• View in gallery

    The trends and correlations between the resistance rates of enterococcus and antibiotic consumption during 2010–2019. VR E. faecalis = vancomycin-resistant enterococcus faecalis; VR E. faecium = vancomycin-resistant enterococcus faecium; VRE = vancomycin-resistant enterococcus.

  • 1.

    Murray BE, 1990. The life and times of the Enterococcus. Clin Microbiol Rev 3: 4665.

  • 2.

    Emori TG, Gaynes RP, 1993. An overview of nosocomial infections, including the role of the microbiology laboratory. Clin Microbiol Rev 6: 428442.

    • Search Google Scholar
    • Export Citation
  • 3.

    Schaberg DR, Culver DH, Gaynes RP, 1991. Major trends in the microbial etiology of nosocomial infection. Am J Med 91: 72S75S.

  • 4.

    Guzman Prieto AM, van Schaik W, Rogers MR, Coque TM, Baquero F, Corander J, Willems RJ, 2016. Global emergence and dissemination of enterococci as nosocomial pathogens: attack of the clones? Front Microbiol 7: 788.

    • Search Google Scholar
    • Export Citation
  • 5.

    Uttley AH, George RC, Naidoo J, Woodford N, Johnson AP, Collins CH, Morrison D, Gilfillan AJ, Fitch LE, Heptonstall J, 1989. High-level vancomycin-resistant enterococci causing hospital infections. Epidemiol Infect 103: 173181.

    • Search Google Scholar
    • Export Citation
  • 6.

    Ramsey AM, Zilberberg MD, 2009. Secular trends of hospitalization with vancomycin-resistant enterococcus infection in the United States, 2000–2006. Infect Control Hosp Epidemiol 30: 184186.

    • Search Google Scholar
    • Export Citation
  • 7.

    Edelsberg J, Weycker D, Barron R, Li X, Wu H, Oster G, Badre S, Langeberg WJ, Weber DJ, 2014. Prevalence of antibiotic resistance in US hospitals. Diagn Microbiol Infect Dis 78: 255262.

    • Search Google Scholar
    • Export Citation
  • 8.

    Government of Taiwan, 2018. Taiwan Nosocomial Infection Surveillance (TNIS) 2018 Report. Available at: https://www.cdc.gov.tw/Category/MPage/4G8HuDdUN1k4xaBJhbPzKQ. Accessed December 11, 2019.

    • Search Google Scholar
    • Export Citation
  • 9.

    DiazGranados CA, Zimmer SM, Klein M, Jernigan JA, 2005. Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis 41: 327333.

    • Search Google Scholar
    • Export Citation
  • 10.

    Lloyd-Smith P, Younger J, Lloyd-Smith E, Green H, Leung V, Romney MG, 2013. Economic analysis of vancomycin-resistant enterococci at a Canadian hospital: assessing attributable cost and length of stay. J Hosp Infect 85: 5459.

    • Search Google Scholar
    • Export Citation
  • 11.

    Goldmann DA, Weinstein RA, Wenzel RP, Tablan OC, Duma RJ, Gaynes RP, Schlosser J, Martone WJ, 1996. Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals. A challenge to hospital leadership. JAMA 275: 234240.

    • Search Google Scholar
    • Export Citation
  • 12.

    Meyer E, Gastmeier P, Deja M, Schwab F, 2013. Antibiotic consumption and resistance: data from Europe and Germany. Int J Med Microbiol 303: 388395.

    • Search Google Scholar
    • Export Citation
  • 13.

    Remschmidt C, Behnke M, Kola A, Peña Diaz LA, Rohde AM, Gastmeier P, Schwab F, 2017. The effect of antibiotic use on prevalence of nosocomial vancomycin-resistant enterococci- an ecologic study. Antimicrob Resist Infect Control 6: 95.

    • Search Google Scholar
    • Export Citation
  • 14.

    Saxena S, Priyadarshi M, Saxena A, Singh R, 2019. Antimicrobial consumption and bacterial resistance pattern in patients admitted in I.C.U at a tertiary care center. J Infect Public Health 12: 695699.

    • Search Google Scholar
    • Export Citation
  • 15.

    Zhang D, Hu S, Sun J, Zhang L, Dong H, Feng W, Lei J, Dong Y, 2019. Antibiotic consumption versus the prevalence of carbapenem-resistant gram-negative bacteria at a tertiary hospital in China from 2011 to 2017. J Infect Public Health 12: 195199.

    • Search Google Scholar
    • Export Citation
  • 16.

    Yoon YK, Park GC, An H, Chun BC, Sohn JW, Kim MJ, 2015. Trends of antibiotic consumption in Korea according to national reimbursement data (2008–2012): a population-based epidemiologic study. Medicine (Baltimore) 94: e2100.

    • Search Google Scholar
    • Export Citation
  • 17.

    Hu FP et al. 2016. Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005–2014. Clin Microbiol Infect 22 (Suppl 1): S9S14.

    • Search Google Scholar
    • Export Citation
  • 18.

