y, Moses AE. Vancomycin-resistant enterococci in long-term care facilities. Infect Control Hosp Epidemiol. 2009;30:786–9.

    Article  Google Scholar 

  10. Goossens H. Spread of vancomycin-resistant enterococci: differences between the United States and Europe. Infect Control Hosp Epidemiol. 1998;19:546–51.

    Article  CAS  Google Scholar 

  11. Handwerger S, Raucher B, Altarac D, Monka J, Marchione S, Singh KV, et al. Nosocomial outbreak due to enterococcus faecium highly resistant to vancomycin, penicillin, and gentamicin. Clin Infect Dis. 1993;16:750–5.

    Article  CAS  Google Scholar 

  12. Gilmore MS, Clewell DB, Ike Y, Shankar N, editors. Enterococci: from commensals to leading causes of drug resistant infection. Boston: Massachusetts Eye and Ear Infirmary; 2014.

    Google Scholar 

  13. Prabaker K, Weinstein RA. Trends in antimicrobial resistance in intensive care units in the United States. Curr Opin Crit Care. 2011;17:472–9.

    Article  Google Scholar 

  14. Werner G, Coque TM, Hammerum AM, Hope R, Hryniewicz W, Johnson A, et al. Emergence and spread of vancomycin resistance among enterococci in Europe. Euro Surveill: Bull Europeen Sur les maladies transmissibles = European communicable disease bulletin. 2008;13(47):19046.

  15. Garcia-Garrote F, Cercenado E, Bouza E. Evaluation of a new system, VITEK 2, for identification and antimicrobial susceptibility testing of enterococci. J Clin Microbiol. 2000;38:2108–11.

    Article  CAS  Google Scholar 

  16. Bloise I, Corcuera MT, García-Rodríguez J, Mingorance J. Microbial identification in the clinical microbiology laboratory using MALDI-TOF-MS. Methods Mol Biol. 2022;2420:207–16.

    Article  Google Scholar 

  17. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; 31st ed. (M100-S31); 2021.

    Google Scholar 

  18. Weiner LM, Webb AK, Limbago B, Dudeck MA, Patel J, Kallen AJ, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011-2014. Infect Control Hosp Epidemiol. 2016;37:1288–301.

    Article  Google Scholar 

  19. Esmail MAM, Abdulghany HM, Khairy RM. Prevalence of multidrug-resistant enterococcus faecalis in hospital-acquired surgical wound infections and bacteremia: concomitant analysis of antimicrobial resistance genes. Infect Dis (Auckl). 2019;12:1178633719882929. eCollection.

    Article  Google Scholar 

  20. Zhou W, Zhou H, Sun Y, Gao S, Zhang Y, Cao X, et al. Characterization of clinical enterococci isolates, focusing on the vancomycin-resistant enterococci in a tertiary hospital in China: based on the data from 2013 to 2018. BMC Infect Dis. 2020;20(1):356.

    Article  CAS  Google Scholar 

  21. Kaushik D, Mohan M, Borade DM, Swami OC. Ampicillin: rise fall and resurgence. J Clin Diagnost Res. 2014;8:Me01–3.

    Article  CAS  Google Scholar 

  22. Peechakara BV, Basit H, Gupta M. Ampicillin. In: StatPearls. Treasure Island: Publishing, S; 2022.

    Google Scholar 

  23. Pryka RD, Rodvold KA, Rotschafer JC. Teicoplanin: an investigational glycopeptide antibiotic. Clin Pharm. 1988;7:647–58.

    CAS  Google Scholar 

  24. Babul N, Pasko M. Teicoplanin: a new glycopeptide antibiotic complex. Drug Intell Clin Pharmacy. 1988;22:218–26.

    Article  CAS  Google Scholar 

  25. Calain P, Krause KH, Vaudaux P, Auckenthaler R, Lew D, Waldvogel F, et al. Early termination of a prospective, randomized trial comparing teicoplanin and flucloxacillin for treating severe staphylococcal infections. J Infect Dis. 1987;155:187–91.

