Understanding Antimicrobial Susceptibility Profile of Finegoldia Magna An Insight To An Untrodden Path

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Shetty et al.

Annals of Clinical Microbiology and Antimicrobials (2023) 22:30 Annals of Clinical Microbiology
https://doi.org/10.1186/s12941-023-00583-1
and Antimicrobials

RESEARCH Open Access

Understanding antimicrobial susceptibility


profile of Finegoldia magna: an insight to an
untrodden path
Seema Shetty1,2†, Renuka Anegundi1†, Padmaja Ananth Shenoy1,2* and Shashidhar Vishwanath1,2

Abstract
Background Finegoldia magna (formerly known as Peptococcus magnus or Peptostreptococcus magnus) belonging
to phylum Firmicutes, class Clostridia and genus Finegoldia, is the only species known to cause infections in human
beings. Amongst Gram positive anaerobic cocci, F. magna is known to be the most virulent with a high pathogenic
potential. Significant upsurge in antimicrobial resistance among anaerobes has been documented by various studies.
F. magna is known to be susceptible to most of the anti-anaerobic antimicrobials, however, multidrug resistant
strains are being reported in literature. The present study was undertaken to highlight the role of F. magna in clinical
infections and to analyze their antimicrobial susceptibility patterns.
Methods The present study was conducted in a tertiary care teaching hospital in Southern India. 42 clinical isolates
of F. magna recovered from diverse clinical infections between January 2011 to December 2015 were studied. These
isolates were subjected to antimicrobial susceptibility testing against metronidazole, clindamycin, cefoxitin, penicillin,
chloramphenicol and linezolid.
Results Among the 42 isolates studied, majority of them were revived from diabetic foot infections (31%) followed
by necrotizing fasciitis (19%) and deep-seated abscesses (19%). All the F. magna isolates showed good in-vitro activity
against metronidazole, cefoxitin, linezolid and chloramphenicol. Clindamycin and penicillin resistance were observed
against 9.5% and 2.4% of the isolates respectively. However, β-lactamase activity was not detected.
Conclusion The antimicrobial resistance among anaerobes varies from pathogen to pathogen and region to region.
Hence, a deep understanding of resistance pattern is necessary for better management of clinical infections.
Keywords Anaerobic cocci, Finegoldia magna, Antimicrobial resistance, Metronidazole, Clindamycin Resistance


These authors contributed equally to this work.
*Correspondence:
Padmaja Ananth Shenoy
[email protected]
1
Department of Microbiology, Kasturba Medical College, Manipal,
Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
2
Manipal Centre for Infectious Diseases, Prasanna School of Public Health,
Manipal Academy of Higher Education, Manipal, Karnataka, India

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Shetty et al. Annals of Clinical Microbiology and Antimicrobials (2023) 22:30 Page 2 of 5

