Pseudomonas aeruginosa remains the dominant pathogen in osteomyelitis of the temporal bone

Abstract

Objective

Osteomyelitis of the temporal bone (OTB) is a rare inflammatory disease that can spread from the ear canal to adjacent soft tissue and bone structures. This expansion is challenging to treat and thus can become life-threatening. The detection of the causative pathogen is crucial for successful therapy. Current studies have revealed a diverse spectrum of pathogenic microorganisms in OTB. The aim of our study was to compare the microbiological background of our OTB-patients with data in recent literature.

Material and Methods

In this retrospective, single-center study patients diagnosed with OTB over a 10-year period were included (n=39). We analyzed the microbiological spectrum, clinical symptoms, radiological findings and course of the disease.

Results

Most common symptoms were otalgia (n=29, 74.4%) and otorrhea (n=24, 61.5%). Microbiological assessment showed most frequently P. aeruginosa (n=21, 53.8%) and the detection of this pathogen was associated with increased CRP levels (p<0.05). Computed tomography showed a washed-out bone texture of the petrous bone in 38 patients (97.4%). During the follow-up period 10 patients (25.6%) reported an improvement of symptoms, whereas 23 patients (59.0%) described their persistence. Four patients (10.3%) died.

Conclusions

In contrast to recently published data, in our patient cohort P. aeruginosa remains the most common and challenging causative pathogen of OTB. Therefore, when selecting an empirical therapy attention should always be given to its efficacy against this pathogen.

Keywords

Otitis externa - Osteomyelitis - Temporal bone - Pseudomonas aeruginosa - Skull base

Introduction

Osteomyelitis of the temporal bone (OTB), also referred to as otitis externa maligna, is a rare but serious disease with an increasing incidence over the past decades [1] [2]. The diagnosis is primarily based on radiological, clinical and microbiological findings. A diabetic metabolic state or immunosuppression are considered to be decisive risk factors [3] [4] [5]. While the first symptoms of OTB, such as chronic otalgia and otorrhea, may be rather unspecific, the short- and long-term consequences can be severely threatening. Some of the most feared complications are cranial nerve palsies and inflammatory involvement of intracranial structures [6] [7] [8] [9]. In addition to the high risk of possible irreversible morbidity, mortality rates are reported to reach 20–50% in complicated cases [10] [11] [12]. Due to the wide range of unspecific clinical symptoms and the absence of standardized diagnostic criteria [13] [14] [15], it is challenging to make an exact diagnosis in an early stage of the disease. However, a rapid diagnosis is important for the timely initiation of therapy and thus the clinical outcome. The identification of the underlying pathogen is essential to initiate an effective antibiotic treatment [16] [17] [18] [19] [20] [21] [22].

In one of the most fundamental studies, which defined the central characteristics of OTB back in 1987, Pseudomonas aeruginosa was described to be not only the main pathogen but its presence was even one of the key diagnostic criteria of OTB [23]. Henceforth, P. aeruginosa has remained the most frequently detected pathogen in this disease [6] [12] [24] [25] [26]. However, a current study reported an increasingly heterogeneous spectrum of microorganisms. In particular, a progressively dominant role of methicillin-resistant S. aureus (MRSA) has been observed, especially in conjunction with a history of ear surgery [27].

In this study, which covered a period of 10 years, we aimed to evaluate whether changes in the pathogen spectrum could also be observed in our patient group.

Material and Methods

Patients

All patients diagnosed with OTB at our department from January 2010 to April 2020 were included in this retrospective study (n=39). The diagnostic criteria were: Clinical findings of otitis externa, lack of response to previous local and systemic therapy and computed tomography signs of an invasive inflammatory disease of the temporal bone originating from the external auditory canal. The patient data (age, sex, symptoms, potential risk factors) and the provided treatment were taken from archived and/or electronic medical records. A follow-up of the patients’ clinical course and outcome was conducted until May 2024 (follow-up period, 19.8 ± 15.8 months; range, 0–58 months). We performed a classification of the outcome in three categories based on the documented anamnestic data during the follow-up period: (i) improvement of symptoms, (ii) persistence of symptoms and (iii) death.