    Murray BE, 2000. Vancomycin-resistant enterococcal infections. N Engl J Med 342: 710721.

  • 19.

    Fridkin SK, Edwards JR, Courval JM, Hill H, Tenover FC, Lawton R, Gaynes RP, McGowan JE Jr., 2001. Intensive care antimicrobial resistance epidemiology (ICARE) project and the national nosocomial infections surveillance (NNIS) system hospitals. The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. Adult intensive care units. Ann Intern Med 135: 175183.

    • Search Google Scholar
    • Export Citation
  • 20.

    Livornese LL Jr. et al. 1992. Hospital-acquired infection with vancomycin-resistant Enterococcus faecium transmitted by electronic thermometers. Ann Intern Med 117: 112116.

    • Search Google Scholar
    • Export Citation
  • 21.

    Harbarth S, Cosgrove S, Carmeli Y, 2002. Effects of antibiotics on nosocomial epidemiology of vancomycin-resistant enterococci. Antimicrob Agents Chemother 46: 16191628.

    • Search Google Scholar
    • Export Citation
  • 22.

    Weinstein JW, Roe M, Towns M, Sanders L, Thorpe JJ, Corey GR, Sexton DJ, 1996. Resistant enterococci: a prospective study of prevalence, incidence, and factors associated with colonization in a university hospital. Infect Control Hosp Epidemiol 17: 3641.

    • Search Google Scholar
    • Export Citation
  • 23.

    Gouliouris T, Warne B, Cartwright EJP, Bedford L, Weerasuriya CK, Raven KE, Brown NM, Török ME, Limmathurotsakul D, Peacock SJ, 2018. Duration of exposure to multiple antibiotics is associated with increased risk of VRE bacteraemia: a nested case-control study. J Antimicrob Chemother 73: 16921699.

    • Search Google Scholar
    • Export Citation
  • 24.

    Donskey CJ, Chowdhry TK, Hecker MT, Hoyen CK, Hanrahan JA, Hujer AM, Hutton-Thomas RA, Whalen CC, Bonomo RA, Rice LB, 2000. Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients. N Engl J Med 343: 19251932.

    • Search Google Scholar
    • Export Citation
  • 25.

    Brook I, Wexler HM, Goldstein EJ, 2013. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev 26: 526546.

  • 26.

    Warren DK, Nitin A, Hill C, Fraser VJ, Kollef MH, 2004. Occurrence of co-colonization or co-infection with vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus in a medical intensive care unit. Infect Control Hosp Epidemiol 25: 99104.

    • Search Google Scholar
    • Export Citation
  • 27.

    Furuno JP et al. 2005. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci co-colonization. Emerg Infect Dis 11: 15391544.

    • Search Google Scholar
    • Export Citation
  • 28.

    Reyes K, Malik R, Moore C, Donabedian S, Perri M, Johnson L, Zervos M, 2010. Evaluation of risk factors for coinfection or cocolonization with vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus. J Clin Microbiol 48: 628630.

    • Search Google Scholar
    • Export Citation
  • 29.

    de Niederhäusern S, Bondi M, Messi P, Iseppi R, Sabia C, Manicardi G, Anacarso I, 2011. Vancomycin-resistance transferability from VanA enterococci to Staphylococcus aureus. Curr Microbiol 62: 13631367.

    • Search Google Scholar
    • Export Citation
  • 30.

    Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK, 2008. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol 29: 9961011.

    • Search Google Scholar
    • Export Citation
  • 31.

    Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O’Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK, 2009. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the infectious diseases society of America. Clin Infect Dis 49: 145.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 889 85 0
Full Text Views 496 303 12
PDF Downloads 221 186 13
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Correlation between Nosocomial Carriage of Vancomycin-Resistant Enterococci and Antimicrobial Use in Taiwan

View More View Less
  • 1 Department of Pharmacy, MacKay Memorial Hospital, Taipei, Taiwan;
  • | 2 MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan;
  • | 3 Division of Infectious Disease, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan;
  • | 4 MacKay Medical College, New Taipei City, Taiwan;
  • | 5 Department of Internal Medicine, St. Joseph’s Hospital, Yunlin County, Taiwan

ABSTRACT

A rapid increase of nosocomial vancomycin-resistant enterococci (VRE) from 23.3% in 2009 to 44.5% in 2018 among all the medical centers in Taiwan was found. The aim of the study was to explore the relationship between antimicrobial usage and prevalence of VRE. We conducted the study between January 2010 and December 2019 in a tertiary teaching hospital in Taiwan. Antibiotic consumption was expressed as defined daily doses (DDDs) per 1,000 patient-days (PDs). The trend in antibiotic consumption and VRE prevalence were analyzed by regression analysis with yearly data. Pearson’s correlation analysis was used to determine the relationship between antibiotic consumption and the prevalence of VRE. The total consumption of antibiotics increased significantly from 450.6 DDDs/1,000 PDs in 2010 to 520.1 DDDs/1,000 PDs in 2019 (P = 0.013). Positive correlations were found between the prevalence of vancomycin-resistant Enterococcus faecium and the consumption of amoxicillin/clavulanate, vancomycin, and carbapenems, which included meropenem (P < 0.05). The increase in total VRE prevalence was significantly correlated with increased consumption of vancomycin and carbapenems, which included meropenem (P < 0.05). This 10-year study in a hospital demonstrated changes in antimicrobial use, which may have affected VRE prevalence in the hospital. We found a rise in nosocomial VRE prevalence was associated with the use of specific antimicrobial agents.

