10.14639/0392-100X-N1985
Objective. This study aims to assess the frequency, bacteriology, biofilm characteristics and management of skin flap infection (SFI) following cochlear implantation (CI). Methods. The study enrolled 1,251 patients receiving CI in the First Affiliated Hospital of Fujian Medical University between August 2001 and March 2021. Scanning electron microscopy (SEM) was utilised to characterise the aetiology of infection. A proposed classification system was applied to optimise treatments for post-operative skin flap infection. Results. After CI, SFI was reported in 16 patients (1.28%) and occurred more frequently in patients under 6 years of age. Of all SFI cases Staphylococcus aureus was the most common pathogen for flap infection, with 8 cases (50%) and bacterial biofilm was evident within the jelly-like substance on the surface of implanted devices in SFI patients. A two-stage classification was proposed to optimise the treatment schemes. Conservative therapy was recommended for stage I cases and surgical treatment for stage II patients. Conclusions. Paediatric patients are more susceptible to SFI after CI, which may be attributed to the formation of bacterial biofilm. The proposed classification can facilitate the management of SFI.
text/xml
1827-675X
1985
en
Chang Lin
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
management
The biofilm characteristics and management of skin flap infection following cochlear implantation
Text.Serial.Journal
https://www.actaitalica.it/
42
Otology
2022-09-30
2021-12-28
2022-10-12
2022-10-12
372-379
1
Chang Lin
2022/09/30
10.14639/0392-100X-N1985
372
Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China; * X, Chen and Y. Chen contributed equally to this work as first author.
1827-675X
management
en
379
The biofilm characteristics and management of skin flap infection following cochlear implantation
https://www.actaitalica.it/article/download/1985/853
42
ACTA OTORHINOLARYNGOLOGICA ITALICA 2022;42:372-379; doi: 10.14639/0392-100X-N1985




Otology


The biofilm characteristics and management of skin
flap infection following cochlear implantation
Caratteristiche del biofilm e gestione dell’infezione da flap cutaneo dopo impianto
cocleare
Xihang Chen*, Yuqing Chen*, Rong Zhang, Shengnan Ye, Zhongyang Lin, Shengqing Nian, Chang Lin
Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
*
  X, Chen and Y. Chen contributed equally to this work as first author.


SUMMARY
Objective. This study aims to assess the frequency, bacteriology, biofilm characteristics and
management of skin flap infection (SFI) following cochlear implantation (CI).
Methods. The study enrolled 1,251 patients receiving CI in the First Affiliated Hospital
of Fujian Medical University between August 2001 and March 2021. Scanning electron
microscopy (SEM) was utilised to characterise the aetiology of infection. A proposed
classification system was applied to optimise treatments for post-operative skin flap in-
fection.
Results. After CI, SFI was reported in 16 patients (1.28%) and occurred more frequently in
patients under 6 years of age. Of all SFI cases Staphylococcus aureus was the most common
pathogen for flap infection, with 8 cases (50%) and bacterial biofilm was evident within
the jelly-like substance on the surface of implanted devices in SFI patients. A two-stage
classification was proposed to optimise the treatment schemes. Conservative therapy was
recommended for stage I cases and surgical treatment for stage II patients.
Conclusions. Paediatric patients are more susceptible to SFI after CI, which may be at-
tributed to the formation of bacterial biofilm. The proposed classification can facilitate the
management of SFI.                                                                                    Received: December 25, 2021
                                                                                                      Accepted: April 29, 2022
KEY WORDS: cochlear implant, flap infection, biofilm, scanning electron microscope,