This study was approved by the local Research Ethics Committee (file numbers 20–673 and 20–673_1).

Microbiological diagnostics, radiological imaging and laboratory diagnostics

Microbiological diagnostics were performed for all OTB patients (n=39). Samples were taken from the affected ear pre- or intraoperatively. Routine diagnostic microbiological and laboratory procedures were performed under strict quality-assured conditions according to DIN EN ISO 15189 standards (certificate number D-ML-13102–01–00).

Clinical specimens were streaked onto various solid culture media: Columbia blood agar, chocolate agar, MacConkey agar, Schaedler agar and Sabouraud dextrose agar. Then the samples were inoculated into thioglycolate bouillon for an enrichment culture (agar and bouillon from Oxoid, Wesel, Germany). In the next step, the agar plates were incubated under aerobic culture conditions at 36±1 °C for at least 48h and in case of Sabouraud dextrose agar for 7 days. Schaedler agar and thioglycolate bouillon were incubated anaerobically at 36±1 °C for 7 days. Media were inspected daily for microbial growth. The detected microorganisms were identified by the VITEK MS system and analyzed for their antimicrobial resistance by using the VITEK 2 system (BioMérieux).

All patients (n=39) underwent routine blood tests (blood count, electrolytes, inflammation parameters). All patients (n=39) underwent computed tomography (CT) of the temporal bone as part of the radiological diagnostics. In n=17 cases (43.6%) an additional magnetic resonance imaging (MRI) of the skull was performed.

Statistics

The correlation of the detection of microbial pathogens with various patient parameters was evaluated using the Wilcoxon-Mann-Whitney U-test. The Kolmogorov-Smirnov test with Lilliefors correction was utilized as a pre-test to check the normal distribution assumption. Moreover, contingency table tests, Chi-square tests or exact Fisher tests as well as correlation tests (according to Pearson or Spearman) were also used for data analysis. The influence of individual quantitative and dichotomous patient characteristics on the occurrence of different events (death, pathogen detection or other events) was tested by univariate logistic regression.

The data are presented as mean and standard deviation. In principle, statistical tests were performed bilaterally and with a significance level of alpha=5%. SPSS 22.0 (SPSS Inc., Chicago, IL, U.S.A.) was used to statistically analyse the data. The graphs were created with GraphPadPrism 10.2.3. (GraphPad Software, Boston, MA, U.S.A.).

Results

Patient characteristics, radiological findings, treatment and clinical course

The patient group with OTB identified during the study period (n=39) included 32 male (82.1%) and 7 female (17.9%) patients with an average age of 73.2 (±14.1) years (range, 44–100 years). Three predominant symptoms were reported: otalgia in 29 patients (74.4%), otorrhea in 24 (61.5%) and hearing loss in 21 patients (53.8%). Facial nerve palsy occurred in 12 cases (30.8%). There was no statistical correlation between clinical findings and the detected pathogen spectrum (p>0.05).

In a considerable number of patients (n=33, 84.6%) predisposing factors were identified. Among the most common were diabetes mellitus (n= 26, 66.7%) and arterial hypertension (n=23, 59.0%).

CT imaging revealed a washed-out bone texture of the temporal bone in 38 patients (97.4%), obstructions of the auditory canal, mastoid and middle ear in 31 patients (79.5%) and lysis and destruction of the temporal bone in 30 patients (76.9%). MRI morphologically, 14 of the examined cases (82.4%) had a soft tissue affection and 13 cases (76.5%) each had a T1 signal reduction and T2 signal increase ([Table 1]). However, there was no statistical correlation between the radiological and microbiological findings (p>0.05).

Table 1 Radiological findings.