Introduction may not be of clinical benefit but in turn would pose an


Gram positive anaerobic cocci (GPAC) form an integral increased burden on patient care and economic conse-
part of normal human microbiota colonizing surfaces quences. In addition, rampant over-the-counter usage of
of skin, mouth, gastrointestinal and urogenital system empirical antimicrobials with lack of awareness regard-
[1]. These GPAC are often considered as opportunistic ing their increasing resistance trends can result in rise
pathogens and are significantly recovered from diverse and spread of multidrug resistant anaerobic superbugs
clinical infections constituting 25–30% of all clinical [1, 2, 9]. In this regard, the knowledge and availability of
anaerobic isolates [1–3]. The most commonly isolated antimicrobial resistance data becomes crucial to tackle
GPAC in infectious clinical materials include Peptostrep- the emergence and transmissibility of antimicrobial resis-
tococcus anaerobius, Finegoldia magna, Peptoniphilus tance. The present work was undertaken to highlight the
asaccharolyticus and Parvimonas micra. F. magna is one role of F. magna in clinical infections with special refer-
of the most common anaerobic pathogens accounting to ence to their antimicrobial resistance patterns.
5–12% of all anaerobic isolates and 20–38% of all GPAC
[3]. Materials and methods
The genus Finegoldia belongs to the phylum Fir- Study population and study design
micutes, class Clostridia and is named after the Ameri- The present study was conducted in the Department of
can Microbiologist S. M. Finegold [1, 2]. F. magna Microbiology, a constituent of a tertiary care teaching
(formerly known as Peptococcus magnus or Peptostrepto- hospital in Southern India. A total of 42 clinical isolates
coccus magnus) is the lone species of clinical importance of F. magna which were recovered from diverse clini-
in this genus [2]. F. magna is known to cause a variety of cal infections between January 2011 to December 2015
clinical infections ranging from deep-seated infections were included in this study. All these strains were isolated
to life-threatening conditions such as endocarditis, pros- from various clinical specimens including pus aspirates,
thetic joint infections and necrotizing pneumonia [1–4]. soft tissue specimens, bone and body fluids, obtained
The infections associated with GPAC are usually polymi- from diverse infectious sites and were stored at -80◦C in
crobial in nature, however, F. magna is often isolated in skimmed milk broth until further analysis.
pure cultures [4]. Several virulence factors produced by
this pathogen are known to influence disease pathogen- Sample processing and identification
esis [1–3]. The stored isolates were revived on anaerobic blood agar
Antimicrobial resistance among anaerobes is witness- (HiMedia Labs, Mumbai, India) and were incubated for
ing a significant upsurge in the recent years worldwide 72 h at 37◦C in Whitley A35 Anaerobic workstation
[5]. Though, GPAC are usually susceptible to commonly (Don Whitley Scientific, Shipley, UK). Prior to antimi-
used anaerobic antimicrobials, increasing resistance crobial susceptibility testing, the identification of the iso-
trends and significant difference in susceptibility profile lates was confirmed by Matrix‑assisted laser desorption/
among different species of GPAC have been reported in ionization‑time of flight mass spectrometry (Vitek MS,
literature [5, 6]. Variable resistance to penicillin (7–10%), bioMerieux Inc., France). β‑lactamase production was
metronidazole (5–10%) and clindamycin (7–20%) have detected using nitrocephin impregnated paper disks (BD
been reported amongst GPAC [1, 7]. F. magna has shown BBL Cefinase, Becton Dickinson and Co, Sparks, USA)
lower resistance rates (10–20%) to clindamycin, met- [10].
ronidazole and penicillin, while higher resistance rates
(> 20%) have been demonstrated against erythromycin Antimicrobial susceptibility testing
and tetracycline [2]. Owing to these study findings, it The minimum inhibitory concentrations (MIC) of F.
becomes very essential to diagnose and identify isolates magna isolates were determined by reference agar
from diverse clinical infectious materials up to species dilution method and/or antimicrobial gradient diffu-
level. sion method (E test, bioMerieux Inc., Marcy L’Etoile,
Unlike aerobic counterparts, the anaerobic culture and France). The antimicrobial susceptibility was determined
susceptibility testing is not routinely performed in most against six antimicrobial agents, of which metronidazole,
of the clinical laboratories due to its stringent culture clindamycin, cefoxitin, penicillin and chloramphenicol
techniques, cost-effectiveness and lack of expertise [8]. were tested using agar dilution method, while linezolid
As most of the anaerobic infections are polymicrobial in was analyzed using E test method. The agar dilution
nature, there is practice of using empirical antimicrobials (Wadsworth method) was performed following Clini-
such as metronidazole and clindamycin in treating infec- cal and Laboratory Standard Institute (CLSI) guidelines
tions in clinical settings. In view of reduced susceptibil- M11-A6 (CLSI 2013) [11] on Wilkin-Chalgren agar with
ity to penicillin, clindamycin and metronidazole among Gram-positive anaerobic supplement (HiMedia Labs,
GPAC, the usage of empirical antimicrobial therapy Mumbai, India). The inoculum for each isolate was
Shetty et al. Annals of Clinical Microbiology and Antimicrobials (2023) 22:30 Page 3 of 5

