Comparative MIC evaluation of a generic ceftriaxone by broth microdilution on clinically relevant isolates from an academic hospital complex in South Africa.

We evaluated the in vitro microbiological efficacy of a generic ceftriaxone product against several clinically significant organisms collected from sterile sites. The minimum inhibitory concentration (MIC) of each was determined simultaneously with the reference and the generic ceftriaxone product. Comparative analysis of MICs between the two products for each isolate was performed using both categorical (interpretive) agreement and essential (actual MIC value) agreement. A total of 260 isolates were tested. Overall, there was categorical agreement of 98.9% and essential agreement of 95.8%. The categorical agreement for all isolates (96.7 - 100%) accorded with international standards, as no very major errors were seen and the major error rate was less than 3%. Of the 90 isolates of E. coli (40), Klebsiella spp. (40) and Salmonella spp. (10), 87.6% had an MIC less than or equal to 0.12mg/l. The generic ceftriaxone product showed equivalent efficacy by MIC determination to the reference formulation. Ceftriaxone remains a viable and useful antimicrobial agent against a variety of clinically relevant organisms in our setting.

A Comparative in Vitro Microbiological Evaluation of Generic Meropenem Compounds against the Innovator Compound

Background: Meropenem is a broad-spectrum carbapenem widely used in the treatment of critically ill patients. A generic meropenem product has recently become available in South Africa and we aimed to compare the generic product with the innovator product using established in vitro microbiological testing methods.Method: Comparative minimum inhibitory concentrations (MICs) were determined for 115 clinically relevant isolates using the broth microdilution reference method. Comparative analysis of MIC was done using categorical and essential agreement. A subset of isolates was evaluated using minimum bactericidal concentration (MBC) testing. Results: The overall essential agreement exceeded the international standard of 90. A single major error and six minor errors were detected in 230 comparative MICs. For the 55 Enterobacteriaceae isolates tested; the MIC50 and MIC90 were 0.03 ?g/ml and 0.06 ?g/ml respectively; with no difference between extended-spectrum Beta-lactamase producers (ESBL) and non-ESBL isolates. Bactericidal activity was demonstrated for both generic and innovator products in all isolates tested. For eight of the 11 isolates; the MBC was only twice the MIC.Conclusion: Reference method MIC and MBC testing of a large sample of clinically relevant microorganisms against meropenem has demonstrated comparable in vitro activity between the innovator and generic products. Low MICs and bactericidal activity at concentrations close to the MIC indicate that meropenem remains a useful agent in the treatment of infections caused by ESBL-producing Enterobacteriaceae

Antimicrobial susceptibility testing and profiling of Nocardia species and other aerobic actinomycetes from South Africa: comparative evaluation of broth microdilution versus the Etest.

Nocardiosis is an underrecognized clinical entity in South Africa, for which interspecies epidemiological and clinical differences are poorly understood. The taxonomical state of flux and the lack of a simple antimicrobial susceptibility testing method are partly responsible. Definitive identification is molecularly based, which further complicates the study of this ubiquitous organism, as this methodology is beyond the scope of most routine diagnostic laboratories. The Etest methodology has been proposed as an alternative to the reference broth microdilution method, although there have been a limited number of comparative studies. We profiled 51 clinical isolates of aerobic actinomycetes, including 39 Nocardia species, using sequence-based (16S rRNA) identification. Broth microdilution and Etests were done concurrently on all isolates. The overall level of categorical and essential agreement for broth microdilution and Etest for the Nocardia isolates ranged from 67.5 to 100% and 46.2 to 81.6%, respectively. Very major errors were seen with amikacin, amoxicillin-clavulanate, ciprofloxacin, clarithromycin, and imipenem. For Nocardia species, uniform susceptibility to co-trimoxazole, amikacin, and linezolid was demonstrated, with a 48.8% susceptibility rate to imipenem. Nocardia farcinica (20.5%) and Nocardia cyriacigeorgica (15.4%) were the most commonly identified species among the 82% of isolates identified to species level using 16S rRNA sequences. Furthermore, drug susceptibility patterns demonstrated limited concordance with species identification. Our results suggest that, in a routine diagnostic setting, the Etest is not an acceptable alternative to the reference method of broth microdilution for antimicrobial susceptibility testing. Given the diversity and limited understanding of this group of organisms, further widespread evaluation of clinical isolates, from both clinical and diagnostic perspectives, is warranted.