In the Literature Free

Staphylococcus lugdunensis Endocarditis

Aldman MH, Rasmussen M, Olaison L, Påhlman LI. Endocarditis due to Staphylococcus lugdunensis—a retrospective national registry-based study. Eur J Clin Microbiol Infect Dis 2020. doi: 10.1007/s10096-020-04134-w. Epub ahead of print. PubMed PMID: 33378000.

Aldman and colleagues reviewed cases of endocarditis caused by Staphylococcus lugdunensis, as well as those due to other coagulase-negative staphylococci (CoNS) and to Staphylocococcus aureus that had been recorded in the Swedish Registry of Infective Endocarditis in 2008–2018. The investigators identified 2184 cases of endocarditis during that 10-year period: 1892 due to S. aureus, 262 caused by CoNS other than S. lugdunensis, and 30 due to S. lugdunensis.

Patients with S. aureus endocarditis were significantly younger than those with S. lugdunensis infection, but this difference disappeared when injection drug users were removed from consideration. Of the 30 with S. lugdunenis infection, 21 (70%) had native valve endocarditis, with the aortic valve involved in 18 (60%). Approximately one-fourth of both S. lugdunensis– and S. aureus–infected patients underwent valve surgery while 42% of those with infection due to other CoNS did so, likely related to the fact that infection had frequently involved a prosthetic cardiac valve in the latter group. Sixty percent of patients with S. lugdunensis infection were treated with an isoxazolyl penicillin.

The occurrence of septic embolization was recorded in only 2 (7%) of those with S. lugdunensis endocarditis, compared with 48% and 24% of those with S. aureus and other CoNS infection, respectively—differences that were statistically significant. The 30-day mortality (20%) was more than twice as high in the S. lugdunensis group than in the other 2 groups and death occurred significantly earlier as well.

Published in 2017, a retrospective single-center study in St Louis identified 74 patients with at least 1 positive blood culture yielding S. lugdunensis from 2006 to 2014. Two or more blood cultures were positive in 39 (53%). Almost two-thirds of patients met sepsis criteria on admission [1]. Overall, 11 (15%) had definite or possible endocarditis based on the 2000 modified Duke criteria, while among those with 2 or more positive blood cultures, 10 (25%) of 40 were judged to have had endocarditis. In addition, a literature review led to the finding that 6.3–27.0% of patients with at least 1 positive blood culture had endocarditis. Non and Santos found that bacteremia persisted for more than 3 days in 11% of their entire cohort of 74 patients with S. lugdunensis bacteremia. Only 10 (15%) of 67 isolates were resistant to oxacillin.

Staphylocococcus lugdunesis, which colonizes moist cutaneous areas such as the perineum and axilla, is phylogenetically closely related to S. aureus. Despite that relationship, as well as the fact that it is capable of causing serious infection, including native valve endocarditis, it lacks many of the factors that contribute to virulence of S. aureus [2, 3]. Among those present in the latter but absent in S. lugdunensis are coagulase, although slide coagulase tests may give falsely positive results. Also absent are innate immune evasion proteins, protein A, and enterotoxin. Staphylocococcus lugdunesis does, however, produce a capsular polysaccharide as well as hemolysins and can adhere to von Willebrand’s factor, which may contribute to the ability to cause endocarditis by adherence to injured vascular endothelial cells expressing the factor.

In contrast to other CoNS, S. lugdunensis is generally susceptible to a greater range of antibiotics. Methicillin resistance in this organism was only first described in 2003, 15 years after its designation as a separate named species. Resistance has, however, gradually increased over the years, although it still remains at relatively low levels as evidenced by the 15% prevalence of oxacillin resistance in the report by Aldman and colleagues.

The species name of this organism has an interesting origin. As Julius Caesar wrote, “Gallia est omnis divisa in partes tres.” One of these 3 parts was the province of Gallia Lugdunensis, the capital of which was Lugdunum. Lugdunum became modern-day Lyon, the city where, in 1988, S. lugdunensis received its species name [4].