management                                                                                            Correspondence
                                                                                                      Chang Lin
                                                                                                      Department of Otorhinolaryngology, Head and
RIASSUNTO                                                                                             Neck Surgery of the First Affiliated Hospital of
Obiettivo. Questo studio mira a valutare la frequenza, la batteriologia, le caratteristiche           Fujian Medical University, 20 Cha Zhong Road,
del biofilm e la gestione dell’infezione del lembo cutaneo di ricostruzione (SFI) dopo                Taijiang District, Fuzhou, Fujian, China
l’impianto cocleare (CI).                                                                             Tel./Fax +86 18959166588
Metodi. Lo studio ha arruolato 1.251 pazienti che hanno ricevuto CI nel First Affiliated              E-mail: linc301@yahoo.com
Hospital della Fujian Medical University tra Agosto 2001 e Marzo 2021. Questo studio
ha utilizzato la microscopia elettronica a scansione (SEM) per caratterizzare l’eziologia               How to cite this article: Chen X, Chen Y,
dell’infezione. È stata proposta una classificazione allo scopo di ottimizzare la terapia               Zhang R, et al. The biofilm characteristics
dell’infezione post operatoria del lembo cutaneo.                                                       and management of skin flap infection fol-
Risultati. Dopo CI, SFI è stata segnalata in 16 pazienti (1,28%) e si è verificata più                  lowing cochlear implantation. Acta Otorhi-
frequentemente in pazienti di età inferiore ai 6 anni. Lo studio ha rivelato che lo                     nolaryngol Ital 2022;42:372-379. https://doi.
Staphylococcus aureus era l’agente patogeno più comune per l’infezione del lembo, con 8                 org/10.14639/0392-100X-N1985
casi registrati, equivalenti al 50% di tutti i casi di SFI. D’altra parte, il biofilm batterico era
evidente all’interno della sostanza gelatinosa sulla superficie dei dispositivi impiantati nei        © Società Italiana di Otorinolaringoiatria
                                                                                                      e Chirurgia Cervico-Facciale
pazienti con SFI. La classificazione proposta per ottimizzare gli schemi terapeutici prevede
due stadi. La terapia conservativa è raccomandata per i casi di stadio I e il trattamento
                                                                                                                     OPEN ACCESS
chirurgico per i pazienti di stadio II.
Conclusioni. I pazienti pediatrici sono più suscettibili a SFI dopo CI. La formazione di              This is an open access article distributed in accordance with
                                                                                                      the CC-BY-NC-ND (Creative Commons Attribution-Non-
biofilm batterico può essere la causa di SFI. La classificazione proposta può facilitare la           Commercial-NoDerivatives 4.0 International) license. The
gestione degli SFI.                                                                                   article can be used by giving appropriate credit and mentio-
                                                                                                      ning the license, but only for non-commercial purposes and
PAROLE CHIAVE: impianto cocleare, infezione del lembo, biofilm, microscopio elettronico               only in the original version. For further information: https://
a scansione, gestione                                                                                 creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                              Management of biofilm-related skin flap infections following cochlear implantation




