A Joint Statement of the American Academy of Ophthalmology and the Centers for Disease Control and Prevention

Download statement in PDF   (53K)

Introduction

Background

Ophthalmic Vancomycin Usage

Evidence-Based Recommendations Regarding Vancomycin

Summary of CDC Hospital Infection Control Practices Advisory Committee Recommendations for Preventing the Spread of Vancomycin Resistance

Further Reading

Developed by the AAO-CDC Task Force on Vancomycin Prophylaxis in Ophthalmic Surgery

Introduction

The use of vancomycin prophylaxis in routine, uncomplicated intraocular surgery remains controversial. Surveys indicate that in recent years a significant number of ophthalmologists have begun routinely adding vancomycin to intraocular irrigating solutions. Over the same period, vancomycin resistance has emerged as a serious and growing problem and has prompted the issuance of guidelines calling for restrictions in the routine use of vancomycin. Accordingly, the American Academy of Ophthalmology and Centers for Disease Control and Prevention (CDC) have examined the current evidence regarding the efficacy and potential consequences of routine prophylactic use of vancomycin for intraocular surgery. The purpose of this statement is to summarize these findings and to the extent possible, offer evidence-based recommendations regarding the appropriate use of vancomycin prophylaxis in ophthalmic surgery.

Background

Since 1989, a rapid increase in the incidence of infection and colonization with vancomycin-resistant enterococci (VRE) has been reported at U.S. hospitals. This observation, which has been linked to the trend of rising use of vancomycin, poses important problems because most strains of VRE are resistant to almost all standard anti-enterococcal drugs, including vancomycin, gentamicin and ampicillin.

The recent emergence of decreased vancomycin susceptibility in clinical isolates of Staphylococcus aureus or S. epidermidis is a major public health concern. The vanA gene, which is frequently plasmid-borne and confers high-level resistance to vancomycin, can be transferred in vitro from enterococci to a variety of Gram-positive microorganisms, including S. aureus. In the clinical setting, vancomycin-resistant strains of Staphylococcus haemolyticus have been recovered, and strains of S. aureus and S. epidermidis with only intermediate susceptibility to vancomycin have been isolated. To date, high-level vancomycin resistance in clinical strains of S. epidermidis or S. aureus has not yet been reported, but the potential for this development remains and carries with it serious clinical implications.

In light of these developments, in November 1995, CDC developed and disseminated recommendations calling for prudent use of vancomycin to aid in the prevention and control of the spread of vancomycin resistance. The CDC recommendations discourage the use of vancomycin for routine surgical prophylaxis except, for example, in patients with a documented life-threatening allergy to beta-lactam antibiotics.

Ophthalmic Vancomycin Usage

In contrast to what these CDC guidelines advocate, recent years have witnessed an uptrend in the practice of adding vancomycin to the irrigating solution used during routine cataract surgery. The few published reports of the efficacy of this practice appear to be largely anecdotal and are characterized by inadequate sample size and follow-up, presence of confounding variables (e.g., concurrent changes in surgical technique), and absence of a control group. To date, there have been no well performed retrospective series or adequately controlled prospective studies to examine any potential efficacy benefit (or lack thereof) of this practice. Pharmacokinetic and pharmacodynamic data regarding the delivery of vancomycin and other antibiotics via irrigating fluid are relatively unfavorable. The recommended concentration of vancomycin in solution is relatively low, the temperature of the irrigating solution is generally at room temperature and thus below that required for optimal antimicrobial effect (35-37?C), and clearance of the drug from the anterior chamber occurs quickly. In vitro modeling suggests that irrigating solution delivery of vancomycin is an ineffective means of eradicating an inoculum of susceptible bacteria from the anterior chamber.

While there is no good evidence supporting the microbiologic efficacy of the use of vancomycin in irrigating solutions, neither is there any evidence that vancomycin use in ophthalmology has contributed to the emergence of vancomycin resistance. However, as noted above, information in terms of prospective surveillance is lacking. Clearly, further research is needed to understand the implications of vancomycin use in intraocular surgery prophylaxis.