	Patients (n)	Ratio (%)
Total	39	100.0
Received Imaging
CT	39	100.0
MRI	17	43.6
Localization of the inflammatory process
Otomastoidal	37	94.9
Clivus/ Petrous bone apex	13	33.3
Temporomandibular joint	5	12.8
CT criteria
Obstructions
Auditory canal, mastoid, middle ear	31	79.5
Mastoid, middle ear	2	5.1
Auditory canal, mastoid	2	5.1
Mastoid	3	7.7
Auditory canal	1	2.6
Bone texture alterations
Washed out	38	97.4
Increase of bone density	8	20.5
Mineral salt depletion	3	7.7
Lyses/destructions	30	76.9
Complications (abscess)	5	12.8
MRI criteria (as a proportion of the examinations performed)
T1 signal reduction	13	76.5
T2 signal increase	13	76.5
Contrast agent enhancement	12	70.6
Soft tissue affection	14	82.4

All 39 patients received intravenous antibiotic therapy. In 36 patients (92.3%) the OF was surgically treated and in one case (2.6%) a CT-guided biopsy was performed for histological and microbiological diagnosis. In 12 cases (30.8%) revision surgery had to be performed and 3 patients (7.7%) were operated three times. There was no statistical correlation between the revision rate and the detected pathogen spectrum (p>0.05).

The follow-up period was up to one year for 29 patients (74.4%), up to three years for 6 patients (15.4%) and up to five years for 4 patients (10.3%).

During the follow-up period after therapy 10 patients (25.6%) reported an improvement in their symptoms, half of these patients (n=5) experienced a complete remission of their symptoms. 23 patients (59.0%) complained of persisting symptoms of OTB. 4 patients (10.3%) deceased. There was no statistical correlation between the presence of cranial nerve palsies and a protracted course of the disease or the death of patients (p>0.05). Data such as clinical symptoms, pre-existing illnesses, treatment and clinical course are summarized in [Table 2] and [Table 3].

Table 2 Patient characteristics.

	Patients (n)	Portion (%)
aStandard deviation bChronic obstructive pulmonary disease
Total	39	100.0
Sex
Male	32	82.1
Female	7	17.9
Age, average (± SDa)	73.2 (±14.1)
Symptoms and clinical findings
Otalgia	29	74.4
Otorrhea	24	61.5
Hearing loss	21	53.8
Facial nerve palsy	12	30.8
Hypoglossal nerve palsy	2	5.1
Recurrent laryngeal nerve palsy	1	2.6
Abducens nerve palsy	1	2.6
Glossopharyngeal nerve palsy	1	2.6
Hornerʼs syndrome	1	2.6
Potential risk factors
Diabetes mellitus	26	66.7
Type 1	2	5.1
Type 2	24	61.5
Arterial hypertension	23	59.0
Previous ear-related surgery	9	23.1
Atrial fibrillation	5	12.8
Coronary heart disease	4	10.3
State after apoplex	4	10.3
Hypothyroidism	3	7.7
Benign prostatic hyperplasia	3	7.7
Hypercholesterolaemia	2	5.1
Renal insufficiency	2	5.1
Parkinsonʼs disease	1	2.6
Gout	1	2.6
Ankylosing spondylitis	1	2.6
Acute myeloid leukemia	1	2.6
Obstructive sleep apnea	1	2.6
Cardiac insufficiency	1	2.6
COPDb	1	2.6
Bronchial asthma	1	2.6

Table 3 Treatment and clinical course.

	Patients (n)	Ratio (%)
aincludes primary and revision surgery bincludes changes in initial antibiotic treatment cduring follow-up period
Total	39	100.0
Treatment
Surgical interventiona	36	92.3
Mastoidectomy	21	53.8
Petrosectomy	21	53.8
Radical cavity	11	28.2
Ear canal surgery	11	28.2
Antibiotic treatmentb	39	100
Piperacillin/tazobactam	18	46.2
Ciprofloxacin	14	35.9
Fosfomycin	12	30.8
Ceftazidime	8	20.5
Vancomycin	4	10.3
Clinical coursec
Improvement of symptoms	10	25.6
Persistence of symptoms	23	59.0
Death	4	10.3