Introduction                                                        and inner ears, middle ear mastoiditis, tympanic effusion,
                                                                    or other infections before operation. A brain MRI was con-
For decades, cochlear implantation (CI) has been consid-
                                                                    ducted to reveal potential white matter lesions, and CI was
ered as best therapeutic method for hearing rehabilitation
                                                                    considered for cases with mild and non-progressive white
of patients with severe or profound sensorineural hearing
                                                                    matter lesions. In this study, 72-hour intravenous ceftri-
loss 1,2. Thanks to the advance and popularisation of new-
                                                                    axone was administered for prophylactic anti-infection to
born hearing screening and the revolutionary progress of
                                                                    both children and adults during the first and revision sur-
CI surgical technique, bilateral severe or profound senso-
                                                                    gery. Meanwhile, intravenous clindamycin was used as
rineural hearing loss can be detected earlier, and postoper-
                                                                    alternative antibiotic prophylaxis for patients with penicil-
ative complications have been significantly decreased. To
                                                                    lin allergy. Lastly, the researchers routinely administered
date, CI surgery has been regarded as a safe procedure for
                                                                    amoxicillin-clavulanate or cefaclor orally in outpatients to
auditory rehabilitation, but like any other procedure, com-
                                                                    control infection for seven days. For patients who suffered
plications still may arise. The procedure of implanting the
                                                                    from severe swelling and pain, intravenous antibiotics were
internal device of the cochlear implant is not entirely risk-
                                                                    prescribed for one week, if the patient responded well to
free and may result in complications that require corrective
                                                                    the antibiotic treatment.
surgery. Among the recognised postoperative complica-
                                                                    Patients who developed postoperative infection received
tions of the cochlear implant procedure is skin flap infec-
                                                                    immediate conservative treatment or surgical intervention
tion (SFI), which remains a substantial concern that may
                                                                    when the conservative treatment was ineffective. The con-
induce significant morbidity 2,3.
                                                                    servative treatment was considered ineffective in the fol-
Generally, postoperative CI infections have been classified
                                                                    lowing conditions: (1) post-CI patients with SFI still man-
into minor or major categories and divided into early or de-
                                                                    ifested symptoms such as redness, swelling and pus in the
layed infections according to duration 4,5. Skin flap infection
                                                                    exact location, and accompanied with severe pain, along
(SFI), despite rigorous medical and surgical endeavours,
remains one of the most challenging and devastating modes           with elevated white blood count, C-reactive protein (CRP)
of failure following cochlear implants, which is difficult for      and procalcitonin (PCT), even after receiving treatment;
otologists to predict and which may lead to the removal of          (2) post-CI patients with SFI suffered from refractory im-
the implanted device. Although SFI has been considered as           plant extrusion, thus requiring further surgical treatment;
a common complication following cochlear implantation,              and (3) exposed implant with skin necrosis.
only a few studies have compared the efficacy of conser-
vative and surgical treatments of SFI to date. The current          Conservative treatments
study focused on bacterial biofilm formation-related in-            The researchers routinely administered amoxicillin-clavu-
fections in cochlear implantation, aiming to investigate the        lanate or cefaclor for outpatients to control infection for
frequency and efficacy of management for postoperative              seven days. However, if the patient suffered from severe
infections and to identify the potential causes of the refrac-      swelling and pain, intravenous antibiotics were prescribed
tory SFI. Moreover, this study proposed a system for SFI            for one week. Patients with postoperative infection were
classification that can serve as a framework in determining         treated immediately with ceftriaxone sodium, which can
the most adequate type of treatment for patients.                   penetrate the blood-brain barrier and achieve concentra-
                                                                    tions in the central neural system adequate for the poten-
                                                                    tial infecting pathogen. If the patient suffered from SFI by
Materials and methods                                               methicillin-resistant Staphylococcus aureus (MRSA), the
This study retrospectively reviewed the medical records of          the anti-infection protocol was adjusted according to the re-
1,251 patients who underwent CI to treat profound hearing           sults of pathogen culture and sensitivity analysis results for
loss at the First Affiliated Hospital of Fujian Medical Uni-        one week after revision CI. The pus was drained by needle
versity between August 2001 and March 2021.                         aspiration when the formation was localised in subcutane-
All patients suffered from severe or profound bilateral sen-        ous tissue and sent to pathogen culture for precise antibiot-
sorineural hearing loss (HL, defined as hearing threshold           ic adjustment. A mastoid pressure bandage was applied for
> 70 dB). Before the initial CI, assessments were conduct-          one week after the needle aspiration.
ed for acoustic impedance, auditory brainstem response,
distortion product otoacoustic emissions, transient evoked          Surgical treatments
otoacoustic emissions and steady-state auditory response            Patients unresponsive to conservative treatment received
was conducted. Middle ear high-resolution CT and inner              revision surgery or re-implantation surgery if the revision
ear MRI were performed to rule out deformity in middle              surgery failed. The former consisted of wound debridement,



