The Laryngoscope

C 2017 The American Laryngological,

V
Rhinological and Otological Society, Inc.

MRSA Chronic Bacterial Laryngitis: A Growing Problem

Patrick S. Carpenter, MD ; Katherine A. Kendall, MD

Objectives: Chronic bacterial infection of the larynx is characterized by long-standing hoarseness and exudative laryngi-
tis. Prolonged antibiotic therapy is required to clear the infection, and methicillin-resistant staphylococcus aureus (MRSA)
may be the responsible pathogen. The objective of this study was to describe the presentation, comorbidities, treatment
response, and underlying etiology— including the incidence of MRSA—in our patient population with chronic bacterial
laryngitis.
Methods: A review of patients with a diagnosis of chronic bacterial laryngitis from 2012 to 2016 was performed. Diag-
nosis of chronic bacterial laryngitis was based on clinical history and findings on flexible laryngoscopy. In selected cases, the
diagnosis of bacterial laryngitis was confirmed by operative biopsy. Information regarding clinical presentation and course
was collected.
Results: Twenty-eight patients were included in the study. Twenty-three were treated empirically with Amoxicillin-clav-
ulonic acid for a minimum of 21 days. Twelve of the 23 (52%) had recurrence or nonresolution of infection. Seven of the 12
nonresponders (58%) were found to have MRSA by laryngeal tissue culture. Five patients were treated initially with Sulfa-
methoxazole and trimethoprim, and all resolved the infection without the need for further treatment. There was a nonstatisti-
cally significant increase in smoking and reflux in the MRSA population compared to the non-MRSA group.
Conclusion: MRSA infection was documented in 30% of patients overall with chronic bacterial laryngitis. Based on the
results of the study, a treatment algorithm for management of this unusual patient population is suggested.
Key Words: Chronic, bacterial, laryngitis, methicillin, staph aureus, MSSA, MRSA.
Level of Evidence: 4.
Laryngoscope, 00:000–000, 2017

INTRODUCTION for chronic bacterial laryngitis.3,9 MRSA chronic laryngitis

Chronic laryngitis, or inflammation of the larynx
lasting for greater than 3 weeks, is a complex but
increasingly common problem. Bacterial infection
remains an underrecognized but clinically significant eti-
ology of chronic laryngitis.1 Chronic bacterial laryngitis
can be diagnosed in the setting of chronic dysphonia
with or without dysphagia. Laryngoscopy reveals ery-
thematous and edematous vocal cords and exudative
crusting and purulence (Fig. 1).2 Treatment usually
requires extended targeted antibiotic therapy.3–5 Like all
open-ended passageways in the body, the larynx has
been shown to have normal colonization with bacteria. It
is a disruption of this homeostatic microbiome that is
theorized to contribute strongly to the development of
chronic invasive bacterial laryngitis.6–8
Methicillin-resistant staphylococcus aureus (MRSA)
has been increasingly identified as a pathogen responsible
From the Department of Surgery Division of Otolaryngology–Head
and Neck Surgery, University of Utah Health System (P.C., K.K.), Salt
Lake City, Utah, U.S.A.
Editor’s Note: This Manuscript was accepted for publication on
September 10, 2017.
Presented as a poster presentation at the 120th Annual Meeting
of the Combined Sections Meeting of The Triological Society, San Diego,
California, U.S.A., April 28–29, 2017.
The authors have no funding, financial relationships, or conflicts
of interest to disclose.
Send correspondence to Patrick S. Carpenter, MD, 50 North Medi-
cal Drive, SOM 3C120, Salt Lake City, Utah 84132. E-mail: patrick.car-
penter@hsc.utah.edu
DOI: 10.1002/lary.26955
is difficult to distinguish from non-MRSA chronic bacterial
laryngitis on physical examination4 (Fig. (1 and 2)). Unlike
typical nosocomial MRSA infections, it is unknown if
laryngeal MRSA infections are linked to any specific
patient risk factors.4,5 Previous work has shown that the
diagnosis of MRSA laryngitis can be confirmed with in-
office or operating room (OR) biopsy and culture of the
true vocal fold tissue.4,10 Currently, only eight cases of
MRSA laryngitis have been reported in the literature, but
evidence suggests an increasing incidence.3,4,10,11
Our experience in the voice disorders clinic at a ter-
tiary care hospital is that the symptoms of laryngeal
MRSA infections are subtle in comparison to typical
MRSA infections seen elsewhere in the body.12 The
objective of the study at hand was to assess the inci-
dence in MRSA laryngitis in our patient population with
chronic bacterial laryngitis, evaluate potential risk fac-
tors, and help create a treatment algorithm that may be
used in the management of this growing problem.
MATERIALS AND METHODS
A retrospective review was conducted assessing adult
patients associated with the diagnosis of chronic bacterial laryn-
gitis (International Classification of Diseases, 10th Revision
[ICD-10] J37.0, ICD-9 476.0) seen in the voice disorders clinic
from 2012 to 2016. The study protocol and parameters were
approved by the University of Utah Institutional Review Board
prior to analysis of any patient data. All patients included in
the study had symptoms of dysphonia and persistent voice
changes for a minimum of 3 weeks prior to being evaluated.

