Editor's note: Dr. Rubio and her colleagues have published some interesting new studies regarding the composition of the conjunctival bacterial flora. Because of the studies' relevance to postsurgical endophthalmitis, Cataract & Refractive Surgery Today invited Dr. Rubio and her colleagues to summarize some of their recent published work.– David F. Chang, MD, Chief Medical Editor
Most cases of infectious postsurgical endophthalmitis are caused by patients' own conjunctival bacterial flora.1 Presently, little new or current information about the composition of the conjunctival flora has appeared. This is because the practice of culturing the conjunctiva preoperatively has waned during the last 20 years. However, during this timeframe, the incidence of postsurgical endophthalmitis has actually increased.2-7 My colleagues and I speculate that this rise in endophthalmitis incidence may be attributable to three trends in cataract surgery: (1) the current worldwide reliance upon povidone-iodine solution (sometimes alone, without preoperative antibiotics) as preoperative prophylaxis, when its effectiveness has only been demonstrated for staphylococci among aerobic conjunctival bacteria8,9; (2) the greater use of phacoemulsification, which involves a different means for intraocular contamination10; and (3) possible changes in the composition of the conjunctival flora itself.
This article addresses the increased risk of infectious postsurgical endophthalmitis that might be caused by changes in the preoperative conjunctival bacterial spectrum. We studied the conjunctival flora in our own patient population11 and possible factors that could have altered the bacterial spectrum. These might include (1) misleading or inaccurate analysis due to changes in the culture media used, (2) climatic influences on the conjunctival bacterial flora (eg, affected by the geographic area where patients live),12 and (3) changes in patient demographics (eg, since 1980, the trend has been for cataract surgery to be performed in an increasingly elderly population).13-20METHODS
In order to test our hypotheses, my colleagues and I conducted three studies on the same sample of 4,432 consecutive patients. Each patient's inferior conjunctival cul de sac was cultured during the period of January 1994 to December 1996. We did not exclude any patients from the studies because of other co-existing disease. For any bacterial culture, our database recorded the patient's age and sex, the date of the culture, the date of the surgery, and the date of any hospitalization for postsurgical endophthalmitis. To determine hospitalizations, we performed a retrospective check of computerized codes for the relevant diagnoses and surgical procedures in our hospital.21 We divided the positive, preoperative, conjunctivally culture isolates into nine categories. Two of these were considered nonpathogenic (Coagulase (-) staphylococci and Corynebacteria). The remaining seven categories of bacterial pathogens were categorized as follows: Staphylococcus aureus; Streptococcus pneumoniae; other Streptococcus species; Haemophilus species; gram (-) diplococci, other gram-negative species; and other miscellaneous bacteria. Our microbiological and statistical methods were described in the original scientific reports.11,12
In the first study,11 we looked at the prevalence of positive, preoperative, conjunctival bacterial cultures in our population and compared this prevalence to that reported in other similar surveys published during the last 50 years. In the second study,12 we analyzed the influence of climate on the frequency of positive bacterial cultures. We thought that climate might be relevant because several centers have reported that their incidence of postoperative endophthalmitis varied according to the time of year, with certain months showing a statistically higher frequency.5,22 Our third study looked at how a patient's age affected the frequency of positive, preoperative, conjunctival bacterial cultures. Previous work had demonstrated that approximately 4% of our patients had chronic bacterial colonization of their conjunctivas and that older age increased the likelihood of this situation.23RESULTS
Our frequency of positive, preoperative conjunctival bacterial cultures was statistically significantly different from that of other large samples of patients awaiting cataract surgery before 1980 (Table 1).11,24-27 The quality and sensitivity of the culture media used in the 1980s were inferior to our modern standard (eg, older culture media were unable isolate Haemophilus species). With respect to trends in the incidence of positive cultures during the last 20 years (Table 2),7,28-35 we are seeing a variation in the frequency of cultures positive for bacterial pathogens. However, some of the differences may be attributable to sampling errors due to differences in the sensitivity of the culture media and in the size of the samples.Second Study
This study looked at the frequency of positive preoperative, conjunctival bacterial cultures according to the month, (August was excluded because of insufficient sample size).12 We found that, for typical skin colonizers (Coagulase (+) or (-) staphylococci and Corynebacterium), positive cultures were more common in May and June (Figure 1). For bacteria that often colonize in the respiratory system (Streptococcus, Haemophilus, and gram-negative diplococci), positive cultures were highest in April. The exception was S. pneumoniae, which had two different seasonal peaks (March and November/December). Other Streptococcus species had positive culture peaks in April and September. We attribute these differences to climatic changes in humidity and temperature that affect bacterial growth rates. For example, in Madrid, the average monthly temperature in spring and early autumn varies between 12º and 22ºC (53.6º and 71.6ºF). Our average, monthly, relative humidity varies between 45% and 60% in the spring and between 53% and 72% in the fall. In our sample, the frequency of cultures positive for gram-negative rods (excluding Haemophilus) was not influenced by climatic factors. Most importantly, the incidence of postsurgical endophthalmitis in the warmest 2 months, May and June, was 3.37 times higher than that in the cooler months. The mean daily temperature and mean daily relative humidity for both May and June are intermediate. However, the temperature increases from 6ºC (42.8ºF) in January (the coolest month in Madrid) to 27ºC (80.6ºF) in July (the hottest month in Madrid). Furthermore, the relative humidity in Madrid is at its maximum from December through January and decreases to its minimum in July.