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X. Chen et al.




cleaning up granulation tissue in the bone groove, rinsing de-   years (Tab. II). The onset of SFI symptoms ranged from
vices with 3% hydrogen peroxide, normal saline and 1% io-        20 days to 3 years after the implantation, affecting 14 right
dophor repeatedly, before covering the groove with suitable      ears (87.5%), 1 left ear (6.25%) and 1 bilaterally (6.25%).
anterosuperior temporal muscle. The latter involved explant-     Gender was not significantly different (p > 0.05). Laterality
ing receiver/stimulator but saving the electrode in cochlear     showed a significant difference (p < 0.05), but paired sta-
to avoid fibrosis and cochlear ossification, and implanting a    tistics revealed no significance (p > 0.05 for all three paired
new implant in the contralateral side. A 3-day administration    statistics). Three post-CI children (3/16) encountered mild
of ceftriaxone followed both surgical treatments.                skin injury after the first CI, and two patients reported sen-
                                                                 sitivity to cicatricial diathesis.
Scanning electron microscopy
The jelly-like biofilm on the surface of the receiver/stim-      Clinical management
ulator was rinsed with phosphate-buffered saline (PBS) 3         Among the 16 children, 3 were cured by conservative meth-
times (1 minute per time), and soaked in 1% osmic acid           ods (3/16, 18.75%) and 13 by surgery (13/16, 81.25%). In
solution at < 4°C for two hours. Next, samples were sequen-      the surgery group, 3 patients were cured by revision surgery
tially dehydrated in 30, 50, 70, 85, 95 and 100% ethanol for     (3/13, 23.08%) (p > 0.05) and 10 received re-implantation sur-
15 minutes each, respectively. After the CO2 critical dry-       gery after initial revision surgery (10/13, 76.92%) (p < 0.05).
point and correcting the position and orientation, samples       Among all infectious symptoms (Tab. III), skin redness was
were placed on the platform for sputter-coated with gold in      reported in 2 patients (2/16, 12.5%), in which 1 was cured
a vacuum condition and examined in a high vacuum of 20           by conservative methods and the other by revision surgery.
kv under a scanning electron microscope (SEM; American           Subcutaneous pus formation was found in 4 patients (4/16,
FEI company, model Quanta 450). Multiple bacterial bio-          25%), in which two were cured by conservative methods
films in the SEM areas of each specimen were observed by         and two by re-implantation surgery. Pus was managed by
multiple magnifications (50-10,000 times).                       needle aspiration in 7 patients (7/16, 43.75%), one by revi-
The formation of bacterial biofilms was diagnosed when           sion surgery (1/7, 14.3%) and 6 by re-implantation surgery
images met three criteria: (1) dense accumulation of bacte-      (6/7, 85.7%). The implant was exposed in 3 patients and
rial cells; (2) he presence of a polysaccharide matrix around    rescued by re-implantation surgery (100%).
bacterial cells; and (3) firm surface binding 6.                 The results showed no significant differences in therapeu-
                                                                 tic efficacy between conservative and surgical treatments
Statistical analysis                                             (p > 0.05) in skin redness or subcutaneous pus formation,
The two-sided statistical analyses in this study were per-       but a noticeable significance was seen for punctured pus
formed using SPSS software (version 26.0; SPSS Inc., Chi-        when re-implantation was compared with either revision
cago, IL, USA). Differences among categorical variables          surgery or conservative treatment (p < 0.05, respectively).
were assessed by Fisher’s test as appropriate, including         The effectiveness of revision surgery was not statistically
sex, age, implant side, different regimens and outcomes.         different in any symptom groups (p > 0.05) (Fig. 1). All
P-values of less than 0.05 indicated statistical significance.   patients received long-term follow-up, the mean duration
Lastly, this study employed a 95% confidence interval.           of which was 5.1 ± 3.4 years after final treatment.

                                                                 Scanning electron microscopy
Results
                                                                 On the images by scanning electron microscopy (Fig. 2),
Demographic and clinical characteristics of patients             microorganisms consistent with Staphylococcus aureus or
receiving cochlear implantations                                 Staphylococcus epidermidis and exopolymeric matrix were
A total of 1,251 CI cases (739 males, 59.05% and 512 fe-         found over the surface of the stimulator-receiver, but not
males, 40.95%) were enrolled (Tab. I), with CI performed         on the electrode array. A large mesh was observed in the
on 898 right ears (71.79%), 337 left ears (26.90%), and 16       middle of the grid.
bilateral ears (1.28%); surgery age ranged from 10 months
to 63 years old, with a mean age of 7.3 years and a median       Histopathological examination
age of 3.5 years. All cases were operated by the same senior     Granulation tissue appeared in the bone groove, and foam-
surgeon between August 2001 and March 2021.                      like tissue cells surrounding the receiver/stimulator were
A total of 16 SFI patients were reported in the entire CI        visualised in granulation tissue by haematoxylin-eosin
patient cohort (1.28%, 8 males and 8 females), who were          staining, indicating that the symptoms of SFI cases can be
all under 6 years of age (p < 0.05), with a mean age of 3.09     attributed to a chronic inflammatory reaction (Fig. 2).



374
                                                                                   Management of biofilm-related skin flap infections following cochlear implantation




