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Prophylactic Antibiotics in Cataract Operations

      The rationale for prophylactic antibiotics in cataract operations must be continually reevaluated in light of cost-effectiveness and adverse reactions. The principles learned from wound infections associated with general surgical procedures should be applied to the limited knowledge about the rare event of endophthalmitis. Herein the literature on experimental and clinical wound infections in general surgical procedures is reviewed, with analysis of microbial flora, pathophysiology of wound infections, and pharmacokinetics of antibiotics. Experimental and clinical studies on prophylactic antibiotics to prevent endophthalmitis are reviewed, including information on topically applied antibiotics, chemical antisepsis, and administration of subconjunctival, intracameral, and systemic antibiotics. In addition, the benefits, limitations, and risks of the various types of prophylactic antibiotics are discussed. Because of the limited data on prophylactic antibiotics in cataract operations, providing dogmatic statements is difficult. General recommendations are offered based on the currently available literature, and a stratified approach is suggested based on wound construction and number of anterior segment maneuvers.
      Of the 23 million patients who undergo a surgical procedure in the United States each year, about 920,000 have postoperative wound infections.
      • Haley RW
      • Culver DH
      • Morgan WM
      • White JW
      • Emori TG
      • Hooton TM
      Identifying patients at high risk of surgical wound infection: a simple multivariate index of patient susceptibility and wound contamination.
      Rates of infection vary with the classification of the wound by level of bacterial contamination, by surgical procedure or site, by host risk factors, and by variation in surgical technique (Table 1).
      • Olson M
      • O'Connor M
      • Schwartz ML
      Surgical wound infections: a 5-year prospective study of 20,193 wounds at the Minneapolis VA Medical Center.
      Wound infections double the expected postoperative stay and increase hospital costs fivefold. Wound infections represent 14% of adverse events associated with hospitalization, and in 18% of patients, they are responsible for disabling injuries that persist for more than 6 months;
      • Leape LL
      • Brennan TA
      • Laird N
      • Lawthers AG
      • Localio AR
      • Barnes AB
      • et al.
      The nature of adverse events in hospitalized patients: results of the Harvard Medical Practice Study II.
      thus, wound infections are a major medical and economic concern.
      • Wenzel RP
      Preoperative antibiotic prophylaxis [editorial].
      Table 1Classification of Wound by Level of Bacterial Contamination and Rate of Postsurgical Infections
      Modified from Paradisi and Corti.
      • Paradisi F
      • Corti G
      Which prophylactic regimen for which surgical procedure?.
      By permission.
      Infection rate (%)
      ClassificationNo antibiotic prophylaxisAntibiotic prophylaxis
      • I.
        Clean wound
        • Elective
        • Closed primarily
        • No inflammation
        • No violation of mucosal surfaces
      5.10.8
      • II.
        Clean-contaminated wound
        • Nontraumatic
        • Mucosal surfaces entered
        • Mechanical damage
        • Clean procedure in immunocompromised patient
      10.11.3
      • III.
        Contaminated wound
        • Traumatic
        • Spillage of viscous contents
        • Major break in technique
      21.910.2
      • IV.
        Dirty wound
        • Traumatic
        • Perforated viscous
        • Presence of purulent inflammation
      Host risk factors for postoperative infection include obesity, diabetes, increased health complexity (that is, three or more diagnoses at time of dismissal), infection at another site, contaminated procedure, prolonged preoperative stay, prolonged operation (more than 2 hours), abdominal operation, and carriage rate of Staphylococcus aureus by the patient.
      • Wenzel RP
      Preoperative antibiotic prophylaxis [editorial].
      Surgeon-associated risk factors have also been identified. Higher risks are associated with carriage rate of S. aureus and Streptococcus pyogenes by the surgeon, and lower risks are associated with increasing technical skill of the surgeon, shorter procedures, and a higher number of procedures.
      • Wenzel RP
      Preoperative antibiotic prophylaxis [editorial].
      Properties of the bacteria that determine whether an infection becomes established include the virulence and number of microorganisms, the portal of entry, and the host defense mechanisms encountered.
      Antibiotic prophylaxis in surgery refers to the administration of antibiotic agents to the patient with the aim of preventing infection associated with the operative procedure. In a modern hospital setting, 30 to 50% of antibiotic orders are for prophylaxis,
      • Shapiro M
      Perioperative prophylactic use of antibiotics in surgery: principles and practice.
      although many antibiotics are inappropriately administered according to the principles subsequently outlined. Protocols evaluating prophylactic antibiotics have a pronounced economic influence on health care inasmuch as clinicians choose therapeutic regimens based on interpretation of studies, regulatory agencies analyze the data when approving drugs for specific indications, and pharmaceutical companies determine which drugs to develop and market.
      • Platt R
      Methodologie aspects of clinical studies of perioperative antibiotic prophylaxis.
      The many issues surrounding studies on prophylactic antibiotics make conducting, evaluating, and interpreting difficult. Some of these issues are selection of the appropriate procedure for evaluation, choice of a meaningful outcome, comparison of outcomes among comparable groups, unbiased assessment of outcome, assessment of the number of patients needed to provide statistical power, and appropriateness of generalizing results to other venues.
      • Platt R
      Methodologie aspects of clinical studies of perioperative antibiotic prophylaxis.
      Numerous well-organized and controlled trials during the past several decades have demonstrated that appropriately administered prophylactic antibiotics decrease the risk of postoperative infection by at least 50% in comparison with no treatment and effectively reduce overall costs (Table 1).
      • Shapiro M
      Perioperative prophylactic use of antibiotics in surgery: principles and practice.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      Antibiotic therapy in conjunction with an operation is effective, however, only if administered correctly.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      Postoperative wound infections: the influence of ultraviolet irradiation of the operating room and various other factors; report of an ad hoc committee of the Committee on Trauma, Division of Medical Sciences, National Academy of Sciences—National Research Council.
      The scientific rationale for the current methods of prescribing antibiotic prophylaxis in general surgical procedures was established by the experiments performed by Burke
      • Burke JF
      The effective period of preventive antibiotic action in experimental incisions and dermal lesions.
      and Miles and associates,
      • Miles AA
      • Miles EM
      • Burke J
      The value and duration of defence reactions of the skin to the primary lodgement of bacteria.
      who confirmed that antibiotics must be administered before tissue contamination in order to be maximally effective. The information and principles obtained from multiple experiments and the clinical experience of general surgeons are reviewed and extrapolated to the more limited data on antibiotic prophylaxis in cataract operations.

      MICROBIAL FLORA IN THE SURGICAL ENVIRONMENT

      Knowledge of the specific bacteria in the operating room environment and the bacteria constituting the endogenous flora at various body sites is the basis for anticipating the bacteria likely to be responsible for postoperative infection and for making an empiric choice of prophylactic antibiotic. The operating room flora are predominantly aerobic organisms because most anaerobes are unable to survive or multiply in the oxygen concentration of room air. The most common pathogens in this environment are S. aureus, S. epidermidis, and species of coliforms, pseudomonas, citrobacter, enterobacter, and clostridium. Other microorganisms present are usually not recognized as pathogens in general surgical procedures, although they may have a role in endophthalmitis.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      The bacteria responsible for post-surgical infections are often members of the endogenous microflora of the specific operative site.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      No single antibiotic for prophylaxis exists because of the varied composition of the polymicrobial microflora in different sites of the body.