Laryngoscope 00: Month 2017 Carpenter and Kendall: MRSA Chronic Bacterial Laryngitis
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Fig. 1. MRSA laryngitis flexible laryngoscopy findings before and
after treatment. Pretreatment MRSA laryngitis with classic vocal
fold irregularity and crusty purulence. Posttreatment resolution of
laryngitis after 9 weeks of Bactrim.
MRSA 5 methicillin-resistant staphylococcus aureus. [Color figure
can be viewed in the online issue, which is available at www.laryn-
goscope.com.]
Full head and neck evaluation in the clinic on each patient
included a flexible laryngoscopy exam. Physical exam findings
of vocal cord crusting, erythema of cords, and edema of cords
were considered suggestive of chronic bacterial laryngitis, and
patients were thus included in the study. All patients were fol-
lowed for a minimum of 30 days. Items reviewed for each
patient included documentation from history and physical
examination, culture results, biopsy results, operative reports,
and recorded flexible endoscopy exams.
Patients were initially treated empirically with either
amoxicillin/clavulanic acid (Augmentin) or trimethoprim/sulfa
(Bactrim). Follow-up visits were scheduled 3 to 4 weeks after
initiation of oral antibiotic therapy. Patients were judged to
have improvement after treatment based on normalization of
vocal fold characteristics on flexible endoscopic imaging, com-
bined with subjective improvement per patient report. Individu-
als who improved after treatment with Augmentin were
deemed to be MRSA-negative patients. If patients continued to
be symptomatic and had little improvement in laryngeal find-
ings after a 3-week course of empiric antibiotic therapy, biopsies
Fig. 2. Comparison in flexible laryngoscopy exams between
MRSA and non-MRSA chronic bacterial laryngitis. No significant
physical exam differences between MRSA (A) and non-MRSA (B)
bacterial chronic laryngitis. Both exams consistent with edema-
tous vocal cords, crusting, and purulence.
MRSA 5 methicillin-resistant staphylococcus aureus. [Color figure
can be viewed in the online issue, which is available at www.laryn-
goscope.com.]
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were obtained in the OR using microlaryngeal forceps. Tissue
samples were sent for routine culture and sensitivities, gram
stain, and pathologic analysis. Oral antibiotic therapy was initi-
ated based on results of the culture and sensitivities. Follow-up
was continued at 1-month intervals. Response to treatment was
determined by both improvement of dysphonia and resolution of
abnormality on flexible laryngoscopy.
RESULTS
Patient Demographics
A total of 28 patients met the inclusion criteria for
chronic bacterial laryngitis. Nine patients were female,
and 21 were male. Ages ranged from 33 to 69 years old.
Eight patients in the study had diabetes type 2 treated
with either oral medications or insulin at the time of
presentation. Twenty (71%) patients were being treated
with a proton pump inhibitor (PPI) for reflux. Only one
patient had a recent hospitalization. There were 17
patients actively smoking at first office visit, and 16 who
drank alcohol regularly. Only nine patients had been
treated with antibiotics prior to presentation to the lar-
yngologist. The average duration of voice change prior to
presentation in the voice clinic was 82 days (range 10–
220 days) (Table I).
Diagnostic and Treatment Results
Of the 28 patients who met criteria for chronic bacte-
rial laryngitis, 23 of the patients were initially treated
with amoxicillin/clavulanic acid (high dose typically Aug-
mentin 875 mg/125 mg, one tab twice daily for 30 days).
Five individuals were prescribed sulfamethaxazole/tri-
methoprim at the first clinic visit (high dose, typically
Bactrim DS, 800 mg/160 mg two tabs twice daily for
30 days). Of the 23 patients treated with Augmentin, 11
individuals demonstrated significant improvement or
complete resolution of symptoms and findings at their
follow-up appointment 1 month later. In this cohort of
patients, the median duration of treatment until complete
resolution of laryngitis was 40 days (range: 21–90 days).
TABLE I.
General Patient Characteristics, Demographics, and Common
Comorbidities
Number of patients 28
Age (median) 46 years
Sex (percent female) 61%
Duration of dysphonia prior 82 days (range 10–220 days)
to ENT evaluation
Diabetes 29%
PPI Using 71%
Smoking 61%
Nasopharyngeal flexible Erythema, irregular vocal fold
laryngoscopy exam findings margins, dry crusting
PPI usage criteria was met only if patient currently taking medicine
at time of exam. Smoking was defined as having > 10-pack year history
and currently smoking in past 6 months. Nasopharyngeal flexible laryngos-
copy exams were similar between groups
ENT 5ear, nose, throat; PPI 5 proton pump inhibitor.
Carpenter and Kendall: MRSA Chronic Bacterial Laryngitis
 TABLE II.
MRSA-Positive Specific Patient Characteristics
Nasopharyngeal Flexible
Patient Age Gender Diabetes PPI-Positive Smoking Duration SX Laryngoscopy Findings