INTRODUCTION

Enterococci are Gram-positive, facultatively anaerobic cocci that are considered commensal organisms of the human gastrointestinal tract; however, they can also be pathogenic. Two major species, Enterococcus faecalis and Enterococcus faecium, are particularly pathogenic for humans.1 Enterococcal species can cause a variety of nosocomial infections, including urinary tract infections, bacteremia, endocarditis, and meningitis, particularly in more severely ill patients who have been hospitalized for long periods of time and/or have received multiple antibiotics.2,3

The incidence of enterococcal infections has been increasing steadily since the late 1970s.4 Colonization and clinical infection with vancomycin-resistant enterococci (VRE) were first described in Europe in the 1980s.5 One study found that in the United States, the rate of hospitalization with VRE increased from 4.60 hospitalizations/100,000 people in the year 2003 to 9.48 hospitalizations/100,000 in 2006.6 Nowadays, 87% of E. faecium strains from nosocomial infections are vancomycin resistant, whereas this is only 14% for E. faecalis.7 The prevalence of vancomycin-resistant E. faecium (VR E. faecium) has increased from 52.8% in 2009 to 67.1% in 2018 in the intensive care units of all the medical centers in Taiwan.8

An increase in mortality was noted in patients with bacteremia caused by VRE compared with vancomycin-susceptible enterococci (VSE).9 Furthermore, patients suffering from VRE-related infections required longer hospital days and had higher mortality and medical costs.10 Several studies have also indicated direct links between antibiotic consumption and the emergence of resistant strains in hospitals.1114 Therefore, delineating the relationship between antimicrobial usage profile in hospitals and the prevalence of VRE is imperative to solving the problem of antimicrobial resistance in hospitals. The aims of the study were several fold. First, we wished to determine the pattern of antimicrobial usage in our hospital over the past 10 years. Second, we attempted to clarify the VRE prevalence during this same period. Finally, we sought to elucidate the relationship between annual antibiotic consumption and the trends of nosocomial VRE prevalence.

METHODS

Study design and setting.

This study was conducted at the MacKay Memorial Hospital in northern Taiwan between January 2010 and December 2019. MacKay Memorial Hospital, a medical center with 1,130 beds and more than 2,800 inpatient cases per month, has adopted the Taiwan CDC guidelines for nosocomial infection control since 2003. MacKay Memorial Hospital has established an antimicrobial stewardship program, which is implemented by a collaboration of infectious disease physicians and pharmacists. When prescribing broad-spectrum antibiotics, clinicians have to justify this action in the medical record. At the same time, a computer management system places a limit on the number of days a certain antibiotic can be prescribed, and infectious disease specialists are notified to consult and evaluate antibiotic use.

Antibiotic consumption.

Antimicrobial agents were classified based on the anatomical therapeutic chemical classification system. Defined daily dose was developed by the WHO and was defined as the assumed average maintenance dose per day for a drug used for its main indication. Antibiotic consumption was expressed as the number of DDDs/1,000 patient-days (DDDs/1,000 PDs). Data on annual consumption of penicillins (ampicillin, oxacillin sodium, ampicillin/sulbactam, amoxicillin/clavulanate, and piperacillin/tazobactam), cephalosporins (cefazolin, cefoxitin, cefmetazole, cefotaxime, ceftazidime, ceftriaxone, cefepime, and cefpirome), quinolones (ciprofloxacin, levofloxacin, and moxifloxacin), glycopeptides (vancomycin and teicoplanin), carbapenems (meropenem and imipenem/cilastatin), and aminoglycosides (gentamicin and amikacin) from 2010 to 2019 were obtained from the pharmacy department of the hospital. Data for all intravenous antimicrobial use were included in this study, excluding oral agents.

Microbiology data.

MacKay Memorial Hospital’s clinical microbiology laboratory provided data on bacterial identification and antimicrobial susceptibility testing. All positive clinical specimens (VS E. faecalis, VS E. faecium, VR E. faecalis, and VR E. faecium) between 2010 and 2019 were included whether involved in colonization or infection. In patients with multiple VRE isolates during the same hospital stay, only the first isolate was included. Vancomycin-resistant enterococci isolates from outpatient clinics or the emergency department were excluded. Identification and susceptibility testing were performed by use of the VITEK-2 system (bioMérieux, La Balme les Grottes, France) in the microbiological laboratory of the hospital.

Statistical analysis.