Table I. Demographic and clinical characteristics of the 1,251 patients with cochlear implants.
                                               Infection                        P-value                                     No infection                        Total
                                                n = 16                         (95% CI)                                      n = 1235                         n = 1251
 Gender                                                                                 0.457
                                                                                    (0.257, 1.849)
   Male                                             8 (0.64%)                                                                    731                        739( 59.1%)
   Female                                           8 (0.64%)                                                                    504                        512 (40.9%)
 Age                                                                                    0.017*
                                                                                    (0.975, 0.991)
    ≤6                                              16 (1.28%)                                                                   930                        946 (75.6%)
    >6                                                   0                                                                       305                        305 (24.4%)
 Side implanted                                                                          0.038*
    Right                                               14                                                                       884                       898 (71.78%)
    Left                                                 1                                                                       336                       337 (26.93%)
    Bilateral                                            1                                                                        15                        16 (1.28%)
 Pathogen
    MSSA                                            5 (31.25%)
    MRSA                                            3 (18.75%)
    MSSE                                             2 (12.5%)
    MRSE                                             2 (12.5%)
    P. aeruginosa                                    1 (6.25%)
    S. hominis                                       1 (6.25%)
    None detected                                    2 (12.5%)
 Treatment for last time
    Conservation                                    3 (18.75%)                                                                    -
    Surgical treatments
       Revision surgery                             3 (18.75%)                                                                    -
       Re-implant surgery                           10 (62.5%)                                                                    -
MSSA: methicillin-sensitive Staphylococcus aureus; MRSA: methicillin-resistant Staphylococcus aureus; MRSE: methicillin-resistant Staphylococcus epidermidis; MSSE: methicillin-
sensitive Staphylococcus epidermidis; P. aeruginosa: Pseudomonas aeruginosa; S. hominis: Staphylococcus hominis; 95% CI: 95% Confidence Interval. * P < 0.05.



Discussion                                                                                 flap can serve as a facilitating index to stratify clinical man-
                                                                                           ifestations (Fig. 3):
Postoperative infection is one of the most common com-                                     • Stage I. Complete skin with redness and swelling or
plications 5,7, following cochlear implantation, and conser-                                  subcutaneous pus formation that can be adequately ad-
vative treatments are suggested to be primary and first-line                                  dress by conservative treatment
treatment. For post-CI infection, a routine procedure may                                  • Stage II. A skin defect or flap rupture with implant de-
sequentially involve antibiotic treatments, pus puncture, re-                                 vice extrusion that can be remedied by re-implantation.
vision surgery and re-implantation 8, which does not take                                  Of note, in the current study, revision surgery was attempt-
into account the specific clinical postoperative manifesta-                                ed to prevent the receiver/stimulator from explant, which
tions of CI and may cause refractory SFI. Therefore, a more                                proved to be ineffective at Stage II. Thus, re-implantation
accurate and efficient staging system is needed.                                           plays a vital role in the prognosis of patients at Stage II.
In the current study, the integrity of local skin was an index                             This classification system is proposed to address post-op-
that significantly influenced the diagnosis and efficacy of                                erative infection. It can promote the accuracy and effec-
treatments for post-CI infection. Before the skin ruptures,                                tiveness of a specific treatment, relieving pain and reducing
oral or intravenous antibiotic therapy was prescribed. Punc-                               hospitalisation and costs. However, due to a lack of ade-
ture and aetiology-guided antibiotics were administered af-                                quate samples, the effectiveness of conservative treatments
ter abscess formation. Once the integrity of the skin flap                                 for Stage I was statistically insignificant, which needs fur-
was breached, most patients needed to be cured by re-im-                                   ther research.
plantation. These findings suggest that the integrity of skin                              In addition, this classification system was only applied for



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X. Chen et al.




Table II. Clinical data of the 16 patients with skin flap infection after cochlear implantation.
 NO Gender           Age       Hospitalisation       Side of         Post-op        Clinical manifestations                Pathogen                      Prognosis
                    (y/o)          (days)           infection         (days)
 1          F         2.75              2                 Left             20              Ulcer and purulent                MRSA               Revision Surgery + Cured
 2          M           5               2                 Left            1095                Skin redness                   MSSA               Revision Surgery + Cured
 3          F           1               4                 Right            300              Partial prolapse                 MRSE                Explant + right implant
 4          F         2.75              2                 Right           210              Ulcer and purulent                MRSE                 Explant + left implant
 5          F           5               4                 Right           912                Ear discharge               P. aeruginosa            Explant + left implant
 6          M         1.83              3                 Right           365              Ulcer and purulent                MSSE                 Explant + left implant
 7          M           4               3                 Right           150              Ulcer and purulent                MSSE                 Explant + left implant
 8          M         2.75              3                 Right            60                Completely out                  MSSA                        Explant
 9          F         1.08              2                 Right            30              Abscess formation                 MSSA                  Puncture + Cured
 10         F           4               5                 Right           365              Ulcer and purulent              S. hominis             Explant + left implant
 11         M           2               3                 Right           730              Abscess formation                   ND                 Explant + left implant
 12         F         1.33              3                 Right            45              Ulcer and purulent                MSSA                 Explant + left implant
 13         M          4                0                 Right           365                 Skin redness                   MRSA                  Puncture + Cured
 14         M          6                0                 Right           730              Abscess formation                 MRSA                  Puncture + Cured
 15         M          3                3                 Right            60               Partial prolapse                 MSSA                 Explant + left implant
 16         M          3                2                 Right           300          Skin redness and purulent               Nil              Revision Surgery + Cured
MSSA: methicillin-sensitive Staphylococcus aureus; MRSA: methicillin-resistant Staphylococcus aureus; MSSE: methicillin-sensitive Staphylococcus epidermidis; MRSE: methicillin-
resistant Staphylococcus epidermidis; P. aeruginosa: Pseudomonas aeruginosa; S.hominis: Staphylococcus hominis; ND: not detected.