      PATHOPHYSIOLOGY OF WOUND INFECTION

      Some bacteria are true pathogens with a capacity to invade tissue and cause destruction on the basis of elaboration of toxins or enzymes or by other invasive properties. Other bacteria have relatively low virulence but may possess intrinsic resistance to antibiotics or develop rapid resistance through various extrachromosomal mechanisms. These less virulent bacteria may become more dominant after antibiotic kill of the more pathogenic bacteria or because of poor host defense mechanisms or enhanced growth.
      The microbial events occurring at the wound site have been detailed.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      After a surgical incision, the wound becomes contaminated despite reduction of surface bacteria and aseptic surgical technique. Bacteria find a fertile ground in a traumatized operative site. Host defenses respond to both traumatized tissue and bacteria by using similar humoral and cellular mechanisms that are initiated primarily by phagocytes. The number of bacteria contaminating a wound is important in determining the establishment of infection.
      When 106 organisms per gram of tissue is exceeded, the risk of infection increases.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      When correctly administered preoperatively, a prophylactic antibiotic diffuses into the wound and is present to encounter potential invading bacteria even before the host defenses are completely activated.
      • Citak MS
      • Cue JI
      • Peyton JC
      • Malangoni MA
      The critical relationship of antibiotic dose and bacterial contamination in experimental infection.
      The time that the wound is open is the “vulnerable period.”
      • Burke JF
      The effective period of preventive antibiotic action in experimental incisions and dermal lesions.
      If administered too early, the antibiotics are eliminated before the incision is made and may not be present in the wound during the vulnerable period. Numerous experimental surgical studies have demonstrated that prophylactic antibiotics are maximally effective if given preoperatively and are significantly less effective or ineffective when administered postoperatively.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.

      PHARMACOKINETICS OF PROPHYLACTIC ANTIBIOTICS

      The distribution of antibiotics in the body after systemic administration follows simple kinetics with a two-compartment model, the central compartment (vascular) and the peripheral compartment (tissue).
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      • Condon RE
      • Wittmann DH
      The use of antibiotics in general surgery.
      The concentration of the drug in the vascular compartment reflects the amount of drug traveling to the tissues, the amount of drug rediffusing from the tissues, and the metabolism and excretion of the drug. After an intravenous bolus of an antibiotic, the serum concentration peaks transiently (Fig. 1). The tissue concentration lags behind this serum increase but then continues to increase even while the serum concentration is decreasing (alpha phase). The distribution to the tissue and the redistribution into the vascular system reach a balance, followed by a slow, often parallel decrease in the antibiotic concentration in both compartments (beta phase). The biologic half-life of an antimicrobial agent is the numeric expression of the serum concentration-time curve during this beta phase. After equilibrium, the concentration in the tissue is usually higher than the serum concentration because antibiotics are more rapidly eliminated from the serum by renal, hepatic, or other routes. The tissue concentration of prophylactic antibiotics in surgical procedures should be above the “breakpoint” (bacterial sensitivity) during the vulnerable period when the wound is open.
      Figure thumbnail gr1
      Fig. 1Relationships of pharmacokinetic properties and timing of administration of antibiotic prophylaxis (see text for complete details). IV = intravenously. (From Ulualp and Condon.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      By permission.)
      Two major types of bactericidal activity have been observed with antibiotics.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      Some antibiotics demonstrate a continual increase in the rate and extent of bactericidal activity in conjunction with increasing antibiotic concentration. This concentration-dependent bactericidal pattern is observed with aminoglycosides, quinolones, and metronida-zole.
      • Condon RE
      • Wittmann DH
      The use of antibiotics in general surgery.
      • Craig WA
      • Ebert SC
      Killing and regrowth of bacteria in vitro: a review.
      With other antibiotics, the subsequent bactericidal rate is not related to concentration but rather to exposure, although higher concentrations of the drug may result in an earlier onset of bactericidal activity. This exposure-dependent type is the major pattern observed with β-lactam antibiotics and vancomycin.
      • Craig WA
      • Ebert SC
      Killing and regrowth of bacteria in vitro: a review.