Antibiotic consumption was obtained from the computerized database in the pharmacy department. The trends in annual antimicrobial consumption and prevalence of E. faecalis and E. faecium within the study period were analyzed by regression analysis. Pearson’s correlation coefficient was used to determine the relationship between antibiotic consumption and trends in resistance. All of the data were analyzed using Minitab 17 software (Minitab, LLC, State College, PA). Probability values of P < 0.05 were considered statistically significant.

RESULTS

Annual antibiotic consumption.

The total consumption of antibiotics increased significantly from 450.6 DDDs/1,000 PDs in 2010 to 520.1 DDDs/1,000 PDs in 2019 (β = +5.704, P = 0.013, Table 1), an increase of 15.4%. Quinolones were noted to have the largest variation in consumption, although their consumption also increased significantly (β = +3.559, P = 0.004). In Table 1, the consumption of many other classes of antibiotics showed significant increases, including penicillins, glycopeptides, and carbapenems (P < 0.005). Antibiotics with significantly decreased annual use in the past 10 years (2010–2019) were aminoglycosides (β = −2.840, P = 0.000).

Table 1

Trends in the annual consumption of antibiotic classes and representative antimicrobial agents during 2010–2019

Class/antimicrobial agentAntimicrobial consumption (defined daily doses/1,000 patient-days) by year
2010201120122013201420152016201720182019TrendSlope (β)P-value
Penicillins155.3149.7162.5163.7162.9170.2157.2167.7170.4167.2Increasing significantly1.6140.019
Ampicillin25.127.936.636.836.137.737.035.235.230.2Increasing0.5550.278
Oxacillin sodium39.931.734.128.524.930.219.419.119.515.3Decreasing significantly−2.4470.000
Ampicillin/sulbactam25.417.324.720.824.723.522.522.018.817.6Decreasing−0.4180.224
Amoxicillin/clavulanate35.237.637.940.338.843.745.857.259.659.3Increasing significantly2.9640.000
Piperacillin/tazobactam29.635.329.237.238.435.232.634.337.244.8Increasing significantly0.9600.046
Cephalosporins148.0156.0184.8185.6179.9182.3188.7173.1166.1168.8Increasing1.2740.426
Cefazolin63.958.862.858.351.652.148.646.441.639.2Decreasing significantly−2.7490.000
Cefoxitin19.422.128.229.424.316.211.517.021.022.1Decreasing−0.6090.339
Cefmetazole7.17.011.310.511.231.332.623.116.115.8Increasing1.7380.092
Cefotaxime6.76.35.95.35.95.59.39.310.89.7Increasing significantly0.5260.008
Ceftazidime11.411.714.814.514.813.913.011.212.713.0Decreasing−0.0120.942
Ceftriaxone19.625.232.540.039.638.644.642.643.346.0Increasing significantly2.5860.000
Cefepime10.224.819.916.720.211.515.715.214.818.1Decreasing−0.2080.686
Cefpirome9.80.19.511.112.313.213.48.45.85.1Increasing0.0040.994
Quinolones46.849.050.760.262.165.267.776.571.077.7Increasing significantly3.5590.004
Ciprofloxacin15.216.720.824.521.422.321.625.022.329.2Increasing significantly1.0780.004
Levofloxacin20.421.018.721.626.431.532.834.037.033.8Increasing significantly2.1060.000
Moxifloxacin11.311.211.214.214.311.413.217.611.814.8Increasing0.3760.110
Glycopeptides30.136.134.837.742.438.039.335.641.952.5Increasing significantly1.4980.011
Vancomycin6.16.37.47.16.96.36.75.79.39.7Increasing0.2580.071
Teicoplanin24.029.827.430.535.531.632.629.932.742.8Increasing significantly1.2390.013
Carbapenems28.934.433.834.330.933.535.932.136.938.0Increasing significantly0.5990.038
Meropenem17.022.924.325.520.725.731.827.433.135.9Increasing significantly1.7040.001
Imipenem/cilastatin11.911.59.48.810.27.84.14.73.82.1Decreasing significantly−1.1040.000
Aminoglycosides41.636.234.530.827.023.621.318.917.915.9Decreasing significantly−2.8400.000
Gentamicin34.830.129.627.223.620.619.517.215.813.8Decreasing significantly−2.2780.000
Amikacin6.86.15.03.63.43.01.81.62.12.1Decreasing significantly−0.5610.000
Total450.6461.3501.1512.2505.2512.7510.2503.8504.3520.1Increasing significantly5.7040.013

The prevalence of VRE.

A total of 8,792 enterococci isolates (E. faecalis and E. faecium) were collected. Of these isolates, 1,834 (20.9%) were VRE (VR E. faecalis and VR E. faecium) and 6,958 (79.1%) were VSE (VS E. faecalis and VS E. faecium). Among VRE, 47 (2.6%) were VR E. faecalis and 1,787 (97.4%) were VR E. faecium. The trend in the annual prevalence of VR E. faecalis remained stable (β = 0.042, P > 0.05) and that of VR E. faecium and total VRE increased from 2010 to 2019, but was not significantly different (β = 6.782 and 6.824, P > 0.05). The data are listed in Table 2 and Figure 1.