Evidence-Based Recommendations Regarding Vancomycin

There is a lack of prospective controlled trial evidence regarding either potential positive or negative consequences of the use of vancomycin in ophthalmic surgical prophylaxis, whether given topically or as an intraocular instillation. It also should be noted that there appears to be no prospective controlled trial evidence in the peer-reviewed literature supporting the efficacy of antibiotic prophylaxis of any type given more than 2 hours preoperatively or for more than one day postoperatively. Further, prolonged postoperative topical antibiotic administration may predispose to the development of antimicrobial resistance.

In light of these observations, it would appear that prudence and perhaps even restraint should be exercised in the selection of appropriate antimicrobial agents for routine prophylaxis in intraocular surgery. In the hospital setting, the AAO and the CDC recommend that the routine prophylactic use of vancomycin for ocular topical application or irrigation be discouraged. In outpatient settings, ophthalmic surgeons should carefully consider the potential benefits and adverse consequences of routine use of vancomycin for their patients and the public health. Alternatives to vancomycin use include immediate preoperative periocular application and topical instillation of antiseptics such as povidoneiodine; preoperative use of broad spectrum topical antimicrobials; subconjunctival antibiotic injection immediately preceded by subconjunctival anesthetic injection to minimize discomfort; and collagen shieldmediated antibiotic delivery. Selection of the particular antibiotic(s) to be used in these settings should be based on several factors, including activity spectrum (i.e., both Gram-positive and Gram-negative activity is generally desirable), local susceptibility patterns, evolving resistance trends, and cost.

To aid in the development of definitive recommendations for usage, the AAO and CDC recommend that the following be undertaken by the clinical and research communities:

• Studies of the rates of postoperative infections associated with common intraocular procedures performed using modern operative techniques;
• Development of experimental systems (e.g., in vitro and animal models) and clinical measures (e.g., quantitation of bacterial contamination in anterior chamber aspirates) that can be used as surrogate endpoints to predict and compare potential efficacy of various antimicrobial prophylactic regimens;
• Case-control analysis of the influence, if any, of antimicrobial regimens on the incidence of postoperative endophthalmitis; Ideally, a large-scale prospective study designed to document and/or compare the efficacy of antimicrobial use in ocular surgery;
• Monitoring and reporting of longitudinal and geographical trends in ocular pathogen antimicrobial resistance; and
• Studies of the comparative microbiological efficacy and consequences of various antimicrobial prophylactic regimens.

Summary of CDC Hospital Infection Control Practices Advisory Committee Recommendations for Preventing the Spread of Vancomycin Resistance

Prevention and control of the spread of vancomycin resistance require coordinated, concerted effort from both institutions and health care professionals and can be achieved only if each of the following elements is addressed: 1.) prudent vancomycin use by clinicians; 2.) education of medical staff regarding vancomycin resistance; 3.) early detection and prompt reporting of vancomycin resistance in enterococci and other Grampositive microorganisms by both hospital-based and outpatient-based microbiology laboratories; and 4.) immediate implementation of appropriate infection control measures to prevent person-to-person transmission of vancomycin-resistant nosocomial pathogens.

All hospitals, clinics, outpatient surgery centers, and other healthcare delivery settings, even those in which vancomycin-resistant nosocomial pathogens have never been detected, should develop a comprehensive antimicrobial use plan to provide education for their medical staff, oversee surgical prophylaxis, and develop guidelines for the proper use of vancomycin. Guidelines should conform to the CDC recommendations regarding situations in which vancomycin use is acceptable and those in which the use of vancomycin should be discouraged.