Table III. The prognosis of optional treatments for skin flap infections.
                                                        Conservative treatment                                   Surgical treatment                         P-value
             Feature                                   Antibiotics or/and           Revision          Re-implant                P-value                     (95% CI)
                                                           Puncture                 surgery            surgery                  (95% CI)
 Stage I     Skin redness                                         1                     1                   0                      0.99                      0.464
                                                                                                                               (0.3,1.484)               (0.225,1.113)
             Skin complete with pus formation                     2                     1                   1
 Stage II    A skin defect with purulent                          0                     1                   6                   0.00012*                   0.00001*
             infection                                                                                                       (0.016,0.642)              (0.000,0.0898)
             Partial out                                          0                     0                   2
             Completely out                                       0                     0                    1
 Total       -                                                    3                     3                   10
95% CI, 95% Confidence Interval. * P < 0.05.



post-CI SFI patients with positive bacterial culture results.                               ed that the device’s function can be affected after SFI 9,10,
Skin injury, from antenna pressure stratified by the Na-                                    which is related to persistent infection and hypersensitivity
tional Pressure Ulcer Advisory Panel 5 and foreign body                                     caused by the infection 9. Therefore, such complications
response including knot and device, is not involved in the                                  should also be considered.
current classification system. Similar symptoms from in-                                    The postoperative infection rate in this study is similar
fection, antenna pressure and foreign body response may                                     to that of several previous studies, within the range of
battle the decision on a correct system, which needs more                                   1.6~8.2%11. The incidence of complications has remained
comprehensive study.                                                                        stable for many decades 5,12, no matter how experienced the
It is worth mentioning that no apparent malfunctions were                                   surgeon is with cochlear implantation. This study revealed
reported after cochlear implants, which suggests that post-                                 that all patients with SFI were under the age of 6 years,
CI infection only affects the bone groove and skin flap                                     which may be attributed to malnutrition and potential trau-
where the receiver/stimulator is located while the cochlear                                 ma to the implanted site from daily activities, resulting in
electrodes are safe. However, some studies have report-                                     skin reactions and thinning of the flap. Staphylococcus au-



376
                                                                             Management of biofilm-related skin flap infections following cochlear implantation




                                                                                   Figure 2. Scanning electron microscopic images of implants and histopatho-
                                                                                   logical images of bacteria-suspected material due to severe skin flap necrosis
                                                                                   with the stimulator-receiver exposure. (A) Cocci were imbedded in exopoly-
                                                                                   meric matrix over the receiver/stimulator (5000×); (B) the electrode array was
                                                                                   clear (50×); (C) Cocci were embedded in exopolymeric matrix over the re-
                                                                                   ceiver/stimulator. Large mesh was observed in the middle of the grid (5000×);
                                                                                   (D) histopathological findings showed chronic inflammation, with epithelium in
Figure 1. Local symptoms of different classifications on the stimulator/re-
                                                                                   the foci absent, granulation tissue formed and foam-like tissue cells aggregat-
ceiver sites. (A-B) the pus formed under the skin, with the skin integrity pre-
                                                                                   ed in the tissue section of granulation in the bottom of bone groove.
served. Features such as (A) and (B) were designated as stage I, in which
conservative treatment was the preferred treatment; (C) implant was partly
exposed; (D) implant was completely exposed. Features such as (C) and (D)
were designated as stage II, in which the re-implant surgery was the preferred
treatment.