    Article  CAS  Google Scholar 

  26. Hollenbeck BL, Rice LB. Intrinsic and acquired resistance mechanisms in enterococcus. Virulence. 2012;3:421–33.

    Article  Google Scholar 

  27. Kristich CJ, Rice LB, Arias CA. Enterococcal infection treatment and antibiotic resistance. In: Gilmore MS, Clewell DB, Ike Y, Shankar N, editors. Enterococci: from commensals to leading causes of drug resistant infection. Boston: Massachusetts Eye and Ear Infirmary; 2014.

    Google Scholar 

  28. Ramsey AM, Zilberberg MD. Secular trends of hospitalization with vancomycin-resistant enterococcus infection in the United States, 2000-2006. Infect Control Hosp Epidemiol. 2009;30(2):184–6.

    Article  Google Scholar 

  29. Mascini EM, Troelstra A, Beitsma M, Blok HE, Jalink KP, Hopmans TE, et al. Genotyping and preemptive isolation to control an outbreak of vancomycin-resistant enterococcus faecium. Clin Infect Dis. 2006;42(6):739.

    Article  CAS  Google Scholar 

  30. Hong HJ, Hutchings MI, Buttner MJ. Biotechnology and Biological Sciences Research Council, UK. Vancomycin resistance VanS/VanR two-component systems. Adv Exp Med Biol. 2008;631:200–13.

    Article  CAS  Google Scholar 

  31. Reichman DE, Greenberg JA. Reducing surgical site infections: a review. Rev Obstet Gynecol. 2009;2(4):212–21.

    Google Scholar 

  32. Sidhwa F, Itani KM. Skin preparation before surgery: options and evidence. Surg Infect. 2015;16(1):14–23.

    Article  Google Scholar 

  33. Swenson BR, Hedrick TL, Metzger R, Bonatti H, Pruett TL, Sawyer RG. Effects of preoperative skin preparation on postoperative wound infection rates: a prospective study of 3 skin preparation protocols. Infect Control Hosp Epidemiol. 2009;30(10):964–71.

    Article  Google Scholar 

  34. Eichel VM, Boutin S, Frank U, Weigand MA, Heininger A, Mutters NT, et al. Impact of discontinuing contact precautions and enforcement of basic hygiene measures on nosocomial vancomycin-resistant enterococcus faecium transmission. J Hosp Infect. 2022;121:120–7.

    Article  CAS  Google Scholar 

  35. Kojima K, Nakamura T, Habiro T, Waraya M, Hayashi K, Ishii KI. Examination of the efficacy of olanexidine gluconate for surgical site infections in colorectal cancer elective surgery. J Infect Chemother. 2021;27(12):1729–34.

    Article  CAS  Google Scholar 

  36. NIHR Global Research Health Unit on Global Surgery. Routine sterile glove and instrument change at the time of abdominal wound closure to prevent surgical site infection (ChEETAh): a pragmatic, cluster-randomised trial in seven low-income and middle-income countries. Lancet. 2022;400(10365):1767–76. Epub 2022 Oct 31.

    Article  Google Scholar 

  37. Wang ZX, Jiang CP, Cao Y, Ding YT. Systematic review and meta-analysis of triclosan-coated sutures for the prevention of surgical-site infection. Br J Surg. 2013;100(4):465–73.

    Article  CAS  Google Scholar 

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Authors and Affiliations



GZ, GM, MP, and SM have collected the data in the manuscript under the supervision of AM. AM has designed the study. GZ, GM, MP, DK, and MP have written the first draft of the manuscript. DK and EDB have provided important supervision to the manuscript. All authors reviewed and approved the manuscript.

Corresponding author

Correspondence to Marios Papadakis.

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The study was approved by the Ethical committee of the University Hospital of Heraklion, Heraklion, Crete, Greece (Reference number 26262/2022). Informed consent was obtained from all subjects and legal guardians to participate in this study.

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Zacharopoulos, G.V., Manios, G.A., Papadakis, M. et al. Comparative activities of ampicillin and teicoplanin against Enterococcus faecalis isolates. BMC Microbiol 23, 5 (2023).

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