Microbiological and laboratory findings

The microbiological findings could be divided into five pathogen-related groups: gram-negative rods (n=26, 66.7%), gram-positive cocci (n=16, 41.0%), fungi (n=10, 25.6%), gram-positive rods (n=6, 15.4%) and anaerobes (n=5, 12.8%). A patient age over 78 years was significantly correlated with the presence of an infection with gram-negative rods (p<0.05, [Fig. 1]). The bacteria most frequently detected from cultures of smears were P. aeruginosa (gram-negative rod) in 21 patients (53.8%) and S. aureus (gram-positive coccus) in 6 patients (15.4%), followed by Enterococcus faecalis (gram-positive coccus) and Corynebacterium spp. (gram-positive rod) in 3 patients (7.7%) each. In addition, fungi were found in 10 patients (25.6%). Here, the most frequent types were: Candida parapsilosis (n=4, 10.3%) and Candida albicans (n=3, 7.7%) ([Table 4]). In the samples of 3 patients (7.7%) no microbial growth was detected. In all other cases (n=36) an antibiogram and antimycogram were performed. There was no association between the detected microbial spectrum including P. aeruginosa and a history of previous ear surgery (n=9; p>0.05, [Fig. 2]).

Table 4 Microbiological spectrum.

	Patients (n)	Portion (%)
aGram-negative rods bGram-positive cocci cGram-positive rods dAnaerobes
Bacterial pathogens
Pseudomonas aeruginosaa	21	53.8
Staphylococcus aureusb	6	15.4
Enterococcus faecalisb	3	7.7
Corynebacterium spp.c	3	7.7
Cutibacterium acnesc	3	7.7
Streptococcus spp.b	2	5.1
Staphylococcus epidermidisb	2	5.1
Finegoldia magnad	2	5.1
Proteus vulgarisa	1	2.6
Enterococcus faeciumb	1	2.6
Escherichia colia	1	2.6
Stenotrophomonas maltophiliaa	1	2.6
Staphylococcus warnerib	1	2.6
Serratia marcescensa	1	2.6
Prevotella orisd	1	2.6
Bacteroides spp.d	1	2.6
Fusobacterium nucleatumd	1	2.6
Coagulase-negative staphylococcib	1	2.6
Proteus mirablisa	1	2.6
Fungal pathogens
Candida parapsilosis	4	10.3
Candida albicans	3	7.7
Candida glabrata	1	2.6
Aspergillus flavus	1	2.6
Aspergillus fumigatus	1	2.6

Fig. 1 Association between the detection of gram-negative rods and patient age (≤ 78 years, 19 patients; >78 years, 20 patients). *p<0.05.

Fig. 2 Detection of Pseudomonas aeruginosa and previous ear surgery (9 patients with previous ear surgery; 30 patients without previous ear surgery). ns, not significant.

With regard to P. aeruginosa, the most frequently detected microorganism, all isolates were susceptible to piperacillin/tazobactam, ceftazidime, cefepime, imipenem and meropenem. Two isolates (9.5%) were found to be resistant against fosfomycin. There was no significant correlation between the detection of P. aeruginosa and a fatal outcome (p > 0.05).

The laboratory blood tests showed that leukocytosis was present in only 8 patients (20.5%) with an average of 10.5 (±2.7) leukocytes/nl (reference value 4–10 leukocytes/nl). No correlation between the detected pathogens and leukocytosis was detected (p > 0.05). However, an elevated concentration of the C-reactive protein (CRP) was detected in 35 patients (89.7%) with an average value of 5.1 (±3.6) mg/dl (reference value 0.0–0.5 mg/dl). The detection of P. aeruginosa was significantly associated with an increased CRP value (p<0.05, [Fig. 3]).

Fig. 3 Association between the CRP value (reference value 0.0–0.5 mg/dl) and Pseudomonas aeruginosa detection (Pseudomonas-positive, 21 patients; Pseudomonas-negative, 18 patients). *p<0.05.