reus, Staphylococcus epidermidis and Pseudomonas aeru-
ginosa are recognised as the most easily-colonised bacteria
on the surface of implants in most studies 2,5,8. However, for
most SFI cases in the research centre, conservative treat-
ment, even guided by culture results, cannot thoroughly
eradicate SFI, which may relapse in weeks or months.
A jelly-like substance on the flap-covered side of the re-
ceiver-stimulator concentrated in the centre and scattered
around it, which turned out to be a bacterial biofilm by
SEM. It can be suspected that biofilm formation has a more
significant impact on the recurrent SFI than antibiotic re-
sistant strains.
It was possible to remove the granulation tissue around the
implant and soak the receiver-stimulator of the implant with
1.5% hydrogen peroxide and aqueous solution of betadine
for 30 minutes as reported by Skrivan et al. 13 The implants
were subsequently covered with part of temporalis for pro-                         Figure 3. The flow chart of the management of SFI. If initial symptoms are
                                                                                   classified as Stage I, conservative treatments and/or pus drainage and etiolo-
tection, but the results were negative. Grover et al. chose
                                                                                   gy-guided antibiotics are preferred. If initial symptoms are classified as Stage
to re-grind a new bone groove located away from the orig-                          II or Stage I patients are irresponsive to the prescribed treatments, the surgical
inal bone groove and infected area to place the receiver 3.                        treatments, especially re-implantation is necessary.



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X. Chen et al.




This method can be used as a reference, but may potentially         The position of CI incision also impacts the infection rate.
damage the skull of patients, making them vulnerable to             Kabelka et al. found that the postoperative SFI rate of the
intracranial trauma when hit by force.                              incision behind the ear was about 15 times lower than that
Biofilm is easily found on the surface of the device and            of the incision in the ear 5. Gawecki et al. found that when
mostly distributed in the centre of the device 9. This may          a short C-type incision behind the ear was compared with
be due to the absence of a silicone package over the mag-           a long incision, the infection rate decreased from 2.43%
netic pole in the centre of the receiver/stimulator, which          (11/452) to 1.28% (8/624) 5. In this study, all cases were op-
indicates the need for design and material improvements             erated with a short C-type incision behind the ear, and the
of receiver-stimulators to reduce the possibility of post-CI        overall infection rate was lower than in many institutions 11.
infection. Tea tree oil (the essential oil of Melaleuca) has        Ceftriaxone injection is generally used as a preventive med-
been demonstrated to remove methicillin-resistant Staphy-           ication for 3 days after the initial surgery. Valdecasas et al. 5
lococcus aureus from the surface of implants 14-16. Bioactive       reported that the postoperative infection rate was signifi-
glass such as S53P4, as a promising tool containing sodium          cantly reduced when patients with titanium-silicon-coated
oxide, phosphorus pentoxide, silicon dioxide and calcium            implants received 6 weeks of clarithromycin post-operative
oxide, can successfully inhibit the mature bacterial biofilm        instead of only a preoperative dose (relative risk reduction
on the surface of the implanted receiver/stimulator 17-19. Us-
                                                                    of 8:1). They hypothesised that the presence of biofilms on
ing polymer composite sponges with inherent antibacteri-
                                                                    these specific implant surfaces plays a primary role and that
al, haemostatic, inflammation-modulating in surgery may
                                                                    clarithromycin has potential bacteriostatic and bacteriocid-
prevent biofilm dispersal 20. However, the availability and
                                                                    al properties at low and high doses, respectively.
safety of these materials await further exploration.
                                                                    However, this study has some limitations given its retro-
Bacterial biofilm is a complex ecosystem. Multi-microbial
                                                                    spective nature. The number of patients who suffered from
aggregates composed of various bacteria are embedded in
exopolysaccharides (EPS), mainly composed of polysaccha-            SFI was limited, and the results of this study should be
rides, protein-nucleic acids and lipids 21. Antibiotics only in-    confirmed in well-controlled, prospective, randomised con-
hibit the planktonic bacteria released by the biofilm, but fail     trolled studies of clinical cases.
to eliminate the biofilm 22. Bacteria are generally located in
the middle layer of the membrane and are wrapped with the           Conclusions
EPS 23, making it difficult for antibiotics to penetrate all bio-
                                                                    In summary, we propose a staging system to classify the
film layers and eliminate the bacteria. On the other hand, the
                                                                    treatment of SFI, which may optimise individual treat-
implanted cochlear may provide acquired conditions for the
                                                                    ment strategies and reduce hospitalisations and costs for
biofilm to resist the environmental changes and the human
                                                                    patients. Bacterial aetiological analysis reveals that bacte-
immune system 24, which usually terminates when the an-
tenna is removed from the body through a procedure 22. This         rial biofilm contributes to recurrent CI infections, which
complexity may explain the recurrent bacterial infection and        can be cured by re-implantation. Younger patients with CI
the irresponsive antibiotic treatment.                              surgery are at a high risk of refractory repeated infection,
We presume that implant rejection may occur in some cas-            indicating a need of efficient follow-up strategies for this
es instead of the biofilm-related infection, which can ex-          patient population.
plain repeated infection after revision surgery. However,
they can be cured by re-implantation surgery, and bacteria          Acknowledgements
can be present in pus around the receiver/stimulator. Thus,         The authors are grateful to Professor Hongzhi Huang
rejection may not be the direct and primary cause of the            (School of Arts and Sciences, Fujian Medical University)
flap infection.                                                     for reviewing this manuscript for clarity.
Aseptic enhancement during the initial surgery can alle-
viate the suffering of patients and preserve the expensive          Conflict of interest statement
devices by inhibiting the biofilm formation. CI surgery can         The authors declare no conflict of interest.
only commence after the complete resolution of inflam-
mation in the ears 5. Preoperative skin preparation signifi-        Funding
cantly reduces the postoperative infection rate 25, including       This research was supported by National Key R&D Pro-
waxing the patient’s hair a few days before CI, cleansing the       gram of China, which is funded by Ministry of Science
patients’ external auditory canal with 70% alcohol daily with       and Technology of the People’s Republic of China (No.
0.5% chlorhexidine, and wiping the surgical skin area 5.            2020YFC2005204).