      SYSTEMATIC APPROACH TO PROPHYLACTIC ANTIBIOTICS

      Several principles have evolved from experimental and clinical studies of surgical procedures to guide the surgeon in effectively using prophylactic antibiotics to decrease the rate of and cost associated with surgical infection.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      • Condon RE
      • Wittmann DH
      The use of antibiotics in general surgery.
      Eight principles are subsequently presented, with some caveats and controversy outlined.
      Choose an Appropriate Indication.—The procedure must be associated with a probability of contamination or with a postoperative infection rate that can be decreased with antibiotic prophylaxis such that the benefit exceeds the risk of administering the antibiotic.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      In clean-contaminated surgical procedures (class II), prophylactic antibiotics have been demonstrated unequivocally to be efficacious. Antibiotics in contaminated (class III) and dirty (class IV) wounds are used more for therapy than for prophylaxis; thus, their value as a prophylaxis is difficult to establish.
      • Weitekamp MR
      • Caputo GM
      Antibiotic prophylaxis: update on common clinical uses.
      For clean cases (class I), the effectiveness of prophylactic antibiotics is difficult to establish, and this is the most controversial area.
      • Wittmann DH
      • Condon RE
      Prophylaxis of postoperative infections.
      Controlled clinical trials have been unable to establish with any degree of statistical power the efficacy of antibiotic prophylaxis in this setting.
      • Hopkins CC
      Antibiotic prophylaxis in clean surgery: peripheral vascular surgery, noncardiovascular thoracic surgery, herniorrhaphy, and mastectomy.
      For the most part, extrapolations have been made from clean-contaminated cases (class II) to guide an approach to neurosurgical, vascular, cardiac, and ophthalmic surgical procedures (Table 1).
      Antibiotic prophylaxis has not generally been recommended in clean general surgical procedures (that is, breast, thorax, and hernia) because of the low rate of infection (less than 3%). The inability to establish a benefit, plus the small risk of administering the antibiotic, has led to an opinion that prophylactic antibiotics do not outweigh the potential risk except in situations in which the risk of an infection developing is increased because of the complexity of the overall health status of the patient, impaired defense mechanisms, lengthy duration of the operation, or use of a prosthesis.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      • Culver DH
      • Horan TC
      • Gaynes RP
      • Marione WJ
      • Jarvis WR
      • Emori TG
      • et al.
      Surgical wound infection rates by wound class, operative procedure, and patient risk index: National Nosocomial Infections Surveillance System.
      Recent studies of antibiotic prophylaxis in patients undergoing clean operations resulted in a higher than anticipated rate of infection as well as a significant reduction in the rate of infection.
      • Hopkins CC
      Antibiotic prophylaxis in clean surgery: peripheral vascular surgery, noncardiovascular thoracic surgery, herniorrhaphy, and mastectomy.
      • Lewis RT
      • Weigand FM
      • Mamazza J
      • Lloyd-Smith W
      • Tataryn D
      Should antibiotic prophylaxis be used routinely in clean surgical procedures: a tentative yes.
      Infectious disease experts are hesitant to make specific recommendations in ocular surgical procedures, citing insufficient data.
      • Weitekamp MR
      • Caputo GM
      Antibiotic prophylaxis: update on common clinical uses.
      • Ludwig KA
      • Carlson MA
      • Condon RE
      Prophylactic antibiotics in surgery.
      • Paluzzi RG
      Antimicrobial prophylaxis for surgery.
      • Dellinger EP
      • Gross PA
      • Barrett TL
      • Krause PJ
      • Martone WJ
      • McGowan Jr, JE
      • et al.
      Quality standard for antimicrobial prophylaxis in surgical procedures (Infectious Diseases Society of America).
      Prophylactic antibiotics are recommended in cardiac, vascular, neurosurgical, orthopedic, and plastic surgical procedures (with implants) on the basis of infection rates greater than 2% without antibiotics, prolonged procedure, and devastating effects of infection.
      • Weitekamp MR
      • Caputo GM
      Antibiotic prophylaxis: update on common clinical uses.
      Determine the Potential Pathogen.—Hospitals and ambulatory surgical units are required to have a functioning infection surveillance program. Current antibiotic sensitivities of the bacteria recovered from wounds, from other surgical infections, and from hospital nosocomial infections must be analyzed and discussed with the medical staff.
      • Dellinger EP
      • Gross PA
      • Barrett TL
      • Krause PJ
      • Martone WJ
      • McGowan Jr, JE
      • et al.
      Quality standard for antimicrobial prophylaxis in surgical procedures (Infectious Diseases Society of America).
      Choose an Effective Antibiotic.—Studies have shown that an effective antibacterial agent for prophylaxis does not need to cover all actual or potential pathogens as long as the more virulent bacterial spectrum is covered.
      • Stone HH
      Basic principles in the use of prophylactic antibiotics.
      Choose the Least Toxic and Least Expensive Antibiotic.—The antibiotic selected should be relatively safe, easy to administer, and cost-effective and should have minimal toxic and allergic side effects. Many clinical studies compare only new agents with each other, and older agents are deleted, a suggestion that they are obsolete when in fact they may perform just as well or better.
      • Sturm AW
      Effects of a restrictive antibiotic policy on clinical efficacy of antibiotics and susceptibility patterns of organisms.
      Regulating the use of selected or even all antibiotics by hospital committees, infectious disease experts, or even federal agencies is supported. Some investigators believe strongly that first-generation cephalosporins should be used for prophylaxis and that second- and third-generation cephalosporins should be limited to therapeutic use,
      • Scher KS
      • Bernstein JM
      • Arenstein GL
      • Sorensen C
      Reducing the cost of surgical prophylaxis.
      especially because no convincing evidence shows that the second- or third-generation drugs have postoperative infection rates lower than those with first-generation cephalosporins when used in prophylaxis.
      • Scher KS
      • Bernstein JM
      • Arenstein GL
      • Sorensen C
      Reducing the cost of surgical prophylaxis.
      Administer a Completely Effective and Appropriately Timed Antibiotic.—Systemic administration of the antibiotic should be at the appropriate time to achieve effective tissue concentration during the vulnerable period when the surgical wound is open. With most intravenously administered antibiotics, the most effective time for administration is within 2 hours of the operation.
      • Ulualp K
      • Condon RE
      Antibiotic prophylaxis for scheduled operative procedures.
      • Classen DC
      • Evans RS
      • Pestotnik SL
      • Horn SD
      • Menlove RL
      • Burke JP
      The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection.
      Organisms inoculated into wounds are most susceptible to antibiotics when the drug is present in the tissue before the bacteria are introduced. The introduction of antibiotic therapy 3 hours or longer after experimental contamination has no observable effect on the lesion size,
      • Burke JF
      The effective period of preventive antibiotic action in experimental incisions and dermal lesions.
      and the introduction of antibiotics at the completion of the procedure has minimal or no effect. As the operative time increases, the efficacy of the preoperative antibiotic decreases,
      • Shapiro M
      Perioperative prophylactic use of antibiotics in surgery: principles and practice.
      and a second administration is needed for prolonged procedures. In the presence of trauma or with excess fluid expansion, higher doses of antibiotics are necessary because of the increased elimination rate.
      • Reed II, RL
      • Ericsson CD
      • Wu A
      • Miller-Crotchett P
      • Fischer RP
      The pharmacokinetics of prophylactic antibiotics in trauma.
      On the basis of these five principles, a review of available studies indicates that 64 to 96% of prophylactic antibiotics are administered incorrectly.
      • Curley P
      • Duignan J
      • Bouchier-Hayes D
      Prophylactic antibiotic use in four Dublin teaching hospitals.
      Administer for a Brief Period.—A single preoperative antibiotic is sufficient, with repetition based on the length of the procedure, the pharmacokinetics of the selected drug, and the antibiotic serum concentration determined by the fluid expansion of the patient. In most class II general surgical cases, the antibiotics should be discontinued 24 hours postoperatively. No evidence states that antibiotics administered after this time frame are necessary or efficacious.
      • Paradisi F
      • Corti G
      Which prophylactic regimen for which surgical procedure?.
      • Wenzel RP
      Preoperative antibiotic prophylaxis [editorial].
      If the Prophylactic Fails, Use Another Antibiotic for Therapy.—The bacteria isolated from postoperative infections when customary prophylaxis has been given are frequently resistant to the prophylactic agent administered. Therefore, therapeutic agents should generally be excluded from prophylactic use for a specific anatomic area.
      • Stone HH
      Basic principles in the use of prophylactic antibiotics.
      Avoid Antibiotics That Are Useful in the Treatment of Sepsis.—Preserving the potent antibiotics for their role in serious infection is desirable. Despite the market trend, the older antibiotics continue to function well for prophylaxis. Infectious disease experts, surgeons, and epidemiologists may express divergent views on this point depending on their philosophy of individual patient rights, the surgeon's responsibility, and the role of public-health officials who must be advocates for society.

      PROPHYLACTIC ANTIBIOTICS IN ELECTIVE CATARACT OPERATIONS

      Prophylactic antibiotics are used in many clinical situations in ophthalmology, including before elective anterior segment operations (for example, cataract, glaucoma, and penetrating keratoplasty), before vitrectomy, in association with repair of corneal and scleral lacerations, with use of scleral buckles, at the time of removal of foreign bodies from the interior or exterior surface of the eye, after a corneal abrasion, after suture removal, in corneal storage media, and in the presence of a cystic conjunctival bleb. Ophthalmologists also consider using prophylactic antibiotics in patients with a history of endocarditis who are undergoing an operation and in those who have a human bite or tick bite. Because of controversy and inadequate data, the effectiveness of ophthalmic prophylactic regimens in all these situations cannot be confirmed. In view of the large financial resources expended in this area and the potential adverse economic and medical effects without a demonstrable public benefit, recommendations must be examined periodically. Through the Joint Commission on Accreditation of Hospitals, hospitals and ambulatory surgical units are mandated to review their policies and offer recommendations periodically. Correspondingly, other agencies are demanding scrutiny because of cost-outcome analysis and risk of adverse reactions.
      • Dellinger EP
      • Gross PA
      • Barrett TL
      • Krause PJ
      • Martone WJ
      • McGowan Jr, JE
      • et al.
      Quality standard for antimicrobial prophylaxis in surgical procedures (Infectious Diseases Society of America).
      • Sack RB
      Prophylactic antibiotics? The individual versus the community [editorial].
      The appropriate use of prophylactic antibiotics in cataract operations is difficult to determine because of the rarity of endophthalmitis and the imprecise criteria used to define endophthalmitis (especially in the older studies). No one study has an acceptable study design, execution, confirmatory data, and statistical analysis to establish a definitive role for prophylactic antibiotics. Rather, an accumulation of data may lead to a consensus.
      • Starr MB
      Prophylactic antibiotics for ophthalmic surgery.
      • Olson M
      • O'Connor M
      • Schwartz ML
      Surgical wound infections: a 5-year prospective study of 20,193 wounds at the Minneapolis VA Medical Center.