Discussion

OTB is a chronic progressive disease that, if left untreated, can spread through the petrous bone and base of the skull, thus causing life-threatening complications [10] [12] [28] [29]. Effective and targeted antimicrobial therapy is essential for the management of this disease. Therefore successful identification of the causal pathogen is key [16] [17] [21] [22]. In recent decades P. aeruginosa has been known to be the main pathogen of OTB [12] [23] [30] [31]. Chen et al. [27] compared the spectrum of pathogens in patients with OTB in Taiwan during the periods 1990–2001 and 2002–2011. Although it should be noted that the patients in these two groups were heterogeneous in terms of a number of characteristics (e.g. proportion of diabetic patients), data revealed a change in the spectrum of pathogens with an increasing prevalence of MRSA, especially in patients with previous ear-related surgeries [27].

In contrast to these findings, our results revealed a persistent dominance of P. aeruginosa. We detected P. aeruginosa in more than half of the patients (n=21, 53.8%), whereas S. aureus was found in only 6 patients (15.4%). Notably, MRSA was not detected among our study population. Moreover, there was no correlation between a history of previous ear-related surgery and the observed microbial spectrum (p>0.05). The discrepancy in the frequency of detected MRSA cases might be biased by the different prevalences of MRSA in Germany and Taiwan: recent data show a MRSA prevalence in Taiwan between 17 and 27% [32], whereas in Germany it is reported to be significantly lower at approximately 8.5% [33].

The increasing development of antimicrobial resistance represents a threat to the effectiveness of an early treatment of the assumed pathogen. Nearly 10% of the P. aeruginosa isolates detected in our patient cohort turned out to be resistant against fosfomycin. P. aeruginosa is known to have intrinsic resistance against a variety of antibiotics and an outstanding capacity to acquire resistance mechanisms during treatment [34] [35]. These findings suggest a progressive development of resistance and thus an increasing complexity of OTB therapy.

The diagnostic criteria for OTB are inconsistent in the literature, which complicates timely diagnosis. Clinical findings of otitis externa, which showed a lack of response to previous local and systemic therapy, as well as radiological signs of invasive inflammation of the temporal bone starting from the auditory canal are listed as core findings of the disease [14] [15]. In our study, a CT scan of the temporal bone was performed in all cases at the time of diagnosis, which showed the extent of the bony inflammatory process. In some cases, an additional MRI of the skull was performed to identify soft tissue affections. The routine use of MRI in the diagnosis of OTB could facilitate the diagnosis in the future and improve the assessment of the inflammatory spread of the disease [6].

In our cohort a high proportion of patients (92.3%) underwent surgical treatment of the inflammatory process. There is a lack of consensus in the literature regarding the necessity of a surgical approach in the treatment of OTB. While many authors support debridement [14] [15], other authors limit the surgical procedure only for the purpose of a biopsy for histological and microbiological examination of the tissue removed [13].

Our results confirm previous findings that OTB is a disease of elderly patients [17] [21] [27] [36]. Interestingly, we observed a significant correlation between patient age and the presence of gram-negative rods – mainly P. aeruginosa. Moreover, our data show that an elevation in the CRP value is significantly correlated with the presence of a P. aeruginosa infection. Thus, in elderly OTB patients – the wide majority of the affected – with high CRP levels a specific pathogen spectrum can be anticipated and consequently a calculated antibiotic therapy covering P. aeruginosa can be initiated even before microbiological results are available. To our knowledge, the significant correlation between an elevated CRP value and detection of P. aeruginosa has not yet been described in the literature. In contrast to CRP levels, leukocyte count does not appear to be a predictive factor for the underlying pathogen.

In our study, no correlation between the detected spectrum of microorganisms and mortality was found. Nonetheless, our follow-up data underline that OTB is a serious disease with high morbidity rates and partial symptom persistence (59% in our patient cohort) even after extensive therapy confirming data from previous studies [10] [16] [21].