References

OMADACYCLINE AND NONTUBERCULOUS MYCOBACTERIA—FOCUS ON MYCOBACTERIUM ABSCESSUS

Brown-Elliott BA, Wallace RJ Jr. In vitro susceptibility testing of omadacycline against nontuberculous mycobacteria (NTM). Antimicrob Agents Chemother 2020. doi: 10.1128/AAC.01947-20. Epub ahead of print. PubMed PMID: 33288634.

Treatment of infections due to nontuberculous mycobacteria (NTM) is a challenge that is being encountered by clinicians with increasing frequency. That challenge primarily resides in the frequent resistance of many species to multiple antimicrobials. In some cases, such as many due to Mycobacterium abscessus, prolonged administration of parenterally administered antibiotics proves necessary due to a lack of active orally bioavailable agents. As a consequence, significant effort is being made to identify effective alternative antibiotics, especially ones which can be administered by mouth. One such newer antibiotic of interest is a member of the aminomethylcyine subclass of tetracyclines, omadacycline.

Brown-Elliott and Wallace determined the omadacycline minimum inhibitory concentrations (MICs) of 70 rapidly growing mycobacteria (RGM) and 41 slowly growing mycobacteria (SGM), using a broth dilution method according to Clinical and Laboratory Standards Institute (CLSI) standards. The activity of omadacycline against SGM was variable, with an MIC range of 0.06 µg/L to >16 µg/L and an MIC₅₀ range of 8 µg/mL to µg/ml. It was, however, more highly active in vitro against RGM, with an MIC range of 0.03 µg/mL to 1 µg/mL. Interpretation of the omadacycline MIC results are, however, affected by the phenomenon of trailing. Trailing, commonly seen with RGM, is the result of reduced but persistent growth at dilutions above the MIC. In order to deal with this phenomenon, MICs were read at 2 levels: 80% inhibition—the point at which trailing began but without significant change in growth at subsequent dilutions—and 100% inhibition. Omadacycline MICs were up to 3 concentrations lower when read at 80% inhibition than at 100%. Against 20 M. abscessus subsp. abscessus isolates, the MIC₅₀ was 0.06 µg/mL at 80% inhibition and 0.12 µg/mL at 100% inhibition. Among the multiple antibiotics tested, the only one with activity comparable to that of omadacycline against M. abscessus subsp. abscessus was tigecycline (MIC₅₀/₉₀ of 0.12 and 0.25 µg/mL).

Omadacycline also had potent activity against other SGM. At 100% inhibition, the highest MIC results (MIC₉₀ = 0.5 µg/L) among the SGM were seen with Mycobacterium chelonae, Mycobacterium immunogenum, and Mycobacterium mucogenicum groups.

In another study, Chew and colleagues [1] tested 211 M. abscessus isolates against a variety of antibiotics other than omadacycline, but including vancomycin, dalbavancin, telavancin, oritavancin, rifabutin, delafloxacin, tigecycline eravacycline, clofazimine, and bedaquiline. The most active included 2 tetracylines, tigecycline (MIC₅₀/MIC₉₀ of 0.5/1.0 µg/mL) and eravacycline (0.12/0.25 µg/mL), as well as clofazimine (0.12/0.25 µg/mL) and bedaquiline (0.06/0.12 µg/mL).

The activity of omadacycline, as well as tigecycline and eravacycline, is due to the fact that it is not significantly affected by common tetracycline resistance mechanisms such as ribosomal protection by tetM, tetO, and tetS or by efflux mechanisms encoded by tetK and tetL. It is also presumably not affected by the tetracycline destructase MabTetX, which causes high-level resistance to tetracycline and doxycycline in M. abscessus [2].

Omadacycline has in vitro activity similar to that of tigecycline (and eravacycline) against M. abscessus, but it has the important virtue of being available in an orally bioavailable form, increasing its usefulness in the treatment of an infection that requires prolonged antimicrobial administration. Published clinical experience to date appears to be limited to a total of 5 patients [3, 4]. Although all had clinical improvement or cure of infection, each received it in association with other antimicrobials, making assessment of any resultant benefit impossible.

References