sinusitis

Article
Contemporary Update on the Microbiology of Paranasal Sinusitis
Margaret B. Mitchell 1,2, * , Alan D. Workman 1,2 , Richard Lu 1 and Neil Bhattacharyya 1,2

1 Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA

2 Department of Otolaryngology-Head & Neck Surgery, Massachusetts Eye & Ear, 243 Charles Street,
Boston, MA 02114, USA
* Correspondence: [email protected]; Tel.: +1-617-573-3653; Fax: +1-617-384-8488

Abstract: Background: Sinusitis, whether acute or chronic, is likely due at least in part to disruptions
in the microbiota of the paranasal sinuses. Sinus cultures are often employed to guide medical
treatment. Objective: To quantify the contemporary microbiology of the paranasal sinuses and better
understand the utility of paranasal sinus cultures. Methods: We identified patients from 2018 to 2019
with sinus cultures taken by an otolaryngologist in the outpatient setting in our healthcare system
with a concurrent diagnosis of acute or chronic rhinosinusitis. These cultures were analyzed based
on their culture type and result. The most commonly isolated bacteria were further analyzed by
species; Staphylococcus resistance patterns were analyzed as well. Results: A total of 2302 culture
samples were collected: 2012 (87%) bacterial, 287 (13%) fungal, and 3 (0.1%) mycobacterial cultures.
The results of more than half (1142, 57%) of these bacterial cultures were positive for a named genus,
while those of 592 (29%) were positive for normal sinus flora and 16 (0.8%) for normal oral flora, and
those of 183 (9%) showed no growth. The results of another 79 (4%) bacterial cultures were positive
for unnamed bacteria, which were not further classified (e.g., Gram-negative rods). Of the positive
bacterial cultures with named genera, the most common genera identified was Staphylococcus (383,
34%). Of these, the most common species of Staphylococcus was S. aureus (311, 81%), 42 of which (14%)
showed methicillin resistance (MRSA). Of the fungal cultures, 265 (92%) resulted in no growth, and
all three mycobacterial cultures showed no growth. Conclusions: In contrast to fungal cultures, the
majority (57%) of sinus bacterial cultures showed positive results, with the identification of a named
genus, highlighting the potential utility of this assay in guiding medical therapy.

Citation: Mitchell, M.B.; Workman, Keywords: sinusitis; rhinosinusitis; chronic rhinosinusitis; medical therapy of chronic rhinosinusitis;
A.D.; Lu, R.; Bhattacharyya, N. acute sinusitis; Staphylococcus aureus; MRSA; sinus culture; Propionibacterium; Haemophilus
Contemporary Update on the
Microbiology of Paranasal Sinusitis.
Sinusitis 2024, 8, 13–19. https://
doi.org/10.3390/sinusitis8020003 1. Introduction
Academic Editor: José Laerte Boechat Rhinosinusitis, whether acute, recurrent, or chronic, is thought to be at least in part
characterized by the disruption of the microbiological landscape of the nasal and sinus
Received: 12 June 2024
cavities. This landscape consists of the natural microbiota of the sinuses and its interactions
Revised: 9 July 2024
with the surrounding immune system. The types of disruptions that occur can vary widely
Accepted: 11 July 2024
and may have implications for treatment approach. For example, in the case of acute
Published: 16 July 2024
sinusitis, there are often changes within the microflora composition through new bacterial
or viral pathogens or through an imbalance of naturally occurring sinus flora [1]. This
latter process, where naturally occurring bacteria may become more pro-inflammatory
Copyright: © 2024 by the authors. or invasive, has been termed dysbiosis, and presents a more nuanced picture in patients
Licensee MDPI, Basel, Switzerland. presenting with acute on chronic changes in symptoms [1,2]. Moreover, patients with
This article is an open access article unresolving sinus symptoms after 12 weeks that suffer from chronic rhinosinusitis (CRS)
distributed under the terms and may also have underlying immune system disruptions in addition to—or even triggered
conditions of the Creative Commons by—sinus dysbiosis [1]. This is evidenced by studies demonstrating that nasal lavage
Attribution (CC BY) license (https:// samples from patients with CRS stimulate IL-5 activation in peripheral leukocytes from
creativecommons.org/licenses/by/ healthy controls [3,4].
4.0/).