prepared to adjust the turbidity to 1.0 McFarland stan- Discussion


dard. The inoculated plates were incubated in anaerobic F. magna is a clinically important GPAC with high patho-
atmosphere for 48 h. The lowest concentration at which a genic potential. It is frequently recovered from soft tis-
marked reduction in the growth was observed, was con- sue infections, diabetic foot infections, deep-seated
sidered as the MIC of the individual antimicrobial agent. abscesses, bone and joint infections [1, 2, 4–6]. In this
The E test was performed on anaerobic blood agar as per study, majority of the isolations were achieved from dia-
manufacturer’s guidelines and results were read after betic foot infections (31%), necrotizing fasciitis (19%) and
48 h of incubation. MIC was recorded at the point where deep-seated abscesses (19%). F. magna is known to elabo-
the elliptical zone intersected with the strip. The MIC rate range of putative virulence factors including protein
value was interpreted as per the CLSI guidelines M11- L, peptostreptococcal albumin binding protein (PAB),
A6 (CLSI 2013) [10]. B. fragilis ATCC 25285 was used as subtilisin-like proteinase (SufA) and F. magna adhesion
the reference strain for quality control of susceptibility Factor (FAF) in addition to production of collagenase
testing. enzyme. The collagenase production leads to breakdown
of collagen which is abundantly present in skin, tendons,
Results cartilage and bones. This results in loss of tissue integ-
Majority of F. magna isolates were recovered from dia- rity and breakdown of amino acids there by producing
betic foot infections (n = 13, 31%) followed by deep- favorable environment for growth and multiplication of
seated abscesses (n = 8, 19%) and cases of necrotizing asaccharolytic organism like F. magna.. There are reports
fasciitis (n = 8, 19%). The other clinical conditions noted mentioning the ability of F. magna in producing biofilms
were chronic osteomyelitis (n = 6), chronic non-healing which may in turn interfere with the targeted antimicro-
ulcer (n = 3), wet gangrene (n = 3) and chronic suppura- bial therapy [1, 12, 13]. Thus, better understanding of
tive otitis media (n = 2). Deep-seated abscesses included the bacterial properties and their virulence mechanisms
intra-abdominal abscess (n = 4), puerperal breast abscess would assist the clinicians in accurate treatment and
(n = 1), abdominal wall abscess (n = 1), perianal abscess management of these infections.
(n = 1) and hand abscess (n = 1). Of the 42 F. magna iso- Performing the antimicrobial susceptibility testing of
lates, 21 showed monomicrobial anaerobic growth and anaerobic bacteria would be an expensive affair requir-
were majorly isolated from cases of diabetic foot infec- ing experienced laboratory staff and adequate resources
tions, deep-seated abscesses and chronic osteomyelitis. which may not be feasible in all settings. The agar dilu-
Good in-vitro susceptibility was observed in all the iso- tion method, broth microdilution method or gradient
lates of F. magna against metronidazole, cefoxitin, line- tests (E test, spiral gradient test) are the various methods
zolid and chloramphenicol. A marked resistance towards used for determining MICs for anaerobic organisms [8].
clindamycin was observed in 9.5% (n = 4) isolates while The practice of incorporating metronidazole disk (5 µg)
only one strain was found to be resistant to penicillin in routine anaerobic culture plates and further testing of
(2.4%). β-lactamase activity was not detected in any of those isolates (showing zone size of less than 15 mm) for
the isolates. Table 1 illustrates the MIC50 and MIC90 aerotolerance tests can rule out the presence of faculta-
values of tested antimicrobial agents and their suscepti- tive anaerobic bacteria [3, 8]. The European Committee
bility patterns in F. magna. on Antimicrobial Susceptibility Testing (EUCAST) had
proposed disk diffusion susceptibility testing for anaer-
obes, which was found to be beneficial in fast grow-
ing organisms like B. fragilis. However, in view of poor
growth and varied results (in comparison to reference
agar dilution method), this technique is yet to be stan-
dardized for testing GPAC [14].
Table 1 MIC50 and MIC90 values of tested antimicrobial agents
Antimicrobial resistance trends among anaerobes is
and their susceptibility patterns in F. magna
highly diverse and dynamic, variability being observed
Antimicrobial agent MIC (µg/mL) S R
(%) (%) between species, regions and clinical set ups. Metroni-
MIC50 MIC90 Range
dazole, a 5-nitroimidazole derivative is a common and
Penicillin 0.125 0.5 0.125-4 97.6 2.4
Cefoxitin 2 4 2–4 100 -
long known antimicrobial for empirical therapy. Several
Metronidazole 0.5 4 0.25-8 100 -
complex mechanisms are implicated in the development
Clindamycin 2 4 0.25-16 90.5 9.5
of metronidazole resistance. There are reports of increas-
Chloramphenicol 1 2 0.25-4 100 - ing resistance trends towards metronidazole among B.
Linezolid 0.25 0.5 0.016-0.5 100 - fragilis group. In contrast, F. magna is known to be sus-
MIC, minimum inhibitory concentration; MIC50/90, MIC values for 50% and 90% ceptible to the commonly used anti-anaerobic antimicro-
of the organisms; S, susceptible; R, resistant bials [1, 2]. However, some studies have highlighted the
Shetty et al. Annals of Clinical Microbiology and Antimicrobials (2023) 22:30 Page 4 of 5