The limitations of this study relate to its retrospective and monocentric character and the rather small study population which is due to the rarity of the disease. Moreover, the lethal outcomes in our patient series could not be causally attributed to OTB. Therefore, no disease-related mortality rate can be derived from our cohort. Furthermore, the long-term effects of OTB on quality of life and secondary complications were not systematically recorded. These parameters could be included as primary endpoints of future studies.

Conclusion

Our results do not confirm a shift in the microbial spectrum of OTB toward MRSA. P. aeruginosa appears to remain the major pathogen of this devastating disease. Thus, we propose that especially in a typical OTB patient cohort of elderly patients an empiric, calculated antibiotic therapy covering P. aeruginosa should be initiated. Owing to the increasing prevalence of antibiotic resistances the choice of an adequate and effective therapy can become increasingly difficult. Effective monitoring and surveillance systems will be necessary to evaluate the future development of resistance in order to establish the most effective empiric antibiotic treatment.

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgement

The authors would like to thank Dr Annette Lehn and Natalie Filmann (Institute of Biostatistics and Mathematical Modelling) for their support with the statistical analysis.

• Literatur

• 1 Johnson AK, Batra PS. Central skull base osteomyelitis: an emerging clinical entity. The Laryngoscope 2014; 124: 1083-1087
• 2 Lucente FE, Parisier SC. James R. Chandler: “Malignant external otitis”. (Laryngoscope. 1968; 78: 1257–1294). The Laryngoscope 1996; 106: 805-807
• 3 Long DA, Koyfman A, Long B. An emergency medicine-focused review of malignant otitis externa. Am J Emerg Med 2020; 38: 1671-1678
• 4 Hobson CE, Moy JD, Byers KE. et al. Malignant Otitis Externa: Evolving Pathogens and Implications for Diagnosis and Treatment. Otolaryngology-head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 2014; 151: 112-116
• 5 Lee SK, Lee SA, Seon SW. et al. Analysis of Prognostic Factors in Malignant External Otitis. Clin Exp Otorhinolaryngol 2017; 10: 228-235
• 6 Auinger AB, Arnoldner C. Current management of skull base osteomyelitis. Current opinion in otolaryngology & head and neck surgery 2021; 29: 342-348
• 7 Brenner A, Cavel O, Shendler G. et al. CT findings in temporal bone sites in skull base osteomyelitis from malignant otitis externa. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology – Head and Neck Surgery 2023; 280: 2687-2694
• 8 Reñé R, Mas A, Villabona CM. et al. Otitis externa maligna and cranial neuropathy. Neurologia 1990; 5: 222-227
• 9 Rubin Grandis J, Barton F, Yu VL. The changing face of malignant (necrotising) external otitis: clinical, radiological, and anatomic correlations. The Lancet. Infectious diseases 2004; 4: 34-39
• 10 Bhandary S, Karki P, Sinha BK. Malignant otitis externa: a review. Pacific health dialog 2002; 9: 64-67
• 11 Carfrae MJ, Kesser BW. Malignant otitis externa. Otolaryngologic clinics of North America 2008; 41: 537-49
• 12 Tisch M, Maier H. Malignant external otitis. Laryngo- rhino- otologie 2006; 85: 763-769
• 13 Hutson KH, Watson GJ. Malignant otitis externa, an increasing burden in the twenty-first century: review of cases in a UK teaching hospital, with a proposed algorithm for diagnosis and management. The Journal of laryngology and otology 2019; 133: 356-362
• 14 Glikson E, Sagiv D, Wolf M. et al. Necrotizing otitis externa: diagnosis, treatment, and outcome in a case series. Diagn Microbiol Infect Dis 2017; 87: 74-78
• 15 Soudry E, Hamzany Y, Preis M. et al. Malignant external otitis: analysis of severe cases. Otolaryngology-head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 2011; 144: 758-762