Sinusitis 2024, 8, 13–19. https://doi.org/10.3390/sinusitis8020003 https://www.mdpi.com/journal/sinusitis

Sinusitis 2024, 8 14

While many classes of disruptions (e.g., bacterial, immunological, etc.) have been
described, there is currently a poor understanding of the relationship that exists between
these disruptions and a clinical presentation of rhinosinusitis [5]. To that end, characterizing
nasal microbiology is an essential step to understand the clinical significance of nasal
bacterial composition. Furthermore, understanding this relationship may shed light on the
utility of sinus nasal cultures and subsequent antibiotic treatment for rhinosinusitis.
Previous studies have described the microbiology of the paranasal sinuses of both
healthy patients and patients with CRS: paranasal sinus cultures from both groups of
patients most commonly grow Staphylococcus, Propiononibacterium, Corynebacterium, and
Streptococcus species [6–9]. Studies comparing healthy controls versus patients with CRS
note variations in both certain types of bacteria present on sinus cultures between the two
groups—like higher rates of Haemophilus and Escherichia coli [10] as well as Staphylococ-
cus [11] in patients with CRS vs. healthy controls—as well as reduced bacterial diversity
in patients with CRS [12]. However, among patients with CRS, there still is significant
bacterial diversity, especially between patients of certain phenotypes, like those with CRS
with purulence or CRS with asthma [13].
Most studies, however, are limited by their sample size and are confined to a single
institution [7,8,13], limiting their generalizability. We sought to analyze a large microbio-
logical dataset corresponding to sinusitis in a large metropolitan healthcare system among
otolaryngologists practicing in multiple different institutions to obtain a contemporary
update on the microbiology of sinusitis. Such data would offer insight into the current
microbiological landscape as well as provide information on the utility of sinus culture
data in the management of acute and chronic sinusitis.

2. Materials and Methods

We conducted a retrospective analysis of paranasal sinus cultures collected during
calendar years 2018 through 2019 within our healthcare system. This study was approved
by the Committee on Clinical Investigations of our institution (Mass General Brigham). All
sinus culture specimens collected at an outpatient otolaryngology visit corresponding to a
visit diagnosis of acute or chronic sinusitis were extracted from our clinical patient data
registry. Cultures were processed in CLIA-certified laboratories across our hospital system
and processed via standard institutional protocols.
All bacterial, fungal, and mycobacterial paranasal sinus cultures collected during
this time frame were included in analysis. Cultures were analyzed based on their culture
type (bacterial, fungal, mycobacterial) and culture result (no growth vs. named bacteria
or fungal/mycobacterial genera). The most common bacteria were then analyzed at the
species level as well.
Additional subgroup analyses were conducted for Staphylococcal species and in partic-
ular for Staphylococcus aureus. All Staphylococcus aureus cultures were sent for sensitivity
testing. In the interest of brevity, we excluded in our tables all bacteria constituting less than
0.5% of the subset (e.g., less than 0.5% of cultures resulting in a named bacterial genera).

3. Results
A total of 2302 cultures were collected during this time period. Of these, 2012 (87.4%)
were submitted as bacterial cultures, 287 (12.5%) were submitted as fungal cultures, and
3 (0.1%) were submitted as mycobacterial cultures (Table 1). As noted in Table 1, 61% of
bacterial cultures were positive for bacterial growth, whereas 39% exhibited no growth or
normal flora.
Sinusitis 2024, 8 15

Table 1. Sinus cultures by type and associated positivity rates.

Type of Culture and Isolate Type Cultures Results (n) Percentage of Culture Type
Bacterial (N = 2012)
Named bacteria identified (positive cultures) 1142 56.8%
Unnamed bacteria identified * 79 3.9%
No growth 183 9.1%
Normal sinus flora 592 29.4%
Normal oral flora 16 0.8%
Fungal (N = 287)
No growth 265 92.3%
Growth without genus result 19 6.6%
Growth with genus result 3 1.1%
Mycobacterial (N = 3)
No growth 3 100.0%
Description: Number of paranasal sinus cultures by media type and associated positivity rates. * Unnamed
includes Gram-negative rods, Gram-positive rods, etc.

Of the fungal cultures, 92% had no growth; of the fungal cultures with growth, genus
results were available for three (one each of Candida, Penicullum, and Scedosporium). All
three mycobacterial cultures were negative.
Of the positive bacterial cultures, there was a mix of cultures from bacteria that were
aerobic bacteria vs. facultative or obligate anaerobic bacteria: about half were aerobic (533,
47%), a third facultatively anaerobic (378, 33%), and then the remaining 231 (20%) obligate
anaerobes. These bacteria cultures consisted of slightly more Gram-positive bacteria than
Gram-negative (644 cultures of Gram-positive [56%] versus 498 Gram-negative [44%]
bacteria), and spanned 32 genera, as shown in Table 2.

Table 2. Frequency of genera of bacteria among positive cultures.