GPAC Gram positive anaerobic cocci


resistance to metronidazole among GPAC including F. MIC minimum inhibitory concentration
magna [15, 16]. In this study, none of the isolates showed CLSI Clinical and Laboratory Standard Institute
resistance to metronidazole which was in line with other PAB peptostreptococcal albumin binding protein
SufA subtilisin-like proteinase
studies [13, 17–20]. However, this study did not focus on FAF  F. magna adhesion Factor
analyzing the genetic mechanisms of drug resistance. EUCAST European Committee on Antimicrobial Susceptibility Testing
Clindamycin is another empirical drug commonly used
Acknowledgements
in treatment of anaerobic infections [14]. Variable rates Authors would like to acknowledge Manipal Academy of Higher Education,
of clindamycin resistance have been mentioned in lit- Manipal for the support to carry out this study.
erature ranging between 3 and 51% [5, 6, 15, 18, 21, 22].
Author contributions
This high resistance rates towards clindamycin could be S.S. and R.A. contributed to data collection and analysis. P.A.S. contributed
attributed to alteration in target site by RNA methylase to material preparation, data collection and analysis and drafted the first
and presence of erm gene [5]. Compared to other stud- manuscript. S.V. contributed to manuscript editing and review. S.S, R.A, P.A.S
and S.V. have read and approved the final version of the manuscript.
ies, we noted a decreased resistance rate (9.5%) towards
clindamycin in our setup. Funding
GPAC are generally known to be susceptible to The authors declare that no funds, grants, or other support were received
during the preparation of this manuscript.
β-lactam group, β-lactam β-lactamase inhibitors, car-
bapenems and cephalosporins. In the present study, Data availability
one F. magna isolate was found to be resistant to peni- All data generated or analyzed during this study are included in this
manuscript.
cillin (2.4%) although no β-lactamase activity was dem-
onstrated. There are varied reports for in-vitro activity
Declarations
of β-lactams among anaerobic bacteria with high rates
of resistance being depicted in B. fragilis group [23]. Ethical approval and consent to participate
Although good in-vitro activity of penicillin has been The study was conducted in accordance with the Declaration of Helsinki
and this study was approved by the Institutional Ethical Committee of
noted in F. magna, the resistance rates towards β-lactam Kasturba Medical College & Kasturba Hospital, Manipal (IEC1:41/2022 dated
group has been reported among other GPAC, particularly 09-02-2022). This study was solely laboratory based and hence, the need for
in P. anaerobius isolates [5]. Chloramphenicol, although informed consent was waived off by the institutional ethical committee.

not used routinely [9], has shown good susceptibility Consent for publication
rates among anaerobic genera with an exception to study Not applicable.
by Lee et al. [18] where two isolates of F. magna (n = 15)
Competing interests
showed high MIC values (16–32 mg/L) and were found The authors declare no competing interests.
to be resistant. Good linezolid activity has been depicted
in literature against GPAC which was concordant with Received: 25 January 2023 / Accepted: 11 April 2023
our study [5, 7, 17, 24]. Multidrug resistant F. magna have
been emerging and are being reported in some studies. In
a study conducted by Shilnikova and Dmitrieva, a mul-
tidrug resistant F. magna was reported from mediastinal
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