378
                                                                        Management of biofilm-related skin flap infections following cochlear implantation




Author contributions                                                          10
                                                                                   Del Pozo JL. Biofilm-related disease. Expert Rev Anti Infect Ther
                                                                                   2018;16:51-65. https://doi.org/10.1080/14787210.2018.1417036
XC and YC contributed equally to this work as first author.                   11
                                                                                   McAllister K, Linkhorn H, Gruber M, et al. The effect of soft tis-
XC and CL conceived and designed the study. XC and YC                              sue infections on device performance in adult cochlear implant re-
analysed the data, generated the figures and wrote the man-                        cipients. Otol Neurotol 2017;38:694-700. https://doi.org/10.1097/
uscript. ZL and SN collected the data. RZ and SY provided                          MAO.0000000000001387
critical revision. All authors read and approved the article.                 12
                                                                                   Hsieh HS, Lee CY, Wu HP, et al. Pressure ulcers and skin infections
                                                                                   after cochlear implantation: a delayed yet serious issue. Int J Pedi-
                                                                                   atr Otorhinolaryngol 2020;138:110241. https://doi.org/10.1016/j.
Ethical consideration                                                              ijporl.2020.110241.
The Ethics Committee of the First Affiliated Hospital of                      13
                                                                                   Skrivan J, Drevinek P. A case report of a cochlear implant infection –
Fujian Medical University approved the study (2016-138).                           a reason to explant the device? Cochlear Implants Int 2016;17:246-
                                                                                   249. https://doi.org/10.1080/14670100.2016.1227019
The procedures and protocols implemented in the conduct                       14
                                                                                   Farnan TB, McCallum J, Awa A, et al. Tea tree oil: in vitro effica-
of this study strictly adhered to the requirements established                     cy in otitis externa. J Laryngol Otol 2005;119:198-201. https://doi.
by the ethics committee and institutional review board of                          org/10.1258/0022215053561495
the First Affiliated Hospital of Fujian Medical University                    15
                                                                                   Brady A, Loughlin R, Gilpin D, et al. In vitro activity of tea-tree oil
and followed the requirements of the World Medical As-                             against clinical skin isolates of meticillin-resistant and -sensitive
                                                                                   Staphylococcus aureus and coagulase-negative staphylococci grow-
sociation’s Declaration of Helsinki.                                               ing planktonically and as biofilms. J Med Microbiol 2006;55(Pt
All participants included in the study signed informed consent.                    10):1375-1380. https://doi.org/10.1099/jmm.0.46558-0
                                                                              16
                                                                                   Brady AJ, Farnan TB, Toner JG, et al. Treatment of a cochlear im-
                                                                                   plant biofilm infection: a potential role for alternative antimicrobial
Availability of data and material                                                  agents. J Laryngol Otol 2010;124:729-738. https://doi.org/10.1017/
The raw data are available on request.                                             S0022215110000319
                                                                              17
                                                                                   Hoing B, Kirchhoff L, Arnolds J, et al. Bioactive glass granules
                                                                                   inhibit mature bacterial biofilms on the surfaces of cochlear im-
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