My colleagues and I observed that the higher frequency of conjunctival bacteria in our patients during the month of May was mainly due to the typical skin bacteria, which are the predominant bacteria on the conjunctiva. Nevertheless, the frequency of bacteria typical of the respiratory system increases twice a year, in the spring and autumn. When there is a low frequency of the typical respiratory bacteria, however, the vision of patients affected by endophthalmitis due to the aforementioned bacteria was worse among those in the Endophthalmitis Vitrectomy Study.36 Furthermore, the mean age of patients with endophthalmitis caused by these bacteria was lower than that of patients with endophthalmitis caused by staphylococci.37-39Third Study
In our third study (currently unpublished) most bacterial categories' frequency of positive, preoperative, conjunctival cultures was significantly higher in patients older than 74 years of age (Figure 2). The exception was coagulase (-) staphylococci. Age did not seem to affect the frequency of either S. pneumoniae or Haemophilus positive cultures. The climatic variable for these species may have been the overriding factor.12,23 S. aureus, Streptococcus species (excluding S. pneumoniae), and gram-negative rods (except Haemophilus) were significantly more common in the older group of patients (>74 years) (Figure 2). Many of these patients were chronically colonized with these pathogens. In our study, positive bacterial cultures were more common in men versus women, regardless of age (Figure 3).CONCLUSION
We found that the spectrum and frequency of positive preoperative conjunctival bacterial cultures can be affected by the following factors:
•The size of the patient population (a small sample size could more easily under- or overestimate the frequency of a scarce bacterial pathogen);
•the improper use of exclusion criteria so that only healthy patients are analyzed;
•the adequacy of the culture media used (eg, some species of Haemophilus failed to be isolated if supplemented Agar-chocolate medium was not used);
•climatic variables (average temperature and humidity); and
•the age and gender demographics of the study population.
Corroborating our conclusions, Li et al40 reported that nonsurgical risk factors for postsurgical endophthalmitis included an age greater than 80 years and having surgery during winter. In Perth, Australia, where the study was conducted, the mean temperatures in winter are similar to our spring and autumnal mean temperatures. Two additional studies similarly concluded that both elderly patients and male patients have an elevated risk for postsurgical endophthalmitis.41,42
Taken as a whole, these studies suggest that the risk of postcataract endophthalmitis is affected by climate as well as by gender and age. Conjunctival cultures show a correlation between a greater incidence of positive cultures and warmer climate, male gender, and older age. The ideal prophylactic regimen may need to better factor in gender, age, and seasonal variation in the composition of the bacterial conjunctival flora. Prospective studies will be needed to determine if more customized approaches can decrease the risk.
Elisa Fernández Rubio, PhD, is a clinical analyst at the Ophthalmic Institute Laboratory, Department of Ophthalmology, “Gregorio Marañon” University General Hospital, Madrid, Spain. Dr. Fernández Rubio may be reached at +34 91 58 67 326; email@example.com. Speaker MG, Milch FA, Shah MK, et al. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology. 1991;98:639-649.
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