Table 2

Trends in the annual isolates of E. faecalis and E. faecium during 2010–2019

Isolates of Enterococcus2010201120122013201420152016201720182019Slope (β)P-value
E. faecalis
 VS E. faecalis5745234844234395575896477397160.0420.913
 VR E. faecalis5694015179
 VR E. faecalis (%)0.91.11.80.90.00.20.80.20.81.2
E. faecium
 VS E. faecium1001051191241181821121301611166.7820.107
 VR E. faecium167185184135122179175169212259
 VR E. faecium (%)62.663.860.752.150.849.661.056.556.869.1
 Total8468197966866799198819471,1191,100
 Vancomycin-resistant Enterococcus rate (%)20.3323.3224.2520.2617.9719.5920.4317.9519.5724.366.8240.130

E. faecalis = Enterococcus faecalis; E. faecium = Enterococcus faecium; VR E. faecalis = vancomycin-resistant Enterococcus faecalis; VR E. faecium = vancomycin-resistant Enterococcus faecium; VS E. faecalis = vancomycin-susceptible Enterococcus faecalis; VS E. faecium = vancomycin-susceptible Enterococcus faecium.

Figure 1.
Figure 1.

The trends and correlations between the resistance rates of enterococcus and antibiotic consumption during 2010–2019. VR E. faecalis = vancomycin-resistant enterococcus faecalis; VR E. faecium = vancomycin-resistant enterococcus faecium; VRE = vancomycin-resistant enterococcus.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 3; 10.4269/ajtmh.20-0842

Relationship between antibiotic consumption and the rates of resistance.

Table 3 provided the correlations between the resistance rates of enterococci and antimicrobial consumption during the past 10 years. Positive correlations were found between VR E. faecium and the consumption of amoxicillin/clavulanate, vancomycin, and carbapenems, which included meropenem, with coefficients of 0.640, 0.690, 0.697, and 0.702 (P < 0.05), respectively. The rise in VR E. faecalis was positively correlated with the increased consumption of vancomycin (coefficients: 0.643, P < 0.05). The increase in rates of total VRE was significantly correlated with increased consumption of vancomycin and carbapenems, which included meropenem, with coefficients of 0.701, 0.702, and 0.693 (P < 0.05), respectively.

Table 3

Correlations between the resistance rates of enterococci and antimicrobial consumption during 2010–2019

Correlation
Vancomycin-resistant Enterococcus faecalisVancomycin-resistant Enterococcus faeciumTotal vancomycin-resistant Enterococcus
Class/antimicrobial agent*CoefficientP-valueCoefficientP-valueCoefficientP-value
Penicillins−0.1640.6510.2330.5180.2060.568
Ampicillin−0.3270.356−0.3000.399−0.3090.385
Oxacillin sodium−0.0130.972−0.4120.237−0.3890.267
Ampicillin/sulbactam−0.4200.226−0.5990.068−0.5970.068
Amoxicillin/clavulanate0.1580.6630.6400.0460.6150.058
Piperacillin/tazobactam0.0380.9180.4010.2510.3810.278
Cephalosporins−0.2130.555−0.2850.425−0.2860.424
Cefazolin−0.0130.971−0.5470.101−0.5170.126
Cefoxitin0.2830.428−0.1760.627−0.1430.694
Cefmetazole−0.3180.3700.1220.7370.0900.806
Cefotaxime0.3110.3820.6260.0530.6140.059
Ceftazidime−0.0280.938−0.2910.415−0.2760.440
Ceftriaxone−0.1000.7830.2260.5310.2050.571
Cefepime0.2520.4820.0060.9870.0260.944
Cefpirome−0.5110.131−0.5350.111−0.5450.103
Quinolones−0.1390.7010.3970.2560.3630.303
Ciprofloxacin0.0530.8850.3830.2740.3650.299
Levofloxacin−0.1380.7040.4500.1910.4130.235
Moxifloxacin−0.3810.277−0.0920.800−0.1170.747
Glycopeptides0.2400.5040.5600.0930.5460.102
Vancomycin0.6430.0450.6900.0270.7010.024
Teicoplanin0.1170.7470.4850.1550.4670.174
Carbapenems0.5740.0830.6970.0250.7020.024
Meropenem0.4010.2510.7020.0240.6930.026
Imipenem/cilastatin−0.2140.552−0.6180.057−0.5990.067
Aminoglycosides0.1980.840−0.4460.196−0.4140.234
Gentamicin0.0430.907−0.4960.145−0.4630.178
Amikacin0.1870.605−0.2360.511−0.2070.565

The consumption of antibiotic was expressed as defined daily doses per 1,000 patients/days (DDDs/1,000 PDs).

The probability values of P < 0.05 were considered statistically significant.