Bacteria Genus Number of Cultures Percentage

Staphylococcus 383 33.5% *
Propionibacterium 145 12.7%
Haemophilus 101 8.8%
Pseudomonas 94 8.2%
Streptococcus 83 7.3%
Klebsiella 45 3.9%
Prevotella 41 3.6%
Escherichia 35 3.1%
Moraxella 31 2.7%
Serratia 29 2.5%
Fusobacterium 26 2.3%
Enterobacter 24 2.1%
Stenotrophomonas 17 1.5%
Peptoniphilus/Peptostreptococcus 15 1.3%
Proteus 15 1.3%
Citrobacter 9 0.8%
Corynebacterium 8 0.8%
Acinetobacter 6 0.5%
Enterococcus 6 0.5%
Description: Number of paranasal sinus cultures of each bacterial genus. * Note these percentages use the total
number of cultures resulting in named bacteria genera (1142) as denominator.

Of the Staphylococcus cultures, 325 (85%) had speciated results, the vast majority of
which were Staphylococcus aureus (311 cultures, 96%), and only a minority of which (42,
[11%]) showed methicillin resistance (Table 3). Many of the other commonly found bacteria
(Propionbacterium, Haemophilus, Pseudomonas, Streptococcus, Klebsiella, Prevotella) did have
speciation results available and are shown in Table 4.
Sinusitis 2024, 8 16

Table 3. Frequency of Staphylococcus species within cultures (n = 383).

Staphylococcus Species Number of Cultures Percentage

Staphylococcus aureus—MSSA 311 81.2%
Staphylococcus aureus—MRSA 42 11.0%
Staphylococcus epidermidis 6 1.6%
Staphylococcus lugdenesis 3 0.8%
Staphylococcus intermedius 3 0.8%
Staphylococcus cohnii 1 0.3%
Staphylococcus saprophyticus 1 0.3%
Staphylococcus, not speciated 58 15.1%
Description: Staphylococcus sinus cultures of each species as well as those demonstrating methicillin resistance.
MSSA: methicillin-sensitive Staphylococcus aureus; MRSA: methicillin-resistant Staphylococcus aureus.

Table 4. Frequency of species within common non-Staphylococcus bacteria within cultures.

Bacteria Genus and Species Number of Cultures Percentage within Genus

Propionibacterium 145
Propionibacterium acnes 132 91.0%
Propionibacterium granulosum 13 9.0%
Haemophilus 101
Haemophilus influenzae 88 87.1%
Haemophilus, not speciated 13 12.8%
Pseudomonas 94
Pseudomonas aeruginosa 92 97.8%
Pseudomonas stutzeri 1 1.1%
Pseudomonas, not speciated 1 1.1%
Streptococcus 83
Streptococcus pneumoniae 46 55.4%
Streptococcus intermedius 2 2.2%
Streptococcus pyogenes 1 1.2%
Streptococcus, not speciated 35 42.2%
Klebsiella 45
Klebsiella oxytoca 22 48.9%
Klebsiella pneumonaie 21 46.7%
Klebsiella ozaenae 1 2.2%
Prevotella 41
Prevotella oralis 10 24.3%
Prevotella melaninogenica 7 17.1%
Prevotella loescheii 5 12.2%
Prevotella intermedia 4 9.8%
Prevotella oris 4 9.8%
Prevotella denticola 3 7.3%
Prevotella bivia 3 7.3%
Prevotella buccae 2 4.9%
Prevotella, not speciated 3 7.3%
Description: Number of paranasal sinus cultures of non-Staphylococcus named genera.

4. Discussion
Our study provides a contemporary detailed analysis of the sinus microbiology in a
broad population of patients across our healthcare system. The large majority of cultures
taken were bacterial (2012 of 2302, 87%), and importantly, more than half (57%) of these
bacterial cultures were positive, identifying a named genus as a target for potential medical
therapy and thus supporting the utility of paranasal sinus cultures as a means to guide
antibiosis. The use of antibiosis in CRS, however, is controversial: while prior guidelines
did recommend culture-directed antibiotic treatment for CRS exacerbations [14,15], newer
guidelines have taken a more nuanced approach, recommending antibiotics only in certain
circumstances, like the acute presentations of rhinosinusitis or chronic symptoms in a
patient with immunodeficiency [16]. Additionally, in patients who have undergone surgery,
infections after endoscopic sinus surgery have been shown to arise not from colonizing
Sinusitis 2024, 8 17