• 16 Slattery 3rd WH, Brackmann DE. Skull base osteomyelitis. Malignant external otitis. Otolaryngologic clinics of North America 1996; 29: 795-806
• 17 Ali T, Meade K, Anari S. et al. Malignant otitis externa: case series. The Journal of laryngology and otology 2010; 124: 846-851
• 18 Bhat V, Aziz A, Bhandary SK. et al. Malignant Otitis Externa – A Retrospective Study of 15 Patients Treated in a Tertiary Healthcare Center. The journal of international advanced otology 2015; 11: 72-76
• 19 Devaraja K, Nayak DR. Malignant otitis externa with subsequent internal jugular vein thrombosis and hypoglossal palsy: a report and review of literature. Journal of otology 2020; 15: 112-116
• 20 Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. S2k Leitlinie Kalkulierte parenterale Initialtherapie bakterieller Erkrankungen bei Erwachsenen. 2019 Zugriff am 22. Februar 2025 unter: https://register.awmf.org/assets/guidelines/082–006l_S2k_Parenterale_Antibiotika_2019–08-abgelaufen.pdf
• 21 Koch U. Malignant otitis externa. Laryngol Rhinol Otol 1983; 62: 276-279
• 22 Mortazavi MM, Khan MA, Quadri SA. et al. Cranial Osteomyelitis: A Comprehensive Review of Modern Therapies. World neurosurgery 2018; 111: 142-153
• 23 Cohen D, Friedman P. The diagnostic criteria of malignant external otitis. The Journal of laryngology and otology 1987; 101: 216-221
• 24 Franco-Vidal V, Blanchet H, Bebear C. et al. Necrotizing external otitis: a report of 46 cases. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 2007; 28: 771-773
• 25 Mani N, Sudhoff H, Rajagopal S. et al. Cranial nerve involvement in malignant external otitis: implications for clinical outcome. The Laryngoscope 2007; 117: 907-910
• 26 Thio D, Reece P, Herdman R. Necrotizing otitis externa: a painless reminder. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology – Head and Neck Surgery 2008; 265: 907-910
• 27 Chen J-C, Yeh C-F, Shiao A-S. et al. Temporal bone osteomyelitis: the relationship with malignant otitis externa, the diagnostic dilemma, and changing trends. TheScientificWorldJournal 2014; 2014: 591714
• 28 Rajasekaran V, Mohanraj L, Prabhu ND. Silent otitis media with multiple intracranial complications. BMJ Case Rep 2024; 17
• 29 Faizal B, Nair L, Pavithran J. et al. Role of surgery along with antimicrobials in refractory skull base osteomyelitis – A prospective observational study. Clin Otolaryngol 2024; 49: 640-651
• 30 Chapman PR, Choudhary G, Singhal A. Skull Base Osteomyelitis: A Comprehensive Imaging Review. AJNR. American journal of neuroradiology 2021; 42: 404-413
• 31 Krishnakumar L, Vinayakumar V, Suchit Roy BR. et al. Skull Base Osteomyelitis- Marauders of the Skull. Indian J Otolaryngol Head Neck Surg 2024; 76: 1770-1774
• 32 Wu M, Tong X, Liu S. et al. Prevalence of methicillin-resistant Staphylococcus aureus in healthy Chinese population: A system review and meta-analysis. PloS one 2019; 14: e0223599
• 33 Robert Koch Institut. Aktuelle Daten und Informationen zu Infektionskrankheiten und Public Health Epidemiologisches Bulletin. Zugriff am 22. Februar 2025 unter: https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2021/Ausgaben/40_21.pdf?__blob=publicationFile
• 34 Pang Z, Raudonis R, Glick BR. et al. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnology advances 2019; 37: 177-192
• 35 Laborda P, Hernando-Amado S, Martínez JL. et al. Antibiotic Resistance in Pseudomonas. Advances in experimental medicine and biology 2022; 1386: 117-143
• 36 Kloth C, Beck A, Sollmann N. et al. Imaging of Pathologies of the Temporal Bone and Middle Ear: Inflammatory Diseases, Their Mimics and Potential Complications-Pictorial Review. Tomography 2023; 9: 2190-2210

Publikationsverlauf

Eingereicht: 30. März 2025

Angenommen nach Revision: 11. August 2025

Artikel online veröffentlicht:
16. September 2025