DISCUSSION

In this study, we explored the trends in the annual consumption of antibiotic during the 10-year period and determined the relationship between VRE and antibiotic use at a Taiwanese teaching hospital. The first finding of this study was that the total consumption of antibiotics increased significantly from 450.6 DDDs/1,000 PDs to 520.1 DDDs/1,000 PDs during the past 10 years. Widespread use of four major classes of antimicrobial agents including quinolones, penicillins, glycopeptides, and carbapenems in this hospital was noted, as evidenced by a significant rise in their consumption. This rise in total consumption of antibiotics contrasted with a previous study during a 7-year period at a tertiary-care teaching hospital in China.15 However, there was a similar increase in the consumption of glycopeptides and carbapenems,15,16 which was likely due to the rise in the incidence of nosocomial infection caused by multidrug-resistant bacteria, especially extended-spectrum β-lactamase-producing Gram-negative bacteria, VRE, and methicillin-resistant staphylococcus aureus (MRSA) in hospitals worldwide.17 Decreased use of aminoglycosides was found in our study. It was presumed that concern over the nephrotoxicity associated with aminoglycosides was the main cause of this decline.

Second, the prevalence of VRE and VR E. faecium increased in our study from 2010 to 2019, but was not significantly different (β = 6.782 and 6.824, P > 0.05). The prevalence of VR E. faecium had reached 69.1% in 2019 (Table 2). This finding paralleled that found previously, as VR E. faecium prevalence reached 67.1% in all the medical centers in Taiwan in 2018.8 This serves as a reminder that it is imperative to restrain a continued rise in VRE in hospitals. Third, we also found the increase of VRE especially VR E. faecium in our study, which was significantly associated with the increasing consumption of some antimicrobial agents, particularly amoxicillin/clavulanate, vancomycin, and meropenem (P < 0.05). The most commonly observed risk factor for hospital acquisition of VRE is previous treatment with antimicrobials,18 particularly vancomycin and cephalosporins.19 In another report, VRE colonization or infection was associated with a longer duration of therapy with ceftazidime.20 Positive correlations between the prevalence of VRE and use of carbapenems (r = 0.801, P < 0.001) and glycopeptides (r = 0.76, P < 0.001) were also found,13 although data in their study were collected for only 2 years. In their study of intensive care units, Meyer et al.12 reported that VR E. faecium was not correlated with vancomycin use (correlation coefficient [CC] = 0.43, P = 0.190) but was negatively correlated with the use of cephalosporins (CC = −0.86, P = 0.001). Our findings partly concurred with previous observations. Although the relationship between consumption of cephalosporins and VRE was not found, we were the first to discover that VR E. faecium was positively correlated with the usage of amoxicillin/clavulanate.

Many antimicrobial agents may facilitate the spread of VRE through different mechanisms.21 Use of multiple agents with a broad spectrum of activity may predispose patients to colonization with resistant enterococci, probably via alteration of the normal bowel flora.22 A retrospective study also indicated that longer exposures to vancomycin, fluoroquinolones, or meropenem were associated with VRE bacteremia. That was because longer courses of fluoroquinolones and meropenem may promote gut colonization with hospital-adapted strains of E. faecium.23 Harbarth et al.21 found that in patients colonized with VRE, multiple antimicrobial agent exposure may inhibit other bacteria and enhance bacterial overgrowth with VRE in the gut, especially because the antimicrobial agents used were considered most active against Gram-negative or anaerobic bacteria.24 In our study, the use of broad-spectrum antibiotics such as vancomycin and meropenem most likely resulted in similar gut colonization with VRE, which explains why vancomycin and meropenem use were positively associated with increased VRE isolates. As for amoxicillin/clavulanate, it was speculated that it may be effective in treating anaerobic infections caused by beta-lactamase–producing bacteria,25 essentially selecting out VRE.

Patients simultaneously coinfected or co-colonized with both VRE and MRSA were also studied in several studies.2628 Transmission of vancomycin resistance from enterococci containing vanA gene to MRSA is found.29 Vancomycin-resistant VR E. faecalis rather than E. faecium were associated with co-colonization or coinfection with MRSA,28 although the vancomycin resistance rate in E. faecium is higher than that in E. faecalis.30 As we knew, glycopeptides such as vancomycin and teicoplanin were the first choice for treatment of MRSA. Therefore, we presumed that increasing glycopeptide consumption might be potentially causing rise in VRE. This concurred with the results found in our study.

Patients with VRE bacteremia need to be treated, and currently, the antibiotics of choice are daptomycin or linezolid. Treatment is not recommended for asymptomatic colonization of VRE in urine or stool. Combination antimicrobial therapy is used only in the treatment of enterococcal bacteremia with suspected endocarditis or critical illness, and reasonable therapeutic choices are dependent on susceptibility.31

There were several limitations in our report. This study was only conducted in one tertiary-care teaching hospital and was retrospective. Data on antimicrobial use were aggregated according to DDD measurement unit, and VRE prevalence was not directly correlated with individual exposure to antimicrobial agents. Finally, the development of bacterial resistance in hospitals was multifactorial. Although inappropriate use of antimicrobial agents certainly contributed to high selection pressure, failure to adhere to hospital infection control measures also played a role.

