Our data differ from the previous three reports describing high levels of sulfonamide resistance but are strikingly similar to the low incidence (2%) of sulfonamide resistance seen by Lai et al. (9
) in a study of Nocardia
isolates in Taiwan and an earlier study in South Africa with 0% sulfonamide resistance in 39 isolates (12
). Similarly, in a recent study of 1,641 U.S. Nocardia
isolates, the investigators found only 2% of the isolates studied to be resistant to TMP-SMX. N. pseudobrasiliensis
and N. transvalensis
complex isolates were sulfonamide resistant, while no other Nocardia
species in their study showed resistance (17
The disparity between the data is of interest, since all of the reporting laboratories in this study are geographically diverse. This fact suggests that some factor other than geographic location may play a major role in the susceptibility patterns that are reported, with the most probable factor being a methodological or interpretational difference.
The MICs of sulfonamides, including TMP-SMX, are based on an 80% inhibition endpoint of growth compared to the growth control without drug rather than no growth or 100% inhibition, as is standard for other antimicrobials (4
). In a recent CLSI multicenter study among six laboratories using the same strains of Nocardia
and the same lot numbers of susceptibility panels, media, etc., multiple laboratories reported discrepancies in MIC interpretations for sulfonamides (5
). This multicenter study showed that careful training and close scrutiny of the 80% inhibition endpoint were necessary to produce accurate MIC results. We believe the differences in resistance to sulfonamides reported in the current and prior studies may reflect similar issues of reading the 80% endpoint.
The current study and the CLSI multicenter study emphasized the necessity for laboratory proficiency testing with unusual organisms, such as Nocardia
). Unfortunately, there is no standardized proficiency testing program currently available, including from the College of American Pathologists (CAP). Thus, the exchange of organisms between two or more accredited laboratories is the best current means to meet this criterion. Another recommendation to help in training laboratory personnel to better interpret MICs, would be the establishment of a number of control strains of Nocardia
with known (and consensus) susceptibility patterns.
Significant concerns about recent reports detailing the significant increase in sulfonamide resistance among numerous Nocardia
spp. prompted this study. It is generally accepted that the incidence of nocardial disease is increasing (2
), and TMP-SMX remains the drug of choice for treatment (2
). We suggest that future studies with the currently approved CLSI susceptibility testing method involve a representative set of the previously identified sulfonamide-susceptible and -resistant strains of N. cyriacigeorgica
, N. farcinica
, and N. nova
. We consider this to be necessary to preserve the traditional approach to empirical therapy of significant infections involving Nocardia
spp., which almost always includes a sulfonamide preparation (TMP-SMX). If significant levels of sulfonamide resistance are detected in these previous or future isolates, further investigation of the mechanism(s) of resistance would be indicated. CLSI advocates that all clinically significant isolates of Nocardia
be identified by currently accepted molecular methods and that antimicrobial susceptibility testing be performed as a guide to therapy (4
). In conclusion, our study strongly suggests that reporting of resistance to TMP-SMX must take note of the inherent difficulties of reading MIC wells and should be supported by one or more of the above recommendations.