In Vitro Activity of Minocycline against U.S. Isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus Species Complex, Stenotrophomonas maltophilia, and Burkholderia cepacia Complex: Results from the SENTRY Antimicrobial Surveillance Program, 2014 to 2018

Abstract

We evaluated the activity of minocycline and comparator agents against a large number of Stenotrophomonas maltophilia (n = 1,289), Acinetobacter baumannii-Acinetobacter calcoaceticus species complex (n = 1,081), and Burkholderia cepacia complex (n = 101) isolates collected from 2014 to 2018 from 87 U.S. medical centers spanning all 9 census divisions. The isolates were collected primarily from hospitalized patients with pneumonia (1,632 isolates; 66.0% overall), skin and skin structure infections (354 isolates; 14.3% overall), bloodstream infections (266 isolates; 10.8% overall), urinary tract infections (126 isolates; 5.1% overall), intra-abdominal infections (61 isolates; 2.5% overall), and other infections (32 isolates; 1.3% overall). Against the A. baumannii-A. calcoaceticus species complex, colistin was the most active agent, exhibiting MIC50/90 values at ≤0.5/2 μg/ml and 92.4% susceptibility. Minocycline ranked second in activity, with MIC50/90 values at 0.25/8 μg/ml and susceptibility at 85.7%. Activity for these two agents was reduced against extensively drug-resistant and multidrug-resistant isolates of the Acinetobacter baumannii-Acinetobacter calcoaceticus species complex. Only two agents showed high levels of activity (susceptibility, >90%) against S. maltophilia, minocycline (MIC50/90, 0.5/2 μg/ml; 99.5% susceptible) and trimethoprim-sulfamethoxazole (MIC50/90, ≤0.5/1 μg/ml; 94.6% susceptible). Minocycline was active against 92.8% (MIC90, 4 μg/ml) of trimethoprim-sulfamethoxazole-resistant S. maltophilia isolates. Various agents exhibited susceptibility rates of nearly 90% against the B. cepacia complex isolates; these were trimethoprim-sulfamethoxazole (MIC50/90, ≤0.5/2 μg/ml; 93.1% susceptible), ceftazidime (MIC50/90, 2/8 μg/ml; 91.0% susceptible), meropenem (MIC50/90, 2/8 μg/ml; 89.1% susceptible), and minocycline (MIC50/90, 2/8 μg/ml; 88.1% susceptible). These results indicate that minocycline is among the most active agents for these three problematic potential pathogen groups when tested against U.S. isolates.

Activity of Potential Alternative Treatment Agents for Stenotrophomonas maltophilia Isolates Nonsusceptible to Levofloxacin and/or Trimethoprim-Sulfamethoxazole

“…Among the tetracyclines, minocycline was as active as or more active than tigecycline, eravacycline, and omadacycline and demonstrated the highest susceptibility (78.6%) against the most difficult-to-treat group of isolates nonsusceptible to both levofloxacin and TMP-SMZ. These results are consistent with those of a recent study by Flamm et al, who reported that 64/69 (92.8%) TMP-SMZ-resistant S. maltophilia isolates (including 54/69 levofloxacin-NS isolates) were susceptible to minocycline (20). While rare in the clinical setting, we did identify three S. maltophilia isolates nonsusceptible to levofloxacin, minocycline, and TMP-SMZ, and no agent tested in this study was active against all three of these isolates.…”

“…Bacterial isolates were specifically chosen by their phenotypic resistance to first-line agents to elucidate potential alternative treatment options, although this obviously enriched the sample with isolates outside the normal MIC distribution, which may not accurately reflect the activity of the antimicrobial agents tested in routine clinical practice (17,38). A recent evaluation of 1,289 isolates of S. maltophilia (20). Additional limitations include the number of isolates, lack of molecular analysis of all isolates, and exclusion of pipeline agents that may have activity against MDR S. maltophilia (e.g., cefiderocol and aztreonam-avibactam).…”

“…Additional agents with reliably high susceptibility rates against S. maltophilia include tetracycline derivatives like minocycline and tigecycline. Minocycline displays susceptibility rates similar to those of TMP-SMZ, and anecdotal data suggest that clinical outcomes with minocycline and TMP-SMZ monotherapy do not significantly differ (12,15,17,19,20). Despite these data and availability of interpretive susceptibility criteria (21), minocycline is rarely used clinically for the treatment of S. maltophilia due in large part to the fact that many clinical microbiology labs do not specifically perform susceptibility testing for minocycline (22).…”

A 10-year single-center experience on Stenotrophomonas maltophilia resistotyping in Szeged, Hungary

“…However, the adverse effect-profile of these drugs and the low serum concentrations achieved by tigecycline should also be taken into consideration [45]. Besides this, concerns have been raised that the frequent use of minocycline for the therapy of Acinetobacter calcoaceticus-baumannii complex may lead to the emergence of resistance in S. maltophilia [46].…”

Multidrug Resistance (MDR) and Collateral Sensitivity in Bacteria, with Special Attention to Genetic and Evolutionary Aspects and to the Perspectives of Antimicrobial Peptides—A Review

“…The mechanisms of disease caused by A. baumannii strains have recently been reviewed by Morris et al [ 8 ]. The latest review on the resistance mechanisms of A. baumannii [ 542 ] focuses on XDR resistance.…”