      RISK OF ENDOPHTHALMITIS AFTER ANTERIOR SEGMENT SURGICAL PROCEDURES

      Postoperative eye infections are more likely to appear as an endophthalmitis rather than as a wound infection. Data are unavailable on the frequency of wound infections associated with eye operations, which would allow comparison with other general surgical procedures. When wound infection occurs, it can lead to endophthalmitis, but the frequency has not been determined. A large series of studies has determined, however, the risk of endophthalmitis after various anterior segment procedures. Before prophylactic antibiotics were used, the rate of endophthalmitis after a cataract operation was 0.21 to 1.0%.
      • Allen HF
      • Mangiaracine AB
      Bacterial endophthalmitis after cataract extraction.
      With the development of newer surgical techniques and the use of prophylactic antibiotic strategies, the incidence of culture-proven endophthalmitis was 0.072% for 23,625 cataract operations (primarily extracapsular cataract surgical procedures) from 1984 to 1989.
      • Kattan HM
      • Flynn Jr, HW
      • Pflugfelder SC
      • Robertson C
      • Forster RK
      Nosocomial endophthalmitis survey: current incidence of infection after intraocular surgery.
      This compares with a rate of 0.11% for penetrating keratoplasty, 0.051% for vitrectomy through the pars plana, and 0.061% for surgical treatment of glaucoma in the same time span from the same hospital.
      • Kattan HM
      • Flynn Jr, HW
      • Pflugfelder SC
      • Robertson C
      • Forster RK
      Nosocomial endophthalmitis survey: current incidence of infection after intraocular surgery.
      Medicare data analyzed in hospitalized patients showed a frequency of 0.17% after intracapsular cataract extraction and 0.12% after extracapsular cataract extraction or phacoemulsification.
      • Javitt JC
      • Vitale S
      • Canner JK
      • Street DA
      • Krakauer H
      • McBean AM
      • et al.
      National outcomes of cataract extraction: endophthalmitis following inpatient surgery.
      This converts to approximately 1,200 cases of endophthalmitis per year in the United States, based on 1.2 million cataract operations per year.
      The presence of the posterior capsule after cataract surgical procedures is associated with a greater resistance to endophthalmitis, as suggested by experimental studies in primates
      • Beyer TL
      • O'Donnell FE
      • Goncalves V
      • Singh R
      Role of the posterior capsule in the prevention of postoperative bacterial endophthalmitis: experimental primate studies and clinical implications.
      and confirmed by a 4.5 to 14.0 increased risk of endophthalmitis when an anterior vitrectomy was performed in a large series of Medicare patients.
      • Javitt JC
      • Vitale S
      • Canner JK
      • Street DA
      • Krakauer H
      • McBean AM
      • et al.
      National outcomes of cataract extraction: endophthalmitis following inpatient surgery.
      • Menikoff JA
      • Speaker MG
      • Marmor M
      • Raskin EM
      A case-control study of risk factors for postoperative endophthalmitis.
      The risk of endophthalmitis is also increased in patients with diabetes;
      • Kattan HM
      • Flynn Jr, HW
      • Pflugfelder SC
      • Robertson C
      • Forster RK
      Nosocomial endophthalmitis survey: current incidence of infection after intraocular surgery.
      in patients with deficits in local or systemic defense mechanisms; in those with preoperative external ocular infections; and in those with a vitreous wick, suture removal, previous operation, wound abnormalities, or the presence of a postoperative filtrating bleb. A sutureless cataract operation occasionally allows postoperative entry of bacteria into the eye.
      • Stonecipher KG
      • Parmley VC
      • Jensen H
      • Rowsey JJ
      Infectious endophthalmitis following sutureless cataract surgery.
      The risk associated with implants is increased perhaps because of the binding of bacteria with subsequent secretion of protective slimes. The risk of adherence to polypropylene implant haptics may be increased in comparison with polymethylmethacrylate implants.
      • Raskin EM
      • Speaker MG
      • McCormick SA
      • Wong D
      • Menikoff JA
      • Pelton-Henrion K
      Influence of haptic materials on the adherence of staphylococci to intraocular lenses.