Further Reading

1. CDC: Recommendations for Preventing the Spread of Vancomycin Resistance. Morb Mort Wkly Rep 1995; 44(RR-12):1-13.
   
2. CDC: Vancomycin Resistance: From the Hospital Infection Control Practices Advisory Committee (HICPAC) of the CDC. Drug Benefit Trends 1996; 8:22-27.
   
3. Smith TL, Pearson ML, Wilcox KR, et al: Emergence of vancomycin resistance in Staphylococcus aureus. NEJM 1999; 340:493-501.
   
4. Uttley AH, George RC, Naidoo J, et al: High-level vancomycin-resistant enterococci causing hospital infections. Epidemiol Infect 1989; 103:173-181.
   
5. Leclercq R, Derlot E, Weber M, et al: Transferable vancomycin and teicoplanin resistance in Enterococcus faecium. Antimicrob Agents Chemother 1989; 33:10-15.
   
6. Noble WC, Virani Z, Cree R: Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC12201 to Staphylococcus aureus. FEMS Microbiol Lett 1992; 72:195-198.
   
7. Veach LA, Pfaller MA, Barrett M, et al: Vancomycin resistance in Staphylococcus haemolyticus causing colonization and bloodstream infection. J Clin Microbiol 1990; 28:2064-2068.
   
8. Degener JE, Heck MEOC, Vanleeuwen WJ, et al: Nosocomial infection by Staphylococcus haemolyticus and typing methods for epidemiological study. J Clin Microbiol 1994; 32:2260-2265.
   
9. Rubin LG, Tucci V, Cercenado E, et al: Vancomycinresistant Enterococcus faecium in hospitalized children. Infect Control Hosp Epidemiol 1992; 13:700-705.
   
10. Handwerger S, Raucher B, Altarac D, et al: Nosocomial outbreak due to Enterococcus faecium highly resistant to vancomycin, penicillin, and gentamicin. Clin Infect Dis 1993; 16:750-755.
    
11. Montecalvo MA, Horowitz H, Gedris C, et al: Outbreak of vancomycin-, ampicillin-, and aminoglycoside- resistant Enterococcus faecium bacteremia in an adult oncology unit. Antimicrob Agents Chemother 1994; 38:1363-1367.
    
12. Boyce JM, Opal SM, Chow JW, et al: Outbreak of multi-drug resistant Enterococcus faecium with transferable vanB class vancomycin resistance. J Clin Microbiol 1994; 32:1148-1153.
    
13. Livornese LL Jr, Dias S, Samel C, et al: Hospitalacquired infection with vancomycin-resistant Enterococcus faecium transmitted by electronic thermometers. Ann Intern Med 1992; 117:112-116.
    
14. Shay DK, Maloney SA, Montecalvo M, et al: Epidemiology and mortality risk of vancomycin-resistant enterococcal bloodstream infections. J Infect Dis 1995; 172:993-1000.
    
15. Morris JG Jr, Shay DK, Hebden JN, et al: Enterococci resistant to multiple antimicrobial agents, including vancomycin. Establishment of endemicity in a university medical center. Ann Int Med 1995; 123:150-159.

Developed by the AAO-CDC Task Force on Vancomycin Prophylaxis in Ophthalmic Surgery

David G. Hwang, MD, FACS, Chair - University of California, San Francisco

Eduardo C. Alfonso, MD - Bascom Palmer Eye Institute, Miami

Michael Barza, MD - Infectious Disease Specialist, Carney Hospital, Dorchester, Massachusetts

Jules L. Baum, MD - Boston Eye Associates

Jerold S. Gordon, MD - University of Pittsburgh Medical Center

Regis P. Kowalski, MS - Assistant Professor, Clinical Ophthalmology, University of Pittsburgh Medical Center

Terrence P. O'Brien, MD - Wilmer Eye Institute, Baltimore

Theresa L. Smith, MD - Investigation and Prevention Branch, Hospital Infections Program, Centers for Disease Control and Prevention

Approved by the AAO Quality of Care Secretariat and the Centers for Disease Control and Prevention, October 1999