1 59 M No Yes Yes 12 mo *Leukoplakia, erythema, VF crusting

2 50 F No Yes Yes 1 mo Irregular VF, crusting, erythema
3 38 F No Yes Yes 5 mo Irregular VF, crusting, erythema
4 45 M No Yes Yes 1 mo Edematous and irregular VF
5 58 M No Yes Yes 6 mo Irregular crusting VF, erythema
6 51 M No Yes Yes 3 mo VF edema, dried crusting
7 32 F No No No 1 mo VF erythema, crusting, irregular margins

Characteristics of chronic bacterial laryngitis patients who tested positive for MRSA.
*Patient had in-situ carcinoma, in addition to MRSA.
F 5 female; M 5 male; mo 5 months; MRSA 5 methicillin-resistant staphylococcus aureus; SX 5 symptoms; VF 5 vocal fold.

Twelve individuals initially treated with Augmentin
did not show any evidence of improvement at follow-up
appointment at 1 month (52%). Ten of those patients
were then taken to the OR for microlaryngoscopy and
biopsy of vocal folds. Seven of the biopsies were positive
for MRSA; two biopsies showed methicillin-sensitive
staph aureus (MSSA); and one biopsy showed inflamma-
tory tissue with anaerobic bacteria. All patients who
underwent biopsy were treated with high-dose oral Bac-
trim or doxycycline (one patient had end-stage renal dis-
ease, a contraindication for Bactrim treatment). The
median duration of treatment until resolution of signs
and symptoms was 69 days in this group (range 42–112
days). Two individuals who failed Augmentin at 1 month
declined to undergo a biopsy. These individuals were
treated empirically with extended Bactrim therapy, as
above, and both achieved resolution of laryngitis (42 and
60 days, respectively).
The five patients who were treated initially with
empiric Bactrim all responded to treatment and did not
require operative biopsy. They achieved resolution of
symptoms at a median of 42 days on antibiotics.
The general comorbidities between MRSA-positive
group and MRSA-negative group were examined. There
was a higher prevalence of males in the MRSA-positive
group when compared to MRSA-negative group. There
was an increased odds ratio (6.85) of being a smoker in
the MRSA-positive group; however, it was not statisti-
cally significant. Also, there was an increased odds ratio
(3) of active PPI use in the MRSA-positive group; how-
ever, this also was not statistically significant (Table II
and Table III).
DISCUSSION
It has been over 200 years since one of the first
published descriptions of laryngitis and attempts at
treatment.13 Most clinical cases of infectious laryngitis
are due to acute viral infection and run a relatively
short clinical course without the need for medical inter-
vention. Prolonged or chronic laryngitis (greater than 3
weeks duration) is most commonly attributed to gastro-
esophageal reflux disease.14 Increasingly, however, pro-
longed dysphonia without response to treatment with
antireflux medications may be recognized as due to
invasive bacterial laryngitis.3,4 The hallmarks of the con-
dition are exudates, erythema, and swelling of the vocal
folds and/or supraglottic larynx on physical examination
(Fig. 1). There was little difference in the physical exam
findings between MRSA-positive and MRSA-negative
patients in our cohort (Fig. 2).
This current study describes the clinical course of
patients with chronic bacterial laryngitis seen at a ter-
tiary care center and considers possible risk factors for
MRSA as the infectious etiology. Although only eight
prior reports of MRSA laryngitis exist in the literature,
this study increases the number of described biopsy-
proven MRSA laryngitis cases by seven, for an overall
incidence of biopsy-proven MRSA in this study of 30%.
Furthermore, the actual incidence of MRSA in the study
population may have been higher because eight of the
28 patients in the study (25%) were treated empirically
with trimethoprim/sulfa, with complete response, and
also may have had MRSA.
At the outset of the study period, empiric treatment
with Augmentin was prescribed given that the common
sinus and ear pathogens are Streptococcus pneumoniae,
Haemophilus influenzae, and Moraxella catarrhalis.15,16
Once it became clear that over half the patients did not
respond to this empiric treatment, biopsy and culture
were performed and demonstrated a 30% overall inci-
dence of MRSA and a 70% incidence of MRSA in nonres-
ponding patients. These results prompted a shift in the
TABLE III.
Comparison of Characteristics Between MRSA Chronic Laryngitis
and Non-MRSA Chronic Laryngitis
MRSA- Non- Odds Confidence
Positive MRSA Ratio Interval
Patients 7 14
Age (median) 46 49
Sex (% female) 43% 58%
Smoking 6 (86%) 6 (42%) 6.85 4.27, 0.38
PPI Use 6 (86%) 8 (57%) 3 2.66, 0.55
Patients treated empirically with Bactrim (N 5 5) were excluded from
both MRSA-positive and MRSA-negative groups. The individuals who failed
initial treatment but declined operative biopsy were excluded from both
groups (n 5 2). Confidence intervals were calculated using a P < 0.05.
MRSA 5 methicillin-resistant staphylococcus aureus.