      ORGANISMS AND SOURCE OF ENDOPHTHALMITIS

      Currently, the most common organisms in endophthalmitis after cataract operations in the United States are S. epidermidis and other coagulase-negative staphylococci; they predominate in 50 to 90% of cases.
      • Han DP
      • Wisniewski SR
      • Wilson LA
      • Barza M
      • Vine AK
      • Doft BH
      • et al.
      Spectrum and susceptibilities of microbiologie isolates in the Endophthalmitis Vitrectomy Study.
      Less commonly, S. aureus, streptococcus, enterococcus, and other gram-positive or gram-negative organisms are involved and may be associated with a prognosis that is less favorable. Polymicrobial growth occurs in about 10% of cases. This shift toward S. epidermidis during the past several decades is probably less related to a change in the periocular flora than to the effect of prophylactic antibiotics, the increased instrumentation and irrigation of the wound, and possibly the role of an intraocular lens implant as a binding site for a relatively nonvirulent organism.
      The primary sources of most organisms in infectious endophthalmitis are the patient's own eyelids and conjunctiva, which routinely harbor coagulase-negative staphylococci, S. aureus, Propionibacterium acnes, and streptococcus. Bacteriophage typing of staphylococci from cases of endophthalmitis and, more recently, use of molecular DNA fingerprinting techniques
      • Speaker MG
      • Milch FA
      • Shah MK
      • Eisner W
      • Kreiswirth BN
      Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis.
      have confirmed the role of the patient's own flora. Less common but potentially important causes of endophthalmitis are associated with contaminated instruments, lenses, or irrigating solutions; respiratory flora of the operating room personnel; and major breaks in sterile techniques.
      • Starr MB
      Prophylactic antibiotics for ophthalmic surgery.
      A small inoculum of organisms is frequently introduced into the eye during cataract surgical procedures; various studies report rates of 43% after extracapsular cataract extraction or phacoemulsification,
      • Dickey JB
      • Thompson KD
      • Jay WM
      Anterior chamber aspirate cultures after uncomplicated cataract surgery.
      ‘ 24 to 32% after extracapsular cataract operation,
      • Sherwood DR
      • Rich WJ
      • Jacob JS
      • Hart RJ
      • Fairchild YL
      Bacterial contamination of intraocular and extraocular fluids during extracapsular cataract extraction.
      • Chikara DK
      • Manners T
      • Chapman F
      • Stoddart MG
      • Hill D
      • Jenkins D
      Lack of effect of preoperative norfloxacin on bacterial contamination of anterior chamber aspirates after cataract surgery.
      and 1 to 24% after phacoemulsification.
      • Samad A
      • Solomon LD
      • Miller MA
      • Mendelson J
      Anterior chamber contamination after uncomplicated phacoemulsi-fication and intraocular lens implantation.
      • Assalian A
      • Thompson P
      • St-Antoine P
      • Lemire J
      • Duperre J
      • Demers JP
      • et al.
      Anterior chamber fluid contamination after uncomplicated phacoemulsification.
      • Manners TD
      • Chitkara DK
      • Marsh PJ
      • Stoddart MG
      Anterior chamber aspirate cultures in small incision cataract surgery.
      • Gimbel HV
      • Sun R
      • DeBroff BM
      • Yang HM
      Anterior chamber fluid cultures following phacoemulsification and posterior chamber lens implantation.
      The need for a control culture has been emphasized by several investigators.
      • Assalian A
      • Thompson P
      • St-Antoine P
      • Lemire J
      • Duperre J
      • Demers JP
      • et al.
      Anterior chamber fluid contamination after uncomplicated phacoemulsification.
      • Towler H
      Aqueous contamination during small incision cataract surgery: a lesson in study design [editorial].
      The organisms in the anterior chamber are identical to those on the surface during extracapsular cataract surgical procedures in 62% of cases.
      • Ariyasu RG
      • Nakamura T
      • Trousdale MD
      • Smith RE
      Intraoperative bacterial contamination of the aqueous humor.
      Although the organisms isolated from the anterior chamber correlate with the organisms on the preoperative conjunctiva and also with those frequently isolated in infectious endophthalmitis, the number of organisms is extremely small and within the clearing capacity of the anterior chamber, as determined by experimental ocular studies done decades ago
      • Maylath FR
      • Leopold IH
      Study of experimental intraocular infection. I. The recoverability of organisms inoculated into ocular tissues and fluids. II. The influence of antibiotics and cortisone, alone and combined, on intraocular growth of these organisms.
      and corresponding to experimental studies of general surgical techniques. This may relate to immunoglobin and complement or to the trabecular mesh-work filtration.
      • Samad A
      • Solomon LD
      • Miller MA
      • Mendelson J
      Anterior chamber contamination after uncomplicated phacoemulsi-fication and intraocular lens implantation.
      • Maylath FR
      • Leopold IH
      Study of experimental intraocular infection. I. The recoverability of organisms inoculated into ocular tissues and fluids. II. The influence of antibiotics and cortisone, alone and combined, on intraocular growth of these organisms.
      The role of the electrostatic forces of the implant in allowing bacteria to adhere to the lens surface has been controversial. Implants placed on the external ocular surface are able to attract bacteria in 26% of cases.
      • Vafidis GC
      • Marsh RJ
      • Stacey AR
      Bacterial contamination of intraocular lens surgery.
      Staphylococci especially have a unique ability to adhere to and proliferate on polymer surfaces, specifically intraocular lenses. Once attached, these organisms secrete an extracellular slime matrix that protects against antibiotics and host defense mechanisms. Heparin surface modification may decrease this bacterial adherence.
      The anterior chamber has a better capability for clearing bacterial organisms than does the vitreous. Experimental studies demonstrated that 1,000 colony-forming units of S. aureus in the anterior chamber are necessary to induce endophthalmitis in the normal rabbit eye or in eyes in which extracapsular cataract operations have been performed but that only 14 colony-forming units are needed if the posterior capsule is open.
      • Records RE
      • Iwen PC
      Experimental bacterial endophthalmitis following extracapsular lens extraction.
      In a primate model, 10,000 colony-forming units of S. aureus were necessary to induce endophthalmitis when the posterior capsule was intact.
      • Beyer TL
      • O'Donnell FE
      • Goncalves V
      • Singh R
      Role of the posterior capsule in the prevention of postoperative bacterial endophthalmitis: experimental primate studies and clinical implications.