CONCLUSION

This 10-year study in a hospital revealed that significant changes in antimicrobial use might have affected antimicrobial resistance of enterococci at the hospital. Implementation of antimicrobial stewardship program and adherence to appropriate infection control measures to control the spread of VRE are fundamental in hospitals. Therefore, we are looking forward to providing these research data to clinicians and decision-makers in the hopes of improving antibiotic prescription strategies to restrain a continued rise in VRE.

ACKNOWLEDGMENTS

We thank Tung-Hsu Hou from the National Yunlin University of Science and Technology for our assistance in statistical analysis and Alice Ying-Jung Wu from the Division of Infectious Diseases, Department of Medicine, Mackay Memorial Hospital, for correcting grammatical errors.

REFERENCES

  • 1.

    Murray BE, 1990. The life and times of the Enterococcus. Clin Microbiol Rev 3: 4665.

  • 2.

    Emori TG, Gaynes RP, 1993. An overview of nosocomial infections, including the role of the microbiology laboratory. Clin Microbiol Rev 6: 428442.

    • Search Google Scholar
    • Export Citation
  • 3.

    Schaberg DR, Culver DH, Gaynes RP, 1991. Major trends in the microbial etiology of nosocomial infection. Am J Med 91: 72S75S.

  • 4.

    Guzman Prieto AM, van Schaik W, Rogers MR, Coque TM, Baquero F, Corander J, Willems RJ, 2016. Global emergence and dissemination of enterococci as nosocomial pathogens: attack of the clones? Front Microbiol 7: 788.

    • Search Google Scholar
    • Export Citation
  • 5.

    Uttley AH, George RC, Naidoo J, Woodford N, Johnson AP, Collins CH, Morrison D, Gilfillan AJ, Fitch LE, Heptonstall J, 1989. High-level vancomycin-resistant enterococci causing hospital infections. Epidemiol Infect 103: 173181.

    • Search Google Scholar
    • Export Citation
  • 6.

    Ramsey AM, Zilberberg MD, 2009. Secular trends of hospitalization with vancomycin-resistant enterococcus infection in the United States, 2000–2006. Infect Control Hosp Epidemiol 30: 184186.

    • Search Google Scholar
    • Export Citation
  • 7.

    Edelsberg J, Weycker D, Barron R, Li X, Wu H, Oster G, Badre S, Langeberg WJ, Weber DJ, 2014. Prevalence of antibiotic resistance in US hospitals. Diagn Microbiol Infect Dis 78: 255262.

    • Search Google Scholar
    • Export Citation
  • 8.

    Government of Taiwan, 2018. Taiwan Nosocomial Infection Surveillance (TNIS) 2018 Report. Available at: https://www.cdc.gov.tw/Category/MPage/4G8HuDdUN1k4xaBJhbPzKQ. Accessed December 11, 2019.

    • Search Google Scholar
    • Export Citation
  • 9.

    DiazGranados CA, Zimmer SM, Klein M, Jernigan JA, 2005. Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis 41: 327333.

    • Search Google Scholar
    • Export Citation
  • 10.

    Lloyd-Smith P, Younger J, Lloyd-Smith E, Green H, Leung V, Romney MG, 2013. Economic analysis of vancomycin-resistant enterococci at a Canadian hospital: assessing attributable cost and length of stay. J Hosp Infect 85: 5459.

    • Search Google Scholar
    • Export Citation
  • 11.

    Goldmann DA, Weinstein RA, Wenzel RP, Tablan OC, Duma RJ, Gaynes RP, Schlosser J, Martone WJ, 1996. Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals. A challenge to hospital leadership. JAMA 275: 234240.

    • Search Google Scholar
    • Export Citation
  • 12.

    Meyer E, Gastmeier P, Deja M, Schwab F, 2013. Antibiotic consumption and resistance: data from Europe and Germany. Int J Med Microbiol 303: 388395.

    • Search Google Scholar
    • Export Citation
  • 13.

    Remschmidt C, Behnke M, Kola A, Peña Diaz LA, Rohde AM, Gastmeier P, Schwab F, 2017. The effect of antibiotic use on prevalence of nosocomial vancomycin-resistant enterococci- an ecologic study. Antimicrob Resist Infect Control 6: 95.

    • Search Google Scholar
    • Export Citation
  • 14.

    Saxena S, Priyadarshi M, Saxena A, Singh R, 2019. Antimicrobial consumption and bacterial resistance pattern in patients admitted in I.C.U at a tertiary care center. J Infect Public Health 12: 695699.

    • Search Google Scholar
    • Export Citation
  • 15.

    Zhang D, Hu S, Sun J, Zhang L, Dong H, Feng W, Lei J, Dong Y, 2019. Antibiotic consumption versus the prevalence of carbapenem-resistant gram-negative bacteria at a tertiary hospital in China from 2011 to 2017. J Infect Public Health 12: 195199.

