We appreciate Dr Crama’s comments regarding our recent study of the use of quantitative real-time polymerase chain reaction (qPCR) in the diagnosis and management of postoperative endophthalmitis. Dr Crama raises several important points that we address herein.
Our study did indeed include patients up to 12 months after cataract extraction. However, the large majority of patients in our study (53 of 64, or 82.8%) were known to have sought treatment within 6 weeks of surgery. Although Dr Crama is correct that this differs from the inclusion criteria of similar studies, the vast majority of patients in our study also sought treatment within the 6-week timeframe used by other investigators. In fact, one of the studies cited by Dr Crama, that of Bispo and associates, included patients with either endogenous or postoperative endophthalmitis; among the latter group, 91.7% had an acute onset of symptoms, which is comparable with our study.
Furthermore, in our study, the sensitivity of culture and qPCR among patients seeking treatment within 6 weeks of surgery did not differ significantly from that of the full cohort. Among these 53 patients with acute postoperative endophthalmitis, the sensitivity of traditional culture was 35.8%, and the sensitivity of qPCR was 60.3% (compared with 34% and 66%, respectively, among the full 64-patient cohort). In the acute endophthalmitis group, 19 patients had positive culture results, and of these, qPCR detected 16s DNA in 18 patients. As noted in our original article, in the single patient with a culture-positive, but qPCR-negative, sample, the identified pathogen was a Nocardia species. Among the 34 culture-negative samples in the acute endophthalmitis group, qPCR results also were negative in 20 cases. In the remaining 14 culture-negative cases, qPCR successfully detected high copy numbers of 16s bacterial rDNA, indicating the presence of bacterial infection.
Dr Crama also notes that some prior studies have reported rates of positive culture results as high as 66% to 69%. Although these rates of culture positivity are admirable, such results are not consistent across the literature, and other well-designed studies have shown a rate of culture positivity as low as 10%. Indeed, even among the references cited by Dr Crama, the study by Bispo and associates reports a culture positivity rate of only 47.6%. Therefore, we still believe that it is a valid conclusion that our culture positivity rate of 34% is within the range of previously reported values.
Although the range of culture positivity is wide, we believe the more important point is that several studies have shown that qPCR can increase the pathogen yield further when used as an adjunct to traditional culture. As discussed in our original study, we believe qPCR is a promising investigational technique that may enhance rapid pathogen identification in patients with signs of bacterial endophthalmitis.