      PROPHYLACTIC ANTIBIOTICS FOR PREVENTING ENDOPHTHALMITIS

      Endophthalmitis that occurs today is usually associated with prophylactic antibiotics. Therefore, a logical conclusion might be that prophylactic antibiotics are not indicated in cataract operations or even that they are ineffective. In view of our ability to pinpoint the source and identity of most organisms and because of the devastating complications of endophthalmitis (that is, blindness), a systematic approach can be developed based on the extensive accumulated studies.
      Two approaches have been used in the prophylaxis of endophthalmitis. One involves a preoperative reduction in the number of organisms on the surface of the eye by using topically applied antibiotics or antiseptics. The other involves administration of antibiotics to ocular tissues during the perisurgical (preoperative, intraoperative, and postoperative) period by the subconjunctival, systemic, or intracameral route.
      Bacterial colonization is present in 55 to 100% of the conjunctiva in normal patients preoperatively.
      • Singer TR
      • Isenberg SJ
      • Apt L
      Conjunctival anaerobic and aerobic bacterial flora in paediatric versus adult subjects.
      • Boes DA
      • Lindquist TD
      • Fritsche TR
      • Kalina RE
      Effects of povidone-iodine chemical preparation and saline irrigation on the perilimbal flora.
      In the absence of prophylactic antibiotics, up to 74% of patients may harbor pathogens capable of causing endophthalmitis on the eyelids or conjunctiva, and 61% carry S. epidermidis.
      • Walker CB
      • Claoue CM
      Incidence of conjunctival colonization by bacteria capable of causing postoperative endophthalmitis.
      The presence of staphylococci on the eyelid increases the risk of a postoperative infection.
      • Heaven CJ
      • Mann PJ
      • Boase DL
      Endophthalmitis following extracapsular cataract surgery: a review of 32 cases.
      The organisms on the eyelid or conjunctiva are frequently transitory, however, and the presence of staphylococcal species varies extremely from day to day even with topically applied antibiotics.
      • Allansmith MR
      • Anderson RP
      • Butterworth M
      The meaning of preoperative cultures in ophthalmology.
      • Bialasiewicz AA
      • Welt R
      Preoperative microbiologie diagnosis before elective intraocular interventions and prevention of infection with tobramycin eyedrops: results of a multicenter study.
      The consensus in the literature is that conjunctival and eyelid cultures are not cost-effective if used to confirm the absence of pathogenic bacteria.
      • Starr MB
      Prophylactic antibiotics for ophthalmic surgery.
      Preoperative Topically Applied Antibiotics.—The issue of antibiotics applied topically for days before an operation has been the subject of several studies, and information cannot be drawn from the general surgical literature. Topically applied antibiotics used for a brief preoperative regimen can decrease the number of eyelid and conjunctival bacteria in comparison with no treatment. The degree of bacterial reduction depends on the antibiotic selected, the frequency and duration of antibiotic use, the bacterial species present, and the antibiotic sensitivities.
      • Starr MB
      Prophylactic antibiotics for ophthalmic surgery.
      Established antibiotics often provide coverage comparable to that with newer drugs.
      • Everett SL
      • Kowalski RP
      • Karenchak LM
      • Landsittel D
      • Day R
      • Gordon YJ
      An in vitro comparison of the susceptibilities of bacterial isolates from patients with conjunctivitis and blepharitis to newer and established topical antibiotics.
      Although experimental studies have suggested an inoculum load that may eventuate in general surgical wound infection, no in vivo studies have been done on bacterial populations to suggest a safe level of ocular surface contamination. Conversely, decreasing the number of bacteria may be effective, as demonstrated in experimental studies of general surgical procedures.
      • Stone HH
      Basic principles in the use of prophylactic antibiotics.
      • Mackowiak PA
      The normal microbial flora.
      Allen and Mangiaracine
      • Allen HF
      • Mangiaracine AB
      Bacterial endophthalmitis after cataract extraction.
      were the first investigators to suggest a decreased incidence of endophthalmitis with the use of prophylactic topically applied antibiotics. Chloramphenicol and gentamicin were standard preoperative antibiotics. One study found that the number of organisms on the eyelid and conjunctiva was unaffected with use of either topically applied chloramphenicol or trimethoprim-polymyxin B sulfate during a 16-day perioperative period,
      • Bell TA
      • Slack M
      • Harvey SG
      • Gibson JR
      The effect of trimethoprim-polymyxin B sulphate ophthalmic ointment and chloramphenicol ophthalmic ointment on the bacterial flora of the eye when administered to the operated and un-operated eyes of patients undergoing cataract surgery.
      whereas another study found 100% eradication of all organisms except S. epidermidis with use of either trimethoprim-polymyxin B sulfate or tobramycin during the perioperative period.
      • Osher RH
      • Amdahl LD
      • Cheetham JK
      Antimicrobial efficacy and aqueous humor concentration of preoperative and postoperative topical trimethoprim/polymyxin B sulfate versus tobramycin.
      The fluoroquinolones are important new antimicrobial agents with broad-spectrum activity, low resistance, minimal toxicity, and desirable pharmacokinetics. Topical 0.3% ofloxacin applied preoperatively achieved mean aqueous humor levels of 0.338 ug/mL, which were significantly better than those achieved with 0.3% ciprofloxacin and 0.3% norfloxacin probably because of intrinsic solubility properties.
      • Donnenfeld ED
      • Schrier A
      • Perry HD
      • Aulicino T
      • Gombert ME
      • Snyder R
      Penetration of topically applied cipro-floxacin, norfloxacin, and ofloxacin into the aqueous humor.
      This level of ofloxacin approaches the minimal inhibitory concentration of 90% of S. epidermidis, S. aureus, and gram-negative organisms. Data on preoperative topically applied 0.3% ofloxacin confirmed a mean concentration of 0.53 Ug/mL.
      • Donnenfeld ED
      • Schrier A
      • Perry HD
      • Aulicino T
      • Gombert ME
      • Snyder R
      Penetration of topically applied cipro-floxacin, norfloxacin, and ofloxacin into the aqueous humor.
      Topically applied trimethoprim-polymyxin B sulfate and tobramycin have also been shown to have limited penetration into the anterior chamber.
      • Osher RH
      • Amdahl LD
      • Cheetham JK
      Antimicrobial efficacy and aqueous humor concentration of preoperative and postoperative topical trimethoprim/polymyxin B sulfate versus tobramycin.
      Antibiotic-soaked collagen shields, as a drug delivery device, placed either preoperatively or postoperatively provide a pulsed type of drug release.
      • Peyman GA
      • Daun M
      Prophylaxis of endophthalmitis.
      Studies on drug release have shown wide fluctuations among specific drugs, and drug toxicity is a concern, especially in a time of nonsutured wounds.
      • Starr MB
      • Lally JM
      Antimicrobial prophylaxis for ophthalmic surgery.
      Preoperative Chemical Preparation of the Eye.The use of chemical antiseptics in the operating room before surgical incision is effective in both general surgical and ophthalmologic procedures. Irrigation with saline alone may actually increase the bacterial yield.
      • Isenberg S
      • Apt L
      • Yoshimuri R
      Chemical preparation of the eye in ophthalmic surgery. I. Effect of conjunctival irrigation.
      The number of conjunctival organisms can be decreased substantially with a single instillation of 5% povidone-iodine solution to the conjunctival surface just before surgical incision.
      • Apt L
      • Isenberg SJ
      • Yoshimori R
      • Spierer A
      Outpatient topical use of povidone-iodine in preparing the eye for surgery.
      • Speaker MG
      • Menikoff JA
      Prophylaxis of endophthalmitis with topical povidone-iodine.
      This approach was comparable to a 3-day course of topically applied antibiotics.
      • Isenberg SJ
      • Apt L
      • Yoshimori R
      • Khwarg S
      Chemical preparation of the eye in ophthalmic surgery. IV. Comparison of povidone-iodine on the conjunctiva with a prophylactic antibiotic.
      • Apt L
      • Isenberg S
      • Yoshimori R
      • Paez JH
      Chemical preparation of the eye in ophthalmic surgery. III. Effect of povidone-iodine on the conjunctiva.
      Reduction was even greater with the combination of 3 days of topically applied Neosporin and 5% povidone-iodine at the time of operation,
      • Apt L
      • Isenberg SJ
      • Yoshimori R
      • Spierer A
      Outpatient topical use of povidone-iodine in preparing the eye for surgery.
      • Isenberg SJ
      • Apt L
      • Yoshimori R
      • Khwarg S
      Chemical preparation of the eye in ophthalmic surgery. IV. Comparison of povidone-iodine on the conjunctiva with a prophylactic antibiotic.
      which resulted in 83% sterilization of the conjunctiva. Both 5% and 0.02% povidone-iodine decrease the bacterial load similarly.
      • Grimes SR
      • Hollsten D
      • Nauschuetz WF
      • Whiddon RG
      • Trevino SB
      Effect of povidone-iodine irrigation on the preoperative chemical preparation of the eye.