    • Search Google Scholar
    • Export Citation
  • 16.

    Yoon YK, Park GC, An H, Chun BC, Sohn JW, Kim MJ, 2015. Trends of antibiotic consumption in Korea according to national reimbursement data (2008–2012): a population-based epidemiologic study. Medicine (Baltimore) 94: e2100.

    • Search Google Scholar
    • Export Citation
  • 17.

    Hu FP et al. 2016. Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005–2014. Clin Microbiol Infect 22 (Suppl 1): S9S14.

    • Search Google Scholar
    • Export Citation
  • 18.

    Murray BE, 2000. Vancomycin-resistant enterococcal infections. N Engl J Med 342: 710721.

  • 19.

    Fridkin SK, Edwards JR, Courval JM, Hill H, Tenover FC, Lawton R, Gaynes RP, McGowan JE Jr., 2001. Intensive care antimicrobial resistance epidemiology (ICARE) project and the national nosocomial infections surveillance (NNIS) system hospitals. The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. Adult intensive care units. Ann Intern Med 135: 175183.

    • Search Google Scholar
    • Export Citation
  • 20.

    Livornese LL Jr. et al. 1992. Hospital-acquired infection with vancomycin-resistant Enterococcus faecium transmitted by electronic thermometers. Ann Intern Med 117: 112116.

    • Search Google Scholar
    • Export Citation
  • 21.

    Harbarth S, Cosgrove S, Carmeli Y, 2002. Effects of antibiotics on nosocomial epidemiology of vancomycin-resistant enterococci. Antimicrob Agents Chemother 46: 16191628.

    • Search Google Scholar
    • Export Citation
  • 22.

    Weinstein JW, Roe M, Towns M, Sanders L, Thorpe JJ, Corey GR, Sexton DJ, 1996. Resistant enterococci: a prospective study of prevalence, incidence, and factors associated with colonization in a university hospital. Infect Control Hosp Epidemiol 17: 3641.

    • Search Google Scholar
    • Export Citation
  • 23.

    Gouliouris T, Warne B, Cartwright EJP, Bedford L, Weerasuriya CK, Raven KE, Brown NM, Török ME, Limmathurotsakul D, Peacock SJ, 2018. Duration of exposure to multiple antibiotics is associated with increased risk of VRE bacteraemia: a nested case-control study. J Antimicrob Chemother 73: 16921699.

    • Search Google Scholar
    • Export Citation
  • 24.

    Donskey CJ, Chowdhry TK, Hecker MT, Hoyen CK, Hanrahan JA, Hujer AM, Hutton-Thomas RA, Whalen CC, Bonomo RA, Rice LB, 2000. Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients. N Engl J Med 343: 19251932.

    • Search Google Scholar
    • Export Citation
  • 25.

    Brook I, Wexler HM, Goldstein EJ, 2013. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev 26: 526546.

  • 26.

    Warren DK, Nitin A, Hill C, Fraser VJ, Kollef MH, 2004. Occurrence of co-colonization or co-infection with vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus in a medical intensive care unit. Infect Control Hosp Epidemiol 25: 99104.

    • Search Google Scholar
    • Export Citation
  • 27.

    Furuno JP et al. 2005. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci co-colonization. Emerg Infect Dis 11: 15391544.

    • Search Google Scholar
    • Export Citation
  • 28.

    Reyes K, Malik R, Moore C, Donabedian S, Perri M, Johnson L, Zervos M, 2010. Evaluation of risk factors for coinfection or cocolonization with vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus. J Clin Microbiol 48: 628630.

    • Search Google Scholar
    • Export Citation
  • 29.

    de Niederhäusern S, Bondi M, Messi P, Iseppi R, Sabia C, Manicardi G, Anacarso I, 2011. Vancomycin-resistance transferability from VanA enterococci to Staphylococcus aureus. Curr Microbiol 62: 13631367.

    • Search Google Scholar
    • Export Citation
  • 30.

    Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK, 2008. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol 29: 9961011.

    • Search Google Scholar
    • Export Citation
  • 31.

    Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O’Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK, 2009. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the infectious diseases society of America. Clin Infect Dis 49: 145.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to Chun-Ming Lee, Department of Internal Medicine, St. Joseph’s Hospital, No. 74, Sinsheng Rd., Huwei Township, Yunlin County 63201, Taiwan. E-mail: leecm4014@yahoo.com.tw

Authors’ addresses: Mei-Chun Lee, Chien-Hung Lu, and Wei-Ying Lee, Department of Pharmacy, MacKay Memorial Hospital, Taipei, Taiwan, E-mails: a5787@mmh.org.tw, horng22@mmh.org.tw, and lwy88@mmh.org.tw. Chun-Ming Lee, Department of Internal Medicine, St. Joseph’s Hospital, Yunlin County, Taiwan, E-mail: leecm4014@yahoo.com.tw.

Save