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Fig. 3. Proposed treatment algorithm for chronic bacterial laryngi-
tis patients. Flex scope – flexible nasopharyngeal laryngoscopy
findings are 5 vocal fold crusting, irregular vocal fold margins, ery-
thema of vocal fold, and edema of vocal fold.
Abx 5 antibiotics; CBL 5 chronic bacterial laryngitis; PPI 5 proton
pump inhibitor; RF 5 risk factor; Tx 5 treatment. [Color figure can
be viewed in the online issue, which is available at www.laryngo-
scope.com.]
empiric approach to treatment at the outset prescribing
trimethoprim/sulfa, resulting in an improved overall ini-
tial response rate to empiric therapy (100% of 7 patients)
(Fig. 3).
Other studies of chronic bacterial laryngitis have
shown that responsible pathogens may be similar to
deep neck space infections, with Staphylococcus aureus
predominating.4,10,17 Our data confirms this finding;
however, in contrast to those previous studies, this study
found an increased prevalence of MRSA in the patient
population. Seventy percent of patients who underwent
biopsy (n 5 10) for refractory chronic laryngitis were pos-
itive for MRSA. Patients with MRSA were more likely to
be male, smokers, and actively taking reflux medication,
although these factors were not statistically significant.
It is possible that other geographical and environmental
differences play a role in increasing the incidence of
MRSA in this outpatient population. In addition, all
patients with biopsy-proven MRSA had undergone prior
empiric antibiotic treatment that likely impacted the
makeup of the infectious flora at the time of culture.5
Otherwise, the study patient population did not have
any of the previously established risk factors for MRSA
infection.12 In particular, Shah et. al. suggested that a
history of diabetes may predispose to MRSA laryngitis.
Although eight of our chronic laryngitis patients had
type 2 diabetes, none of our MRSA-positive patients had
a history of diabetes.4 Thus, our study was unable to
identify specific patient factors leading to the conditions
necessary for disruption of the normal laryngeal homeo-
stasis and allowing for invasive infection, especially
MRSA infection.
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4
Based on the results of this study, a protocol for
treatment of exudative laryngitis due to bacterial infection
is proposed (Fig. 3). Clinical differentiation of patients
with MRSA-positive laryngitis from those infected with
other organisms is difficult. Other authors have advocated
for in-office laryngeal swabs for culture prior to initiation
of antibiotic treatment.4 Further study is needed to deter-
mine accuracy of this technique relative to tissue biopsy
in the OR.18 Our treatment regimen allows for 1 month of
empiric treatment with trimethoprim/sulfa as the initial
antibiotic choice, and if failed, operative biopsy for tissue
culture and antibiotic sensitivities. Trimethoprim/sulfa is
generally well tolerated and inexpensive. In our subse-
quent experience, initial treatment of the condition with
antibiotics effective against MRSA has had a 100% suc-
cess rate without the need for biopsy.
Prolonged treatment is generally needed to clear
the infection.3–5 Patients are counseled at the initiation
of therapy that they will likely require 6 to 9 weeks of
treatment. Reasons for this prolonged treatment require-
ment are not well established. Possible factors include a
relatively low vascularity of the laryngeal tissues, espe-
cially the lamina propria, patient factors predisposing to
infection, and increased virulence of involved organisms.
Limitations with our study should not be over-
looked. Although this is the largest study population
described to date, the retrospective nature of the review
and the small study population limit the ability to inter-
pret risk factors with much significance. Assumptions
regarding infectious organisms were also made, and not
all patients had confirmation with operative biopsy—
leading to a possible underestimation of the incidence of
MRSA in the population. Further research should con-
tinue to expand upon risk factors and other clinical fea-
tures that may help guide the otolaryngologist to
diagnosis and treatment of this disease.
CONCLUSION
MRSA chronic laryngitis may be more common
than previously thought. It is reasonable to treat high-
risk patients with MRSA effective antibiotics empirically
given the high prevalence in our population. Curative
treatment requires extended high-dose targeted antibi-
otic treatment. If there is no response to treatment at 1
month, we recommend operative biopsy for confirmation
of infectious agent and sensitivities.
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