      Povidone-iodine is an effective disinfectant with rapid activity against bacteria, fungi, viruses, protozoa, and spores.
      • Boes DA
      • Lindquist TD
      • Fritsche TR
      • Kalina RE
      Effects of povidone-iodine chemical preparation and saline irrigation on the perilimbal flora.
      • Zamora JL
      Chemical and microbiologie characteristics and toxicity of povidone-iodine solutions.
      Several studies have confirmed a lack of surface toxicity, although povidone-iodine should be washed from the surface of the eye with saline in view of potential endothelial toxicity.
      • Garcia-Ferrer FJ
      • Murray PR
      • Pepose JS
      Corneal endothelial toxicity of DexSol corneal storage medium supplemented with povidone-iodine [letter].
      Subconjunctival Injection of Antibiotics.—A single subconjunctival injection of an antibiotic can achieve bactericidal levels in the anterior chamber for a brief time and can eliminate all but an overwhelming infection. Subconjunctival administration of antibiotics bypasses the corneal epithelial barrier and allows high concentrations of drug to diffuse into the corneal stroma and the aqueous humor. Studies of the rabbit model have confirmed good penetration into the anterior segment with subconjunctival injection of antibiotics (for example, β-lactam drugs, vancomycin, and aminoglycosides), and the limited data on humans are similar.
      • Barza M
      Antibacterial agents in the treatment of ocular infections.
      Antibiotic concentration declines rapidly in a few hours. With all antibiotics, including vancomycin, gentamicin, ceftriaxone, ceftazidime, ceftizoxime, and cefotaxime, vitreous concentration after a single subconjunctival injection has been extremely low.
      • Barza M
      • Lynch E
      • Baum JL
      Pharmacokinetics of newer cephalosporins after subconjunctival and intravitreal injection in rabbits.
      • Barza M
      • Doft B
      • Lynch E
      Ocular penetration of ceftriaxone, ceftazidime, and vancomycin after subconjunctival injection in humans.
      • Rubinstein E
      • Triester G
      • Avni I
      • Schwartzkopf R
      The intravitreal penetration of cefotaxime in man following systemic and subconjunctival administrations.
      The third-generation cephalosporins do not seem to be more effective than the first-generation cephalosporins.
      • Barza M
      • Lynch E
      • Baum JL
      Pharmacokinetics of newer cephalosporins after subconjunctival and intravitreal injection in rabbits.
      On the basis of studies of general surgical procedures, subconjunctival antibiotics are best delivered preoperatively; thus, the antibiotic is present in the anterior chamber at the time the organisms are introduced and is maximally effective.
      Subconjunctival injection of antibiotics (gentamicin, ceftazidime, and ceftriaxone) has decreased the incidence of experimental endophthalmitis in animal models, but findings are less conclusive in humans despite several clinical studies.
      • McMillan JJ
      • Mead MD
      Prophylactic subconjunctival antibiotics after cataract extraction—evaluation of their desirability and efficacy.
      In two recent series of patients with endophthalmitis after anterior segment surgical treatment, 30 of 31
      • Speaker MG
      • Menikoff JA
      Prophylaxis of endophthalmitis with topical povidone-iodine.
      and 17 of 17
      • Kattan HM
      • Flynn Jr, HW
      • Pflugfelder SC
      • Robertson C
      • Forster RK
      Nosocomial endophthalmitis survey: current incidence of infection after intraocular surgery.
      received subconjunctival antibiotics as prophylaxis. Subconjunctival gentamicin as a prophylactic is associated with significant ocular morbidity. Gentamicin is likely to be associated with conjunctival hyperemia, edema, capillary closure, and anterior chamber reaction.
      • Jenkins CD
      • McDonnell PJ
      • Spalton DJ
      Randomised single blind trial to compare the toxicity of subconjunctival gentamicin and cefuroxime in cataract surgery.
      • Sanders R
      • MacEwen CJ
      • Haining WM
      A comparison of prophylactic, topical and subconjunctival treatment in cataract surgery.
      Retinal ischemia has occurred after inadvertent intraocular injection.
      • Campochiaro PA
      • Conway BP
      Aminoglycoside toxicity—a survey of retinal specialists: implications for ocular use.
      Investigators have suggested that prophylactic subconjunctival aminoglycosides should not be used in routine ocular surgical procedures because of questionable efficacy, rare severe adverse reactions, cost considerations, and limited spectrum against preoperative conjunctival flora.
      • McMillan JJ
      • Mead MD
      Prophylactic subconjunctival antibiotics after cataract extraction—evaluation of their desirability and efficacy.
      Alternatives to gentamicin include cefuroxime,
      • Jenkins CD
      • McDonnell PJ
      • Spalton DJ
      Randomised single blind trial to compare the toxicity of subconjunctival gentamicin and cefuroxime in cataract surgery.
      ceftazidime, cefazolin,
      • Campochiaro PA
      • Conway BP
      Aminoglycoside toxicity—a survey of retinal specialists: implications for ocular use.
      vancomycin, and ciprofloxacin.
      Systemic Administration of Antibiotics.—Although most systemic antibiotics penetrate into the aqueous humor to some extent, the penetration into the vitreous is minimal. Systemic therapy alone for bacterial endophthalmitis has not proved effective.
      • Doft BH
      The endophthalmitis vitrectomy study [editorial].
      Even therapeutic antibiotics such as gentamicin and cefotaxime cannot reliably achieve therapeutic levels in the human vitreous.
      • Rubinstein E
      • Triester G
      • Avni I
      • Schwartzkopf R
      The intravitreal penetration of cefotaxime in man following systemic and subconjunctival administrations.
      Nonetheless, prolonged systemic administration is sometimes able to achieve some antibiotic levels.
      The fluoroquinolones, especially ofloxacin, have several pharmacokinetic characteristics for better intraocular uptake in comparison with previous antibiotic agents. After topical (applied six times preoperatively), oral (a single 200-mg dose), or intravenous (200 mg) administration, ofloxacin achieved satisfactory concentrations in the anterior chamber that were higher than the minimal inhibitory concentration for many bacteria in endophthalmitis.
      • von Gunten S
      • Lew D
      • Paccolat F
      • Vaudaux P
      • Brazitikos PD
      • Leuenberger PM
      Aqueous humor penetration of ofloxacin given by various routes.
      An oral dose of 750 mg of ciprofloxacin achieved a concentration in the aqueous humor of 0.53 μg/mL, which is higher than the minimal inhibitory concentration of most strains.
      • Lesk MR
      • Ammann H
      • Marcil G
      • Vinet B
      • Lamer L
      • Sebag M
      The penetration of oral ciprofloxacin into the aqueous humor, vitreous, and subretinal fluid of humans.
      Oral administration of ciprofloxacin also achieved significantly higher human intravitreal levels than historical comparisons with cefazolin, penicillin, vancomycin, or gentamicin, although not adequate by either oral or intravenous route to treat bacterial endophthalmitis alone.
      • Lesk MR
      • Ammann H
      • Marcil G
      • Vinet B
      • Lamer L
      • Sebag M
      The penetration of oral ciprofloxacin into the aqueous humor, vitreous, and subretinal fluid of humans.
      • Kowalski RP
      • Karenchak LM
      • Eller AW
      The role of ciprofloxacin in endophthalmitis therapy.
      • el Baba FZ
      • Trousdale MD
      • Gauderman WJ
      • Wagner DG
      • Liggett PE
      Intravitreal penetration of oral ciprofloxacin in humans.
      Several other systemic quinolones have achieved high levels in the aqueous humor and vitreous, especially in comparison with conventional antibiotics; however, activity against streptococcus is still limited.
      • Bron AM
      • Pechinot AP
      • Garcher CP
      • Guyonnet GA
      • Kazmierczak AM
      • Schott DA
      • et al.
      The ocular penetration of oral sparfloxacin in humans.
      Intracameral Administration of Antibiotics.—Intraocular use of antibiotics, either as a specific injection into the anterior chamber or as a concentration in irrigating fluids, has a few proponents.
      • Peyman GA
      Aminoglycoside toxicity [letter].
      • Dickey JB
      • Thompson KD
      • Jay WM
      Intraocular gentamicin sulfate and postcataract anterior chamber aspirate cultures.
      • Borhani H
      • Peyman GA
      • Wafapoor H
      Use of vancomycin in vitrectomy infusion solution and evaluation of retinal toxicity.
      • Gimbel HV
      • Sun R
      • DeBrof BM
      Prophylactic intracameral antibiotics during cataract surgery: the incidence of endophthalmitis and corneal endothelial cell loss.
      This route is associated with a narrow therapeutic efficacy (that is, the toxic dose is similar to the therapeutic dose). Aminoglycosides are neurotoxic and retinotoxic, and the endothelium is especially vulnerable. These drugs should be avoided in the presence of a broken or absent posterior capsule. Studies on the safety or efficacy of intracameral administration of antibiotics are inadequate and show major risks of dilution error. Exposure for such a brief period as with intraocular irrigating solutions may be ineffective.
      • Gritz DC
      • Cevallos AV
      • Smolin G
      • Whitcher Jr, JP
      Antibiotic supplementation of intraocular irrigating solutions: an in vitro model of antibacterial action.