bacteria but instead from de novo bacteria, necessitating cultures to guide antibiosis [17].
In fact, there is evidence of improved patient quality of life after endoscopic surgery with
antibiosis directed by intraoperative cultures [18], although another study suggested these
cultures may not be cost effective, requiring a cost of USD 4300 for one culture to change
management for a patient [19].
The use of sinus cultures to guide antibiosis assumes a pathogen that can be targeted
medically can be identified with this assay. However, given that acute or chronic sinusitis
can in part be characterized not just by the introduction of external pathogens but also
the overgrowth of naturally occurring pathogens, in conjunction with possible immune
dysregulation, the interpretation of sinus culture results can be difficult, as these alone do
not holistically describe a patient’s sinus microbiological environment. Our data demon-
strate this diagnostic challenge: the most common bacteria identified—Staphylococcus (34%
of positive cultures), Propionibacterium (13%), and Haemophilus (9%), and Streptococcus
(4%)—can all inhabit the sinuses of healthy, asymptomatic individuals [6–9]. Unfortunately,
there currently are no readily available clinical diagnostic tools to determine if a patient’s
symptoms stem directly from the overgrowth of this one genus versus a more nuanced
disruption of this patient’s microbiota. In addition, even in cultures that exhibited bacteria
non-native to the sinuses, this assay does not differentiate between colonization versus
active infection, a critical nuance for patients with results of Pseudomonas [20] (8%) or
methicillin-resistant Staphylococcus aureus [21] (4%). There may be a role for more advanced
culture assays, such as DNA sequencing analysis (DNAsa) [22,23]. This method, in contrast
to standard cultures, does identify more organisms, and may be of utility in more complex
patients with recurrent or polymicrobial infections, or to predict response to surgical in-
terventions [13,24]; however, the cost-effectiveness of these more advanced techniques is
yet to be investigated. Our study did not utilize these molecular biological techniques for
our analysis given that our aim was to collect as many cultures as possible for a broader
understanding of paranasal sinus microbiology; however, for the analysis of a smaller
cohort of patients, these may provide a higher diagnostic yield.
Our study, on the other hand, does seem to negate the utility of fungal cultures, given
that the large majority (92%) resulted in no growth. Other studies have shown higher
positivity rates for fungal cultures, which likely vary with geography [25,26]. Otherwise,
our study largely echoes the microbiological findings of other studies in terms of the
most common bacteria found in the paranasal sinuses (see Table 3) [1,11], especially with
the finding of S. aureus being the most frequent bacteria found among Staphylococcus
cultures, although our study does find in particular a dominant presence of S. aureus versus
coagulase-negative Staphylococcus compared to other studies (see Table 4). Like other
studies, we found Staphylococcus and Propionibacterium to be the most common genera [11].
Given the size of our study, it is the first to provide a breakdown of this size at the species
level for multiple bacteria in the sinuses (Propionibacterium, Haemophilis, Pseudomonas,
Prevotella, etc.) and shows a broad range of bacteria, both in terms of genera identified in
Table 3, as well as across aerobic vs. anaerobic bacteria (see Table 2). The lack of positivity
in mycobacterial cultures is consistent with other studies given the rarity of this type of
infection in the sinuses [27].
Our study certainly has several limitations given it was performed in a single-hospital
system, and we did not include data that could have clarified the extent of symptoms that
the patients were experiencing at the time of culture collection as well as prior or during
antibiotic use. However, our goal was to broadly describe the contemporary microbiology
of the paranasal sinuses, and not to compare the flora of patients with certain diagnoses or
symptoms with that of controls. We also did not differentiate patients into those with acute
or chronic sinusitis—again to more broadly comment on paranasal sinus microbiology;
investigating these patient subsets individually may more specifically identify short- versus
long-term microbiological disruptions and should be the focus of future studies. Moreover,
some patients in our dataset may have more than one culture and thus be over-represented,
and there may be heterogeneity in culture collection techniques across providers. We did
Sinusitis 2024, 8 18

not investigate the specific indication for different types of cultures (e.g., mycobacterial). We
also did not examine antibiotic resistance among bacteria outside of MRSA versus MSSA
species. We are pursuing an additional study to assess time-dependent changes in microbial
resistance in CRS. Additionally, these data were collected before the COVID-19 pandemic,
which may have changed the microbiology of some patients’ sinuses both acutely as well
as in the long term [28].

5. Conclusions
Our study analyzed over 2000 sinus cultures collected across a healthcare system in a
calendar year. The large majority of these were bacterial cultures, over half of which showed
positive results, identifying a named bacterial genus that could be targeted with antibiosis.
The most commonly identified bacteria in the cultures were Staphylococcus, Propionbacterium,
Haemophilus, Pseudomonas, and Streptococcus. The most common species of Staphylococcus
bacteria was S. aureus, with only a small portion (11%) of the cultures showing methicillin
resistance. The large majority of fungal cultures resulted in no growth, suggesting their
lack of utility. While our study shows that sinus cultures can identify bacterial genera,
it is controversial whether antibiosis directed at these bacteria leads to the symptomatic
improvement or restoration of microbiological homeostasis in the paranasal sinuses.

Author Contributions: All authors participated in the conceptualization, methodology, formal data
curation and analysis, and original draft writing. All authors participated in review and editing of
the manuscript. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: This study was approved by the IRB of our institution, Mass
General Brigham, under protocol 2004P000887.
Informed Consent Statement: Written consent was not required nor obtained given deidentified
patient data was utilized for the study.
Data Availability Statement: The data used in the study is not publicly available given associated
with our institution.
Conflicts of Interest: The authors declare no conflicts of interest.

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