      RECOMMENDATIONS FOR PROPHYLAXIS IN ELECTIVE CATARACT OPERATIONS

      Postoperative endophthalmitis has decreased in association with use of prophylactic antibiotics; however, the specific antibiotic, dose, and timing of administration remain debatable. Current patterns of use prevent construction of a well-designed study. Drawing from studies of general surgical procedures is inappropriate because of the lack of ocular penetration after systemic administration of antibiotics. Specific recommendations are difficult to establish because of insufficient data.
      Antibiotic prophylaxis in ophthalmologic procedures has drawbacks. Cost is a major concern.
      • Alfonso EC
      • Flynn Jr, HW
      Controversies in endophthalmitis prevention: the risk for emerging resistance to vancomycin [editorial].
      Toxicity and allergy are rare but severe problems. Altering the normal ocular flora is an associated risk. The development of resistant organisms is a central issue in the controversy surrounding prophylactic use of antibiotics in general surgical and ophthalmologic procedures.
      • Sack RB
      Prophylactic antibiotics? The individual versus the community [editorial].
      • Alfonso EC
      • Flynn Jr, HW
      Controversies in endophthalmitis prevention: the risk for emerging resistance to vancomycin [editorial].
      • Tomasz A
      Multiple-antibiotic-resistant pathogenic bacteria: a report on the Rockefeller University workshop.
      • Murray BE
      Can antibiotic resistance be controlled? [editorial].
      No data confirm that short-term topically administered prophylactic antibiotics affect the resistance pattern. Nonetheless, a multitude of ophthalmology patients receive prophylactic antibiotics each year. The fluoroquinolones have been overused in ophthalmologic procedures, and the increase in resistance patterns in a brief period is striking. One-third of cases of endophthalmitis may be resistant to prophylactic antibiotics.
      • Kattan HM
      • Flynn Jr, HW
      • Pflugfelder SC
      • Robertson C
      • Forster RK
      Nosocomial endophthalmitis survey: current incidence of infection after intraocular surgery.
      The risk is high that organisms isolated from the anterior chamber and from endophthalmitis will be resistant to gentamicin, tobramycin, and cefazolin.
      • Ariyasu RG
      • Nakamura T
      • Trousdale MD
      • Smith RE
      Intraoperative bacterial contamination of the aqueous humor.
      Reports of increased resistance among the bacteria common in endophthalmitis suggest a potential for failure of both prophylaxis and treatment. Recent recommendations from the Centers for Disease Control and Prevention specifically discourage the use of vancomycin for routine surgical prophylaxis because of the increase in vancomycin-resistant organisms.
      • Centers for Disease Control and Prevention
      Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC).
      Knowledge about the source of infectious bacteria in endophthalmitis constitutes the rationale for recommending prophylaxis of endophthalmitis and other infection control efforts. Stratifying prophylaxis based on the degree of risk has been applied in other surgical disciplines
      • Pollock AV
      Surgical prophylaxis—the emerging picture.
      and has been suggested in ophthalmology.
      • Menikoff JA
      • Speaker MG
      • Marmor M
      • Raskin EM
      A case-control study of risk factors for postoperative endophthalmitis.
      External ocular infections should be treated preoperatively. Topically applied antibiotics decrease the conjunctival bacterial count and are a reasonable choice for 1 to 3 days before surgical treatment. Trimethoprim-polymyxin B sulfate is a combination antibiotic that has broad-spectrum activity against gram-positive and gram-negative infections and is effective against ocular surface infections; it may also have some penetration into the anterior chamber.
      • Osher RH
      • Amdahl LD
      • Cheetham JK
      Antimicrobial efficacy and aqueous humor concentration of preoperative and postoperative topical trimethoprim/polymyxin B sulfate versus tobramycin.
      Neosporin or Polysporin could also function in this role. Gentamicin, a prior standard, is effective against some staphylococci and many gram-negative organisms, but it is ineffective against some strains of S. aureus, S. epidermidis, Streptococcus, some gram-negative organisms, and most anaerobes.
      Povidone-iodine solution is the best antiseptic and is recommended for both the skin (10%) and the conjunctiva (5%). It must be washed from the conjunctival surface to avoid endothelial toxicity. A combination of topically applied antibiotics and povidone-iodine is beneficial.
      • Apt L
      • Isenberg SJ
      • Yoshimori R
      • Spierer A
      Outpatient topical use of povidone-iodine in preparing the eye for surgery.
      Isolation of the eyelids by appropriate draping is a prophylactic technique.
      A swift, skillful, and uncomplicated operation with a small incision introduces the least number of organisms into the anterior chamber. Larger incisions are associated with an increased number of organisms in the conjunctival culture postoperatively.
      • Stonecipher KG
      • Parmley VC
      • Jensen H
      • Rowsey JJ
      Infectious endophthalmitis following sutureless cataract surgery.
      A complicated operation associated with large wounds, frequent introduction of instruments, and especially a communication with the vitreous increases the risk of endophthalmitis. For an uncomplicated operation, the addition of subconjunctival antibiotics may be superfluous; for a complicated operation, they should be considered. Ideally, subconjunctival antibiotics should be administered preoperatively; thus, the antibiotic is present in the wound and anterior chamber at the time the organisms are introduced. Although gentamicin has been a standard, other antibiotic combinations may be appropriate because of the significant external and intraocular toxicity and increasing resistance associated with gentamicin. The combination of vancomycin and ceftazidime has broad-spectrum activity, but this approach is expensive and violates the principle of avoiding therapeutic antibiotics for prophylactic use.
      • Centers for Disease Control and Prevention
      Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC).
      Based on the frequency of S. epidermidis, the general surgical literature suggests the use of a first-generation cepha-losporin (for example, cefazolin).
      • Wittmann DH
      • Condon RE
      Prophylaxis of postoperative infections.
      The effectiveness of intracameral administration of antibiotics has not been thoroughly tested, and because of the narrow therapeutic index, this route of administration cannot be currently recommended. Short-term systemic antibiotic use deserves reconsideration in view of the new information on fluoro-quinolones, although definitive studies are unavailable.
      Prolonging the use of antibiotics after a cataract operation has little rationale in either the ophthalmic or the surgical setting.
      • Kaiser AB
      Antimicrobial prophylaxis in surgery.
      A sutureless cataract operation may allow introduction of bacteria into the anterior chamber, although one study did not support this concept.
      • Turkalj JW
      • Carlson AN
      • Manos JP
      • Apple DJ
      Is the sutureless cataract incision a valve for bacterial inoculation?.
      For postoperative use in ophthalmic surgical procedures, 5% povidone-iodine ophthalmic solution is more effective in reducing the conjunctival bacterial flora during the first postoperative day than is a topically administered antibiotic.
      • Apt L
      • Isenberg SJ
      • Yoshimori R
      • Chang A
      • Lam GC
      • Wachler B
      • et al.
      The effect of povidone-iodine solution applied at the conclusion of ophthalmic surgery.

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